Pulmonology - Study Guide PDF

1 Pulmonology
Left shift
Oxygen
Dissociation
Curve
Breath
Sounds Normal
Breath
Sounds Adventitious
Vocal
Resonance
Physical Exam
Hb has greater affinity for O2
O2blood = O2tissue = hypoxia
temperature
Decreased temperature slows transfer of O2 blood
CO2
tissue
pH
Hyperventilation
Right Shift
temperature
O2blood = hypoxemia
Fever tissues req. more O2
CO2
Hypoventilation
pH
Vesicular
Soft, low-pitched
Heard over most lung fields
Inspiration > expiration
Bronchovesicular Medium pitched
Heard over main bronchus and (R) upper posterior lung
Inspiration = expiration
Bronchotracheal Loud, high-pitched
Only heard over trachea
Expiration slightly > inspiration
Discontinuous
Heard more often in inspiration
Crackles (Rales)
Not usually cleared by coughing
Small airways forced open in destructive fashion
Dry or wet
Fine, medium or coarse
Continuous
Rhonchi
Fog horn or snoring quality
Air passing through obstructed airway
Usually clear with cough
Continuous
Musical, high-pitched sound
Wheezes
Forceful airflow through a constricted airway
Most commonly heard with asthma diffuse, usually bilateral
Unilateral wheezing in pediatrics FB aspiration
Pleural sound
Like leather rubbing together
Rub
Inflamed pleural spaces rubbing together
Evanescent
Dependent on amount of fluid in pleural space
Egophany
E heard as A
AKA transmitted voice sounds
Bronchophany
99 sounds louder and clearer
Assess anywhere that adventitious sounds are heard
Increased transmission of voice airless lung
Whispered pectoriloquey
Whispered sounds are clearer
Compiled by Abbie Pettigrew, class of 2016
2 Pulmonology
Function
Cough
Causes
Pathophysiology
Timing
Complications
Evaluation
Treatment
Definition
Dyspnea
Timing
Pathophysiology
Evaluation
Treatment
Common Symptoms
Clears the tracheobronchial tree of mucous, foreign particles, and noxious aerosols
May impair sleep, social functioning
Acute respiratory infection
Pulmonary embolism
Acute
Pneumonia
Pulmonary edema
Aspiration
Low-grade chronic bronchitis
Smokers
Increased intensity, intractability of pre-existing cough lung cancer
Chronic
Upper airway cough syndrome (PND)
GERD
Non-Smokers
Asthma
ACE-I induced
Initiated through a complex reflex arc
Involuntary Stimulated cough centers in respiratory tract send impulses to cough center in medulla
Gender-related differences in cough reflex sensitivity F>M to develop chronic cough
Acute
<3 weeks
Persistent
3-8 weeks
Chronic
>8 weeks
Fatigue
Headache
Rib fractures (ribs 5-7)
Insomnia
Urinary incontinence
Timing of cough
Nasal discharge
H&P
Wheezing
Sputum production
Frequent throat clearing
CXR
Especially in smokers, patients with fever or weight loss
Unexplained cough >3-6 weeks
Eliminate irritant exposures smoke,
Persistent cough after URI
Treat underlying cause
occupational agents
think asthma
An uncomfortable awareness of breathing, not appropriate to the level of exertion
Acute
Onset minutes-hours
Chronic
Develops over weeks-months
Bronchospasm
Pulmonary edema
Respiratory
Pulmonary infection (bronchitis, pneumonia)
Pneumothorax
Pulmonary embolism
Upper airway obstruction
Acute
Acute MI
Cardiovascular
Cardiac tamponade
CHF
Anemia
Deconditioning
Other
DKA
Anxiety disorder
Asthma
Interstitial lung disease
Chronic
COPD
Cardiomyopathy
Fever
Chest pain
H&P
Cardiac/chest exam
Cough
Vital signs
Oximetry
CBC
Spirometry
Diagnostics
ABG
CXR
ECG
-
Treat the cause
Oxygen
Pulmonary rehabilitation
Treat anxiety
3 Pulmonology
Definition
Types
Hemoptysis
Pathophysiology
Causes
Origins
Evaluation
Treatment
Tumor Risk
Factors
Expectoration of blood originating below the vocal cords

Ranges from blood streaking of sputum to gross blood without sputum
Trivial
Mild
Massive/life-threatening (200-600 mL in 24 h)
Most likely from bronchial arteries
Mimics = URI bleeding, upper GI bleeding
Bronchitis
Pneumonia
Bronchogenic carcinoma
Infection
Parenchymal
Goodpastures syndrome
Disease
Other auto-immune d/o
Pulmonary
AV malformation
Vascular Disorders Pulmonary embolism
Foreign body
Other
Airway or parenchymal trauma
H&P
Hematocrit
CXR
UA, renal function
>40 years
Warrants aggressive work-up
>40 pack-year smoking history
>1 week of hemoptysis
Iatrogenic (drugs, radiation)

Cocaine
Elevation pulmonary capillary pressure (MS, LVH)

Iatrogenic (e.g. PA catheter)
Fistula formation (vessel-tracheobronchial tree)
Idiopathic
Coag studies
Bronchoscopy, HRCT
4 Pulmonology
Obstructive Airway Disease

General
Asthma
Spirometry
Inflammation narrowed airway reduced airflow

More distal involvement can create alveolar destruction
Low FEV1/VC ratio below 70% predicted (based on age, sex, height)
Episodic wheezing and SOB
Definition
Wheezing due to air forced through narrow airways, worse on expiration
Allergies (IgE) dust mite, cockroach droppings
Hyper-reactive airways from
Induced occupation exposure, viruses, environment, exercise, inhaled toxins
Etiology
Mast cells
Cellular Elements
Eosinophils
CD4 lymphs
Environment
Infection
Stress
Triggers
Allergies
Sinuses
Exercise
GERD
Childhood allergic asthma Dissipates as immune system grows up
Natural
Waxes/wanes depending on inducing causes
History
Acquired Asthma
Persistent reactivity predisposes to COPD
Reduced FEV1/FCV
Spirometry
Increased RV
Allergens
Control of
Sulfite sensitivity no shrimp, dried fruit, processed potatoes, beer,
Tobacco smoke
Factors
wine
Rhinitis IN steroids + antihistamine/decongestants
Contributing
Medication interactions no BB; risk reaction to ASA/NSAIDs
Sinusitis promote drainage; abx when appropriate
to Asthma
Occupational exposures avoidance, ventilation, respiratory protection
GERD no eating within 3h bed, elevate head 6-8in,
Severity
Viral respiratory infections annual influenza vaccine
meds
Intermittent
SABA PRN
Step Preferred
Alternative
2
Low-dose ICS
Cromolyn, LTRA, Nedocromil, Theophylline
Persistent
3
Low-dose ICS + LABA or medium-dose ICS
Low-dose ICS + either LTRA, Theophylline, or Zileutron
Daily
4
Medium-dose ICS + LABA
Medium-dose ICS + either LTRA, Theophylline, or Zileutron
Medications
5
High-dose
ICS
+
LABA
AND
consider
Omalizumab
for
patients with allergies
Treatment
6
High-dose ICS + LABA + oral corticosteroid AND consider Omalizumab for patients with allergies
Consult with asthma specialist if step 4+ care req. (consider at step 3)
Before stepping up, check adherence, environmental control, comorbid conditions)
Step down if possible (and asthma well-controlled at least 3 months)
At each step, patient education + environmental control + management of comorbidities
Steps 2-4: consider subQ allergen immunotherapy for patients with allergic asthma
-
5 Pulmonology
Triggers
Infections
Acute exposures to allergens
Variants
Potentially
Fatal Asthma
Exacerbations
Treatment
Exercise/cold air
Stress
Progressive worsening (1-3 days)

History of near fatal asthma/intubations
Risk Factors
Frequent hospitals/ED (>2/years)
Co-morbidities (CV, COPD, psych, drug abuse))
Beta-agonists
Backbones
Steroids
Severity (% Baseline Peak Flow)
Mild (>80%)
Moderate (50-80%)
Increase beta agonist
Severe (<50%)
Anaphylactic-like reaction
(sudden death) massive
bronchoconstriction + mucus
filling airway
Frequent medications (>2 puffs/month)

Poor socio-economic status
Treatment
If on inhaled steroid, double dose
Add/increase oral steroid
Add/increase oral steroid
Proceed to ED
Asthma
Staging (> 12
years)
Intermittent, mild, moderate, severe

Based on symptoms, night-time wakening, need for rescue inhalers, interference with normal activity, lung function
Classification of Severity
Components of Severity
Persistent
Intermittent
Mild
Moderate
Severe
>2 days/week but
Symptoms
< 2 days/week
Daily
Throughout the day
not daily
Nighttime
>1x/week but not
< 2x/month
3-4x/month
Often 7x/week
awakenings
nightly
>2 days/week, but
Impairment
SABA use for
not daily and not
Several times per
Normal FEV1/FVC:
symptom control
< 2 days/week
Daily
more than 1x on any
day
8-19 years = 85%
(not EIB prevention)
day
20-39 years = 80%
Interferes with
40-59 years = 75%
None
Minor limitation
Some limitation
Extremely limited
normal activity
60-80 years = 70%
Normal FEV1
FEV1 > 60% but <
between
FEV1 < 60% predicted
FEV1 > 80% predicted 80% predicted
Lung function
exacerbations
FEV1/FVC reduced
FEV1/FVC normal
FEV1/FVC reduced
FEV1 > 80% predicted
>5%
5%
FEV1/FCV normal
0-1/year
>2/year
Exacerbations
Consider severity and interval since last exacerbation
Risk
requiring oral
Frequency and severity may fluctuate over time for patients in any severity category
corticosteroids
Relative annual risk of exacerbations may be related to FEV 1
6 Pulmonology
A systemic
disease
Chronic airway inflammation spills inflammatory cytokines into circulation, which can injury other
organs
COPD
Chronic
Bronchitis
Etiology
Natural History
Fixed airway obstruction involving

alveoli
Distal predominant
(alveoli/small airways)
Active respiratory
drive
(= dyspnea)
Pink puffer
Distant breath sounds
Middle age/elderly
Reduced DLCO
Hyperinflation
Cor pulmonale late
Near normal PO2/PCO2

until late
Reduced respiratory
drive
Blue bloater
Wheeze/rhonchi
Hyperinflation
Cor pulmonale
Lo PO2/hi PCO2
chronically
Proximal predominant
(large airways)
Cough, phlegm (mucous
Middle age/elderly
gland hypertrophy)
Inhaled toxins tobacco, indoor cooking
Anti-protease deficiencies (only 40% of smokers get COPD)
Airway remodeling in persistent asthma
Depends on tobacco exposure and sensitivity
I: Mild
Fixed airway obstruction
Based on
spirometry
GOLD Staging
FEV1/FVC < 70%

FEV1 > 80%
With or without
symptoms
Staging
Airway
Beyond
Spirometry
Function
Spirometry is insensitive
to:
CT scan Chest
Exercise intolerance
Risk of exacerbations
Combined Assessment of COPD

Radiology
ASCVD
Renal insufficiency
Neuro-myopathy
Osteoporosis
Cachexia, debility
Disease dyspnea deconditioning
Downward spiral in function
Emphysema
Classes A, B, C, D
II: Moderate
III: Severe
FEV1/FVC < 70%

50% < FEV1 <
80%
With or without
symptoms
FEV1/FVC < 70%

30% < FEV1 <
50%
With or without
symptoms
IV: Very Severe

FEV1/FVC < 70%
FEV1 < 30% or
presence of
chronic
respiratory failure
or R heart failure
Alveolar destruction/emphysema
Trapped gas
Dyspnea vs cough vs hypoxemia

Impairments that may/may not be rel. to COPD
Spirometry only loosely tied
Spirometry (GOLD)
Dyspnea (mMRC, CAT)
Exacerbation risk (per exacerbation history)
Not that useful

Air trapping
7 Pulmonology
NonPharmacologic
Pharmacologic
COPD
Treatment
Oxygen
Surgery
Overview
Management
Acute
Exacerbation
Consequences
Prevention
Tobacco cessation (+ pharmacologic treatment)

Physical activity
Pulmonary rehabilitation (classes B, C, D) education, exercise, psycho-social support
Flu and pneumococcal vaccination
Patient
Recommended 1st Choice
Alternative
Other Possible Treatments
LAMA or
SAMA PRN or
A
LABA or
Theophylline
SABA PRN
SABA and SAMA
LAMA or
SABA and/or SAMA
B
LAMA and LABA
LABA
Theophylline
LAMA and LABA or
ICS + LABA or
SABA and/or SAMA
C
LAMA and PDE4-inh. or
LAMA
Theophylline
LABA and PDE4-inh.
ICS + LABA and LAMA or
Carbocysteine
ICS + LABA and PDE4-inh. or
D
ICS + LABA and/or LAMA
SABA and/or SAMA
LAMA + LABA or
Theophylline
LAMA and PDE4-inh.
For hypoxemia (< 89%)
Clear reduction in mortality in patients with fixed hypoexmia
Data not present for episodic hypoexmia, but prescribed and paid for by Medicare)
Transplantation Reserved for very select patients
Lung Volume
Removes overdistended, non-functional lungs to allow more room for normal lung to expand and puts
Reduction
diaphragm at a better rest point
Surgery
Works to improve mortality and exercise tolerance if hyper-inflated areas are present at the apices (?)
Defined clinically
Usually have an infectious trigger
Must rule out PE, CHF, PNA, etc.
The same medications as
Bronchodilators
Antibiotics
maintenance, but increased
Steroids (PO or IV)
NPPV (cautiously)
doses
Oxygen (PRN)
Negative impact on quality of life
Increased mortality
Impact on symptoms and lung function
Accelerated lung function decline
Increased economic costs
Clinical
Proper diagnosis/staging/prescribing per guidelines
Understanding complex medication regimens
Patient
Barriers to Effective
Adherence to treatment plans
COPD Management
Access to clinicians
System
Proper discharge planning
Access to pulmonary rehabilitation
8 Pulmonology
Definition
Etiology
Bronchiectasis
Presentation
Diagnostics
Treatment
Abnormal dilation of the bronchi resulting from inflammation and permanent destructive changes in elastic and muscular layers of the
bronchial walls
May be localized or diffusion
Usually caused by recurrent or chronic severe infections necrotizing pneumonia (i.e. S. aureus), TB, atypical mycobacteria infection (MAI),
viral (measles), fungal (histoplasmosis, coccidiodomycosis)
Allergic bronchopulmonary aspergillosis
Localized anatomic obstruction (FB, tumor, broncholith), extrinsic compression (LAD)
Chronic cough, foul-smelling sputum, SOB, abnormal chest sounds, fatigue
Blood-streaked sputum common; massive hemoptysis may occur
Clubbing may be present
Periodic exacerbations d/t bacterial infections (P. aeruginosa, S. pneumo, H. flu) common
PFTs
Varying degrees of obstruction
Normal or increased interstitial markings
CXR
Tram tracks classic (parallel lines in peripheral lung fields)
Test of choice for diagnosis, more sensitive for detection of dilated airways
HRCT
Lack of airway tapering at lung periphery, airways larger in diameter than accompanying blood vessel
Bronchoscopy
Maybe for localized, to assess for endobronchial abnormalities
Assess for fungal, mycobacterial organisms
Sputum Culture
ID bacterial pathogens during exacerbation
Underlying Cause
Remove obstruction, treat infection, etc.
Aerosolized Antibiotics
Suppression of bacterial growth if associated with CF
Airway Clearance,
Questionable benefit
Postural Drainage
Bronchodilators
Symptomatic relief
Removal of badly damaged, isolated segment of bronchietic lung
Surgery
Resection of obstruction
Occasionally salvage therapy in resection of site with uncontrolled hemorrhage
Airway protection
Hemoptysis
ID bleeding site
Bronchial artery angiography + embolization of causative bleeding vessels
9 Pulmonology
Diagnostic
Tests
Pathophysiology
Cystic Fibrosis
Genetics
Presentation
at Time of
Diagnosis
Cystic fibrosis transmembrane regulator gene is located on chromosome 7

Encodes a glycoprotein that is a chloride and bicarbonate transporter
>2,000 known mutations only 250 are known to cause CF
Mutations are autosomal recessive
Most common lethal genetic disorder in white population (1:29 carriers, 1:3,000 live births affected; 1,000 new diagnoses/year)
Defect
Result
Example
Classification
Normal
Protein at cell surface, with an open channel that allows flow of Cl- and HCO3I
No synthesis
G542X
Most common
II
Block in processing
F508del
Golgi degrades protein d/t abnormalities
III
Block in regulation
Dysfunctional channel at cell surface
G551D
IV
Altered conductance
Doesnt move chloride well, can move HCO3R117H
Functional protein that is 1) under-produced, or
V
Reduced synthesis
A445E
2) not remaining at cell surface proper length of time
Immunoreactive
Blood test
trypsinogen (IRT)
Pancreatic enzyme that is elevated in pancreatic-insufficient CF patients
Newborn
Second tier
Screening
Genetic Testing
For 23 most common alleles
Identifies 90% CF cases (lower for African or Hispanic Americans)
Confirmation of Newborn Screening
Sweat
<40 normal
Quantitative pilocarpine iontophoresis
Chloride
40-60 borderline/inconclusive
Can only be done at CF centers
Testing
>60 positive for CF
Cannot be done until 3 weeks of age
Buccal smear/serum
DNA Testing
For remaining mutations
Assess CFTR function in airways looking at Cl- and
Nasal
Over age 9, requires cooperative patient
Na+ movement at the epithelial layer of the nose and
Potential
Causes with borderline sweat test, only one mutation
lungs
Difference
Primarily a research test
CFTR gene defect defective ion transport airway surface liquid depletion defective mucociliary clearance mucus obstruction
Mucus obstruction infection inflammation mucus obstruction, etc.
Innate immune system of lungs
Normal Function Hydrates epithelial surfaces, binds and clears bacteria through ciliary movement, detoxifies and clears
Airway
particulates, protects against oxidants and proteases
Mucus
Decreased sol layer (periciliary liquid) means cilia stick together and arent able to fully extend, propel
CF Patient
mucus defective mucus clearance
Other Organs Cilia problems hold true for other organs with cilia = sinuses, GI tract, pancreas
Newborn screening
Failure to thrive
Recurrent pulmonary infections
Meconium ileus
Poorly controlled asthma
Manifestations General
Overview
Pulmonary
Manifestations
Gastro
intestinal
Cystic Fibrosis
Phenotypes
10 Pulmonology
Each mutation is associated with a certain percent of CFTR function, leading to various clinical manifestations
As CFTR function decreases < 5%, disease manifestations emerge
Dont have great severity scale for lung function, talk about severity in terms of pancreatic function
Classification
% Normal CFTR Function
CF Manifestations
50-100%
No known abnormality asymptomatic heterozygotes, normal persons
Normal
10-49%
No known abnormality
Mild
<10%
Congenital absence of vas deferens
<5%
Clinically demonstrable sweat abnormality (plus above)
Classic
<4.5%
Progressive pulmonary infection (plus above)
<1%
Pancreatic exocrine deficiency (plus above)
General
Growth failure
Vitamin deficiencies (vitamin A, D, E, K)
Nose/Sinuses Nasal polyps
Sinusitis
Liver
Fatty liver
Clogging of vessels in liver
Gallbladder
Cirrhosis
Gallstones
Jaundice
Bones
Frequent fractures
Osteoporosis
Arthritis
Stomach/
Meconium ileus
Strictures around the intestines
Obstruction of the intestines
Intestines
Rectal prolapse
Appendicitis
Reflux disease
Females: delayed or no periods,
Reproductive Males: infertility
All: delayed puberty
50% infertile
Pancreas/
Pancreatitis
Diabetes/glucose intolerance
Spleen
Pancreatic insufficiency
Enlarged dysfunctional spleen
Widening of the bronchioles
Lung collapse
Lungs
Pneumonia
Asthma
Hemoptysis
Respiratory failure
Chronic cough
Amount depends on mucus production, efficacy at removing it
Chest pain
Due to chronic cough
Dyspnea
Difficulty getting O2 across the mucus
Sputum production
Bronchiectasis
Due to recurrent infection, chronic inflammation
Pneumothorax
Due to popping open bronchi
Massive
Hemoptysis
Due to erosion into pulmonary vasculature (bronchial artery) from
Complications
bronchiectasis
Ultimate outcome
Respiratory failure
Goal of treatment is to delay and prevent this via aggressive mucus
management
Failure to thrive
Pancreas not providing necessary enzymes
Fat malabsorption
Results in failure to thrive and vitamin deficiency
Thick stool causes intestinal blockage in utero, sometimes eroding through intestine and causing failure in utero
Meconium ileus
or inability to pass meconium after birth, leading to bowel perforation
11 Pulmonology
Gastrointestinal
Manifestations
Pancreatitis
Cystic Fibrosis
Infectious
Disease
Endocrine
If pancreatic sufficient (mild, class III/IV)
Rectal Prolapse
Bowel obstruction
Complications
Gallbladder disease/gallstones
Liver failure/cirrhosis/portal hypertension
Esophageal varices and bleeding
Fibrosing colonopathy
Thick, sticky stool results in constant straining

Distal intestinal obstruction syndrome
Most commonly at junction of small and large intestines
Inflammation of pancreatic ducts spreads to gall ducts, liver
From use of enzymes (meds), which, in excess, cause scarring of

the colon resulting in stricture or stenosis
Chronic pancreatitis
Recurrent Infections
Frequently leading to worsening symptoms
S. aureus, P. aeruginosa
Multi-antibiotic resistant organisms MRSA
Burkholderia cepacia complex
Atypical Infections
Nontuberculosis mycobacterium (NTM)
Fungal Aspergillus fumigatus/ABPA
By Age
Adults P. aeruginosa (starting at age 8-10)
Peds Staph, H. flu
Pancreas starts to die because of duct problems, meaning cell function and thus insulin
production decreases
Glucose Intolerance/Diabetes
Start to see age > 15 years
Can delay age at onset if preserve pancreatic function
50% of patients have by age 40
Electrolyte
Imbalances
Mortality
Problems moving chloride, bicarbonate, and sodium throughout the body

Hypochloremic dehydration
Median survival is 40 years

Primary COD is respiratory complications (> 75% patients)
Provide adequate dietary support
Promote mucus clearance
Goals
Control respiratory tract infections
Decrease progressive decline in lung function
Quarterly visits with yearly labs and CXR
Outpatient
Evaluation by entire team (MD, nursing, social work,
nutrition, PT)
Treatment
PFT
Pulmonary
Monitoring
Endocrine
General
Sputum Culture
CXR
DEXA
OFTT
CBC with diff, PT/PTT
Immunizations
-
Aggressively treating new infections

Emphasis on living with CF (rather than reactively
treating diseases)
Every visit
Small airways (FEF25-75) deteriorate before large airways (FEV1, then FVC)
As obstruction increases, concomitant increase in gas trapping (RV/TLC)
Finally, reversal of RV/TLC with severe restriction due to fibrosis
Every visit
Yearly or with exacerbations
Bone health
Diabetes
Over age 12 or when indicated

Yearly after age 10
Influenza vaccination yearly

12 Pulmonology
Higher calorie intake
Pancreatic dysfunction
Nutrition
Fat soluble vitamin

supplementation
Nutrition and lung function
Cystic Fibrosis
Treatment
Mechanical
Mucous Clearance
Medical
120-130% general population (>3,000 cal/day)

High fat, high protein, high calorie
Salt supplementation (newborn-2 years)
Pancreatic enzyme replacement
2000 lipase units/kg with meals and snacks (max 2,500 units/kg/meal)
Do not substitute generic enzyme preps
Vitamins A, D, E, K
Minerals (Ca, Fe, Zn) included in A/D/E/K MVI
Go hand-in-hand
As BMI improves, FEV1 improves (and converse)
Postural drainage and percussion 1st 2 years of life
Autogenic drainage
Active cycle of breathing (ACB) technique huff breathing
A special type of cough deep inspiration allows more mucus to come up
High frequency chest compression (HFCC) vest
Oscillating devices that go around the chest (smallest fits 2 yo)
Oral oscillators (Acapella, Flutter) natural vibration against lungs
Exercise
Positive expiratory pressure
Breaks down DNA in bacteria, WBCS
Rh-DNAse (Pulmozyme, Dornase)
to help thin mucus
Adds NaCl to airways, causing osmosis
Hypertonic saline
and increasing periciliary fluid layer
Hydrates lungs
Mucomist (n-acetylcysteine)
Increases fluid in periciliary layer
Increases ciliary beat frequency
Dilates airways
Albuterol
Control of
Infections
Genetic
Therapy
Chronic oral antibiotics

Chronic intermittent inhaled antibiotics
Intermittent IV antibiotics
Why?
Ivacaftor
(VX-770)
Lumacaftor
(VX-809)
Out of favor 2/2 increased bacterial resistance, emergence of new pathogens

All targeted against P. aeruginosa
Inhaled tobramycin vs aztreonam vs colistin
Used at times of flare-up, decline in lung function
Lung function deteriorates 2-3%/year in CF patients
Rate of decline is 4-5%/year in those with chronic infections, frequent exacerbations
With every exacerbation, patients baseline lung function decreases by about 2%
-
Results: 11-12% improvement of FEV1 from baseline,

5% improvement of sweat test values, 7 lb sustained
weight gain in first 24 weeks, 8 point QOL
improvement
Used in patients with G551D mutations (now more)

Potentiator molecule that binds CFTR and augments its
function (opens the channel) useful in class III-V mutations
Studied in homozygous F508del patients (50% CF pts)

Results: 2.8-3.3% improvement in FEV1, 5% improvement in BMI, 3.1 improvement in QOL (highest dose), 30-40% decrease
in pulmonary exacerbations
13 Pulmonology
Symptoms
Acute Pulmonary Exacerbation
Cystic Fibrosis
Signs
Treatment
Increased cough
Increased sputum
Change in quality of sputum
Dyspnea
Poor appetite
Fatigue
School or work absence
Decreased exercise tolerance
Weight loss
New findings on PE tachypnea,
Decreased PFTs
Fever
retractions, rhonchi, wheezes
Hypoxia
New findings on CXR
Goal: decreased endobronchial burden of disease (vs. organism eradication in PNA)
Pseudomonas biofilms will affect in vitro antibiotic susceptibility testing (so agents known to be susceptible may/may not
clear infection)
Oral antibiotics against appropriate microbes x14-21 days
Outpatient
Increase airway clearance to 3-4 times/day
Follow-up to determine efficacy of outpatient management
IV antibiotics for 14-21 days with appropriate coverage (2 anti-Pseudomonal agents usu.
aminoglycoside + B-lactam)
Airway clearance 4 times/day
Inpatient
Appropriate nutrition monitor weight, for insulin resistance
Careful monitoring for toxicity/complications
Monitor for hypoxemia, respiratory failure
Respiratory rate/work of breathing
Sputum production
Has respiratory status improved to baseline?
Spirometry
O2 requirement
Exercise tolerance
Discharge Criteria
Appetite
Has nutritional status improved to baseline?
Weight
Insulin resistance, control of diabetes
Has energy level returned to baseline?
14 Pulmonology
Pulmonary Embolic Disease
Virchows
Triad
VTE Risk Factors
Clinical
Molecular
Deep Vein
Thrombosis
Summary
Signs/
Symptoms
Differential
Imaging
1. Stasis
2. Venous injury (incl. surgery, trauma, inflammatory condition)
3. Hypercoagulability (factor deficiencies, excessive coagulants, inflammatory states incl. illness and cancer)
Previous VTE
Surgery (classically hip, knee)
Stroke
Malignancy
Pregnancy/post-partum
MI
Age > 70
Nephrotic syndrome
Varicose veins
Obesity
Severe medical illness (i.e. CHF, ARDS)
Oral contraceptives
Prolonged bed rest
Reduced mobility
Antithrombin III deficiency
Prothrombin G20210A mutation
Protein C deficiency
Hyperhomocysteinemia
Inherited
Protein S deficiency
Elevated factor XI levels
Heparin cofactor 2 deficiency
Elevated factor VIII levels
Activated protein C resistance
Myeloproliferative disease
Lupus anticoagulant
Acquired
Hyperhomocysteinemia
Anticardiolipin antibodies
Antiphospholipid antibodies
No other risk factors
Who should be
Young patients
Helps determine treatment course
tested?
Unusual clot location
Acquired thrombophilia Lupus anticoagulant
Hormonal
Oral contraceptive
HRT
Tamoxifen
Surgery/trauma
CHF, MI
Conditions
Cancer
Nephrotic syndrome and inflammatory bowel
Immobility
Leg or arm
Pain, tenderness, swelling, warmth/erythema
Sensation of muscle cramping
May be acute, or develop over days
Symptoms neither sensitive nor specific for DVT
Risk factors, often, but not always obvious & may not be present at all
DVT
Trauma/hematoma
Postphlebetic syndrome
Muscle cramp
Cellulitis
Bakers cyst
Ultrasound
Most common
Most practical
Contrast venography
Gold standard
Rarely done
MRI
Very accurate
CT Scan
Also accurate
15 Pulmonology
Physiologic
Effects
Pulmonary Embolism
Symptoms
Physical
Exam
Hypoxemia
Pulmonary vascular resistance, pulmonary arterial pressure increase:
Areas of lung are ventilated but underperfused, resulting in
1. Anatomic reduction in cross-sectional area of pulmonary
V/Q mismatch
vascular bed
Pulmonary blood flow is redistributed to regions with lower
2. Functional hypoxia-induced pulmonary vasoconstriction
V/Q arterial hypoexmia
RV Failure
R heart failure is cause of death
Pressure overload on RV dilation, hypokinesis, tricuspid regurgitation
When severe, elevated RVEDP can compress R coronary artery subendocardial ischemia
Less Common
Cough
Classic: sudden onset dyspnea + pleuritic chest pain
Leg swelling
Angina (RV ischemia)
Leg pain
Hemoptysis (pulmonary infarction)
Palpitations
Syncope/presyncope (cor pulmonale)
Wheezing
Anginal CP
-
Most common: tachypnea,

tachycardia
10-20% have signs of
proximal DVT
RV lift
Inspiratory crackles
Loud pulmonary component of P2
Expiratory wheezing
Pleural rub
Diaphoresis
Hypotension
Fever
Homans sign
Cyanosis
Pleural effusion
Pulmonary infiltrates
Depends on the settings

Acute PE may occur in the setting of other
disorders that may cause similar symptoms
symptoms may be falsely blamed on
underlying condition
CXR
Atelectasis
Differential
Pneumonia/infection
Obstructive lung disease
CHF
MSK disease
Wells
Criteria
Diagnostics
Imaging
Acute MI
Anxiety
Any cardiopulmonary disease causing
dyspnea, CP, hemoptysis, etc.
Prior DVT or PE = +1.5

Alternative diagnosis less likely = +3
Score 0-1 = low risk
HR >100 = +1.5
Hemoptysis = +1
Score 2-6 = intermediate risk
Recent surgery/immobility = +1.5
Cancer = +1
Score >6 = high risk
Signs of DVT = +3
Breakdown product of a thrombus
Negative VTE unlikely; positive could be a number of things
D-Dimer
Sensitive, not specific
Order with low-moderate suspicion
Sinus tachycardia
Atrial arrhythmia, A fib, sinus tach, PAC, SVT
ECG
R heart strain, RAD, RBBB, S1Q3T3
Inferior q waves, TWI, large p wave, P wave pulmonale
ABG
Hypoxemia
Respiratory alkalosis
High alveolar-to-arterial oxygen tension gradient
Pulmonary arteriogram
Gold standard
Rarely done
Ventilation-perfusion scan
See smaller vessels better than on CT
CT Angiography
Most common test
Spiral CT misses smaller PEs
Compression ultrasound
If cant do lung study
MRI
Less data
16 Pulmonology
Options
Anticoagulants
Pulmonary Embolism
Severity
Massive
Submassive
Nonmassive
Heparin
LMWH
Warfarin
DTI
IVC Filter
NOACS
Treatment
Reversal
of
Agents
UFH/warfarin
IVC filter
LMWH/warfarin
Systemic thrombolytic therapy
Direct thrombin inhibitors
Local thrombolytic therapy
Consider thrombolytics, embolectomy, pressors, anticoagulants, filter
Consider thrombolytics (systemic vs. catheter-directed)
Anticoagulation
If high bleeding risk or very unstable and considering lytics
Caution with renal insufficiency
Enoxaparin, tinzaparin, dalteparin, fondaparinux (subQ)
Heparin
Warfarin
Dabigatran (DTI)
Factor Xa
inhibitors
Acute
Treatment
ACCP
Prevention
Admission
Orders
If history of HIT
Via IV
Bivalirudin, argatroban
If anticoagulation is absolutely contraindicated or with recurrence on therapy
DTI = dabigatran
Factor Xa inhibitors = rivaroxaban, apixiban, edoxaban
Wears off quickly, can reverse with protamine sulfate
Vitamin K, FFP, prothrombin complex concentrate
FFP wont help
No reversal
Advantages over UFH:
Increased bioavailability (LMWH > UFH)
QD or BID subQ delivery
Monitoring not gen. required
Outpatient therapy facilitated
Lower rate of HIT
Longer duration decreases recurrence, but increases risk of bleeding
3 months if condition reversible
After 3 months, risk is 25% over next 5 years
Low-moderate risk of bleeding continues indefinitely
Consider continuing indefinitely (40% recurrence at 5 years)
LMWH
ACCP: For patients with high clinical suspicion of
DVT or PE, we recommend treatment with
anticoagulants while awaiting the outcome of
diagnostic tests
Provoked
Duration
Unprovoked
Recurrent
For acutely ill
CHF
patients
Severe respiratory distress
admitted with
Or confined to bed with 1+ addl RF, incl. active CA, previous VTE, sepsis, acute neurologic disease, IBD
we recommend thromboprophylaxis with LMWH, LDUH, or fondaparinux
Every patient admitted should be considered

for prophylaxis most will require it
Enoxaparin, rivaroxaban, or heparin

Pneumatic compression, elastic stockings
17 Pulmonology
Pulmonary Vascular Disease

High blood pressure in the lungs
-
Not specific with regards to arteries vs veins, or to causation

May be more commonly pulmonary venous, associated with left heart/valve disease, or other parenchymal lung disorders
-
2. PH Owing to L Heart
Disease
WHO Classification
Pulmonary Hypertension (PH)
1. Pulmonary Artery
Hypertension
Idiopathic vs heritable vs drug/toxin

Associated with PAH: connective tissue disease, congenital heart disease, portal HTN, HIV infection,
schistosomiasis (5%)
Associated with significant venous/capillary involvement (PVOD, PCH) and persistent PH of the newborn
L heart or valvular disease
Most common cause of PH
Pulmonary venous etiology
Treating with specific pulm. artery vasodilator may worsen pulm. venous congestion and cause pulmonary
edema
Parenchymal lung disease

No long-term data for pulmonary vasodilator use
Correlates better with low O2 levels than PFTs
Protective mechanism VQ matching
Destruction of lung and vascular tissue
Muscularization of pulmonary arteries
Hypercapnia increases
Mortality increased significantly
4. Chronic Thromboembolic
PH (CTEPH)
Best therapy is surgical, not medical
5. PH with Unclear or
Multifactorial Causes
Sarcoid
Myeloproliferative
3. PH Owing to Lung Disease

and/or Hypoxemia
Obstructive Lung Diseases:

COPD, asthma, CF, bronchiectasis, bronchiolitis
obliterans
Central Origin of Resp. Insuffiency:

Central alveolar hypoventilation, obesityhypoventilation syndrome, sleep apnea syndrome
Restrictive Lung Diseases:
Neuromuscular diseases, kyphoscoliosis,
thoracoplasty, sequelae of pulmonary TB,
sarcoidosis, pneumoconiosis, drug-rel. lung
diseases, extrinsic allergic alveolitis, CT diseases,
idiopathic interstitial pulmonary fibrosis
ESRD
Sarcoma hemoglobinopathy
18 Pulmonology
Very specific disease

Pathology attributable to abnormal
vascular process
>25 mmHg at rest
<15 mmHg
>3 woods units (240 dynes)
Progressive, incurable disease of the small pulmonary arteries characterized by vascular cell
proliferation, aberrant remodeling, and thrombus in situ
Pulmonary Artery Hypertension (PAH)
WHO Definition
Natural History
Via cardiac catheterization
Progressive elevation of PAP

Gradual onset of symptoms
DOE
Limitation of exercise capacity
Progressive deterioration
Increased RV afterload
RV failure and progressive decline in C.I.
Symptoms at rest
Death
Collagen vascular disease
1. Risk factors and
Congenital heart disease
associated conditions
Portal HTN
Susceptibility
Abnormal BMPR2 gene
Pathology
Progression
Common Initial
Symptoms
Physical Exam
Mean pulmonary artery pressure

Pulmonary capillary wedge pressure
Pulmonary vascular resistance
2.
Vascular injury
3.
Disease progression
Endothelial dysfunction
Vascular smooth muscle dysfunction
Loss of response to short-acting vasodilator trial
HIV
Drugs and toxins
Pregnancy
Other genetic factors
nitric oxide synthesis
prostacyclin production
thromboxane production
endothelin production
Impaired voltage-gated K+ channel
Presymptomatic/compensated Symptomatic/decompensating Declining/decompensating
Mild: can be asymptomatic

More advanced: SOB, CP,
(pre)syncope
Presence of PH
Most common: exertional SOB

Dyspnea
Alter activity to accommodate symptoms
Fatigue
Progression leads to heart failure symptoms
Syncope or near-syncope
RHF swelling, early satiety, fatigue, syncope
Dizziness
Chest pain
Palpitations
May be insidious, not recognized, or attributed to other
Leg edema
conditions
Cough
Loud pulmonary component of P2 (listen at apex)
RV lift (L parasternal)
Systolic murmur (TR, inspiratory augmentation)
Diastolic murmur (PR)
RV S3, RV S4
Early systolic click
Midsystolic ejection murmur
19 Pulmonology
Physical Exam
Presence of RV Failure
General
Diagnostic
Studies
Predictors of
Mortality
Treatment
JVD with V wave, increased A wave

Hepatojugular reflux
RV S3
Hepatomegaly
Cyanosis
Clubbing
Peripheral edema
Ascites
Pulsatile liver
Low BP, low PP, cool extremities
Crackles
Hyperinflation
R ventricular hypertrophy
RV strain
R axis deviation
R atrial enlargement
- RV enlargement into retrosternal clear space
CXR
- Peripheral hypovascularity (pruning)
- Prominent proximal pulmonary arteries
- Info about severity (estimated pulmonary artery pressure, RV dimensions and function)
Echo
- Info about potential causes (LV failure, valvular lesions, congenital heart tises with L-to-R shunts)
Confirm echo findings
Required when PAH
Survey for L heart disease (measure wedge pressure or LVEDP)
suspected
Measure CO, calculate PVR
Cardiac
1. Look for WHO
Exclude systemic to pulmonary shunts
classification parameters
Cath
Establish severity and prognosis
2. Acute vasodilator
Acute vasodilator challenge
challenge
Refine diagnosis
PFTs, V/Q scans, polysomnography or overnight oximetry, autoantibody tests, HIV
To determine other causes
Other
serology, LFTs
- Higher pulmonary artery pressure
- Absence of response to vasodilators
- Depressed cardiac index (CI < 2.0 L/min/m2)
- Poor NYHA or WHO (class IV) functional status at diagnosis
- Elevated RA pressure (> 20 mmHg)
- Poor 6-minute walk results
Improve of symptoms
Prevent clinical worsening
Not curable, but is
Improve functional
Improve survival
Goals of Therapy treatable
class/exercise capacity
Support/reverse acute decompensated R heart
Improve hemodynamics
failure, hypoxemia
Treat any underlying contributing disorders and O2 (all pt w/ hypoxemia)
manage respiratory or heart failure symptoms
Salt and volume intake, diuretics
Only acute vasodilator responders should be tried on CCB
therapy (use in low output could worsen RHF)
Risk stratify and consider specific pulmonary
Fall in mPAP > 10 mmHg
Vasodilator
vasodilator therapy
+PAPm (absolute) > 40 mmHg
Management
Response
+ normal CO
Oxygen rest, exertion, sleep
Salt and fluid restriction/diuretics
Sleep study (CPAP, BiPAP)
Oral anticoagulation
Ancillary Therapy
Cardiopulm. rehab when out of acute
Some data for digoxin
failure (aerobic activity)
Exercise/activity prescription based on
Weight management/dietary
stability
EKG
20 Pulmonology
Cor Pulmonale
Class
Options
-
Epoprostenol (IV)
Treprostinil (IV, SQ)
Iloprost (inhaled)
Treprostinil (inhaled or
oral)
Bosentan (PO)
Ambrisentan (PO)
Macitanten (PO)
PDE5 Inhibitors
Sildenafil (PO)
Tadalafit (PO)
Guanylase
Cyclase
stimulator
Riociquat
Prostacyclin Derivatives
FDA-Approved
Therapies
Endothelin Receptor
Antagonists
Nitric
Oxide
Pathways
Oral CCBs
Follow-Up
Side Effects
-
Flushing
Headache
N/V/D
Jaw pain
Leg pain
Hypotension
Nasal congestion
Abnormal hepatic
function
Epistaxis
HA
Dyspepsia
Flushing
Dizziness
Syncope
Delivery site complications
(pain, infection, cough,
thrombosis, infusion
interruption)
Anemia
Edema
Teratogenic
Diarrhea
Visual change
Contraindicated with use of
nitrates, cannot use both PDE5
and GC
Indicated in small subset of patients with mild-moderate symptoms who demo significant reduction in pulmonary pressure with acute
CCB challenge
Careful evaluation and follow-up are necessary to continually titrate therapy
At 4 weeks
Repeat 6 minute walk at each visit
Severely ill with IV therapy
Then monthly or up to 3
Labs to assess chemistry, BNP
months
Echo Q6-12 months
Other studies (PFTs, CXR, CT) PRN symptoms
Oral therapy
Every 3-4 months
-
Vasodilator therapy delays or obviates need

Only for patients with severe disease despite intensive medical
therapy
Lung Transplant
At some point, may be an option, but presents a new disease

state
Acute
Decompensated
RHF
Correct secondary causes

Most often (even with low BP), giving volume is not useful and may worsen the outcome
Support systemic blood pressure (pressor)
Initiate or increase specific vasodilator therapy as soon as safely possible with nitric oxide, prostacyclins
Hypertrophy/enlargement of the R ventricle related to hypoxic lung disease

-
Most often seen with COPD, but now extended to others, including
kyphoscoliosis, interstitial lung disease, PSA
Physiology
May result in edema

Pretends poor prognosis in all cases
Lung vasculature constricts in response to low O2, high CO2, acidosis

May be protective in COPD, ILD, sarcoid, acute lung injury, or infection
Body attempts to best match ventilation and perfusion
Selective pulmonary vasodilators may create VQ mismatch (inhaled less likely to do so because get greatest delivery to ventilated
areas)
21 Pulmonology
Acid Base Disorders

Carbonic acid (H2CO3)
Types of
Acids &
Bases
Buffers
HendersonHasselbach
Equation
Kidney
Function
Noncarbonic acid
Organic Acids
Organic Bases
Mineral Acids
Mineral Bases
HA H+ + A+
HA = acid, H = cation, A = anion

+
H +
HCO3-
H2CO3 H2O + CO2
HCO3-, lactate, -hydroxybutyrate

H+, HCl, H2SO4, H2PO4
OH-, NH3, SO4-, HPO4-
Ammoniagenesis
2. What is the pH?

3. What is the primary
process?
4. Is the compensation
adequate?
5. What is the anion gap?
Compound that binds H+ when [H+] rises and releases it when [H+] falls
Body buffers are primarily weak acids
pH = 6.1 + log [HCO3-]/[CO2]

Base/Acid
Metabolic/Respiratory
to maintain pH, if HCO3- rises, then CO2 has to decrease (and vice versa)
Cell: H2O + CO2 H2CO3 HCO3- + H+
Acidifying Urine
1. What is the clinical

scenario?
Analysis of
Acid-Base
Status
CO2 produced by metabolism of carbohydrates and fats

Majority of acid produced each day
Exhaled as CO2 at the lungs
Acid produced by metabolism of proteins (i.e. sulfur-containing AA H2SO4)
Must be excreted by the kidneys (nonvolatile)
CO2, lactic acid, -hydroxybutyric acid
Protein
metabolis
m NH3
-
HCO3-
blood
H2CO3 HCO3- + H+
H+ urine
NH3 + H+ NH4+ (urine)
Vomiting, diarrhea, renal failure, toxin ingestion, respiratory failure, hyperventilation
<7.4 = acidemia
>7.4 = alkalemia
Primary Process
Metabolic Acidosis
Metabolic Alkalosis
Respiratory Acidosis
Respiratory Alkalosis
Winters
Formula
Na+ - (HCO3- + Cl-)

Calculate AG =
pH
Metabolic acidosis
Metabolic alkalosis
Acute respiratory acidosis
Chronic respiratory acidosis
Acute respiratory alkalosis
Chronic respiratory alkalosis
Corrected HCO3- =
HCO3
CO2
pCO2 = 1.5 x HCO3 + 8 + 2
For every pCO2 of 10 mm, pH by 0.08

Normal = 12
If corrected HCO3- = 24
Pure AGMA
22 Pulmonology
Uses
Arterial
Blood Gas
Measures
Bicarb
Condition
Patients AG normal AG (12)
AG + patients HCO3-
If corrected HCO3- < 24
AGMA + NAGMA
AGMA + addl metabolic
If corrected HCO3- > 24
acidosis
Help in diagnosis
Monitor acid-base balance
Measure respiratory function
Assess oxygenation
Make changes in treatment (i.e. ventilator settings)
Assess pressure of O2 for therapy
pH
H+ concentration
7.35-7.45
HCO3Bicarbonate
22-26
pCO2
Pressure of CO2
35-45
SaO2
Oxygen saturation
95-100
pO2
Pressure of O2
80-100
BE
Base excess
+/-2
Calc. from pH and pCO2 ( directly measured)
So compare to level on Chem7 if is btw 1-2, means chemically possible to eval. ABG
6. What is the corrected

bicarbonate?
pH
HCO3-
CO2
Primary Alteration
Secondary Response
Mechanism of Secondary Response
[HCO3-]plasma
paCO2
Hyperventilation
[HCO3-]plasma
paCO2
Hypoventilation
Respiratory
Acidosis
paCO2
[HCO3-]plasma
Respiratory
Alkalosis
paCO2
[HCO3-]plasma
Signs and Symptoms

-
Metabolic
Acidosis
Metabolic
Alkalosis
LOC coma
Weakness, DTRs
Tachycardia CO CO
hypotension, dysrhythmia
Kussmauls respirations
Warm, flushed skin and mucous
membranes
Anorexia, nausea, vomiting
K+
HCO3- with rising pCO2
Shallow, slow breathing
Anxiety and irritability
+ Chvosteks sign + Trousseaus sign
[K+], [Ca2+]
Paresthesias, muscle cramping, weakness
Tetany and seizures
Tachycardia, + hypotension, palpitations
Treatment
Causes
MUDPILERS
Hydration
Correction of underlying cause
(Sodium bicarbonate not routinely
given)
Antiemetic medications
Monitor electrolytes and replace as
indicated potassium-sparing diuretic
Seizure precautions
Chloride responsive NaCl
Chloride resistant adrenalectomy vs.
potassium-sparing diuretic
AGMA
Condition
Acid titration of tissue buffers

Transient in acid excretion and sustained
enhancement of HCO3- reabsorption by kidney
Alkaline titration of tissue buffers
Transient suppression of acid excretion
Sustained of HCO3- reabsorption by kidney
Methanol
Uremia
Diabetic/starvation
ketoacidosis
Paraldehyde/phenoformin
Isopropryl alcohol, isoniazid
NAGMA
Metabolic
Acidosis
Metabolic
Alkalosis
Chloride
Responsive
Lactic acidosis
Ethylene glycose/ethyl alcohol
Rhabdomyolysis
Salicylates
Hyperalbuminemia, iatrogenic
USEDCRAP
Ureterosigmoidostomy
Small bowel fistula
Excess chloride
Diarrhea
GI: vomiting, NG suction, Cl
wasting diarrhea, villous
adenoma
Exogenous alkali
Cystic fibrosis
Chloride Resistant
Carbonic anhydrate
inhibitor/CRF
Renal tubular acidosis
Addisons disease
Pancreatic fistula
Renal: diuretic use,
carbenicillin, PCN,
sulfate, phosphate,
post-hypercapnia
Achlorhydria
Hypertensive
Adrenal disease
Exogenous steroids
Normotensive
Bartter or Gitelman syndrome

Hypokalemia
Milk-alkali syndrome
Refeeding alkalosis
Excessive alkali
administration
23 Pulmonology
Respiratory
Acidosis
Respiratory
Alkalosis
LOC
Weakness, DTRs
Ineffective respiratory efforts
[K+] in acute respiratory acidosis
Tachycardia CO CO
hypotension, dysrhythmia
Maintain patients airway with

enhanced gas exchange: meds, O2,
pulmonary toilet, ventilatory support
Monitor ABGs to make appropriate
adjustments
Modify diet to low carb, high fat
Acute
Chronic
CNS depression
Neuromuscular
disease
Impaired lung
mechanics
COPD
Pickwickian
syndrome
Acute airway obstruction

Acute respiratory disease
Thoracic cage limitations
Chronic neuromuscular
disease
Rapid, deep respirations

CHEAPCHIPS
Anxiety and irritability
Monitor ABGs periodically
CNS
Hypermetabolic state
+ Chvosteks sign + Trousseaus sign
Decrease respiratory rate: focused
Hypotension
Insufficient oxygenation
+
2+
[K ], [Ca ]
breathing, decrease breaths/minute
Excess mechanical ventilation
Psychogenic
Atelectasis
Paresthesias, muscle cramping, weakness
on ventilator, O2 therapy
Salicylates
Pain
Tetany and seizures
Antianxiety medications
Sepsis
Cirrhosis
Tachycardia, + hypotension, palpitations
Lungs fail to eliminate CO2 (hypoventilation)
COPD: chronically pCO2, acidosis; elevated pCO2 is the only stimulus
Respiratory
Most commonly caused by a disturbance of
for their respiratory drive, so if you normalize CO2 the brain no longer
Acidosis
alveolar ventilation (lung, CNS, neuromuscular)
sense the need to breath and patient may become somnolent
Respiratory
Alkalosis
Physiology
Metabolic
Acidosis
Lungs eliminate too much CO2 (hyperventilation)

Loss of bicarbonate without change in net charge (H+ binds a base we do not pee sparks!)
Acid without Cl- added
Anion Gap
HCO3- used to buffer acidic byproducts (i.e. ketoacids, lactic acid, methanol),
Na+ - (HCO3- + Cl-) > 12
resulting in formation of unmeasured anions (Cl- + HCO3-) term = anion
(AGMA)
gap
Pure loss of HCO3- in exchange for Cl-, so (Cl- + HCO3-) term
Results in hyperchloremia
Renal tubular acidosis kidney not acidifying the urine
Renal Cause
Kidney achieves acid/base balance by secreting NH4+
Diarrhea HCO3- loss
Extra-Renal
Kidney responds by HCO3- production NH4+ urinary
Cause
secretion
UAG = U[Na] + U[K] U[Cl]
Non-Anion Gap
Normal = -10 to +10
Na+ - (HCO3- + Cl-) < 12
(NAGMA)
Used to detect NH4+ excreted with Cl- (NH4+ not measured)
To
Na + K < Cl
distinguish,
Means theres electrical room for NH4+
calculate
< -10 = extra-renal
and kidney making it acidifying urine in
urine anion
face of acidemia
gap (UAG)
Na + K > Cl
> + 10 = renal
Means less room for NH4+ and kidney not
making it, not doing job
24 Pulmonology
By either:
Due to reabsoprtive threshold
Addition of bicarbonate,
Na+ reabsorption at distal tubule H+
Loss of acid, or
and K+ leaking into urine
Loss of fluid containing proportionally more Cl- than HCO3The kidney has a functional, reabsorptive threshold for HCO3- if [HCO3-]plasma is high, HCO3- spills into urine
Hypochloremia HCO3- displaces ClHypokalemia H+ leaves cell (to acidify alkalotic blood), K+ enters cell (to maintain electrical neutrality)
o Also aldosterone = Na+ = K+
H+ loss from ECF space
Generation
Contraction alkalosis
HCO3- retention
Pathogenesis Chronic
Decreased ECF/Cl depletion
Hypercapnia
Maintenance
Persistent mineralocorticoid
Potassium depletion (profound)
excess
Urine chloride < 15 mEq/L
Loss of HCl from emesis
Metabolic
In hypovolemia, kidneys try to consider Na+, H2O, and Cl- low
( alkalosis + hypovolemia)
U[Cl]
Alkalosis
Chloride Responsive
Loss of Cl- in emesis = relatively more HCO3Saline responsive (corrects
relative HCO3- because HCO3- in pancreatic juices not released
volume contraction)
due to low acidity of chyme entering duodenum)
Extracellular fluid contraction
Urine chloride > 15 mEq/L
HCO3- absorbed Cl- dumped (maintain electric neutrality)
Associated with minteralcorticoid
aldosterone production Na+ resorption at DCT
Saline unresponsive (no
hypernatremia excess HCO3- absorption alkalosis
Chloride Resistant
volume loss)
o Heart corrects by sensing excess Na+, H2O ANP
release Na+, H2O diuresis
Associated with hypokalemia
To maintain neutrality: HCO3- absorption K+ excretion
H+ moves cell blood, so K+ moves blood cell
Normal = 12
Difference between unmeasured anions and
Na+ + UC. = Cl- + HCO3- + UA
More unmeasured cations than anions
unmeasured cations
Na+ - (HCO3- + Cl-) = UA UC = anion gap
Unmeasured cations (UC): Ca2+, Mg2+
Unmeasured anions (AC): albumin3-, PO3-, SO42A primary in
HCO3-
Physiology
Anion Gap
25 Pulmonology
Pulm.
Defenses
Lower Respiratory Tract Infections

Mechanical
Epiglottis
Cough reflex
Mucociliary clearance
Innate
Immune
System
Humoral (lysozyme, lactoferrin, IgA, collectins, e.g. surfactant proteins)

Cellular (alveolar macrophages, PPRs)
Altered temperature, rigors, sweats, cough + sputum, dyspnea, chest pain

Fatigue, myalgias, abdominal pain (esp. peds), anorexia, headache
Infection at the level of the alveoli
Rales
Exam
Opacity
CXR
Patient in ambulatory setting
Community Acquired Pneumonia (CAP)
Patient in extended care, on home infusion therapy, long-term hemodialysis within past 30
Outpatients Health Care Associated Pneumonia (HCAP)
days, home wound care, exposure to family members with resistant pathogens,
hospitalization >2 days within past 90 days
Hospital Acquired Pneumonia (HAP)
Onset >48 hours after hospital admission
Inpatients Ventilator Associated Pneumonia (VAP)
Onset >48 hours after initiation of intubation and mechanical ventilation
#1 Streptococcus pneumoniae
CAP
Gram negative enterics (E. coli, K. pneumoniae, Enterobacter spp.)
Other gram negative aerobics (Acinetobacter, Citrobacter, Proteus, Serratia, Pseudomonas spp.)
HAP/HCAP
S. aureus (including MRSA)
S. pneumo colonizes 5-10% of healthy adults
Most common etiology of CAP & a likely etiology in culture negative Complications: bacteremia, meningitis,
Pneumococcal
CAP
otitis media, sinusitis
High mortality post-splenectomy
Sputum: Gram-positive diplococci
Pneumonia
Vaccination available (PCV13, PPSV23) recommended for all adults
CXR: local infiltrates
> 65 & younger with co-morbid risks (including all smokers)
Serotype B and nontypable cause most pneumonias
Etiology
Sputum: small, Gram-negative rods
Haemophilus
Not distinguishable from other causes (clinical/radiographic)
Treatment: covered adequately by most
More common in smokers
influenzae
empiric regimens
Hib vaccinations have decreased carriage rates
Atypical
May have associated non-respiratory
Mycoplasma
Typical presentation
syndromes (CNS, transverse myelitis,
Occurs in up to 1/3 CAP outpatients when serologic testing
immune hemolytic anemia)
pneumoniae
performed
Atypical, intracellular organism
Urinary antigen diagnostic, only detects
Legionella
Found in aquatic environments
serogroup 1 (~80%)
pneumophila
Incidence vary, likely due to differences in local epidemiology
CXR: often has multi-lobar appearance
Pneumonia
Symptoms
26 Pulmonology
Gram negative
pneumonia
Staphylococcal
Pneumoniae
Chlamydia
pneumoniae
Etiology
Pneumonia
Atypical
TWAR agent
Diagnosis difficult (true incidence unknown)
50% of 20 year olds have evidence of past infection
Re-infection throughout life appears common
Uncommon in outpatients
10% CAP patients admitted (highest in ICU)
Increased risk (enterics, P. aeruginosa): medical co-morbidities
(diabetes, EtOH, heart disease, lung disease), recent abx therapy
Uncommon in CAP
Relatively common complication post-influenza
Increasing cases of CA-MRSA (think about if have 1) Staph risk factors
and 2) very fulminant pneumonia)
Enteric Gram-negative organisms
Anaerobes
Organism associated with chronic

inflammatory disease (atherosclerosis)
May cavitate or produce empyema
May cause necrotizing infiltrates

May cause pneumatoceles in children
Risk Factors
-
Aspiration
Pneumonia
Neurologic dysphagia
Anatomic or functional abnormalities of upper GI
tract (GERD, s/p esophagectomy)
Nursing home residence
Changes in consciousness (drug overdose, general
anesthesia, LOC; cannot protect airway as well)
5-15% of CAP
After inhalation of oropharyngeal or gastric contents (event not
usually witnessed)
Correlates with volume of aspirated material
XR: changes in dependent lung segments

May leads to necrotizing pneumonia,
empyema, or lung abscess
Clinical
Symptoms
Not a good tool for discriminating etiology
About 30% with viral prodrome
Physical Signs
Not different enough to be discriminatory
Mental status changes

Degree of fever, hypertension, shock
CXR
Tests for
Etiologic Agent
Evaluation
Labs
Sputum Sample
Urinary
Antigens
Outpatient
None considered standard
Hospitalized
2 pre-treatment blood cultures
Serologic tests not considered helpful

If hospitalized: CBC, BUN, electrolytes, LFTs, O2 saturation, HIV (15-54 years)
Get before initiating antibiotic treatment
Negative not helpful
Positive may be helpful
More invasive sampling (transthoracic aspiration, bronchoscopy)
reserve for selected patients
Induced sputum for M. tuberculosis, Pneumocystic carinii
-
Expectorated sputum Gram stain and

culture
Deep cough specimen

Transported and processed within a few
hours of collection
Culture contingent on cytologic exam,
except for Mycobacteria, Legionella
Pneumococcal: polysaccharide cell wall antigen 50-80% sensitive, 90% specific (poor in peds); used to augment blood
cultures and sputum
Legionella: tests for serogroup 1 only
27 Pulmonology
Are Diagnostic When
Pneumonia
Evaluation
Cultures
1st - In vs
Outpatient
Probable etiologic agent from uncontaminated specimen (blood, pleural fluid)

A likely pathogen that doesnt colonize upper airways (M. tuberculosis, Legionella spp., P carinni,
influenza virus, RSV, parainfluenza, adenovirus, SARS coronavirus, Histoplasma capsulatum, Coccidioides immitis,
Blastomyces dermatitidis)
Compatible clinical syndrome with

stain or culture of likely pulmonary pathogen in respiratory secretions (expectorated
Are Probably Diagnostic
sputum or bronchoscopic secretions)
When
Should be significant growth with quantitative culture or moderate/heavy growth with
semiquantitative culture
Will influence antibiotic choices
Assess pre-existing conditions that compromise safety of home care
Make a clinical judgment (takes precedence over scoring/prediction formulas)
Formulas: CURB-65 vs PSI (home-care risk classes)
Risk-Class Mortality Rates for Pt w/ PNA
Developed largely for ED
Class I-II
Low mortality, recommend out-patient care
populations
Class III
Recommend brief in-patient care
Port Prediction - Use an online tool
Class IV-V
Recommend in-patient care
Model for CAP - Considers: co-morbid
Stratifies patients into high and low risk for pneumonia mortality
illnesses, certain exam
Prediction rule focuses on recognizing low risk patients and not overestimating
findings, certain labs
severity of illness
Has been extrapolated from ED use for use in defining need for hospitalization
-
ICU Admission
Treatment
Septic shock requiring

vasopressors
Respiratory failure
requiring mechanical
ventilation
Also
Consider
RR > 30
PaO2/FiO2 < 250
Multilobar infiltrates
Confusion
Uremia (BUN > 20)
Leukopenia (< 4,000)
Thrombocytopenia (<
100 K)
Hypothermia (core temp
< 36 C)
Hypotension with
aggressive fluid
resuscitation
Antibiotic
Regimen
Initial Therapy
Empiric
Based on treatment out-patient vs in-patient floor vs in-patient ICU

Underlying co-morbidities and risk for specific pathogen
Age > 65
Immune-suppressive illness
Factors that Risk of
-lactam therapy within past 6
(including therapy with
Drug-Resistant
months
corticosteroids)
Pneumococci Infection
Alcoholism
Exposure to a child in a day care
Multiple medical co-morbidities
center
Residence in nursing home
Underlying cardiopulmonary disease
Enterics
Multiple medical co-morbidities
Factors that Risk of
Recent antibiotic therapy
Infection with Gram
Structural lung disease (bronchiectasis)
Negatives
Corticosteroid therapy (> 10d prednisone)
P. aeruginosa
Broad-spectrum abx (> 7d in past month)
Malnutrition
28 Pulmonology
Location
Modifiers
No
cardiopulmonary
disease or other
modifying
factors
Pneumonia
Outpatient
Cardiopulmonary
disease or other
modifying
factors
Organisms
-
S. pneumoniae
M. pneumoniae
C. pneumoniae (alone or mixed)
H. influenzae
Respiratory viruses
Misc. (Legionella, M. tuberculosis,
endemic fungi)
50-90% - no etiology identified
Same plus
Drug resistant S. pneumoniae
Enteric Gram-negatives
Misc. (M. catarrhalis, aspirations
(anaerobes)
-
Treatment
Antibiotic
Regimen
Resistance
-
Inpatient
Therapy
Advanced generation macrolide
(azithromycin or clarithromycin)
OR
Doxycycline
(if allergic to or intolerant of macrolides)
Anti-pneumococcal fluoroquinolone
OR
Macrolide + -lactam
(oral cepodoxime, cefuroxime, high-dose amoxicillin (1 g
Q8h), amox/clav, or parenteral ceftriaxone followed by
PO cefpodoxime)
(High dose amox, macrolide (azith., clarith.) added to
cover H. flu)
Alternative: doxycycline
Difference between the groups is driver by possibility of drug resistant S.
pneumoniae any opportunity to treat more narrowly may emergence of
resistant strains
Increased mortality and suppurative complications with more resistant S.
pneumo
Antipneumococcal fluoroquinolone (covering
for DR organisms)
Same as basic outpatient

OR
Macrolide + -lactam
(cefotaxime, ceftriaxone, ampicillin/sulbactam, highdose ampicillin)
Alternative: doxycycline
ICU
No risks for P.
aeruginosa
S. pneumoniae (DRSP)
Legionella spp.
H. influenzae
Enteric Gram-negatives
S. aureus
M. pneumoniae
Respiratory viruses
Misc.: C. pneumoniae, M. tuberculosis,
Pneumocystis, endemic fungi
-lactam
AND
Macrolide (azithromycin)
OR
Fluoroquinolone
PCN allergic: cefotaxime, ceftriaxone,
aztreonam
29 Pulmonology
-lactam
ICU
Risks for P.
aeruginosa
Antibiotic
Regimen
Pneumonia
Duration of
Therapy
Should be anti-pseudomonal & anti-pneumococcal

(Cefipime, imipenem, meropenem,
piperacillin/tazobactam, aztreonam)
AND
Antipseudomonal quinolone (ciprofloxacin)
CAP: Most will

respond within 3
days
Initial antibiotics
dont require change
in first 72 hours
(unless deteriorate,
specific organism
identified)
Up to 10% CAP
patients wont
respond to initial
Usually 5 days
and afebrile 4872 hours
Treatment
Duration of
Hospitalization
During 24 hours prior to discharge home, patient should have

no more than 1 of the following
(unless baseline)
-
OR
Anti-pseudomonal -lactam
AND
Aminoglycoside
AND
Macrolide (azithromycin) or nonpseudomonal fluoroquinolone
S. pneumoniae
Until afebrile 72 hours
M. pneumoniae
No well established
C. pneumoniae
7-14 days
Legionella spp.
10-21 days
Pathogens that cause

pulmonary necrosis S.
aureus, P. aeruginosa,
Klebsiella, anaerobes
Complications (lung
abscess, empyema)
Temperature > 37.8 C
Pulse > 100
Respiratory rate > 24
Systolic BP < 90
O2 < 90%
> 2 weeks
Antibiotics dont penetrate
necrotic tissue well
Extended therapy
Inability to maintain oral intake
Causes of Delayed Response
NonResponders
Causes of
Deterioration/ Early
Progression
Early
Deterioration
(< 72 hours)
Delayed
Deterioration
Resistant organism
Parapneumonic effusion/empyema (repeat CXR)
Nosocomial superinfection
Misdiagnosis
Drug fever
More severe illness at presentation (may develop organ failure)
Resistant organism
Metastatic infection (empyema, meningitis, arthritis; due to bacteremia)
Misdiagnosis (PE, vasculitis, CHF)
ARDS
Nosocomial superinfection
Exacerbation of underlying disease
Intercurrent acute illness (PE, MI, renal failure)
30 Pulmonology
Pneumonia
Parapneumonic
Effusions and
Empyema
Complications
Lung Abscess
Performance
Guidelines
Follow-Up
Etiologies
Influenza
Parapneumonic effusions big enough to tap should be tapped at presentation

Lights Criteria (pH, protein, LDH, glucose) to assess whether effusion is likely to become complicated (indicates
drainage)
Adequate drainage, even in absence of empyema, is done with goal of preventing formation of a pleural rind and a
trapped lung dont wait to drain
Empyema: requires prolonged therapy (at least 4-6 weeks)
Necrotized, has formed a wall around it

Complication of aspiration usually
Require prolonged therapy (at least 4-6 weeks)
Include empiric therapy for anaerobics
Blood cultures prior to antibiotic therapy

Antibiotic therapy initiated within 4 hours after registration for
Smoking cessation counseling
hospitalized patient
Pneumococcal screening and/or vaccination
Initial antibiotics consistent with current recommendations
Influenza screening/vaccination
Assessment of oxygenation within 8 hours of admission
Follow to radiologic resolution (may take 2-3 months)
Be sure not to miss lung cancer mimicking pneumonia, post-obstructive pneumonia, and pneumonia that was actually vasculitis
Influenza
RSV
Coronavirus (SARS, MERS)
Primary varicella infection
Epidemiology
Viral Infection
Uncomplicated
Signs and
Symptoms
Cause of ~226,000 hospitalizations/year in US

Hospitalizations highest in patients > 65 years and < 0-4 years
Associated with ~36,000 deaths/year in US
Incubation period = 1-4 days

Resolution = 3-7 days
Common
Death rates highest in persons < 2 years, > 65 years, with

chronic medical conditions
Death rates have almost doubled in recent years
Peak activity in Nov-May
Abrupt onset of constitutional and respiratory symptoms

Fever, myalgia, headache, malaise, nonproductive cough, sore throat, rhinitis
Children: OM, nausea, vomiting
Cough and malaise can persist >2 weeks
Susceptible patients (hyper-reactive airway, + asthma diagnosis) may cough for 4-6
weeks
Febrile seizures
Encephalopathy
Myocarditis, pericarditis
Transverse myelitis
Reyes syndrome
Myositis
Exacerbation of underlying medical conditions (pulmonary, cardiac)
Primary viral pneumonia
Secondary bacterial infection (pneumococcus, S. aureus) during flu or 7-14 days after clinical resolution
MRSA superinfection (rel. to increased ped deaths in 2006-07)
Uncommon
Complications
31 Pulmonology
1918
Pandemic
Treatment
Influenza
Viral Infection
Diagnosis
Vaccination
Influenza A (H1N1) by recent molecular

analysis, strain origin unclear
Mutation in hemagglutinin gene conferred
Similar to 2009s H1N1
binding preference for predominant sialic acid
in the human RT and likely contributed to
extreme virulence
Viral cultures are optimal from nasopharyngeal specimens and require specific viral media
Rt-PCR widely available with sensitivity in mid-90s
Collect specimen within first 4 days of illness
Rapid Diagnostic Tests (<30 min)
Some unable to identify B or distinguish A vs B
Consider adjunct viral culture if (+) test during low activity or (-) test during high activity
4 drugs licensed
Initiate within 48 hours of symptom onset 1) decrease symptoms, duration of illness (1-2 days), 2) may decrease infectivity
Primary prevention is 70-90% effective in healthy adults
Ostelmavir
Effective against A and B
5 days
Inhaled powder not recd for
Zanamivir
Effective against A and B
5 days
asthma, COPD
Paramivir
Parenteral
Single dose
Recent FDA approval
Increased resistance to
Increasing resistance
What to know?
influenza A strains to
of H1N1 strains of
Where to find current surveillance data
Viral Resistance
amantadine, rimatadine (not
influenza A to
Test A vs B when possible
recd for rx since 2006)
ostelmavir
Yearly CDC recs to guide therapy
Everyone over age 6 months
Individuals at
Age 6 months to 18 years, > 50 years
Chronic medical conditions (various)
increased risk for
Pregnancy
Nursing home residents
Who needs one?
complications:
Long-term ASA therapy
Those living with or caring for high risk individuals
Healthcare workers
Inactivated vaccine (>6 months)
Healthy individuals only
Not in children <5 with possible reactive airways,
Live, attenuated vaccine (2-49 years)
history of wheezing
Options
Not for use during pregnancy
Three viral strains included (2 A H3N1, H1N1, 1 B)
1st time vaccination in children under 9 requires 2 doses
Vaccination continues throughout flu season
Healthy, < 65 years
Prevents 70-90% of disease
Elderly, those with chronic medical conditions
Prevents 30-70% of hospitalization
Efficacy
Prevents 50-60% of hospital admissions or
Elderly nursing home residents
pneumonia
Prevents 80% of influenza-related mortality
-
High infection rates (35-50%)

Activity in summer/fall
Rapidly fatal
High mortality in the young and healthy
Pulmonary hemorrhage and pulmonary edema
32 Pulmonology
Mycobacterial
Pneumonia
Epidemiology
Tuberculosis
Transmission
Pathogenesis
Primary
Infection
Prior TB XR
Evidence
M. tuberculosis
Atypical mycobacterium: M. avium intracellulare, M. kansasii (Midwest), M. chelonae (more rapidly growing)
CXR can all look similar
Foreign born cases represent majority of total cases now (decline in US born cases)
Among US born cases, 42% are African American
Top 5 countries of Birth (2005-09): Mexico, Philippines, Vietnam, India, China
Rates of drug resistance higher in foreign born cases
Highest rates in US: CA, NY, WA, FL, TX, southern states
Spread by airborne route droplet nuclei (generated by RT, 1-5 microns)
Infectiousness of patient
Transmission affected by:
Environmental conditions
Duration of exposure
Most exposed persons dont become infected
Once inhaled, bacteria establish in the lung
2-12 weeks after inhalation: the cellular immune response limits activity; infection detectable by skin test
Primary phase of infection is typically clinically and radiographically unapparent
Granulomas on pleural surface may lead to pleural
Cough, fever
Like any other
effusions (generally resolve spontaneously, ~30% have
XR: infiltrates in mid or lower lung fields, hilar
pneumonia
no XR involvement of lung parenchyma)
adenopathy, cavitation
TB empyema less common
Healed primary infection:
Dense pulmonary nodules + calcification
Ghon lesion (peripheral calcified granuloma)
Apical fibrosis and volume loss
May be normal CXR
Apical pleural capping/thickening
Upper lobe bronchiectasis
findings convey lower risk of future progression to active dz
The presence of M. tuberculosis organisms without symptoms or

radiographic evidence of TB disease
Latent TB
Infection
(LTBI)
Treatment
Reduces risk that infection will develop into

TB disease
Certain groups have higher risk for
developing TB disease after infection
Before
beginning
treatment:
Exclude diagnosis of TB
Ensure patient has no history of
adverse reactions resulting
from prior LTBI treatment
Persons are
Asymptomatic
Not infectious
Give LTBI Treatment To

Highest risk groups
Immunocompromised
Recent contacts
XR indicates previous TB
Other high-risk groups
Patients with no risks
Diagnosis
TST
QuantiFERON assay
If M. tuberculosis test result is
> 5 mm
> 10 mm
> 15 mm
33 Pulmonology
Small number of persons soon after infection

5-10% persons with untreated LTBI sometime during infection
~10% patients with HIV and untreated LTBI per year
Cough
Hemoptysis
Weight loss
Fatigue
Other lung infections (anaerobic)
Fever
Decreased appetite
and carcinoma can mimic
Night sweats
Chest pain
Upper lobe infiltrates (particularly apical and posterior segments)
Cavitation common
Miliary pattern seen in hematogenous spread (very immune compromised; only on CT)
Pay attention to infection control during collection
Obtain 3 specimens for smear and culture, at least 8 hours
Nucleic Acid Amplification can speed diagnosis,
apart
doesnt r/o TB in smear (-) disease
Positive AFB smear gives presumptive diagnosis in proper
Interferon based assays cant distinguish latent vs
setting (not definitive)
active
Culture = gold standard
Routine drug susceptibility testing
LTBI progresses to active TB disease in

-
Clinical
Presentation
CXR
-
Lab
Evaluation Sputum
Tuberculosis
When to consider
initiating
Reactivation
TB Disease
Basic Principles
Treatment
Positive AFB smear

Dont delay because of negative AFB smear if high clinical suspicion 1) history cough + weight loss,
2) characteristic findings on CXR, 3) emigration from high-incidence country
Provide safety, most effective therapy in shortest time

Multiple drugs to which organisms are susceptible
Never add a single drug to failing regimen
Ensure adherence to therapy (i.e. DOT)
First-Line
Antituberculosis
Drugs
Second-Line
(for MDR, lower cure rates)
Isoniazid (INH)
Rifampin (RIF)
Pyrazinamide (PZA)
Ethambutol (EMB)
Rifapentine
Streptomycin (SM))
Cycloserine
p-aminosalicyclic acid
Ethionamide
Capreomycin
Not FDA-approved for TB use: amikacin or kanamycin,
levofloxacin, moxifloxacin, gatifloxacin
34 Pulmonology
Standard 4 drug regimens for 2 months

One excludes PZA
Additional 4 months (or 7 months)
Cavitary pulmonary disease and + sputum cultures at completion of initial
phase
When
Once-weekly INH and rifapentine started in continuation phase and sputum
to
specimen collected at end of initial phase is culture positive
Continuation extend?
HIV infection with positive 2-month sputum culture
Phase
Initial phase excluded PZA
Cavitary disease and positive sputum culture at 2 months associated with
Why
increased relapse in clinical trials
extend? Extended continuation phase decreased relapses in silicotuberculosis (20%
3%)
4 regimens recommended to treat culture-positive TB differ primarily in dosing intervals in continuation
phase
High clinical suspicion for active T despite negative
CXR
No other diagnosis
smears based on:
Clinical symptoms
Positive TST
Initial Phase
Tuberculosis
Preferred
Regimen
Treatment
Reactivation
TB Disease
Algorithm
to Guide
Treatment
of CultureNegative TB
Patient placed on initial phase regimen (INH, RIF, EMB, PZA) for 2 months
YES
Continue treatment for culture-positive TB

Give continuation-phase treatment of
Was there
Is initial
YES
INH/RIF daily or twice weekly for 2 months
symptomatic or
culture
CXR improvement
NO
Discontinue treatment
positive?
after 2 months of
NO
Patient presumed to have LTBI
treatment?
Treatment completed
Monthly sputum for AFB smear and culture (until 2 consecutive cultures negative)
Serial sputum smears Q2 weeks to assess early response
Additional drug-susceptibility tests if culture-positive after 3 months of treatment
Periodic (minimum monthly) evaluation to assess adherence and ID adverse reactions
At completion of initial treatment phase for patient with initial negative cultures
Monitoring
Repeat CXR
At end of treatment for patient with culture-negative TB
Generally not necessary for patients with culture-positive TB
Renal function, AST/ALT, bilirubin, PLT count if abnormalities at baseline
Visual acuity & color vision monthly if EMB used (>2 months or doses >15-20 mg/kg)
Completion primarily defined by number of ingested doses within specific time frame
Determining
Consider therapy interrupted if target doses not met within specified time period
Drug
3 months initial phase
Compliance Specified doses must be administered within
6 months 4-month continuation phase
Drug resistance
Renal insuffiency
HIV
Special Situations
Liver disease
Children and adolescents
Extrapulmonary TB
Pregnancy and breastfeeding
35 Pulmonology
Pneumoconiosis
Occupational Lung Disease

following exposure to
inorganic dusts
Some combination of inflammation and fibrotic injury, with

later almost always predominating
Defined pathologically
Documentation of fibrosis
Clinical Definition requires
Acute
Silicosis
Chronic
Pathology
Diagnosis
Imaging
Mycobacterial Silicosis
Lung Cancer
History of significant exposure

Absence of confounders
Classic: silicosis, coal workers pneumoconiosis, asbestosis

Symmetric on imaging (particle distribution is symmetrical)
CXR (radiologist or B reader)

CT scan of chest
Know industries, job titles, descriptions
Cigarette smoking
Granulomatous disease
Not seen often anymore
10 years
Mining, foundry work
Diagnosis
Evidence of fibrosis
demands
History of exposure
Lack of confounders
Fibrotic disease of the lungs following silica exposure
Simple
No attributable mortality
XR, CT, pathology Small opacities, up to 10 mm in diameter
Symptoms
Most frequently asymptomatic
No changes in PFTs usually
No changes in ABGs
Characterized by lesions larger than 10 mm in diameter
Chronic
There can be mortality
Symptoms
Shortness of breath cough, productive of phlegm wheezes
Restriction most common
Exam
Can be normal
Crackles, wheezes
Silica nodule (whirled collection of collagen)
Polarizable
Evidence of fibrosis (pathology, CXR, CT)
Can have a negative CXR mild, usually have positive CT
Can have negative CT very mild
Simple
CXR or CT
Profusion of small opacities (< 10 mm)
Rounded
Upper lobe predominance
Complicated or Progressive Massive Fibrosis
Large opacity (> 10 mm diameter)
Mycobacterial infection can complicate the clinical course
-
IARC has classified silica as a carcinogen (1.2-1.4 relative risk)

A mass in patients with silica exposure should be biopsied (dont assume it is complicated silicosis)
36 Pulmonology
Overview
A group of 6 commercially valuable fibers

Amphiboles and serpentines differential in biological effect, human disease (amphiboles > serpentines)
Current uses: rare in US; roofing, cement, and brakes uses chrysotile (serpentine)
Related Diseases
Pleural plaques/thickening Asbestosis
Laryngeal cancer
Mesothelioma
Lung cancer
Related Lung Injuries
Asbestos Exposure
Dose-Disease Relationship
Pleural Plaques
Mesothelioma
Lung Cancer
Asbestosis
Pleural
Pleural effusion, rounded atelectasis

Pleural plaques and thickening
Mesothelioma
Parenchymal
Bronchitis, small airway disease, pneumonitis
Asbestosis
Lung cancer
Dose of Asbestos
US Incidence
Disease
<1 fiber-year
Total number = large
Pleural plaques and thickening
1 fiber-year
Total number = 2,500-3,000
Mesothelioma
25 fiber-years
Total number = small
Asbestosis, lung cancer
Marker of exposure
CXR: plaque involvement (can look like ILD), almost always
Rarely associated with abnormalities of pulmonary function
bilateral
No impact on mortality
Also seen with trauma, pneumonia, TB
2,500 cases/year in US
Unilateral
Uniformly fatal in 12-18 months
Locally invasive
Therapies are all ineffective (incl. extra-pleural
Late metastases
pneumonectomy)
Pleural plaques seen in asbestos-related
Men: 60-80% related to asbestos
Women: <50% related to asbestos (other radiation,
contrast)
170,000 lung cancers/year in US
Need either a fiber burden or asbestosis to prove
Asbestos and tobacco have a synergistic relationship in
relationship
inducing lung cancer
Fibrotic interstitial lung - No such thing as chronic asbestosis
Symptomatic (SOB)
PFTs: restriction
injury associated with Simple
Crackles
on
exam
O2: hypoxemia
very high occupational
Fibrosis
B
read
of
CXR
Linear markings at the base
exposure to fibers
Criteria
Pleural abnormalities present in >70%
CT Scan (spiral and HR)
Irregular markings at bases
Similar to UIP involvement in IPF
Biopsy
Unusual
Interstitial fibrosis with asbestos bodies
Linear or beaded = buzzwords
Imaging
Concomittant pleural plaques and lower lone-predominant fibrotic changes on CXR or
CT
Granulomatous, interstitial, bronchohilar

Most common are thought to be related to
Follows repeated inhalation and immune
farming, ventilation system, birds
sensitization
A lot of overlap between acute, subacute,
Response/injury to organic dusts or low MW
chronic
chemical antigens
A lot of overlap with inhalational fevers
Extrinsic Allergic Alveolitis
Imaging CXR
Nonspecific infiltrates in mid and upper lung fields
CT
Ground-glass opacities, centrilobular nodules, mosaic attenuation patterns from
airway obstruction
Chronic: emphysema, lower lobe honeycombing may be present
Over 300 agents have been found that can cause occupational asthma
One in 10 patients with adult-onset asthma could be attributed to work exposure
Prevalence varies in different industries
MW > 1,000 Daltons
Symptoms consistent with asthma
High MW
(usually 25-50 kD)
Immediate or dual reactions (rarely late alone)
Cross-shift decrements in pulmonary function
Diagnosis: peak flow >20% after working
Mediated by IgE or IgG antibodies
Positive skin test reaction = exposure + sensitization
Specific antigens = exposures only
Skin tests, ELISA, RAST available for only a few proteins
Animal, bird, fungal proteins
Lab workers, pigeon breeders, bakery workers, farmers, grain handlers, poultry workers, woodworkers,
detergent workers, pharmaceutical workers
MW < 1,000 Daltons
Symptoms consistent with asthma
Low MW
pulmonary function during/after exposure
Methalcholine positive and diminishes after removal from worksite (2 weeks)
Testing is difficult because hapten activity and variable latency
Some act as haptens, combining with carrier proteins to become allergenic
Highly variable latency
Many more antigens
Metals, isocyanates, acid anhydrides, pharmaceuticals (TDI, MDI, HIDI, fluxes, Cr, Ni, Co, Pt)
Exposure to NO2, brown gas
An occupational hazard in farm silos, especially within first 2 weeks of silo being filled with fresh silage
Silo-Fillers
Disease
Occupational Asthma
Hypersensitivity
Pneumonitis
37 Pulmonology
Group of
immunologically
mediated pulmonary
diseases, which follow
repeated exposure to a
wide variety of dusts
Latent Illness Phase
Typically occurring within

1st hour post-exposure
Symptom severity is dose
related
Resolves over 2-8 weeks
Mild cough and wheezing
Delayed Illness Phase
Sudden onset of fever, chills, cough, dyspnea and generalized lung crackles
Acute Illness Phase
Low-concentration
Cough, dyspnea, fatigue, upper airway

irritation, ocular irritation
Medium concentration and duration
Cyanosis (MetHb), vomiting, vertigo, LOC
High concentration
ARDS, laryngeal spasm, bronchiolar spasm,
reflex respiratory arrest, asphyxia
May be totally asymptomatic
-
Lung biopsy: BOOP
38 Pulmonology
Medical Disease
Coal Workers Pneumoconiosis
Black Lung
Diagnosis
Imaging
Simple
Chronic
Pathology
Absent Features
Mixed Dust Pneumoconiosis

Berylliosis
Flock Workers Lung

Popcorn Workers Lung

Diffuse fibrotic lung reaction to coal dust
Accumulation of dust in the lungs and tissue reaction to its presences
Need tenure of 10 years in underground mining
Lay term for collected of diseases defined legally as associated
ILD, COPD, PNA, any lung disease impacted by coal
with coal dust exposure
dust
Need 10 years in underground mining
All disease associated with lung cancer
Dependent on available tissue and pathological interpretation, or
Evidence of fibrosis (CT, CXR)
meeting the same 3 criteria for clinical diagnosis of
History of exposure (10+ years)
pneumoconiosis
Lack of confounders
Small, rounded opacities <10 mm in diameter
Comparable to silicosis
Upper lobe predominance (esp. complicated lesions)
CT more sensitive, specific than XR
Can have negative CXR Mild, diagnosis dependent on CT or
Can have negative CT very mild, very rare, pathology
pathology, usually CT positive
shows coal macules
Symptoms: most frequently none
Fibrotic disease of the lungs following coal dust
Exam: usually normal
exposure
Mortality: no increase
XR/CT/pathology showing small opacities, up to 10
PFTs: unchanged
mm diameter
Symptoms: SOB, cough
Exam: may be abnormalities on lung exam
Mortality: can be increased
PFTs: can show changes, most frequently restrictive
Pathology: a fluid like ink emitting following cutting of mass
Coal macule localized to the region of the terminal bronchus
Inflammation, fibrosis, dust
Equivalent of acute silicosis
Complication of Mycobacterial infection
Issue of lung cancer
Most frequently refers to lung disease following exposure to silicate and some other dust
Characterized by lesions > 10 mm diameter
Can be accompanied by cutaneous problems (ulcer, granuloma)

Can be acute, subacute, chronic
Miners, aerospace industry
Presentation can be comparable to sarcoidosis
Workers in nylon flocking industry
Increased risk for interstitial disease, designated FWL
ILD after exposure to synthetic textile fibers
-
Bronchiolitis obliterans inflammatory and fibrotic

obstruction of small airways
Symptoms: SOB
Exam: crackles
PFTs: Restriction
CXR/CT: evidence of diffuse fibrotic injury
Treatment: systemic corticosteroids, removal from
exposure
Initiated by damage to epithelium of small airways
Unrecognized exposures participate
NOx, Cl2, COCl2, O3, H2S, SO2, organic and inorganic dusts
39 Pulmonology
Reactive Airway
Dysfunction Syndrome
Irritant induced asthma with a non-immunologic mechanism

History of exposure to irritant preceding onset of
respiratory symptoms in subject without prior respiratory
symptoms
Symptoms: asthma-like, hyper-reactivity, within 24 hours

of exposure (no latency period)
Treatment: inhaled and oral steroids
Follow-up: necessary, because significant number wont
improve and require continued therapy
Smoke Inhalation
Carbon Monoxide Poisoning
Immediate ABC assessment, with CPR PRN

Intubation if: stridor, use of accessory respiratory muscles, significant respiratory distress, hypoexmia, hypoventilation,
deep burns to face/neck, blistering or edema of oropharynx look for edema or blistering on laryngoscopy if present,
intubate
100% FiO2 supplemental O2 if dont require ventilation; send ABG and standard labs (incl. lactate, toxicology screen), do
H&P, CXR
Monitor for development of upper airway compromise (d/t thermal injury; often within 24 hours, manage by intubation
until upper edema subsides) and lower airway sequelae (d/t direct toxin damage, tends to occur within 12-36 hours,
manage with aerosolized bronchodilators)
Potential complications (3-4 days later): increased secretions, obstruction of distal airways, atelectasis, bronchopneumonia,
ARDS, hypermetabolism
CO binds hemoglobin with affinity 210 times greater than that of O2 and causes L shift of Hb dissociation curve
Should be presumed in any patient who presents after smoke inhalation until excluded by normal carboxyhemoglobin level
Clinical
CNS (acute and delayed), cardiovascular, renal (myoglobinuria), pulmonary
Depend on % HbCO level
Diagnosis
Good occupation and environmental history
High suspicion, especially in unconscious patients in right setting
Measure HbCO by CO-oximetry (not detected on pulse ox or ABG; active smoker up to 8-10%)
Treatment
Oxygen
Half-life of HbCO
Room air: 4-6 hours
100% O2: 40-80 min
HBO: 15-30 min
Hyperbaric O2
Transient or prolonged LOC
Neurologic signs (incl. delayed neuropsychiatric symptoms)
Cardiovascular dysfunction (arrhythmias, ischemia)
Severe lactic acidosis
HbCO level >20-25%
40 Pulmonology
Interstitial Lung Disease
Pathophysiology
Interstitium
Differential
Diagnosis
Course of
Illness
A virtual space between the alveoli, containing the capillary bed

Bounded by basement membranes of 1) alveolar and 2) capillary endothelial cells
Involving interstitium, alveolar space, small airways, vessels, pleura
More accurate name is Diffuse Parenchymal Lung Disease (DPLD)
Broad spectrum of ~200 separate clinical entities
Diffuse
Common Features
Affect parenchyma primarily (not airway)
Variable amounts of inflammation (treatable) and fibrosis (scar)
Normal lung parenchyma = neat, lacy, thin alveolar walls
Pathology
Fibrosis = interstitial thickening of alveolar walls (increased diffusion distance for O2/CO2)
Injury inflammation repair
resolution
Biology of Lung
fibrosis architectural distortion progressive fibrosis
Injury/Repair
Unresolved issues
Does it require recurrent injury?
Uncontrolled inflammation?
Unresolved fibroproliferation?
Restrictive
lung
pathology
Reduced compliance stiff lungs, smaller volumes
Physiologic Consequences
Impaired gas exchange
Exercise-induced hypoexmia
of Tissue Remodeling
Secondary pulmonary HTN
1. Something the patient has been exposed to (environmental, med,
Stop exposure
What is the cause?
chemo, occupational)?
Mild immunosuppression
2. The patients body attacking itself (autoimmune, sarcoid, vasculitis)
Heavy immunosuppression
3. A disease of poorly understood etiology (idiopathic pulmonary fibrosis)
No treatment available
(classically)
Now anti-fibrotic meds
Mimics of DPLD
Diffuse neoplasia (lymphoma, lymphagitis carcinomatosis, bronchoalveolar cell carcinoma)

Infections (PCP)
Bronchiolitis
CHF
Chronic aspirations
Acute, Subacute
Mimics of infection pneumonia and ARDS
Acute = days-weeks, subacute = weeks-months

Dyspnea + cough, rapid progression to respiratory
failure
Infiltrates, fever
Months-years
Inspiratory crackles
Subtle interstitial infiltrates
Fibrotic, occupational lung disease
IPF, NSIP, chronic hypersensitivity, occupational lung disease,

connective tissue disease-related ILD
Chronic
AIP, acute eosinophilic pneumonia, acute hypersensitivity pneumonitis,

COP, subacute hypersensitivity, drug-induced ILD, Lofgrens syndrome
41 Pulmonology
Demographics
Gender
Age
Family history
Smoking history
Medications
History
Environmental
Occupational
Respiratory
Females
Male
Young
Age > 60
Age 50-60
Familial PF, Hermansky-Pudlak, metabolic storage disease
LAM exclusive
IPF, PLCH (slight predominance)
Sarcoidosis, PLCH
IPF
NSIP
Smokers
Non-smokers
IPF, DIP, RB-ILD, PLCH

Hypersensitivity pneumonia
Some with well-known associations (www.pneumotox.com)

Chemotherapy, some antibiotics, anti-arrhythmics
Hypersensitivity pneumonitis
Pigeons, parakeets
Damp basement
Hot tubs, saunas, humidifiers
Woodworking
Pneumoconioses, hypersensitivity
Mining
pneumonitis
Sandblasting
Welding, shipyard, pipe fitters, electricians, automatic mechanics
Poultry workers
Aerospace, nuclear industry, computer, other electronics
Farming
Animal handling
Productive, hemoptysis Broncheoalveolar carcinoma, bronchiectasis, granulomatosis with
Cough
polyangiitis
Almost all
Wheeze
Extrapulmonary
Associated
Symptoms
Physical Exam
Labs
PFTs
HEENT
Respiratory
Cardiovascular
Extremities
Skin
Musculoskeletal
Neurologic
ESR, CRP
ANA
Restrictive spirometry
Acid reflux
Muscle weakness
Raynauds phenomenon
Sicca syndrome
Rash
Joint pain, swelling, deformity
GI symptoms
Hematuria
Dry eyes, dry mouth, hair loss
Crackles, wheeze, inspiratory squeak
Split, accentuated 2nd heart sound; elevated JVD, LEE
Clubbing, cyanosis
Rashes (especially on hands and face)
Muscle weakness; joint swelling
Focal changes
RF, CCP
RNP
Scl-70
Ro/La
-
Chronic eosinophilic pneumonia, Churg-Strauss, Allergic

Bronchopulmonary Aspergillosis
IPD, scleroderma, MCTD
Polymyositis
Scleroderma, MCTD
Sjogrens, other CTD
Sarcoidosis, dermatomyositis
RA, scleroderma, lupus, sarcoidosis
Inflammatory bowel disease
Pulmonary-renal syndrome
Scarring of lungs and distortion of parenchyma shrunken lungs
CPL, aldolase
Anti-tRNA-synthetase antibodies
Reduced DLCO
42 Pulmonology
CXR
Conventional CT
High-Resolution CT
Imaging
-
Biopsy
Abnormal in most cases
Findings can be subtle
Greater sensitivity
Lower resolution than HRCT
Details at the level of the pulmonary lobule

Inspiratory/expiratory (delineates air trapping vs GGO)
Prone (atelectasis vs fibrosis in dependent regions)
Sensitive and specific

Fine-tune with added protocols
Usually non-specific
Rarely needed with careful H&P, review of labs and imaging
Multisystem granulomatous disorder of unknown etiology
Pathophysiology
Most commonly affects young and middle-aged adults of African American and northern European descent
Epidemiology
Well-formed, non-caseating, epitheloid cell granulomas
Pathology
Exclude local sarcoid-like reactions and known causes of granuloma (tumor, fungus, mycobacterial infection)
Usually seen on bronchoscopic biopsy
Bilateral hilar lymphadenopathy
Common
Pulmonary infiltrates
Ocular lesions
Clinical
Skin lesions: erythema nodosum (acute; raised, red, tender bumps on anterior legs), lupus pernio (chronic;
discolored, indurated plaques on nose, cheeks, lips, ears)
Manifestations
Liver
Salivary glands
Muscles
Less Common
Spleen
Heart
Bones
Lymph nodes
Nervous system
CXR
With BHL
HRCT
Various patterns: GGO, nodules, fibrosis, mass, consolidation, cysts, bronchial wall thickening
Upper/mid lung predominance, bronchocentric distribution
Septal beading
Stage
Finding
Spontaneous Resolution
Stage I usually incidental finding on CXR
Stage IV scarring doesnt improve; see
0
Normal
?
architectural distortion
I
BHL
75%
II
BHL + pulmonary infiltrate
50%
III
Pulmonary infiltrate alone
<10%
IV
Pulmonary fibrosis
0%
Clinical and radiographic
1)
Asymptomatic,
abnormal CXR
Clinical Syndromes
findings need to be supported
2) Chronic respiratory symptoms
Diagnosis by histology
3) Lofgrens syndrome: fever, BHL, erythema nodosum, arthralgias
4) Extrapulmonary symptoms (uveitis, hepatitis, hypercalcemia, skin lesions, etc.)
Decision to Treat
1) Is it progressing? 2) Is it symptomatic? 3) Is it reversible?
ECG, blood count, LFTs, chemistry (esp. Ca2+), eye exam
Other testing PRN signs, sx
Tailored to the setting Assess other organ involvement
Setting
Treatment
Duration
Radiographic Stages
Sarcoidosis
Steroid
Therapy
Asymptomatic, low burden of disease

Asymptomatic, PFT abnormality or radiographic infiltrate
Pulmonary symptoms or evidence of extrapulmonary disease
Steroid side effects or progression despite steroids
Observation
Unknown
Corticosteroids, 20-40 mg/day x1-3 months, tapered to
5-10 mg/day
Steroid sparing agents (MTX, chloroquine, pentoxifylline, anti-TNF)
Until resolution
-12 months, follow for relapse,
consider chronic therapy
Unknown
43 Pulmonology
Pulmonary-Renal Syndromes
Characterized by
necrotizing
granulomatous
inflammation
Wegeners Granulomatosis
aka
Granulomatosis with Polyangiitis
Nasal, sinus, pulmonary,
(GPA)
renal involvement
possible
Presentation
Chest CT
Characterized by
glomerulonephritis,
pulmonary hemorrhage,
and anti-GBM antibodies
Labs
Renal Biopsy
Presentation
Goodpastures Syndrome
aka
Anti-GBM Antibody Disease
Chest CT
Labs
Renal Biopsy
Constitutional symptoms: fever, migratory arthralgias, malaise,

anorexia, weight loss
Blood nasal discharge, hemoptysis, hematuria
Nodules, cavitations, consolidations, and/or areas of ground glass

ANCA (antineutrophil cytoplasmic antibodies) present in >90% of
cases
Renal insufficiency, hematuria, proteinuria
Asymptomatic hematuria + normal/near normal renal function: mild
focal and segmental glomerulonephritis
AKI: diffuse necrotizing and crescentic glomerulonephritis
Rapid renal insufficiency, cough, pulmonary infiltrates, occasional
hemoptysis
Systemic signs and symptoms typically absent
Nonspecific patchy GGO (diffuse hemorrhage; typically sparing
subpleural space)
Anti-GBM (anti-glomerular basement membrane) Ab present in
>90% of cases
Renal insufficiency, hematuria, proteinuria
Crescending glomerulonephritis
Immunofluorescence microsopy: linear deposition of IgG along
glomerular capillaries and occasionally the distal tubules
44 Pulmonology
Solitary Pulmonary Nodule
Pulmonary Neoplasms
Evaluation
<3 cm in diameter
Completely surrounded by lung tissue
Probability of cancer <5%
Serial CXR
Old films, calcium, patient age, smoking status, lesion size
Smooth vs lobulated vs speculated vs irregular border
Lesion Shape
Granulated vs laminated vs diffuse vs popcorn vs stippled vs eccentric
Calcification
Evaluate for nodal abnormalities
CT Scan
Look for additional nodules
Tumor: increased uptake
Contrast
Benign: decreased uptake
Fleischner Society has recommendations for follow-up
Sensitivity for cancer: ~95%
Lesions >1 cm
Specificity for cancer: ~60-80%
Bronchoalveolar cell carcinoma
PET Scan
False negatives - Carcinoid tumors
Small lesions (<1 cm)
Follow-up CXR
Cancer: 60% (>2 cm)
Sensitivity
Benign: poor (may be bad sample)
Cancer: 100%
Specificity
Bronchoscopy
Pneumothorax
Complications
Hemorrhage
Allows for airway examination
Needle directly into lung tissue via chest wall
Mostly for peripheral lesions
Cancer: 90-95%
Sensitivity
TTNA
Benign: <50%
Cancer: >95%
Specificity
Complications - Pneumothorax, bleeding
Known diagnosis from bronchoscopy or TTN
>50% probability of cancer
Resection
Costly
Big surgery with significant pain and long recovery
Morbidity
Malignant
Causes
Benign
Primary lung cancer (esp. adenocarcinoma), bronchial carcinoid tumors and metastatic foci from
extrapulmonary malignancies (metastatic melanoma, sarcoma, colon, kidney, breast, testicle
Benign tumors of the lung (hamartomas), infectious granulomas, lung abscess, vascular abnormalities,
rounded atelectasis, pseudotumor
45 Pulmonology
Age
Smoking history
Probability of an SPN being malignant increases with patient age
Probability of lung cnacer is greater when SPN in individual with heavy smoking history
SPN
Size
Benign vs
Malignant
Radiographic
Findings
Borders
Calcification
Tumor Markers
Demographics
EGFR mutation
TKI Treatment
KRSA Mutation
ALK
Translocation
Epidemiology
Etiology
Larger lesions area more likely to be malignant

Absence of change in size for >2 years
dramatically likelihood of malignancy
Benign
Smooth, discrete
Malignant
Spiculated, irregular
Benign
Diffuse, central,
laminated (onionskin), popcorn
Malignant
Peripheral eccentric
Associated with adenocarcinoma

Women
Non-smokers
Asian
Excludes possibility of KRAS mutation
Erlotinib, Gefitinib
A PO chemotherapy with minimal side effects
Superior progression-free survival
Median 2 year survival is 50% with TKI therapy in stage IV
Smoker
Worse prognosis
Higher mortality if treated with EGFR inhibitors
Occurs downstream of EGFR, meaning usually dont have EGFR mutation
Fusion gene between ALK (anaplastic lymphoma kinase) and EML4 (echinoderm microtubule-associated protein-like 4) genes produces
a protein that functions like an oncokinase in NSCLC
EML4-ALK fusion gene is detected in 5% NSCLC
Crizotinib, an ALK inhibitor, has been associated with a favorable response
1.3 million cases/year worldwide (2009)
Estimated 221,200 new cases/year (2015)
Estimated 158,040 deaths/year (2015)
Most common cancer death in US
90%
Benzo-a Pyrene = 1 carcinogen
Tobacco, active exposure
10-30x risk a non-smoker
Dose-dependent risk
5%
Tobacco, passive exposure
10-15%
Genetic predisposition
PAH, asbestos, chromium, arsenic, nickel
Occupational exposure
Radon, asbestos, indoor air pollution, cooking with wood
Environmental exposure
46 Pulmonology
Small cell carcinoma
Histologic Types
Bronchogenic
Carcinoma
20%
Squamous
Adenocarcinoma
Large cell
Mixed
Non-small cell carcinoma

Metastatic
Other
Carcinoid, bronchial gland, sarcoma
Epidemiology
Presentation
Association
-
Small Cell
Squamous Cell
Adenocarcinoma
Most common in males

>95% of patients are
smokers
30-40% of primary tumors

Most common cell type in
females
Weakest association with
tobacco (but still primarily
tobacco related)
20-30%
30-40%
10%
Generally
hilar/mediastinal
origin; also
neuroendocrine
Usually
hilar/endobronchial
in origin
Generally peripheral
in origin
Associated with
paraneoplastic
syndromes SIADH,
Cushing syndrome,
myopathy/neuropathy
(i.e. Eaton-Lambert),
CNS dysfunction
Treatment
-
Most
chemotherapy
sensitive cell
type (also
returns quickly)
No evidence that
surgery improves
outcomes
Prognosis
-
Cavitation common
May be associated
with hypercalcemia
(paraneoplastic)
Bronchoalveolar subtype may resemble pneumonia adenocarcinoma

in situ, which is pneumonia-like but doesnt clear; it can take years to
grow or cause trouble, ground glass on CT
Radiosensitive, chemotherapy resistant

Resectable if caught early
Large Cell
~12% primary tumors
Usually peripheral in
origin
Resectable if
caught early
(rare)
-
Lung Cancer
Symptoms
Primary Tumor
Very early
metastasis,
very aggressive
Likes to
metastasize to
the brain
Poorer
prognosis than
other nonsmall cell
tumors
Rapidly
growing
None until advanced disease
Central/Endobronchial
Peripheral
Cough
SOB
Hemoptysis
Chest wall pain
Cough
Wheezing/stridor
Post-obstructive pneumonia
47 Pulmonology
Nodal Spread
Regional Spread
Local Spread
Lung Cancer
Symptoms
Brain Mets
Extrathoracic
Bony Mets
Adrenal Mets
Weight loss
Anorexia
Fatigue
Fever
Hypercalcemia
Hyponatremia
Cushing Syndrome
Eaton-Lambert
Neuropathy
Systemic
Paraneoplastic
Syndromes
Endocrine
Neurologic
Tracheal/esophageal obstruction
Hoarseness
Paralyzed hemidiaphragm
SVC syndrome
Chest wall pain
Pleural effusion
Horners syndrome (ptosis, miosis, anhidrosis)
Brachial plexopathy
Seizure
Headache
Aphasia, paresis
Confusion
Pathologic fracture
Spinal cord compression
Bone marrow invasion
Addisons (unuual)
PTH hormone
SIADH
ACTH-like
Small cell
All types
Squamous cell
Small cell
Small cell
Skeletal/connective tissue
Lung Cancer
Screening
Diagnosis
Hilar/Mediastinal
Masses
~4 new cases/year/100 patients with history of heavy smoking, > 45 years

80% detected by CXR, 20% by serology
Tend to be resectable
No difference in survival in large, randomized study
Age 55-80
30 pack year smoking history
Screening Eligibility
Quit smoking <15 years prior
Annual LDCT
CXR
USPSTF
Radiographic
CXR
Bronchoscopy
Diagnostic
TTNA
Surgery
Thoracocentesis
CT
Exophytic tumor: ~95% sensitivity; submucosal: ~80% sensitivity

Complications: bleeding, respiratory failure, infection, arrhythmia
Rarely indicated for hilar mass
Sensitivity 90-95%
Complications: PTX, hemorrhage
Rarely indicated
Mediastinoscopy often preferred
Pleural effusion in ~1/3 NSCLC patients initial can detect malignancy in 65%, repeat can detect in
30% (in whom initial negative)
48 Pulmonology
Small Cell
Limited Disease
Extensive Disease
Confined to one hemithorax & to one group of regional lymph

nodes
70%
NSCLC
Clinical
Surgical
Diagnostic
Methods
Clinical
Staging
30%
Tumor < 2 cm
Tumor < 3 cm
Tumor < 2, > 3
T1
cm
Tumor >3 , > 5
Tumor > 3 cm or involved mainstem bronchus
T2a
cm
T2
or causes collapse of lung to hilum
T2b
Tumor > 5, < 7
Tumor
cm
Tumor > 7 cm or invading chest wall, diaphragm, mediastinal pleura,
pericardium or < 2 cm from carina, or atelectasis of entire lung, or separate
T3
nodule in same lung
Tumor invading mediastinum, heart, trachea, carina, vertebral body, or satellite
T4
lesion in different lobe of ipsilateral lung
No positive lymph nodes
N0
Ipsilateral peribronchial or hilar nodes
N1
Nodes
Ipsilateral mediastinal or subcarinal nodes
N2
Contralateral mediastinal or hilar nodes, any scalene or supraclavicular nodes
N3
No distant metastases
M0
Distant
M1a
Pleural effusion (ipsi or contralateral),
Metastases
metastases
pulmonary nodule in contralateral lung
M1
present
M1b
Distant metastases
Carcinoma in situ
0
T1N0M0
T2aN0M0
IA
IB
T1N1M0,
T2aN1M0,
T2bN0M0
IIB
T2bN1M0, T3N0M0
IIA
Stages
T3N1M0, T1-3N2M0, T4N0-1M0
IIIB
T1-4N3M0, T4N2M0
IIIA
Any T, any N, M1a-b
IV
CT, PET, other diagnostic procedures
No surgery
Primarily via assessment of lymph nodes (improved 5-year survival for stage IA disease compared to clinical)
CT Scanning
~60% sensitive
~80% specific
PET Scanning
~80% sensitive
~80% specific
Nodes
Low specificity means appropriate staging requires some kind of mediastinal invasion, unless done
via endosonography, performing LN needle biopsy
Metastases - Abdominal CT, head CT, bone scan, PET scan
T1a
T1b
Staging
Pathologic Staging
Physiologic Staging
Required for every patient

To determine ability to
undergo surgery
Bronchoscopy with needle aspirate, mediastinocopy, resection
Spirometry, blood gases, quantitative VQ scans, exercise testing

49 Pulmonology
SCLC
Limited Stage
Extensive Stage
NSCLC
Stages I and II
Stage IIIA
Treatment
Stage IIIB
-
Stage IV
New Agents
Combination chemotherapy/XRT
Prophylactic brain irradiation
Combination chemotherapy
Radiation for brain mets if present
Resection
Chemotherapy (stage IB, II)
Resection if possible
Neoadjuvant chemo often used
~30% patients technically resectable
High dose radiotherapy for those with
disease confined to chest
Chemo often given in conjunction
Radiotherapy to symptomatic site +
chemotherapy
Targets for specific, antibody-based therapy
(EGFR-TKI, EML4-ALK inhibitor)
Low associated side effects
5 year survival 15-25%

50% patients with complete remission
5 year survival < 5%
30% complete remission
5 year survival - ~50%
5 year survival - ~30% (if resected)
Median survival - ~12 months

5 year survival - ~5% (disease confined to
chest)
Median survival - < 6 months
Median survival with chemo 8-12 months
Roughly double progression-free survival

No change in long-term mortality
Pleural Disease
Pleural Anatomy
Visceral pleura
Parietal pleura
Microscopic
Malignant
Pleural
Mesothelioma
Normally produces small amount of fluid
Serous membrane covering chest wall
Normally secretes and reabsorbs pleural fluid
5 layers
1. Mesothelial cells, 2. Submesothelial connective tissue layer, 3. Superficial elastic

layer, 4. Loose connective tissue layer, 5. Deep fibroelastic layer
Allows movement of lung relative to chest wall

Provides a route for removal of lung edema
Normal fluid formation = 0.02 mL/kg/hour

Normally formed and absorbed by parietal pleura
Formation described by Starlings law fluid flux is related to hydrostatic pressure (vasculature pleural space) and
osmotic pressure (pleural space vasculature)
Incidence
Rare, with declining incidence in US but increasing worldwide
Etiology
Strong association with occupational asbestos exposure (amphibole > chyrsotile)

25-50% off cases are sporadic disease
Physiology
Arises from parietal pleural; may also involve peritoneum, tunica vacinalis
Epithelioid, sarcomatoid, biphasic
Prognosis
Poor response to surgery and chemotherapy
Functions
Pleural
Physiology
Serous membrane covering lung
Pleural Fluid
Formation
50 Pulmonology
Pain caused by acute pleural inflammation resulting from irritation of the parietal pleura
-
Pain
Pleuritis
Causes
Treatment
Localized, sharp, and fleeting

Worsened by coughing, sneezing, deep breathing, and movement
May be referred to ipsilateral shoulder when central portion of diaphragmatic pleura is irritated
Young and otherwise healthy viral respiratory infections, pneumonia
Rib fracture
Presence of pleural effusion, pleural thickening, or air in the pleural space requires further diagnostic and
therapeutic measures
Treating underlying disease
Pain relief: analgesics, anti-inflammatory drugs
Cough control in pleuritic chest pain: codeine, other opioids (if retention of airway secretions not likely)
Intercostal nerve blocks: sometimes helpful, benefit usually transient
Pleural fluid formation exceeds reabsorption

-
Pleural Effusion
Causes
Excess production of fluid

Plugged lymphatic reabsorption (normally have ability to absorb 20x normal production)
One of the most common causes
Usually bilateral, occasionally R > L
Treatment: diuretics
Increased Phydrostatic (little Poncotic) fluid movement capillary beds to pleural space
CHF
Exceeds ability of lymphatics to reabsorb fluid
May also be direct flow from fluid leaking into alveolar space, through lung
parenchyma, and into pleural space (not clear)
Other most common cause
Lung ~40%, breast ~25%, lymphoma ~10%
Diagnosis: pleural fluid cytology (occasionally needle or surgivvcal biopsy)
Can be quite symptomatic (SOB)
Treatment: therapeutic thoracentesis, drainage with sclerosis, tunneled pleural
Malignancy
catheter
Hydrostatic: Pparietal = Pvisceral
Tumor cytokines leaky vasculature (including proteins) oncotic Ppleural
decrease fluid reabsorption to vasculature
Tumor may also line pleural space and obstruct the route of fluiud reabsorption
Associated with pneumonia
Treatment: tap if > 1 cm free flowing fluid on CXR
Parapneumonic
Complicated: pus in pleural space, positive Gram stain, pleural glucose < 50, pleural
fluid pH < 7.2; treatment immediate chest tube placement
Usually R-sided
Cirrhosis
Often due to sump mechanism
Causes volume overload
Usually associated with CHF too
Renal Insufficiency
Often seen in dialysis patients with poor diet compliance, insufficient dialysis
51 Pulmonology
Transudative CHF, cirrhosis, renal insufficiency

Exudative parapneumonic, malignancy, mesothelioma, TB, PE, rheumatic (lupus, RA), viral, post-surgical
Inflammatory
Exudative
Meets > 1 Lights criteria
Hydrostatic problem
Transudative
Meets 0 Lights criteria
Pleural protein/serum protein > 0.5
Lights
Pleural LDH/serum LDH > 0.6
Criteria
Pleural LDH >2/3 upper limit of normal for serum
Types
Pleural Effusions
Symptoms
SOB, + chest pain (most common complaints)
Thoracentesis
Diagnosis
CXR
US
Transudative
Treatment
Hemothorax
Exudative
Pleural fluid with hematocrit > 50% of serum

hematocrit
Spontaneous
Causes
Determine exudative vs transudative

Fluid cent for cell count, glucose, gram stain, cytology, amylase, pH, cholesterol
and triglycerides
Decubitus films show fluid well
More sensitive; lets you mark position for thoracentesis

Diuretics
More complicated, because of various causes
Causes: trauma, TB, tumor, PE

Usually requires chest tube to prevent scarring
Associated with subpleural blebs, smoking, tall stature
54% risk of recurrence in 4 years
Primary
Men: 18-28/100,000
Women: 1-6/100,00
Associated with pulmonary fibrosis, emphysema
Secondary
Traumatic
Iatrogenic
Other
Tension
Pneumothorax
British
Thoracic
Society
Guidelines
Treatment
-
Related to procedures
Can cause cardiovascular compromise
Requires emergent surgical treatment to prevent death
Small: < 2 cm from chest wall

Large: > 2 cm from chest wall
Asymptomatic, small
Observation
Symptomatic or large
Aspiration
Primary
Recurrent or failed repeat aspiration
Chest tube
Asymptomatic, small, < 50 yo
Aspiration
Secondary
Symptomatic, large, > 50 yo
Chest tube
Avoid suction for 48 hours if pneumothorax has been present > 24 hours, to prevent re-expansion pulmonary edema,
which can throw the patient into respiratory failure
52 Pulmonology
Obstructive Sleep Apnea

Sleep
Disordered
Breathing
Apnea
Hypopnea
Sleep Apnea
A group of conditions associated with abnormal

respiratory function due to heightened physiologic
variation during sleep
Affects > 5% US population
Complete cessation of airflow for 10 seconds
-
Obstructive
Central
Mixed
Influences on
Ventilation
Hypoxic drive to breath reduced

Ventilatory response to PaCO2 diminished
Behavioral control system input diminished
Everyone experiences occasional episodes of apnea and hypopnea

while sleeping
Significant decrease in airflow
Increased frequency and

duration of apneic and hypopnic
episodes
Normal physiologic variations

during sleep:
Ventilatory effort persists but

not airflow because of
transient obstruction of upper
airway
Most common
Men > women
Overweight, obese
Complete airway occlusion airflow stops
hypoexmia, hypercapnia
Ventilatory effort is absent for Rare
duration of apneic episode
Seen mostly in men
Usually have normal body habitus
Due to decreased central respiratory drive
Absent ventilatory effort precedes upper airway obstruction during apneic episode
Arterial pCO2, pH, pO2, and brainstem tissue pH

Monitored by peripheral and central chemoreceptors
Obesity-Hypoventilation
Syndrome
(Pickwickian Syndrome)
Hyperventilation
Syndromes
Alveolar hypoventilation appears to result from a combination

of 1) blunted ventilator drive and 2) increased mechanical load
imposed upon the chest by obesity
Voluntary hyperventilation returns the PCO2 and PO2 toward
normal values
Most also suffer from OSA
Treatment:
Weight loss
NPPV helpful for some
Respiratory stimulates may be helpful
Goals of Therapy
Improvement in hypoexmia, hypercapnia,
erythrocytosis, and cor pulmonale
Caused by variety of conditions
An increase in alveolar ventilation that leads to hypocapnia

Central Neurogenic Monotonous, sustained pattern of rapid and deep breathing seen in comatose patients with
brainstem injury of multiple causes
Hyperventilation
Hyperpnea, paresthesias,
Exclude organic causes
Acute
carpopedal spasm, tetany,
anxiety
Chronic
Breathing through pursed lips or through nose with one

nostril pinched, rebreathing expired gas from paper bag (
respiratory alkaemia and assoc. sx)
Anxiolytic drugs may be useful
Various nonspecific symptoms, including fatigue, dyspnea, anxiety, palpitations, and dizziness
Diagnosis established if symptoms reproduced during voluntary hyperventilation
53 Pulmonology
Pathophysiology
Causes of
Occlusion
Risk Factors
Presentation
Clinical Exam
Cyclic episodes of airway occlusion hypoxia and hypercapnia arousal from sleep occlusion resolved airway opened
Sympathetic tone during airway occlusion hypertension, vasoconstriction
Intrathoracic pressure increasingly more negative with inspiration
Loss of pharyngeal tone

Narrow upper airway
Pharynx passively collapses during inspiration
Micrognathia
Macroglossia
Obesity
Tonsillary hypertrophy
Male gender
Age (middle aged, older adults)
Obesity
Abnormal upper airway anatomy (increased neck diameter)
Alcohol and sedatives and increase/contribute to loss of pharyngeal tone
Also Associated:
URIs may cause narrowing of upper airway
Tobacco abuse
Hypothyroidism
Daytime somnolence
Recent weight gain
Patient Complaints
Recurrent awakenings
Cognitive impairment
Morning headaches
Impotence
Fatigue
Loud snoring
Personality changes
Sleep Partner
Episodic breathing cessation
Depressive symptoms
Complaints
Restlessness (movement) during sleep
Often normal
Elevated BP
May observe:
Pulmonary HTN, peripheral edema (signs of R heart failure)
1.
STOP-Bang
Scoring
2.
3.
Consequences
Stratify patients for

unrecognized OSA
Guide
perioperative
precautions
Triage patients for
diagnosis and
treatment
Snoring
Tired
Observed
blood Pressure
BMI
Age
Neck circumference
Gender
Hypertension
Nocturnal arrhythmias
Pulmonary HTN
Increased risk for CV event (CAD)
Do you snore loudly (louder than talking or loud enough

to be heard through closed doors)?
Do you often feel tired, fatigued, or sleepy during
daytime?
Has anyone observed you stopping breathing during
sleep?
Do you have or are you being treated for high BP?
> 35
> 50 years
> 40
Male
Results
High risk: yes to 3+
items
Low risk: yes to < 3
items
These conditions should prompt

provider to consider presence of
other clinical evidence of OSA
54 Pulmonology
Overnight
Polysomnography
Diagnosis
ECG, EEG, limb movements, and O2

saturations measured during sleep
CXR, PFTs
Lab Findings
Treatment
Required for formal diagnosis

OSA = airflow cessation occurs despite
repeated muscular efforts to breath
(confirmed on EEG)
Will distinguish central vs obstructive and
can r/o other sleep disturbances
Not helpful in most cases
May be normal
Erythrocytosis
CO elevated (Pickwickian)
ABG showing hypercapniea, hypoxia
Behavioral - Weight loss
Avoid sedative use
Medical
Continuous
Positive Airway
Pressure (CPAP)
Bilevel
Ventilation
(BiPAP)
Surgical
Tobacco cessation
Avoid alcohol use
Positive pressure splints the upper airway
First line therapy
Proper fit is the key to compliance (high non-compliance rates)
Increased FRC allowing alveoli to be recruited tduring ventilation,
Mechanism
increasing oxygenation, decreaseing work of breathing, and
increase in intrathoracic pressure = decrease cardiac workload
Nasal congestion
Complications
Mouth breathing
Claustrophobia
Non-invasive positive airway pressure ventilation
One pressure for inspiration and another, lower pressure for expiration (the difference
between the 2 pressures = pressure support, which can result in / ventilation)
Patients with comorbid pulmonary disease or Pickwickian
To address narrow upper airway

Uvulopalatopharyngoplasty (UPPP) Nasal Septoplasty
Tracheostomy
Etc.
Resect soft tissue of pharynx and

soft palate, including uvula
May be helpful when nasal septum
abnormality present
Limited evidence for effective

relief
Can be very successful in pt w/
specific anatomical abnormality
that can be corrected
Definitive treatment
Reserved for patients with life-threatening arrhythmias or severe disease that has failed
all other treatment options
Consequences: scarring, stoma and airway infections, speech difficulty
Difficult to care for and maintain, especially in obese patients
Supplemental O2 is not adequate (may prolong apneic episodes)
Mouthguards (hold mandible forward) have modest evidence to suggest efficacy in relieving apnea, but compliance
generally poor
55 Pulmonology
Pulmonary Imaging
Inspiratory CXR
Expiratory CXR
Silhouette Sign
Standard protocol
Best images of lungs due to high contrast with air
With lungs expanded, more tissue in the path of the XR beam
Expiratory films used to identify air trapping, by a foreign
body for example (lung appears hyper-inflated)
Bronchovascular crowding, mediastinum appears enlarged
Can obscure disease
Often seen with pts on ventilators
Cannot distinguish between two adjacent structures of the same radiographic density that are adjacent to one another
Abnormal diaphragm position may indicate serious pathology
Abnormal
Diaphragm
Findings
Obscured hemi-diaphragm
Maybe due to adjacent lung disease
Pneumoperitoneum
Free intra-abdominal air under the diaphragm, a sign of bowel obstruction

Seen as crescents of relatively low density (black)
R shoulder be slightly above L
Causes: damage to phrenic nerve, lung disease causing volume loss, congenital
causes (i.e. diaphragmatic hernia), trauma to diaphragm
Raised hemi-diaphragm
Disorder
XR
COPD
Increased lung space
Pneumothorax
Pulmonary edema
Pleural effusion
Pneumonia
Atelectasis
Viral
Bronchitis Infectious
Pulmonary TB
Lung Tumors
Lymphoma
Sarcoid
CT
Air outside the lung space

Best demod on expiratory film
Increased opacity of the lung
Increased opacity outside the lung fields, particularly in costophrenic margins
Lateral decubitus film shows layering out of free pleural fluid
Increased lucency outside the lung fields, particularly in the
Spine fluid layers and apical cap
costophrenic margins
Minimum fluid for detection: lateral = 75 mL, frontal = 200 mL
Increased opacity (lightness) in the lung field (could be atelectasis)
Increased lucency in the lung field
Collapse of pulmonary alveoli is evident as white patches or lines in the lung fields
Increased density with reduced volume of lung tissue
Subtle prominence of central bronchial markings; peribronchial cuffing
Thickening of bronchial walls and peribronchial cuffing visible ring shadows, tram tracks (parallel lines)
Usually in the upper lobes
Chronic associated with calcification
Soft-tissue masses in the lung fields
Often large soft tissue masses in the anterosuperior mediastinum
Bilateral hilar lymphadenopathy, pulmonary infiltrate, pulmonary
fibrosis
Various patterns (GGO, nodules, fibrosis, masses, consolidation,

cysts, bronchial wall thickening); upper/mid lung predominance,
bronchocentric distribution; septal beading
56 Pulmonology
Pulmonary CT
Common
Indications
Pulmonary
Embolism
CXR
CT with
contrast
(Angiography) -
Thoracentesis
CXR abnormality
Lung tumor
Mediastinal mass
Aortic injury, dissection, or aneurysm
Complicated infection (septic embolic, immunocompromised, recent thoracic surgery)
PE (Spiral CT CT pulmonary arteriography)
Often normal
Most common and most preferred
Patient needs good kidney function (Cr < 1.5)
Be sure no contrast allergy
V/Q Scan
Preferred if patient has contrast allergy or is pregnant

PE is characterized by ventilation but no perfusion = VQ mismatch
Studies based on probability depending on percent
Ventilation = inhaled radiotracer; perfusion = venous injection of another radiotracer
Pulmonary
Arteriogram
Gold standard
Rarely used
MRI
Not a lot of data on use

Generally not first line choice
Invasive procedure that entails insertion of needle into pleural

space for removal of fluid
Diagnostic
Therapeutic
In patient with pleural effusion

of unknown cause
Drain large effusion leading to
respiratory compromise
57 Pulmonology
Pulmonary Function Testing

Pulse Oximetry
Used to monitor arterial O2

saturation levels (SaO2) in
patients at risk for hypoxemia
Measures amount of gas a subject

can voluntarily move
FVC
FEV1
Post-Medication
Flow-Volume Curve (Loop)
Lung Volume
Testing
Peak Expiratory
Flow Rate (PEFR)
Diffusing Capacity
(DLCO)
Goals of PFTs
Measuring functional residual

capacity (lung gas volume at rest
point)
-
FEV1/FVC
Spirometry
Increased fraction of inspired oxygen (FiO2), hyperventilation

Hypoventilation, inadequate O2 in inspired air (suffocation),
atelectasis, mucus plug, bronchospasm, PTX, pulmonary edema,
Decreased
ARDS, restrictive lung disease, atrial or ventricular cardiac septal
defects, severe hypoventilation states, PE
6 seconds as normal to get vital capacity out
Initially measuring large airway function, towards the end measuring small airway
function
Amount of air that can be forcefully expelled from a maximally inflated lung position
Increased
Volume forced exhaled in the first second of FVC

Should always be > 0.7
If < 0.7 because 1) too weak for test, 2) narrow major airways
Broncho-Dilators (4 puffs agonist)
Increase by 15% considered significant
Diagnostic of asthma when FEV1 > 20%
Methacholine (up to 8 mg/mL)
Dose response defines severity
Allows better assessment of airway
characteristics at low lung volumes
FEV25-75 = mean flow during midIn setting of normal FEV1/FVC, abnormal
exhalation
flow volume curve suggests early airway
disease
Techniques
Plethysmography
Inert gas dilution
Nitrogen washout
Maximum airflow rate during forced expiration
Diffusing capacity of the lung amount of gas exchanged across the alveolar-capillary membrane per minute
CO used because CO has high Hb affinity and small concentration necessary
Vc: capillary blood volume
Inhaling small concentrations CO
CO Uptake Measured
CO Uptake Dependent On
Dm: alv-cap membrane
Holding breath 10 seconds
By:
properties, surface areas
Measuring exhaled CO
Airflow obstruction (COPD, asthma)
Characterize Disease - Lung restriction (pleural and parenchymal disorders)
Does not diagnose disease
Neuro-muscular dysfunction (e.g. weakness)
Pathophysiology
Vascular disorders (PE, pulmonary HTN)
Quantitate
Dysfunction
Disability assessment
Risk evaluation (surgery, medications)
58 Pulmonology
PFT Value Predicted by
95% Confidence Intervals for Normal
Normal Values
Grading Severity
Disease
Asthma
Obstructed
Bronchitis
Emphysema
Restricted
Neuromuscular
Vascular
Age, height, sex
Spirometry: 80-120% of predicted

Others: 70-130% of predicted
Mild
Moderate
Severe
Very severe
> 80% of predicted value

50-80% of predicted value
30-50% of predicted value
< 30% of predicted value
FEV1/FVC
FVC
RV
DLCO
Normal
Decreased*
Normal
Increased*
Normal
Decreased
Normal
Increased
Normal
Decreased
Normal
Increased
Decreased
Reversible to large degree with

bronchodilator use
COPD: rates (FEV1, FEF25-75, FEF2001200), abnormal airflow curves, RV and
ERV, VC
Normal
Decreased
Decreased
Normal/Decreased
Restricted = reduction of lung volume
Decreased
Decreased
Increased
Normal
Normal
Normal
Normal
Decreased
*during exacerbations, methacholine
Sputum Cultures
Sputum
Sampling
Sputum
Cultures
Expectorated matter from the trachea,

bronchi, and lungs through the mouth
Best collected when patient awakes in the morning

Collect at least 1 teaspoon in a sterile container + alcohol
Usually obtain by having patient cough after taking several deep breaths
Endotracheal
Suctioned sputum from ET or tracheostomy tube
Small amounts of physiologic solution are injected through a fiberoptic bronchoscope

into a specific area of the lung, while the rest of the lung is sequestered by an inflated
balloon
Bronchoalveoelar lavage (BAL)
The fluid is then aspirated and inspected for pathogens, malignant cells, and mineral
bodies
Preliminary reports in 24 hours, cultures
Obtained to determine the presence of
1st Gram stain
take at least 48 hours
2nd bacterial culture
pathogenic bacteria in patients with
Sputum cultures for fungus, M.
respiratory infections, such as pneumonia - Also, drug sensitivity testing
tuberculosis 4-6 weeks
Culture never indicated
Bronchitis
Consider CAP vs HAP, aspiration, age or
Indications
immunocompromised patient, atypical
Pneumonia
infections (culture negative)
- Skilled initiative against anticipated pathogens
Communicate suspicion of unusual
Empiric Treatment - Important factors: cost, yield, expected agent
infections to lab
59 Pulmonology
Clinical Pearls
Respiratory
Cultures
Reasons to Obtain
Culture
Acid-Fast
Bacilli (AFB)
Stain
KOH/Wet Prep
Epidemiologic significance
Antimicrobial susceptibilities to detect resistance
Provides targets treatment helpful in multiple drug
allergies, drug interactions, renal or hepatic
insufficiencies, immunocompromised
Consider alternative test to culture (e.g.

serologic study)
Aspiration pneumonia treatment takes into
consideration lack of anaerobic culture
CXR findings not always pathognomonic
CAP vs HAP critical
Squamous epithelial cells
Oral mucosal contamination
Neutrophils
Absences not predictive in neutropenic or immunocompromised patient

Numerous WBC = infection
Macrophages
Eosinophils
Activated phagocytic cells common in fungal, acid-fast, and some atypical bacterial infections
Allergic reaction or parasitic infection
Mucus strands
Mechanically cleanse respiratory tract

Direct attack of inhaled bacteria via antibodies (primarily IgA) and lysosomes
Bacteria, fungi, or AFB
Distinguish normal flora from pathogens
Sputum
Cellular
Elements
Gram Stain
Done to evaluate lower respiratory tract specimen quality

to culture
-
Acceptable: < 10 squamous epithelial cells/low power field

Induced specimens, BAL, and bronchial brushings or biopsy
dont require screening gram stain
Mycobacterium
tuberculosis
Fungal Cultures
S. pneumoniae
M. catarrhalis
Meningococci
H. influenzae
Collect serial early AM sputum cultures x3

Cultures incubated 5 weeks for final report
+ TB always reported to state health department
for contact evaluation
Important in immunocompromised,
immunosuppressed, or post-antibiotic patients
Cultures incubated for several weeks before culture
results finalized
Lancet-shaped Gram positive cocci in pairs

Gram-negative diplococci, often visible within cytoplasm
of neutrophils
Often visible within cytoplasm of neutrophils
If positive, presumptively treat for TB in appropriate

clinical picture
Stain as low as 20% sensitive
Candida albicans
Aspergillus
Histoplasmosis
Blastomycosis
Coccidiosis
Zygomycosis
60 Pulmonology
Tuberculosis Testing
-
Goal of Testing
Who should be
tested?
Mantoux
Method
Tuberculin
Skin
Testing
(TST)
Positive
Reactions
Anergy
Detect latent TB and treat patients who would benefit from

Only test individuals that would benefit from
treatment
treatment presume a positive TST would require
Detecting Mycobacterium tuberculosis complex
treatment
Suspected of having TB (suspicious CXR, productive cough with negative routine cultures, hemoptysis, undetermined
weight loss)
At risk for progression to active TB
At increased risk for LTBI (HC workers, recent transplant organ recipients, HIV patients, recent immigrants, IVDA, those in
close contact to someone known to have TB)
At low risk for LTBI, but tested for other reasons (e.g., entrance to college)
Geographically high risk, housing high risk (shelters, migrant farm camps, prison/jail, nursing homes)
Administer 5 units (0.1 mL) of PPD intradermal to the volar forearm
Measure induration, not erythema at 48-72 hours
If positive, check again 4-5 days later to be certain a severe skin reaction hasnt occured
Requires 2-12 weeks to develop an immune response to TB = delayed type hypersensitivity mediated by T cells
Once positive, reaction usually persists for life
HIV+ patients, recent +TB contact, fibrotic CXR findings, s/p organ transplant, immunocompromised
Induration > 5
patient, medications (TNF alpha antagonists, prednisone >15 mg/day)
mm
Induration > 10
mm
Reactor
Contraindications -
False Positives
Immigrants <5 years from high prevalence country, injection drug users, residents/employees of
congregate settings (hospital, nursing home, prison, shelter), mycobacteriology lab, children <4 years,
infants/children/adolescents exposed to adults in high-risk categories, co-morbid risk factors
Any person, including persons with no known risk factors for TB
Induration > 15 mm
Inability react to skin tests because of
weakened immune system
Notes
Two-Step Testing
Control with Candida injection to determine if immune system is

functioning
Latent TB may elicit + PPD

Boosting: patient with latent TB may have negative TB if
tested years after infection
BCG vaccine usually elicits + PPD

If PPD positive and adequately treated, no need to ever
re-test PPD (will always be positive)
Patient with previously documented
Patient with positive PPD for 1st time
Convertor
negative PPD who now tests positive
Active TB, BCG vaccination, skin rash that would make interpretation difficult
2nd test positive: latent TB or prior BCG vaccine;
st
If 1 PPD is negative, retest in 2-3 weeks to access for
reactor
delayed memory response
2nd test negative: probably not infected
Infection with non-tuberculosis
mycobacteria
Previous BCG vaccination
Incorrect method of administration
or interpretation of reaction
False
Negatives
Anergy
Recent TB infection (within 8-10 weeks exposure) or
overwhelming TB infection
Very remote TB infection
Age < 6 months
Incorrect method or interpretation, dosing or storage
61 Pulmonology
Whole
Blood
InterferonGamma
Release
Assay
Whole blood test

for use as an aid in
diagnosing M.
tuberculosis
infection
Measure of patients cell-mediated immune response to TB

infection
Examples: QuantiFERON-TB Gold, QFT
Diagnoses active TB in patients recently exposed to or

suspected to have T infection
More specific test for LTBI
Can help exclude BCG or non-TB mycobacterium
T cells of patients previously infected with M. tuberculosis will produce high levels of interferon gamma
As antigens used arent shared by BCG or other mycobacterium, low cross reactivity
ELISA
Because TB is usually infective to the lungs due to inhalation of airborne infectious material, the CXR often demonstrates results (Ghon complex) of
the acute granulomatous infection
Ex vivo T-cell
based assay
CXR
AFB Smear
TB C&S
Obtain AFB cultures and smears x3 (early AM specimens) to evaluate for active disease
Indicated in any patient with persistent productive cough, night sweats, anorexia, weight loss, fever, and hemoptysis
Diagnosis of TB can be made only by ID and culture of M. tuberculosis in the specimen
After taking up dye, M. tuberculosis is not decolorzed by acid alcohol (= acid fast) and is seen as a red, rodshaped organism
62 Pulmonology
Asthma Pharmacotherapy
Asthma Severity
Classification
Treatment
Rule of Twos
Quick Relief
Class
Symptoms: Day/Night
Mild Intermittent
Step 1
Mild Persistent
Step 2
Moderate Persistent
Step 3-4
Severe Persistent
Step 5-6
Intermittent
Persistent Daily
Medications
PEF or FEV1
PEF Variability
> 80%
< 20%
> 80%
20-30%
> 60% - <80%
> 30%
< 60%
> 30%
< 2 days/week
< 2 nights/month
> 2/week but < 1/day
> 2 nights/month
Daily
> 1 night/week
Continual/frequency
SABA PRN
Step Preferred
Alternative
2
Low-dose ICS
Cromolyn, LTRA, Nedocromil, Theophylline
3
Low-dose ICS + LABA or
Low-dose ICS + either LTRA, Theophylline, or Zileutron
medium-dose ICS
4
Medium-dose ICS + LABA
Medium-dose ICS + either LTRA, Theophylline, or Zileutron
5
High-dose ICS + LABA AND consider Omalizumab for patients with allergies
6
High-dose ICS + LABA + oral corticosteroid AND consider Omalizumab for patients with allergies
Consult with asthma specialist if step 4+ care req. (consider at step 3)
Before stepping up, check adherence, environmental control, comorbid conditions)
Step down if possible (and asthma well-controlled at least 3 months)
At each step, patient education + environmental control + management of comorbidities
Steps 2-4: consider subQ allergen immunotherapy for patients with allergic asthma
Shift from PRN inhaler to scheduled inhaler
Quick-relief inhaler > 2x/week
Awaken at night > 2x/month
Refill quick-relief inhaler > 2x/year
Medications
Information
Short-Acting
Inhaled 2 Agonists
Albuterol (Ventolin, Proventil)

Levoalbuterol (Xopenex)
Pirbuterol (Maxair)
Anticholinergics
Ipratropium (Atrovent; short-acting)

Tiotropium (Spiriva; long-acting)
Systemic
Corticosteroids
Prednisone
Methylprednisolone
Prednisolone
Indicated for intermittent episodes of bronchospasm

Used PRN for chronic asthma
Treatment of choice for management of EIB is albuterol 15 min. before exercise
Increasing up or > 1 canister/month need to intensify anti-inflammatory
therapy
May have added benefit with agonist in severe exacerbations
No long-term effectiveness shown
Tiotropium no role for asthma
Same mechanism as inhaled corticosteroids
Continue until patient achieves 80% of personal best or symptoms resolve
(usually 3-10 days)
Adults: 40-80 mg/day oral prednisone
63 Pulmonology
Action Plans
Integrate into every

step of care
Patient Education
Long Term Treatment
Goal
Class
Inhaled
corticosteroids
Leukotriene
Modifiers
Mast Cell
Stabilizers
Long-Acting
Inhaled 2
Agonists
Guide to be used at home/school

Based on personal best
Decrease inflammation
> 80%
Green zone
50-80%
Yellow zone
<50%
Red zone
Basic facts about asthma
Roles of asthma medications
Environmental control measures
Inhaler techniques
Medications
-
Continue meds as prescribed

Double ICS and schedule SABA
Go to ER, start PO steroid
Self-monitoring skulls
Appropriate rescue actions
Vaccines (influenza, pneumococcal)
Information
Potent anti-inflammatory agent

Primary agent in adults with persistent asthma
Function: prevent symptoms; suppress, reverse, and control inflammation
Inhaled route used in long-term management similar efficacy between ICS agents when given in equivalent doses
Decreases frequency of exacerbations
Oral thrush
Dysphonia
Cough
Adverse Effects Inhaled
Systemic
Osteoporosis
Cushings syndrome
Glucose intolerance
Peptic ulcers
Fluid and electrolyte disturbances
Ocular cataracts
Weight gain
Behavioral disturbances
Ways to decrease risk Spacer
Rinse mouth
Use lowest effective dose
Children
Monitor growth? Effect on adult height
Antagonist of pro-inflammatory effects of leukotrienes
Montelukast (singular)
More rapid onset than ICS
Zafirlukast
Potential role as alternative to low-dose ICS in mild persistent asthma
Zileuton
Can attenuate EIB
ADRs: rare, few cases of LFT changes
Inhibit inflammatory cellular activation and mediator release, early and late
Cromolyn
allergen-induced bronchorestriction
Seldom used
Takes 2 weeks for therapeutic response (4-6 week trial recommended)
Effective for seasonal asthma and EIB prevention
Only prescribe in combo with ICS in patients with moderate-severe asthma
Salmeterol (Serevent)
Stimulate 2 receptors in the airways: smooth muscle relaxation, airway
Formoterol (Foradil)
opening, hyper-responsiveness
Q12 hour does maintains bronchodilation for 24 hours
Do NOT use for acute symptoms
ADR: tachycardia, tremor, EKG changes if overdose
FDA banned use of single-agent LABAs for asthma
Peds requiring addition of LABA to ICS use combination product
Long Term Treatment
64 Pulmonology
CorticosteroidLABA
Combination
Anti-IgE
Monoclonal Ab
Fluticasone/salmeterol (Advair)
Budesonide/formoterol (Symbicort)
Mometasone/formoterol (Dulera)
Do not exceed recommended dosage because of beta agonist component
Omalizumab (Xolair)
Nebulizers
Albuterol
Metaproterenol
Lavabuterol
Ipratropium
Recombinant DNA-derived murine/human monoclonal Ab indicated for

moderate-severe or severe allergic asthma
Inhibits binding of IgE to mast cell
1 benefit is frequency/severity of exacerbations
Ideal patient: frequent exacerbations, high CS dose, poor pulmonary function
SQ, high cost, risk of anaphylaxis
Turn liquid medication into fine mist that is easily inhaled
Dosage higher than inhaled due to particle size
Useful in peds and elderly
Spacers
Peak Flow
Meters
Ex
ac
erb
ati
on
s
Decreases in expiratory
airflow
Triggers
Risk of AsthmaRelated Death

Medications
Key Points
90% of patients use MRI inappropriately

Use of spacers removes need for good hand-breath coordination
Results in decreased oropharyngeal deposition and enhanced delivery to the lungs
Recommended for all patients using ICS; not needed for DPI
Azmacort MRI manufactured with small, attached, in-line spacer
Monitoring device that measures peak expiratory flow
Fastest speed at which one can blow air out of the lungs
Should be done in AM and between 12:00-14:00 for 2-3 weeks to establish personal best, then daily
Objective measures of lung function (spirometry, PEF) are more reliable indicators of severity than symptoms
All patients at some risk (appropriate use of ICS decreases risk)
Can be life-threatening
URI
Exercise
Pet dander
Smoke
Cockroaches
Some foods
Dust
Cold air
GERD
Mold
Emotional extremes
Allergies
Pollen
Prior exacerbation
Poor awareness of asthma symptoms
Major psychosocial or psych illness
2+ hospitalizations/3+ ED visits in past Lower SES
Other co-morbidities (CV disease,
year
Illicit drug use
other lung disease)
2+ canisters SABA/month
2.5-5 mg Q20 minutes x3 doses, then 2.5-10 mg Q1-4 hours
Albuterol
PRN, or 10-15 mg/hour continuously
40-80 mg/day in 1-2 divided doses until PEF reached 70%
Corticosteroids (prerdnisone, methylprednisolone,
predicted or personal best
prednisolone)
Frequent assessment
Use SABA frequently/continuously
Maintain O2 saturation
Use of corticosteroids
65 Pulmonology
COPD Pharmacotherapy
Based on postbronchodilator
FEV1
GOLD
Guidelines
(2007)
COPD
Staging
GOLD 1
Mild
GOLD 2
Moderate
GOLD 3
Severe
GOLD 4
Very severe
Stage 1
-
Stage 2
Stage 3
Stage 4
Reduce risk factors; influenza, pneumo vaccination

Short-acting bronchodilator PRN (anticholinergic or beta2-agonist)
Scheduled long-acting bronchodilator (LAMA or LABA)
Rehab
Inhaled steroids (ICS), esp. if mult. exac.
-
Smoking cessation
Living with COPD
Other Treatments
FEV1/FVC < 0.70

FEV1 > 80% predicted
FEV1/FVC < 0.70
50% < FEV1 < 80% predicted
FEV1/FVC < 0.70
30% < FEV1 < 50% predicted
FEV1/FVC < 0.70
FEV1 <30% predicted or, FEV1 <50% predicted + chronic resp. failure
Oxygen
Pulmonary rehab
Other support
Greatest capacity to influence natural history of COPD (slows rate of PFT decline)
Keep air in home clean

Cook near open window/door
Stay at home during times of heavy air pollution
Keep door/window open if heating with kerosene
Take medications as prescribed
Influenza and pneumococcal vaccinations
Supplemental O2 has shown mortality benefit in
chronically hypoxemic patients
Continuous 15-18 hours/day better than nocturnal
Optimize pharmacotherapy first
Goal: PaO2 to > 60 mmHg
Improves exercise capacity
Reduces perceived breathlessness
Improved health-related QOL
Reduces anxiety and depression
Improves survival
Benefits extend beyond period of training
Exercise training
Nutrition counseling
Disease education
Oxygen
Consider surgery
Patients likely to benefit from O2

Resting PaO2 < 55 mmHg or SaO2 < 88% (clinically
stable)
PaO2 < 55-60 mmHg or SaO2 < 89% (evidence of cor
pulmonale, CHF, polycythemia)
66 Pulmonology
Medications
2-Agonists
Albuterol
Anticholinergics
Ipratropium
(Atrovent)
SABA +
Anticholinergic
2-Agonists
Albuterol/
Ipratropium
Anticholinergics
Long-Acting Bronchodilators
COPD Medications
Short-Acting
Bronchodilators
Class
Salmeterol
Formoterol
Indacaterol
Tiotropium (Spiriva)
Aclidinium (Tudorza)
Umeclidinium
(Anora Ellipta)
Information
Role in therapy is PRN symptom relief (schedule if chronically symptomatic)

Bronchodilator of choice for acute exacerbations
Less bronchodilation than in asthma
Greater dilation than inhaled 2-agonists in COPD patients with fewer side effects and slower
onset of action
Use hasnt been associated with mortality benefit
Do not exceed recommended dosage because beta-agonist component
Use increasing in COPD due to evidence of improvements in PFTs vs ipratropium
First QD INH LABA for treatment of airflow obstruction

No combo with ICS available
Compared to tiotropium: equal efficacy on FEV1, not as effective at reducing exacerbations
Shouldnt be initiated in patients with acute deterioration of COPD
May produce clinically significant ADR: HR, BP, QT interval prolongation
Boxed safety warning (for asthma, no evidence toward COPD)
Some studies have shown improvement in FEV1 compared to
Precautions:
ipratropium
Dry mouth
No acute relief of bronchospasm
IOP
Also approved for reducing COPD exacerbations
Urinary
retention
Improvements in bronchodilation generally comparable to tiotropium
No acute relief of bronchospasm
Combo with Vilanterol (LAMA/LABA)
DPI
Shown no benefit on altering decline in pulm. fxn in COPD patients

AE: dysphonia,
Can reduce exacerbations and improve health status in stage 3 and 4
oral candidiasis
Withdrawal can precipitate exacerbation
LABA + ICS more effective than either alone, dont exceed recd dose (d/t agonist component)
FDA indication to decrease risk of exacerbations in severe COPD with chronic
Roflumilast (Daliresp)
Selective
bronchitis and hx of acute exacerbations
phosphodiesterase 4
MoA: cAMPintracellular in lung cells
Significant improvement seen only in 20-pack year hx when ICS not allowed
inhibitor (PDE4 inhibitor)
No trials to assess effects on exacerbations when added to fixed-dose LABA/ICS
Long-term use not recommended
Oral corticosteroids
Not recommended
Methylxanthines (Theophylline)
Less effective and less well-tolerated than LABA
May have some benefit in relief of breathlessness when added to salmeterol
Low doses may reduce exacerbations
Inhaled Corticosteroids
(ICS)
Meds
67 Pulmonology
Not recommended
Help loosen mucus
Benefits are small
Routine use not recommended
Not recommended
Patients with 2-3 cardinal symptoms (1
must be sputum purulence):
Expectorants
Antitussives
Respiratory stimulants (doxapram)
Antibiotics
Non-invasive intermittent ventilation
Objective
AECOPD
Acute
Maintenance
Antibiotics
Relieve dyspnea
Reduce airway inflammation
Improve lung function
Eradicate infections
Reduce risk of new exacerbations
Oral Treatment
-lactam (PCN, ampicillin,
amoxicillin)
TCN
TMP/SMX
-
Amox/clav
In patients at risk for Pseudomonas:

FQ (Cipro, Levo high dose)
Improves acute respiratory failure
sputum volume
sputum purulence
dyspnea
pH, pCO2
respiratory rate
length of hospital stay
Improves survival
Strategy
SABA + short-acting anticholinergic
Systemic corticosteroids (prednisone 40 mg QD x5 days)
Antibiotics (cover Gram +, P. aeruginosa)
Smoking cessation
dose/frequency or bronchodilator or add 2nd agent
Immunizations (influenza, pneumonia)
Pulmonary rehab
Self-management support
Alternative Oral Treatment
Parenteral Treatment
Amox/clav
Macrolides (azithromycin,
clarithromycin)
2nd or 3rd gen. cephalosporin
Ketolide (telithromycin)
Fluoroquinolone (levo or moxi)
Amp/sulbactam
2nd or 3rd gen. cephalosphorin
Fluoroquinolone (levo or moxi)
FQ (Cipro, Levo high dose)
-lactam with P. aeruginosa activity
68 Pulmonology
Lower Respiratory Tract Infection Therapeutics
Guiding Principles
Pathogens
Host
Drug
Targeted Abx
Choices Based
On:
Antibiotic
Options
Macrolides/ Azalides
Respiratory
Fluoroquinolones
Cephalosporins
Likelihood of resistance (local antibiogram, ICU?, CAP vs HAP, prior abx, long-term care)
Age, comorbidities, allergies, pregnancy, organ function, invasive devices, immune status
Spectrum, efficacy, kinetics, safety profile, cost/convenience
Diagnosis (site, likely pathogen)
Shorter courses generally preferred
Severity of illness, site of care
Likelihood of resistance
Comorbidities, special populations
Advantages
Disadvantages
Limited activity against PRSP (activity not added by -lactamase

inhibitor)
Allergy
No activity against atypical pathogens
GI adverse events (most due to -lactamase inhibitor
Type 1
Severe, anaphylactic
Non-type 1
Rash, pruritus
Intolerance
NOT an allergy
Implications: inability to use PCN and related drugs
Accurate history to parse out true allergy essential
Objective testing possible
Macrolide: erythromycin, Good activity against typical and atypical pathogens
Increasing resistance in S. pneumo (~30clarithromycin
Can be used in PCN-allergic patients
40%)
QD-BID dosing
Erythromycin lacks activity against H. flu
Azalide: azithromycin
Pediatric experience
Drug interactions (macrolides)
AEs: QTc prolongation (macrolides), GI
intolerance (most prominent with
erythromycin)
Good activity against typical and atypical respiratory
Emerging (infrequent) resistance in S.
tract pathogens, including PRSP and BLPHI
pneumo
Levofloxacin
Excellent oral bioavailability
Safety concerns: cardiac (QTc effects),
Moxifloxacin
Can be used in PCN-allergic patients
glucose homeostasis, CNS, tendon rupture
Gemifloxacin
QD dosing
CI in peds
Short-course therapy
Potential for collateral damage
Variable activity against PRSP (PO cefixime, cefpodoxime prefd; IV
cefotaxime, ceftriaxone prefd)
Low potential for drug interactions
PCN prefd for doc. PCN-susceptible S. pneumo
Pediatric use
Allergy
Favorable safety profile
No activity against atypical respiratory tract pathogens
Expense
-
Penicillin + lactamase inhibitor
Proven efficacy against some typical respiratory

pathogens
Amoxicillin is inexpensive
Adding -lactamase inhibitors gives additional activity
against H. flu and M. cat
High dose amoxicillin (90 mg/kg/d) overcomes
intermediate S. pneumo resistance
Pediatric use
Preferred for documented PCN-sensitive S. pneumo
Allergy
Considerations in Empiric
Choice of Antibiotics
69 Pulmonology
TMP/SMX
Tetracyclines
(Doxycycline)
High Risk for

Complications
Influenza
Who to treat
When to Treat
How long to treat

Inexpensive
BID dosing
Pediatric use
Inexpensive
BID dosing
Activity against typical and atypical pathogens common
in RTIs
Children >2 years, adults > 65 years
Chronic conditions
Immunosuppression (d/t medications, HIV infection)
Pregnant or postpartum (within 2 weeks after delivery)
-
High rates of resistance among both S. pneumo and H. flu (~30-40%)

Allergy
No activity against atypical respiratory tract pathogens
GI intolerance
Allergy
CI in children
Use restricted to patients with: moderate-mild infection & low risk
resistance
<19 years receiving long-term ASA therapy
American Indians/Alaska natives
Morbidly obese (BMI > 40)
Residents of nursing homes and other chronic-care facilities
All hospitalized patients with suspected influenza

Severe, complicated, progressive illness
Populations at risk for complications
Outpatients consider for any previously healthy, symptomatic outpatient not at high risk with confirmed/suspected illness on
basis of clinical judgment within <48 h onset (neuraminidase inhibitors reduce duration of symptoms by ~1 day in healthy w/
uncomplicated)
As early as possible (ideally within 48 hours)
Oseltamivir beneficial >72 hours in children with uncomplicated flu illness
Oseltamivir up to 4-5 days after illness associated with lower risk for severe outcomes
DONT WAIT FOR LAB CONFORMATION
5 days
Longer courses for patients remaining severely ill after 5 days of treatment can be considered
Neuraminidase
Inhibitors
Use
Population
Osteltamivir
(Tamiflu, PO)
Treatment
Any age
Chemoprophylaxis
> 3 months
Zanamivir (Relenza,
INH)
Treatment
> 7 years
Chemoprophylaxis
> 5 years
Not Recommended
N/A
Underlying respiratory disease

(e.g., COPD, asthma)
Adverse Events
Nausea, vomiting
Periodic skin reactions
Sporadic, transient
neuropsychiatric events
Oropharyngea Bronchitis,
l or facial
cough
edema
HA, dizziness
Diarrhea,
ENT infections
nausea
Sinusitis, nasal
S&S
70 Pulmonology
Peramivir (Rapivab,
Treatment
> 18 years
N/A
Diarrhea
Serious skin reactions
Sporadic, transient
neuropsychiatric events
Flu
IV)
Post-Exposure
Prophylaxis/ Outbreaks
Annual vaccination is best

way to prevent influenza
Condition
Pneumonia
COPD/Smoking
Advanced age
Alcoholism
Critical Care
HIV Infection
Aspiration
Structural lung dz (bronchiectasis, CF)
Principles
Post-exp. Prophylaxis for high-risk patients = 7 days after most recent known
exposure if started within 48 hours of exposure
Control of outbreaks in LTC facilities, hospitals = minimum 2 weeks
chemoprophylaxis, up to 1 week after most recent known case IDd
Common Agents
H. flu, P. aeruginosa, Legionella spp., S. pneumo, M. cat,
C. pneumo
S. pneumo, H. flu, gram-negative bacilli, S. aureus
S. pneumo, oral anaerobes, K. pneumo, Acinetobacter
spp., M. tuberculosis
Gram-negative bacilli, S. aureus
S. pneumo, H. flu, tuberculosis, PCP, endemic fungi
Gram-negative enteric pathogens, oral anaerobes
P. aeruginosa, B. cepacia, S. aureus
Population
Community Acquired
Pneumonia
Comorbidities or antimicrobial < 3 months

Or region with high-rate of infection with high-level
macrolide-resistance S. pneumo
Population/Special
Concerns
Empiric Antibiotic Treatment

Inpatient
Inpatient, non-ICU
treatment
Inpatients, ICU treatment
Gram-negatives
Gram-negatives
MRSA, Pseudomonas and other Gramnegatives
Gram-negative, PCP (only if indicated), fungi,
TB
Anaerobes
MRSA, Pseudomonas and other Gramnegatives
Preferred Treatments
Previously healthy, no antimicrobial < 3 months
Empiric Antibiotic Treatment

Outpatient
Expand Coverage To
Pseudomonas and other Gram-negatives
Macrolide (azithromycin, clarithromycin)

Doxycycline
Respiratory fluoroquinolone (gemifloxacin,
levofloxacin, moxifloxacin)
-lactam (high-dose amoxicillin, high-dose
amox/clav; cefpodoxime, cefuroxime) +
macrolide
Preferred Treatments
Respiratory fluoroquinolone (gemifloxacin, levofloxacin,
moxifloxacin)
-lactam (cefotaxime, ceftriaxone, ertapenem IV) + macrolide
(azithromycin, clarithromycin)
-lactam (cefotaxime, ceftriaxone, ertapenem IV) + azithromycin
(PO, IV)
Respiratory fluoroquinolone
Ciprofloxacin or levofloxacin
71 Pulmonology
If suspected Pseudomonas
If suspected CA-MRSA
Overall improvement
Leukocytosis resolves
Appropriate
Response to
Therapy
Community Acquired Pneumonia
Switch to Oral Therapy
Antipneumococcal,
antipseudomonal -lactam
(cefepime, ceftazidime, piperacillintazobactam, meropenem,
imipenem, doripenem IV)
PLUS EITHER
To above, add
3 days
4-5 days
Hemodynamically stable
Fever disappears
CXR improvement
Improving clinically
Pneumonitis
Aspiration
Pneumonia
CA-MSRA CAP
NOT ROUTINE for empiric therapy (unless severe, ICU)
Age
<5 years
Empiric
Treatmen
t of
Bacterial
CAP In
Children
Outpatient
> 5 years
Patient Factors/Site of
Care
Inpatient
H. influenzae type B, S.
pneumoniae immunized
Local PCN resistance in invasive
strains of pneumococcus
minimal
Aminoglycoside (gentamicin,
tobramycin) + azithromycin
Aminoglycoside + respiratory
fluoroquinolone
Vancomycin
Linezolid
2-4 days
30 days (6 mo in elderly)
Able to ingest medications
Supportive therapy (O2)

Prevention
Role of antibiotics unclear
-lactam + -lactamase inhibitor (Amox/Clav PO,
Piperacillin-tazobactam)
Empiric therapy: vancomycin, linezolid
Presumed Bacterial
Normally functioning
GI tract
Presumed Atypical
Amoxicillin PO (90 mg/kg/day in 2 doses)
Azithromycin PO
Alternatives: amoxicillin (90/mg/kg/day in 2

doses)/clavulanate PO
Alternatives: clarithromycin PO
Amoxicillin PO (90 mg/kg/day in 2 doses to

max of 4 g/day) + macrolide
Azithromycin POO
Alternatives: amoxicillin (90/mg/kg/day in 2

doses, max 4 g/day)/clavulanate PO
Alternatives: clarithromycin PO,

erythromycin, doxycycline (children
>7 years)
Presumed Bacterial
Presumed Atypical
Ampicillin or PCN G
Azithromycin + -lactam
Alternatives: ceftriaxone or cefotaxime;

addition of vancomycin or clindamycin for
suspected CA-MRSA
Alternatives: clarithromycin or
erythromycin; doxycycline (>7 years),
levofloxacin (reach growth maturity
or cant tolerate macrolides)
72 Pulmonology
Empiric Therapy
Empiric Therapy
Continued
Treatment
Nosocomial Pneumonia
Not fully immunized for H. flu

type b and S. pneumo
Local PCN resistance in invasive
strains of pneumococcus is
significant
Ceftriaxone or cefotaxime
Addition of vancomycin or clindamycin for
suspected CA-MRSA
Azithromycin (in addition to lactam, if diagnosis in doubt)
Alternatives: levofloxacin; addition of vanc or

clinda for susp. CA-MRSA
Alternatives: clarithromycin or
erythromycin; doxycycline (>7 years),
levofloxacin (reach growth maturity
or cant tolerate macrolides)
NO
Limited spectrum
YES
Broad spectrum
S. pneumo
Ceftriaxone
H. flu
Or
MRI
Levo, moxi, or ciprofloxacin
Abx-sensitive, enteric, Gram-neg
Or
bacilli (E. coli, K. pneumoniae,
Ampicillin/sulbactam
Enterobacter spp., Proteus spp., S.
Or
marcescans)
Ertapenem
See above
Antipseudomonal cephalosphorin (cefepime, ceftazidime)
MDR pathogens (P. aeruginosa, K.
Or
pneumoniae (ESBL+), Acinteopacter
Antipseudomonal carbepenem (imipenem or meropenem)
spp, MRSA)
Or
L. pneumophila
Beta-lactam/beta-lactamase inhibitor (piperacillin-tazobactam)
Plus
Antipseudomonal FQ (Cipro, levo)
Or
Aminoglycoside (amikacin, gent, tobra)
Plus
Linezolid or vancomycin
NO
Cultures negative
Search for other pathogens, complications, diagnoses or sites of infection
Cultures positive
Adjust antibiotic treatment
Search for other pathogens, complications, diagnoses or sites of infection
YES
Cultures negative
Consider stopping antibiotics
Cultures positive
De-escalate antibiotics, if possible
Treat selected patients 7-8 days and reassess
Improvement with appropriate therapy anticipated in 48-72 hours
Traditional duration = 10-14 days
Trend toward greater rates of relapse with P. aeruginosa, Acinetobacter
Good response, no P. aeruginosa or Acinetobacter may shorten to as short as 7 days
Aminoglycoside-containing regiment? Stop therapy after 5-7 days if improving
Late onset (> 5 days) or risk factors for MDR pathogens
No Known RF for MDR

Pathogens, Early Onset, Any
Disease Severity
Late Onset, or Risk Factors for

MDR Pathogens, All Disease
Severity
Clinical Improvement at 4872 Hours?
Duration of Therapy
73 Pulmonology
Chronic Bronchitis Acute Exacerbations
Bronchitis
Acute
Bronchitis
Adults
Pertussis
Inhaled bronchodilators/corticosteroids
Insufficient data for routine use
Antitussives
Questionable benefit in productive cough
Antibiotics
NO
Who benefits from

Antibiotics?
Controversial
No role for long-term prophylactic therapy

with antibiotics for chronic bronchitis
Outpatient (Oral)
Inpatient (IV or
PO)
Treatment Options
Consider if severe
symptoms, hypoxia,
FEV <35% predicted
Adjuncts
Principles
Therapy
Patients with > 4 exacerbations in past year

Patients with comorbidities (asthma, CAD,
diabetes, heart disease)
Need for home O2
Steroid-dependent
Marked airway obstruction (FEV1 < 50%
predicted)
Amoxicillin/clavulanate
Cephalosporin (Cefpodoxime, cefuroxime
axetil)
Macrolide (azithro, claritro; NOT erythro)
Respiratory fluoroquinolone (levo, moxi, gemi)
Respiratory fluoroquinolone (IV/PO)
Cefuroxime (IV/PO)
Ceftriaxone (IV)
Piperacillin-tazobactam (IV)
Corticosteroids (INH, PO, IV)
Beta-agonists
Anticholinergics (INH) ipratropium,
tiotropium)
Isolate for 5 days from start of treatment

Early treatment within first few weeks will lessen coughing paroxysms and prevent spread
Reduction in treatment response after first few weeks
Macrolides (azithromycin in children < 1 month)
TMP/SMX
74 Pulmonology
Tuberculosis Pharmacology
Cultures/Drug
Susceptibility
Drug
Resistance
Direct
Observed
Therapy
(DOT)
Initiating
Treatment
Gold standard for confirming TB

Culture all specimens, even if smear negative
Results 4-14 days when liquid medium systems used
If culture-positive, do susceptibility testing (INH, RIF, EMB on initial isolate)
Any one TB drug
Mono-resistant
Poly-resistant
Multidrug resistant (MDR TB) Extensively drug resistant
(XDR TB)
Increased Risk for Drug

Resistance
At least INH and RIF

INF, RIF, AND resistant to any fluoroquinolone AND at least 1 of the 3 injectable (e.g., amikacin,
kanamycin, or capreomycin)
History of treatment with TB drugs

Contacts of person with drug-resistant TB
Foreign-born from high prevalent drug resistant areas
Smears or cultures positive despite 2 months of treatment
Inadequate treatment regimens for >2 weeks
Patients not on DOT in the past or who had irregular treatment
Health care worker watches patient swallow each dose

Preferred for all patients reduces total number of doses and encounters
Can reduce acquired drug resistance, treatment failure, and relapse
Nearly all regimens can be intermittent if given as DOT
Before Initiating
Treatment for
LTBI
Rule out TB disease (i.e. wait for culture results)

Determine prior history of treatment for LTBI or TB disease
Assess risks and benefits of treatment
Determine current and previous drug therapy
First-Line
Drugs
Treatment
Options
At least any 2 TB drugs (but not both INH and RIF)
Antituberculosis
Drugs
SecondLine
Drugs
Isoniazid (INH)
Rifampin (RIF) Rifabutin (RBT), Rifapentine (RPT)
Pyrazinamide (PZA)
Ethambutol (EMB)
Streptomycin (SM)
Cycloserine
p-Aminosalicylic acid
Ethionamide
Amikacin or kanamycin
Capreomycin
Levofloxacin
Moxifloxacin
Bedaquine
75 Pulmonology
Drug
Regimen
-
INH
-
Treatment
Options
Latent TB
9 mo (preferred)
daily
OR
Intermittent via DOT
Option for 6 months
12 weekly doses via

DOT
Indications/Comment
-
Also may be used during

pregnancy and breastfeeding
(with pyridoxine
supplementation)
6 mo QD or BIW (less
effective) may be used if
unable to complete 9 mo
Otherwise healthy > 12 years
HIV+ otherwise healthy and
NOT on ART
Exclusions
-
INH + RPT
-
Daily x4 months
Daily x2 months
RIF
RIF + PZA
Basic Principles
Active Disease
Most Common
Treatment
6 mo regiment excludes:
HIV+ wit previous
pulmonary TB disease,
children, and/or
immunosuppressed
Pregnancy: give with
pyridoxine
< 12 years
HIV+ receiving ART
Pregnant or women
expecting to become
pregnant
Presumed INH or RIF
resistance
Intolerance to INH
Exposure to INH-resistant TB
If RIF cannot be used, RBT
may be subbed (e.g. HIV+
receiving protease inhibitors)
-
No longer recommended
d/t association with severe
liver injury
Provided safest, most effective therapy in the shortest time

Multiple drugs to which organisms are susceptible
Never add single drug to failing regimen
Ensure adherence to therapy
2 months
Initial Phase - Standard 4 drug regimens (INH, RIF, PZA, EMB)
One regimen excludes PZA
Usually INH + RIF x 4 months
Extend to 7 months if:
o Cavitary pulmonary disease AND + sputum cultures at completion of initial phase (2 mo)
Continuation
o Initial phase excluded PZA
Phase
o Qweek INH and RPT is started in continuation phase and sputum specimen collected at
end of initial phase is culture +
o HIV-infected with + 2 month sputum culture
For patients receiving medications having unacceptable reactions
New Role of
Rifabutin (RBT)
with RIF (e.g. HIV/AIDS)
Rifamycin
Used in Qweek cont. phase for HIV-neg. adults with drug-susceptible
Rifapentine (RPT)
Drugs
non-cavitary TB and neg. AFB smears at completion of initial phase
76 Pulmonology
Caused by
Adverse Reactions
Hepatitis
Signs and Symptoms
Comments
Abdominal pain, abnormal LFT, fatigue, lack of

appetite, nausea, vomiting, yellowish
skin/eyes, dark urine, flu-like illness, fever 3+
days
Peripheral neuropathy
Tingling sensation in hands and feet
GI intolerance
Upset stomach, vomiting, lack of appetite
Arthralgia, arthritis
Joint aches
Increased uric acid
Gout (rare)
Eye damage
Blurred or changed vision

Changed color vision
Easy bruising, slow blood clotting
Upset stomach
Rash, sunburn-like reaction
NUMERUS due to enzyme induction (usually
lessens effect of interacting drug)
Orange sweat, urine, tears
Permanently stained soft contact lenses
INH, PZA, RIF
INH
Common
Adverse
Reactions
PZA
EMB
RIF, RBT, RPT
RIF
Thrombocytopenia
GI intolerance
Phototoxicity
DRUG INTERACTIONS
Discoloration of body fluids
Patient
Baseline
All patients
Examinations Patients at risk for hepatitis B or C
Recommended Patients taking EMB
HIV-infected patients
Patient
All patients
Monitoring
During
Treatment
Patients taking EMB

Extrapulmonary TB
HIV-infected, pregnancy or early post-partum,
chronic liver disease, regular EtOH use, abnormal
baseline results, high risk or signs of toxicity
Mild INH-induced LFT in

up to 20%, usually return to
normal
risk: HIV, hx liver disease,
regular EtOH consumption,
pregnancy or postpartum,
other hepatotoxins
risk: alcoholism, diabetes,
malnutrition give these
people pyridoxine
Recommended Test
AST, ALT, bilirubin, alkaline phosphatase, serum creatinine, platelet count
Serologic tests
Test visual acuity (Snellen chart) and color vision (Ishihara)
Obtain CD4+ lymphocyte count
Recommendations
Repeat monthly clinical evaluations (possible ADRs, adherence)
Sputum AFB Q2 weeks
Monthly sputum AFB/culture (until 2 consecutive cultures negative
Additional susceptibility tests if culture positive after 3 months
Question monthly regarding visual disturbances
Repeat Qmonth Snellen and Ishihara if dose >15-20 mg/kg or >2 mo
Evaluation depends on sites involved and ease specimens can be obtained
Repeat lab monitoring for hepatotoxicity
77 Pulmonology
Pregnant or breastfeeding
Infants/children
Special
Populations
HIV
Extrapulmonary disease
Liver
Kidney
Organ dysfunction
Failure/relapse
XDR/MDR
Treatment
Failure
A positive culture after

4 months of treatment
in whom medication
ingestion was insured
Pyridoxine supplement
Avoid streptomycin
Avoid EMB
Three times weekly regimens
Use DOT
Multiple rifamycin drug interactions with ART
Use DOT
NOT Qweek continuation phase INH + RPT
BIW INH-RIF or INH-RBT shouldnt be used with CD4+ < 100
Risk of reactivation syndrome
Generally similar to pulmonary disease
Close Contacts
Increase interval, NOT dose
Add at least THREE new drugs
Consult an expert
Early Indications -
TST or IGRA +
Evaluate for latent
infection and active
disease
Might need to avoid hepatotoxic agents
TST or IGRA -
Symptoms dont improve in 2 months of therapy

Symptoms worsen after improving initially
Culture results + after 2 months of treatment
Culture results become + after being -
No prior history
Documented history of completed
LTBIB treatment
Low risk
High risk (children <4, HIV,
immunocompromised) and/or high risk of
progression to disease once infected
Single new drug should NEVER be

added to a failing regimen (may
lead to acquired resistance to
that drug)
Add at least three new drugs to
the existing regimen
High priority for LTBI treatment
No treatment
Retested in 8-10 weeks
Rule out active disease
Initiate treatment for latent infection
Retest in 8-10 weeks: stop if negative
(although immunocompromised may be
given full course regardless)

Pulmonology - Study Guide PDF

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1 Pulmonology

Compiled by Abbie Pettigrew, class of 2016

Treat the cause

Compiled by Abbie Pettigrew, class of 2016

Expectoration of blood originating below the vocal cords

Iatrogenic (drugs, radiation)

Elevation pulmonary capillary pressure (MS, LVH)

Compiled by Abbie Pettigrew, class of 2016

Obstructive Airway Disease

Inflammation narrowed airway reduced airflow

Compiled by Abbie Pettigrew, class of 2016

Progressive worsening (1-3 days)

Frequent medications (>2 puffs/month)

Intermittent, mild, moderate, severe

Compiled by Abbie Pettigrew, class of 2016

Fixed airway obstruction involving

Distant breath sounds

Cor pulmonale late

Near normal PO2/PCO2

FEV1/FVC < 70%

Combined Assessment of COPD

Disease dyspnea deconditioning

Downward spiral in function

FEV1/FVC < 70%

FEV1/FVC < 70%

IV: Very Severe

Dyspnea vs cough vs hypoxemia

Not that useful

Compiled by Abbie Pettigrew, class of 2016

Tobacco cessation (+ pharmacologic treatment)

Compiled by Abbie Pettigrew, class of 2016

Compiled by Abbie Pettigrew, class of 2016

Cystic fibrosis transmembrane regulator gene is located on chromosome 7

If pancreatic sufficient (mild, class III/IV)

Thick, sticky stool results in constant straining

Inflammation of pancreatic ducts spreads to gall ducts, liver

From use of enzymes (meds), which, in excess, cause scarring of

Problems moving chloride, bicarbonate, and sodium throughout the body

Median survival is 40 years

Aggressively treating new infections

Over age 12 or when indicated

Influenza vaccination yearly

Higher calorie intake

Fat soluble vitamin

120-130% general population (>3,000 cal/day)

Chronic oral antibiotics

Out of favor 2/2 increased bacterial resistance, emergence of new pathogens

Results: 11-12% improvement of FEV1 from baseline,

Used in patients with G551D mutations (now more)

Studied in homozygous F508del patients (50% CF pts)

Acute Pulmonary Exacerbation

Compiled by Abbie Pettigrew, class of 2016

Pulmonary Embolic Disease

VTE Risk Factors

Most common: tachypnea,

Depends on the settings

Prior DVT or PE = +1.5

Every patient admitted should be considered

Enoxaparin, rivaroxaban, or heparin

Compiled by Abbie Pettigrew, class of 2016

Pulmonary Vascular Disease

Not specific with regards to arteries vs veins, or to causation

Pulmonary Hypertension (PH)