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Bronsiectazii

aspecte clinice
si imagistice
Bejan Marina
Conducator teza:

Definitie

Bronsiectazia(gr.bronkostub;ektasis-dilatatie)
reprezinta o dilatatie
ireversibila si anormala a
bronsiilor de calibru
mediu,datorata distrugerii
componentelor elastice si
musculare ale peretelui
bronsic. Poate fi: locala,
interesand caile respiratorii
dintr-o regiune limitata a
parenchimului pulmonar, sau
difuza: cu o distributie mai
larga.

Istoric

1808 - Profesorul Cayol observa prima data bronsiectazia


1819 - Laenec realizeaza prima descriere clinico patologica a bolii
1878 - Graucher atrage atentia ca bronsiectaziile TBC nu sunt rare
1880 - Grawitz sustine teoria originii congenitale a bronsiectaziei
polichistice
1904 - Couvelaire descrie un fat cu bronsii dilatate, argument
important in favoarea bronsiectaziilor congenitale
1927 - Sergent, Cotlenot, Couvreux arata rolul sclerozei pleuropulmonare in geneza bronsiectaziilor
1933 - descrierea sindromului Kartagener
1942 - Faberg discuta relatia dintre fibroza chistica a pancreasului si
bronsiectazie
1949 - Liebow, Hallas, Lindskog descriu ectaziile arterei bronsice;
1950 - Lecs prezinta relatia tuse convulsive a?? bronsiectazie, iar
Jones, Peck, Woodruff si Willis au aratat ca din 34 de copii cu
obstructie bronsica, la 24 s-a dezvoltat bronsiectazia.

Epidemiologie
Bronsiectazia este o cauza majora de mortalitate si morbiditate in tarile subdezvoltate unde
conditiile economice sunt precare, vaccinurile impotriva infectiilor de tract respirator sunt
rare, nu exista resurse pentru a administra antibioticele adecvate in caz de infectii
respiratorii si prevalenta TBC-ului pulmonary este crescuta.
In decursul ultimelor decenii s-a inregistrat in Europa si America de Nord o scadere dramatica
a cazurilor de bronsiectazie, atribuita extensiei antibioterapiei si vaccinurilor profilactice.
Aceste date au consolidate ipoteza conform careia majoritatea bronsiectaziilor sunt
dobandite postnatal si sunt in stransa legatura cu infectiile bronhopulmonare severe ale
copilariei (rujeola, tusea convulsive, tuberculoza) si in acelasi timp au restrans aria
bronsiectaziei congenitale, multa vreme supraevaluata.
Factorii genetici intervin in geneza unui grup relative redus de bronsiectazii.
Primele studii pe scara larga pentru a determina incidenta bronsiectaziilor a fost realizata in
1953 fiind examinata populatia din Bredford,oras din Marea Britanie.Autorii au identificat o
incidenta a bronsiectaziilor de 1.3 la 1,000 populatie.
Studii mai recente realizate pe cohort in Finlanda,Noua-Zelanda si SUA.
Studiile din Finlanda arata o incidenta de 2,7 la 100.000;cele din Noua-Zelanda 3,7 la
100,000.
In SUA au fost realizate studii pe grupe de virste de pacienti ce estima prevalent de 4,2 la
100,000 la persoanele ce au virsta cuprinsa intre 18-34 ani,si incidenta de 271,8 la
100,000 pentru pacientii cu virsta >75 ani.

Etiologie
BRONCHIECTASIS
Broncholith
Retraction of parenchima
Obstruction by foreign body
Neoplastic obstruction
Cartilage deficiency
Cilia syndrome
Host defenses down(agammaglobulinemia)
Infection
Emphysema
Cystic fibrosis Chronic granulomatous disease
Tuberculosis
ABPA
Swyer-James syndrome
Inhalation injury(ammonia,gastric acid)
Sarcoidosis

Factori predispozanti
Infectii
Factors Predisposing to Bronchiectasis
Category
Examples and Comments
Bacterial
Bordetella pertussis
Haemophilus influenzae
Klebsiellaspp.
Moraxella catarrhalis
Mycoplasma pneumoniae
Pseudomonas aeruginosa
Staphylococcus aureus
Fungal
Aspergillusspp.
Histoplasma capsulatum
Mycobacterial
Mycobacterium tuberculosis
Nontuberculous mycobacteria
Viral
Adenovirus
Herpes simplex virus
Influenza
Measles
Respiratory syncytial virus

Anomalii congenitale
1-Antitrypsin deficiency
If severe, can cause bronchiectasis
Ciliary defects
Can cause bronchiectasis, sinusitis, otitis media,
and male infertility
50% of patients with primary ciliary dyskinesia
have situs inversus
Kartagener syndrome (clinical triad of dextrocardia,
sinus disease, situs inversus)
Cystic fibrosis
Causes viscous secretions due to defects in Na and
Cl transport
Often complicated byP. aeruginosaorS.
aureuscolonization

Obstructia
Airway obstruction
Cancer
Endobronchial lesion
Extrinsic compression
Due to tumor mass or lymphadenopathy
Foreign body
Aspirated or intrinsic (eg, broncholith)
Mucoid impaction
Allergic bronchopulmonary aspergillosis
Postoperative
After lobar resection, due to kinking or
twisting of remaining lobes

Imunodeficiente
Immunodeficiencies
Primary
Chronic granulomatous disease
Complement deficiencies
Hypogammaglobulinemia,
particularly common variable
immunodeficiency
Secondary
HIV infection
Immunosuppressants

Patologii sistemice
Connective tissue and systemic disorders
RA
Commonly causes bronchiectasis (frequently subclinical), more
often in men and in patients with long-standing RA
Sjgren syndrome
Bronchiectasis possibly due to increased viscosity of bronchial
mucous, which leads to obstruction, poor clearance, and chronic
infection
SLE
Bronchiectasis in up to 20% of patients via unclear mechanisms
Inflammatory bowel disease
Bronchopulmonary complications occurring after onset of
inflammatory bowel disease in up to 85% and before onset in 10
to 15%
Bronchiectasis more common in ulcerative colitis but can occur in
Crohn disease
Relapsing polychondritis

Defecte structurale congenitale


Lymphatic
Yellow nail syndrome
Tracheobronchial
Williams-Campbell syndrome (cartilage
deficiency)
Tracheobronchomegaly (eg, Mounier-Kuhn
syndrome)
Vascular
Pulmonary sequestration (a congenital
malformation in which a nonfunctioning mass of
lung tissue lacks normal communication with
the tracheobronchial tree and receives its
arterial blood supply from the systemic
circulation)

Inhalarea gazelor
toxice
Ammonia
Chlorine
Nitrogen dioxide
Direct airway damage
altering structure and
function

Cauze infectioase:
Infectii respiratorii cu Klebsiella, Stafilococ,
Diplococus pneumoniae, Haemophylus influenzae
Mucusul secretat in exces poate obstrua lumenul bronsic si
poate duce in timp la aparitia bronsiectaziilor

Infectii tuberculoase:
Fibroza cicatriciala, retractii, deformari bronsice, stenoze
cicatriciale

Congenitale:

Traheobronhomegalia
Sdr. Williams-Campbell (caracter familial):

Deficitul/absenta cartilajului bronsic

Dilatatii generalizate, dinamica bronsica mult alterata

Boala polichistica

Chisturi centrale (unice, nu comunica cu bronhia)


Chisturi periferice (multiple, pot afecta ambii plamani)

Sechestratia pulmonara

Congenitale:
Mucoviscidoza:

Sdr. Kartagener

Este perturbata secretia mucusului traheobronsic


Bronhoreea vascoasa ingreuneaza drenajul si favorizeaza infectiile
repetate
In final dilatatii bronsice
Situs inversus + sinuzita + bronsiectazii

Sdr. Mounier-Kuhn
Sdr.Ehlers-Danlos
Deficit de alfa1-antitripsina
Hipogamaglobulinemie

Scaderea rezistentei la infectii bronsiectazii

Cauze obstructive:

Corpi straini
Tumori endobronsice benigne
Cancere bronsice

Produc stagnarea secretiilor care ulterior


determina dilatatii prin presiunea
exercitata asupra peretilor bronsici

Cauze locale:

Astm, BPOC

Alte cauze de obstructii bronsice extra-/intraluminale


(tumori, corpi straini, adenopatii)
Pneumonii extinse bacteriene

Hipersecretie de mucus, sputa aderenta, retentie cronica de


secretii bronsice, favorizarea infectiilor respiratorii
Complicatie rara

Produc leziuni bronsice bronsiectazii

Inhalarea de gaze corozive (SO2, amoniac)


Aspiratia recurenta de secretii gastrice

Aspergiloza bronhopulmonara alergica


Stari de imunodeficienta:
a. imunodeficienta comuna variabila
b. Agamaglobulinemia X-lincata
c. Patologii granulomatoase cronice
d. Deficienta de Ac seria Ig G
e. Imunodeficienta secundara
f. Imunosupresia drug-indusa
g. Neoplasme hematologice
h. Transplant-alogenic de oase

In patologii sistemice
- Boli tesut conjunctiv (PR, LES,
Sogren, sarcoidoza)
- S. Marfan, amiloidoza
Sindromul unghilor galbene: lifedem, efuziune
pleurala

Clasificare dupa Murray:

Bronsiectazii
localizate:
Cu plaman anterior
normal

Pneumonia stafilococica
Alte infectii abcedate

Obstructia bronsica

Corpi straini, tumori,


stenoze
Compresie extrinseca

Bronsiectazii
generalizate:
Cu origine pulmonara

Astm
Infectie abcedata
Aspiratie gastrica recurenta
Inhalare de gaze corozive

Cu origine sistemica
Fibroza chistica
Diskinezie ciliara
Imunodeficiente umorale

La orice invazie bacteriana sistemul


imun atit celular cit si umoral
reactioneaza promp pentru combaterea
agentului patogen

Fiziopatologie

Fenomene locale:

Microorganismele:

Alterarea mucoasei
Raspunsul inflamator al gazdei
Acumularea secretiilor purulente
Colonizarea bacteriana
Elibereaza endotoxine si enzime proteolitice
PMN activate de fagocitele agentilor infectiosi elibereaza proteaze
(elastaza neutrofilica) cu rol in intretinerea procesului inflamator
al mucoasei bronsice

Aceste procese impreuna cu elementul obstructiv


elemente patogenice in producerea dilatatiilor bronsice

Bronsiectazia determina:
Suprimarea tesutului pulmonar functional
Cresterea spatiului mort respirator

la nivelul dilatatiilor nu se face schimba gazos iar


alveolele tributare sunt hipoventilate

Hipoventilatie Hipoxie Reflex alveolocapilar Hipertensiune in mica


circulatie IVD

Patogeneza bronsiectaziilor
:Cercul vicios

Bronsiectazia poate fi:


Unilaterala (70%)
Bilaterala (30%)

Localizare:
Cel mai frecvent in lobii inferiori
LIS de 3 ori mai afectat decat LID
(probabil datorita posibilitatilor diferite de
drenaj al secretiilor)

Morfopatologie
Dilatarea se produce in bronhiile de marime
mijlocie si apoi progreseaza spre cele de calibru
mai mic
Substrat major inflamatia peretelui bronsic:
duce la alterarea si apoi distrugerea componentelor elastice
si musculare
duce la metaplazia scuamoasa a epiteliului bronsic

Tesutul pulmonar sanatos adiacent tractioneaza


bronhia si duce la dilatarea caracteristica

Clasificare
anatomopatologica
1. Cilindrice sau fuziforme

Dilatare de tip tubular (bronhia are contur liniar)


Bronhografic opacitate care se termina brusc (dop de mucus)
Alterare structurala redusa

2. Varicoase sau moniliforme

Dilatatii neregulate ce alterneaza cu zone de stenoza


Diametrul nu diminua cu progresia spre periferie
Alterari structurale mai importante

3. Sacciforme sau chistice

Dilatare foarte accentuata a bronhiilor (capat aspect chistic odata cu


progresia spre periferie)
Polipoza epiteliului bronsic e caracteristica acestui tip
Proces inflamator foarte accentuat si extins in vecinatate (interstitiu
pulmonar si chiar parenchim)

Microscopic

Diferite grade de distructie si inflamatie la nivelul peretelui bronsic:


Cele mai mari leziuni bronsiectaziile sacciforme (toti constituentii peretelui
sunt inlocuiti de tesut fibros)
Mucoasa bronsica:
ulceratii, zone de metaplazie
Epiteliul respirator:
inlocuit de celule epidermoide neciliate
frecvent infiltrat inflamator, foliculi limfatici

Submucoasa:

Capilare dilatate, aspect angiomatos, frecente


anastomoze intre circulatia sistemica si cea
pulmonara (explica hemoptiziile)

Stratul mioelastic:

Leziuni mari, ireversibile


Muschi atrofiati
Tunica elastica aproape disparuta
Cartilaje reduse

Manifestari clinice
Debut:

Insidios

Acut:

1.
2.
3.
4.
5.

In majoritatea cazurilor
Bronsiectaziile neinfectate raman mute multa vreme
Bronsita/viroza respiratorie tusea si expectoratia se accentueaza si se
instaleaza definitiv
Hemoptizii mici

Tuse cronica
Expectoratie purulenta
Febra
Astenia fizica
Scaderea ponderala

1.Expectoratia
Simptomul dominant
De multe ori abundenta, in procesele supurative pana la 500 ml/24ore
(de obicei 100-300 ml/zi)
Eliminata in special dimineata sau la schimbarea pozitiei (toaleta
bronsica matinala)
Aspect predominant purulent, se depoziteaza in vasul de colectare in
3 straturi:
Inferior (purulent) puroi, detritus celular
Mijlociu (mucos)
Superior (seros)

Inodora, poate deveni fetida daca se dezvolta germeni anaerobi in


cavitati mari
Contine germeni Gram + si Gram -

2. Tusea
Usoara sau persistenta
Intermitenta in cursul zilei
Suparatoare dimineata sau la schimbarea pozitiei

3. Hemoptizia
Frecventa (40-70% din cazuri)
Amploare variabila (sputa cu striuri sanguinolente
hemoptizii mari, grave, uneori fatale)
Ca urmare a necrozei epiteliului bronsic sau prin ruptura
anastomozelor dintre vasele bronsice si cele pulmonare

4. Dispneea
Relativ rara
La bolnavi cu forme extinse sau in cursul exacerbarilor

5. Pneumonii recidivante
Ca urmare a episoadelor inflamatorii
Imbogatirea semnelor locale:
Accentuarea dispneei
Febra
Alterarea starii generale

Diagnostic examen clinic


Examenul clinic al toracelui in zonele corespunzatoare unei
bronsiectazii este destul de incostant.
Inspectia:putem vizualiza ca si in toate patologiile pulmonare
cronice hipocratismul digital,cianoza,pletora(policitemia
secundara ),deficit ponderal in stari avansate de hipoxie.
Auscultatia:Poate fi auzita orice combinatie de
cracmente,ronchus-uri sau wheezing,toate acestea reflectind
prezenta afectarii cailor respiratorii,care contin secretii sunt
accentuate in exacerbari acute.
Pacientii cu boala severa,raspindita,in mod particular cei cu
hipoxemie cronica pot asocia cord pulmonar si insuficienta
cardiara dreapta si respectiv edem periferic ,hepatomegalie.

Diagnostic:examen de
laborator

Analiza de sputa sputa analiza poate consolida diagnosticul de bronsiectazii i aduga informaii semnificative n
ceea ce privete poteniala etiologie. (Frotiu Gram, Ziehl-Neelsen sau Giemsa). Investigatie la flora nespecifica (metoda
culturala) cu antibiograma. Examenul sputei evidentiaza caracterul ei (sero-muco-purulent, muco-purulent sau purulent)
si germenii cauzali (examen bacteriologic).
Infecie cronic bronica cu nonmucoid Pseudomonas aeruginosa devine mult mai frecvente la pacienii cu bronsiectazii
non-CF. Prezena eozinofilelor sugereaz specii de Aspergillus, dei aceast constare nu este sigura in diagnosticarea de
ABPA.
Efectua un frotiu i cultur din sput pentru micobacterii i ciuperci.
AGS hemograma complet este de multe ori anormala la pacienii cu bronsiectazii. Constatrile tipice sunt
nespecifice si includ anemia i leucocitoza cu un procent crescut de neutrofile si VSH crescut. Un procent crescut de
eozinofile este un criteriu pentru ABPA. Alternativ, policitemia secundar poate fi observata n cazurile avansate de
hipoxie cronica .
Cantitative imunoglobulina niveluri cantitative de imunoglobulina , inclusiv subclase IgG, IgM i IgA, sunt utile pentru
a exclude hipogamaglobulinemia. specifici la Haemophilus influenzae si vaccinuri pneumococice pot fi utile.
Quantitative Alpha1-Antitrypsin Levels
Quantitative serum alpha1-antitrypsin (AAT) levels de folosesc in diagnostucul deficitului de alfa 1-anitripsina.Este
sugestiv istoricul familiar agravant,caracteristicele clinice de emfizem si debutul patologiei la o virsta >45 ani si lipsa
factorilorde risc ca :fumatul,expunerea la noxe profesionale.
Pilocarpine Iontophoresis (Sweat TePilocarpine iontophoresis (sweat test) este un criteriu standard pentru
diagnosticul CF. Cu toate acestea, analiza genetic a devenit standardul i pot fi efectuate pentru a cuta dovezi de
mutaii in concordan cu CF i s cautarea variantelor poteniale, cum ar fi sindromul Young.
st)
Aspergillus Precipitins i ser IgE totale niveluri Aspergillus precipitins i nivelurile de IgE totale serice sunt
importante n diagnosticul ABPA.Criteriile pendtru diagnosticul ABPA include IgE serica totala mai mare 1000 IU/mL or
a greater than 2-fold rise from baseline.
Factor de Screening teste reumatoide autoimune i alte teste de screening pentru boli autoimune pot fi efectuate
n stabilirea clinicii corespunztoare. De exemplu, un test de anticorpi antinucleari (ANA).
Examinarea prin microscopie electronica a spermei si a apiteliului respirator este utila din determinarea Diskineziei
mucociliare primare sdr.Kartagener
Testul la HIV

Explorari functionale
respiratorii
Rezultatele testelor respiratorii functionale pot fi normale in cazul in care avem
bronsiectazii unice de dimensiuni mici sau anormale cind este vorba de procese
bilaterale difuze.Explorarile funcionale pot reflecta comorbiditati care predispun la
aparitia bronsiectaziilor,ofera o informativitate majora ce tine de gradul de
deteriorare a functiei respiratorii.
Cel mai frecvent tip de disfunctie ventilatorie de tip obstructiv,pacientii cu
bronsiectazii au rate mai ridicate de declin annual al volumului expirator fortat in 1
secunda(FEV1).La pacientii cu bronsiectazii non-CF factori de risc pentru un delin
rapid al FEV1 include colonizarea cu Pseudomonas aeruginosa i concentraii mai
ridicate de markeri proinflamatorii.
Obstructia cailor respiratorii in bronsiectazii in unele cazuri nu e reversibila la
terapia cu bronhodilatatoare.Sunt anumite grupuri de pacienti ce raspund la
bronhodilatatoare.
Disfunctiile ventilatorii de tip restrictiv apar in procese bilaterale in stadii avansate
cu grad mare de fibroza,caracteristica pentru bronsiectazii de tractiune post-TBC.

Diagnostic
Imagistica joac un rol crucial n diagnosticul i monitorizarea bronsiectaziilor i gestionarea
complicaiilor. Radiografia toracic este utila ca un instrument de screening initial si n
timpul exacerbarior acute, dar are sensibilitate i specificitate limitata.
High-Resolution tomografia computerizat (HRCT) este standard pentru diagnosticul
i cuantificarea bronsiectaziilor, furnizarea de informaii detaliate morfologice si de referinta.
Tomografia computerizat (CT) este, de asemenea, e valoroasa n diagnosticare i
gestionarea complicaiilor. Supravegherea de rutin folosind HRCT se afl n discuie , n
special n fibroza chistica (CF), n cazul n care progresele n tratament ,au crescut
considerabil sperana de via, dar doza de radiaie cumulativ rmne o preocupare.
Imagistica prin rezonanta magnetica este o tehnic n evoluie, care ofer
informaii att structurale cit i funcionale.
Avantajul este lipsa de radiaii ionizante. Limitri includ costul, disponibilitatea i Rezoluia
spaial inferioar comparativ cu CT. Tehnica n continuare necesit evaluare, dar are
beneficiile poteniale de exemplu la pacientii cu CF.
Evaluare a clearance-ul mucociliary folosind scintigrafia radionuclid pot fi de
valoare, n special n dezvoltarea rezistentei la droguri.

Tomografia computerizata (HRCT) poseda o


sensibilitate de 84-97%
si specificitate de 82-99%,dar poate fi si mai
mare la centrele de sesizare.
Avantaje:noninvazivitatea ,evitarea posibilelor
reactii alergice la substanta de contrast .
Cele 3 forme de bronsiectazii n clasificarea Reid
pot fi vizualizate de HRCT.

Radiografia

A 27-year-old man diagnosed with reactive airway disease as a


child was examined because of frequent respiratory infections. The
posteroanterior chest radiograph shows ill-defined pulmonary
nodular opacities, mild scoliosis, and moderate overaeration

Additional nonspecific radiographic findings in bronchiectasis include the


following:
Volume loss related to mucous plugging and associated crowding of the
pulmonary vasculature - Actual destruction of lung parenchyma and/or pulmonary
fibrosis may be present
Abnormal lung opacities related to inflammation, scars, and/or mucous plugging
Signs of compensatory hyperinflation of the unaffected lung
Loss of definition of the central bronchi and vessels, related to central interstitial
lung disease and retained secretions
Traction bronchiectasis occurs in the case of pulmonary fibrosis. In pulmonary
fibrosis, honeycombing and distortion can be visible radiographically. However,
the radiographic diagnosis of traction bronchiectasis can be difficult, unless the
surrounding lung is opacified.[81]Patients with bronchiectasis are at increased risk
for pneumonia. Chest radiography can be used for detection and follow-up of
pneumonia associated with bronchiectasis.

Computed Tomography

HRCT realizata la 1-2 mm cu intervale de sectiune la 10 mm


(WL)700 Unitati Hounsfield (WW) 1000 UH.Pentru a obtine o
imagine relevanta a lobului mediu si a lingulei este necesara
rotirea la un unghi de 20 .

]
In cazul bronsiectaziilor chistice:
Ciorchine de
struguri:acest semn tipic
in bronsiectaziile de tip
sacciform apar intr-un
sindrom de condensare
retractil.

High-resolution computed tomography scan in


a 75-year-old man with cystic bronchiectasis.

This high-resolution computed tomography scan in a


13-year-old female adolescent shows left lower-lobe
bronchiectasis, which is secondary to tuberculosis.

In bronsiectaziile cilindrice :
Inel cu pecete:apare in momentul cind
raportul bronhoarterial creste.Calibrul
bronhiei si a vasului adiacent in norma
este de 1-1,5;atunci cind bronhia
depaseste limita de 1,5 ia apare mai
dilatata(inelul)si vasul adiacent
(pecetele).
Diametrul bronhiilor adiacente pleurei
si mediastinului pot atinge 1cm dar e
mai putin specifica.

Deget de
manusa:hiperdensitati ale
tesutului moale cu aspect
de ramificatii tubulare sau
in deget de manusa in
forme de V sau Y.Este dat
de bronhiile dilatate
unplute cu mucus(impact
mucoid)

Axial HRCT (lung window) shows a mosaic pattern. There is


central bronchiectasis with mucoid impaction in many of
the bronchiectatic cavities (thin arrow). Also seen are
centrilobular nodules in a tree-in-bud pattern (bold arrow)

CT scan of thorax in a patient with IPF showing typical


basal, sub-pleural, honeycomb shadowing and traction
bronchiectasis.
HarrisonCough20139:9 doi:10.1186/1745-9974-9-9

Fagure de miere:spatii chistice eariene


grupate de 0,3-1,0cm diametru
situate bazal subpleural.Peretii
chisturilor sunt peretii bronhiilor
dilatate si ingrosateeste o afectare
ireversibila.Este prezenta in fibroza
avansata in bronsiectazii realizate prin
tractiune.
Vizualizam peretii ingrosati ai
bronhiilor si in unele cazul in cavitatile
chistice niveluri hidro-aerice.

Sina de
tramvai:peretii
ingrosati ai
bronhiilor in
sectiune
orizontala apar
ca hiperdensitati
liniare paralele.

The high-resolution computed tomography scan


demonstrates findings of fluid-filled dilated bronchi in a 65year-old man with bronchiectasis in the left lower lobe.

Bronsiectazii varicoase
Sirag de margele:
Alternarea zonelor de
dilatatie bronsica cu zone
de constringere a
diametrului bronhiilor .

Commonly associated with bronchiectasis are


the following:
Bronchial thickening
Centrilobular nodularity related to bronchiolitis
Mucous plugging
Bronchial arterial dilatation
Air trapping
Volume loss or hyperinflation

Degree of confidence
Except for extremely obese patients and examinations compromised by
motion, volumetric imaging of the chest provides a very high degree of
confidence to confirm or deny the diagnosis of bronchiectasis. HRCT scanning
has a sensitivity of 96% and a specificity of 93%,[3]as compared with
bronchography.
Bronchial measurements may vary with the use of different WLs and WWs.[19]
Some patients without bronchiectasis have a 1.49:1 bronchus-to-artery ratio;
however, the ratio is reliable only if it is greater than 1.5. If the ratio is less
than 1.5, other signs, such as bronchial wall thickening and lack of tapering,
should be present for the diagnosis of bronchiectasis.
Bronchial wall thickening is optimally seen with a WW of 1000 HU and a WL of
700 HU; higher WL and other WW readings are associated with artifactual wall
thickening.[20]This finding is not specific and is also seen in patients with
asthma and in those who smoke.

False positives/negatives
The variability of the bronchus-to-artery ratio at high altitudes and in patients with
pulmonary hypertension may result in an overdiagnosis because of vasoconstriction in these
conditions. The bronchial diameter relative to the adjacent pulmonary artery also increases
with increasing altitude.[88]
In patients with consolidation, dilated bronchi may not be seen. Cardiac and respiratory
artifacts may obscure the results or mimic subtle bronchiectasis in the left lower lobe.
Rarely, histiocytosis X and cavitating pulmonary masses mimic cystic bronchiectasis.
Traction bronchiectasis occurs in patients with interstitial fibrosis and results from fibrous
tethering of the bronchial wall. Traction bronchiectasis is not a true bronchial disorder.
The patients age should be considered, since the bronchoarterial ratio increases with age.
[89]In rare instances in adults, but more frequently in pediatric patients, bronchiectasis can
be reversible.
A dilated, cystic bronchus should be distinguished from a bulla, since a bronchial cyst has a
perceptible wall, while a bulla does not.
At times, severely dilated bronchi with associated volume loss can simulate honeycombing

Magnetic Resonance Imaging

Datorita noilor tehnologii in Rezonanta Magnetica Nucleara cum ar


fi:RMN cu heliu -3 hiperpolarizat si xenonul-129 hiperpolarizat (sunt
substante de contrast gazoase )care ne ofera date despre anumiti
parametri functionali:Ventilatia regionala,concentratia locala de
oxigen si microstructura pulmonilor folosind coeficientul partial de
difuzie.Vizualizarea structurii morfologice modificarilor tisulare si
vasculare a perfuziei regionale.Capacitatea de rezolutie spatiala
ramine inferioara fata de CT.
RMN cu folosireasubstantei de contrast Gadolinium.
Folosirea pe scara larga a RMN e limitata de costul ridicat si de
accesibilitatea redusa,aceasta investigatie este recomandata
pacientilor de virsta frageda sau persoanelor cu CF care realizeara
multiple explorari imagistice pentru a evita iraierea.

Nuclear Imaging

Patients with bronchiectasis can suffer from chronic productive cough,


recurrent infections, and hemoptysis. V/Q scanning can be useful in
determining whether surgical resection is appropriate therapy, especially for
hemoptysis. In one series, 23 of 66 patients treated surgically had
hemoptysis as a symptom. V/Q scanning demonstrated undiminished
perfusion in cylindrical bronchiectasis, but areas of cystic or mixed cystic and
cylindrical bronchiectasis showed perfusion defects. If a patient has a scan
showing less than 10% perfusion of a bronchiectatic region, those patients
can benefit from surgical resection of that nonfunctional region. [96]
Degree of confidence
The purpose of a V/Q scan is to determine perfused versus nonperfused
areas of lung rather than to make a diagnosis of bronchiectasis. Different
diseases can cause nonperfused areas of lung, so V/Q is used in conjunction
with CT or MRI.

Angiography

Hemoptysis is symptomatic of a potentially life-threatening condition and warrants urgent and comprehensive evaluation of
the lung parenchyma, airways, and thoracic vasculature.
Multidetector-row CT angiography permits noninvasive, rapid, and accurate assessment of the cause and consequences of
hemorrhage into the airways and helps guide subsequent management. [75, 97]The combined use of thin-section axial scans
and more complex reformatted images allows clear depiction of the origins and trajectories of abnormally dilated systemic
arteries that may be the source of hemorrhage and that may require embolization.
The vasculature, pulmonary parenchyma, and airways can be assessed with Multidetector CT angiography. In disorders with
chronic lung inflammation, including bronchiectasis, abnormal collateral systemic vessels form in the affected parts of the
lung. These collateral bronchial arteries appear as tortuous vessels and can bleed. Occasionally, nonbronchial systemic
arteries or pulmonary arteries bleed. Multiplanar reformatted images are used for identifying the origins and courses of
these vessels.
Bronchiectasis, chronic bronchitis, lung malignancy, tuberculosis, and chronic fungal infection are some of the most common
underlying causes of hemoptysis and are easily detected with CT angiography.
Results from multidetector CT angiography can be used to direct therapeutic angiography for bronchial or pulmonary arterial
embolization or surgical resection.
Degree of confidence
Occasionally, an examination is limited by artifact from patient motion, data depletion from a very large patient, or timing of
contrast bolus. Otherwise, multidetector row CT usually demonstrates the vasculature and the pulmonary parenchyma well.
False positives/negatives
No large series using current CT techniques has been published for hemoptysis assessment. In a series of 22 patients, using
16-detector row CT, bronchial (100%) and nonbronchial (62%) arteries causing hemoptysis were visible, with most traceable
throughout their length.[98]Substantial technological advances in CT since then allow more detailed visualization.

Bronhoscopie

Bronhoscopia(edem al
mucoasei, hipersecretie).
Bronhoscopia nu este, n general, utila
n diagnosticarea bronsiectaziilor, dar
poate fi util n identificarea
anomaliilor care stau la baza aparitiei
lor, cum ar fi tumorile, corpuri strine,
sau alte leziuni. Bronhoscopia cu lavaj
bronhoalveolar pot fi utilizata pentru
recoltare si cultura si a determina
microorganismele ce colonizeaza
tractul respirator.Bronhoscopia cu
biopsie si examen histologic au o
informativitate inalta.

Diagnostic Diferential

Pneumonie prin aspiratie


Pneumonie bacteriana
Astm bronsic
Bronsita cronica
BPCO
Fibroza chistica
Boala de reflux gastro-esofagian
Tubeculoza pulmonara
Emfizem pulmonar
Deficit de Alfa1 -Antitripsina

Tratament
Obiectivele tratamentului
Reducerea simptomelor
Reducerea complicatiilor
Controlul exacerbarilor
Reducerea morbiditatii si mortalitatii

Supportive Treatment
The following general measures are recommended:
Smoking cessation
Avoidance of second-hand smoke
Adequate nutritional intake with supplementation, if necessary
Immunizations for influenza and pneumococcal pneumonia [87, 88]
Confirmation of immunizations for measles, rubeola, and pertussis
Oxygen therapy is reserved for patients who are hypoxemic with
severe disease and end-stage complications, such as cor pulmonale.
Patients with cystic fibrosis (CF) should be cared for at specialized CF
treatment centers that address all aspects of the disease, including
nutritional and psychologic aspects.

Antibiotic Therapy
Antibiotics have been the mainstay of treatment for more than 40 years. Oral, parenteral, and aerosolized antibiotics are used, depending on the clinical situation.
In acute exacerbations, broad-spectrum antibacterial agents are generally preferred. However, if time and the clinical situation allows, sampling of respiratory secretions during an
acute exacerbation may allow treatment with antibiotics based on specific species identification.
Acceptable choices for the outpatient who is mild to moderately ill include any of the following:
Amoxicillin
Tetracycline
Trimethoprim-sulfamethoxazole
A newer macrolide (eg, azithromycin [6]or clarithromycin[7, 8])
A second-generation cephalosporin
A fluoroquinolone
In general, the duration of antibiotic therapy for mild to moderate illness is 7-10 days.
For patients with moderate-to-severe symptoms, parenteral antibiotics, such as an aminoglycoside (gentamicin, tobramycin) and an antipseudomonal synthetic penicillin, a thirdgeneration cephalosporin, or a fluoroquinolone, may be indicated. Patients with bronchiectasis from CF are often infected with mucoidPseudomonasspecies, and, as such,
tobramycin is often the drug of choice for acute exacerbation.
Infection withMycobacterium aviumcomplex (MAC) provides special treatment challenges. For the treatment of MAC in the setting of bronchiectasis, the American Thoracic
Society recommends a 3- to 4-drug treatment regimen with clarithromycin, rifampin, ethambutol, and possibly streptomycin that is continued until the patient's culture results are
negative for 1 year. The typical duration of therapy may be 18-24 months.
Regular antibiotic regimens
Some patients with chronic bronchial infections may need regular antibiotic treatment to control the infectious process. Some clinicians prefer to prescribe antibiotics on a regular
basis or for a set number of weeks each month.
The oral antibiotics of choice are the same as those mentioned previously. Potential regimens include daily antibiotics for 7-14 days of each month, alternating antibiotics for 7-10
days with antibiotic-free periods of 7-10 days, or a long-term daily dose of antibiotics. For patients with severe CF and bronchiectasis, intermittent courses of intravenous
antibiotics are sometimes used. [89, 90]
Aerosolized antibiotics
In the past several years, the nebulized route of antibiotic administration has received more attention because it is capable of delivering relatively high concentrations of drugs
locally with relatively few systemic adverse effects. [91]This is particularly beneficial in treating patients with chronic infection fromP aeruginosa. Currently, inhaled tobramycin is
the most widely used nebulized treatment for patients with bronchiectasis from either CF or non-CF causes of bronchiectasis. [92, 93, 94, 95, 96]Gentamicin[97]and colistin[98]have also
been used.
No significant studies have examined the long-term use of inhaled antibiotics in patients with non-CF bronchiectasis. A study by Govan et al found sustained long-term benefit (12
mo) of inhaled gentamicin in this subgroup, along with an acceptable side effect profile. [99]Optimal dosing regimen of inhaled gentamicin still needs to be elucidated.

Bronchial Hygiene
Good bronchial hygiene is paramount in the treatment of bronchiectasis, because of the tenacious sputum and defects in
clearance of mucus in these patients. Postural drainage with percussion and vibration is used to loosen and mobilize
secretions.
Devices available to assist with mucus clearance include flutter devices, [100, 101]intrapulmonic percussive ventilation
devices, and incentive spirometry.[102]Although consistent benefits from these techniques are lacking and vary with
patient motivation and knowledge, a review did report improvement in patients cough-related quality of life scores. [103]
A relatively new device called the "Vest" system is a pneumatic compression device/vest that is worn by the patient
periodically throughout the day. It is essentially technique independent and has variable success, especially in patients
with CF. Significant controlled trials have not been performed in patients with non-CF bronchiectasis.
Nebulization with concentrated (7%) sodium chloride solutions appears to be beneficial, particularly in patients with CFrelated bronchiectasis.[104, 105, 106]Mucolytics, such as acetylcysteine, are also often tried but do not appear to be universally
beneficial. However, maintaining adequate general hydration, which may improve the viscidity of secretions, is important.
Aerosolized recombinant DNase has been shown to benefit patients with CF. [107, 108]This enzyme breaks down DNA
released by neutrophils, which accumulates in the airways in response to chronic bacterial infection. However,
improvement has not been definitively shown in patients with bronchiectasis from other causes. [109]
Bronchodilator Therapy
Bronchodilators, including beta-agonists and anticholinergics, may help some patients with bronchiectasis, presumably
reversing bronchospasm associated with airway hyperreactivity and improving mucociliary clearance. [110, 111, 112]Highquality, large, randomized clinical trials of bronchodilator treatment in bronchiectasis have not been performed, however.

Anti-inflammatory Therapy
The rationale of anti-inflammatory therapy is to modify the inflammatory response caused by the microorganisms associated with bronchiectasis and subsequently
reduce the amount of tissue damage. Inhaled corticosteroids, [113]oral corticosteroids,[114]leukotriene inhibitors,[115]and nonsteroidal anti-inflammatory agents[115]have
all been examined.
Although evidence suggests some benefit from the use of these agents, findings are not universally definitive. One study reported that inhaled corticosteroids are
beneficial compared with placebo in patients with bronchiectasis, particularly those with associatedP aeruginosainfections.[116]
A double-blind, placebo controlled 6-week crossover study with 20 patients using beclomethasone dipropionate (750 mcg bid) showed reduced mean sputum volume
and improved forced expiratory volume in 1 second (FEV1) at 6 weeks. A similar study of 24 patients using fluticasone propionate (500 mcg bid) showed reduced
sputum leukocyte density and reduced levels of inflammatory mediators but no change in pulmonary function.
A study by Tsang et al showed benefit of inhaled fluticasone in patients with chronicP aeruginosainfection and bronchiectasis.[116]Another study showed
improvement in quality-of-life scores with inhaled steroids in patients with steady-state bronchiectasis. [117]
Azithromycin has known anti-inflammatory properties and long-term use has been studied in patients with both CF and non-CF bronchiectasis. In non-CF patients,
azithromycin has been shown to decrease exacerbations and improve spirometry and microbiologic profiles. [118, 119]In CF patients a meta-analysis suggests that it
improves lung function, especially in those patients colonized withPseudomonas.[106]
A practical approach is to use tapering oral corticosteroids and antibiotics for acute exacerbations and to consider inhaled corticosteroids for daily use in patients
with significant obstructive physiology on pulmonary function testing and evidence of reversibility suggesting airway hyperreactivity. However, Kapur et al reported
that the evidence supporting the use of inhaled steroids in adults with stable bronchiectasis is insufficient. [120]
Adjunctive Surgical Resection
Surgery is an important adjunct to therapy in some patients with advanced or complicated disease. [121]Surgical resection for bronchiectasis can be performed with
acceptable morbidity and mortality in patients of any age. [94, 122, 123]
In general, surgery should be reserved for patients who have focal disease that is poorly controlled by antibiotics. The involved bronchiectatic sites should be
completely resected for optimal symptom control. Other indications for surgical intervention may include the following:
Reduction of acute infective episodes
Reduction of excessive sputum production
Massive hemoptysis (Alternatively, bronchial artery embolization may be attempted for the control of hemoptysis.)
Foreign body or tumor removal
Consideration in the treatment of MAC orAspergillusspecies infections
Complications of surgical intervention include empyema, hemorrhage, prolonged air leak, and persistent atelectasis.
Patient selection plays an important role in perioperative mortality rates, which may be as low as 1% in the surgical treatment of segmental or even multisegmental
bronchiectasis.

Lung Transplantation
Single- or double-lung transplantation has been used as treatment of severe bronchiectasis, predominantly
when related to CF. In general, consider patients with CF and bronchiectasis for lung transplantation when
FEV1falls below 30% of the predicted value. Female patients and younger patients may need to be considered
sooner.
Consultations
A pulmonologist or other practitioner skilled in caring for patients with bronchiectasis should be consulted. All
patients with CF should be referred to a regional center with the resources and trained personnel to care for
patients with CF, including nutritional and psychological care.
Long-Term Monitoring
The interval of follow-up care is determined by the patient's clinical condition and associated conditions or
causes. Patients with CF should optimally be monitored at a center specialized in the care of CF.
Medication Summary
No specific medical therapy exists for the treatment of bronchiectasis. Pharmacologic therapy focuses on the
treatment of infectious exacerbations that these patients commonly experience, most often in the form of an
acute bronchitis-type syndrome.
The most widely accepted and commonly used medications in the treatment of acute infectious processes
associated with bronchiectasis include antibiotics, beta-agonists, inhaled corticosteroids, and expectorants.
Other more controversial medications have been previously mentioned in this article for completeness but are
not discussed here.

Antibiotics
Class Summary
These are the mainstays of treatment of patients with bronchiectasis and infectious exacerbations. The route of antibiotic administration varies with the overall clinical condition, with most patients doing well on outpatient regimens. Some patients benefit from a set regimen
of antibiotic therapy, such as therapy for 1 week of every month.
The choice of antibiotic is provider dependent, but, in general, the antibiotic chosen should have a reasonable spectrum of coverage, including the most common gram-positive and gram-negative organisms. Treatment of the patient who is more ill or the patient with CF
often requires intravenous anti-Pseudomonasspecies coverage with an aminoglycoside, most often in combination with an antipseudomonal synthetic penicillin or cephalosporin. Aerosolized tobramycin has been found effective in patients with cystic fibrosis (CF).
View full drug information
Clarithromycin (Biaxin)
Clarithromycin is a semisynthetic macrolide antibiotic that reversibly binds to P site of 50S ribosomal subunit of susceptible organisms and may inhibit RNA-dependent protein synthesis by stimulating dissociation of peptidyl t-RNA from ribosomes, causing bacterial growth
inhibition.
View full drug information
Azithromycin (Zithromax, Zmax)
Azithromycin is an azalide, a subclass of the macrolide antibiotics. Following oral administration, it is absorbed rapidly and widely distributed throughout body. Its mechanism of action is interference with microbial protein synthesis.
Azithromycin is effective against a wide range of organisms, including the most common gram-positive and gram-negative organisms. It has additional coverage of so-called atypical infections, such as Chlamydia, Mycoplasma, and Legionella species. This agent is indicated
for treatment of patients with mild-to-moderate infections, including acute bronchitic infections that may be observed with bronchiectasis.
View full drug information
Trimethoprim and sulfamethoxazole (Septra DS, Bactrim DS)
Trimethoprim-sulfamethoxazole is a synthetic combination antibiotic. Each tab contains 80 mg of trimethoprim and 400 mg of sulfamethoxazole. It is rapidly absorbed after oral administration. The mechanism of action involves blockage of 2 consecutive steps in
biosynthesis of nucleic acids and proteins needed by many microorganisms.
This agent provides coverage for common forms of both gram-positive and gram-negative organisms, including susceptible strains of Streptococcus pneumoniae and Haemophilus influenzae. It is indicated in the treatment of acute and chronic bronchitic symptoms in
patients with bronchiectasis.
View full drug information
Doxycycline (Doryx, Oraxyl, Vibramycin)
Doxycycline is a broad-spectrum, synthetically derived bacteriostatic antibiotic in the tetracycline class. It is an alternative agent for patients who cannot be given macrolides or penicillins.
Doxycycline is almost completely absorbed, concentrates in bile, and is excreted in urine and feces as a biologically active metabolite in high concentrations. It inhibits protein synthesis and, thus, bacterial growth by binding to 30S and possibly 50S ribosomal subunits of
susceptible bacteria. It may block dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest.
View full drug information
Levofloxacin (Levaquin)
Fluoroquinolones should be used empirically in patients likely to develop exacerbation due to resistant organisms to other antibiotics. Levofloxacin is rapidly becoming a popular choice in pneumonia. It is the L stereoisomer of the D/L parent compound ofloxacin, the D form
being inactive.
This agent is good for monotherapy, with extended coverage against Pseudomonas species and excellent activity against pneumococcus. It acts by inhibition of DNA gyrase activity. Bioavailability of the oral form reportedly is 99%.
View full drug information
Tobramycin (TOBI)
Tobramycin is an aminoglycoside specifically developed for administration with a nebulizer system. When inhaled, it is concentrated in airways, where it exerts an antibacterial effect by disrupting protein synthesis. Tobramycin is active against a wide range of gram-negative
organisms, including P aeruginosa. It is indicated for treatment of patients with CF and P aeruginosa infection.
View full drug information
Gentamicin
A water-soluble injectable antibiotic of aminoglycoside group, gentamicin acts by inhibiting normal protein synthesis; it is active against variety of pathogenic organisms, including P aeruginosa. For treatment of Pseudomonas species, it is often used in combination with an
antipseudomonal synthetic penicillin or cephalosporin.
In patients with bronchiectasis, gentamicin (or other aminoglycosides) may be indicated in setting of severe respiratory tract infection or CF. Dosing regimens are numerous; adjust dose based on creatinine clearance (CrCl) and changes in volume of distribution. Gentamicin
may be administered IV or IM.
View full drug information
Amikacin
Amikacin irreversibly binds to the 30S subunit of bacterial ribosomes; it blocks the recognition step in protein synthesis and causes growth inhibition. It is indicated for gram-negative bacterial coverage of infections resistant to gentamicin and tobramycin. Amikacin is
effective against P aeruginosa. Use patient's ideal body weight (IBW) for dosage calculation. The same principles of drug monitoring for gentamicin apply to amikacin.

Inhaled Beta Agonist


Class Summary
Although no long-term studies have been performed with inhaled beta-agonists, these medications are routinely used in patients with bronchiectasis for multiple reasons. Bronchiectasis may
cause an obstructive defect on pulmonary function testing that may respond to inhaled beta-agonists. Many older patients with bronchiectasis often have a concomitant illness, such as chronic
obstructive pulmonary disease, that responds to inhaled beta-agonists.
Finally, in the acute infectious bronchitic exacerbation that occurs in patients with bronchiectasis, patients may develop transient obstructive airway physiology that may improve with an inhaled
beta-agonist. Along these same lines, many patients are started on inhaled steroids for long-term airway stabilization, but the efficacy of these medications in bronchiectasis is questionable, and
any effect simply may be secondary to the treatment of other concomitant obstructive airway diseases.
View full drug information
Salmeterol (Serevent Diskus)
By relaxing the smooth muscles of the bronchioles in conditions associated with bronchitis, emphysema, asthma, or bronchiectasis, salmeterol can relieve bronchospasms. It also may facilitate
expectoration.
Salmeterol has been shown to improve symptoms and morning peak flows. It may be useful when bronchodilators are used frequently. More studies are needed to establish the role for these
agents.
The bronchodilating effect of salmeterol lasts >12 h. This agent is used on a fixed schedule in addition to regular use of anticholinergic agents. When salmeterol is administered at high or more
frequent doses than recommended, the incidence of adverse effects is higher.
View full drug information
Albuterol sulfate (Proventil, Ventolin)
Albuterol is a relatively selective beta2-adrenergic bronchodilator that, when inhaled, relaxes bronchial smooth muscle and inhibits release of mediators of immediate hypersensitivity from cells,
especially mast cells.
Albuterol is administered in a metered-dose aerosol unit for oral inhalation. It is indicated for prevention and relief of bronchospasm from any cause, including those observed in patients with
bronchiectasis.
Inhaled Corticosteroids
Class Summary
Studies suggest a benefit of inhaled corticosteroids in bronchiectasis, although the optimal dosing remains to be determined. No significant studies of oral steroid therapy in patients with
bronchiectasis have been performed.
View full drug information
Beclomethasone (Qvar)
Beclomethasone inhibits bronchoconstriction mechanisms, produces direct smooth muscle relaxation, and may decrease the number and activity of inflammatory cells, in turn decreasing airway
hyperresponsiveness. It is readily absorbed through the nasopharyngeal mucosa and GI tract. It has a weak hypothalamic-pituitary-adrenal (HPA) axis inhibitory potency when applied topically.
Various dose preparations are available and must be titrated in conjunction with other medications the patient is taking; most inhaled oral medications have an effect in 24 hours.
View full drug information
Fluticasone inhaled (Flovent Diskus)
Fluticasone may decrease the number and activity of inflammatory cells, in turn decreasing airway hyperresponsiveness. It also has vasoconstrictive activity.

Expectorants
Class Summary
One of the hallmarks of bronchiectasis is a chronic, thick, viscid sputum production. In
bronchiectasis, it is extremely difficult for the body's natural mucociliary clearance
mechanisms to adequately clear the sputum produced. Although definitive evidence is
lacking, expectorants are expected to increase respiratory tract fluid secretions and to
help loosen phlegm and bronchial secretions.
By reducing the viscosity of secretions, expectorants increase the efficacy of the
mucociliary clearance system. Expectorants are often marketed in combination with
decongestants, which may provide some patients additional relief.
View full drug information
Guaifenesin (Mucinex)
The product contains 600 mg of guaifenesin in a sustained-release formulation intended
for oral administration. It increases respiratory tract fluid secretions and helps to loosen
phlegm and bronchial secretions. Humibid LA and guaifenesin are indicated for patients
with bronchiectasis complicated by tenacious mucus and/or mucous plugs.

Complicatii

Prognostic
Prognoza pentru persoanele cu bronsiectazii
depinde de cauza sa i pe ct de bine sunt
prevenite sau controlate infectiile si alte
complicatii. Persoanele cu patologii ciexistente, cum ar fi bronit cronic sau
emfizem, i oameni care au complicaii, cum
ar fi hipertensiune pulmonara sau cor
pulmonar, tind s aib un prognostic mai
ru.

Referinta:
1.http://emedicine.medscape.com /article/354167-overview#showall
2. http://www.slideshare.net/tmihaescu/semne-in-imagistica-toracica-ct
3. http://thorax.bmj.com/

4. European Respiratory Monograph 52: Bronchiectasis 2011. 52, 4467.


5.The New England Journal of Medicine346:13831393, 2002.

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