Bronchopulmonary Dysplasia:

Seeing premature infants into

adulthood
Jennifer Landry md F.R.C.P.(C)
Respiratory Epidemiology & Clinical Research Unit
Division of Respiratory Medicine
McGill University Health Center
McGill University
Faculty disclosure
No conflict of interest to declare
Case 1, V.V.
32 weeks preterm male infant
1.73 kg (3.8 lbs)
Born from a 35 y.o. healthy G
3
P
2
A
0
, repeat C-
section (after administration of betamethasone)
Pregnancy complicated by moderate
oligohydramnios
APGAR score of 3
1
and 7
5
V.V.
Intubated at birth for respiratory distress
syndrome of the newborn, for 7 days
Patent ductus arteriosus, closed with 1 dose of
indomethacin
Supplemental oxygen until 7 months of age
Treated with HCTZ, spironolactone until age 2
7 admissions for asthma exacerbation as a
child
18 years later
V.V. 18 y.o. male, college student
Non-smoker, sedentary lifestyle
Frequent URTI with wheezing episodes
Mild dyspnea on exertion, relieved by inhaled
SABA
Mild kyphosis on physical exam
Chronic changes
in medical aspect
of both upper
lobes
Slightly
hyperlucent lower
lobes
Pulmonary function test at age 18
FEV
1
: 2.11 l (59% predicted), by 19% post-BP
FVC: 4.28 l (110%)
Ratio: 49
TLC: normal
FRC: 162%
RV: 223%
D
L
CO: 90%
Moderate airflow obstruction with a
significant bronchodilator response
Severe hyperinflation and gas
trapping
Normal diffusion capacity
Stage 1 exercise test
Predicted VO
2
max: 65%
Arterial desaturation to 91% at the end of the
effort
(Intracardiac shunt excluded by contrast
echocardiogram)
Case 2, S.B.
20 y.o. female
P.M.Hx. of severe asthma and
Underdeveloped lung from prematurity
In the past 12 months:
4 ER visits
3 hospitalizations
2 months of absenteeism from work
6 weeks of systemic corticosteroids in the past 3
months
S.B.
Born at 30 weeks, hospitalized for the first 2 1/2
years of life
Diagnosed with severe bronchopulmonary
dysplasia and pulmonary hypertension
PAP
s
: 104 mmHg
Dilated right ventricle, mild TR, no intracardiac
shunt
Normal left ventricular function
Pulmonary function test at age 20
FEV
1
: 1.18 l (35% predicted), no post-BP
FVC: 2.29 l (60%)
Ratio: 51
TLC: normal
FRC: 116%
RV: 244%
D
L
CO: 50%
Severe airflow obstruction with
no reversibility
Severe air trapping
Decreased diffusion capacity
Diffuse emphysematous changes
Diffuse emphysematous changes
Area of air trapping
What is Bronchopulmonary
dysplasia?
Form of chronic lung disease that develops in preterm
neonates treated with oxygen and positive-pressure
ventilation
Damage to the lung during a critical stage of lung
growth may result in significant pulmonary dysfunction
Strong relationship between alveolar & vascular
development (impaired alveolarization and dysmorphic
vascular growth)
Pathogenesis of BPD
Prenatal Inflammation
- Chorioamnionitis
- Fetal Infection
Postnatal Lung Injury
- Oxygen (high/low)
- Mechanical Ventilation
- Infection
- Inflammation
Premature Lung
Decreased Vascular Growth
Decreased Alveolarization
Bronchopulmonary dysplasia
1: Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med 2001;163(7):1723-9
BPD definition & severity
Definition of BPD
1
:
Need for supplemental oxygen for at least 28 days
Assessment for severity done at 36 weeks CGA (or 56
days of life if born after 32 weeks)
Severity graded on need for FiO
2
at time of assessment
Mild: room air
Moderate: FiO
2
<0.30
Severe: FiO
2
0.30 or positive pressure ventilation
Relevance of BPD in adulthood
Long-term effects of poor airway growth and airway
remodelling?
Fixed airway obstruction, hyperinflation and gas trapping
Hyperactive airways
Effects of impaired, truncated antenatal lung growth on
FEV
1
decline?
Substantially reduced maximal values
Will the rate of decline with advancing age parallel that among healthy
persons or will it be accelerated?
Emerging theory about BPD being a vascular disease
FEV
1
decline with age
Baraldi E, Filippone M. Chronic lung disease after premature birth. N Engl J Med. 2007; 357:1946-1955.
Historical cohort
Chart review of all premature birth of children admitted
between 1980 and 1992 at the Montreal Childrens
Hospital (n=1192)
Neonatal characteristics and predictors of long-term
outcome
Maternal factors (age, parity, smoking status, medical and obstetrical
history)
Neonatal factors (birth weight, gestational age, APGAR, type/duration of
mechanical ventilation, oxygen administration, secondary diagnoses and
treatments)
Rate of readmission and diagnoses
Pulmonary function test, radiological studies, chronic medication use
Long-term complications of prematurity (low vision,
neurological/developmental deficit, ADHD, hearing difficulty)
Premature infants versus BPD
Premature BPD
n 319 322
Birth weight 1.82 kg 1.11 kg
Gestational age 229 days 195 days
APGAR 1 5.8 4.1
APGAR 5 7.7 6.4
Gender () 55.8% 59.0%
Maternal age 25.3 years 26.4 years
Mean LOS 42.4 days 139.8 days
Mortality 11.3% 16.7%
Healthcare utilization (at the MCH)
*
Hospitalization: mean of 4.7 (6.1)
most of them (3.0) before the age of 2
Mean LOS: 11.2 (29.3) days
At mean age of 6.2:
54% are using short-acting -agonists
20.4% on inhaled corticosteroids
Above the age of 13:
50% on short-acting -agonists
35% on inhaled corticosteroids
87.5% still have reported radiological abnormalities
*: potential for selection bias (loss to follow-up)
Long-term complications among
BPD cases
52.8% diagnosed with developmental delays initially
21.2% with neurological impairments
7.98% with ADHD (5.29% in general population)
17.9% with low vision
11.4% with hearing problems
34.5% with asthma (11.5% overall pediatric population)
4.35% with Cor Pulmonale
Pulmonary functions in BPD cases,
by initial diseases severity*
Mild BPD Moderate BPD Severe BPD p-value
Mean age 14.0 13.8 14.1 0.62
FEV
1
% 93.5 65.6 52.2 0.006
FVC % 103.0 87.5 85.1 0.19
FEV
1
/FVC 83.8 69.1 63.5 0.06
FEF
50
83.3 46.2 30.9 0.001
TLC % 105.7 102.6 111.8 0.37
FRC % 104.0 113.0 145.2 0.07
RV % 121.3 159.0 194.3 0.29
* As defined by the NIH consensus definition, Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med 2001;163(7):1723-9.
RAMQ cohort study
Retroactive cohort study of subjects born prematurely
and residing in the province of Quebec
ICD-9 codes: 765.* + (770.7) or (769.*)
n= 3442, of which 776 with BPD
Method: RAMQ databases from 1980 to present
Med-echo (hospitalizations, diagnosis, LOS), medical and
pharmaceutical services
25 years of data on the healthcare utilization of BPD
survivors (still living in Quebec)
893 subjects matching the previous MCH cohort
(including 237 BPD subjects (74%))
Demographics of BPD subjects
776 subjects with BPD (237 subjects matching with the
MCH cohort (n: 322), 74%)
Data on paired subjects used to validate RAMQ
database:
PPV (ICD-9 code 770.7): 90.2%
NPV: 80.7%
Mean age in 2008: 19 years
Mortality rate: 3.1% (after an initial rate of 16.6% during
the perinatal period)
Mean age of death: 4.38 years
Main cause: Cor Pulmonale
Healthcare utilization of BPD
Mean number of hospital admission: 5.0 (vs 2.9)
Principal diagnoses: asthma, acute bronchiolitis/bronchitis,
BPD, pneumonia, OM and other pulmonary problems
The leading causes of admission (first 6th) were lung-related
Mean length of stay: 75 days (vs 29 days)
Mean number of ER or out-patient visits/year: 6.6
(vs 4.8)
Cost for medications: 513$/year (more than 2x
control)
Conclusions
Moderate and severe BPD seem to be associated with
an obstructive pathology in adolescence/early adulthood
Significant component of bronchial hyper-responsiveness
in ex-premature infants with BPD
BPD Long-term impact
Respiratory health
Quality of life
Healthcare utilization
Need to define the natural history of adult BPD
Need to define the impact of improved neonatal care on
the pathophysiology of BPD (new vs old BPD)
Current: Prospective cohort study
Disease characteristics, QOL and effects of prematurity
on young adults with BPD
Study outcomes:
Yearly for 3 years:
Symptoms and quality of life, as studied with dyspnea index and
QOL questionnaires (HADS, SF-36v2 and SGRQ)
FEV
1
, FVC, FEV
1
/FVC ratio, TLC, FRC, RV and D
L
CO, post-
bronchodilator response on FEV
1
and FVC
Healthcare utilization
At baseline:
PC
20
for diagnosis of bronchial hyper-responsiveness
V
D
/V
T
, VO
2
max, P
ET
CO
2
, P
ET
O
2
, AT, cardiac output and exercise
tolerance
Collaborators: Dr. D. Berube (HSJ), Dr. Canakis (MCH),
Dr. Ernst (JGH)
Thanks
Dr. Larry Lands
Dr. Dick Menzies
Dr. James Martin
Dr. Michael Davis
Thanks