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 Children’s
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 β-agonists
• 20.4% on inhaled corticosteroids
• Above the age of 13:
• 50% on short-acting β-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

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