Childhood Course of Lung Function in Survivors of Bronchopulmonary Dysplasia FREE

To the Editor: Bronchopulmonary dysplasia (BPD) is the primary respiratory complication of premature birth, associated with a reduced maximal lung function that may carry a risk of a chronic obstructive pulmonary disease (COPD)–like phenotype developing later in life.¹ There is little prospective evidence about the evolution of lung function in long-term survivors of BPD.

This prospective study was performed between October 1992 and April 2008 with 17 survivors of BPD. Maximum flow at functional residual capacity (Vmax_FRC) was measured at age 2 years² and lung function at ages 9³ and 15 years. Bronchopulmonary dysplasia was defined as oxygen dependence persisting at 28 days in infants born with a weight less than 1250 g.³

Two control groups matched for sex and age (within 6 months) comprised 34 healthy children born at term and 17 children born preterm without BPD who had spirometry performed at age 9 years and again at age 14 to 15 years. Lung function measurements were compared using z scores.^4- 5 The study was approved by the University Hospital of Padua ethics committee, and parents provided written consent.

The study had a power of at least 84%, with a 2-sided significance level of .05, to detect a between-groups effect size of 1.0 or more. Repeated measures analysis of variance, t test, and linear regression were used for data analysis with SAS version 9.1.3 for Windows (SAS Institute Inc, Cary, North Carolina).

The BPD group showed consistent lung function tracking, indicated by no significant change in mean z score between ages 2 years (Vmax_FRCz score, −1.48; 95% confidence interval [CI], −2.19 to −0.77), 9 years (z score for forced expiratory volume in 1 second [FEV₁], −1.74, 95% CI, −2.27 to −1.21), and 15 years (FEV₁z score, −1.71; 95% CI, −2.60 to −0.82; P = .62) (Table). There was no change in mean z score for spirometry variables between ages 9 and 15 years in the control groups. Values for FEV₁ were significantly lower in the BPD group than in premature non-BPD and term-born children at both 9 and 15 years old. Prematurely born non-BPD participants also had significantly lower FEV₁ values than the term-born controls.

The prematurely born children showed no correlation between birth weight or gestational age and spirometry results. Among BPD participants, the z scores for Vmax_FRC at 2 years old (zVmax_FRC) were correlated with the z scores for FEV₁ (zFEV₁) at age 15 years (r = 0.74, P < .001) and with the individual differences in zFEV₁ between 9 and 15 years (Figure). zFEV₁ declined significantly (P = .01) between 9 and 15 years in the 9 BPD survivors with Vmax_FRC less than the 5th percentile at age 2 years (corresponding to a zVmax_FRC <−1.64⁵) but increased (P = .01) in the 8 individuals with Vmax_FRC greater than the 5th percentile (Figure); the former did not differ from the latter in perinatal-neonatal characteristics and somatic growth. Those below the 5th percentile had a lower annual rate of FEV₁ growth compared with those above the 5th percentile (160 mL/y; 95% CI, 109 to 211 mL/y, vs 245 mL/y; 95% CI, 202 to 288 mL/y; P = .01) and a significantly lower zFEV₁ at 15 years (−2.77; 95% CI, −3.90 to −1.64; vs −0.52; 95% CI, −1.44 to 0.40; P = .003).

Early lung injuries may influence lifetime respiratory health. In the general population, low Vmax_FRC values shortly after birth are a primary risk factor for airflow obstruction in adulthood.⁶ While our findings should be considered preliminary because of the small sample size, severe early airflow obstruction at 2 years identified survivors of BPD at greater risk of disrupted lung growth during their childhood, suggesting a guarded long-term respiratory prognosis. Patients with better airflow at 2 years showed an improvement in lung function in later childhood, suggesting some degree of functional recovery. In addition, our findings suggest that preterm delivery without BPD may also affect long-term lung function, although to a lesser extent than in patients with BPD.