Prediction of lung function and lung density of young adults who had bronchopulmonary dysplasia

Abstract

COPD risk is jointly determined by fetal lung development, lung growth rate and lung growth duration leading to the maximally attained level of lung function in early adulthood. Bronchopulmonary dysplasia (BPD) is considered a developmental arrest of alveolarisation. Long-term outcome studies of adult survivors born before the introduction of surfactant therapy ("old BPD") showed impaired lung function. We aimed to predict adult lung function and lung density in a cohort of premature infants born in the surfactant era, representing "new BPD". We studied a cohort of young adults born between 1987 and 1998, with (n=36) and without (n=28) BPD, treated in a single centre. Their perinatal characteristics and pulmonary function in infancy were studied by regression analysis for correlation with adult lung function and tissue lung density, all expressed by z-scores, at a mean age of 19.7±1.1 and 21±2.2 years, respectively. Although BPD adults had on average lower forced expiratory volume in 1 s (zFEV₁)/forced vital capacity (FVC) and zFEV₁ than those without, 55% of the BPD group had zFEV1/FVC values above the lower limit of normal (LLN). Moreover, above LLN values of diffusing capacity of the lung for carbon monoxide (zD _LCO) was present in 89% of BPD adults and lung density in 71%. Only higher oxygen supply (F _IO2) at 36 weeks post-conception of BPD subjects had a trend with lower zFEV₁ (B=-6.4; p=0.053) and lower zD _LCO (B=-4.1; p=0.023) at adulthood. No statistically significant predictors of new BPD were identified.

FIGURE 1

Patient disposition. Flow chart of the participants. Seven healthy prematurely (HP) born infants could not be located for the study. However, one subject, who was not measured in infancy, could be included in the adult group. Three refused to participate and one moved abroad leaving 14 HP participants. Of the hyaline membrane disease (HMD) subjects, 5 could not be located at adult age leaving 14 HMD participants. Of those with bronchopulmonary dysplasia (BPD), 2 passed away during infancy, 2 could not be located, 2 have moved abroad, 3 refused to participate and 3 were severely mentally handicapped, precluding them to participate at adulthood leaving 36 BPD participants. As clinical data of HP and HMD groups revealed no differences (supplementary table S1), all data of these two groups were combined to qualify as non-BPD (non-BPD, n=28). Thus, in total, 28 non-BPD served as controls and 36 BPD subjects were analysed in the study. All HP subjects were White except for one from Indonesia and two from North African, one HMD and one BPD subject was from Indonesia.

FIGURE 2

Spirometry, gas exchange and lung density at young adulthood. Box plots for lung function parameters of 28 non-BPD subjects (dark box) and 36 BPD subjects (light box) who had spirometry, gas transfer and lung density measured. *: significant difference between groups after correction for birth weight and smoking history (p<0.005);. +: outlier.

FIGURE 3

Distribution of forced expiratory volume in 1 s (zFEV₁) with and without airway obstruction in the bronchopulmonary dysplasia (BPD) group. In the BPD group (55%) had a normal zFEV₁/forced vital capacity (FVC) (defined by z-score >−1.64), 16 of whom had a zFEV₁ above the lower limit of normal (LLN), while those with a zFEV₁/FVC below the LLN (n=15 of 33) had a mean zFEV₁ of −3.09, (−4.89 to −1.22, min to max).

FIGURE 4

Relation between inspiratory oxygen fraction (F_IO2) at 36 weeks of gestational corrected age (GCA) and forced expiratory volume in 1 s (zFEV₁) or zFEV₁/forced vital capacity (FVC) at adulthood. Airflow limitation (zFEV₁) and airway obstruction (zFEV₁/FVC) in 29 NCLD adult subjects in relation to the F_IO2 at 36 weeks after conception measured while treated with oxygen administered to the spontaneously breathing infant, either in an incubator or in an oxygen tent. Regression analysis for zFEV₁ revealed B=−6.4, with p=0.053, and B=−3,2, with p=0.29 for zFEV₁/FVC.