Characterising airway obstructive, dysanaptic and PRISm phenotypes of prematurity-associated lung disease.

Abstract

Although obstructive airway disease has been shown to be associated with prematurity, other spirometry phenotypes are less well described. We characterised abnormal spirometry phenotypes in preterm-born children, including prematurity-associated obstructive lung disease (POLD, forced expiratory volume in 1 s (FEV₁)<lower limit of normal (LLN), FEV₁/forced vital capacity (FVC)<LLN), prematurity-associated preserved ratio of impaired spirometry (pPRISm, FEV₁<LLN, FEV₁/FVC≥LLN) and prematurity-associated dysanapsis (pDysanapsis, FEV₁≥LLN, FEV₁/FVC<LLN), and associated them with early life factors, bronchodilator responsiveness and fractional exhaled nitric oxide (FE_NO). 768 children, aged 7-12 years, underwent FE_NO measurements and spirometry before and after salbutamol. Groups were compared using parametric tests; multinomial regression was used. 22.6% of 544 preterm-born (mean gestation: 31 weeks) and 9.2% of 195 term-born children, with satisfactory data available, were classified into one of four abnormal spirometry groups. Each phenotype was generally more prevalent in preterm-born children than in the term-born children. For the preterm group, POLD-reversible (4.4%) was associated with increased FE_NO, bronchopulmonary dysplasia (BPD) and intrauterine growth restriction. POLD-fixed group (3.3%) did not have increased FE_NO but was associated with BPD. 41% of the pDysanapsis group (5.9%) had bronchodilator response, 31% had increased FE_NO and was associated with postnatal weight gain. In the pPRISm group (9%), 13% responded to bronchodilators, FE_NO was not increased and was non-significantly associated with body mass index (p=0.064). Further to airway obstruction, we describe airway dysanapsis and pPRISm spirometry phenotypes in survivors of prematurity, both of which have poor outlook in other disease groups. By identifying specific phenotypes, targeted therapy can be developed to improve long-term outcomes.