Impaired exercise outcomes with significant bronchodilator responsiveness in children with prematurity‐associated obstructive lung disease

Abstract

Introduction: Preterm-born children have their normal in-utero lung development interrupted, thus are at risk of short-and long-term lung disease. Spirometry and exercise capacity impairments have been regularly reported in preterm-born children especially those who developed chronic lung disease of prematurity (CLD) in infancy.However, specific phenotypes may be differentially associated with exercise capacity. We investigated exercise capacity associated with prematurityassociated obstructive (POLD) or prematurity-associated preserved ratio of impaired spirometry (pPRISm) when compared to preterm-and term-controls with normal lung function. Materials and Methods: Preterm-and term-born children identified through home screening underwent in-depth lung function and cardiorespiratory exercise testing, including administration of postexercise bronchodilator, as part of the Respiratory Health Outcomes in Neonates (RHiNO) study.Results: From 241 invited children, aged 7-12 years, 202 underwent exercise testing including 18 children with POLD (percent predicted (%)FEV 1 and FEV 1 / FVC < LLN); 12 pPRISm (%FEV 1 < LLN and FEV 1 /FVC ≥ LLN), 106 preterm-controls (PT c , %FEV 1 ≥ LLN) and 66 term-controls (T c , %FEV 1 > 90%). POLD children had reduced relative workload, peak O 2 uptake, CO 2 production, and minute ventilation compared to T c , and used a greater proportion of their breathing reserve compared to both control groups. pPRISm and PT c children also had lower O 2 uptake compared to T c . POLD children had the greatest response to postexercise bronchodilator, improving their %FEV 1 by 19.4% (vs 6.3%, 6% 6.3% in pPRISm PT c, T c , respectively; p < .001). Conclusion:Preterm-born children with obstructive airway disease had the greatest impairment in exercise capacity, and significantly greater response to postexercise bronchodilators. These classifications can be used to guide treatment in children with POLD.

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

“…We have shown that there are three different phenotypes that may respond to bronchodilators, some of which are associated with increased FE NO and atopy. We have also recently showed that preterm-born children with POLD have decreased exercise capacity as well as increased functional residual capacity (FRC) and residual volume (RV) when compared with term-born controls 32. In contrast, those with pPRISm had intermediate decreases in exercise capacity measures but had decreased FRC and RV.…”

Peripheral airway dysfunction in prematurity‐associated obstructive lung disease identified by oscillometry

“…Also of interest were the oscillometry measures following exercise. A greater number of children from the POLD group did not achieve maximal exercise testing, and those children with POLD had lower exercise capacity, 20 which may be a mixture of impaired lung function, respiratory symptoms and deconditioning. 38 While exercise is known to potentially cause bronchoconstriction confirmed T A B L E 4 Oscillometry change scores from postexercise to postexercise bronchodilator for preterm obstructive lung disease (POLD), preterm preserved ratio impaired spirometry (pPRISm), preterm (PTc), and term (Tc) controls.…”

“…17,18 We have recently described the prematurity-associated PRISm (pPRISm) phenotype 19 and also showed that this phenotype is associated with impaired exercise capacity with reduced O 2 uptake at peak exercise using a cycle ergometer, with little postexercise bronchodilator response. 20 Along with low functional residual and total lung capacities, this perhaps suggests a fixed structural lung disease in a pediatric preterm PRISm population that may have significant long-term impact given the outcomes identified from adult studies. 20 Oscillometry is likely to provide significant information about how the airways and lung tissues may be affected after preterm birth, especially during exercise when dynamic changes of the respiratory mechanics are occurring.…”

“…20 Along with low functional residual and total lung capacities, this perhaps suggests a fixed structural lung disease in a pediatric preterm PRISm population that may have significant long-term impact given the outcomes identified from adult studies. 20 Oscillometry is likely to provide significant information about how the airways and lung tissues may be affected after preterm birth, especially during exercise when dynamic changes of the respiratory mechanics are occurring. We hypothesized that differences in respiratory mechanics using oscillometry can be demonstrated at baseline, after maximal exercise and after postexercise bronchodilator when preterm-born children with different spirometric phenotypes are compared with term-born controls.…”

“…This is an important concept as PRISm is associated with longer term poor cardiorespiratory outcomes and with all‐cause mortality in adult populations 17,18 . We have recently described the prematurity‐associated PRISm (pPRISm) phenotype 19 and also showed that this phenotype is associated with impaired exercise capacity with reduced O 2 uptake at peak exercise using a cycle ergometer, with little postexercise bronchodilator response 20 . Along with low functional residual and total lung capacities, this perhaps suggests a fixed structural lung disease in a pediatric preterm PRISm population that may have significant long‐term impact given the outcomes identified from adult studies 20 …”