Lung abnormalities do not influence aerobic capacity in school children born preterm.

PURPOSE: Children born preterm have impaired lung function and altered lung structure. However, there are conflicting reports on how preterm birth impacts aerobic exercise capacity in childhood. We aimed to investigate how neonatal history and a diagnosis of bronchopulmonary dysplasia (BPD) impact the relationship between function and structure of the lung, and aerobic capacity in school-aged children born very preterm. METHODS: Preterm children (≤ 32 w completed gestation) aged 9-12 years with (n = 38) and without (n = 35) BPD, and term-born controls (n = 31), underwent spirometry, lung volume measurements, gas transfer capacity, a high-resolution computer tomography (CT) scan of the chest, and an incremental treadmill exercise test. RESULTS: Children born preterm with BPD had an elevated breathing frequency to tidal volume ratio compared to term controls (76% vs 63%, p = 0.002). The majority (88%) of preterm children had structural changes on CT scan. There were no differences in peak V̇O2 (47.1 vs 47.7 mL/kg/min, p = 0.407) or oxygen uptake efficiency slope when corrected for body weight (67.6 vs 67.3, p = 0.5) between preterm children with BPD and term controls. There were no differences in any other exercise outcomes. The severity of structural lung disease was not associated with exercise outcomes in this preterm population. CONCLUSION: Children born preterm have impaired lung function, and a high prevalence of structural lung abnormalities. However, abnormal lung function and structure do not appear to impact on the aerobic exercise capacity of preterm children at school age.

Telehealth spirometry for children with cystic fibrosis.

AIM: We assessed the feasibility of telehealth spirometry assessments for children with cystic fibrosis (CF) living in a regional setting. METHOD: Patients with acceptable computer hardware at home were provided with a SpiroUSB (Vyaire) spirometer. Spirometry was performed during 'home admissions' or for ongoing home monitoring in children living outside metropolitan Melbourne. At the end of the session, the family forwarded the data to the Royal Children's Hospital, Melbourne. RESULTS: Twenty-two patients aged 7 to 17 years participated, with spirometry successful in 55 of 59 (93%) attempted sessions according to American Thoracic Society/European Respiratory Society criteria. The median distance between the subject's home and the hospital was 238 km (range 62-537 km) which equated to a travel time saving of 5 hours and 34 min per hospital visit. CONCLUSION: Home-based telehealth spirometry is feasible in children with CF and can support the CF team during home-based admissions and for ongoing outpatient monitoring.

Increased prevalence of expiratory flow limitation during exercise in children with bronchopulmonary dysplasia.

Evidence regarding the prevalence of expiratory flow limitation (EFL) during exercise and the ventilatory response to exercise in children born preterm is limited. This study aimed to determine the prevalence of EFL as well as contributing factors to EFL and the ventilatory response to exercise in preterm children with and without bronchopulmonary dysplasia (BPD). Preterm children (≤32 weeks gestational age) aged 9-12 years with (n=64) and without (n=42) BPD and term controls (n=43), performed an incremental treadmill exercise test with exercise tidal flow-volume loops. More preterm children with BPD (53%) had EFL compared with preterm children without BPD (26%) or term controls (28%) (p<0.05). The presence of EFL was independently associated with decreased forced expiratory volume in 1 s/forced vital capacity z-score and lower gestational age (p<0.05). There was no difference in peak oxygen uptake between preterm children with BPD and term controls (48.0 versus 48.4 mL·kg-1·min-1; p=0.063); however, children with BPD had a lower tidal volume at peak exercise (mean difference -27 mL·kg-1, 95% CI -49- -5; p<0.05). Children born preterm without BPD had ventilatory responses to exercise similar to term controls. Expiratory flow limitation is more prevalent in children born preterm with BPD and is associated with airway obstruction and a lower gestational age.

Lung function trajectories throughout childhood in survivors of very preterm birth: a longitudinal cohort study.

BACKGROUND: Data on longitudinal respiratory follow-up after preterm birth in the surfactant era are scarce and of increasing importance, with concerns that preterm survivors are destined for early onset chronic obstructive airway disease. We aimed to comprehensively assess lung function longitudinally from early childhood to mid-childhood in very preterm children (≤32 weeks gestation), and to explore factors negatively impacting on lung function trajectories. METHODS: Preterm children (with and without bronchopulmonary dysplasia) and healthy term children as controls were studied. All preterm participants were born at 32 weeks' gestation or earlier at King Edward Memorial Hospital, Perth, WA, Australia, between 1997 and 2003. Bronchopulmonary dysplasia was defined as at least 28 days of supplemental oxygen requirement as assessed at 36 weeks' post-menstrual age. Spirometry, oscillatory mechanics, gas exchange, lung volumes, and respiratory symptoms were assessed at three visits, two in early childhood (4-8 years) and one in mid-childhood (9-12 years). CT of the chest was done in preterm children in mid-childhood. Respiratory symptoms were documented via questionnaire at each visit. Data were analysed longitudinally using linear mixed models. FINDINGS: 200 very preterm children (126 with bronchopulmonary dysplasia and 74 without bronchopulmonary dysplasia) and 67 healthy term control children attended 458 visits between age 4 and 12 years. Chest CT was done on 133 preterm children at a mean age of 10·9 (SD 0·6) years. Preterm children, with and without bronchopulmonary dysplasia, had declines in spirometry z-scores over time compared with controls: forced expiratory volume in 1 s (FEV1), forced expiratory flow at 25-75% of the pulmonary volume, and FEV1/forced vital capacity all declined by at least 0·1 z-score per year in children with bronchopulmonary dysplasia (all p<0·001). Respiratory mechanics and gas exchange also deteriorated over time in children with bronchopulmonary dysplasia (relative to term controls, respiratory system reactance at 8 Hz decreased by -0·05 z-score per year [95% CI -0·08 to -0·01; p=0·006] and diffusing capacity of the lungs for carbon monoxide decreased by -0·03 z-score per year [95% CI -0·06 to -0·01; p=0·048]). Preterm children with bronchial wall thickening on chest CT (suggestive of inflammation) had bigger decreases in spirometry outcomes through childhood. For example, children with bronchial wall thickening on chest CT had an FEV1 z-score decline of -0·61 (95% CI -1·03 to-0·19; p=0·005) more than those without. Similarly, children exposed to tobacco smoke, those with earlier gestation, or those requiring more neonatal supplemental oxygen declined at a faster rate. INTERPRETATION: Lung function trajectories are impaired in survivors of very preterm birth. Survivors with bronchopulmonary dysplasia, ongoing respiratory symptoms, or CT changes reflecting inflammation have the poorest trajectories and might be at increased risk of lung disease in later life. Close targeted pulmonary follow-up of these individuals is necessary. FUNDING: National Health and Medical Research Council grants APP634519, APP1073301 (to SJS), APP1077691 (to JJP), and APP1025550 (to GLH), Princess Margret Hospital Foundation, and Raine Medical Foundation.

Altered lung structure and function in mid-childhood survivors of very preterm birth.

RATIONALE: Survivors of preterm birth are at risk of chronic and lifelong pulmonary disease. Follow-up data describing lung structure and function are scarce in children born preterm during the surfactant era. OBJECTIVES: To obtain comprehensive data on lung structure and function in mid-childhood from survivors of preterm birth. We aimed to explore relationships between lung structure, lung function and respiratory morbidity as well as early life contributors to poorer childhood respiratory outcomes. METHODS: Lung function was tested at 9-11 years in children born at term (controls) and at ≤32 weeks gestation. Tests included spirometry, oscillatory mechanics, multiple breath nitrogen washout and diffusing capacity of the lung for carbon monoxide. Preterm children had CT of the chest and completed a respiratory symptoms questionnaire. MAIN RESULTS: 58 controls and 163 preterm children (99 with bronchopulmonary dysplasia) participated. Preterm children exhibited pulmonary obstruction and hyperinflation as well as abnormal peripheral lung mechanics compared with term controls. FEV1 was improved by 0.10 z-scores for every additional week of gestation (95% CI 0.028 to 0.182; p=0.008) and by 0.34 z-scores per z-score increase in birth weight (0.124 to 0.548; p=0.002). Structural lung changes were present in 92% of preterm children, with total CT score decreased by 0.64 (-0.99 to -0.29; p<0.001) for each additional week of gestation. Obstruction was associated with increased subpleural opacities, bronchial wall thickening and hypoattenuated lung areas on inspiratory chest CT scans (p<0.05). CONCLUSIONS: Abnormal lung structure in mid-childhood resulting from preterm birth in the contemporary era has important functional consequences.

Lung CT imaging in patients with bronchopulmonary dysplasia: A systematic review.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is a common respiratory complication of preterm birth and associated with long-term respiratory sequelae. Chest computed tomography (CT) is a sensitive tool to obtain insight in structural lung abnormalities and may be a predictor for later symptoms. OBJECTIVES: To give an overview of chest CT scoring methods that are used to evaluate chest CT scans of BPD patients. To review which structural lung abnormalities are described in children and adults with BPD and whether these are related to clinical outcomes. METHODS: An extensive literature search was conducted for relevant studies on chest CT imaging in patients born preterm with BPD. RESULTS: We retrieved 316 original papers of which 16 articles and three abstracts fulfilled our inclusion criteria. Overall, we identified nine different semi-quantitative scoring methods. Chest CT scans revealed structural abnormalities in >85% of BPD patients. These abnormalities are decreased pulmonary attenuation, opacities, bronchial wall thickening, and consolidations. Some have been found to be negatively correlated with lung function and respiratory symptoms. CONCLUSIONS: None of the currently described scoring systems are appropriately validated or superior over another. Future studies are needed to generate a validated and universal chest CT quantitative scoring method for patients with BPD. Pediatr Pulmonol. 2016; 51:975-986. © 2016 Wiley Periodicals, Inc.

Air trapping on chest CT is associated with worse ventilation distribution in infants with cystic fibrosis diagnosed following newborn screening.

BACKGROUND: In school-aged children with cystic fibrosis (CF) structural lung damage assessed using chest CT is associated with abnormal ventilation distribution. The primary objective of this analysis was to determine the relationships between ventilation distribution outcomes and the presence and extent of structural damage as assessed by chest CT in infants and young children with CF. METHODS: Data of infants and young children with CF diagnosed following newborn screening consecutively reviewed between August 2005 and December 2009 were analysed. Ventilation distribution (lung clearance index and the first and second moment ratios [LCI, M(1)/M(0) and M(2)/M(0), respectively]), chest CT and airway pathology from bronchoalveolar lavage were determined at diagnosis and then annually. The chest CT scans were evaluated for the presence or absence of bronchiectasis and air trapping. RESULTS: Matched lung function, chest CT and pathology outcomes were available in 49 infants (31 male) with bronchiectasis and air trapping present in 13 (27%) and 24 (49%) infants, respectively. The presence of bronchiectasis or air trapping was associated with increased M(2)/M(0) but not LCI or M(1)/M(0). There was a weak, but statistically significant association between the extent of air trapping and all ventilation distribution outcomes. CONCLUSION: These findings suggest that in early CF lung disease there are weak associations between ventilation distribution and lung damage from chest CT. These finding are in contrast to those reported in older children. These findings suggest that assessments of LCI could not be used to replace a chest CT scan for the assessment of structural lung disease in the first two years of life. Further research in which both MBW and chest CT outcomes are obtained is required to assess the role of ventilation distribution in tracking the progression of lung damage in infants with CF.

Identifying peroxidases and their oxidants in the early pathology of cystic fibrosis.

We aimed to determine whether myeloperoxidase (MPO) is the main peroxidase present in the airways of children with cystic fibrosis (CF) and to assess which oxidants it produces and whether they are associated with clinical features of CF. Children with CF (n=54) and without CF (n=16) underwent bronchoscopy and bronchoalveolar lavage (BAL) for assessment of pulmonary infection and inflammation. BAL fluid was analyzed for MPO, halogenated tyrosines as markers of hypohalous acids, thiocyanate, and protein carbonyls. MPO was the only peroxidase detected in BAL samples from children with CF and its concentration was markedly higher than in controls. Levels of 3-chlorotyrosine and 3-bromotyrosine in proteins were higher in the CF group. They correlated with neutrophils and MPO. The concentration of thiocyanate in BAL samples was below 1µM. Protein carbonyl levels correlated with MPO and halogenated tyrosines in patients with CF. Levels of MPO and halogenated tyrosines were higher in children with infections, especially Pseudomonas aeruginosa, and in the presence of respiratory symptoms. They also correlated with the Kanga clinical score. Our findings suggest that MPO produces hypobromous acid as well as hypochlorous acid in the airways of children with CF and that these oxidants are involved in the early pathogenesis of CF.