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.

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 Clearance Index and Structural Lung Disease on Computed Tomography in Early Cystic Fibrosis.

RATIONALE: The lung clearance index is a measure of ventilation distribution derived from the multiple-breath washout technique. It has been suggested as a surrogate for chest computed tomography to detect structural lung abnormalities in individuals with cystic fibrosis (CF); however, the associations between lung clearance index and early structural lung disease are unclear. OBJECTIVES: We assessed the ability of the lung clearance index to reflect structural lung disease on the basis of chest computed tomography across the entire pediatric age range. METHODS: Lung clearance index was assessed in 42 infants (ages 0-2 yr), 39 preschool children (ages 3-6 yr), and 38 school-age children (7-16 yr) with CF before chest computed tomography and in 72 healthy control subjects. Scans were evaluated for CF-related structural lung disease using the Perth-Rotterdam Annotated Grid Morphometric Analysis for Cystic Fibrosis quantitative outcome measure. MEASUREMENTS AND MAIN RESULTS: In infants with CF, lung clearance index is insensitive to structural disease (κ = -0.03 [95% confidence interval, -0.05 to 0.16]). In preschool children with CF, lung clearance index correlates with total disease extent. In school-age children, lung clearance index correlates with extent of total disease, bronchiectasis, and air trapping. In preschool and school-age children, lung clearance index has a good positive predictive value (83-86%) but a poor negative predictive value (50-55%) to detect the presence of bronchiectasis. CONCLUSIONS: These data suggest that lung clearance index may be a useful surveillance tool to monitor structural lung disease in preschool and school-age children with CF. However, lung clearance index cannot replace chest computed tomography to screen for bronchiectasis in this population.

Progressive ventilation inhomogeneity in infants with cystic fibrosis after pulmonary infection.

Measures of ventilation distribution are promising for monitoring early lung disease in cystic fibrosis (CF). This study describes the cross-sectional and longitudinal impacts of pulmonary inflammation and infection on ventilation homogeneity in infants with CF.Infants diagnosed with CF underwent multiple breath washout (MBW) testing and bronchoalveolar lavage at three time points during the first 2 years of life.Measures were obtained for 108 infants on 156 occasions. Infants with a significant pulmonary infection at the time of MBW showed increases in lung clearance index (LCI) of 0.400 units (95% CI 0.150-0.648; p=0.002). The impact was long lasting, with previous pulmonary infection leading to increased ventilation inhomogeneity over time compared to those who remained free of infection (p<0.05). Infection with Haemophilus influenzae was particularly detrimental to the longitudinal lung function in young children with CF where LCI was increased by 1.069 units for each year of life (95% CI 0.484-1.612; p<0.001).Pulmonary infection during the first year of life is detrimental to later lung function. Therefore, strategies aimed at prevention, surveillance and eradication of pulmonary pathogens are paramount to preserve lung function in infants with CF.

Long-term medical and psychosocial outcomes in congenital diaphragmatic hernia survivors.

OBJECTIVE: Survival rates for congenital diaphragmatic hernia (CDH) are increasing. The long-term outcomes of CDH survivors were compared with a healthy control group to assess the morbidity for guidance of antenatal counselling and long-term follow-up programmes. PARTICIPANTS AND DESIGN: Participants born with CDH in Western Australia 1993-2008 were eligible with matched controls from the general population. Participants had comprehensive lung function tests, echocardiogram, low-dose chest CT scan and completed a Strengths and Difficulties Questionnaire (SDQ) and quality of life (QOL) questionnaire. RESULTS: 34 matched case-control pairs were recruited. Demographic data between groups were similar. Cases were smaller at follow-up (weight Z-score of -0.2vs0.3; p=0.03; height Z-score of -0.3vs0.6; p=0.01). Cases had lower mean Z-scores for forced expiratory volume in 1 s (FEV1) (-1.49 vs -0.01; p=0.004), FEV1/forced vital capacity (-1.92 vs -1.2; p=0.009) and forced expiratory flow at 25-75% (FEF25-75) (-1.18vs0.23; p=0.007). Cases had significantly worse respiratory mechanics using forced oscillation technique. Subpleural triangles architectural distortion, linear opacities and scoliosis on chest CT were significantly higher in cases. Prosthetic patch requirement was associated with worse lung mechanics and peak cough flow. Cases had significantly higher rates of gastro-oesophageal reflux disease (GORD) and GORD medication usage. Developmental delay was significantly higher in cases. More cases had a total difficulties score in the high to very high range (25% vs 0%, p=0.03) on the SDQ and reported lower objective QOL scores (70.2 vs 79.8, p=0.02). CONCLUSION: Survivors of CDH may have significant adverse long-term medical and psychosocial issues that would be better recognised and managed in a multidisciplinary clinic.

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.

Multiple breath washout cannot be used for tidal breath parameter analysis in infants.

BACKGROUND: Multiple breath washout (MBW) testing with SF6 gas mixture is routinely used to assess ventilation distribution in infants. It is currently unknown whether SF6 changes tidal breathing parameters during MBW in infants. We investigated if SF6 does change tidal breathing parameters in infants and whether a separate tidal breathing trace prior to MBW testing is necessary. METHODS: Tidal breathing during MBW was compared to standard tidal breathing in room air in healthy infants (n = 38), preterm infants (n = 41), and infants with cystic fibrosis (n = 41). Outcomes included inspiratory and expiratory times (TI and TE ), time to peak tidal inspiratory and expiratory flow (tPTIF and tPTEF), tidal volume (VT ), respiratory rate (f), and minute ventilation (VE ). RESULTS: Breath times were all significantly increased for both healthy (TE : -0.0790 [-0.10566, -0.05217]; mean difference [95% confidence intervals]) and CF (-0.109 [-0.15235, -0.06607]) infants during the MBW wash-in (P < 0.001). Healthy infants and those with CF showed decreased f during MBW wash-in (P < 0.001); however, no change in VT, resulting in a decreased VE (0.154 (0.086, 0.222) and 0.128 (0.069, 0.186) for healthy and CF infants, respectively, P < 0.001). Preterm infants experienced a decreased VE during both wash-in (0.134 [0.061, 0.207]; P < 0.001) and wash-out phases of MBW (P < 0.05). CONCLUSION: There are differences in tidal breathing parameters during MBW testing with SF6 in infants. It is, therefore, important to measure a separate tidal breathing trace in room air, prior to MBW testing to ensure rigour of tidal breath indices derived from analysis.