Unravelling the respiratory health path across the lifespan for survivors of preterm birth.

Many survivors of preterm birth will have abnormal lung development, reduced peak lung function and, potentially, an increased rate of physiological lung function decline, each of which places them at increased risk of chronic obstructive pulmonary disease across the lifespan. Current rates of preterm birth indicate that by the year 2040, around 50 years since the introduction of surfactant therapy, more than 700 million individuals will have been born prematurely-a number that will continue to increase by about 15 million annually. In this Personal View, we describe current understanding of the impact of preterm birth on lung function through the life course, with the aim of putting this emerging health crisis on the radar for the respiratory community. We detail the potential underlying mechanisms of prematurity-associated lung disease and review current approaches to prevention and management. Furthermore, we propose a novel way of considering lung disease after preterm birth, using a multidimensional model to determine individual phenotypes of lung disease-a first step towards optimising management approaches for prematurity-associated lung disease.

Long-term expiratory airflow of infants born moderate-late preterm: A systematic review and meta-analysis.

Background: Moderate-late preterm (MLP; 32 to <37 weeks' gestation) birth is associated with reduced expiratory airflow during child, adolescent and adult years. However, some studies have reported only minimal airflow limitation and hence it is unclear if clinical assessment in later life is warranted. Our aim was to compare maximal expiratory airflow in children and adults born MLP with term-born controls, and with expected norms. Methods: We systematically reviewed studies reporting z-scores for spirometric indices (forced expired volume in 1 second [FEV1], forced vital capacity [FVC], FEV1/FVC ratio and forced expiratory flow at 25-75% of FVC [FEF25-75%]) from participants born MLP aged five years or older, with or without a term-born control group from 4 databases (MEDLINE, CINAHL, Embase, Emcare). Publications were searched for between the 22nd of September 2021 to the 29th of September 2021. A meta-analysis of eligible studies was conducted using a random effects model. The study protocol was published in PROSPERO (CRD #42021281518). Findings: We screened 4970 articles and identified 18 relevant studies, 15 of which were eligible for meta-analysis (8 with term-born controls and 7 without). Compared with controls, MLP participants had lower z-scores (mean difference [95% confidence interval] I2) for FEV1: -0.22 [-0.35, -0.09] 49.3%, FVC: -0.23 [-0.4, -0.06] 71.8%, FEV1/FVC: -0.11 [-0.20 to -0.03] 9.3% and FEF25-75%: -0.27 [-0.41 to -0.12] 21.9%. Participants born MLP also had lower z-scores, on average, when compared with a z-score of 0 (mean [95% CI] I2) for FEV1: -0.26 [-0.40 to -0.11] 85.2%, FVC: -0.18 [-0.34 to -0.02] 88.3%, FEV1/FVC: -0.24 [-0.43 to -0.05] 90.5% and FEF25-75%: -0.33 [-0.54 to -0.20] 94.7%. Interpretation: Those born MLP had worse expiratory airflows than those born at term, and compared with norms, although reductions were modest. Clinicians should be aware that children and adults born MLP may be at higher risk of obstructive lung disease compared with term-born peers. Funding: This work is supported by grants from the National Health and Medical Research Council (Centre of Research Excellence #1153176, Project grant #1161304); Medical Research Future Fund (Career Development Fellowship to J.L.Y Cheong #1141354) and from the Victorian Government's Operational Infrastructure Support Programme. C. Du Berry's PhD candidature is supported by the Melbourne Research Scholarship and the Centre of Research Excellence in Newborn Medicine.

Is cardiorespiratory disease associated with increased susceptibility of SARS-CoV-2 in children?

BACKGROUND: There are limited data in pediatric populations evaluating whether chronic cardiorespiratory conditions are associated with increased risk of coronavirus disease 2019 (COVID-19). We aimed to compare the rates of chronic cardiac and respiratory disease in children testing positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2[+]) compared with those testing negative (SARS-CoV-2[-]) at our institution. METHOD: Prospective cohort with nested case-control study of all children tested by polymerase chain reaction (PCR) for SARS-CoV-2 by nasopharyngeal/oropharyngeal sampling between March and October 2020. Children were identified prospectively via laboratory notification with age and sex-matching of SARS-CoV-2[+] to SARS-CoV-2[-] (1:2). Clinical data were extracted from the electronic medical record. RESULTS: In total, 179 SARS-CoV-2[+] children (44% females, median age 3.5 years, range: 0.1-19.0 years) were matched to 391 SARS-CoV-2[-] children (42% female, median age 3.7 years, range: 0.1-18.3 years). The commonest comorbidities showed similar frequencies in the SARS-CoV-2[+] and [-] groups: asthma (n = 9, 5% vs. n = 17, 4.4%, p = 0.71), congenital heart disease (n = 6, 3.4% vs. n = 7, 1.8%, p = 0.25) and obstructive sleep apnoea (n = 4, 2.2% vs. n = 10, 2.3%, p = 0.82). In the SARS-CoV-2[+] group, the prevalence of symptomatic disease was similar among children with and without cardiorespiratory comorbidities (n = 12, 75% vs. n = 103, 57%, p = 0.35). A high proportion of children hospitalized with SARS-CoV-2 infection had cardiac comorbidities (23.8%). CONCLUSIONS: In this single site data set, rates of pre-existing cardiorespiratory disease were similar in SARS-CoV-2[+] and SARS-CoV-2[-] children. Rates of symptomatic infection were similar between children with and without cardiorespiratory comorbidity. High rates of comorbid cardiac disease were observed among hospitalized children with COVID-19 warranting further research to inform vaccine prioritization.

Associations between peak oxygen uptake, lung function, and bronchiectasis in children with cystic fibrosis in the era of CFTR modulators.

BACKGROUND: With the emergence of cystic fibrosis transmembrane conductance regulator (CFTR) modulators, forced expiratory volume in 1 s (FEV1 ) may become a less sensitive measure of pulmonary disease progression in children with cystic fibrosis (CF). Increasing evidence shows that peak oxygen uptake (VO2peak ) is a strong predictor of prognosis in CF. The primary aim of this study was to describe the associations between peak oxygen uptake, lung function, and bronchiectasis in children with CF in the era of CFTR modulators. METHODS: Spirometry and a maximal cardiopulmonary exercise test (CPET) were performed on the same day and compared to markers of disease severity. Markers of disease severity included a number of pulmonary exacerbations resulting in hospital admission within the preceding 12 months, body mass index, Pseudomonas aeruginosa (PsA) infection, and bronchiectasis. RESULTS: Fifty-two subjects (24 female) with CF participated in the study with a mean (SD) age of 13.8 (2.4) years, range 8-18 years. Forty-nine participants met satisfactory criteria for a maximal CPET. A significant correlation was found between relative VO2peak %predicted and FEV1 %predicted (r = .546, p < .001). A total of 4/49 children demonstrated an impaired aerobic capacity despite normal spirometry. Participants who had experienced one or more pulmonary exacerbations in the previous 12 months had a significantly lower relative VO2peak %predicted (p = .02). CONCLUSIONS: In children with CF who have mild pulmonary disease, there is significant correlation between FEV1 and VO2peak . In all, 8.2% of participants had an abnormal CPET result despite normal spirometry, and preceding pulmonary exacerbations were associated with poorer CPET outcomes. CPET may offer important prognostic information for clinical decision making in this new era of CFTR modulators.