Background: The marked heterogeneity in CF disease complicates selection of those most likely to benefit from existing or emergent treatments. Objective: We aimed to predict progression of bronchiectasis in preschool children with CF. Methods: Using data collected up to three years of age, in the Australian Respiratory Early Surveillance Team for CF (AREST CF) cohort study, clinical information, chest computed tomography (CT) scores and biomarkers from bronchoalveolar lavage were assessed in a multivariable linear regression model as predictors for CT bronchiectasis at age 5-6. Results: Follow-up at 5-6 years was available in 171 children. Bronchiectasis prevalence at 5-6 was 134/171 (78%) and median bronchiectasis score 3 (range 0-12). The internally validated multivariate model retained eight independent predictors accounting for 37% (Adjusted R2) of the variance in bronchiectasis score. The strongest predictors of future bronchiectasis were: pancreatic insufficiency, repeated intravenous treatment courses, recurrent lower respiratory infections in the first 3 years of life and lower airway inflammation. Dichotomizing the resulting prediction score at a bronchiectasis score of above the median resulted in a diagnostic odds ratio of 13 (95% CI 6.3-27) with a positive and negative predictive values of 80% (95%CI 72%-86%) and 77% (95% CI 69%-83%) respectively. Conclusion: Early assessment of bronchiectasis risk in children with CF is feasible with reasonable precision at a group level, which can assist in high-risk patient selection for interventional trials. The unexplained variability in disease progression at individual patient level remains high, limiting the use of this model as a clinical prediction tool.

Objective: To determine the potential longer-term effects of maternal antenatal respiratory syncytial virus (RSV) vaccination, we examined the association between cord-blood RSV-neutralizing antibodies (RSV-NA) and RSV infections in the first 2-years of life, RSV-NA at 3-years, and respiratory health to age 5-years. Methods: Two community-based Australian birth cohorts were combined. For children with at least one atopic parent, paired serum RSV-NA levels were compared in cord-blood and at age 3-years. Weekly nasal swabs were collected in one cohort and during acute respiratory infections (ARI) in the other. Wheeze history up to age 5-years and physician-diagnosed asthma at 5-years was collected by parent report. Results: In 264 children, each log10 increase of cord-blood RSV-NA level was associated with 37% decreased risk (adjusted incidence-rate-ratio (aIRR) 0.63; 95% confidence interval (CI): 0.40–1.01) of RSV-ARI and 49% decreased risk (aIRR 0.51; 95%CI: 0.25–1.02) of RSV acute lower respiratory infections (ALRI) at 12–24 months of age. However, higher cord-blood RSV-NA was associated with increased risk of all-cause ALRI (aIRR 1.29; 95%CI: 0.99–1.69), wheeze-associated ALRI (aIRR 1.75; 95%CI: 1.08–2.82) and severe ALRI (aIRR 2.76; 95%CI: 1.63–4.70) at age 6–<12 months. Cord-blood RSV-NA was not associated with RSV-ARI in the first 6-months, RSV-NA levels at 3-years, or wheeze or asthma at 5-years. Conclusions: Higher levels of cord-blood RSV-NA did not protect against RSV infections during the first 6-months-of-life, time-to-first RSV-ARI, or wheeze or asthma in the first 5-years of life. Additional strategies to control RSV-related illness in childhood are needed.

Background: Wheeze-associated disorders are common in childhood, associated with considerable morbidity, if not detected and treated. Under diagnosis of asthma remains a problem, especially in resource-limited settings. Methods: We used a validated school-based screening questionnaire to detect children likely to have asthma. Children with positive screening were referred to the Pulmonology Department for clinical review and lung function testing. We compared asthma-like symptoms, activity limitation, school absence and health service utilization before and after in those diagnosed with, and treated for asthma. Results: 6400 children, from a potential population of 70,000 were screened between 2010 and 2016, with 900 (14.1%) screening positive. Lung function data were available from 578 (64.2%) children (5.7 to 6.5 years old). Asthma was confirmed in 549 children; 438 were treated with short acting bronchodilator alone and 111 with inhaled corticosteroids. Asthma control improved in 58% of children, with fewer daytime [mean 4.7 (SD1.9), vs 11.1 (0.6) days per week, p<0.001] and nocturnal [4.3 (1.1) vs 0.89 (0.5) days per month, p<0.001] symptoms. Activity improved and fewer school days were lost due to asthma [12.8 (3.0) vs 1.9 (0.9) days in past 3 months, p<0.001] in over 50% of children. Emergency department visits were reduced [1.8 (0.7) vs 0.3 (0.2) visits in past 3 months, p<0.001] in over 80% of children. Conclusions: Asthma under diagnosis remains a problem in Argentina. Our school-based assessment is an effective tool for detecting children with undiagnosed asthma. Instituting effective asthma treatment in these children reduces symptoms and improves control.

Background: Abnormal wound repair is implicated in asthma pathogenesis. The nose is the point of first contact with the environment, yet wound repair ability of the nasal epithelium has received little attention. We sought to determine the impact of atopy and asthma on wound healing of nasal epithelium. Methods: Primary nasal epithelial cells harvested from adult volunteers classified into mutually exclusive groups [healthy (H), atopic non-asthmatic (ANA), non-atopic asthmatic (NAA) and atopic asthmatic (AA)] were grown into well-differentiated epithelium at the air-liquid interface. The ability of the epithelium to heal a mechanical wound was determined under various conditions. Results: Wound healing rate (%/hour) was slowest in ANA (2.9±1.8, vs 4.3±1.9 in H, p=0.02). Healing rates of AA (3.8±1.0) and NAA (4.1±1.1) were not different from H. Exogenous IL-13 slowed healing (2.2±1.1 vs 4.0±1.3, p<0.002) across all subject groups (p<0.001). However, blocking endogenous IL-13 had no effect on wound healing (p=0.68). Blocking endogenous EGF markedly slowed wound healing (0.6±0.4 vs 4.1±1.9, p=0.006), whereas adding exogenous EGF had no effect (p=0.58). Wound healing was significantly faster (4.4±1.0 vs 3.4±0.9, p=0.013) in subjects (6 AA, 9 NAA) who took regular inhaled corticosteroids prior to cell harvesting. Infecting epithelial cultures with RSV 6 days prior to wounding slowed healing in all groups (p<0.001). Prior inhaled steroids also improved wound healing following RSV infection (P<0.001). Conclusion: Nasal epithelium from atopic adults heal wounds more slowly. Inhaled corticosteroids taken in vivo prior to harvest influence their responses in vitro, improving wound healing.