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Introduction There is epidemiological evidence to suggest that events in childhood influence lung growth and constitute a significant risk for adult COPD. The aim of the study is to evaluate for an association between childhood asthma and adult COPD. Methods This longitudinal, prospective study of 6–7-year-old children with asthma has been regularly reviewed every 7 years to the current analysis at 50 years of age. Participants completed respiratory questionnaires and lung function spirometry with postbronchodilator response. At the age of 50, subjects were classified to the following subgroups: non-asthmatics, asthma remission, current asthma and COPD which was defined by FEV1 to FVC ratio postbronchodilator of less than 0.7. Results Of the remaining survivors, 346 participated in the current study (participation rate of 76%) of whom 197 completed both questionnaire and lung function testing. As compared with children without symptoms of wheeze to the age of 7, (non-asthmatics) children with severe asthma had an adjusted 32 times higher risk for developing COPD (95% CI 3.4 to 269). In this cohort, 43% of the COPD group had never smoked. There was no evidence of a difference in the rate of decline in FEV1 (mL/year, 95th CI) between the COPD group (17, 10 to 23) and the other groups: non-asthmatics (16, 12 to 21), asthma remission (20, 16 to 24) and current asthma (19, 13 to 25). Conclusions Children with severe asthma are at increased risk of developing COPD.

Abstract Rationale Better understanding of evolution of lung function in infants with cystic fibrosis (CF) and its association with pulmonary inflammation and infection is crucial in informing both early intervention studies aimed at limiting lung damage and the role of lung function as outcomes in such studies. Objectives To describe longitudinal change in lung function in infants with CF and its association with pulmonary infection and inflammation. Methods Infants diagnosed after newborn screening or clinical presentation were recruited prospectively. FVC, forced expiratory volume in 0.5 seconds (FEV0.5), and forced expiratory flows at 75% of exhaled vital capacity (FEF75) were measured using the raised-volume technique, and z-scores were calculated from published reference equations. Pulmonary infection and inflammation were measured in bronchoalveolar lavage within 48 hours of lung function testing. Measurements and Main Results Thirty-seven infants had at least two successful repeat lung function measurements. Mean (SD) z-scores for FVC were −0.8 (1.0), −0.9 (1.1), and −1.7 (1.2) when measured at the first visit, 1-year visit, or 2-year visit, respectively. Mean (SD) z-scores for FEV0.5 were −1.4 (1.2), −2.4 (1.1), and −4.3 (1.6), respectively. In those infants in whom free neutrophil elastase was detected, FVC z-scores were 0.81 lower (P = 0.003), and FEV0.5  z-scores 0.96 lower (P = 0.001), respectively. Significantly greater decline in FEV0.5  z-scores occurred in those infected with Staphylococcus aureus (P = 0.018) or Pseudomonas aeruginosa (P = 0.021). Conclusions In infants with CF, pulmonary inflammation is associated with lower lung function, whereas pulmonary infection is associated with a greater rate of decline in lung function. Strategies targeting pulmonary inflammation and infection are required to prevent early decline in lung function in infants with CF.

BackgroundCross-sectional studies implicate neutrophilic inflammation and pulmonary infection as risk factors for early structural lung disease in infants and young children with cystic fibrosis (CF). However, the longitudinal progression in a newborn screened population has not been investigated.AimTo determine whether early CF structural lung disease persists and progresses over 1 year and to identify factors associated with radiological persistence and progression.Methods143 children aged 0.2–6.5 years with CF from a newborn screened population contributed 444 limited slice annual chest CT scans for analysis that were scored for bronchiectasis and air trapping and analysed as paired scans 1 year apart. Logistic and linear regression models, using generalised estimating equations to account for multiple measures, determined associations between persistence and progression over 1 year and age, sex, severe cystic fibrosis transmembrane regulator (CFTR) genotype, pancreatic sufficiency, current respiratory symptoms, and neutrophilic inflammation and infection measured by bronchoalveolar lavage.ResultsOnce detected, bronchiectasis persisted in 98/133 paired scans (74%) and air trapping in 178/220 (81%). The extent of bronchiectasis increased in 139/227 (63%) of paired scans and air trapping in 121/264 (47%). Radiological progression of bronchiectasis and air trapping was associated with severe CFTR genotype, worsening neutrophilic inflammation and pulmonary infection.DiscussionCT-detected structural lung disease identified in infants and young children with CF persists and progresses over 1 year in most cases, with deteriorating structural lung disease associated with worsening inflammation and pulmonary infection. Early intervention is required to prevent or arrest the progression of structural lung disease in young children with CF.

Background. Child tuberculosis contact screening and management can enhance case finding and prevent tuberculosis disease. It is universally recommended but rarely implemented in tuberculosis-endemic settings. The World Health Organization (WHO)–recommended symptom-based screening approach could improve implementation but has not been prospectively evaluated. Methods. We conducted a cohort study of children who were close contacts of pulmonary tuberculosis patients in Indonesia from August 2010 to December 2012. We performed clinical assessment, tuberculin skin test, and chest radiography in all eligible children irrespective of symptoms at baseline. Mycobacterial culture and Xpert MTB/RIF assay were performed on sputum from children with persistent symptoms of suspected tuberculosis. Children were managed according to WHO guidelines and were prospectively followed for 12 months. Results. A total of 269 child contacts of 140 index cases were evaluated. At baseline, 21 (8%) children had tuberculosis diagnosed clinically; an additional 102 (38%) had evidence of infection without disease. Of children with any tuberculosis-related symptoms at baseline, 21% had tuberculosis diagnosed compared with none of the asymptomatic children (P < .001). After 12 months of follow-up, none of the 99 eligible young child contacts (<5 years) who received isoniazid preventive therapy (IPT) had developed disease compared with 4 of 149 (2.6%) asymptomatic older children who did not receive IPT. Conclusions. Symptom-based screening is an effective and simple approach to child tuberculosis contact management that can be implemented at the primary healthcare level.

Abstract Rationale The promise of newborn screening (NBS) for cystic fibrosis (CF) has not been fully realized, and the extent of improvement in respiratory outcomes is unclear. We hypothesized that significant lung disease was present at diagnosis. Objectives To determine the extent of lung disease in a geographically defined population of infants with CF diagnosed after detection by NBS. Methods Fifty-seven infants (median age, 3.6 mo) with CF underwent bronchoalveolar lavage and chest computed tomography (CT) using a three-slice inspiratory and expiratory protocol. Measurements and Main Results Despite the absence of respiratory symptoms in 48 (84.2%) of infants, a substantial proportion had lung disease with bacterial infection detected in 12 (21.1%), including Staphylococcus aureus (n = 4) and Pseudomonas aeruginosa (n = 3); neutrophilic inflammation (41. 4 × 103 cells/ml representing 18.7% of total cell count); proinflammatory cytokines, with 44 (77.2%) having detectable IL-8; and 17 (29.8%) having detectable free neutrophil elastase activity. Inflammation was increased in those with infection and respiratory symptoms; however, the majority of those infected were asymptomatic. Radiologic evidence of structural lung disease was common, with 46 (80.7%) having an abnormal CT; 11 (18.6%) had bronchial dilatation, 27 (45.0%) had bronchial wall thickening, and 40 (66.7%) had gas trapping. On multivariate analysis, free neutrophil elastase activity was associated with structural lung disease. Most children with structural lung disease had no clinically apparent lung disease. Conclusions These data support the need for full evaluation in infancy and argue for new treatment strategies, especially those targeting neutrophilic inflammation, if the promise of NBS for CF is to be realized.

IntroductionThe skin is an important barrier against environmental allergens, but infants have relatively impaired skin barrier function. There is evidence that impaired skin barrier function increases the risk of allergic sensitisation, atopic dermatitis (AD) and food allergy. We hypothesise that regular prophylactic use of emollients, particularly those that are designed to improve skin barrier structure and function, will help prevent these conditions. With the aim of determining if application of a ceramide-dominant emollient two times per day reduces the risk of AD and food allergy, we have commenced a multicentre phase III, outcome assessor blinded, randomised controlled trial of this emollient applied from birth to 6 months.Methods and analysisInfants (n=760) with a family history of allergic disease will be recruited from maternity hospitals in Melbourne. The primary outcomes are as follows: the presence of AD, assessed using the UK Working Party criteria, and food allergy using food challenge, in the first 12 months of life as assessed by a blinded study outcome assessor. Secondary outcomes are as follows: food sensitisation (skin prick test), skin barrier function, AD severity, the presence of new onset AD after treatment cessation (between 6 and 12 months) and the presence of parent reported AD/eczema. Recruitment commenced in March 2018.Ethics and disseminationThe PEBBLES Study is approved by the Human Research Ethics Committees of the Royal Children’s Hospital (RCH) (#37090A) and the Mercy Hospital for Women (2018–008). Parents or guardians will provide written informed consent. Outcomes will be disseminated through peer-reviewed publications and presented at scientific conferences.Trial registration numbersACTRN12617001380381 and NCT03667651.

Background Newborn screening allows novel treatments for cystic fibrosis (CF) to be trialled in early childhood before irreversible lung injury occurs. As respiratory exacerbations are a potential trial outcome variable, we determined their rate, duration and clinical features in preschool children with CF; and whether they were associated with growth, lung structure and function at age 5 years. Methods Respiratory exacerbations were recorded prospectively in Australasian CF Bronchoalveolar Lavage trial subjects from enrolment after newborn screening to age 5 years, when all participants underwent clinical assessment, chest CT scans and spirometry. Results 168 children (88 boys) experienced 2080 exacerbations, at an average rate of 3.66 exacerbations per person-year; 80.1% were community managed and 19.9% required hospital admission. There was an average increase in exacerbation rate of 9% (95% CI 4% to 14%; p<0.001) per year of age. Exacerbation rate differed by site (p<0.001) and was 26% lower (95% CI 12% to 38%) in children receiving 12 months of prophylactic antibiotics. The rate of exacerbations in the first 2 years was associated with reduced forced expiratory volume in 1 s z scores. Ever having a hospital-managed exacerbation was associated with bronchiectasis (OR 2.67, 95% CI 1.13 to 6.31) in chest CT scans, and lower weight z scores at 5 years of age (coefficient −0.39, 95% CI −0.74 to −0.05). Conclusions Respiratory exacerbations in young children are markers for progressive CF lung disease and are potential trial outcome measures for novel treatments in this age group.

In children, intermittent asthma is the most common pattern and is responsible for the majority of exacerbations. Montelukast has a rapid onset of action and may be effective if used intermittently. To determine whether a short course of montelukast in children with intermittent asthma would modify the severity of an asthma episode. Children, aged 2-14 years with intermittent asthma participated in this multicenter, randomized, double-blind, placebo-controlled clinical trial over a 12-month period. Treatment with montelukast or placebo was initiated by parents at the onset of each upper respiratory tract infection or asthma symptoms and continued for a minimum of 7 days or until symptoms had resolved for 48 hours. A total of 220 children were randomized, 107 to montelukast and 113 to placebo. There were 681 treated episodes (345 montelukast, 336 placebo) provided by 202 patients. The montelukast group had 163 unscheduled health care resource utilizations for asthma compared with 228 in the placebo group (odds ratio, 0.65; 95% confidence interval, 0.47-0.89). There was a nonsignificant reduction in specialist attendances and hospitalizations, duration of episode, and beta-agonist and prednisolone use. Symptoms were reduced by 14% and nights awakened by 8.6% (p = 0.043), and days off from school or childcare by 37% and parent time off from work by 33% (p < 0.0001 for both). A short course of montelukast, introduced at the first signs of an asthma episode, results in a modest reduction in acute health care resource utilization, symptoms, time off from school, and parental time off from work in children with intermittent asthma.

Abstract Rationale Progressive lung damage in cystic fibrosis (CF) starts in infancy, and early detection may aid preventative strategies. Objectives To measure lung function in infants with CF diagnosed by newborn screening and describe its association with pulmonary infection and inflammation. Methods Infants with CF (n = 68, 6 weeks to 30 months of age) and healthy infants without CF (n = 49) were studied. Forced vital capacity, FEV0.5, and forced expiratory flows at 75% of exhaled vital capacity (FEF75) were measured using the raised-volume rapid thoracoabdominal compression technique. Forty-eight hours later, infants with CF had bronchoalveolar lavage (BAL) for assessment of pulmonary infection and inflammation. Measurements and Main Results In the CF group, the deficit in FEV0.5  z score increased by −0.77 (95% confidence interval, −1.14 to −0.41; P < 0.001) with each year of age. The mean FEV0.5  z score did not differ between infants with CF and healthy control subjects less than 6 months of age (−0.06 and 0.02, respectively; P = 0.87). However, the mean FEV0.5  z score was lower by 1.15 in infants with CF who were older than 6 months of age compared with healthy infants (P < 0.001). FVC and FEF75 followed a similar pattern. Pulmonary infection and inflammation in BAL samples did not explain the lung function results. Conclusions Lung function, measured by forced expiration, is normal in infants with CF at the time of diagnosis by newborn screening but is diminished in older infants. These findings suggest that in CF the optimal timing of therapeutic interventions aimed at preserving lung function may be within the first 6 months of life.