Impact of early life geohelminths on wheeze, asthma, and atopy in Ecuadorian children at 8 years.

Background: Early-life exposures to geohelminths may protect against the development of wheeze/asthma and atopy. Objective: Study effect of maternal geohelminths and infections in children during the first 5 years of life on atopy, wheeze/asthma, and airways reactivity/inflammation at 8 years. Methods: Birth cohort of 2,404 neonates followed to 8 years in rural Ecuador. Data on wheeze/asthma were collected by questionnaire and atopy by skin prick test (SPT) reactivity to 9 allergens. We measured airways reactivity to bronchodilator, fractional exhaled nitric oxide (FeNO), and nasal eosinophilia. Stool samples were examined for geohelminths by microscopy. Results: 1,933 (80.4%) children were evaluated at 8 years. Geohelminths were detected in 45.8% of mothers and in 45.5% of children to 5 years. Frequencies of outcomes at 8 years were: wheeze (6.6%), asthma between 5 and 8 years (7.9%), SPT (14.7%), airways reactivity (10%), and elevated FeNO (10.3%) and nasal eosinophilia (9.2%). Any maternal geohelminth was associated with reduced prevalence of SPT (OR 0.72). Childhood T. trichiura infections were associated with reduced wheeze (OR 0.57) but greater parasite burdens with A. lumbricoides were associated with increased wheeze (OR 2.83) and asthma (OR 2.60). Associations between maternal geohelminths and wheeze/asthma were modified by atopy. Parasite-specific effects on wheeze/asthma and airways reactivity and inflammation were observed in non-atopic children. Conclusions: Our data provide novel evidence for persistent effects of in utero geohelminth exposures on childhood atopy but highlight the complex nature of the relationship between geohelminths and the airways. Registered as an observational study (ISRCTN41239086).

Lumacaftor-ivacaftor-associated health stabilisation in adults with severe cystic fibrosis

IntroductionLumacaftor-ivacaftor (LUM-IVA) has been shown to improve clinical outcomes in cystic fibrosis (CF) patients homozygous for Phe508del with ppFEV1>40%. We assessed the clinical utility of LUM-IVA in all eligible adult CF patients with ppFEV1<40% treated for at least 1 year under a single centre managed access program.MethodsFollowing clinical optimisation eligible patients (n=40) with ppFEV1<40% were commenced on LUM-IVA and monitored for tolerance and clinical outcomes including health service utilisation, pulmonary function, weight and body composition. Twenty-four patients reached 1 year of treatment by the time of evaluation. Six discontinued due to adverse events (five for increased airways reactivity) and 3 underwent lung transplantation.ResultsIn comparison to the year prior to LUM-IVA commencement, significant reductions (median/year) were observed in the treatment year in the number of pulmonary exacerbations requiring hospitalisation (3 to 1.5, p=0.002); hospitalisation days (27 to 17, p=0.0002) and intravenous antibiotic days (45 to 27, p=0.0007). Mean change in ppFEV1 was −2.10(se 1.18)% per year in the year prior, with the decline reversed in the year following (+1.45(se 1.13)% per year, p=0.035) although there was significant heterogeneity in individual responses. Mean weight gain at 1 year was 2.5±4.1 kg; p=0.0007), comprising mainly fat mass (mean 2.2 kg). The proportion of patients with severe underweight (BMI<18.5 kg·m−2) decreased from 33% at baseline to 13% at 1 year (p=0.003).ConclusionThis real-world evaluation study demonstrated benefits over several clinical domains (infective exacerbations requiring hospitalisation, intravenous antibiotics, pulmonary function decline and nutritional parameters) in CF patients with severe lung disease.

Childhood Asthma: Update

Definition and Pathophysiology Asthma is a reversible airways disease characterized by both smooth muscle hyperreactivity and airway inflammation. During the 1970s and early 1980s the focus was on smooth muscle constriction, and it was believed that better bronchodilators would greatly diminish our difficulties in controlling this condition. This, unfortunately, was not the case. The emphasis of therapy today has turned to airway inflammation. Lung biopsies from patients who have asthma show destruction of respiratory epithelium, basement membrane thickening, and inflammatory cellular infiltrate. Among the infiltrating cells are eosinophils, macrophages, and neutrophils that are called to the site of inflammation by the chemotactic products released by activated mast cells. Upon their arrival, these cells release their own products of inflammation, which amplify this immunologic response. A variety of neuropeptides also play a role, some serving to stabilize and others to destabilize the airway. One result of this airway inflammation is airways reactivity, also known as bronchial hyperresponsiveness. A common example of this scenario is the child who has allergic asthma and encounters a problematic allergen. This child has immunoglobulin E (IgE) to this allergen bound to mast cells in his or her airway. Upon exposure to the allergen, the binding of IgE and antigen triggers mast cell mediator release within minutes.