Clinical efficacy and satisfaction of a digital wheeze detector in a multicentre randomised controlled trial: the WheezeScan study.

Introduction: Wheezing is common in preschool children and its clinical assessment often challenging for caretakers. This study aims to evaluate the impact of a novel digital wheeze detector (WheezeScan™) on disease control in a home care setting. Methods: A multicentre randomised open-label controlled trial was conducted in Berlin, Istanbul and London. Participants aged 4-84 months with a doctor's diagnosis of recurrent wheezing in the past 12 months were included. While the control group followed usual care, the intervention group received the WheezeScan™ for at-home use for 120 days. Parents completed questionnaires regarding their child's respiratory symptoms, disease-related and parental quality of life, and caretaker self-efficacy at baseline (T0), 90 days (T1) and 4 months (T2). Results: A total of 167 children, with a mean±sd age of 3.2±1.6 years, were enrolled in the study (intervention group n=87; control group n=80). There was no statistically significant difference in wheeze control assessed by TRACK (mean difference 3.8, 95% CI -2.3-9.9; p=0.2) at T1 between treatment groups (primary outcome). Children's and parental quality of life and parental self-efficacy were comparable between both groups at T1. The evaluation of device usability and perception showed that parents found it useful. Conclusion: In the current study population, the wheeze detector did not show significant impact on the home management of preschool wheezing. Hence, further research is needed to better understand how the perception and usage behaviour may influence the clinical impact of a digital support.

Prolonged respiratory failure responds to conventional therapy in isolated homocysteine remethylation defects.

Isolated remethylation defects are rare inherited diseases caused by a defective remethylation of homocysteine to methionine, preventing various essential methylation reactions to occur. Patients present with a systemic phenotype, which can especially affect the central and peripheral nervous systems leading to epileptic encephalopathy, developmental delay and peripheral neuropathy. Respiratory failure has been described in some cases, caused by both central and peripheral neurological involvement. In published cases, the genetic diagnosis and initiation of appropriate therapy were rapidly performed following respiratory failure and led to a rapid recovery of respiratory insufficiency within days. Here, we present two infantile-onset cases of isolated remethylation defects, cobalamine (Cbl)G and methylenetetrahydrofolate reductase (MTHFR) deficiencies, which were diagnosed after several months of respiratory failure. Disease modifying therapy based on hydroxocobalamin and betaine was initiated and shows a progressive improvement and enabled weaning off respiratory support after 21 and 17 months in CblG and MTHFR patients respectively. We show that prolonged respiratory failure responds to conventional therapy in isolated remethylation defects, but can require a sustained period of time before observing a full response to therapy.

Racial bias in recruitment to clinical trials on paediatric asthma.

Asthma is now the commonest chronic disease of childhood, but not all children with asthma receive equivalent standards of medical care which influences their clinical outcomes. In this paper we sought to determine the proportion of participants in registered clinical trials relating to paediatric or adolescent asthma over the last decade that were from white and non-white backgrounds. We searched the ClinicalTrials.gov database for all completed interventional studies between the dates 1st January 2011 and 1st January 2021 that were on the topic of 'asthma', and included participants below 18 years of age. Of the 500 studies returned, 208 had results available on the ClinicalTrials.gov website. In total, of the 112,327 patients studied, almost 69 % (77,333) of the patients were described as White or Caucasian, and fewer than 13 % (14,189) were described as Black, African, or African-American. Overall, approximately 30 % of study participants - some 34,207 children - were from non-white backgrounds. To redress this imbalance, researchers designing clinical trials must ensure that their study populations are as representative of the target population for the intervention as possible.

Respiratory virus type to guide predictive enrichment approaches in the management of the first episode of bronchiolitis: A systematic review.

It has become clear that severe bronchiolitis is a heterogeneous disease; even so, current bronchiolitis management guidelines rely on the one-size-fits-all approach regarding achieving both short-term and chronic outcomes. It has been speculated that the use of molecular markers could guide more effective pharmacological management and achieve the prevention of chronic respiratory sequelae. Existing data suggest that asthma-like treatment (systemic corticosteroids and beta2-agonists) in infants with rhinovirus-induced bronchiolitis is associated with improved short-term and chronic outcomes, but robust data is still lacking. We performed a systematic search of PubMed, Embase, Web of Science, and the Cochrane's Library to identify eligible randomized controlled trials to determine the efficacy of a personalized, virus-dependent application of systemic corticosteroids in children with severe bronchiolitis. Twelve studies with heterogeneous methodology were included. The analysis of the available results comparing the respiratory syncytial virus (RSV)-positive and RSV-negative children did not reveal significant differences in the associatons between systemic corticosteroid use in acute episode and duration of hospitalization (short-term outcome). However, this systematic review identified a trend of the positive association between the use of systematic corticosteroids and duration of hospitalization in RSV-negative infants hospitalized with the first episode of bronchiolitis (two studies). This evidence is not conclusive. Taken together, we suggest the design for future studies to assess the respiratory virus type in guiding predictive enrichment approaches in infants presenting with the first episode of bronchiolitis. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42020173686.

Personal monitoring to reduce exposure to black carbon in children with asthma: a pilot study.

Using an advice-based intervention in a cohort of children with asthma, designed to reduce personal pollution exposure, a mean reduction in black carbon exposure of 34% was found, the primary reduction happening within the home environment https://bit.ly/301Xemt.

ERS International Congress 2020: highlights from the Paediatric Assembly.

In this review, the Paediatric Assembly of the European Respiratory Society (ERS) presents a summary of the highlights and most relevant findings in the field of paediatric respiratory medicine presented at the virtual ERS International Congress 2020. Early Career Members of the ERS and Chairs of the different Groups comprising the Paediatric Assembly discuss a selection of the presented research. These cover a wide range of research areas, including respiratory physiology and sleep, asthma and allergy, cystic fibrosis, respiratory infection and immunology, neonatology and intensive care, epidemiology, bronchology and lung and airway development. Specifically, we describe the long-term effect in lung function of premature birth, mode of delivery and chronic respiratory conditions such as cystic fibrosis. In paediatric asthma, we present risk factors, phenotypes and their progression with age, and the challenges in diagnosis. We confirm the value of the lung clearance index to detect early lung changes in cystic fibrosis. For bronchiectasis treatment, we highlight the importance of identifying treatable traits. The use of biomarkers and genotypes to identify infants at risk of long-term respiratory morbidity is also discussed. We present the long-term impact on respiratory health of early life and fetal exposures to maternal obesity and intrauterine hypoxia, mechanical ventilation hyperoxia, aeroallergens, air pollution, vitamin A deficient intake and bronchitis. Moreover, we report on the use of metabolomics and genetic analysis to understand the effect of these exposures on lung growth and alveolar development. Finally, we stress the need to establish multidisciplinary teams to treat complex airway pathologies.

Airway dendritic cell maturation in children exposed to air pollution.

Urban particulate matter (PM) enhances airway dendritic cell (DC) maturation in vitro. However, to date, there are no data on the association between exposure to urban PM and DC maturation in vivo. We sought to determine whether exposure of school-age children (8 to 14 y) to PM was associated with expression of CD86, a marker of maturation of airway conventional DCs (cDC). Healthy London school children underwent spirometry and sputum induction. Flow cytometry was used to identify CD86 and CCR7 expression on cDC subsets (CD1c+ cDC2 and CD141+ cDC1). Tertiles of mean annual exposure to PM ≤ 10 microns (PM10) at the school address were determined using the London Air Quality Toolkit model. Tertiles of exposure from the 409 children from 19 schools recruited were; lower (23.1 to 25.6 µg/m3, n = 138), middle (25.6 to 26.8 µg/m3, n = 126), and upper (26.8 to 31.0 µg/m3, n = 145). DC expression was assessed in 164/370 (44%) children who completed sputum induction. The proportion (%) of cDC expressing CD86 in the lower exposure tertile (n = 47) was lower compared with the upper exposure tertile (n = 49); (52% (44 to 70%) vs 66% (51 to 82%), p<0.05). There was a higher percentage of cDC1 cells in the lower tertile of exposure (6.63% (2.48 to 11.64) vs. 2.63% (0.72 to 7.18), p<0.05). Additionally; children in the lower exposure tertile had increased FEV1 compared with children in the upper tertile; (median z-score 0.15 (-0.59 to 0.75) vs. -0.21 (-0.86 to 0.48), p<0.05. Our data reveal that children attending schools in the highest areas of PM exposure in London exhibit increased numbers of "mature" airway cDCs, as evidenced by their expression of the surface marker CD86. This data is supportive of previous in vitro data demonstrating an alteration in the maturation of airway cDCs in response to exposure to pollutants.

Use of cleaner-burning biomass stoves and airway macrophage black carbon in Malawian women.

Exposure to particulate matter (PM) from burning of biomass for cooking is associated with adverse health effects. It is unknown whether or not cleaner burning biomass-fuelled cookstoves reduce the amount of PM inhaled by women compared with traditional open fires. We sought to assess whether airway macrophage black carbon (AMBC) - a marker of inhaled dose of carbonaceous PM from biomass and fossil fuel combustion - is lower in Malawian women using a cleaner burning biomass-fuelled cookstove compared with those using open fires for cooking. AMBC was assessed in induced sputum samples using image analysis and personal exposure to carbon monoxide (CO) and PM were measured using Aprovecho Indoor Air Pollution meters. A fossil-fuel exposed group of UK women was also studied. Induced sputum samples were obtained from 57 women from which AMBC was determined in 31. Median AMBC was 6.87µm2 (IQR 4.47-18.5) and 4.37µm2 (IQR 2.57-7.38) in the open fire (n=11) and cleaner burning cookstove groups (n=20), respectively (p=0.028). There was no difference in personal exposure to CO and PM between the two groups. UK women (n=5) had lower AMBC (median 0.89µm2, IQR 0.56-1.13) compared with both Malawi women using traditional cookstoves (p<0.001) and those using cleaner cookstoves (p=0.022). We conclude that use of a cleaner burning biomass-fuelled cookstove reduces inhaled PM dose in a way that is not necessarily reflected by personal exposure monitoring.

Carbonaceous particulate matter on the lung surface from adults living in São Paulo, Brazil.

OBJECTIVES: We therefore sought to identify the exposures associated with lung surface in long-term residents of São Paulo, Brazil. METHODS: Lung surface carbon were analyzed in 72 autopsy specimens by image analysis. Smoking history, measured PM10 nearest to the home, distance to main road, and distance-weighted traffic density were used as exposure variables. Data are summarized as median (IQR), and compared by Mann Whitney Test, with correlations done by Spearman's correlation. RESULTS: There was no association between lung surface and age or gender. There was no statistically significant association in lung surface between smokers and non-smokers 6.74 cm2 (3.47 to 10.02) versus 5.20cm2 (2.29 to 7.54), and there was no significant association between lung surface carbon and exposure to environmental PM and markers of traffic exposure. CONCLUSION: We did not find a statistically significant association between lung surface and smokers and non-smokers, and no statistically significant association between lung surface carbon and environmental exposure variables. These results suggest that lung surface carbon in long-term residents of São Paulo may predominately be from environmental PM, but the most appropriate environmental exposure marker remains unclear.

Asthma control in London secondary school children.

OBJECTIVE: The asthma control test (ACT) is a validated tool for assessing control in asthmatic children aged 12 years and older. Using the ACT, we sought to assess asthma control and knowledge in London secondary school children. METHODS: Secondary schools in London, UK, participated in this study. Children with doctor-diagnosed asthma were invited to complete an online questionnaire that included the ACT and questions about asthma. Suboptimal asthma control was defined as an ACT score of ≤ 19 out of a maximum score of 25. Data are summarised as median and interquartile range (IQR), and were analysed by either Mann-Whitney test, or chi-square test. A p value of < 0.05 was considered significant. RESULTS: A total of 799 children completed the questionnaire; 689 (86.2%) were included for analysis. Suboptimal asthma control was reported by 49.6% of students. Over a third (42.4%) of students prescribed a short-acting ß2-agonist inhaler felt uncomfortable using it at school, and 29.2% (n = 173) reported not using this inhaler when wheezy. 56.4% (n = 220) of those with regular inhaled corticosteroids did not take them as prescribed, and 41.7% did not know what this inhaler was for. Suboptimal control was associated with a greater proportion of students reporting that they were 'somewhat', 'hardly' or 'not at all' comfortable using inhalers at school (52.7% vs 29.1%, p < 0.01) and outside school (22.8% vs. 14.8%, p < 0.01). CONCLUSIONS: Suboptimal asthma control and poor asthma knowledge are common in London schoolchildren.