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Background Underdiagnosis and low levels of asthma control are frequent occurring problems in patients with asthma. Objective The study aim was to evaluate the ability of non-invasive inflammatory markers in exhaled breath to predict exacerbations of childhood asthma, and to assess the time course of changes in these exhaled markers before, during and after exacerbations. Methods The design was a prospective one-year longitudinal study. Regular two-month visits at the outpatient clinic were performed. Forty children with asthma (aged 6-16 years) participated. The primary outcome measure was the occurrence of an exacerbation. Assessment was made of the presence and severity of pulmonary symptoms, use of medication, and measurements of forced expiratory volume in 1 s using home monitor. The following independent parameters were assessed during outpatient visits: (1) exhaled nitric oxide, (2) inflammatory markers in exhaled breath condensate: acidity, nitrite, hydrogen peroxide, interleukin-1α, -5, -13, interferon-γ, (3) lung function, (4) asthma control score. Results Thirty-eight of 40 children completed the study. Sixteen children developed exacerbations, of which ten were moderate and six severe. Univariate Cox regression analysis revealed that condensate acidity, interleukin-5 and asthma control score were significant predictors of an asthma exacerbation ( P < 0.05). In the multivariate Cox regression analysis, exacerbations were best predicted by the asthma control score and by the level of interleukin-5 in exhaled breath condensate (Wald scores of 7.19 and 4.44, P = 0.007 and P = 0.035 respectively). The predicted survival curve of this multivariate model showed a two times reduced risk on exacerbations in the category of children with the 10% most optimal values of IL-5 and asthma control score. Conclusions and Clinical Relevance Both exhaled breath condensate interleukin-5 level and asthma control score were significant predictors of asthma exacerbations. These findings open up the possibility of assessing the potential of such parameters to titrate asthma treatment in future studies. [ABSTRACT FROM AUTHOR]

Background: Asthma is a chronic inflammatory disease of the airways but recent studies have shown that alveoli are also subject to pathophysiological changes. This study was undertaken to compare hydrogen peroxide (H2O2) concentrations in different parts of the lung using a new technique of fractioned breath condensate sampling. Methods: In 52 children (9-17 years, 32 asthmatic patients, 20 controls) measurements of exhaled nitric oxide (FENO), lung function, H2O2 in exhaled breath condensate (EBC) and the asthma control test (ACT) were performed. Exhaled breath condensate was collected in two different fractions, representing mainly either the airways or the alveoli. H2O2 was analysed in the airway and alveolar fractions and compared to clinical parameters. Results: The exhaled H2O2 concentration was significantly higher in the airway fraction than in the alveolar fraction comparing each single pair (p = 0.003, 0.032 and 0.040 for the whole study group, the asthmatic group and the control group, respectively). Asthma control, measured by the asthma control test (ACT), correlated significantly with the H2O2 concentrations in the alveolar fraction (r = 0.606, p = 0.004) but not with those in the airway fraction in the group of children above 12 years. FENO values and lung function parameters did not correlate to the H2O2 concentrations of each fraction. Conclusion: The new technique of fractionated H2O2 measurement may differentiate H2O2 concentrations in different parts of the lung in asthmatic and control children. H2O2 concentrations of the alveolar fraction may be related to the asthma control test in children. [ABSTRACT FROM AUTHOR]

Summary: Asthma is a complex disease with a significant inflammatory component characterized by repeated episodes of exacerbation and inflammatory changes in both large and peripheral airways. The clinical course of childhood asthma varies substantially among individuals. The reasons why the clinical course of asthma displays persistence and even progression in some children but is intermittent in others remains unclear. Children with asthma are different from adults with asthma. Inflammatory involvement in children with asthma appears to be localised more in peripheral than central airways, and the inflammatory phenotype displays differences from adults. Children with acute asthma display a dominant eosinophilic inflammatory phenotype instead of the neutrophilic phenotype that is seen in adults with acute asthma. Corticosteroids do not alter the natural history of the disease and may not prevent progressive decline of lung function in the subset of severe asthma. The underlying inflammatory mechanisms involved in the decline of lung function remains to be elucidated. Non-invasive biomarkers for monitoring lung function and inflammation are needed in children to track and monitor pathological changes in the distal airways, as is the development of therapeutic strategies that effective to peripheral airway in this vulnerable population. This review summarises our present understanding of airway inflammatory phenotypes in children with asthma and factors determining disease severity in exacerbations of asthma, and focuses on studies evaluating relationships between clinical features and the dominant inflammatory phenotypes in disease prognosis in a variety of asthma populations. This presents the crucial steps for describing the strategies associated with improvements for paediatric asthma care. [ABSTRACT FROM AUTHOR]

Defining atopy in children with severe, therapy-resistant asthma is complex. There is currently no gold standard test; both skin prick testing (SPT) and allergen-specific IgE (sIgE) are used. Furthermore, atopy is increasingly considered to be a spectrum, not an all-or-none phenomenon. SPTs and sIgE cannot be used interchangeably, and if both tests are not performed, opportunities for intervention will be missed. Furthermore, the severity of atopy will be defined differently by the two tests. Cross-sectional study of 47 children with severe, therapy-resistant asthma, mean age 11.8 years, range 5.3-16.6 years, who underwent SPT, and measurement of total and sIgE as part of their clinical work-up. Overall, 42/47 (89%) were atopic (defined as either one positive SPT or sIgE). There was 98% concordance between the two tests in classifying atopy. When each allergen was considered individually, in 40/200 (20%), the SPT and sIgE results were discordant, most commonly in 25/200 (12.5%), the SPT was negative and the sIgE was positive. House dust mite and cat sensitization were more likely detected by sIgE, but dog sensitization by SPT. When atopy was quantified, the sum of sIgEs compared with the sum of SPT weal diameter showed a moderate correlation ( r=0.44, P<0.001). Total IgE increased with an increasing number of positive sIgEs ( P=0.028), but not significantly with increasing numbers of positive SPTs. SPT and sIgE identify group prevalence of atopy equally well; however, for individual allergens, concordance is poor, and when used to quantify atopy, SPTs and sIgE were only moderately correlated. In a clinical setting, if allergen avoidance is contemplated in children with severe, therapy-resistant asthma, both tests should be performed in order to detect sensitization. Cite this as: J. Frith, L. Fleming, C. Bossley, N. Ullmann and A. Bush, Clinical & Experimental Allergy, 2011 (41) 948-953. [ABSTRACT FROM AUTHOR]

Summary: Objective: To evaluate the efficacy and safety of three doses of ciclesonide (with or without spacer) in children with persistent asthma. Patients and methods: This was a multicentre, double-blind, placebo-controlled, 12-week study of ciclesonide 40, 80 or 160 μg (once daily pm). Children (6–11 years) were randomised 1:1 to treatment via a metered dose inhaler (MDI) or MDI plus spacer. The primary variable was change from baseline in mean morning peak expiratory flow (PEF). Secondary variables included: time to first lack of efficacy (LOE), asthma control, forced expiratory volume in 1 s (FEV1), asthma symptom score and quality of life (QoL). Safety assessments included: adverse events (AEs), urinary cortisol excretion and body height. Results: In total, 1073 children received treatment. At endpoint, mean morning PEF significantly improved with all doses of ciclesonide vs. placebo. There was no difference over placebo in time to first LOE, but ciclesonide was superior to placebo on asthma control, symptom score, FEV1 and QoL. There were no differences between the spacer or non-spacer subgroups. The incidences of AEs were comparable between treatment groups (approximately 35%) and there were no between-group differences in body height or urinary cortisol. Conclusions: Ciclesonide 40–160 μg once daily is effective and well tolerated in children with persistent asthma; its efficacy and safety are unaffected by the use of a spacer. clinicaltrials.gov registration number: NCT00384189. [ABSTRACT FROM AUTHOR]

Summary: ‘Paediatric asthma: everything that seemed to be certain no longer is’, holds the promise of leaving you with more questions than answers at the end of this review of paediatric asthma 2008–2009. This has often been true for asthma research, in particular over the past few years. Research with direct consequences for a clinician managing children with wheezing or asthma is discussed such as limitations in the characterisation of asthma phenotypes and the influence of early viral infections on asthma and the development of atopic sensitisation. It appears that wheezing in preschool children with specific viral pathogens confers differential rates of asthma risk. Viruses and day-care shift respiratory morbidity to an early age when it is more troublesome than at a later age but are not protective for sensitisation or asthma. What needs to be further explored is the relationship between viruses and recurrent wheeze or asthma in studies with stringently defined phenotypes including personal atopic status, timing of infection, and severity of infection. A modification of preschool wheeze phenotypes or replacement by other phenotypes that have been defined with the application of different methods is needed. Oral corticosteroids should not be prescribed in preschool children with acute mild to moderate viral wheeze, unless a severe outcome is anticipated or if the child has a classic atopic phenotype. Despite initial high expectations, FeNO was proven not to be beneficial for routine monitoring of asthma treatment. [ABSTRACT FROM AUTHOR]

The authors were given the charge of providing a vision of the future in paediatric respirology. Themes selected for being ripe for this visionary analysis include bronchopulmonary dysplasia (BPD), asthma, cystic fibrosis (CF), lung infections, obstructive sleep disordered breathing (OSDB) and pulmonary diagnostics and monitoring. A profound reduction or elimination of BPD is seen. Given the strong genetic component of this disease, genetic biomarkers will likely be identified that will permit much earlier recognition of BPD susceptibility and potentially the ability to modify disease course by altering gene expression. The ultimate prevention of BPD will be to prevent prematurity, but recognition of both the genetic basis of BPD and the inflammatory background should lead to improved prevention and therapy. A clear understanding and definition of asthma phenotypes will lead to more specific and targeted therapy, earlier detection and prevention, better monitoring of severity and adherence to therapy, lower mortality and decreased inappropriate diagnosis of asthma. The greatest opportunities in asthma care will likely come through tools to improve adherence to effective therapy. Also, areas are identified where better therapies are needed such as in patients with severe mucus hypersecretion (secretory hyperresponsiveness) especially in those with life-threatening asthma. The future of CF is easier to foresee with early successes seen in clinical trials. After the expected ability to correct the CF transmembrane regulator, care will need to change and additional research will be needed. Additionally, the face of CF is changing with more adults than children presently having the disease. This will necessitate changes to our approach to treating this disease in a fortunately aging population. If we are going to affect the worldwide lung health of children, we will need to address respiratory infections particularly pneumonia, tuberculosis and HIV-associated infections. Preventive, diagnostic and treatment strategies will shape the future face of these problems. The availability of inexpensive, readily available, and rapid molecular techniques to identify true infection (including HIV and tuberculosis) may permit earlier use of effective therapy while preventing the inappropriate use of antibiotics for common viral diseases. Sleep medicine will continue to be an important aspect of paediatric pulmonology. The evaluation of OSDB cannot rely on full-night attended polysomnography due to limited access. Identifying reliable markers of end organ dysfunction in children with OSDB may permit more rapid identification of patients in need of intervention like CPAP and assisted breathing. In addition, management options, as an alternative to adenotonsilectomy, are listed with a call for further research. Pulmonary diagnostics and monitoring will see the development and refinement of tools like the lung clearance index and the analysis of exhaled gasses, volatiles and dissolved biomarkers of inflammation as techniques that might help clinicians identify both the initiation of inflammation while it is more amenable to therapy, and to identify more readily the early changes associated with chronic lung diseases in children. The authors hope that these visionary articles will generate comments, arguments, inspiration, and perhaps even motivate funding agencies. [ABSTRACT FROM AUTHOR]

Szabó A, Mezei G, Kővári É, Cserháti E. Depressive symptoms amongst asthmatic children’s caregivers. Pediatr Allergy Immunol 2010: 21: e667–e673. © 2009 John Wiley & Sons A/S We wanted to find out, whether the number of depressive symptoms is higher amongst asthmatic children’s caregivers, compared to international data, to the Hungarian population average, and to parents of children with chronic renal disease. Are these depressive symptoms connected to the children’s psychological status, asthma severity or current asthma symptoms? One-hundred and eight, 7- to 17-yr-old asthmatic children were enrolled, who have been treated at the Semmelweis University, First Department of Pediatrics. Children were suffering from asthma for at least 1 yr, with a median of 8 yr (1–16 yr), they started to develop asthmatic symptoms between the age of 0.5–14 yr (median: 3 yr). We also identified 27 children with chronic renal diseases and their caregivers, who functioned as a control group. Children were asked to complete the Hungarian-validated versions of the Child Depression Inventory, the Spielberger State Anxiety Inventory for Children and the Juniper Pediatric Asthma Quality of Life Questionnaire. Asthma severity and current symptoms were also documented, 56% had no symptoms on the preceding week. Caregivers were asked to complete the Hungarian versions of the Beck Depression Inventory (BDI) short form, the Spielberger Anxiety Inventory and the Juniper Pediatric Asthma Caregivers’ Quality of Life Questionnaire. Caregivers of asthmatic children had significantly more depressive symptoms (7.73 ± 6.69 s.d.) than the age-specific normal population (p < 0.01). Caregivers of renal patients also experience more depressive symptoms (9.61 ± 7.43 s.d.) than their healthy peers, but difference between the two chronic diseases’ group did not prove to be significant. Asthmatic children’s caregivers who scored more points on the BDI than the population average suffer from more anxiety symptoms, but their quality of life is not worse than the caregivers’ with less depressive points. Depressive symptoms were neither connected to the children’s psychological and asthmatic symptoms nor quality of life. Amongst caregivers of asthmatic children, at least mild depressive symptoms were represented amongst 39% of men and 33% of women. Gender difference was not significant, despite observations in the normal Hungarian population. Amongst caregivers of renal patients, depressive symptoms were represented in 14% of men and 50% of women. Gender difference was significant. (p = 0.05). Significant difference was observed between male asthmatic and renal caregivers, albeit difference was not significant between the female groups. No difference was found in depressive symptoms according to caregivers’ level of education. Caregivers of children with asthma have more depressive symptoms than the average Hungarian population, but their results do not differ from caregivers taking care of children with chronic renal diseases. Caregivers of asthmatic children having at least mild depressive symptoms tend to have higher anxiety symptoms as well. Up to date, childhood chronic disease management and long-term care should also focus on parental psychology, mainly on depression and anxiety, as prevalence is higher than in the average population. [ABSTRACT FROM AUTHOR]

Aim: The aim of this exploratory study was to identify those factors associated with asthma control assessed according to GINA Guidelines. Method: 809 (56% female) subjects with asthma were recruited consecutively from both specialist and primary care centres. Asthma control was assessed over a 4-week follow-up period using a composite measure. A multivariate analysis was performed, in which asthma control was included as the dependent variable and several explanatory variables were included as independent variables. Results: Analysis performed on the whole population rendered gender (p=0.003), the type of physician (p<0.001), and age group (p<0.001), as significant factors associated with asthma control. In adults, gender (p=0.001), asthma severity (p<0.001), and type of physician (p<0.001) were significant, and only asthma severity was significant (p=0.043) in children. Conclusions: After model adjustment, we suggest that being female, suffering from more severe asthma, or being attended by a primary care physician, could pose a significantly higher risk of having poorly controlled asthma in adults. [ABSTRACT FROM AUTHOR]

Background and objective: More than 50% of patients with childhood asthma enter clinical remission by puberty, although 40–50% of these people will probably develop asthma symptoms during early adulthood. The mechanism of relapsing asthma in early adulthood remains unclear. This study determined the characteristics of young adults whose asthma remitted either during or before adolescence. Methods: A comparative study was performed on 24 students whose childhood asthma had gone into clinical remission by puberty (remission group), 25 atopic students with no history of asthma (atopy group) and 19 non-atopic students without allergic diseases (control group). Examinations included spirometry, levels of serum-specific IgE-antibodies, airway responsiveness to methacholine, exhaled nitric oxide (eNO) and evidence of airway inflammation in induced sputum. Results: Airway responsiveness ( P < 0.01), eosinophil counts in sputum ( P < 0.05) and the prevalence of sensitization to Dermatophagoides forinae ( P < 0.01) were significantly higher, and FEF25–75% and FEF75% ( P < 0.01) were significantly lower in the remission group than in the atopy and control groups. Furthermore, 50% and 33% of the remission group had airway hyper-responsiveness (AHR) and sputum eosinophilia, respectively. The eNO levels in the remission ( P < 0.01) and atopy ( P < 0.05) groups were significantly higher than in controls. Remission group members with AHR had a significantly longer period of childhood asthma, a shorter period of remission and greater airway eosinophilic inflammation than those without AHR ( P < 0.05). Conclusion: One half of young adults with childhood asthma that remitted either during or before adolescence continued to have evidence of AHR and airway eosinophilic inflammation, and might be at risk of future relapse. [ABSTRACT FROM AUTHOR]

Although sublingual immunotherapy (SLIT) is accepted to be a viable alternative of specific-allergen immunotherapy, the efficacy of long-term SLIT in asthmatic children is not well established. The efficacy of 3 yr of SLIT in addition to pharmacotherapy was compared with pharmacotherapy alone in a prospective, open, parallel-group, controlled study. Children with asthma aged 4–16 yr, sensitive to house dust mite (HDM) were followed up for a run-in period of 1 yr and then grouped as those who would receive SLIT + pharmacotherapy (n = 62) or pharmacotherapy alone (n = 28). All patients were evaluated based on symptom-medication scores and lung function tests every 3 months, as well as skin-prick test and serum total immunoglobulin E (IgE) levels annually for 3 yr. Children in the SLIT + pharmacotherapy group demonstrated significantly lower mean daily dose and annual duration of inhaled corticosteroid (ICS) usage when compared with controls. At the end of the 3 yr, within-group comparisons revealed statistically significant decreases in the dose and duration of ICS only in the SLIT group. Furthermore, 52.4% of subjects in the SLIT + pharmacotherapy group were able to discontinue ICS treatment for at least 6 months, which was only 9.1% for the pharmacotherapy group. Three years of SLIT as an adjunct to pharmacotherapy resulted in reduction of both the duration and dose of ICSs and successful discontinuation of ICSs along with improvement in lung functions in HDM-allergic children with asthma. [ABSTRACT FROM AUTHOR]

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Objective: The prevalence of asthma among children has been increasing in the United States and it is estimated that there are approximately 5 million children with asthma. This cross-sectional survey sought to estimate the prevalence of asthma and asthma symptoms and potential risk factors among children aged 16 and younger, in a largely rural population in the USA.Methods: This study was a telephone survey of 1500 households in the South Plains/Panhandle region of Texas. Parents of children were interviewed with a response rate of 64%. Having been diagnosed with asthma by a physician and a report of wheezing in the last 12 months were used as dependent variables in multivariate logistic regressions with several sociodemographic and environmental factors as potential confounders.Results: The age-adjusted prevalence of asthma and wheezing among children were approximately 15 and 18%, respectively. The prevalence of asthma was highest (20%) among children aged 11-16 (P < 0.001). Living in urban areas was associated significantly with asthma and wheezing. Non-Hispanic blacks reported significantly increased odds of asthma in their children (adjusted odds ratio (OR) = 2.04, 95%CI 1.02-4.08), whereas Mexican-Americans reported significantly reduced odds of asthma (adjusted OR = 0.48, 95%CI 0.29-0.78) and wheezing (adjusted OR = 0.58, 95%CI 0.37-0.89) in their children. The odds of asthma (adjusted OR = 1.78, 95%CI 1.09-2.92) and wheezing (adjusted OR = 2.45, 95%CI 1.52-3.95) was highest among children in the highest body mass index quartile. No significant association with pet ownership and exposure to second-hand smoke with asthma and wheezing was observed in this study.Conclusion: Urban residence, non-Hispanic black and Mexican-American race/ethnicity, and being overweight were significantly associated with the increased risk of asthma and/or wheezing. [ABSTRACT FROM AUTHOR]

Background-Few studies have evaluated the asthmatic airway in childhood. The aim of this study was to assess the histopathological changes occurring in the bronchi of children with moderate asthma using light and electron microscopy. Methods-Bronchial biopsy specimens from 10 children with moderate asthma (seven boys) of mean (SD) age 9.3 (3.8) years (range 5-14) were examined by light and electron microscopy. Patients had not had a respiratory infection for at least one month and they had not been treated with steroids or sodium cromoglycate for four weeks before the study. Bronchoscopy was performed under general anaesthesia using a Karl Storz rigid paediatric bronchoscope. Biopsy materials were stained with uracyl acetate and lead citrate and evaluated under a Zeiss-10) electron microscope and light microscope. Results-The most important finding was thickening and hyalinisation of the basement membrane in nine patients. The ciliated epithelial cells showed loss of cilia in some cases. Overactive fibroblasts were consistently found. Six patients had degranulating mast cells and lymphocyte infiltration in the submucosa. Eosinophils were seen in only one biopsy sample. Conclusion-Children with moderate asthma develop bronchial inflammation similar to the reaction observed in adults. However, in our study the inflammation was rich in lymphocytes rather than eosinophils. [ABSTRACT FROM AUTHOR]

Rationale: Severe acute paediatric asthma may require treatment escalation beyond systemic corticosteroids, inhaled bronchodilators and low-flow oxygen. Current large asthma datasets report parenteral therapy only., Objectives: To identify the use and type of escalation of treatment in children presenting to hospital with acute severe asthma., Methods: Retrospective cohort study of children with an emergency department diagnosis of asthma or wheeze at 18 Australian and New Zealand hospitals. The main outcomes were use and type of escalation treatment (defined as any of intensive care unit admission, nebulised magnesium, respiratory support or parenteral bronchodilator treatment) and hospital length of stay (LOS)., Measurements and Main Results: Of 14 029 children (median age 3 (IQR 1-3) years; 62.9% male), 1020 (7.3%, 95% CI 6.9% to 7.7%) had treatment escalation. Children with treatment escalation had a longer LOS (44.2 hours, IQR 27.3-63.2 hours) than children without escalation 6.7 hours, IQR 3.5-16.3 hours; p<0.001). The most common treatment escalations were respiratory support alone (400; 2.9%, 95% CI 2.6% to 3.1%), parenteral bronchodilator treatment alone (380; 2.7%, 95% CI 2.5% to 3.0%) and both respiratory support and parenteral bronchodilator treatment (209; 1.5%, 95% CI 1.3% to 1.7%). Respiratory support was predominantly nasal high-flow therapy (99.0%). The most common intravenous medication regimens were: magnesium alone (50.4%), magnesium and aminophylline (24.6%) and magnesium and salbutamol (10.0%)., Conclusions: Overall, 7.3% children with acute severe asthma received some form of escalated treatment, with 4.2% receiving parenteral bronchodilators and 4.3% respiratory support. There is wide variation treatment escalation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Machine learning (ML) holds great potential for predicting clinical outcomes in heterogeneous chronic respiratory diseases (CRD) affecting children, where timely individualised treatments offer opportunities for health optimisation. This paper identifies rate-limiting steps in ML prediction model development that impair clinical translation and discusses regulatory, clinical and ethical considerations for ML implementation. A scoping review of ML prediction models in paediatric CRDs was undertaken using the PRISMA extension scoping review guidelines. From 1209 results, 25 articles published between 2013 and 2021 were evaluated for features of a good clinical prediction model using the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) guidelines.Most of the studies were in asthma (80%), with few in cystic fibrosis (12%), bronchiolitis (4%) and childhood wheeze (4%). There were inconsistencies in model reporting and studies were limited by a lack of validation, and absence of equations or code for replication. Clinician involvement during ML model development is essential and diversity, equity and inclusion should be assessed at each step of the ML pipeline to ensure algorithms do not promote or amplify health disparities among marginalised groups. As ML prediction studies become more frequent, it is important that models are rigorously developed using published guidelines and take account of regulatory frameworks which depend on model complexity, patient safety, accountability and liability., Competing Interests: Competing interests: GD reports personal fees from Chiesi Ltd and Vertex Pharmaceuticals, outside the submitted work. SS reports personal fees from Chiesi Pharmaceuticals and the European Respiratory Society, and leadership roles for the American Thoracic Society PFT committee, and the European Respiratory Society: Global Lung Function Initiative Network. NS reports Elsevier paediatric pathology textbook royalties (author), outside the submitted work., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Background: Hospitalisation for bronchiolitis is a risk factor for asthma and impaired lung function during childhood, but outcomes in young adults are poorly described. Our primary aim was to study the prevalence of asthma and atopy, and lung function at 17-20 years of age after bronchiolitis in infancy and, secondarily, the impact of viral aetiology (respiratory syncytial virus (RSV) vs non-RSV) and sex on these outcomes., Methods: This Norwegian cohort study enrolled 225 young adults hospitalised for bronchiolitis in infancy during 1996-2001 and 167 matched control subjects. The follow-up included questionnaires for asthma and examinations of lung function and atopy. Outcomes were analysed by mixed effects regressions., Results: Current asthma was more frequent in the postbronchiolitis group versus the control group: 25.1% (95% CI 19.0% to 31.2%) vs 13.1% (95% CI 7.9% to 18.2%), but not atopy: 44.3% (95% CI 37.1% to 51.5%) vs 48.2% (95% CI 40.5% to 55.8%), adjusted predicted proportions (95% CIs). Asthma prevalence did not differ between the RSV group and the non-RSV group: 24.0% (95% CI 16.1% to 32.0%) vs 23.8% (95% CI 12.8% to 34.7%) nor between sexes. Forced expiratory volume in 1 s (FEV 1 ), the ratio FEV 1 /forced vital capacity (FVC), and forced expiratory flow between 25% and 75% of FVC, were lower in the postbronchiolitis group., Conclusion: Young adults hospitalised for bronchiolitis had higher prevalence of asthma, but not atopy, and a more obstructive lung function pattern than control subjects. The asthma prevalence was high after both RSV bronchiolitis and non-RSV bronchiolitis, and there was no difference between sexes. Bronchiolitis in infancy is associated with respiratory morbidity persisting into young adulthood., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Uncontrolled asthma is associated with substantial morbidity. While fast-acting bronchodilators provide quick relief from asthma symptoms, their use as rescue fails to address the underlying inflammation. Combining a short-acting beta 2 -agonist, such as albuterol (salbutamol), with an inhaled corticosteroid, such as budesonide, in a single inhaler as rescue therapy could help control both bronchoconstriction and inflammation, and reduce the risk of asthma exacerbations., Methods and Analysis: The Phase 3 MANDALA study was designed to determine the efficacy of albuterol in combination with budesonide (albuterol/budesonide 180/160 µg or 180/80 µg, two actuations of 90/80 µg or 90/40 µg, respectively) versus albuterol (180 µg, two actuations of 90 µg) as rescue therapy in adult, adolescent and paediatric patients with moderate-to-severe asthma. This event-driven study enrolled symptomatic patients (3000 adults/adolescents and 100 children aged 4-11 years) who experienced ≥1 severe asthma exacerbation in the previous year and were receiving maintenance therapy for ≥3 months prior to study entry. The primary efficacy endpoint was time-to-first severe asthma exacerbation., Ethics and Dissemination: The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki, and that are consistent with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use and Good Clinical Practice and the applicable regulatory requirements., Trial Registration: NCT03769090., Competing Interests: Competing interests: BEC is an advisor for, has received consultancy fees from, and is on the speakers’ bureau for AstraZeneca, Boehringer Ingelheim, Genentech, GlaxoSmithKline, Novartis, Regeneron and Sanofi Genzyme. FCA is an employee of Avillion. LR was an employee of Avillion when the study was conducted. EJ and CC are employees of AstraZeneca. AP reports grants, personal fees, non-financial support and other from GlaxoSmithKline, Boehringer Ingelheim, Chiesi Farmaceutici, TEVA, grants, personal fees and non-financial support from AstraZeneca and Menarini, personal fees, non-financial support and other from Mundipharma, Zambon, Novartis and Sanofi/Regeneron, personal fees from Roche and Edmondpharma and grants from Fondazione Maugeri and Fondazione Chiesi, outside the submitted work., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Abstract Background Asthma is a chronic inflammatory disease of the airways but recent studies have shown that alveoli are also subject to pathophysiological changes. This study was undertaken to compare hydrogen peroxide (H2O2) concentrations in different parts of the lung using a new technique of fractioned breath condensate sampling. Methods In 52 children (9-17 years, 32 asthmatic patients, 20 controls) measurements of exhaled nitric oxide (FENO), lung function, H2O2 in exhaled breath condensate (EBC) and the asthma control test (ACT) were performed. Exhaled breath condensate was collected in two different fractions, representing mainly either the airways or the alveoli. H2O2 was analysed in the airway and alveolar fractions and compared to clinical parameters. Results The exhaled H2O2 concentration was significantly higher in the airway fraction than in the alveolar fraction comparing each single pair (p = 0.003, 0.032 and 0.040 for the whole study group, the asthmatic group and the control group, respectively). Asthma control, measured by the asthma control test (ACT), correlated significantly with the H2O2 concentrations in the alveolar fraction (r = 0.606, p = 0.004) but not with those in the airway fraction in the group of children above 12 years. FENO values and lung function parameters did not correlate to the H2O2 concentrations of each fraction. Conclusion The new technique of fractionated H2O2 measurement may differentiate H2O2 concentrations in different parts of the lung in asthmatic and control children. H2O2 concentrations of the alveolar fraction may be related to the asthma control test in children.