Preschool Wheeze Research Articles

Clinical and bronchial parameters associated with the exacerbation frequency of severe preschool wheezers

Clinical and bronchial parameters associated with the exacerbation frequency of severe preschool wheezers

17q21 Variants Disturb Mucosal Host Defense in Childhood Asthma.

Rationale: The strongest genetic risk factor for childhood-onset asthma, the 17q21 locus, is associated with increased viral susceptibility and disease-promoting processes.Objectives: To identify biological targets underlying the escalated viral susceptibility associated with the clinical phenotype mediated by the 17q21 locus.Methods: Genome-wide transcriptome analysis of nasal brush samples from 261 children (78 healthy, 79 with wheezing at preschool age, 104 asthmatic) within the ALLIANCE (All-Age-Asthma) cohort, with a median age of 10.0 (range, 1.0-20.0) years, was conducted to explore the impact of their 17q21 genotype (SNP rs72163891). Concurrently, nasal secretions from the same patients and visits were collected, and high-sensitivity mesoscale technology was employed to measure IFN protein levels.Measurements and Main Results: This study revealed that the 17q21 risk allele induces a genotype- and asthma/wheeze phenotype-dependent enhancement of mucosal GSDMB expression as the only relevant 17q21-encoded gene in children with preschool wheeze. Increased GSDMB expression correlated with the activation of a type-1 proinflammatory, cell-lytic immune, and natural killer signature, encompassing key genes linked to an IFN type-2-signature (IFNG, CXCL9, CXCL10, KLRC1, CD8A, GZMA). Conversely, there was a reduction in IFN type 1 and type 3 expression signatures at the mRNA and protein levels.Conclusions: This study demonstrates a novel disease-driving mechanism induced by the 17q21 risk allele. Increased mucosal GSDMB expression is associated with a cell-lytic immune response coupled with compromised airway immunocompetence. These findings suggest that GSDMB-related airway cell death and perturbations in the mucosal IFN signature account for the increased vulnerability of 17q21 risk allele carriers to respiratory viral infections during early life, opening new options for future biological interventions.The All-Age-Asthma (ALLIANCE) cohort is registered at www.clinicaltrials.gov (pediatric arm, NCT02496468).

Inflammatory related plasma proteins involved in acute preschool wheeze.

Preschool wheeze is a risk factor for asthma development. However, the molecular mechanism behind a wheezing episode is not well understood. Our aims were to assess the association of plasma proteins with acute preschool wheeze and to study the proteins with differential expression at the acute phase at revisit after 3months. Additionally, to investigate the relationship between protein expression and clinical parameters. We measured 92 inflammatory proteins in plasma and clinical parameters from 145 children during an episode of preschool wheeze (PW) and at the revisit after 3months (PW-R, n=113/145) and 101 healthy controls (HC) aged 6-48months in the GEWAC cohort using the antibody-mediated proximity extension-based assay (Olink Proteomics, Uppsala). Of the 74 analysed proteins, 52 were differentially expressed between PW and HC. The expression profiles of the top 10 proteins, Oncostatin M (OSM), IL-10, IL-6, Fibroblast growth factor 21 (FGF21), AXIN1, CXCL10, SIRT2, TNFSF11, Tumour necrosis factor β (TNF-β) and CASP8, could almost entirely separate PW from HC. Five out of 10 proteins were associated with intake of oral corticosteroids (OCS) 24h preceding blood sampling (OSM, CASP8, IL-10, TNF-β and CXCL10). No differences in protein expression were seen between PWs with or without OCS in comparison to HC. At the revisit after 3months, differential protein expressions were still seen between PW-R and HC for three (IL-10, SIRT2 and FGF21) of the 10 proteins. Our results contribute to unravelling potential immunopathological pathways shared between preschool wheeze and asthma.

From preschool wheezing to asthma: Environmental determinants.

Wheezing is common among preschool children, representing a group of highly heterogeneous conditions with varying natural history. Several phenotypes of wheezing have been proposed to facilitate the identification of young children who are at risk of subsequent development of asthma. Epidemiological and immunological studies across different populations have revealed the key role of environmental factors in influencing the progression from preschool wheezing to childhood asthma. Significant risk factors include severe respiratory infections, allergic sensitization, and exposure to tobacco smoke. In contrast, a farming/rural environment has been linked to asthma protection in both human and animal studies. Early and intense exposures to microorganisms and microbial metabolites have been demonstrated to alter host immune responses to allergens and viruses, thereby driving the trajectory away from wheezing illness and asthma. Ongoing clinical trials of candidate microbes and microbial products have shown promise in shaping the immune function to reduce episodes of viral-induced wheezing. Moreover, restoring immune training may be especially important for young children who had reduced microbial exposure due to pandemic restrictions. A comprehensive understanding of the role of modifiable environmental factors will pave the way for developing targeted prevention strategies for preschool wheezing and asthma.

Recurrence of wheeze in preschool aged children: a retrospective cohort study in primary care

Abstract Background Approximately 1 in 7 children with wheeze will be admitted to hospital for treatment, often leading to repeat visits to emergency departments and hospital admissions. The UK lags other wealthy countries in the management of preschool wheeze and has amongst the highest rates of asthma deaths in Europe. There were reports that wheeze and asthma admissions to hospitals fell during the Covid-19 pandemic lockdowns, but the changing community incidence is unknown. We aimed to report the changing incidence of recurrent wheeze across the Covid-19 pandemic. Methods Using data from the UK Clinical Practice Datalink, a nationally representative sample of the UK population, we followed a cohort of 57,603 children aged 1-5 years who consulted their general practitioner with their first wheeze attack between January 2009 and July 2020. We calculated the incidence of wheezing recurrence by calendar year. We will calculate the incidence rate ratios for recurrent wheeze by level of area-based deprivation whilst accounting for potential confounders including child age, sex, birth weight, gestation age, ethnicity, comorbidities, bronchiolitis, maternal smoking, maternal asthma, and maternal age at birth. Results The incidence of recurrent preschool wheeze remained stable across the Covid-19 pandemic (e.g., 2019: 27% vs 2020: 23%) even though total wheeze events in general practice fell from 3,135 in 2019 to 1,280 in 2020. Conclusions Around a quarter of children with wheeze have repeat visits to the GP. Our next steps are to identify preventive actions to reduce the risks of recurrent wheeze for children presenting with their first wheeze attack in primary care. Key messages • Around a quarter of children will have a repeat visit to the GP for wheeze within the first year after their initial wheeze attack. • The incidence of recurrent preschool wheeze remained stable across the Covid-19 pandemic.

Increased breath naphthalene in children with asthma and wheeze of the All Age Asthma Cohort (ALLIANCE)

Exhaled breath contains numerous volatile organic compounds (VOCs) known to be related to lung disease like asthma. Its collection is non-invasive, simple to perform and therefore an attractive method for the use even in young children. We analysed breath in children of the multicenter All Age Asthma Cohort (ALLIANCE) to evaluate if ‘breathomics’ have the potential to phenotype patients with asthma and wheeze, and to identify extrinsic risk factors for underlying disease mechanisms. A breath sample was collected from 142 children (asthma: 51, pre-school wheezers: 55, healthy controls: 36) and analysed using gas chromatography–mass spectrometry (GC/MS). Children were diagnosed according to Global Initiative for Asthma guidelines and comprehensively examined each year over up to seven years. Forty children repeated the breath collection after 24 or 48 months. Most breath VOCs differing between groups reflect the exposome of the children. We observed lower levels of lifestyle-related VOCs and higher levels of the environmental pollutants, especially naphthalene, in children with asthma or wheeze. Naphthalene was also higher in symptomatic patients and in wheezers with recent inhaled corticosteroid use. No relationships with lung function or TH2 inflammation were detected. Increased levels of naphthalene in asthmatics and wheezers and the relationship to disease severity could indicate a role of environmental or indoor air pollution for the development or progress of asthma. Breath VOCs might help to elucidate the role of the exposome for the development of asthma. The study was registered at ClinicalTrials.gov (NCT02496468).

Predictors of asthma control differ from predictors of asthma attacks in children: The Swiss Paediatric Airway Cohort.

It is unclear if predictors of asthma attacks are the same as those of asthma symptom control in children. We evaluated predictors for these two outcomes in a clinical cohort study. The Swiss Paediatric Airway Cohort (SPAC) is a multicentre prospective clinical cohort of children referred to paediatric pulmonologists. This analysis included 516 children (5-16 years old) diagnosed with asthma. At baseline, we collected sociodemographic information, symptoms, personal and family history and environmental exposures from a parental baseline questionnaire, and treatment and test results from hospital records. Outcomes were assessed 1 year later by parental questionnaire: asthma control in the last 4 weeks as defined by GINA guidelines, and asthma attacks defined as any unscheduled visit for asthma in the past year. We used logistic regression to identify and compare predictors for suboptimal asthma control and asthma attacks. At follow-up, 114/516 children (22%), reported suboptimal asthma control, and 114 (22%) an incident asthma attack. Only 37 (7%) reported both. Suboptimal asthma control was associated with poor symptom control at baseline (e.g. ≥1 night wheeze/week OR: 3.2; 95% CI: 1.7-6), wheeze triggered by allergens (2.2; 1.4-3.3), colds (2.3; 1.4-3.6) and exercise (3.2; 2-5), a more intense treatment at baseline (2.4; 1.3-4.4 for Step 3 vs. 1), history of preschool (2.6; 1.5-4.4) and persistent wheeze (2; 1.4-3.2), and exposure to tobacco smoke (1.7; 1-2.6). Incident asthma attacks were associated with previous episodes of severe wheeze (2; 1.2-3.3) and asthma attacks (2.8; 1.6-5 for emergency care visits), younger age (0.8; 0.8-0.9 per 1 year) and non-Swiss origin (0.3; 0.2-0.5 for Swiss origin). Lung function, exhaled nitric oxide (FeNO) and allergic sensitization at baseline were not associated with control or attacks. Children at risk of long-term suboptimal asthma control differ from those at risk of attacks. Prediction tools and preventive efforts should differentiate these two asthma outcomes.

Recent trends in asthma diagnosis, preschool wheeze diagnosis and asthma exacerbations in English children and adolescents: a SABINA Jr study

BackgroundAsthma-related burden remains poorly characterised in children in the UK. We quantified recent trends in asthma prevalence and burden in a UK population-based cohort (1‒17-year-olds).MethodsThe Clinical Practice Research Datalink Aurum...

Basic clinical management of preschool wheeze.

Preschool wheeze is very common and often difficult to treat. Most children do not require any investigations; only a detailed history and physical examination to ensure an alternative diagnosis is not being missed; and the differential diagnosis, and hence investigation protocols for the child in whom a major illness is suspected, shows geographical variation. The pattern of symptoms may be divided into episodic viral and multiple trigger to guide treatment, but the pattern of symptoms must be re-assessed regularly. However, symptom patterns are a poor guide to underlying pathology. Attention to the proper use of spacers, and adverse environmental exposures such as tobacco smoke exposure, is essential. There are no disease-modifying therapies, so therapy is symptomatic. This paper reviews recent advances in treatment, including new data on the place of leukotriene receptor antagonists, prednisolone for acute attacks of wheeze, and antibiotics, based on new attempts to understand the underlying pathology in a way that is clinically practical.

Bronchodilator response by interrupter technique to guide management of preschool wheeze

ObjectiveWe examined relationships between clinical features and pulmonary function before and after inhaled corticosteroid (ICS) treatment in wheezy preschool children, and specifically, whether measuring bronchodilator response (BDR) could predict benefit...

Bacterial Microbiota of Asthmatic Children and Preschool Wheezers’ Airways—What Do We Know?

Asthma is the most chronic pulmonary disease in pediatric population, and its etiopathology still remains unclear. Both viruses and bacteria are suspected factors of disease development and are responsible for its exacerbation. Since the launch of The Human Microbiome Project, there has been an explosion of research on microbiota and its connection with various diseases. In our review, we have collected recent data about both upper- and lower-airway bacterial microbiota of asthmatic children. We have also included studies regarding preschool wheezers, since asthma diagnosis in children under 5 years of age remains challenging due to the lack of an objective tool. This paper indicates the need for further studies of microbiome and asthma, as in today’s knowledge, there is no particular bacterium that discriminates the asthmatics from the healthy peers and can be used as a potential biological factor in the disease prevalence and treatment.

Pre-school wheeze hospital presentations: A demographic profile and review of clinical management.

Pre-school wheeze is a common hospital presentation in Australasia. The aim of this study was to describe the regional hospital presentation and cost of pre-school wheeze. Audit of children diagnosed with pre-school wheeze at two hospitals in Auckland, New Zealand from October 2017 to September 2019. Guideline adherence was determined. One hundred and ninety-two children made 247 pre-school wheeze hospital presentations. Pre-school wheeze accounted for a larger proportion of acute hospital presentations for Māori versus non-Māori children (rate ratio 1.76, 95% confidence intervals 1.32-2.31). Hospital representations with pre-school wheeze occurred in 38/192 (20%) children. The proportion with a pre-school wheeze representation was larger for Māori than non-Māori (30% vs. 16%, P = 0.02). Pre-school wheeze event median length of stay increased as household deprivation increased (P = 0.01). Clinical severity of 247 pre-school wheeze episodes was mild (n = 64, 26%), moderate (n = 153, 62%) and severe (n = 30, 12%). Of 244 episodes, inhaled bronchodilators only were given for 149 (61%), oxygen for 54 (22%) and intravenous treatment for 41 (17%). Hospital guideline use was evident in 164/247 (66%) episodes. Neither clinical severity nor treatment intensity varied with child sex, age or ethnicity or household deprivation. The estimated median (interquartile range) direct medical costs of each pre-school wheeze episode were NZ$1279 (NZ$774-2158). In Auckland, pre-school wheeze accounts for a larger proportion of acute hospital presentations for Māori compared with non-Māori and Māori children have increased odds of pre-school wheeze readmissions. Length of hospital stay for pre-school wheeze episodes increased with household deprivation. In this audit pre-school wheeze guideline adherence was poor.

The ADEM2 project: early pathogenic mechanisms of preschool wheeze and a randomised controlled trial assessing the gain in health and cost-effectiveness by application of the breath test for the diagnosis of asthma in wheezing preschool children

BackgroundThe prevalence of asthma-like symptoms in preschool children is high. Despite numerous efforts, there still is no clinically available diagnostic tool to discriminate asthmatic children from children with transient wheeze at preschool age. This leads to potential overtreatment of children outgrowing their symptoms, and to potential undertreatment of children who turn out to have asthma. Our research group developed a breath test (using GC-tof–MS for VOC-analysis in exhaled breath) that is able to predict a diagnosis of asthma at preschool age. The ADEM2 study assesses the improvement in health gain and costs of care with the application of this breath test in wheezing preschool children.MethodsThis study is a combination of a multi-centre, parallel group, two arm, randomised controlled trial and a multi-centre longitudinal observational cohort study. The preschool children randomised into the treatment arm of the RCT receive a probability diagnosis (and corresponding treatment recommendations) of either asthma or transient wheeze based on the exhaled breath test. Children in the usual care arm do not receive a probability diagnosis. Participants are longitudinally followed up until the age of 6 years. The primary outcome is disease control after 1 and 2 years of follow-up. Participants of the RCT, together with a group of healthy preschool children, also contribute to the parallel observational cohort study developed to assess the validity of alternative VOC-sensing techniques and to explore numerous other potential discriminating biological parameters (such as allergic sensitisation, immunological markers, epigenetics, transcriptomics, microbiomics) and the subsequent identification of underlying disease pathways and relation to the discriminative VOCs in exhaled breath.DiscussionThe potential societal and clinical impact of the diagnostic tool for wheezing preschool children is substantial. By means of the breath test, it will become possible to deliver customized and high qualitative care to the large group of vulnerable preschool children with asthma-like symptoms. By applying a multi-omics approach to an extensive set of biological parameters we aim to explore (new) pathogenic mechanisms in the early development of asthma, creating potentially interesting targets for the development of new therapies.Trial registrationNetherlands Trial Register, NL7336, Date registered 11–10-2018.

Pediatric Asthma: Where Has Montelukast Gone?

At its introduction in the management of pediatric asthma, montelukast was regarded as a potentially revolutionary drug due to its mechanism of action and easy clinical applicability. Nevertheless, its use in daily practice and evidence from clinical trials have shown that, rather than a radical change in the approach to asthmatic children, montelukast more likely represents a second-line medication that is useful when inhaled steroids alone fail in providing adequate symptom control. Furthermore, increasingly reported side effects have raised concerns regarding its safety. In the last decade, several studies have tried to better define the strengths and drawbacks of montelukast both in preschool wheezing and school-age asthma. The present review summarizes the literature published on this topic since 2010, highlighting the often-controversial results and the unanswered questions regarding the role of montelukast in pediatric asthma. Moreover, advances in the understanding of the mechanisms of action of montelukast are reported. The main finding emerging from the present analysis is that montelukast application is likely to be useful in a subset of asthmatic children rather than in large groups of patients. Future studies should focus on the identification of biomarkers able to predict which patients will benefit from montelukast to achieve a more tailored prescription.

ERS International Congress 2022: highlights from the Paediatrics Assembly.

This review has been prepared by the Early Career Members and Chairs of the European Respiratory Society (ERS) Assembly 7: Paediatrics. We here summarise the highlights of the advances in paediatric respiratory research presented at the ERS International Congress 2022. The eight scientific groups of this Assembly cover a wide range of research areas, including respiratory physiology and sleep, asthma and allergy, cystic fibrosis (CF), respiratory infection and immunology, neonatology and intensive care, respiratory epidemiology, bronchology, and lung and airway developmental biology. Specifically, we report on abstracts presented at the congress on the effect of high altitude on sleep, sleep disorders, the hypoxic challenge test, and measurements of ventilation inhomogeneity. We discuss prevention of preschool wheeze and asthma, and new asthma medications. In children with CF, we describe how to monitor the effect of CF transmembrane conductance regulator modulator therapy. We present respiratory manifestations and chronic lung disease associated with common variable immunodeficiency. Furthermore, we discuss how to monitor respiratory function in neonatal and paediatric intensive care units. In respiratory epidemiology, we present the latest news from population-based and clinical cohort studies. We also focus on innovative and interventional procedures for the paediatric airway, such as cryotherapy. Finally, we stress the importance of better understanding the molecular mechanisms underlying normal and abnormal lung development.

Risk Factors Affecting Development and Persistence of Preschool Wheezing: Consensus Document of the Emilia-Romagna Asthma (ERA) Study Group.

Wheezing at preschool age (i.e., before the age of six) is common, occurring in about 30% of children before the age of three. In terms of health care burden, preschool children with wheeze show double the rate of access to the emergency department and five times the rate of hospital admissions compared with school-age asthmatics. The consensus document aims to analyse the underlying mechanisms involved in the pathogenesis of preschool wheezing and define the risk factors (i.e., allergy, atopy, infection, bronchiolitis, genetics, indoor and outdoor pollution, tobacco smoke exposure, obesity, prematurity) and the protective factors (i.e., probiotics, breastfeeding, vitamin D, influenza vaccination, non-specific immunomodulators) associated with the development of the disease in the young child. A multidisciplinary panel of experts from the Emilia-Romagna Region, Italy, addressed twelve key questions regarding managing preschool wheezing. Clinical questions have been formulated by the expert panel using the PICO format (Patients, Intervention, Comparison, Outcomes). Systematic reviews have been conducted on PubMed to answer these specific questions and formulate recommendations. The GRADE approach has been used for each selected paper to assess the quality of the evidence and the degree of recommendations. Based on a panel of experts and extensive updated literature, this consensus document provides insight into the pathogenesis, risk and protective factors associated with the development and persistence of preschool wheezing. Undoubtedly, more research is needed to improve our understanding of the disease and confirm the associations between certain factors and the risk of wheezing in early life. In addition, preventive strategies must be promoted to avoid children's exposure to risk factors that may permanently affect respiratory health.

Probability of successful inhaled corticosteroids cessation in preschool wheezers: a predictive score.

Predictors of less successful ICS cessation were the following: perinatal oxygen use, allergic rhinitis, blood eosinophil count > 500 cell/mm3, and previous ICS use > 6months. A simple predictive score developed in this study may help general practitioners to be more confident in making a decision regarding the discontinuation of ICS after initial therapeutic trials. • Early allergic sensitization is associated with reduced chances of inhaled corticosteroid cessation at school age. • Prolonged ICS is associated with the emergence of adverse effect and discontinuing too early can result in recurrence symptoms. • Requirement of oxygen support within 7 days after birth in term neonate is a postnatal factor associated with less successful ICS cessation. • We propose a simple predictive tool with easily available clinical parameters (perinatal oxygen use, allergic rhinitis, blood eosinophil count, parental asthma history, and duration of previous ICS use) to determine the timing of inhalational corticosteroid cessation in preschool wheezers.

Bronchial Remodeling-based Latent Class Analysis Predicts Exacerbations in Severe Preschool Wheezers.

Rationale: Children with preschool wheezing represent a very heterogeneous population with wide variability regarding their clinical, inflammatory, obstructive, and/or remodeling patterns. We hypothesized that assessing bronchial remodeling would help clinicians to better characterize severe preschool wheezers. Objectives: The main objective was to identify bronchial remodeling-based latent classes of severe preschool wheezers. Secondary objectives were to compare cross-sectional and longitudinal clinical and biological data between classes and to assess the safety of bronchoscopy. Methods: This double-center prospective study (NCT02806466) included severe preschool wheezers (1-5 yr old) requiring fiberoptic bronchoscopy. Bronchial remodeling parameters (i.e., epithelial integrity, reticular basement membrane [RBM] thickness, mucus gland, fibrosis and bronchial smooth muscle [BSM] areas, the density of blood vessels, and RBM-BSM distance) were assessed and evaluated by latent class analysis. An independent cohort of severe preschool wheezers (NCT04558671) was used to validate our results. Measurements and Main Results: Fiberoptic bronchoscopy procedures were well tolerated. A two-class model was identified: Class BR1 was characterized by increased RBM thickness, normalized BSM area, the density of blood vessels, decreased mucus gland area, fibrosis, and RBM-BSM distance compared with Class BR2. No significant differences were found between classes in the year before fiberoptic bronchoscopy. By contrast, Class BR1 was associated with a shorter time to first exacerbation and an increased risk of both frequent (3 or more) and severe exacerbations during the year after bronchoscopy in the two cohorts. Conclusions: Assessing bronchial remodeling identified severe preschool wheezers at risk of frequent and severe subsequent exacerbations with a favorable benefit to risk ratio.

Management of Preschool Wheezing: Guideline from the Emilia-Romagna Asthma (ERA) Study Group.

Preschool wheezing should be considered an umbrella term for distinctive diseases with different observable and measurable phenotypes. Despite many efforts, there is a large gap in knowledge regarding management of preschool wheezing. In order to fill this lack of knowledge, the aim of these guidelines was to define management of wheezing disorders in preschool children (aged up to 5 years). A multidisciplinary panel of experts of the Emilia-Romagna Region, Italy, addressed twelve different key questions regarding the management of preschool wheezing. Clinical questions have been formulated by the expert panel using the PICO format (Patients, Intervention, Comparison, Outcomes) and systematic reviews have been conducted on PubMed to answer these specific questions, with the aim of formulating recommendations. The GRADE approach has been used for each selected paper, to assess the quality of the evidence and the degree of recommendations. These guidelines represent, in our opinion, the most complete and up-to-date collection of recommendations on preschool wheezing to guide pediatricians in the management of their patients, standardizing approaches. Undoubtedly, more research is needed to find objective biomarkers and understand underlying mechanisms to assess phenotype and endotype and to personalize targeted treatment.

Lung lavage inflammatory patterns and pathogen profiles in preschool children with problematic wheeze

Practicing clinicians regularly encounter the preschool child with intermittent episodes of wheeze. Preschool wheezing episodes account for a large burden of unscheduled ambulatory care visits and hospitalizations across the globe. Recurrent episodes of acute wheeze are often referred to as “problematic.” However, guidelines to treat these children are not based on solid evidence. There are few clinical trials applicable to real-world practice to direct treatment of problematic wheeze. 1 Bacharier LB Guilbert TW Mauger DT Boehmer S Beigelman A Fitzpatrick AM et al. Early administration of azithromycin and prevention of severe lower respiratory tract illnesses in preschool children with a history of such illnesses: a randomized clinical trial. JAMA. 2015; 314: 2034-2044 Crossref PubMed Scopus (193) Google Scholar , 2 Fitzpatrick AM Jackson DJ Mauger DT Boehmer SJ Phipatanakul W Sheehan WJ et al. Individualized therapy for persistent asthma in young children. J Allergy Clin Immunol. 2016; 138 (1608-1618.e12) Abstract Full Text Full Text PDF PubMed Scopus (164) Google Scholar , 3 Wallace A Sinclair O Shepherd M Neutze J Trenholme A Tan E et al. Impact of oral corticosteroids on respiratory outcomes in acute preschool wheeze: a randomised clinical trial. Arch Dis Child. 2021; 106: 339-344 Crossref PubMed Scopus (4) Google Scholar A helpful study by Bacharier et al 1 Bacharier LB Guilbert TW Mauger DT Boehmer S Beigelman A Fitzpatrick AM et al. Early administration of azithromycin and prevention of severe lower respiratory tract illnesses in preschool children with a history of such illnesses: a randomized clinical trial. JAMA. 2015; 314: 2034-2044 Crossref PubMed Scopus (193) Google Scholar found that a burst of azithromycin given early during an episode of virus-triggered wheeze in preschool children with a history of recurrent wheeze was effective in preventing the progression of symptoms. Azithromycin treatment was effective in not only the first but subsequent wheeze episodes over 1 year. Although guidelines on the management of preschool wheeze have been published, inconsistencies prevail as to the endorsement of azithromycin to treat acute exacerbations.