Improvement in Lung Clearance Index and Chest Computed Tomography Scores with Elexacaftor/Tezacaftor/Ivacaftor Treatment in People with Cystic Fibrosis Aged 12 Years and Older - The RECOVER Trial.

Rationale: Clinical trials have shown that use of elexacaftor/tezacaftor/ivacaftor (ETI) is associated with improvements in sweat chloride, pulmonary function, nutrition, and quality of life in people with cystic fibrosis (CF). Little is known about the impact of ETI on ventilation inhomogeneity and lung structure. Objectives: RECOVER is a real-world study designed to measure the impact of ETI in people with CF. The primary endpoints were lung clearance (lung clearance index; LCI2.5) and FEV1. Secondary endpoints included spirometry-controlled chest computed tomography (CT) scores. Methods: The study was conducted in seven sites in Ireland and the United Kingdom. Participants ages 12 years and older who were homozygous for the F508del mutation (F508del/F508del) or heterozygous for F508del and a minimum-function mutation (F508del/MF) were recruited before starting ETI and were followed up over 12 months. LCI2.5 was measured using nitrogen multiple breath washout (MBW) at baseline and at 6 and 12 months. Spirometry was performed as per the criteria of the American Thoracic Society and the European Respiratory Society. Spirometry-controlled chest CT scans were performed at baseline and at 12 months. CT scans were scored using the Perth Rotterdam Annotated Grid Morphometric Analysis (PRAGMA) system. Other outcome measures include weight, height, Cystic Fibrosis Quality of Life Questionnaire-Revised (CFQ-R), and sweat chloride. Measurements and Main Results: One hundred seventeen people with CF ages 12 and older were recruited to the study. Significant improvements were seen in LCI scores (-2.5; 95% confidence interval [CI], -3.0, -2.0) and in the percents predicted for FEV1 (8.9; 95% CI, 7.0, 10.9), FVC (6.6; 95% CI, 4.9, 8.3), and forced expiratory flow between 25% and 75% of expired volume (12.4; 95% CI, 7.8, 17.0). Overall PRAGMA-CF scores reflecting airway disease improved significantly (-3.46; 95% CI, -5.23, -1.69). Scores for trapped air, mucus plugging, and bronchial wall thickening improved significantly, but bronchiectasis scores did not. Sweat chloride levels decreased in both F508del/F508del (-43.1; 95% CI, -47.4, -38.9) and F508del/MF (-42.8; 95% CI, -48.5, -37.2) groups. Scores on the Respiratory Domain of the CFQ-R improved by 14.2 points (95% CI, 11.3, 17.2). At 1 year, sweat chloride levels were significantly lower for the F508del/F508del group compared with scores for the F508del/MF group (33.93 vs. 53.36, P < 0.001). Conclusions: ETI is associated with substantial improvements in LCI2.5, spirometry, and PRAGMA-CF CT scores in people with CF ages 12 years and older. ETI led to improved nutrition and quality of life. People in the F508del/F508del group had significantly lower sweat chloride on ETI treatment compared with the F508del/MF group. Clinical trial registered with www.clinicaltrials.gov (NCT04602468).

The clinical impact of Lumacaftor-Ivacaftor on structural lung disease and lung function in children aged 6-11 with cystic fibrosis in a real-world setting.

BACKGROUND: Data from clinical trials of lumacaftor-ivacaftor (LUM-IVA) demonstrate improvements in lung clearance index (LCI) but not in FEV1 in children with Cystic Fibrosis (CF) aged 6-11 years and homozygous for the Phe508del mutation. It is not known whether LUM/IVA use in children can impact the progression of structural lung disease. We sought to determine the real-world impact of LUM/IVA on lung structure and function in children aged 6-11 years. METHODS: This real-world observational cohort study was conducted across four paediatric sites in Ireland over 24-months using spirometry-controlled CT scores and LCI as primary outcome measures. Children commencing LUM-/IVA as part of routine care were included. CT scans were manually scored with the PRAGMA CF scoring system and analysed using the automated bronchus-artery (BA) method. Secondary outcome measures included rate of change of ppFEV1, nutritional indices and exacerbations requiring hospitalisation. RESULTS: Seventy-one participants were recruited to the study, 31 of whom had spirometry-controlled CT performed at baseline, and after one year and two years of LUM/IVA treatment. At two years there was a reduction from baseline in trapped air scores (0.13 to 0.07, p = 0.016), but an increase from baseline in the % bronchiectasis score (0.84 to 1.23, p = 0.007). There was no change in overall % disease score (2.78 to 2.25, p = 0.138). Airway lumen to pulmonary artery ratios (AlumenA ratio) were abnormal at baseline and worsened over the course of the study. In 28 participants, the mean annual change from baseline LCI2.5 (-0.055 (-0.61 to 0.50), p = 0.85) measurements over two years were not significant. Improvements from baseline in weight (0.10 (0.06 to 0.15, p < 0.0001), height (0.05 (0.02 to 0.09), p = 0.002) and BMI (0.09 (0.03 to 0.15) p = 0.005) z-scores were seen with LUM/IVA treatment. The mean annual change from baseline ppFEV1 (-2.45 (-4.44 to 2.54), p = 0.66) measurements over two years were not significant. CONCLUSION: In a real-world setting, the use of LUM/IVA over two years in children with CF aged 6-11 resulted in improvements in air trapping on CT but worsening in bronchiectasis scores. Our results suggest that LUM/IVA use in this age group improves air trapping but does not prevent progression of bronchiectasis over two years of treatment.

Sleep disordered breathing in children with Down syndrome in the Republic of Ireland.

Down syndrome (DS) is associated with a complex respiratory phenotype, including obstructive sleep apnea syndrome (OSAS). The study explored parent-reported prevalence and presentation of OSAS symptoms in children and adolescents with DS in Ireland. It also investigated treatment and compliance in those who have OSAS. A cross-sectional survey was distributed to parents registered with Down Syndrome Ireland (DSI) (n = 1,343). Data was collated and analyzed using SPSS v23. The response rate was 393 (29%). Twenty-one percent of parents (n = 84) reported a diagnosis of OSAS in their child. The parents of children reported as compliant with continuous positive airway pressure (CPAP) were more likely to report a perceived benefit of treatment (p = .018). Ninety-two percent (n = 212) of children without a formal diagnosis of OSAS had at least one symptom (median 4 symptoms) of the condition. This, the largest survey of parental reporting of OSAS or its symptoms, demonstrates a high reported prevalence of symptoms in children and adolescents with DS in Ireland without a formal diagnosis of OSAS, indicating under-recognition. In treated patients, perception of the benefit of CPAP correlated with reported compliance, suggesting a need for tailored education.

Multiorgan involvement and management in children with Down syndrome.

AIM: To review multiorgan involvement and management in children with Down syndrome (DS). METHODS: A literature review of articles from 1980 to 2019 using the MEDLINE interface of PubMed was performed using the following search terms- [Down syndrome] or [Trisomy 21] AND [Cardiology] or [Respiratory] or [neurodevelopment] or [epilepsy] or [musculoskeletal] or [immune system] or [haematological] or [endocrine] or [gastrointestinal] or [ophthalmological] or [Ear Nose Throat] or [dermatology] or [renal]. RESULTS: Congenital heart disease particularly septal defects occur in over 60% of infants with DS and 5%-34% of infants develop persistent pulmonary hypertension of the newborn irrespective of a diagnosis of congenital heart disease. Early recognition and management of aspiration, obstructive sleep apnoea and recurrent lower respiratory tract infections (LRTI) could reduce risk of developing pulmonary hypertension in later childhood. Children with DS have an increased risk of autistic spectrum disorder, attention deficit disorder and epilepsy particularly infantile spasms, which are associated with poor neurodevelopmental outcomes. Congenital anomalies of the gastrointestinal and renal system as well as autoimmune diseases, coeliac disease, arthropathy, thyroid dysfunction fold diabetes mellitus and dermatological conditions are more common. Hearing and visual anomalies are also well recognised association with DS (Table 1). CONCLUSION: Children with DS are at an increased risk of multiorgan comorbidities. Organ-specific health surveillance may provide holistic care for the children and families with DS throughout childhood.

A case of COVID-19 in a patient with a univentricular heart post total cavopulmonary connection (Fontan) surgery.

Coronavirus disease 2019 (COVID-19) has caused a global pandemic which has affected patients and healthcare systems around the world. Patients with underlying health conditions seem to be more severely affected. There are limited reports of patients with univentricular circulations and COVID 19; thus, we report a case of COVID-19 in a patient with a univentricular circulation.

Laps or lengths? The effects of different exercise programs on asthma control in children.

INTRODUCTION: Exercise training has been shown in numerous studies to improve lung function and asthma control in children with asthma. Swimming has been shown to be of benefit in children with asthma, but which form of exercise is better for asthmatics has not been determined to date. The aim of this study was to examine if swimming improved lung function and asthma symptoms in asthmatic children when compared with different forms of exercise and a control group. METHODS: Subjects with asthma were randomly assigned to either one of three different exercise training groups (swimming, football, and basketball) or a control group. Spirometry was performed before and after and the subjects were asked to keep asthma diaries and perform daily peak flow measurements. RESULTS: 41 children and adolescents between the ages of 9 and 16 participated in the study. After completing the training, children across all three exercise programs had significantly higher forced vital capacity (FVC) percentage values when compared to the control group. The swimming group demonstrated a significant increase in the percentage peak expiratory flow (PEF) following the exercise program when compared with the control group (78.3 ± 9.3 versus 89.0 ± 14.9, p = 0.04). All children on exercise training programs reported an improvement in their asthma symptoms via asthma diaries. CONCLUSION: This study suggests that a swimming training program is more beneficial in terms of peak flow measurements when compared with other exercise training programs.

Comparison of rhinovirus antibody titers in children with asthma exacerbations and species-specific rhinovirus infection.

BACKGROUND: Asthma exacerbations are associated with human rhinovirus (HRV) infections, and more severe exacerbations are associated with HRV-C. We have previously shown that the HRV-C-specific antibody response is low in healthy adult sera and that most of the antibody to HRV-C is cross-reactive with HRV-A. OBJECTIVES: To compare the antibody response to each HRV species in asthmatic and nonasthmatic children in whom the type of HRV infection was known. METHODS: Total and specific IgG1 binding to HRV viral capsid protein antigens of HRV-A, -B, and -C were tested in the plasma from nonasthmatic children (n = 47) and children presenting to the emergency department with asthma exacerbations (n = 96). HRV, found in most of the children at the time of their exacerbation (72%), was analyzed using molecular typing. RESULTS: Asthmatic children had higher antibody responses to HRV. The titers specific to HRV-A, and to a lesser extent HRV-B, were higher than in nonasthmatic controls. The species-specific responses to HRV-C were markedly lower than titers to HRV-A and HRV-B in both asthmatic and nonasthmatic children (P < .001). The titers both at presentation and after convalescence were not associated with the HRV genotype detected during the exacerbation. CONCLUSIONS: The higher total anti-HRV antibody titers of asthmatic children and their higher anti-HRV-A and -B titers show their development of a heightened antiviral immune response. The low species-specific HRV-C titers found in all groups, even when the virus was found, point to a different and possibly less efficacious immune response to this species.

A longitudinal study of lung function from 1†month to 18†years of age.

BACKGROUND: Our hypothesis was that factors associated with wheeze will be associated with changes in lung function trajectory between 1 month and 18 years of age. METHODS: Measurements of lung function were made in individuals aged 1, 6 and 12 months (V'maxFRC), and also at ages 6, 12 and 18 years (FEF(25-75)). Changes in lung function over time relative to sex, a history of asthma, maternal asthma and other factors were explored using random coefficient models. RESULTS: Lung function (maximal flow at functional residual capacity in infants and FEF(25-75) in children) was determined in 241 individuals at 1 month, 192 at 6 months, 164 at 12 months, 106 at 6 years, 183 at 12 years and 141 at 18 years. In the multivariable model, maternal asthma (mean reduction in lung function 9.8%), flow limitation (mean reduction 17.4%), infant atopy (mean reduction 12.6%) and maternal smoking (mean reduction in lung function 8.1%) were acting independently. When interactions with time were sought, the reduction in lung function associated with maternal asthma and infant atopy were consistent over time, but % lung function increased in boys by a mean of 1%/year compared with girls, in flow-limited individuals by 3.0%/year and by 0.9%/year for those exposed to maternal smoking during pregnancy compared to other cohort members. CONCLUSIONS: Decrements in lung function in 18-year-olds associated with maternal asthma and early onset atopy may be determined by 1 month of age. Low initial lung function in some individuals can 'recover' in some settings.

Knowledge, attitudes and practices of Irish doctors regarding stop smoking care and electronic cigarettes.

BACKGROUND: Smoking continues to cause harm on a huge scale in Ireland. Doctors can help this harm through providing safe, effective and clinically sound stop smoking care, but the needs of Irish doctors in this area are largely uncharted. AIMS: We assessed the knowledge, attitudes and practices of Irish doctors regarding stop smoking care and electronic cigarettes. METHODS: An Internet-based cross-sectional survey was administered to members of the Royal College of Physicians in Ireland and the Irish College of General Practitioners. Descriptive statistics for key parameters were derived and factors associated with more consistent practice of brief intervention, a key component of stop smoking care, were analysed using chi-square testing. RESULTS: There were 250 responses (58.7% female, 53.0% aged under 45 years, 55.1% graduated in medicine before 2000 and 57.2% worked in general practice). Most (84.9%) reported often or always asking about patient's smoking behaviour, and most (86.1%) reported often or always advising patients to stop. However, providing or arranging effective stop smoking care was weak and less consistently practised, and while most (91.4%) saw it as a responsibility, few doctors (28.5%) agreed they were sufficiently trained in this area of clinical care. Confidence in the knowledge of e-cigarettes was poor. CONCLUSIONS: While there is a strong reservoir support and areas of good reported practice in stop smoking care among doctors in Ireland, the development of their knowledge and skills in arranging effective care should be supported if doctors are to fulfil their huge potential role in tackling the harm caused by smoking.

Reduction in abdominal symptoms (CFAbd-Score), faecal M2-pyruvate-kinase and Calprotectin over one year of treatment with Elexacaftor-Tezacaftor-Ivacaftor in people with CF aged ≥12 years - The RECOVER study.

BACKGROUND: RECOVER is a multicentre post-approval study of Elexacaftor/Tezacaftor/Ivacaftor (ETI) in pwCF in Ireland and the UK. The CFAbd-Score is the first validated CF-specific patient reported outcome measure (PROM) focusing on gastrointestinal symptoms; it comprises 28 items in 5 domains. In a preliminary study, we previously reported reductions in abdominal symptoms (AS) in pwCF after 26 weeks of ETI-therapy using the CFAbd-Score. AIM: to assess changes in AS in a second, large cohort and explore novel GI-biomarkers of gut inflammation and cell-proliferation in pwCF over one year of ETI-therapy. METHODS: Participants were recruited as part of the RECOVER study at 8 sites (Ireland&UK). The CFAbd-Score was administered prior to ETI-initiation, and subsequently at 1,2,6 and 12 months on treatment. Faecal M2-pyruvate kinase (M2-PK) and calprotectin (FC) were quantified in samples collected at baseline, 1 and 6 months. RESULTS: 108 CFAbd-Scores and 73 stool samples were collected at baseline. After 12 months of ETI-therapy, total CFAbd-Scores had significantly declined (15.0±1.4→9.8±1.2pts/p<0.001), and so had all its five domains of "pain" (16.9±2.0pts→9.9±1.8pts/p<0.01), "GERD" (14.4±1.8→9.9±1.6/p<0.05), "disorders of bowel movements" (19.2±1.4→14.1±1.5/p<0.01), "appetite" (7.0±1.1→4.6±1.2/p<0.01) and "impaired-QoL" (13.3±1.9→7.5±1.5/p<0.001). Levels of M2-PK and FC significantly decreased during ETI-therapy. DISCUSSION: In-depth analysis of AS with the CFAbd-Score reveals a statistically significant, clinically relevant and sustained improvement with ETI. We attribute this to high sensitivity of the implemented CF-specific PROM, developed and validated following FDA-guidelines. Furthermore, for the first time during ETI-therapy a significant decline in faecal M2-PK, a marker of inflammation and cell-proliferation, was found, in parallel to FC.

The Management of Asymptomatic Congenital Pulmonary Airway Malformation: Results of a European Delphi Survey.

Consensus on the optimal management of asymptomatic congenital pulmonary airway malformation (CPAM) is lacking, and comparison between studies remains difficult due to a large variety in outcome measures. We aimed to define a core outcome set (COS) for pediatric patients with an asymptomatic CPAM. An online, three-round Delphi survey was conducted in two stakeholder groups of specialized caregivers (surgeons and non-surgeons) in various European centers. Proposed outcome parameters were scored according to level of importance, and the final COS was established through consensus. A total of 55 participants (33 surgeons, 22 non-surgeons) from 28 centers in 13 European countries completed the three rounds and rated 43 outcome parameters. The final COS comprises seven outcome parameters: respiratory insufficiency, surgical complications, mass effect/mediastinal shift (at three time-points) and multifocal disease (at two time-points). The seven outcome parameters included in the final COS reflect the diversity in priorities among this large group of European participants. However, we recommend the incorporation of these outcome parameters in the design of future studies, as they describe measurable and validated outcomes as well as the accepted age at measurement.

Infants without apparent risk factors with aspiration as a cause of respiratory symptoms - a retrospective study.

BACKGROUND: Dysphagia is common in children born prematurely or those with neuromuscular conditions or airway malformations. Few studies have reported on children with isolated dysphagia and there is significant variation in the literature regarding clinical outcomes. AIMS: The aim of this study was to characterise the clinical presentation of children with isolated dysphagia as well as the diagnostic evaluation, treatment strategies and clinical outcomes. METHODS: A retrospective chart review was conducted of children with isolated dysphagia presenting to a tertiary paediatric centre over a 10-year period. RESULTS: We describe these patients' presentation, clinical feeding assessment findings, radiological findings, treatment strategies and outcomes. Seventeen children were identified. Recurrent respiratory tract infections were the most common presentation (82%). Oral feeds were continued in 9 (53%) with the remaining being NG fed. Gastrostomy tubes were required for long-term nutrition in 6/8 (75%) of these cases. At follow-up, 11/17 (65%) had resolution of symptoms and are on full oral feeds. The mean age at resolution is 3.45 years. Of those who required gastrostomy 50% have had them removed. CONCLUSION: Isolated dysphagia should be considered in children presenting with recurrent, otherwise unexplained respiratory symptoms. Resolution can take a number of years.

Efficacy and adherence of noninvasive ventilation treatment in children with Down syndrome.

OBJECTIVE: Children with Down syndrome (DS) have an increased prevalence of obstructive sleep apnea (OSA). Noninvasive ventilation (NIV) is a common modality of OSA treatment in this cohort. This study aimed to measure adherence and efficiency of NIV delivery in children with DS. STUDY DESIGN: This was a retrospective cohort study involving 106 children with confirmed OSA and home NIV with downloadable data capacity. Children were divided into DS (n = 44) and non-DS cohorts (n = 62). Adherence, clinical outcomes apnea-hypopnoea index (AHI), positive airway pressure delivery, and leakage were recorded and compared between DS and non-DS cohorts and within the DS cohort based on past surgical history. RESULTS: Significantly greater NIV usage was observed in the DS cohort, they showed more consistent use with an increased percentage of days used relative to their non-DS counterparts (78.95 ± 2.26 vs. 72.11 ± 2.14, p = .031). However, despite greater usage, poorer clinical outcomes in the form of increased AHI (p = .0493) was observed in the DS cohort, where significantly greater leakage was also shown 41.00 ± 1.61 L/min versus 36.52 ± 1.18 L/min (p = .022). Twenty children with DS had prior cardiac surgery; compliance across all parameters was significantly reduced relative to those without. CONCLUSION: These data confirm that satisfactory NIV adherence is achievable in children with DS. However, we have identified excessive system leak at the machine-patient interface as a factor, which could undermine NIV efficacy in children with DS.

Defining Age-specific Relationships of Respiratory Syncytial Virus and Rhinovirus Species in Hospitalized Children With Acute Wheeze.

BACKGROUND: Acute wheezing is one of the most common hospital presentations for young children. Respiratory syncytial virus (RSV) and rhinovirus (RV) species A, B and the more recently described species C are implicated in the majority of these presentations. However, the relative importance and age-specificities of these viruses have not been defined. Hence, this study aimed to establish these relationships in a large cohort of prospectively recruited hospitalized children. METHODS: The study cohort was 390 children 0-16 years of age presenting with acute wheezing to a children's emergency department, 96.4% being admitted. A nonwheezing control population of 190 was also recruited. Nasal samples were analyzed for viruses. RESULTS: For the first 6 months of life, RSV was the dominant virus associated with wheezing (P < 0.001). From 6 months to 2 years, RSV, RV-A and RV-C were all common but none predominated. From 2 to 6 years, RV-C was the dominant virus detected (50-60% of cases), 2-3 times more common than RV-A and RSV, RSV decreasing to be absent from 4 to 7 years. RV-B was rare at all ages. RV-C was no longer dominant in children more than 10 years of age. Overall, RV-C was associated with lower mean oxygen saturation than any other virus (P < 0.001). Controls had no clear age distribution of viruses. CONCLUSION: This study establishes a clear profile of age specificity of virus infections causing moderate to severe wheezing in children: RSV as the dominant cause in the first 6 months and RV-C in preschool-age children.

Paediatric asthma deaths in Ireland: 2006-2016.

BACKGROUND: Asthma is the commonest chronic condition in childhood but mortality from asthma during childhood is a rare occurrence. No national review into asthma deaths in children in Ireland has been performed to date. AIM: The aim of this study was to review all cases of mortality from asthma in the paediatric population over a 10-year period in Ireland. The objective was to identify risk factors contributing to asthma deaths in children. METHODS: A retrospective chart review was performed on cases reported to the National Paediatric Mortality Register (NPMR) with asthma as the primary cause of death. RESULTS: Eleven cases were reported. Consent was obtained for six cases. Median age at death was 11.8 years. All patients presented to the Emergency Department (ED) in asystole. Fifty percent of patients had acute symptoms prior to the fatal episode. None of the patients was attending secondary services. Only 60% had a written personalised asthma action plan (PAAP). CONCLUSION: Our data suggests that most patients present in extremis and have little warning signs of severity of the attack. Better education on recognition of symptoms and initiation of action plans is required.

Neonatal screening programme for CF: Results from the Irish Comparative Outcomes Study (ICOS).

The introduction of NBS in Ireland in July 2011, provided a unique opportunity to investigate clinical outcomes using a comparative historical cohort study. Clinical cohort: children clinically diagnosed with CF born 1 July 2008 to 30 June 2011, and NBS cohort: children diagnosed with CF through NBS born 1 July 2011 to 30 June 2016. Clinical data were collected from the CF Registry of Ireland, medical charts, and data on weight/height before diagnosis from public health nurses and family doctors. SPSS was used for analysis. A total of 232 patients were recruited (response 93%) (93 clinically diagnosed, 139 NBS-detected). Following exclusions of meconium ileus (MI) (40), diagnosis outside Ireland (4), and being designated as CFSPID (2), a total of 77 clinically diagnosed patients and 109 NBS detected children were included in analysis. Over half were homozygous for F508del mutation. Being clinically diagnosed was independently associated with hospitalization for infective exacerbation of CF < 36 months (OR, 2.80; 95%CI 1.24-6.29). Diagnosis to first acquisition of Pseudomonas aeruginosa was significantly longer in NBS than clinically detected; from birth there was no significant difference. Weight and length/height were significantly greater in NBS cohort at 6 and 12 months. We provide evidence of improved growth, reduced hospitalization for acute exacerbations, and delayed P. aeruginosa acquisition (from diagnosis) to age 3 for the NBS cohort. Screening practices likely account for the non-significant difference in P. aeruginosa acquisition from birth.

Viral respiratory infections and the oropharyngeal bacterial microbiota in acutely wheezing children.

Acute viral wheeze in children is a major cause of hospitalisation and a major risk factor for the development of asthma. However, the role of the respiratory tract microbiome in the development of acute wheeze is unclear. To investigate whether severe wheezing episodes in children are associated with bacterial dysbiosis in the respiratory tract, oropharyngeal swabs were collected from 109 children with acute wheezing attending the only tertiary paediatric hospital in Perth, Australia. The bacterial community from these samples was explored using next generation sequencing and compared to samples from 75 non-wheezing controls. No significant difference in bacterial diversity was observed between samples from those with wheeze and healthy controls. Within the wheezing group, attendance at kindergarten or preschool was however, associated with increased bacterial diversity. Rhinovirus (RV) infection did not have a significant effect on bacterial community composition. A significant difference in bacterial richness was observed between children with RV-A and RV-C infection, however this is likely due to the differences in age group between the patient cohorts. The bacterial community within the oropharynx was found to be diverse and heterogeneous. Age and attendance at day care or kindergarten were important factors in driving bacterial diversity. However, wheeze and viral infection were not found to significantly relate to the bacterial community. Bacterial airway microbiome is highly variable in early life and its role in wheeze remains less clear than viral influences.