"He's not fat, he just has asthma": a qualitative study exploring weight management in families living with pediatric asthma.

ObjectiveChildren and young people living with asthma have an increased risk of overweight/obesity, leading to increased severity of asthma symptoms. Weight management has been recommended to improve asthma symptoms, however, there is limited understanding of how this is experienced or how children and young people with asthma and their families wish to be supported. The aim of this study was to explore parents and children/young people's views and experiences of managing weight while living with asthma, and to identify acceptable strategies for support.Methods: A qualitative methodological approach was taken to facilitate rich understanding of families' insights into weight management while living with asthma. In-depth interviews were conducted with nine families living with pediatric asthma (n = 9 parents, 9 young people). Data were analyzed using a Framework approach.Results: Findings indicated that family engagement with weight management behaviors was primarily influenced by perceptions of risk regarding asthma outcomes and beliefs about asthma control. Families also reported weight management engagement to be influenced by perceptions of the food environment, perceptions of the exercise environment (e.g. weather, anticipated social outcomes) and the availability of weight management support. Participants sought tailored support which gave consideration to the asthma-obesity interaction. It was suggested that this would help reduce perceptions of weight stigma in consultations, thereby supporting behavioral changes.Conclusions: Individualized weight management plans that consider families concerns about asthma-related risk are needed to manage weight in children and young people living with asthma.

Neutrophils in asthma: the good, the bad and the bacteria.

Airway inflammation plays a key role in asthma pathogenesis but is heterogeneous in nature. There has been significant scientific discovery with regard to type 2-driven, eosinophil-dominated asthma, with effective therapies ranging from inhaled corticosteroids to novel biologics. However, studies suggest that approximately 1 in 5 adults with asthma have an increased proportion of neutrophils in their airways. These patients tend to be older, have potentially pathogenic airway bacteria and do not respond well to classical therapies. Currently, there are no specific therapeutic options for these patients, such as neutrophil-targeting biologics.Neutrophils comprise 70% of the total circulatory white cells and play a critical defence role during inflammatory and infective challenges. This makes them a problematic target for therapeutics. Furthermore, neutrophil functions change with age, with reduced microbial killing, increased reactive oxygen species release and reduced production of extracellular traps with advancing age. Therefore, different therapeutic strategies may be required for different age groups of patients.The pathogenesis of neutrophil-dominated airway inflammation in adults with asthma may reflect a counterproductive response to the defective neutrophil microbial killing seen with age, resulting in bystander damage to host airway cells and subsequent mucus hypersecretion and airway remodelling. However, in children with asthma, neutrophils are less associated with adverse features of disease, and it is possible that in children, neutrophils are less pathogenic.In this review, we explore the mechanisms of neutrophil recruitment, changes in cellular function across the life course and the implications this may have for asthma management now and in the future. We also describe the prevalence of neutrophilic asthma globally, with a focus on First Nations people of Australia, New Zealand and North America.

Paediatric and adolescent asthma: A narrative review of telemedicine and emerging technologies for the post-COVID-19 era.

Children and young people with asthma need regular monitoring to maintain good asthma control, prevent asthma attacks and manage comorbidities. The COVID-19 pandemic has resulted in healthcare professionals making fundamental changes to the way healthcare is delivered and for patients and families adapting to these changes. Comprehensive remotely delivered, technology-based healthcare, closer to the patients home (reducing hospital footfall and possibly reducing carbon footprint) is likely to be one of the important collateral effects of the pandemic. Telemedicine is anticipated to impact everyone involved in healthcare - providers and patients alike. It is going to bring changes to organization, work areas and work culture in healthcare. Healthcare providers, policymakers and those accessing healthcare services will experience the impact of technology-based healthcare delivery. Telemedicine can play an exciting role in the management of childhood asthma by delivering high-quality care closer to the child's home. However, unlike adults, children still need to be accompanied by their carers for virtual care. Policymakers will need to take into account potential additional costs as well as the legal, ethical and cultural implications of large scale use of telemedicine. In this narrative review, we review evidence regarding the role of telemedicine and related emerging technologies in paediatric and adolescent asthma. Although there are gaps in the current knowledge, there is evidence demonstrating the important role of telemedicine in management of childhood and adolescent asthma. However, there is an urgent need for healthcare researchers and policymakers to focus on improving the technologies and address the disparities in accessing novel technology-based management strategies to improve asthma care.

Nebulization procedures for children with unknown viral status during the COVID-19 pandemic.

During the Covid19 pandemic there has been much discussion about in-hospital procedures that may generate aerosols. One such procedure, that has led to confusion and concern, is nebulisation of children. In this paper, we discuss the evidence around whether nebulisation procedures generate aerosols, and offer strategies around nebulisation of children with asthma.

Collateral impact of COVID-19: why should children continue to suffer?

The COVID-19 pandemic caused by SARS-COV-2 virus fortunately resulted in few children suffering from severe disease. However, the collateral effects on the COVID-19 pandemic appear to have had significant detrimental effects on children affected and young people. There are also some positive impacts in the form of reduced prevalence of viral bronchiolitis. The new strain of SARS-COV-2 identified recently in the UK appears to have increased transmissibility to children. However, there are no large vaccine trials set up in children to evaluate safety and efficacy. In this short communication, we review the collateral effects of COVID-19 pandemic in children and young people. We highlight the need for urgent strategies to mitigate the risks to children due to the COVID-19 pandemic. What is Known: • Children and young people account for <2% of all COVID-19 hospital admissions • The collateral impact of COVID-19 pandemic on children and young people is devastating • Significant reduction in influenza and respiratory syncytial virus (RSV) infection in the southern hemisphere What is New: • The public health measures to reduce COVID-19 infection may have also resulted in near elimination of influenza and RSV infections across the globe • A COVID-19 vaccine has been licensed for adults. However, large scale vaccine studies are yet to be initiated although there is emerging evidence of the new SARS-COV-2 strain spreading more rapidly though young people. • Children and young people continue to bear the collateral effects of COVID-19 pandemic.

Impaired airway epithelial cell wound-healing capacity is associated with airway remodelling following RSV infection in severe preschool wheeze.

BACKGROUND: Respiratory syncytial virus (RSV) causes exacerbations of asthma and preschool wheeze (PSW). However, the anti-viral and repair responses of the bronchial epithelium in children with severe therapy-resistant asthma (STRA) and PSW are poorly understood. METHODS: Children with STRA (age 12 [6-16] years), PSW (age 2 [1-5] years) and non-asthmatic controls (age 7 [2-14] years) underwent bronchoscopy with endobronchial brushings and biopsies. Anti-viral, wound injury responses were quantified in biopsies and primary bronchial epithelial cells (PBECs) in response to RSV, poly(I:C), house dust mite (HDM) or IL-33 using RT-qPCR, Luminex and live cell imaging. Collagen deposition and tissue expression of epithelial growth factor receptor (EGFR), IL-33 and receptor ST2 were investigated in bronchial biopsies. RESULTS: PBECs from STRA and PSW had increased TLR3 gene expression and increased secretion of anti-viral and pro-inflammatory cytokines (IFN-γ, IL-6 and IL-13) in response to RSV compared to controls. Exposure of PBECs to concomitant TLR3 agonist poly(I:C) and HDM resulted in a significant reduction in epithelial cell proliferation in PSW compared to controls. Wound-healing was also impaired in PSW compared to controls at baseline and following IL-33 stimulation. In addition, tissue EGFR expression was significantly reduced in PSW and correlated with collagen deposition in endobronchial biopsies. CONCLUSIONS: Despite increased anti-viral responses, preschool children with severe wheeze had impaired airway epithelial proliferative responses following damage. This might be connected to the low expression of EGFR in PSW which may affect epithelial function and contribute to asthma pathogenesis.

Pulmonary type-2 innate lymphoid cells in paediatric severe asthma: phenotype and response to steroids.

Children with severe therapy-resistant asthma (STRA) have poor control despite maximal treatment, while those with difficult asthma (DA) have poor control from failure to implement basic management, including adherence to therapy. Although recognised as clinically distinct, the airway molecular phenotype, including the role of innate lymphoid cells (ILCs) and their response to steroids in DA and STRA is unknown.Immunophenotyping of sputum and blood ILCs and T-cells from STRA, DA and non-asthmatic controls was undertaken. Leukocytes were analysed longitudinally pre- and post-intramuscular triamcinolone in children with STRA. Cultured ILCs were evaluated to assess steroid responsiveness in vitroAirway eosinophils, type 2 T-helper (Th2) cells and ILC2s were significantly higher in STRA patients compared to DA and disease controls, while IL-17+ lymphoid cells were similar. ILC2s and Th2 cells were significantly reduced in vivo following intramuscular triamcinolone and in vitro with steroids. Furthermore, asthma attacks and symptoms reduced after systemic steroids despite persistence of steroid-resistant IL-17+ cells and eosinophils.Paediatric STRA and DA have distinct airway molecular phenotypes with STRA characterised by elevated type-2 cells. Systemic corticosteroids, but not maintenance inhaled steroids resulted in improved symptom control and exacerbations concomitant with a reduction in functional ILC2s despite persistently elevated IL-17+ lymphoid cells.

Intraepithelial neutrophils in pediatric severe asthma are associated with better lung function.

BACKGROUND: Neutrophils and IL-17A have been linked mechanistically in models of allergic airways disease and have been associated with asthma severity. However, their role in pediatric asthma is unknown. OBJECTIVES: We sought to investigate the role of neutrophils and the IL-17A pathway in mediating pediatric severe therapy-resistant asthma (STRA). METHODS: Children with STRA (n = 51; age, 12.6 years; range, 6-16.3 years) and controls without asthma (n = 15; age, 4.75 years; range, 1.6-16 years) underwent clinically indicated fiberoptic bronchoscopy, bronchoalveolar lavage (BAL), endobronchial brushings, and biopsy. Neutrophils, IL-17A, and IL-17RA-expressing cells and levels of IL-17A and IL-22 were quantified in BAL and biopsies and related to clinical features. Primary bronchial epithelial cells were stimulated with IL-17A and/or IL-22, with and without budesonide. RESULTS: Children with STRA had increased intraepithelial neutrophils, which positively correlated with FEV1 %predicted (r = 0.43; P = .008). Neutrophilhigh patients also had better symptom control, despite lower dose maintenance inhaled steroids. Submucosal neutrophils were not increased in children with STRA. Submucosal and epithelial IL-17A-positive cells and BAL IL-17A and IL-22 levels were similar in children with STRA and controls. However, there were significantly more IL-17RA-positive cells in the submucosa and epithelium in children with STRA compared with controls (P = .001). Stimulation of primary bronchial epithelial cells with IL-17A enhanced mRNA expression of IL-17RA and increased release of IL-8, even in the presence of budesonide. CONCLUSIONS: A proportion of children with STRA exhibit increased intraepithelial airway neutrophilia that correlated with better lung function. STRA was also characterized by increased airway IL-17RA expression. These data suggest a potential beneficial rather than adverse role for neutrophils in pediatric severe asthma pathophysiology.

Electronic monitoring of adherence to inhaled corticosteroids: an essential tool in identifying severe asthma in children.

International guidelines recommend that severe asthma can only be diagnosed after contributory factors, including adherence, have been addressed. Accurate assessment of adherence is difficult in clinical practice. We hypothesised that electronic monitoring in children would identify nonadherence, thus delineating the small number with true severe asthma.Asthmatic children already prescribed inhaled corticosteroids were prospectively recruited and persistence of adherence assessed using electronic monitoring devices. Spirometry, airway inflammation and asthma control were measured at the start and end of the monitoring period.93 children (62 male; median age 12.4 years) were monitored for a median of 92 days. Median (range) monitored adherence was 74% (21-99%). We identified four groups: 1) good adherence during monitoring with improved control, 24% (likely previous poor adherence); 2) good adherence with poor control, 18% (severe therapy-resistant asthma); 3) poor adherence with good control, 26% (likely overtreated); and 4) poor adherence with poor control, 32%. No clinical parameter prior to monitoring distinguished these groups.Electronic monitoring is a useful tool for identifying children in whom a step up in treatment is indicated. Different approaches are needed in those who are controlled when adherent or who are nonadherent. Electronic monitoring is essential in a paediatric severe asthma clinic.

Assessment of corticosteroid response in pediatric patients with severe asthma by using a multidomain approach.

BACKGROUND: There is no agreed upon definition of systemic corticosteroid response in asthmatic children. Moreover, pediatric severe therapy-resistant asthma (STRA) is heterogeneous, and thus response to steroids is unlikely to be uniform in all patients. OBJECTIVE: We sought to evaluate the utility of a multidomain approach incorporating symptoms, lung function, and inflammation to determine steroid responsiveness in pediatric patients with STRA. METHODS: Eighty-two children (median age, 12 years) with STRA received a clinically indicated dose of intramuscular steroid. Changes in 4 separate domains were assessed 4 weeks after intramuscular triamcinolone acetonide: normalization of (1) symptoms (Asthma Control Test score, >19/25 or 50% increase), (2) spirometric results (FEV1 ≥80% of predicted value or ≥15% increase), (3) fraction of exhaled nitric oxide levels (<24 ppb), and (4) sputum eosinophil counts (<2.5%). Fifty-four of 82 children had complete data in all 4 domains. RESULTS: Twenty-three (43%) of 54 children had a symptom response, 29 (54%) of 54 had a lung function response, 28 (52%) of 54 had a fraction of exhaled nitric oxide response, and 29 (54%) of 54 had a sputum eosinophil response. Although a similar proportion of children responded to systemic corticosteroids in each domain, there were no reliable predictors of a response pattern. Seven (13%) of 54 were complete responders (response in all domains), 8 (15%) of 54 were nonresponders (no response in any domain), and 39 (72%) of 54 were partial responders (response in ≥1 domain). CONCLUSIONS: A multidomain evaluation of systemic steroid responsiveness using pragmatic clinical assessments confirms childhood STRA is heterogeneous and that a complete response in symptoms and inflammatory and physiologic parameters is rare. Individual response patterns to systemic steroids might be useful in guiding the choice of add-on therapies in each child as a step toward achieving personalized medicine.

'Will anybody listen?' Parents' views on childhood asthma care: a qualitative study.

BACKGROUND: Asthma is the most common chronic disease in children, resulting in considerable morbidity and healthcare utilisation, especially in geographical areas with high deprivation. Parents play a pivotal role in children's asthma management. AIM: To explore the views of parents whose children have asthma, regarding barriers and facilitators to receiving adequate asthma care. DESIGN & SETTING: A qualitative study conducted in an urban, multi-ethnic setting with high socioeconomic deprivation and paediatric asthma-related hospital admissions. METHOD: The study used a pragmatic approach underpinned by a perspective of critical realism. Parents of children with asthma were recruited through purposive and convenience sampling, and data were collected through semi-structured interviews. Transcripts were analysed using thematic analysis, facilitated by NVivo12 software. RESULTS: Ten parents participated in nine interviews. Six themes were identified relating to the following: (1) the establishment of a new life dynamic following a diagnosis of asthma; (2) the turbulent and drawn-out process of asthma diagnosis; (3) the roles and expectations of the partnership established between parents and healthcare services; (4) the importance of schools in asthma management; (5) sources and access to relevant information; and (6) the importance of social support networks. Parents frequently felt unsupported and misunderstood, particularly during the diagnostic process. CONCLUSION: Unmet parental educational and emotional needs, particularly around the time of diagnosis, were identified as a key barrier to adequate asthma management. Deeper understanding of gaps in support can instruct asthma care delivery and inform co-produced interventions, thus improving asthma outcomes in children.

Post-hospitalisation asthma management in primary care: a retrospective cohort study.

BACKGROUND: Clinical guidelines recommend that patients admitted to hospital for asthma attacks are reviewed in primary care following hospital discharge. AIM: To evaluate asthma management in primary care following a hospital admission for asthma and its associations with patient characteristics. DESIGN AND SETTING: A retrospective cohort study using English primary care data from the Clinical Practice Research Datalink Aurum database and linked Hospital Episode Statistics Admitted Patient Care data. METHOD: Patients with asthma aged ≥5 years who had at least one asthma-related hospital admission from 1 January 2017 to 31 December 2019 were included. The primary outcome was a composite of any of the following delivered in primary care within 28 days from hospital discharge: asthma review, asthma management plan, asthma medication prescriptions, demonstration of inhaler technique, or smoking cessation counselling. The association between patient characteristics and delivery of clinical care was assessed using logistic regression. RESULTS: The study included 17 457 patients. A total of 10 515 (60.2%) patients received the primary outcome within 28 days of hospital discharge. There were 2311 (13.2%) who received an asthma review, 1459 (8.4%) an asthma management plan, 9996 (57.3%) an asthma medication, 1500 (8.6%) a demonstration of inhaler technique, and 52 (1.2% of smokers) had smoking cessation counselling. Patients from Black ethnic minority groups received less of this care (27%-54% lower odds, depending on age). However, short-acting bronchodilator prescriptions in the previous year were associated with an increased likelihood of the primary outcome. CONCLUSION: A significant proportion of patients do not receive timely follow-up in primary care following asthma-related admissions to hospital, particularly among Black ethnic minority groups.

Risk factors for asthma-related hospital and intensive care admissions in children, adolescents and adults: a cohort study using primary and secondary care data.

BACKGROUND: Asthma remains a common cause of hospital admissions across the life course. We estimated the contribution of key risk factors to asthma-related hospital and intensive care unit (ICU) admissions in children, adolescents and adults. METHODS: This was a UK-based cohort study using linked primary care (Clinical Practice Research Datalink Aurum) and secondary care (Hospital Episode Statistics Admitted Patient Care) data. Patients were eligible if they were aged 5 years and older and had been diagnosed with asthma. This included 90 989 children aged 5-11 years, 114 927 adolescents aged 12-17 years and 1 179 410 adults aged 18 years or older. The primary outcome was asthma-related hospital admissions from 1 January 2017 to 31 December 2019. The secondary outcome was asthma-related ICU admissions. Incidence rate ratios adjusted for demographic and clinical risk factors were estimated using negative binomial models. Population attributable fraction (PAF) was estimated for modifiable risk factors. RESULTS: Younger age groups, females and those from ethnic minority and lower socioeconomic backgrounds had an increased risk of asthma-related hospital admissions. Increasing medication burden, including excessive use of short-acting bronchodilators, was also strongly associated with the primary outcome. Similar risk factors were observed for asthma-related ICU admissions. The key potentially modifiable or treatable risk factors were smoking in adolescents and adults (PAF 6.8%, 95% CI 0.9% to 12.3% and 4.3%, 95% CI 3.0% to 5.7%, respectively), and obesity (PAF 23.3%, 95% CI 20.5% to 26.1%), depression (11.1%, 95% CI 9.1% to 13.1%), gastro-oesophageal reflux disease (2.3%, 95% CI 1.2% to 3.4%), anxiety (2.0%, 95% CI 0.5% to 3.6%) and chronic rhinosinusitis (0.8%, 95% CI 0.3% to 1.3%) in adults. CONCLUSIONS: There are significant sociodemographic inequalities in the rates of asthma-related hospital and ICU admissions. Treating age-specific modifiable risk factors should be considered an integral part of asthma management, which could potentially reduce the rate of avoidable hospital admissions.

Treating severe paediatric asthma with mepolizumab or omalizumab: a protocol for the TREAT randomised non-inferiority trial.

INTRODUCTION: A minority of school-aged children with asthma have persistent poor control and experience frequent asthma attacks despite maximal prescribed maintenance therapy. These children have higher morbidity and risk of death. The first add-on biologic therapy, omalizumab, a monoclonal antibody that blocks immunoglobulin (Ig)E, was licensed for children with severe asthma in 2005. While omalizumab is an effective treatment, non-response is common. A second biologic, mepolizumab which blocks interleukin 5 and targets eosinophilic inflammation, was licensed in 2018, but the licence was granted by extrapolation of adult clinical trial data to children. This non-inferiority (NI) trial will determine whether mepolizumab is as efficacious as omalizumab in reducing asthma attacks in children with severe therapy resistant asthma (STRA) and refractory difficult asthma (DA). METHODS AND ANALYSIS: This is an ongoing multicentre 1:1 randomised NI open-label trial of mepolizumab and omalizumab. Up to 150 children and young people (CYP) aged 6-17 years with severe asthma will be recruited from specialist paediatric severe asthma centres in the UK. Prior to randomisation, children will be monitored for medication adherence for up to 16 weeks to determine STRA and refractory DA diagnoses. Current prescribing recommendations of serum IgE and blood eosinophils will not influence eligibility or enrolment. The primary outcome is the 52-week asthma attack rate. Bayesian analysis using clinician-elicited prior distributions will be used to calculate the posterior probability that mepolizumab is not inferior to omalizumab. Secondary outcomes include Composite Asthma Severity Index, Paediatric Asthma Quality of Life Questionnaire, lung function measures (forced expiratory volume in one second (FEV1), bronchodilator reversibility), fractional exhaled nitric oxide, Asthma Control Test (ACT), health outcomes EuroQol 5 Dimension (EQ-5D) and optimal serum IgE and blood eosinophil levels that may predict a response to therapy. These outcomes will be analysed in a frequentist framework using longitudinal models. ETHICS AND DISSEMINATION: The study has been approved by the South Central-Berkshire Research Ethics Committee REC Number 19/SC/0634 and had Clinical Trials Authorisation from the Medicines and Healthcare Products Regulatory Agency (MHRA) (EudraCT 2019-004085-17). All parents/legal guardians will give informed consent for their child to participate in the trial, and CYP will give assent to participate. The results will be published in peer-reviewed journals, presented at international conferences and disseminated via our patient and public involvement partners. TRIAL REGISTRATION NUMBER: ISRCTN12109108; EudraCT Number: 2019-004085-17.

Pseudomembranous colitis in cystic fibrosis.

Cystic fibrosis (CF) patients may require frequent courses of antibiotics and repeated hospital admissions. Although children with CF have high carriage rate for C.difficile, they rarely develop colitis. Pseudomembranous colitis is more common in adult post lung transplant CF patients. Although rare, paseudomembranous colitis should be considered in CF patients presenting with abdominal symptoms even in the absence of diarrhoea.

Influence of parental anxiety and beliefs about medicines on feeding and exercise in children living with asthma.

This study's primary objective was to establish differences in beliefs about medicines, levels of asthma-related anxiety and diet and exercise behaviours between parents of children with well controlled and poorly controlled asthma. Secondary objectives were to explore how asthma control might shape relationships between parental cognitions and parenting practices concerning paediatric asthma. Parents of children with asthma aged 10-16 years (N = 310) completed standardised questionnaires measuring beliefs about medicines, parental asthma-related anxiety, parenting attitudes towards child activity, parental feeding and asthma control. Parents of children with poorly controlled asthma reported significantly greater asthma medication necessity and concern, asthma-related anxiety, control of child activity, pressure to exercise and unhealthy feeding practices. Moderation analyses indicated that the relationship between parental concern about asthma medicine and parental control of child activity was strongest in children with poorly controlled asthma. Also, the relationship between parental asthma-related anxiety and use of food to regulate child emotion was only significant when asthma was poorly controlled. Parental beliefs about asthma medicines and asthma-related anxiety may indirectly influence asthma outcomes through unhealthy parenting practices around exercise and diet. Eliciting and understanding parents' perceptions of asthma medications and anxiety may facilitate personalised interventions to improve asthma control.