Paul Stephen McNamara

Aim: The respiratory syncytial virus (RSV) is a predominant aetiology of early‐life respiratory infections. This systematic review and meta‐analysis compared the cell types involved in airways inflammation in children with and without RSV, noting that immune responses can influence long‐term complications and may involve different inflammatory cells. Method: We searched for relevant studies published in English on PubMed, Embase, Google Scholar and Web of Science until 31 August 2025. Bias assessment was performed using the Joanna Briggs Institute Critical Appraisal Checklist. Heatmaps were generated and forest plots were created, with I ² values over 40% indicating heterogeneity. Results: The search identified 126 studies and a quantitative meta‐analysis was conducted on six studies that comprised 202 with RSV and 97 unaffected controls. Compared to the controls, children with RSV showed increased percentages of neutrophils and decreased macrophages in their bronchoalveolar lavage fluid. Forest plots revealed that the pooled standard mean differences and 95% confidence intervals for neutrophil and macrophage percentages were 2.12 (1.74 to 2.50) and −3.14 (−4.16 to −2.12), respectively. Conclusion: Overall, this systematic review and meta‐analysis suggested that neutrophils predominated in the airways of children with RSV. This highlights the value of investigating these in future studies.

Objectives: This prospective surveillance study aimed to estimate the burden of laboratory-confirmed respiratory syncytial virus (RSV) in under 3-year-olds in the United Kingdom. Setting: The study was implemented in Merseyside and Bristol, encompassing 11 primary care sites, 5 walk-in centres, 2 secondary care hospitals and 2 tertiary care hospitals. Participants: Children aged under 3 years presenting with lower respiratory tract infection (LRTI) symptoms were included, with a substudy in primary care recruiting children with upper respiratory tract infection (URTI). Primary and secondary outcome measures: The primary outcome of the study was the prevalence of RSV infection in primary, secondary and tertiary healthcare settings. Secondary outcomes included severity outcomes (rates of hospitalisation and high dependency care admissions), risk factors for severe disease, economic burden of disease and coinfection prevalence. Results: 2000 children were included in the analysis (410 primary care and 1590 secondary/tertiary care). 318 were included in the URTI substudy. RSV prevalence was 50.0% (95% CI 46.7% to 53.3%) in children admitted to hospital via emergency departments (ED), 36.3% (95% CI 31.7% to 41.0%) in ED discharges, 36.5% (95% CI 24.7% to 49.6%) in primary care (LRTI) and 12.7% (95% CI 8.6% to 17.9%) in primary care URTI. Healthy term-born children accounted for 70.1% of RSV hospitalisations. Risk factors for severe disease included any level of prematurity, age <3 months and congenital cardiac disease. RSV-positive cases incurred a higher mean cost per participant (£1811, 95% CI £1720 to £1903) than RSV-negative cases (£1295, 95% CI £1220 to £1370). Conclusions: The findings revealed a substantial burden associated with RSV. Even moderate prematurity was a risk factor for severe disease, and these children may not benefit from maternal RSV vaccination due to missed late gestation antibody transfer. Furthermore, they would not be eligible for Nirsevimab under UK guidance, which supports consideration of broadening eligibility to include these children.

Background: Improvements in neonatal and paediatric care in recent decades have increased the survival of children with non-progressive neurological impairment. Respiratory disease in children with neurological impairment is common, with symptoms difficult to manage and lower respiratory tract infection occurring frequently. To reduce these, prophylactic antibiotics are being increasingly used, but the type, duration and dose of antibiotics can vary considerably, and there is limited evidence about their effectiveness in children and young people. A joint United Kingdom and Australia multicentre, randomised, double-blind, placebo-controlled trial comparing 52 weeks of azithromycin to placebo in children and young people with neurological impairment at risk of lower respiratory tract infection (PARROT) was planned to address this gap. PARROT was a multicentre, parallel group, blinded, pragmatic randomised controlled trial of 52-week duration with a planned sample size of 500 (250 in each arm) participants with neurological impairment. The primary outcome was the proportion of children and young people hospitalised with lower respiratory tract infection over the 52-week period. Results: In total, 90 children and young people (62 in Australia, 28 in the United Kingdom) aged 3–17 years, with a diagnosed non-progressive, non-neuromuscular neurological impairment, who had persistent respiratory symptoms were randomised (1 : 1) to receive azithromycin or placebo. Baseline demographic and clinical characteristics were relatively well balanced across the two treatment groups and countries. Overall, mean (standard deviation) age was 9.2 (4.4) years, with 64% of participants having cerebral palsy, 67% being non-ambulant and 54% being totally tube-fed. At baseline, mean (standard deviation) numbers of hospital admissions with lower respiratory tract infection in the preceding year were 1.8 (2.0)/year, and general practitioner attendances 3.3 (3.0)/year. The PARROT trial was closed early to recruitment due to challenges arising from the COVID-19 pandemic. Sixty-five (72%) participants (azithromycin n = 30, placebo n = 35) completed 52 weeks of treatment and were not withdrawn early from the trial. Regarding the primary outcome, 11 (36.7%) in the azithromycin group were hospitalised with lower respiratory tract infection and 9 (25.7%) in the placebo group [absolute risk reduction 0.11 (95% confidence interval −0.12 to 0.33), relative risk 1.43 (95% confidence interval 0.68 to 2.97)]. Analysis of secondary outcome data was limited by the number of missing data, but parent-reported quality of life for young person and parent, sleep amount/quality for young person and parent, and respiratory symptoms were similar between groups and countries. Limitations: As PARROT was stopped early and was consequently underpowered, it is not possible to say whether azithromycin prophylaxis is any more effective than placebo in reducing the proportion of children admitted to hospital with lower respiratory tract infection after a 52-week period. Conclusions and future work: Although we cannot comment on the effectiveness of prophylactic antibiotics in this context, we can draw some useful conclusions from this trial. Thus, the importance placed by families on hospitalisation and its prevalence in both treatment groups, even during the pandemic, would suggest that this is an appropriate primary outcome measure for future trials in this high-risk group of children and young people. Furthermore, the high attrition rate and large numbers of missing data, specifically for questionnaire-based outcomes at later follow-up points, should encourage researchers to be mindful of minimising trial burden to families for any future trials wherever possible. Funding: This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number 16/17/01.

To guide adolescent asthma management, evidence of treatment efficacy and safety is needed. We searched multiple databases for randomised control trials (RCTs) of pharmaceutical asthma therapies recruiting adolescents and adults between 2015 and 2023 to ascertain the proportion of adolescents recruited. 81 RCTs were identified, with 49 (60.5%) not reporting the number/proportion of adolescents recruited. Where the proportion of adolescents was reported, this ranged between 1% and 49% (median 6.1%). Only 7 (8.6%) trials reported adolescent subgroup data. In published asthma RCTs, it is frequently unclear whether adolescents have been recruited, with the proportion low when reported. Consideration is needed when using this data to manage adolescent asthma. CRD42021233497

Background Despite significant clinical improvements, there is evidence of persisting airway inflammation in people with cystic fibrosis (CF) established on elexacaftor/tezacaftor/ivacaftor (ETI) therapy. As CF is a multi-system disease, systemic immune profiles can reflect local inflammation within the lungs and other organs. Understanding systemic inflammation after ETI therapy may reveal important translational insights. This study aims to profile systemic inflammatory changes and relate these to the well-documented improvements observed with ETI therapy. Methods We conducted a single-centre longitudinal study with 57 CF subjects initiating ETI therapy. All participants were Phe508del homozygous or Phe508del/minimal function. Blood samples were collected pre-ETI and 3–12 months post-therapy initiation. Analyses included mass spectrometry-based proteomics, a multiplex immunoassay, and flow cytometry for peripheral immune cell counts and phenotype. Controls samples were provided by 29 age-matched healthy controls. Results Systemic inflammation reduced with ETI therapy; however, the immune profile remained distinct from healthy controls. ETI reduced neutrophil counts and was associated with a more mature, less inflammatory phenotype, as well as a shift towards an immune resolving state associated with increased CD206 expression. Cytokines known to influence neutrophil levels reduced with therapy. Despite ETI therapy, neutrophil and monocyte counts remained elevated compared with healthy controls. There was no obvious association between the ETI-related improvements in systemic inflammation and lung function. Conclusions Patients with CF showed evidence of persisting systemic inflammation despite ETI therapy, which may have long-term potentially adverse effects on respiratory and other organ systems.

Background Despite significant clinical improvements, there is evidence of persisting airway inflammation in people with cystic fibrosis established on Elexacaftor/tezacaftor/ivacaftor (ETI) therapy. As CF is a multi-system disease, systemic immune profiles can reflect local inflammation within the lungs and other organs. Understanding systemic inflammation after ETI therapy may reveal important translational insights. This study aims to profile systemic inflammatory changes and relate these to the well-documented improvements observed with ETI therapy. Methods We conducted a single-centre longitudinal study with 57 CF subjects initiating ETI therapy. All participants were Phe508del homozygous or Phe508del/minimal function. Blood samples were collected pre-ETI and 3-12 months post-therapy initiation. Analyses included mass spectrometry-based proteomics, a multiplex immunoassay, and flow cytometry for peripheral immune cell counts and phenotype. Controls samples were provided by 29 age-matched healthy controls. Results Systemic inflammation reduced with ETI therapy; however, the immune profile remained distinct from healthy controls. ETI reduced neutrophil counts and was associated with a more mature, less inflammatory phenotype, as well as a shift toward an immune resolving state associated with increased CD206 expression. Cytokines known to influence neutrophil levels reduced with therapy. Despite ETI therapy, neutrophil and monocyte counts remained elevated compared to healthy controls. There was no obvious association between the ETI-related improvements in systemic inflammation and lung function. Conclusions Patients with CF show evidence of persisting systemic inflammation despite ETI therapy, this may have long term potentially adverse effects on respiratory and other organ systems.

Respiratory exacerbations are a frequent cause of hospitalisation in children with severe neurodisability (ND). Direct aspiration of food/saliva, reflux aspiration of gastric contents or a combination of both is thought to be a common cause of respiratory symptoms and disease, particularly when this occurs ‘silently’. A number of aspiration biomarkers, including bile acids and pepsin, have been proposed, however, no gold-standard diagnostic tests are currently available. In children with severe ND at high risk of both direct and reflux aspiration, we analysed lower airway samples for saliva- and/or gastric-specific proteins with biomarker potential.