Daily Respiratory Research Analysis

BACKGROUND: Identification of chronic obstructive pulmonary disease (COPD) diagnosed before 50 years of age ("young COPD") will help enable the study of preventive and therapeutic interventions for classically diagnosed COPD in later life. However, there remains uncertainty about the definition of young COPD and its prognostic significance. METHODS: We assessed the prevalence of young COPD, defined here as spirometric airflow obstruction plus symptoms of cough, phlegm, and dyspnea or 10 or more pack-years of smoking, among 18-to-49-year-old participants from four pooled, prospective U.S. cohorts. We evaluated the association of young COPD with premature mortality and respiratory and cardiovascular events over follow-up, using multivariable-adjusted proportional hazards models. RESULTS: Among 10,680 participants (median age, 40 years; 56.8% women; 41.7% Black; 51.1% unexposed to smoking), the prevalence of people meeting our case definition of young COPD was 4.5%. Compared with nonobstructed participants, the adjusted hazard ratio (an adjusted hazard ratio greater than unity indicates more incident cases) for participants with young COPD for death before 75 years of age was 1.43 (95% confidence interval [CI], 1.19 to 1.73; P<0.001); for incident hospitalization or death due to chronic lower respiratory disease, the adjusted hazard ratio was 2.56 (95% CI, 2.05 to 3.20); for coronary heart disease, the adjusted hazard ratio was 1.12 (95% CI, 0.85 to 1.47); and for heart failure, the adjusted hazard ratio was 1.72 (95%CI, 1.26 to 2.35). The hazards of the clinical outcomes in participants with simple obstruction (spirometric obstruction without symptoms and <10 pack-years; prevalence, 2.4%) were similar to those of nonobstructed participants. CONCLUSIONS: Young COPD was present in 4.5% of adults under 50 years of age in the cohorts examined. The diagnosis was associated with premature mortality as well as respiratory and heart-failure events. (Funded by the National Heart, Lung, and Blood Institute and others.).

RATIONALE: Respiratory viruses are the leading cause of lower respiratory tract infection and hospitalisation in infants and young children. Respiratory syncytial virus (RSV) is the main infectious agent in this population. Palivizumab is administered intramuscularly every month for five months in the first RSV season to prevent serious RSV lower respiratory tract infection in children. Given its high cost, it is essential to know if palivizumab continues to be effective in preventing severe RSV disease in children. OBJECTIVES: To assess the effects of palivizumab in preventing severe RSV infection in children. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, LILACS, CINAHL, Scopus, and two trials registers from the inception of each database to July 2024 with no language or publication status restrictions. ELIGIBILITY CRITERIA: We included randomised controlled trials (RCTs) and cluster-RCTs in children 0 to 24 months of age of any gender, regardless of RSV infection history, comparing palivizumab given at a dose of 15 mg/kg once a month (maximum five doses) with placebo, no intervention, or standard care. OUTCOMES: The critical outcomes were hospitalisation due to RSV infection, all-cause mortality, and adverse events. Important outcomes were hospitalisation due to respiratory-related illness, length of hospital stay, RSV infection, number of wheezing days, days of supplemental oxygen, intensive care unit length of stay, and mechanical ventilation days. RISK OF BIAS: We used Cochrane's RoB 2 tool to assess risk of bias. SYNTHESIS METHODS: We conducted meta-analyses using random-effects models to calculate risk ratios (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes, both with 95% confidence intervals (CI). We used GRADE to assess the certainty of evidence for each outcome. INCLUDED STUDIES: We included one new trial in this update, bringing the total number of RCTs to six studies with 3611 children. All studies were parallel RCTs assessing the effects of 15 mg/kg of palivizumab every month for up to five months, compared to placebo or no intervention in an outpatient setting, although one study also included hospitalised infants, and another study administered palivizumab intranasally. Most of the included studies were conducted in children with a high risk of severe RSV infection due to comorbidities like bronchopulmonary dysplasia or congenital heart disease. SYNTHESIS OF RESULTS: Systemic palivizumab reduces hospitalisation due to RSV infection at two years' follow-up (RR 0.44, 95% CI 0.30 to 0.64; I² = 23%; 5 studies, 3343 participants; high-certainty evidence). Based on 98 hospitalisations per 1000 participants in the placebo group, this corresponds to 43 (29 to 62) per 1000 participants in the palivizumab group. Intranasal palivizumab may increase hospitalisation due to RSV infection compared to placebo or no intervention at two years' follow-up (RR 2.33, 95% CI 0.64 to 8.48; 1 study, 94 participants; low-certainty evidence due to serious concerns about imprecision). Based on 64 hospitalisations per 1000 participants in the placebo group, this corresponds to 149 (41 to 541) per 1000 participants in the palivizumab group. Palivizumab probably results in little to no difference in mortality at two years' follow-up (RR 0.69, 95% CI 0.42 to 1.15; I² = 0%; 5 studies, 3343 participants; moderate-certainty evidence due to concerns about imprecision). Based on 23 deaths per 1000 participants in the placebo group, this corresponds to 16 (10 to 27) per 1000 participants in the palivizumab group. Palivizumab probably results in little to no difference in adverse events at 150 days' follow-up (RR 1.08, 95% CI 0.85 to 1.38; I² = 0%; 4 studies, 3099 participants; moderate-certainty evidence due to concerns about imprecision). Based on 78 cases per 1000 participants in the placebo group, this corresponds to 84 (66 to 107) per 1000 participants in the palivizumab group. Palivizumab probably results in a slight reduction in hospitalisation due to respiratory-related illness at two years' follow-up (RR 0.80, 95% CI 0.65 to 0.99; I² = 41%; 6 studies, 3437 participants; moderate-certainty evidence due to concerns about imprecision). Systemic palivizumab may result in a large reduction in RSV infection at two years' follow-up (RR 0.33, 95% CI 0.20 to 0.55; I² = 0%; 3 studies, 554 participants; low-certainty evidence due to serious concerns about imprecision). Intranasal palivizumab may increase RSV infection compared to placebo or no intervention at two years' follow-up (RR 1.64, 95% CI 0.87 to 3.08; 1 study, 94 participants; low-certainty evidence due to serious concerns about imprecision). Systemic palivizumab also reduces the number of wheezing days at one-year follow-up (RR 0.39, 95% CI 0.35 to 0.44; 1 study, 429 participants; high-certainty evidence). Intranasal palivizumab may result in little to no difference in the mean fraction of wheezing days (mean fraction of wheezing days of 0.94, 95% CI -1.9 to 3.5; 1 study, 93 participants; low-certainty evidence). The risk of bias in outcomes across all studies was similar and predominantly low. AUTHORS' CONCLUSIONS: Based on the available evidence, prophylaxis with systemic palivizumab reduces hospitalisation due to RSV infection and probably results in little to no difference in mortality. Intranasal palivizumab may increase hospitalisation due to RSV infection. Palivizumab probably results in little to no difference in adverse events. Moreover, palivizumab probably results in a slight reduction in hospitalisation due to respiratory-related illness. Systemic palivizumab may result in a large reduction in RSV infections, whilst intranasal palivizumab may increase RSV infection. Systemic palivizumab also reduces the number of wheezing days, whilst intranasal palivizumab may result in little to no difference in the mean fraction of wheezing days. These results may be applicable to children with a high risk of severe RSV infection due to comorbidities. Further research is needed to establish the effect of palivizumab in children with other comorbidities known as risk factors for severe RSV disease (e.g. immune deficiencies) and other social determinants of the disease, including children living in low- and middle-income countries, tropical regions, children lacking breastfeeding, living in poverty, or members of families in overcrowded situations. FUNDING: This Cochrane review had no dedicated funding. REGISTRATION: Protocol (2020): doi.org/10.1002/14651858.CD013757 First review version (2021): doi.org/10.1002/14651858.CD013757.pub2.

IMPORTANCE: The Advisory Committee on Immunization Practices and the Centers for Disease Control and Prevention recommend seasonal administration of maternal vaccine (MV) or nirsevimab to protect infants in the first year of life from respiratory syncytial virus (RSV) infections. Differences in uptake, costs, and efficacy between these agents may affect cost-effectiveness depending on the timing of administration. OBJECTIVE: To evaluate the clinical outcomes and cost-effectiveness of no intervention, MV, and nirsevimab administration during the entire RSV season and separately for each monthly birth cohort from October through February. DESIGN, SETTING, AND PARTICIPANTS: This economic evaluation used a Markov model to analyze cost-effectiveness from a societal perspective, applying a willingness-to-pay threshold of $150 000 per quality-adjusted life-year (QALY). Participants included infants born in the US during the RSV season. Data were accrued from October 2023 to June 2024 and analyzed from July 2024 to May 2025. INTERVENTIONS: MV, nirsevimab administration, or no intervention. MAIN OUTCOMES AND MEASURES: The primary outcome was the incremental cost-effectiveness ratio (cost per QALY gained). Clinical outcomes included the number of hospitalizations, outpatient infections, and deaths averted. Probabilistic sensitivity analyses were conducted. RESULTS: An estimated monthly birth cohort of 299 277 infants was included in the analysis. Compared with no intervention, MV was cost-saving for infants in the October, November, and December cohorts and cost-effective in the January but not the February cohorts ($504 517/QALY). For infants born in the combined cohort (October-February), MV was cost-effective at $19 562/QALY. Compared with MV, nirsevimab was cost-effective only in October ($67 178/QALY) and November ($88 531/QALY). During the RSV season, MV was projected to avert 45 558 outpatient visits, 7154 hospitalizations, and 12 deaths; nirsevimab was projected to avert 92 265 outpatient visits, 11 893 hospitalizations, and 19 deaths. The probability of no intervention being cost-effective during the RSV season was 19.8%; MV, 62.2%; and nirsevimab, 18.0%. CONCLUSIONS AND RELEVANCE: In this economic evaluation of RSV prevention interventions, administration of MV in the first 4 months of and throughout the viral season could be cost-effective. Across the entire RSV season, nirsevimab was cost-effective compared with MV only in October and November. Intervention use may be optimized by restricting administration to select months. Further study is needed to assess transmission dynamics to refine cost-effectiveness outcomes.