Daily Respiratory Research Analysis

BACKGROUND: In August 2023, the Centers for Disease Control and Prevention recommended nirsevimab, a long-acting monoclonal antibody, for all U.S. infants aged <8 months entering or born during their first respiratory syncytial virus (RSV) season. Our aim was to estimate nirsevimab effectiveness against RSV-associated emergency department (ED) encounters and hospitalisation among U.S. infants during the 2023-2024 RSV season. METHODS: We conducted a test-negative analysis using electronic health record (EHR) data from 6 healthcare systems, including ED encounters and hospitalizations with a diagnosis of RSV-like illness (RLI) during October 8, 2023-March 31, 2024, among infants aged <8 months as of October 1, 2023, or born during the study period. Nirsevimab effectiveness was estimated by comparing children who received nirsevimab with those who did not among RSV-positive and RSV-negative encounters, adjusting for age, race and ethnicity, sex, calendar day, and geographic region and excluding infants whose mother received RSV vaccination during pregnancy. FINDINGS: Among 5039 ED encounters with RLI among infants in their first RSV season, 2045 (41%) were RSV-positive and 446 (9%) received nirsevimab, with a median time since dose of 52 days (interquartile range [IQR]: 27-84 days). Among 1025 hospitalizations with RLI among infants in their first RSV season, 605 (59%) were RSV-positive and 95 (9%) received nirsevimab, with a median time since dose of 48 days (IQR: 24-82 days). Nirsevimab effectiveness was 77% (95% CI: 69%-83%) against RSV-associated ED encounters and 98% (95% CI: 95%-99%) against RSV-associated hospitalisation. INTERPRETATION: Nirsevimab was effective in preventing RSV-associated ED encounters and hospitalisation among infants in their first RSV season, with greatest protection against hospitalisation. However, these estimates reflect a short interval from nirsevimab administration to RLI onset. Since nirsevimab is a passive immunization and concentration is expected to wane over time, it is important to continue monitoring effectiveness to assess effectiveness with increased time since dose. FUNDING: This work was supported by the Centers for Disease Control and Prevention (contracts 75D30121D12779 to Westat and 75D30123C18039 to Kaiser Foundation Hospitals).

BACKGROUND: Recent surveys suggest that asthma remains inadequately controlled in more than 50% of adults with asthma despite guideline-based standard therapy. Small airways are often under-recognised as major sites of airway obstruction and inflammation. This might be related to lack of assessment with current tools such as impulse oscillometry, and thus under-treatment might explain inadequate control. Small airway dysfunction, which is common in adults with well controlled asthma, might represent an important biomarker of future risk of exacerbations. We aimed to investigate whether small airway dysfunction is present in patients with well controlled asthma and, if so, whether it is a risk factor for future exacerbations in this population. METHODS: The observational Assessment of Small Airways Involvement in Asthma (ATLANTIS) study included 773 extensively characterised patients with asthma aged 18-65 years from 29 primary and specialty clinics in nine countries from June 30, 2014, to March 3, 2017. Patients were required to be diagnosed with asthma at least 6 months before inclusion based on evidence of airway hyper-responsiveness, bronchodilator reversibility, or peak expiratory flow variability. Patients were required to have stable asthma, defined as no asthma exacerbations and regular asthma treatment at a consistent dose for 8 weeks before baseline visits. The current analysis included patients with well controlled asthma, defined as an Asthma Control Questionnaire (ACQ-6) score of less than 0·75 at baseline. Small airway dysfunction was defined, based on deviation from predicted values of impulse oscillometry parameters, as a Z score of more than 1·645 for R5-R20 (resistance at 5 Hz minus resistance at 20 Hz) and AX (area of reactance) and a Z score of less than -1·645 for X5 (reactance at 5 Hz), with additional analyses exploring severe small airway dysfunction (Z score of 3 or -3). ATLANTIS is registered with ClinicalTrials.gov, NCT02123667. FINDINGS: Of 773 patients, ACQ-6 assessments were available for 772 patients. Among these patients, 384 (50%) were classified as having well controlled asthma, and small airway dysfunction was present in 108 (36% [95% CI 30-41]) of 304 patients with impulse oscillometry data available for R5-R20, 89 (34% [28-42]) of 261 patients with data for AX, and 79 (26% [21-31]) of 303 patients with data for X5. In the multivariable analysis, we found that R5-R20-defined small airway dysfunction was associated with increased risk of future exacerbations, independent of age, sex, smoking status, Global Initiative for Asthma steps 4-5, previous exacerbations, percentage of predicted FEV

INTRODUCTION: The aim of this study was to assess the relative vaccine effectiveness (rVE) of cell-based versus egg-based quadrivalent influenza vaccines (QIVc versus QIVe) in preventing test-confirmed influenza during the 2023-2024 US influenza season. METHODS: rVE was estimated using a test-negative design applied to a large, linked, real-world dataset. QIVc or QIVe recipients aged 6 months-64 years who were tested for influenza within ± 7 days of an acute respiratory or febrile illness were included. rVE was estimated using doubly robust logistic regression. Analyses were performed for the full, pediatric, adult, outpatient and high-risk populations and by influenza type. Public health impact was assessed using a compartmental influenza burden averted model. RESULTS: The analysis included 2119 QIVc-cases, 14,750 QIVc-controls, 14,559 QIVe-cases, and 75,351 QIVe-controls. QIVc was superior to QIVe in preventing test-confirmed influenza with an rVE of 19.8% (95% CI 15.7-23.8%) in the full population, and with rVEs of 19.6% (13.6-25.3%) in the pediatric population aged 6 months-17 years and 18.5% (12.1-24.5%) in adults aged 18-64 years. Consistent results were observed for all sensitivity and subgroup analyses against any influenza. If all vaccinated individuals aged 6 months-64 years in the US received QIVc over QIVe, an estimated 2,379,395 additional symptomatic illnesses would have been prevented, with proportionate reductions in related complications. CONCLUSIONS: Our analysis showed superior effectiveness of QIVc over QIVe in preventing test-confirmed influenza among persons aged 6 months-64 years, and provided the first demonstration of superiority in pediatric populations from 6 months of age. A Graphical Abstract is availible for this article. Most influenza vaccines are produced in hens’ eggs. When vaccine viruses are grown in eggs, mutations may occur that promote better growth in eggs but reduce the effectiveness of the vaccine against circulating human influenza viruses. We compared the effectiveness of egg-based influenza vaccines (QIVe; egg-based quadrivalent influenza vaccine) with QIVc (cell-based quadrivalent influenza vaccine), made by growing vaccine virus in cell lines from mammals. We measured the relative vaccine effectiveness (rVE) of these vaccines in preventing influenza illness. The rVE describes the additional protective benefit provided by one vaccine relative to another. We found that QIVc was significantly more effective in preventing influenza infection among people aged 6 months to 64 years during the 2023–2024 influenza season in the United States: the rVE was +19.8%. Therefore, of the people who would remain unprotected after vaccination with QIVe, vaccination with QIVc would have additionally protected 19.8% of this remaining population. Similar results are seen when we specifically look at either children, adults, or those with health problems that increase the risk of serious influenza complications (rVE ranging from +14.7% to +24.3%). We estimated that if all those aged 6 months to 64 years who were vaccinated during the 2023–2024 US influenza season had received QIVc instead of QIVe, an additional 2.4 million symptomatic influenza illnesses would have been prevented, along with 1.1 million outpatient visits, 14,940 hospitalizations, and 574 deaths. Our data support the benefit of QIVc over QIVe in people aged 6 months to 64 years.