Daily Respiratory Research Analysis
Three advances stand out today in respiratory science and care: a NEJM randomized trial shows the TSLP inhibitor tezepelumab markedly reduces polyp burden, symptoms, and the need for surgery/systemic steroids in severe CRSwNP; a Nature Medicine phase 1/2 study demonstrates a single multicomponent mRNA vaccine (influenza + SARS-CoV-2) is well-tolerated and immunogenic; and a Lancet Regional Health study derives and externally validates an impulse oscillometry-based equation to predict abnormal FE
Summary
Three advances stand out today in respiratory science and care: a NEJM randomized trial shows the TSLP inhibitor tezepelumab markedly reduces polyp burden, symptoms, and the need for surgery/systemic steroids in severe CRSwNP; a Nature Medicine phase 1/2 study demonstrates a single multicomponent mRNA vaccine (influenza + SARS-CoV-2) is well-tolerated and immunogenic; and a Lancet Regional Health study derives and externally validates an impulse oscillometry-based equation to predict abnormal FEV1, enabling simpler COPD screening.
Research Themes
- Biologics targeting epithelial alarmins (TSLP) for chronic airway disease
- Next-generation multicomponent mRNA vaccination for respiratory pathogens
- Noninvasive lung function screening using impulse oscillometry and predictive modeling
Selected Articles
1. Tezepelumab in Adults with Severe Chronic Rhinosinusitis with Nasal Polyps.
In a 52-week, randomized, placebo-controlled trial in adults with severe, uncontrolled CRSwNP, tezepelumab significantly improved nasal polyp and congestion scores and reduced SNOT-22 and Lund-Mackay scores. Notably, indications for polyp surgery (HR 0.02) and systemic glucocorticoid use (HR 0.12) were dramatically reduced versus placebo.
Impact: Demonstrates robust efficacy of TSLP blockade across multiple clinically meaningful endpoints, including avoidance of surgery and systemic steroids in severe CRSwNP.
Clinical Implications: Tezepelumab provides a biologic option that can reduce surgical referrals and systemic steroid exposure in severe CRSwNP, complementing standard intranasal steroids and sinus care and potentially benefiting patients across T2-high and T2-low endotypes.
Key Findings
- Tezepelumab improved total nasal-polyp score (mean difference −2.07; 95% CI −2.39 to −1.74) at week 52.
- Nasal congestion improved (mean difference −1.03; 95% CI −1.20 to −0.86) with P<0.001.
- Patient-reported outcomes improved: SNOT-22 (−27.26), loss-of-smell (−1.00), total symptom score (−6.89).
- CT extent decreased (Lund-Mackay −5.72).
- Marked reductions in polyp surgery indication (0.5% vs 22.1%; HR 0.02) and systemic glucocorticoid use (5.2% vs 18.3%; HR 0.12).
Methodological Strengths
- Randomized, placebo-controlled design with 52-week follow-up and clear coprimary endpoints.
- Comprehensive secondary and time-to-event outcomes including surgery and systemic steroid use.
Limitations
- Industry-funded trial; generalizability beyond trial centers may vary.
- Adults only; long-term safety and durability beyond 52 weeks remain to be established.
Future Directions: Head-to-head comparisons with other biologics, biomarker-defined responder analyses (including T2-low), and real-world effectiveness/surgery avoidance studies are warranted.
BACKGROUND: Treatment with tezepelumab has been effective for sinonasal symptoms in patients with severe, uncontrolled asthma and a history of chronic rhinosinusitis with nasal polyps, but its efficacy and safety in adults with severe, uncontrolled chronic rhinosinusitis with nasal polyps is unknown. METHODS: We randomly assigned adults with physician-diagnosed, symptomatic, severe chronic rhinosinusitis with nasal polyps to receive standard care and either tezepelumab (at a dose of 210 mg) or placebo subcutaneously every 4 weeks for 52 weeks. The coprimary end points were the changes from baseline in the total nasal-polyp score (range, 0 to 4 [for each nostril]; higher scores indicate greater severity) and the mean nasal-congestion score (range, 0 to 3; higher scores indicate greater severity) at week 52. Key secondary end points assessed in the overall population were the loss-of-smell score, the total score on the Sinonasal Outcome Test (SNOT-22; range, 0 to 110; higher scores indicate greater severity), the Lund-Mackay score (range, 0 to 24; higher scores indicate greater severity), the total symptom score (range, 0 to 24; higher scores indicate greater severity), and the first decision to treat with nasal-polyp surgery or use of systemic glucocorticoid therapy, or both, assessed in time-to-event analyses (individual and composite). RESULTS: In total, 203 patients were assigned to receive tezepelumab and 205 to receive placebo. At week 52, the patients who received tezepelumab had significant improvements in the total nasal-polyp score (mean difference vs. placebo, -2.07; 95% confidence interval [CI], -2.39 to -1.74) and the mean nasal-congestion score (-1.03; 95% CI, -1.20 to -0.86) (P<0.001 for both scores). Tezepelumab significantly improved the loss-of-smell score (mean difference vs. placebo, -1.00; 95% CI, -1.18 to -0.83), SNOT-22 total score (-27.26; 95% CI, -32.32 to -22.21), Lund-Mackay score (-5.72; 95% CI, -6.39 to -5.06), and total symptom score (-6.89; 95% CI, -8.02 to -5.76) (P<0.001 for all scores). Surgery for nasal polyps was indicated in significantly fewer patients in the tezepelumab group (0.5%) than in the placebo group (22.1%) (hazard ratio, 0.02; 95% CI, 0.00 to 0.09); there was significantly less use of systemic glucocorticoids with tezepelumab (5.2%) than with placebo (18.3%) (hazard ratio, 0.12; 95% CI, 0.04 to 0.27) (P<0.001 for both time-to-event analyses). CONCLUSIONS: Tezepelumab therapy led to significantly greater reductions in the size of nasal polyps, the severity of nasal congestion and sinonasal symptoms, and the use of nasal-polyp surgery and systemic glucocorticoids than placebo in adults with severe, uncontrolled chronic rhinosinusitis with nasal polyps. (Funded by AstraZeneca and Amgen; WAYPOINT ClinicalTrials.gov number, NCT04851964.).
2. mRNA-based seasonal influenza and SARS-CoV-2 multicomponent vaccine in healthy adults: a phase 1/2 trial.
In this randomized phase 1/2 study, the single-injection multicomponent mRNA-1083 vaccine showed acceptable reactogenicity and safety and elicited influenza and SARS-CoV-2 immune responses similar to or higher than licensed comparators by day 29. These data support phase 3 development and the feasibility of combined seasonal respiratory vaccination.
Impact: Combining protection against two major respiratory pathogens into one mRNA shot could streamline immunization programs, improve uptake, and enhance preparedness for seasonal surges.
Clinical Implications: If confirmed in phase 3, clinicians could offer a single annual mRNA dose covering influenza and SARS-CoV-2, reducing logistical burden and potentially improving coverage in older or multimorbid populations.
Key Findings
- Randomized phase 1/2 interim analysis (28 days) showed most solicited reactions were Grade 1–2; unsolicited AEs were similar across groups.
- mRNA-1083 induced influenza and SARS-CoV-2 immune responses comparable to or higher than licensed quadrivalent influenza and bivalent mRNA-1273 vaccines at day 29.
- Supports proceeding to phase 3 evaluation of combined seasonal respiratory vaccination.
Methodological Strengths
- Randomized, multi-arm early-phase design with predefined reactogenicity, safety, and immunogenicity endpoints.
- Head-to-head immunogenicity comparisons with licensed influenza and SARS-CoV-2 vaccines.
Limitations
- Short follow-up (28 days) without clinical efficacy endpoints.
- Sample size and detailed cohort numbers not provided in the abstract; durability and rare safety events remain unknown.
Future Directions: Proceed to phase 3 efficacy and durability testing across age strata, coadministration studies, and real-world effectiveness; evaluate variant-updated antigens and manufacturing scalability.
A multicomponent vaccine targeting several seasonal respiratory pathogens may provide simultaneous protection in a single-injection regimen. We present interim (28 days) findings from a phase 1/2 study of an mRNA-based multicomponent vaccine (mRNA-1083), encoding seasonal influenza and SARS-CoV-2 antigens. Adults (18-79 years) were randomly assigned to receive different compositions of mRNA-1083 at varying dose levels on day 1. The primary study objectives were reactogenicity through 7 days and safety through 28 days postvaccination, and the secondary study objective was immunogenicity against vaccine-matched influenza and SARS-CoV-2 strains at day 29 assessed by hemagglutination inhibition and pseudovirus neutralization assays, respectively. The multicomponent mRNA-1083 vaccine was generally well-tolerated, with most solicited adverse reactions being Grade 1 or 2 in severity. The incidence of unsolicited adverse events was similar across vaccine groups. mRNA-1083 induced immune responses against influenza and SARS-CoV-2 that were, in general, similar to or higher than those achieved with licensed quadrivalent influenza (standard or high dose) and SARS-CoV-2 (bivalent mRNA-1273) vaccines. These data support ongoing phase 3 evaluation of the mRNA-1083 vaccine. ClinicalTrials.gov registration: NCT05827926 .
3. Impulse oscillometry-derived equation for prediction of abnormal FEV
Using paired spirometry and IOS from five tertiary centers, investigators derived a multivariable equation to predict pre-BD FEV1 and externally validated it in 9,586 patients. The IOS-based approach enables prediction of abnormal FEV1 from tidal-breathing measurements, supporting scalable COPD screening.
Impact: Transforms COPD case-finding by replacing forced maneuvers with a tidal-breathing test linked to a validated predictive model, improving feasibility in community and resource-limited settings.
Clinical Implications: Primary care could deploy IOS with the predictive equation to triage patients for confirmatory spirometry, broadening access to COPD screening and earlier diagnosis.
Key Findings
- Developed a multivariable linear regression model predicting pre-BD FEV1 from IOS in 15,113 patients.
- Externally validated the prediction in an independent cohort of 9,586 patients across tertiary centers.
- Findings support IOS-based screening to identify abnormal FEV1 and potential COPD in community/primary care settings.
Methodological Strengths
- Very large derivation dataset with independent external validation across multiple hospitals.
- Use of routinely collected paired IOS–spirometry data to build a practical, implementable tool.
Limitations
- Details of model performance metrics (e.g., R², MAE/AUC thresholds) are not presented in the abstract.
- Hospital-based Chinese cohorts may limit generalizability; prospective community validation is needed.
Future Directions: Prospective community-based validation, integration into primary care workflows and devices, and evaluation of clinical/health-economic impact on COPD case-finding.
BACKGROUND: The diagnosis of chronic obstructive pulmonary disease (COPD) is based on spirometry that requires a forced expiratory manoeuvre, which is laborious and difficult for mass screening. Impulse oscillometry (IOS) is easier than spirometry and performed with tidal breathing. We sought to develop an equation for predicting forced expiratory volume in 1 s (FEV METHODS: Data from patients who simultaneously underwent spirometry and IOS were obtained from databases at five tertiary hospitals in China. Multivariable linear regression analysis was used to develop a predictive model for pre-bronchodilator (BD) FEV FINDINGS: Using 15,113 patients and externally validated with 9586 patients, the model estimated FEV INTERPRETATION: This equation could be useful to screen for COPD particularly in community and primary care settings. FUNDING: The Financial Budgeting Project of Beijing Institute of Respiratory Medicine.