Daily Respiratory Research Analysis
Three impactful studies advance respiratory medicine and public health: (1) the IASLC proposes TNM staging refinements for pulmonary neuroendocrine carcinoma (SCLC/LCNEC), validating new N and M subcategories; (2) a global analysis of asthma (GBD 2021) shows sustained high incidence through 2050 and underscores causal roles for high BMI and smoking; and (3) a large US Veterans cohort compares COVID-19, influenza, and RSV severity, showing higher long-term mortality for COVID-19 and attenuation w
Summary
Three impactful studies advance respiratory medicine and public health: (1) the IASLC proposes TNM staging refinements for pulmonary neuroendocrine carcinoma (SCLC/LCNEC), validating new N and M subcategories; (2) a global analysis of asthma (GBD 2021) shows sustained high incidence through 2050 and underscores causal roles for high BMI and smoking; and (3) a large US Veterans cohort compares COVID-19, influenza, and RSV severity, showing higher long-term mortality for COVID-19 and attenuation with vaccination.
Research Themes
- Oncologic staging and prognostication in pulmonary neuroendocrine carcinoma
- Global respiratory disease burden, risk factors, and forecasting
- Comparative severity of respiratory viral infections and vaccination impact
Selected Articles
1. The International Association for the Study of Lung Cancer Staging Project: The Database and Proposal for the Revision of the Staging of Pulmonary Neuroendocrine Carcinoma in the Forthcoming Ninth Edition of the TNM Classification for Lung Cancer.
Using a large international database, the IASLC validated proposed TNM9 refinements for pulmonary NEC: N2a/N2b for single versus multiple ipsilateral mediastinal/subcarinal stations and M1c sub-stratification (M1c1 vs M1c2). These changes held robustly for SCLC; LCNEC showed consistent stage–survival gradients despite smaller numbers.
Impact: Staging governs prognosis, trial eligibility, and management; validating TNM9 refinements in NEC will standardize care and research globally.
Clinical Implications: Adopt TNM9 for SCLC/LCNEC, using N2a/N2b to distinguish single vs multiple ipsilateral mediastinal stations and M1c1/M1c2 to stratify extrathoracic metastatic burden; this should inform prognosis, surgical/RT decisions, and trial stratification.
Key Findings
- Validated N2 subcategories: N2a (single ipsilateral mediastinal/subcarinal station) vs N2b (multiple stations) in SCLC.
- Validated M1c sub-stratification: M1c1 (multiple lesions in one extrathoracic organ system) vs M1c2 (multiple organ systems).
- LCNEC data showed decreasing survival with increasing clinical/pathologic stages despite smaller sample sizes.
Methodological Strengths
- Large, international, contemporary cohort (2011–2019) with survival endpoints.
- Robust survival analyses (Kaplan–Meier, log-rank, Cox) aligned to TNM8 and validating TNM9 proposals.
Limitations
- LCNEC analyses were limited by smaller numbers, restricting full validation across all subgroups.
- Retrospective registry design may harbor residual staging or treatment heterogeneity.
Future Directions: Prospective validation of TNM9 in LCNEC, integration with molecular subtyping, and alignment with treatment algorithms and trial eligibility criteria.
INTRODUCTION: Pulmonary high-grade neuroendocrine carcinoma (NEC) includes SCLC and large cell NEC (LCNEC). The seventh and eighth editions of the TNM classification for lung cancer confirmed the applicability of this staging system for SCLC. With the proposal of N2 and M1c subcategories for the ninth edition classification, we assessed the applicability to NECs. METHODS: The database included NEC cases diagnosed between January 2011 and December 2019. Eligible cases, with valid survival time and eighth edition TNM stage, were classified as pure SCLC, combined SCLC with NSCLC, and LCNEC. Survival was calculated using the Kaplan-Meier method, pairwise differences using a log-rank test, and prognostic groups using a Cox regression analysis. RESULTS: There were 6181 pure and combined SCLC and 697 LCNEC cases available. For SCLC, survival outcome analyses included 4453 cases with clinical stage and 583 with pathologic stage data. The corresponding numbers for LCNEC were 585 and 508. The SCLC data validated the ninth edition classification for lung cancer, including the proposed new subcategories, N2a, single-station ipsilateral mediastinal or subcarinal lymph node involvement, and N2b, involvement of multiple ipsilateral or subcarinal stations. The data also validated the subcategorization of M1c into M1c1 (multiple lesions in a single extrathoracic organ system) and M1c2 (involvement of multiple extrathoracic organ systems). The LCNEC data were insufficient for complete survival analysis, but the available data reported decreasing survival with increasing clinical and pathologic stages. CONCLUSIONS: The ninth edition TNM classification applies to patients with NEC and is the appropriate standard for use in clinical practice.
2. Global, regional, national burden of asthma from 1990 to 2021, with projections of incidence to 2050: a systematic analysis of the global burden of disease study 2021.
This GBD-based analysis shows sustained high global asthma incidence through 2050, a rising contribution of high BMI to DALYs since 1990, and Mendelian randomization evidence that high BMI and smoking causally increase asthma risk. Incidence/prevalence track positively with SDI, while mortality/DALYs track negatively.
Impact: Provides up-to-date global burden estimates with causal inference and forecasts, directly informing prevention strategies (obesity/smoking) and long-term planning.
Clinical Implications: Prioritize weight management and smoking cessation in asthma prevention; anticipate sustained service demand to 2050; tailor interventions by SDI and age/sex patterns.
Key Findings
- Global age-standardised asthma incidence projected to remain high from 2022 to 2050 (BAPC model).
- High BMI’s contribution to asthma DALYs increased by 4.3% worldwide between 1990 and 2021.
- Mendelian randomization supports causal effects of high BMI and smoking on asthma risk.
- Incidence/prevalence correlate positively with SDI; mortality/DALYs correlate negatively.
Methodological Strengths
- Combines GBD estimates with joinpoint trends, MR for causality, and BAPC forecasting.
- Large-scale, standardized global datasets enabling cross-country comparisons.
Limitations
- Reliance on secondary data and modeling assumptions; heterogeneity in data quality across regions.
- MR limited by available instruments and potential pleiotropy.
Future Directions: Integrate environmental exposures (air pollution), refine BMI-smoking joint effects, and validate forecasts with prospective surveillance.
BACKGROUND: Asthma is the second leading cause of mortality among chronic respiratory illnesses. This study provided a comprehensive analysis of the burden of asthma. METHODS: Data on asthma were extracted from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021. We focused on the effects of age, sex, risk factors, and the socio-demographic index (SDI) on the burden of asthma and calculated the average annual percent change (AAPC) via joinpoint regression. Two-sample Mendelian randomization (MR) was adopted to estimate the causal relationships between risk factors and asthma. The Bayesian age-period-cohort (BAPC) model was used to predict incidence patterns of asthma from 2022 to 2050. FINDINGS: In 2021, there was an observed prevalence of asthma, with 3,340 cases per 100,000 people. Males who were below 20 years old had a greater prevalence of asthma. The incidence and prevalence correlated positively with the SDI, whereas mortality and disability-adjusted life years (DALYs) correlated negatively. The contribution of high body mass index (BMI) to asthma DALYs increased by 4.3% worldwide between 1990 and 2021. MR studies have confirmed that high BMI and smoking can increase the risk of asthma. The prediction results indicated that the global age-standardised incidence rate will remain high from 2022 to 2050. INTERPRETATION: The global mortality of patients with asthma is a significant concern. The analysis of the burden of asthma can help formulate public health policies, allocate resources, and prevent asthma. FUNDING: This study was supported by the National Natural Science Foundation of China; Program for Young Talents of Basic Research in Universities of Heilongjiang Province; Marshal Initiative Funding; Mathematical Tianyuan Fund of the National Natural Science Foundation of China; XingLian Outstanding Talent Support Program 2024.
3. Severity and Long-Term Mortality of COVID-19, Influenza, and Respiratory Syncytial Virus.
Across two seasons and >140,000 veterans, COVID-19 had higher 180-day mortality than influenza/RSV; 30-day outcomes converged in 2023–2024. Vaccination mitigated severity and long-term mortality differences, with no mortality gap between COVID-19 and influenza among vaccinated individuals.
Impact: Directly informs adult vaccination policies and resource planning by quantifying comparative severity and long-term mortality across major respiratory viruses.
Clinical Implications: Promote up-to-date COVID-19 and influenza vaccination in older/high-risk adults; anticipate prolonged follow-up needs after COVID-19; refine triage during co-circulation seasons.
Key Findings
- In 2023–2024, 30-day hospitalization risk: COVID-19 16.2%, influenza 16.3%, RSV 14.3% (COVID-19 vs RSV RD 1.9%).
- COVID-19 had higher 180-day mortality than influenza and RSV in both seasons (e.g., 2023–2024 RD vs influenza 0.8%).
- Vaccination attenuated severity and mortality differences; among vaccinated, mortality did not differ between COVID-19 and influenza.
Methodological Strengths
- Large, national EHR cohort with inverse probability weighting across two respiratory seasons.
- Direct same-day testing comparison mitigates misclassification across pathogens.
Limitations
- Predominantly older male veterans limit generalizability to broader populations.
- Residual confounding and changes in variant/therapeutics across seasons may influence outcomes.
Future Directions: Extend analyses to diverse populations, evaluate variant-specific risks, and quantify vaccine-effect heterogeneity by platform and timing.
IMPORTANCE: SARS-CoV-2, influenza, and respiratory syncytial virus (RSV) contribute to many hospitalizations and deaths each year. Understanding relative disease severity can help to inform vaccination guidance. OBJECTIVE: To compare disease severity of COVID-19, influenza, and RSV among US veterans. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study analyzed national US Veterans Health Administration electronic health record data of nonhospitalized veterans who underwent same-day testing for SARS-CoV-2, influenza, and RSV, and were diagnosed with a single infection between August 1, 2022, and March 31, 2023, or between August 1, 2023, and March 31, 2024. EXPOSURES: Infection with SARS-CoV-2, influenza, or RSV. MAIN OUTCOMES AND MEASURES: Following inverse probability weighting, the cumulative incidence and risk differences (RDs) were calculated for the primary outcomes of 30-day hospitalization, intensive care unit admission, and death, as well as the secondary outcome of long-term death extending through 180 days. RESULTS: Among 68 581 patients included in the 2022 to 2023 cohort (6239 [9.1%] with RSV, 16 947 [24.7%] with influenza, and 45 395 [66.2%] with COVID-19) and 72 939 in the 2023 to 2024 cohort (9748 [13.4%] with RSV, 19 242 [26.4%] with influenza, and 43 949 [60.3%] with COVID-19), the median (IQR) age was 66 (53-75) years, and 123 090 (87.0%) were male. During the 2023 to 2024 season, the 30-day risk of hospitalization was similar for COVID-19 (16.2%) and influenza (16.3%) but lower for RSV at 14.3% (RD for COVID-19 vs RSV, 1.9% [95% CI, 0.9%-2.9%]; RD for influenza vs RSV, 2.0% [95% CI, 0.8%-3.3%]). The 30-day risk of death during the 2022 to 2023 season was slightly higher for COVID-19 (1.0%) compared with influenza (0.7%) (RD, 0.4% [95% CI, 0.1%-0.6%]) or RSV (0.7%) (RD, 0.4% [95% CI, 0.1%-0.6%]) but similar during the 2023 to 2024 season. Mortality risk at 180 days was higher for COVID-19 during both seasons (2023-2024 RD for COVID-19 vs influenza, 0.8% [95% CI, 0.3%-1.2%]; RD for COVID-19 vs RSV, 0.6% [95% CI, 0.1%-1.1%]). Higher mortality in both seasons was observed for veterans without COVID-19 vaccination in the previous year compared to veterans without seasonal influenza vaccination. In contrast, among groups vaccinated against their respective infections, there were no mortality differences at any time point between COVID-19 and influenza. CONCLUSIONS AND RELEVANCE: This cohort study showed that, during the 2022 to 2023 season, infection with SARS-CoV-2 was associated with more severe disease outcomes than influenza or RSV, whereas differences were less pronounced during the 2023 to 2024 season. During both seasons, RSV remained a milder illness, whereas COVID-19 was associated with higher long-term mortality. Vaccination attenuated differences in disease severity and long-term mortality.