Daily Respiratory Research Analysis
Three impactful respiratory studies stood out: an AI-guided approach enabled nonexpert clinicians to acquire diagnostic-quality lung ultrasound images; barcoded SARS-CoV-2 revealed exposure-dependent transmission bottlenecks and the upper airway as the primary source; and a large cohort of never-smokers undergoing LDCT screening showed no sex-based differences in outcomes, underscoring overdiagnosis concerns.
Summary
Three impactful respiratory studies stood out: an AI-guided approach enabled nonexpert clinicians to acquire diagnostic-quality lung ultrasound images; barcoded SARS-CoV-2 revealed exposure-dependent transmission bottlenecks and the upper airway as the primary source; and a large cohort of never-smokers undergoing LDCT screening showed no sex-based differences in outcomes, underscoring overdiagnosis concerns.
Research Themes
- AI-enabled diagnostic imaging in respiratory care
- Mechanisms of respiratory virus transmission bottlenecks
- Lung cancer screening policy in never-smokers
Selected Articles
1. Artificial Intelligence-Guided Lung Ultrasound by Nonexperts.
In a multicenter diagnostic validation (n=176), trained nonexpert healthcare professionals using AI guidance achieved diagnostic-quality 8-zone lung ultrasound in 98.3% (95% CI 95.1%-99.4%) of cases, statistically indistinguishable from expert-acquired studies (difference 1.7%; 95% CI -1.6% to 5.0%). Masked expert readers validated image quality, and analyses followed intention to treat.
Impact: Demonstrates that AI can standardize and democratize LUS acquisition, potentially expanding access to high-value cardiopulmonary imaging in resource-limited settings.
Clinical Implications: Enables task-shifting of LUS acquisition to trained nonexperts, supporting triage for dyspnea, heart failure, and pulmonary edema. Could underpin scalable point-of-care ultrasound programs and tele-expertise workflows.
Key Findings
- AI-guided THCPs produced diagnostic-quality LUS in 98.3% (95% CI 95.1%-99.4%) of studies.
- No significant difference in image quality versus LUS experts (difference 1.7%; 95% CI -1.6% to 5.0%).
- Multicenter, masked expert panel validation; intention-to-treat analysis on 176 participants.
Methodological Strengths
- Multicenter prospective diagnostic validation with masked expert adjudication
- Intention-to-treat analysis and preregistration (NCT05992324)
Limitations
- Did not assess downstream clinical outcomes (e.g., management changes, patient outcomes)
- Generalizability beyond trained THCPs and participating sites remains to be tested
Future Directions: Evaluate impact on clinical decision-making, outcomes, and cost-effectiveness; assess performance in diverse settings, including prehospital and low-resource environments; integrate with tele-ultrasound workflows.
IMPORTANCE: Lung ultrasound (LUS) aids in the diagnosis of patients with dyspnea, including those with cardiogenic pulmonary edema, but requires technical proficiency for image acquisition. Previous research has demonstrated the effectiveness of artificial intelligence (AI) in guiding novice users to acquire high-quality cardiac ultrasound images, suggesting its potential for broader use in LUS. OBJECTIVE: To evaluate the ability of AI to guide acquisition of diagnostic-quality LUS images by trained health care professionals (THCPs). DESIGN, SETTING, AND PARTICIPANTS: In this multicenter diagnos
2. Barcoded SARS-CoV-2 viruses define the impact of duration and route of exposure on the transmission bottleneck in a hamster model.
Using >200 isogenic barcoded SARS-CoV-2 variants in hamsters, longer and more direct exposures increased the transmission bottleneck, and barcode enumeration across upper and lower airways showed the upper airway as the primary source of transmitted virus. The barcoded-virus platform provides a rigorous tool to quantify transmission dynamics.
Impact: Introduces a powerful methodological platform to dissect transmission events and quantify bottlenecks, informing vaccine and nonpharmaceutical interventions and viral evolution models.
Clinical Implications: While preclinical, findings support targeting upper airway viral load and minimizing prolonged/direct exposure in infection control. Barcoding approaches can inform variant fitness and transmission risk assessments.
Key Findings
- Generated a pool of >200 isogenic, 6-nt barcoded SARS-CoV-2 variants via reverse genetics.
- Longer and more direct exposure increased the transmission bottleneck size.
- Barcode profiling across nasal turbinates, trachea, and lungs identified the upper airway as the primary source of transmitted virus.
Methodological Strengths
- Barcoded reverse-genetics platform enabling quantitative transmission mapping
- Controlled in vivo exposure paradigms with tissue-resolved barcode enumeration
Limitations
- Hamster model may not fully recapitulate human transmission dynamics
- Barcoding, while designed isogenic, could still subtly affect fitness or detection biases
Future Directions: Translate to human challenge or household transmission studies; integrate with immune status and variant-specific fitness; apply to other respiratory viruses to generalize bottleneck principles.
The transmission bottleneck, defined as the number of viruses shed from one host to infect another, is an important determinant of the rate of virus evolution and the level of immunity required to protect against virus transmission. Despite its importance, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission bottleneck remains poorly characterized. We adapted a SARS-CoV-2 reverse genetics system to generate a pool of >200 isogenic SARS-CoV-2 viruses harboring specific 6-nucleotide barcodes, infected donor hamsters with this pool, and exposed contact hamsters to paired infected donors, varying the duration and route of exposure. Following exposure, the nasal turbinates, trachea, and lungs were collected and the number of barcodes in each tissue was enumerated. We found that longer and more direct exposures increased the transmission bottleneck and that the upper airway is the primary source of transmitted virus in this model. Together, these findings highlight the utility of barcoded viruses as tools to rigorously study virus transmission.
3. Gender Disparities and Lung Cancer Screening Outcomes Among Individuals Who Have Never Smoked.
Among 21,062 never-smokers undergoing opportunistic LDCT in South Korea, screen-detected lung cancers were predominantly stage 0–I adenocarcinoma in both sexes, with no significant sex-based differences in diagnosis rates, stage, histology, or lung cancer–specific death. Findings suggest similar overdiagnosis risks for men and women and limited benefit from indiscriminate LDCT in never-smokers.
Impact: Offers high-quality, sex-stratified evidence on LDCT screening in never-smokers, informing policy debates in regions with rising INS incidence and widespread opportunistic screening.
Clinical Implications: Supports reframing LDCT screening policy for never-smokers toward targeted risk-based strategies rather than indiscriminate screening, to mitigate overdiagnosis.
Key Findings
- In 21,062 never-smokers, 176 screen-detected lung cancers were mostly stage 0–I adenocarcinoma in both sexes.
- No significant sex-based differences in lung cancer diagnosis, stage distribution, histology, or lung cancer–specific deaths.
- Five-year lung cancer–specific survival was 97.7% (women) and 100% (men) for screen-detected cases, indicating potential overdiagnosis.
Methodological Strengths
- Large multicenter cohort with long follow-up (mean ~84 months)
- Adjusted analyses with sex-stratified outcomes and cause-specific mortality
Limitations
- Retrospective analysis of opportunistic screening with potential selection bias
- Low event counts for lung cancer–specific death limit precision
Future Directions: Develop and validate risk models for never-smokers to guide targeted LDCT; evaluate net benefit including overdiagnosis and radiation harms; assess environmental and genetic risk modifiers.
IMPORTANCE: Lung cancer in individuals who have never smoked (INS) is a growing global concern, with a rapidly increasing incidence and proportion among all lung cancer cases. Particularly in East Asia, opportunistic lung cancer screening (LCS) programs targeting INS have gained popularity. However, the sex-specific outcomes and drawbacks of screening INS remain unexplored, with data predominantly focused on women. OBJECTIVE: To compare LCS outcomes between Asian women and men with no smoking history. DESIGN, SETTING, AND PARTICIPANTS: This multicenter cohort study was conducted at health checkup centers in South Korea from 2009 to 2021. Participants included individuals aged 50 to 80 years with no smoking history who underwent low-dose computed tomography (LDCT) screening. Data were retrospectively analyzed from November 2023 to June 2024. EXPOSURES: Opportunistic LDCT screening for lung cancer. MAIN OUTCOMES AND MEASURES: Participants were followed up until December 2022 for the outcome of death. Lung cancer diagnosis, diagnostic characteristics, clinical course, and lung cancer-specific deaths (LCSD) were compared between women and men. RESULTS: A total of 21 062 participants (16 133 [76.6%] women and 4929 [23.4%] men) with a mean (SD) age of 59.8 (7.2) years were included. From baseline screening, 176 participants (139 women [0.9%] and 37 men [0.8%]) were diagnosed with lung cancer (screen-detected); 131 of 139 women (94.3%) and 33 of 37 men (89.2%) were diagnosed with stage 0 to I disease, with 133 of 139 women (95.7%) and 36 of 37 men (97.3%) having adenocarcinoma. There were no significant sex-based differences in stage or histologic type distribution. Among the 21 062 screened individuals, LCSD was reported in 8 women and 3 men during a mean (SD) follow-up of 83.8 (41.7) months. Multivariable analyses found no significant association between sex and cumulative hazards of lung cancer diagnosis (adjusted hazard ratio [aHR], 0.90 [95% CI, 0.64-1.26] for men vs women) or LCSD (aHR, 1.06 [95% CI, 0.28-4.00] for men vs women). The estimated 5-year lung cancer-specific survival rate was 97.7% for women and 100% for men with screen-detected lung cancer, showing no significant sex differences. CONCLUSIONS AND RELEVANCE: In this cohort study of Asian individuals with no smoking history who underwent LDCT screening, no significant sex-based differences were detected in lung cancer diagnosis, stage distribution, or LCSD. These findings suggest that men and women who have never smoked would experience similar risks of overdiagnosis with little to no benefit when exposed to indiscriminate screening.