Daily Respiratory Research Analysis
Three impactful studies inform respiratory-related care across oncology, rheumatology, and emergency medicine. A target-trial–emulated VA cohort suggests TNF inhibitors do not worsen outcomes versus non-TNF biologics in rheumatoid arthritis–associated interstitial lung disease. KL-6 monitoring shows strong diagnostic performance for immune checkpoint inhibitor–induced pneumonitis (especially outside NSCLC), and a large ED analysis documents major shifts toward video laryngoscopy and rocuronium w
Summary
Three impactful studies inform respiratory-related care across oncology, rheumatology, and emergency medicine. A target-trial–emulated VA cohort suggests TNF inhibitors do not worsen outcomes versus non-TNF biologics in rheumatoid arthritis–associated interstitial lung disease. KL-6 monitoring shows strong diagnostic performance for immune checkpoint inhibitor–induced pneumonitis (especially outside NSCLC), and a large ED analysis documents major shifts toward video laryngoscopy and rocuronium with stable first-pass success in community settings.
Research Themes
- Management of rheumatoid arthritis–associated interstitial lung disease (RA-ILD)
- Biomarker surveillance for immune checkpoint inhibitor–induced pneumonitis
- Trends and outcomes in emergency airway management
Selected Articles
1. Advanced therapies in US veterans with rheumatoid arthritis-associated interstitial lung disease: a retrospective, active-comparator, new-user, cohort study.
In a target-trial–emulated, propensity-matched VA cohort of RA-ILD patients, initiation of TNF inhibitors yielded similar risks of respiratory hospitalization, all-cause mortality, and respiratory mortality compared with non-TNF biologics/tsDMARDs. The findings argue against blanket avoidance of TNF inhibitors in RA-ILD.
Impact: Challenges longstanding caution about TNF inhibitors in RA-ILD and may directly alter therapeutic algorithms. High methodological rigor enhances credibility of practice change.
Clinical Implications: TNF inhibitors need not be categorically avoided in RA-ILD; selection can be individualized based on arthritis control, ILD severity, and comorbidities, pending comparative efficacy trials.
Key Findings
- After propensity matching (n=237 vs 237), adjusted hazard ratio for the composite of death and respiratory hospitalization did not differ (aHR 1.21, 95% CI 0.92–1.58).
- No significant differences for respiratory hospitalization (aHR 1.27), all-cause mortality (aHR 1.15), or respiratory mortality (aHR 1.38) between TNF and non-TNF groups.
- Results were consistent across secondary, sensitivity, and subgroup analyses over up to 3 years of follow-up.
Methodological Strengths
- Target trial emulation with active-comparator, new-user design and propensity score matching.
- Multi-source outcomes from VA, Medicare, and National Death Index with up to 3-year follow-up.
Limitations
- Observational design with potential residual confounding and selection bias.
- Population predominantly male US veterans, which may limit generalizability.
Future Directions: Conduct randomized or high-quality comparative effectiveness trials of TNF vs non-TNF agents in RA-ILD and evaluate outcomes across ILD patterns and fibrosis progression.
BACKGROUND: Uncertainty exists regarding patient outcomes when using TNF inhibitors versus other biological and targeted synthetic disease-modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis-associated interstitial lung disease (ILD). We compared survival and respiratory hospitalisation outcomes following initiation of TNF-inhibitor or non-TNF inhibitor biological or targeted synthetic DMARDs for treatment of rheumatoid arthritis-associated ILD. METHODS: We did a retrospective, active-comparator, new-user, observational cohort study with propensity score matching following the target trial emulation framework using US Department of Veterans Affairs (VA) electronic and administrative health records. VA health-care enrollees with rheumatoid arthritis-associated ILD and no previous receipt of ILD-directed therapies (eg, antifibrotics) who initiated a TNF inhibitor or non-TNF inhibitor between Jan 1, 2006, and Dec 31, 2018, were included. Propensity score matching was performed using demographics, health-care use, health behaviours, comorbidity burden, rheumatoid arthritis-related severity factors, and ILD-related severity factors, including baseline forced vital capacity. Study outcomes were respiratory hospitalisation, all-cause mortality, and respiratory-related death over follow-up of up to 3 years, from VA, Medicare, and National Death Index data. People with lived experience of rheumatoid arthritis-associated ILD were not involved in the design or conduct of this study. FINDINGS: Of 1047 patients with rheumatoid arthritis-associated-ILD who initiated biological or targeted synthetic DMARDs, we matched 237 patients who had initiated TNF inhibitors and 237 who had initiated non-TNF inhibitors (mean age 68 years [SD 9]); 434 (92%) of 474 were male and 40 (8%) were female. Death and respiratory hospitalisation did not significantly differ between groups (adjusted hazard ratio 1·21 [95% CI 0·92-1·58]). Respiratory hospitalisation (1·27 [0·91-1·76]), all-cause mortality (1·15 [0·83-1·60]), and respiratory mortality (1·38 [0·79-2·42]) did not differ between groups. Secondary, sensitivity, and subgroup analyses supported the primary findings. INTERPRETATION: In US veterans with rheumatoid arthritis-associated ILD, no difference in outcomes were seen between those who started TNF inhibitors compared to those starting non-TNF biological or targeted synthetic DMARDs. These data do not support systematic avoidance of TNF inhibitors in all people with rheumatoid arthritis-associated ILD. Comparative efficacy trials in patients with rheumatoid arthritis-associated ILD are needed given the potential for residual confounding and selection bias in observational studies. FUNDING: US Department of Veterans Affairs.
2. Krebs von den Lungen-6 surveillance in immune checkpoint inhibitor-induced pneumonitis.
KL-6 rose markedly at onset of ICI-induced pneumonitis, yielding an AUC of 0.903 (cut-off 1.52× baseline) in non-NSCLC cancers and identifying both symptomatic and asymptomatic events. Predictive performance was lower in NSCLC, suggesting tumor-specific considerations for biomarker surveillance.
Impact: Provides a practical, quantitative trigger for early pneumonitis detection during ICI therapy, potentially minimizing treatment interruptions and steroid exposure.
Clinical Implications: Consider baseline and serial KL-6 monitoring for patients on ICIs, especially non-NSCLC, with action thresholds near 1.5× baseline to prompt imaging and specialist review.
Key Findings
- In non-NSCLC patients (n=382), pneumonitis cases showed KL-6 increase from 222.0 to 743.0 U/mL (p<0.0001) with AUC 0.903; optimal cut-off was 1.52× pre-treatment KL-6.
- KL-6 rose regardless of pneumonitis severity and detected both symptomatic and asymptomatic events in non-NSCLC.
- Steroid-unresponsive cases showed further KL-6 rise at 1 month (to 1078 U/mL), whereas steroid-responsive patients did not.
- In NSCLC (n=118), AUC was 0.683, indicating limited utility for pneumonitis detection.
Methodological Strengths
- Prospective-style serial biomarker monitoring across a sizable cohort with stratification by tumor type.
- Robust diagnostic metrics (AUC, sensitivity, specificity) and clinically actionable cut-off defined relative to baseline.
Limitations
- Single-biomarker approach without external validation cohorts limits generalizability.
- Retrospective ascertainment and potential confounding by underlying ILD, radiation, or tumor-related lung injury.
Future Directions: Prospective, multi-center validation of KL-6 algorithms integrated with imaging and clinical triggers; investigate multi-marker panels and tumor-specific thresholds.
BACKGROUND: The immune-related adverse event (irAE), pneumonitis, is a potentially fatal complication of immune checkpoint inhibitors (ICIs). Preventing its progression is crucial, emphasizing the need for effective screening tests. We evaluated the feasibility of using Krebs von den Lungen-6 (KL-6), a marker for interstitial pneumonitis, as a screening tool for pneumonitis. METHODS: We examined 500 patients with cancer divided into two groups: those with cancer other than non-small cell lung cancer (NSCLC) (Group 1, n=382) and those with NSCLC (Group 2, n=118). KL-6 levels were monitored before and during ICI treatment and analyzed for their correlation with pneumonitis. RESULTS: In Group 1, 37 patients (9.7%) developed pneumonitis. KL-6 levels were significantly elevated at irAE onset (pre: 222.0 U/mL, post: 743.0 U/mL, p<0.0001). Receiver operating characteristic curve analysis showed an area under the curve (AUC) of 0.903 (sensitivity 81.1%, specificity 91.6%) with a cut-off value 1.52 times pre-KL-6 levels, indicating that KL-6 is a reliable biomarker for pneumonitis. In these patients, the KL-6 level increased regardless of pneumonitis severity and was significantly elevated in patients with both symptomatic (pre: 205.0 U/mL, post: 674.5 U/mL, p<0.0001) and asymptomatic pneumonitis (pre: 314.0 U/mL, post: 743.0 U/mL, p<0.0001) at irAE onset. After irAE treatment, KL-6 levels in steroid-responsive patients remained unchanged; however, steroid-unresponsive patients had a significant increase in KL-6 levels at 1 month (1078 U/mL, p=0.031) compared with at irAE onset (678.0 U/mL). In Group 2, 24 patients (20.3%) developed irAE pneumonitis, with KL-6 levels elevated (pre: 360.5 U/mL, post: 506.5 U/mL, p=0.029) and an AUC of 0.683, indicating that KL-6 was less reliable in patients with NSCLC. CONCLUSIONS: KL-6 is a viable screening biomarker in ICI-induced pneumonitis, particularly in patients without NSCLC. In patients with NSCLC, the significance of KL-6 monitoring is limited as it is not effective for detecting ICI-induced pneumonitis; their treatment is typically managed by pulmonary specialists. Early detection through KL-6 monitoring facilitates timely intervention for ICI-induced pneumonitis, potentially preventing treatment interruptions and reducing the need for immunosuppressants.
3. Intubation Practices in Community Emergency Departments.
Across 11,475 community ED intubations, the use of video laryngoscopy and rocuronium rose substantially from 2015–2022, while first-pass success remained approximately 80.5% with very low failure. Despite technical advances, mortality among intubated patients remained high through 1 year.
Impact: Provides real-world airway management benchmarks and documents rapid adoption of video laryngoscopy and non-depolarizing neuromuscular blockade in community settings.
Clinical Implications: Supports routine availability and training in video laryngoscopy and rocuronium-based RSI in community EDs, with attention to post-intubation critical care given persistently high mortality.
Key Findings
- Video laryngoscopy use increased from 27.4% to 77.7% (difference 50.3%, 95% CI 44.2–56.4%) between 2015 and 2022.
- Rocuronium use increased from 33.9% to 61.9% (difference 28%, 95% CI 21.1–34.9%).
- First-pass success was 80.5% with a failure rate of 0.2% across 11,475 intubations.
- Intubated patients had high all-cause mortality at 24 hours (19.7%), 7 days (29.4%), 30 days (38.4%), and 1 year (45.4%).
Methodological Strengths
- Large, multicenter dataset spanning 8 years and 15 community EDs.
- Detailed capture of medications, techniques, attempts, and longitudinal mortality.
Limitations
- Retrospective design with potential documentation bias and unmeasured confounding.
- Lack of granular physiologic data (e.g., hypoxemia severity) limits causal inference on outcomes.
Future Directions: Prospective registries linking preoxygenation strategies, device choice, operator factors, and physiologic trajectories to outcomes; quality improvement targeting post-intubation care pathways.
STUDY OBJECTIVE: This study analyzes emergency medicine airway management trends and outcomes among community emergency departments. METHODS: A multicenter, retrospective chart review was conducted on 11,475 intubations from 15 different community emergency departments between January 1, 2015, and December 31, 2022. Data collected included patient's age, sex, rapid sequence intubation medications, use of cricoid pressure, method of intubation, number of attempts, admission diagnosis, and all-cause mortality rates. RESULTS: Active cardiopulmonary resuscitation occurred in 11.4% of intubations. When rapid sequence intubation was employed, the most frequently used induction agents were etomidate (91.6%), propofol (4.3%), and ketamine (4.1%). From 2015 to 2022, the use of rocuronium (versus succinylcholine) increased from 33.9% to 61.9%, a difference of 28% (95% confidence interval [CI] 21.1% to 34.9%). During the same period, video laryngoscopy (versus direct laryngoscopy) increased from 27.4% to 77.7%, a difference of 50.3% (95% CI 44.2% to 56.4%). Only 46% of intubations used cricoid pressure. Physicians had a first-pass success rate of 80.5% and a failure rate of 0.2%. The most common documented admission diagnoses among intubated patients were respiratory etiologies (27.8%), neurologic causes (21.4%), and sepsis (16.0%). All-cause mortality rates were high for intubated patients at 24 hours (19.7%), 7 days (29.4%), 30 days (38.4%), and 1 year (45.4%). CONCLUSION: Physicians intubating in community emergency departments have similar rates of first-pass success and failure seen in academic Level-1 trauma centers despite treating medically sick patients with high all-cause mortality rates. Dramatic shifts in choice of paralytic and method for intubation were seen.