Daily Respiratory Research Analysis
A multicenter randomized trial shows that ultrasound elastography-guided pleural biopsy improves sensitivity for diagnosing malignant pleural effusion without compromising safety. A large population-based cohort quantifies the markedly elevated risk and mortality associated with nontuberculous mycobacterial disease after solid-organ transplantation. Real-world causal analyses indicate that systemic therapies—including glucocorticoids and antifibrotics—significantly slow lung function decline in
Summary
A multicenter randomized trial shows that ultrasound elastography-guided pleural biopsy improves sensitivity for diagnosing malignant pleural effusion without compromising safety. A large population-based cohort quantifies the markedly elevated risk and mortality associated with nontuberculous mycobacterial disease after solid-organ transplantation. Real-world causal analyses indicate that systemic therapies—including glucocorticoids and antifibrotics—significantly slow lung function decline in progressive pulmonary fibrosis, supporting “despite management” criteria for antifibrotic eligibility.
Research Themes
- Diagnostic innovation in pleural disease
- Transplant infectious risk and outcomes
- Real-world effectiveness of antifibrotics in progressive pulmonary fibrosis
Selected Articles
1. Ultrasonic Elastography-guided Pleural Biopsy
In a multicenter randomized trial, elastography-guided pleural biopsy achieved higher sensitivity (85%) for malignant pleural effusion than standard ultrasound-guided biopsy, with similar safety. Elastography targeting likely enriches sampling of stiffer malignant pleura across pleural thickness strata.
Impact: This RCT directly informs diagnostic pathways for pleural effusions by demonstrating superior yield without added harm. It operationalizes tissue stiffness mapping to guide biopsy, an immediately adoptable technique in experienced centers.
Clinical Implications: Consider UEPB when malignancy is suspected to increase diagnostic sensitivity, particularly where initial cytology is nondiagnostic. Training sonographers to integrate elastography into pleural workups could reduce repeat procedures and expedite oncology care.
Key Findings
- UEPB demonstrated higher sensitivity for malignant pleural effusion than standard TUSPB (85.0%).
- Safety profile of UEPB was similar to TUSPB.
- Trial was multicenter and randomized (NCT05781659), supporting generalizability.
Methodological Strengths
- Multicenter randomized design with prospective allocation
- Trial registration with prespecified outcomes
Limitations
- Comparator sensitivity and subgroup performance by pleural thickness not fully detailed in abstract
- Operator experience and learning curve effects not elaborated
Future Directions: Define training standards and learning curves for UEPB; assess cost-effectiveness and impact on time-to-diagnosis; evaluate performance across different pleural thicknesses and tumor histologies.
BACKGROUND: Traditional thoracic ultrasound-guided pleural biopsy (TUSPB) is considered the initial method for histological diagnosis; however, its sensitivity for detecting malignant pleural effusion (MPE) is limited. Ultrasound elastography can be used to differentiate MPE from benign diseases by evaluating pleural stiffness. This study aimed to investigate whether ultrasonic elastography-guided pleural biopsy (UEPB) offers diagnostic accuracy superior to that of TUSPB for pleural effusions. METHODS: In this multicentre, randomised trial (ClinicalTrials.gov ID: NCT05781659), patients with pleural effusion of unknown origin were enrolled and randomized (1:1) to undergo either UEPB or TUSPB. The primary outcome measured was the sensitivity of UEPB in diagnosing MPE; the secondary outcomes were the diagnostic rate of the two methods in patients with different pleural thicknesses, and the safety of UEPB. FINDINGS: In total, 232 patients with pleural effusion were enrolled, 228 of whom were included in the analysis. The sensitivity for detecting MPE was significantly greater in the UEPB group than that in the TUSPB group (85.00% [51/60] INTERPRETATION: UEPB was superior to TUSPB in the diagnosis of MPE with a similar safety profile.
2. Nontuberculous Mycobacterial Disease in Solid-Organ Transplant Recipients and the General Population.
In a population-based matched cohort of 138,175 individuals, solid-organ transplant recipients—especially lung recipients—had dramatically higher risk of nontuberculous mycobacterial disease (aHR 177 for lung; 8.9 for other organs) versus controls. MAC- and RGM-associated disease conferred increased long-term mortality in both lung and nonlung transplant recipients.
Impact: The study provides robust, generalizable estimates of NTM-D risk and mortality after transplantation, informing screening and prophylaxis strategies across transplant programs.
Clinical Implications: Transplant programs should consider risk-stratified screening for NTM (especially in lung recipients), early diagnostic evaluation of respiratory symptoms, and tailored antimicrobial strategies. Pre- and post-transplant counseling should address NTM risk and surveillance.
Key Findings
- Solid-organ transplantation was associated with markedly increased NTM-D risk vs matched controls (lung aHR 177.34; other organs aHR 8.89).
- NTM-D due to MAC and RGM increased long-term mortality in both lung and nonlung recipients.
- Rigorous, culture-based case definitions and province-wide linkage enhanced validity.
Methodological Strengths
- Population-based design with 1:10 matching by age, sex, and region
- Longitudinal follow-up with Cox models and species-specific analyses
Limitations
- Observational design susceptible to residual confounding
- Potential misclassification of exposure or outcomes inherent to administrative data
Future Directions: Evaluate targeted screening intervals, environmental exposures, and prophylaxis in high-risk subgroups; integrate microbiome and immune profiling to refine risk prediction.
IMPORTANCE: Single-center studies suggest that solid-organ transplant recipients (SOTRs) with nontuberculous mycobacterial disease (NTM-D) face increased mortality, particularly in the presence of comorbidities such as chronic lung disease. Large-scale studies are needed to quantify the risk of NTM-D and its impact on mortality in this population. OBJECTIVE: To compare the risk of NTM-D between the general population and SOTRs, stratified by lung and nonlung transplants, and to assess whether NTM-D is associated with increased mortality risk in SOTRs. DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study was conducted in Ontario, Canada, from April 1, 2002, to December 31, 2018. Adult SOTRs were matched 1:10 with general population controls by age, sex, and region. Analyses were conducted from January 2024 to March 2025. EXPOSURE: Solid-organ transplantation. MAIN OUTCOMES AND MEASURES: The primary outcome was NTM-D, defined as isolation of NTM from blood, tissues, or respiratory samples (≥2 sputum cultures with the same species or 1 bronchoscopic or lung biopsy culture). The secondary outcome was all-cause mortality in the SOTR cohort at 1 year and by the end of follow-up (March 31, 2021). Cox proportional hazard models were used to estimate the risk of outcomes. RESULTS: The study included 138 175 individuals (49 611 female [35.9%]; mean [SD] age, 51.87 [12.99] years), comprising 12 564 SOTRs (7674 kidney, 2419 liver, 1257 lung, 584 heart, 563 kidney-pancreas, and 67 multiorgan recipients) and 125 611 matched controls. During the study period, 368 SOTRs (2.92%) and 127 controls (0.10%) developed NTM-D. Receipt of a lung transplant (adjusted hazard ratio [aHR], 177.34; 95% CI, 79.65-394.82) or other solid-organ transplant (aHR, 8.89; 95% CI, 5.90-13.40) were both associated with increased risk of NTM-D compared with controls. NTM-D by Mycobacterium avium complex (MAC) and rapidly growing mycobacteria (RGM) were associated with significant long-term mortality in lung SOTRs (MAC aHR, 1.66; 95% CI, 1.35-2.04; RGM aHR, 2.33; 95% CI, 1.59-3.39) and nonlung SOTRs (MAC aHR, 2.12; 95% CI, 1.36-3.29; RGM aHR, 2.25; 95% CI, 1.07-4.74). CONCLUSIONS AND RELEVANCE: In this cohort study of SOTRs and the general population, both lung transplantation and other solid-organ transplantation were associated with a significantly elevated risk of NTM-D, which was linked to a higher mortality risk. These findings highlight the need for preventive and screening strategies.
3. Effectiveness of antifibrotic treatment in real-world patients with progressive pulmonary fibrosis.
Across 1,754 non-IPF ILD patients, antifibrotics were associated with improved estimated survival in PF-ILD and in PPF that progressed despite appropriate management, but not in the broader PPF definition. Advanced causal methods (parametric G-formula, time-varying Cox, IPW) yielded consistent findings.
Impact: The study clarifies which PPF definitions identify patients most likely to benefit from antifibrotics in routine care, informing policy and guideline criteria.
Clinical Implications: Antifibrotic initiation may be most justified in PF-ILD and in PPF with documented progression despite appropriate non-antifibrotic management. Programs should operationalize ‘despite management’ criteria and monitor outcomes using causal analytic frameworks.
Key Findings
- Antifibrotics were associated with higher estimated survival in PF-ILD and PPF ‘despite management’.
- No clear survival advantage in the broader PPF group defined by 12-month progression criteria.
- Causal analyses (parametric G-formula, time-varying Cox, IPW) produced consistent results.
Methodological Strengths
- Large multicenter real-world cohort with predefined progression phenotypes
- Use of advanced causal inference methods (parametric G-formula, IPW, time-varying Cox)
Limitations
- Retrospective observational design with potential residual confounding and selection bias
- Heterogeneity of background management and progression ascertainment across centers
Future Directions: Prospective trials to validate ‘despite management’ criteria; harmonize progression definitions and embed pragmatic randomization to confirm survival benefit.
PURPOSE: The suitability of progressive pulmonary fibrosis (PPF) as a criterion for antifibrotic use remains uncertain. We aimed to evaluate the effectiveness of antifibrotics for patients with different criteria of progressive non-idiopathic pulmonary fibrosis interstitial lung disease (non-IPF ILD). MATERIAL AND METHODS: In this multicenter, retrospective cohort study, we estimated the effect of antifibrotic drugs in three cohorts of PF-ILD (progression within 24 months under standard non-antifibrotic therapy, as in the INBUILD trial), PPF (progression within 12 months based on ATS/ERS/JRS/ALAT guidelines), and PPF "despite management" (a subset of PPF with progression despite appropriate non-antifibrotic therapy). Analyses used the parametric G-formula, the time-varying Cox hazard model, and inverse probability weighting (IPW). RESULTS: Among 1754 patients with non-IPF ILD, 327, 567, and 326 patients were diagnosed with PF-ILD (134 antifibrotics, 193 non-antifibrotics), PPF (149 antifibrotics, 418 non-antifibrotics), and PPF "despite management" (115 antifibrotics, 211 non-antifibrotics), respectively. Using the parametric G-formula, antifibrotic therapy was associated with higher estimated survival in PF-ILD, with statistically significant differences during the first three years, and with a consistent survival advantage in the PPF "despite management" cohort. In contrast, no clear survival benefit was observed in the PPF cohort. These findings were consistent with the time-varying Cox hazard model and IPW analysis results. CONCLUSION: Our results demonstrate antifibrotic therapy was associated with higher estimated survival in patients with PF-ILD in a real-world setting, suggesting the importance of including "despite management" as a criterion for antifibrotic therapy eligibility in the PPF diagnosis.