Daily Respiratory Research Analysis

BACKGROUND: Cancer cachexia, frequently observed in patients with non-small cell lung cancer, is associated with reduced immunotherapy efficacy and poor prognosis. Despite the Fearon criteria being widely used to define cachexia, its relevance in Asian populations remains uncertain. Recently, the Asian Working Group for Cachexia (AWGC) proposed novel diagnostic criteria adapted for Asian body compositions. However, it remains unclear whether the outcomes or predictive value for immunotherapy differ between the AWGC and Fearon definitions. In addition, the AWGC-specific cachexia subgroup, previously regarded as noncachexia under Fearon's definition, has not been fully characterized. METHODS: We retrospectively analysed 411 Japanese patients with advanced PD-L1-high non-small cell lung cancer who received first-line PD-1/PD-L1 monotherapy or chemoimmunotherapy. Survival outcomes and clinical and nutritional indices were compared using both the AWGC and Fearon criteria. The patients were subsequently classified into three groups: (1) noncachexia, (2) A-only cachexia (meeting only the AWGC criteria), and (3) A+F cachexia (meeting both criteria). The small subgroup meeting only Fearon's criteria (n = 13) was excluded from analysis. RESULTS: Per the AWGC definition, 168 patients (40.9%) were classified as having cachexia compared to 62 (15.1%) according to the Fearon definition. AWGC-defined cachexia was associated with shorter overall survival (OS) (18.2 vs. 48.5 months, adjusted HR 1.539, p = 0.003), while progression-free survival (PFS) under PD-1/PD-L1 inhibitor therapy or chemoimmunotherapy showed a nonsignificant trend (7.1 vs. 13.0 months, adjusted HR 1.253, p = 0.072). Fearon-defined cachexia similarly predicted worse OS (18.4 vs. 37.7 months, adjusted HR 1.743, p = 0.002) but not PFS (5.9 vs. 11.4 months, adjusted HR 1.326, p = 0.081). In the three-group comparisons, the A-only cachexia group (n = 119) showed intermediate characteristics: Compared with the noncachexia group, they had lower BMI, higher C-reactive protein and poorer nutritional indices (prognostic nutritional and geriatric nutritional risk indices); compared with the A+F cachexia group, they had higher BMI, lower C-reactive protein and better nutritional indices. The PFS in the A-only cachexia group was comparable with that in the noncachexia group; however, the OS was significantly shorter (21.8 vs. 48.5 months, p = 0.0002). Compared with the A+F cachexia group, the A-only cachexia group showed no significant differences but demonstrated a favourable trend toward better PFS (adjusted HR 0.72, p = 0.096) and OS (adjusted HR 0.66, p = 0.051). CONCLUSION: The AWGC and Fearon criteria demonstrated comparable prognostic values. The A-only cachexia subgroup, previously regarded as noncachexia, retained responsiveness to immunotherapy but exhibited significantly shorter survival, underscoring its clinical relevance as a previously unrecognized at-risk group.

RATIONALE: Advanced polysomnographic (PSG) metrics reflecting the physiological causes and consequences of sleep apnea may enable precision medicine in research settings, but their feasibility in routine clinical practice has yet to be demonstrated. OBJECTIVE: Assess (1) the generalizability of PSG metrics from research to clinical cohort, and (2) their associations with a broad range of comorbid diseases, many of which have not been previously examined. METHODS: PSG metrics including endotypes (eg, loop gain) and physiological burdens (eg, hypoxic burden) were estimated from diagnostic polysomnographs of 6,427 participants at Mass General Brigham (MGB; Boston, MA). Comorbid conditions analyzed from MGB's medical record system included 9 representative cardio-metabolic and respiratory diseases, as well as 408 prevalent diseases. Associations were assessed using modified Poisson and LASSO regression. RESULTS: The sample included 62% females, age: 52.9 ± 16.8 years, and apnea-hypopnea index (AHI) 21.4 ± 15.9 events/hr. Associations between endotypes and demographics/obesity-related factors were consistent with prior observational studies (median difference in β = 0.03SD). After adjusting for AHI, older age was associated with lower heart rate (-0.40SD) and arousal burdens (-0.23SD), while higher BMI was associated with increased hypoxic burden (0.25SD). Having demonstrated that there is reasonable concordance with published data, our subsequent analysis identified distinct and clinically meaningful associations between advanced PSG metrics and comorbid conditions. Specifically, elevated loop gain, ventilatory burden, and hypoxic burden were associated with hypertension, diabetes, and renal failure; increased ventilatory instability was associated with cardiovascular disease; and reduced collapsibility and ventilatory instability with chronic airway obstruction. Even after LASSO-based selection, no single PSG metric consistently predicted risk across all comorbidities; ventilatory instability showed the most associations among endotypic traits, and heart rate burden among physiological burdens, underscoring the heterogeneity of OSA pathophysiology. CONCLUSIONS: Phenome-wide analyses of a large clinical cohort demonstrate the real-world feasibility and clinical relevance of extracting advanced PSG metrics, supporting their potential to identify personalized, mechanism-specific intervention targets for sleep apnea.

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality. Pulmonary rehabilitation (PR) is central to COPD management; however, individuals with musculoskeletal limitations, obesity, or reduced tolerance to land-based rehabilitation (LBR) may benefit from water-based rehabilitation (WBR). To evaluate the comparative effectiveness of WBR, LBR, and control interventions on exercise capacity (EC) and health-related quality of life (HRQoL) in adults with COPD using a systematic review and network meta-analysis (NMA). Randomized controlled trials (RCTs) involving adults with COPD were searched in PubMed, Cochrane Library, PEDro, and Bibliothèque nationale du Luxembourg from inception to July 13, 2025. The primary outcomes were EC, measured using the 6-Minute Walk Test (6MWT), Incremental Shuttle Walk Test (ISWT), and Endurance Shuttle Walk Test (ESWT), and HRQoL, assessed using the Chronic Respiratory Disease Questionnaire (CRDQ) and St. George's Respiratory Questionnaire (SGRQ). The Risk of bias was assessed using the Risk of Bias 2.0 tool (RoB 2.0). A frequentist NMA was used to estimate the comparative effects and intervention rankings. The certainty of the evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluations approach (GRADE). Nine RCTs (n = 323) were included in the analysis. WBR was associated with clinically meaningful improvements in EC, particularly in endurance performance (ESWT) and shuttle walking (ISWT), with several effects exceeding the established minimal clinically important difference (MCID) thresholds. HRQoL outcomes were heterogeneous: WBR improved selected CRDQ and SGRQ domains, whereas LBR ranked highest for overall HRQoL. The NMA ranking suggested that WBR had the highest probability of being the most effective intervention for EC and combined EC+HRQoL outcomes, whereas LBR ranked highest for HRQoL alone. Heterogeneity was low for EC, moderate for HRQoL, and high for the combined outcomes. The certainty of evidence ranged from moderate (EC) to low (combined outcomes). WBR is a viable alternative to LBR for improving EC in individuals with COPD and may be particularly beneficial for those with reduced mobility or limited tolerance to land-based training. However, given the limited number of trials and variability across studies, these findings should be interpreted with caution. High-quality and adequately powered RCTs are required to confirm the long-term effects and real-world applicability of these findings.