Respiratory medicine最新文献

Background: While non-invasive ventilation (NIV) is recommended for managing acute exacerbations of chronic obstructive pulmonary disease (AECOPD), it has a 30-40% failure rate when delivered using pressure support ventilation (PSV). Adaptive support ventilation with IntelliSync (ASVi) synchronizes breath initiation and cycling to match patient's requirements. We conducted a feasibility study to inform design of a larger trial and compared NIV failure rates using PSV or ASVi in patients with AECOPD.

Materials and methods: We conducted a single-center, randomized controlled trial from December 2023 to April 2025 in subjects with AECOPD. Subjects were randomized (1:1) to receive NIV using PSV or ASVi. The primary outcome was NIV failure, defined as the need for airway intubation. Key secondary outcomes included the asynchrony index and 28-day all-cause mortality.

Results: We included 55 consecutive subjects with AECOPD (ASVi, n = 26; PSV, n = 29), with a mean age of 63 years. NIV failure occurred in15.4% (4/26) with ASVi versus 31% (9/29) with PSV, representing a 50% relative risk reduction (absolute difference 15.6%, 95% CI: -6.2%-37.5%, P = 0.17). Asynchrony index was similar between groups (22.6 ± 17.8 ASVi vs. 21.5 ± 16.7 PSV, P = 0.83). ASVi was associated with significantly greater patient comfort (P = 0.048) and shorter hospital stay (3.9 ± 2.9 vs 5.8 ± 4.0 days, P = 0.021).

Conclusion: This study demonstrates that ASVi is safe, feasible to implement, and associated with improved patient comfort and significantly reduced hospital stay in AECOPD. The observed 50% relative reduction in NIV failure rates, although not statistically significant, represents a clinically meaningful effect that warrants evaluation in a larger trial.

Purpose: Amikacin (AMK) is a widely used therapeutic drug monitoring (TDM)-recommended treatment for nontuberculous mycobacterial pulmonary disease (NTM-PD). However, its optimal dosage and TDM target remain unclear. In this study, we aimed to clarify the relationship between AMK exposure, ototoxicity, and efficacy.

Methods: Patients with NTM-PD treated with AMK at Fukujuji Hospital were retrospectively included in this study. The correlation between AMK exposure, measured by peak and trough levels and the area under the concentration-time curve (AUC), ototoxicity, and culture conversion was analyzed using the Mann-Whitney U test and Cox regression analysis. A population pharmacokinetic/pharmacodynamic (PPK/PD) model was developed to predict ototoxicity using TDM measurements.

Results: A total of 185 patients were enrolled. The median AMK dose and observation period were 500 (interquartile range [IQR], 500-600) mg/day and 45.8 (IQR, 31.3-76.5) months, respectively. Ototoxicity and culture conversion were observed in 39% and 54% of the enrolled patients, respectively, after initiating AMK. The median time to the development of ototoxicity was 69 (IQR; 43-97) days. Neither ototoxicity nor culture conversion was associated with AMK exposure, including its minimum inhibitory concentration. However, the cumulative AUC was significantly higher in patients who developed ototoxicity (P < 0.001) than in those without ototoxicity. The developed PPK/PD model enabled calculation of cumulative AUC from TDM data and prediction of ototoxicity onset.

Conclusion: Cumulative AMK exposure was associated with ototoxicity, and our findings allow prediction of ototoxicity onset using AMK TDM data.

Objective: To evaluate the prognostic value of Red Blood Cell Distribution Width-Albumin Ratio (RAR) in patients with obstructive sleep apnea (OSA) complicated by critical illness for all-cause mortality.

Methods: Based on the MIMIC-IV database, 2,536 OSA patients (first ICU admission) were enrolled and divided into four quartiles (Q1-Q4) according to RAR. Kaplan-Meier survival analysis, multivariate Cox regression (adjusted for age, gender, SOFA/APSIII), and subgroup analysis using restricted cubic spline (RCS) were employed to verify associations.

Results: The 30-day/365-day mortality rates in Q4 group (RAR≥5.55) were significantly higher than those in Q1 group (P<0.001). Adjusted HR for 30-day mortality in Q4 group was 2.06 (95% CI: 1.30-3.37), and 365-day HR was 2.19 (95% CI: 1.49-3.25). RCS confirmed a linear positive correlation between RAR and mortality (non-linear P>0.05).

Conclusion: Elevated RAR is associated with increased all-cause mortality risks at 30,90,180, and 365 days in patients with severe OSA, serving as an independent predictor of mortality risk in this population. As a low-cost, readily available biomarker based on routine blood tests, RAR can provide a reference for risk stratification in ICU patients with severe OSA.

Background: Lung cancer patients with interstitial pneumonia (IP) have limited treatment options due to the risks associated with therapeutic intervention. The underlying causes of IP in these patients are diverse, and there is currently no detailed molecular pathological classification or an established understanding of the effectiveness of anti-fibrotic medications such as nintedanib. This study aimed to elucidate the mechanism of action of nintedanib by analyzing differential RNA expression between normal and fibrotic lung tissues from lung cancer patients with IP.

Methods: RNA was analyzed from the non-tumor lung tissue of 7 patients with IP who received nintedanib before surgery. Non-tumor lung tissue was obtained from 12 lung cancer patients without IP complications who underwent radical surgery between 2017 and 2022 from the tissue bank of our institution. Fibrotic lung tissue from six IP patients who received nintedanib before surgery and 7 who did not (where RNA analysis was possible). Gene expression and microenvironmental analyses were performed using RNA sequencing data.

Results: Nintedanib modulated inflammation in non-tumor lung tissue, suppressing PLA2G2D and upregulating CST2 and MMP11, suggesting minimal impact on normal tissue and a favorable safety profile. In fibrotic lung lesions, nintedanib suppressed MUC6, ITLN1, and AREG expression. xCell2 analysis indicated reduced plasma cells and increased smooth muscle, muscle, adipocyte, and endothelial cells, suggesting normalization of tissue remodeling.

Interpritation: Nintedanib appears to exert anti-inflammatory effects and promote tissue repair in non-tumor lung, while facilitating tissue remodeling in fibrotic areas, indicating potential benefits in patients with interstitial pneumonia and lung cancer.

Background: Exercise modalities that target upper-airway and respiratory muscles may modify obstructive sleep apnea (OSA) severity.

Objective: To synthesize randomized controlled trials (RCTs) of resistance training (RT), oropharyngeal training (OT), and respiratory muscle training (RMT) on OSA severity (apnea-hypopnea index, AHI) and daytime sleepiness (Epworth Sleepiness Scale, ESS).

Methods: PubMed, EBSCO, and Scopus were searched (1 Jan 2015-31 Jan 2025). Of 1,805 records identified, 13 RCTs (n=429) met eligibility. Random-effects meta-analyses were performed within modality.

Results: OT reduced AHI (mean difference, MD -7.55 events·h^-1, 95% CI -13.39 to -1.71; p=0.02). RMT reduced AHI (MD -3.73 events·h^-1, -7.44 to -0.03; p=0.049). RT showed no significant change (MD -5.88 events·h^-1, -17.25 to 5.49; p=0.16). Across modalities, ESS showed no consistent, clinically meaningful improvement. Heterogeneity was substantial for RT trials for AHI and for OT trials in ESS, reflecting variability in protocols, duration, and participant characteristics.

Conclusions: When analyzed within modality, OT and RMT are associated with reductions in AHI, whereas RT alone does not demonstrate a significant effect. Symptom change measured by ESS was not consistently observed. These findings support OT and RMT as adjunctive options for reducing physiological OSA severity, while underscoring the need for standardized protocols, longer follow-up, and patient-important outcomes.

Background: Systemic inflammation, nutritional depletion, and immune dysregulation are common in asthma, yet no composite indicator has been prospectively linked to long-term survival; accordingly, the association between the C-Reactive Protein-Albumin-Lymphocyte (CALLY) index and all-cause mortality in U.S. adults with asthma was examined.

Methods: We analyzed 3,887 asthma participants aged ≥18 years from the National Health and Nutrition Examination Survey (NHANES) 1999-2010, linked to the National Death Index (NDI) through December 2019. Cox regression estimated hazard ratios (HR) per CALLY quartile and per one-unit increase in In-transformed CALLY, adjusting for sociodemographic, lifestyle and comorbidity covariates. Non-linearity was assessed with restricted cubic splines; subgroup analyses tested effect consistency.

Results: During a median 157 months, 729 deaths occurred (18.8% mortality). Higher CALLY was associated with younger age, lower BMI and fewer comorbidities. After full adjustment, each unit increase in CALLY conferred a 19% lower mortality risk (HR 0.81, 95 % CI 0.76-0.86). The dose-response gradient remained linear across the entire distribution, and the inverse association was consistently observed across all predefined strata.

Conclusion: In this cohort, a higher CALLY index was independently associated with lower all-cause mortality among adults with asthma; prospective studies are warranted to confirm this association.

Aims: To compare physical, functional and inflammatory characteristics between adults with severe asthma and controls with and without obesity, and to evaluate factors associated with sarcopenia and muscle quality.

Methods: This cross-sectional study included four groups: adults with severe asthma and controls (without respiratory diseases), stratified by the presence or absence of obesity. Assessments included lung function, asthma outcomes, clinical variables, body composition, sarcopenia, muscle quality index (MQI), muscle function and strength, six-minute walk distance (6MWD), and inflammatory markers.

Results: A total of 233 participants were included (140 with severe asthma, 93 controls). The group with obesity and severe asthma showed worse core function, limb strength, MQI and 6MWD, compared to the other groups (P<0.0001 for all). No significant differences were observed in lean mass (P=0.123) or in the prevalence of sarcopenia (P=0.291) between groups. Inflammatory markers were elevated in asthma, regardless of obesity. A multiple linear regression model including age, sex, asthma, fat mass, lower limb strength and 6MWD explained 43.3% of the variability in appendicular skeletal muscle mass index (ASMMI).

Conclusion: Obesity plays a key role in muscle dysfunction on core, upper, and lower limb muscle groups. This reinforces the need for integrated clinical approaches addressing both asthma and obesity.

Background: Underlying immune modifications are offered by the Polyvalent Chemical Bacterial Lysate OM-85 (i.e., anti-viral properties, enhancement of the epithelium barrier function, and induction of a tolerance landscape in the lungs). This secondary post hoc analysis used data from the OMRIA study, to assess the effect of add-on OM-85 on reducing the risk for exacerbations of any origin in adults with difficult-to-treat T2-high asthma.

Methods: The Oral Bacterial Lysate OM-85 Prevents Respiratory Tract Infections in Asthma (OMRIA) study enrolled adults with T2-high asthma frequently exacerbating, under standard of care asthma therapy (SoC), who were started on OM-85 (two 3-month courses with a 3-month treatment-off period in between). Patients were assigned to two groups (OM-85 plus SoC n=70 and SoC group n=67) and all AEXs and OCS bursts were recorded throughout a 12-month period. A clinical categorization to identify infectious and non-infectious AEXs was also applied: 1. Asthma symptoms alone (non-infectious), 2. Combined asthma and common cold symptoms (infectious), 3. Combined asthma and bronchitis, sinusitis, or pneumonia symptoms (infectious).

Results: The weighted with propensity scores analyses (Poisson and negative binomial regression model), verified the statistically significant decreases in the average numbers of AEXs and OCS bursts reported in OMRIA study, in patients treated with OM-85. Same tendencies were recorded in each AEX class (class 1-non-infectious: 50.5% decrease, classes 2 and 3-infectious: 72.2% and 89.8% decrease, respectively).

Conclusion: This secondary post hoc analysis supports the therapeutic benefit of OM-85 in patients with T2-high asthma who have frequent exacerbations despite adherence to SoC asthma therapy.

Background: Bronchiectasis is a chronic airway disease characterized by persistent inflammation and structural damage, with substantial clinical and etiologic heterogeneity. Although previous studies have identified associations between blood cells and bronchiectasis, the causal relationships remain unclear. Moreover, the mechanisms underlying blood cell perturbation responses and their potential mediation by immune cells in disease progression are largely unexplored.

Methods: Two-sample Mendelian randomization (MR) analysis was used to explore genetically predicted associations among immune cell traits, blood cell perturbation response phenotypes, and bronchiectasis, based on genome-wide association study summary data. Mediation MR analysis was further applied to assess whether immune cells mediate these associations. Multiple sensitivity analyses, including tests for heterogeneity and horizontal pleiotropy, were performed to evaluate the validity and robustness.

Results: Five blood cell perturbation response phenotypes and twenty-nine immune cell traits showed significant genetically predicted associations with bronchiectasis. Mediation analysis showed that natural killer (NK) cell absolute count partially mediated the causal effect between the eosinophil perturbation response and bronchiectasis, with a mediation proportion of 9.626%. CD38 on transitional B cells mediated the causal effect between the monocyte perturbation response and bronchiectasis, with a mediation proportion of 10.580%. Additionally, CD45 on NK cells played a mediating role in the association between the white blood cell perturbation response and bronchiectasis, with a mediation proportion of 10.651%.

Conclusion: This study systematically explores genetically predicted associations between blood cell perturbation responses and bronchiectasis and highlights potential immune-mediated pathways. These exploratory findings provide novel genetic insights into the pathogenesis of bronchiectasis and identify potential therapeutic targets for future strategies.

Purpose: The aim of this study was to identify perceived cognitive impairment and its associated factors in patients newly diagnosed with lung cancer.

Methods: This cross-sectional analysis utilized pretreatment data sourced from an ongoing multicenter longitudinal investigation (registration: ChiCTR2300076232). A total of 340 participants were enrolled between September 2023 and March 2024 from two public hospitals in Anhui Province, China. The well-validated Chinese version of the FACT-Cog was used to collect the information of perceived cognitive function. Data on sociodemographic and clinical characteristics, as well as cancer-related symptoms were obtained through structured questionnaires and medical records.

Results: 170 Patients newly diagnosed with lung cancer and 170 non-cancer controls matched in age and gender. Patients scored significantly lower on the FACT-Cog and four subscales than controls (all P < 0.05). The prevalence of perceived cognitive impairment in patients was 15.3%, which was significantly higher than 6.5% in controls (P = 0.009). Multivariate regression analysis revealed that fatigue [(95% CI: -2.527 ∼ -1.701); P < 0.001], gender [(95% CI: -15.722 ∼ -4.670); P < 0.001], age [(95% CI: -0.711 ∼ -0.082); P = 0.014] and depression [(95% CI: 0.222 ∼ 1.963); P = 0.014] emerged as significant predictors of perceived cognitive impairment, explaining 54.5% of the total variance (P < 0.001).

Conclusions: Patients newly diagnosed with lung cancer exhibited a significant decrement in cognitive function compared to controls. Healthcare professionals ought to provide prompt attention and implement early rehabilitative interventions to prevent further cognitive decline subsequent to the initiation of systemic treatment.