Advances in respiratory medicine最新文献

Background: Corisin, a microbiota-derived proapoptotic peptide, has emerged as a key mediator of epithelial injury, inflammation, and acute exacerbation in fibrotic lung disease. Although acute corisin inhibition prevents exacerbations in experimental models, its therapeutic impact on established pulmonary fibrosis remains unclear. This study evaluated the short-term efficacy of corisin neutralization in advanced transforming growth factor-β1 (TGF-β1)-driven lung fibrosis.

Methods: Male TGF-β1 transgenic mice with established fibrosis were allocated to computed tomography-matched groups and treated intraperitoneally with an anti-corisin monoclonal antibody (clone 21A) or control IgG every two days for one week. Bronchoalveolar lavage fluid (BALF) analysis, histopathology, assessment of apoptosis, Ashcroft scoring, and lung hydroxyproline quantification were performed on day 8.

Results: Anti-corisin treatment significantly reduced BALF inflammatory cell counts, including macrophages and lymphocytes. Histological analyses demonstrated decreased alveolar epithelial apoptosis, reduced collagen deposition, and significantly lower Ashcroft fibrosis scores. Lung hydroxyproline content was also markedly decreased, indicating attenuation of extracellular matrix accumulation.

Conclusions: Short-term neutralization of microbiota-derived corisin rapidly alleviates inflammation, epithelial injury, and fibrotic remodeling in advanced TGF-β1-induced pulmonary fibrosis. These findings identify corisin as an upstream driver of ongoing fibrogenesis and support its potential as a therapeutic target in progressive fibrotic lung disease.

Background: Obstructive sleep apnea (OSA) affects quality of life and increases cardiovascular risk. Nocturnal oxygen therapy (NOT) offers a potential alternative for patients intolerant to CPAP. The objective of this study was to compare NOT and continuous positive airway pressure (CPAP) by evaluating five-year survival in patients with obstructive sleep apnea.

Methods: A retrospective cohort study was conducted using propensity score matching (PSM) methodology. A PSM analysis was conducted to reduce selection bias due to differences in baseline characteristics between patients using CPAP and those receiving oxygen therapy. Balance between treated and untreated groups was assessed using standardized mean differences. A PSM was estimated using a logistic regression model, matching patients adherent to CPAP therapy to those treated with NOT.

Results: A total of 497 patients with a confirmed diagnosis of OSA were included in the analysis. The mean age was 62.1 years (SD13.6), and 54.3% (270/497) were male. Overall, 42.1% (209/497) of the patients were over 65 years old. Of the total, 303 patients received CPAP therapy and 194 received NOT. After PSM, a matched cohort of 370 patients (185 per group) was obtained. The CPAP-treated group showed a significantly lower residual Apnea-Hypopnea Index compared to the oxygen therapy group (3.9, IQR: 1.8-6.5 vs. 15, IQR:7.5-29.1; p < 0.001), indicating better physiological control of respiratory events. Treatment with CPAP was associated with a significantly lower risk of mortality compared with NOT across analytical approaches, including weighted logistic regression (OR = 0.11; 95% CI 0.02-0.48; p = 0.004) and PSM with bootstrap estimation (ATT = -0.12; 95% CI -0.22 to -0.01; p = 0.030).

Conclusions: In this cohort, higher five-year survival was observed among patients with OSA treated with CPAP compared with those receiving supplemental oxygen. These findings indicate a favorable association between CPAP use and long-term outcomes, supporting its role as the preferred first-line therapy in patients with OSA.

Pulmonary hypertension associated with interstitial lung disease (PH-ILD) is a progressive condition with limited treatment options and associated with high mortality rates. Inhaled treprostinil (iTre) is the only approved therapy for PH-ILD and has been shown to improve exercise capacity and delay disease progression. However, the conventional outpatient titration schedule requires 8-16 weeks to achieve therapeutic dosing, which may delay clinical benefit in those with advanced disease. We conducted a retrospective study of six patients with severe PH-ILD admitted to a tertiary academic center for initiation of iTre using a rapid inpatient uptitration protocol. iTre was started at 3 breaths four times daily (QID) and increased by 2 additional breaths every 12-24 h as tolerated, aiming for ≥9-12 breaths QID within one week under close monitoring. All six patients achieved target dosing without dose reduction or interruption. At three-month follow-up, mean pulmonary artery pressure decreased from 42 ± 5.5 to 35.2 ± 4.5 mmHg, pulmonary vascular resistance from 8.0 ± 1.2 to 6.0 ± 0.9 WU, and cardiac index increased from 2.05 ± 0.13 to 2.15 ± 0.12 L/min/m². No readmissions occurred within 90 days. This study demonstrates that rapid inpatient uptitration of iTre in severe PH-ILD is feasible and well-tolerated, with preliminary evidence of short-term hemodynamic improvement.

Background: Nintedanib and pirfenidone are two anti-fibrotic agents for diseases within the interstitial lung diseases (ILDs) spectrum. Here, we provide a comprehensive analysis regarding treatment persistence and adherence rates for the Greek territory.

Methods: This was a retrospective cohort study of patients initiating anti-fibrotic treatment during the period 2019-2023, utilizing data extracted from the National Electronic Prescription Database. Treatment persistence was defined as the duration from the date of the first prescription to the end of follow-up, death, or switching to another agent. Adherence was estimated based on the Medication Possession Ratio (MPR) metric.

Results: Overall, 2112 patients were analyzed. The majority were naive, male patients with a diagnosis of idiopathic pulmonary fibrosis (IPF). The overall median treatment persistence was 40.2 months (95% CI: 35.5-44.6). Women and treatment-naive patients demonstrated longer median treatment persistence compared to their counterparts, while older patients demonstrated the lowest median persistence rates. Adherence levels remained high across the follow-up period (90%). Diagnosis of IPF and gastrointestinal comorbidities were associated with a higher risk of discontinuation.

Conclusions: We have generated novel data concerning the factors that affect patients' outcomes under anti-fibrotic therapy. These findings may provide helpful insights for the therapeutic management of ILDs.

Introduction: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality. Early identification and timely intervention for COPD exacerbations can reduce hospitalizations and complications, as well as improve patient outcomes. Methods: To develop and evaluate predictive models for COPD exacerbations using machine learning (ML), we performed a retrospective study using intensive care unit patient records. Records including 31,667 clinical notes and 10,489 vital signs were used to train and validate two machine learning models to predict COPD exacerbations in patients with known or suspected COPD. Predictive performance was evaluated for support vector machine, quadratic discriminant analysis, and adaptive boosting algorithms using area under the receiver operating characteristic curve (AUC). Results: The clinical note-based support vector machine model achieved an AUC of 0.81 and accuracy of 84.0% in predicting COPD exacerbations. Data from patient monitors and hospital information systems provided sufficient information for accurate prediction, demonstrating the utility of combining physiological signals with clinical text data. Discussion: Clinically available patient data and vital signs can effectively predict COPD exacerbations, potentially enabling earlier interventions, improved outcomes, and reduced healthcare burden. These findings suggest that integrating unstructured clinical notes with structured vital signs using ML frameworks may improve early detection of exacerbation risk, thus enabling appropriate patient counseling, triage, and treatment based on COPD severity.

Introduction: This document presents recommendations of the Polish Respiratory Society on discharge instructions following hospitalization for an exacerbation of chronic obstructive pulmonary disease (COPD). Methods: The Delphi method was applied to achieve consensus among independent experts. Results: Fourteen recommendations were formulated. Experts emphasized that discharge summaries require clear graphical and editorial design to ensure readability for both patients and healthcare professionals. The involvement of a multidisciplinary team was recommended to provide coherent and comprehensive documentation. Discharge instructions should be discussed with the patient during hospitalization and supplemented with standardized educational materials provided separately. These materials should cover inhaler technique, smoking cessation, physical activity, pulmonary rehabilitation, and vaccination. For patients with respiratory failure, home oxygen therapy or non-invasive ventilation must be addressed. Discharge recommendations should highlight modifications in baseline COPD treatment and management of comorbidities. A personalized action plan for future exacerbations is essential, and dietary consultation is advised. Finally, discharge summaries should specify follow-up appointments and include prescriptions for inhaled medications. Conclusions: The Polish Respiratory Society recommends that discharge instructions be provided to all patients hospitalized for a COPD exacerbation.

Background: Elderly-onset sarcoidosis > 65 (EOS) is rare and occurs in patients over 65. Studies on its incidence, clinical features, and treatment are limited, and its link to malignancy remains complex. Objectives: In this study, we aimed to analyze the possible association between malignancy and the occurrence of sarcoidosis in elderly patients over 65 years old. Design: Monocentric, nested retrospective case-control study. Material and Methods: A retrospective study analyzed newly diagnosed sarcoidosis patients in the Loewenstein Lung Center, Baden-Württemberg, Germany, categorizing them into younger-onset (<65 years) and elderly-onset (≥65 years). Demographic data, smoking status, medical history, symptoms, diagnostic methods, and any prior malignancy history were collected. Results: A total of 447 patients were included (365 patients within the group of younger-onset sarcoidosis and 82 patients with EOS). The median age of the younger-onset group was 47 (47 [23-63] years), compared to 69 (69 [65-84] years), p ≤ 0.001. Female patients were more prevalent in the group of elderly-onsets (54.9%) compared to the younger-onset group (35.9%), corresponding to an odds ratio of 2.2 (95% CI: 1.3-3.5, p: 0.002). Regarding the past history of malignancy, patients who had a positive history of malignancy were more prevalent among the elderly-onset group (29.6%) compared to the younger-onset group (5%) [OR (95% CI): 8.1 (4.1-15.8), p ≤ 0.001]. In multivariable logistic regression analysis with malignancy as the outcome, increasing age at sarcoidosis diagnosis was independently associated with a higher likelihood of prior malignancy (adjusted OR 1.08 per year, 95% CI 1.04-1.12), whereas sex, smoking status, and cardiometabolic comorbidity (diabetes and/or hypertension) were not independently associated. Conclusions: Elderly-onset sarcoidosis (EOS) is a less frequent variant of sarcoidosis with limited data regarding the possible risk factors. The increased prevalence of malignancy observed among patients with elderly-onset sarcoidosis appeared to be largely driven by age rather than a distinct EOS-specific effect. Age-adjusted analyses are essential when interpreting malignancy risk in sarcoidosis, and future age-matched prospective studies are needed to clarify potential biological links and guide evidence-based screening strategies.

This systematic review and meta-analysis aimed to evaluate the efficacy and safety of carbocisteine in reducing chronic obstructive pulmonary disease (COPD) exacerbations based on evidence from randomized controlled trials (RCTs). A comprehensive literature search was conducted across PubMed, Embase, Cochrane Library, and ClinicalTrials.gov. RCTs comparing carbocisteine (1500 mg/day) with placebo in COPD patients, with a minimum follow-up of six months, were included. Data on exacerbation rates and adverse events were extracted and analyzed using a random-effects model. Four RCTs involving 1746 patients met inclusion criteria. Pooled analysis showed that carbocisteine significantly reduced the annual rate of acute exacerbations compared to placebo (WMD = -0.40; 95% CI: -0.69 to -0.11), with no significant increase in adverse events (OR = 1.02; 95% CI: 0.76 to 1.37). Mechanistically, carbocisteine improves mucociliary clearance, suppresses airway inflammation, reduces oxidative stress, and may hinder bacterial colonization. Carbocisteine is associated with a significant reduction in COPD exacerbations and demonstrates a favorable safety profile. It may serve as an effective adjunctive therapy in patients with frequent exacerbations and mucus hypersecretion.

High-flow nasal cannula (HFNC) therapy is frequently described as a positive pressure modality, yet this classification lacks mechanistic support. This critical narrative review integrates experimental, computational, and clinical evidence to examine the established physiological mechanisms underlying HFNC, with emphasis on precise terminology. The study clarifies that labeling HFNC as "positive pressure" is conceptually inaccurate, as the system delivers transient, flow-dependent pressures characteristic of open-circuit administration. Evidence is synthesized to quantify the relative contributions of nasopharyngeal dead-space clearance versus emergent pressure generation. Unlike CPAP, HFNC produces pressures ranging from 0.2 to 13.5 cmH₂O, determined by airway geometry, leak magnitude, and mouth position. Fluid dynamic modeling using Bernoulli and Darcy-Weisbach equations demonstrates oscillatory rather than sustained pressures, with magnitudes linked to nasopharyngeal Reynolds numbers (2400-6000) and turbulent energy dissipation (30-60%). Clinical efficacy persists despite variable pressures, reflecting synergistic mechanisms: inspiratory flow matching (40-50% reduction in work of breathing), dead-space clearance (CO₂ reduction, r = -0.77, p < 0.05), emergent pressure effects (10-20%), and thermal humidification (10-20%). Electrical impedance tomography reveals heterogeneous alveolar recruitment, with high-potential (54%) and low-potential (46%) phenotypes. Based on these mechanistic insights, this review proposes the term "emergent hydrodynamic pressure" to accurately describe HFNC's transient, flow-dependent pressures. This terminology differentiates HFNC from conventional positive pressure systems and aligns language with the principles of fluid dynamics and respiratory physiology.

Background/objectives: Community-acquired pneumonia (CAP) is classified into typical and atypical forms, with Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella pneumophila being the most common atypical pathogens and Streptococcus pneumoniae and Haemophilus influenzae the most common typical organisms. This study aimed to compare the prevalence, demographics, and clinical outcomes of hospitalized typical and atypical CAP patients.

Methods: A cross-sectional study was conducted from January 2016 to June 2022 at two tertiary hospitals in Riyadh, Saudi Arabia. All inpatients diagnosed with CAP by imaging and clinical findings were included, excluding viral cases. Outcomes measured included pathogen testing and identification, hospitalization duration, ICU stay, and in-hospital mortality.

Results: Among 1238 CAP hospitalizations, 65% underwent molecular testing, with atypical pathogens detected in 17 cases (2.09%). Mycoplasma pneumoniae was the most common organism. The cases had an almost equal male-to-female ratio. Mean hospitalization was 12 days overall versus 4 days for atypical pneumonia. Of 265 ICU admissions, none tested positive for atypical CAP. Overall mortality was 6.94%, with no deaths in atypical pneumonia positive patients.

Conclusions: PCR molecular testing was performed in 65% of patients hospitalized with CAP, and atypical pneumonia organisms were uncommon in these patients, with Mycoplasma pneumoniae being the most common. Clinical outcomes were more favorable for these patients. Expanding molecular testing may improve pathogen detection and guide target management.