Therapeutic Advances in Respiratory Disease最新文献

Background: Pulmonary rehabilitation (PR) is a cornerstone of chronic obstructive pulmonary disease (COPD) management, but exercise intolerance often limits its effectiveness. Non-invasive positive pressure ventilation (NPPV) during PR may enhance training tolerance and outcomes, yet the overall evidence remains uncertain.

Objectives: To evaluate the effects of adding NPPV to PR on exercise capacity, dyspnea, and respiratory muscle strength in patients with COPD.

Design: Systematic review and meta-analysis of randomized controlled trials (RCTs).

Data sources and methods: We searched PubMed, Web of Science, Embase, the Cochrane Library, and CINAHL from inception to December 2024 for RCTs evaluating NPPV combined with PR in patients with COPD. Two reviewers independently assessed risk of bias using the Cochrane Risk of Bias Assessment Tool for Randomized Trials (RoB 2), extracted data, and performed analyses using RevMan 5.3.

Results: A total of 17 RCTs (489 participants; predominantly GOLD stage III-IV) were included. NPPV + PR significantly improved 6-minute walk distance (MD = 29.1 m, 95% CI: 3.6-54.6), incremental shuttle walk test distance (MD = 21.8 m, 95% CI: 5.0-38.7), peak oxygen uptake (SMD = 0.53, 95% CI: 0.23-0.83), maximal inspiratory pressure (Pimax; MD = 5.8 cmH₂O, 95% CI: 1.0-10.7), and maximal expiratory pressure (Pemax; MD = 14.9 cmH₂O, 95% CI:4.1-25.7). Significant reductions were observed in blood lactate levels (MD = -0.49 mmol/L, 95% CI:-0.79 to -0.19), BORG dyspnea score (MD = -1.1, 95% CI: -1.7 to -0.6), and mMRC scale (MD = -0.3, 95% CI: -0.5 to -0.1). No significant effect was found on quality of life.

Conclusion: Adding NPPV to exercise-based PR provides clinically meaningful improvements in exercise capacity, dyspnea, and respiratory muscle strength in patients with COPD who have significant exercise limitation. NPPV may be a valuable adjunct to optimize PR outcomes in this population.

Trial registration: This review was prospectively registered in PROSPERO (CRD42023486598).

Background: Research into safe and effective treatments for alpha-1 antitrypsin deficiency (AATD) has been ongoing for more than four decades. There is still a high medical need for better treatment options: Safe, effective, and convenient therapies that target both the lungs and other AATD organ manifestations are eagerly awaited by patients.

Objectives: The purpose of this study is to provide a quantitative clinical-regulatory insight into the current status of the Food and Drug Administration (FDA) and European Medicines Agency (EMA) orphan drug approvals and designations for compounds intended to treat AATD.

Design: A cross-sectional approach was applied, involving a one-time comprehensive search of relevant databases.

Methods: The primary endpoint of this study was to determine the number and nature of FDA and EMA-approved orphan drugs. The secondary endpoint was the registration of compounds with orphan drug designation status. All database searches were performed since the inception of the FDA database in 1983 and the EMA database in 2000, as well as for all compounds listed in the FDA and EMA drug label databases up to 20 January 2025. The search terms 'antitrypsin' and 'proteinase' were used.

Results: In 1987, the FDA approved the first human alpha1-proteinase inhibitor, representing the only approved active substance (5%) out of 20 with orphan drug designation in the FDA for the treatment of AATD. Conversely, the EMA has granted orphan drug designation to nine active substances, though none of these have yet been approved. However, there are several new active substances that have been granted orphan drug designation: oral neutrophil elastase inhibitor (FDA 2021, EMA 2025), IgG4 Fc-bound recombinant human AAT (FDA 2022), HSV vector therapy (FDA 2023), and A1AT modulator/protein folding stabiliser (FDA 2023, EMA 2024). Furthermore, the development of RNA interference therapeutics has progressed in the United States and Europe.

Conclusion: The development of new therapies may offer expanded treatment options for patients with AATD in the future. In addition to pulmonary manifestations, extrapulmonary manifestations could also be treated in the future.

Asthma is a heterogeneous chronic respiratory disease driven by diverse inflammatory pathways that vary across patients. The recognition of distinct molecular endotypes has led to the development of targeted biologic therapies that have transformed the management of moderate-to-severe asthma. However, selecting the most appropriate biologic therapy for each patient remains challenging. Health providers often rely on trial-and-error approaches that may delay disease control, increase costs, and expose patients to unnecessary side effects. Biomarkers are key to precision asthma care, as they provide objective measures of underlying disease mechanisms. Established biomarkers such as blood eosinophil count, fractional exhaled nitric oxide, and serum total immunoglobulin E are important for identifying type 2-high asthma. Sputum biomarkers offer direct insight into airway inflammation, but their use is limited by technical complexity and availability across centers. Emerging biomarkers, including proteomic, transcriptomic, metabolomic, and genomic biomarkers, show promise in further refining biologic therapy selection. In addition, digital biomarkers derived from electronic health records, wearable devices, and artificial intelligence-based algorithms offer new opportunities to capture real-world changes in disease and treatment response. Non-medical drivers of health, particularly socioeconomic factors, are increasingly recognized as modifiers of biologic effectiveness and may also be helpful in selecting biologic therapies. This review summarizes the existing evidence on established and emerging biomarkers used to guide biologic therapy selection in asthma. Integrating multiple biomarkers will be essential to improve biological selection, monitor response, and ultimately achieve the goal of remission in asthma.

Pulmonary intravascular large B-cell lymphoma (PIVLBCL) is an extremely rare subtype of extranodal diffuse large B-cell lymphoma (DLBCL). This hematologic malignancy exhibits nonspecific radiological features, including ground glass opacities (GGOs), often leading to misdiagnosis as interstitial lung disease (ILD). We present a 51-year-old female hairdresser with progressive dyspnea and 20 years of occupational hair dye exposure. Initially, she was misdiagnosed with chronic bronchitis due to a persistent dry cough. Then her initial chest CT demonstrated diffuse bilateral GGOs with isolated diffusion capacity of the lungs for carbon monoxide (DLCO) reduction (46.1% predicted) and normal spirometry, which led to a second misdiagnosis as hypersensitivity pneumonitis (HP). Despite initial improvement with corticosteroids, respiratory deterioration occurred during tapering. Finally, transbronchial lung cryobiopsy (TBCB) confirmed PIVLBCL, showing intravascular lymphoid proliferation (CD20+/BCL-6+/Ki-67≈80%). The R-CHOP chemotherapy treatment led to a complete remission for her, and the DLCO improved to 68% of the predicted value at the 6-month follow-up. A literature review of 75 PIVLBCL patients revealed that fever (74.7%) and dyspnea (65.3%) were the predominant presentations. GGOs were observed in 54.7% of cases, with frequent misdiagnosis as ILD (31.8%) or pneumonia (31.8%). TBCB provided definitive diagnostic evidence, demonstrating its clinical utility in resolving ambiguous pulmonary opacities. Clinicians should maintain high suspicion for PIVLBCL when encountering diffuse GGOs with isolated DLCO reduction, even without classic risk factors.

Background: Composite nutritional and immune indices (NIIs) have been associated with chronic lung diseases (CLDs). However, systematic research on their associations with different CLD subtypes and potential threshold patterns remains limited.

Objectives: To examine cross-sectional associations between multiple NII and CLD subtypes, and to explore potential linear/nonlinear relationships and threshold ranges using a representative dataset.

Design: Cross-sectional, population-based study using National Health and Nutrition Examination Survey (NHANES) data.

Methods: Data were obtained from the US NHANES from 2007 to 2012. Participants aged 18-79 years with complete blood and baseline data were included. Survey-weighted regression models were used to assess associations between NIIs and CLDs. Restricted cubic spline (RCS) regression models were employed to explore linear/nonlinear relationships and potential threshold ranges.

Results: The study included 5837 participants (mean age 49.82 ± 16.15). Regression analyses revealed significant associations between NIIs and CLDs across different ranges. RCS analysis identified thresholds for each NII: prognostic nutritional index (PNI) levels > 46.04 showed a significant inverse association with emphysema and chronic bronchitis. Elevated platelet-to-lymphocyte ratio (PLR) (>113.57) and MLR (>0.14) were positively associated with these conditions. systemic immune-inflammation index (SII) (>429.43) and neutrophil-to-lymphocyte ratio (NLR) (>0.99) were associated with a higher prevalence of asthma, emphysema, and chronic bronchitis.

Conclusion: In this cross-sectional population-based study, NIIs were associated with different CLD subtypes, with evidence of potential threshold patterns. These findings may help inform future epidemiological studies and hypothesis generation, while causal inference and clinical application require further longitudinal validation.

Background: Postoperative recovery following lung cancer surgery can be challenging owing to various cardiorespiratory complications. Pulmonary rehabilitation is crucial during both the preoperative and postoperative periods. However, because of limited resources and accessibility, innovative approaches are necessary to improve rehabilitation outcomes. This study aimed to evaluate the effectiveness of the RehabLung App, a novel AI-based mobile application integrating vision recognition, gamified feedback, and web-based patient management to support personalized lung rehabilitation through telerehabilitation and real-time monitoring.

Objectives: This study outlines the protocol for a randomized controlled trial involving patients with lung cancer undergoing thoracic surgery.

Design: Assessor-blinded (single-blind), two-arm, parallel-group randomized controlled trial (1:1 allocation) conducted at a single medical center.

Methods and analysis: The intervention will include individualized exercise prescriptions delivered five times per week for 8 weeks via the App, which adapts based on weekly assessments of clinical parameters and real-time performance data. Primary outcomes include forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC), as well as cardiopulmonary fitness assessed at baseline and at postoperative weeks 5 and 8. Secondary outcomes include respiratory muscle strength, diaphragmatic function, and user satisfaction, which are evaluated using a custom questionnaire informed by technology acceptance models. In addition, clinically meaningful endpoints will be collected, including morbidity, mortality, and length of stay. Frailty will be assessed preoperatively using the Clinical Frailty Scale, and validated patient-reported outcomes (EORTC QLQ-C30) will be administered to evaluate quality of life and symptom burden.

Ethics: The study has been approved by the Institutional Review Board at National Cheng Kung University Hospital (A-ER-111-055).

Discussion: We hypothesize that patients using the RehabLung App may demonstrate improvements in pulmonary function, exercise tolerance, diaphragmatic function, and rehabilitation adherence compared with those receiving standard care. The system's real-time feedback and risk alerts may facilitate timely intervention and could potentially improve engagement.

Conclusion: The implementation of the RehabLung App in lung cancer surgery care may enhance the effectiveness and accessibility of pulmonary rehabilitation. This protocol describes an AI-enhanced telerehabilitation system that may support individualized recovery strategies and could potentially improve both clinical outcomes and patient engagement.

Trial registration: Registration Date;2024,09,19; ClinicalTrials.gov (Identifier: NCT06600503).

Background: The British Thoracic Society (BTS) currently recommends pre-flight clinical assessment of all symptomatic patients with interstitial lung disease (ILD). This may include hypoxic challenge testing (HCT) to determine whether supplemental in-flight oxygen is required, but it is not universally available.

Objectives: (1) To validate a previously published pre-flight assessment algorithm in predicting outcomes of HCT in ILD. (2) Compare the sensitivity and specificity of the original algorithm to an amended version published in the BTS clinical statement on air travel.

Design: Single centre, cohort study.

Methods: A single-centre retrospective cohort analysis of ILD patients attending for HCT between March 2017 and April 2023.

Results: A total of 126 patients with a diagnosis of ILD underwent HCT. Median forced vital capacity 75.0% predicted (interquartile range (IQR) 24.8) and transfer factor for carbon monoxide 45.8% predicted (IQR 18.6). Diagnosis of idiopathic pulmonary fibrosis in 50.8% (n = 64). A total of 18 individuals became hypoxic during the test (a fall of PaO₂ to <6.6 kPa or oxygen saturations (SpO₂) < 85% pO₂, 'failed HCT'). The pre-flight algorithm demonstrated moderate sensitivity (69.4%, identifying most 'passed' cases correctly, 43/62) and good specificity (83.3%, most 'failed' cases correctly identified, 10/12). A total of 52 (41.2%) patients would have been referred for HCT, with 11.5% (n = 6) requiring in-flight oxygen ('failed' HCT). The modified BTS algorithm demonstrated a moderate sensitivity of 70.3% (45/64) and good specificity of 83.3% (10/12). In both algorithms, 29 patients would have been advised in-flight oxygen, whilst only 10 of these required supplementary oxygen according to HCT. There were two divergences in algorithmic outcomes, both arising from patients without desaturation on exercise, resulting in two fewer HCT using the BTS algorithm and correctly advising 'no supplemental oxygen' was required.

Conclusion: In this validation study, the practical pre-flight algorithm demonstrates good specificity and moderate sensitivity for predicting HCT outcomes. The BTS modified algorithm demonstrates comparable sensitivity and specificity. Additional work is required to further develop practical guidance to reduce both the number of HCT advised and the proportion of patients incorrectly advised to arrange supplemental in-flight oxygen.

Corynebacterium jeikeium is an uncommon but increasingly recognized cause of invasive infection, usually affecting immunocompromised patients. Empyema due to C. jeikeium has not been previously reported in an immunocompetent adult. We describe the first case and review the existing literature on non-diphtherial Corynebacterium-related empyema to highlight diagnostic and therapeutic challenges. A 26-year-old previously healthy man presented with 5 days of pleuritic chest pain, fever, and productive cough. Chest computed tomography revealed a large, loculated left pleural effusion with an air-fluid level. Initial thoracentesis yielded frank pus, confirming empyema, but the patient declined immediate drainage and was started on intravenous cefoperazone/sulbactam and moxifloxacin. His condition worsened, prompting repeat thoracentesis and catheter drainage. Culture of pleural fluid grew C. jeikeium, leading to a switch to intravenous vancomycin and meropenem. The patient improved rapidly, with defervescence, normalization of inflammatory markers, and complete radiographic resolution. He remained well at the 3-month follow-up. A literature review identified only four previous cases of non-diphtherial Corynebacterium-related empyema, all in patients with significant comorbidities. This case demonstrates that C. jeikeium can cause empyema even in immunocompetent hosts. Early microbiological diagnosis, timely pleural drainage, and appropriate antimicrobial therapy, particularly vancomycin, are critical for successful outcomes. Increased awareness and case reporting will help refine management strategies for this rare but clinically relevant pathogen.

Background: Subglottic cysts (SGCs) are a rare disease with a high misdiagnosis rate.

Objectives: We aim to improve the diagnostic and management ability of pediatricians for SGCs by analyzing the clinical characteristics of confirmed cases.

Design: Observational, retrospective cohort studyMethods:We enrolled children diagnosed with SGCs admitted to the Children's Hospital of Chongqing Medical University between January 2010 and December 2022. Clinical characteristics data were collected and analyzed retrospectively. Patients were regularly followed up for 1 year post-treatment or discharge.

Results: Eleven children were included in this retrospective study. There were nine (9/11, 81.8%) males and two (2/11, 18.2%) females, and the median age was 15 months. Eight (72.7%) were premature. Seven (63.6%) patients had a history of intubation. The common manifestations were stridor (72.7%), wet cough (72.7%), shortness of breath (72.7%), and dyspnea (54.5%). The average diagnosis time was 7 months. The most common comorbidity was laryngopharyngeal reflux disease (LPRD, 45.5%), followed by laryngomalacia (27.3%), bronchopulmonary dysplasia (27.3%), bronchial stenosis (18.2%), and adenoid hypertrophy ( 18.2%). The obstruction degree of SGCs was "3" (51%-75% occlusion) or higher in eight (72.7%) patients. Two (18.2%) patients experienced recurrence after initial cyst aspiration and subsequently underwent successful laryngoscopy marsupialization. Ultimately, eight (72.7%) patients achieved complete recovery after endoscopic marsupialization.

Conclusion: SGCs should be considered in the differential diagnosis of children, especially those with a history of prematurity and/or perinatal intubation, who present with stridor, wet cough, and respiratory distress. Endoscopic evaluation is crucial for both definitive diagnosis and guiding effective treatment.

Hereditary bronchiectasis comprises a group of rare monogenic disorders, with cystic fibrosis (CF) and primary ciliary dyskinesia (PCD) representing the major subtypes. Exome sequencing (ES) remains a central modality for molecular diagnosis; however, it leaves more than half of clinically suspected cases unresolved, largely because it cannot reliably detect copy number variations, deep intronic variants, pseudogene-associated variants, and frequent identification of variants of uncertain significance (VUS). This case series describes five hereditary bronchiectasis cases with initial ES-negative results or VUS findings, illustrating the diagnostic utility of targeted genetic approaches. Systematic re-evaluation-including updated bioinformatic pipelines, familial segregation analyses, genome sequencing, RNA sequencing, and functional assays-such as minigene analysis-enabled the reclassification of VUS and the identification of pathogenic variants, leading to definitive diagnoses of PCD or CF in all individuals. Our findings demonstrate that a multimodal strategy integrating ES reanalysis, advanced genomic technologies, and functional validation is critical for resolving previously undiagnosed cases. Furthermore, emerging multiomics integration, artificial intelligence-driven variant interpretation, and global data-sharing frameworks are positioned to further increase diagnostic precision and support the development of targeted therapies for hereditary bronchiectasis.