Therapeutic Advances in Respiratory Disease最新文献

Background: Pulmonary segmentectomy is increasingly recognized as a viable alternative to lobectomy for early stage non-small-cell lung cancer (NSCLC), offering comparable oncological outcomes with potentially reduced morbidity. Identifying reliable predictors for postoperative complications and prolonged air leak (PAL) is crucial for optimizing patient selection. While multifactorial scoring systems exist, their complexity limits clinical utility and the predictive value of single factors, such as forced expiratory volume in 1s (FEV₁) and diffusing capacity for carbon monoxide (DL_CO), remains underexplored.

Objectives: This study aimed to evaluate the ability of preoperative FEV₁ and DL_CO to predict complications (Clavien-Dindo ⩾ 3a) and PAL in patients undergoing pulmonary segmentectomy.

Design: A retrospective, single-center study compared outcomes between patients undergoing segmentectomy (n = 33) and lobectomy (n = 126) for NSCLC.

Methods: Patient characteristics, complication rates, and PAL incidence were analyzed. Logistic regression and ROC curve analyses assessed the predictive accuracy of FEV₁ and DL_CO for complications and PAL.

Results: Baseline characteristics, including FEV₁ and DL_CO, were comparable between the segmentectomy and lobectomy groups (p > 0.05). FEV₁ was identified as a significant predictor of complications, with lower values associated with increased risk. DL_CO exhibited an even stronger predictive value for complications in the segmentectomy cohort, with an AUC of 0.924, indicating excellent predictive accuracy. In contrast, neither FEV₁ nor DL_CO demonstrated significant predictive value for PAL, which occurred in 30% of segmentectomy and 20% of lobectomy patients (p > 0.05).

Conclusion: Preoperative FEV₁ and DL_CO are valuable predictors of complications (Clavien-Dindo ⩾ 3a) in pulmonary segmentectomy, with DL_CO showing high predictive accuracy. However, their inability to reliably predict PAL highlights the need for multifactorial models to enhance risk assessment. Despite the limited sample size, our findings align with larger studies and reinforce the clinical utility of FEV₁ and DL_CO for preoperative risk stratification in segmentectomy patients.

Chronic obstructive pulmonary disease (COPD) refers to a group of lung diseases that are distinct in underlying aetiology but share a common disease course of persistent and progressive airflow restriction. People living with COPD, as well as the people who care for them, frequently have severe and unmet physical and psychosocial needs, including breathlessness, fatigue, cough, anxiety and depression. Early proactive palliative care is well placed to address these needs, yet it is frequently under-utilised in this group. This narrative review aimed to identify core components of palliative care and examine how existing models of care are implemented to better understand which models can best serve the needs of people with COPD. Symptom palliation, advance care planning, and support for caregivers emerged as the common components underpinning both generalist and specialist models of palliative care. Models of proactive palliative care were diverse in terms of where and how care was delivered as well as which health professionals were involved. Five key models of palliative care were identified: (1) multi-disciplinary integrated services, (2) nurse-led care, (3) hospice and residential aged care, (4) home-based care, and (5) telemonitoring and telehealth. Each model describes a diverse set of interventions and many of these share common elements, including the normalisation of palliative principles within routine care and the provision of diverse delivery settings to accommodate individual preferences and needs. Successful palliative care models must be practical, accessible and innovative to respond to individuals' complex and evolving needs, foster multi-disciplinary collaboration and input and optimally utilise local healthcare resources.

Idiopathic pulmonary fibrosis (IPF) is often regarded as the archetypal progressive fibrosing interstitial lung disease (ILD). The term "progressive pulmonary fibrosis" (PPF) generally describes progressive lung fibrosis in an individual with an ILD other than IPF. Both IPF and PPF are associated with loss of lung function, worsening dyspnea and quality of life, and premature death. Current treatments slow the decline in lung function but have side effects that may deter the initiation or continuation of treatment. There remains a high unmet need for additional therapies that can be used alone or in combination with current therapies to preserve lung function in patients with IPF and PPF. Phosphodiesterase-4 (PDE4) is an enzyme involved in the regulation of inflammatory processes. Pre-clinical studies have shown that preferential inhibition of PDE4B has anti-inflammatory and antifibrotic effects and a lower potential for gastrointestinal adverse events than pan-PDE4 inhibition. The preferential PDE4B inhibitor nerandomilast demonstrated efficacy in preserving lung function in a phase II trial in patients with IPF and is under investigation in phase III trials as a treatment for IPF and PPF.

Background: Lower limb aerobic exercise is the core component of pulmonary rehabilitation for chronic obstructive pulmonary disease (COPD) patients. The optimal intensity and type (e.g., interval or continuous) of exercise training remains to be determined.

Objectives: We aimed to evaluate the optimal intensities and types of lower limb aerobic exercise in patients with COPD.

Design: Systematic review and network meta-analysis of randomized controlled trials.

Data sources and methods: The PubMed, Web of Science, Embase, and the Cochrane Central Register of Controlled Trials were searched for relevant data. The interventions were classified according to their intensity and type as high-intensity interval training (HIIT), high-intensity continuous training (HICT), moderate-intensity continuous training (MICT), and low-intensity continuous training (LICT). We assessed exercise capacity using peak work rate (Wpeak) and the 6-min walking test (6-MWT). Lung function was evaluated by measuring peak minute ventilation (VE) and the percentage of predicted FEV₁ (FEV₁pred%). Dyspnea was assessed using the Modified Medical Research Council (mMRC) scale. Quality of life was measured with the Chronic Respiratory Questionnaire (CRQ).

Results: Fifteen studies were identified (979 subjects). HIIT showed the greatest improvement in Wpeak, 6-MWT, VE, and mMRC compared to usual care (MD 18.48 (95% CI 12.35, 24.60), 67.73 (34.89, 100.57), 6.26 (2.81, 9.72), and -0.53 (-0.89, -0.17), respectively) and showed the improvement in CRQ (MD 10.80 (95% CI 1.65, 19.95)). MICT showed improvement in Wpeak and 6-MWT (MD 18.28 (95% CI 11.20, 25.22), 61.92 (28.34, 95.51)) similar to HICT (MD 16.08 (95% CI 8.19, 23.84), 64.64 (28.70, 100.57)) and showed the highest improvement in CRQ compared to usual care (MD 10.83 (95% CI 1.68, 19.98)). LICT significantly improved Wpeak compared to usual care (MD 13.47 (95% CI 4.77, 22.13)). The quality of evidence for outcomes varied from very low to moderate.

Conclusion: HIIT and MICT might be optimal training approaches for patients with COPD. LICT exhibited limited clinical efficacy. While HICT was as effective as MICT, it caused more dyspnea.

Trial registration: This systematic review and network meta-analysis was prospectively registered with PROSPERO (No. CRD 42024520134).

Background: Chronic obstructive pulmonary disease (COPD) is a condition causing chronic physical symptoms, psychological burdens, as well as social consequences. This contributes to a major decrease in quality of life (QoL). Palliative care (PC) is a person-centered approach intended to relieve physical, psychological, social, and spiritual suffering. Despite international practice guidelines, patients with COPD have limited access to PC, mostly during end-of-life (EoL) care. It is therefore important to explore healthcare professionals' (HPs) point of view about PC to improve access for COPD patients to PC.

Objectives: This study aimed to describe the perceptions of HPs working with COPD patients in Switzerland in different settings on PC provision, implementation, access, and organization. Additionally, we aimed to identify gaps, barriers, training needs, and solutions for HPs related to PC needs.

Design: This is a cross-sectional survey study with quantitative and open-ended questions.

Methods: We used an electronic survey sent to HPs working with patients suffering from COPD in the inpatient, outpatient, and home-based settings.

Results: A total of 56 out of 98 participants (57%) answered the questionnaire of which 41.1% were nurses. 47.2% of participants were uncertain about the good timing of addressing COPD patients to PC and did it after several acute exacerbations, during EoL, or at the request of the patient. 45.5% did not know the availability of a local specialized PC. Lack of skills/training was identified as one of the hindering factors to discuss EoL (42.9% N = 56).

Conclusion: Despite recognizing the importance of PC, several barriers were identified, including a lack of knowledge about when to initiate a PC and limited utilization of tools for identifying PC needs. Multidisciplinary teamwork and the identification of a nurse coordinator could improve earlier referrals to PC and improve QoL for COPD patients.

Background: Interstitial lung disease (ILD) is the main clinical feature of antisynthetase syndrome (ASS). In the absence of randomized controlled trials to guide therapy, treatment strategies are often extrapolated from other diseases, mainly systemic sclerosis (SSc).

Objectives: Our aim was to evaluate the dynamics of ILD severity following immunosuppressive treatment (IST) in ASS compared to SSc.

Design: A multicenter retrospective observational study.

Methods: ASS (n = 22) and SSc (n = 32) subjects with ILD were included in the registries of three medical centers. All patients received ISTs. We analyzed changes in forced vital capacity (FVC) and diffusion capacity for carbon monoxide corrected for hemoglobin (DLCOc) after treatment initiation using linear mixed-effects models. Changes in high-resolution chest CT scans were analyzed by a radiologist blinded to clinical data.

Results: The median (interquartile range) age was 66 (59-71), 72% were females, and 81% of IST included mycophenolate mofetil (MMF). Baseline demographics, comorbidities, and pulmonary functions were similar between the groups. Among the ASS group, the mixed-effects models showed significant improvements in FVC% (F = 11.3, p < 0.01) and DLCOc% (F = 7.1, p = 0.015) after treatment initiation over time, while in the SSc group, there were no significant changes in FVC% (F = 0.4, p = 0.551) and DLCOc% (F = 0.8, p = 0.384). Changes in FVC% and DLCOc% were higher in the ASS group compared with SSc (p = 0.017 and p < 0.01, respectively), which persisted after adjustment to steroid use and in a sub-analysis of patients with serial pre- and post-IST pulmonary functions. Both groups had improved total CT scores after IST, without changes in other radiologic scores.

Conclusion: Immunosuppressive treatment, mostly with MMF, was associated with significant improvement of FVC% and DLCOc% in ASS, compared to their stabilization only in SSc. This should encourage future randomized controlled studies of MMF in ASS patients.

Background: REMIT is the first real-world study of mepolizumab effectiveness in patients with severe asthma (SA) in Taiwan.

Objectives: The primary objective evaluated changes in clinically significant exacerbations (CSEs; defined as use of oral corticosteroids (OCS) or emergency department (ED) visits and/or hospitalizations) in the 12 months pre- and post-mepolizumab treatment. Secondary objectives assessed changes in the number of CSEs requiring ED visits/hospitalizations and daily maintenance OCS (mOCS) dosage 12 months pre- and post-mepolizumab treatment. Three- and four-component clinical remissions were analyzed based on OCS-free, exacerbation-free, and asthma control (± stability in lung function).

Design: REMIT was a retrospective, observational, self-controlled study analyzing patients in Taiwan with SA who were newly prescribed subcutaneous mepolizumab 100 mg Q4W.

Methods: Data were extracted from records of 15 medical centers in Taiwan for patients indexed between November 1, 2018 and October 31, 2020.

Results: A total of 170 patients were included: mean age at index date, 58.7 years; 53.5% female; 100% Chinese; 7.1% with chronic rhinosinusitis with nasal polyps, 1.8% with eosinophilic granulomatosis with polyangiitis, 1.2% with hypereosinophilic syndrome; and 55.7% with blood eosinophil count >300/µL. Pre-treatment, 71.2% had ⩾2 exacerbations, and 28.7% were on mOCS; 75.3% had no prior biologic treatment, and 24.7% had switched from other biologics. Most patients (80.0%) completed ⩾10 mepolizumab doses. Following the first mepolizumab administration (index date), CSEs reduced by 46.0% (rate ratio (RR): 0.545, 95% confidence interval (CI): 0.418-0.710; p < 0.0001) in the 12 months post-index. Exacerbations requiring ED visits/hospitalization reduced by 46.9% (RR: 0.531, 95% CI: 0.349-0.808; p = 0.0031). Median mOCS dose reduced by 100% by end of study and 81.8% of patients discontinued mOCS post-treatment. After 1 year of mepolizumab treatment, 28% and 23% patients achieved three- and four-component clinical remission, respectively.

Conclusion: Mepolizumab use in a patient population in Taiwan with SA significantly reduced CSEs and mOCS use in routine clinical practice.

Eosinophilic granulomatosis with polyangiitis (EGPA), as a heterogeneous component of antineutrophil cytoplasmic antibody-associated vasculitis, may be induced by a series of environmental and genetic factors, involved with a variety of immune cells and immune components, and presented with various clinical manifestations, with multiple organs and systems (respiratory, skin, heart, kidney, nerve, etc.) involved. The choice of glucocorticoid (GC) dosage and immunosuppressant in traditional treatment strategies varies greatly from individual to individual and is not universally applicable in all the EGPA phenotype spectrum, especially in relapsing or refractory diseases. With the understanding of the heterogeneity of EGPA, a variety of therapeutic approaches are emerging and improving the traditional treatment model. In this review, we summarized the heterogeneity of EGPA etiology and pathogenesis. Clinical and pathological manifestations of the same organ involved also show significant differences and there are even gender differences. Biological treatments that mainly target type 2 inflammatory pathways are widely used in clinical practice for remission induction and maintenance of EGPA. Targeted biological therapy has shown excellent performance in reducing GC dosage and controlling symptoms and recurrence. However, a large number of high-quality randomized controlled studies are still under research for relapsing or refractory EGPA with special organ involvement. We believe that EGPA has a highly heterogeneous phenotype spectrum, and the treatment patterns targeting key molecules in the pathogenesis are of great value for individual treatment of EGPA.

Background: Radial endobronchial ultrasound (r-EBUS) is a minimally invasive procedure used to evaluate pulmonary lesions suspicious of cancer. Current information on the effect of combining different sampling tools used during r-EBUS or the addition of linear EBUS (EBUS-TBNA) on its diagnostic performance is limited.

Objectives: To evaluate the effect on diagnostic performance of the systematic addition of different sampling tools and EBUS-TBNA during r-EBUS, as well as the rate of peri-procedural complications.

Design: This was an observational, analytical cohort study designed to evaluate diagnostic accuracy.

Methods: We calculated diagnostic accuracy statistics and used the Cochran-Armitage statistical test to assess the effect of combining techniques on diagnostic performance. Diagnostic success (DS) was defined as true positives and true negatives, while diagnostic failure was defined as false positives and false negatives.

Results: A total of 309 patients were included, with a mean age of 67.9 years (standard deviation: 10.97); 50.8% (157/309) were male. The bronchial washing had a DS rate of 49%, while bronchial brushing showed a DS rate of 61%. The combination of bronchial washing and bronchial brushing improved the r-EBUS performance to 63%. Combining bronchial washing, bronchial brushing, and transbronchial biopsy increased the performance to 70%, and the addition of EBUS-TBNA raised the diagnostic performance to 80% (p < 0.001; Cochran-Armitage test). The overall complication rate was 6.4% (20/309), with pneumothorax occurring in 1.2% (4/309), bronchospasm in 3.8% (12/309), and bleeding in 1.2% (4/309).

Conclusion: The use of multiple sampling tools significantly contributes to the DS of r-EBUS, particularly with the addition of EBUS-TBNA. This approach maintains a low complication rate.