Therapeutic Advances in Respiratory Disease最新文献

Background: Chronic cough (CC) has a negative effect on patients' quality of life and everyday activities. Emotional reactions are an important aspect of how patients deal with illness, and CC can lead to feelings of uncertainty, loss of control, helplessness, self-consciousness, embarrassment, worry, fear, frustration, irritability, and anger.

Objectives: To assess the emotions related to bouts of cough in patients with refractory or unexplained chronic cough (RCC/UCC), using a validated questionnaire.

Design: This was a multicenter, non-interventional study.

Methods: Patients with RCC/UCC were recruited from hospital outpatient clinics in Spain. The impact of RCC/UCC on patients' emotions was assessed using the self-reported Discrete Emotions Questionnaire (DEQ), which assesses eight distinct situationally induced state emotions, scored on a Likert scale from 1 to 7, with higher scores indicating that the emotion is experienced to a greater degree.

Results: The survey was completed by 190 patients (148 women, 42 men; mean age 58.0 years) of whom 120 had RCC and 70 had UCC (mean cough duration 6.3 years). Highest mean (SD) scores were seen for the anger subscale (3.6 (1.7)) and anxiety subscale (3.3 (1.6), followed by the disgust (2.6 (1.5)), fear (2.6 (1.7)), and sadness (2.5 (1.5)) subscales. The same pattern was seen in subgroups by gender and by diagnosis (RCC or UCC). There were no significant differences in mean scores for any subscale between patients with RCC and those with UCC. Cough severity and the presence of cough-related stress urinary incontinence (SUI) were independently associated with negative emotion subscale scores.

Conclusion: Among patients with RCC/UCC, bouts of cough triggered negative emotions such as anger, anxiety, disgust, fear, and sadness, as evaluated using a validated questionnaire. Results were similar for RCC and UCC. Increasing cough severity and the presence of SUI were independently associated with higher (worse) scores for negative emotions.

Background: Afatinib is indicated for patients with advanced-stage non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations, including uncommon mutations. However, the differences in survival benefits between patients with different types of EGFR mutations remain unclear.

Objectives: This study aimed to compare the effectiveness of afatinib treatment in patients harboring the EGFR-G719X mutation with that in patients carrying other uncommon EGFR mutations.

Design: This was a retrospective study.

Methods: Ninety-two patients with locally advanced and metastatic NSCLC, of whom 49 patients with EGFR-G719X mutations that were both single and compound, and 43 patients harbored other uncommon EGFR mutations, who were treated with afatinib as first-line treatment. The patients were followed up and evaluated every 3 months or when there were symptoms of progressive disease. The endpoints were the objective response rate (ORR), time-to-treatment failure (TTF), and overall survival (OS).

Results: The average ages of patients with the EGFR-G719X and uncommon EGFR mutations were 62.7 years and 63.1 years, respectively. There were no significant differences in sex or smoking history between the two groups. In total, 28.6% of patients with the G719X mutation and 23.3% of patients with other mutations had brain metastases. The ORR of patients with the G719X mutation was 79.6%, which was 10% higher than that of patients with other EGFR mutations. Patients harboring the EGFR-G719X mutation had median TTF and median OS periods of 19.3 months and 31.4 months, respectively, which were significantly higher than those of patients carrying other mutations at 11.2 months. Subgroup analysis showed that TTF and OS benefits were observed in female patients, patients without brain metastasis, and patients with good performance status who harbored the G719X mutation.

Conclusion: Patients with the EGFR-G719X mutation achieve significantly better TTF and OS benefits than those with other uncommon EGFR mutations.

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: 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).

Obstructive sleep apnea (OSA) is a sleep-breathing disorder with repetitive total or partial airway occlusion events. Its importance lies in the high prevalence and presence in all age groups and on cardiovascular (CV), metabolism, neurocognitive function, mental health, and overall quality of life. Furthermore, the coexistence of multiple comorbidities in patients suffering from OSA plays an essential role in these entities' development, perpetuation, and clinical control. In the past years, efforts have been made to understand the pathophysiology of each event, the spectrum of the disease, and the different phenotypes, as well as to refine the diagnostic process and, thus, direct treatment toward a more comprehensive and personalized approach. Many uncertainties remain regarding which patients are at higher CV risk and who derive the greatest benefit from treatment. In this promising scenario, new tools have been developed, including advanced diagnostic technologies, molecular biomarkers, and predictive statistic models tailored for precision medicine. However, to effectively understand and manage this heterogeneous and complex pathology, well-designed studies are essential to validate precision medicine models and ensure their efficient integration into routine clinical practice in a simple, accessible, and practical manner. In this article, we present a comprehensive review of the most relevant scientific evidence concerning the diagnosis and treatment of OSA. We examine significant cluster studies available to date and aim to provide the reader with personalized recommendations for diagnosing and treating OSA. Additionally, we propose new pathways for advancing precision medicine in the field of sleep-disordered breathing.