Therapeutic Advances in Respiratory Disease最新文献

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.

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.

Palliative care is essential for patients with chronic pulmonary diseases, especially in low- and middle-income countries (LMICs). Chronic respiratory diseases (CRDs), such as chronic obstructive pulmonary disease and interstitial lung diseases, cause significant morbidity and mortality globally, with a heavy burden in LMICs. Despite the need, access to palliative care in LMICs is limited, leading to inadequate symptom management and support. Palliative care benefits include improved quality of life, reduced healthcare costs, and increased patient and family satisfaction. However, barriers in LMICs, including limited resources, infrastructure, and trained providers, as well as cultural and regulatory challenges, hinder care delivery. Early integration of palliative care for patients with CRDs can enhance outcomes and reduce healthcare utilization, yet it remains underutilized in these regions. This review highlights the challenges and impact of palliative care for CRDs in these regions. Addressing these issues requires regulatory reforms, provider education, and investments in healthcare infrastructure. Solutions include national policies, training healthcare professionals, telemedicine, and research collaborations. Understanding and addressing barriers to palliative care in LMICs is crucial for improving care quality and outcomes for patients with CRDs.

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: Pirfenidone (PFD) is commonly applied for antifibrotic treatment in patients with idiopathic pulmonary fibrosis but has rarely been studied in cases with connective tissue disease-associated interstitial lung diseases (CTD-ILDs).

Objectives: We aimed to examine the efficacy of PFD in patients with CTD-ILD based on real-world data.

Design: A retrospective cohort study.

Methods: This study assessed the clinical features of CTD-ILD patients with or without a 6-month PFD treatment. A linear mixed effects model was employed to evaluate the effectiveness of PFD in alleviating lung function changes. Differences in response to PFD were analyzed based on CTD subtype, imaging classification, and pattern of pulmonary function at baseline.

Results: A total of 289 patients with CTD-ILD were included, with 155 (53.6%) receiving PFD treatment and the remaining constituting the control group. Patients with the usual interstitial pneumonia (UIP) pattern were more likely to receive PFD treatment, and a relatively lower proportion of cases in the PFD group received immunosuppressive therapies compared to the control group (p < 0.05). At the 6-month follow-up, patients in the PFD group demonstrated a more significant improvement in forced vital capacity (FVC) and diffusion capacity for carbon monoxide (DLCO) (ΔFVC%: 2.9% vs 0.45%, p = 0.009; ΔDLCO%: 1.9% vs -1.1%, p = 0.004). In the linear mixed model analysis, there was a statistically significant group-time interaction between FVC% and DLCO% changes over time (FVC%: β = 4.52, p < 0.001; DLCO%: β = 4.13, p = 0.003). Furthermore, subgroup analysis indicated that pirfenidone may have superior therapeutic effects in patients with systemic sclerosis (SSc)-associated ILD, non-UIP pattern, and restrictive pattern of lung function at baseline.

Conclusion: This study provided real-world data demonstrating the effectiveness of PFD in terms of lung function improvement in patients with CTD-ILD.

Background: Pediatric bronchiectasis is a common respiratory disease in children. The use of video-assisted thoracoscopic surgery (VATS) for its treatment remains controversial.

Objectives: The objective of our study was to compare and analyze the clinical efficacy of thoracoscopic surgery and thoracotomy in the treatment of pediatric bronchiectasis and summarize the surgical treatment experience of VATS in children with bronchiectasis.

Design: Retrospective single-center cohort study.

Methods: A retrospective analysis was conducted on the clinical data of 46 pediatric patients who underwent surgery with bronchiectasis at the Children's Hospital of Chongqing Medical University from May 2015 to May 2023. The patients were divided into two groups: the VATS group (25 cases) and the thoracotomy group (21 cases). Comparative analysis was performed on various parameters including basic clinical data, surgical methods, operation time, intraoperative blood loss, transfusion status, postoperative pain, postoperative mechanical ventilation time, chest tube drainage time, length of hospital stay, incidence of complications, and follow-up information.

Results: There were no statistically significant differences between the two groups of patients in terms of age, weight, gender, etiology, duration of symptoms, site of onset, and comorbidities (p > 0.05). The operation time in the VATS group was longer than that in the thoracotomy group (p < 0.001). However, the VATS group had better outcomes in terms of intraoperative blood loss, transfusion status, postoperative pain, postoperative mechanical ventilation time, chest tube drainage time, and length of hospital stay (p < 0.05). The incidence of postoperative complications in the VATS group was lower than that in the thoracotomy group, although the difference was not statistically significant (p = 0.152). Follow-up data showed no statistically significant difference in the surgical treatment outcomes between the two groups (p = 0.493).

Conclusion: The incidence of complications and mortality in surgical treatment of bronchiectasis is acceptable. Compared with thoracotomy surgery, VATS has advantages such as smaller trauma, less pain, faster recovery, and fewer complications. For suitable pediatric patients with bronchiectasis, VATS is a safe and effective surgical method.

Background: Although high-flow nasal cannula (HFNC) oxygenation is currently recommended to prevent desaturation during sedation for bronchoscopy, there is no consensus on an optimal flow rate.

Objective: To determine the optimal oxygen flow rate for HFNC to effectively prevent desaturation during sedation for bronchoscopy.

Design: Prospective, randomized, and controlled study.

Methods: Patients (n = 240) scheduled for bronchoscopy were randomized to receive HFNC with propofol sedation (fraction of inspired oxygen, 100%) at one of six flow rates of 10, 20, 30, 40, 50, and 60 L/min, designated as groups 1-6, respectively.

Results: The incidence of desaturation significantly decreased by increasing the oxygen flow rate (42.5%, 17.5%, 15%, 10%, 2.5%, and 0% for groups 1-6, respectively, p < 0.0001). The optimal oxygen flow rate for HFNC determined by probit regression to effectively prevent desaturation in 95% of patients was 43.20 (95% confidence interval, 36.43-55.96) L/min. The requirement for airway intervention was significantly decreased by increasing the oxygen flow rate.

Conclusion: An HFNC flow rate of 50-60 L/min is recommended to prevent desaturation during sedation for bronchoscopy.

Registration: NCT05298319 at ClinicalTrials.gov.

Background: Given the rarity of tracheobronchopathia osteochondroplastica (TO), many young doctors in primary hospitals are unable to identify TO based on bronchoscopy findings.

Objectives: To build an artificial intelligence (AI) model for differentiating TO from other multinodular airway diseases by using bronchoscopic images.

Design: We designed the study by comparing the imaging data of patients undergoing bronchoscopy from January 2010 to October 2022 by using EfficientNet. Bronchoscopic images of 21 patients with TO at Anhui Chest Hospital from October 2019 to October 2022 were collected for external validation.

Methods: Bronchoscopic images of patients with multinodular airway lesions (including TO, amyloidosis, tumors, and inflammation) and without airway lesions in the First Affiliated Hospital of Guangzhou Medical University were collected. The images were randomized (4:1) into training and validation groups based on different diseases and utilized for deep learning by convolutional neural networks (CNNs).

Results: We enrolled 201 patients with multinodular airway disease (38, 15, 75, and 73 patients with TO, amyloidosis, tumors, and inflammation, respectively) and 213 without any airway lesions. To find multinodular lesion images for deep learning, we utilized 2183 bronchoscopic images of multinodular lesions (including TO, amyloidosis, tumor, and inflammation) and compared them with images without any airway lesions (1733). The accuracy of multinodular lesion identification was 98.9%. Further, the accuracy of TO detection based on the bronchoscopic images of multinodular lesions was 89.2%. Regarding external validation (using images from 21 patients with TO), all patients could be diagnosed with TO; the accuracy was 89.8%.

Conclusion: We built an AI model that could differentiate TO from other multinodular airway diseases (mainly amyloidosis, tumors, and inflammation) by using bronchoscopic images. The model could help young physicians identify this rare airway disease.