Therapeutic Advances in Respiratory Disease最新文献

Background: Prior pulmonary tuberculosis (PTB) might be associated with the development of chronic obstructive pulmonary disease (COPD). However, the impact of prior PTB on the risk of incident COPD has not been studied in a large prospective cohort study of the European population.

Objectives: This study aimed to investigate the association of prior PTB with the risk of COPD.

Design: Prospective cohort study.

Methods: A multivariable Cox proportional model was used to estimate the hazard ratio (HR) and 95% confidence interval (95% CI) for the association of prior PTB with COPD. Subgroup analyses were further conducted among individuals stratified by age, sex, body mass index, smoking status, drinking status, physical activity, and polygenic risk score (PRS).

Results: The study involved a total of 216,130 participants, with a median follow-up period of 12.6 years and 2788 incident cases of COPD. Individuals with a prior history of PTB at baseline had an 87% higher risk of developing incident COPD compared to those without such history [adjusted hazard ratio (aHR) = 1.87; 95% confidence interval (CI): 1.26-2.77; p = 0.002]. Subgroup analysis revealed that individuals having prior PTB history presented a higher risk of incident COPD among individuals who were aged from 50 to 59 years with aHR of 2.47 (1.02-5.95, p = 0.044), older than 59 years with aHR of 1.81 (1.16-2.81, p = 0.008), male with aHR of 2.37 (1.47-3.83, p < 0.001), obesity with aHR of 3.35 (2.16-5.82, p < 0.001), previous smoking with aHR of 2.27 (1.39-3.72, p < 0.001), current drinking with aHR of 1.98 (1.47-3.83, p < 0.001), low physical activity with aHR of 2.62 (1.30-5.26, p = 0.007), and low PRS with aHR of 3.24 (1.61-6.53, p < 0.001), as well as high PRS with aHR of 2.43 (1.15-5.14, p = 0.019).

Conclusion: A history of PTB is an important independent risk factor for COPD. Clinical staff should be aware of this risk factor in patients with prior PTB, particularly in countries or regions with high burdens of PTB.

Background: Self-expandable metallic stents (SEMS) are increasingly used in the management of both malignant and nonmalignant airway stenosis. There are multiple stents available in the market; however, the current literature on the efficacy and safety of newly available 3rd generation SEMS (Bonastent) is extremely limited and only has data from single center studies.

Objectives: To report the efficacy and early (<7 days) and late (⩾7 days) complications in patients with central airway obstruction (CAO) treated with Bonastent placement at two institutions.

Design: We performed a retrospective analysis of data of consecutive patients who underwent therapeutic bronchoscopy and Bonastent placement at two tertiary care university hospitals between January 2019 and November 2023.

Methods: Bonastent deployment was performed in the operating room. Stents were deployed using rigid or flexible bronchoscopy under direct visualization with a flexible bronchoscope and in conjunction with fluoroscopic guidance. We then analyzed the effectiveness, short-term, and long-term complications of Bonastent placement.

Results: A total of 107 Bonastents® were placed in 96 patients. The most common etiology of CAO was malignancy, 92.7% (n = 89), followed by excessive dynamic airway collapse (EDAC) and post-intubation tracheal stenosis. Seventy-three patients (76%) had improvement in symptoms or imaging within 7 days of stent placement, including successful liberation from mechanical ventilation in a patient with CAO. Early complications occurred in seven patients (two-airway bleeding, two-mucus plugging that improved with airway clearance, two-stent migrations, and one-cough).Late complications occurred in 23 patients (1-stent migration requiring revision bronchoscopy and replacement of airway stent, 11-mucus plugging, 6-granulation tissue, 2-pneumonia, 1-cough, 1-tumor ingrowth/stent fracture, 1-airway emergency due to excessive granulation tissue obstructing the distal end of the stent and had a failed cricothyroidotomy leading to death). Overall, the early complication rate was 7.3% (7/96) and late complication rate was 23.9% (23/96).

Conclusion: Our study is the first multicenter study that found a good safety profile with a low complication rate after tracheobronchial Bonastent placement with improvement in symptoms soon after stent placement.

Severe asthma (SA) poses a significant challenge to management and treatment, leading to a reduced quality of life and a heavy burden on society and healthcare resources. Bronchial thermoplasty (BT) has emerged as a non-pharmacological intervention for SA, demonstrating its efficacy and safety in improving patients' quality of life and reducing exacerbation rates for over a decade. In particular, BT encounters various obstacles in its clinical application. Since asthma is characterized by high heterogeneity, not all patients derive effective outcomes from BT. Furthermore, current knowledge of markers that indicate response to BT remains limited. Recent research has shed light on the intricate mechanism of action of BT, which extends beyond simple smooth muscle ablation. Therefore, to enhance the clinical practice and implementation of BT, this paper aims to elucidate the mechanism of action and identify potential markers associated with BT response.

Background: The presence of anti-melanoma differentiation-associated gene 5 (MDA5) antibodies in dermatomyositis (DM) is associated with an increased risk of developing rapidly progressive interstitial lung disease (RP-ILD) and a poor prognosis.

Objectives: We aimed to explore whether tofacitinib could improve the prognosis of Anti-MDA5 antibody positive DM-interstitial lung disease (ILD).

Design: Systematic review and meta-analysis.

Data sources and methods: Studies were included if they compared mortality rate and infection events in patients with anti-MDA5 antibody positive DM-associated ILD who were treated with or without tofacitinib.

Results: The systematic review and meta-analysis included a total of 148 patients from four cohort studies. Fifty-eight patients with anti-MDA5 antibody positive DM-ILD who received combined treatment-containing tofacitinib were enrolled in the experimental group. Additionally, 90 DM-ILD patients who did not receive tofacitinib-based therapy were included in the control group. The pooled risk ratio (RR) for all-cause mortality was 0.61 (95% CI, 0.41-0.91, p = 0.02) with I² = 0 indicating no heterogeneity among the included studies. For virus infection risk, the pooled RR was 1.92 (95% CI, 0.90-4.10, p = 0.09), while bacterial and fungal infection-associated RRs were found to be 1.29 (95% CI, 0.65-2.55, p = 0.47) and 1.15 (95% CI, 0.46-2.89, p = 0.77), respectively. There was no statistically significant difference in infection risk between the two groups, and no heterogeneity was observed.

Conclusion: Our findings suggest that tofacitinib may reduce the risk of all-cause mortality in patients with anti-MDA5 antibody-positive DM-ILD without an increased risk of additional infections.

Trial registration: PROSPERO: CRD42023445427; https://www.crd.york.ac.uk/prospero/.

Cystic fibrosis (CF) causes life-shortening respiratory and systemic disease due to dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel. Highly effective modulator therapies (HEMT) improve the lives of many people with cystic fibrosis (PwCF) by correcting the structure and function of the defective CFTR channel at the molecular level. Despite these advancements, a subset of patients-termed modulator-refractory CF-continues to experience two or more pulmonary exacerbations per year requiring hospitalization or intravenous antibiotics, regardless of other modulator benefits. This underrecognized group represents an emerging challenge within the CF community. We discuss the benefits and limitations of current CFTR modulator therapies and the urgent need to investigate this emerging at-risk population. While HEMT improves lung function, decreases exacerbations, reduces the need for lung transplantation, and lowers mortality, increasing evidence shows that not all patients benefit equally. At the University of Virginia, nearly 6% of adults with CF exhibit the modulator-refractory phenotype. The driving factors of modulator-refractory CF are likely multifactorial, including genetic variations, variable immune responses, preexisting bronchiectasis, microbiological colonization, preexisting comorbid conditions, and environmental and socioeconomic factors. This perspective review recognizes and defines modulator-refractory CF as a distinct emerging clinical phenotype in the post-modulator era. Understanding this phenotype is crucial for reducing morbidity and mortality, and for improving the quality of life for PwCF. Raising awareness of modulator-refractory CF will help the community address this population and perform further research to identify causes. The emergence of modulator-refractory CF highlights a significant gap in our current treatment landscape and provides an opportunity to develop innovative therapeutic strategies that may benefit the entire CF community, ensuring that no person with CF is left behind.

Background: Pulmonary arterial hypertension (PAH) is a life-threatening, progressive disease often diagnosed late in its course.

Objectives: To present patient-reported data that were captured within a large, multinational, point-in-time survey of PAH-treating physicians and their patients to better understand the diagnostic journey.

Design: Cross-sectional survey conducted in five European countries (EU5), Japan and the USA.

Methods: PAH-treating pulmonologists, cardiologists, rheumatologists or internists (USA only) completed a patient record form (PRF) for the next four consecutive adult PAH patients they saw; these patients filled in a patient self-completion (PSC) form on an anonymous, voluntary basis. Our report focuses on patient data; data are from PSC forms unless stated otherwise.

Results: Physician-reported PRFs and self-completed PSC forms were obtained for 1152 and 572 patients, respectively. Patients' mean (SD) age was 59.1 (14.0) years, 55.6% were female, and 57.3% had idiopathic PAH. Patient-reported data showed an average delay of 17.0 months between symptom onset and PAH diagnosis. This is longer than physicians estimated (13.8 months): this disparity may be partly due to the time taken by patients to consult a physician about their symptoms [9.6 months overall, longest in the USA (15.3 months)]. Most patients (71.6%) initially consulted primary care physicians about their symptoms and 76.4% of patients were referred to a specialist. Misdiagnoses occurred in 40.9% of patients [most frequent in the USA (51.3%), least common in Japan (27.6%)] and they saw an average of 2.9 physicians overall (3.5 in EU5 versus 2.0 in Japan/USA) before being diagnosed. Diagnosis was most often made by cardiologists (50.4%) or pulmonologists (49.3%).

Conclusion: Our data suggest that diagnostic delay in PAH results from patient- and physician-related factors, which differ across regions and include lack of awareness of PAH on both sides. Development of better screening strategies may help address this barrier to timely PAH diagnosis.

Background: Ventilator-induced lung injury (VILI) presents a grave risk to acute respiratory failure patients undergoing mechanical ventilation. Low tidal volume (LTV) ventilation has been advocated as a protective strategy against VILI. However, the effectiveness of limited driving pressure (plateau pressure minus positive end-expiratory pressure) remains unclear.

Objectives: This study evaluated the efficacy of LTV against limited driving pressure in preventing VILI in adults with respiratory failure.

Design: A single-centre, prospective, open-labelled, randomized controlled trial.

Methods: This study was executed in medical intensive care units at Siriraj Hospital, Mahidol University, Bangkok, Thailand. We enrolled acute respiratory failure patients undergoing intubation and mechanical ventilation. They were randomized in a 1:1 allocation to limited driving pressure (LDP; ⩽15 cmH₂O) or LTV (⩽8 mL/kg of predicted body weight). The primary outcome was the acute lung injury (ALI) score 7 days post-enrolment.

Results: From July 2019 to December 2020, 126 patients participated, with 63 each in the LDP and LTV groups. The cohorts had the mean (standard deviation) ages of 60.5 (17.6) and 60.9 (17.9) years, respectively, and they exhibited comparable baseline characteristics. The primary reasons for intubation were acute hypoxic respiratory failure (LDP 49.2%, LTV 63.5%) and shock-related respiratory failure (LDP 39.7%, LTV 30.2%). No significant difference emerged in the primary outcome: the median (interquartile range) ALI scores for LDP and LTV were 1.75 (1.00-2.67) and 1.75 (1.25-2.25), respectively (p = 0.713). Twenty-eight-day mortality rates were comparable: LDP 34.9% (22/63), LTV 31.7% (20/63), relative risk (RR) 1.08, 95% confidence interval (CI) 0.74-1.57, p = 0.705. Incidences of newly developed acute respiratory distress syndrome also aligned: LDP 14.3% (9/63), LTV 20.6% (13/63), RR 0.81, 95% CI 0.55-1.22, p = 0.348.

Conclusions: In adults with acute respiratory failure, the efficacy of LDP and LTV in averting lung injury 7 days post-mechanical ventilation was indistinguishable.

Clinical trial registration: The study was registered with the ClinicalTrials.gov database (identification number NCT04035915).

Background: Different types of inflammatory processes and fibrosis have been implicated in the pathogenesis of interstitial lung disease (ILD), a heterogeneous, diffuse, parenchymal lung disease. Acute exacerbation (AE) of ILD is characterized by significant respiratory deterioration and is associated with high mortality rates. Several serum oncomarkers have been used to determine the prognosis of ILD; however, the prognostic value of serum oncomarker levels in patients with AE-ILD remains unclear.

Objective: To evaluate the prognostic value of serum oncomarker levels in patients with AE-ILD and its main subtypes.

Design: Retrospective study.

Methods: The serum levels of 8 oncomarkers in 281 patients hospitalized with AE-ILD at our institution between 2017 and 2022 were retrospectively reviewed. The baseline characteristics and serum oncomarker levels were compared between the survival and non-survival groups of AE-ILD and its main subtypes. Multivariate logistic regression analysis was performed to identify independent prognosis-related markers, and the best prognostic predictor was analyzed using receiver operating characteristic curve (ROC) analysis.

Result: Idiopathic pulmonary fibrosis (IPF; n = 65), idiopathic nonspecific interstitial pneumonia (iNSIP; n = 26), and connective tissue disease-associated interstitial lung disease (CTD-ILD; n = 161) were the three main subtypes of ILD. The in-hospital mortality rate among patients with AE-ILD was 21%. The serum oncomarker levels of most patients with AE-ILD and its main subtypes in the non-survival group were higher than those in the survival group. Multivariate analysis revealed that ferritin and cytokeratin 19 fragments (CYFRA21-1) were independent prognostic risk factors for patients hospitalized with AE-ILD or AE-CTD-ILD. CYFRA21-1 was identified as an independent prognostic risk factor for patients hospitalized with AE-IPF or AE-iNSIP.

Conclusion: CYFRA21-1 may be a viable biomarker for predicting the prognosis of patients with AE-ILD, regardless of the underlying subtype of ILD. Ferritin has a prognostic value in patients with AE-ILD or AE-CTD-ILD.

The two patients included in the study had mixed and refractory post-tuberculosis tracheobronchial stenosis (PTTS), having experienced unsuccessful interventional therapies such as balloon dilation and V-shaped stent placement before the operation. Following the secure placement of L-shaped silicone stents, examinations with a fiberbronchoscope during the first and third months post-operation revealed a significant reduction in bronchial mucosa inflammation for both patients. Additionally, the opening diameter of the upper and lower branch segments increased, and chest CT scans indicated a noticeable absorption of left pulmonary lesions. Three months post-operation, fiberbronchoscopy confirmed the stable fixation of the stent without any movement. The patients exhibited substantial improvements in pulmonary function, dyspnea index, and blood gas analysis, with no reported adverse complications. After 7 months, a follow-up fiberbronchoscope for one case revealed excellent stent fixation. Simultaneously, the chest CT scan indicated favorable re-expansion. The placement of L-shaped silicone stents proves effective in preventing displacement, alleviating airway stenosis or obstruction, and ensuring the safety and efficacy of PTTS treatment - particularly in cases where V-shaped silicone stent placement has failed. To our knowledge, this is the first study describing the L-shaped silicone stent in two patients with PTTS.