Therapeutic Advances in Respiratory Disease最新文献

Background: Impaired quality of life (QoL) among pulmonary arterial hypertension (PAH) patients has been often attributed to increased symptomatology, functional disability, and poor mental health; however, the unique impact that PAH treatments may exert on the daily lives of patients remains underexplored.

Objectives: To gain insight into the day-to-day challenges associated with receiving non-oral PAH treatments, and the specific impact these may exert on patients' QoL, above and beyond that exerted by PAH itself.

Design: Explanatory sequential mixed methods design.

Methods: Eighty-three PAH patients provided information on demographic and clinical characteristics, and completed measures of symptomatology, functional disability, QoL, psychological well-being, and perceived stress. Nine of these patients also participated in a focused group discussion and interviews.

Results: No group differences in symptomatology and functional disability were observed between patients receiving oral-only and non-oral PAH therapy; however, patients on non-oral therapy reported poorer QoL, after taking into consideration the effect of relevant covariates (i.e., age, level of symptomatology and functional disability, psychological well-being, and perceived stress) that could have confounded the observed group differences in QoL. Participants who started on non-oral medications acknowledged they had experienced significant improvements in health status. However, they also stated that transitioning from oral to non-oral therapy elicited great apprehension and that non-oral therapy regimens interfered with daily activities, resulted in added difficulties for self-management, and negatively impacted their subjective well-being.

Conclusion: Non-oral therapy regimens may pose challenges beyond those posed by PAH itself, potentially resulting in an added burden to the QoL of PAH patients.

Background: Incidental and screen-detected pulmonary nodules are common. The increasing capabilities of advanced diagnostic bronchoscopy will increase bronchoscopists' procedural volume necessitating optimization of procedural scheduling and workflow.

Objectives: The objectives of this study were to determine total time in the procedure room, total bronchoscopy procedure time, and robotic-assisted bronchoscopy procedure time longitudinally and per specific procedure performed.

Design: A single-center observational study of all consecutive patients undergoing shape-sensing robotic-assisted bronchoscopy (RAB) biopsy procedures for the evaluation of pulmonary lesions with variable probability for malignancy.

Methods: Chart review to collect patient demographics, lesion characteristics, and procedural specifics. Descriptive and comparative statistics are reported.

Results: Actual bronchoscopy procedure time may decrease with increased institutional experience over time, however, there is limited ability to reduce non-bronchoscopy related time within the procedure room. The use of cone beam computed tomography (CBCT), rapid on-site evaluation (ROSE), and performance of staging endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) in a single procedure are each associated with additional time requirements.

Conclusion: Institutional procedural block times should adapt to the nature of advanced diagnostic bronchoscopy procedures to allow for the accommodation of new modalities such as RAB combined with other technologies including radial endobronchial ultrasound, CBCT, ROSE, and staging linear EBUS. Identifying institutional median procedural times may assist in scheduling and ideal block time utilization.

Background: Lymphangioleiomyomatosis (LAM) is a rare multisystemic disorder characterized by the proliferation of abnormal smooth muscle-like cells. Although serum vascular endothelial growth factor-D (VEGF-D) is currently used as a diagnostic biomarker for LAM, its diagnostic value in Korean patients is unclear.

Objectives: To evaluate the diagnostic value of serum VEGF-D for LAM in Korean patients.

Design: A multicenter prospective cohort study.

Methods: Serum samples were prospectively collected from five medical institutions, from patients with LAM (n = 40) and controls (n = 24; healthy participants = 3, other cystic lung diseases = 13, idiopathic pulmonary fibrosis = 4, idiopathic nonspecific interstitial pneumonia = 4). Serum VEGF-D levels were measured using the enzyme-linked immunosorbent assay, and the diagnostic value was evaluated using receiver operating characteristic (ROC) curve analysis.

Results: The mean age of patients with LAM was 44.5 years, and all were female (controls: 47.8 years; female: 70.8%, p < 0.001). The serum VEGF-D levels were significantly higher in patients with LAM than those in the control group (median: 708.9 pg/mL vs 325.3 pg/mL, p < 0.001). In the ROC curve analysis, serum VEGF-D levels showed good predicting performance for LAM diagnosis (area under the curve = 0.918) with an optimal cut-off value of 432.7 pg/mL (sensitivity = 85.0%, specificity = 87.5%). When 800 pg/mL was used as the cut-off value, the specificity of serum VEGF-D for LAM diagnosis increased to 100.0%.

Conclusion: Our results suggest that serum VEGF-D may be a useful biomarker for diagnosing LAM in Korean patients, similar to previous reports.

Background: Patients with mediastinal lymph node enlargement (MLNE) are diagnosed depending on lymph node biopsy. Whereas, how to obtain larger tissue masses from mediastinal lymph nodes and improve the diagnostic yield of the disease remains to be investigated.

Objectives: Aiming to assess the diagnostic value of endobronchial ultrasound-guided intranodal forceps biopsy via transbronchial laser photoablation (EBUS-IFB-TLP) in patients with MLNE.

Design: A prospective, self-controlled study.

Methods: This study was conducted on 67 MLNE patients requiring a lymph node biopsy for diagnosis at the Henan Provincial People's Hospital and the Fuwai Central China Cardiovascular Hospital in China, from January 2020 to December 2022. Each patient underwent endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA group) and EBUS-IFB-TLP (EBUS-IFB-TLP group) on the same mediastinal lymph node for biopsies. The operation time, diagnostic efficiency, and complication rates of the two biopsy methods were compared.

Results: The number of diagnosed patients in the EBUS-IFB-TLP and the EBUS-TBNA groups was 65 (97.0%) and 57 (85.1%), respectively (p = 0.021). In the EBUS-IFB-TLP group, 28 cases (96.6%) were diagnosed with lung cancer and were classified into different epithelial types. In the EBUS-TBNA group, there were 27 cases (93.1%) diagnosed with lung cancer, of which 26 (89.7%) were classified into different epithelial types. There were 37 (97.4%) and 30 (78.9%) non-lung cancer patients diagnosed in the EBUS-IFB-TLP and EBUS-TBNA groups, respectively (p = 0.039), while 27 cases (96.4%) of sarcoidosis in the EBUS-IFB-TLP group and 20 cases (71.4%) of sarcoidosis in the EBUS-TBNA group were diagnosed (p = 0.016). The percentages of intraoperative mild to moderate bleeding complications were 23.9% (16/67) and 14.9% (10/67) in the EBUS-IFB-TLP and in the EBUS-TBNA groups, respectively (p = 0.109).

Conclusion: This study demonstrated that EBUS-IFB-TLP could be a feasible and effective method in the diagnosis of patients with MLNE, presenting an analogous safety profile compared with EBUS-TBNA. Further studies are needed to verify the diagnostic performance of EBUS-IFB-TLP for MLNE.

Lung cancer represents the second most frequent neoplasm and the leading cause of neoplastic death among both women and men, causing almost 25% of all cancer deaths. Patients undergoing lung resection-both for primary and secondary tumors-require careful preoperative cardiopulmonary functional evaluation to confirm the safety of the planned resection, to assess the maximum tolerable volume of resection or to exclude surgery, thus shifting the therapeutic approach toward less invasive options. Cardiopulmonary reserve, pulmonary lung function and mechanical respiratory function represent the cornerstones of preoperative assessment of patients undergoing major lung resection. Spirometry with carbon monoxide diffusing capacity, split function tests, exercise tests and cardiologic evaluation are the gold standard instruments to safely assess the entire cardiorespiratory function before pulmonary resection. Although pulmonary mechanical and parenchymal function, together with cardiorespiratory compliance represent the mainstay of preoperative evaluation in thoracic surgery, the variables that are responsible for fitness in patients who have undergone lung resection have expanded and are being continually investigated. Nevertheless, because of the shift to older patients who undergo lung resection, a global approach is required, taking into consideration variables like frailty status and likelihood of postoperative functional deterioration. Finally, the decision to go ahead with surgery in fragile patients being consideredfor lung resection should be evaluated in a multispecialty preoperative discussion to provide a personalized risk stratification. The aim of this review is to focus on preoperative evaluation of cardiopulmonary reserve and surgical risk stratification of patients candidate for lung cancer resection. It does so by a literature search of clinical guidelines, expert consensus statements, meta-analyses, clinical recommendations, book chapters and randomized trials (1980-2022).

Background: A significant decline in pulmonary exacerbation rates has been reported in CF patients homozygous for F508del treated with lumacaftor/ivacaftor. However, it is still unclear whether this reduction reflects a diminished microbiological burden.

Objectives: The aim of this study was to determine the impact of lumacaftor/ivacaftor on the bacterial and fungal burden.

Design: The study is a prospective multicenter cohort study including 132 CF patients homozygous for F508del treated with lumacaftor/ivacaftor.

Methods: Clinical parameters as well as bacterial and fungal outcomes 1 year after initiation of lumacaftor/ivacaftor were compared to data from 2 years prior to initiation of the treatment. Changes in the slope of the outcomes before and after the onset of treatment were assessed.

Results: Lung function measured as ppFEV1 (p < 0.001), body mass index (BMI) in adults (p < 0.001), and BMI z-score in children (p = 0.007) were improved after initiation of lumacaftor/ivacaftor. In addition, the slope of the prevalence of Streptococcus pneumoniae (p = 0.007) and Stenotrophomonas maltophilia (p < 0.001) shifted from positive to negative, that is, became less prevalent, 1 year after treatment, while the slope for Candida albicans (p = 0.009), Penicillium spp (p = 0.026), and Scedosporium apiospermum (p < 0.001) shifted from negative to positive.

Conclusion: The current study showed a significant improvement in clinical parameters and a reduction of some of CF respiratory microorganisms 1 year after starting with lumacaftor/ivacaftor. However, no significant changes were observed for Pseudomonas aeruginosa, Staphylococcus aureus, or Aspergillus fumigatus, key pathogens in the CF context.

Intracavitary pulmonary aspergilloma is a persistent and life-threatening infection that carries a mortality rate of up to 15%. It occurs when Aspergillus species gain entry to an existing lung cavity. In the absence of definitive treatment, patients may succumb to severe complications such as massive hemoptysis, cachexia, or secondary infections. Aspergillomas often show limited response to antifungal medications, mainly due to insufficient drug concentrations within the cavities. Surgery is frequently the preferred treatment option, but it poses significant risks, and many individuals are ineligible due to underlying health issues. We present the most extensive non-surgical fungal ball cohort to date, managed using an innovative multimodal strategy that combines antifungal therapy before and after bronchoscopic debulking. This was a cross-sectional observational study. For those who cannot undergo surgery, our medical center has pioneered a multimodal approach to aspergilloma resection. This approach combines bronchoscopic endoscopy with antifungal therapy and has been applied successfully to more than 18 patients that are presented in this series. The median age of the cohort was 58 years (range: 32-73), with an equal sex distribution. The mean percent predicted FEV₁ was 65.3%. The mean follow-up duration was 3.6 years (range: 0.5-10 years). The cohort receiving antifungals systematically prior to debridement showed a reduction of the pre-existing cavity (40.38 mm versus 34.02 mm, p = 0.021). Across the 18 patients during the follow-up period, 94% remained recurrence-free (defined by symptoms and radiology). Our study fills a critical knowledge gap regarding the significance of initiating antifungal treatment before bronchoscopic debulking and presents a viable approach in these cases for which there is a current unmet therapeutic need.

Background: Benralizumab is a monoclonal antibody treatment for severe eosinophilic asthma (SEA). Few studies investigated its role in airway inflammation and its correlation with lung function.

Objectives: The aim of the present study is to assess its effect after 1 year of treatment, focusing on airway inflammation.

Design: This is a retrospective observational study, in an Italian tertiary reference centre specialised in diagnosis and management of severe asthma patients.

Methods: We conducted a monocentric retrospective study including SEA patients treated with benralizumab for 1 year. Clinical, functional and inflammatory data were collected at baseline, 6 (T6) and 12 (T12) months.

Results: Twenty-two SEA patients on benralizumab were included. We observed a reduction in exacerbations rate and systemic steroid treatment (p < 0.0001) as well as an improvement in asthma control (p < 0.0001), health-related quality of life (p = 0.017) and lung function pre-BD FEV1 (L) (p = 0.02) and percentage (p = 0.004) and post-BD FEV1 (L) (p = 0.01) and percentage (p = 0.003) from baseline to T6 and T12. A reduction in sputum eosinophil percentage was observed at T6 and T12 (p < 0.005). We found a positive correlation between the variation of sputum eosinophils percentage and FEV1 (L) at T12 (rho = -0.79, p = 0.04). Moreover, the improvement of FEF_25%-75% from baseline to 6 (rho = -0.53, p = 0.03) and 12 (rho = -0.62, p = 0.01) months negatively correlated with the duration of asthma disease.In our cohort 12/22 patients were super-responders at T6 and 15/22 at T12. Furthermore, clinical remission was reached by 12/22, and all of them obtained blood and sputum eosinophils counts normalisation.

Conclusion: Our data confirm that it is a rapid and effective treatment for SEA acting on clinical, functional, systemic and airway inflammatory outcomes. Our results highlight the role of induced sputum as a promising non-invasive technique to investigate pathophysiologic mechanisms in severe asthma treated with biologics. Finally, a negative correlation between small airway improvement and the duration of asthma may suggest that a prompt referral to asthma centres may delay lung function worsening. Additional studies are needed to investigate more in-depth the role of induced sputum in the management of asthma, response to treatment and remission.

Background: The efficacy of behavioral cough suppression therapy (BCST) for refractory chronic cough (RCC) and unexplained chronic cough (UCC) remains unclear due to limited evidence from small-scale single-center studies.

Objective: To compile and assess the quality of evidence from randomized controlled trials to evaluate the effectiveness of BCST.

Design: This study included randomized controlled studies and self-controlled studies related to BCST involving adult patients with RCC or UCC.

Data sources and methods: We conducted an extensive search of various English and Chinese databases (e.g., PubMed, CNKI, CBM, VIP, and Wanfang Data Journal Full-text Database) and the Clinical Trial Registration website up to April 2024. The selected studies underwent meta-analysis to investigate the impact of BCST on the patient's quality of life and cough frequency.

Results: The included 12 studies showed that BCST significantly improved the Leicester Cough Questionnaire scores of the patients (MD = 4.50, 95% CI (4.03, 4.97), p < 0.001) compared to the simple verbal education group. In addition, a significant reduction in objective cough frequency was observed in patients compared to before BCST, with a statistically significant difference (MD = -8.06, 95% CI (-9.71, -6.41), p < 0.001). Other measures of cough symptoms, such as symptom scores, Visual Analog Scale (VAS) scores, and Cough Severity Index (CSI) also showed improvement.

Conclusion: This meta-analysis revealed positive therapeutic effects of BCST in patients with RCC/UCC, potentially advancing its application in broader clinical settings.

Trial registration: This study was registered on PROSPERO with the registration number CRD42024530746.

What is this summary about?This summary describes the results of a clinical study called MANDALA that was published in the New England Journal of Medicine in 2022. In the MANDALA study, researchers looked at a new asthma rescue inhaler that contains both albuterol and budesonide in a single inhaler (known as albuterol-budesonide, AIRSUPRA™). This summary describes the results for people aged 18 yearsand older who took part in the study.