Therapeutic Advances in Respiratory Disease最新文献

Pulmonary arterial hypertension (PAH) is a rare but fatal disease characterized by progressive vascular remodeling, which results in increased pulmonary vascular resistance and elevated pulmonary arterial pressure. These changes are detrimental to the right ventricle (RV). If not treated, it can eventually lead to maladaptive RV structural changes, right heart failure, and death. Late diagnosis at an advanced stage remains a significant issue that limits the effectiveness of existing treatments. PAH pathophysiology is mediated by several molecular pathways that act on different cell types, including endothelial cells, smooth muscle cells, and fibroblasts. These cells exhibit cancer-like properties, including increased proliferation, resistance to apoptosis, and metabolic reprogramming. This review provides new insights into clinical and diagnostic research on PAH. Herein, we discuss classification systems, their relevance and significance in PAH, innovative imaging techniques, and genetic testing to identify hereditary risk factors. The potential of artificial intelligence to improve disease detection and management is also discussed in the context of diagnostic workflows. Overall, we aim to provide new insights in this review and emphasize the critical need for early diagnosis, personalized treatment strategies, and continued innovation in PAH care to improve patient outcomes and quality of life.

Background: Bronchoscopic lung volume reduction (BLVR) can be an effective treatment for highly selected patients with severe emphysema but only half of carefully selected patients derive clinical benefit. Two commercially available platforms exist to help determine candidacy for BLVR via quantitative analysis of computed tomography (CT) scans.

Objectives: To determine if the two commercially available quantitative platforms identified the same patient population that may benefit from BLVR.

Design: A multicenter, retrospective cohort study.

Methods: Consecutive patients referred for BLVR between January 1, 2022 and March 31, 2023 at three medical centers in the United States with the same CT scan submitted for quantitative analysis to two commercially available platforms to determine BLVR candidacy were analyzed. The primary outcome of interest was whether quantitative analysis provided different recommendations for individual patients. The recommendation to proceed with BLVR was based on a prespecified algorithm using criteria established in clinical trials for each quantitative platform, respectively.

Results: A total of 83 patients referred for BLVR across three centers were included; patients were a median 67 years old, had a median post bronchodilator FEV1 of 30% predicted (IQR: 25, 38), a median residual volume of 220% predicted (IQR: 185, 268), and 29 (34.9%) received endobronchial valves. A total of 26 patients (31.3%) received different recommendations from the two quantitative platforms.

Conclusion: In this cohort of patients evaluated for BLVR across multiple medical centers, nearly a third of patients received different recommendations based on the platform utilized for valve assessment. This suggests that the selection process for BLVR may warrant refinement.

Chronic obstructive pulmonary disease (COPD) is a prevalent respiratory condition associated with increased morbidity and mortality, particularly during respiratory infections such as influenza. The interaction between COPD and influenza is multifaceted, involving compromised immune responses, chronic inflammation, and impaired lung function. Influenza infection can exacerbate COPD, leading to acute exacerbations, hospitalizations, and higher mortality. This review examines the pathophysiological mechanisms underlying the exacerbation of COPD by influenza, evaluates its impact on patient outcomes, and explores the role of comorbidities in shaping disease severity. We also assess the effectiveness of influenza vaccination in preventing severe outcomes and discuss strategies to improve vaccination uptake among COPD patients. Current evidence highlights the importance of tailored prevention and management approaches, as well as the need for further research into biomarkers and optimal therapeutic strategies to mitigate the burden of influenza on COPD populations.

Background: Pulmonary rehabilitation (PR) has demonstrated efficacy in managing long COVID-19, underscoring the need to refine and tailor PR strategies for optimal patient outcomes.

Objectives: To evaluate the impact of PR on patients with long COVID-19 and to compare the efficacy of different types and durations of PR interventions.

Design: Systematic review and meta-analysis.

Data sources and methods: We systematically searched randomized controlled trials (RCTs) of the effectiveness of PR in long COVID-19 patients published before April 2024. The primary outcomes were physical capacity assessed by the 6-minute walking test (6MWT), lung function measured by forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC), health-related quality of life (HRQoL), and fatigue. Secondary outcomes were thirty-second sit-to-stand test (30STST), handgrip strength tests, maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), dyspnea, depression, anxiety, perceived effort, and adverse events.

Results: A total of 37 studies with 3363 patients were included. Compared to controls, PR improved physical capacity (6MWT, 30STST, handgrip), lung function (FEV1, FVC, MIP, MEP), HRQoL, fatigue, dyspnea, and anxiety but did not reach statistical significance for depression. Subgroup analyses of PR duration indicated that programs of ⩽4 weeks improved 6MWT; those between 4 and 8 weeks significantly improved 6MWT, lung function (FEV1, FVC), HRQoL, and reduced fatigue; and programs over 8 weeks improved HRQoL and reduced fatigue. Exercise type analysis revealed that breathing exercises improved 6MWT, lung function (FEV1, FVC), and HRQoL; multicomponent exercises enhanced 6MWT performance and reduced fatigue; the combination of both types improved 6MWT, FEV1 (L), FVC (%pred), HRQoL, and reduced fatigue.

Conclusion: PR improves physical capacity, lung function, and quality of life and alleviates dyspnea, fatigue, and anxiety in long COVID-19 patients. A 4- to 8-week PR program and a combination of both breath exercises and multicomponent training is most effective for managing long-term COVID-19 syndromes.

Trial registration: PROSPERO ID: CRD42024455008.

Background: Although the clinical role of bronchoalveolar lavage (BAL) in interstitial lung disease (ILD) has been suggested by previous studies, its clinical utility remains debatable.

Objectives: We aimed to evaluate the clinical implications of combining quantitative computed tomography (QCT) and BAL fluid cellular analysis in patients with fibrotic ILD.

Design: This study was a retrospective, single-center study.

Methods: We analyzed patients with fibrotic ILD who underwent BAL in specific lung locations and used deep-learning-based QCT. Correlations between BAL cellular components and QCT parameters were assessed for both the whole lung and the tested lobe, and survival outcomes and disease progression were evaluated.

Results: Among 163 patients, no significant difference was observed in BAL cellular analysis between radiologic usual interstitial pneumonia (UIP) and non-UIP groups (for all, p > 0.05). BAL neutrophil levels showed weak positive correlation with fibrosis score (whole lung: r = 0.308, p < 0.001; tested lobe: r = 0.200; p = 0.010). While BAL cellular analysis alone showed no difference in 3-year survival, a high fibrosis score (⩾20%) independently predicted 3-year mortality (hazard ratio 4.62, p = 0.002). In patients with fibrosis score ⩾10%, high BAL neutrophils (>4.5%) indicated greater 1-year fibrosis progression (log-rank test, p = 0.029). In steroid-treated patients, BAL lymphocytosis (⩾15%) was associated with a trend toward an improved prognosis (p = 0.073); however, within this group, those with fibrosis scores ⩾20% had worse outcomes in the 3-year survival rate (median survival: 16.4 months vs not reached, p = 0.039).

Conclusion: Although BAL fluid cellular analysis alone does not differentiate radiologic patterns or offer prognostic values, elevated BAL neutrophil levels combined with a high fibrosis score on CT may help to identify patients at higher risk of early fibrosis progression.

The interstitial lung diseases (ILDs) are a heterogeneous and complex group of diseases. The treatable trait (TT) model represents a shift in ILD management, away from traditional diagnostic labels towards a more individualised, trait-focused approach. This review explores the application of the TT paradigm to ILD, identifying key traits across the aetiological, pulmonary, extrapulmonary and behavioural domains. By addressing these traits, the TT model offers a framework to improve outcomes in ILD through multidisciplinary management with a precision medicine focus. Further research is necessary to evaluate the overall impact of this TT model on ILD care.

Background: Pulmonary fibrosis is a severe, progressive form of interstitial lung disease associated with increased morbidity and mortality. Pulmonary hypertension often accompanies severe pulmonary fibrosis and is also associated with worse outcomes. Antifibrotic therapy and pulmonary vasodilator therapy have demonstrated clinical benefits in pulmonary fibrosis and pulmonary hypertension, respectively. However, the benefit of combined antifibrotic and pulmonary vasodilator therapy in patients with both pulmonary fibrosis and pulmonary hypertension is less established.

Objectives: We aimed to determine the effectiveness of a combination pulmonary vasodilator and antifibrotic therapy with regard to transplant-free survival and six-minute walk distance improvement in patients with pulmonary fibrosis and pulmonary hypertension.

Design: This was a retrospective cohort study of patients with pulmonary fibrosis (idiopathic pulmonary fibrosis, combined pulmonary fibrosis and emphysema, and other fibrotic interstitial lung disease) and pulmonary hypertension diagnosed via right heart catheterization. Patients received antifibrotic therapy with or without pulmonary vasodilator therapy.

Methods: Patients who received combination antifibrotic therapy and pulmonary vasodilator therapy were compared to those prescribed antifibrotic therapy alone. Transplant-free survival and change in six-minute walk distance were compared between the two groups. Multivariable Cox regression was performed to determine predictors of transplant-free survival.

Results: Patients who received antifibrotic and pulmonary vasodilator therapy had significantly improved transplant-free survival (log rank p = 0.001). Treatment with antifibrotic and pulmonary vasodilator therapy was significantly and independently associated with reduced risk of death or lung transplantation (HR 0.24, 95% CI 0.06-0.93, p = 0.04). These patients had worse pulmonary hemodynamics than those receiving antifibrotic therapy alone.

Conclusion: We found a potential survival benefit when pulmonary vasodilator therapy was given in combination with antifibrotic therapy in patients with pulmonary fibrosis and pulmonary hypertension. This may be reflective of a pulmonary vascular phenotype among those with pulmonary fibrosis and pulmonary hypertension. Further trials are needed to better elucidate which patients benefit from combination therapy.

SummaryWhat is this summary about?● This is a plain language summary of two articles originally published in The New England Journal of Medicine and The Lancet Respiratory Medicine. These articles presented the results of GALATHEA and TERRANOVA, two clinical studies that took place across 41 countries. ○ GALATHEA and TERRANOVA measured how patients' COPD changed from before their first benralizumab (10, 30, or 100 mg) injection, to after 56 weeks of treatment. ○ In both studies, benralizumab was compared with placebo. ○ To see whether benralizumab treatment would benefit any particular patients included in these studies, researchers carried out an additional analysis following the main studies of GALATHEA and TERRANOVA.

Alpha 1 antitrypsin deficiency (AATD) is a genetic disorder that alters the functionality and/or serum levels of alpha 1 antitrypsin (AAT). Dysfunctional forms of AAT, or low levels of serum AAT, predispose affected individuals to pulmonary complications. When AATD-associated lung disease develops, the most common pulmonary pathology is emphysema. The development of emphysema and decline in lung function varies by AATD genotype and is accelerated by risk factors, such as smoking. To improve the understanding and treatment of AATD, emerging knowledge and unresolved questions need to be discussed. Here we focus on developments in the areas of disease pathogenesis, biomarkers, and clinical endpoints for trials in AATD, as well as barriers to treatment. The clinical impact of AATD on lung function is highly variable and highlights the complexity of AATD pathogenesis, in which multiple underlying processes are involved. Reduced levels of functional AAT disrupt the protease-antiprotease homeostasis, leading to a loss of neutrophil elastase inhibition and the breakdown of elastin within the lung interstitium. Inflammatory processes also play a critical role in the development of AATD-associated lung disease, which is not yet fully understood. Biomarkers associated with the disease and its complications may have an important role in helping to address AATD underdiagnosis and evaluating response to treatment. To improve access to treatment, the problem of underdiagnosis needs to be addressed and the provision of therapeutic options needs to become uniform. Patients should also be empowered to play a key role in the self-management of the disease. Advancing our understanding of the disease will ultimately improve the life expectancy and quality of life for patients affected by AATD.