Therapeutic Advances in Respiratory Disease最新文献

Background: Social determinants of health (SDOH) and health-related social needs (HRSN) drive disparities in lung function, nutrition, and survival in People with Cystic Fibrosis (PwCF). Addressing HRSN can improve access to care, yet standardized screening and intervention methods remain underutilized.

Objectives: The aim of this project was to develop, test, and refine a remote HRSN screening and intervention model across multiple cystic fibrosis (CF) centers.

Design: A multicenter, prospective Quality Improvement (QI) initiativeMethods:Four CF centers, serving both pediatric and adult populations, piloted an electronic HRSN screening tool and a remote social need intervention strategy. Developed collaboratively with CF clinicians and patient and family partners (PFPs), the tool assesses nine HRSN domains. Multidisciplinary teams, including PwCF, held regular meetings to tailor implementation to each site's existing clinical workflow and staff structure. Over 1 year, each site conducted iterative Plan-Do-Study-Act (PDSA) cycles every 2 weeks to refine the screening process, sharing adaptations across centers.

Results: All four CF centers successfully implemented the remote HRSN screening and intervention workflows, completing 26 iterative PDSA cycles to refine site-specific processes. Study site meetings were held with multidisciplinary attendance at 100% of meetings. The screening tool was integrated into pre-visit planning and telehealth workflows, allowing for social worker follow-up of identified needs. Multidisciplinary collaboration from all sites resulted in the generation of a comprehensive library of local and regional resources to support unmet needs identified during screening. Narrative patient testimonial highlighted the screening tool's effectiveness in facilitating discussions about social needs and connecting individuals to available resources from the perspective of PwCF.

Conclusion: Our study has shown that HRSN screening and intervention are feasible, adaptable and acceptable to PwCF. Next steps include gathering comprehensive data on screening and intervention rates, domains of unmet social needs across regions, and sustainability interventions. Expanding HRSN screening and intervention to other CF Centers can provide data to support public policy and advocacy initiatives for reducing health disparities driven by SDOH.

In the management of difficult-to-treat and severe asthma, the incorporation of a Long-Acting Muscarinic Antagonist (LAMA) into a regimen of Inhaled Corticosteroids plus Long-Acting β₂ agonists (ICS/LABA) represents a viable add-on therapeutic strategy. Historically, this approach required the use of separate inhalers; however, the recent advent of "single-inhaler triple therapy" (SITT) provided a valuable alternative. One such formulation is the extrafine combination of beclomethasone dipropionate (BDP), fluticasone furoate (FF), and glycopyrronium bromide (GB), which is delivered via a single pressurized metered-dose inhaler (pMDI). Clinical trials, including the TRIMARAN and TRIGGER studies, alongside subsequent post-hoc analyses, have elucidated the benefits of this SITT at both 87/5/9 μg and 172/5/9 μg dosing regimens administered daily. Findings indicated a significant improvement in respiratory function and a reduction in the frequency of exacerbations among patients with uncontrolled asthma. The BDP/FF/GB SITT confirmed efficacy and safety across various ethnic groups (including Caucasian, Japanese, and Chinese populations) and across different age cohorts (adults and adolescents), although it still remains unapproved for individuals under 18 years of age. The use of a single pMDI facilitates the deposition of extra- fine particles from all three active ingredients in the small airways enhancing therapeutic effectiveness. Moreover, the consolidation of medications into one device may improve patients' adherence by mitigating the risks associated with device mismanagement and ensuring optimal drug delivery. The cost-effectiveness analysis of the BDP/FF/GB SITT suggests favorable outcomes compared to traditional ICS/LABA and ICS/LABA plus tiotropium combinations. Additional data will be forthcoming from the ongoing real-life TRIMAXIMIZE observational study.

Background: Cystic fibrosis (CF) is characterized by chronic neutrophilic inflammation in the airways. Elexacaftor/tezacaftor/ivacaftor (ETI) therapy has demonstrably improved clinical outcomes and quality of life in people with CF (pwCF), but its effects on systemic inflammatory parameters remain unclear.

Objective: To evaluate the impact of ETI on systemic inflammation in children and adolescents with CF.

Design: Retrospective, dual-center observational, propensity score-matching study of pediatric pwCF on ETI.

Methods: PwCF aged ⩽ 18 years treated with ETI at two Italian reference centers were included in this study. Data on immunoglobulins (Ig) (A, G, and M), γ-globulin, leukocyte levels, percent predicted forced expiratory volume in the first second (ppFEV1), sweat chloride (SC) concentration, and sputum cultures were collected at baseline, 12, and 24 months of treatment. Laboratory data of a control group (pwCF, not in ETI therapy, same demographic characteristics as the study group) were also collected.

Results: Sixty-six patients (30 males, median age: 12 years, F508del homozygous: 23) were included. Mean IgG levels (SD) significantly decreased (p = 0.001) from 1168.20 mg/dl (344.41) at baseline to 1093.05 mg/dl (258.73; 12 months) and 1092.87 mg/dl (232.42; 24 months). Similar reductions were observed for IgA and γ-globulin; IgM reduction was not statistically significant. Leukocyte levels also decreased significantly from 8.04 × 10³/µl (3.23 × 10³) at baseline to 6.61 × 10³/µl (1.74 × 10³) (12 months) and 6.45 × 10³/µl (1.70 × 10³; 24 months). As for the control group, no significant changes in the levels of Ig, leukocytes, and γ-globulin were detected throughout the study period (p > 0.05).The mean (SD) ppFEV1 and the overall mean (SD) SC concentration significantly decreased during the follow-up. Regarding cultures, 18 (27%) of the 27 patients positive (41%) for Staphylococcus aureus at baseline became negative during treatment. Three patients (4%) with persistently positive cultures for Pseudomonas aeruginosa during the first 12 months, became negative after 24 months. One patient (1.5%), with a baseline positive culture for Pseudomonas Aeruginosa, showed negative cultures after 12 months.

Conclusion: ETI treatment improved respiratory outcomes and significantly reduced values of IgG, IgA, γ-globulin, and leukocytes, suggesting an effect on the systemic inflammatory response. Further research is warranted to elucidate the role of inflammatory parameters in monitoring response to therapy.

Background: Pneumonia is one of the most common complications after lung resection. However, there are currently no reports of postoperative pneumonia in patients with bronchiectasis.

Objectives: Our study aims to construct a new nomogram to predict the risk of postoperative pneumonia in patients with localized bronchiectasis.

Design: The clinical data of patients with localized bronchiectasis from April 2012 to August 2022 were retrospectively analyzed.

Methods: Independent risk factors were identified through simple linear regression and multiple linear regression analysis, and a new nomogram was constructed based on independent risk factors. The validity of the nomogram was evaluated using the consistency index (C-index), receiver operating characteristic curve, calibration chart, and decision curve analysis chart.

Results: The new nomogram prediction model included five independent risk factors: tuberculosis history, smoking history, platelet-lymphocyte ratio (PLR), diffusing capacity of the lung for carbon monoxide, and controlled nutritional status score. The area under the curve of the prediction model is 0.870 (95% CI: 0.750-0.892), showing good discrimination ability, and the probability threshold was set at 0.2013. In addition, the calibration curve shows that the nomogram has good calibration. In the decision curve, the nomogram model showed good clinical net benefit.

Conclusion: This study is the first to construct a nomogram prediction model for postoperative pneumonia of localized bronchiectasis, which can more accurately and directly assess the risk probability of postoperative pneumonia, and provide certain help for clinicians in prevention and treatment decisions.

In this review, we discuss the risks and adverse effects reported for the current Food and Drug Association (FDA)-approved biologics used in the management of asthma, including omalizumab, benralizumab, dupilumab, mepolizumab, reslizumab, and tezepelumab. Our review focuses on the risk of hypersensitivity reactions, infection, and malignancy. Where relevant, we have included information regarding the risk of cardiovascular disease and eosinophilia, and we have included specific information regarding vaccine use among patients receiving the above biologics. We also review currently available data regarding the use of biologics in the context of pregnancy. Our goal is to provide a comprehensive resource for providers utilizing these agents, so that they may adequately counsel patients about the risks of therapy and identify adverse events if they occur.

Background: The relationship between albumin-corrected anion gap (ACAG) and in-hospital mortality in critically ill patients with COPD remains unclear.

Objective: This study investigated the association between ACAG levels and the risk of in-hospital mortality in critically ill patients with COPD.

Design: A retrospective cohort study.

Methods: This study uses data from the Medical Information Mart for Intensive Care (MIMIC-IV) database. The receiver operating characteristic (ROC) curve was used to determine the optimal threshold for ACAG, and participants were divided into two categories based on this threshold. The primary outcome was in-hospital mortality. We employed univariable and multivariable logistic regression analyses and Kaplan-Meier (KM) survival curves to assess the relationship between ACAG and the risk of in-hospital mortality. Moreover, subgroup analyses were conducted.

Results: A total of 2121 patients (54.7% male) were enrolled in the study. The in-hospital mortality rate was 18.9%. In patients with elevated ACAG levels, the in-hospital mortality rate was significantly higher than in those with lower ACAG levels (27.7% vs 11.3%, p < 0.001). Multivariate logistic regression analysis indicated that even after mitigating for potential confounders, patients in the high ACAG group had significantly greater odds of in-hospital mortality across all models (Model I: OR = 3.000, 95% CI: 2.383-3.777, p < 0.001; Model II: OR = 3.021, 95% CI: 2.397-3.808, p < 0.001; Model III: OR = 1.916, 95% CI: 1.458-2.519, p < 0.001). Patients with elevated ACAG levels have more than twice the risk of in-hospital mortality compared to those with lower levels (hazard ratio (HR): 2.1277, 95% CI: 1.7490-2.5884).

Conclusion: This study demonstrates that elevated ACAG levels are strongly associated with an increased risk of in-hospital mortality in critically ill COPD patients, suggesting that ACAG could serve as a potential predictor of adverse outcomes in this patient population.

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.