Therapeutic Advances in Respiratory Disease最新文献

Bronchiectasis is a chronic, complex, and heterogeneous respiratory disease characterized by irreversible bronchial dilation, persistent airway inflammation, and recurrent infections. Traditionally viewed from a lung-centered perspective, its pathophysiology has been explained by the "vicious cycle" hypothesis, later refined into the more dynamic concept of the "vicious vortex." However, emerging evidence highlights the pivotal role of comorbidities in influencing disease progression, symptom burden, and prognosis. This review explores the evolving understanding of bronchiectasis by integrating comorbidities into current pathophysiological frameworks. We illustrate how coexisting conditions interact with components of the vicious vortex, amplifying airway inflammation, impairing host defenses, and disrupting clearance mechanisms. We summarize evidence on the prevalence, clinical impact, and prognostic significance of key comorbidities and discuss their implications for patient management. Finally, we emphasize the importance of an integrated, multidisciplinary approach and the emerging role of the treatable traits framework, which focuses on identifying clinically relevant, biologically measurable, and modifiable traits-regardless of whether they are etiological or nonetiological. In this sense, we propose a conceptual "Copernican Revolution" in bronchiectasis care: recognizing comorbidities not as secondary features, but as potential drivers of disease trajectory. By adopting this pragmatic strategy, clinicians can optimize quality of life, achieve patient-centered care, and improve outcomes in this condition.

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.

Background: The escalating morbidity and mortality of chronic obstructive pulmonary disease (COPD) necessitates improved diagnostic approaches for comorbid infections. COPD patients exhibit heightened susceptibility to opportunistic pathogens like Nocardia species due to compromised airway defenses and frequent glucocorticoid/immuno-suppressant use. Despite its clinical significance, Nocardia infection remains diagnostically challenging due to nonspecific presentations and imaging features.

Objectives: To develop and validate a diagnostic model integrating clinical characteristics and risk factors for COPD complicated by Nocardia infection.

Design: A retrospective analysis was conducted on clinical data from 586 patients diagnosed with COPD and Nocardia infection, including clinical symptoms, laboratory tests, imaging findings, and treatment outcomes. Patients were screened according to inclusion and exclusion criteria and divided into two groups: COPD with Nocardia infection group (infection group) and COPD-only group (control group).

Methods: This retrospective study analyzed 586 COPD patients (2019-2024), stratified into Nocardia-infected (n = 289) and noninfected (n = 297) cohorts. Demographic, laboratory, pulmonary function, and imaging data were collected. Multivariate logistic regression identified independent predictors, which informed a nomogram model. Model performance was assessed via concordance index (C-index), calibration curves, and ROC analysis.

Results: Independent risk factors included hemoptysis (OR = 1.99, 95% CI: 0.76-5.26), lymphocyte count (OR = 6.81, 95% CI: 4.06-11.42), hemoglobin (OR = 1.01, 95% CI: 0.99-1.03), and pulmonary function parameters (FEV₁/FVC ratio OR = 12.47, 95% CI: 1.25-124.16). The model demonstrated excellent discrimination (C-index: 0.895 infected, 0.829 noninfected) and calibration (mean absolute error: 0.127-0.170). ROC analysis revealed AUCs of 0.896 (95% CI: 0.90-0.97) and 0.830 (95% CI: 0.77-0.89) for infected and noninfected groups, respectively.

Conclusion: This validated nomogram provides a clinically actionable tool for early Nocardia detection in COPD patients, addressing a critical diagnostic gap. External validation is warranted to confirm generalizability.

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.

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.

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.