Therapeutic Advances in Respiratory Disease最新文献

Cases of pulmonary squamous cell carcinoma (SCC) metastases to the nasal region are highly uncommon and frequently manifest with poor prognosis. However, the use of anti-programmed cell death protein 1 (PD-1) inhibitors in pulmonary SCC with nasal metastasis has not been documented. In this study, a case of pulmonary SCC metastasizing to the nose was discussed. Nasal nodules appeared in the patient; initially, these were considered benign lesions. It was determined following a pathological biopsy that the patient had nasal metastases of lung SCC. The lung tumor had decreased after two cycles of standard chemotherapy (paclitaxel + carboplatin); however, the nasal tumor continued to grow. Consider that nasal metastases are not responsive to chemotherapy. A multidisciplinary consultation believed that immunotherapy had potential benefits for metastatic tumors and decided to use a chemotherapy + immunotherapy regimen. The nasal metastatic tumor gradually returned to normal as a result of the combination of standard chemotherapy and immunotherapy (Tislelizumab) from the third cycle onward. After six cycles of combined treatment, the patient began maintenance monotherapy. During treatment, the patient's condition remained stable without progression or distant metastasis. This case highlights the potential of combining anti-PD-1 therapy with standard chemotherapy as an effective salvage strategy for chemotherapy-refractory nasal metastases of pulmonary squamous cell carcinoma, thereby contributing to improved patient survival.

Background: Limited data exist on idiopathic pulmonary fibrosis (IPF) incidence and risk factors in elderly populations, making early intervention and preventive strategies challenging. Further research is needed to address this gap and improve outcomes.

Objectives: This study used the Korean National Health Insurance Service (NHIS) database to investigate factors associated with the development of IPF in elderly people.

Design: A retrospective cohort study was conducted to evaluate risk factors for IPF in an elderly population.

Methods: This study evaluated 1,250,901 participants aged 75 years and older with health screening examination records in the NHIS database from 2012 to 2015. Cox proportional hazards regression models were used to assess the associations between IPF risk and demographics, lifestyle factors, and comorbidities, and subgroup analyses were used to explore multifactor interactions.

Results: During a median follow-up of 7.4 years, 3955 participants developed IPF, for an incidence rate of 0.38 per 1000 person-years. Elderly participants (aged 75-85 years) exhibited higher IPF incidence than extremely elderly participants (⩾85 years) (0.40 vs 0.17 per 1,000 person-years, p < 0.01), though the difference was not significant in the multivariable analysis. The factors independently associated with increased IPF risk were male sex (adjusted hazard ratio [aHR] = 2.56, 95% confidence interval [CI] = 2.35-2.78), high body mass index (BMI) (aHR=1.45, 95% CI = 1.34-1.56 ), smoking (aHR = 1.24, 95% CI = 1.13-1.37 for ever-smokers < 20 pack-years [PYs]; aHR = 1.28, 95% CI = 1.17-1.39 for ever-smokers ⩾ 20 PYs), dyslipidemia (aHR = 1.17, 95% CI = 1.08-1.26), chronic kidney disease (aHR = 1.08, 95% CI = 1.01-1.16), and chronic obstructive pulmonary disease (COPD) (aHR = 1.49, 95% CI = 1.37-1.63). Additive or synergistic effects were observed among sex, BMI, smoking, and dyslipidemia, notably among males, and interactions between COPD and smoking status modulated IPF risk.

Conclusion: Male sex, high BMI, smoking, and dyslipidemia might additively or synergistically increase the IPF risk among elderly people, highlighting the need for targeted prevention strategies in those populations.

Background: Nontuberculous mycobacterial pulmonary disease (NTM-PD) is a chronic lung infection associated with persistent respiratory symptoms and diminished health-related quality of life (HRQoL). As with other chronic conditions, increased levels of anxiety and depression can impact prognosis and HRQoL.

Objectives: To describe the prevalence of anxiety and depression and to identify HRQoL domains that are correlated with mental health in patients with NTM-PD.

Design: A cross-sectional observational study of adults with self-reported or clinically confirmed NTM-PD.

Methods: Participants with NTM-PD enrolled in two studies (n = 40 interview + surveys and n = 230 completing electronic surveys only) at four U.S. sites. Inclusion criteria were age >18 years, English-speaking, and U.S. residence. In-person enrolled participants met ATS/IDSA criteria and had symptom documentation in medical records; remotely enrolled participants self-reported NTM-PD and symptoms. Data collected included demographics, GAD-7 and PHQ-8 (anxiety and depression screening, respectively), QOL-B Respiratory Symptoms Scale (RSS), selected PROMIS short forms (Fatigue 7a, Cognitive Function 6a, Sleep Disturbance 4a), and Patient Global Impression of Severity of NTM-PD symptoms (PGIS). Interview-only participants completed the GAD-7, PHQ-8, QOL-B RSS, and were evaluated for cognitive functioning using the computerized Symbol Digit Modalities Test (oral version).

Results: The study population was predominantly female (57%/91% in the interview/survey studies, respectively) and aged >65 years (50%/77.4%). Overall, 18%/14% screened positive for anxiety and 32%/18% for depression. Participants screening positive for anxiety or depression had significantly lower QOL-B RSS, cognitive function, and sleep scores, and higher fatigue. Fatigue showed the strongest correlation with mental health outcomes, particularly with those screening positive for depression (ρ = 0.644, p < 0.05).

Conclusion: Mental health symptoms are strongly correlated with worse HRQoL outcomes in NTM-PD. These findings underscore the need for the implementation of routine mental health screening and interventions in NTM-PD care.

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: 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.