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: Previous studies have proposed exercise capacity as a mortality predictor in individuals with interstitial lung disease (ILD). However, limited information is available regarding whether maintaining exercise is associated with improved survival in individuals with ILD.

Objectives: We aimed to evaluate the association between exercise maintenance and mortality in individuals with ILD using a longitudinal, large population-based database.

Design: This retrospective cohort study used the Korean National Health Insurance claims-based database.

Methods: We analyzed a total of 3850 individuals with ILD who underwent two consecutive health screening examinations. The study exposure was the change in exercise habits between the two examinations, with individuals classified as exercisers (exercise maintainers and exercise non-maintainers) or non-exercisers. The primary outcome was mortality. We adjusted for age, sex, body mass index (BMI), smoking status, alcohol status, economic status, residential area, and comorbidities.

Results: During a median follow-up of 7.2 (interquartile range, 5.6-9.2) years, the incidence rate of death for exercisers was lower than that of non-exercisers (341.28 per 10,000 person-years (PY) vs 401.81 per 10,000 PY). Multivariable Cox regression analysis showed that the risk of mortality was substantially lower in exercisers compared to non-exercisers (adjusted hazard ratio (aHR): 0.82, 95% confidence interval (CI): 0.72-0.94). The risk of reduction for death was correlated with exercise adherence, with the lowest risk among exercise maintainers (aHR: 0.78 (0.66-0.92)) followed by exercise non-maintainers (aHR: 0.85 (0.73-0.99)), compared to non-exercisers. In subgroup analyses, BMI and economic status had a significant interaction in the association between exercise and mortality. The risk of death was lower in individuals with a lower BMI and higher economic status compared to their counterparts.

Conclusion: Among individuals with ILD, the risk of death was inversely correlated with the level of exercise adherence, cautiously suggesting the importance of exercise maintenance in individuals with ILD.

Background: Cardiovascular disease (CVD) risks are increasing in people with cystic fibrosis (pwCF). While cholesterol levels were historically low in pwCF, higher levels after initiating highly effective modulator therapy (HEMT) have been reported. Mechanisms are unclear and there is little guidance on screening.

Objectives: To evaluate serum lipid changes at multiple timepoints after ivacaftor initiation, and to assess current screening practices for CVD risk factors among CF providers.

Design: This was a post-hoc correlative analysis of prospectively collected clinical data and serum samples from the GOAL cohort study. Cross-sectional survey methodology was also employed.

Methods: We evaluated serum lipids (total cholesterol (TC), low-density lipoprotein (LDL), and high-density lipoprotein (HDL)) at baseline, 3- and 18 months after ivacaftor initiation using samples from the GOAL study biorepository. We also surveyed CF providers across the United States on their CVD risk screening practices.

Results: Fifty GOAL participants' samples were analyzed. Using the repeated measures model, TC significantly varied by visit (p = 0.004), driven by a significant increase from baseline at 3 months (mean difference 9.4 mg/dL). This difference diminished by 18 months. BMI was a significant covariate for TC. No significant differences by visit were detected in LDL or HDL. Seventy-five respondents participated in the survey (response rate 5.6%; 41 adult providers, 18 pediatric providers, and 10 providers caring for both) with 67% reporting no lipid screening policy existed in their center. In the past year, 29% of adult providers prescribed lipid-lowering therapy, 54% started anti-hypertensive medications, and 48% initiated ischemic cardiac evaluations for pwCF.

Conclusion: TC significantly increased within 3 months of initiating ivacaftor, but subsequently diminished toward baseline by 18 months. Lipid screening practices among CF providers were variable and providers are increasingly being confronted with managing CVD risk factors. Partnering with primary care providers is likely to become increasingly important in CF care models.

Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is the main cause of hospitalization and death of patients with chronic obstructive pulmonary disease. This is largely due to bacterial resistance caused by clinical antibiotic abuse and the limited efficacy of current treatment strategies in managing noninfectious AECOPD, which presents a significant challenge for clinicians. Therefore, it is urgent for clinical treatment and prevention of AECOPD to fully understand the specific mechanism of AECOPD in the immune system and master the key differences between infectious factors and noninfectious factors. This article systematically discusses AECOPD triggered by various factors, including the activation of immune system, the recruitment and activation of inflammatory cells and the role of specific inflammatory responses, and through a comprehensive review of the literature, this article expounds the existing targeted diagnosis and treatment methods and technologies at different stages in order to provide new ideas and strategies for clinical prevention and treatment of AECOPD.

Lung cancer and chronic non-malignant respiratory disease cause pervasive, multifactorial suffering for patients and informal carers alike. Palliative care aims to reduce suffering and improve quality of life for patients and their families. An established evidence base exists that has demonstrated the essential role of specialist palliative care for people with lung cancer. Emerging evidence supports similar benefits among people with chronic respiratory disease. Many lessons can be learnt from lung cancer care, particularly as the model of care delivery has transformed over recent decades due to major advances in the diagnostic pathway and the development of new treatments. This narrative review aims to summarize the evidence for specialist palliative care in lung cancer and chronic respiratory disease, by highlighting seven key lessons from lung cancer care that can inform the development of proactive, integrated models of palliative care among those with chronic respiratory disease. These seven lessons emphasize (1) managing challenging symptoms; (2) the efficacy of specialist palliative care; (3) the importance of providing specialist palliative care integrated with disease-directed care according to patients' needs not prognosis; (4) the need for new models of collaborative palliative care, (5) which are culturally appropriate and (6) able to evolve with changes in disease-directed care. Finally, we discuss (7) some of the critical research gaps that persist and reduce implementation in practice.

Background: Chronic glucocorticoid therapy is known to heighten the risk of secondary pulmonary infections. However, the impact of cumulative glucocorticoid dosage (CGD) on mortality risk in patients who develop community-acquired pneumonia (CAP) while undergoing glucocorticoid therapy remains inadequately explored.

Objectives: This study aims to clarify the relationship between CGD and mortality outcomes in immunocompromised patients with CAP.

Design: This study is a retrospective cohort analysis utilizing data from the DRYAD database.

Methods: We examined data from 561 patients diagnosed with CAP who had received either oral or intravenous glucocorticoids prior to their CAP diagnosis. To evaluate the effect of CGD on mortality risk, we employed piecewise linear regression and Cox regression analyses, adjusting for relevant confounders.

Results: Among the study population, the median CGD was 4 g of methylprednisolone (interquartile range 2.16-8.80 g). The 30-, 60-, and 90-day mortality rates were 22.28%, 25.13%, and 25.49%, respectively. Piecewise linear regression analysis revealed a nonlinear relationship between methylprednisolone dose and mortality risk, indicating a threshold effect at a methylprednisolone level of 20 g. In addition, Cox regression analysis showed a significantly higher mortality risk in patients with CGD exceeding 40 g of methylprednisolone compared to those with CGD between 20 and 40 g, after adjusting for potential confounding factors (adjusted HR 5.16, 95% CI: 1.16-22.99, p < 0.05).

Conclusion: CAP occurring in close proximity to recent high doses of steroids is associated with pathogens typically seen in immunocompromised hosts and is linked to higher mortality compared to usual CAP.

Background: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects motor neurons, resulting in muscle weakness, loss of function, and ultimately death due to respiratory failure. Due to the lethal prognosis of ALS, respiratory muscle training has been proposed as a potentially beneficial intervention.

Objectives: To systematically review the efficacy of respiratory muscle training on lung function and respiratory muscle strength in ALS patients.

Design: A systematic review and meta-analysis of randomized controlled trials.

Data sources and methods: Articles published in PubMed, PEDro, Scopus, and Web of Science databases up to July 2024. The Preferred Reporting Items for Systematic reviews and Meta-Analyses 2020 statement guideline was followed. Included studies had (1) ALS patients, (2) respiratory muscle training, (3) physical exercise, usual care or no intervention were provided as a comparison group, (4) assessments of lung function, respiratory muscle strength, quality of life, survival, fatigue, and functional capacity outcome measures, and (5) a randomized controlled trial design. Methodological quality was analyzed using the PEDro scale, and risk of bias with the Cochrane Collaboration Risk of Bias Tool. Meta-analyses were performed with Review Manager software.

Results: Five randomized controlled trials with 170 participants were included. The results showed that respiratory muscle training improved muscle strength, particularly maximum expiratory and inspiratory pressures. One study suggested inspiratory muscle training as a survival predictor in ALS patients. No significant effects were observed in forced vital capacity or quality of life. No adverse effects were reported.

Conclusion: Respiratory muscle training improves ventilatory function, particularly respiratory muscle strength, in people with ALS. While evidence is limited, it shows promise as an adjuvant therapy to enhance quality of life and survival. It has been registered in the PROSPERO (CRD42024568235).