Therapeutic Advances in Respiratory Disease最新文献

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.

We report a case of tracheobronchial amyloidosis (TBA) in a 55-year-old woman with newly diagnosed primary Sjögren's syndrome (SS), presenting with persistent cough, hemoptysis, and dry mucosal symptoms. Chest CT showed thickened airway walls and cystic lung changes, while bronchoscopy revealed nodular lesions with exposed vessels. Congo red staining confirmed amyloid deposition with κ light-chain dominance, consistent with AL amyloidosis. Despite immunosuppressive therapy, airway lesions persisted, highlighting the challenge of managing localized amyloidosis in SS. This case underscores the need for early recognition of TBA in SS patients presenting with respiratory symptoms.

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).

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: 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: Unplanned extubation (UE) in intensive care units (ICUs) is a significant patient safety concern, associated with increased morbidity and healthcare utilization; the reported rates of UE vary from 1% to 15%. There is sparse data on the effects of multiple performance improvement (PI) strategies to decrease the rate of UE, particularly in inner-city ICU populations. This study evaluates the impact of PI strategies on UE rates and associated patient outcomes in an adult ICU.

Objectives: To determine the impact of performance improvement (PI) strategies on rates of unplanned extubation (UE), reintubation, tracheostomy, mortality, and length of hospital stay in ICU patients.

Design: Retrospective cohort studyMethods:This retrospective observational study included 6,397 mechanically ventilated patients admitted to a single tertiary ICU between 2015 and 2023. Three distinct time periods were compared: Period 1 (2015-2017, pre-PI), Period 2 (2018-2020, early-PI), and Period 3 (2021-2023, sustained-PI). Demographics, sedation practices, UE characteristics, and outcomes were analyzed using logistic regression.

Results: UE incidence declined significantly from 3.79% in Period 1 to 2.17% in Period 3 (p = 0.002). Reintubation rates dropped from 45.2% to 26.7% (p = 0.011), and tracheostomy rates from 19.0% to 2.2% (p < 0.001). Multivariate analysis showed reduced odds of reintubation in Periods 2 (OR = 0.219, p = 0.001) and 3 (OR = 0.345, p = 0.021) and reduced odds of tracheostomy in Period 3 (OR = 0.011, p = 0.016). Risk factors for reintubation included the absence of prior intubation history and not undergoing spontaneous breathing trials. Older age (⩾71 years) and positive urine toxicology for opiates were strongly associated with tracheostomy.

Conclusion: Implementation of PI strategies significantly reduced rates of unplanned extubation, reintubation, and tracheostomy. These findings support continued quality improvement initiatives in ICU airway management.

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.