Canadian respiratory journal最新文献

Objective: To evaluate the effectiveness of respiratory muscle training (RMT) on respiratory symptom severity and symptom duration in adults with chronic obstructive pulmonary disease (COPD) and to appraise the certainty of the evidence.

Methods: We searched seven databases and included parallel-group randomized controlled trials (RCTs) comparing RMT plus guideline-based care versus control. Meta-analyses were conducted in RevMan using fixed- or random-effects models as appropriate. Risk of bias was assessed using RoB 2. Certainty of evidence was assessed using the GRADE approach. Because multiple outcomes were analysed, we controlled the false discovery rate using the Benjamini-Hochberg (BH) procedure across prespecified meta-analysed outcomes and report both unadjusted and BH-adjusted p values.

Results: Seven RCTs (n = 1171) were included. No trial reported symptom duration in a way that matched our prespecified definition. Compared with control, RMT reduced dyspnoea (mMRC; unadjusted p = 0.003; BH-adjusted p = 0.007; moderate certainty) and improved health-related quality of life (SGRQ; unadjusted p < 0.00001; BH-adjusted p = 3.5e - 05; moderate certainty). Lung function effects were mixed: FVC improved (MD = 0.37 L, 95% CI 0.33 to 0.40; unadjusted p < 0.00001; BH-adjusted p = 3.5e - 05; low certainty) and FEV1/FVC improved (MD = 1.84%, 95% CI 0.29 to 3.39; unadjusted p = 0.02; BH-adjusted p = 0.035; low certainty), while FEV1 did not differ significantly (MD = 0.18 L, 95% CI -0.04 to 0.40; unadjusted p = 0.11; BH-adjusted p = 0.11; low certainty). Evidence for overall symptom burden and exercise capacity was uncertain: CAT (unadjusted p = 0.06; BH-adjusted p = 0.07; very low certainty) and 6MWD (unadjusted p = 0.05; BH-adjusted p = 0.07; very low certainty).

Conclusion: In adults with COPD, adding RMT to guideline-based care probably reduces dyspnoea and improves health-related quality of life (moderate certainty). Evidence for benefits on overall symptom burden, lung function, and exercise capacity is low to very low, and the effect on symptom duration remains unknown due to the lack of reporting.

Background: Respiratory syncytial virus (RSV) is one of the important pathogens found in patients with acute respiratory infection (ARI), but there are few studies on RSV infection among elderly people in China.

Methods: This study collected data on the RSV-infected population among the hospitalized patients with ARI admitted to the Department of Respiratory Medicine of our hospital from November 2023 to February 2024 and analyzed the clinical data of the elderly (≥ 60 years old) grouped by age. Patients admitted to other departments (e.g., general internal medicine, geriatrics) were not included, potentially introducing selection bias toward more severe respiratory presentations.

Results: The total infection rate was 12.16%, and the main symptoms were cough (97.78%), sputum (95.56%), and dyspnea (68.89%); 100% of the patients had comorbidity, and 97.78% of the patients had two or more comorbidities. Laboratory findings were mainly elevated CRP (84.4%), lymphopenia (64.44%), elevated hs-cTni (51.11%), elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) (37.78%), decreased PaO₂ (88.89%), and elevated PaCO₂ (44.44%). The rate of mixed bacterial and viral infection was 37.78%; 95.56% of the patients had lung imaging changes; 100% of the patients received respiratory therapy support, and 91.11% of the patients used antibiotics. The discharge rate was 93.33%, and the mortality rate was 6.67%.

Conclusion: There was no obvious abnormal seasonality in the infection rate; the infection rate, the proportion of lymphopenia, and the proportion of respiratory failure were higher than in most other studies. The statistical data are only statistically significant in terms of the decrease in PaO₂/FiO₂ (P/F ratio), the elevation in the NT-proBNP, and some imaging performances. It may be that the number of samples is not large enough to cause the difference to be insignificant. Furthermore, this study exclusively included patients admitted to the Respiratory Medicine Department, which may reflect department-specific referral bias and potentially underestimate the true burden of RSV in the broader elderly population. Patients admitted to other departments (e.g., general internal medicine, geriatrics) were not included, potentially introducing selection bias toward more severe respiratory presentations.

[This corrects the article DOI: 10.1155/2024/4505905.].

Objective: This study aims to investigate the regulatory role and mechanism of hypoxia-inducible transcription Factor 1 (HIF-1α) in alveolar epithelial cell function under hypoxic conditions using A549 cells as a surrogate model.

Methods: Human A549 alveolar epithelial cells were used as the experimental model. HIF-1α expression was modulated by siRNA knockdown or plasmid overexpression. qRT-PCR quantified HIF-1α, SP-C, and vascular endothelial growth factor (VEGF) mRNA levels, and Western blotting evaluated the corresponding proteins and apoptosis-related markers (cleaved Caspase 3, Bcl-2, Bax). Cell counting kit 8 (CCK-8) assessed A549 cell viability, while transwell assays measured migration (uncoated membrane) and invasion (Matrigel-coated membrane). Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining detected the apoptosis. Enzyme-linked immunosorbent assay (ELISA) quantified VEGF secretion, and tube-formation assays evaluated the proangiogenic effects of A549-conditioned media on human umbilical vein endothelial cells (HUVECs).

Results: Hypoxia markedly increased HIF-1α and VEGF expression while reducing SP-C expression in A549 cells. HIF-1α knockdown decreased VEGF expression and angiogenesis, restored cell viability, and suppressed migration, invasion, and apoptosis. In contrast, HIF-1α overexpression further enhanced angiogenesis, promoted migration and invasion, and increased apoptosis.

Conclusions: HIF-1α is a key regulator of hypoxia-induced functional changes in alveolar epithelial cells, influencing cell viability, migration, invasion, apoptosis, VEGF production, and proangiogenic activity. These findings highlight their potential as a therapeutic target in hypoxia-related lung injury.

Interstitial lung disease (ILD) refers to a collection of respiratory conditions characterized by inflammation of the lung parenchyma, alveolar irritation, and fibrosis of the interstitial tissue. Traditional research methods are often unable to completely reveal the complex mechanism of ILD occurrence and development. However, advancements in single-cell sequencing technology in recent years have opened up a novel avenue for investigating ILD. This review summarizes recent single-cell-sequencing advances in the major interstitial lung diseases-idiopathic pulmonary fibrosis (IPF), pneumoconiosis, and connective tissue disease-associated ILD (CTD-ILD)-and outlines future research priorities.

Background: Observational studies of raised dietary antioxidants suggest a beneficial effect on respiratory health; however, findings from interventional trials have been inconsistent or null. Few studies have specifically targeted individuals exposed to high levels of environmental oxidants, where the antioxidant effects may be more pronounced.

Objectives: To investigate whether genetically elevated serum levels of dietary antioxidants are causally associated with improved lung function and whether these effects differ with exposure to oxidative stress.

Methods: We conducted a two-sample Mendelian randomization (MR) study using summary-level data for genetic associations with serum levels of ascorbic acid (vitamin C), retinol (vitamin A), and β-carotene from published genome-wide association studies. Outcome data on forced expiratory volume in one second (FEV₁) and forced vital capacity (FVC) were derived from individual-level data from over 285,000 UK Biobank participants. We used linear regression to estimate SNP-outcome associations and applied the Wald ratio to derive causal estimates using published SNP-exposure effect sizes.

Results: We found no consistent evidence that genetically elevated serum antioxidant levels are associated with improved lung function. There was no evidence of effect modification by exposures linked to oxidative stress, including cigarette smoke, air pollution, or dietary factors.

Conclusions: Our findings align with those of previous interventional studies, showing no consistent causal relationship between dietary antioxidants and respiratory health. Moreover, we found no strong support for targeted interventions to increase serum antioxidant levels in people exposed to high levels of environmental oxidants (Wellcome Grant ID: 209207/Z/17/Z and 225195/Z/22/Z).

Background: It was important to find better therapeutic drugs for idiopathic pulmonary fibrosis (IPF), and in our previous study, Yifei decoction (YFT) alleviated IPF. A deeper understanding of its mechanisms of action could aid in the development of novel treatment strategies.

Methods: We established an IPF mouse model by administering bleomycin (BLM), followed by treatment with YFT. Histopathological analysis of lung tissue was conducted to evaluate the effects of YFT, along with transcriptomic profiling to identify key regulatory molecules involved in its therapeutic action. Immunofluorescence staining was performed for TRKA and surfactant protein C (SP-C) in IPF lung slices. A549 cells were induced with TGF-β1 to assess the effect of YFT on alveolar epithelial cells, and cells overexpressing TRKA were constructed. Western blotting analysis was performed to detect EMT- and PI3K/AKT pathway-related protein levels, and an EdU proliferation assay was conducted to measure the proliferation of A549 cells.

Results: YFT intervention reduced pathological lung injury in BLM-treated mice. GO enrichment analysis revealed enrichment of DEGs in the extracellular matrix and proteinaceous extracellular matrix. Analysis of the enriched KEGG pathways revealed enrichment of the PI3K-AKT signaling pathway. YFT also decreased the number of SP-C⁺/TRKA⁺ cells in lung tissues, inhibited the expression of TRKA, and reduced the NGF concentration in TGF-β1-stimulated A549 cells. YFT reduced TRKA, PI3K, and AKT phosphorylation levels, EMT, and cell proliferation. However, these effects were eliminated when TRKA was overexpressed.

Conclusion: YFT might regulate the NGF/TRKA/PI3K/AKT pathway to alleviate pulmonary fibrosis by reducing EMT and cell proliferation. This study laid the groundwork for future research on the possible enhancement of the therapeutic effect of YFT when YFT is combined with other medications.

Pulmonary sarcoidosis and asthma can present identical symptoms, making clinical evaluation difficult if the two diseases overlap. Diagnostic challenges often lead to either overdiagnosis of asthma in patients with confirmed sarcoidosis or withholding appropriate asthma treatment. The true prevalence of patients with bronchial hyperresponsiveness, the hallmark of asthma, among sarcoidosis patients remains unknown, although it is suspected to be significantly higher compared to the general population. Therefore, a positive bronchial challenge test, often considered crucial for confirming asthma in symptomatic individuals with normal spirometry, should not be regarded as decisive in patients with pulmonary sarcoidosis. However, the coexistence of both diseases is possible and should always be considered. Caution is advised as patients prematurely and incorrectly diagnosed with asthma are exposed to unnecessary medical costs and lifelong treatment. Nevertheless, inhaled glucocorticosteroids and bronchodilators may be temporarily used in sarcoidosis patients because of their beneficial effect on symptom control, regardless of a concurrent asthma diagnosis. Despite the existing evidence that patients with sarcoidosis can develop asthma and atopy, the complex cellular pathways and genetic predispositions involved in the pathogenesis of both diseases remain largely unknown. To address these issues in clinical practice, the article aims to discuss the mechanisms involved in the etiopathogenesis of asthma and sarcoidosis and to analyze the available diagnostic and therapeutic methods relevant to both conditions.

Background: Acute respiratory distress syndrome (ARDS) is associated with high mortality rates in critically ill patients. Renopulmonary interplay remains crucial in contributing to the outcomes in patients with ARDS. While the role of acute kidney injury has been widely explored in these patients, there remains an unmet need in the literature about the impact of chronic kidney disease (CKD) in these patients.

Research question: Is there a quantifiable association between CKD and in-hospital outcomes in patients with ARDS?

Study design and methods: We utilized a retrospective study design to compare descriptive statistics and outcomes in patients with ARDS with or without CKD. Pearson's chi-square test was used to compare categorical variables, while the Wilcoxon rank sum test was used for continuous variables. We also performed multivariate logistic regression analyses for each outcome and adjusted for demographics and comorbidities. Lastly, we conducted a sensitivity analysis using propensity score-matched outcomes between these groups.

Results: Among 479,450 patients with ARDS, 17.6% also had CKD, while 82.4% did not. Patients with ARDS and CKD were older (median age: 71 years vs. 60 years, p < 0.001) and comprised a greater proportion of males (59.4% vs. 55.9%, p < 0.001). CKD was associated with increased odds of in-hospital mortality (adjusted odds ratio [aOR] 1.29, p < 0.001), acute heart failure (aOR 1.26, p < 0.001), ventricular arrhythmias (aOR 1.16, p < 0.001), cardiogenic shock (aOR 1.10, p = 0.044), major adverse cardiovascular events (aOR 1.29, p < 0.001), and length of stay ≥ 7 days (aOR 1.05, p = 0.033).

Interpretation: Our study provides insights into the magnitude of impact renal diseases may have on the outcomes of patients with ARDS. Further prospective studies are warranted to establish more substantial epidemiological evidence of this relationship to tailor the management of such patients.

Background: Traumatic tracheal stenosis is characterized by airway granular proliferation after trauma, which may lead to asphyxy. Abnormal activation of the ADAM17/TGF-β1 pathway may trigger excessive repair and airway fibrosis. TAPI-1 is an effective inhibitor of ADAM17, which blocks the "extracellular cleavage release" of inflammatory factors (such as TNF-α) and proliferation signals (such as EGFR ligand TGF-α) by specifically inhibiting ADAM17 (tumor necrosis factor converting enzyme). Silicone stents are considered an important method for the treatment of airway stenosis. This study aimed to investigate the role and potential mechanism of TAPI-1 combined with silicone stents in alleviating severe tracheal stenosis after trauma.

Methods: Tracheal epithelial cells were stimulated with GM-CSF and then treated after 24 h by lentivirus-mediated ADAM17 RNAi and mitomycin C. A model of severe traumatic tracheal stenosis was established in Beagle dogs. Mitomycin C, TAPI-1, and TAPI-1 combined with a silicone stent were applied to treat tracheal stenosis in the animals. The changes in the trachea were directly observed using bronchoscopy. The viability and proliferation of epithelial cells were measured using CCK-8 assay. The mRNA and protein expressions of ADAM17, TGF-β1, and fibronectin 1 were detected by qRT-PCR and western blotting. The pathological changes in traumatic tracheal stenosis were analyzed by hematoxylin and eosin staining.

Results: Lentivirus-mediated ADAM17 RNAi significantly inhibited the proliferation of tracheal epithelial cells induced by GM-CSF and suppressed the ADAM17/TGF-β1 signaling pathway in vitro. Moreover, TAPI-1 combined with silicone stents significantly alleviated traumatic tracheal stenosis in Beagle dogs, and TAPI-1 markedly inhibited the ADAM17/TGF-β1 signaling pathway in vivo. In conclusion, it was showed that TAPI-1 combined with silicone stents can significantly alleviate severe traumatic tracheal stenosis in Beagle dogs by inhibiting the ADAM17/TGF-β1 signaling pathway and expanding the narrowed trachea.

Conclusions: TAPI-1 combined with silicone stents can be considered as a novel therapeutic approach for treating severe tracheal stenosis after trauma.