Canadian respiratory journal最新文献

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.

Background: The COVID-19 pandemic has led to a variety of long-term complications, with COVID-19-induced idiopathic pulmonary fibrosis (IPF) becoming a major concern. However, the underlying mechanisms, effective therapeutic strategies, and long-term prognosis of COVID-19-related pulmonary fibrosis remain unclear.

Methods: This study utilized Mendelian randomization (MR) analysis and single-cell RNA sequencing (scRNA-seq) to systematically investigate the molecular mechanisms underlying COVID-19-induced pulmonary fibrosis. MR analysis was conducted to assess causal relationships, while scRNA-seq provided detailed insights into the cellular and molecular processes involved in fibrosis.

Results: MR analysis revealed a significant association between COVID-19 infection and the development of IPF (OR = 1.15, 95% CI = 1.05-1.25, p = 0.001), whereas the reverse causality-IPF increasing the risk of COVID-19 infection-was not significant. Mediation analysis identified lactate metabolism as a crucial intermediary pathway in COVID-19-induced IPF (OR = 1.30, 95% CI = 1.09-1.55, p = 0.003). scRNA-seq confirmed the central role of lactate metabolism in pulmonary fibrosis, particularly in lung epithelial cells. The key lactate transport gene, SLC16A4, was found to play a significant role in the progression of fibrosis. Additionally, cellular interaction analysis revealed that lung epithelial cells interacted with fibroblasts via the PDGFC-PDGFRA signaling axis, promoting fibrosis.

Conclusion: This study uncovers a critical mechanism by which COVID-19 promotes pulmonary fibrosis through the regulation of lactate metabolism in lung epithelial cells, with SLC16A4 playing a pivotal role. These findings highlight the potential of targeting this metabolic pathway as a therapeutic approach for pulmonary fibrosis, offering new directions for future antifibrotic treatment strategies.

Background: Although post-COVID-19 interstitial lung abnormalities (ILAs) are common, the use of antifibrotic agents to prevent their onset and progression is controversial. We aimed to investigate the effectiveness and safety of pirfenidone to mitigate the onset and progression of ILAs in patients with severe COVID-19.

Methods: We systematically searched literature published before July 21, 2025, from PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, China Biology Medicine, Weipu, and Wanfang databases, without language limitation. Randomized controlled trials and cohort studies that evaluated the effect of pirfenidone on COVID-19-induced ILAs were included. Risk of bias was determined using the Revised Cochrane Randomized Trial Risk Bias Tool Version 2 and the Newcastle-Ottawa Scale. The efficacy and safety of pirfenidone for ILAs in COVID-19 were analyzed by Review Manager 5.4 software.

Results: Eight studies were included, comprising 335 patients in pirfenidone treatment groups and 302 controls. Risk of bias ranged from low to moderate. Pirfenidone significantly decreased chest high-resolution CT (HRCT) scores during early- and late-stage COVID-19 and significantly improved forced expiratory volume in 1 s, especially in late-stage COVID-19. Pirfenidone treatment was associated with statistically nonsignificant trends toward improved forced vital capacity and decreased all-cause mortality. Furthermore, HRCT scores, pulmonary function, and inflammatory cytokine levels following pirfenidone treatment were superior to those obtained after glucocorticoid therapy. The incidence of gastrointestinal adverse events was higher in the pirfenidone than the control group, but no serious adverse events or fatalities occurred.

Conclusion: Pirfenidone therapy may mitigate ILAs and preserve pulmonary function among survivors of COVID-19 pneumonia. Furthermore, pirfenidone exhibited acceptable safety and tolerability profiles.

Objective: Pulmonary fibrosis may develop in patients with severe clinical conditions, especially those with high inflammatory indicators. We aimed to investigate the 15-month follow-up clinical outcomes in patients with moderate-to-severe COVID-19 pneumonia treated with colchicine and to evaluate its potential in preventing post-COVID pulmonary fibrosis.

Method: This study, beginning with a retrospective analysis of 1489 selected patients, and a follow-up assessment of 155 patients conducted 15 months after hospital discharge. This study included 90 patients presenting with COVID-19 pneumonia with severity ranging from moderate to severe who were treated with colchicine alongside standard care, and 65 patients who did not receive colchicine were included in the control group to serve as a comparator. Patients who received colchicine treatment were included in Group 1, and those that did not in Group 2.

Results: From admission to the 15-month follow-up, patients receiving colchicine exhibited a significant regression in chest CT abnormalities when compared with the control group (p < 0.05). Additionally, 65.6% (n = 59) of the colchicine group experienced symptomatic improvement, significantly higher than 35.4% (n = 23) in the control group (p < 0.05). Ninety patients who received colchicine treatment had Stage 3, 4, or 5, and only 28 had Stage 3, 4, or 5 pulmonary fıbrosis at the end of 15 months. After 15 months of follow-up, all 20 patients initially classified as Stage 5 who received colchicine remained at Stage 5 pulmonary fibrosis, whereas in the control group, 2 patients (3.1%) were fibrosis-free, and the others presented with Stage 1 (n = 23; 35.4%), Stage 3 (n = 23; 35.4%), Stage 4 (n = 9; 13.8%), or Stage 5 (n = 8; 12.3%) pulmonary fibrosis.

Conclusion: This study demonstrates that colchicine therapy might reduce pulmonary fibrosis progression in individuals affected by COVID-19 pneumonia. Clinicians should consider colchicine treatment to prevent pulmonary fibrosis.

Radiation pneumonitis can result in respiratory dysfunction and progress to radiation fibrosis, and in severe cases, respiratory failure may occur. Hence, we investigated the effects of Oroxylin A from Scutellaria baicalensis in radiation pneumonia (RP) and the underlying mechanism. Oroxylin A improved pulmonary fibrosis, reduced oxidative stress, and promoted cell growth in model of RP. Oroxylin A suppressed ferroptosis and induced Nrf2 protein expressions in liver cells of model of RP. Moreover, Nrf2 inhibitor reduced the effects of Oroxylin A on pulmonary fibrosis in model of RP by oxidative stress. Collectively, these data suggest that Oroxylin A from Scutellaria baicalensis improved pulmonary fibrosis of RP through ferroptosis by Nrf2 axle.