Canadian respiratory journal最新文献

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.

This article probed the value of systemic inflammatory response index (SIRI) in the early diagnosis and short-term prognostic assessment of severe pneumonia (SPM) in the elderly. First, 266 elderly patients with pneumonia were retrospectively included and allocated into SPM and N-SPM groups as per APACHE-II scores. Correlations of SIRI with APACHE-II scores, CRP, and PCT were analyzed. Patients were followed up for 28 days, and SPM patients were allocated into death and survival groups based on survival status. The values of SIRI for early diagnosis and short-term prognostic assessment of elderly SPM patients were evaluated. Influencing factors for short-term death in elderly SPM patients were screened. SIRI levels were high in elderly SPM patients and were positively correlated with APACHE II scores and CRP and PCT levels. SIRI had a high predictive value for the occurrence (AUC = 0.843) and 28-day survival (AUC = 0.806) of SPM. High SIRI levels elevated the risk of 28-day mortality in elderly SPM patients. APACHE II scores (HR = 1.125) and SIRI (HR = 1.977) were independent risk factors for short-term death in elderly SPM patients. Overall, SIRI has a certain value for the early diagnosis and prognostic assessment of elderly SPM patients.

Background: Gastroesophageal reflux disease (GERD) and obstructive sleep apnea (OSA) may negatively impact idiopathic pulmonary fibrosis (IPF), but data on their concurrent contributions are lacking. We aimed to test the contributions of GERD and sleep-disordered breathing (SDB) to IPF outcomes.

Methods: We performed a cross-sectional, exploratory study on subjects with IPF. Clinically established GERD diagnosis, questionnaires (Nocturnal GERD Symptom Severity and Impact Questionnaire [N-GSSIQ], the NIH Patient-Reported Outcomes Measurement Information System [PROMIS] sleep impairment and fatigue scales, and Short Form-36 [SF-36]), full pulmonary function tests (PFT), six-minute walk test (6MWT), and nocturnal polysomnography (PSG) were obtained.

Results: Among n = 24 subjects, 17 (71%) had clinically diagnosed GERD. N-GSSIQ scores indicated a nocturnal burden, which was adversely related to sleep impairment (p = 0.010) and daytime fatigue (p = 0.001), tiredness (p = 0.026) and SF-36 social functioning (p = 0.005), energy/fatigue (p = 0.015), pain (p = 0.030), and health change in the prior year (p = 0.035). From PSG, GERD correlated with worse sleep architecture (GERD diagnosis, all p < 0.05) and periodic leg movements index (PLMI) (N-GSSIQ, p = 0.02). GERD was not associated with pulmonary or exercise physiology. Overall, apnea-hypopnea index (AHI) was (median [25% quartile, 75% quartile]) 18.2 (8.1, 27.8)/h, and 19 (79%) subjects had OSA (AHI ≥ 5/h), with most (15/19 [79%]) having moderate or severe disease. SDB measures adversely related to gas exchange and distance walked (all p < 0.05).

Conclusions: A nocturnal burden of GERD was detected and related to sleep disruption, including PLMs, and to daytime complaints. SDB/OSA, of a severity known to have significant health consequences, was common; it was adversely related to pulmonary diffusion and exercise capacity. These findings call for comprehensive, early evaluation of GERD and OSA for improved IPF outcomes.

Background: Noncystic fibrosis (non-CF) bronchiectasis is a chronic respiratory disease characterized by irreversible bronchial dilation, with an increasing global prevalence and substantial clinical burden. Despite the advances in symptomatic management, the underlying molecular mechanisms remain poorly understood. Transcription factor DP-1 (TFDP1) and cell division cycle protein 27 (CDC27), which are implicated in tumorigenesis and cell cycle regulation, have not been explored in bronchiectasis.

Methods: Gene expression data from the Gene Expression Omnibus dataset GSE97298 (27 patients with bronchiectasis vs. nine healthy controls) were analyzed to identify differentially expressed genes (DEGs) using edgeR (log₂ fold-change value ≥ 1.2, adj.p < 0.05). Protein-protein interaction (PPI) networks were constructed using STRING software. Clinical validation included 71 patients with bronchiectasis and 29 healthy controls. TFDP1 and CDC27 mRNA levels were quantified using real-time polymerase chain reaction. Regulatory relationships were assessed using ChIP-seq data (Cistrome DB), and pathway enrichment was performed using clusterProfiler to explore the potential molecular mechanisms of action of TFDP1 and CDC27 in non-CF bronchiectasis.

Results: In total, 355 DEGs were identified (45 upregulated and 310 downregulated genes). TFDP1 and CDC27 were significantly upregulated in patients with bronchiectasis (p < 0.01) and exhibited a strong positive correlation (r = 0.6104, p < 0.0001). ChIP-seq confirmed TFDP1 binding to the CDC27 promoter region. Enrichment analysis revealed TFDP1-associated DEGs involved in the cell cycle. TFDP1 expression was correlated with the bronchiectasis severity index (r = 0.2904, p < 0.05).

Conclusion: This study demonstrated the synergistic upregulation of TFDP1 and CDC27 in bronchiectasis and explored cell cycle regulation as an important potential mechanism by which TFDP1 and CDC27 contribute to the development of bronchiectasis. Therefore, TFDP1 may serve as a biomarker of disease severity.

Background: There is a known association between coagulation abnormalities and idiopathic pulmonary fibrosis (IPF), but it remains unclear whether anticoagulant treatment can extend the lifespan of IPF patients. This systematic review and meta-analysis aim to evaluate the efficacy and safety of anticoagulants in patients with IPF.

Methods: A comprehensive search was conducted in PubMed, Embase, Cochrane, and Web of Science from their inception until June 30, 2024, with an English language restriction. We selected clinical studies that met the inclusion criteria after reviewing titles, abstracts, and full texts.

Results: Three randomized controlled trials and five prospective studies, including 2185 patients, were analyzed. Compared to standard treatment, anticoagulants did not significantly affect overall mortality in IPF patients. However, excluding studies with warfarin monotherapy, other anticoagulants extended patient survival (OR = 0.56, 95% CI [0.33, 0.95], p = 0.03). Anticoagulants were associated with significantly increased adverse events (OR = 2.48, 95% CI [1.16, 5.32], p = 0.68) but improved lung function (forced vital capacity, FVC), increased lung capacity, and reduced plasma D-dimer levels. No significant differences were observed in the 6-min walk test (6MWT) or diffusing capacity of the lungs for carbon monoxide (DLCO).

Conclusion: The study suggests that anticoagulants may extend the lifespan of IPF patients and improve lung function. However, they also increase the risk of adverse events such as bleeding. However, there is an increased risk of adverse events, such as bleeding. This may be due to the distinct mechanisms of action, risk profiles, and clinical outcomes of each drug, although the exact causes remain unclear. Further meta-analyses based on individual patient data are needed to confirm these findings.

Background: Muscle weakness is a clinically significant complication of interstitial lung disease (ILD) that worsens dyspnea, fatigue, and quality of life, but its epidemiology and clinical impact remain understudied.

Methods: In this cross-sectional study of 107 ILD patients, peripheral muscle weakness was defined as handgrip strength (HGS) < 28.0 kg (males) or < 18.0 kg (females), and respiratory muscle weakness as maximal inspiratory pressure (MIP) < 80% predicted. Assessments included pulmonary function, echocardiography, diaphragm ultrasound, 6-min walk distance (6MWD), short physical performance battery (SPPB), quality of life, and psychological status. Multivariate logistic regression identified the predictors of muscle weakness.

Results: Peripheral muscle weakness (66.4%) was associated with older age, lower BMI, worse pulmonary function, reduced 6MWD, and higher right ventricular systolic pressure (RVSP) (all p < 0.05). Calf circumference (OR 0.774, 95% CI 0.659-0.910) and 6MWD (OR 0.991, 95% CI 0.985-0.998) independently predicted peripheral weakness. Respiratory muscle weakness (46.7%) correlated with older age, lower BMI, impaired lung function, and higher peripheral weakness rates. Biomass fuel exposure (OR 7.855, 95% CI 1.587-38.890) and 6MWD (OR 0.742, 95% CI 0.648-0.850) were significant determinants. Both weakness types led to significant declines in diffusion capacity, physical function, and quality of life (p < 0.05), without ILD subtype differences.

Conclusion: ILD patients with muscle weakness show impaired lung function, reduced physical capacity, and poorer quality of life. Calf circumference and 6MWD influence peripheral weakness, while biomass exposure and grip strength influence respiratory weakness.

Background: Elevated Th-22 cells and IL-22 are linked to chronic obstructive pulmonary disease (COPD); however, their mechanisms are not fully elucidated. This study aimed to evaluate the therapeutic effects of AG490 and fezakinumab in a cigarette smoke-induced COPD mouse model.

Methods: Cigarette smoke-induced COPD mice were divided into Air, CS, AG490, and Fezakinumab groups. We assessed BALF TH-22 cell levels, IL-22 levels and lung tissue (lung tissue were taken from the same anatomical site of the left lower lobe) histopathological changes, IL-22R1 expression, and protein expression of Jak1, TYK2, STAT3, p-STAT3, Caspase3, Bax, and Bcl-2.

Results: Th-22 and IL-22 expressions were higher in the CS group than those in the Air group. Both the AG490 and Fezakinumab groups had reduced levels compared with the CS group but remained higher than the Air group. Similarly, IL-22R1 expression was higher in the CS group than in the Air group, while both AG490 and Fezakinumab groups exhibited lower expression than the CS group. H&E staining indicated less severe airway remodeling, alveolar enlargement, and inflammatory cell infiltration in the AG490 and Fezakinumab groups compared with the CS group. Western blot analysis revealed higher levels of JAK1, p-STAT3, and Caspase3 and lower levels of STAT3 and Bcl-2 in the CS group than those in the Air group. Both AG490 and Fezakinumab groups exhibited lower levels of JAK1, p-STAT3, and Caspase3 than the CS group, while Fezakinumab groups exhibited lower levels of STAT3 and higher levels of Bcl-2 than the CS group.

Conclusions: Th-22 cells and IL-22 play crucial roles in COPD pathogenesis. Fezakinumab and AG490 mitigate airway remodeling, alveolar enlargement, and pulmonary tissue inflammatory cell infiltration by modulating JAK/STAT pathways and apoptosis. These results suggest promising targeted therapies for COPD, potentially improving patient outcomes by addressing inflammatory mechanisms.