Additional file 1 of Unraveling the causality between chronic obstructive pulmonary disease and its common comorbidities using bidirectional Mendelian randomization

Additional file 1: Figure S1. Plots for "leave-one-out" analysis for the causal impact of COPD on potentially causal comorbidities. Figure S2. Plots for "leave-one-out" analysis for the causal impact ofpotentially causal comorbidities on COPD

Additional file 2 of Unraveling the causality between chronic obstructive pulmonary disease and its common comorbidities using bidirectional Mendelian randomization

Additional file 2: Table S1. STROBE-MR checklist of Mendelian randomization study. Table S2. The comprehensive retrieved results of traits corresponding to SNPs in Penoscanncer V2 and GWAS catalog. Table S3. Comprehensive details of incorporated SNPs for each disease investigated (R2<0.001). Table S4. Sample overlap rate between exposure and outcome and potential bias. Table S5. The UVMR results of COPD to its frequently coexisting comorbidities (R2<0.001). Table S6. Pleiotropy and heterogeneity analysis of concerned forward UVMR analysis (R2<0.001). Table S7. The reverse UVMR results of COPD to its frequently coexisting comorbidities (R2<0.001). Table S8. Pleiotropy and heterogeneity analysis of concerned reverse UVMR analysis (R2<0.001). Table S9. The MVMR results with adjusting the smoking exposure (R2<0.001). Table S10. Comprehensive details of incorporated SNPs for each disease investigated (R2<0.01). Table S11. The UVMR results of COPD to its frequently coexisting comorbidities (R2<0.01). Table S12. Pleiotropy and heterogeneity analysis of concerned forward UVMR analysis (R2<0.01). Table S13. The reverse UVMR results of COPD to its frequently coexisting comorbidities (R2<0.01). Table S14. Pleiotropy and heterogeneity analysis of concerned reverse UVMR analysis (R2<0.01)

Bronchiectasis in patients with antineutrophil cytoplasmic antibody-associated vasculitis: a case control study on clinical features and prognosis

Bronchiectasis was reported in 2%-40% of patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV), but there were no studies on the prevalence, risk factors and impact of AAV-associated bronchiectasis in Chinese patients. AAV patients were retrospectively enrolled. The clinical, laboratory and imaging features and the prognosis were analyzed and compared between those with and without bronchiectasis. Bronchiectasis was present in 48/212 (22.6%) of our AAV patients, among whom 41 were confirmed in 210 patients (19.5%) who received chest HRCT at the initial diagnosis of AAV. There were more women and fewer smokers in those with bronchiectasis as compared to those without. Cases with positive anti-MPO were more likely to have bronchiectasis (26.2%), and those with bronchiectasis were more likely to be anti-MPO positive (93.8%). Patients who had a diagnosis of bronchiectasis before AAV were more likely to have nervous system involvement, while patients without bronchiectasis had higher 24h proteinuria. The presence of bronchiectasis showed no significant effect on the 1, 3, 5-year survival. Nearly 20% of patients showed bronchiectasis on chest HRCT at the initial diagnosis of AAV, and positivity of anti-MPO was associated with bronchiectasis in a Chinese cohort of AAV patients.</p

Odd ratios for the association between comorbid bronchiectasis and risk for isolation of a potentially pathogenic microorganism.

<p>Odd ratios for the association between comorbid bronchiectasis and risk for isolation of a potentially pathogenic microorganism.</p

Odd ratios for the association between comorbid bronchiectasis and risk for severe airway obstruction.

<p>Odd ratios for the association between comorbid bronchiectasis and risk for severe airway obstruction.</p

Flowchart of process of literature review and selection.

<p>Flowchart of process of literature review and selection.</p

Characteristics of Included Studies in the Meta-analysis.

<p>Characteristics of Included Studies in the Meta-analysis.</p

Odd ratios for the association between comorbid bronchiectasis and risk for mortality.

<p>Odd ratios for the association between comorbid bronchiectasis and risk for mortality.</p

Odd ratios for the association between comorbid bronchiectasis and risk for COPD exacerbations.

<p>Odd ratios for the association between comorbid bronchiectasis and risk for COPD exacerbations.</p

Data_Sheet_1_Transient Receptor Potential Cation Channel Subfamily V Member 4 Mediates Pyroptosis in Chronic Obstructive Pulmonary Disease.docx

TRPV4, a calcium permeable cation selective channel, was found to be involved in chronic obstructive pulmonary disease (COPD) through releasing ATP and IL-1β. Pyroptosis, a newly discovered pro-inflammatory cell death, was induced by cigarette smoke (CS) in airway epithelial cells (AECs). More recent studies indicated that blocking Ca2+ influx effectively inhibited pyroptosis. Therefore, we asked whether TRPV4 mediated CS-induced pyroptosis of AECs and hence participated in the pathogenesis of COPD. We found that pyroptosis and TRPV4 were upregulated in AECs from patients with COPD and long-term CS-exposed mice. Moreover, pharmacological inhibition or knockdown of TRPV4 function alleviated CS extract (CSE)-induced pyroptosis by inhibiting NACHT, LRP, PYD domains-containing protein 3 (NLRP3) inflammasome/activated caspase-1/gasdermin D pathway, decreasing the number of PI positive cells and lactate dehydrogenase (LDH) release, decreasing the expression of pro- inflammatory interleukin gene (IL)-1β, IL-8, and IL-18 expression, as well as increasing anti-inflammatory gene expression [NAD(P)H quinone dehydrogenase 1 (NQO1), superoxide dismutase 2 (mitochondrial) (MNSOD), and catalase, (CAT)]. Moreover, pharmacological inhibition or knockdown of TRPV4 function significantly relieved CSE-induced mitochondrial damage including decreased mitochondrial membrane potential, mitochondrial fusion protein (OPA1, MFN2) expression, and increased mitochondrial fission protein (DRP1, MFF) expression. Taken together, these findings indicate that TRPV4 mediates AEC pyroptosis via NLRP3/caspase-1/GSDMD pathway in COPD.</p