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Despite extensive exploration of asthma, the mechanism of asthma has not been fully elucidated. Cough variant asthma (CVA) is considered as precursor to classical asthma (CA). Comparative study between CA and CVA may be helpful in further understanding the pathogenesis of asthma.Peripheral blood mononuclear cells (PBMCs) were isolated from CVA, CA and healthy adults. Each group consisted of five cases. Total RNA was extracted from the PBMCs. Agilent 4 × 44 K human genome oligo microarray was used to detect whole genome expression. Allogeneic clustering, Gene Ontology and KEGG analysis were performed to investigate differentially expressed genes (DEGs). Then, ten candidate genes were screened and verified by real-time PCR.Gene expressions were significantly different among the three groups, with 202 DEGs between the CA and the CVA groups. The Gene Ontology analysis suggested that the DEGs were significantly enriched in 'histone H4-K20 demethylation' and 'antigen processing and presentation of endogenous antigens'.The pathogenesis of CVA and CA may be related to genes such as

Background: Influenza was an independent risk factor for invasive pulmonary aspergillosis (IPA). In light of increasing incidence and mortality of influenza associated aspergillosis, our study summarized risk factors, clinical characteristics, and prognostic factors of developing aspergillosis in immunocompetent hosts with influenza to further screen high-risk population and improve outcome.Methods: We reviewed the patient characteristics, laboratory examinations, radiological imaging, and microbiology data of 72 influenza patients with IPA and 84 influenza patients without IPA admitted to West China Hospital.Result: Our study shown that aspergillosis co-infection increased overall mortality of severe influenza from 22.6 to 52.8%, along with higher white blood count (WBC) (10.9 ± 5.0 vs. 8.4 ± 3.3, P = 0.016), Neutrophiles (9.5 ± 5.0 vs. 7.0 ± 3.8, P = 0.023), procalcitonin (PCT) (8.6 ± 15.9 vs. 1.2 ± 2.1, P = 0.009), and a lower CD4+ T cell count (189.2 ± 135.3 vs. 367.1 ± 280.0, P = 0.022) in death group. No impact of age, gender, underlying diseases, immunosuppressive agents and steroids use, CD4+ T cell count on incidence of influenza associated aspergillosis was observed. But influenza associated aspergillosis cases mostly accompanied with more H1N1 subtype (91.7 vs. 79.8%, P = 0.037) and higher level of C-reactive protein (CRP) (117.6 ± 88.1 vs. 78.5 ± 75.2, P = 0.017) and interleukin 6 (IL-6) (133.5 ± 149.2 vs. 69.9 ± 100.0, P = 0.021) than those without aspergillosis.Conclusion: Aspergillosis co-infection in severe influenza patients can lead to a significant increased mortality, which was associated with severe respiratory failure due to mixed infection and immunosuppression. Pulmonary excessive inflammatory response was related with IPA co-infection.

Background High-flow nasal cannula (HFNC) oxygen therapy has been recommended for use in coronavirus disease 2019 (COVID-19) patients with acute respiratory failure and many other clinical conditions. HFNC devices produced by different manufacturers may have varied performance. Whether there is a difference in these devices and the extent of the differences in performance remain unknown. Methods Four HFNC devices (AIRVO 2, TNI softFlow 50, HUMID-BH, and OH-70C) and a ventilator with an HFNC module (bellavista 1000) were evaluated. The flow was set at 20, 25, 30, 35, 40, 45, 50, 60, 70, and 80 L/min, and the FiO2 was set at 21%, 26%, 30%, 35%, 40%, 45%, 50%, 60%, 70%, 80%, and 90%. Then, one side of the cannulas was clipped to simulate the compression, bending, or blocking of the nasal cannulas. The flow and FiO2 of the delivered gas were recorded and compared among settings and devices. Results The actual-flow and actual-FiO2 delivered by different settings and devices varied. AIRVO 2 had superior performance in flow and FiO2 accuracy. bellavista 1000 and OH-70C had good performance in the accuracy of actual-flows and actual-FiO2, respectively. bellavista 1000 and HUMID-BH had a larger flow range from 10 to 80 L/min, but only bellavista 1000 could provide a stable flow with an excessive resistance up to 60 L/min. TNI softFlow 50 had the best flow compensation and could provide sufficient flow with excessive resistance at 20–50 L/min. Conclusions The variation in flow, FiO2 settings, and devices could influence the actual-flow and actual-FiO2 delivered. AIRVO 2 and OH-70C showed better FiO2 accuracy. TNI softFlow 50, bellavista 1000, and HUMID-BH could lower the risk of insufficient flow support due to accidental compression or blocking of the cannulas. In addition, ventilators with HFNC modules provided comparable flow and FiO2 and could be an alternative to standalone HFNC devices.

Objective To analyze acute exacerbation of chronic obstructive pulmonary disease(AECOPD) readmission events and to determine whether neutrophil-to-lymphocyte ratio(NLR) and bilirubin level are associated with readmission after discharge due to AECOPD .Methods A total of 170 patients with AECOPD were included. Patients were stratified into the readmission group if patients have two or more readmission within 2 years of the previous discharge and non-readmission group with one readmission or none within 2 years of the last discharge. Basic characteristics, laboratory examinations and clinical data of them were collected retrospectively and compared between these two groups. Then the patients were separated by the cutoffs of NLR and bilirubin level. The number of all-cause readmission within 2 years, time to first COPD-related readmission, 1-year and 2-year COPD-related readmission, 1-year and 2-year all-cause mortality were compared between groups respectively .Results Compared with readmission group, patients of non-readmission group had shorter length of hospital stay(P=0.034), more systemic corticosteroids use(P=0.007), higher NLR(P=0.001), higher bilirubin levels(P=0.010) and lower eosinophils counts(P=0.001). NLR and bilirubin level at admission can significantly influence the number of all-cause readmission(p=0.002, PConclusion For patients with AECOPD, longer hospital stay and less use of systemic corticosteroids may be associated with higher risk of readmission. NLR and bilirubin level at admission may be related to the number of all-cause readmission. Bilirubin can be regarded as a biomarker to predict readmission rates within 2 years after discharged throughout the course of disease.

Severe acute radiation pneumonitis (SARP) is a life-threatening complication of thoracic radiotherapy. Pre-treatment pulmonary function (PF) may influence its incidence. We have previously reported on the incidence of SARP among patients with moderate pulmonary dysfunction who received definitive concurrent chemoradiotherapy (dCCRT) for non-small cell lung cancer (NSCLC). The clinical outcomes, dose–volume histograms (DVH), and PF parameters of 122 patients (forced expiratory volume in 1 s [FEV1%]: 60–69%) receiving dCCRT between 2013 and 2019 were recorded. SARP was defined as grade ≥3 RP occurring during or within 3 months after CCRT. Logistic regression, receiver operating characteristics curves (ROC), and hazard ratio (HR) analyses were performed to evaluate the predictive value of each factor for SARP. Univariate and multivariate analysis indicated that the ratio of carbon monoxide diffusing capacity (DLCO%; odds ratio [OR]: 0.934, 95% confidence interval [CI] 0.896–0.974, p = 0.001) and mean lung dose (MLD; OR: 1.002, 95% CI 1.001–1.003, p = 0.002) were independent predictors of SARP. The ROC AUC of combined DLCO%/MLD was 0.775 (95% confidence interval [CI]: 0.688–0.861, p = 0.001), with a sensitivity and specificity of 0.871 and 0.637, respectively; this was superior to DLCO% (0.656) or MLD (0.667) alone. Compared to the MLD-low/DLCO%-high group, the MLD-high/DLCO%-low group had the highest risk for SARP, with an HR of 9.346 (95% CI: 2.133–40.941, p = 0.003). The DLCO% and MLD may predict the risk for SARP among patients with pre-treatment moderate pulmonary dysfunction who receive dCCRT for NSCLC. Prospective studies are needed to validate our findings.

Figure S1. Beggâ s test for publication bias on pre-bronchodilator FEV1 (L). Figure S2. Meta-regression plot of mean difference for pre-bronchodilator FEV1 (L) predicted by treatment duration. Figure S3. Meta-regression plot of mean difference for pre-bronchodilator FEV1 (L) predicted by asthma severity. Figure S4. Meta-regression plot of mean difference for pre-bronchodilator FEV1 (L) predicted by concomitant treatment. Figure S5. The effect of CRTH2 antagonists used as monotherapy or add-on therapy versus placebo on pre-bronchodilator FEV1% predicted. Figure S6. The effect of CRTH2 antagonists used as monotherapy or add-on therapy versus placebo on post-bronchodilator FEV1 (L). Figure S7. The effect of CRTH2 antagonists used as monotherapy or add-on therapy versus placebo on FVC. Figure S8. The effect of CRTH2 antagonists used as monotherapy or add-on therapy versus placebo on severe adverse events. Figure S9. The effect of CRTH2 antagonists used as monotherapy or add-on therapy versus placebo on treatment related adverse events. Figure S10. The effect of CRTH2 antagonists used as monotherapy or add-on therapy versus placebo on adverse events leading to treatment withdrawal. Figure S11. Beggâ s test for publication bias on adverse event. Figure S12. Meta-regression plot of risk ratio for adverse events predicted by treatment duration. Figure S13. Meta-regression plot of risk ratio for adverse events predicted by concomitant treatment. Figure S14. Meta-regression plot of risk ratio for adverse events predicted by asthma severity. (DOCX 10650 kb)

SETTING Genetic predisposition, in addition to smoking, is known to play a key role in susceptibility to chronic obstructive pulmonary disease (COPD). Several candidate genes have been proposed for COPD, including surfactant protein B (SFTPB). However, large studies in populations with different ethnic backgrounds and environments are required to clarify the role of SFTPB in COPD. OBJECTIVE We investigated the association of SFTPB polymorphisms with COPD susceptibility and lung function in a Chinese Han population. DESIGN Four single nucleotide polymorphisms (SNPs) in the SFTPB gene were genotyped in 680 COPD patients and 687 controls. Allele frequencies and genotype distributions were compared between cases and controls and the potential relationships between these SNPs and lung function were investigated. Associations between haplotypes and COPD susceptibility were also assessed. RESULTS The SFTPB exon polymorphism rs1130866 significantly protected subjects from COPD (adjusted P = 0.004) and was associated with an increase in forced expiratory volume in 1 s (FEV(1)) (adjusted P = 0.014). CONCLUSIONS SFTPB variants are associated with COPD susceptibility and lung function in the Chinese Han population.

Genome-wide association studies (GWAS) and integrative genomic approaches have demonstrated significant associations between chronic obstructive pulmonary disease (COPD) and polymorphisms of the X-ray repair cross-complementing protein 5 gene (XRCC5) in non-Asian populations. We investigated whether XRCC5 polymorphisms might be associated with COPD susceptibility and COPD-related phenotypes in the Chinese Han population. Nine single nucleotide polymorphisms (SNPs) (rs3821104, rs12470053, rs207936, rs3770498, rs6704622, rs3770492, rs4674066, rs7573191, and rs207906) in the XRCC5 gene were genotyped in a case-control study including 680 COPD patients and 687 controls. To estimate the strength of association, odds ratios (ORs) were calculated and the effects of potentially confounding variables were tested by logistic regression analysis. The association between haplotypes and COPD outcome was also assessed. Our data identified that the SNP rs207936 was associated with COPD with an adjusted P value of 0.038, which was also found when analyzing only data of current smokers (P = 0.046). No significant associations were found between any of the SNPs and pulmonary function. Eight SNPs (rs3821104, rs12470053, rs207936, rs3770498, rs6704622, rs3770492, rs4674066, and rs7573191) showed strong linkage disequilibrium (R2 ≥ 0.9). Two major haplotypes were observed and showed a significant difference between case and control groups (P = 0.0054 and 0.0081, respectively). The present study showed that the XRCC5 locus might be a contributor to COPD susceptibility in the Chinese Han population.

Objectives Genome-wide association studies (GWAS) and integrative genomics approaches have demonstrated significant associations between chronic obstructive pulmonary disease (COPD) and FAM13A polymorphisms in non-Asian populations. The aim of this study was to investigate whether FAM13A polymorphisms would be associated with COPD susceptibility and COPD-related phenotypes in a Chinese Han population. Methods Seven single nucleotide polymorphisms (SNPs) (rs7671167, rs10007590, rs2869966, rs2869967, rs2045517, rs1903003, rs6830970) in FAM13A gene were genotyped in a case–control study (680 COPD patients and 687 controls). Allele frequencies and genotype distributions were compared between patients and controls. To estimate the strength of association, odds ratios (OR) (with 95% CI) were calculated and potential confounding variables were tested by using logistic regression analysis. Results Statistical analysis revealed that SNP rs7671167 was associated with COPD in former smokers with adjusted P-value of 0.026. Five SNPs (rs7671167, rs2869966, rs2869967, rs2045517, and rs6830970) were associated with FEV1/FVC ratio in the entire cohort and rs6830970 was associated with FEV1/FVC ratio in COPD cases (P range 0.003–0.034). Borderline associations with FEV1/FVC ratio were found for rs2869966, rs2869967 and rs2045517 among cases (P = 0.05). Six SNPs (rs7671167, rs2869966, rs2869967, rs2045517, rs1903003, rs6830970) showed strong linkage disequilibrium (r2 ≥ 0.9). Four major haplotypes were observed but showed no significant difference between case and control groups (P = 0.2356, 0.1273, 0.6266 and 0.3006 respectively). Conclusions The current study suggests that the FAM13A locus might be a contributor to COPD susceptibility in Chinese Han population.

Gastroesophageal reflux disease (GERD) may be a potential risk factor for exacerbations of chronic obstructive pulmonary disease (COPD). The aim of the present study was to explore the association of GERD risk with exacerbations of COPD. Patients with COPD were consecutively recruited, and COPD Assessment Test (CAT) and Reflux Diagnostic Questionnaire (RDQ) were administered. If the CAT score was 5 points higher than that taken in the stable states, the patient was considered as having exacerbations of COPD. A RDQ score of ≥ 12 is defined high GERD risk. Univariate and multivariate logistic regression analyses were performed to evaluate the relationship between high GERD risk and exacerbations of COPD. Among 386 patients with COPD, the mean CAT score was 18.3 ± 6.6, and 76 (19.7%) patients had exacerbations during the 1-year follow-up. The mean RDQ score was 10.1 ± 4.7, and 132 (34.2%) patients were identified as having high GERD risk. Multivariate logistic regression analyses revealed that the high GERD risk (odds ratio, 2.31; 95% confidence interval, 1.29-3.87) was an independent risk factor of COPD exacerbations. In conclusion, high GERD risk appears to be associated with higher odds for COPD exacerbations.

Background The diagnostic values of interferon-gamma release assays (IGRA) in tuberculosis (TB) vary a lot with different site of infections, with especially higher sensitivities in chronic forms of TB such as tuberculosis of the lymph node. We conducted a meta-analysis to comprehensively evaluate the overall accuracy of diagnostic IGRA for tuberculous lymphadenitis. Methods Pubmed, Web of Science, EMBASE, Wanfang and CNKI databases up to February 17, 2017 were searched to identify published studies. The study quality was evaluated using the QUADAS-2 checklist. The pooled estimates of diagnostic parameters were generated using a bivariate random-effects model and summary receiver operating characteristic (SROC) curves were used to summarize global performance. Results A total of ten qualified studies, performed in Korea or China, including 1,084 patients, were enrolled in this meta-analysis. The pooled estimates of diagnostic accuracy were as follows: sensitivity, 0.89 (95% CI [0.85–0.92]); specificity, 0.81 (95% CI [0.77–0.83]); positive likelihood ratio (PLR), 4.25 (95% CI [2.79–6.47]); negative likelihood ratio (NLR), 0.16 (95% CI [0.12–0.22]); and area under the curve (AUC) was 0.93. According to subgroup analyses, studies conducted using QuantiFERON-TB, in Korean population and focusing on cervical lymphadenitis exhibited relative higher specificity while lower sensitivity. No evidence of publication bias was identified. Conclusions IGRA exhibits high diagnostic accuracy in tuberculous lymphadenitis. The diagnostic value of IGRA differed by different IGRA methods, ethnicity and lymphadenitis location. Our conclusion may be more applicable to population from TB prevalent areas.

Summary Gastroesophageal reflux disease (GERD) may make asthma difficult to control and may be a potential risk factor for frequent asthma exacerbations, but the mechanisms of the relationship between GERD and not well-controlled asthma remain unclear. The aim of this study was to explore the association of GERD with asthma control in adults. Patients with asthma were consecutively recruited, and Asthma Control Test (ACT) and Reflux Diagnostic Questionnaire scores were determined. The patients were categorized into not well-controlled asthma and well-controlled asthma groups according to the ACT score. Univariate and multivariate logistic regression analyses were performed to evaluate the relationship between GERD and not well-controlled asthma. Seven hundred and sixty-eight patients with asthma were enrolled. The mean ACT score was 18.2 ± 3.6, and there were 161 (21.0%) patients with not well-controlled asthma. The Reflux Diagnostic Questionnaire score was 10.5 ± 4.7, and 212 (27.6%) patients were complicated by GERD. Multivariate logistic regression analyses revealed the independent association of GERD with not well-controlled asthma (odds ratio, 3.12; 95% confidence interval, 1.53–4.88) after other established contributors to asthma control were adjusted. In conclusion, there is an association of GERD with not well-controlled asthma, independent of other potential contributors to asthma control.

Aim The appropriate selection of hospitalized patients for venous thromboembolism(VTE) prophylaxis is an important unresolved issue. We sought to validate the Caprini model, a famous individual VTE risk assessment model(RAM), in hospitalized Chinese patients. Methods We performed a retrospective case-control study among unselected hospitalized patients admitted to a comprehensive hospital in China. A total of 347 patients were confirmed to have VTE during hospitalization, and 651 controls were randomly selected to match the patients according to medical service. Both the patients and controls were retrospectively assessed for the risk of VTE using the Caprini RAM. Results The average Caprini cumulative risk score in the patients was significantly higher than that observed in the controls(4.69±2.58 vs 3.16±1.82, p＜0.0001). Compared with that observed in the low-risk group, a classification of high-risk according to the Caprini model was associated with a 1.65-fold increased risk of VTE(95%CI 1.05-2.61), while that of highest-risk was associated with a 4.84-fold increased risk of VTE(95%CI 3.06-7.64). After further stratifying the highest risk level with a cumulative risk score of ≥5 into scores of 5-6, 7-8 and ≥9, the patients with a score of 5-6 were found to exhibit a 3.33-fold increased risk of VTE(95%CI 2.06-5.40), those with a score 7-8 exhibited a 9.41-fold increased risk of VTE(95%CI 4.90-18.08) and those with a score of ≥9 exhibited a 24.69-fold(95%CI 7.98-76.40) increased risk of VTE compared with their low-risk counterparts. Conclusions Our study suggests that the Caprini RAM can be used to effectively stratify hospitalized Chinese patients into VTE risk categories based on individual risk factors. The classification of the highest risk level with a cumulative risk score of ≥5 provided significantly more clinical information, and further stratification of this group of patients is needed.

Recent genome-wide association studies have shown associations between variants at five loci (TNS1, GSTCD, HTR4, AGER and THSD4) and chronic obstructive pulmonary disease (COPD) or lung function. However, their association with COPD has not been proven in Chinese Han population, nor have COPD-related phenotypes been studied. The objective of this study was to look for associations between five single nucleotide polymorphisms (SNP) in these novel candidate genes and COPD susceptibility or lung function in a Chinese Han population.Allele and genotype data on 680 COPD patients and 687 healthy controls for sentinel SNP in these five loci were investigated. Allele frequencies and genotype distributions were compared between cases and controls, and odds ratios were calculated. Potential relationships between these SNP and COPD-related lung function were assessed.No significant associations were found between any of the SNP and COPD in cases and controls. The SNP (rs3995090) in HTR4 was associated with COPD (adjusted P = 0.022) in never-smokers, and the SNP (rs2070600) in AGER was associated with forced expiratory volume in 1 s (FEV1 %) predicted (β = -0.066, adjusted P = 0.016) and FEV1 /forced vital capacity (β = -0.071, adjusted P = 0.009) in all subjects.The variant at HTR4 was associated with COPD in never-smokers, and the SNP in AGER was associated with pulmonary function in a Chinese Han population.

The hedgehog signaling pathway plays an important role in lung morphogenesis and cellular responses to lung injury. Genome-wide association studies (GWAS) and integrative genomics approaches have demonstrated the associations between HHIP polymorphisms and chronic obstructive pulmonary disease (COPD) and in non-Asian populations. Here we investigated whether HHIP polymorphisms would also be associated with COPD susceptibility and COPD-related phenotypes in a Chinese Han population. In the present case–control study a total of 680 COPD patients and 687 healthy control subjects were recruited. Six single nucleotide polymorphisms (SNPs) (rs1828591, rs13118928, rs6817273, rs10519717, rs12504628, rs13147758) were selected for genotyping. Allele frequencies and genotype distributions were compared between patients and controls. To estimate the strength of association, odds ratios (OR) (with 95% CI) were calculated and potential confounding variables were tested by using logistic regression analysis. Association between haplotypes and COPD outcome was also assessed. We identified that SNP rs12504628 was associated with FEV1/FVC ratio among cases ( P = 0.0460). Moreover, the HHIP SNP rs10519717 was associated with the severity of disease (adjusted P -value = 0.0300). The six SNPs showed strong linkage disequilibrium (r 2 ≥ 0.9). Three major haplotypes were observed but showed no significant difference between case and control groups ( P = 0.4532, 0.0875, and 0.3484, respectively). In conclusion, our study suggests that the HHIP gene may be involved in COPD susceptibility in Chinese Han population.

Chronic obstructive pulmonary disease (COPD) is known to be a systemic inflammatory disease which affects the function of many organs, and the low bone mineral density (BMD) may be the result of systemic inflammation. The aim of the present study was to explore the association of BMD with systemic inflammation in patients with clinically stable COPD. BMD and inflammatory markers, including C-reactive protein, tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6), were determined in all the recruited patients with clinically stable COPD. The patients were classified according to T scores, and the relationship between BMD with markers of systemic inflammation and that with other osteoporosis risk factors was assessed. There were no differences in age, female sex, body composition, tobacco exposure, and the use of respiratory medications among these groups. As the abnormality of BMD went severer, COPD patients with osteoporosis had significantly higher levels of systemic inflammation than those with either normal BMD or osteopenia. The presence of systemic inflammation was associated with a greater likelihood of low BMD, and multivariate logistic regression analysis showed that TNF-α and IL-6 were independent predictors of low BMD. It can be concluded that systemic inflammation is a significantly independent predictor of low BMD in patients with clinically stable COPD.