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Zhang Y.,Guangzhou University | Jiang M.,First Affiliated Hospital of Guangzhou Medical University | Li Q.,Sun Yat Sen University | Liang W.,Guangzhou University | And 3 more authors.
PLoS ONE | Year: 2016

Introduction Recently, genome-wide association studies (GWAS) in Caucasian populations have identified an association between single nucleotide polymorphisms (SNPs) in the CHRNA5-A3- B4 nicotinic acetylcholine receptor subunit gene cluster on chromosome 15q25, lung cancer risk and smoking behaviors. However, these SNPs are rare in Asians, and there is currently no consensus on whether SNPs in CHRNA5-A3-B4 have a direct or indirect carcinogenic effect through smoking behaviors on lung cancer risk. Though some studies confirmed rs6495308 polymorphisms to be associated with smoking behaviors and lung cancer, no research was conducted in China. Using a case-control study, we decided to investigate the associations between CHRNA3 rs6495308, CHRNB4 rs11072768, smoking behaviors and lung cancer risk, as well as explore whether the two SNPs have a direct or indirect carcinogenic effect on lung cancer. Methods A total of 1025 males were interviewed using a structured questionnaire (204 male lung cancer patients and 821 healthy men) to acquire socio-demographic status and smoking behaviors. Venous blood samples were collected to measure rs6495308 and rs11072768 gene polymorphisms. All subjects were divided into 3 groups: non-smokers, light smokers (1-15 cigarettes per day) and heavy smokers (>15 cigarettes per day). Results Compared to wild genotype, rs6495308 and rs11072768 variant genotypes reported smoking more cigarettes per day and a higher pack-years of smoking (P<0.05). More importantly, among smokers, both rs6495308 CT/TT and rs11072768 GT/GG had a higher risk of lung cancer compared to wild genotype without adjusting for potential confounding factors (OR = 1.36, 95%CI = 1.09-1.95; OR = 1.11, 95%CI = 1.07-1.58 respectively). Furthermore, heavy smokers with rs6495308 or rs11072768 variant genotypes have a positive interactive effect on lung cancer after adjustment for potential confounding factors (OR = 1.13, 95%CI = 1.01-3.09; OR = 1.09, 95%CI = 1.013.41 respectively). However, No significant associations were found between lung cancer risk and both rs6495308 and rs11072768 genotypes among non-smokers and smokers after adjusting for age, occupation, and education. Conclusion This study confirmed both rs6495308 and rs11072768 gene polymorphisms association with smoking behaviors and had an indirect link between gene polymorphisms and lung cancer risk. © 2016 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Source

Gao Y.-H.,Zhengzhou University | Zhao H.-S.,Zhengzhou University | Zhang F.-R.,Zhengzhou University | Gao Y.,First Affiliated Hospital of Guangzhou Medical University | And 3 more authors.
PLoS ONE | Year: 2015

Background Previous studies have suggested that asthmatic patients often have comorbid depression; however, temporal associations remain unclear. Objectives To determine whether depression predicts asthma and, conversely, whether asthma predicts depression. Methods A literature search was conducted without language restrictions using Pubmed, Embase, Cochrane and PsycINFO for studies published before January, 2015. Papers referenced by the obtained articles were also reviewed. Only comparative prospective studies with reported risk estimates of the association between depression and asthma were included. In order to investigate whether one of these conditions was predictive of the other, studies were excluded if enrolled participants had pre-existing depression or asthma. A randomeffects model was used to calculate the pooled risk estimates for two outcomes: depression predicting asthma and asthma predicting depression. Results Seven citations, derived from 8 cohort studies, met our inclusion criteria. Of these, six studies reported that depression predicted incident adult-onset asthma, including 83684 participants and 2334 incident cases followed for 8 to 20 years. Conversely, two studies reported that asthma predicted incident depression. These studies involved 25566 participants and 2655 incident cases followed for 10 and 20 years, respectively. The pooled adjusted relative risks (RRs) of acquiring asthma associated with baseline depression was 1.43 (95% CI, 1.281.61) (P0.001). The adjusted RRs for acquiring depression associated with baseline asthma was 1.23 (95% CI, 0.722.10) (P = 0.45). Conclusions Depression was associated with a 43% increased risk of developing adult-onset asthma. However, asthma did not increase the risk of depression based on limited studies. Further prospective studies ascertaining the true association between asthma and subsequent risk of depression are warranted. © 2015 Gao et al. Source

Guan W.-J.,First Affiliated Hospital of Guangzhou Medical University | Jiang M.,First Affiliated Hospital of Guangzhou Medical University | Gao Y.-H.,Zhengzhou University | Li H.-M.,First Affiliated Hospital of Guangzhou Medical University | And 4 more authors.
International Journal of Tuberculosis and Lung Disease | Year: 2016

BACKGROUND: Unsupervised learning technique allows researchers to identify different phenotypes of diseases with complex manifestations. OBJECTIVES : To identify bronchiectasis phenotypes and characterise their clinical manifestations and prognosis. METHODS : We conducted hierarchical cluster analysis to identify clusters that best distinguished clinical characteristics of bronchiectasis. Demographics, lung function, sputum bacteriology, aetiology, radiology, disease severity, quality-of-life, cough scale and capsaicin sensitivity, exercise tolerance, health care use and frequency of exacerbations were compared. RESULTS : Data from 148 adults with stable bronchiectasis were analysed. Four clusters were identified. Cluster 1 (n = 69) consisted of the youngest patients with predominantly mild and idiopathic bronchiectasis with minor health care resource use. Patients in cluster 2 (n= 22), in which post-infectious bronchiectasis predominated, had the longest duration of symptoms, greater disease severity, poorer lung function, airway Pseudomonas aeruginosa colonisation and frequent health care resource use. Cluster 3 (n=16) consisted of elderly patients with shorter duration of symptoms and mostly idiopathic bronchiectasis, and predominantly severe bronchiectasis. Cluster 4 (n = 41) constituted the most elderly patients with moderate disease severity. Clusters 2 and 3 tended to have a greater risk of bronchiectasis exacerbations (P = 0.06) than clusters 1 and 4. CONCLUSION: Identification of distinct phenotypes will lead to greater insight into the characteristics and prognosis of bronchiectasis. © 2016 The Union. Source

Guan W.-J.,First Affiliated Hospital of Guangzhou Medical University | Gao Y.-H.,Zhengzhou University | Li H.-M.,First Affiliated Hospital of Guangzhou Medical University | Yuan J.-J.,First Affiliated Hospital of Guangzhou Medical University | And 2 more authors.
PLoS ONE | Year: 2015

Background: Mounting evidence supports the notion of "one airway, one disease." Objective To determine whether chronic rhinosinusitis (CRS) poses adverse impacts on Chinese adults with bronchiectasis. Methods: We enrolled 148 consecutive adults with clinically stable bronchiectasis. CRS diagnosed based on the 2012 EP3OS criteria. We systematically evaluated the bronchiectasis etiology, radiology, lung function, sputum bacteriology, airway inflammatory biomarkers, Bronchiectasis Severity Index, cough sensitivity and healthcare resource utilization. All patients were prospectively followed-up for 1 year to examine the frequency of bronchiectasis exacerbations (BEs). Results: Forty-seven patients (31.8%) were diagnosed as having CRS. Bronchiectasis etiologies did not vary statistically between CRS and no-CRS group. There was a trend towards non-sta-tistically higher Bronchiectasis Severity Index [6.4±3.4 vs. 5.0(6.0), P = 0.19], a higher proportion of patients with BEs needing hospitalization before enrollment (48.9% vs. 29.7%, P =0.13), poorer FVC[78.2±19.8% vs. 82.2(16.8)%, P = 0.54] and FEV1 [68.2±24.8%vs. 74.8(21.2)%, P = 0.29], a higher prevalence of Pseudomonas aeruginosa isolated (36.2% vs. 26.7%, P = 0.27) or colonized in sputum (36.2% vs. 21.8%, P = 0.12) and greatercapsaicin cough sensitivity [C 2:3.9(123.0) μmol/L vs. 11.7(123.0) μmol/L, P = 0.81; C 5:62.5(996.0) μmol/L vs. 250.0(973.0) μmol/L, P = 0.32]. Patients with CRS had significantly greater risks of experiencing BEs during follow-up (P = 0.02 for negative binominal regression test). Conclusion: Chinese adults with bronchiectasis appear to have a lower prevalence of CRS than that in western countries. There was a trend towards greater adverse impacts on bronchiectasis in patients with CRS. Studies with greater sample sizes might help to resolve this issue. In future clinical practice, physicians should be vigilant to the screening of concomitant CRS in bronchiectasis so as to better improve patient's healthcare. Our findings may be of clinical significance in that proper treatment of upper airway symptoms due to CRS will be the prevention of infection or re-infection of the tracheobronchial tree, which should be addressed for the future management of bronchiectasis. Copyright: © 2015 Guan et al. Source

Guan W.-J.,First Affiliated Hospital of Guangzhou Medical University | Gao Y.-H.,Zhengzhou University | Xu G.,Guangzhou First Peoples Hospital | Lin Z.-Y.,First Affiliated Hospital of Guangzhou Medical University | And 6 more authors.
PLoS ONE | Year: 2014

Background: Cough hypersensitivity has been common among respiratory diseases.Objective: To determine associations of capsaicin cough sensitivity and clinical parameters in adults with clinically stable bronchiectasis.Methods: We recruited 135 consecutive adult bronchiectasis patients and 22 healthy subjects. History inquiry, sputum culture, spirometry, chest high-resolution computed tomography (HRCT), Leicester Cough Questionnaire scoring, Bronchiectasis Severity Index (BSI) assessment and capsaicin inhalation challenge were performed. Cough sensitivity was measured as the capsaicin concentration eliciting at least 2 (C2) and 5 coughs (C5).Results: Despite significant overlap between healthy subjects and bronchiectasis patients, both C2 and C5 were significantly lower in the latter group (all P< 0.01). Lower levels of C5 were associated with a longer duration of bronchiectasis symptoms, worse HRCT score, higher 24-hour sputum volume, BSI and sputum purulence score, and sputum culture positive for P. aeruginosa. Determinants associated with increased capsaicin cough sensitivity, defined as C5 being 62.5 μmol/L or less, encompassed female gender (OR: 3.25, 95%CI: 1.35-7.83, P< 0.01), HRCT total score between 7-12 (OR: 2.57, 95%CI: 1.07- 6.173, P = 0.04), BSI between 5-8 (OR: 4.05, 95%CI: 1.48-11.06, P< 0.01) and 9 or greater (OR: 4.38, 95%CI: 1.48-12.93, P< 0.01).Conclusion: Capsaicin cough sensitivity is heightened in a subgroup of bronchiectasis patients and associated with the disease severity. Gender and disease severity, but not sputum purulence, are independent determinants of heightened capsaicin cough sensitivity. Current testing for cough sensitivity diagnosis may be limited because of overlap with healthy subjects but might provide an objective index for assessment of cough in future clinical trials. © 2014 Guan et al. Source

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