2017年慢性气道疾病防治研究进展
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摘要
慢性气道疾病在我国呼吸疾病中占绝大多数。2017年全球慢性阻塞性肺疾病(慢阻肺)防治指南提出了最新的病情评估分类标准,而近年来慢阻肺主流治疗开始以长效双支气管舒张剂代替吸入皮质激素加长效支气管舒张剂。噻托溴胺对早期慢阻肺(包括无症状的)患者疗效显著,首次提出慢阻肺防治战略重心前移观点。哮喘研究则更为侧重于疾病临床表型的划分以及炎症通路分子机制,随着对哮喘发病机制认识的加深,目前已有多种针对Th2通路的新药已被证实实行个体化治疗的良好应用前景,针对中性粒细胞炎症通路、KIT通路等的新药有效性临床试验也为不同表型的哮喘提供新的治疗手段。我国近年来支气管扩张研究在病因学、细菌学、临床分型等方面取得较快进展,各地研究中心的建立将为今后深入探讨支气管扩张的发病机制、寻找干预潜在靶点、探索不同药物干预对患者预后的影响提供重要的理论依据。
Chronic airway diseases constitute the majority of mortality of respiratory diseases in China.The 2017 Global Initiative for Chronic Obstructive Lung Disease has proposed a novel scheme for classification of disease severity.The mainstream for chronic obstructive pulmonary disease(COPD) management has shifted to the combination of long acting β_2 agonists(LABA) and long acting muscarinic cholinergic antagonists instead of inhaled corticosteroid and LABA.Tiotropium was effective in early COPD with little or even without symptoms.The manangement strategy on COPD may be moving to the upper stream(early intervention).Greater interest has been focusing on clinical phenotyping and inflammatory pathways in asthma.The greater understanding of the pathogenesis of asthma has been associated with the clinical trial progress which suggests that multiple medications targeting at Th2 pathways may provide benefits for implementing personalized therapy.Medications targeting at neutrophilic airway inflammation and blockade of KIT pathways are expected to provide novel rationales for managing asthma with different phenotypes.There has been a considerable progress in bronchiectasis research in China,particularly in terms of etiology,bacteriology and clinical phenotying investigations.The establishment of bronchiectasis research centers in China may help better understanding of the pathogenesis of bronchiectasis,thus identifying potential targets for intervention,which may provide crucial rationale for future intervention to improve the long-term prognosis.
Chronic airway diseases constitute the majority of mortality of respiratory diseases in China.The 2017 Global Initiative for Chronic Obstructive Lung Disease has proposed a novel scheme for classification of disease severity.The mainstream for chronic obstructive pulmonary disease(COPD) management has shifted to the combination of long acting β_2 agonists(LABA) and long acting muscarinic cholinergic antagonists instead of inhaled corticosteroid and LABA.Tiotropium was effective in early COPD with little or even without symptoms.The manangement strategy on COPD may be moving to the upper stream(early intervention).Greater interest has been focusing on clinical phenotyping and inflammatory pathways in asthma.The greater understanding of the pathogenesis of asthma has been associated with the clinical trial progress which suggests that multiple medications targeting at Th2 pathways may provide benefits for implementing personalized therapy.Medications targeting at neutrophilic airway inflammation and blockade of KIT pathways are expected to provide novel rationales for managing asthma with different phenotypes.There has been a considerable progress in bronchiectasis research in China,particularly in terms of etiology,bacteriology and clinical phenotying investigations.The establishment of bronchiectasis research centers in China may help better understanding of the pathogenesis of bronchiectasis,thus identifying potential targets for intervention,which may provide crucial rationale for future intervention to improve the long-term prognosis.
引文
1Allinson JP,Hardy R,Donaldson GC,et al.Combined impact of smoking and early-life exposures on adult lung function trajectories.Am J Respir Crit Care Med,2017,196(8):1021-1030.
2Liu S,Zhou Y,Liu S,et al.Association between exposure to ambient particulate matter and chronic obstructive pulmonary disease:results from a cross-sectional study in China.Thorax,2017,72(9):788-795.
3Li MH,Fan LC,Mao B,et al.Short-term exposure to ambient fine particulate matter increases hospitalizations and mortality in COPD:a systematic review and Meta-analysis.Chest,2016,149(2):447-458.
4Zhao D,Zhou Y,Jiang C,et al.Small airway disease:a different phenotype of early stage COPD associated with biomass smoke exposure.Respirology,2017.doi:10.1111/resp.1317.
5Fernandes L,Gulati N,Fernandes Y,et al.Small airway imaging phenotypes in biomass-and tobacco smoke-exposed patients with COPD.ERJ Open Res,2017,3(2):pii:00124-2016.doi:10 .1183/23120541.00124-2016.
6Polosukhin VV,Richmond BW,Du RH,et al.Secretory Ig A deficiency in individual small airways is associated with persistent inflammation and remodeling.Am J Respir Crit Care Med,2017,195(8):1010-1021.
7Zhou Y,Zhong N,Li XC,et al.Tiotropium in early-stage chronic obstructive pulmonary disease.N Engl J Med,2017,377(10):923-935.
8Zhong N,Wang C,Yao W,et al.Prevalence of chronic obstructive pulmonary disease in China:a large,population-based survey.Am J Respir Crit Care Med,2007,176(8):753-760.
9Mapel DW,Dalal AA,Blanchette CM,et al.Severity of COPD at initial spirometry-confirmed diagnosis:data from medical charts and administrative claims.Int J Chron Obstruct Pulmon Dis,2011,6:573-581.
10Aaron SD,Tan WC,Bourbeau J,et al.Diagnostic instability and reversals of chronic obstructive pulmonary disease diagnosis in individuals with mild to moderate airflow obstruction.Am J Respir Crit Care Med,2017,196(3):306-314.
11Schermer TR,Robberts B,Crockett AJ,et al.Should the diagnosis of COPD be based on a single spirometry test?.NPJ Prim Care Respir Med,2016,26:16059.
12The Global Initiative for Chronic Obstructive Lung Disease.Global strategy for the diagnosis,management,and prevention of chronic obstructive pulmonary disease:2018 report.(2017-11-01)[2017-12-12 ].http://goldcopd.org/wp-content/uploads/2017/11/GOLD-2018-v6.0-FINAL-revised-20-Nov_WMS.pdf.
13Zhong N,Wang C,Zhou X,et al.LANTERN:a randomized study of QVA149 versus salmeterol/fluticasone combination in patients with COPD.Int J Chron Obstruct Pulmon Dis,2015,10:1015-1026.
14Wedzicha JA,Banerji D,Chapman KR,et al.Indacaterolglycopyrronium versus salmeterol-fluticasone for COPD.N Engl J Med,2016,374(23):2222-2234.
15Martinez FJ,Fabbri LM,Ferguson GT,et al.Baseline symptom score impact on benefits of glycopyrrolate/formoterol metereddose inhaler in COPD.Chest,2017,152(6):1169-1178.
16Rabe KF,Calverley PMA,Martinez FJ,et al.Effect of roflumilast in patients with severe COPD and a history of hospitalisation.Eur Respir J,2017,50(1):pii:1700158.
17Vestbo J,Papi A,Corradi M,et al.Single inhaler extrafine triple therapy versus long-acting muscarinic antagonist therapy for chronic obstructive pulmonary disease(Trinity):a double-blind,parallel group,randomised controlled trial.Lancet,2017,389(182):1919-1929.
18Pavord ID,Chanez P,Criner GJ,et al.Mepolizumab for eosinophilic chronic obstructive pulmonary disease.N Engl J Med,2017,377(17):1613-1629.
19林江涛,王文巧,周新,等.我国中心城市支气管哮喘患者急性发作征兆及其自我管理水平的调查分析.中华医学杂志,2017,97(30):2329-2332.
20林江涛,王文巧,周新,等.我国30个省市城区门诊支气管哮喘患者控制水平的调查结果.中华结核和呼吸杂志,2017,40(7)494-498.
21Mao B,Yang JW,Lu HW,et al.Asthma and bronchiectasis exacerbation.The Eur Respir J,2016,47:1680-1686.
22Qu YL,Liu J,Zhang LX,et al.Asthma and the risk of lung cancer:a meta-analysis.Oncotarget,2017,8(7):11614-11620.
23Wang Y,Liu K,Hu K,et al.Impact of obstructive sleep apnea on severe asthma exacerbations.Sleep Med,2016,26:1-5.
24Israel E,Reddel HK.Severe and difficult-to-treat asthma in adults.N Engl J Med,2017,377(10):965-976.
25Rossios C,Pavlidis S,Hoda U,et al.Sputum transcriptomics reveal upregulation of IL-1 receptor family members in patients with severe asthma.J Allergy Clin Immunol,2017.doi:10.1016/j.jaci.
26Schleich F,Demarche S,Louis R.Biomarkers in the management of difficult asthma.Curr Top Med Chem,2016,16(14):1561-1573.
27Li N,Qiu R,Yang Z,et al.Sputum microbiota in severe asthma patients:relationship to eosinophilic inflammation.Respir Med,2017,131:192-198.
28Yao X,Sun Y,Wang W,et al.Interleukin(IL)-25:pleiotropic roles in asthma.Respirology,2016,21(4):638-647.
29Zhang Y,Xu Y,Liu S,et al.Scaffolding protein Gab1 regulates myeloid dendritic cell migration in allergic asthma.Cell Res,2016,26(11):1226-1241.
30Ma X,Sun Z,Zhai P,et al.Effect of follicular helper T cells on the pathogenesis of asthma.Exp Ther Med,2017,14(2):967-972.
31Gong F,Qian C,Zhu H,et al.Circulating follicular T-helper cell subset distribution in patients with asthma.Allergy Asthma Proc,2016,37(6):154-161.
32杜春玲,徐侃,闵智慧,等.外周血CD4+记忆T细胞的表型及其与支气管哮喘严重程度的相关性.中华医学杂志,2017,97(30):2333-2337.
33Pelaia G,Canonica GW,Matucci A,et al.Targeted therapy in severe asthma today:focus on immunoglobulin E.Drug Des Devel Ther,2017,11:1979-1987.
34Li J,Kang J,Wang C,et al.Omalizumab improves quality of life and asthma control in Chinese patients with moderate to severe asthma:a randomized phaseⅢstudy.Allergy Asthma Immunol Res,2016,8(4):319-328.
35Hanania NA,Korenblat P,Chapman KR,et al.Efficacy and safety of lebrikizumab in patients with uncontrolled asthma(LAVOLTAⅠand LAVOLTAⅡ):replicate,phase 3,randomised,doubleblind,placebo-controlled trials.Lancet Respir Med,2016,4(10):781-796.
36Bjermer L,Lemiere C,Maspero J,et al.Reslizumab for inadequately controlled asthma with elevated blood eosinophil levels:a randomized phase 3 study.Chest,2016,150(4):789-798.
37Ortega HG,Liu MC,Pavord ID,et al.Mepolizumab treatment in patients with severe eosinophilic asthma.N Engl J Med,2014,371(13):1198-1207.
38Corren J,Parnes JR,Wang L,et al.Tezepelumab in adults with uncontrolled asthma.N Engl J Med,2017,377(10):936-946.
39Gibson PG,Yang IA,Upham JW,et al.Effect of azithromycin on asthma exacerbations and quality of life in adults with persistent uncontrolled asthma(AMAZES):a randomised,double-blind,placebo-controlled trial.Lancet,2017,390(195):659-668.
40Koutsoubari I,Papaevangelou V,Konstantinou GN,et al.Effect of clarithromycin on acute asthma exacerbations in children:an open randomized study.Pediatr Allergy Immunol,2012,23(4):385-390.
41Wang G,Wang F,Gibson PG,et al.Severe and uncontrolled asthma in China:a cross-sectional survey from the Australasian Severe Asthma Network.J Thorac Dis,2017,9(5):1333-1344.
42Gonem S,Berair R,Singapuri A,et al.Fevipiprant,a prostaglandin D2 receptor 2 antagonist,in patients with persistent eosinophilic asthma:a single-centre,randomised,double-blind,parallel-group,placebo-controlled trial.Lancet Respir Med,2016,4(9):699-707.
43Dong X,Huang N,Li W,et al.Systemic reactions to dust mite subcutaneous immunotherapy:a 3-year follow-up study.Allergy Asthma Immunol Res,2016,8(5):421-427.
44农英,苏楠,林江涛,等.支气管热成形术治疗重度支气管哮喘的有效性和安全性研究.中华结核和呼吸杂志,2016,39(3):177-182.
45张清玲,张筱娴,谢佳星,等.支气管热成形术治疗重度支气管哮喘的初步临床观察.中华结核和呼吸杂志,2016,39(3):183-188.
46Mao Y,Zhan YQ,Huang YX.Vitamin D and asthma:A Mendelian randomization study.Ann Allergy Asthma Immunol,2017,119:83-97.
47Kang YB,Cai Y,Zhang H.Gut microbiota and allergy/asthma:from pathogenesis to new therapeutic strategies.Allergol Immunopathol(Madr),2017,45(3):305-309.
48Cahill KN,Katz HR,Cui J,et al.KIT inhibition by imatinib in patients with severe refractory asthma.N Engl J Med,2017,376(20):1911-1920.
49Tian BP,Xia LX,Bao ZQ,et al.Bcl-2 inhibitors reduce steroidinsensitive airway inflammation.J Allergy Clin Immunol,2017,140(2):418-430.
50Sun Q,Liu L,Wang H,et al.Constitutive high expression of protein arginine methyltransferase 1 in asthmatic airway smooth muscle cells is caused by reduced micro RNA-19a expression and leads to enhanced remodeling.J Allergy Clin Immunol,2017140 (2):510-524.e3.
51Koopmans T,Gosens R.Revisiting asthma therapeutics:focus on WNT signal transduction.Drug Discov Today,2017.doi:10 .1016/j.drudis.2017.09.001.
52Yao L,Zhao H,Tang H,et al.Blockade ofβ-catenin signaling attenuates toluene diisocyanate-induced experimental asthma.Allergy,2017,72(4):579-589.
53Chalmers JD,Crichton M,Goeminne PC,et al.The European multicentre bronchiectasis audit and research collaboration(EMBARC):experiences from a successful ERS clinical research collaboration.Breathe(Sheff),2017,13(3):180-192.
54Mcdonnell MJ,Aliberti S,Goeminne PC,et al.Comorbidities and the risk of mortality in patients with bronchiectasis:an international multicentre cohort study.Lancet Respir Med,2016,4(12):969-979.
55Chalmers JD,Moffitt KL,Suarez-Cuartin G,et al.Neutrophil elastase activity is associated with exacerbations and lung function decline in bronchiectasis.Am J Respir Crit Care Med,2017,195(10):1384-1393.
56Hill AT,Haworth CS,Aliberti S,et al.Pulmonary exacerbation in adults with bronchiectasis:a consensus definition for clinical research.Eur Respir J,2017,49(6).doi:10.1183/13993003.00051-2017.
57Bedi P,Chalmers JD,Graham C,et al.A randomized controlled trial of atorvastatin in patients with bronchiectasis infected with pseudomonas aeruginosa:a proof of concept study.Chest,2017,152(2):368-378.
58Guan WJ,Gao YH,Xu G,et al.Aetiology of bronchiectasis in Guangzhou,southern China.Respirology,2015,20(5):739-748.
59Qi Q,Wang W,Li T,et al.Aetiology and clinical characteristics of patients with bronchiectasis in a Chinese Han population:a prospective study.Respirology,2015,20(6):917-924.
60Gao YH,Guan WJ,Xu G,et al.The role of viral infection in pulmonary exacerbations of bronchiectasis in adults:a prospective study.Chest,2015,147(6):1635-1643.
61Guan WJ,Gao YH,Xu G,et al.Sputum matrix metalloproteinase-8and-9 and tissue inhibitor of metalloproteinase-1 in bronchiectasis:clinical correlates and prognostic implications.Respirology,2015,20(7):1073-1081.
62Guan WJ,Gao YH,Li HM,et al.Impacts of co-existing chronic rhinosinusitis on disease severity and risks of exacerbations in chinese adults with bronchiectasis.PLo S One,2015,10(9):e0137348.
63Yang X,Xu Y,Jin J,et al.Chronic rhinosinusitis is associated with higher prevalence and severity of bronchiectasis in patients with COPD.Int J Chron Obstruct Pulmon Dis,2017,12:655-662.
64Gao YH,Guan WJ,Zhu YN,et al.Anxiety and depression in adult outpatients with bronchiectasis:associations with disease severity and health-related quality of life.Clin Respir J,2017.doi:10 .1111/crj.12695.
2Liu S,Zhou Y,Liu S,et al.Association between exposure to ambient particulate matter and chronic obstructive pulmonary disease:results from a cross-sectional study in China.Thorax,2017,72(9):788-795.
3Li MH,Fan LC,Mao B,et al.Short-term exposure to ambient fine particulate matter increases hospitalizations and mortality in COPD:a systematic review and Meta-analysis.Chest,2016,149(2):447-458.
4Zhao D,Zhou Y,Jiang C,et al.Small airway disease:a different phenotype of early stage COPD associated with biomass smoke exposure.Respirology,2017.doi:10.1111/resp.1317.
5Fernandes L,Gulati N,Fernandes Y,et al.Small airway imaging phenotypes in biomass-and tobacco smoke-exposed patients with COPD.ERJ Open Res,2017,3(2):pii:00124-2016.doi:10 .1183/23120541.00124-2016.
6Polosukhin VV,Richmond BW,Du RH,et al.Secretory Ig A deficiency in individual small airways is associated with persistent inflammation and remodeling.Am J Respir Crit Care Med,2017,195(8):1010-1021.
7Zhou Y,Zhong N,Li XC,et al.Tiotropium in early-stage chronic obstructive pulmonary disease.N Engl J Med,2017,377(10):923-935.
8Zhong N,Wang C,Yao W,et al.Prevalence of chronic obstructive pulmonary disease in China:a large,population-based survey.Am J Respir Crit Care Med,2007,176(8):753-760.
9Mapel DW,Dalal AA,Blanchette CM,et al.Severity of COPD at initial spirometry-confirmed diagnosis:data from medical charts and administrative claims.Int J Chron Obstruct Pulmon Dis,2011,6:573-581.
10Aaron SD,Tan WC,Bourbeau J,et al.Diagnostic instability and reversals of chronic obstructive pulmonary disease diagnosis in individuals with mild to moderate airflow obstruction.Am J Respir Crit Care Med,2017,196(3):306-314.
11Schermer TR,Robberts B,Crockett AJ,et al.Should the diagnosis of COPD be based on a single spirometry test?.NPJ Prim Care Respir Med,2016,26:16059.
12The Global Initiative for Chronic Obstructive Lung Disease.Global strategy for the diagnosis,management,and prevention of chronic obstructive pulmonary disease:2018 report.(2017-11-01)[2017-12-12 ].http://goldcopd.org/wp-content/uploads/2017/11/GOLD-2018-v6.0-FINAL-revised-20-Nov_WMS.pdf.
13Zhong N,Wang C,Zhou X,et al.LANTERN:a randomized study of QVA149 versus salmeterol/fluticasone combination in patients with COPD.Int J Chron Obstruct Pulmon Dis,2015,10:1015-1026.
14Wedzicha JA,Banerji D,Chapman KR,et al.Indacaterolglycopyrronium versus salmeterol-fluticasone for COPD.N Engl J Med,2016,374(23):2222-2234.
15Martinez FJ,Fabbri LM,Ferguson GT,et al.Baseline symptom score impact on benefits of glycopyrrolate/formoterol metereddose inhaler in COPD.Chest,2017,152(6):1169-1178.
16Rabe KF,Calverley PMA,Martinez FJ,et al.Effect of roflumilast in patients with severe COPD and a history of hospitalisation.Eur Respir J,2017,50(1):pii:1700158.
17Vestbo J,Papi A,Corradi M,et al.Single inhaler extrafine triple therapy versus long-acting muscarinic antagonist therapy for chronic obstructive pulmonary disease(Trinity):a double-blind,parallel group,randomised controlled trial.Lancet,2017,389(182):1919-1929.
18Pavord ID,Chanez P,Criner GJ,et al.Mepolizumab for eosinophilic chronic obstructive pulmonary disease.N Engl J Med,2017,377(17):1613-1629.
19林江涛,王文巧,周新,等.我国中心城市支气管哮喘患者急性发作征兆及其自我管理水平的调查分析.中华医学杂志,2017,97(30):2329-2332.
20林江涛,王文巧,周新,等.我国30个省市城区门诊支气管哮喘患者控制水平的调查结果.中华结核和呼吸杂志,2017,40(7)494-498.
21Mao B,Yang JW,Lu HW,et al.Asthma and bronchiectasis exacerbation.The Eur Respir J,2016,47:1680-1686.
22Qu YL,Liu J,Zhang LX,et al.Asthma and the risk of lung cancer:a meta-analysis.Oncotarget,2017,8(7):11614-11620.
23Wang Y,Liu K,Hu K,et al.Impact of obstructive sleep apnea on severe asthma exacerbations.Sleep Med,2016,26:1-5.
24Israel E,Reddel HK.Severe and difficult-to-treat asthma in adults.N Engl J Med,2017,377(10):965-976.
25Rossios C,Pavlidis S,Hoda U,et al.Sputum transcriptomics reveal upregulation of IL-1 receptor family members in patients with severe asthma.J Allergy Clin Immunol,2017.doi:10.1016/j.jaci.
26Schleich F,Demarche S,Louis R.Biomarkers in the management of difficult asthma.Curr Top Med Chem,2016,16(14):1561-1573.
27Li N,Qiu R,Yang Z,et al.Sputum microbiota in severe asthma patients:relationship to eosinophilic inflammation.Respir Med,2017,131:192-198.
28Yao X,Sun Y,Wang W,et al.Interleukin(IL)-25:pleiotropic roles in asthma.Respirology,2016,21(4):638-647.
29Zhang Y,Xu Y,Liu S,et al.Scaffolding protein Gab1 regulates myeloid dendritic cell migration in allergic asthma.Cell Res,2016,26(11):1226-1241.
30Ma X,Sun Z,Zhai P,et al.Effect of follicular helper T cells on the pathogenesis of asthma.Exp Ther Med,2017,14(2):967-972.
31Gong F,Qian C,Zhu H,et al.Circulating follicular T-helper cell subset distribution in patients with asthma.Allergy Asthma Proc,2016,37(6):154-161.
32杜春玲,徐侃,闵智慧,等.外周血CD4+记忆T细胞的表型及其与支气管哮喘严重程度的相关性.中华医学杂志,2017,97(30):2333-2337.
33Pelaia G,Canonica GW,Matucci A,et al.Targeted therapy in severe asthma today:focus on immunoglobulin E.Drug Des Devel Ther,2017,11:1979-1987.
34Li J,Kang J,Wang C,et al.Omalizumab improves quality of life and asthma control in Chinese patients with moderate to severe asthma:a randomized phaseⅢstudy.Allergy Asthma Immunol Res,2016,8(4):319-328.
35Hanania NA,Korenblat P,Chapman KR,et al.Efficacy and safety of lebrikizumab in patients with uncontrolled asthma(LAVOLTAⅠand LAVOLTAⅡ):replicate,phase 3,randomised,doubleblind,placebo-controlled trials.Lancet Respir Med,2016,4(10):781-796.
36Bjermer L,Lemiere C,Maspero J,et al.Reslizumab for inadequately controlled asthma with elevated blood eosinophil levels:a randomized phase 3 study.Chest,2016,150(4):789-798.
37Ortega HG,Liu MC,Pavord ID,et al.Mepolizumab treatment in patients with severe eosinophilic asthma.N Engl J Med,2014,371(13):1198-1207.
38Corren J,Parnes JR,Wang L,et al.Tezepelumab in adults with uncontrolled asthma.N Engl J Med,2017,377(10):936-946.
39Gibson PG,Yang IA,Upham JW,et al.Effect of azithromycin on asthma exacerbations and quality of life in adults with persistent uncontrolled asthma(AMAZES):a randomised,double-blind,placebo-controlled trial.Lancet,2017,390(195):659-668.
40Koutsoubari I,Papaevangelou V,Konstantinou GN,et al.Effect of clarithromycin on acute asthma exacerbations in children:an open randomized study.Pediatr Allergy Immunol,2012,23(4):385-390.
41Wang G,Wang F,Gibson PG,et al.Severe and uncontrolled asthma in China:a cross-sectional survey from the Australasian Severe Asthma Network.J Thorac Dis,2017,9(5):1333-1344.
42Gonem S,Berair R,Singapuri A,et al.Fevipiprant,a prostaglandin D2 receptor 2 antagonist,in patients with persistent eosinophilic asthma:a single-centre,randomised,double-blind,parallel-group,placebo-controlled trial.Lancet Respir Med,2016,4(9):699-707.
43Dong X,Huang N,Li W,et al.Systemic reactions to dust mite subcutaneous immunotherapy:a 3-year follow-up study.Allergy Asthma Immunol Res,2016,8(5):421-427.
44农英,苏楠,林江涛,等.支气管热成形术治疗重度支气管哮喘的有效性和安全性研究.中华结核和呼吸杂志,2016,39(3):177-182.
45张清玲,张筱娴,谢佳星,等.支气管热成形术治疗重度支气管哮喘的初步临床观察.中华结核和呼吸杂志,2016,39(3):183-188.
46Mao Y,Zhan YQ,Huang YX.Vitamin D and asthma:A Mendelian randomization study.Ann Allergy Asthma Immunol,2017,119:83-97.
47Kang YB,Cai Y,Zhang H.Gut microbiota and allergy/asthma:from pathogenesis to new therapeutic strategies.Allergol Immunopathol(Madr),2017,45(3):305-309.
48Cahill KN,Katz HR,Cui J,et al.KIT inhibition by imatinib in patients with severe refractory asthma.N Engl J Med,2017,376(20):1911-1920.
49Tian BP,Xia LX,Bao ZQ,et al.Bcl-2 inhibitors reduce steroidinsensitive airway inflammation.J Allergy Clin Immunol,2017,140(2):418-430.
50Sun Q,Liu L,Wang H,et al.Constitutive high expression of protein arginine methyltransferase 1 in asthmatic airway smooth muscle cells is caused by reduced micro RNA-19a expression and leads to enhanced remodeling.J Allergy Clin Immunol,2017140 (2):510-524.e3.
51Koopmans T,Gosens R.Revisiting asthma therapeutics:focus on WNT signal transduction.Drug Discov Today,2017.doi:10 .1016/j.drudis.2017.09.001.
52Yao L,Zhao H,Tang H,et al.Blockade ofβ-catenin signaling attenuates toluene diisocyanate-induced experimental asthma.Allergy,2017,72(4):579-589.
53Chalmers JD,Crichton M,Goeminne PC,et al.The European multicentre bronchiectasis audit and research collaboration(EMBARC):experiences from a successful ERS clinical research collaboration.Breathe(Sheff),2017,13(3):180-192.
54Mcdonnell MJ,Aliberti S,Goeminne PC,et al.Comorbidities and the risk of mortality in patients with bronchiectasis:an international multicentre cohort study.Lancet Respir Med,2016,4(12):969-979.
55Chalmers JD,Moffitt KL,Suarez-Cuartin G,et al.Neutrophil elastase activity is associated with exacerbations and lung function decline in bronchiectasis.Am J Respir Crit Care Med,2017,195(10):1384-1393.
56Hill AT,Haworth CS,Aliberti S,et al.Pulmonary exacerbation in adults with bronchiectasis:a consensus definition for clinical research.Eur Respir J,2017,49(6).doi:10.1183/13993003.00051-2017.
57Bedi P,Chalmers JD,Graham C,et al.A randomized controlled trial of atorvastatin in patients with bronchiectasis infected with pseudomonas aeruginosa:a proof of concept study.Chest,2017,152(2):368-378.
58Guan WJ,Gao YH,Xu G,et al.Aetiology of bronchiectasis in Guangzhou,southern China.Respirology,2015,20(5):739-748.
59Qi Q,Wang W,Li T,et al.Aetiology and clinical characteristics of patients with bronchiectasis in a Chinese Han population:a prospective study.Respirology,2015,20(6):917-924.
60Gao YH,Guan WJ,Xu G,et al.The role of viral infection in pulmonary exacerbations of bronchiectasis in adults:a prospective study.Chest,2015,147(6):1635-1643.
61Guan WJ,Gao YH,Xu G,et al.Sputum matrix metalloproteinase-8and-9 and tissue inhibitor of metalloproteinase-1 in bronchiectasis:clinical correlates and prognostic implications.Respirology,2015,20(7):1073-1081.
62Guan WJ,Gao YH,Li HM,et al.Impacts of co-existing chronic rhinosinusitis on disease severity and risks of exacerbations in chinese adults with bronchiectasis.PLo S One,2015,10(9):e0137348.
63Yang X,Xu Y,Jin J,et al.Chronic rhinosinusitis is associated with higher prevalence and severity of bronchiectasis in patients with COPD.Int J Chron Obstruct Pulmon Dis,2017,12:655-662.
64Gao YH,Guan WJ,Zhu YN,et al.Anxiety and depression in adult outpatients with bronchiectasis:associations with disease severity and health-related quality of life.Clin Respir J,2017.doi:10 .1111/crj.12695.