咳嗽变异性哮喘病理机制及治疗的研究进展

doi:10.19983/j.issn.2096-8493.20220135

摘要/Abstract

摘要：

咳嗽变异性哮喘是一种特殊类型的哮喘,也是我国成人和儿童慢性咳嗽的最常见原因,早期诊断及治疗可以预防咳嗽变异性哮喘发展为典型哮喘。随着研究的深入,咳嗽变异性哮喘的病理机制及治疗有了新的发现,笔者将近年来咳嗽变异性哮喘的研究进展做一综述,以供临床参考。

关键词: 哮喘, 咳嗽, 病理过程, 治疗应用, 总结性报告(主题)

Abstract:

Cough variant asthma (CVA) is a special type of asthma and is the most common cause of chronic cough in Chinese adults and children. Early diagnosis and treatment can prevent CVA from developing into typical asthma. With further research, we have new findings on the pathological mechanism and treatment of CVA. Therefore, we reviewed the progress of CVA in recent years for clinical reference.

Key words: Asthma, Cough, Pathologic processes, Therapeutic uses, Consensus development conferences as topic

中图分类号:

R256.12

娄南南, 郭晶, 马香, 盖中涛. 咳嗽变异性哮喘病理机制及治疗的研究进展[J]. 结核与肺部疾病杂志, 2022, 3(6): 521-525. doi: 10.19983/j.issn.2096-8493.20220135

Lou Nannan, Guo Jing, Ma Xiang, Gai Zhongtao. Research progress in pathological mechanism and treatment of cough variant asthma[J]. Journal of Tuberculosis and Lung Disease, 2022, 3(6): 521-525. doi: 10.19983/j.issn.2096-8493.20220135

参考文献 69

[1]	Lai K, Chen R, Lin J, et al. A prospective, multicenter survey on causes of chronic cough in China. Chest, 2013, 143(3): 613-620. doi:10.1378/chest.12-0441. doi: S0012-3692(13)60138-5 URL pmid: 23238526
[2]	Yu X, Kong L, Jiang W, et al. Etiologies associated with chronic cough and its clinical characteristics in school-age children. J Thorac Dis, 2019, 11(7): 3093-3102. doi:10.21037/jtd.2019.07.36. doi: 10.21037/jtd.2019.07.36 URL pmid: 31463138
[3]	Chen X, Peng WS, Wang L. Etiology analysis of nonspecific chronic cough in children of 5 years and younger. Medicine (Baltimore), 2019, 98(3): e13910. doi:10.1097/md.0000000000013910. doi: 10.1097/md.0000000000013910 URL
[4]	中国儿童慢性咳嗽病因构成比研究协作组. 中国儿童慢性咳嗽病因构成比多中心研究. 中华儿科杂志, 2012, 50(2): 83-92. doi:10.3760/cma.j.issn.0578-1310.2012.02.002. doi: 10.3760/cma.j.issn.0578-1310.2012.02.002 URL
[5]	Glauser FL. Variant asthma. Ann Allergy, 1972, 30(8): 457-459. pmid: 5044498
[6]	Corrao WM, Braman SS, Irwin RS. Chronic cough as the sole presenting manifestation of bronchial asthma. N Engl J Med, 1979, 300(12): 633-637. doi:10.1056/nejm197903223001201. doi: 10.1056/nejm197903223001201 URL
[7]	Matsumoto H, Niimi A, Takemura M, et al. Prognosis of cough variant asthma: a retrospective analysis. J Asthma, 2006, 43(2): 131-135. doi:10.1080/02770900500498477. doi: 10.1080/02770900500498477 URL pmid: 16517429
[8]	Simpson JL, Scott R, Boyle MJ, et al. Inflammatory subtypes in asthma: assessment and identification using induced sputum. Respirology, 2006, 11(1): 54-61. doi:10.1111/j.1440-1843.2006.00784.x. doi: 10.1111/j.1440-1843.2006.00784.x URL pmid: 16423202
[9]	Hastie AT, Mauger DT, Denlinger LC, et al. Baseline sputum eosinophil+neutrophil subgroups’ clinical characteristics and longitudinal trajectories for NHLBI Severe Asthma Research Program (SARP 3) cohort. J Allergy Clin Immunol, 2020, 146(1): 222-226. doi:10.1016/j.jaci.2020.01.039. doi: 10.1016/j.jaci.2020.01.039 URL
[10]	李红雯, 林江涛, 农英, 等. 支气管哮喘患者气道炎症表型分布及其与控制水平的相关性. 中华医学杂志, 2019, 99(22): 1692-1697. doi:10.3760/cma.j.issn.0376-2491.2019.22.002. doi: 10.3760/cma.j.issn.0376-2491.2019.22.002 URL
[11]	Demarche SF, Schleich FN, Henket MA, et al. Effectiveness of inhaled corticosteroids in real life on clinical outcomes, sputum cells and systemic inflammation in asthmatics: a retrospective cohort study in a secondary care centre. BMJ Open, 2017, 7(11): e018186. doi:10.1136/bmjopen-2017-018186. doi: 10.1136/bmjopen-2017-018186 URL
[12]	Shi B, Li W, Hao Y, et al. Characteristics of inflammatory phenotypes among patients with asthma: relationships of blood count parameters with sputum cellular phenotypes. Allergy Asthma Clin Immunol, 2021, 17(1): 47. doi:10.1186/s13223-021-00548-z. doi: 10.1186/s13223-021-00548-z URL pmid: 33975625
[13]	Hastie AT, Mauger DT, Denlinger LC, et al. Mixed Sputum Granulocyte Longitudinal Impact on Lung Function in the Severe Asthma Research Program. Am J Respir Crit Care Med, 2021, 203(7): 882-892. doi:10.1164/rccm.202009-3713OC. doi: 10.1164/rccm.202009-3713OC URL
[14]	Pavord ID, Holliday M, Reddel HK, et al. Predictive value of blood eosinophils and exhaled nitric oxide in adults with mild asthma: a prespecified subgroup analysis of an open-label, parallel-group, randomised controlled trial. Lancet Respir Med, 2020, 8(7): 671-680. doi:10.1016/s2213-2600(20)30053-9. doi: 10.1016/S2213-2600(20)30053-9 URL pmid: 32171064
[15]	Balzar S, Wenzel SE, Chu HW. Transbronchial biopsy as a tool to evaluate small airways in asthma. Eur Respir J, 2002, 20(2): 254-259. doi:10.1183/09031936.02.00261102. doi: 10.1183/09031936.02.00261102 URL pmid: 12212952
[16]	Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention. 2022-04-06.
[17]	Kuyper LM, Paré PD, Hogg JC, et al. Characterization of airway plugging in fatal asthma. Am J Med, 2003, 115(1): 6-11. doi:10.1016/s0002-9343(03)00241-9. doi: 10.1016/s0002-9343(03)00241-9 URL pmid: 12867228
[18]	Hamid Q, Song Y, Kotsimbos TC, et al. Inflammation of small airways in asthma. J Allergy Clin Immunol, 1997, 100(1): 44-51. doi:10.1016/s0091-6749(97)70193-3. doi: 10.1016/s0091-6749(97)70193-3 URL
[19]	Postma DS, Brightling C, Baldi S, et al. Exploring the relevance and extent of small airways dysfunction in asthma (ATLANTIS): baseline data from a prospective cohort study. Lancet Respir Med, 2019, 7(5): 402-416. doi:10.1016/s2213-2600(19)30049-9. doi: 10.1016/S2213-2600(19)30049-9 URL pmid: 30876830
[20]	Kraft M, Richardson M, Hallmark B, et al. The role of small airway dysfunction in asthma control and exacerbations: a longitudinal, observational analysis using data from the ATLANTIS study. Lancet Respir Med, 2022, 10(7):661-668. doi:10.1016/s2213-2600(21)00536-1. doi: 10.1016/S2213-2600(21)00536-1 URL pmid: 35247313
[21]	Krings JG, Goss CW, Lew D, et al. Quantitative CT metrics are associated with longitudinal lung function decline and future asthma exacerbations: Results from SARP-3. J Allergy Clin Immunol, 2021, 148(3): 752-762. doi:10.1016/j.jaci.2021.01.029. doi: 10.1016/j.jaci.2021.01.029 URL
[22]	Jiang D, Wang Z, Shen C, et al. Small airway dysfunction may be an indicator of early asthma: findings from high-resolution CT. Ann Allergy Asthma Immunol, 2019, 122(5): 498-501. doi:10.1016/j.anai.2019.02.024. doi: 10.1016/j.anai.2019.02.024 URL
[23]	Gao J, Wu F, Wu S, et al. Inflammatory Subtypes in Classic Asthma and Cough Variant Asthma. J Inflamm Res, 2020, 13: 1167-1173. doi:10.2147/jir.S269795. doi: 10.2147/JIR.S269795 URL pmid: 33376381
[24]	Gao J, Wu H, Wu F. Small airway dysfunction in patients with cough variant asthma: a retrospective cohort study. BMC Pulm Med, 2021, 21(1): 49. doi:10.1186/s12890-021-01419-4. doi: 10.1186/s12890-021-01419-4 URL pmid: 33536015
[25]	Matsuoka H, Niimi A, Matsumoto H, et al. Inflammatory subtypes in cough-variant asthma: association with maintenance doses of inhaled corticosteroids. Chest, 2010, 138(6): 1418-1425. doi:10.1378/chest.10-0132. doi: 10.1378/chest.10-0132 URL pmid: 20671058
[26]	Rybka-Fraczek A, Dabrowska M, Grabczak EM, et al. Inflammatory Phenotypes of Cough Variant Asthma as Response Predictors to Anti-Asthmatic Therapy. J Inflamm Res, 2022, 15: 595-602. doi:10.2147/jir.S343411. doi: 10.2147/JIR.S343411 URL pmid: 35115807
[27]	Niimi A, Amitani R, Suzuki K, et al. Eosinophilic inflammation in cough variant asthma. Eur Respir J, 1998, 11(5): 1064-1069. doi:10.1183/09031936.98.11051064. doi: 10.1183/09031936.98.11051064 URL pmid: 9648956
[28]	Yoo Y, Koh YY, Kang H, et al. Sputum eosinophil counts and eosinophil cationic protein levels in cough-variant asthma and in classic asthma, and their relationships to airway hypersensitivity or maximal airway response to methacholine. Allergy, 2004, 59(10): 1055-1062. doi:10.1111/j.1398-9995.2004.00655.x. doi: 10.1111/j.1398-9995.2004.00655.x URL pmid: 15355463
[29]	Wang Y, Zhao L, Chen F, et al. Diagnostic Value of Fractional Exhaled Nitric Oxide and Small Airway Function in Differentiating Cough-Variant Asthma from Typical Asthma. Can Respir J, 2021, 2021:9954411. doi:10.1155/2021/9954411. doi: 10.1155/2021/9954411 URL
[30]	Lai K, Zhan W, Wu F, et al. Clinical and Inflammatory Characteristics of the Chinese APAC Cough Variant Asthma Cohort. Front Med (Lausanne), 2021, 8: 807385. doi:10.3389/fmed.2021.807385. doi: 10.3389/fmed.2021.807385 URL
[31]	Woodruff PG, Modrek B, Choy DF, et al. T-helper type 2-driven inflammation defines major subphenotypes of asthma. Am J Respir Crit Care Med, 2009, 180(5): 388-395. doi:10.1164/rccm.200903-0392OC. doi: 10.1164/rccm.200903-0392OC URL
[32]	Berry A, Busse WW. Biomarkers in asthmatic patients: Has their time come to direct treatment? J Allergy Clin Immunol, 2016, 137(5): 1317-1324. doi:10.1016/j.jaci.2016.03.009. doi: 10.1016/j.jaci.2016.03.009 URL pmid: 27155028
[33]	Kuruvilla ME, Lee FE, Lee GB. Understanding Asthma Phenotypes, Endotypes, and Mechanisms of Disease. Clin Rev Allergy Immunol, 2019, 56(2): 219-233. doi:10.1007/s12016-018-8712-1. doi: 10.1007/s12016-018-8712-1 URL
[34]	Zhong NS, Chen RC, Yang MO, et al. Is asymptomatic bronchial hyperresponsiveness an indication of potential asthma? A two-year follow-up of young students with bronchial hyperresponsiveness. Chest, 1992, 102(4): 1104-1109. doi:10.1378/chest.102.4.1104. doi: 10.1378/chest.102.4.1104 URL pmid: 1395752
[35]	Westerhof GA, Coumou H, de Nijs SB, et al. Clinical predictors of remission and persistence of adult-onset asthma. J Allergy Clin Immunol, 2018, 141(1): 104-109.e3. doi:10.1016/j.jaci.2017.03.034. doi: S0091-6749(17)30662-0 URL pmid: 28438546
[36]	Almqvist L, Rönmark E, Stridsman C, et al. Remission of adult-onset asthma is rare: a 15-year follow-up study. ERJ Open Res, 2020, 6(4): 00620-2020. doi:10.1183/23120541.00620-2020. doi: 10.1183/23120541.00620-2020 URL
[37]	Thomas D, McDonald VM, Pavord ID, et al. Asthma remission: what is it and how can it be achieved? Eur Respir J, 2022, 60(5): 2102583. doi:10.1183/13993003.02583-2021. doi: 10.1183/13993003.02583-2021 URL
[38]	Gao J, Wu HG, Wu F. Small Airways Dysfunction and Bronchial Hyper-Responsiveness in Cough Variant Asthma. Int J Gen Med, 2020, 13: 1427-1434. doi:10.2147/IJGM.S286144. doi: 10.2147/IJGM.S286144 URL pmid: 33324088
[39]	Liu W, Chen H, Zhang D, et al. A retrospective study of clinical features of cough variant asthma in Chinese adults. Allergy Asthma Clin Immunol, 2019, 15: 3. doi:10.1186/s13223-019-0318-5. doi: 10.1186/s13223-019-0318-5 URL pmid: 30675172
[40]	Obase Y, Shimoda T, Kishikawa R, et al. Trigger of bronchial hyperresponsiveness development may not always need eosinophilic airway inflammation in very early stage of asthma. Allergy Rhinol (Providence), 2016, 7(1): 1-7. doi:10.2500/ar.2016.7.0145. doi: 10.2500/ar.2016.7.0145 URL
[41]	Carroll N, Elliot J, Morton A, et al. The structure of large and small airways in nonfatal and fatal asthma. Am Rev Respir Dis, 1993, 147(2): 405-410. doi:10.1164/ajrccm/147.2.405. doi: 10.1164/ajrccm/147.2.405 URL
[42]	Arafah MA, Raddaoui E, Kassimi FA, et al. Endobronchial biopsy in the final diagnosis of chronic obstructive pulmonary disease and asthma: a clinicopathological study. Ann Saudi Med, 2018, 38(2): 118-124. doi:10.5144/0256-4947.2018.118. doi: 10.5144/0256-4947.2018.118 URL pmid: 29620545
[43]	Ferreira DS, Carvalho-Pinto RM, Gregório MG, et al. Airway pathology in severe asthma is related to airflow obstruction but not symptom control. Allergy, 2018, 73(3): 635-643. doi:10.1111/all.13323. doi: 10.1111/all.13323 URL pmid: 28960335
[44]	Niimi A, Matsumoto H, Minakuchi M, et al. Airway remo-delling in cough-variant asthma. Lancet, 2000, 356(9229): 564-565. doi:10.1016/s0140-6736(00)02584-8. doi: 10.1016/s0140-6736(00)02584-8 URL pmid: 10950236
[45]	Irwin RS, Ownbey R, Cagle PT, et al. Interpreting the histopathology of chronic cough: a prospective, controlled, comparative study. Chest, 2006, 130(2): 362-370. doi:10.1378/chest.130.2.362. doi: 10.1378/chest.130.2.362 URL pmid: 16899833
[46]	Cui S, Ito I, Nakaji H, et al. Induction of airway remodeling and persistent cough by repeated citric acid exposure in a guinea pig cough model. Respir Physiol Neurobiol, 2019, 263: 1-8. doi:10.1016/j.resp.2019.02.002. doi: S1569-9048(18)30315-X URL pmid: 30738972
[47]	Niimi A, Torrego A, Nicholson AG, et al. Nature of airway inflammation and remodeling in chronic cough. J Allergy Clin Immunol, 2005, 116(3): 565-570. doi:10.1016/j.jaci.2005.07.010. doi: 10.1016/j.jaci.2005.07.010 URL
[48]	中华医学会呼吸病学分会哮喘学组. 支气管哮喘防治指南(2020年版). 中华结核和呼吸杂志, 2020, 43(12): 1023-1048. doi:10.3760/cma.j.cn112147-20200618-00721. doi: 10.3760/cma.j.cn112147-20200618-00721 URL
[49]	中华医学会呼吸病学分会哮喘学组. 咳嗽的诊断与治疗指南(2021). 中华结核和呼吸杂志,2022, 45(1): 13-46. doi:10.3760/cma.j.cn112147-20211101-00759. doi: 10.3760/cma.j.cn112147-20211101-00759 URL
[50]	Schleich F, Demarche S, Louis R. Biomarkers in the Management of Difficult Asthma. Curr Top Med Chem, 2016, 16(14): 1561-1573. doi:10.2174/1568026616666151015093406. doi: 10.2174/1568026616666151015093406 URL pmid: 26467509
[51]	Ntontsi P, Loukides S, Bakakos P, et al. Clinical, functional and inflammatory characteristics in patients with paucigranulocytic stable asthma: Comparison with different sputum phenotypes. Allergy, 2017, 72(11): 1761-1767. doi:10.1111/all.13184. doi: 10.1111/all.13184 URL pmid: 28407269
[52]	中华医学会变态反应分会呼吸过敏学组筹, 中华医学会呼吸病学分会哮喘学组. 中国过敏性哮喘诊治指南(第一版,2019年). 中华内科杂志, 2019, 58(9): 636-655. doi:10.3760/cma.j.issn.0578-1426.2019.09.004. doi: 10.3760/cma.j.issn.0578-1426.2019.09.004 URL
[53]	Hardy J, Baggott C, Fingleton J, et al. Budesonide-formoterol reliever therapy versus maintenance budesonide plus terbutaline reliever therapy in adults with mild to moderate asthma (PRACTICAL): a 52-week, open-label, multicentre, superio-rity, randomised controlled trial. Lancet, 2019, 394(10202): 919-928. doi:10.1016/S0140-6736(19)31948-8. doi: S0140-6736(19)31948-8 URL pmid: 31451207
[54]	Tong X, Liu T, Li Z, et al. Is It Really Feasible to Use Budesonide-Formoterol as Needed for Mild Persistent Asthma? A Systematic Review and Meta-Analysis. Front Pharmacol, 2021, 12: 644629. doi:10.3389/fphar.2021.644629. doi: 10.3389/fphar.2021.644629 URL
[55]	Côté A, Russell RJ, Boulet LP, et al. Managing Chronic Cough Due to Asthma and NAEB in Adults and Adolescents: CHEST Guideline and Expert Panel Report. Chest, 2020, 158(1): 68-96. doi:10.1016/j.chest.2019.12.021. doi: S0012-3692(20)30045-3 URL pmid: 31972181
[56]	Amir Najim Abood HA, Al-Musawi ZM, Hussein AM, et al. Effects of nebulized budesonide plus salbutamol and nebulized salbutamol monotherapy on mild to moderate acute exacerbation of asthma in children: A comparative study. J Pak Med Assoc, 2021, 71(Suppl 9)(12):S29-S34.
[57]	Ducharme FM, Ni Chroinin M, Greenstone I, et al. Addition of long-acting beta2-agonists to inhaled steroids versus higher dose inhaled steroids in adults and children with persistent asthma. Cochrane Database Syst Rev, 2010(4): CD005533. doi:10.1002/14651858.CD005533.pub2. doi: 10.1002/14651858.CD005533.pub2 URL
[58]	Ohkura N, Fujimura M, Hara J, et al. Methacholine-induced cough as an indicator of bronchodilator-responsive cough. Pulm Pharmacol Ther, 2020, 64: 101962. doi:10.1016/j.pupt.2020.101962. doi: 10.1016/j.pupt.2020.101962 URL
[59]	Sun W, Liu HY. Montelukast and Budesonide for Childhood Cough Variant Asthma. J Coll Physicians Surg Pak, 2019, 29(4): 345-348. doi:10.29271/jcpsp.2019.04.345. doi: 10.29271/jcpsp.2019.04.345 URL
[60]	Xu Z, Meng L, Xie Y, et al. lncRNA PCGEM1 strengthens anti-inflammatory and lung protective effects of montelukast sodium in children with cough-variant asthma. Braz J Med Biol Res, 2020, 53(7): e9271. doi:10.1590/1414-431x20209271. doi: 10.1590/1414-431X20209271 URL pmid: 32520202
[61]	Wang XP, Yang LD, Zhou JF. Montelukast and budesonide combination for children with chronic cough-variant asthma. Medicine (Baltimore), 2018, 97(30): e11557. doi:10.1097/md.0000000000011557. doi: 10.1097/md.0000000000011557 URL
[62]	Lin J, Wang Z, Qiu C, et al. A multicenter, prospective, observational study on montelukast monotherapy or montelukast-based combinations treating cough variant asthma. J Thorac Dis, 2020, 12(11): 6573-6585. doi:10.21037/jtd-20-1989. doi: 10.21037/jtd-20-1989 URL pmid: 33282359
[63]	Tang Q, Lei H, You J, et al. Evaluation of efficiency and safety of combined montelukast sodium and budesonide in children with cough variant asthma: A protocol for systematic review and meta-analysis. Medicine (Baltimore), 2021, 100(25): e26416. doi:10.1097/MD.0000000000026416. doi: 10.1097/MD.0000000000026416 URL
[64]	Chen L, Huang M, Xie N. The effect of montelukast sodium plus budesonide on the clinical efficacy, inflammation, and pulmonary function in children with cough variant asthma. Am J Transl Res, 2021, 13(6): 6807-6816. pmid: 34306431
[65]	Zhang Y, Li B. Effects of montelukast sodium plus budesonide on lung function, inflammatory factors, and immune levels in elderly patients with asthma. Ir J Med Sci, 2020, 189(3): 985-990. doi:10.1007/s11845-019-02167-5. doi: 10.1007/s11845-019-02167-5 URL
[66]	Takemura M, Niimi A, Matsumoto H, et al. Clinical, physiological and anti-inflammatory effect of montelukast in patients with cough variant asthma. Respiration, 2012, 83(4): 308-315. doi:10.1159/000332835. doi: 10.1159/000332835 URL pmid: 22094623
[67]	Mirsadraee M, Sabbagh Sajadieh Z, Ghafari S, et al. Cromolyn, a New Hope for Limited Treatment of Neutrophilic Asthma: a Phase Ⅱ Randomized Clinical Trial. Tanaffos, 2019, 18(3): 208-214.
[68]	朱晓弘, 涂金伟, 代继宏. 丙酸氟替卡松、孟鲁斯特钠、酮替芬治疗儿童咳嗽变异性哮喘的临床疗效观察. 中国当代儿科杂志, 2019, 21(4): 393-398. doi:10.7499/j.issn.1008-8830.2019.04.017. doi: 10.7499/j.issn.1008-8830.2019.04.017 URL
[69]	Wei H, Li W, Jiang Z, et al. Clinical efficacy of montelukast sodium combined with budesonide or combined with loratadine in treating children with cough variant asthma and influence on inflammatory factors in the serum. Exp Ther Med, 2019, 18(1): 411-417. doi: 10.3892/etm.2019.7574. doi: 10.3892/etm.2019.7574 URL pmid: 31258680