Inhaled corticosteroids improve lung function, airway hyper‑responsiveness and airway inflammation but not symptom control in patients with mild intermittent asthma: A meta‑analysis

Du,Wei; Zhou,Ling; Ni,Yingmeng; Yu,Yuanyuan; Wu,Fang; Shi,Guochao

doi:10.3892/etm.2017.4694

Inhaled corticosteroids improve lung function, airway hyper‑responsiveness and airway inflammation but not symptom control in patients with mild intermittent asthma: A meta‑analysis

Authors:
- Wei Du
- Ling Zhou
- Yingmeng Ni
- Yuanyuan Yu
- Fang Wu
- Guochao Shi
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Affiliations: Department of Pulmonary Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China, Department of Geratology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China
Published online on: June 27, 2017 https://doi.org/10.3892/etm.2017.4694
Pages: 1594-1608
Copyright: © Du et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

It remains controversial whether inhaled corticosteroid (ICS) should be used in patients with intermittent asthma. The present study aimed to assess the effect of ICS compared with placebo or other therapies in patients with intermittent asthma. Medline, Embase and CNKI databases were searched up to June 2016 and a meta‑analysis was conducted. The findings demonstrated that in adult patients, when compared with placebo, ICS increased forced expiratory volume in 1 sec FEV1 [standardized mean difference (SMD), 0.51; 95% confidence interval (CI), 0.22‑0.80] and alleviated airway hyper‑responsiveness, which was indicated as log transformed PC20FEV1 (concentrations of methacholine when there was a fall in FEV1 ≥20%; SMD, 0.87; 95% CI, 0.60 to 1.14). ICS also reduced fractional exhaled nitric oxide (FeNO) levels [weighted mean difference (WMD), ‑12.57 parts per billion (ppb; a unit of NO concentration in exhaled air); 95% CI ‑15.88 to ‑9.25 ppb]. However, symptom scores did not change after ICS treatment (SMD, ‑0.26; 95% CI, ‑0.52 to 0). When compared with leukotriene receptor antagonists (LTRA), ICS had no advantage in increasing FEV1 (WMD, 0.04 l; 95% CI, ‑0.06 to 0.13 l), reducing sputum eosinophil percentage (WMD, ‑6%; 95% CI, ‑12.38 to 0.38%) or symptom scores (SMD, 0.44; 95% CI, ‑0.02 to 0.9). However, in child patients, ICS significantly (P<0.05) increased the possibility of symptom control when compared with placebo [relative risk (RR), 8; 95% CI, 1.04 to 61.52] or LTRA (RR, 2.67; 95% CI, 0.39 to 18.42). In conclusion, ICS improves lung function and alleviates airway hyper‑responsiveness and airway inflammation but cannot influence symptom scores, and has no advantage over LTRA in terms of lung function improvement and airway inflammation control in adult patients with mild intermittent asthma. However, in children, the benefit of ICS in symptom control is more significant than with LTRA.

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1	Feng X and Lin J: An Epidemiology Survey On The Prevalence And Associated Risk Factors Of Asthma Among Adults In China. Peking Union Medical College Press; Beijing: pp. 942014
2	Global Initiative for Asthma (GINA), . From the Global Strategy for Asthma Management and Prevention. 2015.http://www.ginasthma.orgMarch 5–2016
3	Humbert M, Holgate S, Boulet LP and Bousquet J: Asthma control or severity: That is the question. Allergy. 62:95–101. 2007. View Article : Google Scholar : PubMed/NCBI
4	Dusser D, Montani D, Chanez P, de Blic J, Delacourt C, Deschildre A, Devillier P, Didier A, Leroyer C, Marguet C, et al: Mild asthma: An expert review on epidemiology, clinical characteristics and treatment recommendations. Allergy. 62:591–604. 2007. View Article : Google Scholar : PubMed/NCBI
5	Israel E and Drazen JM: Treating mild asthma-when are inhaled steroids indicated? N Engl J Med. 331:737–739. 1994. View Article : Google Scholar : PubMed/NCBI
6	Van den Toorn LM: Clinical implications of airway inflammation in mild intermittent asthma. Ann Allergy Asthma Immunol. 92:589–594; quiz 595–7, 658. 2004. View Article : Google Scholar : PubMed/NCBI
7	Pedersen F, Holz O, Kanniess F, Zielen S, Schulze J, Gillissen A, von Berg A, Berdel D, Beier J, Beeh K, et al: Longitudinal measurement of airway inflammation over one year in children and adults with intermittent asthma. BMC Res Notes. 7:9252014. View Article : Google Scholar : PubMed/NCBI
8	Higgins JPT, Deeks JJ and Altman DG: Analysing data and undertaking meta-analysesCochrane Handbook for Systematic Reviews of Interventions. Higgins JPT and Green S: John Wiley & Sons; Chichester, UK: pp. 243–296. 2008
9	Castro H Ponce, Rodríguez Espino S and Rodríguez Orozco AR: Administration of budesonide (inhaled steroid) to children to control intermittent asthma. Rev Alerg Mex. 56:9–12. 2009.(In Spanish). PubMed/NCBI
10	Jatakanon A, Kharitonov S, Lim S and Barnes PJ: Effect of differing doses of inhaled budesonide on markers of airway inflammation in patients with mild asthma. Thorax. 54:108–114. 1999. View Article : Google Scholar : PubMed/NCBI
11	Boulet LP, Turcotte H, Prince P, Lemière C, Olivenstein R, Laprise C, Larivée P, Bégin P and Laviolette M: Benefits of low-dose inhaled fluticasone on airway response and inflammation in mild asthma. Respir Med. 103:1554–1563. 2009. View Article : Google Scholar : PubMed/NCBI
12	Bousquet J, Meziane H, Chanez P, Mueser M and Umile A: The response of two different dosages of beclometasone dipropionate suspension for nebulization versus a standard dose of beclometasone dipropionate via a metered-dose inhaler on bronchoprovocation testing in adults with asthma. Respir Med. 97 Suppl B:11–14. 2003. View Article : Google Scholar
13	Dahlén B, Lantz AS, Ihre E, Skedinger M, Henriksson E, Jörgensen L, Ekström T, Dahlén SE and Larsson K: Effect of formoterol with or without budesonide in repeated low-dose allergen challenge. Eur Respir J. 33:747–753. 2009. View Article : Google Scholar : PubMed/NCBI
14	Ehrs PO, Sundblad BM and Larsson K: Effect of fluticasone on markers of inflammation and quality of life in steroid-naive patients with mild asthma. Clin Respir J. 4:51–58. 2010. View Article : Google Scholar : PubMed/NCBI
15	Gyllfors P, Dahlén SE, Kumlin M, Larsson K and Dahlén B: Bronchial responsiveness to leukotriene D4 is resistant to inhaled fluticasone propionate. J Allergy Clin Immunol. 118:78–83. 2006. View Article : Google Scholar : PubMed/NCBI
16	Haahtela T, Tamminen K, Malmberg LP, Zetterström O, Karjalainen J, Ylä-Outinen H, Svahn T, Ekström T and Selroos O: Formoterol as needed with or without budesonide in patients with intermittent asthma and raised NO levels in exhaled air: A SOMA study. Eur Respir J. 28:748–755. 2006. View Article : Google Scholar : PubMed/NCBI
17	Reddel HK, Belousova EG, Marks GB and Jenkins CR: Does continuous use of inhaled corticosteroids improve outcomes in mild asthma? A double-blind randomised controlled trial. Prim Care Respir J. 17:39–45. 2008. View Article : Google Scholar : PubMed/NCBI
18	Rüdiger JJ, Gencay M, Yang JQ, Bihl M, Tamm M and Roth M: Fast beneficial systemic anti-inflammatory effects of inhaled budesonide and formoterol on circulating lymphocytes in asthma. Respirology. 18:840–847. 2013. View Article : Google Scholar : PubMed/NCBI
19	Mendes ES, Campos MA, Hurtado A and Wanner A: Effect of montelukast and fluticasone propionate on airway mucosal blood flow in asthma. Am J Respir Crit Care Med. 169:1131–1134. 2004. View Article : Google Scholar : PubMed/NCBI
20	Pizzichini MM, Kidney JC, Wong BJ, Morris MM, Efthimiadis A, Dolovich J and Hargreave FE: Effect of salmeterol compared with beclomethasone on allergen-induced asthmatic and inflammatory responses. Eur Respir J. 9:449–455. 1996. View Article : Google Scholar : PubMed/NCBI
21	Lim S, Jatakanon A, John M, Gilbey T, O'connor BJ, Chung KF and Barnes PJ: Effect of inhaled budesonide on lung function and airway inflammation. Assessment by various inflammatory markers in mild asthma. Am J Respir Crit Care Med. 159:22–30. 1999. View Article : Google Scholar : PubMed/NCBI
22	Stanković I, Pejcić T, Milenković B, Jovanović D and Rancić M: Is there any point in a corticosteroid treatment of intermittent asthma? Scientific World Journal. 7:1082–1089. 2007. View Article : Google Scholar : PubMed/NCBI
23	Tamaoki J, Isono K, Taira M, Tagaya E, Nakata J, Kawatani K and Nagai A: Role of regular treatment with inhaled corticosteroid or leukotriene receptor antagonist in mild intermittent asthma. Allergy Asthma Proc. 29:pp. 189–196. 2008; View Article : Google Scholar : PubMed/NCBI
24	Wongtim S, Mogmued S, Chareonlap P and Limthongkul S: Effect of inhaled corticosteroids on bronchial hyperresponsiveness in patients with mild asthma. Asian Pac J Allergy Immunol. 13:81–85. 1995.PubMed/NCBI
25	Haahtela T, Järvinen M, Kava T, Kiviranta K, Koskinen S, Lehtonen K, Nikander K, Persson T, Selroos O, Sovijärvi A, et al: Effects of reducing or discontinuing inhaled budesonide in patients with mild asthma. N Engl J Med. 331:700–705. 1994. View Article : Google Scholar : PubMed/NCBI
26	Papi A: Treatment strategies in mild asthma. Curr Opin Pulm Med. 15:29–34. 2009. View Article : Google Scholar
27	Koh MS and Irving LB: The natural history of asthma from childhood to adulthood. Int J Clin Pract. 61:1371–1374. 2007. View Article : Google Scholar : PubMed/NCBI
28	Fuhlbrigge AL and Kelly HW: Inhaled corticosteroids in children: Effects on bone mineral density and growth. Lancet Respir Med. 2:487–496. 2014. View Article : Google Scholar : PubMed/NCBI
29	O'Byrne PM, Barnes PJ, Rodriguez-Roisin R, Runnerstrom E, Sandstrom T, Svensson K and Tattersfield A: Low dose inhaled budesonide and formoterol in mild persistent asthma: The OPTIMA randomized trial. Am J Respir Crit Care Med. 164:1392–1397. 2001. View Article : Google Scholar : PubMed/NCBI
30	Busse WW, Pedersen S, Pauwels RA, Tan WC, Chen YZ, Lamm CJ and O'Byrne PM; START Investigators Group, : The inhaled steroid treatment as regular therapy in early asthma (START) study 5-year follow-up: Effectiveness of early intervention with budesonide in mild persistent asthma. J Allergy Clin Immunol. 121:1167–1174. 2008. View Article : Google Scholar : PubMed/NCBI
31	Juniper EF, Kline PA, Vanzieleghem MA, Ramsdale EH, O'Byrne PM and Hargreave FE: Effect of long-term treatment with an inhaled corticosteroid (budesonide) on airway hyperresponsiveness and clinical asthma in nonsteroid-dependent asthmatics. Am Rev Respir Dis. 142:832–836. 1990. View Article : Google Scholar : PubMed/NCBI
32	Lemière C, Ernst P, Olivenstein R, Yamauchi Y, Govindaraju K, Ludwig MS, Martin JG and Hamid Q: Airway inflammation assessed by invasive and noninvasive means in severe asthma: Eosinophilic and noneosinophilic phenotypes. J Allergy Clin Immunol. 118:1033–1039. 2006. View Article : Google Scholar : PubMed/NCBI
33	Green RH, Brightling CE, Pavord ID and Wardlaw AJ: Management of asthma in adults: Current therapy and future directions. Postgrad Med J. 79:259–267. 2003. View Article : Google Scholar : PubMed/NCBI