OpenLB
Open Library of Bioscience
Advanced Search
Aging clinical and experimental research
Jul, 2021;33 (7): 1771-1782.

Inhaled corticosteroids and risk of influenza in patients with asthma: a meta-analysis of randomized controlled trials.

Hong Chen, Zhibo Xu, Jing Yang, Lan Huang, Ke Wang
Author Information
  1. Hong Chen: Respiratory Diseases Laboratory, Chengdu Second People's Hospital, No. 10 Qingyun South Street, Chengdu, 610017, China.
  2. Zhibo Xu: Respiratory Diseases Laboratory, Chengdu Second People's Hospital, No. 10 Qingyun South Street, Chengdu, 610017, China.
  3. Jing Yang: Department of Respiratory Medicine and Critical Care Medicine, West China Hospital, Sichuan University, No. 37 Guo Xue Xiang, Chengdu, 610041, China.
  4. Lan Huang: Respiratory Diseases Laboratory, Chengdu Second People's Hospital, No. 10 Qingyun South Street, Chengdu, 610017, China.
  5. Ke Wang: Department of Respiratory Medicine and Critical Care Medicine, West China Hospital, Sichuan University, No. 37 Guo Xue Xiang, Chengdu, 610041, China. restudy@yeah.net. ORCID
PMID: 33026595 DOI: 10.1007/s40520-020-01688-9

Abstract

BACKGROUND: It was reported that inhaled corticosteroids (ICS) treatment may affect local immunity and microbial community of the airway. However, whether ICS treatment increases the risk of influenza in patients with asthma remains unclear. This meta-analysis aimed to compare the risk of influenza between ICS and non-ICS treatment in patients with asthma.
METHODS: PubMed, Embase, Cochrane Library and Clinical Trials.gov were searched from inception until November 2019. Randomized controlled trials (RCTs) were included that compared ICS treatment with non-ICS treatment on the risk of influenza in patients with asthma. Meta-analyses were conducted by the Peto approach and Mantel-Haenszel approach with corresponding 95% CIs.
RESULTS: Nine trials involving 6486 patients were included in this meta-analysis. The risk of influenza was not different between ICS treatment and the control groups (Peto OR: 1.01, 95% CI 0.74-1.37, P = 0.95). The results of subgroup analyses based on durations (long-term and short-term treatment), doses (high-, medium- and low-dose treatment) and types (fluticasone and budesonide treatment) of ICS were consistent with the above pooled results. Moreover, subgroup analysis based on patients' age also revealed that use of ICS did not increase the risk of influenza. Results of the two meta-analysis approaches were similar.
CONCLUSIONS: Use of ICS does not increase the risk of influenza in patients with asthma. This study adds to safety evidence of ICS as a regular controller treatment for patients with asthma.

Keywords

Asthma Influenza Inhaled corticosteroids (ICS) Meta-analysis Risk factors

References

  1. Global Initiative for Asthma (2019) Global strategy for asthma management and prevention. https://ginasthma.org . (Accessed 26 June 2019).
  2. Thomson NC, Spears M (2013) Inhaled corticosteroids for asthma: on-demand or continuous use. Expert Rev Respir Med 7:687–699. https://doi.org/10.1586/17476348.2013.836062 [DOI: 10.1586/17476348.2013.836062]
  3. Fukushima C, Matsuse H, Saeki S et al (2005) Salivary IgA and oral candidiasis in asthmatic patients treated with inhaled corticosteroid. J Asthma 42:601–604. https://doi.org/10.1080/02770900500216259 [DOI: 10.1080/02770900500216259]
  4. Singh S, Amin AV, Loke YK (2009) Long-term use of inhaled corticosteroids and the risk of pneumonia in chronic obstructive pulmonary disease: a meta-analysis. Arch Intern Med 169:219–229. https://doi.org/10.1001/archinternmed.2008.550 [DOI: 10.1001/archinternmed.2008.550]
  5. Yang M, Du Y, Chen H et al (2019) Inhaled corticosteroids and risk of pneumonia in patients with chronic obstructive pulmonary disease: a meta-analysis of randomized controlled trials. Int Immunopharmacol 77:105950. https://doi.org/10.1016/j.intimp.2019.105950 [DOI: 10.1016/j.intimp.2019.105950]
  6. Ni S, Fu Z, Zhao J et al (2014) Inhaled corticosteroids (ICS) and risk of mycobacterium in patients with chronic respiratory diseases: a meta-analysis. J Thorac Dis 6:971–978. https://doi.org/10.3978/j.issn.2072-1439.2014.07.03 [DOI: 10.3978/j.issn.2072-1439.2014.07.03]
  7. Yang M, Chen H, Zhang Y et al (2017) Long-term use of inhaled corticosteroids and risk of upper respiratory tract infection in chronic obstructive pulmonary disease: a meta-analysis. Inhal Toxicol 29:219–226. https://doi.org/10.1080/08958378.2017.1346006 [DOI: 10.1080/08958378.2017.1346006]
  8. McKeever T, Harrison TW, Hubbard R et al (2013) Inhaled corticosteroids and the risk of pneumonia in people with asthma: a case-control study. Chest 144:1788–1794. https://doi.org/10.1378/chest.13-0871 [DOI: 10.1378/chest.13-0871]
  9. Bansal V, Mangi MA, Johnson MM et al (2015) Inhaled corticosteroids and incident pneumonia in patients with asthma: systematic review and meta-analysis. Acta Med Acad 44:135–158. https://doi.org/10.5644/ama2006-124.141 [DOI: 10.5644/ama2006-124.141]
  10. Yang M, Zhang Y, Chen H et al (2019) Inhaled corticosteroids and risk of upper respiratory tract infection in patients with asthma: a meta-analysis. Infection 47:377–385. https://doi.org/10.1007/s15010-018-1229-y [DOI: 10.1007/s15010-018-1229-y]
  11. Vasileiou E, Sheikh A, Butler C et al (2017) Effectiveness of influenza vaccines in asthma: a systematic review and meta-analysis. Clin Infect Dis 65:1388–1395. https://doi.org/10.1093/cid/cix524 [DOI: 10.1093/cid/cix524]
  12. Nair H, Brooks WA, Katz M et al (2011) Global burden of respiratory infections due to seasonal influenza in young children: a systematic review and meta-analysis. Lancet 378:1917–1930. https://doi.org/10.1016/S0140-6736(11)61051-9 [DOI: 10.1016/S0140-6736(11)61051-9]
  13. Molinari NA, Ortega-Sanchez IR, Messonnier ML et al (2007) The annual impact of seasonal influenza in the US: measuring disease burden and costs. Vaccine 25:5086–5096. https://doi.org/10.1016/j.vaccine.2007.03.046 [DOI: 10.1016/j.vaccine.2007.03.046]
  14. Ritchie AI, Jackson DJ, Edwards MR et al (2016) Airway epithelial orchestration of innate immune function in response to virus infection a focus on asthma. Ann Am Thorac Soc 13:55–63
  15. Gill MA, Bajwa G, George TA et al (2010) Counterregulation between the FcepsilonRI pathway and antiviral responses in human plasmacytoid dendritic cells. J Immunol 184:5999–6006. https://doi.org/10.4049/jimmunol.0901194 [DOI: 10.4049/jimmunol.0901194]
  16. Papadopoulos NG, Christodoulou I, Rohde G et al (2011) Viruses and bacteria in acute asthma exacerbations–a GA2 LEN-DARE systematic review. Allergy 66:458–468. https://doi.org/10.1111/j.1398-9995.2010.02505.x [DOI: 10.1111/j.1398-9995.2010.02505.x]
  17. Shamseer L, Moher D, Clarke M et al (2015) Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ 350:g7647. https://doi.org/10.1136/bmj.g7647 [DOI: 10.1136/bmj.g7647]
  18. Higgins JP, Altman DG, Gøtzsche PC et al (2011) The Cochrane collaboration's tool for assessing risk of bias in randomised trials. BMJ 343:d5928. https://doi.org/10.1136/bmj.d5928 [DOI: 10.1136/bmj.d5928]
  19. Bradburn MJ, Deeks JJ, Berlin JA et al (2007) Much ado about nothing: a comparison of the performance of meta-analytical methods with rare events. Stat Med 26:53–77. https://doi.org/10.1002/sim.2528 [DOI: 10.1002/sim.2528]
  20. Sweeting MJ, Sutton AJ, Lambert PC (2004) What to add to nothing? Use and avoidance of continuity corrections in meta-analysis of sparse data. Stat Med 23:1351–1375. https://doi.org/10.1002/sim.1761 [DOI: 10.1002/sim.1761]
  21. Higgins JP, Thompson SG, Deeks JJ et al (2003) Measuring inconsistency in meta-analyses. BMJ 327:557–560. https://doi.org/10.1136/bmj.327.7414.557 [DOI: 10.1136/bmj.327.7414.557]
  22. Guyatt G, Oxman AD, Sultan S et al (2013) GRADE guidelines: 11. Making an overall rating of confidence in effect estimates for a single outcome and for all outcomes. J Clin Epidemiol 66:151–157. https://doi.org/10.1016/j.jclinepi.2012.01.006 [DOI: 10.1016/j.jclinepi.2012.01.006]
  23. Chuchalin A, Jacques L, Frith L (2008) Salmeterol/fluticasone propionate via Diskus once daily versus fluticasone propionate twice daily in patients with mild asthma not previously receiving maintenance corticosteroids. Clin Drug Investig 28:169–181. https://doi.org/10.2165/00044011-200828030-00004 [DOI: 10.2165/00044011-200828030-00004]
  24. Berger WE, Bleecker ER, O'Dowd L et al (2010) Efficacy and safety of budesonide/formoterol pressurized metered-dose inhaler: randomized controlled trial comparing once- and twice-daily dosing in patients with asthma. Allergy Asthma Proc 31:49–59. https://doi.org/10.2500/aap.2010.31.3309 [DOI: 10.2500/aap.2010.31.3309]
  25. Woodcock A, Bateman ED, Busse WW et al (2011) Efficacy in asthma of once-daily treatment with fluticasone furoate: a randomized, placebo-controlled trial. Respir Res 12:132. https://doi.org/10.1186/1465-9921-12-132 [DOI: 10.1186/1465-9921-12-132]
  26. Busse WW, Bleecker ER, Bateman ED et al (2012) Fluticasone furoate demonstrates efficacy in patients with asthma symptomatic on medium doses of inhaled corticosteroid therapy: an 8-week, randomised, placebo-controlled trial. Thorax 67:35–41. https://doi.org/10.1136/thoraxjnl-2011-200308 [DOI: 10.1136/thoraxjnl-2011-200308]
  27. Meltzer EO, Kuna P, Nolte H et al (2012) Mometasone furoate/formoterol reduces asthma deteriorations and improves lung function. Eur Respir J 39:279–289. https://doi.org/10.1183/09031936.00020310 [DOI: 10.1183/09031936.00020310]
  28. O'Byrne PM, Woodcock A, Bleecker ER et al (2014) Efficacy and safety of once-daily fluticasone furoate 50 mcg in adults with persistent asthma: a 12-week randomized trial. Respir Res 15:88. https://doi.org/10.1186/s12931-014-0088-z [DOI: 10.1186/s12931-014-0088-z]
  29. Busse WW, Bateman ED, O'Byrne PM et al (2014) Once-daily fluticasone furoate 50 mcg in mild-to-moderate asthma: a 24-week placebo-controlled randomized trial. Allergy 69:1522–1530. https://doi.org/10.1111/all.12480 [DOI: 10.1111/all.12480]
  30. Meltzer EO, Pearlman DS, Eckerwall G et al (2015) Efficacy and safety of budesonide administered by pressurized metered-dose inhaler in children with asthma. Ann Allergy Asthma Immunol 115:516–522. https://doi.org/10.1016/j.anai.2015.09.007 [DOI: 10.1016/j.anai.2015.09.007]
  31. Beasley R, Holliday M, Reddel HK et al (2019) Controlled Trial of Budesonide-formoterol as needed for mild asthma. N Engl J Med 380:2020–2030. https://doi.org/10.1056/NEJMoa1901963 [DOI: 10.1056/NEJMoa1901963]
  32. Ek A, Larsson K, Siljerud S et al (1999) Fluticasone and budesonide inhibit cytokine release in human lung epithelial cells and alveolar macrophages. Allergy 54:691–699. https://doi.org/10.1034/j.1398-9995.1999.00087.x [DOI: 10.1034/j.1398-9995.1999.00087.x]
  33. Hogg JC, Chu FS, Tan WC et al (2007) Survival after lung volume reduction in chronic obstructive pulmonary disease: insights from small airway pathology. Am J Respir Crit Care Med 176:454–459. https://doi.org/10.1164/rccm.200612-1772OC [DOI: 10.1164/rccm.200612-1772OC]
  34. Fauci AS, Dale DC, Balow JE (1976) Glucocorticosteroid therapy: mechanisms of action and clinical considerations. Ann Intern Med 84:304–315. https://doi.org/10.7326/0003-4819-84-3-304 [DOI: 10.7326/0003-4819-84-3-304]
  35. Schleimer RP (2004) Glucocorticoids suppress inflammation but spare innate immune responses in airway epithelium. Proc Am Thorac Soc 1:222–230. https://doi.org/10.1513/pats.200402-018MS [DOI: 10.1513/pats.200402-018MS]
  36. Zhang L, Prietsch SO, Mendes AP et al (2013) Inhaled corticosteroids increase the risk of oropharyngeal colonization by Streptococcus pneumoniae in children with asthma. Respirology 18:272–277. https://doi.org/10.1111/j.1440-1843.2012.02280.x [DOI: 10.1111/j.1440-1843.2012.02280.x]
  37. Cates CJ, Jefferson TO, Rowe BH (2013) Vaccines for preventing influenza in people with asthma. Cochrane Database Syst Rev 22:000364
  38. Hale BG, Albrecht RA, García-Sastre A (2010) Innate immune evasion strategies of influenza viruses. Future Microbiol 5:23–41. https://doi.org/10.2217/fmb.09.108 [DOI: 10.2217/fmb.09.108]
  39. Cazeiro C, Silva C, Mayer S et al (2017) Inhaled corticosteroids and respiratory infections in children with asthma: a meta-analysis. Pediatrics. https://doi.org/10.1542/peds.2016-3271 [DOI: 10.1542/peds.2016-3271]
  40. Dong YH, Chang CH, Wu FL et al (2014) Use of inhaled corticosteroids in patients with COPD and the risk of TB and influenza: a systematic review and meta-analysis of randomized controlled trials. a systematic review and meta-analysis of randomized controlled trials. Chest 145:1286–1297. https://doi.org/10.1378/chest.13-2137 [DOI: 10.1378/chest.13-2137]
  41. Singh S, Loke YK (2012) Drug safety assessment in clinical trials: methodological challenges and opportunities. Trials 13:138. https://doi.org/10.1186/1745-6215-13-138 [DOI: 10.1186/1745-6215-13-138]

Grants

  1. 2015-HM0100621-SF/Chengdu Science and Technology Project

MeSH Term

Adrenal Cortex Hormones
Anti-Asthmatic Agents
Asthma
Humans
Influenza, Human
Randomized Controlled Trials as Topic

Chemicals

Adrenal Cortex Hormones
Anti-Asthmatic Agents
Journal Article Meta-Analysis Review
Article has an altmetric score of 1

Word Cloud

Created with Highcharts 10.0.0ICStreatmentriskinfluenzapatientsasthmameta-analysiscorticosteroidstrialsnon-ICScontrolledincludedPetoapproach95%resultssubgroupbasedincreaseInhaledBACKGROUND:reportedinhaledmayaffectlocalimmunitymicrobialcommunityairwayHoweverwhetherincreasesremainsunclearaimedcompareMETHODS:PubMedEmbaseCochraneLibraryClinicalTrialsgovsearchedinceptionNovember2019RandomizedRCTscomparedMeta-analysesconductedMantel-HaenszelcorrespondingCIsRESULTS:Nineinvolving6486differentcontrolgroupsOR:101CI074-137P = 095analysesdurationslong-termshort-termdoseshigh-medium-low-dosetypesfluticasonebudesonideconsistentpooledMoreoveranalysispatients'agealsorevealeduseResultstwoapproachessimilarCONCLUSIONS:Usestudyaddssafetyevidenceregularcontrollerasthma:randomizedAsthmaInfluenzaMeta-analysisRiskfactors

Similar Articles

Cited By (1)