CT: Conceptualization, Investigation, Writing—original draft, Writing—review & editing. AC: Conceptualization, Investigation, Writing—review & editing, Supervision. Both authors read and approved the submitted version.
Conflicts of interest
The authors declare that they have no conflicts of interest.
Ethical approval
Not applicable.
Consent to participate
Not applicable.
Consent to publication
Not applicable.
Availability of data and materials
The primary data for this systematic review were sourced online from the databases listed in the Methods section. Referenced articles are accessible on PubMed, EBSCO, UpToDate, Medline, and Google Scholar. Additional supporting data are available from the corresponding author upon request.
Open Exploration maintains a neutral stance on jurisdictional claims in published institutional affiliations and maps. All opinions expressed in this article are the personal views of the author(s) and do not represent the stance of the editorial team or the publisher.
References
Porsbjerg C, Melén E, Lehtimäki L, Shaw D. Asthma.Lancet. 2023;401:858–73. [DOI] [PubMed]
Bleecker ER, Menzies-Gow AN, Price DB, Bourdin A, Sweet S, Martin AL, et al. Systematic Literature Review of Systemic Corticosteroid Use for Asthma Management.Am J Respir Crit Care Med. 2020;201:276–93. [DOI] [PubMed] [PMC]
Waljee AK, Rogers MA, Lin P, Singal AG, Stein JD, Marks RM, et al. Short term use of oral corticosteroids and related harms among adults in the United States: population based cohort study.BMJ. 2017;357:j1415. [DOI] [PubMed] [PMC]
Maijers I, Kearns N, Harper J, Weatherall M, Beasley R. Oral steroid-sparing effect of high-dose inhaled corticosteroids in asthma.Eur Respir J. 2020;55:1901147. [DOI] [PubMed]
Kachroo P, Stewart ID, Kelly RS, Stav M, Mendez K, Dahlin A, et al. Metabolomic profiling reveals extensive adrenal suppression due to inhaled corticosteroid therapy in asthma.Nat Med. 2022;28:814–22. [DOI] [PubMed] [PMC]
Patel R, Naqvi SA, Griffiths C, Bloom CI. Systemic adverse effects from inhaled corticosteroid use in asthma: a systematic review.BMJ Open Respir Res. 2020;7:e000756. [DOI] [PubMed] [PMC]
Lipson DA, Crim C, Criner GJ, Day NC, Dransfield MT, Halpin DMG, et al. Reduction in All-Cause Mortality with Fluticasone Furoate/Umeclidinium/Vilanterol in Patients with Chronic Obstructive Pulmonary Disease.Am J Respir Crit Care Med. 2020;201:1508–16. [DOI] [PubMed] [PMC]
Yang M, Du Y, Chen H, Jiang D, Xu Z. Inhaled corticosteroids and risk of pneumonia in patients with chronic obstructive pulmonary disease: A meta-analysis of randomized controlled trials.Int Immunopharmacol. 2019;77:105950. [DOI] [PubMed]
Calverley PM, Anderson JA, Celli B, Ferguson GT, Jenkins C, Jones PW, et al. Salmeterol and Fluticasone Propionate and Survival in Chronic Obstructive Pulmonary Disease.N Engl J Med. 2007;356:775–89. [DOI] [PubMed]
Beech A, Lea S, Li J, Jackson N, Mulvanny A, Singh D. Airway Bacteria Quantification Using Polymerase Chain Reaction Combined with Neutrophil and Eosinophil Counts Identifies Distinct COPD Endotypes.Biomedicines. 2021;9:1337. [DOI] [PubMed] [PMC]
Lea S, Beech A, Baker J, Gaskell R, Pindolia D, Dikwa AB, et al. Differential responses of COPD macrophages to respiratory bacterial pathogens.ERJ Open Res. 2022;8:00044–2022. [DOI] [PubMed] [PMC]
Yang IA, Ferry OR, Clarke MS, Sim EH, Fong KM. Inhaled corticosteroids versus placebo for stable chronic obstructive pulmonary disease.Cochrane Database Syst Rev. 2023;3:CD002991. [DOI] [PubMed] [PMC]
Janson C, Larsson K, Lisspers KH, Ställberg B, Stratelis G, Goike H, et al. Pneumonia and pneumonia related mortality in patients with COPD treated with fixed combinations of inhaled corticosteroid and long acting β2 agonist: observational matched cohort study (PATHOS).BMJ. 2013;346:f3306. [DOI] [PubMed] [PMC]
Morjaria JB, Rigby A, Morice AH. Inhaled Corticosteroid use and the Risk of Pneumonia and COPD Exacerbations in the UPLIFT Study.Lung. 2017;195:281–8. [DOI] [PubMed] [PMC]
Rabe KF, Martinez FJ, Ferguson GT, Wang C, Singh D, Wedzicha JA, et al.; ETHOS Investigators. Triple Inhaled Therapy at Two Glucocorticoid Doses in Moderate-to-Very-Severe COPD.N Engl J Med. 2020;383:35–48. [DOI] [PubMed]
Pu X, Liu L, Feng B, Wang M, Dong L, Zhang Z, et al. Efficacy and Safety of Different Doses of Systemic Corticosteroids in COPD Exacerbation.Respir Care. 2021;66:316–26. [DOI] [PubMed]
Papi A, Vestbo J, Fabbri L, Corradi M, Prunier H, Cohuet G, et al. Extrafine inhaled triple therapy versus dual bronchodilator therapy in chronic obstructive pulmonary disease (TRIBUTE): a double-blind, parallel group, randomised controlled trial.Lancet. 2018;391:1076–84. [DOI] [PubMed]
Ekbom E, Quint J, Schöler L, Malinovschi A, Franklin K, Holm M, et al. Asthma and treatment with inhaled corticosteroids: associations with hospitalisations with pneumonia.BMC Pulm Med. 2019;19:254. [DOI] [PubMed] [PMC]
Leung JM, Sin DD. Inhaled corticosteroids in COPD: the final verdict is….Eur Respir J. 2018;52:1801940. [DOI] [PubMed]
Agusti A, Fabbri LM. Inhaled steroids in COPD: when should they be used?Lancet Respir Med. 2014;2:869–71. [DOI] [PubMed]
Calverley PM, Boonsawat W, Cseke Z, Zhong N, Peterson S, Olsson H. Maintenance therapy with budesonide and formoterol in chronic obstructive pulmonary disease.Eur Respir J. 2003;22:912–9. [DOI] [PubMed]
Lipson DA, Barnhart F, Brealey N, Brooks J, Criner GJ, Day NC, et al.; IMPACT Investigators. Once-Daily Single-Inhaler Triple versus Dual Therapy in Patients with COPD.N Engl J Med. 2018;378:1671–80. [DOI] [PubMed]
Anzueto A, Ferguson GT, Feldman G, Chinsky K, Seibert A, Emmett A, et al. Effect of Fluticasone Propionate/Salmeterol (250/50) on COPD Exacerbations and Impact on Patient Outcomes.COPD. 2009;6:320–9. [DOI] [PubMed]
Tashkin DP, Rennard SI, Martin P, Ramachandran S, Martin UJ, Silkoff PE, et al. Efficacy and Safety of Budesonide and Formoterol in One Pressurized Metered-Dose Inhaler in Patients with Moderate to Very Severe Chronic Obstructive Pulmonary Disease: Results of a 6-Month Randomized Clinical Trial.Drugs. 2008;68:1975–2000. [DOI] [PubMed]
Löfdahl CG, Postma DS, Pride NB, Boe J, Thorén A. Possible protection by inhaled budesonide against ischaemic cardiac events in mild COPD.Eur Respir J. 2007;29:1115–9. [DOI] [PubMed]
Sandelin M, Mindus S, Thuresson M, Lisspers K, Ställberg B, Johansson G, et al. Factors associated with lung cancer in COPD patients.Int J Chron Obstruct Pulmon Dis. 2018;13:1833–9. [DOI] [PubMed] [PMC]
Raymakers AJN, Sadatsafavi M, Sin DD, FitzGerald JM, Marra CA, Lynd LD. Inhaled corticosteroids and the risk of lung cancer in COPD: a population-based cohort study.Eur Respir J. 2019;53:1801257. [DOI] [PubMed]
Price D, Yawn B, Brusselle G, Rossi A. Risk-to-benefit ratio of inhaled corticosteroids in patients with COPD.Prim Care Respir J. 2013;22:92–100. [DOI] [PubMed] [PMC]
Jenkins CR, Jones PW, Calverley PM, Celli B, Anderson JA, Ferguson GT, et al. Efficacy of salmeterol/fluticasone propionate by GOLD stage of chronic obstructive pulmonary disease: analysis from the randomised, placebo-controlled TORCH study.Respir Res. 2009;10:59. [DOI] [PubMed] [PMC]
Janson C, Johansson G, Ställberg B, Lisspers K, Olsson P, Keininger DL, et al. Identifying the associated risks of pneumonia in COPD patients: ARCTIC an observational study.Respir Res. 2018;19:172. [DOI] [PubMed] [PMC]
Festic E, Bansal V, Gupta E, Scanlon PD. Association of Inhaled Corticosteroids with Incident Pneumonia and Mortality in COPD Patients; Systematic Review and Meta-Analysis.COPD. 2016;13:312–26. [DOI] [PubMed] [PMC]
Agustí A, Celli BR, Criner GJ, Halpin D, Anzueto A, Barnes P, et al. Global Initiative for Chronic Obstructive Lung Disease 2023 Report: GOLD Executive Summary.Eur Respir J. 2023;61:2300239. [DOI] [PubMed] [PMC]
Savran O, Godtfredsen N, Sørensen T, Jensen C, Ulrik CS. COPD patients prescribed inhaled corticosteroid in primary care: time for re-assessment based on exacerbation rate and blood eosinophils?Respir Res. 2021;22:54. [DOI] [PubMed] [PMC]
Kato M, Tomii K, Hashimoto K, Nezu Y, Ishii T, Jones CE, et al. The IMPACT Study - Single Inhaler Triple Therapy (FF/UMEC/VI) Versus FF/VI And UMEC/VI In Patients With COPD: Efficacy And Safety In A Japanese Population.Int J Chron Obstruct Pulmon Dis. 2019;14:2849–61. [DOI] [PubMed] [PMC]
Cosío BG, Jahn A, Iglesias A, Shafiek H, Busquets X, Agustí A. Haemophilus influenzae induces steroid-resistant inflammatory responses in COPD.BMC Pulm Med. 2015;15:157. [DOI] [PubMed] [PMC]
Agusti A, Fabbri LM, Singh D, Vestbo J, Celli B, Franssen FME, et al. Inhaled corticosteroids in COPD: friend or foe?Eur Respir J. 2018;52:1801219. [DOI] [PubMed]
Culpitt SV, Rogers DF, Shah P, Matos C, Russell RE, Donnelly LE, et al. Impaired Inhibition by Dexamethasone of Cytokine Release by Alveolar Macrophages from Patients with Chronic Obstructive Pulmonary Disease.Am J Respir Crit Care Med. 2003;167:24–31. [DOI] [PubMed]
Khalaf RM, Lea SR, Metcalfe HJ, Singh D. Mechanisms of corticosteroid insensitivity in COPD alveolar macrophages exposed to NTHi.Respir Res. 2017;18:61. [DOI] [PubMed] [PMC]
Kaur M, Singh D. Neutrophil Chemotaxis Caused by Chronic Obstructive Pulmonary Disease Alveolar Macrophages: The Role of CXCL8 and the Receptors CXCR1/CXCR2.J Pharmacol Exp Ther. 2013;347:173–80. [DOI] [PubMed]
Chen H, Deng ZX, Sun J, Huang Q, Huang L, He YH, et al. Association of Inhaled Corticosteroids With All-Cause Mortality Risk in Patients With COPD: A Meta-analysis of 60 Randomized Controlled Trials.Chest. 2023;163:100–14. [DOI] [PubMed]
Cho KH, Kim YS, Linton JA, Nam CM, Choi Y, Park E. Effects of inhaled corticosteroids /long-acting agonists in a single inhaler versus inhaled corticosteroids alone on all-cause mortality, pneumonia, and fracture in chronic obstructive pulmonary disease: A nationwide cohort study 2002–2013.Respir Med. 2017;130:75–84. [DOI] [PubMed]
André S, Conde B, Fragoso E, Boléo-Tomé JP, Areias V, Cardoso J, et al. COPD and Cardiovascular Disease.Pulmonology. 2019;25:168–76. [DOI] [PubMed]
Rabe KF, Hurst JR, Suissa S. Cardiovascular disease and COPD: dangerous liaisons?Eur Respir Rev. 2018;27:180057. [DOI] [PubMed] [PMC]
Morgan AD, Zakeri R, Quint JK. Defining the relationship between COPD and CVD: what are the implications for clinical practice?Ther Adv Respir Dis. 2018;12:1753465817750524. [DOI] [PubMed] [PMC]
Calverley PMA, Anderson JA, Celli B, Ferguson GT, Jenkins C, Jones PW, et al.; TORCH Investigators. Cardiovascular events in patients with COPD: TORCH Study results.Thorax. 2010;65:719–25. [DOI] [PubMed]
Lee TA, Pickard AS, Au DH, Bartle B, Weiss KB. Risk for Death Associated with Medications for Recently Diagnosed Chronic Obstructive Pulmonary Disease.Ann Intern Med. 2008;149:380–90. [DOI] [PubMed]
Gadhvi K, Kandeil M, Raveendran D, Choi J, Davies N, Nanchahal S, et al. Inhaled Corticosteroids and Risk of Cardiovascular Disease in Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Regression.Chronic Obstr Pulm Dis. 2023;10:317–27. [DOI] [PubMed] [PMC]
Jing X, Li Y, Xu J. Risk of Cardiovascular Events Associated with Inhaled Corticosteroid Treatment in Patients with Chronic Obstructive Pulmonary Disease: A Meta-Analysis.Can Respir J. 2018;2018:7097540. [DOI] [PubMed] [PMC]
Ioannides AE, Kallis C, Whittaker HR, Quint JK. Inhaled corticosteroids and major cardiovascular events in people with chronic obstructive pulmonary disease.Thorax. 2025;80:67–75. [DOI] [PubMed]
Mattishent K, Thavarajah M, Blanco P, Gilbert D, Wilson AM, Loke YK. Meta-Review: Adverse Effects of Inhaled Corticosteroids Relevant to Older Patients.Drugs. 2014;74:539–47. [DOI] [PubMed]
Dekhuijzen PNR, Batsiou M, Bjermer L, Bosnic-Anticevich S, Chrystyn H, Papi A, et al. Incidence of oral thrush in patients with COPD prescribed inhaled corticosteroids: Effect of drug, dose, and device.Respir Med. 2016;120:54–63. [DOI] [PubMed]
Buhl R. Local oropharyngeal side effects of inhaled corticosteroids in patients with asthma.Allergy. 2006;61:518–26. [DOI] [PubMed]
Fukushima C, Matsuse H, Tomari S, Obase Y, Miyazaki Y, Shimoda T, et al. Oral candidiasis associated with inhaled corticosteroid use: comparison of fluticasone and beclomethasone.Ann Allergy Asthma Immunol. 2003;90:646–51. [DOI] [PubMed]
Castellana G, Castellana M, Castellana C, Castellana G, Resta E, Carone M, et al. Inhaled Corticosteroids And Risk Of Tuberculosis In Patients With Obstructive Lung Diseases: A Systematic Review And Meta-Analysis Of Non-randomized Studies.Int J Chron Obstruct Pulmon Dis. 2019;14:2219–27. [DOI] [PubMed] [PMC]
Brode SK, Campitelli MA, Kwong JC, Lu H, Marchand-Austin A, Gershon AS, et al. The risk of mycobacterial infections associated with inhaled corticosteroid use.Eur Respir J. 2017;50:1700037. [DOI] [PubMed]
Lee CH, Kim K, Hyun MK, Jang EJ, Lee NR, Yim J. Use of inhaled corticosteroids and the risk of tuberculosis.Thorax. 2013;68:1105–13. [DOI] [PubMed]
Larsson K, Janson C, Lisspers K, Jørgensen L, Stratelis G, Telg G, et al. Combination of budesonide/formoterol more effective than fluticasone/salmeterol in preventing exacerbations in chronic obstructive pulmonary disease: the PATHOS study.J Intern Med. 2013;273:584–94. [DOI] [PubMed]
Suissa S, Patenaude V, Lapi F, Ernst P. Inhaled corticosteroids in COPD and the risk of serious pneumonia.Thorax. 2013;68:1029–36. [DOI] [PubMed] [PMC]
Tashkin DP, Celli B, Senn S, Burkhart D; UPLIFT Study Investigators. A 4-Year Trial of Tiotropium in Chronic Obstructive Pulmonary Disease.N Engl J Med. 2008;359:1543–54. [DOI] [PubMed]
Kew KM, Seniukovich A. Inhaled steroids and risk of pneumonia for chronic obstructive pulmonary disease.Cochrane Database Syst Rev. 2014;2014:CD010115. [DOI] [PubMed] [PMC]
Lee JH, Park YH, Kang DR, Lee SJ, Lee MK, Kim S, et al. Risk of Pneumonia Associated with Inhaled Corticosteroid in Patients with Chronic Obstructive Pulmonary Disease: A Korean Population-Based Study.Int J Chron Obstruct Pulmon Dis. 2020;15:3397–406. [DOI] [PubMed] [PMC]
Zhang Q, Li S, Zhou W, Yang X, Li J, Cao J. Risk of Pneumonia with Different Inhaled Corticosteroids in COPD Patients: A Meta-Analysis.COPD. 2020;17:462–9. [DOI] [PubMed]
Archontakis Barakakis P, Tran T, You JY, Hernandez Romero GJ, Gidwani V, Martinez FJ, et al. High versus Medium Dose of Inhaled Corticosteroid in Chronic Obstructive Lung Disease: A Systematic Review and Meta-Analysis.Int J Chron Obstruct Pulmon Dis. 2023;18:469–82. [DOI] [PubMed] [PMC]
Nagai A. Guidelines for the diagnosis and management of chronic obstructive pulmonary disease: 3rd edition.Nihon Rinsho. 2011;69:1729–34. Japanese. [PubMed]
Dabscheck E, George J, Hermann K, McDonald CF, McDonald VM, McNamara R, et al. COPD-X Australian guidelines for the diagnosis and management of chronic obstructive pulmonary disease: 2022 update.Med J Aust. 2022;217:415–23. [DOI] [PubMed]
Godara N, Godara R, Khullar M. Impact of inhalation therapy on oral health.Lung India. 2011;28:272–5. [DOI] [PubMed] [PMC]
Kargul B, Tanboga I, Ergeneli S, Karakoc F, Dagli E. Inhaler medicament effects on saliva and plaque pH in asthmatic children.J Clin Pediatr Dent. 1998;22:137–40. [PubMed]
Molimard M, Raherison C, Lignot S, Balestra A, Lamarque S, Chartier A, et al. Chronic obstructive pulmonary disease exacerbation and inhaler device handling: real-life assessment of 2935 patients.Eur Respir J. 2017;49:1601794. [DOI] [PubMed]
Tuğrul E. The Relationship Between Inhaler Use and Oral Problems in Patients with COPD and Affecting Factors: A Cross-Sectional Study.Florence Nightingale J Nurs. 2022;30:196–201. [DOI] [PubMed] [PMC]
Roland NJ, Bhalla RK, Earis J. The Local Side Effects of Inhaled Corticosteroids: Current Understanding and Review of the Literature.Chest. 2004;126:213–9. [DOI] [PubMed]
Galván CA, Guarderas JC. Practical Considerations for Dysphonia Caused by Inhaled Corticosteroids.Mayo Clin Proc. 2012;87:901–4. [DOI] [PubMed] [PMC]
Rachelefsky GS, Liao Y, Faruqi R. Impact of inhaled corticosteroid-induced oropharyngeal adverse events: results from a meta-analysis.Ann Allergy Asthma Immunol. 2007;98:225–38. [DOI] [PubMed]
Ishizuka T, Hisada T, Aoki H, Yanagitani N, Kaira K, Utsugi M, et al. Gender and age risks for hoarseness and dysphonia with use of a dry powder fluticasone propionate inhaler in asthma.Allergy Asthma Proc. 2007;28:550–6. [DOI] [PubMed]
Williamson IJ, Matusiewicz SP, Brown PH, Greening AP, Crompton GK. Frequency of voice problems and cough in patients using pressurized aerosol inhaled steroid preparations.Eur Respir J. 1995;8:590–2. [DOI]
Melani AS, Croce S, Fabbri G, Messina M, Bargagli E. Inhaled Corticosteroids in Subjects with Chronic Obstructive Pulmonary Disease: An Old, Unfinished History.Biomolecules. 2024;14:195. [DOI] [PubMed] [PMC]
Toogood JH, Jennings B, Greenway RW, Chuang L. Candidiasis and dysphonia complicating beclomethasone treatment of asthma.J Allergy Clin Immunol. 1980;65:145–53. [DOI] [PubMed]
Yang IA, Clarke MS, Sim EH, Fong KM. Inhaled corticosteroids for stable chronic obstructive pulmonary disease.Cochrane Database Syst Rev. 2012;2012:CD002991. [DOI]
van Boven JF, de Jong-van den Berg LT, Vegter S. Inhaled corticosteroids and the occurrence of oral candidiasis: a prescription sequence symmetry analysis.Drug Saf. 2013;36:231–6. [DOI] [PubMed]
Sulica L. Laryngeal Thrush.Ann Otol Rhinol Laryngol. 2005;114:369–75. [DOI] [PubMed]
Nunes FP, Bishop T, Prasad ML, Madison JM, Kim DY. Laryngeal Candidiasis Mimicking Malignancy.Laryngoscope. 2008;118:1957–9. [DOI] [PubMed]
Aun MV, Ribeiro MR, Costa Garcia CL, Agondi RC, Kalil J, Giavina-Bianchi P. Esophageal Candidiasis—An Adverse Effect of Inhaled Corticosteroids Therapy.J Asthma. 2009;46:399–401. [DOI] [PubMed]
Baeck M, Pilette C, Drieghe J, Goossens A. Allergic contact dermatitis to inhalation corticosteroids.Eur J Dermatol. 2010;20:102–8. [DOI] [PubMed]
García AP, Tovar V, de Barrio M, Villanueva A, Tornero P. Contact allergy to inhaled budesonide.Contact Dermatitis. 2008;59:60–1. [DOI] [PubMed]
Guillot B. Adverse skin reactions to inhaled corticosteroids.Expert Opin Drug Saf. 2002;1:325–9. [DOI] [PubMed]
Baeck M, Goossens A. Patients with airborne sensitization/contact dermatitis from budesonide-containing aerosols ‘by proxy’.Contact Dermatitis. 2009;61:1–8. [DOI] [PubMed]
Lung Health Study Research Group; Wise R, Connett J, Weinmann G, Scanlon P, Skeans M. Effect of Inhaled Triamcinolone on the Decline in Pulmonary Function in Chronic Obstructive Pulmonary Disease.N Engl J Med. 2000;343:1902–9. [DOI] [PubMed]
Burge PS, Calverley PM, Jones PW, Spencer S, Anderson JA, Maslen TK. Randomised, double blind, placebo controlled study of fluticasone propionate in patients with moderate to severe chronic obstructive pulmonary disease: the ISOLDE trial.BMJ. 2000;320:1297–303. [DOI] [PubMed] [PMC]
Cumming RG, Mitchell P, Leeder SR. Use of Inhaled Corticosteroids and the Risk of Cataracts.N Engl J Med. 1997;337:8–14. [DOI] [PubMed]
Wang JJ, Rochtchina E, Tan AG, Cumming RG, Leeder SR, Mitchell P. Use of Inhaled and Oral Corticosteroids and the Long-term Risk of Cataract.Ophthalmology. 2009;116:652–7. [DOI] [PubMed]
Drummond MB, Dasenbrook EC, Pitz MW, Murphy DJ, Fan E. Inhaled Corticosteroids in Patients With Stable Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-analysis.JAMA. 2008;300:2407–16. [DOI] [PubMed] [PMC]
Scanlon PD, Connett JE, Wise RA, Tashkin DP, Madhok T, Skeans M, et al.; Lung Health Study Research Group. Loss of Bone Density with Inhaled Triamcinolone in Lung Health Study II.Am J Respir Crit Care Med. 2004;170:1302–9. [DOI] [PubMed]
Wong CA, Walsh LJ, Smith CJ, Wisniewski AF, Lewis SA, Hubbard R, et al. Inhaled corticosteroid use and bone-mineral density in patients with asthma.Lancet. 2000;355:1399–403. [DOI] [PubMed]
Silva DR, Coelho AC, Dumke A, Valentini JD, de Nunes JN, Stefani CL, et al. Osteoporosis Prevalence and Associated Factors in Patients With COPD: A Cross-Sectional Study.Respir Care. 2011;56:961–8. [DOI] [PubMed]
Romme EA, Geusens P, Lems WF, Rutten EP, Smeenk FW, van den Bergh JP, et al. Fracture prevention in COPD patients; a clinical 5-step approach.Respir Res. 2015;16:32. [DOI] [PubMed] [PMC]
Warrington TP, Bostwick JM. Psychiatric Adverse Effects of Corticosteroids.Mayo Clin Proc. 2006;81:1361–7. [DOI] [PubMed]
Jordan A, Sivapalan P, Eklöf J, Vestergaard JB, Meteran H, Saeed MI, et al. The Association between Use of ICS and Psychiatric Symptoms in Patients with COPD—A Nationwide Cohort Study of 49,500 Patients.Biomedicines. 2021;9:1492. [DOI] [PubMed] [PMC]
Singh M, Agarwal V, Jindal D, Pancham P, Agarwal S, Mani S, et al. Recent Updates on Corticosteroid-Induced Neuropsychiatric Disorders and Theranostic Advancements through Gene Editing Tools.Diagnostics (Basel). 2023;13:337. [DOI] [PubMed] [PMC]
Nasereddin L, Alnajjar O, Bashar H, Abuarab SF, Al-Adwan R, Chellappan DK, et al. Corticosteroid-Induced Psychiatric Disorders: Mechanisms, Outcomes, and Clinical Implications.Diseases. 2024;12:300. [DOI] [PubMed] [PMC]
Alturaymi MA, Almadhi OF, Alageel YS, Bin Dayel M, Alsubayyil MS, Alkhateeb BF. The Association Between Prolonged Use of Oral Corticosteroids and Mental Disorders: Do Steroids Have a Role in Developing Mental Disorders?Cureus. 2023;15:e37627. [DOI] [PubMed] [PMC]
Kang HR, Hong SH, Ha SY, Kim TB, Lee EK. Differences in the risk of mood disorders in patients with asthma-COPD overlap and in patients with COPD alone: a nationwide population-based retrospective cohort study in Korea.Respir Res. 2019;20:80. [DOI] [PubMed] [PMC]
Pandya D, Puttanna A, Balagopal V. Systemic Effects of Inhaled Corticosteroids: An Overview.Open Respir Med J. 2014;8:59–65. [DOI] [PubMed] [PMC]
Jarad NA, Wedzicha JA, Burge PS, Calverley PM. An observational study of inhaled corticosteroid withdrawal in stable chronic obstructive pulmonary disease.ISOLDE Study Group. Respir Med. 1999;93:161–6. [DOI] [PubMed]
van der Valk P, Monninkhof E, van der Palen J, Zielhuis G, van Herwaarden C. Effect of Discontinuation of Inhaled Corticosteroids in Patients with Chronic Obstructive Pulmonary Disease. The COPE Study.Am J Respir Crit Care Med. 2002;166:1358–63. [DOI] [PubMed]
Wouters EF, Postma DS, Fokkens B, Hop WC, Prins J, Kuipers AF, et al.; COSMIC (COPD and Seretide: a Multi-Center Intervention and Characterization) Study Group. Withdrawal of fluticasone propionate from combined salmeterol/fluticasone treatment in patients with COPD causes immediate and sustained disease deterioration: a randomised controlled trial.Thorax. 2005;60:480–7. [DOI] [PubMed] [PMC]
Choudhury AB, Dawson CM, Kilvington HE, Eldridge S, James WY, Wedzicha JA, et al. Withdrawal of inhaled corticosteroids in people with COPD in primary care: a randomised controlled trial.Respir Res. 2007;8:93. [DOI] [PubMed] [PMC]
Magnussen H, Disse B, Rodriguez-Roisin R, Kirsten A, Watz H, Tetzlaff K, et al.; WISDOM Investigators. Withdrawal of Inhaled Glucocorticoids and Exacerbations of COPD.N Engl J Med. 2014;371:1285–94. [DOI] [PubMed]
Magnussen H, Tetzlaff K, Bateman ED, Watz H, Kirsten AM, Wouters EFM, et al. Lung function changes over time following withdrawal of inhaled corticosteroids in patients with severe COPD.Eur Respir J. 2016;47:651–4. [DOI] [PubMed]
Chapman KR, Hurst JR, Frent SM, Larbig M, Fogel R, Guerin T, et al. Long-Term Triple Therapy De-escalation to Indacaterol/Glycopyrronium in Patients with Chronic Obstructive Pulmonary Disease (SUNSET): A Randomized, Double-Blind, Triple-Dummy Clinical Trial.Am J Respir Crit Care Med. 2018;198:329–39. [DOI] [PubMed]
Myers TR. Guidelines for asthma management: a review and comparison of 5 current guidelines.Respir Care. 2008;53:751–67: discussion 767. [PubMed]
Holt S, Suder A, Weatherall M, Cheng S, Shirtcliffe P, Beasley R. Dose-response relation of inhaled fluticasone propionate in adolescents and adults with asthma: meta-analysis.BMJ. 2001;323:253–6. [DOI] [PubMed] [PMC]
Ingelf J, Ekelund J, Carlsson LG. Meta-analysis on dose-response relationship of inhaled steroids must be done in homogenous asthma populations.Eur Respir J. 2004;24:513. [DOI] [PubMed]
Chipps B, Taylor B, Bayer V, Shaikh A, Mosnaim G, Trevor J, et al. Relative efficacy and safety of inhaled corticosteroids in patients with asthma: Systematic review and network meta-analysis.Ann Allergy Asthma Immunol. 2020;125:163–70.e3. [DOI] [PubMed]
Bloom CI, de Preux L, Sheikh A, Quint JK. Health and cost impact of stepping down asthma medication for UK patients, 2001-2017: A population-based observational study.PLoS Med. 2020;17:e1003145. [DOI] [PubMed] [PMC]
Marks GB, Correll PK, Williamson M. Asthma in Australia 2005.Med J Aust. 2005;183:445–6. [DOI] [PubMed]
Covvey JR, Johnston BF, Wood F, Boyter AC. Changes to inhaled corticosteroid dose when initiating combination inhaler therapy in long-acting β agonist-naïve patients with asthma: a retrospective database analysis.Thorax. 2014;69:1056–8. [DOI] [PubMed]
Daley-Yates PT. Inhaled corticosteroids: potency, dose equivalence and therapeutic index.Br J Clin Pharmacol. 2015;80:372–80. [DOI] [PubMed] [PMC]
Oakley RH, Cidlowski JA. The biology of the glucocorticoid receptor: new signaling mechanisms in health and disease.J Allergy Clin Immunol. 2013;132:1033–44. [DOI] [PubMed] [PMC]
Barnes PJ. Corticosteroid effects on cell signalling.Eur Respir J. 2006;27:413–26. [DOI] [PubMed]
Clark AR. MAP kinase phosphatase 1: a novel mediator of biological effects of glucocorticoids?J Endocrinol. 2003;178:5–12. [DOI] [PubMed]
Dostert A, Heinzel T. Negative Glucocorticoid Receptor Response Elements and their Role in Glucocorticoid Action.Curr Pharm Des. 2004;10:2807–16. [DOI] [PubMed]
Lewis-Tuffin LJ, Cidlowski JA. The Physiology of Human Glucocorticoid Receptor β (hGRβ) and Glucocorticoid Resistance.Ann N Y Acad Sci. 2006;1069:1–9. [DOI] [PubMed]
Ito K, Barnes PJ, Adcock IM. Glucocorticoid Receptor Recruitment of Histone Deacetylase 2 Inhibits Interleukin-1β-Induced Histone H4 Acetylation on Lysines 8 and 12.Mol Cell Biol. 2000;20:6891–903. [DOI] [PubMed] [PMC]
Charmandari E, Kino T, Chrousos GP. Familial/Sporadic Glucocorticoid Resistance: Clinical Phenotype and Molecular Mechanisms.Ann N Y Acad Sci. 2004;1024:168–81. [DOI] [PubMed]
Chung KF, Wenzel SE, Brozek JL, Bush A, Castro M, Sterk PJ, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma.Eur Respir J. 2014;43:343–73. [DOI] [PubMed]
Papi A, Contoli M, Adcock IM, Bellettato C, Padovani A, Casolari P, et al. Rhinovirus infection causes steroid resistance in airway epithelium through nuclear factor κB and c-Jun N-terminal kinase activation.J Allergy Clin Immunol. 2013;132:1075–85.e6. [DOI] [PubMed]
Huang YJ, Nariya S, Harris JM, Lynch SV, Choy DF, Arron JR, et al. The airway microbiome in patients with severe asthma: Associations with disease features and severity.J Allergy Clin Immunol. 2015;136:874–84. [DOI] [PubMed] [PMC]
Liang Z, Zhang Q, Thomas CM, Chana KK, Gibeon D, Barnes PJ, et al. Impaired macrophage phagocytosis of bacteria in severe asthma.Respir Res. 2014;15:72. [DOI] [PubMed] [PMC]
Okamoto K, Tanaka H, Ogawa H, Makino Y, Eguchi H, Hayashi S, et al. Redox-dependent Regulation of Nuclear Import of the Glucocorticoid Receptor.J Biol Chem. 1999;274:10363–71. [DOI] [PubMed]
Robinson DS, Campbell DA, Durham SR, Pfeffer J, Barnes PJ, Chung KF, et al.; Asthma and Allergy Research Group of the National Heart and Lung Institute. Systematic assessment of difficult-to-treat asthma.Eur Respir J. 2003;22:478–83. [DOI] [PubMed]
Silkoff PE, Moore WC, Sterk PJ. Three Major Efforts to Phenotype Asthma: Severe Asthma Research Program, Asthma Disease Endotyping for Personalized Therapeutics, and Unbiased Biomarkers for the Prediction of Respiratory Disease Outcome.Clin Chest Med. 2019;40:13–28. [DOI] [PubMed]
Brown PH, Teelucksingh S, Matusiewicz SP, Greening AP, Crompton GK, Edwards CR. Cutaneous vasoconstrictor response to glucocorticoids in asthma.Lancet. 1991;337:576–80. [DOI] [PubMed]
Lane SJ, Vaja S, Swaminathan R, Lee TH. Effects of prednisolone on bone turnover in patients with corticosteroid resistant asthma.Clin Exp Allergy. 1996;26:1197–201. [PubMed]
Heaney LG, Busby J, Bradding P, Chaudhuri R, Mansur AH, Niven R, et al. Remotely Monitored Therapy and Nitric Oxide Suppression Identifies Nonadherence in Severe Asthma.Am J Respir Crit Care Med. 2019;199:454–64. [DOI] [PubMed]
Dweik RA, Boggs PB, Erzurum SC, Irvin CG, Leigh MW, Lundberg JO, et al.; American Thoracic Society Committee on Interpretation of Exhaled Nitric Oxide Levels (FENO) for Clinical Applications. An Official ATS Clinical Practice Guideline: Interpretation of Exhaled Nitric Oxide Levels (FeNO) for Clinical Applications.Am J Respir Crit Care Med. 2011;184:602–15. [DOI] [PubMed] [PMC]
Khatri SB, Iaccarino JM, Barochia A, Soghier I, Akuthota P, Brady A, et al. Use of Fractional Exhaled Nitric Oxide to Guide the Treatment of Asthma: An Official American Thoracic Society Clinical Practice Guideline.Am J Respir Crit Care Med. 2021;204:e97–109. [DOI] [PubMed] [PMC]
Bourdin A, Bjermer L, Brightling C, Brusselle GG, Chanez P, Chung KF, et al. ERS/EAACI statement on severe exacerbations in asthma in adults: facts, priorities and key research questions.Eur Respir J. 2019;54:1900900. [DOI] [PubMed]
Bourdin A, Adcock I, Berger P, Bonniaud P, Chanson P, Chenivesse C, et al. How can we minimise the use of regular oral corticosteroids in asthma?Eur Respir Rev. 2020;29:190085. [DOI] [PubMed] [PMC]
Dvorin EL, Ebell MH. Short-Term Systemic Corticosteroids: Appropriate Use in Primary Care.Am Fam Physician. 2020;101:89–94. [PubMed]
Israel E, Banerjee TR, Fitzmaurice GM, Kotlov TV, LaHive K, LeBoff MS. Effects of inhaled glucocorticoids on bone density in premenopausal women.N Engl J Med. 2001;345:941–7. [DOI] [PubMed]
Agertoft L, Pedersen S. Effects of long-term treatment with an inhaled corticosteroid on growth and pulmonary function in asthmatic children.Respir Med. 1994;88:373–81. [DOI] [PubMed]
Johnson M. Pharmacodynamics and pharmacokinetics of inhaled glucocorticoids.J Allergy Clin Immunol. 1996;97:169–76. [DOI] [PubMed]
Ayres JG, Bateman ED, Lundbäck B, Harris TA. High dose fluticasone propionate, 1 mg daily, versus fluticasone propionate, 2 mg daily, or budesonide, 1.6 mg daily, in patients with chronic severe asthma. International Study Group.Eur Respir J. 1995;8:579–86. [PubMed]
Demoly P, Jaffuel D, Mathieu M, Sahla H, Godard P, Michel FB, et al. Glucocorticoid insensitive asthma: a one year clinical follow up pilot study.Thorax. 1998;53:1063–5. [DOI] [PubMed] [PMC]
Heffler E, Madeira LNG, Ferrando M, Puggioni F, Racca F, Malvezzi L, et al. Inhaled Corticosteroids Safety and Adverse Effects in Patients with Asthma.J Allergy Clin Immunol Pract. 2018;6:776–81. [DOI] [PubMed]
Aljebab F, Choonara I, Conroy S. Systematic review of the toxicity of short-course oral corticosteroids in children.Arch Dis Child. 2016;101:365–70. [DOI] [PubMed] [PMC]
Sweeney J, Patterson CC, Menzies-Gow A, Niven RM, Mansur AH, Bucknall C, et al. Comorbidity in severe asthma requiring systemic corticosteroid therapy: cross-sectional data from the Optimum Patient Care Research Database and the British Thoracic Difficult Asthma Registry.Thorax. 2016;71:339–46. [DOI] [PubMed]
Ekström M, Nwaru BI, Hasvold P, Wiklund F, Telg G, Janson C. Oral corticosteroid use, morbidity and mortality in asthma: A nationwide prospective cohort study in Sweden.Allergy. 2019;74:2181–90. [DOI] [PubMed] [PMC]
Bourdin A, Molinari N, Vachier I, Pahus L, Suehs C, Chanez P. Mortality: a neglected outcome in OCS-treated severe asthma.Eur Respir J. 2017;50:1701486. [DOI] [PubMed]
Bourdin A, Fabry-Vendrand C, Ostinelli J, Ait-Yahia M, Darnal E, Bouee S, et al. The Burden of Severe Asthma in France: A Case-Control Study Using a Medical Claims Database.J Allergy Clin Immunol Pract. 2019;7:1477–87. [DOI] [PubMed]
Matsumoto H, Ishihara K, Hasegawa T, Umeda B, Niimi A, Hino M. Effects of Inhaled Corticosteroid and Short Courses of Oral Corticosteroids on Bone Mineral Density in Asthmatic Patients: A 4-Year Longitudinal Study.Chest. 2001;120:1468–73. [DOI] [PubMed]
Price DB, Trudo F, Voorham J, Xu X, Kerkhof M, Ling Zhi Jie J, et al. Adverse outcomes from initiation of systemic corticosteroids for asthma: long-term observational study.J Asthma Allergy. 2018;11:193–204. [DOI] [PubMed] [PMC]
Sullivan PW, Ghushchyan VH, Globe G, Schatz M. Oral corticosteroid exposure and adverse effects in asthmatic patients.J Allergy Clin Immunol. 2018;141:110–6.e7. [DOI] [PubMed]
Voorham J, Xu X, Price DB, Golam S, Davis J, Zhi Jie Ling J, et al. Healthcare resource utilization and costs associated with incremental systemic corticosteroid exposure in asthma.Allergy. 2019;74:273–83. [DOI] [PubMed] [PMC]
Ross SA, Dzida G, Vora J, Khunti K, Kaiser M, Ligthelm RJ. Impact of weight gain on outcomes in type 2 diabetes.Curr Med Res Opin. 2011;27:1431–8. [DOI] [PubMed]
Kelly HW, Natta MLV, Covar RA, Tonascia J, Green RP, Strunk RC, et al.; CAMP Research Group. Effect of Long-term Corticosteroid Use on Bone Mineral Density in Children: A Prospective Longitudinal Assessment in the Childhood Asthma Management Program (CAMP) Study.Pediatrics. 2008;122:e53–61. [DOI] [PubMed] [PMC]
El-Dorry G, Ashry H, Ibrahim T, Elias T, Alzaree F. Bone Density, Osteocalcin and Deoxypyridinoline for Early Detection of Osteoporosis in Obese Children.Open Access Maced J Med Sci. 2015;3:413–9. [DOI] [PubMed] [PMC]
Ducharme FM, Chabot G, Polychronakos C, Glorieux F, Mazer B. Safety Profile of Frequent Short Courses of Oral Glucocorticoids in Acute Pediatric Asthma: Impact on Bone Metabolism, Bone Density, and Adrenal Function.Pediatrics. 2003;111:376–83. [DOI] [PubMed]
Price D, Castro M, Bourdin A, Fucile S, Altman P. Short-course systemic corticosteroids in asthma: striking the balance between efficacy and safety.Eur Respir Rev. 2020;29:190151. [DOI] [PubMed] [PMC]
Amelink M, Hashimoto S, Spinhoven P, Pasma HR, Sterk PJ, Bel EH, et al. Anxiety, depression and personality traits in severe, prednisone-dependent asthma.Respir Med. 2014;108:438–44. [DOI] [PubMed]
Kemp JP, Osur S, Shrewsbury SB, Herje NE, Duke SP, Harding SM, et al. Potential Effects of Fluticasone Propionate on Bone Mineral Density in Patients With Asthma: A 2-Year Randomized, Double-Blind, Placebo-Controlled Trial.Mayo Clin Proc. 2004;79:458–66. [DOI] [PubMed]
Tattersfield AE, Town GI, Johnell O, Picado C, Aubier M, Braillon P, et al. Bone mineral density in subjects with mild asthma randomised to treatment with inhaled corticosteroids or non-corticosteroid treatment for two years.Thorax. 2001;56:272–8. [DOI] [PubMed] [PMC]
Sosa M, Saavedra P, Valero C, Guañabens N, Nogués X, Pino-Montes Jd, et al.; GIUMO Study Group. Inhaled Steroids Do Not Decrease Bone Mineral Density But Increase Risk of Fractures: Data from the GIUMO Study Group.J Clin Densitom. 2006;9:154–8. [DOI] [PubMed]
Langhammer A, Norjavaara E, de Verdier MG, Johnsen R, Bjermer L. Use of inhaled corticosteroids and bone mineral density in a population based study: the Nord-Trøndelag Health Study (the HUNT Study).Pharmacoepidemiol Drug Saf. 2004;13:569–79. [DOI] [PubMed]
Sasagawa M, Hasegawa T, Kazama JJ, Koya T, Sakagami T, Suzuki K, et al. Assessment of Bone Status in Inhaled Corticosteroid User Asthmatic Patients with an Ultrasound Measurement Method.Allergol Int. 2011;60:459–65. [DOI] [PubMed]
McKeever T, Harrison TW, Hubbard R, Shaw D. Inhaled Corticosteroids and the Risk of Pneumonia in People With Asthma: A Case-Control Study.Chest. 2013;144:1788–94. [DOI] [PubMed]
Qian CJ, Coulombe J, Suissa S, Ernst P. Pneumonia risk in asthma patients using inhaled corticosteroids: a quasi-cohort study.Br J Clin Pharmacol. 2017;83:2077–86. [DOI] [PubMed] [PMC]
Kim MH, Rhee CK, Shim JS, Park SY, Yoo KH, Kim BY, et al. Inhaled Corticosteroids in Asthma and the Risk of Pneumonia.Allergy Asthma Immunol Res. 2019;11:795–805. [DOI] [PubMed] [PMC]
Smeeth L, Boulis M, Hubbard R, Fletcher AE. A population based case-control study of cataract and inhaled corticosteroids.Br J Ophthalmol. 2003;87:1247–51. [DOI] [PubMed] [PMC]
Gani F, Caminati M, Bellavia F, Baroso A, Faccioni P, Pancera P, et al. Oral health in asthmatic patients: a review: Asthma and its therapy may impact on oral health.Clin Mol Allergy. 2020;18:22. [DOI] [PubMed] [PMC]
Arafa A, Aldahlawi S, Fathi A. Assessment of the oral health status of asthmatic children.Eur J Dent. 2017;11:357–63. [DOI] [PubMed] [PMC]
Sag C, Ozden FO, Acikgoz G, Anlar FY. The effects of combination treatment with a long-acting β2-agonist and a corticosteroid on salivary flow rate, secretory immunoglobulin A, and oral health in children and adolescents with moderate asthma: a 1-month, single-blind clinical study.Clin Ther. 2007;29:2236–42. [DOI] [PubMed]
del-Río-Navarro BE, Corona-Hernández L, Fragoso-Ríos R, Berber A, Torres-Alcántara S, Cuairán-Ruidíaz V, et al. Effect of salmeterol and salmeterol plus beclomethasone on saliva flow and IgA in patients with moderate-persistent chronic asthma.Ann Allergy Asthma Immunol. 2001;87:420–3. [DOI] [PubMed]