Intermittent and mild persistent asthma: how therapy has changed
Keywords:
Allergy, asthma control, asthma exacerbations, asthma severity, children, inhaled corticosteroids, GINA, pediatric asthma, type 2 inflammationAbstract
In the last few years much attention has been focused on research on severe asthma and the role of biologicals in its treatment, also in children. However, mild asthma is way more common in childhood and still causes as many as 30-40% of asthma exacerbations requiring emergency consultation. The management of “intermittent” and “mild persistent” asthma phenotypes is still a matter of debate, even if the role of inhaled corticosteroids, both continuous and intermittent, is a cornerstone in this field. Nevertheless, updates on the strategies to manage these patients are coming, since evidence emerged on the role of inflammation also in these asthma phenotypes as well as on the potential side effect and risks of short-acting beta 2 agonists overuse, which is common in patients for which they have been prescribed as the only as-needed treatment. Unsurprisingly, international guidelines, including GINA, are starting to recommend associating a corticosteroid when using a reliver. In this paper we overview the (r)evolution regarding the management of intermittent and mild persistent asthma. We also focus on the importance of knowing the chemical and physical characteristics of drugs and inhaler devices in order to optimize the treatment and reach the distal airways, as well as of trying to achieve a good compliance to treatments, especially in adolescents, for which it is currently possible to rely also on new digital health technologies.
References
Dusser D, Montani D, Chanez P, et al. Mild asthma: an expert review on epidemiology, clinical characteristics and treatment recommendations. Allergy 2007;62:591-604.
Hancox RJ, Cowan JO, Flannery EM, Herbison GP, McLachlan CR, Taylor DR. Bronchodilator tolerance and rebound bronchoconstriction during regular inhaled beta-agonist treatment. Respir Med 2000;94:767-71.
Stanford RH, Shah MB, D’Souza AO, Dhamane AD, Schatz M. Short acting-beta-agonist use and its ability to predict future asthma-related outcomes. Ann Allergy Asthma Immunol 2012;109:403-7.
Martinez FD, Chinchilli VM, Morgan WJ, et al. Use of beclomethasone dipropionate as rescue treatment for children with mild persistent asthma (TREXA): a randomized, double-blind, placebo-controlled trial. Lancet 2011;377:650-7.
Licari A, Marseglia G, Tosca MA, Ciprandi G. Asthma control in children and adolescents: a study in clinical practice. J Asthma 2020;57:645-7.
Tosca MA, Marseglia GL, Ciprandi G. The real-world “ControL’Asma" study: a national taskforce on asthma control in children and adolescents. Allergol Immunopathol (Madr) 2021;49:32-9.
Braido F, Brusselle G, Guastalla D, et al. Determinants and impact of suboptimal asthma control in Europe: the international cross-sectional and longitudinal assessment on asthma control (LIAISON) study. Respir Res 2016;17:51.
Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention 2021. Available at: www.ginasthma.org. Accessed on August 4, 2021.
Asher MI, Montefort S, Björkstén B, et al. Worldwide time trends in the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and eczema in childhood: ISAAC Phases One and Three repeat multicountry cross-sectional surveys. Lancet 2006;368:733-43.
Gibson GJ, Loddenkemper R, Sibille Y, Lundbäck B. European lung white book- respiratory health and disease in europe. Available at https://www.ers-education.org. Accessed on August 4, 2021.
Baldacci S, Simoni M, Maio S, et al. Prescriptive adherence to GINA guidelines and asthma control: An Italian cross-sectional study in general practice. Respir Med 2019;146:10-17.
Rabe KF, Adachi M, Lai CK, et al. Worldwide severity and control of asthma in children and adults: the global asthma insights and reality surveys. J Allergy Clin Immunol 2004;114:40-47.
Zureik M, Neukirch C, Leynaert B, Liard R, Bousquet J, Neukirch F. Sensitisation to airborne moulds and severity of asthma: cross-sectional study from European Community respiratory health survey. Br Med J 2002;325:411-14.
Firoozi F, Lemière C, Beauchesne MF, Forget A, Blais L. Development and validation of database indexes of asthma severity and control. Thorax 2007;62:581-87.
Com-Ruelle L, Crestin B, Dumesnil S. L’asthme en France selon les stades de sévérité. Paris: CREDES 2000;1290.
Liard R, Leynaert B, Zureik M, Beguin FX, Neukirch F. Using global initiative for asthma guidelines to assess asthma severity in populations. Eur Respir J 2000;16:615-20.
Kalayci O, Abdelateef H, Pozo Beltrán CF, et al. Challenges and choices in the pharmacological treatment of non-severe pediatric asthma: a commentary for the practicing physician. World Allergy Organ J 2019;12:100054.
Prosperi MC, Sahiner UM, Belgrave D, et al. Challenges in identifying asthma subgroups using unsupervised statistical learning techniques. Am J Respir Crit Care Med 2013;188:1303-12.
Deliu M, Yavuz TS, Sperrin M, et al. Features of asthma which provide meaningful insights for understanding the disease heterogeneity. Clin Exp Allergy 2018;48:39-47.
Deliu M, Belgrave D, Sperrin M, Buchan I, Custovic A. Asthma phenotypes in childhood. expert Rev Clin Immunol 2017;13:705-13.
Ferrante G, La Grutta S. The burden of pediatric asthma. Frontiers in Pediatrics 2018;6:186.
Bateman ED, Reddel HK, O'Byrne PM, et al. As needed budesonide-formoterol versus maintenance budesonide in mild asthma. N Engl J Med 2018;378:1877-87.
Barnes CB, Ulrik CS. Asthma and adherence to inhaled corticosteroids: current status and future perspectives. Respir Care 2015;60:455-68.
Beasley R, Weatherall M, Shirtcliffe P, Hancox R, Reddel HK. Combination corticosteroid/beta-agonist inhaler as reliever therapy: a solution for intermittent and mild asthma? J Allergy Clin Immunol 2014;133:39-41.
Muneswarao J, Hassali MA, Ibrahim B, Saini B, Ali IAH, Verma AK. It is time to change the way we manage mild asthma: an update in GINA 2019. Respir Res 2019;20:183.
O'Byrne PM, Jenkins C, Bateman ED. The paradoxes of asthma management: time for a new approach? Eur Respir J 2017;50:1701103.
Wardlaw AJ, Dunnette S, Gleich GJ, Collins JV, Kay AB. Eosinophils and mast cells in bronchoalveolar lavage in subjects with mild asthma. Relationship to bronchial hyperreactivity. Am Rev Respir Dis 1988;137:62-69.
Foresi A, Bertorelli G, Pesci A, Chetta A, Olivieri D. Inflammatory markers in bronchoalveolar lavage and in bronchial biopsy in asthma during remission. Chest 1990;98:528-35.
Suissa S, Ernst P, Boivin JF, et al. A cohort analysis of excess mortality in asthma and the use of inhaled beta-agonists. Am J Respir Crit Care Med 1994;149:604-10.
Abramson MJ, Bailey MJ, Couper FJ, et al. Are asthma medications and management related to deaths from asthma? Am J Respir Crit Care Med 2001;163:12-8.
Drazen JM, Israel E, Boushey HA, et al. Comparison of regularly scheduled with as-needed use of albuterol in mild asthma. Asthma Clinical Research Network. N Engl J Med 1996;335:841-47.
Dennis SM, Sharp SJ, Vickers MR, et al. Regular inhaled salbutamol and asthma control: the TRUST randomised trial. Therapy working group of the National Asthma Task Force and the mrc general practice research framework. Lancet 2000;355:1675-79.
Suissa S, Ernst P, Benayoun S, Baltzan M, Cai B. Low-dose inhaled corticosteroids and the prevention of death from asthma. N Engl J Med 2000;343:332-36.
Suissa S, Ernst P, Kezouh A. Regular use of inhaled corticosteroids and the long-term prevention of hospitalisation for asthma. Thorax 2002;57:880-84.
Billington CK, Penn RB, Hall IP. Beta(2) agonists. Handb Exp Pharmacol 2017;237:23-40.
Magee JS, Pittman LM, Jette-Kelly LA. Paradoxical bronchoconstriction with short-acting beta agonist. Am J Case Rep 2018;19:1204-07.
Papi A, Canonica GW, Maestrelli P, et al. Rescue use of beclomethasone and albuterol in a single inhaler for mild asthma. N Engl J Med 2007;356:2040-52.
Nelson HS, Weiss ST, Bleecker ER, Yancey SW, Dorinsky PM. The salmeterol multicenter asthma research trial: a comparison of usual pharmacotherapy for asthma or usual pharmacotherapy plus salmeterol. Chest 2006;129:15-26.
Martin MJ, Harrison TW. Is it time to move away from short-acting beta agonists in asthma management? Eur Respir J 2019;53:1802223.
Royal College of Physicians. Why asthma still kills: the national review of asthma deaths (NRAD) confidential enquiry report 2014. Available at: https://www.asthma.org.uk/globalassets/campaigns/nrad-full-report.pdf. Accessed on August 4, 2021.
O'Byrne PM, FitzGerald JM, Bateman ED, et al. Inhaled combined budesonide-formoterol as needed in mild asthma. N Engl J Med 2018;378:1865-76.
Domingo C, Rello J, Sogo A. As-needed ICS-LABA in mild asthma: what does the evidence say? Drugs 2019;79:1729-37.
Fingleton J, Hardy J, Baggott C, et al. Description of the protocol for the PRACTICAL study: a randomised controlled trial of the efficacy and safety of ICS/LABA reliever therapy in asthma. BMJ Open Resp Res 2017;4:e000217.
Beasley R, Holliday M, Reddel HK, et al. Controlled trial of budesonide–formoterol as needed for mild asthma. N Engl J Med 2019;380:2020-30.
Pavord ID, Beasley R, Agusti A, et al. After asthma – redefining airways diseases. A Lancet commission. Lancet 2018;391:350-400.
Kuruvilla ME, Lee FE, Lee GB. Understanding asthma phenotypes, endotypes, and mechanisms of disease. Clin Rev Allergy Immunol 2019;56:219-33.
Fainardi V, Santoro A, Caffarelli C. Preschool wheezing: Trajectories and long-term treatment. Front Pediatr 2020;8:240
Di Cicco M, D'Elios S, Peroni DG, Comberiati P. The role of atopy in asthma development and persistence. Curr Opin Allergy Clin Immunol 2020;20:131-37.
Licari A, Manti S, Marseglia A, et al. Biologics in children with allergic diseases. Curr Pediatr Rev 2020;16:140-7.
Rodriguez-Martinez CE, Sossa-Briceño MP, Castro-Rodriguez JA. Predictors of response to medications for asthma in pediatric patients: a systematic review of the literature. Pediatr Pulmonol 2020;55:1320-31.
Fitzpatrick AM, Bacharier LB, Jackson DJ, et al. Heterogeneity of mild to moderate persistent asthma in children: confirmation by latent class analysis and association with 1-year outcomes. J Allergy Clin Immunol Pract 2020;8:2617-27.
Teach SJ, Gergen PJ, Szefler SJ, et al. Seasonal risk factors for asthma exacerbations among inner-city children. J Allergy Clin Immunol 2015;135:1465-24.
Hoch HE, Calatroni A, West JB, et al. Can we predict fall asthma exacerbations? Validation of the seasonal asthma exacerbation index. J Allergy Clin Immunol 2017;140:1130-7.
Hamid, Song Y, Kotsimbos TC, Minshall E, et al. Inflammation of small airways in asthma. J Allergy Clin Immunol 1997;100:44-51.
Usmani OS. Treating the small airways. Respiration 2012;84:441-53.
Nave R, Mueller H. From inhaler to lung: clinical implications of the formulations of ciclesonide and other inhaled corticosteroids. Int J Gen Med 2013;6:99-107.
Laube BL, Janssens HM, de Jongh FHC, Devadason SG, Dhand R, Diot P. What the pulmonary specialist should know about the new inhalation therapies. Eur Respir J 2011;37:1308-417.
Dolovich MB, Dhand R. Aerosol drug delivery developments in device design and clinical use. Lancet 2011;377:1032-45.
Lavorini F, Pedersen S, Usmani OS. Aerosol Drug Management Improvement Team (ADMIT). Dilemmas, confusion, and misconceptions related to small airways directed therapy. Chest 2017;151:1345-55.
Usmani OS. Small airway disease in asthma pharmacological considerations. Curr Opin Pulm Med 2015;21:55-67.
Hatley RHM, Parker J, Pritchard JN, von Hollen D. Variability in delivered dose from pressurized metered-dose inhaler formulations due to a delay between shake and fire. J Aerosol Med Pulm Drug Deliv 2017;30:71-9.
Acerbi D, Brambilla G, Kottakis I. Advances in asthma and COPD management: delivering CFC-free inhaled therapy using Modulite technology. Pulm Pharmacol Ther 2007;20:290-303.
Iwanaga T, Tohda Y, Nakamura S, Suga Y. The Respimat ® Soft Mist Inhaler: implications of drug delivery characteristics for patients. Clin Drug Investig 2019;39:1021-30.
Papadopoulos NG, Čustović A, Cabana MD, et al. Pediatric asthma: an unmet need for more effective, focused treatments. Pediatr Allergy Immunol 2019;30:7-16.
Kagen S, Garland A. Asthma and Allergy Mobile Apps in 2018. Curr Allergy Asthma Rep 2019;19:6.
Ferrante G, Licari A, Marseglia GL, La Grutta S. Digital health interventions in children with asthma. Clin Exp Allergy 2021;51:212-20.
Matricardi PM, Dramburg S, Alvarez-Perea A, et al. The role of mobile health technologies in allergy care: an EAACI position paper. Allergy 2020;75:259-72.
Downloads
Published
License
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Transfer of Copyright and Permission to Reproduce Parts of Published Papers.
Authors retain the copyright for their published work. No formal permission will be required to reproduce parts (tables or illustrations) of published papers, provided the source is quoted appropriately and reproduction has no commercial intent. Reproductions with commercial intent will require written permission and payment of royalties.
How to Cite
