medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/ms2026-121medsovet-10245Research ArticleХРОНИЧЕСКИЕ ЗАБОЛЕВАНИЯ ЛЕГКИХCHRONIC PULMONARY DISEASESВозможности экстрамелкодисперсной комбинации беклометазона дипропионата/гликопиррония бромида/формотерола фумарата в терапии тяжелой бронхиальной астмыPotential for the extrafine combination of beclomethasone dipropionate, glycopyrronium bromide and formoterol fumarate in the treatment of severe bronchial asthmahttps://orcid.org/0000-0003-2742-3794ТрофименкоИ. Н.TrofimenkoI. N.

Трофименко Ирина Николаевна - д.м.н., доцент, заведующая кафедрой клинической аллергологии и пульмонологии.

664049, Иркутск, микрорайон Юбилейный, д. 100

Irina N. Trofimenko - Dr. Sci. (Med.), Assistant Professor, Head of Department of Clinical Allergology and Pulmonology.

100, Microdistrict Yubileynyy, Irkutsk, 664049

tin11@mail.ruhttps://orcid.org/0000-0003-3702-9635ИвановА. Ф.IvanovA. F.

Иванов Александр Федорович - к.м.н., доцент кафедры клинической аллергологии и пульмонологии.

664049, Иркутск, микрорайон Юбилейный, д. 100

Aleksandr F. Ivanov - Cand. Sci. (Med.), Assistant Professor of the Department of Clinical Allergology and Pulmonology.

100, Microdistrict Yubileynyy, Irkutsk, 664049

afivanov@rambler.ruhttps://orcid.org/0000-0003-4340-4278НашатыреваМ. С.NashatyrevaM. S.

Нашатырева Мария Сергеевна - к.м.н., ассистент кафедры пропедевтики внутренних болезней.

664003, Иркутск, ул. Красного Восстания, д. 1

Maria S. Nashatyreva - Cand. Sci. (Med.), Assistant of the Department of Propaedeutics of Internal Diseases.

1 Krasnogo Vosstaniya St., Irkutsk, 664003

volga-89@list.ruИркутская государственная медицинская академия последипломного образованияРоссияIrkutsk State Medical Academy of Postgraduate EducationRussian FederationИркутский государственный медицинский университетРоссияIrkutsk State Medical UniversityRussian Federation202614072026091017Copyright © Трофименко И.Н., Иванов А.Ф., Нашатырева М.С., 20262026Трофименко И.Н., Иванов А.Ф., Нашатырева М.С.Trofimenko I.N., Ivanov A.F., Nashatyreva M.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/10245

Тяжелая бронхиальная астма (ТБА) остается сложной клинической проблемой, ассоциированной со значительным бременем заболевания, частыми обострениями и снижением качества жизни. Несмотря на современные возможности контролирующей ингаляционной терапии высокими дозами ингаляционных глюкокортикостероидов (ИГКС) в комбинации с бета-2-агонистами длительного действия (ДДБА), у значительной части пациентов с ТБА контроля над заболеванием достигнуть не удается. В течение последнего десятилетия произошел кардинальный пересмотр роли тройной ингаляционной терапии, включающей ИГКС, ДДБА и антихолинергический препарат длительного действия (ДДАХ). Систематический поиск проведен в электронных базах данных PubMed, Web of Science, Меdline. Данные рандомизированных контролируемых исследований, метаанализов и реальной клинической практики показывают, что тройная терапия экстрамелкодисперсной комбинацией беклометазона дипропионата, гликопиррония бромида и формотерола фумарата (БДП/ГБ/Фор) способствует существенному улучшению течения БА, достоверно чаще приводит к нормализации ограничения воздушного потока у пациентов с астмой по сравнению с двойной терапией ИГКС/ДДБА, уменьшая выраженность легочной гиперинфляции, что ассоциируется с улучшением контроля БА и качества жизни, а также снижением риска обострений. Важным аспектом лечения ТБА является определение того, может ли тройная терапия отсрочить необходимость назначения биологических препаратов при неконтролируемой ТБА. Анализ проведенных исследований показывает, что тройная экстрамелкодисперсная комбинация БДП/ГБ/Фор не только улучшает функцию легких и снижает риск обострений, но и воздействует на воспаление, ремоделирование дыхательных путей (ДП), снижая выраженность дисфункции малых ДП и потребность в назначении генно-инженерных биологических препаратов (ГИБП) при ТБА. Если изначально тройная комбинация рассматривалась как опция выбора перед назначением ГИБП, то данные современных исследований и пересмотр международных рекомендаций Global Initiative for Asthma (GINA) позиционируют ее как необходимый и рациональный шаг для абсолютного большинства пациентов с ТБА.

Severe bronchial asthma (SBA) remains a challenging clinical problem associated with a significant disease burden, frequent exacerbations, and a worsened quality of life. Despite modern inhaled therapy options, including high doses of inhaled glucocorticosteroids (ICS) in combination with long-acting beta-2 agonists (LABAs), a large number of patients remain inadequately controlled. In recent years, one therapeutic advance in severe asthma has been the introduction of triple-inhaler therapy combining ICS, long-acting beta-agonists (LABAs), and long-acting muscarinic antagonists (LAMAs). An important question in the management of severe asthma is whether triple therapy can delay or eliminate the need for biological agents. A systematic search was performed in the electronic databases PubMed, Web of Science, and Medline. The findings revealed that extrafine beclomethasone – formoterol – glycopyrronium significantly improved lung function, reduced the risk of asthma worsening and the occurrence of exacerbations, and allowed patients to achieve sustained disease control without biological therapy. This was accompanied by significant improvements in symptoms, small airway function, and peripheral inflammation. Consequently, the inhaled triple combination ICS/LABA/LAMA may be considered a first-line treatment strategy for severe asthma, with the potential to enhance disease management and postpone the need for initiating biologic agents.

тяжелая неконтролируемая бронхиальная астматройная ингаляционная терапияИГКС/ДДБА/ДДАХдисфункция малых дыхательных путейфиксированная бронхиальная обструкциявоспаление дыхательных путейsevere uncontrolled asthmatriple inhalation therapyICS/LABA/LAMAsmall airway dysfunctionfixed airflow obstructionairway inflammationReferencesYuan L, Tao J, Wang J, She W, Zou Y, Li R et al. Global, regional, national burden of asthma from 1990 to 2021, with projections of incidence to 2050: a systematic analysis of the global burden of disease study 2021. EClinicalMedicine. 2025;80:103051. https://doi.org/10.1016/j.eclinm.2024.103051.Yuan L, Tao J, Wang J, She W, Zou Y, Li R et al. Global, regional, national burden of asthma from 1990 to 2021, with projections of incidence to 2050: a systematic analysis of the global burden of disease study 2021. EClinicalMedicine. 2025;80:103051. https://doi.org/10.1016/j.eclinm.2024.103051.Авдеев СН, Айсанов ЗР, Архипов ВВ, Астафьева НГ, Баранов АА, Белевский АС и др. Бронхиальная астма: клинические рекомендации. 2024. Режим доступа: https://cr.minzdrav.gov.ru/view-cr/359_3#doc_a1.Авдеев СН, Айсанов ЗР, Архипов ВВ, Астафьева НГ, Баранов АА, Белевский АС и др. Бронхиальная астма: клинические рекомендации. 2024. Режим доступа: https://cr.minzdrav.gov.ru/view-cr/359_3#doc_a1.Ayik S, Karadeniz G, Tatlı T, Dinçel B. Predictive parameters of uncontrolled asthma in the real world: a prospective study. J Asthma. 2025;62(5):767–776. https://doi.org/10.1080/02770903.2024.2441881.Ayik S, Karadeniz G, Tatlı T, Dinçel B. Predictive parameters of uncontrolled asthma in the real world: a prospective study. J Asthma. 2025;62(5):767–776. https://doi.org/10.1080/02770903.2024.2441881.Bagnasco D, Ansotegui I, Baiardini I, Benfante A, Bernstein JA, Bikov A et al. Triple inhaled therapy in asthma: Beliefs, behaviours and doubts. Pulm Pharmacol Ther. 2024;87:102333. https://doi.org/10.1016/j.pupt.2024.102333.Bagnasco D, Ansotegui I, Baiardini I, Benfante A, Bernstein JA, Bikov A et al. Triple inhaled therapy in asthma: Beliefs, behaviours and doubts. Pulm Pharmacol Ther. 2024;87:102333. https://doi.org/10.1016/j.pupt.2024.102333.Архипов ВВ, Айсанов ЗP, Авдеев CН. Эффективность комбинаций ингаляционных глюкокортикостероидов и длительно действующих β-агонистов в условиях реальной медицинской практики: результаты многоцентрового кросс-секционного исследования у российских пациентов с бронхиальной астмой. Пульмонология. 2021;31(5):613–626. https://doi.org/10.18093/0869-0189-2021-31-5-613-626.Arkhipov VV, Aisanov ZR, Avdeev SN. Effectiveness of inhaled corticosteroids and long-acting β-agonists combinations in real clinical practice: results of a multicenter cross-sectional study in Russian patients with asthma. Pulmonologiya. 2021;31(5):613–626. (In Russ.) https://doi.org/10.18093/0869-0189-2021-31-5-613-626.Трушенко НВ, Левина ЮА, Бахарева АА, Абророва БН, Авдеев СН. Назначение препаратов по требованию для лечения бронхиальной астмы – смена парадигмы? Медицинский совет. 2025;19(20):20–28. https://doi.org/10.21518/ms2025-503.Trushenko NV, Levina YuA, Bakhareva АА, Abrorova DN, Avdeev SN. As-Needed medication for asthma treatment:A paradigm shift? Meditsinskiy Sovet. 2025;19(20):20–28. (In Russ.) https://doi.org/10.21518/ms2025-503.Caminati M, Vaia R, Furci F, Guarnieri G, Senna G. Uncontrolled Asthma: Unmet Needs in the Management of Patients. J Asthma Allergy. 2021;14:457–466. https://doi.org/10.2147/JAA.S260604.Caminati M, Vaia R, Furci F, Guarnieri G, Senna G. Uncontrolled Asthma: Unmet Needs in the Management of Patients. J Asthma Allergy. 2021;14:457–466. https://doi.org/10.2147/JAA.S260604.Braido F. Failure in asthma control: reasons and consequences. Scientifica. 2013;2013:549252. https://doi.org/10.1155/2013/549252.Braido F. Failure in asthma control: reasons and consequences. Scientifica. 2013;2013:549252. https://doi.org/10.1155/2013/549252.Calzetta L, Aiello M, Frizzelli A, Bertorelli G, Chetta A. Small airways in asthma: from bench-to-bedside. Minerva Med. 2022;113(1):79–93. https://doi.org/10.23736/S0026-4806.21.07268-2.Calzetta L, Aiello M, Frizzelli A, Bertorelli G, Chetta A. Small airways in asthma: from bench-to-bedside. Minerva Med. 2022;113(1):79–93. https://doi.org/10.23736/S0026-4806.21.07268-2.Casale TB, Foggs MB, Balkissoon RC. Optimizing asthma management: Role of long-acting muscarinic antagonists. J Allergy Clin Immunol. 2022;150(3):557–568. https://doi.org/10.1016/j.jaci.2022.06.015.Casale TB, Foggs MB, Balkissoon RC. Optimizing asthma management: Role of long-acting muscarinic antagonists. J Allergy Clin Immunol. 2022;150(3):557–568. https://doi.org/10.1016/j.jaci.2022.06.015.Toskala E, Kennedy DW. Asthma risk factors. Int Forum Allergy Rhinol. 2015;5(S1):S11–S16. https://doi.org/10.1002/alr.21557.Toskala E, Kennedy DW. Asthma risk factors. Int Forum Allergy Rhinol. 2015;5(S1):S11–S16. https://doi.org/10.1002/alr.21557.Cottini M, Licini A, Lombardi C, Bagnasco D, Comberiati P, Berti A. Small airway dysfunction and poor asthma control: a dangerous liaison. Clin Mol Allergy. 2021;19(1):7. https://doi.org/10.1186/s12948-021-00147-8.Cottini M, Licini A, Lombardi C, Bagnasco D, Comberiati P, Berti A. Small airway dysfunction and poor asthma control: a dangerous liaison. Clin Mol Allergy. 2021;19(1):7. https://doi.org/10.1186/s12948-021-00147-8.Israel E, Reddel HK. Severe and Difficult-to-Treat Asthma in Adults. N Engl J Med. 2017;377(10):965–976. https://doi.org/10.1056/NEJMra1608969.Israel E, Reddel HK. Severe and Difficult-to-Treat Asthma in Adults. N Engl J Med. 2017;377(10):965–976. https://doi.org/10.1056/NEJMra1608969.Hekking PW, Wener RR, Amelink M, Zwinderman AH, Bouvy ML, Bel EH. The prevalence of severe refractory asthma. J Allergy Clin Immunol. 2015;135(4):896–902. https://doi.org/10.1016/j.jaci.2014.08.042.Hekking PW, Wener RR, Amelink M, Zwinderman AH, Bouvy ML, Bel EH. The prevalence of severe refractory asthma. J Allergy Clin Immunol. 2015;135(4):896–902. https://doi.org/10.1016/j.jaci.2014.08.042.Yaghoubi M, Adibi A, Safari A, FitzGerald JM, Sadatsafavi M. The Projected Economic and Health Burden of Uncontrolled Asthma in the United States. Am J Respir Crit Care Med. 2019;200(9):1102–1112. https://doi.org/10.1164/rccm.201901-0016OC.Yaghoubi M, Adibi A, Safari A, FitzGerald JM, Sadatsafavi M. The Projected Economic and Health Burden of Uncontrolled Asthma in the United States. Am J Respir Crit Care Med. 2019;200(9):1102–1112. https://doi.org/10.1164/rccm.201901-0016OC.Buhl R, Heaney LG, Loefroth E, Larbig M, Kostikas K, Conti V, Cao H. One-year follow up of asthmatic patients newly initiated on treatment with medi-umor high-dose inhaled corticosteroid-long-acting β2-agonist in UK primary care settings. Respir Med 2020;162:105859. https://doi.org/10.1016/j.rmed.2019.105859.Buhl R, Heaney LG, Loefroth E, Larbig M, Kostikas K, Conti V, Cao H. One-year follow up of asthmatic patients newly initiated on treatment with medi-umor high-dose inhaled corticosteroid-long-acting β2-agonist in UK primary care settings. Respir Med 2020;162:105859. https://doi.org/10.1016/j.rmed.2019.105859.Śliwiński P, Antczak A, Barczyk A, Białas AJ, Czajkowska-Malinowska M, Jahnz-Różyk K et al. 2024 Update on Position Statement by Experts from the Polish Society of Allergology and the Polish Respiratory Society on the Evaluation of Efficacy and Effectiveness of Single Inhaler Triple Therapies in Asthma Treatment. Adv Respir Med. 2024;92(6):452–465. https://doi.org/10.3390/arm92060041.Śliwiński P, Antczak A, Barczyk A, Białas AJ, Czajkowska-Malinowska M, Jahnz-Różyk K et al. 2024 Update on Position Statement by Experts from the Polish Society of Allergology and the Polish Respiratory Society on the Evaluation of Efficacy and Effectiveness of Single Inhaler Triple Therapies in Asthma Treatment. Adv Respir Med. 2024;92(6):452–465. https://doi.org/10.3390/arm92060041.Papi A, Fabbri LM, Kerstjens HAM, Rogliani P, Watz H, Singh D. Inhaled long-acting muscarinic antagonists in asthma – A narrative review. Eur J Intern Med. 2021;85:14–22. https://doi.org/10.1016/j.ejim.2021.01.027.Papi A, Fabbri LM, Kerstjens HAM, Rogliani P, Watz H, Singh D. Inhaled long-acting muscarinic antagonists in asthma – A narrative review. Eur J Intern Med. 2021;85:14–22. https://doi.org/10.1016/j.ejim.2021.01.027.Muiser S, Gosens R, van den Berge M, Kerstjens HAM. Understanding the role of long-acting muscarinic antagonists in asthma treatment. Ann Allergy Asthma Immunol. 2022;128(4):352–360. https://doi.org/10.1016j.anai.2021.12.020.Muiser S, Gosens R, van den Berge M, Kerstjens HAM. Understanding the role of long-acting muscarinic antagonists in asthma treatment. Ann Allergy Asthma Immunol. 2022;128(4):352–360. https://doi.org/10.1016j.anai.2021.12.020.Fernández Aracil C, García Ródenas MDM, Hernández Blasco LM. Triple Therapy in Asthma. Open Respir Arch. 2025;7(3):100439. https://doi.org/10.1016/j.opresp.2025.100439.Fernández Aracil C, García Ródenas MDM, Hernández Blasco LM. Triple Therapy in Asthma. Open Respir Arch. 2025;7(3):100439. https://doi.org/10.1016/j.opresp.2025.100439.Gosens R, Gross N. The mode of action of anticholinergics in asthma. Eur Respir J. 2018;52(4):1701247. https://doi.org/10.1183/13993003.01247-2017.Gosens R, Gross N. The mode of action of anticholinergics in asthma. Eur Respir J. 2018;52(4):1701247. https://doi.org/10.1183/13993003.01247-2017.Mahay G, Zysman M, Guibert N, Barnig C, Guilleminault L, Dupin C. Long-acting muscarinic antagonists (LAMA) in asthma: What is the best strategy? Respir Med Res. 2025;87:101157. https://doi.org/10.1016/j.resmer.2025.101157.Mahay G, Zysman M, Guibert N, Barnig C, Guilleminault L, Dupin C. Long-acting muscarinic antagonists (LAMA) in asthma: What is the best strategy? Respir Med Res. 2025;87:101157. https://doi.org/10.1016/j.resmer.2025.101157.Agache I, Adcock IM, Akdis CA, Akdis M, Bentabol-Ramos G, van den Berge M et al. The Bronchodilator and Anti-Inflammatory Effect of Long-Acting Muscarinic Antagonists in Asthma: An EAACI Position Paper. Allergy. 2025;80(2):380–394. https://doi.org/10.1111/all.16436.Agache I, Adcock IM, Akdis CA, Akdis M, Bentabol-Ramos G, van den Berge M et al. The Bronchodilator and Anti-Inflammatory Effect of Long-Acting Muscarinic Antagonists in Asthma: An EAACI Position Paper. Allergy. 2025;80(2):380–394. https://doi.org/10.1111/all.16436.Chapman DG, Berend N, King GG, Salome CM. Increased airway closure is a determinant of airway hyperresponsiveness. Eur Respir J. 2008;32(6):1563–1569. https://doi.org/10.1183/09031936.00114007.Chapman DG, Berend N, King GG, Salome CM. Increased airway closure is a determinant of airway hyperresponsiveness. Eur Respir J. 2008;32(6):1563–1569. https://doi.org/10.1183/09031936.00114007.Cazzola M, Calzetta L, Rogliani P, Puxeddu E, Facciolo F, Matera MG. Interaction between corticosteroids and muscarinic antagonists in human airways. Pulm Pharmacol Ther. 2016;36:1–9. https://doi.org/10.1016/j.pupt.2015.11.004.Cazzola M, Calzetta L, Rogliani P, Puxeddu E, Facciolo F, Matera MG. Interaction between corticosteroids and muscarinic antagonists in human airways. Pulm Pharmacol Ther. 2016;36:1–9. https://doi.org/10.1016/j.pupt.2015.11.004.Jacoby DB, Yost BL, Kumaravel B, Chan-Li Y, Xiao HQ, Kawashima K, Fryer AD. Glucocorticoid treatment increases inhibitory m(2) muscarinic receptor expression and function in the airways. Am J Respir Cell Mol Biol. 2001;24(4):485–491. https://doi.org/10.1165/ajrcmb.24.4.4379.Jacoby DB, Yost BL, Kumaravel B, Chan-Li Y, Xiao HQ, Kawashima K, Fryer AD. Glucocorticoid treatment increases inhibitory m(2) muscarinic receptor expression and function in the airways. Am J Respir Cell Mol Biol. 2001;24(4):485–491. https://doi.org/10.1165/ajrcmb.24.4.4379.Braido F, Vlachaki I, Nikolaidis GF, Tzelis D, Barouma I, Piraino A et al. Single inhaler with beclometasone, formoterol, and glycopyrronium versus triple therapies in adults with uncontrolled asthma: a systematic review and meta-analysis. Sci Rep. 2025;15(1):4191. https://doi.org/10.1038/s41598-025-88374-w.Braido F, Vlachaki I, Nikolaidis GF, Tzelis D, Barouma I, Piraino A et al. Single inhaler with beclometasone, formoterol, and glycopyrronium versus triple therapies in adults with uncontrolled asthma: a systematic review and meta-analysis. Sci Rep. 2025;15(1):4191. https://doi.org/10.1038/s41598-025-88374-w.Cazzola M, Rogliani P, Matera MG. Might It Be Appropriate to Anticipate the Use of Long-Acting Muscarinic Antagonists in Asthma? Drugs. 2023;83(11):957–965. https://doi.org/10.1007/s40265-023-01897-2.Cazzola M, Rogliani P, Matera MG. Might It Be Appropriate to Anticipate the Use of Long-Acting Muscarinic Antagonists in Asthma? Drugs. 2023;83(11):957–965. https://doi.org/10.1007/s40265-023-01897-2.Quaranta VN, Montagnolo F, Portacci A, Dragonieri S, Granito M, Rociola G et al. Steady Quiet Asthma Without Biologics: One-Year Outcomes of SingleInhaler Triple Therapy for Severe Asthma with Small Airway Dysfunction. J Clin Med. 2025;14(15):5602. https://doi.org/10.3390/jcm14155602.Quaranta VN, Montagnolo F, Portacci A, Dragonieri S, Granito M, Rociola G et al. Steady Quiet Asthma Without Biologics: One-Year Outcomes of SingleInhaler Triple Therapy for Severe Asthma with Small Airway Dysfunction. J Clin Med. 2025;14(15):5602. https://doi.org/10.3390/jcm14155602.Ridolo E, Milanese M, Barone A, Nicoletta F, Ottoni M, Cosini FF et al. Extrafine formulation of beclomethasone dipropionate/formoterol fumarate/ glycopyrronium bromide delivered via pressurized metered-dose inhaler in the treatment of asthma: a review. Ther Adv Respir Dis. 2025;19:17534666251332076. https://doi.org/10.1177/17534666251332076.Ridolo E, Milanese M, Barone A, Nicoletta F, Ottoni M, Cosini FF et al. Extrafine formulation of beclomethasone dipropionate/formoterol fumarate/ glycopyrronium bromide delivered via pressurized metered-dose inhaler in the treatment of asthma: a review. Ther Adv Respir Dis. 2025;19:17534666251332076. https://doi.org/10.1177/17534666251332076.Kerstjens HAM, Maspero J, Chapman KR, van Zyl-Smit RN, Hosoe M, Tanase AM et al. Once-daily, single-inhaler mometasone – indacaterol – glycopyrronium versus mometasone – indacaterol or twice-daily fluticasonesalmeterol in patients with inadequately controlled asthma (IRIDIUM): a randomised, double-blind, controlled phase 3 study. Lancet Respir Med. 2020;8(10):1000–1012. https://doi.org/10.1016/S2213-2600(20)30190-9.Kerstjens HAM, Maspero J, Chapman KR, van Zyl-Smit RN, Hosoe M, Tanase AM et al. Once-daily, single-inhaler mometasone – indacaterol – glycopyrronium versus mometasone – indacaterol or twice-daily fluticasonesalmeterol in patients with inadequately controlled asthma (IRIDIUM): a randomised, double-blind, controlled phase 3 study. Lancet Respir Med. 2020;8(10):1000–1012. https://doi.org/10.1016/S2213-2600(20)30190-9.Virchow JC, Kuna P, Paggiaro P, Papi A, Singh D, Corre S et al. Single inhaler extrafine triple therapy in uncontrolled asthma (TRIMARAN and TRIGGER): two double-blind, parallel-group, randomised, controlled phase 3 trials. Lancet. 2019;394(10210):1737–1749. https://doi.org/10.1016/S0140-6736(19)32215-9.Virchow JC, Kuna P, Paggiaro P, Papi A, Singh D, Corre S et al. Single inhaler extrafine triple therapy in uncontrolled asthma (TRIMARAN and TRIGGER): two double-blind, parallel-group, randomised, controlled phase 3 trials. Lancet. 2019;394(10210):1737–1749. https://doi.org/10.1016/S0140-6736(19)32215-9.Gessner C, Kornmann O, Maspero J, van Zyl-Smit R, Krüll M, Salina A et al. Fixed-dose combination of indacaterol/glycopyrronium/mometasone furoate once-daily versus salmeterol/fluticasone twice-daily plus tiotropium once-daily in patients with uncontrolled asthma: A randomised, Phase IIIb, non-inferiority study (ARGON). Respir Med. 2020;170:106021. https://doi.org/10.1016/j.rmed.2020.106021.Gessner C, Kornmann O, Maspero J, van Zyl-Smit R, Krüll M, Salina A et al. Fixed-dose combination of indacaterol/glycopyrronium/mometasone furoate once-daily versus salmeterol/fluticasone twice-daily plus tiotropium once-daily in patients with uncontrolled asthma: A randomised, Phase IIIb, non-inferiority study (ARGON). Respir Med. 2020;170:106021. https://doi.org/10.1016/j.rmed.2020.106021.Lee LA, Bailes Z, Barnes N, Boulet LP, Edwards D, Fowler A et al. Efficacy and safety of once-daily single-inhaler triple therapy (FF/UMEC/VI) versus FF/VI in patients with inadequately controlled asthma (CAPTAIN): a double-blind, randomised, phase 3A trial. Lancet Respir Med. 2021;9(1):69–84. https://doi.org/10.1016/S2213-2600(20)30389-1.Lee LA, Bailes Z, Barnes N, Boulet LP, Edwards D, Fowler A et al. Efficacy and safety of once-daily single-inhaler triple therapy (FF/UMEC/VI) versus FF/VI in patients with inadequately controlled asthma (CAPTAIN): a double-blind, randomised, phase 3A trial. Lancet Respir Med. 2021;9(1):69–84. https://doi.org/10.1016/S2213-2600(20)30389-1.Papi A, Singh D, Virchow JC, Canonica GW, Vele A, Georges G. Normalisation of airflow limitation in asthma: Post-hoc analyses of TRIMARAN and TRIGGER. Clin Transl Allergy. 2022;12(4):e12145. https://doi.org/10.1002/clt2.12145.Papi A, Singh D, Virchow JC, Canonica GW, Vele A, Georges G. Normalisation of airflow limitation in asthma: Post-hoc analyses of TRIMARAN and TRIGGER. Clin Transl Allergy. 2022;12(4):e12145. https://doi.org/10.1002/clt2.12145.Singh D, Virchow JC, Canonica GW, Vele A, Kots M, Georges G, Papi A. Determinants of response to inhaled extrafine triple therapy in asthma: analyses of TRIMARAN and TRIGGER. Respir Res. 2020;21(1):285. https://doi.org/10.1186/s12931-020-01558-y.Singh D, Virchow JC, Canonica GW, Vele A, Kots M, Georges G, Papi A. Determinants of response to inhaled extrafine triple therapy in asthma: analyses of TRIMARAN and TRIGGER. Respir Res. 2020;21(1):285. https://doi.org/10.1186/s12931-020-01558-y.Öztürk BÖ, Sözener ZÇ, Metan EÜ, Aydın Ö, Bavbek S, Mungan D. The use of a long-acting muscarinic antagonist in the treatment of asthma: A tertiary asthma center experience. Allergol Immunopathol. 2024;52(6):62–71. https://doi.org/10.15586/aei.v52i6.1121.Öztürk BÖ, Sözener ZÇ, Metan EÜ, Aydın Ö, Bavbek S, Mungan D. The use of a long-acting muscarinic antagonist in the treatment of asthma: A tertiary asthma center experience. Allergol Immunopathol. 2024;52(6):62–71. https://doi.org/10.15586/aei.v52i6.1121.Han A, Deng S, Yu J, Zhang Y, Jalaludin B, Huang C. Asthma triggered by extreme temperatures: From epidemiological evidence to biological plausibility. Environ Res. 2023;216(2):114489. https://doi.org/10.1016/j.envres.2022.114489.Han A, Deng S, Yu J, Zhang Y, Jalaludin B, Huang C. Asthma triggered by extreme temperatures: From epidemiological evidence to biological plausibility. Environ Res. 2023;216(2):114489. https://doi.org/10.1016/j.envres.2022.114489.Papi A, Virchow JC, Singh D, Kots M, Vele A, Georges G, Canonica GW. Extrafine triple therapy and asthma exacerbation seasonality: TRIMARAN and TRIGGER post hoc analyses. J Allergy Clin Immunol. 2021;148(1):262–265. https://doi.org/10.1016/j.jaci.2021.01.007.Papi A, Virchow JC, Singh D, Kots M, Vele A, Georges G, Canonica GW. Extrafine triple therapy and asthma exacerbation seasonality: TRIMARAN and TRIGGER post hoc analyses. J Allergy Clin Immunol. 2021;148(1):262–265. https://doi.org/10.1016/j.jaci.2021.01.007.Rogliani P, Ritondo BL, Calzetta L. Triple therapy in uncontrolled asthma: a network meta-analysis of phase III studies. Eur Respir J. 2021;58(3):2004233. https://doi.org/10.1183/13993003.04233-2020.Rogliani P, Ritondo BL, Calzetta L. Triple therapy in uncontrolled asthma: a network meta-analysis of phase III studies. Eur Respir J. 2021;58(3):2004233. https://doi.org/10.1183/13993003.04233-2020.Kim LHY, Saleh C, Whalen-Browne A, O’Byrne PM, Chu DK. Triple vs Dual Inhaler Therapy and Asthma Outcomes in Moderate to Severe Asthma: A Systematic Review and Meta-analysis. JAMA. 2021;325(24):2466–2479. https://doi.org/10.1001/jama.2021.7872.Kim LHY, Saleh C, Whalen-Browne A, O’Byrne PM, Chu DK. Triple vs Dual Inhaler Therapy and Asthma Outcomes in Moderate to Severe Asthma: A Systematic Review and Meta-analysis. JAMA. 2021;325(24):2466–2479. https://doi.org/10.1001/jama.2021.7872.Maiorano A, Ferrante Bannera A, Lupia C, Pastore D, Chiarella E, Piazzetta GL et al. Real-World Efficacy of Beclomethasone Dipropionate/Formoterol Fumarate/Glycopyrronium on Diaphragmatic Workload Assessed by Ultrasound and Lung Function in Patients with Uncontrolled Asthma. Adv Respir Med. 2025;93(5):40. https://doi.org/10.3390/arm93050040.Maiorano A, Ferrante Bannera A, Lupia C, Pastore D, Chiarella E, Piazzetta GL et al. Real-World Efficacy of Beclomethasone Dipropionate/Formoterol Fumarate/Glycopyrronium on Diaphragmatic Workload Assessed by Ultrasound and Lung Function in Patients with Uncontrolled Asthma. Adv Respir Med. 2025;93(5):40. https://doi.org/10.3390/arm93050040.Dragonieri S, Quaranta VN, Portacci A, Carpagnano GE. Can single-inhaler Beclometasone Dipropionate/Formoterol Fumarate/Glycopyrronium therapy postpone or save biologics for severe asthma? Pulm Pharmacol Ther. 2023;83:102270. https://doi.org/10.1016/j.pupt.2023.102270.Dragonieri S, Quaranta VN, Portacci A, Carpagnano GE. Can single-inhaler Beclometasone Dipropionate/Formoterol Fumarate/Glycopyrronium therapy postpone or save biologics for severe asthma? Pulm Pharmacol Ther. 2023;83:102270. https://doi.org/10.1016/j.pupt.2023.102270.Gessner C, Russell REK, Greulich T, Lommatzsch M, Suppli Ulrik C, Pohl W et al. Real-World Effectiveness and Safety of Single Inhaler Triple Therapy with Beclometasone/ Formoterol/ Glycopyrronium in Moderate to Severe Asthma: TriMaximize Study. J Asthma Allergy. 2026;19:582286. https://doi.org/10.2147/JAA.S582286.Gessner C, Russell REK, Greulich T, Lommatzsch M, Suppli Ulrik C, Pohl W et al. Real-World Effectiveness and Safety of Single Inhaler Triple Therapy with Beclometasone/ Formoterol/ Glycopyrronium in Moderate to Severe Asthma: TriMaximize Study. J Asthma Allergy. 2026;19:582286. https://doi.org/10.2147/JAA.S582286.Canonica GW, Blasi F, Paggiaro P, Heffler E, Braido F, Brussino L et al. Biologics as well as inhaled anti-asthmatic therapy achieve clinical remission: Evidence from the Severe Asthma Network in Italy (SANI). World Allergy Organ J. 2024;18(1):101016. https://doi.org/10.1016/j.waojou.2024.101016.Canonica GW, Blasi F, Paggiaro P, Heffler E, Braido F, Brussino L et al. Biologics as well as inhaled anti-asthmatic therapy achieve clinical remission: Evidence from the Severe Asthma Network in Italy (SANI). World Allergy Organ J. 2024;18(1):101016. https://doi.org/10.1016/j.waojou.2024.101016.Kraft M, Richardson M, Hallmark B, Billheimer D, Van den Berge M, Fabbri LM 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. https://doi.org/10.1016/S2213-2600(21)00536-1.Kraft M, Richardson M, Hallmark B, Billheimer D, Van den Berge M, Fabbri LM 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. https://doi.org/10.1016/S2213-2600(21)00536-1.Postma DS, Brightling C, Baldi S, Van den Berge M, Fabbri LM, Gagnatelli A 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. https://doi.org/10.1016/S2213-2600(19)30049-9.Postma DS, Brightling C, Baldi S, Van den Berge M, Fabbri LM, Gagnatelli A 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. https://doi.org/10.1016/S2213-2600(19)30049-9.Galant SP, Kuks PJM, Kole TM, Kraft M, Siddiqui S, Fabbri LM et al. Assessment of the role of small airway dysfunction in relation to exacerbation risk in patients with well controlled asthma (ATLANTIS): an observational study. Lancet Respir Med. 2025;13(11):990–1000. https://doi.org/10.1016/S2213-2600(25)00283-8.Galant SP, Kuks PJM, Kole TM, Kraft M, Siddiqui S, Fabbri LM et al. Assessment of the role of small airway dysfunction in relation to exacerbation risk in patients with well controlled asthma (ATLANTIS): an observational study. Lancet Respir Med. 2025;13(11):990–1000. https://doi.org/10.1016/S2213-2600(25)00283-8.

The authors declare that there are no conflicts of interest present.