Small airway involvement in bronchial asthma and chronic obstructive pulmonary disease: From understanding pathophysiology to optimizing therapy

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Abstract

Small airway involvement (SAI) is a clinically important yet often underestimated component of bronchial asthma and chronic obstructive pulmonary disease (COPD). In this review, SAI is considered both as small airways disease, associated with structural and morphological changes in the bronchioles, and as small airway dysfunction, manifested by peripheral airflow obstruction, ventilation heterogeneity, premature expiratory airway closure, air trapping, and dynamic hyperinflation. A mismatch between symptom burden and standard spirometric indices is frequently related to small airway dysfunction, which is only partly captured by FEV1. The review summarizes current concepts of small airway pathophysiology in asthma and COPD, outlines a diagnostic approach using functional tests and imaging modalities, and substantiates therapeutic strategies that take drug deposition in the peripheral bronchial tree into account. The role of comorbidities and practical aspects of patient management in primary care are addressed separately.

About the authors

Oleg M. Uryasev

Academician I.P. Pavlov Ryazan State Medical University

Author for correspondence.
Email: uryasev08@yandex.ru
ORCID iD: 0000-0001-8693-4696
SPIN-code: 7903-4609
Scopus Author ID: 57195313767

MD, Dr. Sci. (Medicine), Professor, Head of the Department of Faculty Therapy named after Professor V.Ya. Garmash

Russian Federation, Ryazan

Eduard S. Belskikh

Academician I.P. Pavlov Ryazan State Medical University

Email: ed.bels@yandex.ru
ORCID iD: 0000-0003-1803-0542
SPIN-code: 9350-9360
Scopus Author ID: 57195313786

MD, PhD (Medicine), Associate Professor of the Department of Faculty Therapy named after Professor V.Ya. Garmash

Russian Federation, Ryazan

Irina B. Ponomareva

Academician I.P. Pavlov Ryazan State Medical University

Email: docib@yandex.ru
ORCID iD: 0000-0002-0273-4388
SPIN-code: 3984-1944
Scopus Author ID: 57201763814

MD, PhD (Medicine), Associate Professor of the Department of Faculty Therapy named after Professor V.Ya. Garmash

Russian Federation, Ryazan

Sergey I. Glotov

Academician I.P. Pavlov Ryazan State Medical University

Email: sergeyglot@mail.ru
ORCID iD: 0000-0002-4445-4480
SPIN-code: 7524-9816
Scopus Author ID: 57203780371

MD, PhD (Medicine), Associate Professor of the Department of Faculty Therapy named after Professor V.Ya. Garmash

Russian Federation, Ryazan

Elena V. Aftaeva

Academician I.P. Pavlov Ryazan State Medical University

Email: aftaeva.elena@gmail.com
ORCID iD: 0009-0002-6573-7460
SPIN-code: 9877-2615
Scopus Author ID: 57223230731

MD, Assistant at the Department of Cardiovascular, Endovascular and X-Ray Surgery and Diagnostic Imaging

Russian Federation, Ryazan

Elena M. Goldina

Regional Clinical Hospital, Ryazan

Email: goldina.71@mail.ru
ORCID iD: 0009-0003-2780-1510

MD, PhD (Medicine), Head of the Department of Pulmonology

Russian Federation, Ryazan

References

  1. Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention. 2025 report. URL: https://ginasthma.org/wp-content/uploads/2025/05/GINA-2025_tracked-for-archive-WMSA.pdf (date of access – 08.02.2026).
  2. Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for prevention, diagnosis and management of COPD. 2026 report (v1.3; 8 Dec 2025). URL: https://goldcopd.org/wp-content/uploads/2025/12/GOLD-REPORT-2026-v1.3-8Dec2025_WMV.pdf (date of access – 08.02.2026).
  3. Macklem PT, Mead J. Resistance of central and peripheral airways measured by a retrograde catheter. J Appl Physiol. 1967;22(3):395–401. PMID: 4960137. https://doi.org/10.1152/jappl.1967.22.3.395
  4. Mead J. The lung’s “quiet zone”. N Engl J Med. 1970;282(23):1318–19. PMID: 5442364. https://doi.org/10.1056/NEJM197006042822311
  5. Котляров С.Н. Скрининг спирометрии в оценке хронической обструктивной болезни легких на уровне первичного звена медицинской помощи. Российский медико-биологический вестник имени академика И.П. Павлова. 2011;19(1):91–95. [Kotlyarov SN. Spirometry screening in evaluation of chronic obstructive pulmonary disease at primary care. Rossiyskiy mediko-biologicheskiy vestnik imeni akademika I.P. Pavlova = I.P. Pavlov Russian Medical Biological Herald. 2011;19(1):91–95 (In Russ.)]. EDN: OKMRAB.
  6. Usmani OS, Han MK, Kaminsky DA, Hogg J, Hjoberg J, Patel N et al. Seven pillars of small airways disease in asthma and COPD: Supporting clinical practice. Chest. 2021;160(4):1147–61. PMID: 33819471. https://doi.org/10.1016/j.chest.2021.03.047
  7. Postma DS, Brightling C, Baldi S, Van den Berge M, Fabbri LM, Gagnatelli A et al.; ATLANTIS study group. Small-airways dysfunction in asthma (ATLANTIS): Baseline results from a prospective cohort. Lancet Respir Med. 2019;7(5):402–16. PMID: 30876830. https://doi.org/10.1016/S2213-2600(19)30049-9. Erratum in: Lancet Respir Med. 2019;7(9):e28. PMID: 30876830. https://doi.org/10.1016/S2213-2600(19)30242-5
  8. Toumpanakis D, Usmani OS. Small airways in asthma: pathophysiology, identification and management. Chin Med J Pulm Crit Care Med. 2023;1(3):171–80. PMID: 39171124. PMCID: PMC11332871. https://doi.org/10.1016/j.pccm.2023.07.002
  9. O’Donnell DE. Hyperinflation, dyspnea, and exercise intolerance in COPD. Proc Am Thorac Soc. 2006;3(2):180–84. PMID: 16565429. https://doi.org/10.1513/pats.200508-093DO
  10. Calverley PMA, Koulouris NG. Flow limitation and dynamic hyperinflation: Key concepts in modern respiratory physiology. Eur Respir J. 2005;25(1):186–99. PMID: 15640341. https://doi.org/10.1183/09031936.04.00113204
  11. Hogg JC, Chu F, Utokaparch S, Woods R, Elliott WM, Buzatu L et al. The nature of small-airway obstruction in COPD. N Engl J Med. 2004;350(26):2645–53. PMID: 15215480. https://doi.org/10.1056/NEJMoa032158
  12. McDonough JE, Yuan R, Suzuki M, Seyednejad N, Elliott WM, Sanchez PG et al. Small-airway obstruction and emphysema in COPD. N Engl J Med. 2011;365(17):1567–75. PMID: 22029978. PMCID: PMC3238466. https://doi.org/10.1056/NEJMoa1106955
  13. Hamid Q, Song Y, Kotsimbos TC, Minshall E, Bai TR, Hegele RG, Hogg JC. Inflammation of small airways in asthma. J Allergy Clin Immunol. 1997;100(1):44–51. PMID: 9257786. https://doi.org/10.1016/S0091-6749(97)70193-3
  14. Dunican EM, Elicker BM, Gierada DS, Nagle SK, Schiebler ML, Newell JD et al.; National Heart Lung and Blood Institute (NHLBI) Severe Asthma Research Program (SARP). Mucus plugs in asthma are associated with eosinophilia and airflow obstruction. J Clin Invest. 2018;128(3):997–1009. PMID: 29400693. PMCID: PMC5824874. https://doi.org/10.1172/JCI95693
  15. Овсянников Е.С., Авдеев С.Н., Будневский А.В. Системное воспаление у больных хронической обструктивной болезнью легких и ожирением. Терапевтический архив. 2020;92(3):13–18. [Ovsyannikov ES, Avdeev SN, Budnevsky AV. Systemic inflammation in patients with chronic obstructive pulmonary disease and obesity. Terapevticheskiy arkhiv = Therapeutic Archive. 2020;92 (3):13–18 (In Russ.)]. EDN: EXZWYY. https://doi.org/10.26442/00403660.2020.03.000265
  16. Verbanck S, Schuermans D, Paiva M, Vincken W. The functional benefit of anti-inflammatory aerosols in the lung periphery. J Allergy Clin Immunol. 2006;118(2):340–46. PMID: 16890756. https://doi.org/10.1016/j.jaci.2006.04.056
  17. Casanova C, Cote C, de Torres JP, Aguirre-Jaime A, Marin JM, Pinto-Plata V, Celli BR. Inspiratory-to-total lung capacity ratio predicts mortality in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2005;171(6):591–97. PMID: 15591470. https://doi.org/10.1164/rccm.200407-867OC
  18. Cho JL, Villacreses R, Nagpal P, Guo J, Pezzulo AA, Thurman AL et al. Quantitative chest CT assessment of small airways disease in post-acute SARS-CoV-2 infection. Radiology. 2022;304(1):185–92. PMID: 35289657. PMCID: PMC9270680. https://doi.org/10.1148/radiol.212170
  19. Будневский А.В., Овсянников Е.С., Лабжания Н.Б. Сочетание хронической обструктивной болезни легких и метаболического синдрома: патофизиологические и клинические особенности. Терапевтический архив. 2017;89(1):123–127. [Budnevsky AV, Ovsyannikov ES, Labzhania NB. Chronic obstructive pulmonary disease concurrent with metabolic syndrome: Pathophysiological and clinical features. Terapevticheskiy arkhiv = Therapeutic Archive. 2017;89(1):123–127 (In Russ.)]. EDN: XXELYT. https://doi.org/10.17116/terarkh2017891123-127
  20. Трибунцева Л.В., Будневский А.В., Иванчук Ю.С., Шкатова Я.С., Токмачев Р.Е. Коморбидная патология у пациентов с бронхиальной астмой: обзор литературы. Наука молодых (Eruditio Juvenium). 2021;9(1):136–146. [Tribuntseva LV, Budnevsky AV, Ivanchuk YuS, Shkatova YaS, Tokmachev RE. Comorbid pathology in patients with bronchial asthma: Literature review. Nauka molodykh (Eruditio Juvenium) = Science of the Young (Eruditio Juvenium). 2021;9(1):136–146 (In Russ.)]. EDN: RWFIYQ. https://doi.org/10.23888/HMJ202191136-146
  21. Трибунцева Л.В., Авдеев С.Н., Будневский А.В., Прозорова Г.Г., Кожевникова С.А. Сочетанное влияние мультиморбидности и повышенного индекса массы тела на контроль бронхиальной астмы и качество жизни пациентов. Российский медико-биологический вестник имени академика И.П. Павлова. 2023;31(1):37–48. [Tribuntseva LV, Avdeev SN, Budnevskiy AV, Prozorova GG, Kozhevnikova SA. Combined effect of multimorbidity and increased body mass index on control of bronchial asthma and quality of patients’ life. Rossiyskiy mediko-biologicheskiy vestnik imeni akademika I.P. Pavlova = I.P. Pavlov Russian Medical Biological Herald. 2023;31(1):37–48 (In Russ.)]. EDN: EEVMAY. https://doi.org/10.17816/PAVLOVJ111895
  22. Graham BL, Steenbruggen I, Miller MR, Barjaktarevic IZ, Cooper BG, Hall GL et al. Standardization of spirometry 2019 update: An official ATS/ERS technical statement. Am J Respir Crit Care Med. 2019;200(8):e70–e88. PMID: 31613151. PMCID: PMC6794117. https://doi.org/10.1164/rccm.201908-1590ST
  23. Quanjer PH, Stanojevic S, Cole TJ, Baur X, Hall GL, Culver BH et al.; ERS Global Lung Function Initiative. Multi-ethnic reference values for spirometry for the 3–95-yr age range: The GLI-2012 equations. Eur Respir J. 2012;40(6):1324–43. PMID: 22743675. PMCID: PMC3786581. https://doi.org/10.1183/09031936.00080312
  24. Stanojevic S, Kaminsky DA, Miller MR, Thompson B, Aliverti A, Barjaktarevic I et al. ERS/ATS technical standard on interpretive strategies for routine lung function tests. Eur Respir J. 2022;60(1):2101499. PMID: 34949706. https://doi.org/10.1183/13993003.01499-2021
  25. King GG, Bates J, Berger KI, Calverley P, de Melo PL, Dellaca RL et al. Technical standards for respiratory oscillometry. Eur Respir J. 2020;55(2):1900753. PMID: 31772002. https://doi.org/10.1183/13993003.00753-2019
  26. Савушкина О.И., Астанин П.А., Неклюдова Г.В., Авдеев С.Н., Зайцев А.А. Возможности импульсной осциллометрии в диагностике функциональных нарушений бронхолегочной системы после перенесенного COVID-19. Терапевтический архив. 2023;95(11):924–929. [Savushkina OI, Astanin PA, Nekludova GV, Avdeev SN, Zaytsev AA. The possibilities of impulse oscillometry in the diagnosis of the lung function disorders after COVID-19. Terapevticheskiy arkhiv = Therapeutic Archive. 2023;95(11):924–929 (In Russ.)]. EDN: RLUDOP. https://doi.org/10.26442/00403660.2023.11.202474
  27. Абросимов В.Н., Бяловский Ю.Ю., Субботин С.В., Пономарева И.Б. Объемная капнография: возможности применения в пульмонологической практике. Пульмонология. 2017;27(1):65–70. https://doi.org/10.18093/0869-0189-2017-27-1-65-70. [Abrosimov VN, Byalovskiy YuYu, Subbotin SV, Ponomareva IB. Volumetric capnography: abilities in practical pulmonology. Pul`monologiya = Pulmonology. 2017;27(1):65–70 (In Russ.)]. EDN: YNDNTH. https://doi.org/10.18093/0869-0189-2017-27-1-65-70
  28. 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(5):602–15. PMID: 21885636. PMCID: PMC4408724. https://doi.org/10.1164/rccm.9120-11ST
  29. Galban CJ, Han MK, Boes JL, Chughtai KA, Meyer CR, Johnson TD et al. CT-based biomarker provides unique signature for COPD phenotypes. Nat Med. 2012;18(11):1711–15. PMID: 23042237. PMCID: PMC3493851. https://doi.org/10.1038/nm.2971
  30. Bhatt SP, Soler X, Wang X, Murray S, Anzueto AR, Beaty TH et al.; COPDGene Investigators. Association between functional small airway disease and FEV1 decline in COPD. Am J Respir Crit Care Med. 2016;194(2):178–84. PMID: 26808615. PMCID: PMC5003216. https://doi.org/10.1164/rccm.201511-2219OC
  31. Usmani OS. Treating the small airways. Respiration. 2012;84(6):441–53. PMID: 23154684. https://doi.org/10.1159/000343629
  32. Leach CL, Davidson PJ, Hasselquist BE, Boudreau RJ. Lung deposition of hydrofluoroalkane-134a beclomethasone is greater than that of chlorofluorocarbon fluticasone and chlorofluorocarbon beclomethasone. Chest. 2002;122(2):510–16. PMID: 12171824. https://doi.org/10.1378/chest.122.2.510
  33. Terzano C, Cremonesi G, Girbino G, Ingrassia E, Marsico S, Nicolini G, Allegra L; PRISMA (PRospectIve Study on asthMA control) Study Group. 1-year prospective real life monitoring of asthma control and quality of life in Italy. Respir Res. 2012;13:112. PMID: 23216798. PMCID: PMC3546892. https://doi.org/10.1186/1465-9921-13-112
  34. O’Byrne PM, FitzGerald JM, Bateman ED, Barnes PJ, Zhong N, Keen C et al. Budesonide–formoterol as needed in mild asthma. N Engl J Med. 2018;378(20):1865–76. PMID: 29768149. https://doi.org/10.1056/NEJMoa1715274
  35. Bateman ED, Reddel HK, O’Byrne PM, Barnes PJ, Zhong N, Keen C et al. As-needed budesonide–formoterol versus maintenance budesonide in mild asthma. N Engl J Med. 2018;378(20):1877–87. PMID: 29768147. https://doi.org/10.1056/NEJMoa1715275
  36. Beasley R, Holliday M, Reddel HK, Braithwaite I, Ebmeier S, Hancox RJ et al.; Novel START Study Team. Controlled trial of budesonide–formoterol as needed for mild asthma. N Engl J Med. 2019;380(21):2020–30. PMID: 31112386. https://doi.org/10.1056/NEJMoa1901963
  37. Chan R, Lipworth BJ. Impact of biologic therapy on the small airways asthma phenotype. Lung. 2022;200(6):691–96. PMID: 36239786. PMCID: PMC9675679. https://doi.org/10.1007/s00408-022-00579-2
  38. Menzies-Gow A, Corren J, Bourdin A, Chupp G, Israel E, Wechsler ME et al. Tezepelumab in severe, uncontrolled asthma. N Engl J Med. 2021;384(19):1800–9. PMID: 33979488. https://doi.org/10.1056/NEJMoa2034975
  39. Lipson DA, Barnhart F, Brealey N, Brooks J, Criner GJ, Day NC et al.; IMPACT Investigators. Single-inhaler triple versus dual therapy in COPD. N Engl J Med. 2018;378(18):1671–80. PMID: 29668352. https://doi.org/10.1056/NEJMoa1713901
  40. Rabe KF, Martinez FJ, Ferguson GT, Wang C, Singh D, Wedzicha JA et al.; ETHOS Investigators. Triple inhaled therapy at two glucocorticoid doses in COPD. N Engl J Med. 2020;383(1):35–48. PMID: 32579807. https://doi.org/10.1056/NEJMoa1916046
  41. Watz H, Waschki B, Meyer T, Kretschmar G, Kirsten A, Claussen M, Magnussen H. Decreasing cardiac chamber sizes and associated heart dysfunction in COPD: role of hyperinflation. Chest. 2010;138(1):32–38. PMID: 20190002. https://doi.org/10.1378/chest.09-2810
  42. Bhatt SP, Rabe KF, Hanania NA, Vogelmeier CF, Cole J, Bafadhel M et al.; BOREAS Investigators. Dupilumab for COPD with type 2 inflammation. N Engl J Med. 2023;389(3):205–14. PMID: 37272521. https://doi.org/10.1056/NEJMoa2303951

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