Skip to main content
Log in

Small airways disease in asthma

  • Published:
Current Allergy and Asthma Reports Aims and scope Submit manuscript

Abstract

A mounting body of physiologic and pathologic evidence indicates that asthma involves the central and the more distal airways. In patients with asthma, the peripheral lung accounts for a significant portion of airway resistance and, similar to the large airways, the small airways have been shown to be hyperresponsive to nonspecific stimuli, such as methacholine. Cellular inflammation, consisting of an infiltrate rich with lymphocytes and eosinophils, is present in the small airways of patients with asthma and may be more intense than that observed in the large airways. Clinical assessment of the peripheral airways continues to be a challenge, and new techniques, such as quantitative analysis of chest CT images, have proven to be useful research tools. The recognition of small airways involvement in asthma has clinical relevance, as new formulations of inhaled corticosteroids with smaller particle aerosols may be more effective in addressing this component of asthma.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References and Recommended Reading

  1. Hogg JC: The pathology of asthma. In Asthma: Physiology, Immunopharmacology, and Treatment. Edited by Holgate ST, Austen KF, Lichtenstein LM, Kay AB. London: Academic Press; 1993:110–135.

    Google Scholar 

  2. Huber HL, Loessler K: The pathology of bronchial asthma. Arch Intern Med 1922, 30:689–760.

    Google Scholar 

  3. Weibel ER: Geometry and dimensions of airways conductive and transitory zone. In Morphometry of the Human Lung. New York: Springer-Verlag; 1963:110–135.

    Google Scholar 

  4. Tashkin DP: The role of small airway inflammation in asthma. Allergy Asthma Proc 2002, 23:233–242.

    PubMed  Google Scholar 

  5. Yanai M, Sekizawa K, Ohrui T, et al.: Site of airway obstruction in pulmonary disease: direct measurement of intrabronchial pressure. J Appl Physiol 1991, 72:1016–1023.

    Google Scholar 

  6. Mitchell HW, Cvetkowski R, Sparrow MP, et al.: Concurrent measurement of smooth muscle shortening, lumen narrowing, and flow to acetylcholine in large and small porcine bronchi. Eur Respir J 1998, 12:1053–1061.

    Article  PubMed  CAS  Google Scholar 

  7. Wagner EM, Bleecker ER, Permut S, Liu MC: Direct assessment of small airways reactivity in human subjects. Am J Respir Crit Care Med 1998, 157:447–452.

    PubMed  CAS  Google Scholar 

  8. Ellis JL, Hubbard WC, Meeker S, Unden BJ: Ragweed antigen E and anti-IgE in human central versus peripheral isolated bronchi. Am J Respir Crit Care Med 1994, 150:717–723.

    PubMed  CAS  Google Scholar 

  9. Bentley AM, Meng Q, Robinson DS, et al.: Increases in activated T lymphocytes, eosinophils, and cytokine mRNA expression for granulocyte/macrophage colony-stimulating factor in bronchial biopsies after allergen inhalation in atopic asthmatics. Am J Respir Cell Mol Biol 1993, 8:35–42.

    PubMed  CAS  Google Scholar 

  10. Houston JC, de Navaquez S, Trounce JR: A clinical and pathological study of fatal cases of status asthmaticus. Thorax 1953, 8:207–213.

    Article  PubMed  CAS  Google Scholar 

  11. Dunnill MS: The pathology of asthma, with special reference to changes in the bronchial mucosa. J Clin Pathol 1960, 13:27–33.

    Article  PubMed  CAS  Google Scholar 

  12. Saetta M, DiStafano A, Rosina C, et al.: Quantitative structural analysis of peripheral airways and arteries in sudden fatal asthma. Am Rev Respir Dis 1991, 143:138–143.

    PubMed  CAS  Google Scholar 

  13. Carroll N, Carello S, James A: The distribution of eosinophils and lymphocytes in the large and small airways of asthmatics. Eur Respir J 1997, 10:292–300.

    Article  PubMed  CAS  Google Scholar 

  14. Faul JL, Tormey VJ, Leonard C, et al.: Lung immunopathology in cases of sudden asthma death. Eur Respir J 1997, 10:301–307.

    Article  PubMed  CAS  Google Scholar 

  15. Synek M, Beasley R, Frew AJ, et al.: Cellular infiltration of the airways in asthma of varying severity. Am J Respir Crit Care Med 1996, 154:224–230.

    PubMed  CAS  Google Scholar 

  16. Haley KJ, Sunday ME, Wiggs BR, et al.: Inflammatory cell distribution within and along asthmatic airways. Am J Respir Crit Care Med 1998, 158:565–572.

    PubMed  CAS  Google Scholar 

  17. Hamid Q, Song Y, Kotsimbos C, et al.: Inflammation of small airways in asthma. J Allergy Clin Immunol 1997, 100:44–51.

    Article  PubMed  CAS  Google Scholar 

  18. Balzar S, Wenzel SE, Chu HW: Transbronchial biopsy as a tool to evaluate small airways in asthma. Eur Respir J 2002, 303:254–259.

    Article  Google Scholar 

  19. Kraft M, Martin RJ, Wilson S, et al.: Lymphocyte and eosinophil influx into alveolar tissue in nocturnal asthma. Am J Respir Crit Care Med 1999, 159:228–234.

    PubMed  CAS  Google Scholar 

  20. Bergeron C, Hauber HP, Gotfried M, et al.: Evidence of remodeling in peripheral airways of patients with mild to moderate asthma: effect of hydrofluoralkane-flunisolide. J Allergy Clin Immunol 2005, 116:983–989.

    Article  PubMed  CAS  Google Scholar 

  21. Christodoulopoulos P, Leung DY, Elliott MW, et al.: Increased number of glucocorticoid receptor-beta expressing cells in the airways in fatal asthma. J Allergy Clin Immunol 2000, 106:479–484.

    Article  PubMed  CAS  Google Scholar 

  22. Minshall EM, Hogg JC, Hamid QA: Cytokine mRNA expression in asthma is not restricted to the large airways. J Allergy Clin Immunol 1998, 101:386–390.

    Article  PubMed  CAS  Google Scholar 

  23. Taha RA, Minshall EM, Miotto D, et al.: Eotaxin and monocyte chemotactic proten-4 mRNA expression in small airways of asthmatic and nonasthmatic individuals. J Allergy Clin Immunol 1999, 102:476–483.

    Article  Google Scholar 

  24. Hung CH, Chen LC, Zhang Z, et al.: Regulation of Th2 responses by the pulmonary Clara cell secretory 10-kD protein. J Allergy Clin Immunol 2004, 114:664–670.

    Article  PubMed  CAS  Google Scholar 

  25. Shijubo N, Itoh Y, Yamaguchi T, et al.: Clara cell proteinpositive epithelial cells are reduced in small airways of asthmatics. Am J Respir Crit Care Med 1999, 160:930–933.

    PubMed  CAS  Google Scholar 

  26. McFadden ER, Linden DA: A reduction in maximum midexpiratory flow rate: a spirographic manifestation of small airways disease. Am J Med 1972, 52:725–737.

    Article  PubMed  Google Scholar 

  27. Sutherland ER, Martin RJ, Bowler RP, et al.: Physiologic correlates of distal lung inflammation in asthma. J Allergy Clin Immunol 2004, 113:1046–1050.

    Article  PubMed  Google Scholar 

  28. McCarthy DS, Spencer R, Greene R, Milic-Emili J: Measurement of “closing volume” as a single and sensitive test for early detection of small airway disease. Am J Med 1972, 52:747–753.

    Article  PubMed  CAS  Google Scholar 

  29. Cosio M, Ghezzo Hogg JC, Corbin R, et al.: The relations between structural changes in small airways and pulmonary function tests. N Engl J Med 1978, 122:1277–1281.

    Article  Google Scholar 

  30. In’t Veen JC, Beekman AJ, Bel EH, Sterk PJ: Recurrent exacerbations in severe asthma are associated with enhanced airway closure during stable episodes. Am J Respir Crit Care Med 2000, 161:1902–1906.

    Google Scholar 

  31. Aronsson D, Tufvesson E, Ankerst J, Bjermer L: Allergic rhinitis with hyper-responsiveness differ from asthma in degree of peripheral obstruction during methacholine challenge test. Clin Physiol Funct Imaging 2008, 28:81–85.

    Article  PubMed  Google Scholar 

  32. Song TW, Kim KW, Kim ES, et al.: Utility of impulse oscillometry in young children with asthma. Pediatr Allergy Immunol 2008 Mar 7 (Epub ahead of print).

  33. Berry M, Hargadon B, Morgan A, et al.: Alveolar nitric oxide in adults with asthma: evidence of distal lung inflammation in refractory asthma. Eur Respir J 2005, 25:986–991.

    Article  PubMed  CAS  Google Scholar 

  34. Van Veen IH, Sterk PJ, Schot R, et al.: Alveolar nitric oxide versus measures of peripheral airway dysfunction in severe asthma. Eur Respir J 2006, 27:951–956.

    PubMed  Google Scholar 

  35. Verbanck S, Schuermans D, Paiva M, Vincken W: The functional benefit of anti-inflammatory aerosols in the lung periphery. J Allergy Clin Immunol 2006, 118:340–346.

    Article  PubMed  CAS  Google Scholar 

  36. de Blic J, Scheinmann P: The use of imaging techniques for assessing severe childhood asthma. J Allergy Clin Immunol 2007, 119:808–810.

    Article  PubMed  Google Scholar 

  37. Ueda T, Niimi A, Matsumoto H, et al.: Role of small airways in asthma: investigation using high-resolution computed tomography. J Allergy Clin Immunol 2006, 118:1019–1025.

    Article  PubMed  Google Scholar 

  38. Zeidler MR, Goldin JG, Kleerup EC, et al.: Small airways response to naturalistic cat allergen exposure in subjects with asthma. J Allergy Clin Immunol 2006, 118:1075–1081.

    Article  PubMed  Google Scholar 

  39. Leach CL, Davidson PJ, Hasselquist BE: Lung deposition of hydrofluoroalkane-134a beclomethasone is greater than that of chlorofluorocarbon fluticasone and chlorofluorocarbon beclomethasone: a cross-over study in healthy volunteers. Chest 2002, 122:510–516.

    Article  PubMed  CAS  Google Scholar 

  40. Zeidler M, Corren J: Hydrofluoroalkane formulations of inhaled corticosteroids for the treatment of asthma. Treat Respir Med 2004, 3:35–44.

    Article  PubMed  CAS  Google Scholar 

  41. Richards J, Hirst P, Pitcairn G, et al.: Deposition and pharmacokinetics of flunisolide delivered from pressurized inhalers containing non-CFC and CFC propellants. J Aerosol Med 2001, 14:197–220.

    Article  PubMed  CAS  Google Scholar 

  42. Newman S, Salmon A, Nave R, Drollmann A: High lung deposition of 99mTc-labeled ciclesonide administered via HFA-MDI to patients with asthma. Respir Med 2006, 100:375–384.

    PubMed  Google Scholar 

  43. Busse WW, Branzinsky S, Jacobson K, et al.: Efficacy response of inhaled beclomethasone dipropionate in asthma is proportional to dose and is improved by formulation with a new propellant. J Allergy Clin Immunol 1999, 104:1215–1222.

    Article  PubMed  CAS  Google Scholar 

  44. Corren J, Nelson H, Greos L, et al.: Effective control of asthma with hydrofluoroalkane (HFA) flunisolide delivered as an extra-fine aerosol in asthma patients. Ann Allergy Asthma Immunol 2001, 87:405–411.

    Article  PubMed  CAS  Google Scholar 

  45. Hauber HP, Gotfried M, Newman K, et al.: Effect of HFAflunisolide on peripheral lung inflammation in asthma. J Allergy Clin Immunol 2003, 112:58–63.

    Article  PubMed  CAS  Google Scholar 

  46. Goldin JG, Tashkin DP, Kleerup EC, et al.: Comparative effects of hydrofluoroalkane and chlorofluorocarbon beclomethasone dipropionate inhalation on small airways: assessment with functional helical thin-section computed tomography. J Allergy Clin Immunol 1999, 104:S258–S267.

    Article  PubMed  CAS  Google Scholar 

  47. Cohen J, Douma WR, ten Hacken NH, et al.: Ciclesonide improves measures of small airway involvement in asthma. Eur Respir J 2008, 31:1213–1220.

    Article  PubMed  CAS  Google Scholar 

  48. Zeidler MR, Kleerup EC, Goldin JG, et al.: Montelukast improves regional air-trapping due to small airways obstruction in asthma. Eur Respir J 2006, 27:307–315.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jonathan Corren.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Corren, J. Small airways disease in asthma. Curr Allergy Asthma Rep 8, 533–539 (2008). https://doi.org/10.1007/s11882-008-0097-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11882-008-0097-4

Keywords

Navigation