Skip to main content
Log in

What Long-Term Changes in Lung Function Can Tell Us About Asthma Control

  • Asthma (WJ Calhoun and S Peters, Section Editors)
  • Published:
Current Allergy and Asthma Reports Aims and scope Submit manuscript

Abstract

Asthma severity is typically classified according to lung function, but asthma control in relation to lung function is often harder to define. In this paper, we will review how lung function measured at rest, as well as over time, relates to asthma control. We will explore not only conventional lung function as measured by spirometry, such as peak expiratory flow and forced expiratory volume in 1 s, but also more sophisticated measurements of peripheral airway function related to respiratory system impedance and ventilation heterogeneity. In particular, we will review the emerging area of assessing the fluctuation of lung function over time and how it may correlate to both past and future asthma control.

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

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Expert Panel Report 3. Guidelines for the diagnosis and management of asthma—summary report 2007. US Department of Health and Human Services, National Institutes of Health, National Heart, Lung, and Blood Institute 2007

  2. Turner Warwick M. On observing patterns of airflow obstruction in chronic asthma. Br J Dis Chest. 1977;71:73–86.

    Article  CAS  PubMed  Google Scholar 

  3. Llewellin P et al. The relationship between FEV1 and PEF in the assessment of the severity of airway obstruction. Respirology. 2002;7:333–7.

    Article  PubMed  Google Scholar 

  4. Boushey H et al. National Heart, Lung, and Blood Institute's Asthma Clinical Research Network. Daily versus as-needed corticosteroids for mild persistent asthma. N Engl J Med. 2005;352:1519–28.

    Article  CAS  PubMed  Google Scholar 

  5. Kikuchi Y et al. Chemosensitivity and perception of dyspnea in patients with a history of near-fatal asthma. N Engl J Med. 1994;330:1329–34.

    Article  CAS  PubMed  Google Scholar 

  6. McCoy K et al. Predicting episodes of poor asthma control in treated patients with asthma. J Allergy Clin Immunol. 2006;118:1226–33.

    Article  PubMed  Google Scholar 

  7. Ayres J, Miles J, Barnes P. Brittle asthma. Thorax. 1998;53:315–21.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. An S et al. Airway smooth muscle dynamics: a common pathway of airway obstruction in asthma. Eur Respir J. 2007;29:834–60.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Sferrazza Papa G, Pellegrino G, Pellegrino R. Asthma and respiratory physiology: putting lung function into perspective. Respirology 2014: p. 1-10. This is a comprehensive review of respiratory physiology in asthma that provides the context for understanding lung function in relation to asthma control.

  10. Wechsler ME et al. Asthma Intervention Research 2 Trial Study Group. Bronchial thermoplasty: long-term safety and effectiveness in patients with severe persistent asthma. J Allergy Clin Immunol. 2013;132:1295–302.

    Article  PubMed Central  PubMed  Google Scholar 

  11. Kitch B et al. A single measure of FEV1 is associated with risk of asthma attacks in long-term follow-up. Chest. 2004;126:1875–82.

    Article  PubMed  Google Scholar 

  12. Sont J et al. Clinical control and histopathologic outcome of asthma when using airway hyperresponsiveness as an additional guide to long-term treatment. Am J Respir Crit Care Med. 1999;159:1043–51.

    Article  CAS  PubMed  Google Scholar 

  13. Nuijsink M, Vaessen-Verberne A, Hop WCJ, Serk P, Duiverman E, de Jongste J. Long-term follow-up after two years of asthma treatment guided by airway responsiveness in children. Respir Med. 2013;107:981–6.

    Article  PubMed  Google Scholar 

  14. Koh Y, Park Y, Kim C. Maximal airway response in adolescents with long-term asthma remission and persisting airway sensitivity. Chest. 2002;122:1214–21.

    Article  CAS  PubMed  Google Scholar 

  15. Limb S et al. Irreversible lung function deficits in young adults with a history of childhood asthma. J Allergy Clin Immunol. 2005;116:1213–9.

    Article  PubMed  Google Scholar 

  16. Tai A et al. The association between childhood asthma and adult chronic obstructive pulmonary disease. Thorax. 2014;69:805–10. This study provides the longest follow-up available on children with asthma and their subsequent lung function, and documents the development of fixed airflow limitation in children with severe asthma.

    Article  PubMed  Google Scholar 

  17. Humbles A et al. A critical role for eosinophils in allergic airways remodeling. Science. 2004;305:1776–9.

    Article  CAS  PubMed  Google Scholar 

  18. Dixon A, Irvin C. Early intervention of therapy in asthma. Curr Opin Pulm Med. 2005;11:51–5.

    Article  PubMed  Google Scholar 

  19. Grainge C et al. Effect of bronchoconstriction on airway remodeling in asthma. N Engl J Med. 2011;364:2006–15.

    Article  CAS  PubMed  Google Scholar 

  20. Lipworth B, Manoharan A, Anderson W. Unlocking the quiet zone: the small airway asthma phenotype. Lancet Respir Med. 2014;2:497–506. This is a comprehensive review of small airways physiology and dysfunction in asthma with special emphasis on relationship of small airways to asthma control and implications for treatment.

    Article  PubMed  Google Scholar 

  21. Scichilone N, Battaglia S, Olivieri D, Bellia V. The role of small airways in monitoring the response to asthma treatment: what is beyond FEV1? Allergy. 2009;64:1563–9.

    Article  CAS  PubMed  Google Scholar 

  22. Wagner E, Liu M, Weinmann G, Permutt S, Bleecker E. Peripheral lung resistance in normal and asthmatic subjects. Am J Respir Crit Care Med. 1990;141:584–8.

    CAS  Google Scholar 

  23. Berman A, Liu M, Wagner E, Proud D. Dissociation of bradykinin-induced plasma exudation and reactivity in the peripheral airways. Am J Respir Crit Care Med. 1996;1996(154):418–23.

    Article  Google Scholar 

  24. Kaminsky D et al. Peripheral airways responsiveness to cool, dry air in normal and asthmatic subjects. Am J Respir Crit Care Med. 1995;152:1784–90.

    Article  CAS  PubMed  Google Scholar 

  25. Wagner E, Bleecker E, Permutt S, Liu M. Direct assessment of small airways reactivity in human subjects. Am J Respir Crit Care Med. 1998;157:447–52.

    Article  CAS  PubMed  Google Scholar 

  26. Rao D et al. The utility of forced expiratory flow between 25 % and 75 % of vital capacity in predicting childhood asthma morbidity and severity. J Asthma. 2012;2012(49):586–92.

    Article  Google Scholar 

  27. Mahut B, Peiffer C, Bokov P, Beydon N, Delclaux C. Gas trapping is associated with severe exacerbation in asthmatic children. Respir Med. 2010;104:1230–3.

    Article  PubMed  Google Scholar 

  28. Shi Y, Aledia A, Galant S, George S. Peripheral airway impairment measured by oscillometry predicts loss of asthma control in children. J Allergy Clin Immunol. 2013;131:718. This study specifically documented that abnormal peripheral resistance at baseline predicted poor asthma control at follow-up over the subsequent 8-12 weeks.

    Article  PubMed  Google Scholar 

  29. in't Veen J, Beekman A, Bel E, Serk P. Recurrent exacerbations in severe asthma are associated with enhanced airway closure during stable episodes. Am J Respir Crit Care Med. 2000;161:1902–6.

    Article  Google Scholar 

  30. Farah C et al. The role of small airways in the clinical expression of asthma in adults. J Allergy Clin Immunol. 2012;129:381–7. This study demonstrated that ventilation heterogeneity in the acinar and conductive zones of the lung correlated with asthma control and independently correlated with changes in asthma control in response to inhaled corticosteroid therapy.

    Article  PubMed  Google Scholar 

  31. Farah C et al. Ventilation heterogeneity predicts asthma control in adults following inhaled corticosteroid dose titration. J Allergy Clin Immunol. 2012;130:61–8. This study documented that ventilation heterogeneity in the conductive zones correlated with asthma control during up-titration of inhaled corticosteroids, but ventilation heterogeneity in the acinar zones correlated with asthma control during down-titration of inhaled corticosteroids.

    Article  CAS  PubMed  Google Scholar 

  32. Thompson B et al. Peripheral lung function in patients with stable and unstable asthma. J Allergy Clin Immunol. 2013;131:1322–8. This study uniquely characterized ventilation heterogeneity among patients admitted with an asthma exacerbation compared to a group of patients with stable asthma and found increased ventilation heterogeneity in both the acinar and conductive zones.

    Article  PubMed  Google Scholar 

  33. Kaminsky D. Multiple breath nitrogen washout profiles in asthmatic patients: what do they mean clinically? J Allergy Clin Immunol. 2013;131:1329–30.

    Article  PubMed  Google Scholar 

  34. Venegas J et al. Self-organized patchiness in asthma as a prelude to catastrophic shifts. Nature. 2005;434:777–82.

    Article  CAS  PubMed  Google Scholar 

  35. Manoharan A, Anderson W, Lipworth J, Ibrahim I, Lipworth B. Small airway dysfunction is associated with poorer asthma control. Eur Respir J. 2014;44:1353–5. This study demonstrated that persistent abnormalities in the lung periphery as measured y the FEF 25-75 and frequency dependence of resistance are associated with poor asthma control.

    Article  PubMed  Google Scholar 

  36. Kelly V et al. Respiratory system reactance is an independent determinant of asthma control. J Appl Physiol. 2013;115:1360–9. This study demonstrated that poor asthma control was associated with higher respiratory system reactance, gas trapping (RV/TLC) and ventilation heterogeneity.

    Article  CAS  PubMed  Google Scholar 

  37. Hanon S, Schuermans D, Vincken W, Verbanck S. Irreversible acinar abnormality in well controlled asthma. Respir Med 2014; EPub ahead of print. This study documents residual ventilation heterogeneity in the acinar region of the lung in patients with well controlled asthma, and its lack of response to inhaled corticosteroid therapy, suggesting persistent structural changes in this region.

  38. Anderson W, Zajda E, Lipworth B. Are we overlooking persistent small airways dysfunction in community-managed asthma? Ann Allergy Asthma Immunol. 2012;109:185–9. This study reveals that small airways dysfunction exists in a cross-section of asthma patients in the community despite adequate treatment according to standard-of-care guidelines.

    Article  PubMed  Google Scholar 

  39. Boezen H, Schouten J, Postma D, Rijcken B. Relation between respiratory symptoms, pulmonary function and peak flow variability in adults. Thorax. 1995;50:121–6.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  40. Kamiya K et al. Relationship between sensitivity to dyspnea and fluctuating peak expiratory flow rate in the absence of asthma symptoms. Asia Pac Allergy. 2012;2:49–58.

    Article  PubMed Central  PubMed  Google Scholar 

  41. Thamrin C, Taylor D, Jones S, Suki B, Frey U. Variability of lung function predicts loss of asthma control following withdrawal of inhaled corticosteroid treatment. Thorax. 2010;65:403–8.

    Article  PubMed  Google Scholar 

  42. Matsunaga K et al. Changes in forced expiratory volume in 1 second over time in patients with controlled asthma at baseline. Respir Med. 2014;108:976–82. This study documents that patients with poor asthma control have an accelerated loss of lung function (FEV1) over time.

    Article  PubMed  Google Scholar 

  43. Thamrin C, Stern G. New methods what do they tell us: fluctuation analysis of lung function. Eur Respir Mon. 2010;47:310–24.

    Google Scholar 

  44. Frey U et al. Risk fo severe asthma episodes predicted from fluctuation analysis of airway function. Nature. 2005;438:667–70.

    Article  CAS  PubMed  Google Scholar 

  45. Kaminsky D et al. Detrended fluctuation analysis of peak expiratory flow and its association with destabilization of asthma control. American Thoracic Society 2014; A2675

  46. Thamrin C et al. Predicting future risk of asthma exacerbations using individual conditional probabilities. J Allergy Clin Immunol. 2011;127:1494–502. This study demonstrates how information from the correlation of lung function (PEF) over time and its distribution can be combined on an individual basis to provide prediction of asthma control.

    Article  PubMed  Google Scholar 

  47. Kupczyk M, Dahlen S. Will recording of lung function fluctuation open the door to internet-guided treatment of asthma? Thorax. 2011;66:1019–20.

    Article  PubMed  Google Scholar 

  48. Que C, Kenyon C, Olivenstein R, Macklem P, Maksym G. Homeokinesis and short-term variability of human airway caliber. J Appl Physiol. 2001;91:1131–41.

    CAS  PubMed  Google Scholar 

  49. Lall C et al. Airway resistance variability and response to bronchodilator in children with asthma. Eur Respir J. 2007;30:260–8.

    Article  CAS  PubMed  Google Scholar 

  50. Gulotta C et al. Monitoring the temporal changes of respiratory resistance: a novel test for the management of asthma. Am J Respir Crit Care Med. 2012;185:1330–1. This study measures variability in inspiratory resistance during home monitoring of lung function using the FOT and calculates the probability of asthma exacerbation based on the degree of variability in inspiratory resistance.

    Article  PubMed  Google Scholar 

  51. Robinson P et al. Increased day-to-day variability of forced oscillatory resistance in poorly controlled or persistent pediatric asthma. Chest 2014; Epub ahead of print. In this study, day to day variability in respiratory system resistance was able to differentiate children with controlled vs. uncontrolled asthma attending an asthma summer camp.

  52. Diba C et al. Short-term variability of airway caliber—a marker of asthma? J Appl Physiol. 2007;103:296–304.

    Article  PubMed  Google Scholar 

  53. Viega J et al. Approximate entropy as a measure of the airflow pattern complexity in asthma. Conf Proc IEEE Eng Med Biol Soc. 2010;2010:2463–6.

    Google Scholar 

  54. Viega J, Lopes A, Jansen J, Melo P. Fluctuation analysis of respiratory impedance waveform in asthmatic patients: effect of airway obstruction. Med Biol Eng Comput. 2012;50:1249–59. This study found that the heterogeneity of airway narrowing was increased, but the complexity of the airflow pattern was reduced, in patients with more severe asthma.

    Article  Google Scholar 

  55. Gonem S et al. Airway impedance entropy and exacerbations in severe asthma. Eur Respir J. 2012;40:1156–63. This study demonstrated that the heterogeneity of airway constriction and airway closure, and their fluctuation over time, were associated with asthmatic patients prone to frequent exacerbations.

    Article  PubMed  Google Scholar 

  56. Macklem P. Emergent phenomena and the secrets of life. J Appl Physiol. 2008;104:1844–6.

    Article  PubMed  Google Scholar 

Download references

Compliance with Ethics Guidelines

Conflict of Interest

Dr. Kaminsky and Dr. Irvin have declared no potential conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to David A. Kaminsky.

Additional information

This article is part of the Topical Collection on Asthma

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kaminsky, D.A., Irvin, C.G. What Long-Term Changes in Lung Function Can Tell Us About Asthma Control. Curr Allergy Asthma Rep 15, 3 (2015). https://doi.org/10.1007/s11882-014-0505-x

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11882-014-0505-x

Keywords

Navigation