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(Chest. 2006;130:622-623.)
© 2006 American College of Chest Physicians

Magnitude of Bronchoprotection of Albuterol vs Methacholine

Relationship to Baseline Airway Caliber

Donald W. Cockcroft, MD, FCCP and Beth E. Davis, BSc

Royal University Hospital, University of Saskatchewan, Saskatoon, SK, Canada

Correspondence to: Donald W. Cockcroft, MD, FCCP, Royal University Hospital, Division of Respirology, Critical Care and Sleep Medicine, 103 Hospital Dr, Ellis Hall, Fifth Floor, Saskatoon, SK, S7N 0W8 Canada; e-mail: cockcroft{at}sask.usask.ca

To the Editor:

Airway hyperresponsiveness (AHR) to methacholine likely relates to smooth muscle dysfunction in asthma patients and to a geometric function of reduced airway caliber in COPD patients.1 This geometric phenomenon should contribute to AHR in asthmatic patients with nonreversible obstruction.

Therapy with albuterol markedly protects against methacholine-induced smooth muscle contraction.2345 We hypothesize that the geometric AHR component due to airway narrowing in asthma patients should be less inhibited by the administration of albuterol. In this brief report, we examine data from previous studies2345 in 28 asthmatic patients.

All patients were nonsmokers with no other lung disease. All had refrained from using inhaled ß2-agonists for > 2 weeks (indicating that ß2-agonist tolerance would not affect the magnitude of bronchoprotection), and no patients were using controller medications. Study subjects were chosen only once, sequentially, as follows: 12 patients from one study2; 7 patients from a second study3; 6 patients from a third study4; and 3 patients from a fourth study.5 The provocative concentration of methacholine causing a 20% fall in FEV1 (PC20) was measured before and 10 min after inhaling 2 puffs (200 µg) of albuterol. The bronchoprotective effect of albuterol was expressed as the dose-shift,2345 which is the number of doubling concentrations that the PC20 had improved after albuterol administration. We examined the baseline FEV1 in the 10% strata, with 3 patients between 70 and 79% predicted, 8 patients between 80 and 89% predicted, 10 patients between 90 and 99% predicted, and 7 patients at ≥ 100% predicted.

There was a wide range of bronchoprotection (0.7 to 5.4 doubling doses; mean [± SD] number of doubling doses, 3.2 ± 1.0). There was no overall significant relationship between baseline FEV1 and bronchoprotection; however, in the FEV1 stratified data, a trend emerged (Fig 1 ). The mean bronchoprotection increased from 2.3 doubling concentrations in subjects with an FEV1 in the 70% predicted range to 3.6 doubling concentrations for those with an FEV1 of > 100% predicted. The regression of these four data points is significant (r = 0.96; p = 0.027).


Figure 1
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  		Figure 1.. The vertical axis represents the mean bronchoprotection for each of the four groups in doubling-dose shifts, and the horizontal axis represents the four FEV1 strata (70 to 79%, 80 to 89%, 90 to 99%, and ≥ 100% predicted).

 
These data are not definitive. However, they do support the hypothesis that the AHR component due to airway obstruction is less inhibited by therapy with inhaled ß2-agonists. Confirmation in one or more larger studies comparing this in asthma vs COPD patients would be particularly interesting.

Acknowledgements

The authors wish to thank Jacquie Bramley for assisting in the preparation of this article.

Footnotes

The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. This research was partially supported by the Lung Association of Saskatchewan.

References

  1. Cockcroft, DW, O’Byrne, PM (1993) Mechanisms of airway hyperresponsiveness. Weiss, EB Stein, M eds. Bronchial asthma, mechanisms and therapeutics 3rd ed. ,32-42 Little, Brown and Company. Boston, MA:
  2. Cockcroft, DW, McParland, CP, Britto, SA, et al Regular inhaled salbutamol and airway responsiveness to allergen. Lancet 1993;342,833-837[CrossRef][ISI][Medline]
  3. Cockcroft, DW, Swystun, VA, Bhagat, R Interaction of inhaled beta 2 agonist and inhaled corticosteroid on airway responsiveness to allergen and methacholine. Am J Respir Crit Care Med 1995;152,1485-1489[Abstract]
  4. Bhagat, R, Swystun, VA, Cockcroft, DW Salbutamol-induced increased airway responsiveness to allergen and reduced protection versus methacholine: dose response. J Allergy Clin Immunol 1996;97,47-52[CrossRef][ISI][Medline]
  5. Cockcroft, DW, Swystun, VA, Kalra, S, et al Determination of post-salbutamol methacholine dose shift. Chest 1996;110,579-580[Free Full Text]




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