WJ Gibbons, A Sharma, D Lougheed and PT Macklem
Montreal Chest Hospital Centre, McGill University, Quebec, Canada.

Airway hyperresponsiveness is easily assessed by measuring the concentration or dose of an inhaled agonist that produces a defined response, e.g., PC20 or PD20. However, this measure does not assess excessive bronchoconstriction. We report the results of analyzing bronchial dose-response curves by measuring percent fall in vital capacity (delta FVC%) as the response rather than the PC20. In our analysis, delta FVC% was measured at the PC20, and therefore it was the dependent variable, whereas the concentration of agonist was the independent variable, in contrast to the usual bronchoprovocation tests in which the response is the independent variable and the dose is the dependent variable. We reasoned that a dose-dependent increase in gas trapping with histamine would detect excessive bronchoconstriction as a decrease in FVC; in contrast, PC20 measures only the ease of bronchoconstriction. In 10 patients with mild asthma the reproducibility of delta FVC% when FEV1 fell by 20%, i.e., at the PC20 concentration of histamine, taken from a greater than 6-s FVC on an otherwise standard histamine challenge test was comparable to that of PC20. In 10 healthy asymptomatic subjects there were only trivial falls (0.3%) in FVC to as much as 16 mg/ml histamine. In a retrospective study of 146 patients with mild asthma, the delta FVC% was normally distributed (13.2 +/- 5.5 SD%) and did not correlate with the number of beta 2-agonist prescriptions or the PC20, but it did correlate with the number of prescriptions written per month for oral prednisone (r = 0.55, p < 0.02). We conclude that delta FVC% when FEV1 falls by 20% is a safe method of detecting excessive bronchoconstriction, and it reveals that different asthmatics react in fundamentally different ways to the same agonist. This may be useful in detecting the asthmatic at risk for serious disease.

This article has been cited by other articles:

				J. Cohen, W. R. Douma, N. H. T. ten Hacken, J. M. Vonk, M. Oudkerk, and D. S. Postma Ciclesonide improves measures of small airway involvement in asthma Eur. Respir. J., June 1, 2008; 31(6): 1213 - 1220. [Abstract] [Full Text] [PDF]

				R. L. Sorkness, E. R. Bleecker, W. W. Busse, W. J. Calhoun, M. Castro, K. F. Chung, D. Curran-Everett, S. C. Erzurum, B. M. Gaston, E. Israel, et al. Lung function in adults with stable but severe asthma: air trapping and incomplete reversal of obstruction with bronchodilation J Appl Physiol, February 1, 2008; 104(2): 394 - 403. [Abstract] [Full Text] [PDF]

				Y. Yoo, J. T. Choung, J. Yu, D. K. Kim, S. H. Choi, and Y. Y. Koh Comparison of Percentage Fall in FVC at the Provocative Concentration of Methacholine Causing a 20% Fall in FEV1 Between Patients With Asymptomatic Bronchial Hyperresponsiveness and Mild Asthma Chest, July 1, 2007; 132(1): 106 - 111. [Abstract] [Full Text] [PDF]

				C. Brindicci, K. Ito, P. J. Barnes, and S. A. Kharitonov Differential Flow Analysis of Exhaled Nitric Oxide in Patients With Asthma of Differing Severity Chest, May 1, 2007; 131(5): 1353 - 1362. [Abstract] [Full Text] [PDF]

				C. G. Irvin Lessons from structure-function studies in asthma: myths and truths about what we teach J Appl Physiol, July 1, 2006; 101(1): 7 - 9. [Full Text] [PDF]

				C. Schweitzer, L. T. T. Vu, Y. T. Nguyen, C. Chone, B. Demoulin, and F. Marchal Estimation of the bronchodilatory effect of deep inhalation after a free run in children Eur. Respir. J., July 1, 2006; 28(1): 89 - 95. [Abstract] [Full Text] [PDF]

				R. Pellegrino, V. Brusasco, R. O. Crapo, G. Viegi, J. Wanger, P. Gustafsson, M. R. Miller, R. T. McKay, R. Casaburi, N. McIntire, et al. From the authors Eur. Respir. J., June 1, 2006; 27(6): 1323 - 1324. [Full Text] [PDF]

				R. Pellegrino, V. Brusasco, R. O. Crapo, and G. Viegi From the authors Eur. Respir. J., May 1, 2006; 27(5): 1070 - 1070. [Full Text] [PDF]

				I. H. van Veen, P. J. Sterk, R. Schot, S. A. Gauw, K. F. Rabe, and E. H. Bel Alveolar nitric oxide versus measures of peripheral airway dysfunction in severe asthma Eur. Respir. J., May 1, 2006; 27(5): 951 - 956. [Abstract] [Full Text] [PDF]

				Y. Yoo, J. Yu, D. K. Kim, and Y. Y. Koh Percentage Fall in FVC at the Provocative Concentration of Methacholine Causing a 20% Fall in FEV1 in Symptomatic Asthma and Clinical Remission During Adolescence. Chest, February 1, 2006; 129(2): 272 - 277. [Abstract] [Full Text] [PDF]

				H. C. Haverkamp, J. A. Dempsey, J. D. Miller, L. M. Romer, D. F. Pegelow, A. T. Lovering, and M. W. Eldridge Repeat exercise normalizes the gas-exchange impairment induced by a previous exercise bout in asthmatic subjects J Appl Physiol, November 1, 2005; 99(5): 1843 - 1852. [Abstract] [Full Text] [PDF]

				S Chinn and J P Schouten Reproducibility of non-specific bronchial challenge in adults: implications for design, analysis and interpretation of clinical and epidemiological studies Thorax, May 1, 2005; 60(5): 395 - 400. [Abstract] [Full Text] [PDF]

				F. C. Sciurba Physiologic Similarities and Differences Between COPD and Asthma Chest, August 1, 2004; 126(2_suppl_1): 117S - 124S. [Abstract] [Full Text] [PDF]

				R. L. Sorkness and A. Tuffaha Contribution of airway closure to chronic postbronchiolitis airway dysfunction in rats J Appl Physiol, March 1, 2004; 96(3): 904 - 910. [Abstract] [Full Text] [PDF]

				V. Brusasco and R. Pellegrino Invited Review: Complexity of factors modulating airway narrowing in vivo: relevance to assessment of airway hyperresponsiveness J Appl Physiol, September 1, 2003; 95(3): 1305 - 1313. [Abstract] [Full Text] [PDF]

				A. Corsico, M. Milanese, S. Baraldo, G. L. Casoni, A. Papi, A. M. Riccio, I. Cerveri, M. Saetta, and V. Brusasco Small airway morphology and lung function in the transition from normality to chronic airway obstruction J Appl Physiol, July 1, 2003; 95(1): 441 - 447. [Abstract] [Full Text] [PDF]

				Y. Y. Koh, Y. Park, and C. K. Kim Maximal Airway Response in Adolescents With Long-term Asthma Remission and Persisting Airway Hypersensitivity: Its Profile and the Effect of Inhaled Corticosteroids Chest, October 1, 2002; 122(4): 1214 - 1221. [Abstract] [Full Text] [PDF]

				M. Milanese, E. Crimi, A. Scordamaglia, A. Riccio, R. Pellegrino, G. W. Canonica, and V. Brusasco On the functional consequences of bronchial basement membrane thickening J Appl Physiol, September 1, 2001; 91(3): 1035 - 1040. [Abstract] [Full Text] [PDF]

				C.-L. Que, C. M. Kenyon, R. Olivenstein, P. T. Macklem, and G. N. Maksym Homeokinesis and short-term variability of human airway caliber J Appl Physiol, September 1, 2001; 91(3): 1131 - 1141. [Abstract] [Full Text] [PDF]

				P. Lee, J. Abisheganaden, C.B.E. Chee, and Y.T. Wang A new asthma severity index: a predictor of near-fatal asthma? Eur. Respir. J., August 1, 2001; 18(2): 272 - 278. [Abstract] [Full Text] [PDF]

				G. Cuttitta, F. Cibella, V. Bellia, V. Grassi, S. Cossi, S. Bucchieri, and G. Bonsignore Changes in FVC During Methacholine-Induced Bronchoconstriction in Elderly Patients With Asthma : Bronchial Hyperresponsiveness and Aging Chest, June 1, 2001; 119(6): 1685 - 1690. [Abstract] [Full Text] [PDF]

				D. A. KAMINSKY and M. LYNN Pulmonary Capillary Blood Volume in Hyperpnea-induced Bronchospasm Am. J. Respir. Crit. Care Med., November 1, 2000; 162(5): 1668 - 1673. [Abstract] [Full Text]

				R. B. BANZETT, J. A. DEMPSEY, D. E. O'DONNELL, and M. Z. WAMBOLDT Symptom Perception and Respiratory Sensation in Asthma Am. J. Respir. Crit. Care Med., September 1, 2000; 162(3): 1178 - 1182. [Full Text]

				D. A. KAMINSKY, J. H. T. BATES, and C. G. IRVIN Effects of Cool, Dry Air Stimulation on Peripheral Lung Mechanics in Asthma Am. J. Respir. Crit. Care Med., July 1, 2000; 162(1): 179 - 186. [Abstract] [Full Text]

				J. C. C. M.i.`t VEEN, A. J. BEEKMAN, E. H. BEL, and P. J. STERK Recurrent Exacerbations in Severe Asthma Are Associated with Enhanced Airway Closure During Stable Episodes Am. J. Respir. Crit. Care Med., June 1, 2000; 161(6): 1902 - 1906. [Abstract] [Full Text]

				R. Crapo Guidelines for Methacholine and Exercise Challenge Testing---1999 . THIS OFFICIAL STATEMENT OF THE AMERICAN THORACIC SOCIETY WAS ADOPTED BY THE ATS BOARD OF DIRECTORS, JULY 1999 Am. J. Respir. Crit. Care Med., January 1, 2000; 161(1): 309 - 329. [Full Text]

				D. Stanescu Small Airways Obstruction Syndrome Chest, July 1, 1999; 116(1): 231 - 233. [Abstract] [Full Text] [PDF]

				B. J. MOORE, L. M. VERBURGT, G. G. KING, and P. D. PARE The Effect of Deep Inspiration on Methacholine Dose-response Curves in Normal Subjects Am. J. Respir. Crit. Care Med., October 1, 1997; 156(4): 1278 - 1281. [Abstract] [Full Text] [PDF]

				P. T. MACKLEM The Physiology of Small Airways Am. J. Respir. Crit. Care Med., May 1, 1997; 157(5): 181 - 183. [Full Text]