Isocapnic Hyperventilation for Measuring Airway Hyperresponsiveness in Asthma and in Chronic Obstructive Pulmonary Disease1 • 2 PAUL M. O'BYRNE, E. HELEN RAMSDALE, and FREDERICK E. HARGREAVE Introduction Measurements of airway responsiveness to inhaled chemical bronchoconstrictors (such as methacholine or histamine) have been useful to investigate the presence of asthma. Airway hyperresponsiveness in patients with close to normal airway caliber (FEV, > 70070 predicted normal) suggests the presence of current asthma when this is defined as variable airflow obstruction (1). The severity of airway hyperresponsiveness correlates with the severity of variable airflow obstruction (2) and the amount of treatment needed to control symptoms (3). Many smokers with persisting, irreversible airflow obstruction (chronic obstructive pulmonary disease [COPO)), with a best achievable FEV, of < 700J'0 predicted normal and a ratio of FEV,/VC < 70% also have airway hyperresponsiveness to inhaled chemical bronchoconstrictors (4). The more severe the degree ofairflow obstruction in these patients, the more severe is the airway hyperresponsiveness (5). Therefore, measurements of airway responsiveness to inhaled chemical bronchoconstrictors do not appear to be useful in distinguishing them from asthmatics. Airway responsiveness also can be measured by stimuli that appear to cause bronchoconstriction through the release of mediators from cells within the airways, and may be preferable for distinguishing between patients with asthma and those with COPO. One such method, isocapnic hyperventilation, may be more specific for diagnosing asthma, and it will be briefly reviewed in this report.

Method of Isocapnlc Hyperventilation Hyperventilation has been known to cause bronchoconstriction since the original description by Herxheimer in 1946 (6). The method of isocapnic hyperventilation currently used in our laboratories to administer an airway challenge uses dry, compressed air, which is passed over a cooling coil. Subjects inhale the cold, dry air through a Hans Rudolph valve (Hans Rudolph Inc, Kansas City, MO) divided into an inspiratory and expiratory port. End-tidal CO 2 is continuously measured in the expired air, and CO 2 is added to keep the subjects eucapnic. Subjects breathe at increasing minute volumes, beginning at 7.5 L/rnin, increasing to 15, 30, and 60 L/min and maximal minute ventilation, each period of ventilation lasting 3 min. The response is measured as the change in FEV, from baseline. A dose-response curve is obtained by plotting the incremental increase in minute

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Fig. 1. Change in FE\!, after isocapnic hyperventilation in an asthmatic subject (baseline FE\!,. 2.2 L; methacholine PC... 0.2 mglml) and a subject with COPO (baseline FE\!" 2.1 L; methacholine PC••• 0.24 mg/ml). The asthmatic, but not the patient with COPO, developed bronchoconstrietion after lsocapnie hyperventilation.

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o 7.5

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ventilation (VE) against the change in FEV" and the results expressed as the VE giving a predetennined fall in FEY, (usually 10or 20% fall) (figure 1). A major limitation with the method, however, is that the maximal challenge that can be given is dependent on the maximal voluntary ventilation that can be achieved by the subject being studied. The degree of airway hyperresponsiveness to isocapnic hyperventilation correlates with the degree of airway hyperresponsiveness to inhaled methacholine (7) and histamine (8) in asthmatic subjects.

Airway Responses to Isocapnic Hyperventilation In Patients with Asthma or with COPO In a study examining the airway responses to both inhaled methacholine and isocapnic hyperventilation in smokers, some of whom had airflow obstruction (mean FEY" 71070 predicted; FEV,/VC ratio, 61%), isocapnic hyperventilation caused bronchoconstriction in three of 27 subjects (5). In a group of patients with asthma matched by spirometry (mean FEY" 720J'0 predicted; FEV,/VC ratio, 65%), isocapnic hyperventilation caused bronchoconstriction in 26 of 27 subjects (9). In both groups, the degree of methacholine airway hyperresponsiveness correlated with the severity of the airflow obstruction; however, the severity of the methacholine airway hyperresponsiveness was greater in the asthmatics for any given level of baseline FEV,. Airway responsiveness to isocapnic hyperventilation and methacholine correlated in the asthmatics but not in the smokers. These and other studies have suggested that in patients with COPO the presence-of methacholine airway hyperresponsiveness

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need not indicate the presence of asthma. Also, that the mechanisms causing bronchoconstriction after isocapnic hyperventilation appear to be different in patients with asthma from those in patients with COPO. The results of the study described above indicate that in two well-characterized groups of patients, the positive predictive value for bronchoconstriction after isocapnic hyperventilation for a diagnosis of asthma is 90% compared with 60% for methacholine. However, the tests have not been compared in a population of patients in whom the diagnosis has not yet been established. This is necessary before the place of isocapnic hyperventilation in distinguishing between patients with asthma and COPD is identified. Ideally, however, the results of these tests need to be examined in relation to cytologic or histologic features of the airway inflammation, which will probably be the most useful way of distinguishing between these conditions.

References 1. Hargreave FE, RamsdaleEH, Dolovich J. Mea-

surementof airways responsiveness in clinical practice.In: HargreaveFE, Woolcock AJ, eds.Airway responsiveness measurement and interpretation.

1 Fromthe Asthma Research Group,Department of Medicine, Health Sciences Center, and St. Joseph's Hospital, McMaster University, Hamilton, Ontario, Canada. • Correspondence and requests for repririts should be addressed to Paul M. O'Byrne, Department of Medicine, Health Sciences Center, McMaster University, Hamilton, Ontario L8N 3Z5. Canada.

AM REV RESPIR DIS 1991; 143:1444-1445

ISOCAPNIC HYPERVENTILATION FOR MEASURING AIRWAY HYPERRESPONSIVENESS

Mississauga: Astra Pharmaceuticals, 1985; 122-6. 2. Ryan G, Latimer KM, Dolovich J, Hargreave FE. Bronchial responsiveness to histamine: relationship to diurnal variation of peak flow rates and improvement after bronchodilators. Thorax 1982; 37:423-9. 3. Juniper EF, Frith PA, Hargreave FE. Airway responsiveness to histamine and methacholine: relationship to minimum treatment to control symptoms of asthma. Thorax 1981; 36:575-9. 4. Ramsdell JW, Machtwey FJ, Moser KM. Bron-

chial hyperreactivity in chronic obstructive bronchitis. Am Rev Respir Dis 1982; 126:829-32. 5. Ramsdale EH, Morris MM, Roberts RS, Hargreave FE. Bronchial responsiveness to methacholine in chronic bronchitis: relationship to airflow obstruction and cold air responsiveness. Thorax 1984; 39:912-8. 6. Herxheimer H. Hyperventilation asthma. Lancet 1946; 1:83-7. 7. O'Byrne PM, Ryan G, Morris M, et al. Asthma induced by cold air and its relation to nonspecific

1445 bronchial responsiveness to methacholine. Am Rev Respir Dis 1982; 125:281-5. 8. Heaton RW, Henderson AF, Costello JE Cold air as a bronchial provocation technique. Reproducibility and comparison with histamine and methacholine inhalation. Chest 1984; 86:810-4. 9. Ramsdale EH, Roberts RS, Morris MM, Hargreave FE. Differences in responsiveness to hyperventilation and methacholine in asthma and chronic bronchitis. Thorax 1985; 40:422-6.

Isocapnic hyperventilation for measuring airway hyperresponsiveness in asthma and in chronic obstructive pulmonary disease.

Isocapnic Hyperventilation for Measuring Airway Hyperresponsiveness in Asthma and in Chronic Obstructive Pulmonary Disease1 • 2 PAUL M. O'BYRNE, E. HE...
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