VANDOEUVRE LÈS NANCY, FRANCE—Methacholine testing for bronchial hyperresponsiveness typically includes a diluent control step. A recent study questions this practice, suggesting that it may reduce sensitivity as well as increase the costs and effort involved in testing populations.[1] “Our data do not support the compulsory use of a diluent step when measuring bronchial responsiveness,” said Abraham Bohadana, MD, Research Director at Institut National Santé et Recherche Médical.

DILUENT MAY MASK HYPERRESPONSIVENESS

Two main arguments have been used to support the use of a diluent control in hyperresponsiveness testing, Dr. Bohadana told RESPIRATORY REVIEWS. First, he pointed out, “identification of diluent responders may obviate the need to use methacholine” in severely hyperresponsive individuals who may be endangered by such a challenge. Additionally, a diluent step might serve to train subjects to maximize test performance.

However, Dr. Bohadana argued, response to diluent could mask detection of mild to moderate hyperresponsiveness. A subject is considered a “reactor” if his forced expiratory volume in one second (FEV1) drops more than 20% in response to challenge. “Let us suppose his FEV1 drops 8% after diluent; he is negative,” he offered as an example. This subject might then show a further drop of 14% on methacholine testing. “This subject is negative again—but his FEV1 decreased 22% from the start,” Dr. Bohadana pointed out. “By this reasoning, we obtain false negative [results], and this is extremely important in epidemiological settings.”

In 183 occupationally exposed workers whose baseline FEV1 was at least 60% of expected, Dr. Bohadana and colleagues compared methacholine test findings calculated using either presaline or postsaline FEV1 as the baseline. The subjects underwent spirometry both before and after inhaling a saline aerosol; mean FEV1 dropped significantly (by 1.44%). Three (1.6%) patients whose FEV1 dropped 10% or more were identified; these “saline reactors” were excluded from methacholine challenge.

The remaining 180 subjects were subsequently challenged with three successive doses of methacholine (0.4, 2.8, and 7.6 mmol), and spirometry was performed three minutes after each challenge. Using the criterion of a 20% or greater drop in FEV1, 67 (37.2%) of the subjects were identified as hyperresponsive, regardless of whether presaline or postsaline FEV1 was used as the baseline value. Likewise, 105 (58.3%) of the subjects were classified as nonresponders by both calculation methods. However, eight subjects (4.4%) were misclassified as nonreactors when the postsaline rather than the presaline FEV1 was used as the baseline value.

DILUENT MIMICS METHACHOLINE

The masking problem may be explained by the observation that inhaled diluent sometimes mimics methacholine. “Diluent challenge provokes the same physiological reaction: contraction of muscular fibers of the airways, with an increase in airway resistance and reduction in forced expiratory volumes,” noted Dr. Bohadana. “Receptors in the airway mucosa react to the concentration (osmolarity) of the inhaled fluid,” he explained. Thus diluents, especially distilled water or very concentrated solutions, may elicit nonspecific reactions. Furthermore, adding a diluent step to challenge testing was time consuming.

—Mimi Zucker, PhD