Deep inhalation bronchoprotection.

Whenmethacholine is inhaledwith total lung capacity inhalations, which is the recommended inhalation pattern for the 5-breath dosimeter method,1 as many as a quarter of asthmatic patients can have a false-negative test result.2 It has been suggested to us that high forced expiratory volume in 1 second (FEV1) could explain negative (dosimeter) methacholine test results in patients with asthma. We therefore decided to perform additional analyses on previously published data in 55 asthmatic patients comparing the 2 American Thoracic Society (ATS) methacholine methods.2 Bronchoprotection can be defined as the tendency of a drug or a maneuver to inhibit bronchoconstriction. In these 55 patients, the bronchoprotective effect of the 5deep inhalationswas expressed as the doubling concentration difference between the 2methods. This was calculated by the following formula3: (log dosimeter PC20 – log tidal breathing PC20)/0.3 (where 0.3 is log 2 and PC20 is provocation concentration that caused a decrease in FEV1 of 20%). We looked for linear regression correlation with baseline FEV1 (the FEV1 before the first of the 2 challenges) defined as FEV1 percent predicted, FEV1 absolute (liters), and FEV1:forced vital capacity (FVC) ratio. We also sought correlation with (log) baseline tidal breathing PC20 and (log) dosimeter PC20. For all regressions regarding lung function, there was a nonsignificant correlation for higher FEV1 being associated with greater bronchoprotection (protection vs FEV1 [percent predicted], P! .16; protection vs FEV1 [liters], P ! .24; and protection vs FEV1/FVC ratio, P ! .11). We demonstrated a significant positive correlation between baseline tidal breathing PC20 and bronchoprotection (Fig 1, r ! 0.3, P ! .03). This finding demonstrates that the higher the baseline tidal breathing PC20 the greater the bronchoprotective effect of the deep inhalations. Fourteen of the 55 patients (25%) had negative dosimeter challenge results as previously published.2 In addition, the (expected) positive correlation was seen between the dosimeter PC20 and bronchoprotection (r! 0.81, P" .001). These results indicate that baseline FEV1 is at most a minor determinate of the important bronchoprotective effect of the 5 deep inhalations required to perform the dosimeter methacholine challenge as per guidelines.1 It is possible, in fact likely, that a larger study might have shown statistical significance, but this would be of limited clinical significance. The positive correlation with tidal breathing methacholine response, as previously shown by dichotomizing this population,2 indicates that the deep inhalation bronchoprotection is more likely to occur in those with, as defined by the ATS,1 mild (PC20 of 1–4 mg/mL) to borderline (PC20 of 4–16 mg/mL) airway hyperresponsiveness. Themarked correlation with the dosimeter PC20 is to be expected because the magnitude of the bronchoprotection is primarily determined by the magnitude of the dosimeter PC20. Other features, such as rhinitis7 and obesity,8 have been shown to play a role in the effect of deep inhalations in the airways of individuals without asthma. A larger study in asthmatic patients would be required to investigate these and other potential factors in asthmatic patients. We believe the importance of this bronchoprotective effect is often overlooked. Our data2 demonstrate that a quarter of asthmatic patients with a positive tidal breathing methacholine test result have negative dosimeter test results. This number approaches 50% of patients when addressing those with mild to borderline airway hyperresponsiveness (ie, PC20 of 1–16 mg/mL). This is the range most positive diagnostic methacholine challenge results would be expected to occur. Themajor value of methacholine challenge is the high diagnostic sensitivity and high negative predictive value,4 providing that symptoms are clinically current5 (ie, within the past day or two). We would also like to add the addiDisclosures: Authors have nothing to disclose. Fig. 1. Deep inhalation bronchoprotection vs baseline (tidal breathing) methacholine provocation concentration that caused a decrease in forced expiratory volume in 1 second of 20% (PC20). Bronchoprotection is defined as the doubling dose difference in PC20 between the 2 methods (dosimeter minus tidal breathing). Ann Allergy Asthma Immunol xx (2012) xxx