Calculating the Response to Bronchoconstrictor Aerosol Challenge for Measurement of Airway Responsiveness Second Breath or First Breath, Better Breath or Worse Breath?

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Abstract
The reactivity or responsiveness of the conducting airways is frequently assessed in research and clinical contexts by the dose-response relationship of inhaled bronchoconstrictor aerosols (methacholine, histamine, hypotonie saline). Most frequently the airway response is measured using indices of airflow during forced expiratory maneuvers from total lung capacity (TLC). Under these circumstances, the responsiveness of the airways is markedly affected not only by the dose of aerosol delivered to the conducting airways, but also by the volume history of the respiratory system immediately prior to measurement of forced expiratory airflow. When two or more measurements of airflow are made after each inhaled dose of aerosol, differences in airflow between the first (usually lower) forced expiratory volume in the first second (FEV1) and the "best" (higher, usually last) FEV1 may affect the airway responsiveness calculated from the dose-response curve. We analyzed standard methacholine bronchoconstrictor inhalational challenges in a group of 16 healthy non-smoking young adults and 8 subjects with mild asthma who were on no medications at the time of testing. The difference in forced expiratory volume in the first second between the first and second maximal expiration after methacholine aerosol was directly proportional to the concentration of methacholine inhaled (greater difference at higher doses of methacholine). The magnitude of this difference was greater in the non-asthmatics, who were less responsive to methacholine and who required higher doses of methacholine to produce the same 20% fall in FEV1. Expiratory airflow after inhalation of aerosolized bronchoconstrictors, and hence measured airway responsiveness, is affected by serial lung inflation occurring between deposition of aerosol and the maximal expiratory maneuver. Standardization of inhalational challenge protocols requires consideration of volume history, and thus the number and choice of forced expirations performed, as well as of the aerosol delivery techniques.