Bronchial Provocation Tests
To guarantee a meaningful performance of the MCC, patients had to follow
the preparation guidelines(3, 9). The administration of the MCC was
largely automated according to the 1-concentration-4-step dosimeter
protocol(10) which promises advantages in dosing accuracy and handling.
Briefly, spirometry was performed at baseline as a first step, followed
by four steps, each with the inhalation of methacholine and subsequent
spirometry two minutes after inhalation. With each step the inhaled
methacholine dose was raised, starting from 15 μg and increasing to a
maximum of 720 μg. The exact dose inhaled at each step was determined by
measuring the effective nebulization time at inspiration and referring
it to the drug concentration and nebulizer power. The complete procedure
was realized with the MasterScreenTM Body system
(CareFusion, Höchberg, Germany) powered by the Sentry Suite software
(Version 2.17.66, Hotfix Package 4) with automated control, providing a
real-time visualization of the dose administration and breathing
pattern. To optimize the inhalation process, patients could control
their breathing themselves by a visual computer graphic imitating their
breathing to attain an airflow of 0.5 L/s and to guarantee an
inspiration time of 3 seconds during inhalation. The aerosol for
inhalation was generated directly by the flow-triggered nebulization of
a solution with a constant methacholine concentration (16 mg per mL
isotonic saline(11)) through a mouthpiece of an APSpro jet-type
nebulizer (240 mg/min performance; Medic Aid pro; Sidestream Care
Fusion).
The current, as well as the cumulative, methacholine dose (PD20) which
caused a decrease of FEV1 by more than 20% was
calculated by logarithmic interpolation. The end-of-test criterion was
met if either FEV1 decreased by more than 20% or the
maximum cumulative methacholine dose of 960 μg had been inhaled. The
result of the MCC was assessed as positive if PD20 was lower than 960
μg.