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Methacholine and Ovalbumin Challenges Assessed by Forced Oscillations and Synchrotron Lung Imaging

¹ Université de Picardie Jules Verne, EA4285 Péritox-INERIS and CHU Amiens, Amiens, France; ² Department of Clinical Physiology and Nuclear Medicine, Helsinki University Central Hospital, Helsinki, Finland; ³ European Synchrotron Radiation Facility, ID17, Grenoble, France; ⁴ Department of Physics, University of Helsinki, Helsinki, Finland; ⁵ Geneva Children's Hospital, University Hospitals of Geneva and Geneva University, Geneva, Switzerland; and ⁶ Department of Medical Informatics and Engineering, University of Szeged, Szeged, Hungary

Correspondence and requests for reprints should be addressed to Sam Bayat, M.D., Ph.D., Centre Hospitalier Universitaire d'Amiens, Cardiologie et Pneumo-Allergologie Pédiatriques 1 Place Victor Pauchet, 80054, Amiens Cedex 1, France. E-mail: bayat.sam{at}chu-amiens.fr

Rationale: Methacholine (Mch) is routinely used to assess bronchial hyperreactivity; however, little is known about the differences in the lung response pattern between this provocation and that observed with ovalbumin (Ova) after allergic sensitization.

Objectives: To compare (1) the central versus peripheral effects of Mch and Ova within the lung by combining measurements of airway and tissue mechanics with synchrotron radiation (SR) imaging, and (2) to assess the extent to which mechanical and imaging parameters are correlated.

Methods: We used the low-frequency forced oscillation technique and SR imaging in control (n = 12) and ovalbumin-sensitized (n = 13) rabbits, at baseline, during intravenous Mch infusion (2.5 µg/kg/min, 5.0 µg/kg/min, or 10.0 µg/kg/min), after recovery from Mch, and after intravenous Ova injection (2.0 mg). We compared intravenous Mch challenge with inhaled Mch (125 mg/ml, 90 s) in a separate group of control animals (n = 5).

Measurements and Main Results: Airway conductance and tissue elastance were measured by low-frequency forced oscillation technique. The central airway cross-sectional area, the ventilated alveolar area, and the heterogeneity of specific ventilation were quantified by SR imaging. Mch infusion induced constriction predominantly in the central airways, whereas Ova provocation affected mainly the peripheral airways, leading to severe ventilation heterogeneities in sensitized animals. Mch inhalation affected both conducting and peripheral airways. The correlations between airway conductance and central airway cross-sectional area (R = 0.71) and between tissue elastance and ventilated alveolar area (R = –0.72) were strong.

Conclusions: The pattern of lung response caused by intravenous Mch and Ova are fundamentally different. Although inhaled Mch induces a heterogeneous lung response similar to that observed with intravenous allergen, these similar patterns are due to different mechanisms.

Key Words: asthma • airways • tomography, X-ray computed • synchrotrons • respiratory mechanics

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Methacholine (Mch) is routinely used to assess bronchial hyperreactivity; however, little is known about the differences in the lung response pattern between this provocation and that observed with ovalbumin (Ova) after allergic sensitization. What This Study Adds to the Field Intravenous Mch acts primarily on the central airways, whereas intravenous ovalbumin induces a predominantly peripheral and heterogeneous lung response. The latter pattern is also produced by inhaled Mch, despite a different underlying mechanism.