Methacholine and ovalbumin challenges assessed by forced oscillations and synchrotron lung imaging.
BACKGROUND
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.


OBJECTIVE
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 microg/kg/min, 5.0 microg/kg/min, or 10.0 microg/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).


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.
Bayat
Sam
S
Université de Picardie Jules Verne, EA4285 Péritox-INERIS and CHU Amiens, Amiens, France. bayat.sam@chu-amiens.fr
Strengell
Satu
S
Porra
Liisa
L
Janosi
Tibor Z
TZ
Petak
Ferenc
F
Suhonen
Heikki
H
Suortti
Pekka
P
Hantos
Zoltan
Z
Sovijärvi
Anssi R A
AR
Habre
Walid
W
D000280:Administration, Inhalation; D000403:Airway Resistance / Q000502:physiology; D000485:Allergens / Q000276:immunology; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000503:physiopathology*; D001985:Bronchial Provocation Tests / Q000379:methods*; D016085:Bronchoconstrictor Agents; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007091:Image Processing, Computer-Assisted; D007262:Infusions, Intravenous; D008168:Lung / Q000503:physiopathology; D008170:Lung Compliance / Q000502:physiology; D016210:Methacholine Chloride; D009991:Oscillometry; D010047:Ovalbumin / Q000276:immunology; D012123:Pulmonary Ventilation / Q000502:physiology; D011817:Rabbits; D015656:Respiratory Mechanics / Q000502:physiology*; D017356:Synchrotrons; D014057:Tomography, X-Ray Computed
D000485:Allergens; D016085:Bronchoconstrictor Agents; D016210:Methacholine Chloride; D010047:Ovalbumin