title: Acute cigarette smoke inhalation blunts lung responsiveness to methacholine and allergen in rabbit: differentiation of central and peripheral effects.
abstract: Despite the prevalence of active smoking in asthmatics, data on the short-term effect of acute mainstream tobacco smoke exposure on airway responsiveness are very scarce. The aim of this study was to assess the immediate effect of acute exposure to mainstream cigarette smoke on airway reactivity to subsequent nonspecific and allergenic challenges in healthy control (n = 5) and ovalbumin-sensitized rabbits (n = 6). We combined low-frequency forced oscillations and synchrotron radiation CT imaging to differentiate central airway and peripheral airway and lung parenchymal components of the response to airway provocation. Acute exposure to smoke generated by four successive cigarettes (CS) strongly inhibited the central airway response to subsequent IV methacholine (MCh) challenge. In the sensitized animals, although the response to ovalbumin was also inhibited in the central airways, mainstream CS did not blunt the peripheral airway response in this group. In additional groups of experiments, exposure to HEPA-filtered CS (n = 6) similarly inhibited the MCh response, whereas CO (10,000 ppm for 4 min, n = 6) or nitric oxide inhalation instead of CS (240 ppm, 4 x 7 min, n = 5) failed to blunt nonspecific airway responsiveness. Pretreatment with alpha-chymotrypsin to inhibit endogenous VIP before CS exposure had no effect (n = 4). Based on these observations, the gas phase of mainstream cigarette smoke may contain one or more short-term inhibitory components acting primarily on central airways and inhibiting the response to both specific and nonspecific airway provocation, but not on the lung periphery where both lung mechanical parameters, and synchrotron-imaging derived parameters, showed large changes in response to allergen challenge in sensitized animals.
authors.affiliation: European Synchrotron Radiation Facility, Grenoble, France.
authors.forename: Liisa
authors.initials: L
authors.lastname: Porra
authors.forename: Ferenc
authors.initials: F
authors.lastname: Peták
authors.forename: Satu
authors.initials: S
authors.lastname: Strengell
authors.forename: Kimmo
authors.initials: K
authors.lastname: Neitola
authors.forename: Tibor Z
authors.initials: TZ
authors.lastname: Janosi
authors.forename: Heikki
authors.initials: H
authors.lastname: Suhonen
authors.forename: Pekka
authors.initials: P
authors.lastname: Suortti
authors.forename: Anssi R A
authors.initials: AR
authors.lastname: Sovijärvi
authors.forename: Walid
authors.initials: W
authors.lastname: Habre
authors.forename: Sam
authors.initials: S
authors.lastname: Bayat
mesh_terms: D000280:Administration, Inhalation; D000485:Allergens / Q000494:pharmacology; D000818:Animals; D002248:Carbon Monoxide / Q000009:adverse effects; D002918:Chymotrypsin / Q000494:pharmacology; D008168:Lung / Q000000981:diagnostic imaging / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D010047:Ovalbumin / Q000276:immunology; D011817:Rabbits; D012907:Smoking / Q000009:adverse effects*; D014057:Tomography, X-Ray Computed
chemical_list: D000485:Allergens; D016210:Methacholine Chloride; D002248:Carbon Monoxide; D010047:Ovalbumin; D002918:Chymotrypsin; C117608:alpha-chymotrypsin