title: Role of cellular effectors in the emergence of ventilation defects during allergic bronchoconstriction.
abstract: It is not known whether local factors within the airway wall or parenchyma may influence the emergence and spatial distribution of ventilation defects (VDs), thereby modulating the dynamic system behavior of the lung during bronchoconstriction. We assessed the relationship between the distribution of cellular effectors and the emergence of defects in regional ventilation distribution following allergen challenge. We performed high-resolution K-edge subtraction (KES) synchrotron imaging during xenon inhalation and measured the forced oscillatory input impedance in ovalbumin (OVA)-sensitized Brown-Norway rats (n = 12) at baseline and repeatedly following OVA challenge. Histological slices with best anatomic matching to the computed tomographic images were stained with a modified May-Grunwald Giemsa and immunohistochemical staining with monoclonal anti-rat CD68, in six rats. Slides were digitized and total cells and eosinophils were counted in the walls of bronchi and vessels randomly selected within and outside of VDs on the basis of xenon-KES images. Ventilated alveolar area decreased and ventilation heterogeneity, Newtonian resistance, tissue damping, and elastance increased following OVA challenge. Eosinophil, total cell, and CD68+ counts were significantly higher in the bronchial and vascular walls within vs. outside of the VDs. The minimal central airway diameters during OVA-induced bronchoconstriction were correlated with eosinophil (R = -0.85; P = 0.031) and total cell densities (R = -0.82; P = 0.046) in the airway walls within the poorly ventilated zones. Our findings suggest that allergic airway inflammation is locally heterogeneous and is topographically associated with the local emergence of VDs following allergen challenge.
authors.affiliation: Université de Picardie Jules Verne and Amiens University Hospital, Amiens, France;
authors.forename: Skander
authors.initials: S
authors.lastname: Layachi
authors.forename: Liisa
authors.initials: L
authors.lastname: Porra
authors.forename: Gergely
authors.initials: G
authors.lastname: Albu
authors.forename: Nathalie
authors.initials: N
authors.lastname: Trouillet
authors.forename: Heikki
authors.initials: H
authors.lastname: Suhonen
authors.forename: Ferenc
authors.initials: F
authors.lastname: Peták
authors.forename: Henri
authors.initials: H
authors.lastname: Sevestre
authors.forename: Pekka
authors.initials: P
authors.lastname: Suortti
authors.forename: Anssi
authors.initials: A
authors.lastname: Sovijärvi
authors.forename: Walid
authors.initials: W
authors.lastname: Habre
authors.forename: Sam
authors.initials: S
authors.lastname: Bayat
mesh_terms: D000485:Allergens / Q000276:immunology*; D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000473:pathology; D001980:Bronchi / Q000276:immunology* / Q000473:pathology; D016084:Bronchoconstriction / Q000276:immunology*; D004801:Eosine Yellowish-(YS); D004804:Eosinophils / Q000276:immunology / Q000473:pathology; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D008751:Methylene Blue; D010047:Ovalbumin / Q000276:immunology*; D011650:Pulmonary Alveoli / Q000276:immunology / Q000473:pathology; D012123:Pulmonary Ventilation / Q000276:immunology*; D051381:Rats
chemical_list: D000485:Allergens; C043260:May-Grunwald Giemsa; D010047:Ovalbumin; D008751:Methylene Blue; D004801:Eosine Yellowish-(YS)
keywords: airways; asthma; respiratory mechanics; synchrotrons; tomography; x-ray computed