Chronic Allergic Inflammation Causes Vascular Remodeling and Pulmonary Hypertension in Bmpr2 Hypomorph and Wild-Type Mice

Loss-of-function mutations in the bone morphogenetic protein receptor type 2 (BMPR2) gene have been identified in patients with heritable pulmonary arterial hypertension (PAH); however, disease penetrance is low, suggesting additional factors play a role. Inflammation is associated with PAH and vascular remodeling, but whether allergic inflammation triggers vascular remodeling in individuals with BMPR2 mutations is unknown. Our goal was to determine if chronic allergic inflammation would induce more severe vascular remodeling and PAH in mice with reduced BMPR-II signaling. Groups of Bmpr2 hypomorph and wild-type (WT) Balb/c/Byj mice were exposed to house dust mite (HDM) allergen, intranasally for 7 or 20 weeks to generate a model of chronic inflammation. HDM exposure induced similar inflammatory cell counts in all groups compared to controls. Muscularization of pulmonary arterioles and arterial wall thickness were increased after 7 weeks HDM, more severe at 20 weeks, but similar in both groups. Right ventricular systolic pressure (RVSP) was measured by direct cardiac catheterization to assess PAH. RVSP was similarly increased in both HDM exposed groups after 20 weeks compared to controls, but not after 7 weeks. Airway hyperreactivity (AHR) to methacholine was also assessed and interestingly, at 20 weeks, was more severe in HDM exposed Bmpr2 hypomorph mice versus WT. We conclude that chronic allergic inflammation caused PAH and while the severity was mild and similar between WT and Bmpr2 hypomorph mice, AHR was enhanced with reduced BMPR-II signaling. These data suggest that vascular remodeling and PAH resulting from chronic allergic inflammation occurs independently of BMPR-II pathway alterations

Mouse models to unravel the role of inhaled pollutants on allergic sensitization and airway inflammation

Air pollutant exposure has been linked to a rise in wheezing illnesses. Clinical data highlight that exposure to mainstream tobacco smoke (MS) and environmental tobacco smoke (ETS) as well as exposure to diesel exhaust particles (DEP) could promote allergic sensitization or aggravate symptoms of asthma, suggesting a role for these inhaled pollutants in the pathogenesis of asthma. Mouse models are a valuable tool to study the potential effects of these pollutants in the pathogenesis of asthma, with the opportunity to investigate their impact during processes leading to sensitization, acute inflammation and chronic disease. Mice allow us to perform mechanistic studies and to evaluate the importance of specific cell types in asthma pathogenesis. In this review, the major clinical effects of tobacco smoke and diesel exhaust exposure regarding to asthma development and progression are described. Clinical data are compared with findings from murine models of asthma and inhalable pollutant exposure. Moreover, the potential mechanisms by which both pollutants could aggravate asthma are discussed

Pulmonary function in adults with recent and former asthma and the role of sex and atopy

<p>Abstract</p> <p>Background</p> <p>Pulmonary function is not fully reversible in asthma in children and may continue into adult life. This study was to determine the association between asthma and reduced pulmonary function in adults and the modification by sex and atopic status.</p> <p>Methods</p> <p>A cross-sectional study of 1492 adults aged 18 years or over was conducted in a rural community. Atopy, height, weight, waist circumference (WC) and pulmonary function were measured. Participants with ever asthma were those who reported by questionnaire a history of asthma diagnosed by a physician during lifetime. Participants who had former (only) asthma were those who reported having physician-diagnosed asthma more than 12 months ago. Participants who had recent asthma were those who reported having asthma during the last 12 months.</p> <p>Results</p> <p>Men had higher values of forced vital capacity (FVC) and forced expiratory volume in one second (FEV₁) compared with women, but FEV₁/FVC ratio showed no significant difference between sexes. Atopic status was not related to pulmonary function and the average values of the pulmonary function testing variables were almost the same for non-atopic and atopic individuals. Individuals with ever, recent or former asthma had significant lower values of FEV₁ and FEV₁/FVC ratio than those who reported having no asthma, and the associations tended to be stronger in men than in women. The interaction between atopy and asthma was not statistically significant.</p> <p>Conclusions</p> <p>Adults who reported having recent asthma or former asthma had reduced pulmonary function, which was significantly modified by sex but not by atopic status.</p