Methacholine Inhalation Challenge after Rapid Saline Infusion in Healthy Subjects

Abstract

Five healthy subjects were challenged with methacholine on 2 different days, 1 week apart, the second day after acute intravenous 30 ml/kg 0.9% saline infusion. After infusion, we observed a significant reduction in vital capacity (VC), maximal expiratory volume in 1 s (FEV₁), provocation dose producing a 35% fall in SG_aw(PD₃₅SG_aw) and in 25% of maximal expiratory flow (MEF25), and an increase in the slopes of log dose-response curves. Our results suggest an increased bronchial reactivity in acute minimal interstitial lung edema.

Precapillary pulmonary hypertension leads to reversible bronchial hyperreactivity in rats

“…These findings suggest that structural changes in the lungs due to airway or pulmonary vascular remodeling are not responsible for the observed BHR during PREPHT. These results also point to the fundamental differences between the pathogeneses of PREPHT and POSTPHT, since changes in the airway wall (peribronchial edema and airway wall thickening) and/or pulmonary vascular geometry (perivascular oedema and enlarged vessels) were observed during the latter, and these phenomena were indicated as the major contributor to BHR (7,12,(31)(32)(33)(34). Myofibroblasts present in the lung have been shown to play an important role not only in lung parenchymal remodeling, but also in enhancing bronchoconstriction through the expression of contractile proteins such as α-SMA [22].…”

Inhaled corticosteroids decrease vascularity of the bronchial mucosa in patients with asthma

“…Mitzner and colleagues [22] have used a model of blood engorgement of canine airways in vivo to demonstrate a correlation between wall thickening and luminal narrowing. Furthermore, in normal subjects a rapid intravenous infusion of fluid heightened responsiveness to methacholine to within the asthmatic range [23]. Thus, the indirect effect of oedema associated with vessel proliferation may contribute to both the airway narrowing and subepithelial injury typical of asthma.…”

Airway Remodeling in Asthma: Therapeutic Implications of Mechanisms

“…In humans and in a sheep model, an increase in blood flow was noted after antigen exposure at a time point corresponding to increased airway resistance (51,64). In addition, increased vascular congestion, leading to wall thickening, has been suggested as the basis of exercise-induced asthma, the airway hyperresponsiveness seen in congestive heart failure and in normal subjects after a rapid infusion of intravenous fluids (11,81). Using autopsy material, two groups have shown that there is evidence for increased vascular congestion as measured histologically (12,53).…”