An unexpected finding was elevated levels of sputum fibrinogen and albumin that we attribute to microvascular leakage. This observation is in line with bronchial biopsies of children with chronic cough showing marked increase in the percentage of area of intercellular spaces denoting airway edema . Increased microvascular leakage is reported in other airway conditions including viral infection and smokers with chronic airflow limitation , conditions also associated with neutrophilia. However, in the present study, it also occurred in some subjects in the absence of abnormal sputum cell counts. IL-8 and other proinflammatory mediators, such as substance P, may be involved. buy diabetes drugs
Substance P is a tachykinin localized in a population of nonmyelinated afferent sensory neurons in the respiratory tract. It has a variety of effects on the airways of the lungs including airway constriction in asthmatics, cough, vasodilatation, microvascular leakage, submucosal gland secretion and chemoattraction for eosinophils and neutrophils . Whereas most of the evidence of the effects of substance P on leakage is derived from animal studies, the intradermal injection of substance P causes a wheal in human skin , indicating its capacity to cause microvascular leakage in man. In the present study, substance P levels were strongly correlated with albumin levels but not with fibrinogen. Although this association does not imply causality, it seems reasonable to speculate that substance P could have produced or enhanced microvascular leakage in these patients. Furthermore, our results are in keeping with a recent report by Baumgarten et al , who demonstrated generation of substance P after a nasal challenge with bradykinin, and a strong correlation between nasal mucosa edema and hypersecretion of substance P.