Studies of potential biomarkers in experimental models of acute lung injury (ALI) and from clinical samples from patients with ALI have provided extensive information relating to the pathophysiology of the mechanisms of lung injury and repair. The utility of biomarkers remains still solely part of the research tools to investigate lung injury and repair mechanisms and due to lack of sensitivity and specificity cannot yet be used as a clinical decision tool in patients with either acute lung injury or ARDS. We have reviewed known biomarkers in context of their major biological activity such as inflammatory mediators, coagulation/fibrinolytic mediators, growth factors and the emerging use of proteomics. The continued interest in identifying and studying biomarkers is relevant as it continues to provide important information regarding the mechanisms involved in lung injury and repair and how this may be helpful in the identification and design of future therapeutic targets and strategies as well as hopefully to identify a sensitive and specific biomarker that would be of clinical relevance.

Substance P elicits histamine release from human skin and rodent mast cells. Since neuropeptide-mediated reflexes may be important in asthma, we examined the ability of substance P to stimulate human mast cells obtained at bronchoalveolar lavage (BAL). BAL samples were obtained at routine bronchoscopy from 35 non-preselected patients. Histamine release experiments were performed in a standard manner using substance P and the calcium ionophore A23187. Both substance P (50 microM) and A23187 caused histamine release (median 26.7% range 6.2-62.8% and 32.1%, 7.7-56.8% respectively) which was significantly greater (P < 0.0001) than the spontaneous release (median 15.6%, range 4.1-33.4%), i.e. that in the absence of any stimulus. Substance P induced histamine release was via an energy dependent process and was blocked by preincubation with antimycin A. A significant correlation was observed between substance P induced release and spontaneous release but was not observed with A23187 induced release. Mast cell counts correlated significantly with substance P induced release but not with spontaneous or A23187 induced release. The substance P induced histamine secretion was elicited at similar concentrations to those used with rodent and human skin mast cells. Asthma is associated with increased numbers of mast cells which have both increased spontaneous and stimulated secretory responses. Thus, in vivo, the bronchoconstrictor action of substance P may in part result from activation of mast cells in the bronchial lumen.

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