Abnormalities of Cell and Mediator Levels in Bronchoalveolar Lavage Fluid of Patients with Mild Asthma

Increases in numbers and the activation state of inflammatory cells are typical findings even in patients with mild asthma. Periods of worsening inflammation are characterized by further changes, such as an increased number of eosinophils in patients with nocturnal asthma, an increased number of lymphocytes and basophils after allergen provocation, and an increased number of neutrophils after exposure to toluene diisocyanate. Correlations of bronchoalveolar lavage (BAL) findings with physiologic changes in patients with asthma are helpful but must be analyzed in the context of the difficulties in absolute quantification of cells and mediators in lavage. Correlations have been reported between BAL mast cells, eosinophils, and eosinophilic cationic protein and methacholine PC20 and FEV1. Correlations of other cell types or mediators with physiologic changes are either controversial (as with lymphocytes and their activation) or nonexistent (as with most mediators that have been measured). Ex vivo mediator production may be a useful measure. The ability to measure peripheral resistance directly at the site of inflammation may become an asset of the endobronchial instillation method. Causality can be proved only by selectively adding or removing certain inflammatory mediators through the use of leukotriene synthesis inhibitors, human grade eicosanoids, specific antagonists, agonists, and humanized antibodies. Of these examples, only leukotriene modulation has been evaluated with BAL in studies with human subjects. Whether inflammation and obstruction in patients with asthma result from the lack of certain mediators and/or an excess of others is unknown.