Pulmonary Function Analysis of Bronchoconstriction: A Survey of the Potential Etiological Agents and Mediators Following Cotton Dust Extract Inhalation in Rabbits

M.P. Bishop, P.A. Pilia, W.J. Moorman, and S.K. Ainsworth


 
ABSTRACT

Studies in our laboratory of the proposed etiopathogenic mechanisms of byssinosis have involved mediators of bronchoconstriction (1), i.e. chemotaxins (2), histamine (3), 5-hydroxytryptamine (5-HT) (4), immunaglobulins (5), complement components (6), and arachidonic acid metabolites (7). In vitro bioassays of smooth muscle contractors in cotton dust (7), histamine release (3) and chemotaxins (2), as well as in vivo studies of bronchopulmonary lavage fluid (8) and pulmonary function studies of rabbits (9) and monkeys (10) following cotton dust extract (CDE) inhalation have been analyzed.

The in vitro studies revealed that smooth muscle contrails in response to CDE and cotton bract extract (CBE) and that the CBE induced contraction is abolished by 82% using methysergide (a 5-HT inhibitor). Indomethacin (a prostaglandin (PC) inhibitor) abolishes 100% of the contraction. CDE induced contractions are also totally blocked by indomethacin as well as salicylic acid (PG inhibitor) (7). The in vivo data demonstrated a strong chemotactic response to CDE inhalation in the rabbit with maximum cellular recruitment (68% macrophages and 322 PMNS) occurring at 4 hr post-inhalation. More importantly, the data revealed for the first time, the in vivo release of arachidonic acid metabolites and 5-HT in the lung in response to CDE inhalation (8). These studies support the in situ and in vitro investigations by both Elissalde et al. (11) who demonstrated PGF(2 ) release by guinea pig lung perfused with CDE and Fowler et al. (12) who demonstrated the release of PGF(2 ) by cultured alveolar macrophages after exposure to CBE.

The results of our studies have led to the development of a potential rabbit animal model of the acute byssinotic reaction. Initial studies of the rabbits' pulmonary function (9) revealed that: 1) changes in pulmonary parameters, namely compliance and resistance, could be successfully measured; 2) rabbits respond with substantially increased pulmonary resistance when challenged with histamine, a known bronchoconstrictor; and 3) CDE bronchochallenge also produces substantial changes in resistance values from saline controls.

Recent acquisition of a computerized pulmonary mechanics analyzer has greatly advanced the precision and accuracy, as well as reduced laboratory error, in determining pulmonary function parameters (respiratory flow (RF), transpulmonary pressure (TPP), tidal volume (TV), compliance (C), resistance (R), and respiratory rate (RR)). This computerized technology provides rapid and accurate assessment of airway changes before and after bronchochallenge to proposed etiologic agents and mediators of the acute byssinotic reaction. This paper describes the changes in rabbit pulmonary function following bronchochallenge with CDE, CBE, methacholine (MC), 5-HT, endotoxin, endotoxin depleted CDE (ED CDE), PGF(2 ), and n-formyl methionyl peptide (n-fMet). Various--pulmonary parameters are monitored, i.e. RF, TPP, TV, C, R, and RR. Resistance appears to be the key parameter indicating airway reactivity and therefore receives the greatest emphasis of the various lung function parameters.



Reprinted from 1985 Proceedings: Ninth Cotton Dust Research Conference pp. 178 - 181
©National Cotton Council, Memphis TN

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Document last modified Sunday, Dec 6 1998