Acute pulmonary response to cotton bract extract in monkeys: lung function and effects of mediator modifying...

It is well established that cotton dust inhalation can compromise lung function in textile workers. Challenges with a water-soluble extract of cotton bract (CBE) can also induce reversible airway obstruction in healthy volunteers. We have examined the effect of inhaled CBE in nonhuman primates and have attempted to inhibit the bronchoconstrictive response with mediator modifying compounds. CBE (34 mg/ml or 100 mg/ml) was administered via IPPB for 15 minutes (15 breaths/min) in 12 intubated, anesthetized, adult male monkeys (Macaca fascicularis). Breath-by-breath determinations of pulmonary resistance, dynamic compliance (Cdyn), tidal volume, and breathing frequency were calculated from the transpulmonary pressure (esophageal balloon) and airflow signals and monitored for 2 hr postchallenge. Control challenges with distilled water were also performed in 3 monkeys with the greatest response from CBE. Five animals (42%) were found to respond to CBE with peak % changes in Cdyn greater than 45%. In 3 of these animals, we attempted to blunt the CBE response with chlorpheniramine (0.1 mg/kg i.v.) and a mast cell stabilizer lodoxamide (0.1 mg/ml aerosol). In these 3 animals the mean (+/- SD) peak % changes in Cdyn to CBE alone was -47.4 +/- 1.8. The CBE response following chlorpheneramine was -49 +/- 15.7 and following lodoxamide was -47.0 +/- 5.4. These data suggest that monkeys, like humans, can develop reproducible bronchoconstriction following an aerosol challenge with CBE. Furthermore, this bronchoconstriction in the monkey is probably not explained by the action of histamine or mediator release alone and an acute inflammatory reaction may be involved.