**4. In Vivo Models that Support the Use of Prostacyclin in Reducing Airway Remodeling and Asthmatic Symptoms**

The synthetic prostacyclin analog ONO-1301 reduced allergic inflammation, airway hyperresponsiveness, and remodeling in mice in the ovalbumin model [33]. Mice administered ONO-1301 had decreased goblet-cell metaplasia, reduced airway smooth muscle hypertrophy, and inhibited submucosal collagen deposition [33]. These results support the possibility that prostacyclin may be a potential therapeutic approach to reduce airway remodeling [18,34].

The relationship between cough reflex sensitivity and airway inflammation was investigated by observing the effect of the prostacyclin analog beraprost on asthmatic patients. Unfortunately, beraprost decreased the cough threshold and thus enhanced cough reflex sensitivity in the subjects with asthma [35]. Contrary to these findings, a more recent study examined the role of prostacyclin in the cough response by triggering bronchoconstriction via methacholine chloride (MCh) inhalation in guinea pigs [36]. In animals that were administered a high dose of prostacyclin, the number of coughs induced by bronchoconstriction was significantly decreased, and when an IP antagonist was incorporated, the number of coughs increased [36]. Thus, while there are conflicting reports on the exact effects of prostacyclin on the cough response, there is potential for prostacyclin analogs to reduce a nearly ubiquitous symptom of asthma and allergic inflammation.
