Polymerized Type I Collagen Reverts Airway Hyperresponsiveness and Fibrosis in a Guinea Pig Asthma Model

Asthma is a chronic, heterogeneous and variable disease in which airways inflammation, transient obstruction and hyperresponsiveness are the major features of the illness (Faffe, 2008; Jenkins et al., 2005; Lemanske & Busse, 2010; Sugita et al., 2003). The inflammation in asthma is characterized by eosinophil cell infiltration although neutrophils are also observed in acute asthma exacerbation and in severe asthma patients (Fahy, 2009; Kim & Rhee, 2010; Venge, 2010). A main role of eosinophils and neutrophils in asthma is to release mediators involved in the development of airway pathological structural changes, the called airway remodeling. An important consequence of airway remodeling is the thickening of the airway wall produced by the deposit of extracellular matrix components (Bazan-Perkins et al., 2009; Janson, 2010; Salerno et al., 2009). The enlargement of airway wall could alter the transient airway obstruction in asthma that usually is resolved either spontaneously or after treatment, by inducing a residual and permanent airway obstruction (Broekema et al., 2011; Janson, 2010; Jeffery et al., 2000; Wenzel, 2003). Airway hyperresponsiveness is a crucial physiopathological feature of asthma fundamentally because maintains a relation to the disease magnitude (Busse, 2010; Cockcroft & Davis, 2006; O'Byrne & Inman, 2003; Sugita et al., 2003). Although the mechanism involved in the generation of airway hyperresponsiveness is not attributable to a single but to multiple pathological processes, two main factors could contribute to its development: inflammation and remodeling. In this scenario, it has been observed that the inflammatory factor is associated to inducible, transient and variable hyperresponsiveness while remodeling has been related to persistent airway hyperresponsiveness (Busse, 2010; Cockcroft & Davis, 2006; O'Byrne & Inman, 2003). Additionally, variable hyperresponsiveness occurs mainly in acute asthma while persistent hyperresponsiveness predominantly takes place in chronic or severe asthma (Cockcroft & Davis, 2006; O'Byrne & Inman, 2003; Wenzel, 2003). Nevertheless, independently of its pathological basis, the development of therapeutic strategies reducing the hyperresponsiveness is fundamental in asthma control. Polymerized type I collagen (PtI-collagen) is a composite made with a ┛-irradiated mixture of atelopeptidic porcine type I dermal collagen and polyvinylpyrrolidone that has shown