How early do airway inflammation and remodeling occur?

Eosinophilic airway inflammation and structural airway changes are present in school age asthmatics. When these changes occur, and their relationship, are controversial. Some structural airway changes, up-regulation of collagens 1 and 111, and increased distance between alveolar tethering points, may be antenatal, and independent of inflammation. We have established that there is no eosinophilic inflammation or reticular basement membrane thickening in wheezing infants median age one year; but by age three years, both are present. This accords with cohort studies, showing that children who become persistent wheezers have a drop in lung function in the pre-school years. Thereafter, lung function tracks into middle age, so the preschool years represent window during which an intervention might have long term benefit. Supportive are measurements in blood and bronchoalveolar lavage fluid, implicating the neutrophil as the key inflammatory cell in early wheeze. Models of the pathophysiology of asthma include (1) that eosinophilic inflammation is the primary event, and leads to remodelling as a secondary event, which itself results in progressive airflow obstruction (the least likely model); (2) eosinophilic inflammation is the primary event, but remodelling is protective, preventing worsening AHR. It should be noted that these first two are not mutually exclusive; rbm thickening may be protective, but other components of remodeling, for example increased ASM, may have adverse effects; (3) eosinophilic inflammation and airway remodelling are parallel processes, driven by some underlying 'asthma factor'; and (4) the primary abnormality is not airway inflammation, but some form of disordered airway repair.