The structural changes that occur in the airways of patients who have obstructive lung disease are the result of the host response to tissue injury. This complex process is influenced by both the genetic makeup of the host and the environmental insults which incite the injury. There is marked inter-individual variation in the response to these insults and those who have an exaggerated repair reaction develop more airway obstruction due to fibrosis and scaring. The investigators will take advantage of a large clinical and tissue registry of more than 1400 patients which has been collected over the past 20 years. In addition recent technical advances in the precision of High Resolution Computed Tomography (HRCT) will be used to quantify airway dimensions in life in patients who have Asthma and COPD. The differences in the composition of the connective tissue, and smooth muscle proteins which accumulate in the airway walls of patients with these disorders will be measured using immunohistochemistry, western analysis and measurement of mRNA. The hypotheses that will be tested include: 1) that the airway wall thickening in obstructive airway disease can be measured accurately using HRCT, 2) that abnormal scaring of the airway is related to alterations in the ratios of Platelet Derived Growth Factor (PDGF) and Transforming Growth Factor beta (TGFbeta), and of the relative abundance of the three TGFbeta isoforms TGFbeta1, TGFbeta2, TGFbeta3, 3) that increased airway smooth muscle force generation in airway disease is due to increased expression of contractile proteins by the muscle and increased formation of a compliant extracellular matrix, and 4) that specific gene polymorphisms in key matrix proteins is at the basis of individual susceptibility.
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