**8.4. Role of neutrophils in A1AD**

Very similar to the role they play in traditional COPD, PMNs are both effect and maintain inflammation seen in COPD. As producers of HNE they are responsible for the initial path‐ ology seen in the condition. [67]Under normal circumstances, A1AT is loosely bound to HNE, among other serine proteases. However, in the chronic inflammatory condition associ‐ ated with A1AD, HNE is constantly active and degrades the basement matrix. Furthermore, HNE has been shown to be capable of cleaving the inactive form of MMP-9, pro-MMP-9 to the active form, creating more protease stress on the system. MMP-9 and HNE are capable of degrading multiple matrix proteins present in the lung. This destruction of the basement collagen, elastin, etc. creates a "leaky" vasculature, only making it easier for other immune cells to move into the lung interstitium. [68] This movement of cells and proteins into the intracellular space brings with it fluid from the circulation and edema results. As the pro‐ ducers of HNE, neutrophils are integral to the pathogenesis and continuation of A1AD asso‐ ciated COPD.

#### **8.5. Diagnosis of A1AD**

Diagnosis of A1AD is only made in those cases of COPD where there is an unexplained cause of the condition. A1AT serum levels are measured using enzyme linked adsorbent as‐ says (ELISA), or more recently mass spectrometry. Like CF, there is a spectrum of pheno‐ types that are observed in the condition and they are categorized based upon the circulating levels of A1AT. Patients with the most severe phenotype are those individuals with concen‐ trations less than 15% of normal in their serum. [69]

#### **8.6. Treatment of A1AD**

Because of the nature of the disease treatment of A1AD is very similar to that of traditional COPD, with one exception. Patients with a severe lung phenotype are treated with intrave‐ nous infusion of A1AT isolated from human serum. [70] Additionally, liver transplant has been utilized to address the absence of circulating A1AT. [71] In addition to these therapies, the common treatments for COPD mentioned previously are employed to address the spe‐ cific symptoms of A1AD.
