Photomicrograph of a liver biopsy from a patient with<unk> . The PAS with diastase stain shows the diastase-resistant pink globules that are characteristic of this disease.<unk> is a glycoprotein mainly produced in the liver by hepatocytes, and, in some quantity, by enterocytes, monocytes, and macrophages. In a healthy lung, it functions as an inhibitor against neutrophil elastase, a neutral serine protease that controls lung elastolytic activity which stimulates mucus secretion and CXCL8 release from epithelial cells that perpetuate the inflammatory state. With<unk><unk> , neutrophil elastase can disrupt elastin and components of the alveolar wall of the lung that may lead to emphysema, and hypersecretion of mucus can develop chronic bronchitis. Both conditions are the makeup of chronic obstructive pulmonary disease (COPD). Normal blood levels of<unk> -1<unk>  may vary with analytical method but are typically around<unk> .0-2.7 g/l. In individuals with PiSS, PiMZ and PiSZ genotypes, blood levels of<unk> are reduced to between 40 and 60% of normal levels; this is usually sufficient to protect the lungs from the effects of elastase in people who do not smoke. However, in individuals with the PiZZ genotype,<unk> levels are less than<unk> 5% of normal, and they are likely to develop panlobular emphysema at a young age. Cigarette smoke is especially harmful to individuals with<unk> . In addition to increasing the inflammatory reaction in the airways, cigarette smoke directly inactivates<unk> -1<unk>  by oxidizing essential methionine residues to sulfoxide forms, decreasing the enzyme activity by a factor of 2,000. With<unk><unk> , the pathogenesis of the lung disease is different from that of the liver disease, which is caused by the accumulation of abnormal<unk> proteins in the liver, resulting in liver damage. As such, lung disease and liver disease of<unk><unk>  appear unrelated, and the presence of one does not appear to predict the presence of the other. Between<unk> 0 and<unk> 5% of people with the PiZZ genotype will develop liver fibrosis or liver cirrhosis, because the<unk> is not secreted properly and therefore accumulates in the liver. The mutant Z form of<unk> protein undergoes inefficient protein folding (a physical process where a protein chain achieves its final conformation). 85 percent of the mutant Z form are unable to be secreted and remain in the hepatocyte. Nearly all liver disease caused by<unk> is due to the PiZZ genotype, although other genotypes involving different combinations of mutated alleles (compound heterozygotes) may also result in liver disease. A liver biopsy in such cases will reveal PAS-positive, diastase-resistant inclusions within hepatocytes. Unlike glycogen and other mucins which are diastase sensitive (i.e., diastase treatment disables PAS staining),<unk> deficient hepatocytes will stain with PAS even after diastase treatment - a state thus referred to as "diastase resistant". The accumulation of these inclusions or globules is the main cause of liver injury in<unk><unk> . However, not all individuals with PiZZ genotype develop liver disease (incomplete penetrance), despite the presence of accumulated mutated protein in the liver. Therefore, additional factors (environmental, genetic, etc.) likely influence whether liver disease develops.
Alpha-1 antitrypsin deficiency
Asthma
CHILD syndrome
Reactive airway disease
Mineral dust airway disease
Cystic fibrosis
Yokkaichi asthma
Upper airway resistance syndrome