Neutrophil-mediated lung damage: A new COPD phenotype?

摘要

Chronic obstructive pulmonary disease (COPD) is a menace affecting 300 million people worldwide and is responsible for 3 million deaths annually [1]. Despite this, its pathophysiology is not well understood. It is now well accepted that lung inflammation exists in COPD and that the inflammatory process intensifies with disease progression [2]. The most important environmental risk factor in COPD is cigarette smoking; it is responsible for more than 50% of the cases worldwide. Interestingly, although all smokers eventually develop lung inflammation, only about 15-20% of smokers incur COPD [3]. On the other hand, nearly 100% of smokers with rare genetic mutations in the SERPINA1 gene located in the long arm of chromosome 14 develop lung inflammation and COPD in their 40s and 50s [4]. Nearly 100% of all individuals with the null-null allele in this gene, which encodes for alpha-1-antitrypsin (AlAT) (resulting in undetectable serum Al AT concentrations), develop COPD and 80-100% of those with the S-Z allele (resulting in serum Al AT concentrations of 2.5-7 mmol/1) develop COPD [4].