Alpha-1-antitrypsin-deficiency (AATD) is a genetic predisposition to the development of early chronic obstructive pulmonary disease (COPD), a major worldwide disease that includes conditions such as chronic bronchitis and emphysema. Inflammation of the bronchi and damage to the alveoli usually occur together, leading to a restriction of airflow in the lungs.

Even though 1 in every 100 COPD patients exhibit AATD, there is still limited information on systemic inflammation and on the effect alpha-1-trypsin augmentation therapy (AATD+AUG) and/or exercise might have on circulating inflammatory cytokines in these patients.

Recently, a team of researchers led by Dr. Peter Wagner from the University of California, San Diego, sought to test not only if AATD COPD patients on augmentation therapy would present lower circulating and skeletal muscle inflammatory cytokines when compared to those not receiving the therapy or to non-AATD patients, but also the cytokine response to exercise in these groups of patients.

To test their hypothesis, the researchers collected arterial and femoral venous blood from patients or healthy controls at rest, during and up to 4-hours after 50% maximal 1-hour knee extensor exercise and measured the concentrations of circulating C-reactive protein (CRP), TNFalpha, IL-6 and IL-1beta inflammatory cytokines.

The data showed that circulating CRP was higher in patients with AATD with or without augmentation therapy, when compared to healthy controls, but lower in AATD when compared to non-AATD-COPD patients. Additionally, all three inflammatory cytokines measured were significantly increased in non-AATD COPD compared to AATD COPD, and skeletal muscle TNFalpha was 3-4 fold greater in AATD patients receiving augmentation therapy. However, exercise seemed to show no effect on these cytokines in any groups of patients studied.

Altogether, the researchers concluded that AATD COPD patients do not suffer from the same chronic systemic inflammation than non-AATD COPD ones and that augmentation therapy can help to reduce muscle TNFalpha concentration. These results can help to broaden our understanding of the process of AATD COPD exacerbations, improving disease management and helping the development of new therapeutic targets, eventually leading to a reduction of the mortality related with this condition.