Exfoliation syndrome

Exfoliation syndrome (XFS) is an age-related systemic disorder that is the most recognizable cause of open-angle glaucoma worldwide; with significant variations. It has multiple ocular and systemic associations and is strongly associated with genetic variants of the lysyl oxidase-like gene (LOXL1). In the eye, the most common diagnostic finding consists of white fibrillogranular deposits (exfoliation material; XFM); on the anterior lens surface and pupillary border contributing to exfoliation glaucoma.
XFS is with deposition of XFM in many tissues throughout the body. Such deposits of XFM first identified in 1992 in multiple tissues on autopsy, including heart, brain, lungs, skin, and reproductive organs, suggesting that systemic comorbidities may coexist. Epidemiologic and cohort studies of individuals with XFS suggest a variety of possibly related systemic comorbidities abdominal aortic aneurysms, cardiovascular disease, cerebrovascular disease, pelvic organ prolapse, hernias, cardiac arrhythmias, and hearing loss, to name a few.

Deamination of lysine residues

LOXL1 is 1 of 5 copper-dependent lysyl oxidases (LOX) that catalyze the deamination of lysine residues; allowing for the cross-linking of tropoelastin to form elastin polymer fibers, as well as the cross-linking of elastin to collagen in the extracellular matrix (ECM). LOX is a key enzyme in the stabilization and repair of the ECM and connective tissue in the respiratory system, including bronchioles, bronchi, and trachea; as well as pulmonary arterial wall tissue.
Pathologies of interest have arisen based on the expanding knowledge of the role of LOXL1; an understanding of elastin and ECM disorders, and the knowledge of conditions that occur in the LOXL1-knockout mouse. These include hernia, pelvic organ prolapse; pulmonary emphysematous changes.

Based on LOXL1 enzyme mechanisms and its role in elastin and ECM repair processes; they hypothesized that patients with XFS would have a higher rate of COPD when compared with subjects without XFS, and vice versa. they observed an increased risk of COPD in XFS patients, specifically in those with a history of tobacco use. Our data, however, suggest no evidence of an increased XFS risk in COPD patients.

XFS diagnosis with a COPD

They hypothesize that if there is a genetic predisposition to LOXL1-related XFS; in the presence of tobacco use as the insult, perhaps the elastin repair processes into action are thus altered; such that there is an increase in the subsequent risk of COPD in this subset. However, further work would need to conducted to test this hypothesis. To our knowledge, we are unaware of any other studies looking for an association of an XFS diagnosis with a COPD diagnosis using a large dataset like the UPDB.

In prior clinical observational and longitudinal studies, it has shown that morbidity and mortality are not increased in XFS patients despite a variety of comorbidities, such as abdominal aortic aneurysms; cardiovascular disease, and cerebrovascular disease.

In conclusion, these findings have relevant implications for medical examination recommendations, tobacco precautions, and systemic evaluations for XFS patients. Future research might investigate associations between XFS and other pulmonary diseases that have a strong genetic and elastin emphysematous etiology. Future research is to uncover why patients with both COPD and XFS seem to have a sizable survival advantage over those with COPD alone.