Association between Chronic Obstructive Pulmonary Disease and Exfoliation Syndrome: The Utah Project on Exfoliation Syndrome.

Purpose: Exfoliation syndrome (XFS) is associated with genetic variants of lysyl oxidase-like 1 (LOXL1), a key enzyme in the stabilization of extracellular matrix (ECM) and elastin, and in connective tissue repair. Because patients with chronic obstructive pulmonary disease (COPD) have increased and altered elastin degradation, an association between XFS and COPD was hypothesized and analyzed. Impact of XFS on survival in patients with COPD was evaluated.

Design: Case-case and case-control comparison with 5:1 age- and sex-matched controls.

Subjects: Total of 2943 patients with XFS, 20 589 patients with COPD, and 162 patients with both disorders seen between 1996 and 2015 were identified from Utah Population Database-linked medical records. Controls were selected and matched by sex and birth year to patients in a 5:1 ratio.

Methods: Unconditional logistic regression, using International Classification of Diseases, Ninth Revision codes (365.52 and 366.11) to define XFS and an outcome of COPD (496.0), was used to calculate the odds ratio (OR) to estimate risk of COPD in patients with XFS, adjusting for age and sex. Model covariates included race, obesity, and tobacco use.

Main Outcome Measures: Whether XFS patients have an increased risk of developing COPD; whether COPD patients have an increased risk of XFS; and, in COPD patients, whether survival differs between those with XFS and those without.

Results: In XFS patients, risk of a COPD diagnosis was increased compared with that of non-XFS controls (OR = 1.41; 95% confidence interval [CI], 1.17-1.70; P < 0.0004), particularly in a tobacco users subset (OR = 2.17; 95% CI, 1.15-4.09; P = 0.02). COPD patients and controls with no COPD did not differ in their risk of an XFS diagnosis. COPD patients with XFS had significantly better survival than patients with COPD and no XFS history.

Conclusions: XFS patients may have an increased risk of a COPD diagnosis compared with non-XFS individuals. In COPD patients, risk of XFS was not increased compared with those with no COPD history. In COPD patients with XFS, survival is significantly improved compared with COPD patients with no XFS history.