Cox, Christian W.

Abstract Rationale Granulomatous-lymphocytic interstitial lung disease (GLILD) has emerged as a major cause of morbidity in patients with common variable immunodeficiency (CVID). While GLILD is among the most serious noninfectious pulmonary complications of CVID, risk factors for this condition have not been reported. Objectives To identify clinical, physiologic, and serologic risk factors for GLILD in adults with CVID. Methods Of 345 consecutive adult patients with CVID, we identified 34 in the National Jewish Health research database who had a radiographic-pathologic diagnosis of GLILD evaluated between 2002 and 2014. Each case was age and sex matched to 52 CVID control subjects. We used logistic regression to determine independent predictors of GLILD. A mixed effects model was used to estimate the longitudinal change in percent predicted FVC. Measurements and Main Results: The mean time from CVID diagnosis to GLILD detection was 7.8 years. Compared with matched control subjects, cases were more likely to have a history of autoimmune cytopenia, hypersplenism, polyarthritis, lower marginal zone and switched memory B cells, and restrictive lung function. Multivariate analysis revealed that hypersplenism (odds ratio [OR], 24; 95% confidence interval [CI], 4.5–179.1), polyarthritis (OR, 19; 95% CI, 2.3–206.8), and percent predicted FVC (OR, 0.93; 95% CI, 0.87–0.98) were independently associated with the development of GLILD. The rate of change of percent predicted FVC (slope, P = 0.48) did not vary significantly in patients with GLILD over a mean follow-up of 7 years after diagnosis. Conclusions Hypersplenism and polyarthritis are strong risk factors for GLILD in patients with CVID. Percent predicted FVC remained stable over time in patients with GLILD.

Abstract Rationale Mycobacterium abscessus group lung infection is characterized by low cure rates. Improvement in quality of life may be a reasonable treatment goal. Objectives The objective of this study was to evaluate change in quality of life in response to therapy, predictors of improvement in quality of life, and association of quality of life with traditional outcome measures. Methods Forty-seven patients were treated for Mycobacterium abscessus group lung infection (including one with Mycobacterium chelonae) and were followed prospectively for 2 years between December 2009 and May 2012. St. George’s Respiratory Questionnaire (SGRQ) was administered, chest computed tomography (CT) imaging was carried out, and culture data were collected at multiple time points. Predictors of improvement in the SGRQ total score greater than or equal to a minimal clinically important difference (MCID) at 12 months were evaluated. Measurements and Main Results: Patients were 85% female and 94% white, with a mean age of 65 years. Nine (20%) had a genetic diagnosis of cystic fibrosis (none F508del homozygous). Coinfection with Mycobacterium avium complex occurred in 28% and Pseudomonas in 26%. Chest CT imaging universally indicated bronchiectasis and nodules; 51% had lung cavities. Treatment included a mean of 17 months of antibiotics, and lung resection in 34%. Seventeen patients with M. avium complex (36%) and one with Mycobacterium kansasii were treated for coinfection. The mean SGRQ total score (SD) at baseline was 35 (20). At all follow-up time points, the mean SGRQ total score (SD) was significantly lower (better) than at baseline: 27 (17) at 3 months, P < 0.01; 27 (19) at 6 months, P < 0.01; 27 (20) at 12 months, P < 0.01; and 30 (22) at 24 months, P = 0.02. At 12 and 24 months, respectively, 60% and 56% had improvement greater than or equal to the MCID in SGRQ total score. Improvement greater than or equal to the MCID at 12 months was positively associated with a history of respiratory exacerbation, isolate susceptible to imipenem-cilastatin, and lung resection surgery, and negatively associated with nodules >4 mm in diameter on chest CT imaging, but these associations were not statistically significant in multivariable analysis. At 24 months, 16 patients (48%) with complete data were culture negative for 1 year and had discontinued M. abscessus group treatment. Conclusions Quality of life was a sensitive indicator of treatment response and has the potential to be a useful parameter to guide treatment.