Swigris, Jeffrey J.

Abstract Rationale Dyspnea is a prominent symptom of fibrotic hypersensitivity pneumonitis (fHP), limiting patients’ activity and impairing their quality of life. The University of California San Diego Shortness of Breath questionnaire (UCSD-SOBQ) is a 24-item instrument used to assess dyspnea severity in patients with various respiratory conditions. Objectives This study aimed to examine the reliability and responsiveness of the UCSD-SOBQ score, its validity as a measure of dyspnea severity, and its prognostic value in a prospective cohort with fHP. Methods We conducted psychometric analyses on UCSD-SOBQ response data and assessed the association between score changes and survival in patients with fHP who completed the UCSD-SOBQ and other HP severity metrics at baseline, 6 and 12 months. We introduce the reliable change index (RCI) and the likely change index (LCI) to assess the statistical significance of within-individual change in UCSD scores. Results At baseline, internal consistency was high (Cronbach’s alpha = 0.97). Significant moderately strong correlations were observed between UCSD-SOBQ scores and percent predicted forced vital capacity (FVC%), r = -0.46, percent predicted diffusing capacity of the lung for carbon monoxide (DLCO%), r = -0.32, and Borg dyspnea scores r = 0.56. UCSD-SOBQ scores were significantly different between the lowest and highest strata of FVC% (64.9 ± 18.9 vs. 36.2 ± 22.9), DLCO% and Borg scores. The threshold for worsening within-individual change in the UCSD-SOBQ score at 95% confidence was 12 points. A 1-point higher baseline UCSD-SOBQ score was associated with a 2% increase in the risk of death or transplant (HR 1.02, 95% CI 1.00, 1.04). Conclusions In fHP, the UCSD-SOBQ score is a reliable and valid measure of dyspnea severity, is responsive to change, discriminates patients with differing severities, and is associated with transplant free survival. Additional qualitative data and psychometric analyses could tailor the UCSD-SOBQ to fHP and may further improve its measurement properties.

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.