title: Clinical Predictors of a Diagnosis of Common Variable Immunodeficiency-related Granulomatous-Lymphocytic Interstitial Lung Disease.
abstract: 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.
  
  
  
  To identify clinical, physiologic, and serologic risk factors for GLILD in adults with CVID.
  
  
  
  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.
  
  
  
  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.
  
  
  
  Hypersplenism and polyarthritis are strong risk factors for GLILD in patients with CVID. Percent predicted FVC remained stable over time in patients with GLILD.
authors.affiliation: 1 Department of Pulmonary and Critical Care Medicine.
authors.forename: Amar
authors.initials: A
authors.lastname: Mannina
authors.affiliation: 2 Department of Thoracic Radiology, University of Chicago, Chicago, Illinois.
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Chung
authors.affiliation: 1 Department of Pulmonary and Critical Care Medicine.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Swigris
authors.affiliation: 1 Department of Pulmonary and Critical Care Medicine.
authors.forename: Joshua J
authors.initials: JJ
authors.lastname: Solomon
authors.affiliation: 1 Department of Pulmonary and Critical Care Medicine.
authors.forename: Tristan J
authors.initials: TJ
authors.lastname: Huie
authors.affiliation: 1 Department of Pulmonary and Critical Care Medicine.
authors.forename: Zulma X
authors.initials: ZX
authors.lastname: Yunt
authors.affiliation: 3 Department of Allergy and Immunology.
authors.forename: Tho Q
authors.initials: TQ
authors.lastname: Truong
authors.affiliation: 1 Department of Pulmonary and Critical Care Medicine.
authors.forename: Kevin K
authors.initials: KK
authors.lastname: Brown
authors.affiliation: 4 Department of Pathology, and.
authors.forename: Rosane Duarte
authors.initials: RD
authors.lastname: Achcar
authors.affiliation: 1 Department of Pulmonary and Critical Care Medicine.
authors.forename: Amy L
authors.initials: AL
authors.lastname: Olson
authors.affiliation: 5 Department of Thoracic Radiology, Mayo Clinic, Rochester, Minnesota; and.
authors.forename: Christian W
authors.initials: CW
authors.lastname: Cox
authors.affiliation: 6 Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: Seth J
authors.initials: SJ
authors.lastname: Kligerman
authors.affiliation: 7 Department of Biostatistics and Bioinformatics, National Jewish Health, Denver, Colorado.
authors.forename: Douglas
authors.initials: D
authors.lastname: Curran-Everett
authors.affiliation: 1 Department of Pulmonary and Critical Care Medicine.
authors.forename: Evans R
authors.initials: ER
authors.lastname: Fernández Pérez
mesh_terms: D000328:Adult; D001168:Arthritis / Q000150:complications; D016022:Case-Control Studies; D017074:Common Variable Immunodeficiency / Q000150:complications*; D016208:Databases, Factual; D005260:Female; D006099:Granuloma / Q000473:pathology*; D006801:Humans; D006971:Hypersplenism / Q000150:complications; D007970:Leukopenia / Q000150:complications; D016015:Logistic Models; D008168:Lung / Q000473:pathology; D017563:Lung Diseases, Interstitial / Q000000981:diagnostic imaging* / Q000209:etiology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011859:Radiography; D012307:Risk Factors; D014481:United States
keywords: common variable immunodeficiency; cytopenia; granulomatous lymphocytic interstitial lung disease; polyarthritis; splenomegaly