Basic and clinical immunology
Granulomatous-lymphocytic lung disease shortens survival in common variable immunodeficiency

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Abstract

Background

Common variable immunodeficiency (CVID) is a primary immunodeficiency characterized by low levels of serum immunoglobulins and an inability to make specific antibodies.

Objective

We sought to determine the prevalence, clinical characteristics, and effect on survival of noninfectious pulmonary disease in patients with CVID.

Methods

A retrospective analysis of 69 patients with CVID was performed. Patients were divided into 3 groups on the basis of the type of pulmonary disease present: group 1 (n = 29), no pulmonary disease; group 2 (n = 23), chronic respiratory symptoms without diffuse radiographic abnormalities; and group 3 (n = 18), chronic respiratory symptoms and diffuse radiographic abnormalities. Group 3 patients were divided into 2 subgroups on the basis of the histopathologic pattern seen on biopsy. Group 3A (n = 13) included patients with granulomatous lung disease, lymphocytic interstitial pneumonia, follicular bronchiolitis, and lymphoid hyperplasia, a group of syndromes referred to as granulomatous-lymphocytic interstitial lung disease (GLILD). Group 3B (n = 5) consisted of patients with all other types of interstitial lung disease (ILD).

Results

Fifty-eight percent of patients with CVID had noninfectious pulmonary complications. Group 3A (GLILD) patients had worse prognosis than the other groups, with a median survival of 13.7 versus 28.8 years (P<.001). Lymphoproliferative disease occurred in 31% of patients with GLILD. GLILD was associated with the presence of dyspnea (P<.05); splenomegaly (P<.05); restrictive pulmonary physiology; consolidation, ground-glass, and reticular radiographic abnormalities; and low CD3+ (P<.05) and CD8+ cell populations (P<.01).

Conclusion

ILD is common in patients with CVID. The presence of GLILD was associated with a worse prognosis and increased prevalence of lymphoproliferative disorders.

Section snippets

Study population

After institutional review board approval, the records of 85 patients with a diagnosis of hypogammaglobulinemia seen between 1985 and 2001 at this center were retrospectively reviewed. Demographic, physiologic, radiographic, and immunologic data were abstracted from the medical records. Sixty-nine patients who met the criteria for the definition of CVID11., 12. made up the final cohort of patients. The diagnosis of CVID was made by demonstrating a reduction greater than 2 SDs of the mean in IgG

Pulmonary disorders

The primary pulmonary disorders identified in the entire group are outlined in Table I. Twenty-nine (42%) patients had neither clinically significant chronic respiratory symptoms nor radiologic evidence of pulmonary disease (group 1). Twenty-three (33%) patients had chronic respiratory symptoms without diffuse chest radiographic abnormalities (group 2). All these subjects had airways disease (ie, bronchiectasis or asthma). In line with previous studies, bronchiectasis was the most frequently

Discussion

The purpose of this study was to further characterize the prevalence, clinical findings, and natural history of the noninfectious diffuse parenchymal lung disease complications of CVID. Our most important finding is that patients with GLILD exhibited a reduced survival when compared with patients without this disorder. In the absence of GLILD, median survival was nearly 30 years, whereas in its presence the median survival was reduced by more than 50%.

ILD was common in our patients with CVID.

Acknowledgements

We thank Gabriele Cheatham for secretarial assistance.

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    K. K. Brown and J. M. Routes contributed equally to this article.

    Supported by a grant from the American Academy of Allergy, Asthma and Immunology and the Immunodeficiency Foundation (to JMR); the Andrew Goodman Fellowship Grant (CAB); and National Heart, Lung, and Blood Institute SCOR HL67671 (to KKB and CDC).

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