Predictive Factors for and Complications of Bronchiectasis in Common Variable Immunodeficiency Disorders.

Bronchiectasis is a frequent complication of common variable immunodeficiency disorders (CVID). In a cohort of patients with CVID, we sought to identify predictors of bronchiectasis. Secondly, we sought to describe the impact of bronchiectasis on lung function, infection risk, and quality of life. We conducted an observational cohort study of 110 patients with CVID and an available pulmonary computed tomography scan. The prevalence of bronchiectasis was 53%, with most of these patients (54%) having mild disease. Patients with bronchiectasis had lower median serum immunoglobulin (Ig) concentrations, especially long-term IgM (0 vs 0.25 g/l; p < 0.01) and pre-treatment IgG (1.3 vs 3.7 g/l; p < 0.01). CVID patients with bronchiectasis had worse forced expiratory volume in one second (2.10 vs 2.99 l; p < 0.01) and an annual decline in forced expiratory volume in one second of 25 ml/year (vs 8 ml/year in patients without bronchiectasis; p = 0.01). Patients with bronchiectasis also reported more annual respiratory tract infections (1.77 vs 1.25 infections/year, p = 0.04) and a poorer quality of life (26 vs 14 points in the St George's Respiratory Questionnaire; p = 0.02). Low serum immunoglobulin M concentration identifies patients at risk for bronchiectasis in CVID and may play a role in pathogenesis. Bronchiectasis is relevant because it is associated with frequent respiratory tract infections, poorer lung function, a greater rate of lung function decline, and a lower quality of life.

Abatacept Use Is Associated with Steroid Dose Reduction and Improvement in Fatigue and CD4-Dysregulation in CVID Patients with Interstitial Lung Disease.

BACKGROUND: Interstitial lung disease (ILD) represents a severe clinical manifestation of systemic immune dysregulation in patients with common variable immunodeficiency (CVID). Its treatment often requires systemic immunosuppression beyond corticosteroids. OBJECTIVE: To assess the safety and efficacy of abatacept in patients with CVID and ILD. METHODS: Ten patients with confirmed diagnosis of CVID and ILD were included in a single-center, prospective, open-label, nonrandomized trial. Abatacept was administered subcutaneously at a dose of 125 mg/wk for 12 months. RESULTS: Abatacept was a safe treatment for ILD in CVID except for 1 case of bronchopulmonary aspergillosis. One additional patient terminated the trial prematurely because of recurrent bronchitis. Five of 8 patients treated per protocol benefited from the treatment according to American Thoracic Society/European Respiratory Society criteria. The primary end point of the study was met because single breath diffusing capacity of the lung for carbon monoxide was stable (62.5%) or improved (37.5%) in all patients treated per protocol. Although nodules (71%) and ground-glass opacities (57%) improved in most patients, other computed tomography pathologies were less responsive. Quality of life improved in 87.5% and fatigue in 57% of patients. Abatacept treatment was associated with significant improvement in CD4 T-cell dysregulation, signified by a decrease in serum soluble IL-2 receptor levels and of proliferating Ki67+ CD4 T cells, and a recovery of total lymphocytes, CD4+ T cells, and naive CD4 T cells. CONCLUSIONS: Abatacept may represent a treatment option for CVID-associated ILD. This pilot study demonstrated a good safety profile, steroid-sparing effect, positive immune modulation, and overall positive treatment response especially in quality of life. Larger controlled studies are needed to confirm these findings.

Altered Microbiota, Impaired Quality of Life, Malabsorption, Infection, and Inflammation in CVID Patients With Diarrhoea.

Background: Diarrhoea is the commonest gastrointestinal symptom in patients with common variable immunodeficiency (CVID). Objective: The aim of this study was to describe the prevalence and clinical presentation of chronic and recurrent diarrhoea in the Royal-Free-Hospital (RFH) London CVID cohort, including symptoms, infections, level of inflammation, and microbial diversity. Methods: A cross-sectional study of adult CVID patients (139 out of 172 diagnosed with CVID completed the screening questionnaire). Those with diarrhoea ≥6 days/month had stool and blood samples analysed and completed the short Inflammatory Bowel Disease Questionnaire (sIBDQ). BMI, spleen-size, lymphocytes and gut-microbial diversity were compared. Due to logistical and clinical restraints, not all patients could be analysed on all measures. Results: 46/139 (33.1%) patients had current significant diarrhoea. In patients with past or present diarrhoea, BMI was lower (median 23.7 vs. 26, p = 0.005), malabsorption more common (57.97 vs. 35.71%, p = 0.011). CD4+ lymphocytes were higher in patients with diarrhoea (p = 0.028; n = 138), but CD4+ naïve lymphocytes were significantly higher in non-diarrhoea patients (p = 0.009, N = 28). Nine patients had confirmed or probable current gastrointestinal infections. Calprotectin was >60 µg/g in 13/29 with significant diarrhoea including 9 without infection. SIBDQ revealed a low median score of 4.74. Microbial alpha diversity was significantly lower in CVID patients compared to healthy household controls. There was no significant difference in alpha diversity in relation to antibiotic intake during the 6 weeks prior to providing samples. Conclusion: Patients with CVID and significant diarrhoea had infections, raised calprotectin, malabsorption, a lower BMI, an impaired quality of life (comparable to active IBD), and they differed from non-diarrhoea patients in their lymphocyte phenotyping. Furthermore, microbial diversity was altered. These findings strongly imply that there may be an inflammatory nature and a systemic predisposition to diarrhoea in CVID, which necessitates further investigation.