To the Editor:
We read with great interest the article by Bouvry et al. [1] regarding similarities and differences between interstitial lung disease (ILD) in granulomatous common variable immunodeficiency (CVID) and sarcoidosis. In this retrospective study, differential bronchoalveolar lavage (BAL) cytology was analysed in 14 patients with granulomatous CVID and ILD. The authors found BAL lymphocytosis (>20%) in 11 out of 14 patients and a mean±sd proportion of BAL lymphocytes of 37.3±15.3%. Unlike the sarcoidosis group (5.3±4.0), the CD4/CD8 ratio was low in the analysed patients with granulomatous CVID and ILD (1.6±1.1, n=10) and even <1 in half of the patients (n=5). Bouvry et al. [1] concluded that there are significant differences in differential BAL cytology between sarcoidosis and granulomatous CVID.
We therefore retrospectively analysed a subgroup of 11 CVID patients (seven females and four males) with histologically proven granulomatous disease according to the inclusion criteria used by Bouvry et al. [1] and analysed BAL findings. Patients were 41.5±15.2 years of age and referred to the Centre of Chronic Immunodeficiency, University Medical Centre Freiburg (Freiburg, Germany) between 2003 and 2012. CVID was diagnosed based on the European Society for Immunodeficiencies/Pan-American Group for Immunodeficiency criteria [2]. In nine out of 11 patients, transbronchial biopsy was performed during bronchoscopy. In six (67%) of the biopsies, lymphocytic infiltrations could be detected, which did not fulfil the criteria for lymphocytic interstitial pneumonia. BAL lymphocytes (53.3±19.8%) exceeded 20% in all patients. CD4 cells accounted for 68.7±18.1% and CD8 cells for 16.6±8.2% of BAL cells. In contrast to the results reported by Bouvry et al. [1], we found a high CD4/CD8 ratio of 6.8±7.0 and no patient had a CD4/CD8 ratio <1.5. Moreover, the CD4/CD8 ratio (n=10; r=0.719, p=0.019) and the percentage of BAL CD4 lymphocytes (n=9; r=0.816, p=0.004) correlated negatively with BAL neutrophils (6.5±8.5%). The study by Bouvry et al. [1] showed significant differences in chest high-resolution computed tomography (HRCT) morphology between CVID and sarcoidosis patients. In particular nodules, air bronchograms, halo signs and bronchiectasis predominated in CVID. In line with their findings, in our cohort with proven granulomatous disease, the majority of HRCTs demonstrated macronodular lung involvement (eight out of 11 patients). The two patients with micronodular involvement showed a randomly distributed pattern, which also differs to the characteristic perilymphatic distribution in sarcoidosis, as already shown by Bouvry et al. [1]. Moreover, some patients presented with predominant coarse reticular lines or ground-glass lesions. It is intriguing to speculate whether the difference in CD4/CD8 ratio reflects different forms or stages of pulmonary inflammation in CVID, which may correlate to certain computed tomography morphology. This has been previously described in sarcoidosis, where lower CD4/CD8 ratios and increased neutrophils correlated with progressive, fibrotic disease and the need for steroid treatment [3–5]. In our small CVID cohort, lung function and computed tomography findings were mostly stable during follow-up, suggesting that a high CD4/CD8 ratio in granulomatous CVID is associated with a mild and nonprogressive ILD (table 1). Only two patients showed a deterioration of lung function parameters. Interestingly, both of these patients showed rather low CD4/CD8 ratios in comparison to the total study population (2.0 and 3.8).
In conclusion, in addition to the report by Bouvry et al. [1], we found that in a subgroup of CVID patients with histologically confirmed granuloma formation, BAL cytology resembles sarcoidosis. All patients presented with high BAL lymphocytosis, high CD4/CD8 ratio and the majority with nodular lung disease on computed tomography. Thus, differences in BAL cytology and computed tomography morphology most likely reflect heterogeneity in CVID-associated granulomatous and interstitial lung disease. Our preliminary data suggest a rather favourable prognosis of ILD in this subgroup of CVID with high CD4/CD8 ratio in the BAL. Some of these findings may potentially guide management and predict outcome of these patients, but larger studies are needed to determine diagnostic and prognostic value of specific markers during detailed characterisation of interstitial lung disease in this heterogeneous disease.
Footnotes
Conflict of interest: Disclosures can be found alongside the online version of this article at www.erj.ersjournals.com
- Received February 10, 2013.
- Accepted July 30, 2013.
- ©ERS 2014