Characterization of the PF-ILD phenotype in patients with advanced pulmonary sarcoidosis.

BACKGROUND: Advanced pulmonary sarcoidosis causes significant morbidity and can lead to death. Large trials demonstrated efficacy of antifibrotics in patients with progressive fibrosing interstitial lung diseases (PF-ILD), including a few with sarcoidosis. To date, little is known about this progressive fibrosing phenotype in sarcoidosis. Diffusion capacity of carbon monoxide (DLCO) may be a useful functional marker to screen for advanced pulmonary sarcoidosis. In this study, we describe a cohort with advanced pulmonary sarcoidosis and we gain insights in the progressive fibrosing phenotype in sarcoidosis. METHODS: Patients with sarcoidosis and a DLCO < 50% predicted were included in this retrospective cohort study. First measurement of DLCO < 50% predicted was the baseline. Lung function data, HRCT, pulmonary hypertension (PH) and mortality were collected. Patients with > 10% fibrosis on HRCT meeting the criteria for ILD-progression within 24 months were labelled as PF-ILD. With Cox-regression analysis predictors of mortality were established. RESULTS: 106 patients with a DLCO < 50% predicted were included. Evolution of forced vital capacity (FVC) varied widely between patients from - 34% to + 45% after 2 years follow-up, whereas change in DLCO varied between - 11% and + 26%. Fourteen patients (15%) met the PF-ILD criteria, of whom 6 (43%) died within 10 years versus 10 (13%) in the non PF-ILD group (p = 0.006). PH was present 12 (11%), 56 (53%) demonstrated > 10% fibrosis on HRCT. Independent predictors of mortality and lung transplantation in the whole cohort are PH, PF-ILD and UIP-like pattern. CONCLUSION: In conclusion, within this group with advanced pulmonary sarcoidosis disease course varied widely from great functional improvement to death. PF-ILD patients had higher mortality rate than the mortality in the overall pulmonary sarcoidosis group. Future research should focus on the addition of antifibrotics in these patients. Trial registration retrospectively registered.

Value of serum soluble interleukin-2 receptor as a diagnostic and predictive biomarker in sarcoidosis.

BACKGROUND: Differentiating between interstitial lung diseases (ILD) is challenging. Serum soluble interleukin 2 receptor (sIL-2R) is used as a diagnostic marker in sarcoidosis, but its diagnostic value has not yet been studied in other ILDs like Idiopathic Pulmonary Fibrosis (IPF) or Hypersensitivity Pneumonitis (HP). Also, the prognostic value of sIL-2R in sarcoidosis remains unknown. METHODS: This retrospective cohort study included 121 patients with sarcoidosis, 35 with cHP, 62 with IPF (idiopathic pulmonary fibrosis) and 70 healthy controls. Serum sIL-2R levels were determined at diagnosis. Follow-up data were available for patients with chronic sarcoidosis (n = 64) and patients with non-chronic sarcoidosis (n = 29). RESULTS: Patients with sarcoidosis had higher sIL-2R levels (median 5418 pg/mL) than patients with cHP (median 4015 pg/mL, P = 0.002) and IPF (median 4192 pg/mL, P = 0.034). No differences were found between patients with cHP and IPF. Logistic regression revealed that sIL-2R at diagnosis is a significant predictor of the development of chronic sarcoidosis (OR = 2.1, P = 0.032). CONCLUSION: High levels of sIL-2R are suggestive of sarcoidosis, although a broad overlap exists in sIL-2R levels across sarcoidosis, cHP, and IPF. High levels of sIL-2R might serve as a prognostic biomarker for chronicity.

Bronchoalveolar lavage characteristics correlate with HLA tag SNPs in patients with Löfgren's syndrome and other sarcoidosis.

Genetic susceptibility for sarcoidosis and Löfgren's syndrome (LS) has been associated with prognosis. Human leukocyte antigen (HLA)-DRB1*03 is over-represented in LS, and is associated with a good prognosis, whereas HLA-DRB1*15-positive patients have a more chronic course of sarcoidosis. These HLA-DRB1 types can be easily tagged by single nucleotide polymorphisms (SNPs). Our aim was to evaluate the association between these tag SNPs and bronchoalveolar lavage (BAL) characteristics. In 29 patients, both complete HLA-DRB1* locus genotyping and SNP tagging was performed in parallel. HLA-DRB1 type was inferred from the presence of *03 tag rs2040410 allele A and referred to as *03. HLA-DRB1*15 was inferred from the presence of tag SNP rs3135388 allele A and referred to as *15. For BAL analysis, 122 patients with LS and 165 patients with non-LS sarcoidosis were included. BAL lymphocyte subsets were analyzed by flow cytometry. The presence of tag SNPs completely corresponded with HLA-DRB1*03/*15 genotypes in all 29 patients in whom both HLA-DRB1* genotyping and SNP tagging was performed. In all patients together, *03+ /*15- patients showed a higher CD4+ /CD8+ ratio than *03- /*15+ (P = 0·004) and *03- /*15- (P = 0·001). LS patients with *03+ /*15- had a lower BAL lymphocyte count compared to *03- /*15+  patients (P = 0·011). Non-LS sarcoidosis patients with *03+ /*15- patients showed a decreased CD103+ CD4+ /CD4+ ratio compared to *03- /*15+  patients (P = 0·045) and *03- /*15- patients (P = 0·018). We found that HLA-DRB1*03 and HLA-DRB1*15 can be approximated by genotyping of tag SNPs and corresponds with the degree of lymphocytosis and cell phenotypes in BAL in both LS and non-LS sarcoidosis patients.