Serial CT analysis in idiopathic pulmonary fibrosis: comparison of visual features that determine patient outcome

Aims: Patients with idiopathic pulmonary fibrosis (IPF) receiving antifibrotic medication and patients with non-IPF fibrosing lung disease often demonstrate rates of annualised forced vital capacity (FVC) decline within the range of measurement variation (5.0%–9.9%). We examined whether change in visual CT variables could help confirm whether marginal FVC declines represented genuine clinical deterioration rather than measurement noise. Methods: In two IPF cohorts (cohort 1: n=103, cohort 2: n=108), separate pairs of radiologists scored paired volumetric CTs (acquired between 6 and 24 months from baseline). Change in interstitial lung disease, honeycombing, reticulation, ground-glass opacity extents and traction bronchiectasis severity was evaluated using a 5-point scale, with mortality prediction analysed using univariable and multivariable Cox regression analyses. Both IPF populations were then combined to determine whether change in CT variables could predict mortality in patients with marginal FVC declines. Results: On univariate analysis, change in all CT variables except ground-glass opacity predicted mortality in both cohorts. On multivariate analysis adjusted for patient age, gender, antifibrotic use and baseline disease severity (diffusing capacity for carbon monoxide), change in traction bronchiectasis severity predicted mortality independent of FVC decline. Change in traction bronchiectasis severity demonstrated good interobserver agreement among both scorer pairs. Across all study patients with marginal FVC declines, change in traction bronchiectasis severity independently predicted mortality and identified more patients with deterioration than change in honeycombing extent. Conclusions: Change in traction bronchiectasis severity is a measure of disease progression that could be used to help resolve the clinical importance of marginal FVC declines

The importance of biobank and nationwide registry for lymphangioleiomyomatosis in a small sized country

Introduction: Patient registries combined with the collection of human specimens in biobanks are of great value for facilitating research on orphan diseases, allowing researchers to obtain valid and reliable epidemiological information. This results in an increase of knowledge on epidemiology, course of disease, clinical presentation and underlying biomarkers. The biobank in the St. Antonius Hospital in Nieuwegein, the Netherlands, is used for nationwide registry of patients with lymphangioleiomyomatosis (LAM), an ultra rare interstitial lung disease characterized by smooth muscle proliferation in the lungs. Areas covered: This paper provides a review of the global prevalence and disease characteristics of LAM. Additionally, disease characteristics of patients derived from the nationwide registry in the Netherlands will be described and compared with the literature. Expert opinion: A nationwide registry and biobank for ultra rare diseases such as LAM allows for country-specific insight in epidemiology and clinical characteristics. Active cooperation between health care professionals and patients is of utmost importance to increase general awareness and successful coverage ratio of inclusions. The Dutch LAM registry and biobank will now be able to participate in the global LAM registry of the LAM Foundation International Clinics program, with the purpose of identifying patients and availability for trials and bio-specimens for basic research worldwide, when possible

Efficacy of adalimumab in sarcoidosis patients who developed intolerance to infliximab

BACKGROUND: Tumor necrosis factor-alpha (TNF-α) inhibitors are regarded as the third-line therapy in sarcoidosis, the first choice generally being infliximab. To date, data regarding response to adalimumab in sarcoidosis patients intolerant to infliximab are lacking. The objective of this retrospective observational study was to establish if adalimumab could achieve stabilization or improvement of the disease in refractory sarcoidosis patients who developed intolerance to infliximab. MATERIAL AND METHODS: Sarcoidosis patients referred to St Antonius Interstitial Lung Diseases Center of Excellence, Nieuwegein, The Netherlands, between January 2008 and April 2015 who switched from infliximab to adalimumab were included. Changes in organ function, inflammatory biomarker levels, and adverse events were retrieved from medical records. RESULTS: Out of 142 infliximab treated patients, 18 (13%) had to discontinue treatment due to antibody formation or severe adverse events and switched to adalimumab therapy. Organ function improved in 7 patients (39%), was stable in 6 patients (33%), and worsened in 5 patients (28%) after 12 months of treatment or after 6 months if evaluation after 12 months was not available (n = 4). In none of the patients biomarker levels of soluble interleukin-2 receptor (sIL-2R) deteriorated. Median decrease in sIL-2R was 3614 pg/mL. Most reported adverse event was infection (n = 10). CONCLUSIONS: Adalimumab is an effective alternative for patients intolerant to infliximab. The switch to adalimumab achieved clinical improvement in 39% and stabilization in 33% of patients intolerant to infliximab. Further research is needed to develop guidelines on how to use adalimumab for sarcoidosis in terms of dosing regimen

Efficacy of adalimumab in sarcoidosis patients who developed intolerance to infliximab

BACKGROUND: Tumor necrosis factor-alpha (TNF-α) inhibitors are regarded as the third-line therapy in sarcoidosis, the first choice generally being infliximab. To date, data regarding response to adalimumab in sarcoidosis patients intolerant to infliximab are lacking. The objective of this retrospective observational study was to establish if adalimumab could achieve stabilization or improvement of the disease in refractory sarcoidosis patients who developed intolerance to infliximab. MATERIAL AND METHODS: Sarcoidosis patients referred to St Antonius Interstitial Lung Diseases Center of Excellence, Nieuwegein, The Netherlands, between January 2008 and April 2015 who switched from infliximab to adalimumab were included. Changes in organ function, inflammatory biomarker levels, and adverse events were retrieved from medical records. RESULTS: Out of 142 infliximab treated patients, 18 (13%) had to discontinue treatment due to antibody formation or severe adverse events and switched to adalimumab therapy. Organ function improved in 7 patients (39%), was stable in 6 patients (33%), and worsened in 5 patients (28%) after 12 months of treatment or after 6 months if evaluation after 12 months was not available (n = 4). In none of the patients biomarker levels of soluble interleukin-2 receptor (sIL-2R) deteriorated. Median decrease in sIL-2R was 3614 pg/mL. Most reported adverse event was infection (n = 10). CONCLUSIONS: Adalimumab is an effective alternative for patients intolerant to infliximab. The switch to adalimumab achieved clinical improvement in 39% and stabilization in 33% of patients intolerant to infliximab. Further research is needed to develop guidelines on how to use adalimumab for sarcoidosis in terms of dosing regimen

Analysis of BTNL2 genetic polymorphisms in British and Dutch patients with sarcoidosis

Sarcoidosis is a heterogeneous disorder, both phenotypically and genetically. Two independent studies have recently shown that a functional polymorphism within butyrophilin-like 2 (BTNL2) gene predisposes to sarcoidosis independently of the human leukocyte antigen (HLA)-DRB1 alleles. However, in both studies, data analysis was not stratified by Lo\ua8 fgrens syndrome, a clinically and genetically distinct sarcoidosis subset. BTNL2, potentially encoding an immune coreceptor, is adjacent and in linkage disequilibrium (LD) with HLA-DRB1. We investigated six BTNL2 variants, including the functional rs2076530 (G > A), as well as HLADRB1 alleles, by sequence-specific primers\u2013polymerase chain reaction, in 288 patients and 446 controls from two European countries. In the patient group as a whole, the HLA-DRB1*14 [odds ratio (OR) \ubc 3.1, Pc \ubc 0.0003], DRB1*12 (OR \ubc 2.5, Pc \ubc 0.003), and BTNL2 rs2076530 A allele (OR \ubc 1.49, Pc \ubc 0.002) were all associated with disease susceptibility. However, after exclusion of patients presenting with Lo\ua8 fgrens syndrome and after adjusting for HLA-DRB1 alleles, the association between BTNL2 rs2076530 A and disease disappeared (P \ubc 0.23). By contrast, both HLA-DRB1*14 and DRB1*12 remained strongly significant (OR \ubc 3.60, P < 0.0001 and OR \ubc 3.03, P \ubc 0.003, respectively). BTNL2 haplotype 4, tagged by the rs2076530 G allele, also remained associated with non-Lo\ua8 fgren sarcoidosis after adjusting for HLA-DRB1 alleles (OR 0.37, P \ubc 0.016). In summary, HLA-DRB1*14, DRB1*12, and BTNL2 haplotype 4 \u2013 but not rs2076530 A \u2013 are associated with non-Lo\ua8 fgren sarcoidosis. However, the tight LD across the HLA complex makes it difficult to identify the precise location of the susceptibility locus/i. Larger sample sets from different ethnic groups, finer mapping, and more robust LD analyses across the HLA region are needed