EAACI position paper on occupational rhinitis

The present document is the result of a consensus reached by a panel of experts from European and non-European countries on Occupational Rhinitis (OR), a disease of emerging relevance which has received little attention in comparison to occupational asthma. The document covers the main items of OR including epidemiology, diagnosis, management, socio-economic impact, preventive strategies and medicolegal issues. An operational definition and classification of OR tailored on that of occupational asthma, as well as a diagnostic algorithm based on steps allowing for different levels of diagnostic evidence are proposed. The needs for future research are pointed out. Key messages are issued for each item

Genetic variant I148M in <it>PNPLA3</it> is associated with the ultrasonography-determined steatosis degree in a Chinese population

<p>Abstract</p> <p>Background</p> <p>Nonalcoholic fatty liver disease (NAFLD) is an escalating medical problem worldwide. A nonsynonymous single nucleotide polymorphism rs738409 (I148M) in patatin-like phospholipase domain-containing protein 3 (<it>PNPLA3</it>) predisposes susceptibility to NAFLD; however, its association with steatosis grade is inconsistent in the literature. In particular, there was no significant association found between I148M and steatosis grade in two East Asian-based studies. In this study we aim to investigate whether I148M is associated with the ultrasonography-determined steatosis degree in Chinese adults.</p> <p>Methods</p> <p>203 NAFLD cases and 202 matched controls were recruited. Cases were classified into mild, moderate and severe fatty liver by ultrasonography. Association between I148M and the ultrasonography-determined steatosis degree as well as other clinical parameters was evaluated.</p> <p>Results</p> <p>The I148M variant was associated with the ultrasonography-determined steatosis degree with the M allele frequencies being 0.32, 0.54, and 0.87 in mild (n=105), moderate (n=83), and severe (n=15) cases, respectively (<it>P</it>–value = 7.6×10^-8). We also confirmed the interaction between I148M variation and body mass index towards elevated plasma alanine aminotransferase levels in cases (<it>P</it>–value = 4.4×10^-4).</p> <p>Conclusion</p> <p>The <it>PNPLA3</it> I148M variant is associated with the ultrasonography-determined steatosis degree in Chinese population.</p

Collagen Formation Assessed by N-Terminal Propeptide of Type 3 Procollagen Is a Heritable Trait and Is Associated With Liver Fibrosis Assessed by Magnetic Resonance Elastography

N-terminal propeptide of type 3 procollagen (PRO-C3) is a biomarker of liver fibrosis in nonalcoholic fatty liver disease (NAFLD). This study examines the association between PRO-C3 concentration and liver fibrosis assessed by magnetic resonance elastography (MRE)-measured stiffness (MRE-stiffness) and the heritability of PRO-C3 concentration in a cohort of twins and families with and without NAFLD. We performed a cross-sectional analysis of a well-characterized prospective cohort of 306 participants, including 44 probands with NAFLD-cirrhosis and their 72 first-degree relatives, 24 probands with NAFLD without advanced fibrosis and their 24 first-degree relatives, and 72 controls without NAFLD and their 72 first-degree relatives. Liver steatosis was assessed by magnetic resonance imaging proton density fat fraction, and liver fibrosis was assessed by MRE-stiffness. Serum PRO-C3 was assessed by competitive, enzyme-linked immunosorbent assay. We assessed the familial correlation of PRO-C3 concentration, the shared gene effects between PRO-C3 concentration and liver steatosis and fibrosis, and the association between PRO-C3 concentration and genetic variants in the patatin-like phospholipase domain-containing 3 (PNPLA3), transmembrane 6 superfamily member 2 (TM6SF2), membrane-bound O-acyltransferase domain-containing (MBOAT), and glucokinase regulator (CGKR) genes. In multivariable-adjusted models including age, sex, body mass index, and ethnicity, serum PRO-C3 correlated strongly with liver fibrosis (r(2) = 0.50, P \textless 0.001) and demonstrated robust heritability (h(2) , 0.36; 95% confidence interval [CI], 0.07, 0.59; P = 0.016). PRO-C3 concentration and steatosis had a strong genetic correlation (shared genetic determination: 0.62; 95% CI, 0.236, 1.001; P = 0.002), whereas PRO-C3 concentration and fibrosis had a strong environmental correlation (shared environmental determination: 0.55; 95% CI, 0.317, 0.717; P \textless 0.001). PRO-C3 concentrations were higher in carriers of the TM6SF2 rs58542926-T allele compared with noncarriers: 15.7 (+/- 10.5) versus 10.8 (+/- 5.7) ng/L (P = 0.047). Conclusion: Serum PRO-C3 correlates with MRE-assessed fibrosis, is heritable, shares genetic correlation with liver steatosis and shares environmental correlation with liver fibrosis. PRO-C3 concentration appears to be linked to both fibrosis and steatosis and increased in carriers of the TM6SF2 rs58542926 risk allele