Identification of bile acid-CoA:amino acid N-acyltransferase as the hepatic N-acyl taurine synthase for polyunsaturated fatty acids.

N-acyl taurines (NATs) are bioactive lipids with emerging roles in glucose homeostasis and lipid metabolism. The acyl chains of hepatic and biliary NATs are enriched in polyunsaturated fatty acids (PUFAs). Dietary supplementation with a class of PUFAs, the omega-3 fatty acids, increases their cognate NATs in mice and humans. However, the synthesis pathway of the PUFA-containing NATs remains undiscovered. Here, we report that human livers synthesize NATs and that the acyl-chain preference is similar in murine liver homogenates. In the mouse, we found that hepatic NAT synthase activity localizes to the peroxisome and depends upon an active-site cysteine. Using unbiased metabolomics and proteomics, we identified bile acid-CoA:amino acid N-acyltransferase (BAAT) as the likely hepatic NAT synthase in vitro. Subsequently, we confirmed that BAAT knockout livers lack up to 90% of NAT synthase activity and that biliary PUFA-containing NATs are significantly reduced compared with wildtype. In conclusion, we identified the in vivo PUFA-NAT synthase in the murine liver and expanded the known substrates of the bile acid-conjugating enzyme, BAAT, beyond classic bile acids to the synthesis of a novel class of bioactive lipids.

The Scandinavian baltic pancreatic club (SBPC) database: design, rationale and characterisation of the study cohort.

OBJECTIVES: Chronic pancreatitis (CP) is a multifaceted disease associated with several risk factors and a complex clinical presentation. We established the Scandinavian Baltic Pancreatic Club (SBPC) Database to characterise and study the natural history of CP in a Northern European cohort. Here, we describe the design of the database and characteristics of the study cohort. METHODS: Nine centres from six different countries in the Scandinavian-Baltic region joined the database. Patients with definitive or probable CP (M-ANNHEIM diagnostic criteria) were included. Standardised case report forms were used to collect several assessment variables including disease aetiology, duration of CP, preceding acute pancreatitis, as well as symptoms, complications, and treatments. The clinical stage of CP was characterised according to M-ANNNHEIM. Yearly follow-up is planned for all patients. RESULTS: The study cohort comprised of 910 patients (608 men: 302 women; median age 58 (IQR: 48-67) years with definite 848 (93%) or probable CP 62 (7%). Nicotine (70%) and alcohol (59%) were the most frequent aetiologies and seen in combination in 44% of patients. A history of recurrent acute pancreatitis was seen in 49% prior to the development of CP. Pain (69%) and exocrine pancreatic insufficiency (68%) were the most common complications followed by diabetes (43%). Most patients (30%) were classified as clinical stage II (symptomatic CP with exocrine or endocrine insufficiency). Less than 10% of the patients had undergone pancreatic surgery. CONCLUSION: The SBPC database provides a mean for future prospective, observational studies of CP in the Northern European continent.

Asthma in ear, nose, and throat primary care patients with chronic rhinosinusitis with nasal polyps.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common inflammatory disorder associated with asthma. This association is well described in patients with CRSwNP undergoing endoscopic sinus surgery (ESS); however, some patients are never referred for surgery, and the frequency of asthma in this group is largely unknown. OBJECTIVE: To determine the frequency of asthma in patients with CRSwNP treated in a primary care (PC) setting who have never been referred for surgery and to compare this with ESS patients. METHODS: Fifty-seven patients with CRSwNP who had never undergone ESS were prospectively recruited from nine PC ear, nose, and throat clinics in the Copenhagen area. CRSwNP was diagnosed according to the European Position Paper on Chronic Rhinosinusitis and Nasal Polyps; severity was assessed by using a visual analog scale. Allergy, lung function, and asthma tests (reversibility to ß2-agonist, peak expiratory flow variability, and mannitol challenge) were performed. Findings were compared with our previously published data from patients with CRSwNP referred for surgery. RESULTS: Asthma was diagnosed in 25 patients (44%) based on respiratory symptoms and a positive asthma test; of these, 12 (48%) had undiagnosed asthma prior to study onset. Furthermore, when using the same methods, we found a lower frequency of asthma in PC patients compared with ESS patients (44% versus 65%, p = 0.04). CONCLUSION: A high prevalence of asthma in PC patients with CRSwNP was found. Frequently, asthma was undiagnosed. However, asthma was significantly less prevalent in PC patients compared with patients referred for ESS. The frequent concomitance of asthma, i.e., united airways disease, in PC patients calls for closer collaboration between ear, nose, and throat specialists, and asthma specialists.

Management of chronic rhinosinusitis with nasal polyps and coexisting asthma: A systematic review.

BACKGROUND: Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) and asthma are strongly associated, and patients suffering from both diseases are often difficult to treat. However, no guidelines about the management of patients with CRS and coexisting asthma exist. OBJECTIVE: The purpose of this systematic review was to evaluate the management of CRSwNP and coexisting asthma. METHODS: We systematically searched electronic databases and included clinical trials in which the clinical outcomes after medical or surgical treatment of patients with CRSwNP and asthma were assessed. The strength of the evidence for each outcome was graded on the basis of study quality and consistency in findings. RESULTS: We included seven trials in which the effect of montelukast, omalizumab, erythromycin, and functional endoscopic sinus surgery (FESS) were studied in 317 adults with CRSwNP and asthma. All the interventions improved the majority of subjective and objective nasal outcomes significantly. However, few studies found significant effects on pulmonary function tests. The strength of the evidence was low overall. CONCLUSION: Both FESS and medical interventions with systemic anti-inflammatory drugs improved nasal outcomes, although their efficacy in relation to the lower airways remains unclear. A low number of studies met inclusion criteria for this systematic review, which emphasizes the need for high-quality trials to explore the treatment of patients with CRSwNP and coexisting asthma.