The burden of adult asthma in Finland: impact of disease severity and eosinophil count on health care resource utilization.

Objective: To describe health care resource utilization (HCRU) and associated costs in adult patients referred for specialist asthma care in Southwest Finland, by disease severity and blood eosinophil count (BEC).Methods: This non-interventional, retrospective registry study (GSK ID: HO-17-17558) utilized data from patients >18 years of age on the hospital register of the Hospital District of Southwest Finland. Data extraction was from January 1, 2004 to December 31, 2015; the index date was the first hospital visit within this period with an International Classification of Diseases-10 diagnosis code for asthma or acute severe asthma. Patients were categorized by asthma severity (based on medication use) and BEC (<300 or ≥300 cells/µL). Total and asthma-related HCRU and estimated costs were recorded the year following index and for calendar years 2004-2015.Results: Overall, 14,398 patients were included; 388 had severe asthma at index. BEC was available for 3781 patients; 1434 had a BEC ≥300 cells/µL and 2347 had a BEC <300 cells/µL. A total of 1241 patients had severe asthma; 270 patients had severe eosinophilic asthma (severe asthma and a BEC ≥300 cells/µL). Patients with severe versus non-severe asthma had higher total- and asthma-related outpatient visits, inpatient days, emergency room visits and costs per patient year; those with BEC ≥300 cells/µL versus <300 cells/µL had more outpatient visits. All recorded HCRU and associated costs were highest in patients with severe eosinophilic asthma.Conclusion: This study demonstrated a substantial burden associated with severe and/or eosinophilic asthma for adults in Finland.

Intestinal alkaline phosphatase at the crossroad of intestinal health and disease - a putative role in type 1 diabetes.

BACKGROUND: Patients with type 1 diabetes have shown an increase in circulating cytokines, altered lipoprotein metabolism and signs of vascular dysfunction in response to high-fat meals. Intestinal alkaline phosphatase (IAP) regulates lipid transport and inflammatory responses in the gastrointestinal tract. We therefore hypothesized that changes in IAP activity could have profound effects on gut metabolic homeostasis in patients with type 1 diabetes. METHODS: Faecal samples of 41 nondiabetic controls and 46 patients with type 1 diabetes were analysed for IAP activity, calprotectin, immunoglobulins and short-chain fatty acids (SCFAs). The impact of oral IAP supplementation on intestinal immunoglobulin levels was evaluated in C57BL/6 mice exposed to high-fat diet for 11 weeks. RESULTS: Patients with type 1 diabetes exhibited signs of intestinal inflammation. Compared to controls, patients with diabetes had higher faecal calprotectin levels, lower faecal IAP activities accompanied by lower propionate and butyrate concentrations. Moreover, the amount of faecal IgA and the level of antibodies binding to oxidized LDL were decreased in patients with type 1 diabetes. In mice, oral IAP supplementation increased intestinal IgA levels markedly. CONCLUSION: Deprivation of protective intestinal factors may increase the risk of inflammation in the gut - a phenomenon that seems to be present already in patients with uncomplicated type 1 diabetes. Low levels of intestinal IgA and antibodies to oxidized lipid epitopes may predispose such patients to inflammation-driven complications such as cardiovascular disease and diabetic nephropathy. Importantly, oral IAP supplementation could have beneficial therapeutic effects on gut metabolic homeostasis, possibly through stimulation of intestinal IgA secretion.

Podocyte apoptosis is prevented by blocking the Toll-like receptor pathway.

High serum lipopolysaccharide (LPS) activity in normoalbuminuric patients with type 1 diabetes (T1D) predicts the progression of diabetic nephropathy (DN), but the mechanisms behind this remain unclear. We observed that treatment of cultured human podocytes with sera from normoalbuminuric T1D patients with high LPS activity downregulated 3-phosphoinositide-dependent kinase-1 (PDK1), an activator of the Akt cell survival pathway, and induced apoptosis. Knockdown of PDK1 in cultured human podocytes inhibited antiapoptotic Akt pathway, stimulated proapoptotic p38 MAPK pathway, and increased apoptosis demonstrating an antiapoptotic role for PDK1 in podocytes. Interestingly, PDK1 was downregulated in the glomeruli of diabetic rats and patients with type 2 diabetes before the onset of proteinuria, further suggesting that reduced expression of PDK1 associates with podocyte injury and development of DN. Treatment of podocytes in vitro and mice in vivo with LPS reduced PDK1 expression and induced apoptosis, which were prevented by inhibiting the Toll-like receptor (TLR) signaling pathway with the immunomodulatory agent GIT27. Our data show that LPS downregulates the cell survival factor PDK1 and induces podocyte apoptosis, and that blocking the TLR pathway with GIT27 may provide a non-nephrotoxic means to prevent the progression of DN.