Application of nitric oxide measurements in clinical conditions beyond asthma.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.Fractional exhaled nitric oxide (FeNO) is a convenient, non-invasive method for the assessment of active, mainly Th2-driven, airway inflammation, which is sensitive to treatment with standard anti-inflammatory therapy. Consequently, FeNO serves as a valued tool to aid diagnosis and monitoring in several asthma phenotypes. More recently, FeNO has been evaluated in several other respiratory, infectious, and/or immunological conditions. In this short review, we provide an overview of several clinical studies and discuss the status of potential applications of NO measurements in clinical conditions beyond asthma

Occurrence of liver cirrhosis in England, a cohort study, 1998-2009: a comparison with cancer

OBJECTIVES: There is no routine registration of the occurrence of newly diagnosed cases of cirrhosis in the United Kingdom. This study seeks to determine precise estimates and trends of the incidence of cirrhosis in England, and directly compare these figures with those for the 20 most commonly diagnosed cancers in the United Kingdom. METHODS: We used the Clinical Practice Research Datalink and linked English Hospital Episode Statistics to perform a population-based cohort study. Adult incident cases with a diagnosis of cirrhosis between January 1998 and December 2009 were identified. We described trends in incidence by sex and etiology. We performed a direct standardization to estimate the number of people being newly diagnosed with cirrhosis in 2009, and calculated the change in incidence between 1998 and 2009. RESULTS: A total of 5,118 incident cases of cirrhosis were identified, 57.9% were male. Over the 12-year period, crude incidence increased by 50.6%. Incidence increased for both men and women and all etiology types. We estimated approximately 17,000 people were newly diagnosed with cirrhosis in 2009 in the United Kingdom, greater than that of the fifth most common cancer non-Hodgkin's lymphoma. The percentage change in incidence of cirrhosis between 1998 and 2009 for both men (52.4%) and women (38.3%) was greater than that seen for the top four most commonly diagnosed cancers in the United Kingdom (breast, lung, bowel, and prostate). CONCLUSIONS: The occurrence of cirrhosis increased more than that of the top four cancers during 1998 to 2009 in England. Strategies to monitor and reduce the incidence of this disease are urgently needed

Exhaled nitric oxide and the management of childhood asthma : yet another promising biomarker "has been" or a misunderstood gem

Copyright © 2014 Elsevier Ltd. All rights reserved.Peer reviewedPostprin

Bronchial Responsiveness Is Related to Increased Exhaled NO (FENO) in Non-Smokers and Decreased FENO in Smokers

Rationale Both atopy and smoking are known to be associated with increased bronchial responsiveness. Fraction of nitric oxide (NO) in the exhaled air (FENO), a marker of airways inflammation, is decreased by smoking and increased by atopy. NO has also a physiological bronchodilating and bronchoprotective role. Objectives To investigate how the relation between FENO and bronchial responsiveness is modulated by atopy and smoking habits. Methods Exhaled NO measurements and methacholine challenge were performed in 468 subjects from the random sample of three European Community Respiratory Health Survey II centers: Turin (Italy), Gothenburg and Uppsala (both Sweden). Atopy status was defined by using specific IgE measurements while smoking status was questionnaire-assessed. Main Results Increased bronchial responsiveness was associated with increased FENO levels in non-smokers (p = 0.02) and decreased FENO levels in current smokers (p = 0.03). The negative association between bronchial responsiveness and FENO was seen only in the group smoking less <10 cigarettes/day (p = 0.008). Increased bronchial responsiveness was associated with increased FENO in atopic subjects (p = 0.04) while no significant association was found in non-atopic participants. The reported interaction between FENO and smoking and atopy, respectively were maintained after adjusting for possible confounders (p-values<0.05). Conclusions The present study highlights the interactions of the relationship between FENO and bronchial responsiveness with smoking and atopy, suggesting different mechanisms behind atopy- and smoking-related increases of bronchial responsiveness

A rare IL33 loss-of-function mutation reduces blood eosinophil counts and protects from asthma.

Efst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinnIL-33 is a tissue-derived cytokine that induces and amplifies eosinophilic inflammation and has emerged as a promising new drug target for asthma and allergic disease. Common variants at IL33 and IL1RL1, encoding the IL-33 receptor ST2, associate with eosinophil counts and asthma. Through whole-genome sequencing and imputation into the Icelandic population, we found a rare variant in IL33 (NM_001199640:exon7:c.487-1G>C (rs146597587-C), allele frequency = 0.65%) that disrupts a canonical splice acceptor site before the last coding exon. It is also found at low frequency in European populations. rs146597587-C associates with lower eosinophil counts (β = -0.21 SD, P = 2.5×10-16, N = 103,104), and reduced risk of asthma in Europeans (OR = 0.47; 95%CI: 0.32, 0.70, P = 1.8×10-4, N cases = 6,465, N controls = 302,977). Heterozygotes have about 40% lower total IL33 mRNA expression than non-carriers and allele-specific analysis based on RNA sequencing and phased genotypes shows that only 20% of the total expression is from the mutated chromosome. In half of those transcripts the mutation causes retention of the last intron, predicted to result in a premature stop codon that leads to truncation of 66 amino acids. The truncated IL-33 has normal intracellular localization but neither binds IL-33R/ST2 nor activates ST2-expressing cells. Together these data demonstrate that rs146597587-C is a loss of function mutation and support the hypothesis that IL-33 haploinsufficiency protects against asthma.Netherlands Asthma Foundation University Medical Center Groningen Ministry of Health and Environmental Hygiene of Netherlands Netherlands Asthma Stichting Astma Bestrijding BBMRI European Respiratory Society private and public research funds AstraZeneca ALK-Abello, Denmar

Effects of nicotine nasal spray on atherogenic and thrombogenic factors during smoking cessation

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldOBJECTIVES: To investigate changes in cardiovascular risk factor parameters when stopping smoking and to identify any impact of nicotine nasal spray on these factors. DESIGN AND SUBJECTS: In a placebo-controlled, double-blind 3-month prospective study, nicotine nasal spray (NNS) or a placebo was given to 157 subjects attending a smoking cessation programme. Blood samples from 46 subjects who remained abstinent for 3 months were analysed. Nasal spray use was given on an ad libitum basis. RESULTS: The haemoglobin (Hb) decreased from 149.0 to 143.2 g L(-1) (P<0.001). The haematocrit (Hct) decreased from 44.6 to 42.4% (P<0.001). The mean corpuscular volume (MCV) decreased from 93.4 to 92.3 fl (P<0.001). The mean corpuscular haemoglobin concentration (MCHC) increased from 333.9 to 338.1 g L(-1) (P = 0.029). The white blood cell count (WBC) decreased from 8.4 to 6.6x10(9) L(-1) (P<0.001). The total cholesterol decreased from 5.92 to 5.65 mmol L(-1) (P = 0.015). The high-density lipoprotein cholesterol (HDL) increased from 1.29 to 1.44 mmol L(-1) (P = 0.48) and low-density lipoprotein cholesterol (LDL) decreased from 4.00 to 3.54 mmol L(-1) (P = 0.004). The HDL/LDL ratio increased from 0.36 to 0.46 (P = 0.011). CONCLUSION: Stopping smoking resulted in positive effects on cardiovascular risk factors. Nicotine treatment for as long as 3 months did not have any significant effect on these 'stopping smoking changes'. In smoking cessation, nicotine substitution up to 3 months seems to be safe

Epidemiology of liver cirrhosis morbidity and mortality in Iceland

BACKGROUND: The mortality from liver cirrhosis in Iceland is the lowest in the Western world. OBJECTIVE: To study the epidemiology of liver cirrhosis mortality and morbidity in Iceland and to obtain a reliable separation between alcoholic cirrhosis (AC) and non-alcoholic cirrhosis (NAC) by using multiple data sources. METHODS: The study included the whole population of Iceland. Mortality was studied through death certificate data for the period 1951-90 and morbidity (clinical incidence) through hospital, autopsy and biopsy records for the period 1971-90. RESULTS: The average mortality for AC in age group 20 years and older was 8.6 and for NAC 19.2 per 10(6)/year and the average clinical incidence was 22.1 per 10(6)/year for AC and 25.9 per 10(6)/year for NAC. In the morbidity study 44% of cases were due to AC. In the mortality study 24% of cases were due to AC but the data suggested an underreporting of AC for males at a rate of 30%. There was a significant decrease in AC mortality with time but no change in NAC. Average alcohol consumption of inhabitants aged over 15 years increased from 2.1 to 4.9 litres per year (130%) during the period 1951-90. CONCLUSION: The incidence of cirrhosis in Iceland is very low for both AC and NAC, accounting for only 0.2% of total deaths. The reasons are unknown. The low incidence of AC in Iceland is probably partly due to low alcohol consumption. The decreasing incidence of AC despite 130% increase in alcohol consumption is thought to be due to intensive treatment of alcoholism. A low prevalence of hepatitis B and C probably contributes to the low incidence of NAC