[Diseases connected with work in hay in Iceland. Causes and scientific studies].

Diseases connected with work in hay have been known in Iceland for a long time. In 1981 scientific studies of these diseases were started in Iceland at the request of the Farmers Union. The results of these studies are summarized in this article. In studies of hay a great amount of storage mites, moulds and thermophilic actinomycetes (microlyspora faeni) were found in addition to allergens from mice and pollen. Symptoms caused by hay dust were mainly from nose and eyes in people with positive skin tests, but cough, dyspnea and fever were equally common in those with negative skin tests. The most common causes of allergy in farming families were storage mites and cattle, but allergy to cats, dogs and grass pollen were less common rurally than in the Reykjavik area. When comparing individuals working in heavy hay dust with those working in cleaner air, the former group had a higher likelihood of having a positive precipitin test against micropolyspora faeni, fever after work in hay and airway obstruction. It was shown that Icelandic farmers were more likely to get emphysema than other people irrespective of smoking. In a large study of homes in the Reykjavik area almost no mites were found. In spite of this, positive specific IgE tests against dust mites were equally common as in Uppsala, Sweden, where dust mites were found in 16% of homes. In further studies it was found, that 57% of people in the study had been more and less exposed to hay dust. They had either been raised on a farm, been on a farm in the summer during childhood or owned horses and fed them with hay. We have argued that cross allergy to storage mites may be the cause of a rather common allergy to house dust mites. A new study of middle-aged individuals has shown that allergy to storage mites is a little more common in the Reykjavik area than in Aarhus, Bergen or Uppsala. The most likely explanation is that they have more often been exposed to hay dust.

[Diseases connected with work in hay in Iceland. Haymaking and old data on such diseases].

Diseases connected with work in hay have existed in Iceland since its settlement late in the 9th century. Haymaking was probably easier in those days because of better climate and land quality but became more difficult later when these factors deteriorated. First data on diseases connected with hay are from the early 17th century where the word "haysickness" (in Icelandic "heysótt") is used in a book on treatment of diseases. Later in the century the word is found in a rhyme that says "short of breath due to haysickness". The word "haysickness" is also found in dictionaries from that time. In a book from 1730-40 says: "Haysickness sometimes causes illness and loss of appetite in those that loosen hay in a compressed haystack with a hayneedle or a hook." At the end of the 18th century Jón Pétursson writes a good description of hay diseases: "It cannot be denied that haysickness not taken seriously or long ignored can cause many deaths in this country." Jón Finsen mentions in his doctoral thesis in 1874 that the symptoms of haysickness are different from those of allergy to pollen (hay fever) that had been recently described. In 1870 the Director of Health writes directions for farmers on how to reduce the danger of getting haysickness by using a thin cloth facemask when loosing hay from a haystack.

Prevalence of allergic sensitization to storage mites in Northern Europe.

BACKGROUND: Allergic sensitization to storage mites has mostly been related to occupational exposures like farming, grain/cattle handling, whereas for non-occupational settings, storage mite sensitization has been attributed to cross-reactivity with house dust mite (HDM) allergens. OBJECTIVE: We aimed to describe the prevalence of allergic sensitization to storage mites, co-sensitization to HDM allergens and respiratory symptoms in Denmark, Iceland, Norway and Sweden. METHODS: The population comprised of 1180 participants born 1945-1972 of the third follow-up of the population-based cohort European Community Respiratory Health Survey (ECRHS) in Aarhus, Bergen, Reykjavik and Uppsala. A clinical examination included skin prick tests (SPT) to Lepidoglyphus destructor, Tyrophagus putrescentiae, Acarus siro and common inhalant allergens, as well as standardized interviews. RESULTS: 8% were sensitized to HDM and 10% to storage mite, with some variation by study centre: Reykjavik 13%, Bergen 8% and Aarhus 7%. In Uppsala, only L destructor (3%) was measured. Storage mite sensitization was higher among men (11%) than women (8%). Among storage mite sensitized, 44% were also sensitized to HDM. Storage mite sensitization was associated with asthma and nasal allergies, but not with age, education, pet keeping or place of upbringing. CONCLUSIONS AND CLINICAL RELEVANCE: In this Northern European population-based study, allergic sensitization to storage mite was as common as HDM sensitization. Storage mite sensitization was, independently of HDM sensitization, associated with respiratory symptoms and asthma. Our findings suggest that storage mite sensitization should be evaluated with regard to inclusion into the common inhalant allergen panel in Northern Europe.

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

IL-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 (ß = -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.

Hazelnut allergy across Europe dissected molecularly: A EuroPrevall outpatient clinic survey.

BACKGROUND: Hazelnut allergy is birch pollen-driven in Northern/Western Europe and lipid transfer protein-driven in Spain and Italy. Little is known about other regions and other allergens. OBJECTIVE: Establishing a molecular map of hazelnut allergy across Europe. METHODS: In 12 European cities, subjects reporting reactions to hazelnut (n = 731) were evaluated and sensitization to 24 foods, 12 respiratory allergen sources, and latex was tested by using skin prick test and ImmunoCAP. A subset (124 of 731) underwent a double-blind placebo-controlled food challenge to hazelnut. Sera of 423 of 731 subjects were analyzed for IgE against 7 hazelnut allergens and cross-reactive carbohydrate determinants by ImmunoCAP. RESULTS: Hazelnut allergy was confirmed in 70% of those undergoing double-blind placebo-controlled food challenges. Birch pollen-driven hazelnut sensitization (Cor a 1) dominated in most cities, except in Reykjavik, Sofia, Athens, and Madrid, where reporting of hazelnut allergy was less frequent anyhow. In Athens, IgE against Cor a 8 dominated and strongly correlated with IgE against walnut, peach, and apple and against Chenopodium, plane tree, and mugwort pollen. Sensitization to seed storage proteins was observed in less than 10%, mainly in children, and correlated with IgE to nuts, seeds, and legumes. IgE to Cor a 12, observed in all cities (10% to 25%), correlated with IgE to nuts, seeds, and pollen. CONCLUSIONS: In adulthood, the importance of hazelnut sensitization to storage proteins, oleosin (Cor a 12), and Cor a 8 is diluted by the increased role of birch pollen cross-reactivity with Cor a 1. Cor a 8 sensitization in the Mediterranean is probably driven by diet in combination with pollen exposure. Hazelnut oleosin sensitization is prevalent across Europe; however, the clinical relevance remains to be established.

Kiwifruit allergy across Europe: clinical manifestation and IgE recognition patterns to kiwifruit allergens.

BACKGROUND: Kiwifruit is a common cause of food allergy. Symptoms range from mild to anaphylactic reactions. OBJECTIVE: We sought to elucidate geographic differences across Europe regarding clinical patterns and sensitization to kiwifruit allergens. Factors associated with the severity of kiwifruit allergy were identified, and the diagnostic performance of specific kiwifruit allergens was investigated. METHODS: This study was part of EuroPrevall, a multicenter European study investigating several aspects of food allergy. Three hundred eleven patients with kiwifruit allergy from 12 countries representing 4 climatic regions were included. Specific IgE to 6 allergens (Act d 1, Act d 2, Act d 5, Act d 8, Act d 9, and Act d 10) and kiwifruit extract were tested by using ImmunoCAP. RESULTS: Patients from Iceland were mainly sensitized to Act d 1 (32%), those from western/central and eastern Europe were mainly sensitized to Act d 8 (pathogenesis-related class 10 protein, 58% and 44%, respectively), and those from southern Europe were mainly sensitized to Act d 9 (profilin, 31%) and Act d 10 (nonspecific lipid transfer protein, 22%). Sensitization to Act d 1 and living in Iceland were independently and significantly associated with severe kiwifruit allergy (odds ratio, 3.98 [P = .003] and 5.60 [P < .001], respectively). Using a panel of 6 kiwifruit allergens in ImmunoCAP increased the diagnostic sensitivity to 65% compared with 20% for skin prick tests and 46% ImmunoCAP using kiwi extract. CONCLUSION: Kiwifruit allergen sensitization patterns differ across Europe. The use of specific kiwifruit allergens improved the diagnostic performance compared with kiwifruit extract. Sensitization to Act d 1 and living in Iceland are strong risk factors for severe kiwifruit allergy.

The cost of persistent asthma in Europe: an international population-based study in adults.

BACKGROUND: This study is aimed at providing a real-world evaluation of the economic cost of persistent asthma among European adults according to the degree of disease control [as defined by the 2006 Global Initiative for Asthma (GINA) guidelines]. METHODS: A prevalence-based cost-of-illness study was carried out on 462 patients aged 30-54 years with persistent asthma (according to the 2002 GINA definition), who were identified in general population samples from 11 European countries and examined in clinical settings in the European Community Respiratory Health Survey II between 1999 and 2002. The cost estimates were computed from the societal perspective following the bottom-up approach on the basis of rates, wages and prices in 2004 (obtained at the national level from official sources), and were then converted to the 2010 values. RESULTS: The mean total cost per patient was EUR 1,583 and was largely driven by indirect costs (i.e. lost working days and days with limited, not work-related activities 62.5%). The expected total cost in the population aged 30-54 years of the 11 European countries was EUR 4.3 billion (EUR 19.3 billion when extended to the whole European population aged from 15 to 64 years). The mean total cost per patient ranged from EUR 509 (controlled asthma) to EUR 2,281 (uncontrolled disease). Chronic cough or phlegm and having a high BMI significantly increased the individual total cost. CONCLUSIONS: Among European adults, the cost of persistent asthma drastically increases as disease control decreases. Therefore, substantial cost savings could be obtained through the proper management of adult patients in Europe.

Genomic Signatures of Local Adaptation under High Gene Flow in Lumpfish-Implications for Broodstock Provenance Sourcing and Larval Production.

Aquaculture of the lumpfish (Cyclopterus lumpus L.) has become a large, lucrative industry owing to the escalating demand for "cleaner fish" to minimise sea lice infestations in Atlantic salmon mariculture farms. We used over 10K genome-wide single nucleotide polymorphisms (SNPs) to investigate the spatial patterns of genomic variation in the lumpfish along the coast of Norway and across the North Atlantic. Moreover, we applied three genome scans for outliers and two genotype-environment association tests to assess the signatures and patterns of local adaptation under extensive gene flow. With our 'global' sampling regime, we found two major genetic groups of lumpfish, i.e., the western and eastern Atlantic. Regionally in Norway, we found marginal evidence of population structure, where the population genomic analysis revealed a small portion of individuals with a different genetic ancestry. Nevertheless, we found strong support for local adaption under high gene flow in the Norwegian lumpfish and identified over 380 high-confidence environment-associated loci linked to gene sets with a key role in biological processes associated with environmental pressures and embryonic development. Our results bridge population genetic/genomics studies with seascape genomics studies and will facilitate genome-enabled monitoring of the genetic impacts of escapees and allow for genetic-informed broodstock selection and management in Norway.

Evidence of unidirectional hybridization and second-generation adult hybrid between the two largest animals on Earth, the fin and blue whales.

Biodiversity in the oceans has dramatically declined since the beginning of the industrial era, with accelerated loss of marine biodiversity impairing the ocean's capacity to maintain vital ecosystem services. A few organisms epitomize the damaging and long-lasting effects of anthropogenic exploitation: Some whale species, for instance, were brought to the brink of extinction, with their population sizes reduced to such low levels that may have caused a significant disruption to their reproductive dynamics and facilitated hybridization events. The incidence of hybridization is nevertheless believed to be rare, and very little information exists on its directionality. Here, using genetic markers, we show that all but one whale hybrid sample collected in Icelandic waters originated from the successful mating of male fin whale and female blue whale, thus suggesting unidirectional hybridization. We also demonstrate for the first time the existence of a second-generation adult (male) hybrid resulting from a backcross between a female hybrid and a pure male fin whale. The incidence of hybridization events between fin and blue whales is likely underestimated and the observed unidirectional hybridization (for F1 and F2 hybrids) is likely to induce a reproductive loss in blue whale, which may represent an additional challenge to its recovery in the Atlantic Ocean compared to other rorquals.

Estimating the Risk of Severe Peanut Allergy Using Clinical Background and IgE Sensitization Profiles.

Background: It is not well-understood why symptom severity varies between patients with peanut allergy (PA). Objective: To gain insight into the clinical profile of subjects with mild-to-moderate and severe PA, and investigate individual and collective predictive accuracy of clinical background and IgE to peanut extract and components for PA severity. Methods: Data on demographics, patient history and sensitization at extract and component level of 393 patients with probable PA (symptoms ≤ 2 h + IgE sensitization) from 12 EuroPrevall centers were analyzed. Univariable and penalized multivariable regression analyses were used to evaluate risk factors and biomarkers for severity. Results: Female sex, age at onset of PA, symptoms elicited by skin contact with peanut, family atopy, atopic dermatitis, house dust mite and latex allergy were independently associated with severe PA; birch pollen allergy with mild-to-moderate PA. The cross-validated AUC of all clinical background determinants combined (0.74) was significantly larger than the AUC of tests for sensitization to extract (0.63) or peanut components (0.54-0.64). Although larger skin prick test wheal size, and higher IgE to peanut extract, Ara h 1 and Ara h 2/6, were associated with severe PA, and higher IgE to Ara h 8 with mild-to-moderate PA, addition of these measurements of sensitization to the clinical background model did not significantly improve the AUC. Conclusions: Models combining clinical characteristics and IgE sensitization patterns can help establish the risk of severe reactions for peanut allergic patients, but clinical background determinants are most valuable for predicting severity of probable PA in an individual patient.

Walnut Allergy Across Europe: Distribution of Allergen Sensitization Patterns and Prediction of Severity.

BACKGROUND: Walnut allergy is common across the globe, but data on the involvement of individual walnut components are scarce. OBJECTIVES: To identify geographical differences in walnut component sensitization across Europe, explore cosensitization and cross-reactivity, and assess associations of clinical and serological determinants with severity of walnut allergy. METHODS: As part of the EuroPrevall outpatient surveys in 12 European cities, standardized clinical evaluation was conducted in 531 individuals reporting symptoms to walnut, with sensitization to all known walnut components assessed in 202 subjects. Multivariable Lasso regression was applied to investigate predictors for walnut allergy severity. RESULTS: Birch-pollen-related walnut sensitization (Jug r 5) dominated in Northern and Central Europe and lipid transfer protein sensitization (Jug r 3) in Southern Europe. Profilin sensitization (Jug r 7) was prominent throughout Europe. Sensitization to storage proteins (Jug r 1, 2, 4, and 6) was detected in up to 10% of subjects. The walnut components that showed strong correlations with pollen and other foods differed between centers. The combination of determinants best predicting walnut allergy severity were symptoms upon skin contact with walnut, atopic dermatitis (ever), family history of atopic disease, mugwort pollen allergy, sensitization to cat or dog, positive skin prick test result to walnut, and IgE to Jug r 1, 5, 7, or carbohydrate determinants (area under the curve = 0.81; 95% CI, 0.73-0.89). CONCLUSIONS: Walnut-allergic subjects across Europe show clear geographical differences in walnut component sensitization and cosensitization patterns. A predictive model combining results from component-based serology testing with results from extract-based testing and information on clinical background allows for good discrimination between mild to moderate and severe walnut allergy.

Asthma severity according to Global Initiative for Asthma and its determinants: an international study.

BACKGROUND: The identification of the factors associated with severe asthma may shed some light on its etiology and on the mechanisms of its development. We aimed to describe asthma severity using the Global Initiative for Asthma (GINA) classification and to investigate its determinants in a cross-sectional, population-based sample in Europe. METHODS: In the European Community Respiratory Health Survey II (1999-2002), 1,241 adults with asthma were identified. Severity was assessed using the 2002 GINA classification (intermittent, mild persistent, moderate persistent, severe persistent) and it was related to potential determinants by a multinomial logistic model, using the intermittent group as the reference category for relative risk ratios. RESULTS: About 30% of asthmatic subjects were affected by moderate-to-severe asthma. Sensitization to Cladosporium was associated with a more than 5-fold greater risk of having (mild, moderate or severe) persistent asthma than intermittent asthma. Persistent asthma was positively associated with sensitization to house dust mite, nonseasonal asthma, an older age at asthma onset, and chronic cough and phlegm. Sensitization to cat increased the risk of severe asthma only. Smoking was more strongly associated with asthma severity in men, while rhinitis was more strongly associated with asthma severity in women. CONCLUSIONS: One third of the asthmatic population have moderate-to-severe asthma. Sensitization to perennial indoor allergens, particularly Cladosporium, is strongly associated with asthma severity. The role of smoking and rhinitis in determining asthma severity may differ between the sexes, and it should be further investigated.

Body mass index, weight gain, and other determinants of lung function decline in adult asthma.

BACKGROUND: Little is known about factors associated with lung function decline in asthma. OBJECTIVE: To identify the determinants of FEV(1) decline in adults with asthma with and without airflow obstruction at baseline. METHODS: An international cohort of 638 subjects with asthma (20-44 years old) was identified in the European Community Respiratory Health Survey (1991-1993) and followed up from 1998 to 2002. Spirometry was performed on both occasions. FEV(1) decline was related to potential determinants evaluated at baseline and during the follow-up by random intercept linear regression models. The analyses were stratified by the presence of airflow obstruction (FEV(1)/forced vital capacity < 0.70) at baseline. RESULTS: In the group of individuals without airflow obstruction (n = 544), a faster FEV(1) decline was observed for subjects with intermediate body mass index (BMI) than for lean and obese subjects. FEV(1) decline was associated with weight gain independently of baseline BMI, and this association was stronger in men (20; 95% CI, 10-30, mL/y/kg gained) than in women (6; 95% CI, 1-11, mL/y). In the group of individuals with airflow obstruction (n = 94), the absence of allergen sensitization and a low BMI at baseline were associated with a faster FEV(1) decline, whereas weight gain was not associated with decline. CONCLUSIONS: The detrimental effect of weight gain on FEV(1) decline is particularly relevant in subjects with asthma who still do not have an established airflow obstruction. Our findings support the importance of weight management in asthma and recommend weight loss in overweight or obese individuals with asthma.

Atopy Modifies the Association Between Inhaled Corticosteroid Use and Lung Function Decline in Patients with Asthma.

BACKGROUND: Inhaled corticosteroids (ICSs) are the mainstay of asthma treatment, but response to medication is variable. Patients with allergic inflammation generally show a better short-term response to ICSs; however, studies on predictors of long-term response are few. OBJECTIVE: To assess whether allergic sensitization can modify the association between ICS use and lung function decline over 20 years in adult asthma. METHODS: We used data from the 3 clinical examinations of the European Community Respiratory Health Survey. We measured ICS use (no use, and use for <1.3, 1.3-8, and >8 years) and FEV1 decline among subjects with asthma over the 2 periods between consecutive examinations. We conducted a cohort study combining data of the 2 periods (906 observations from 745 subjects) to assess whether the association between ICS use and FEV1 decline was modified by allergic sensitization (IgE > 0.35 kU/L for any of house-dust mite, timothy grass, cat, or Cladosporium). RESULTS: FEV1 decline was similar for non-ICS users, as well as ICS users for less than 1.3 years, with and without allergic sensitization. However, among subjects on ICSs for a longer period, sensitization was associated with an attenuated decline (Pinteraction = .006): in the group treated for more than 8 years, FEV1 decline was on average 27 mL/y (95% CIBonferroni-adjusted, 11-42) lower for subjects with sensitization compared with nonsensitized subjects. CONCLUSIONS: Our study suggests that biomarkers of atopy can predict a more favorable long-term response to ICSs. Randomized controlled studies are needed to confirm these findings.

Eighty-eight variants highlight the role of T cell regulation and airway remodeling in asthma pathogenesis.

Asthma is one of the most common chronic diseases affecting both children and adults. We report a genome-wide association meta-analysis of 69,189 cases and 702,199 controls from Iceland and UK biobank. We find 88 asthma risk variants at 56 loci, 19 previously unreported, and evaluate their effect on other asthma and allergic phenotypes. Of special interest are two low frequency variants associated with protection against asthma; a missense variant in TNFRSF8 and 3' UTR variant in TGFBR1. Functional studies show that the TNFRSF8 variant reduces TNFRSF8 expression both on cell surface and in soluble form, acting as loss of function. eQTL analysis suggests that the TGFBR1 variant acts through gain of function and together with an intronic variant in a downstream gene, SMAD3, points to defective TGFßR1 signaling as one of the biological perturbations increasing asthma risk. Our results increase the number of asthma variants and implicate genes with known role in T cell regulation, inflammation and airway remodeling in asthma pathogenesis.

The prevalence of plant food allergies: a systematic review.

BACKGROUND: There is uncertainty regarding the prevalence of allergies to plant food. OBJECTIVE: To assess the prevalence of allergies to plant food according to the different subjective and objective assessment methods. METHODS: Our systematic search of population-based studies (since 1990) in the literature database MEDLINE focused on fruits, vegetables/legumes, tree nuts, wheat, soy, cereals, and seeds. Prevalence estimates were categorized by food item and method used (food challenges, skin prick test, serum IgE, parent/self-reported symptoms), complemented by appropriate meta-analyses. RESULTS: We included 36 studies with data from a total of over 250,000 children and adults. Only 6 studies included food challenge tests with prevalences ranging from 0.1% to 4.3% each for fruits and tree nuts, 0.1% to 1.4% for vegetables, and < 1% each for wheat, soy, and sesame. The prevalence of sensitization against any specific plant food item assessed by skin prick test was usually < 1%, whereas sensitization assessed by IgE against wheat ranged as high as 3.6% and against soy as high as 2.9%. For fruit and vegetables, prevalences based on perception were generally higher than those based on sensitization, but for wheat and soy in adults, sensitization was higher. Meta-analyses showed significant heterogeneity between studies regardless of food item or age group. CONCLUSION: Population-based prevalence estimates for allergies to plant products determined by the diagnostic gold standard are scarce. There was considerable heterogeneity in the prevalence estimates of sensitization or perceived allergic reactions to plant food.

Reaction norm analysis reveals rapid shifts toward delayed maturation in harvested Lake Erie yellow perch (Perca flavescens).

Harvested marine fish stocks often show a rapid and substantial decline in the age and size at maturation. Such changes can arise from multiple processes including fisheries-induced evolution, phenotypic plasticity, and responses to environmental factors other than harvest. The relative importance of these processes could differ systematically between marine and freshwater systems. We tested for temporal shifts in the mean and within-cohort variability of age- and size-based maturation probabilities of female yellow perch (Perca flavescens Mitchill) from four management units (MUs) in Lake Erie. Lake Erie yellow perch have been commercially harvested for more than a century, and age and size at maturation have varied since sampling began in the 1980s. Our analysis compared probabilistic maturation reaction norms (PMRNs) for cohorts when abundance was lower and harvest higher (1993-1998) to cohorts when abundance was higher and harvest lower (2005-2010). PMRNs have been used in previous studies to detect signs of evolutionary change in response to harvest. Maturation size threshold increased between the early and late cohorts, and the increases were statistically significant for the youngest age in the western MU1 and for older ages in the eastern MU3. Maturation envelope widths, a measure of the variability in maturation among individuals in a cohort, also increased between early and late cohorts in the western MUs where harvest was highest. The highest rates of change in size at maturation for a given age were as large or larger than rates reported for harvested marine fishes where declines in age and size at maturation have been observed. Contrary to the general observation of earlier maturation evolving in harvested stocks, female yellow perch in Lake Erie may be rapidly evolving delayed maturation since harvest was relaxed in the late 1990s, providing a rare example of possible evolutionary recovery.

Pharmacological treatment of asthma in a cohort of adults during a 20-year period: results from the European Community Respiratory Health Survey I, II and III.

Asthma often remains uncontrolled, despite the fact that the pharmacological treatment has undergone large changes. We studied changes in the treatment of asthma over a 20-year period and identified factors associated with the regular use of inhaled corticosteroid (ICS) treatment. Changes in the use of medication were determined in 4617 randomly selected subjects, while changes in adults with persistent asthma were analysed in 369 participants. The study compares data from three surveys in 24 centres in 11 countries. The use of ICSs increased from 1.7% to 5.9% in the general population and the regular use of ICSs increased from 19% to 34% among persistent asthmatic subjects. The proportion of asthmatic subjects reporting asthma attacks in the last 12 months decreased, while the proportion that had seen a doctor in the last 12 months remained unchanged (42%). Subjects with asthma who had experienced attacks or had seen a doctor were more likely to use ICSs on a regular basis. Although ICS use has increased, only one-third of subjects with persistent asthma take ICSs on a regular basis. Less than half had seen a doctor during the last year. This indicates that underuse of ICSs and lack of regular healthcare contacts remains a problem in the management of asthma.

A loss-of-function variant in ALOX15 protects against nasal polyps and chronic rhinosinusitis.

Nasal polyps (NP) are lesions on the nasal and paranasal sinus mucosa and are a risk factor for chronic rhinosinusitis (CRS). We performed genome-wide association studies on NP and CRS in Iceland and the UK (using UK Biobank data) with 4,366 NP cases, 5,608 CRS cases, and >700,000 controls. We found 10 markers associated with NP and 2 with CRS. We also tested 210 markers reported to associate with eosinophil count, yielding 17 additional NP associations. Of the 27 NP signals, 7 associate with CRS and 13 with asthma. Most notably, a missense variant in ALOX15 that causes a p.Thr560Met alteration in arachidonate 15-lipoxygenase (15-LO) confers large genome-wide significant protection against NP (P = 8.0 × 10-27, odds ratio = 0.32; 95% confidence interval = 0.26, 0.39) and CRS (P = 1.1 × 10-8, odds ratio = 0.64; 95% confidence interval = 0.55, 0.75). p.Thr560Met, carried by around 1 in 20 Europeans, was previously shown to cause near total loss of 15-LO enzymatic activity. Our findings identify 15-LO as a potential target for therapeutic intervention in NP and CRS.

Asthma control in Europe: a real-world evaluation based on an international population-based study.

BACKGROUND: Epidemiologic evidence related to asthma control in patients from the general population is scanty. OBJECTIVES: We sought to assess asthma control in several European centers according to the Global Initiative for Asthma (GINA) guidelines and to investigate its determinants. METHODS: In the European Community Respiratory Health Survey II (1999-2002), 1241 adults with asthma were identified and classified into inhaled corticosteroid (ICS) users and non-ICS users in the last year. Control was assessed in both groups by using the GINA proposal (controlled, partly controlled, and uncontrolled asthma), and it was related to potential determinants. RESULTS: Only 15% (95% CI, 12% to 19%) of subjects who had used ICSs in the last year and 45% (95% CI, 41% to 50%) of non-ICS users had their asthma under control; individuals with uncontrolled asthma accounted for 49% (95% CI, 44% to 53%) and 18% (95% CI, 15% to 21%), respectively. Among ICS users, the prevalence of uncontrolled asthma showed great variability across Europe, ranging from 20% (95% CI, 7% to 41%; Iceland) to 67% (95% CI, 35% to 90%; Italy). Overweight status, chronic cough and phlegm, and sensitization to Cladosporium species were associated with poor control in ICS users. About 65% and 87% of ICS users with uncontrolled and partly controlled asthma, respectively, were on a medication regimen that was less than recommended by the GINA guidelines. CONCLUSION: Six of 7 European asthmatic adults using ICSs in the last year did not achieve good disease control. The large majority of subjects with poorly controlled asthma were using antiasthma drugs in a suboptimal way. A wide variability in asthma control emerged across Europe. CLINICAL IMPLICATIONS: Greater attention should be paid to asthma management and to the implementation of the GINA guidelines.