Hereditary angioedema (HAE) due to C1-INH deficiency is a rare orphan disease characterised by spontaneous attacks of oedema that interrupt the “normal” attack-free state. HAE is known to impact patient quality of life (QoL) and productivity but, despite a recent increase in treatment options, there remains a shortage of data to quantify these important aspects of the HAE disease. Sweha-Reg, a population based census of HAE in Sweden, implemented a retrospective patient survey to address this data gap and define the burden of HAE in Sweden. A retrospective registry study of Swedish patients with HAE (captured by the Sweha-Reg census). Data was collected using a paper-based survey. Patients completed EQ5D-5L questionnaires for attack-free and acute HAE attack states. To be included in the analysis, patients must have suffered an attack in the last 12 months. Questions related to patient demographics (age and sex) and other parameters (such as attack location and severity) were included to better understand the burden of HAE. EQ5D-5L values were estimated for both HAE disease states and then compared with other variables; utilities were also calculated. Patient-reported sick-leave was analysed to understand the factors responsible for productivity loss in patients with HAE. A total of 105 valid responses were analysed from an initial mailing of 139 surveys (76% response rate). 94% of patients reported an attack in the last 12 months. The total number of attacks reported per patient during one year ranged from 1 to 120. A significant reduction in QoL scores between the attack-free and acute attack states of HAE was observed. Also, attack location and severity had a clear impact on the utility values. Results from this Sweha-Reg study provide an insight to the significant impact on QoL and productivity loss that HAE has on patients in Sweden.

BACKGROUNDHereditary angioedema is characterized by recurrent attacks of angioedema of the skin, larynx, and gastrointestinal tract. Bradykinin is the key mediator of symptoms. Icatibant is a selective bradykinin B2 receptor antagonist.METHODSIn two double-blind, randomized, multicenter trials, we evaluated the effect of icatibant in patients with hereditary angioedema presenting with cutaneous or abdominal attacks. In the For Angioedema Subcutaneous Treatment (FAST) 1 trial, patients received either icatibant or placebo; in FAST-2, patients received either icatibant or oral tranexamic acid, at a dose of 3 g daily for 2 days. Icatibant was given once, subcutaneously, at a dose of 30 mg. The primary end point was the median time to clinically significant relief of symptoms.RESULTSA total of 56 and 74 patients underwent randomization in the FAST-1 and FAST-2 trials, respectively. The primary end point was reached in 2.5 hours with icatibant versus 4.6 hours with placebo in the FAST-1 trial (P=0.14) and in 2.0 hours with icatibant versus 12.0 hours with tranexamic acid in the FAST-2 trial (P<0.001). In the FAST-1 study, 3 recipients of icatibant and 13 recipients of placebo needed treatment with rescue medication. The median time to first improvement of symptoms, as assessed by patients and by investigators, was significantly shorter with icatibant in both trials. No icatibant-related serious adverse events were reported.CONCLUSIONSIn patients with hereditary angioedema having acute attacks, we found a significant benefit of icatibant as compared with tranexamic acid in one trial and a nonsignificant benefit of icatibant as compared with placebo in the other trial with regard to the primary end point. The early use of rescue medication may have obscured the benefit of icatibant in the placebo trial. (Funded by Jerini; ClinicalTrials.gov numbers, NCT00097695 and NCT00500656.)

Chromist algae (stramenopiles, cryptophytes, and haptophytes) are major contributors to marine primary productivity. These eukaryotes acquired their plastid via secondary endosymbiosis, whereby an early-diverging red alga was engulfed by a protist and the plastid was retained and its associated nuclear-encoded genes were transferred to the host genome. Current data suggest, however, that chromists are paraphyletic; therefore, it remains unclear whether their plastids trace back to a single secondary endosymbiosis or, alternatively, this organelle has resulted from multiple independent events in the different chromist lineages. Both scenarios, however, predict that plastid-targeted, nucleus-encoded chromist proteins should be most closely related to their red algal homologs. Here we analyzed the biosynthetic pathway of carotenoids that are essential components of all photosynthetic eukaryotes and find a mosaic evolutionary origin of these enzymes in chromists. Surprisingly, about one-third (5/16) of the proteins are most closely related to green algal homologs with three branching within or sister to the early-diverging Prasinophyceae. This phylogenetic association is corroborated by shared diagnostic indels and the syntenic arrangement of a specific gene pair involved in the photoprotective xanthophyll cycle. The combined data suggest that the prasinophyte genes may have been acquired before the ancient split of stramenopiles, haptophytes, cryptophytes, and putatively also dinoflagellates. The latter point is supported by the observed monophyly of alveolates and stramenopiles in most molecular trees. One possible explanation for our results is that the green genes are remnants of a cryptic endosymbiosis that occurred early in chromalveolate evolution; that is, prior to the postulated split of stramenopiles, alveolates, haptophytes, and cryptophytes. The subsequent red algal capture would have led to the loss or replacement of most green genes via intracellular gene transfer from the new endosymbiont. We argue that the prasinophyte genes were retained because they enhance photosynthetic performance in chromalveolates, thus extending the niches available to these organisms. The alternate explanation of green gene origin via serial endosymbiotic or horizontal gene transfers is also plausible, but the latter would require the independent origins of the same five genes in some or all the different chromalveolate lineages.

Background: Asthma patients exhibit an increased rate of loss of lung function. Determinants to such decline are largely unknown and the modifying effect of steroid therapy is disputed. This cross-sectional study aimed to elucidate factors contributing to such decline and the possible modifying effect of steroid treatment.Methods: We analyzed determinants of lung function and airway hyperresponsiveness (AHR) in a Scandinavian study of 2390 subjects from 550 families. Families were selected for the presence of two or more asthmatic children as part of a genetic study, Scandinavian Asthma Genetic Study (SAGA).Results: The primary analysis studied the association between the lung function and delay of inhaled corticosteroids (ICS) after asthma diagnosis among asthmatic children and young adults with a history of regular ICS treatment (N = 919). FEV1 percent predicted (FEV1% pred) was 0.25% lower per year of delay from diagnosis until treatment (p = 0.039). This association was significantly greater in allergy skin prick test negative children. There was no significant influence of gender, age at asthma onset, or smoking. In secondary analysis of the whole population of 2390 asthmatics and non-asthmatics, FEV1% pred was inversely related to having asthmatic siblings (-7.9%; p<0.0001), asthma diagnosis (-2.7%; p = 0.0007), smoking (-3.5%; p = 0.0027), and positive allergy skin prick test (-0.47% per test; p = 0.012), white positively related to being of female gender (1.8%; p = 0.0029). Risk of AHR was higher by having asthmatic siblings (OR 2.7; p<0.0001), being of female gender (OR 2.0; p<0.0001), and having asthma (OR 2.0; P<0.0001).Conclusions: These data suggest that Lung function is lower in asthmatics with delayed introduction of ICS therapy, smoking, and positive allergy skin prick test. Lung function is Lower and AHR higher in female asthmatics and subjects with asthmatic siblings or established asthma. (C) 2007 Elsevier Ltd. All rights reserved.

BACKGROUND:The importance of acquiring comprehensive epidemiological and clinical data on hereditary angioedema has increasingly caught the attention of physicians and scientists around the world. The development of networks and creation of comprehensive policies to improve care of people suffering from rare diseases, such as hereditary angioedema, is a stated top priority of the European Union. Hereditary angioedema is a rare disease, that it may be life-threatening. Although the exact prevalence is unknown, current estimates suggest that it is 1/10,000-1/150,000 individuals. The low prevalence requires combined efforts to gain accurate epidemiological data on the disease and so give us tools to reduce morbidity and mortality, and improve quality of life of sufferers.METHODS:Sweha-Reg is a population-based registry of hereditary angioedema in Sweden with the objectives of providing epidemiological data, and so creates a framework for the study of this disease. The registry contains individual-based data on diagnoses, treatments and outcomes.CONCLUSION:The present manuscript seeks to raise awareness of the existence of Sweha-Reg to stimulate the international collaboration of registries. A synthesis of data from similar registries across several countries is required to approach an inclusive course understanding of HAE.

Background: The majority of Swedish birch pollen (BP)-allergic patients report hypersensitivity to some fruits, nuts and vegetables. Some BP-allergic patients complain ‘I can’t tolerate any fruit’. The main aim of the present study was to answer the question, ‘can BP-allergic patients tolerate some of the exotic fruit, not at present common in Sweden?’ Methods: Consecutive patients ( n  = 397) visiting the participating Allergy Clinics, who had a BP allergy and reported a food hypersensitivity, were asked to fill out questionnaires regarding 66 different fruits and vegetables. Subjects had three alternatives as an answer to each of the food questions: (i) ‘I tolerate it’; (ii) ‘I get symptoms from it’; or (iii) ‘I have not tried this food’. Skin prick tests were performed with pollen allergens. Results: Most patients had experienced reactions to several foods; only 31 patients (8%) reported hypersensitivity to one food only. Some of the fruit had been tried by only a few patients. In addition to earlier well-known BP-related foods, more than 40% of patients who had knowingly eaten Japanese pear and pomegranate said that they had experienced symptoms after eating the fruit. Most patients tolerated pineapple, melon, grapes and citrus fruits, as well as zucchini, lychee, rambutan, mangosteen, ugli, melon pear and cherimoya. Conclusions: Although an allergy to fruit is common among BP-allergic patients, there are several widely available fruits that most patient s tolerate; for instance, pineapple, melon, grapes and citrus fruit. Furthermore, there are many exotic fruits that most patients have not yet tried.

It has been shown that bronchial hyperreactivity in asthmatics specifically allergic to birch pollen is stable during the preseasonal and postseasonal periods and increases during the birch pollen season. Between January and March 1989, warm weather in the southern part of Sweden led to an early emission of hazel and alder pollens. Fourteen asthmatic patients living there were followed and demonstrated an increased nonspecific bronchial hyperreactivity (decreased PC20 methacholine) before the birch pollen season due to a 'priming effect' of related tree pollens.

Challenge tests were performed in patients with food intolerance and allergic rhinitis to evaluate the usefulness of measurement of the eosinophil cationic protein (ECP) of serum to distinguish different allergic reactions. In one group of patients with food intolerance symptom‐induced challenge resulted in a marked decrease of serum‐ECP. The number of blood eosinophils decreased simultaneously in some but not all of these patients. In another group of patients with food intolerance serum‐ECP displayed peak‐like increases followed by a decrease. The decrease in serum‐ECP may reflect that consumption of ECP is a result of idiosyncrasy in the target organ. In allergic rhinitis some patients showed an initial peak–like increase of serum–ECP, which was abolished by pretreatment with disodiumcromoglycate but not by pretreatment with antihistamine. Similar results have previously been demonstrated for allergic asthma. The difference obtained in serum‐ECP upon challenge in typical reagin‐mediated allergy and food intolerance may indicate that the latter is not reagin‐mediated. However, the interpretation of data is difficult because of lack of knowledge regarding the turnover in the circulation of ECP.