Impact of a 1-Year Pediatric Emergency Medicine Training Program for International Medical Graduates.

OBJECTIVES: The Hospital for Sick Children in Toronto has offered a 1-year subspecialty residency training program in pediatric emergency medicine (PEM) to Canadian and internationally trained pediatricians and emergency physicians since 1993. The program is intended to support clinical service delivery while simultaneously offering a unique educational opportunity to Canadian and international physicians who desire 1 year of clinically focused training. We describe the experiences and career outcomes of participants who completed this program. METHODS: Two surveys were sent to the 68 individuals who completed the clinical fellowship program from its inception in 1993 until 2014. A blinded survey focused on the fellowship experience and subsequent career activities. A nonblinded survey subsequently determined whether participants had served as a medical director or training program director. RESULTS: Sixty of the 68 participants (88%) completed the blinded survey. Ninety-one percent were in practice in emergency medicine. Twenty-five percent of the participants were living in Canada, compared with 17% before completing the program. This net migration of 8% was not significant (P = 0.26). Thirty-six of the 50 participants (72%) who applied from outside Canada responded to the nonanonymous survey; 18 (50%) had served as an emergency department medical director, and 18 (50%) reported serving as a PEM training program director. CONCLUSIONS: Many participants attained leadership positions in PEM in countries outside of North America and/or participated in training program development. There was no significant change in the proportion of participants living in North America at the time of application compared with the time of survey completion.

The oldest peracarid crustacean reveals a Late Devonian freshwater colonization by isopod relatives.

Peracarida (e.g. woodlice and side-swimmers) are, together with their sister-group Eucarida (e.g. krill and decapods), the most speciose group of modern crustaceans, suggested to have appeared as early as the Ordovician. While eucarids' incursion onto land consists of mainly freshwater and littoral grounds, some peracarids have evolved fully terrestrial ground-crawling ecologies, inhabiting even our gardens in temperate regions (e.g. pillbugs and sowbugs). Their fossil record extends back to the Carboniferous and consists mainly of marine occurrences. Here, we provide a complete re-analysis of a fossil arthropod-Oxyuropoda-reported in 1908 from the Late Devonian floodplains of Ireland, and left with unresolved systematic affinities despite a century of attempts at identification. Known from a single specimen preserved in two dimensions, we analysed its anatomy using digital microscopy and multispectral macroimaging to enhance the contrast of morphological structures. The new anatomical characters and completeness of Oxyuropoda, together with a phylogenetic analysis with representatives of all major Eumalacostraca groups, indicate that Oxyuropoda is a crown peracarid, part of a clade including amphipods and isopods. As such, Oxyuropoda is the oldest known species Peracarida, and provides evidence that derived peracarids had an incursion into freshwater and terrestrial environments as early as the Famennian, more than 360 Ma.

Post-mortem confirmation of fetal brain abnormalities: challenges highlighted by the MERIDIAN cohort study.

OBJECTIVES: To assess and analyse the concordance between post-mortem findings and in utero magnetic resonance imaging (iuMRI) in the MERIDIAN (MRI to enhance the diagnosis of fetal developmental brain abnormalities in utero) cohort. DESIGN: Prospective cohort study. SETTING: Fetal medicine units in the UK. POPULATION: Pregnant women with a diagnosis of fetal brain abnormality identified on ultrasound at 18 weeks of gestation or later. METHODS: All pregnancies from the MERIDIAN study that resulted in a abortion were included and the rate of uptake and success of post-mortem examinations were calculated. In the cases in which diagnostic information about the fetal brain was obtained by post-mortem, the results were compared with the diagnoses from iuMRI. MAIN OUTCOME MEASURE: Outcome reference diagnosis from post-mortem examination. RESULTS: A total of 155 from 823 pregnancies (19%) ended in a termination of pregnancy and 71 (46%) had post-mortem brain examinations, 62 of which were diagnostically adequate. Hence, the overall rate of successful post-mortem investigation was 40%, and for those cases there was a concordance rate of 84% between iuMRI and post-mortem examination. Detailed information is provided when the results of the post-mortem examination and the iuMRI study differed. CONCLUSIONS: We have shown tissue-validation of radiological diagnosis is hampered by a low rate of post-mortem studies in fetuses aborted with brain abnormalities, a situation further compounded by a 12% rate of autopsy being technically unsuccessful. The agreement between iuMRI and post-mortem findings is high, but our analysis of the discrepant cases provides valuable clues for improving how we provide information for parents. TWEETABLE ABSTRACT: iuMRI should be considered a reliable indicator of fetal brain abnormalities when post-mortem is not performed.

Analysis of 270 fetuses with non-visualization of cavum septi pellucidi and vergae on in-utero magnetic resonance imaging.

OBJECTIVE: To analyze a large retrospective cohort of fetuses in which the cavum septi pellucidi and vergae (CSPV) was not present or was not in its expected position on in-utero magnetic resonance imaging (iuMRI), in order to describe the possible causes of that finding and provide a diagnostic approach to assess such cases in clinical practice using iuMRI. METHODS: This was a retrospective study of fetuses that underwent iuMRI at a single institution, over an 18-year period (2000-2017 inclusive), in which the CSPV was not visualized or was abnormal. All iuMRI studies were reviewed and classified as CSPV being not present, disrupted (visualization of remnants of an otherwise normally placed CSPV) or malpositioned (CSPV was present, but not in its expected position). We describe the neuropathology present in each of the groups. RESULTS: Of the 270 fetuses that met the inclusion criteria, the CSPV was described as malpositioned in 150 (56%), disrupted in 71 (26%) and not present in 49 (18%). Malpositioned CSPV was present only in cases with agenesis of the corpus callosum and three specific patterns of malpositioning are described, depending on the location of the leaflets of the CSPV and fornix. Disrupted CSPV was present in fetuses with hydrocephalus or pathologies causing extensive brain parenchymal injury. Not present CSPV was found in cases with holoprosencephaly or when absence of the CSPV appeared to be an isolated finding. CONCLUSION: We have described a large cohort of fetuses with non-visualization of a normal CSPV on iuMRI and present a categorical classification system based on the CSPV being not present, disrupted or malpositioned. This approach should help in the diagnosis of the underlying cause of a CSPV abnormality. © 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

The rate of brain abnormalities on in utero MRI studies in fetuses with normal ultrasound examinations of the brain and calculation of indicators of diagnostic performance.

AIM: To estimate the rate of unexpected brain abnormalities detected by in utero magnetic resonance imaging (iuMRI) in fetuses without abnormalities at ultrasonography (USS). MATERIALS AND METHODS: A prospective cohort study of pregnant women whose fetus had no structural brain (or body) abnormalities recognised on antenatal ultrasonography. Women were recruited from 12 centres across the UK and underwent iuMRI at 18 gestational weeks or more in the [blinded for review]. The imaging studies were reviewed by an experienced neuroradiologist. The positive and negative predictive values of both USS and iuMRI have been calculated by combining the results of this study with the results from the main [blinded for review] study. RESULTS: One hundred and ninety-eight pregnant women were recruited and underwent iuMRI of 205 fetuses. Brain abnormalities were shown on iuMRI in two fetuses that were not recognised on USS (one case of a focal cortical abnormality and one case of mild ventriculomegaly). The negative predictive value for USS was 99.5% and 100% for iuMRI. CONCLUSIONS: To the authors' knowledge, this is the first study comparing USS and iuMRI in low-risk pregnancies. USS has a comparatively high rule-out for fetal brain abnormalities and should remain the screening tool of choice.

Editorial Commentary: Stump Sparing or Footprint Exposing? Management of the Tibial Remnant During Posterior Cruciate Ligament Reconstruction.

Surgical management of an isolated grade III posterior cruciate ligament tear has been enveloped in debate since the first reconstruction technique report was written by Hey Groves in 1919. With the evolution of arthroscopy, party lines have been drawn over tibial inlay versus transtibial techniques, as well as single- versus double-bundle techniques. More subtle controversy exists regarding autograft versus allograft, outside-in versus inside-out drilling, and treatment of the tibial footprint of the posterior cruciate ligament. New remnant-sparing techniques, using a trans-septal posterior portal, may augment biology, maintain better proprioception, and mitigate abrasive wear at the "killer turn." However, longer-term comparative studies will be necessary to determine the existence of any clinically significant improvement in outcome.

Is Acromioplasty Ever Indicated During Rotator Cuff Repair?

Based on data from a national healthcare insurance carrier in the United States between 2010 and 2012, orthopedic surgeons performed an acromioplasty procedure on 73 to 76% of their arthroscopic rotator cuff repairs. This has remained a prevalent arthroscopic adjunct despite the controversies disputing the role and etiology of external impingement on symptomatic rotator cuff disease. Within the past decade, several randomized studies have demonstrated negligible benefits with acromioplasty performed alongside rotator cuff repair, with no significant differences in either patient-reported outcome scores or retear rates). Conversely, other authors have suggested higher rates of reoperation with rotator cuff repair alone. Critical shoulder angle, an objective measure of lateral acromion extension and glenoid inclination that is considered a gauge of external impingement, has demonstrated an association with rotator cuff tears; Despite this, patient-reported outcomes do not consistently correlate with critical shoulder angle or other variants in acromial morphology after arthroscopic full-thickness rotator cuff repair. Evidenced-based data is currently lacking to support routine use of acromioplasty in all cases of rotator cuff repair. However, the current available studies do present design flaws, namely statistical underpowering, particularly in type III acromion morphology; inadequate short-term follow-up; lack of imaging data to assess cuff healing; and insensitive outcome measures to capture the theorized benefits of subacromial decompression. Additionally, several relevant merits of acromioplasty have been reported, including decreased abrasive wear with prominent type III acromial morphology, release of natural growth factors to improve rotator cuff healing, and improved visualization during rotator cuff repair. Further evaluation is needed to determine the correct indications for acromioplasty in the setting of cuff repair. Current data would indicate that acromioplasty can be used safely at the discretion of the operating surgeon based on preoperative and intraoperative findings.

Should we perform in utero MRI on a fetus at increased risk of a brain abnormality if ultrasonography is normal or shows non-specific findings?

There are a number of reasons why a pregnant woman might be considered to have an increased risk of carrying a fetus with a brain abnormality, but they fall broadly into two groups. First, there may be a relevant family history usually, but not always, when a fetus/child from a previous pregnancy has a developmental brain abnormality and a clinical geneticist judges that there is a risk of recurrence. Second, there may be findings in their current pregnancy that increases the risk of the fetus either having a developmental brain abnormality or accruing acquired brain pathology. Antenatal ultrasonography remains the mainstay of fetal screening and anomaly scanning, but there is now persuasive evidence that in utero magnetic resonance imaging should have an important supporting role. This is important, as more accurate and more certain diagnoses are central to providing parents with accurate information about the likely clinical outcome. In pregnancies at increased risk of brain abnormalities, it is also important to provide the best quality information that the fetal brain is normal to provide reassurance to parents. In this paper, we review the proposition that in utero magnetic resonance imaging should be used in pregnancies at increased risk of brain abnormalities, even if the consultant-led ultrasound examination is normal or showed non-specific findings only.

Microbial characteristics in homes of asthmatic and non-asthmatic adults in the ECRHS cohort.

Microbial exposures in homes of asthmatic adults have been rarely investigated; specificities and implications for respiratory health are not well understood. The objectives of this study were to investigate associations of microbial levels with asthma status, asthma symptoms, bronchial hyperresponsiveness (BHR), and atopy. Mattress dust samples of 199 asthmatics and 198 control subjects from 7 European countries participating in the European Community Respiratory Health Survey II study were analyzed for fungal and bacterial cell wall components and individual taxa. We observed trends for protective associations of higher levels of mostly bacterial markers. Increased levels of muramic acid, a cell wall component predominant in Gram-positive bacteria, tended to be inversely associated with asthma (OR's for different quartiles: II 0.71 [0.39-1.30], III 0.44 [0.23-0.82], and IV 0.60 [0.31-1.18] P for trend .07) and with asthma score (P for trend .06) and with atopy (P for trend .02). These associations were more pronounced in northern Europe. This study among adults across Europe supports a potential protective effect of Gram-positive bacteria in mattress dust and points out that this may be more pronounced in areas where microbial exposure levels are generally lower.

Single-molecule sequencing and Hi-C-based proximity-guided assembly of amaranth (Amaranthus hypochondriacus) chromosomes provide insights into genome evolution.

BACKGROUND: Amaranth (Amaranthus hypochondriacus) was a food staple among the ancient civilizations of Central and South America that has recently received increased attention due to the high nutritional value of the seeds, with the potential to help alleviate malnutrition and food security concerns, particularly in arid and semiarid regions of the developing world. Here, we present a reference-quality assembly of the amaranth genome which will assist the agronomic development of the species. RESULTS: Utilizing single-molecule, real-time sequencing (Pacific Biosciences) and chromatin interaction mapping (Hi-C) to close assembly gaps and scaffold contigs, respectively, we improved our previously reported Illumina-based assembly to produce a chromosome-scale assembly with a scaffold N50 of 24.4 Mb. The 16 largest scaffolds contain 98% of the assembly and likely represent the haploid chromosomes (n = 16). To demonstrate the accuracy and utility of this approach, we produced physical and genetic maps and identified candidate genes for the betalain pigmentation pathway. The chromosome-scale assembly facilitated a genome-wide syntenic comparison of amaranth with other Amaranthaceae species, revealing chromosome loss and fusion events in amaranth that explain the reduction from the ancestral haploid chromosome number (n = 18) for a tetraploid member of the Amaranthaceae. CONCLUSIONS: The assembly method reported here minimizes cost by relying primarily on short-read technology and is one of the first reported uses of in vivo Hi-C for assembly of a plant genome. Our analyses implicate chromosome loss and fusion as major evolutionary events in the 2n = 32 amaranths and clearly establish the homoeologous relationship among most of the subgenome chromosomes, which will facilitate future investigations of intragenomic changes that occurred post polyploidization.

The effects of growing up on a farm on adult lung function and allergic phenotypes: an international population-based study.

RATIONALE: Evidence has suggested that exposure to environmental or microbial biodiversity in early life may impact subsequent lung function and allergic disease risk. OBJECTIVES: To investigate the influence of childhood living environment and biodiversity indicators on atopy, asthma and lung function in adulthood. METHODS AND MEASUREMENTS: The European Community Respiratory Health Survey II investigated ∼10 201 participants aged 26-54 years from 14 countries, including participants' place of upbringing (farm, rural environment or inner city) before age 5 years. A 'biodiversity score' was created based on childhood exposure to cats, dogs, day care, bedroom sharing and older siblings. Associations with lung function, bronchial hyper-responsiveness (BHR), allergic sensitisation, asthma and rhinitis were analysed. MAIN RESULTS: As compared with a city upbringing, those with early-life farm exposure had less atopic sensitisation (adjusted OR 0.46, 95% CI 0.37 to 0.58), atopic BHR (0.54 (0.35 to 0.83)), atopic asthma (0.47 (0.28 to 0.81)) and atopic rhinitis (0.43 (0.32 to 0.57)), but not non-atopic outcomes. Less pronounced protective effects were observed for rural environment exposures. Women with a farm upbringing had higher FEV1 (adjusted difference 110 mL (64 to 157)), independent of sensitisation and asthma. In an inner city environment, a higher biodiversity score was related to less allergic sensitisation. CONCLUSIONS: This is the first study to report beneficial effects of growing up on a farm on adult FEV1. Our study confirmed the beneficial effects of early farm life on sensitisation, asthma and rhinitis, and found a similar association for BHR. In persons with an urban upbringing, a higher biodiversity score predicted less allergic sensitisation, but to a lesser magnitude than a childhood farm environment.

Clinical markers of asthma and IgE assessed in parents before conception predict asthma and hayfever in the offspring.

BACKGROUND: Mice models suggest epigenetic inheritance induced by parental allergic disease activity. However, we know little of how parental disease activity before conception influences offspring's asthma and allergy in humans. OBJECTIVE: We aimed to assess the associations of parental asthma severity, bronchial hyperresponsiveness (BHR), and total and specific IgEs, measured before conception vs. after birth, with offspring asthma and hayfever. METHODS: The study included 4293 participants (mean age 34, 47% men) from the European Community Respiratory Health Survey (ECRHS) with information on asthma symptom severity, BHR, total and specific IgEs from 1991 to 1993, and data on 9100 offspring born 1972-2012. Adjusted relative risk ratios (aRRR) for associations of parental clinical outcome with offspring allergic disease were estimated with multinomial logistic regressions. RESULTS: Offspring asthma with hayfever was more strongly associated with parental BHR and specific IgE measured before conception than after birth [BHR: aRRR = 2.96 (95% CI: 1.92, 4.57) and 1.40 (1.03, 1.91), respectively; specific IgEs: 3.08 (2.13, 4.45) and 1.83 (1.45, 2.31), respectively]. This was confirmed in a sensitivity analysis of a subgroup of offspring aged 11-22 years with information on parental disease activity both before and after birth. CONCLUSION & CLINICAL RELEVANCE: Parental BHR and specific IgE were associated with offspring asthma and hayfever, with the strongest associations observed with clinical assessment before conception as compared to after birth of the child. If the hypothesis is confirmed in other studies, parental disease activity assessed before conception may prove useful for identifying children at risk for developing asthma with hayfever.

PTTG1IP and MAML3, novel genomewide association study genes for severity of hyperresponsiveness in adult asthma.

BACKGROUND: The severity of bronchial hyperresponsiveness (BHR) is a fundamental feature of asthma. The severity of BHR varies between asthmatics and is associated with lack of asthma control. The mechanisms underlying this trait are still unclear. This study aimed to identify genes associated with BHR severity, using a genomewide association study (GWAS) on the slope of BHR in adult asthmatics. METHODS: We performed a GWAS on BHR severity in adult asthmatics from the Dutch Asthma GWAS cohort (n = 650), adjusting for smoking and inhaled corticosteroid use, and verified results in three other cohorts. Furthermore, we performed eQTL and co-expression analyses in lung tissue. RESULTS: In the discovery cohort, one genomewide significant hit located in phosphodiesterase 4D, cAMP-specif (PDE4D) and 26 SNPs with P-values < 1*10-5 were found. None of our findings replicated in adult and childhood replication cohorts jointly. In adult cohorts separately, rs1344110 in pituitary tumour-transforming 1 interacting protein (PTTG1IP) and rs345983 in Mastermind-like 3 (MAML3) replicated nominally; minor alleles of rs345983 and rs1344110 were associated with less severe BHR and higher lung tissue gene expression. PTTG1IP showed significant co-expression with pituitary tumour-transforming 1, the binding factor of PTTG1lP, and with vimentin and E-cadherin1. MAML3 co-expressed significantly with Mastermind-like 2 (MAML2), both involved in Notch signalling. CONCLUSIONS: PTTG1IP and MAML3 are associated with BHR severity in adult asthma. The relevance of these genes is supported by the eQTL analyses and co-expression of PTTG1lP with vimentin and E-cadherin1, and MAML3 with MAML2.

The assessment of fetal brain growth in diabetic pregnancy using in utero magnetic resonance imaging.

AIM: To assess fetal brain growth over the third trimester in pregnant women with diabetes using in utero magnetic resonance imaging (iuMRI) to determine if greater brain growth occurs in type 1 (T1DM) when compared to gestational (GDM) diabetes mellitus. MATERIALS AND METHODS: Each consented participant was scanned at three fixed times during the third trimester using iuMRI. One hundred and fifty-seven patients were approached, 48 participants were recruited, and 36 complete data sets were analysed. Three-dimensional (3D) iuMRI volume data sets were manually segmented using software to construct models of the fetal brain from which brain volumes could be calculated. Inter-rater analysis was performed, and volume differences and growth rates were compared between T1DM and GDM. RESULTS: Recruitment proved difficult with low uptake and high attrition rates (77.1%). Inter-rater analysis revealed excellent correlation (intraclass correlation coefficient=0.93, p<0.001) and agreement with no significant difference between operators (p=0.194). There was no evidence of increased brain volume in the T1DM group. Growth rates between visit 1 and 3 for T1DM and GDM were not significantly different (p=0.095). CONCLUSION: T1DM brain volumes were not significantly larger than GDM volumes and there was no significant divergence of brain growth over the third trimester. Constructing volume models from 3D iuMRI acquisitions is a novel technique that can be used to assess fetal brain growth. No specialist software or knowledge is required. Larger studies attempting to recruit pregnant women in the later stages of pregnancy should employ multicentre recruitment to overcome recruitment difficulties and high attrition rates.

Change in diagnostic confidence brought about by using in utero MRI for fetal structural brain pathology: analysis of the MERIDIAN cohort.

AIM: To measure possible change in diagnostic confidence by performing in utero magnetic resonance imaging (iuMRI) studies on fetuses with brain abnormalities recognised on ultrasonography (US). MATERIALS AND METHODS: The analyses are based on the primary cohort from the prospective MERIDIAN study, which consisted of 570 fetuses with brain abnormalities detected on US, with iuMRI performed within 2 weeks of US and complete outcome reference data. The cohort was recruited between July 2011 and August 2014, and written informed consent was obtained for all participants. They all had indicators of diagnostic confidence measured on US by fetal medicine experts and iuMRI by the reporting radiologists. Three assessments were carried out using the conventional uncorrected (C2-C1%) method, the conventional (C2-C1%) with the Omary correction, and the score-based weighted average method. RESULTS: All three assessments showed statistically significant (p<0·0001) positive effects indicating that iuMRI was potentially beneficial when included in the diagnostic pathway for prenatal structural brain anomalies (in terms of diagnostic confidence). CONCLUSION: These results strongly support the routine clinical use of iuMRI as an adjunct to US when assessing fetuses with structural brain abnormalities.

Building dampness and mold in European homes in relation to climate, building characteristics and socio-economic status: The European Community Respiratory Health Survey ECRHS II.

We studied dampness and mold in homes in relation to climate, building characteristics and socio-economic status (SES) across Europe, for 7127 homes in 22 centers. A subsample of 3118 homes was inspected. Multilevel analysis was applied, including age, gender, center, SES, climate, and building factors. Self-reported water damage (10%), damp spots (21%), and mold (16%) in past year were similar as observed data (19% dampness and 14% mold). Ambient temperature was associated with self-reported water damage (OR=1.63 per 10°C; 95% CI 1.02-2.63), damp spots (OR=2.95; 95% CI 1.98-4.39), and mold (OR=2.28; 95% CI 1.04-4.67). Precipitation was associated with water damage (OR=1.12 per 100 mm; 95% CI 1.02-1.23) and damp spots (OR=1.11; 95% CI 1.02-1.20). Ambient relative air humidity was not associated with indoor dampness and mold. Older buildings had more dampness and mold (P<.001). Manual workers reported less water damage (OR=0.69; 95% CI 0.53-0.89) but more mold (OR=1.27; 95% CI 1.03-1.55) as compared to managerial/professional workers. There were correlations between reported and observed data at center level (Spearman rho 0.61 for dampness and 0.73 for mold). In conclusion, high ambient temperature and precipitation and high building age can be risk factors for dampness and mold in homes in Europe.

The risk of respiratory symptoms on allergen exposure increases with increasing specific IgE levels.

BACKGROUND: The relation between IgE sensitization and allergic respiratory symptoms has usually been evaluated by dichotomizing specific IgE levels. The aim of this study was to evaluate the association between specific IgE levels and risk of symptoms on allergen-related exposure, with special reference to allergen-related asthma-rhinitis comorbidity. METHODS: We considered 6391 subjects enrolled within the European Community Respiratory Health Survey 2, having information on cat/grass/D. pteronyssinus IgE levels and symptoms on exposure to animals/pollen/dust. The risk of oculonasal/asthmalike/both symptoms was evaluated by a multinomial logistic model. RESULTS: A clear positive association was observed between specific IgE levels to cat/grass/mite and the risk of symptoms on each allergen-related exposure (test for trend with P < 0.001). This trend was particularly pronounced when considering the coexistence of asthmalike and oculonasal symptoms. Compared to non-sensitized subjects, subjects with specific IgE to cat >= 3.5 kU/l presented relative risk ratios of 11.4 (95% CI 6.7-19.2), 18.8 (8.2-42.8), and 55.3 (30.5-100.2) when considering, respectively, only oculonasal symptoms, only asthmalike symptoms, or both. A similar pattern was observed when considering specific IgE to grass/mite and symptoms on exposure to pollen/dust. Also the proportion of people using inhaled medicines or visiting a general practitioner for breathing problems in the previous year increased with increasing sum of specific IgE to cat/grass/mite. CONCLUSION: Specific IgE level is the most important predictor of allergen-related symptoms. The risk of both oculonasal/asthmalike symptoms increases with specific IgE levels, suggesting that specific IgE contributes to the 'united airways disease'.

Respiratory hypersensitivity reactions to NSAIDs in Europe: the global allergy and asthma network (GA2 LEN) survey.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most prevalent drugs inducing hypersensitivity reactions. The aim of this analysis was to estimate the prevalence of NSAID-induced respiratory symptoms in population across Europe and to assess its association with upper and lower respiratory tract disorders. METHODS: The GA2 LEN survey was conducted in 22 centers in 15 European countries. Each of 19 centers selected random samples of 5000 adults aged 15-74 from their general population, and in three centers (Athens, Munich, Oslo), a younger population was sampled. Questionnaires including questions about age, gender, presence of symptoms of asthma, allergic rhinitis, chronic rhinosinusitis, smoking status, and history of NSAID-induced hypersensitivity reactions were sent to participants by mail. Totally, 62 737 participants completed the questionnaires. RESULTS: The mean prevalence of NSAID-induced dyspnea was 1.9% and was highest in the three Polish centers [Katowice (4.9%), Krakow (4.8%), and Lodz (4.4%)] and lowest in Skopje, (0.9%), Amsterdam (1.1%), and Umea (1.2%). In multivariate analysis, the prevalence of respiratory reactions to NSAIDs was higher in participants with chronic rhinosinusitis symptoms (Odds Ratio 2.12; 95%CI 1.78-2.74), asthma symptoms in last 12 months (2.7; 2.18-3.35), hospitalization due to asthma (1.53; 1.22-1.99), and adults vs children (1.53; 1.24-1.89), but was not associated with allergic rhinitis. CONCLUSION: Our study documented significant variation between European countries in the prevalence of NSAID-induced respiratory hypersensitivity reactions, and association with chronic airway diseases, but also with environmental factors.

The locus C11orf30 increases susceptibility to poly-sensitization.

A number of genetic variants have been associated with allergic sensitization, but whether these are allergen specific or increase susceptibility to poly-sensitization is unknown. Using data from the large multicentre population-based European Community Respiratory Health Survey, we assessed the association between 10 loci and specific IgE and skin prick tests to individual allergens and poly-sensitization. We found that the 10 loci associate with sensitization to different allergens in a nonspecific manner and that one in particular, C11orf30-rs2155219, doubles the risk of poly-sensitization (specific IgE/4 allergens: OR = 1.81, 95% CI 0.80-4.24; skin prick test/4+ allergens: OR = 2.27, 95% CI 1.34-3.95). The association of rs2155219 with higher levels of expression of C11orf30, which may be involved in transcription repression of interferon-stimulated genes, and its association with sensitization to multiple allergens suggest that this locus is highly relevant for atopy.

House dust-mite allergen exposure is associated with serum specific IgE but not with respiratory outcomes.

Exposure to house dust has been associated with asthma in adults, and this is commonly interpreted as a direct immunologic response to dust-mite allergens in those who are IgE sensitized to house dust-mite. Mattress house dust-mite concentrations were measured in a population-based sample of 2890 adults aged between 27 and 56 years living in 22 centers in 10 countries. Generalized linear mixed models were employed to explore the association of respiratory symptoms with house dust-mite concentrations, adjusting for individual and household confounders. There was no overall association of respiratory outcomes with measured house dust-mite concentrations, even in those who reported they had symptoms on exposure to dust and those who had physician-diagnosed asthma. However, there was a positive association of high serum specific IgE levels to HDM (>3.5 kUA /l) with mattress house dust-mite concentrations and a negative association of sensitization to cat with increasing house dust-mite concentrations. In conclusion, there was no evidence that respiratory symptoms in adults were associated with exposure to house dust-mite allergen in the mattress, but an association of house mite with strong sensitization was observed.