A survey of total IgE reference intervals reported by Scandinavian and British medical laboratories - a need for harmonisation.

OBJECTIVES: There appears to be marked discrepancies between total IgE reference intervals (RIs) in use by many laboratories and those recommended by published studies. The aim of this study was therefore to review total IgE RIs currently reported by Scandinavian and British laboratories and to compare these to published RIs identified by a literature review. METHODS: Relevant laboratories were identified by test directories provided by the national accreditation bodies in Norway, Sweden, Denmark and the UK. Total IgE RIs and their sources were acquired by accessing laboratory user handbooks or by an electronic survey. In addition a literature review of published total IgE RI studies was performed. RESULTS: From 172 accredited laboratories providing total IgE analysis, data was acquired from 122 laboratories. An adult upper reference limit between 81 to 150 kU/L was reported by 89% of these. Denmark and Sweden reported the most harmonised RIs whilst Norway and the UK exhibited the least degree of harmonisation. Published adult (n = 6) and paediatric (n = 6) RI studies reported markedly higher upper limits than those currently in use by the laboratories included in this study. There were also large variations in the number of age strata in use for paediatric RIs. CONCLUSION: This study demonstrates large variations in currently utilised IgE RIs by Scandinavian and British accredited laboratories and most report markedly lower RIs than those recommended by recent RI publications. Many laboratories likely utilise outdated RIs and should consider critically reviewing and updating their RIs.

A new pathway for penicillin delabeling in Norway.

Background: Penicillin allergy is self-reported by 3-10% of patients admitted to hospital. The label is wrong in 90% of the cases and has severe health implications. Penicillin-delabeling can reverse the negative effects of the label, and pathways adapted to local practice are needed. No tools are available in Norway for penicillin delabeling outside an allergy clinic. Objective: To create and validate the first penicillin delabeling pathway applicable outside an allergy clinic in Norway. Methods: An interdisciplinary taskforce created a penicillin allergy delabeling program (PAD) adapted to the Norwegian health care system. This was validated in a prospective, single-center study. Very low-risk and low-risk patients underwent a direct oral penicillin challenge and high-risk patients were referred for allergologic evaluation. Results: One-hundred forty-nine patients declaring penicillin allergy were included. Seventy-four (50%) were very-low- and low risk patients suitable for a direct oral penicillin challenge resulting in only 1 mild reaction. Sixty high-risk patients were eligible for an oral penicillin challenge after allergologic evaluation; 3 patients reacted non-severely. Conclusion: We have created and demonstrated feasibility of the first penicillin delabeling program (PAD) applicable in a hospital setting outside an allergy clinic in Norway. Our data suggest this is safe and beneficial, with 49% patients delabeled through a direct oral penicillin challenge, performed without any serious adverse events, and an overall 87% delabeling rate.

Ascaris exposure and its association with lung function, asthma, and DNA methylation in Northern Europe.

BACKGROUND: Ascaris infections, with a worldwide prevalence above 10%, can cause respiratory pathology. However, long-term effects on lung function in humans are largely unknown. OBJECTIVE: We investigated the associations of Ascaris exposure with lung function, asthma, and DNA methylation. METHODS: Serum Ascaris IgG antibodies were measured in 671 adults aged 18 to 47 years (46% women) from Aarhus, Bergen, and Tartu RHINESSA study centers. Seropositivity was defined as IgG above the 90th percentile. Linear and logistic regressions were used to analyze Ascaris seropositivity as associated with lung function and asthma, adjusted for age, height, and smoking and clustered by center. DNA methylation in blood was profiled by a commercial methylation assay. RESULTS: Ascaris seropositivity was associated with lower FEV1 (-247 mL; 95% CI, -460, -34) and higher odds for asthma (adjusted odds ratio, 5.84; 95% CI, 1.67, 20.37) among men but not women, also after further adjusting for house dust mite sensitivity, consistent across study centers. At a genome-wide level, Ascaris exposure was associated with 23 differentially methylated sites in men and 3 in women. We identified hypermethylation of the MYBPC1 gene, which can regulate airway muscle contraction. We also identified genes linked to asthma pathogenesis such as CRHR1 and GRK1, as well as a differentially methylated region in the PRSS22 gene linked to nematode infection. CONCLUSION: Ascaris exposure was associated with substantially lower lung function and increased asthma risk among men. Seropositive participants had sex-specific differences in DNA methylation compared to the unexposed, thus suggesting that exposure may lead to sex-specific epigenetic changes associated with lung pathology.

Iodine status in women attending Mnazi Mmoja Hospital in Zanzibar: a matched case-control study.

BACKGROUND: Iodine deficiency can have adverse health effects in all age groups affecting growth, development and cognitive functions as well as the incidence of goitre. Worldwide, the most important dietary source of iodine is iodised salt. In Tanzania, iodine intake has varied due to multiple salt suppliers producing iodised salt with varying quality. Zanzibar has faced challenges with the packing, storing and monitoring of salt iodisation, and universal salt iodisation has not been achieved. Furthermore, the number of available studies on the iodine status in Zanzibar are sparse. OBJECTIVE: The main objective of this study is to describe the iodine status of euthyroid female adult patients with and without goitre in Zanzibar. DESIGN AND METHODS: A single-centre matched case-control study was conducted among 48 female patients at the ear, nose and throat clinic of Mnazi Mmoja Hospital, Zanzibar. Blood samples were drawn for serum-analysis of the thyroid hormone profile to confirm that all patients were euthyroid prior to inclusion. Urinary iodine concentrations and the iodine concentration in household salt samples were analysed. A semiquantitative food frequency questionnaire (FFQ) was used to describe trends in the dietary intake of iodine-rich and goitrogenic foods. Clinical examinations were conducted, and the patients were categorised into goitre (cases) and non-goitre (controls) groups. RESULTS: A moderate iodine deficiency (median urinary iodine concentration between 20 and 49 µg/L) was found in patients both with and without goitre. In total, only 35 % of the salt samples were adequately iodised. The salt samples from the cases had a lower average concentration of iodine compared with the controls. The FFQ revealed that the daily consumption of marine fish and the weekly consumption of raw cassava were more frequent in the cases than the controls. CONCLUSION: These findings suggest that iodine deficiency may be a problem in both patients with and without goitre in Zanzibar. The salt iodisation programme may require monitoring and implementation of satisfactory quality control practices as universal salt iodisation is yet to be achieved in Zanzibar.

Idiopathic anaphylaxis. / Idiopatisk anafylaksi.

An acute increase in tryptase levels is a reliable indicator of mast cell activation. Here, we present a case in which acute measurement of tryptase revealed a rare and potentially serious condition. The report is a reminder of how a correct diagnosis can depend on performing the right test at the right time.

Nasal symptoms increase the risk of snoring and snoring increases the risk of nasal symptoms. A longitudinal population study.

PURPOSE: Humans have a preference for nasal breathing during sleep. This 10-year prospective study aimed to determine if nasal symptoms can predict snoring and also if snoring can predict development of nasal symptoms. The hypothesis proposed is that nasal symptoms affect the risk of snoring 10 years later, whereas snoring does not increase the risk of developing nasal symptoms. METHODS: In the cohort study, Respiratory Health in Northern Europe (RHINE), a random population from Denmark, Estonia, Iceland, Norway, and Sweden, born between 1945 and 1973, was investigated by postal questionnaires in 1999-2001 (RHINE II, baseline) and in 2010-2012 (RHINE III, follow-up). The study population consisted of the participants who had answered questions on nasal symptoms such as nasal obstruction, discharge, and sneezing, and also snoring both at baseline and at follow-up (n = 10,112). RESULTS: Nasal symptoms were frequent, reported by 48% of the entire population at baseline, with snoring reported by 24%. Nasal symptoms at baseline increased the risk of snoring at follow-up (adj. OR 1.38; 95% CI 1.22-1.58) after adjusting for age, sex, BMI change between baseline and follow-up, and smoking status. Snoring at baseline was associated with an increased risk of developing nasal symptoms at follow-up (adj. OR 1.22; 95% CI 1.02-1.47). CONCLUSION: Nasal symptoms are independent risk factors for development of snoring 10 years later, and surprisingly, snoring is a risk factor for the development of nasal symptoms.

Non-infectious rhinitis is more strongly associated with early-rather than late-onset of COPD: data from the European Community Respiratory Health Survey (ECRHS).

PURPOSE: Chronic obstructive pulmonary disease (COPD) is associated with several co-morbidities and non-infectious rhinitis (NIR) has emerged as a new possible co-morbidity. The primary aim of this study is to confirm a previously reported association between NIR and COPD in a multicentre population over time. The secondary aim is to investigate the course over time of such an association through a comparison between early- and late-onset COPD. METHODS: This study is part of the European Community Respiratory Health Survey (ECRHS). A random adult population from 25 centres in Europe and one in Australia was examined with spirometry and answered a respiratory questionnaire in 1998-2002 (ECRHS II) and in 2008-2013 (ECRHS III). Symptoms of non-infectious rhinitis, hay fever and asthma, and smoking habits were reported. Subjects reporting asthma were excluded. COPD was defined as a spirometry ratio of FEV1/FVC < 0.7. A total of 5901 subjects were included. RESULTS: Non-infectious rhinitis was significantly more prevalent in subjects with COPD compared with no COPD (48.9% vs 37.1%, p < 0.001) in ECRHS II (mean age 43) but not in ECHRS III (mean age 54). In the multivariable regression model adjusted for COPD, smoking, age, BMI, and gender, non-infectious rhinitis was associated with COPD in both ECRHS II and III. CONCLUSION: Non-infectious rhinitis was significantly more common in subjects with COPD at a mean age of 43. Ten years later, the association was weaker. The findings indicate that NIR could be associated with the early onset of COPD.

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.

Intraoperative anaphylaxis to gelatin-based hemostatic agents: a case report.

Surgiflo Haemostatic Matrix is an absorbable gelatin matrix hemostatic material that has been widely used in various surgical operations to assist hemostasis. Nonetheless, as biologically active agents (contains porcine gelatin), there is potential for allergic reactions to these products. Here, we report the case of a 71-year-old man who had intraoperative anaphylaxis with cardiovascular events to gelatin associated with the use of a topical hemostatic agent (Surgiflo). The patient reported a history of red meat allergy and tick bites during his allergological examination after anaphylaxis. He also had high levels of specific IgE antibodies towards alpha-gal. Special consideration should be given before administering bovine- or porcine-derived gelatin products during surgery to patients with animal-related allergies, such as alpha-gal or gelatin allergy and an atopic background.

Bakers' exposure to flour dust.

We aimed to characterize bakers' personal exposure to airborne flour dust with respect to the health-related aerosol fractions inhalable, extrathoracic, and thoracic dust, and to examine possible production-related determinants of dust exposure. Sixty-eight bakers from 7 bakeries in Bergen, Norway (2009-2012) participated in the exposure assessment, comprising full-shift personal samples of inhalable dust (n = 107) and thoracic dust (n = 61). The relation between possible determinants and exposure was estimated using mixed effects models, while associations between the various aerosol fractions across task groups and type of bakeries were described by Pearson's correlation coefficients. Bakers' overall geometric mean personal exposure to inhalable, extrathoracic, and thoracic dust were 2.6 mg/m3 (95% CI: 2.0, 3.2), 2.2 mg/m3 (95% CI: 1.9, 2.7), and 0.33 mg/m3 (95% CI 0.3, 0.4), respectively. A total of 29% of the measurements of inhalable dust were above the Norwegian Occupational Exposure Limit of 3 mg/m3. The exposure variability of inhalable dust could not be explained by any of the examined production-related determinants, while the daily production volume explained 18% of the variance in thoracic dust exposure. Overall, the thoracic dust represented 15% of the inhalable dust, being rather stable across the production-related determinants. The overall correlation between inhalable and thoracic dust was nevertheless moderate (r = 0.52, p < 0.001), with the highest correlation for craft bakers (r = 0.62) and no correlation during dough forming (r = 0.01). Bakers are exposed to flour dust at a level that most likely represents an excess risk of developing chronic diseases of the respiratory system, and a decrease of present exposure level is imperative. Extrathoracic dust-likely the most relevant sub-fraction in respect to flour-induced sensitization and occupational rhinitis-represented the main proportion of the measured inhalable dust. The variation in correlation coefficients between the dust fractions across bakery types and task groups underlines the need of more knowledge about how these aerosol fractions are distributed across the production process and bakery types.

Incidence of rhinitis and asthma related to welding in Northern Europe.

Welding-related asthma is well recognised but less is known about rhinitis in relation to welding. The aim here, was to study associations between welding, rhinitis and asthma in a general population sample, and factors influencing selection into and out of a welding occupation.Adult-onset asthma and non-infectious rhinitis were investigated in the international multicentre population-based Respiratory Health in Northern Europe (RHINE) study, including 16,191 responders aged 26-54 years. Ever welding (n=2181), welding >25% of working time (n=747), and welding in stainless steel >6 months (n=173) were assessed by questionnaire. Subjects with rhinitis or asthma onset when aged <18 years were excluded. Incidence rates for asthma and rhinitis were calculated from year of disease onset, and start and end of welding job. Cox's proportional hazard models adjusting for age, sex, parental education and study centre, and Kaplan-Meier curves were used.Rhinitis incidence was higher among welders (hazard ratio (HR) 1.4, 95% CI 1.3-1.6), consistent in men and women, and across centres (pheterogeneity=0.4). In men, asthma incidence was higher among welders (HR 1.4, 95% CI 1.04-1.97). Quitting welding was indicated higher after adult-onset rhinitis (HR 1.1, 95% CI 1.0-1.3). Adult-onset rhinitis and asthma was higher among welders, consistent across population samples from Northern Europe. No pre-employment selection was found, whereas selection out of welding jobs was suggested.

Predictors of respiratory sickness absence: an international population-based study.

BACKGROUND: Respiratory tract-related occupational disability is common among adults of working age. We examined occupational vapors, gas, dust, or fume (VGDF) exposure as a predictor of disability, based on respiratory sickness absence among the actively employed, at an early point at which prevention may be most relevant. METHODS: Currently employed European Community Respiratory Health Survey II participants (n = 6,988) were classified into three mutually exclusive, condition/symptom-based categories: physician-diagnosed asthma, self-reported rhinitis, and wheeze/breathlessness (n = 4,772). Logistic regression analysis estimated the odds of respiratory sickness absence (past 12 months) by VGDF exposure. RESULTS: In the condition/symptom groups, 327 (6.9%) reported respiratory sickness absence. Exposure to VGDF was associated with increased odds of respiratory sickness absence: asthma odds ratio [OR] 2.0 (95% confidence interval [CI] 1.1-3.6), wheeze/breathlessness OR 2.2 (95% CI 1.01-4.8); rhinitis OR 1.9 (95% CI 1.02-3.4). CONCLUSION: One in 15 currently employed with asthma, breathlessness, or rhinitis reported respiratory sickness absence. VGDF exposure doubled the odds of respiratory sickness absence, suggesting a focus for disability prevention.

Bronchial responsiveness in bakery workers: relation to airway symptoms, IgE sensitization, nasal indices of inflammation, flour dust exposure and smoking.

BACKGROUND: Bronchial hyperresponsiveness (BHR) is common in bakery workers. The relation between bronchial responsiveness measured with a tidal breathing method and smoking, airway symptoms, IgE-sensitization, nasal indices of inflammation and flour dust exposure have been studied with bronchial responsiveness expressed as a continuous outcome. MATERIAL AND METHODS: Bakery workers (n = 197) were subjected to interviews, questionnaires, allergy tests, workplace dust measurements and bronchial metacholine provocation. Eosinophil cationic protein (ECP) and alpha(2)-macroglobulin were measured in nasal lavage. Bronchial responsiveness was expressed as slope(conc), a measurement based on regressing the per cent reduction in FEV(1) at each provocation step. RESULTS: BHR expressed as slope(conc) was associated with smoking (P = 0.009), asthma symptoms at work (P = 0.001), and occupational IgE sensitization (P = 0.048). After adjusting for baseline lung function the association between BHR and IgE sensitization was no longer present. We demonstrated an association between nasal ECP and BHR (slope(conc) < 3: P = 0.012), but not to alpha(2)-macroglobulin in nasal lavage. No association was seen between BHR and current exposure level of flour dust, number of working years in a bakery or a history of dough-making. CONCLUSION: BHR is related to baseline lung function, work-related asthma symptoms, smoking and nasal eosinophil activity, but not to occupational IgE sensitization and current flour dust exposure when measured with metacholine provocation. The slope(conc) expression seems to be a useful continuous outcome in bronchial responsiveness testing.

Nasal indices of eosinophilic and exudative inflammation in bakery-workers.

AIMS: Rhinitis symptoms frequently occur in bakery-workers. Yet, little is known about the pathophysiology of this condition. The objective of the present study was to examine nasal indices of inflammation in relation to occupational dust exposure, occupational rhinitis according to defined criteria, rhinitis symptoms associated to the workplace, and occupational sensitization in bakery-workers. METHODS: Bakery-workers (n = 197) were subjected to interviews, questionnaires, workplace dust measurements, allergy tests, and nasal lavages with and without histamine. alpha(2)-Macroglobulin and eosinophil cationic protein (ECP) were measured in saline lavages as indices of plasma exudation and eosinophilic activity, respectively. Histamine lavages were employed to explore the nasal exudative responsiveness. RESULTS: alpha(2)-Macroglobulin and ECP increased significantly by increased workplace dust exposure (P< or =0.035). Furthermore, the exudative responsiveness to histamine increased significantly by such exposure (P< or =0.016). Similar patterns were seen in workers with occupational rhinitis and in subjects with rhinitis symptoms associated to the workplace, but not in workers with occupational sensitization. CONCLUSIONS: We conclude that occupational dust exposure in bakery-workers is associated with nasal eosinophilic exudative inflammation. In contrast, occupational sensitization is not a discriminating factor with regard to indices of eosinophilic, exudative inflammation in the present material.

Occupational rhinitis: diagnostic criteria, relation to lower airway symptoms and IgE sensitization in bakery workers.

CONCLUSIONS: The use of different diagnostic criteria has considerable consequences for the prevalence estimates of occupational rhinitis. There is a strong relationship between occupational rhinitis and lower airway symptoms. Storage mites appear to be important occupational allergens in Norwegian bakeries. OBJECTIVES: To study the consequences of various diagnostic criteria on the prevalence of occupational rhinitis, assess the prevalence of IgE sensitization and explore the relationships between upper and lower airway symptoms and between symptoms and IgE sensitization. MATERIAL AND METHODS: A total of 197 employees in 6 bakeries were interviewed and completed a questionnaire. A skin prick test was performed, total and specific IgE were determined and a histamine release test was performed for relevant allergens. The criteria for the diagnosis of occupational rhinitis were based on the 1994 International Consensus Report on Rhinitis. RESULTS: The prevalence of occupational rhinitis varied between 23% and 50%, depending on the criteria used. The occurrence of nasal symptoms was found to precede the development of lower airway symptoms. Occupational rhinitis, both IgE- and non-IgE-mediated, was associated with asthma symptoms. The most frequent causes of sensitization (20%) were different species of storage mites. Storage mite sensitization was related to occupational rhinitis and work exposure.