Birch pollen allergy in Europe.

Birch and other related trees of the families Betulaceae and Fagaceae (alder, hazel, oak, hornbeam, chestnut, and beech) constitute the birch homologous group. This grouping is primarily based on the extensive IgE cross-reactivity of allergen homologs to the major birch allergen Bet v 1. Birch pollen is the most dominant tree pollen in Northern and Central Europe and is a major cause of allergic rhinitis and, possibly, asthma symptoms. Over the last few decades, levels of birch pollen have risen and the period of exposure has increased due to climate changes. Subsequently, the prevalence of birch pollen sensitization has also increased. The cross-reactivity and sequential pollen seasons within the birch homologous group create a prolonged symptomatic allergy period beyond birch pollen alone. Furthermore, many plant food allergens contain homologs to Bet v 1, meaning that the majority of patients with birch pollen allergy suffer from secondary pollen food syndrome (PFS). As a result, the negative impact on health-related quality of life (HRQoL) in patients allergic to birch pollen is significant. The purpose of this manuscript was to narratively review topics of interest such as taxonomy, cross-reactivity, prevalence, clinical relevance, PFS, and HRQoL with regard to birch pollen allergy from a European perspective.

Optimizing diagnostic tests for persulphate-induced respiratory diseases.

BACKGROUND: Persulphates from hair bleaching products are considered the major cause of occupational-rhinitis and asthma in hairdressers. The specific inhalation challenge (SIC) is considered 'reference standard' for diagnosing persulphate-induced asthma and rhinitis; however, the currently validated method of performing SIC with persulphate powder is time consuming with a duration of up to 4 days. The value of skin prick tests (SPTs) and histamine release tests (HRTs) with persulphates is unknown. The aim of this study was to establish a novel rapid SIC with persulphate powder to test for both rhinitis and asthma simultaneously in 1 day. In addition, we assessed the suitability of SPTs and HRTs for detecting persulphate-induced respiratory diseases. METHODS: The study population included 19 hairdressers with a history of work-related rhinitis and/or asthma symptoms, 12 symptomatic controls (10 with concurrent allergic asthma and rhinitis and two with non-allergic asthma), and 40 healthy controls. A previous severe asthmatic reaction and/or anaphylactic reaction to persulphates was considered an exclusion criterion for hairdressers. The 19 hairdressers and 12 symptomatic controls had SIC performed with 3 × 5 min exposures to potassium persulphate powder in a provocation chamber. All participants, including the 40 healthy controls, were subjected also to SPTs and HRTs with three persulphate salts at concentrations of 2-20 % and 0.03-1 %, respectively. RESULTS: None of the symptomatic controls had a nasal or bronchial response to SIC with potassium persulphate. Six hairdressers presented a nasal and two a bronchial response. No severe reactions occurred. No positive SPTs were recorded, neither among hairdressers, symptomatic controls, nor healthy controls. All three groups showed nonspecific non-IgE mediated histamine release to persulphates in HRT. CONCLUSIONS: The proposed method for performing SIC showed a high specificity for detecting persulphate-induced asthma and rhinitis. The rapid SIC was able to produce positive nasal and bronchial responses in symptomatic hairdressers without any severe reactions occurring. SPTs and HRTs cannot predict asthma or rhinitis caused by persulphates.

Inconsistencies in clinical guidelines for obstetric anaesthesia for Caesarean section: a comparison of the Danish, English, American, and German guidelines with regard to developmental quality and guideline content.

BACKGROUND: Anaesthetists need evidence-based clinical guidelines, also in obstetric anaesthesia. We compared the Danish, English, American, and German national guidelines for anaesthesia for Caesarean section. We focused on assessing the quality of guideline development and evaluation of the guidelines' content. METHODS: We compared the four countries' guideline developmental quality by using the Appraisal of Guidelines for Research and Evaluation (AGREE) instrument, an international tool for development and assessment of guidelines. The clinically important content of these countries' guidelines was compared. RESULTS: We found differences in the quality of guideline development in the four countries. The German guidelines scored very low in the AGREE analysis, and the Danish national guideline scored low in the AGREE analysis. The American and British guideline both achieved high scores in the AGREE analysis. We found differences in the content of the four countries' guidelines. The Danish, American, and British guidelines were comprehensive but with some variation in the content. CONCLUSION: Development of national guidelines might benefit from following standardised regulations, such as those used in the AGREE tool. Content of guidelines is not standardised. Recommendations for the content of guidelines might contribute to standardising clinical guidelines.

Antimicrobial disposition in pulmonary epithelial lining fluid of horses. Part I. Sulfadiazine and trimethoprim.

Sulfadiazine (SDZ) and trimethoprim (TMP) concentrations were examined in plasma and pulmonary epithelial lining fluid (PELF), following intravenous and oral administration and compared to minimum inhibitory concentrations (MICs) of common bacterial isolates from equine lower airway infections. SDZ/TMP (25/5 mg/kg) was administered intravenously, intragastric or per os to fed horses, and blood samples were collected before and 11 times, over 24 h, after administration. PELF samples were collected via a tampon device four times after drug administration and analysed for drug concentrations. Additionally, MICs of SDZ and TMP alone and in combination were determined in a selection of clinical respiratory isolates. Bioavailability was 74% for SDZ and 46% for TMP after paste administration in fed horses. The degree of penetration of SDZ and TMP into PELF, as described by AUC(PELF) /AUC(plasma) ratios, was 0.68 and 0.72, respectively, after intravenous administration. After oral administration, the degree of penetration for SDZ and TMP was 0.92 and 0.46, respectively. MIC measurements using SDZ/TMP ratios of 5:1 and 10:1 did not affect the interpretation of the results. The results indicate that clinically relevant drug concentrations of mainly TMP are difficult to maintain in PELF, especially after oral administration of SDZ/TMP.

Antimicrobial disposition in pulmonary epithelial lining fluid of horses, part II. Doxycycline.

Doxycycline concentrations, following two types of oral administration to horses, in pulmonary epithelial lining fluid (PELF) were examined and compared to plasma concentrations. The oral bioavailability was estimated from plasma concentrations achieved after an intravenous study in two horses. Doxycycline (10 mg/kg) was administered either intragastric or as topdressing to nonfasted horses. Blood samples were collected for drug analysis, before and 11 times after administration during 24 h. PELF samples were collected by a tampon device four times after drug administration and analysed for doxycycline concentrations. Another two horses received doxycycline intravenously at a dose of 3 mg/kg and plasma was taken 14 times during a 24- h period. The oral bioavailability of doxycycline was calculated to 17% after intragastric administration and 6% after topdressing administration in nonfasted horses. The degree of penetration of doxycycline into PELF, as described by AUC(PELF) /AUC(plasma) ratios, was 0.87 after intragastric administration. The results indicate that clinically relevant doxycycline concentrations are possible to maintain in PELF after intragastric administration. Furthermore, if bioavailability could be enhanced for per os administration, doxycycline might be a valuable drug for the treatment of lower airway infections in horses.

Antimicrobial disposition in pulmonary epithelial lining fluid of horses, part III. cefquinome.

Cefquinome concentrations, following intravenous and aerosol administration to horses, in pulmonary epithelial lining fluid (PELF) were examined and compared to plasma concentrations. Single dose of cefquinome sulphate (1 mg/kg) was administered intravenously to six horses followed by a single aerosol administration (225 mg) with a wash-out period of 14 days between treatments. After each drug administration, cefquinome concentrations in plasma and PELF, obtained by intrabronchial cotton swabs, were determined. After intravenous administration, cefquinome concentrations in plasma declined fast and were not detectable after 12 h. After aerosol administration, plasma concentrations were low or below limit of quantification (LOQ) during the entire sampling period. The degree of penetration of cefquinome into PELF after intravenous administration as described by the AUC(PELF) /AUC(plasma) ratio was 0.33. Following aerosol administration, cefquinome concentrations in PELF were high, but only detectable for 4 h. Based on AUC values, total cefquinome concentrations in PELF were one-third of total plasma concentrations after intravenous administration together with shorter time above Minimum Inhibitory Concentrations (T > MIC) in PELF, thus twice daily dosing may be required when treating lower airway infections in horses. Lower doses of cefquinome can be administered as aerosols providing high local drug concentrations in lung, but additional optimization of formulation is needed to improve distribution and persistence in lung.

Side-effects of allergen-specific immunotherapy: a prospective multi-centre study.

BACKGROUND AND OBJECTIVE: The safety of allergen-specific immunotherapy (SIT) is a parameter of great interest in the overall assessment of the treatment. A clinical database was developed in order to obtain early warnings of changes in the frequency and severity of side-effects and sufficient data for the evaluation of possible risk factors. METHODS: During a 3-year period, four allergy centres in Copenhagen, Denmark, included data from all patients initiating SIT to a common database. Information on initial allergic symptoms, allergens used for treatment, treatment regimens and systemic side-effects (SSEs) during the build-up phase was collected. RESULTS: A total of 1,038 patients received treatment with 1,709 allergens (timothy, birch, mugwort, house dust mite (HDM), cat, and wasp and bee venom), 23,047 injections in total. Most SIT patients completed the updosing phase without side-effects, but there was a significant difference between allergens: wasp (89%), birch (82%), HDM (81%), cat (74%) and grass (70%) (P=0.004). A total of 582 SSEs were registered in 341 patients. Most side-effects were mild grade 2 reactions (78%). A difference in severity between allergens was observed (P=0.02), with grass giving most problems. The type of allergen but not patient- or centre-related parameters seemed predictive of side-effects. CONCLUSIONS: Allergen extracts differ in their tendency to produce side-effects. Multi-centre studies like the present one allow more patients to be evaluated, and thereby provide a more efficient surveillance of side-effects. Online Internet-based registration to a central national database of every allergen injection would be an even more powerful tool for evaluation of risk factors and surveillance of side-effects.

Allergen-specific immunotherapy in birch- and grass-pollen-allergic rhinitis. II. Side-effects.

BACKGROUND: Allergen-specific immunotherapy (IT) involves the risk of side-effects. Different side-effect profiles have been reported for different allergens, and it would be of great benefit to be able more precisely to predict patient- and allergen-related risk factors. METHODS: Fifty-two patients with rhinoconjunctivitis and allergy to birch as well as grass pollen participated in a 3-year IT study, with a baseline year followed by 2 years of treatment. During the first treatment year, the patients received double-blinded IT with either birch (Betula verrucosa) or grass (Phleum pratense) pollen extracts adsorbed to aluminum hydroxide. The following year, the other allergen extract was added. Assessment of systemic reactions (SRs) was performed, and related to patient pretreatment parameters such as seasonal symptoms and medication requirement, skin prick test (SPT), conjunctival provocation test (CPT), nasal provocation test (NPT), total and specific IgE, basophil histamine release (HR), eosinophil count (EOS), eosinophil cationic protein (ECP), and eosinophil protein X (EPX). RESULTS: In total, 44 and 47 patients started IT with birch- and grass-pollen extracts, respectively. All SRs occurred during the dose-increase phase. No life-threatening SRs were observed. There were a higher number of patients with SRs during IT with grass pollen than IT with birch pollen, 21 vs five patients (P<0.001), with SRs to 3.3% of grass-pollen injections compared to 0.7% of birch-pollen injections (P<0.0001). The SRs of birch-pollen IT were mild, consisting of rhinoconjunctivitis and oral-pharyngeal itching, whereas asthma and urticaria episodes were observed in the grass-pollen IT. No difference was found in sensitivity to birch and grass, when measured by SPT, CPT, NPT, specific IgE, or HR, and no difference was found in age, duration of allergic symptoms, prevalence of asthma, mean seasonal birch/grass symptom score, eye-drop use, or antihistamine or prednisolone intake between the group with and without subsequent SRs to IT. No difference was found in EOS, serum ECP, or EPX, between the group with and without subsequent SRs to IT. CONCLUSIONS: IT with grass-pollen extract seems to be associated with a higher number and more severe SRs than birch-pollen IT. Neither demographic data nor diagnostic tests of allergy such as specific IgE, HR, SPT, CPT, and NPT could identify the patients with subsequent SRs.

Allergen-specific immunotherapy in birch- and grass-pollen-allergic rhinitis. I. Efficacy estimated by a model reducing the bias of annual differences in pollen counts.

BACKGROUND: Evaluation of the efficacy of allergen-specific immunotherapy (IT) with pollen extracts is complicated by annual variation in pollen intensity. Our study aimed to evaluate the efficacy of birch and grass IT, taking into consideration these variations. METHODS: After 1 year of observation, 52 patients with rhinoconjunctivitis and allergy to birch as well as grass pollen were allocated to double-blinded clustered IT with aluminum-adsorbed extract produced from either birch (Betula verrucosa) pollen or grass (PIleum pratense) pollen. After 1 year of treatment, the patients continued IT with their original extract and also received the other extract. During the three consecutive pollen seasons, the rhinoconjunctivitis symptom score and the use of antihistamines, eye-drops, and oral prednisolone were recorded. Longitudinal data analysis was used to investigate the relation between different pollen counts and the magnitude of clinical efficacy. RESULTS: An effect of IT was found on symptom score, antihistamine intake, and eye-drop use for both birch and grass (P values <0.05). The mean reduction in symptom score/medication by IT ranged from 24% to 95%, depending on mean seasonal pollen counts. A minimum mean seasonal grass-pollen count of 20-30 pollen grains m3 was required for the efficacy of grass IT to emerge. CONCLUSIONS: A model was developed for evaluation of efficacy in longitudinal IT studies, taking the differences in annual pollen counts into consideration. The model showed a significant beneficial role of pollen IT in rhinoconjunctivitis patients allergic to birch and grass pollen.

Effects of lamotrigine on behavioral and cardiovascular responses to cocaine in human subjects.

We evaluated the effects of acute pretreatment with lamotrigine, a putative glutamate release inhibitor, on the physiological and behavioral responses to intranasal cocaine in cocaine-dependent volunteers (N = 8). The study employed a double-blind, placebo-controlled, within-subject design. Subjects participated in six experimental sessions. On each study day, placebo, lamotrigine 125 mg, or lamotrigine 250 mg was administered orally in the morning, followed 2 hours later by intranasal cocaine 120 mg/70 kg or placebo. Measurements of heart rate and blood pressure were acquired, and subjects responded to mood state questionnaires at predetermined time intervals. Cocaine alone produced increases in heart rate, blood pressure, and several measures of pleasurable mood and drug effects. Lamotrigine alone produced a mild relaxing effect. Lamotrigine pretreatment altered neither the physiological responses nor the subjective ratings of cocaine's pleasurable or aversive mood effects.

Basophil histamine release, IgE, eosinophil counts, ECP, and EPX are related to the severity of symptoms in seasonal allergic rhinitis.

BACKGROUND: Serum specific IgE, basophil histamine release, and blood eosinophil parameters are associated with allergic rhinitis, but investigations of the relationship to the severity of allergic symptoms are few and conflicting. Our study aimed to investigate the seasonal changes in the following laboratory tests: specific IgE, basophil histamine release, eosinophil counts, and serum and plasma eosinophil cationic protein (ECP) and eosinophil protein X (EPX), and to analyze, in detail, the relationship of each individual test to the severity of symptoms in rhinitis patients allergic to both birch and grass pollen. METHODS: The above tests were performed on blood samples obtained from 49 allergic rhinitis patients during the birch-pollen season, during the grass-pollen season, and after the seasons. Symptom-medication diaries were filled in during both pollen seasons. We used partial least square (PLS) analysis to establish an optimal statistical link between the symptom score and medication and the laboratory tests, in an investigator-independent way. RESULTS: Increases in specific IgE, basophil histamine release, eosinophil counts, serum ECP and EPX, and plasma EPX were observed from the birch-pollen season to the grass-pollen season, followed by a decrease from the grass-pollen season to after the pollen seasons, except for the specific IgE. No seasonal changes in plasma ECP and total IgE were seen. The PLS analysis found a relationship between symptom score and medication and the aggregate laboratory tests (F-test value 40.2, correlation 0.34 for the cumulative relation). However, the variation in laboratory tests could explain only half of the total variation in symptoms and less than a quarter of the total variation in medication. The symptom score and, to a minor degree, medication were especially correlated with the basophil histamine-release results, with a decreasing relevance of specific IgE, eosinophil counts, total IgE, serum and plasma EPX, and serum ECP. Plasma ECP was not related to the symptom score and medication. CONCLUSIONS: A significant relationship between the severity of allergic rhinitis and various allergic inflammatory markers was found but could account for only a minor part of the variation in the patients' evaluation of their disease.