Self-reported adverse reactions to subcutaneous airborne allergen immunotherapy: a real-life, single center study.

Summary: Background. To estimate the prevalence of self-reported adverse reactions (AdR) to subcutaneous airborne allergen immunotherapy (SCIT) and to describe factors associated with its occurrence. Methods. Real-life, observational, descriptive study of all patients treated with SCIT at a Portuguese allergy unit between 03/2017 and 06/2019, and who answered ≥ 1 time to a pre-SCIT evaluation questionnaire assessing the occurrence of local and/or systemic AdR in the previous administration. Results. 939 questionnaires from 231 patients (42% female, 35% with asthma) were included. Most (60%) SCIT preparations had multiple allergens with concentration adjusted to prevent dilution (MA-NoDil), 26% were single allergen with standard concentration (SA-SC), 10% single allergen with higher than standard concentration (SA-HC), and 4% mixtures without concentration adjustment (MA-Dil). SCIT-related AdR were self-reported in 313 (33%) administrations, 97% at the injection site and 11% grade 1 systemic symptoms. In a multivariable model, being a female and having asthma were associated with higher risk of AdR. MA-NoDil SCIT presented a lower risk of AdR compared to SA-SC SCIT. Conclusions. SCIT-related AdR were self-reported in 1/3 of the administrations, most at the injection site. The risk of AdR was higher in females and in patients with asthma. The lower risk of adverse reactions observed in SCIT preparations with multiple allergens with no dilutional effect should be further explored in future, targeted studies.

Mutations analysis of C1 inhibitor coding sequence gene among Portuguese patients with hereditary angioedema.

Mutations that modify the amino acid sequence of C1-INH (except Val458Met) are associated with HAE. More than 200 different mutations scattering the entire C1-INH gene have been reported. The main objective of this study was to report the mutational findings in a HAE cohort of 138 Portuguese patients followed in specialized consultation all over the country. DNA was extracted from peripheral blood with QiaSymphony BioRobot (QIAGEN Portugal). The sequence reactions were performed by using a DNA sequencing kit (Big Dye terminator cycle sequencing v1.1/v3.1 from Applied Biosystems) and sequencing products were immediately submitted to direct sequencing on an Applied Biosystem 3130 DNA Analyser. DNA sequences were analyzed at four different stages. Raw data and sequence alignments of all 8 exons and intron-exon boundaries were performed for each patient individually with SeqScape software and using SERPING1 gene NG_009625 of 24,300 bp (12-March-2011) as reference sequence. Sequence comparisons among patients and controls were performed with software CodonCode Aligner v.3.7 from CodonCode Corp and with Geneious 4.5 from Biomatters Lda. A total of 94 point mutations were observed among patients, and 67% of them were located on exon 8. In addition, we noticed one not described stop codon at position c.1459 C>T in three different patients. Translation termination was also found on exon 3 and 7, as a result of mutations at positions c.481A>7, c.1174C>T. In this population, the prevalence of the missense mutation p.Arg444Cys was 39 out of 42. Mutational analysis revealed 22 different pathogenic mutations, of which 64% were not described on HAE database. Although identification of disease causing mutations is not necessary to establish HAE diagnosis, studies on gene expression and characterization of rearrangements in SERPING1 gene are suggested in order to get new insights on function and genetic tests of C1 inhibitor.

Clinical efficacy of web-based versus standard asthma self-management.

BACKGROUND: Guided self-management is an important component of asthma care. Most trials have evaluated paper-based strategies. The effectiveness of new communication technologies remains uncertain. OBJECTIVES: To compare the feasibility and clinical outcomes of a standard paper-based asthma self-management strategy with web-based strategies. METHODS: In a crossover trial, 21 patients using inhaled corticosteroids and long-acting B2-agonists (mean [SD] age 29 [10] years) were randomly assigned to use a sequence of web-based and paper-based diary and action plan. Quality of life, asthma control, lung function, and airway inflammation were assessed using the Asthma Life Quality Questionnaire (ALQ), Asthma Control Questionnaire (ACQ-5), Mini Asthma Quality of Life Questionnaire (Mini AQLQ), and office spirometry. The ratio of forced expiratory volume in the first second of expiration (FEV1) to peak expiratory flow (PEF) rate (PiKo-1) and fraction of exhaled nitric oxide (FE(NO)) were monitored. The main clinical outcomes were asthma control and FE(NO). Quality of data and adherence to monitoring tools were the main process outcomes. RESULTS: Significant improvements were observed in the AQL and ACQ scores, although lung function did not change. FE(NO) was significantly reduced only after a web-based strategy but a significant period effect occurred (P = .006). There were no differences in clinical outcomes between web-based and paper-based management. No intervention-related adverse effects were observed. Adherence seemed higher with the paper-based strategy (P < .001). However, paper data were unreliable when compared to automatic daily electronic FEV1/PEF records. Twelve patients were very interested in continuing self-management with the web-based approach compared with 2 in using paper tools (P = .002). CONCLUSIONS: Web-based management was feasible, safe, and preferred by patients. Short-term outcomes were at least as good, and data quality was improved.

Use of a common food frequency questionnaire (FFQ) to assess dietary patterns and their relation to allergy and asthma in Europe: pilot study of the GA2LEN FFQ.

BACKGROUND/OBJECTIVES: Comparable international data on food and nutrient intake is often hindered by the lack of a common instrument to assess food intake. The objective of this study was within the Global Allergy and Asthma European Network of Excellence (GA(2)LEN), we developed and piloted a food frequency questionnaire (FFQ) to assess its validity in Europe. SUBJECTS/METHODS: Five countries participating in GA(2)LEN took part in the pilot study. A total of 200 adults aged 31-75 years were invited to complete a FFQ in two occasions and to give a blood sample. The intra-class correlation coefficient (ICC) was used to assess repeatability of the FFQ. Plasma phospholipid fatty acids (FAs) were analysed by gas chromatography. Pearson correlation was used to analyse the correlation between estimated dietary FA intake and plasma phospholipid FA levels. RESULTS: A total of 177 participants (89%) had complete data on FFQ(1) and plasma phospholipid FAs. In all, 152 participants (76%) completed both FFQs. ICCs between macronutrients ranged from 0.70 (saturated FAs) to 0.78 (proteins) and between 0.70 (retinol) and 0.81 (vitamin D) for micronutrients. Dietary n-3 FAs showed a good correlation with total plasma phospholipid n-3 FAs and with docosahexaenoic acid in the whole sample (0.40) and in individual countries. Poor correlations were observed for other FAs. CONCLUSIONS: The GA(2)LEN FFQ is an appropriate tool to estimate dietary intake for a range of nutrients across Europe regardless of cultural and linguistic differences. The FFQ seems to be useful to estimate the intake of n-3 FAs but not other FAs.

Prevalence of aeroallergen sensitization and increased exhaled nitric oxide values in schoolchildren of different socioeconomic status.

BACKGROUND: Screening for allergic diseases allows an early diagnosis to be made, thus reducing socioeconomic burden and enhancing quality of life. We determined the prevalence of elevated exhaled nitric oxide (eNO) levels and sensitization to common airborne allergens in schoolchildren from different socioeconomic backgrounds. MATERIAL AND METHODS: The study population comprised 271 children (136 boys) aged between 8 and 12 years in whom we applied skin prick tests and determined eNO levels. RESULTS: Thirty-five percent of the children were identified as atopic. There was a significantly higher prevalence of atopy in boys (43% vs. 27%). Among the children with a high socioeconomic status, 37% were atopic, compared with 30% of those with a low socioeconomic status. We observed a significantly lower prevalence of pollen sensitization in children of lower socioeconomic status (10% vs. 20%). In the atopic group, 51% had elevated eNO levels, while in the nonatopic group this value was 4%. The mean (SD) eNO level was 33.4 (26.6) ppb in the atopic group and 11.9 (6.4) ppb in the nonatopic group. No differences were found for eNO values in terms of gender or socioeconomic status. CONCLUSIONS: Our results emphasize the high prevalence of atopy in our population and suggest that determination of eNO levels could help to provide an early diagnosis. We also observed the following: (a) a significant difference in mean eNO values between atopic and nonatopic children; (b) a significantly lower prevalence of pollen sensitization in children of lower socioeconomic status; and (c) a higher prevalence of atopy in boys.

Outdoor allergenic fungal spores: comparison between an urban and a rural area in northern Portugal.

BACKGROUND: The frequency and concentration of many airborne fungal spores associated with respiratory allergy symptoms are influenced by geographical and climatic characteristics. OBJECTIVE: The aim of this work was to monitor the distribution of 11 potentially allergenic fungal spore types in 2 regions with different urbanization levels in Northern Portugal: Porto (urban area) and Amares (rural area). METHODS: Airborne fungal spore levels were monitored from 2005 to 2007 using Hirst-type spore traps. The Spearman correlation test was used to analyze the influence of meteorological factors (temperature, relative humidity, and rainfall) on spore concentration. Meteorological data from both areas were compared using the t test, and spore concentrations were compared using the sign test. RESULTS: In both areas, Cladosporium, Agaricus, Aspergillus/Penincillium, Altemaria, Coprinus, and rusts were the most abundant fungal types observed. Most of the analyzed spore types presented maximum values during the summer months, with the exception of Polythrincium, Stemphylium, and Torula, which reached a peak earlier in the year, whereas Aspergillus/Penicillium and Botrytis showed a wider distribution. Temperature had a positive effect on most spore concentrations, and relative humidity and rainfall negatively influenced concentrations ofAlternaia, Cladosporium, Epicoccum, and Torula. CONCLUSIONS: The concentration of all selected spore types was higher in the rural than in the urban area, with higher values registe summer and autumn and lower values found during winter and spring. rainfall, influence airborne concentrations of major allergenic fungal spores.

Immediate hypersensitivity to penicillins with negative skin tests--the value of specific IgE.

The determination of specific IgE in patients with history of penicillins hypersensitivity is simple, safe and widely available. The positive and negative predictive values of this determination, however, are not yet established. In order to evaluate them, we performed specific IgE determination and diagnostic drug challenges in a group of 22 patients with a clear history of immediate penicillins hypersensitivity but negative skin tests. In this sample, the positive and negative predictive values were 29% and 87%, respectively. This seems to indicate that a positive specific IgE is not enough to confirm the diagnosis, and further study is necessary.

Work up of patients with history of beta-lactam hypersensitivity.

INTRODUCTION: Beta-lactam antibiotics are the most frequent cause of antibiotic hypersensitivity reactions. The study of all cases of suspected beta-lactam hypersensitivity is highly important, to avoid the use of less efficient or more expensive alternatives, for fear of a reaction. MATERIALS AND METHODS: Sixty-seven consecutive patients with suspected beta-lactam hypersensitivity reactions were studied. Skin prick tests (SPT), intradermal tests (IDT) and specific IgE determination were performed. In non-immediate reactions, epicutaneous testing was also done. If all were negative, a drug challenge was performed. RESULTS: Sixty-seven patients (54 female symbol), with a mean age + or - SD of 36.6 + or -19.3 years (4-78 years) were studied. The self-reported antibiotics were amoxicillin and amoxicillin/clavulanic acid in 30 (45%), penicillin in 24 (36%), cephalosporins in 11 (16%) and flucloxacillin in 2 (3%). SPT and IDT were positive in 6 patients (9%) and specific IgE in 11 (16%). Only one patient had both positive specific IgE and skin tests. Of the remaining 51 cases, 33 underwent a drug challenge with the culprit antibiotic, with a positive reaction in 2 (6%). In all positive cases and when a drug challenge with the suspected antibiotic was not indicated, a challenge with an alternative drug was done, all with negative results. CONCLUSIONS: Of the 67 studied cases with history of beta-lactam hypersensitivity reactions, 18 (27%) were confirmed after testing. A combination of skin testing, specific IgE determination and drug challenge is necessary since none has sufficient sensitivity to be used alone.

Work up of patients with history of beta-lactam hypersensitivity

Introduction: Beta-lactam antibiotics are the most frequent cause of antibiotic hypersensitivity reactions. The study of all cases of suspected beta-lactam hypersensitivity is highly important, to avoid the use of less efficient or more expensive alternatives, for fear of a reaction. Materials and methods: Sixty-seven consecutive patients with suspected beta-lactam hypersensitivity reactions were studied. Skin prick tests (SPT), intradermal tests (IDT) and specific IgE determination were performed. In non-immediate reactions, epicutaneous testing was also done. If all were negative, a drug challenge was performed. Results: Sixty-seven patients (54 women), with a mean age ± SD of 36.6 ± 19.3 years (4–78 years) were studied. The self-reported antibiotics were amoxicillin and amoxicillin/clavulanic acid in 30 (45%), penicillin in 24 (36%), cephalosporins in 11 (16%) and flucloxacillin in 2 (3%). SPT and IDT were positive in 6 patients (9%) and specific IgE in 11 (16%). Only one patient had both positive specific IgE and skin tests. Of the remaining 51 cases, 33 underwent a drug challenge with the culprit antibiotic, with a positive reaction in 2 (6%). In all positive cases and when a drug challenge with the suspected antibiotic was not indicated, a challenge with an alternative drug was done, all with negative results. Conclusions: Of the 67 studied cases with history of beta-lactam hypersensitivity reactions, 18 (27%) were confirmed after testing. A combination of skin testing, specific IgE determination and drug challenge is necessary since none has sufficient sensitivity to be used alone (AU)

Successful desensitisation to Anastrozole

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Desensitization to methylphenidate--the relevance of continued drug intake for a successful outcome.

Methylphenidate is the treatment of choice in attention-deficit/hyperactivity disorder (ADHD). The authors report the case of a 7 year old boy with ADHD and psoriasis who developed generalised erythema, pruritus and fever 5 hours after the first oral administration of methylphenidate. After 2 days of treatment the drug was discontinued with complete resolution of symptoms. Later on, the drug was re-introduced with recurrence of the same clinical symptoms. Patch tests were performed with negative results. Desensitization was proposed and performed because there is no alternative treatment for ADHD. After the therapeutic dose was achieved, the mother interrupted drug intake because of a misunderstanding of instructions, and a mild rash subsided when another pill was administered. After this event the same desensitization procedure was carefully repeated. Interruption of drug intake during desensitization and consequent recurrence of clinical symptoms highlights the importance of continued exposure to the culprit drug in this kind of procedure. This modified protocol may enable patients with cutaneous reactions to this drug, to maintain therapy without recurrent reactions.

Physical training does not increase allergic inflammation in asthmatic children.

The effects of a 3-month physical training programme on airway inflammation and clinical outcomes were studied in school-aged children with asthma. Subjects with persistent allergic asthma (aged 12.7+/-3.4 yrs; n = 34) were randomly allocated into training and control groups. Exercise consisted of twice-weekly 50-min sessions for 12 weeks. Inflammation was assessed by levels of exhaled nitric oxide, blood eosinophils, eosinophil cationic protein, C-reactive protein, and total and mite-specific immunoglobulin (Ig)E. Lung volumes and bronchial responsiveness to methacholine were determined. The Paediatric Asthma Quality of Life Questionnaire and Paediatric Asthma Caregiver's Quality of Life Questionnaire were used to evaluate activity restrictions, symptoms and emotional stress. The efficacy of the training was assessed by accelerometry. Following the programme, the exercise group spent twice as much time as the controls undertaking moderate-to-vigorous activities. No differences in changes were seen between groups for asthma outcomes. However, total IgE decreased more in the exercise group, as did mite-specific IgE. Training did not increase inflammation in children with persistent asthma, and may have decreased both total and allergen-specific immunoglobulin E levels. It is concluded that there is no reason to discourage asthmatic children with controlled disease to exercise.

Adherence to the Mediterranean diet and fresh fruit intake are associated with improved asthma control.

BACKGROUND: The traditional Mediterranean diet is claimed to possess antioxidant and immune-regulatory properties in several chronic diseases. Typical Mediterranean foods have recently been associated with improvement of symptoms of asthma and rhinitis in children. However the effect of adherence to Mediterranean diet on adult asthma outcomes is unknown. We aimed to investigate the association between adherence to Mediterranean diet and asthma control. METHODS: Cross sectional study of 174 asthmatics, mean (SD) age of 40 (15) years. The patients were defined as controlled, in contrast to noncontrolled, if they showed FEV1 >or= 80% of predicted, exhaled nitric oxide (NO)

Allergic contact blepheroconjunctivitis with phenylephrine eyedrops--the relevance of late readings of intradermal tests.

Allergic reactions to midriatic eyedrops are rare despite extensively used by ophthalmologists. Phenylephrine is responsible for 54-95% of cases reported in literature. We present the case of a 56-year-old man with blepharoconjunctivitis after instillation of phenylephrine 5%, tropicamide 0.5%, oxibuprocaine eyedrops. The patient reported good tolerance to the mentioned drugs. Immediate readings of prick and intradermal tests, performed with the suspected drugs, were negative. Late readings (48 and 72 hours) of epicutaneous tests were also negative. At 72 hours, prick and intradermal tests to phenylephrine were positive. Allergic blepharoconjunctivitis to phenylephrine was diagnosed. Phenylephrine is an extensively used midriatic that can act as a potent sensitizing agent and can be the cause of allergic contact reactions in exposed patients. With this case we illustrate the relevance of late readings of intradermal tests in the diagnosis of late hypersensitivity drug reactions. The authors discuss about possible mechanisms responsible for negative results of epicutaneous tests.