[Guideline for the Diagnosis and Treatment of Asthma - Addendum 2020 - Guideline of the German Respiratory Society and the German Atemwegsliga in Cooperation with the Paediatric Respiratory Society and the Austrian Society of Pneumology]. / S2k-Leitlinie zur Diagnostik und Therapie von Patienten mit Asthma ­ Addendum 2020.

The present addendum of the guideline for the diagnosis and treatment of asthma (2017) complements new insights into the diagnosis and management of asthma as well as for the newly approved drugs for the treatment of asthma. Current, evidence-based recommendations on diagnostic and therapeutic approaches are presented for children and adolescents as well as for adults with asthma.

[Guideline for the Diagnosis and Treatment of Asthma - Guideline of the German Respiratory Society and the German Atemwegsliga in Cooperation with the Paediatric Respiratory Society and the Austrian Society of Pneumology]. / S2k-Leitlinie zur Diagnostik und Therapie von Patienten mit Asthma.

The present guideline is a new version and an update of the guideline for the diagnosis and treatment of asthma, which replaces the previous version for german speaking countries from the year 2006. The wealth of new data on the pathophysiology and the phenotypes of asthma, and the expanded spectrum of diagnostic and therapeutic options necessitated a new version and an update. This guideline presents the current, evidence-based recommendations for the diagnosis and treatment of asthma, for children and adolescents as well as for adults with asthma.

Clinical characteristics and risk profile of patients with elevated baseline serum tryptase

BACKGROUND: The clinical relevance of elevated basal serum tryptase (eBST ≥ 11.4 ng/ml) often remains unclear. METHODS: BST was assessed in 15,298 patients attending our outpatient clinic. Frequency and severity of anaphylaxis was compared in 900 patients with eBST and 900 patients with normal BST. The prevalence of eBST was evaluated in patients with drug reactions, urticaria, gastrointestinal symptoms or venom allergy. Mast cell-associated symptoms were recorded prospectively in 100 patients with eBST and 100 controls using a standardised questionnaire. RESULTS: 5.9% (n = 900) of 15,298 patients had eBST ≥11.4 ng/ml (mean 20 ± 21 ng/ml, 11.4-390 ng/ml). In 47% of them BST was <15.0 and in 78% <20.0 ng/ml. In patients with normal BST (4.5 ± 2.1 ng/ml), mean levels increased continuously with age (0.28 ng/ml per decade; p < 0.001). Fatigue, meteorism, muscle/bone ache, vertigo, tachycardia, flush, palpitations, diarrhoea and oedema were associated with eBST (p < 0.05 to <0.0001) without significant differences between slightly (11.4-20 ng/ml) or strongly (>20 ng/ml) eBST. eBST was significantly associated with adverse reactions to drugs (34%), radio contrast media (15%) and insect stings (24%) (p < 0.05). Anaphylaxis was more common in patients with eBST (21% vs. 14%, p < 0.001). The relative role of insect stings, drugs and food as the most important triggers was similar in patients with elevated and normal BST. Severe reactions (grade 3/4) occurred most often in subjects with BST >20 ng/ml (BST <11.4 mg/ml: 2.8%; 11.5-20 ng/ml: 5.9%; >20 ng/ml: 12.4%). CONCLUSIONS: In clinical practice it appears reasonable to assess BST, besides after anaphylactic reactions also in patients suffering repeatedly from vertigo, flush, tachycardia, palpitations, oedema and nausea. Even patients with slightly eBST have a higher risk of anaphylaxis and experience more severe reactions

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Clinical characteristics and risk profile of patients with elevated baseline serum tryptase.

BACKGROUND: The clinical relevance of elevated basal serum tryptase (eBST ≥ 11.4 ng/ml) often remains unclear. METHODS: BST was assessed in 15,298 patients attending our outpatient clinic. Frequency and severity of anaphylaxis was compared in 900 patients with eBST and 900 patients with normal BST. The prevalence of eBST was evaluated in patients with drug reactions, urticaria, gastrointestinal symptoms or venom allergy. Mast cell-associated symptoms were recorded prospectively in 100 patients with eBST and 100 controls using a standardised questionnaire. RESULTS: 5.9% (n=900) of 15,298 patients had eBST ≥11.4 ng/ml (mean 20 ± 21 ng/ml, 11.4-390 ng/ml). In 47% of them BST was <15.0 and in 78% <20.0 ng/ml. In patients with normal BST (4.5 ± 2.1 ng/ml), mean levels increased continuously with age (0.28 ng/ml per decade; p<0.001). Fatigue, meteorism, muscle/bone ache, vertigo, tachycardia, flush, palpitations, diarrhoea and oedema were associated with eBST (p<0.05 to <0.0001) without significant differences between slightly (11.4-20 ng/ml) or strongly (>20 ng/ml) eBST. eBST was significantly associated with adverse reactions to drugs (34%), radio contrast media (15%) and insect stings (24%) (p<0.05). Anaphylaxis was more common in patients with eBST (21% vs. 14%, p<0.001). The relative role of insect stings, drugs and food as the most important triggers was similar in patients with elevated and normal BST. Severe reactions (grade 3/4) occurred most often in subjects with BST >20 ng/ml (BST <11.4 mg/ml: 2.8%; 11.5-20 ng/ml: 5.9%; >20 ng/ml: 12.4%). CONCLUSIONS: In clinical practice it appears reasonable to assess BST, besides after anaphylactic reactions also in patients suffering repeatedly from vertigo, flush, tachycardia, palpitations, oedema and nausea. Even patients with slightly eBST have a higher risk of anaphylaxis and experience more severe reactions.

Are adverse effects of sildenafil also caused by inhibition of diamine oxidase?

BACKGROUND: Sildenafil citrate (Viagra), a drug used to treat erectile dysfunctions, causes adverse reactions such as headache, flushing or nasal congestion. Sildanefil's potency as inhibitor of diamine oxidase was investigated, as side effects may also be induced by histamine itself due to an impaired histamine metabolism. METHODS: Placental diamine oxidase inhibition experiments were performed with consecutive dilutions of sildenafil citrate (10(-5) to 10(-9) mol/l). In 9 male volunteers in vivo diamine oxidase inhibition was investigated after taking 100 mg sildenafil (Viagra). RESULTS: Sildenafil citrate did not inhibit placental diamine oxidase either in vitro or in vivo. However, infusion of 300 mg of cimetidine inhibited diamine oxidase activity by 27 +/- 7% 15 min after infusion, demonstrating that drugs may inhibit diamine oxidase in vivo. CONCLUSION: As side effects of sildenafil are not caused due to inhibition of diamine oxidase, sildenafil citrate seems to be harmless for patients suffering from histamine intolerance.

Ash (Fraxinus excelsior)-pollen allergy in central Europe: specific role of pollen panallergens and the major allergen of ash pollen, Fra e 1.

BACKGROUND: The role of ash (Fraxinus excelsior) pollen as a cause of spring pollinosis in central Europe has received little attention. It is not clear whether ash pollen is a primary cause of sensitization or whether it is implicated through cross-sensitization to other pollens. METHODS: Over a 22-month period, ash pollen was included in a screening series for inhalant allergies. Pollen data were documented from 1976 through 1999. The frequency of IgE-binding to the ash-specific allergen Fra e 1 and pollen panallergens, respectively, was compared by Western blot between mono- (n = 6), oligo- (n = 16), and polysensitized (n=25) patients. RESULTS: Of 5,416 consecutive patients sensitized to any pollen, 920 (17.6%) had a positive skin prick test to ash. Total pollen counts varied extensively between years (229-5,351) as did peak concentrations (23-837 grains/m3/24 h). Western blotting revealed Fra e 1 sensitization in 100% of monosensitized, 93% of oligosensitized, but only 44% of polysensitized patients. IgE against profilins (Fra e 2), Ca-binding proteins (Fra e 3), and carbohydrate epitopes in the three groups was found in 0/0/17%, 0/19/31%, and 32/72/60%, respectively. At least 50% of sera from patients with Fra e 1 sensitization did not bind with the protein in Western blots under reducing conditions. CONCLUSIONS: Ash pollen should be considered a relevant factor and distinct entity in spring pollinosis. In all, only 20% of positive skin tests to ash appear to result from cross-sensitization to pollen panallergens.

Exposure to formaldehyde and phenol during an anatomy dissecting course: sensitizing potency of formaldehyde in medical students.

BACKGROUND: The sensitizing potency of formaldehyde and phenol during anatomy dissecting was investigated. The objective was to determine whether exposure induces specific IgE or IgG against formaldehyde-albumin or phenol-albumin. METHODS: In 27 medical students, specific IgE against formaldehyde-albumin by RAST plus ELISA and specific IgE against phenol-albumin by ELISA were assessed. In addition, specific IgG against formaldehyde-albumin was assessed in 23 students. Symptoms before and during dissecting were assessed, and indoor formaldehyde and phenol were measured. RESULTS: Mean indoor formaldehyde was 0.265 +/- 0.07 mg/m3, and mean indoor phenol was 4.65 +/- 2.96 mg/m3. Specific IgE/IgG against formaldehyde-albumin was not found at the beginning. Four students developed specific IgE against formaldehyde-albumin (RAST classes of > or =2.0), and all four also had specific IgE in the ELISA, but IgG against formaldehyde-albumin was not found. Specific IgE against phenol-albumin was not seen. Itch and paresthesia of the hands (P<0.00001), dizziness (P<0.008), burning eyes (P<0.01), headache, sneezing, epistaxis, gingival bleeding, oral or pharyngeal itch, and shortness of breath were experienced. CONCLUSIONS: Formaldehyde exposure during dissecting may induce specific IgE, but not IgG, against formaldehyde-albumin. Sensitization did not correlate with symptoms.

The human recombinant histamine releasing factor: functional evidence that it does not bind to the IgE molecule.

BACKGROUND: We have previously shown that the human recombinant histamine releasing factor (HrHRF) caused histamine release from a subset of basophils from donors with allergy, and this release seemed to be dependent on the presence of a certain type of IgE, termed IgE+. IgE molecules that did not support HrHRF-induced histamine release were termed IgE-. However, subsequently we demonstrated that HrHRF primes anti-IgE-antibody-induced histamine release from all basophils, irrespective of the type of IgE on the cell surface. OBJECTIVE: Because these data suggested that HrHRF does not exert its biologic effects by binding to IgE, but rather that it interacted with a surface receptor on the basophil, we wanted to obtain functional evidence that HrHRF did or did not bind to the IgE molecule. METHODS: The rat basophilic leukemia cell line (RBL-SX38), which has been transfected to express a functional human FcepsilonRI (alpha-, beta-, and gamma-chains of the receptor) in addition to the normal rat FcepsilonRI, was used. The presence of the human FcepsilonRI receptor enables these cells to be sensitized with human IgE. Cells were passively sensitized with 1000 ng/mL human IgE+ or 1000 ng/mL human IgE- for 60 minutes at 37 degrees C. Unsensitized cells served as a control. After the cells were washed, 1 x l0(5) cells were stimulated in the presence of 1 mmol/L Ca2+ with 0.1 microg/mL anti-IgE, 40 microg/mL HrHRF, or 40 microg/mL mouse recombinant HRF (MrHRF), which has 96% homology to HrHRF. RESULTS: Mean anti-IgE-induced histamine release was 33% +/- 15%, and there was no difference between IgE+ sensitization (32% +/- 12%) and IgE- sensitization (34% +/- 18%). However, in contrast to human basophil experiments, neither HrHRF (0% +/- 0%) nor MrHRF (3% +/- 5%) caused histamine release in RBL cells sensitized with IgE+. In addition, priming the transfected RBL-SX38 cells or the parental cell line, RBL-2H3 cells, with HrHRF or MrHRF did not increase anti-IgE-induced histamine release. CONCLUSION: The results indicate that HrHRF does not bind to IgE, either IgE+ or IgE-. Therefore it appears likely that rHRF signals through its own specific receptor, which is not expressed or functional on RBL-SX38 or RBL-2H3 cells, but which seems to be expressed on basophils of atopic and nonatopic donors.

Daily variations of serum diamine oxidase and the influence of H1 and H2 blockers: a critical approach to routine diamine oxidase assessment.

OBJECTIVE AND DESIGN: Histamine in food has been shown to induce intolerance reactions mimicking food allergy. These reactions seem to be due to impaired histamine metabolism caused by reduced diamine oxidase activity. To validate routine serum diamine oxidase assessment, daily variations of diamine oxidase were evaluated. METHODS: Blood was drawn from each of 20 healthy volunteers (10 female, 10 male; mean age 32.5 years) every 2 h from 9 a.m. to 5 p.m., and diamine oxidase activity was measured using the C14 putrescine method. To assess possible influences of H1 and H2 blockers on diamine oxidase activity, diphenhydramine, ketotifen, cimetidine, and ranitidine were incubated at pharmacologic concentrations with human placental diamine oxidase (identical to neutrophilic and eosinophilic diamine oxidase). Inhibition of diamine oxidase activity was calculated as the percentage of inhibition versus control. In addition, the known diamine oxidase inhibitors, dihydralazine and aminoguanidine, were used as positive controls. RESULTS: Serum diamine oxidase levels showed no significant daily variations (0.041 +/- 0.025; 0.037 +/- 0.022; 0.041 +/- 0.023; 0.040 +/- 0.023; 0.038 +/- 0.025 nKat/l) and no significant sex differences (female 0.040 +/- 0.028 nKat/l versus male 0.039 +/- 0.019 nKat/l). Antihistamines had no influence on diamine oxidase activity except for cimetidine, which caused 25% inhibition at the highest dose tested ( p < 0.0002) (positive control: aminoguanidine 85% inhibition (p< 0.0001), dihydralazine 68% inhibition (p<0.0001)) and diphenhydramine, which caused 19% increase (p<0.0001) of enzyme activity. CONCLUSION: Serum diamine oxidase levels do not show daily variations allowing assessment anytime during office hours. However, diagnostic interpretation of serum diamine oxidase levels may be difficult.

Oilseed rape pollen is a potentially relevant allergen.

Oilseed rape (Brassica napus) (OSR) is a partly wind-pollinated crop which has been increasingly cultivated both in Europe and overseas. Allergological data about OSR is scarce and controversial. We evaluated the frequency of sensitization to OSR pollen by skin prick test and RAST over a period of 1 yr. Airborne OSR pollen load and the agricultural role of this crop were analysed. Furthermore, six patients were investigated by immunoblot. In 4468 patients with suspect inhalant allergy investigated between June 1994 and May 1995, routine skin prick testing revealed OSR sensitivity in 7.1% of pollen-allergic patients. In all, monovalent sensitization was detected in nine patients. Routine pollen counts showed daily maxima not exceeding 50 grains/m3/24 h, but airborne OSR pollen has continuously increased during the last decade correlating with the increasing acreage. Characterization of OSR allergens by immunoblot revealed major allergens of 6/8 kD, 12/14 kD and in the high molecular weight range at 33, 42, 51, 58/61 and 70 kD. Some OSR proteins may cross-react with birch pollen allergens. In summary, the results suggest that OSR pollen is a moderate but true source of allergy and may sensitize despite low pollen exposure.

Formaldehyde and phenol exposure during an anatomy dissection course: a possible source of IgE-mediated sensitization?

The sensitizing potency of formaldehyde and phenol exposure during 4 weeks of an anatomy dissection course was assessed in 45 medical students. Specific IgE against formaldehyde by RAST and by ELISA and specific IgE against phenol by ELISA were assessed before and after the course. At the start of the course, symptoms, type I allergy, respiratory diseases, and smoking habits were noted. At the end of the course, only symptoms experienced during the dissection lessons were assessed. Indoor formaldehyde levels were measured continuously. The mean indoor formaldehyde level was 0.124 +/- 0.05 ppm, with a minimum of 0.059 ppm and a maximum of 0.219 ppm. Specific IgE against formaldehyde or phenol was found in none of the subjects at the beginning of the course, and no student showed specific IgE against formaldehyde or phenol after the course. Assessment of primarily irritant symptoms during the lesson revealed itch and paraesthesia of hands in 33/45 students (P < 0.00005), headache in 15/45 students, burning eyes in 13/45 students (P < 0.02), dizziness in 8/45 students (P < 0.008), sneezing in 4/45 students, epistaxis in 2/45 students, and shortness of breath in 1/45 students. According to our data, 1-month exposure to formaldehyde and phenol during an anatomy dissection course does not induce specific IgE against formaldehyde or phenol.

Allergic contact dermatitis to artificial fingernails prepared from UV light-cured acrylates.

BACKGROUND: Contact dermatitis from artificial nails made from self-curing acrylic resins is occasionally reported. Recently, UV light-cured products introducing new acrylics have become available. OBJECTIVE: Our purpose was to identify relevant allergens in commercial light-curing products by patch tests and to evaluate the efficacy of "hypoallergenic" products by inclusion into the test series. METHODS: Patients wearing photobonded acrylic nails who had perionychial and subonychial eczema were patch tested with an acrylate battery and "hypoallergenic" commercial products. RESULTS: Triethyleneglycol dimethacrylate, hydroxyfunctional methacrylates, and (meth)-acrylated urethanes proved to be relevant allergens in photobonded nail preparations. Methacrylated epoxy resin sensitization was not observed. All "hypoallergenic" products provoked positive reactions. CONCLUSION: The omission of irritant methacrylic acid in UV-curable products does not reduce the high sensitizing potential of new acrylates. In contrast to the manufacturers' declarations, all "hypoallergenic" products continue to include acrylate functional monomers and therefore continue to cause allergic sensitization.

Histamine in wine. Bronchoconstriction after a double-blind placebo-controlled red wine provocation test.

A 38-year-old woman with a history of seasonal rhinoconjunctivitis reported repeated attacks of wheezing after drinking various alcoholic beverages. Two consecutive histamine provocations using two identical samples of red wine containing 200 micrograms histamine/l and 3,700 micrograms/l, respectively, were performed in a double-blind placebo-controlled fashion to assess a possible histamine-induced bronchoconstriction. Lung function, plasma histamine, skin temperature, pulse rate and symptoms were assessed. In 3 male controls, four consecutive wine tests were performed in a randomised double-blind placebo-controlled fashion. Drinking wine with 3,700 micrograms histamine/l caused coughing and wheezing with a decrease in lung function. Plasma histamine showed an increase at 10 and 20 min and decreased at 30 min both after histamine-rich as well as histamine-poor wine, reaching the peak increase after histamine-rich wine. Controls did not react and plasma histamine levels did not increase. Bronchoconstriction after wine or food rich in histamine seems to be caused by diminished histamine degradation on the basis of reduced activity of diamine oxidase. Histamine in wine may induce bronchoconstriction in patients suffering from histamine intolerance.