Long-term treatment with aspirin desensitization: a prospective clinical trial comparing 100 and 300 mg aspirin daily.

BACKGROUND: The daily dose of aspirin in desensitization in aspirin-sensitive asthmatics with nasal polyps is still a matter of debate. AIMS OF THE STUDY: To compare two doses of aspirin during the first year of desensitization and to evaluate long-term effects on nasal/pulmonary symptoms. METHODS: Patients with positive aspirin provocation test were treated with either 100 or 300 mg aspirin daily. RESULTS: In all patients taking 100 mg aspirin (n = 7) recurrent nasal polyps were observed. No patient experienced reduction of asthma medication or improvement of pulmonary function. In the 300 mg group no recurrent nasal polyps were seen. Asthma medication could be reduced in three patients, pulmonary function was improved in five patients. Thirty-nine consecutively desensitized patients, taking 300 mg aspirin, showed significant improvement of olfaction and polyp-free nasal passages during the first year of therapy. After a median follow-up of 27 months no sinus revision surgery was necessary. CONCLUSIONS: Aspirin desensitization followed by 300 mg aspirin daily is efficacious and results in polyp-free nasal airways, improvement of sense of smell, and reduction of the need for sinus revision surgery for recurrent nasal polyps. Aspirin in a dose of 100 mg daily is not sufficient to effectively reduce nasal and bronchial or pulmonary symptoms and to prevent recurrent nasal polyps by at least the first 12 months of treatment.

Distinct features of chronic rhinosinusitis with and without nasal polyps.

BACKGROUND: Based on the presence of nasal polyps on endoscopy, chronic rhinosinusitis (CRS) may be clinically divided in CRS with nasal polyps and CRS without nasal polyps. It is unclear, whether CRS with nasal polyps and CRS without nasal polyps represent different disease entities or just different stages of one single disease. In case of one disease, only minor histopathological differences between CRS with small early-stage polyps (CRSNP((+))) and CRS without nasal polyps (CRSNP(-)) were expected. METHODS: Patients with CRSNP((+)) confined to the infundibular region or CRSNP(-) were selected. Histochemical and immunohistochemical characterization of ethmoidal mucosa was performed on formalin-fixed and paraffin-embedded tissue specimens. Frequency and distribution of eosinophils, neutrophils, mast cells, IgE(+) cells, macrophages, B- and T-cell subsets, natural killer cells, plasma cells and goblet cells were assessed. In addition, the thickness of the basal membrane was evaluated. RESULTS: Nine CRS patients without detectable polyps, and 11 patients with small early-stage polyps confined to the infundibular region were selected. Despite adjacent polyp stage, the amount of round cell infiltration (P < 0.05), number of eosinophils (P < 0.05), and plasma cells (P < 0.01) significantly differed in the ethmoidal specimens from patients of the two groups. CONCLUSION: Substantial histopathological differences were observed in ethmoidal mucosa of CRSNP((+)) and CRSNP(-) patients. Thus, the results of this investigation support the concept that CRS with nasal polyps and CRS without nasal polyps are two different disease entities rather than different stages of one single disease, but may also be interpreted as a higher degree of inflammation.

[Intraoperative bronchospasm during paranasal sinus surgery -- indicator of aspirin intolerance syndrome?]. / Intraoperativer Bronchospasmus bei Nasennebenhöhlen-Operationen -- Hinweis auf ein Analgetikaintoleranz-Syndrom?

BACKGROUND: The aim of this study was to evaluate whether an intraoperative bronchospasm is more frequent in sinus surgery than in non-sinus surgery, whether its appearance after application of a non-steroidal anti-inflammatory drug (NSAID) is an indicator of an aspirin intolerance syndrome, and whether its appearance can be interpreted as an aspirin provocation test. METHODS: Anaesthesia charts from 5 years were retrospectively analysed whether anaphylactic/allergic reactions or bronchospasm were observed intraoperatively. In these cases the ENT charts of the patients were analysed and the occurrence of an analgesic-induced bronchospasm was assumed according to a probability algorithm. PATIENTS: All operations in general anaesthesia of an otorhinolaryngology clinic were analysed. RESULTS: An intraoperative bronchospasm was observed significantly more often in patients undergoing sinus surgery than during other ENT operations. In 17 of 23 patients a possible/probable analgesic-induced bronchospasm after application of NSAID was found. Diclofenac was intraoperatively given in 3 patients, diclofenac and metamizole in 5 patients, metamizole in 7 patients, paracetamol in 1 patient, and paracetamol and metamizole in 1 patient. CONCLUSIONS: An intraoperative bronchospasm during sinus surgery is not a clear indicator of an aspirin intolerance syndrome. An analgesic-induced bronchospasm can also be observed after paracetamol and metamizole. It can not be interpreted analogous to an aspirin provocation test.

Nasal biomarker profiles in acute and chronic rhinosinusitis.

BACKGROUND: Clinical manifestations of rhinosinusitis include acute rhinosinusitis, chronic rhinosinusitis (CRS) with nasal polyps and CRS without polyps. OBJECTIVE: Possible mechanisms defining these three forms of rhinosinusitis should be investigated assessing biomarker profiles in nasal secretions. METHODS: Fifteen cytokines, three cellular activation markers and total IgE were determined in nasal secretions of seven patients with acute rhinosinusitis, 12 patients with CRS without polyps, 13 patients with CRS with polyps and six healthy controls. Principal component analysis was used to extract relevant factors. RESULTS: Irrespective of the clinical manifestation, all biomarkers assessed were increased in patients with rhinosinusitis when compared with controls (P<0.001). Principal component analysis allowed the extraction of three factors explaining 83% of data variance. The general inflammatory activation was mainly reflected by the first factor. The second factor differentiated acute from CRS. This factor correlated with IL-12, which is involved in pathogen-related immune activation by antigen-presenting cells. It was also positively correlated with IL-4, IL-10 and IL-13, which play an important role in the resolution of infections. The third factor differentiated CRS with polyps from CRS without polyps (P=0.001). It represented IL-5 and nasal IgE (nIgE), whereas eosinophil cationic protein and tryptase were not specific for CRS with polyps. CONCLUSION: In mucosal infection, numerous inflammatory mediators are activated. Simple correlations of few biomarkers with a specific disease process bear the risk of overestimating a possibly unspecific effect. To assess biomarker profiles, more complex analytic tools may be more appropriate to delineate mechanisms underlying mucosal disease. Using principal component analysis, it was found that high nIgE and IL-5 levels are specific for CRS with nasal polyps.

Local production of Aspergillus fumigatus specific immunoglobulin E in nasal polyps.

BACKGROUND: Aspergillus spp. play a significant role in the etiology of immunoglobulin (Ig)E mediated allergic fungal sinusitis (AFS). It is unclear whether Aspergillus spp. are also involved in nasal polyps without the characteristic clinical features of AFS. OBJECTIVES: The frequency of Aspergillus spp. and Aspergillus-specific IgE in nasal lavages and serum of patients with severe nasal polyps (n = 33) without clinical features of AFS should be investigated. STUDY DESIGN: Prospective study. METHODS: An aliquot of nasal lavage fluid was treated with dithiothreitol and examined for Aspergillus fumigatus by culture and an Aspergillus-specific polymerase chain reaction (PCR) assay. An additional aliquot of nasal fluid and serum of the same patient were tested for specific IgE (Unicap, Pharmacia, Freiburg, Germany) to recombinant Aspergillus fumigatus allergen (rAspf) 1 to 6. RESULTS: All patients had negative skin prick tests for Aspergillus fumigatus. Four of 33 (12%) lavage samples were positive for Aspergillus spp. by PCR. In one of these samples, rAspf-specific IgE was detected but none in the serum. Nasal lavage and serum samples of the remaining 29 patients were negative for rAspf-specific IgE. CONCLUSIONS: Aspergillus spp. detection is rare in patients with severe nasal polyps without characteristic clinical features of AFS. Specific IgE in nasal secretions may be elevated in patients with negative skin prick tests and serum IgE. In these cases, immunologic mechanisms similar to AFS may be involved. Fungal etiology has been proposed to underlie severe nasal polyps in general. However, Aspergillus spp. seem not to play a significant role.

[Analysis of the efficacy of specific immunotherapy with house-dust mite extracts in adults with allergic rhinitis and/or asthma]. / Analyse der Effektivität der subkutanen Immuntherapie mit Hausstaubmilbenextrakten bei Erwachsenen mit allergischer Rhinitis und/oder Asthma bronchiale.

BACKGROUND: Allergen specific immunotherapy and allergen reduction are the only therapies in perennial allergic diseases to reduce symptoms in the long term. Specific immunotherapy has the potential to reduce symptoms and the need for medication significantly and furthermore to prevent progression into more severe disease e. g. asthma. METHODS: The clinical value of specific immunotherapy has been studied for the last 30 years. We undertook an analysis of clinical trials of subcutaneous specific immunotherapy with Der p or Der f in adults to assess the efficacy of this controversial form of allergy treatment. RESULTS: A computerized bibliographic search revealed 13 randomised double-blind, placebo-controlled trials of specific immunotherapy with Der p/Der f for rhinitis and/or asthma in adults since 1970. The results extracted included patients symptoms, medication requirements, lung function, specific challenge-tests as titrated nasal, conjunctival or bronchial challenge test and side effects. For studies with continuous outcomes as symptom score and medication score the effect size was obtained by the difference in the scores between the active therapy and the placebo groups. For studies with categorical outcomes as increase or decrease in challenge-tests the results were expressed as odds ratios for improvement against no change and 95 % confidence intervals were calculated. DISCUSSION: Focused on the studies after 1980 there was a significant improvement on symptom score and medication score in the actively treated group compared to the placebo group, while the lung function was not significantly altered. Allergen provocation tests reflect the sensitivity of the shock organ. As the documentation of the clinical effects measured by challenge tests shows a highly significant improvement in the actively treated group, we recommend allergen provocation tests as a useful and sensitive parameter during specific immunotherapy. The risk of life-threatening side effects is low, although severe anaphylactic reactions may be induced. Specific immunotherapy using a standardized house-dust mite extract is effective and safe in adults when administered under optimal conditions.

[The human vomeronasal organ]. / Das vomeronasale Organ des Menschen.

The vomeronasal system in mammals plays an important role in social and reproductive behaviour. Pheromones are airborne chemical signals that are released by an individual into the environment and affects another member of the same species. The human vomeronasal system was commonly regarded as vestigial, but recently new interest is focussed on this chemoreceptor organ, located at the base of the human nasal cavity. Although vomeronasal systems have long been known to exist in all fetal humans, little is known of the growth of this system in adults. We give a summary of the publications to the features, the frequency of occurrence, the ultrastructure, the developmental aspects and the functional significance of the Jacobson's organ in human.

Complement system in healthy term newborns: reference values in umbilical cord blood.

Activation of the complement system occurs in several diseases. For reliable identification of complement activation in neonates, we establish reference ranges of several components in cord blood of healthy term newborns. For this study, cord blood samples were taken from 125 healthy term newborns. Concentrations of C1r, C2, C5, C7, Properdin, and factors D, H, and I were determined by single radial immunodiffusion. C3a and C5a were measured by specific EIA and complement function was measured by hemolytic assays. The results were expressed as 5th percentile, median, and 95th percentile. The following respective concentrations were found: C1r: 27, 47, 65 mg/l; C2: 12.0, 18.0, 24.0 mg/l; C5: 64, 92, 127 mg/l; C7: 32, 60, 89 mg/l; Properdin: 5.6, 9.7, 14.2 mg/l; factor D: 3.6, 5.2, 7.3 mg/l; factor H: 178, 234, 296 mg/l; and factor I: 15, 24, 32 mg/l. The functional activity of the whole complement system was 24%, 43%, 97% and for the alternative pathway 39%, 58%, 76%. The concentration of the activated split products C3a was 4, 65, 255 microg/l and of C5a, 0.11, 0.26, 1.19 microg/l. These reference values may be important for the detection of deficiencies of native complement proteins or perinatal processes leading to an activation of the complement system.