Ronald A. Simon

Rhinosinusitis: Establishing definitions for clinical research and patient care

Background There is a need for more research on all forms of rhinosinusitis. Progress in this area has been hampered by a lack of consensus definitions and the limited number of published clinical trials. Objectives To develop consensus definitions for rhinosinusitis and outline strategies useful in clinical trials. Methods Five national societies, The American Academy of Allergy, Asthma and Immunology; The American Academy of Otolaryngic Allergy; The American Academy of Otolaryngology Head and Neck Surgery; The American College of Allergy, Asthma and Immunology; and the American Rhinologic Society formed an expert panel from multiple disciplines. Over two days, the panel developed definitions for rhinosinusitis and outlined strategies for design of clinical trials. Results Committee members agreed to adopt the term “rhinosinusitis” and reached consensus on definitions and strategies for clinical research on acute presumed bacterial rhinosinusitis, chronic rhinosinusitis without polyposis, chronic rhinosinusitis with polyposis, and classic allergic fungal rhinosinusitis. Symptom and objective criteria, measures for monitoring research progress, and use of symptom scoring tools, quality-of-life instruments, radiologic studies, and rhinoscopic assessment were outlined for each condition. Conclusion The recommendations from this conference should improve accuracy of clinical diagnosis and serve as a starting point for design of rhinosinusitis clinical trials.

Aspirin desensitization treatment of aspirin-sensitive patients with rhinosinusitis-asthma : Long-term outcomes

BACKGROUND Aspirin-sensitive patients with asthma experience continuous inflammation of their nasal and sinus tissues, complicated by recurrent sinusitis, which frequently leads to asthma attacks. Systemic corticosteroid therapy and sinus or polyp surgery are currently required to control underlying rhinosinusitis, and bursts of corticosteroids are used for asthma control. OBJECTIVE After aspirin desensitization therapy, objective measures of respiratory disease activity, linked to the need for systemic corticosteroids and sinus surgery, were studied to determine whether any changes occurred. METHODS Sixty-five aspirin-sensitive patients with asthma underwent aspirin challenge, followed by aspirin desensitization and daily treatment with aspirin over 1 to 6 years (mean, 3.1 years). Clinical outcome measurements before aspirin desensitization treatment and during follow-up were analyzed for the larger group of 65 patients and subgroups (29 patients receiving therapy for 1 to 3 years and 36 patients receiving therapy for 3 to 6 years). RESULTS In the larger group of 65 patients, there were significant reductions in numbers of sinus infections per year (median, 6 to 2), hospitalizations for treatment of asthma per year (median, 0.2 to 0), improvement in olfaction (median, 0 to 2), and reduction in use of systematic corticosteroids (mean, 10.2 to 2.5 mg) with p values less than 0.0001. Numbers of sinus and polyp operations per year were significantly reduced (median, 0.2 to 0; p = 0.004), and doses of nasal corticosteroids (in micrograms) were significantly reduced (mean dose, 139 to 106 micrograms, p = 0.01). Emergency department visits and use of inhaled corticosteroids were unchanged. CONCLUSIONS The results support a role for aspirin desensitization treatment of aspirin-sensitive patients with rhinosinusitis-asthma.

Food allergy: a practice parameter

TABLE OF CONTENTS I. Preface S1 II. Glossary S2 III. Executive Summary S3 IV. Summary Statements S6 V. Classification of Major Food Allergens and Clinical Implications S11 VI. Mucosal Immune Responses Induced by Foods S12 VII. The Clinical Spectrum of Food Allergy S15 VIII. Algorithm and Annotations S18 IX. Prevalence and Epidemiology S21 X. Natural History of Food Allergy S22 XI. Risk Factors and Prevention of Food Allergy S23 XII. Cross-reactivity of Food Allergens S24 XIII. Adverse Reactions to Food Additives S30 XIV. Genetically Modified Foods S32 XV. Diagnosis of Food Allergy S33 XVI. Food-Dependent Exercise-Induced Anaphylaxis S39 XVII. Differential Diagnosis of Adverse Reactions to Foods S40 XVIII. General Management of Food Allergy S44 XIX. Management in Special Settings and Circumstances S45 XX. Future Directions S47 XXI. Appendix: Suggested Oral Challenge Methods S48 XXII. Acknowledgments S49 XXIII. References S50

Long-term effects of aspirin desensitization—Treatment for aspirin-sensitive rhinosinusitis-asthma

One hundred seven known aspirin (ASA)-sensitive patients with rhinosinusitis-asthma were studied from 1975 to 1988. Forty-two of the patients avoided ASA and served as the control group. Thirty-five patients were desensitized to ASA and treated with daily ASA treatment (Rx) for as long as 8 years (mean, 3.75 years) to May 1988 and were designated the continuous group. Thirty patients, initially desensitized to ASA and treated with daily ASA, who stopped Rx permanently after a mean duration of 2 years, were designated the discontinued group. Retrospective analyses of baselines revealed that both continuous and discontinued groups during ASA Rx demonstrated statistically significant reduction in number of hospitalizations per year, emergency room visits per year, outpatient visits per year, upper respiratory infections-sinusitis-antibiotics per year, need for nasal polypectomies and additional sinus operations, and improvement in sense of smell compared to the control group. Simultaneously, the ASA-Rx groups were able to significantly reduce systemic corticosteroid dosage, corticosteroid bursts per year, and, in the continuous group only, significantly reduce inhaled corticosteroids. All three groups maintained control of respiratory symptoms. ASA desensitization followed by long-term daily ASA Rx appears to improve ASA-sensitive rhinosinusitis-asthma and concomitantly allows reduction of systemic corticosteroids.

Aspirin-sensitive rhinosinusitis asthma: a double-blind crossover study of treatment with aspirin

Twenty-five ASA-sensitive patients with rhinosinusitis asthma underwent oral ASA challenges followed by desensitization to the adverse respiratory effects of ASA. We then compared the efficacy of continuous ASA treatment for their respiratory tract disease to that of a placebo treatment during a double-blind crossover study. For this group of 25 patients, there was significant improvement in nasal symptoms and a reduction in use of nasal beclomethasone during the months when they received ASA treatment. Lower respiratory tract symptoms, values of FEV1, and the use of antiasthmatic medications including prednisone were not significantly changed during ASA treatment. Desensitization to ASA followed by ASA treatment appears to significantly alleviate symptoms of rhinosinusitis. However, only half the patients experienced improvement in their asthma symptoms during ASA treatment.

Prevalence of cross-sensitivity with acetaminophen in aspirin-sensitive asthmatic subjects

OBJECTIVE Cross-sensitivity between aspirin and acetaminophen in aspirin-sensitive asthmatic patients has been reported with frequencies ranging from 0% to 29%. The relationship is dose-dependent for acetaminophen challenges, ranging between 300 and 100 mg. METHODS To determine the prevalence of cross-sensitivity to high-dose acetaminophen, we performed single-blind acetaminophen oral challenges with 1000 mg and 1500 mg in 50 aspirin-sensitive asthmatic patients and in 20 non-aspirin-sensitive asthmatic control subjects. RESULTS Overall, 17 of 50 (34%) of aspirin-sensitive asthmatic patients reacted to acetaminophen in doses of 1000 to 1500 mg (95% confidence interval: 20% to 49%). By contrast, none of the 20 non-aspirin-sensitive asthmatic patients reacted to acetaminophen (95% confidence interval: 0% to 14%). This difference was highly significant (p = 0.0013), supporting the hypothesis that cross-sensitivity between aspirin and acetaminophen is unique in aspirin-sensitive asthmatic patients. CONCLUSION Although high-dose ( > 1000 mg) acetaminophen cross-reactions with aspirin were significant with respect to frequency (34%), such reactions included easily reversed bronchospasm in only 22%, and were generally mild. We recommended that high doses of acetaminophen (1000 mg or greater) should be avoided in aspirin-sensitive asthmatic patients.

Aspirin-sensitive asthma: Tolerance to aspirin after positive oral aspirin challenges

Two aspirin-sensitive asthmatic patients underwent oral aspirin challenges for investigative purposes. Folowoing the expected respiratory reaction to aspirin, the patients became refractory to the further adverse effects of aspirin. Additionally they began taking 325 mg aspirin per day, and after 6 and 8 mo aspirin dosage was increased to 650 mg per day. We have noted an improvement in their rhinitis and asthma during this open drug trial. Furthermore, maintenance systemic corticosteroids have been reduced in one patient and discontinued in the other without a decline in lung function values. If these intitial observations are found in a larger number of aspirin-sensitive asthmatic patients, changes in our understanding of the pathogenesis of rhinosinusitis-asthma-aspirin syndrome would follow, and treatment for such asthmatic patients might be improved.

Aspirin-sensitive rhinosinusitis/asthma: spectrum of adverse reactions to aspirin

In order to determine the types of respiratory responses observed during aspirin-induced reactions, 50 consecutive asthmatic patients with a history of aspirin sensitivity underwent prospective oral aspirin challenges between 1979 and 1981. Oral aspirin challenges produced 36 asthmatic responses (33 combined with rhinitis and three purely asthmatic) and six acute rhinoconjunctivitis responses (three combined with mild asthma and three purely rhinoconjunctivitis) but failed to stimulate any reaction in eight patients. The results produced by these challenges were then compared with results recorded during additional aspirin challenges in 28 of these patients, performed after the index challenge in 1979-1981 in 26 patients and in the case of two patients before 1979. The type of respiratory response to aspirin varied significantly in 11 (39%) of the 28 patients and included disappearance of aspirin reactivity in four patients.

Aspirin challenge and desensitization for aspirin-exacerbated respiratory disease: a practice paper

Aspirin desensitization is indicated for patients who have aspirin-exacerbated respiratory disease and whose asthma and/or rhinosinusitis is suboptimally controlled with inhaled corticosteroids and leukotriene-modifying drugs. In this practice paper, the general requirements for aspirin desensitization are presented, the locations where desensitizations can be safely performed are outlined, prechallenge patient preparation is discussed, an oral aspirin challenge protocol is presented, treatment of adverse reactions is reviewed, and maintenance of aspirin desensitization is discussed.

Rational approach to aspirin dosing during oral challenges and desensitization of patients with aspirin-exacerbated respiratory disease

BACKGROUND Aspirin desensitization improves clinical outcomes in most patients with aspirin-exacerbated respiratory disease. Most protocols for desensitization are time-consuming. OBJECTIVE Our objective was to use historical information about the course of aspirin desensitization to enhance the efficiency of the desensitization protocol. METHODS Four hundred twenty subjects with suspected aspirin-exacerbated respiratory disease underwent oral aspirin challenges. Their clinical characteristics were analyzed in relation to features of reactions during aspirin challenges. RESULTS Large (FEV(1) decrease >30%) and moderate (FEV(1) decrease 21% to 30%) bronchial reactions occurred in 9% and 20% of subjects, respectively. Multivariate analysis identified risk factors associated with these larger reactions, including lack of leukotriene modifier use, baseline FEV(1) of less than 80% of predicted value, and previous asthma-related emergency department visits. Seventy-five percent of patients reacted to a provoking dose of either 45 or 60 mg. Only 3% of initial reactions occurred after 150- or 325-mg provoking doses, and none occurred after the 650-mg dose. CONCLUSIONS Most bronchial and naso-ocular reactions during oral aspirin challenges occurred within a narrow dosing range (45-100 mg). Only 1 of 26 patients without risk factors had a moderate reaction.