David A. Mathison

Standardization of bronchial inhalation challenge procedures

A group of investigators interested in the standardization of inhalation challenge techniques was selected by the program directors of the Asthma and Allergic Disease Centers (AADC). This effort has been assisted by the National Institute of Allergic and Infectious Diseases of the National Institutes of Health. At the last meeting of the panel on February 15, 19’75, criteria for procedures and materials used were suggested in order to standardize bronchial inhalation challenges as they pertain to allergic disease.

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.

Aspirin intolerance in asthma: Detection by oral challenge☆☆☆

Abstract Oral aspirin challenge was used to detect aspirin intolerance in selected asthmatic patients who did NOT give a history of asthma following aspirin ingestion. Forty-two asthmatic patients with either nasal polyps, sinusitis, or severe asthma requiring corticosteroid therapy were challenged with aspirin. Under carefully controlled circumstances and at a time when their asthma was stable, patients ingested 640 mg. of aspirin (Ascriptin) after taking all their usual maintenance medications. Several parameters of lung function and clinical symptomatology were followed serially over a 4 hour period. Eight of 42 challenges were positive. When these patients were combined with 14 patients who were intolerant to aspirin by history, the prevalence of aspirin intolerance in our asthmatic population was 8 per cent. Patients who were intolerant to aspirin showed a statistically significant increase in the prevalence of the hallmark criteria of nasal polyps, sinusitis, and steroid dependency when compared to all new asthmatic patients during a 2 year period. Aspirin challenge in selected patients can detect aspirin intolerance not recognized by history alone. These patients can be warned to avoid aspirin ingestion in the future. In addition, their management can be improved by recognizing this variant of the asthma syndrome.

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.

Hypocomplementemia in Chronic Idiopathic Urticaria

A discrete evoking factor or presumed pathophysiologic mechanism is not recognized in the majority of patients with chronic urticaria or angioedema. Two cases are reported in which chronic urticaria was the main manifestation of an immune cutaneous vasculitis associated with hypocomplementemia attributable to classic and alternative mechanisms of complement activation. Among 72 consecutive patients evaluated for chronic urticaria, 10 additional patients with idiopathic urticaria were found to have hypocomplementemia. Of these, two had evidence of classic and alternative mechanisms of complement activation, five had evidence of only classic pathway activation, and three evidence of predominately or exclusively alternative pathway activation. Circulating immune complexes were found in the majority of patients with classic pathway activation. Hypocomplementemia may provide clues to pathophysiologic mechanisms operative in some patients with chronic urticaria.

Potassium Iodide Sensitivity in Four Patients with Hypocomplementemic Vasculitis

During metabolism studies of radiolabeled proteins in 126 participants four patients were suspected of being sensitive to potassium iodide (Kl) because they repeatedly developed urticaria and other symptoms after Kl administration. Two of the four patients suspected of Kl sensitivity and 10 control patients were orally challenged with Kl to document and characterize Kl sensitivity and to evaluate the possible association(s) of Kl sensitivity with urticaria, hypocomplementemia, and vasculitis. The Kl challenges in the two sensitive patients precipitated urticaria, angioedema, polymyalgias, conjunctivitis, and coryza. One of these two patients also developed a severe systemic illness characterized by fever, headache, peritonitis, episcleritis, and pneumonitis. The four sensitive patients were strikingly similar in that they exhibited hypocomplementemia and dermal vasculitis associated with chronic urticaria or systemic lupus erythematosus, suggesting that other patients with similar clinical features may be sensitive to Kl and that Kl may precipitate severe systemic illness in them.