Biomedical subjects
D D Stevenson
Publications and source records attributed to D D Stevenson.
Aspirin-sensitive asthma and rhinosinusitis: current concepts and recent advances.
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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-sensitive rhinosinusitis: the clinical syndrome and effects of aspirin administration.
Nineteen aspirin sensitive adult patients were identified who experienced naso-ocular responses without associated bronchospasm during standardized oral aspirin challenge. These 19 patients exhibited the characteristics of the aspirin triad except asthma. These included hypertrophic rhinitis with or without associated nasal polyps, abnormal sinus roentgenograms, nasal eosinophilia, aspirin-provoked responses of the upper airway identical to those observed in aspirin-sensitive asthmatics, capacity of the upper airway to be desensitized to aspirin, and cross-reactivity and/or cross-desensitization of the upper airway to indomethacin. Of the 17 patients who were treated with daily aspirin after desensitization, 77% experienced improvement in their nasal symptoms.
The absence of detectable complement activation in aspirin-sensitive asthmatic patients during aspirin challenge.
Activation of complement was sought by two independent assay methods, total hemolytic complement (CH50) and C4 activation by rocket immunoelectrophoresis for C4d and C4 in plasma samples obtained from 16 aspirin-sensitive asthmatic patients and four control subjects during provocative oral aspirin challenges. No consistent evidence of significant complement activation was detected in either the asthmatic or control groups when serial measurements were performed. The measurements of CH50 and C4 activation did not change in either arterial or venous samples. These findings indicate that oral aspirin given in dosages that provoke bronchospasm did not activate C4 or significantly decrease serum complement activity.
Desensitization of aspirin-sensitive asthmatics: a therapeutic alternative?
To identify and characterize aspirin sensitivity, over 500 oral aspirin challenges have been performed in patients since 1970. Protocols were developed, and an aspirin desensitization process was created as an extension of the challenge protocol. Without exception, desensitization has been achieved in 66 of 66 consecutive aspirin-sensitive asthmatics. There is also cross-desensitization with nonsteroidal anti-inflammatory drugs (NSAIDs) in the limited number of patients studied. After desensitization with either aspirin or NSAIDs, an interruption of continuous therapy is followed by a reappearance of sensitivity. Patients must be cautioned about this and the possibility of a severe reaction should aspirin be reintroduced after aspirin avoidance for 2-5 days.
Aspirin desensitization in aspirin-sensitive asthmatic patients: clinical manifestations and characterization of the refractory period.
Thirty aspirin-sensitive asthmatic patients underwent incremental, oral aspirin challenge until a "positive reaction" (delta FEV1 greater than or equal to 25%) occurred. After this reaction, aspirin was readministered in an attempt to achieve "desensitization." This was defined as the ability of the patient to ingest 650 mg of aspirin without experiencing upper or lower respiratory-tract symptoms or a decrease in lung function. To determine the "refractory period" following aspirin desensitization, patients were rechallenged after various intervals (days) without aspirin until a positive reaction recurred. All 30 aspirin-sensitive asthmatic patients were successfully desensitized to aspirin. Individual patient refractory periods ranged from less than 2 days to greater than 5 days, with most patients gradually returning to sensitivity between 2 to 4 days. Cross-densensitization with indomethacin and other nonsteroidal anti-inflammatory drugs was also demonstrated. These studies show that aspirin desensitization can be safely achieved in aspirin-sensitive asthmatic patients; however, this desensitization will gradually disappear over several days when additional aspirin is withheld.
Asthma and the home environment.
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Sensitivity to ingested metabisulfites in asthmatic subjects.
While ingesting selected foods and drinks in restaurants, four asthmatic patients reported the sudden onset of severe wheezing and associated anaphylactoid symptoms and signs. Single-blind placebo and potassium metabisulfite (K2S2O5) oral challenges documented asthmatic responses 15 to 30 min after ingestion of K2S2O5. Laboratory investigations failed to demonstrate specific reaginic antibody recognition of K2S2O5 in these patients. Furthermore, their peripheral basophils did not release histamine during in vitro challenges with K2S2O5. It seems likely that additional asthmatic subjects have such sensitivities but are currently assumed to have "food allergies." Such individuals can be suspected of having this sensitivity by history, and oral K2S2O5 challenges can identify asthmatics who are sensitive.
Efficacy of troleandomycin in outpatients with severe, corticosteroid-dependent asthma.
Sixteen severe, corticosteroid-dependent yet resistant outpatient asthmatics were treated with troleandomycin (TAO), a macrolide antibiotic, in an attempt to both induce a clinical remission and reduce methylprednisolone requirements. Within the first 2 wk of initiating TAO therapy, 50% of the patients experienced a greater than 20% increase in forced expiratory volume in 1 sec (FEV1) and 80% noted a greater than 20% increase in forced vital capacity between 25% and 75% (FVC 25%-75%). Maximal increases in FEV1 and FVC 25%-75% were noted in all patients within the first 6 wk on TAO and methylprednisolone. There was a concomitant clinical improvement in all patients. Corticosteroid-induced side effects, gastrointestinal tract discomfort, and elevated serum glutamic pyruvic transaminase (SGPT) were common yet generally transient during TAO and methylprednisolone therapy. After a 4- to 18-mo follow-up 15/16 patients were well-controlled on TAO and methylprednisolone. Methylprednisolone requirements were reduced at least four- to fivefold in most patients during TAO therapy. Normal morning serum cortisol levels were documented after varying intervals in most patients when both TAO (250 mg) and methylprednisolone (4 to 16 mg) could be reduced to alternate-day administration. Only one patient was forced to discontinue therapy due to side effects. The present study extends the effectiveness of TAO therapy to ambulatory asthmatics, establishes a clinical strategy that maximizes benefit/risk factors, and provides practical guidelines for the long-term use of TAO and methylprednisolone.
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.
Hypersensitivity to nonsteroidal antiinflammatory drugs: indications and methods for oral challenges.
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Radiographic contrast media infusions. Measurement of histamine, complement, and fibrin split products and correlation with clinical parameters.
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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.
Radiographic contrast media studies in high-risk patients.
Patients with prior anaphylactoid reactions (AR) to radiographic contrast media (RCM) are at increased risk for another reaction upon repeat exposure to RCM. One hundred one patients, who had prior AR to RCM, who gave informed consent, and who had an essential need for a repeat RCM study, were pretreated with prednisone, 50 mg orally every 6 hours for 3 doses ending one hour prior to RCM study, and diphenhydramine, 50 mg intramuscularly, one hour prior to RCM study. The repeat RCM study was then carried out using standard procedures with resuscitation equipment readily available. Ninety-six patients had no reaction. Five of the 101 (4.95%) developed AR. These AR consisted only of mild urticaria or pruritus. No significant or life-threatening reactions occurred. Pretreatment decreases the risk in this population of patients and is recommended as standard prophylaxis for patients requiring RCM who have had a previous AR.
The relationship of plasma histamine to the activity of bronchial asthma.
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Plasma complement changes during bronchospasm provoked in asthmatic patients.
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