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Biomedical subjects

Ronald A Simon

Publications and source records attributed to Ronald A Simon.

At least 19 recordsLinked to original sources
PubMed2006

Selection of aspirin dosages for aspirin desensitization treatment in patients with aspirin-exacerbated respiratory disease.

BACKGROUND: Aspirin desensitization followed by daily aspirin therapy is effective add-on treatment for patients with aspirin-exacerbated respiratory disease. Prior studies used 650 mg of aspirin twice daily, but studies at lower dosages were inconclusive. OBJECTIVE: We sought to determine the optimal daily dosage of aspirin treatment. METHODS: We studied 137 patients who had undergone successful aspirin desensitization and randomized them into 2 groups, 650 mg twice daily versus 325 mg twice daily. After 1 month, patients either increased or decreased their dosage based on their symptom control and continued that dosage for the remainder of the year. RESULTS: Patients taking either 650 mg twice daily or 325 mg twice daily showed significant improvements in number of sinus infections, sinus operations, and hospitalizations for asthma (all P < .0001). Anosmia, nasal/sinus symptoms, and asthma symptoms also improved in both groups (all P < .03). Systemic corticosteroid dosages decreased by 3- and 4-fold in the 325 mg twice daily and 650 mg twice daily groups, respectively. Of the 137 patients, 32 had adverse effects from or discontinued aspirin therapy: 14 (44%) of 32 from the group randomized to taking 650 mg twice daily and 18 (56%) of 32 from the group randomized to 325 mg twice daily. The most common adverse effect was dyspepsia. CONCLUSION: Both dosages were efficacious, and side effects occurred in both groups at similar frequencies. Some patients initially taking 325 mg twice daily required an increase to 650 mg twice daily for optimal symptom control. CLINICAL IMPLICATIONS: We recommend that patients begin daily aspirin therapy with 650 mg twice daily and subsequently decrease to the lowest effective dosage (usually 325 mg twice daily).

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2006

Effect of leukotriene modifier drugs on the safety of oral aspirin challenges.

BACKGROUND: Aspirin-exacerbated respiratory disease can be diagnosed with oral aspirin challenges and treated with aspirin desensitization. OBJECTIVE: To evaluate whether controller medications, particularly leukotriene modifier drugs, taken during oral aspirin challenges can reduce the risk of severe asthmatic responses. METHODS: The medical records of 676 patients who had undergone oral aspirin challenges, followed by aspirin desensitization, were reviewed. Asthmatic responses were stratified based on severity of bronchospastic response or lack of response. The effect of pretreatment with controller medications on the outcome of oral aspirin challenges was measured. RESULTS: Leukotriene modifier drugs had the most significant effect in protecting the lower airways from severe reactions (P = .004). The protective effect of leukotriene modifier drugs was observed in patients already taking systemic corticosteroids, where the addition of leukotriene modifier drugs significantly shifted the response toward a milder asthmatic response (P < .001). CONCLUSION: Protection from significant aspirin-induced bronchospasm during oral aspirin challenge can be accomplished with leukotriene modifier drugs. The use of a combination of inhaled corticosteroids, long-acting beta-agonists, systemic corticosteroids, and leukotriene modifier drugs stabilized underlying airways in preparation for a reasonably safe and accurate oral aspirin challenge. However, only pretreatment with leukotriene modifier drugs enhanced the safety of oral aspirin challenge in patients with aspirin-exacerbated respiratory disease by significantly decreasing the degree of asthmatic responses. Therefore, outpatient oral aspirin challenges in most well-selected patients appear to be a reasonable decision.

Acetates↗
PubMed2005

Failure of tacrolimus to prevent aspirin-induced respiratory reactions in patients with aspirin-exacerbated respiratory disease.

BACKGROUND: In patients with aspirin-exacerbated respiratory disease (AERD), pretreatment with asthma controller medications (leukotriene modifiers, inhaled or systemic corticosteroids, and salmeterol) partially modifies the severity of aspirin-induced asthmatic reactions. OBJECTIVE: A recent study showed that pretreatment with tacrolimus completely prevented aspirin-induced respiratory reactions and might allow silent aspirin desensitization. METHODS: Ten patients with rhinosinusitis, nasal polyps, and asthma had a history of asthma attacks after ingesting aspirin and nonsteroidal anti-inflammatory drugs. All underwent baseline oral aspirin challenges and had typical respiratory reactions. They were then randomized to receive tacrolimus (0.1 mg/kg weight; 8 patients) or placebo (2 patients) in a double-blind protocol before rechallenge with aspirin using the previous provoking dose of aspirin. In addition, respiratory reactions sustained by 50 consecutive patients with AERD during 2004 were recorded, analyzed, and compared with the tacrolimus/placebo-treated patients to determine whether there were any differences. RESULTS: Tacrolimus pretreatment failed to block respiratory reactions to provoking doses of aspirin in 5 of 8 patients with AERD, and in the other 3 patients did not block higher doses of aspirin. The results of oral aspirin challenges in the control population of 50 patients were compared with either the baseline or postchallenge data from the tacrolimus-pretreated or placebo-pretreated patients with AERD, and there were no significant differences. CONCLUSIONS: Use of tacrolimus as add-on pretreatment to prevent reactions to aspirin in patients with AERD or to achieve the goal of silent aspirin desensitization could not be accomplished.

Administration, Oral↗
PubMed2005

The blocking effect of essential controller medications during aspirin challenges in patients with aspirin-exacerbated respiratory disease.

BACKGROUND: The blocking effect of controller medications for asthma could have an effect on the outcome of aspirin challenges in patients suspected of having aspirin-exacerbated respiratory disease (AERD). OBJECTIVE: To evaluate whether there was any blocking effect of long-acting beta2-agonists, systemic corticosteroids, and/or inhaled corticosteroids alone or as co-therapy with leukotriene modifier drugs (LTMDs). METHODS: Between 1981 and 2004, 678 patients with suspected AERD were admitted for aspirin challenge and desensitization. All patients had asthma, chronic sinusitis, nasal polyposis, and at least 1 historical reaction to a nonsteroidal anti-inflammatory drug. Asthma controller medications taken during aspirin challenge were recorded and analyzed with respect to their potential effects on 4 possible outcomes of aspirin challenge, namely, naso-ocular reaction, lower airway reaction, classic upper and lower airway reaction, or a negative challenge result. RESULTS: When compared with AERD patients who received no controller medications, the combined use of LTMDs, inhaled corticosteroids, and long-acting beta2-agonists led to a statistically significant change in aspirin challenge outcomes (P = .009), mainly shifting the reaction from a classic upper and lower respiratory tract reaction to naso-ocular reactions only. LTMDs appeared to have the strongest effect (P < .001) in blocking lower respiratory tract reactions. Systemic corticosteroids did not have the same effects. Blocking of both upper and lower respiratory tract reactions to aspirin as a result of taking controller medications did not occur. CONCLUSION: Controller medications are frequently needed to stabilize airways of patients with AERD. LTMDs alone or in combination with other controllers blocked lower respiratory tract reactions during aspirin challenge in some patients with AERD but did not change the overall rate of positive aspirin challenge results and did not lead to false-negative challenges.

Administration, Oral↗
PubMed2004

Aspirin sensitivity: implications for patients with coronary artery disease.

CONTEXT: Although acetylsalicylic acid (aspirin) is commonly used for patients with chronic cardiovascular disease, a minority of patients have a sensitivity to acetylsalicylic acid and other nonsteroidal anti-inflammatory drugs. OBJECTIVE: To provide a diagnostic strategy for evaluating and treating patients with aspirin sensitivity, with additional consideration for issues specific to patients with coronary artery disease (CAD). EVIDENCE ACQUISITION: Published articles were identified through a search of MEDLINE and the Cochrane databases using the dates 1966 to June 2004 and the search terms aspirin allergy, coronary artery disease, aspirin desensitization, and aspirin sensitivity. References of retrieved articles were also reviewed for pertinent studies. Articles were included in this review if they were controlled studies, published in the English language, and appeared in a peer-reviewed journal. EVIDENCE SYNTHESIS: The prevalence of aspirin-exacerbated respiratory tract disease is approximately 10% and for aspirin-induced urticaria the prevalence varies from 0.07% to 0.2% of the general population. Aspirin sensitivity is most often manifested as rhinitis and asthma or urticaria/angioedema induced by cross-reacting nonsteroidal anti-inflammatory drugs that inhibit cyclooxygenase 1. The primary mechanism of sensitivity is less often related to drug-specific IgE antibody production leading to urticaria/angioedema and rarely to anaphylaxis. Most patients with acetylsalicylic acid sensitivity are able to undergo desensitization therapy safely and successfully except in cases of chronic idiopathic urticaria. However, there have not been any randomized trials that specifically focus on the efficacy of aspirin desensitization. Furthermore, experience with acetylsalicylic acid desensitization in patients with CAD is very limited. After successful desensitization, acetylsalicylic acid therapy must be indefinitely continued to prevent resensitization. CONCLUSIONS: Acetylsalicylic acid sensitivity is common and desensitization can be performed safely in many patients. Large-scale trials are warranted to determine the safety and efficacy of acetylsalicylic acid desensitization therapy in patients with concomitant CAD because data are currently limited to small case series.

Algorithms↗
PubMed2004

Adverse respiratory reactions to aspirin and nonsteroidal anti-inflammatory drugs.

Aspirin-exacerbated respiratory disease (AERD) is an adult-onset condition that manifests as asthma, rhinosinusitis/nasal polyps, and sensitivity to aspirin and other cyclooxygenase-1 (COX-1)-inhibitor nonsteroidal anti-inflammatory drugs (NSAIDs). There is no cross-sensitivity to highly selective COX-2 inhibitors. AERD is chronic and does not improve with avoidance of COX-1 inhibitors. The diagnosis of AERD is made through provocative challenge testing. Following a positive aspirin challenge, patients can be desensitized to aspirin and NSAIDs. The desensitized state can be maintained indefinitely with continued daily administration. After desensitization, there is an approximately 48-hour refractory period to adverse effects from aspirin. The pathogenesis of AERD remains unknown, but these patients have been shown to have multiple abnormalities in arachidonic acid metabolism and in cysteinyl leukotriene 1 receptors. AERD patients can take up to 650 mg of acetaminophen for analgesic or antipyretic relief. Patients can also use weak COX-1 inhibitors, such as sodium salicylate or choline magnesium trisalicylate. Treatment of AERD patients with antileukotriene medications has been helpful but not preferential when compared with non-AERD patients. An alternative treatment for many AERD patients is aspirin desensitization. This is particularly effective in reducing upper-airway mucosal congestion, nasal polyp formation, and systemic steroids.

Adult↗
PubMed2004

Safety of high-dose rofecoxib in patients with aspirin-exacerbated respiratory disease.

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is characterized by progressive sinusitis, nasal polyposis, and asthma that begins and continues in the absence of exposure to aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs). Cross-sensitivity to all NSAIDs that inhibit cyclooxygenase-1 (COX-1) occurs in these individuals. Reactions to aspirin and NSAIDs in patients with AERD are largely due to inhibition of COX-1. Despite accumulating data on the safety of COX-2 selective inhibitors in AERD, concern still remains that high doses of a COX-2 inhibitor may be sufficient to induce a cross-reaction. OBJECTIVE: To determine whether high-dose rofecoxib cross-reacts in patients with AERD and asthma. METHODS: Sixty asthmatic patients underwent blinded placebo-controlled oral challenges with 50 mg of rofecoxib. Aspirin sensitivity was subsequently confirmed in all patients with the use of single-blinded aspirin challenges. RESULTS: None of the 60 patients experienced any symptoms, changes in nasal examination results, or declines in lung function during rofecoxib challenge. All 60 patients experienced respiratory reactions to aspirin challenge, with a mean provoking dose of 57 mg. The exact 1-sided 95% confidence interval for the underlying probability of 50 mg of rofecoxib inducing respiratory cross-reactions in patients with AERD is 0 to 0.05, or 0% to 5%. CONCLUSIONS: These results confirm the lack of cross-reactivity of aspirin and the highly selective COX-2 inhibitors in AERD. We suggest that it is time for the labeling of highly selective COX-2 inhibitors to reflect these data and for the warning that patients with AERD in particular and asthmatic patients in general avoid selective COX-2 inhibitors to be removed.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2003

Adverse reactions to food additives.

There are thousands of additives used by the food industry for a variety of purposes in the foods we eat. However, only a small number have been implicated in causing adverse reactions in humans. Although there are reported cases of individuals who have reactions to single additives, most of the medical literature involves patients with asthma or chronic idiopathic urticaria/angioedema whose conditions are exacerbated after ingestion of food additives. Many of these reports are characterized by poorly controlled challenge procedures. Recent studies performed under properly controlled conditions imply that sensitivity to food additives in patients with chronic urticaria/angioedema is very uncommon.

Food Additives↗
PubMed2003

Early effects of aspirin desensitization treatment in asthmatic patients with aspirin-exacerbated respiratory disease.

BACKGROUND: Aspirin (ASA)-exacerbated respiratory disease (AERD) is characterized by aggressive inflammation of the respiratory tract and often requires topical and/or systemic corticosteroids to maintain partial control of this disease. Previous studies have revealed that ASA desensitization and subsequent treatment with ASA is associated with clinical improvement in AERD. OBJECTIVE: The aim of the present study was to determine the effect of daily ASA treatment for the first 4 weeks after ASA desensitization. METHODS: Thirty-eight patients underwent ASA oral challenge followed by ASA desensitization and daily ASA therapy. Changes in nasal and asthma symptoms, combined with changes in oral prednisone, were recorded daily during 4 weeks before and after desensitization. Severity of symptoms ranged from a scale of 1 to 5 (1 = asymptomatic and 5 = most severe symptoms). For statistical analyses the sum of nasal symptoms and asthma symptoms was calculated. Olfactory scores were also analyzed. RESULTS: Nasal and asthma symptom scores, as well as olfactory scores, improved significantly (P < 0.0001). For the 15 patients taking prednisone, their mean doses decreased from 10.7 to 5.9 mg daily (P = 0.0003). CONCLUSIONS: Our study suggests that ASA desensitization treatment is effective during the first 4 weeks of daily treatment with ASA.

Adult↗
PubMed2003

Long-term treatment with aspirin desensitization in asthmatic patients with aspirin-exacerbated respiratory disease.

BACKGROUND: Aspirin desensitization treatment is an option to decrease disease activity and reduce the need for systemic corticosteroids in patients with aspirin-exacerbated respiratory disease (AERD). OBJECTIVE: This study was designed to determine whether the clinical courses of patients with AERD improved as early as 6 months after starting aspirin desensitization and to compare this with follow-up evaluations after at least a year. METHODS: Between 1995 and 2000, 172 patients with AERD were admitted to our General Clinical Research Center, were desensitized to and treated with aspirin, were discharged to their home communities, and participated in follow-up interviews and written assessments of their clinical courses. RESULTS: By the first 6 months of aspirin treatment, there were significant reductions in sinus infections and numbers of short courses of prednisone and improvements in sense of smell and general assessment of nasal-sinus and asthma symptoms (P <.0001). These results persisted for 1 to 5 years (P <.0001). Mean prednisone doses decreased from 10.8 mg/d to 8.1 and 3.6 mg/d at 6 months and greater than 1 year, respectively. Of the 172 patients, 24 (14%) discontinued aspirin treatment because of side effects, and 115 (67%) responded to aspirin treatment. After eliminating those who discontinued aspirin treatment because of side effects, the improvement rate was 115 (78%) of 148 patients. Of the 126 patients who completed a year or more of aspirin treatment, 110 (87%) experienced improvement. CONCLUSION: Aspirin desensitization followed by daily aspirin is efficacious by at least the first 6 months of treatment and continues to be effective for up to 5 years of follow-up.

Administration, Inhalation↗
PubMed2003

Prevention and treatment of reactions to NSAIDs.

Avoidance of ASA and other NSAIDs prevents the reactions and careful attention to clinical history along with patient education are important. However, blanket advice to avoid all NSAIDs is no longer reasonable. Except for AERD and chronic urticaria, cross-reactivity with other NSAIDs does not occur. A physician can definitively prove this by giving the patient another NSAID in their office and observing no reaction. Furthermore, for patients with AERD and chronic urticaria, they can be given the new selective COX-2 inhibitors (rofecoxib and celecoxib) without any cross-reactivity. All AERD patients can be desensitized to ASA and treated with ASA indefinitely. However, ASA desensitization in chronic urticaria is not possible. Underlying mild and moderate AERD responds well to topical and systemic corticosteroids and leukotriene modifiers. However, the severe forms of the disease should be desensitized to ASA and treated with this drug on a long term basis. In the future, new drugs that prevent eosinophil activation and chemotaxis or enhance eosinophil apoptosis are likely to be useful. Specific blockers of the second cystLT receptor would also be useful. Ultimately as the genetics of these heterogeneous disorders are unraveled, gene substitution therapy may be the ultimate answer.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2003

Adverse reactions to aspirin and nonsteroidal antiinflammatory drugs (NSAIDs).

BACKGROUND: Aspirin can provoke reactions ranging from respiratory to cutaneous in those susceptible individuals. There has been particular attention looking at the role of cyclooxygenase enzymes and 2 and their role in aspirin exacerbated respiratory disease. OBJECTIVE: Patients who present with a spectrum of allergic and pseudoallergic reactions to aspirin pose a special challenge for the physician. This article discusses proposed classification system, clinical manifestations, pathogenesis of disease, and current treatment options of aspirin related disease. METHODS: Relevant articles in the medical literature were. derived from searching the MEDLINE database. Sources also include review articles, randomized control trials, and standard textbooks of allergy and immunology. RESULTS: Aspirin-exacerbated respiratory disease remains a complex, heterogeneous disease with manvaried clinical presentations. There have been many advances in trying to elucidate the pathogenesis of this disease. The classification system presented will provide greater ease when reading the literature and communicating with one another. Oral aspirin challenge remains the diagnostic test of choice for both respiratory and cutaneous reactions. Aspirin desensitization is an option for those with refractory respiratory disease or who require aspirin for other medical conditions. CONCLUSIONS: This review discusses the challenges in classification, diagnosis and treatment of those patients with a sensitivity to aspirin. Special attention is made to the possible mechanisms mediating disease progression and how specific. Therapies, such as the leukotriene modifiers may be helpful.

Anti-Inflammatory Agents, Non-Steroidal↗