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Biomedical subjects

Donald D Stevenson

Publications and source records attributed to Donald D Stevenson.

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

Clinical and pathologic perspectives on aspirin sensitivity and asthma.

Aspirin and other nonsteroidal anti-inflammatory drugs that inhibit COX-1 induce unique nonallergic reactions, consisting of attacks of rhinitis and asthma. These hypersensitivity reactions occur in a subset of asthmatic subjects, thus identifying them as having this exclusive clinical presentation. We refer to these patients as having aspirin-exacerbated respiratory disease, a disease process that produces devastating eosinophilic inflammation of both the upper and lower respiratory tracts. This review focuses on a description of patients with aspirin-exacerbated respiratory disease, methods available to diagnose their condition, the unique ability of all nonsteroidal anti-inflammatory drugs that inhibit COX-1 to cross-react with aspirin, an update on pathogenesis, and current thoughts about treatment.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2006

Failure to maintain an aspirin-desensitized state in a patient with aspirin-exacerbated respiratory disease.

BACKGROUND: Aspirin desensitization is a useful therapy in patients with aspirin-exacerbated respiratory disease. OBJECTIVE: To describe the clinical course of a man with aspirin-exacerbated respiratory disease who was unable to be desensitized to oral aspirin. METHODS: A standard aspirin desensitization protocol was used to achieve a maximum dose of 650 mg of oral aspirin. The patient initially tolerated this dose of aspirin. RESULTS: Within days of desensitization, the patient began to react to 650 mg of aspirin. Monitored challenge with this dose of aspirin led to marked decrease in forced expiratory volume in 1 second and pronounced nasal and ocular symptoms. CONCLUSIONS: We present a patient with classic aspirin-exacerbated respiratory disease, who despite undergoing a standard aspirin desensitization protocol was unable to maintain his desensitized state.

Administration, Oral↗
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

Aspirin and NSAID sensitivity.

Aspirin and the older nonsteroidal anti-inflammatory drugs (NSAIDs) that block cyclo-oxygenase-1 (COX-1) induce asthma attacks in patients with aspirin-exacerbated respiratory disease and urticaria in patients with chronic idiopathic urticaria. Weak inhibitors of COX-1, such as acetaminophen and salsalate, crossreact also but only with high doses of the drugs. Partial inhibitors of both COX-1 and COX-2, such as nimesulide and meloxicam, also cross-react but only at high drug doses. COX-2 inhibitors do not cross-react; however, all NSAIDs, including the selective COX-2 inhibitors, can sensitize patients and induce urticaria or anaphylaxis on next exposure to the drug.

Anti-Inflammatory Agents, Non-Steroidal↗
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

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

Aspirin-induced asthma: advances in pathogenesis, diagnosis, and management.

In some asthmatic individuals, aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) that inhibit cyclooxygen-ase 1 (COX-1) exacerbate the condition. This distinct clinical syndrome, called aspirin-induced asthma (AIA), is characterized by an eosinophilic rhinosinusitis, nasal polyposis, aspirin sensitivity, and asthma. There is no in vitro test for the disorder, and diagnosis can be established only by provocation challenges with aspirin or NSAIDs. Recent major advances in the molecular biology of eicosanoids, exemplified by the cloning of 2 cysteinyl leukotriene receptors and the discovery of a whole family of cyclooxygenase enzymes, offer new insights into mechanisms operating in AIA. The disease runs a protracted course even if COX-1 inhibitors are avoided, and the course is often severe, many patients requiring systemic corticosteroids to control their sinusitis and asthma. Aspirin and NSAIDs should be avoided, but highly specific COX-2 inhibitors, known as coxibs, are well tolerated and can be safely used. Aspirin desensitization, followed by daily aspirin treatment, is a valuable therapeutic option in most patients with AIA, particularly those with recurrent nasal polyposis or overdependence on systemic corticosteroids.

Aspirin↗
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

Aspirin desensitization in patients with AERD.

All patients with aspirin exacerbated respiratory disease (AERD) can be desensitized to ASA. After achieving this state, patients can then take ASA daily without adverse effect. ASA desensitization can be maintained indefinitely as long as the patient takes ASA each day. Crossdesensitization with older NSAIDs also occurs. After ASA desensitization, patients can take daily ASA in order to treat their underlying respiratory disease. In AERD patients treated with ASA 650 BID for at least a year, 115/172 (67%) improved in their clinical courses while decreasing systemic and topical corticosteroids. Sixteen failed to improve, 24 stopped ASA because of intractable side effects (gastritis or hives) and 17 patients discontinued ASA treatment in the first year of study for unrelated reasons. Therefore, treatment with daily ASA is a significant therapeutic option for patients afflicted with AERD. It should be used for AERD patients who do not respond to topical corticosteroids and leukotriene modifier drugs. Those who respond to systemic steroids or have intractable or recurrent nasal polyps are particularly well-suited for this therapeutic intervention.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2003

Pathogenesis of aspirin-exacerbated respiratory disease.

The underlying respiratory disease is activated by unknown mechanism and results in an intense infiltration of mast cells and eosinophils into the entire respiratory mucosa. These cells synthesize leukotrienes (LTs) at a very high rate and mast cells also release histamine and tryptase and synthesize PGD(2) a vasodilator and bronchoconstrictor. Furthermore, AERD patients under synthesize from arachidonic acid (AA) a peculiar product called lipoxins, which opposes inflammation generated by leukotrienes. Finally, cysLT1 receptors are over expressed and highly responsive to LTE(4), further augmenting the underlying inflammatory disease. This inflammatory condition is partly inhibited by synthesis of PGE(2) through COX-1. PGE(2) partially inhibits 5-lipogygenase conversion of AA to LTA(4) and blocks release of histamine and tryptase from mast cells. When COX-l is inhibited by ASA or NSAIDs, PGE(2) synthesis stops and an enormous release of histamine and synthesis of LTs occurs. The upper respiratory reaction is mediated by both histamine and LTs but the bronchospastic reaction is mediated by LTs. The systemic effects of flush, gastric pain and hives are mediated by histamine. Aspirin desensitization can not be explained by disappearance of LT synthesis since urine LTE(4) levels are still elevated at acute ASA desensitization. However, mast cell products such as histamine, tryptase and PGD(2) are no longer released or synthesized at acute desensitization. It is more likely that a diminution in number or function of cysLT receptors accounts for the diminished inflammatory response found in ASA desensitization.

Anti-Inflammatory Agents, Non-Steroidal↗