Clopidogrel Desensitization: Background and Recommendations for Use of a Rapid (4 Hour) Protocol.

The purpose of this section is to educate the reader on how to successfully manage patients with a hypersensitivity reaction to clopidogrel using desensitization protocol based on various published protocols. Additionally, we will define drug desensitization, and describe the possible mechanism of how desensitization may function as alternative medication. The indications/contraindications for desensitization will be reviewed. The different published clopidogrel desensitization protocols will be discussed. Based on those protocols, we recommend a protocol we feel is safe and efficacious. Clopidogrel is a thienopyridine antiplatelet drug widely used for treatment and also employed for secondary prevention regarding a range of cardiovascular diseases. However, it has been reported to cause hypersensitivity reactions. Ticlopidine is an alternative medication that can be considered when patients have an allergic reaction to clopidogrel. Additionally, ticlopidine is associated with increased risk causing potentially life-threatening adverse reactions to include: Aplastic anemia, reversible neutropenia, and thrombotic thrombocytopenia purpura vs. clopidogrel. Thus, clopidogrel desensitization offers an attractive alternative. Drug desensitization is defined as causing a temporary state of tolerance to a specific medication responsible for a hypersensitivity reaction. Furthermore, drug desensitization can only be maintained by continuous administration of this drug. Discussion: The exact immunologically mediated mechanism of how rapid oral desensitization works is not fully understood and yet to be defined. Ultimately desensitization results in causing antigen-specific mast cell tolerance. Various protocols have been published. The length of desensitization ranged from 2 h using 9 doses to 7 h using 15 doses. Recommendations: Taking the above into account, we recommend using a modification to the protocol that has the largest number of patients to undergo a standardized clopidogrel desensitization. This approach is shorter, as time has immense importance for these patients. Dosing starts at 10 mg dose and with 60 min intervals between doses, this now becomes a 4 h desensitization protocol.

The Utility of the Reflux Symptom Index for Diagnosis of Laryngopharyngeal Reflux in an Allergy Patient Population.

BACKGROUND: Laryngopharyngeal reflux (LPR) is associated with asthma, vocal cord dysfunction, cough, postnasal drainage, and throat irritation. The Reflux Symptom Index (RSI) is a clinical tool to predict the presence of LPR, but a threshold RSI score has never been validated for the diagnosis of LPR in an allergic patient population. OBJECTIVE: To identify the optimal threshold RSI score predictive of LPR in an allergy clinic population. METHODS: The 9-question RSI questionnaire was administered to 84 patients in the Kaiser Permanente San Diego Allergy Department. The patient's allergist (who was blinded to the patient's RSI responses) was asked to determine whether the patient had symptoms consistent with LPR. Each subject's RSI score was then compared with a corresponding physician-based diagnosis. After determining the correlation between the subject's RSI score and physician-diagnosed LPR/supraesophageal reflux, a cutoff level above which LPR/supraesophageal reflux would be highly suspected was calculated on the basis of most optimal balance of sensitivity and specificity determined via a receiver-operating curve analysis. RESULTS: Thirty of the 84 patients (36%) were diagnosed with LPR. The mean RSI score for the group without LPR was 18.3 ± 9.8 (out of 45 possible), while the LPR group's mean was 25.0 ± 8.3 (P < .01). The optimal RSI score cutoff was determined to be 19. An abbreviated questionnaire was also generated using 6 of the RSI questions found to be significantly different between patients with and without LPR. CONCLUSIONS: An RSI score of 19 appears to represent the best threshold for predicting LPR in an allergy clinic patient population.

Effect of misoprostol on patients with aspirin-exacerbated respiratory disease undergoing aspirin challenge and desensitization.

BACKGROUND: Prostaglandin E2 (PGE2) is an anti-inflammatory compound that inhibits 5-lipoxygenase activity. Diminished PGE2 regulation in aspirin-exacerbated respiratory disease (AERD) leads to respiratory reactions on cyclooxygenase 1 inhibition. In vitro studies have found that exogenous PGE2 stabilizes inflammatory mediator release. OBJECTIVE: To examine whether misoprostol (oral prostaglandin E1 analogue) use during aspirin challenge and desensitization might decrease the severity of aspirin-induced symptoms and make desensitization safer for patients with AERD. METHODS: Forty-five patients undergoing aspirin challenge and/or desensitization were randomized to misoprostol (n = 30) or placebo (n = 15) and compared with a group of historical controls (n = 31). Misoprostol (200 µg) was administered at 30 minutes, 90 minutes, and 4 hours after the first dose of nasal ketorolac. Measured end points included change in forced expiratory volume in 1 second (FEV1), peak nasal inspiratory flow rate (PNIF), number of treatments received for induced reactions, and adverse gastrointestinal effects. RESULTS: A difference in FEV1 and PNIF reduction was detected between misoprostol and placebo (P = .03) and misoprostol and historical controls (P = .01), respectively, during nasal ketorolac challenge. No difference was detected among aspirin reactors. Among all reactors, no difference in magnitude was found for FEV1 (P = .13) or PNIF (P = .07) reduction across all 3 groups. Total treatment requirement was similar (P = .14). Patients receiving misoprostol were more likely to report adverse gastrointestinal effects (P = .02). CONCLUSION: The addition of misoprostol to current aspirin challenge and/or desensitization protocols reveals no protective effect in reducing the intensity of nonsteroidal anti-inflammatory drug-induced symptoms and is not recommended based on the findings in this study.

Use of a composite symptom score during challenge in patients with suspected aspirin-exacerbated respiratory disease.

BACKGROUND: Aspirin-exacerbated respiratory disease is characterized by asthma, chronic rhinosinusitis, nasal polyposis, and sensitivity to aspirin and other nonsteroidal anti-inflammatory drugs. Confirmation of the diagnosis requires provocation challenge with resulting upper and/or lower airways reactivity. Currently, determination of a positive challenge result is based solely on clinical judgment that synthesizes subjective symptoms and objective measures, as a concomitant increase in nasal or bronchial airways resistance is measured in only half of patients. OBJECTIVE: To describe a quantitative scoring system, based on symptoms typically reported during provocation challenge, used to identify a positive challenge result. METHODS: A total of 115 patients were asked to record 10 symptoms, rated on a scale from 1 (mild) to 10 (most severe), at regular intervals during intranasal ketorolac with modified oral aspirin challenge performed in our office. Composite scores, a simple sum of all individual scores, were calculated at each time point and compared with baseline, prechallenge values. RESULTS: One hundred of the 115 patients were determined to have a positive challenge result. A statistically significant difference in composite scores was observed in reactors vs nonreactors. All nonreactors recorded an increase in composite score of less than 5, whereas 69% of reactors recorded an increase of 5 or more. CONCLUSION: Our 10-symptom composite score provides a quantitative and comparable measure of symptoms that typically present during a challenge with a positive result. Although an external validation is needed to confirm its diagnostic performance characteristics, a change in composite score of 5 or more appears to be specific to reactors.

Performing Aspirin Desensitization in Aspirin-Exacerbated Respiratory Disease.

Aspirin-exacerbated respiratory disease (AERD) is characterized by chronic rhinosinusitis with nasal polyps, asthma, and reactions to cyclooxygenase-1-inhibiting drugs. This condition is often refractory to standard medical treatments and results in aggressive nasal polyposis that often requires multiple sinus surgeries. Aspirin desensitization followed by daily aspirin therapy is an important treatment option, and its efficacy has been validated in multiple research studies. Aspirin desensitization is not without risk, but specific protocols and recommendations exist to mitigate the risk. Most patients with AERD can undergo aspirin desensitization in an outpatient setting under the supervision of an allergist.

Improvement in Asthma Control Using a Minimally Burdensome and Proactive Smartphone Application.

BACKGROUND: Integrated chronic disease treatment models that enable patient self-care and shared treatment decision making have recently been shown to improve medication adherence and outcomes. Smartphone applications (apps) are a readily available means to enable this model, although sustained user engagement remains a challenge. OBJECTIVE: To assess the efficacy of improving asthma control using a proactive smartphone app without required regular inputs. METHODS: We designed a minimally intrusive smartphone app to provide individualized and timely support to patients with asthma based on the National Asthma Education and Prevention Program guidelines and Scripps management pathways. In this proof-of-concept study, we enrolled 60 adults with poorly controlled asthma to test the usability and effectiveness of this app over a 4-month period. The Asthma Control Test survey was used to assess control before, during, and after app use. As a corollary, a retrospective chart review was also used to assess changes in lung function and prescribed courses of systemic corticosteroids. RESULTS: Our patients, with a mean age of 50 years, reported an improvement in Asthma Control Test scores from 16.6 (inadequate to poor) to 20.5 (controlled) over the study period. Concurrently, there was a 7.9% absolute increase in FEV1, while courses of systemic corticosteroids decreased from 0.5 to 0.3 courses per 6-month period. Fifty-eight of 60 patients completed the final survey, with high satisfaction reported. CONCLUSIONS: This app improved asthma control in a cohort of patients with uncontrolled asthma (age range, 17-82 years), while minimizing burdensome inputs and proactively providing individualized teaching and treatment support. The app and treatment model are scalable to cost-effectively manage chronic disease.

Aspirin-exacerbated respiratory disease: characteristics and management strategies.

Aspirin-exacerbated respiratory disease is a clinical entity comprising chronic rhinosinusitis with nasal polyposis, asthma and intolerance to COX-1 inhibiting drugs. The pathogenesis is not completely understood at this point, but abnormal arachidonic acid metabolism is a key feature in this syndrome. The diagnosis is confirmed only by direct drug challenge. Aspirin desensitization followed by daily aspirin therapy is a useful treatment option in these patients. In this review article are discussed the important characteristics and treatment of aspirin-exacerbated respiratory disease.

A genome sequencing program for novel undiagnosed diseases.

PURPOSE: The Scripps Idiopathic Diseases of Man (IDIOM) study aims to discover novel gene-disease relationships and provide molecular genetic diagnosis and treatment guidance for individuals with novel diseases using genome sequencing integrated with clinical assessment and multidisciplinary case review. Here we describe the operational protocol and initial results of the IDIOM study. METHODS: A total of 121 cases underwent first-tier review by the principal investigators to determine whether the primary inclusion criteria were satisfied, 59 (48.8%) underwent second-tier review by our clinician-scientist review panel, and 17 patients (14.0%) and their family members were enrolled. RESULTS: 60% of cases resulted in a plausible molecular diagnosis, and 18% of cases resulted in a confirmed molecular diagnosis. Two of three confirmed cases led to the identification of novel gene-disease relationships. In the third confirmed case a previously described but unrecognized disease was revealed. In all three confirmed cases a new clinical management strategy was initiated based on the genetic findings. CONCLUSION: Genome sequencing provides tangible clinical benefit for individuals with idiopathic genetic disease, not only in the context of molecular genetic diagnosis of known rare conditions but also in cases where prior clinical information regarding a new genetic disorder is lacking.

Update on aspirin desensitization for chronic rhinosinusitis with polyps in aspirin-exacerbated respiratory disease (AERD).

Aspirin-exacerbated respiratory disease (AERD) is a clinical condition which results in adverse upper and lower respiratory symptoms, particularly rhinitis, conjunctivitis, bronchospasm, and/or laryngospasm, following exposure to cyclooxygenase-1 (COX-1) inhibiting drugs, namely aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs). A provocative aspirin challenge is the gold standard for diagnosis of AERD. Aspirin desensitization and continuous aspirin therapy has been highly efficacious in those patients with suboptimal control of their disease on current available pharmacotherapy or those with other underlying conditions (i.e., cardiovascular disease) who may require frequent treatment with aspirin or NSAIDs. This review article focuses on aspirin desensitization and the management of patients with AERD with a particular emphasis on outcomes in those patients with chronic rhinosinusitis and nasal polyposis.

Supraesophageal Reflux: Correlation of Position and Occurrence of Acid Reflux-Effect of Head-of-Bed Elevation on Supine Reflux.

BACKGROUND: Supraesophageal reflux of gastric contents can contribute to perennial nasopharyngitis, cough, and asthma. However, effective treatment strategies for supraesophageal reflux disease (SERD) remain inadequately defined. OBJECTIVE: The purpose of this study is to assess the prevalence and timing of SERD and to investigate the efficacy of head-of-bed elevation in its treatment. METHODS: A retrospective chart review of patients seen at Scripps Clinic Division of Allergy, Asthma and Immunology was performed who had undergone overnight nasopharyngeal pH monitoring with a commercially available nasopharyngeal pH-monitoring device, Dx-pH Measurement System from Restech, San Diego, Calif. Subjects with reflux were classified based on the position of reflux as either supine only, upright only, or both supine and upright. In a subset of subjects with supine-only reflux, pH monitoring was compared before and after elevating the head of bed 6 inches. RESULTS: Adequate nasopharyngeal pH-monitoring data were obtained for 235 patients. Reflux was detected in 113 (48%) patients. The pattern of reflux observed was 62 (55%) supine only, 4 (4%) upright only, and 47 (42%) upright and supine. Sequential overnight nasopharyngeal pH monitoring before and after head-of-bed elevation was obtained in 13 individuals with supine-only reflux. Ten subjects demonstrated significant improvement, 8 of whom demonstrated complete resolution of supine reflux with 6 inches of head-of-bed elevation. CONCLUSION: This study provides new evidence that SERD frequently occurs in the supine position and that 6 inches of head-of-bed elevation is effective in reducing supine SERD.

Food allergy: a practice parameter update-2014.

This parameter was developed by the Joint Task Force on Practice Parameters, representing the American Academy of Allergy, Asthma & Immunology (AAAAI); the American College of Allergy, Asthma & Immunology (ACAAI); and the Joint Council of Allergy, Asthma & Immunology (JCAAI). The AAAAI and the ACAAI have jointly accepted responsibility for establishing "Food Allergy: A practice parameter update-2014." This is a complete and comprehensive document at the current time. The medical environment is a changing one, and not all recommendations will be appropriate for all patients. Because this document incorporated the efforts of many participants, no single individual, including those who served on the Joint Task Force, is authorized to provide an official AAAAI or ACAAI interpretation of these practice parameters. Any request for information about or an interpretation of these practice parameters by the AAAAI or ACAAI should be directed to the Executive Offices of the AAAAI, ACAAI, and JCAAI. These parameters are not designed for use by pharmaceutical companies in drug promotion.

Supraesophageal reflux disease: a review of the literature.

Supraesophageal reflux disease (SERD), defined as reflux proximal to the upper esophageal sphincter, is a common cause of morbidity of the upper aerodigestive tract, including rhinitis, laryngitis, cough, postnasal drip, and throat clearing. Although SERD has a high prevalence, the ideal means of diagnosing and treating the disease remain poorly defined. Evolving pH monitoring technology and a body of literature with conflicting reports regarding the best means for measuring and interpreting supraesophageal acidic reflux complicates the diagnosis of SERD. Treatment options include empiric acid suppression therapy, lifestyle modification, and surgery. However, limited data regarding the effectiveness of these strategies vary between studies and patient populations. It is the goal of this article to summarize the presentation and pathogenesis of SERD and to integrate the evolving body of literature pertaining to diagnostic and treatment strategies.

Prevalence of sensitivity to food and drug additives in patients with chronic idiopathic urticaria.

BACKGROUND: Chronic idiopathic urticaria (CIU) is defined as the presence of urticaria most days of the week for a period of 6 weeks or longer. There have been reports of food additive sensitivity in CIU previously, but the prevalence has not been precisely determined. OBJECTIVE: To determine the prevalence of reactions to food and drug additives in patients with CIU. METHODS: We challenged 100 patients in our allergy/immunology division with CIU to the 11 additives most commonly associated with reactions: tartrazine (FD&C Yellow 5), potassium metabisulfite, monosodium glutamate, aspartame, sodium benzoate, methyl paraben, butylated hydroxy anisole, butylated hydroxy toluene, FD&C Yellow 6, sodium nitrate, sodium nitrite. All of the patients had a history of CIU for longer than 6 weeks, and 43 reported possible history of food or drug additive sensitivity. Single-blind challenges to all of the additives were performed in the clinic and skin scores were recorded. Subjects with positive challenge tests underwent double-blind placebo controlled challenges. RESULTS: Of 100 subjects, only 2 had a positive urticarial response on single-blind challenge. Neither of these patients had a positive urticarial response on double-blind placebo-controlled challenge. There were no gastrointestinal, respiratory, or other symptom, and no patients reported late reactions. CONCLUSION: We were able to conclude, with 95% confidence intervals that sensitivity to any of the 11 food and drug additives occurs in fewer than 1% of patients with CIU. Food and drug additives appear to be a rare cause of CIU, and avoidance is not recommended.

Cardiovascular prophylaxis and aspirin "allergy".

Aspirin is an important antiplatelet agent in the treatment of cardiovascular disease. Aspirin "allergy" often directs the physician away from this potentially life-saving modality. The majority of patients with a history of "reactions to aspirin" have aspirin/nonsteroidal anti-inflammatory drug (NSAID)-induced gastritis, easy bruisability, or other side effects. The minority of these patients has a "true allergy," referred to as a hypersensitivity reaction. The former group can be started on aspirin without the need for special challenge. Adding a proton-pump inhibitor can often mitigate the gastrointestinal side effects. Patients with aspirin hypersensitivity can be safely challenged with aspirin.

Approach to patients with aspirin hypersensitivity and acute cardiovascular emergencies.

The occurrence of an emergent need for aspirin therapy in an aspirin or nonsteroidal anti-inflammatory drug (NSAID)-"allergic" individual presents one of the more challenging situations the allergist may face. A common request is for the allergist to evaluate an acutely ill patient in a monitored hospitalized setting with a vague and remote history of a "reaction to aspirin." Because of significant diagnostic limitations, introducing aspirin can be very difficult. The concern about the potential for causing anaphylaxis in an acutely ill patient can lead to fear about performing any challenge or desensitization in these patients. The objective of this article was to review the literature regarding aspirin challenges and desensitization in the emergency setting and present a rational approach to administering aspirin to patients that require this drug.

The united allergic airway: connections between allergic rhinitis, asthma, and chronic sinusitis.

BACKGROUND: The united allergic airway is a theory that connects allergic rhinitis (AR), chronic rhinosinusitis, and asthma, in which seemingly disparate diseases, instead of being thought of separately, are instead viewed as arising from a common atopic entity. OBJECTIVE: This article describes patients with such diseases; explores ideas suggesting a unified pathogenesis; elucidates the various treatment modalities available, emphasizing nasal corticosteroids and antihistamines; and provides an update of the literature. METHODS: A literature review was conducted. CONCLUSION: The aggregation of research suggests that AR, asthma, and chronic rhinosinusitis are linked by the united allergic airway, a notion that encompasses commonalities in pathophysiology, epidemiology, and treatment.