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.

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.

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.

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.

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.

Aspirin-exacerbated respiratory disease: burden of disease.

Aspirin-exacerbated respiratory disease (AERD) is characterized by adult onset of asthma, chronic rhinosinusitis (CRS), nasal polyposis, and aspirin sensitivity. In this syndrome, each disease component has deleterious effects on the patient's health and quality of life. Latest figures from the Centers for Disease Control indicate 8.2% of the U.S. population has asthma and among adult asthmatic patients, up to 9% have AERD. Approximately 13% of the population suffers from CRS and 15% of patients with CRS with nasal polyposis have AERD. A review of the impact that each component of AERD has on patients will delineate the considerable burden of AERD, especially when considering the cumulative effects of the tetrad.

Guidelines for the diagnosis and management of food allergy in the United States: report of the NIAID-sponsored expert panel.

Food allergy is an important public health problem that affects children and adults and may be increasing in prevalence. Despite the risk of severe allergic reactions and even death, there is no current treatment for food allergy: the disease can only be managed by allergen avoidance or treatment of symptoms. The diagnosis and management of food allergy also may vary from one clinical practice setting to another. Finally, because patients frequently confuse nonallergic food reactions, such as food intolerance, with food allergies, there is an unfounded belief among the public that food allergy prevalence is higher than it truly is. In response to these concerns, the National Institute of Allergy and Infectious Diseases, working with 34 professional organizations, federal agencies, and patient advocacy groups, led the development of clinical guidelines for the diagnosis and management of food allergy. These Guidelines are intended for use by a wide variety of health care professionals, including family practice physicians, clinical specialists, and nurse practitioners. The Guidelines include a consensus definition for food allergy, discuss comorbid conditions often associated with food allergy, and focus on both IgE-mediated and non-IgE-mediated reactions to food. Topics addressed include the epidemiology, natural history, diagnosis, and management of food allergy, as well as the management of severe symptoms and anaphylaxis. These Guidelines provide 43 concise clinical recommendations and additional guidance on points of current controversy in patient management. They also identify gaps in the current scientific knowledge to be addressed through future research.

Assessment of sensitization risk of a laundry pre-spotter containing protease.

When proteolytic enzymes were first introduced to common laundry detergents in the 1960s, their ability to cause hypersensitivity due to exposure by inhalation was soon recognized as a problem, especially for production workers. Subsequently, formulations and manufacturing methods were developed to minimize exposure to enzymes via inhaled dust particles. Although detergents containing proteases are now considered safe for consumers, the experience with laundry pre-spotter products is not as extensive. Two studies were undertaken to examine the risk of sensitization to protease (i.e. Savinase(®)) used in a trigger-spray laundry pre-spotter product. The first was a laboratory study simulating a very heavy-use scenario in a controlled environment cubical chamber (14.5 m(3)). The product was applied to a series of fabric targets held vertically over a standard washing machine. Eight replicates of the experiment were done, using 30 sprays for each replicate. Airborne particle distributions in the breathing zone were characterized using a TSI particle analyzer. Enzyme concentrations in air were measured using PTFE membrane filters that were frozen until analyzed by an enzyme linked immunosorbent assay (ELISA). Results indicated that aerosol concentrations returned to baseline within 10 min, during which the average enzyme concentration in air was 17 ± 1.6 and 12 ± 0.92 ng/m(3) using low- and high-volume samplers, respectively. The corresponding amount of enzyme that could be inhaled was significantly less than allowed in occupational situations. The second study was a 6-month, controlled-use study involving approximately 100 subjects with confirmed atopic status by skin prick testing with common aeroallergens. The study involved daily exaggerated use of the pre-spotter product for 6 months, with prick testing for the protease carried out at baseline, 3 and 6 months. Results from the clinical study indicated that none of the subjects exhibited reactions that would indicate sensitization to the protease by inhalation. The principal limitations of the study were the relatively small number of subjects and the limited duration (96 completed the entire 6-month exposure program).

Rational approach to aspirin dosing during oral challenges and desensitization of patients with aspirin-exacerbated respiratory disease.

BACKGROUND: Aspirin desensitization improves clinical outcomes in most patients with aspirin-exacerbated respiratory disease. Most protocols for desensitization are time-consuming. OBJECTIVE: Our objective was to use historical information about the course of aspirin desensitization to enhance the efficiency of the desensitization protocol. METHODS: Four hundred twenty subjects with suspected aspirin-exacerbated respiratory disease underwent oral aspirin challenges. Their clinical characteristics were analyzed in relation to features of reactions during aspirin challenges. RESULTS: Large (FEV(1) decrease >30%) and moderate (FEV(1) decrease 21% to 30%) bronchial reactions occurred in 9% and 20% of subjects, respectively. Multivariate analysis identified risk factors associated with these larger reactions, including lack of leukotriene modifier use, baseline FEV(1) of less than 80% of predicted value, and previous asthma-related emergency department visits. Seventy-five percent of patients reacted to a provoking dose of either 45 or 60 mg. Only 3% of initial reactions occurred after 150- or 325-mg provoking doses, and none occurred after the 650-mg dose. CONCLUSIONS: Most bronchial and naso-ocular reactions during oral aspirin challenges occurred within a narrow dosing range (45-100 mg). Only 1 of 26 patients without risk factors had a moderate reaction.

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.

The Difficult-to-Control Asthmatic: A Systematic Approach.

With the judicious use of inhaled corticosteroids, beta2 agonists, and leukotriene modifiers, most patients with asthma are easily controlled and managed. However, approximately 5% of asthmatics do not respond to standard therapy and are classified as "difficult to control." 1 Typically, these are patients who complain of symptoms interfering with daily living despite long-term treatment with inhaled corticosteroids in doses up to 2,000 mug daily. Many factors can contribute to poor response to conventional therapy, and especially for these patients, a systematic approach is needed to identify the underlying causes. First, the diagnosis of asthma and adherence to the medication regimen should be confirmed. Next, potential persisting exacerbating triggers need to be identified and addressed. Concomitant disorders should be discovered and treated. Lastly, the impact and implications of socioeconomic and psychological factors on disease control can be significant and should be acknowledged and discussed with the individual patient. Less conventional and novel strategies for treating corticosteroid-resistant asthma do exist. However, their use is based on small studies that do not meet evidence-based criteria; therefore, it is essential to sort through and address the above issues before reverting to other therapy.

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.