High Constitutive Interleukin 10 Level Interferes With the Immune Response to Varicella-Zoster Virus in Elderly Recipients of Live Attenuated Zoster Vaccine.

INTRODUCTION: Live attenuated zoster vaccine (Zostavax) was used to test the hypothesis that constitutive level of interleukin 10 (IL-10), which may be high in elderly subjects, impairs vaccine efficacy. If constitutive IL-10 impairs vaccine efficacy, the effectiveness of viral vaccines might be improved by transient inhibition of IL-10 before vaccination. METHODS: Zostavax was given to 26 patients (age, 60-80 years). IL-10 and immunity to varicella zoster virus (VZV) were measured at baseline and after vaccination. Fluorescent antibody to membrane antigen (FAMA) assays and glycoprotein enzyme-linked immunosorbent assays (gpELISAs) were used to assess humoral immunity; anti-varicella virus T-cell responses were studied in a subset of subjects. In a prospective animal model, T-cell responses to chimeric vaccines against lymphocytic choriomeningitis virus (LCMV) were assessed in mice that express or lack IL-10. RESULTS: FAMA assays revealed significant boosting (by 4-fold) of humoral immunity, which occurred only in subjects (10 of 26) with a low constitutive IL-10 level (ie, <20 pg/mL); moreover, the Zostavax-induced FAMA and gpELISA responses were inversely related to the constitutive IL-10 level. Significant VZV-specific T-cell responses followed vaccination only in subjects with a low constitutive IL-10 level. Vaccine-induced LCMV-specific T-cell responses in mice lacking IL-10 were greater than in wild-type animals. CONCLUSIONS: A high constitutive IL-10 level adversely affects vaccine efficacy.

Prevalence of aspirin-exacerbated respiratory disease among asthmatic patients: A meta-analysis of the literature.

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is manifested by adult-onset asthma, nasal polyposis, chronic rhinosinusitis, and aspirin sensitivity. Previously reported prevalence rates have been widely variable based on the population studied, method of diagnosis, and definition of aspirin sensitivity. OBJECTIVE: We sought to determine the prevalence of AERD among asthmatic adults. METHODS: A systematic review of databases was performed to identify all clinical trials published on or before June 16, 2013, that evaluated the prevalence of AERD. The studies were clustered into 7 different groups based on underlying disease (asthma, nasal polyps or chronic rhinosinusitis, or both), as well as on the methodology of prevalence determination. RESULTS: A total of 1770 articles were identified, with 27 considered appropriate for inclusion. Prevalence rates of AERD ranged from 5.5% to 12.4% based on study type. Among all studies in asthmatic patients, regardless of method, the prevalence of AERD was 7.15% (95% CI, 5.26% to 9.03%). The prevalence of AERD was highest among patients with severe asthma (14.89% [95% CI, 6.48% to 23.29%]). Among patients with nasal polyps and chronic rhinosinusitis, the prevalence was 9.69% (95% CI, 2.16% to 17.22%) and 8.7% (95% CI, -1.02% to 18.34%), respectively. CONCLUSION: AERD is a distinct and important subtype of asthma and polypoid sinus disease. The prevalence of AERD is 7% in typical adult asthmatic patients and twice that number in patients with severe asthma, which underscores the importance of recognizing this disorder. Early identification of this syndrome is critical in view of the increased morbidity and costs associated with asthma exacerbations and the option to treat patients with AERD with long-term aspirin treatment after desensitization.

Characterization of aspirin allergies in patients with coronary artery disease.

BACKGROUND: Aspirin prevents coronary thrombosis and is used extensively in cardiovascular prophylaxis. However, patients with a prior history of an aspirin "reaction" are routinely denied this medication. OBJECTIVE: To characterize the clinical presentation of a cohort of patients with coronary artery disease (CAD) and aspirin reactions. METHODS: Between 2009 and 2012, using a retrospective computer analysis, information was collected on all patients within a county-wide health care system presenting with CAD and a prior history of aspirin reactions. RESULTS: Of 9,565 patients with CAD, a prior history of aspirin reactions was recorded in 142 patients. Of these 142 patients, 30 (21%) had histories compatible with cutaneous and/or respiratory reactions. The other patients described adverse effects to aspirin, mostly gastrointestinal intolerance and bleeding. Aspirin-induced anaphylaxis was recorded in patients but may have been misdiagnosed, describing instead respiratory hypersensitivity reactions. Of the 142 patients, only 34 (24%) were receiving daily cardiovascular prophylaxis with aspirin. Of 108 patients not receiving aspirin, 25 (17.6%) were prescribed clopidogrel. CONCLUSION: Histories of aspirin reactions in patients with CAD are uncommon, occurring in only 1.5% of our study population. The 21% of patients with histories compatible with aspirin hypersensitivities can be challenged and, if the results are positive, successfully desensitized. Moreover, almost all patients with gastric intolerance to aspirin can be treated with aspirin and a proton pump inhibitor. However, both approaches, which result in restoration of cardiovascular prophylaxis, were seriously underused in our study population.

Use of nasal inspiratory flow rates in the measurement of aspirin-induced respiratory reactions.

BACKGROUND: Nasal ketorolac challenge with modified oral aspirin challenge is a safe and effective alternative for desensitizing patients with aspirin-exacerbated respiratory disease. In addition to clinical judgment, objective tests assessing nasal flow may help in diagnosing nasal reactions. OBJECTIVE: To evaluate the feasibility of peak nasal inspiratory flow (PNIF) as an objective measurement in the assessment of a reaction to nasal ketorolac and to determine changes in PNIF that have adequate sensitivity and specificity. METHODS: One hundred fifty-one patients referred to the Scripps Clinic for aspirin challenge and desensitization and 14 healthy controls participated in the study. Percentages of decrease in PNIF during reactions were compared with the nonreactors' measurements. A receiver operating characteristic curve was constructed to assess the diagnostic performance of PNIF measurement during a clinically positive nasal challenge. RESULTS: A total of 165 subjects participated in the study. One hundred fourteen patients (69.1%) clinically reacted to the nasal ketorolac challenge. There was no statistical difference between nasal reactors and nonreactors regarding sex, baseline forced expiratory volume in 1 second, and use of systemic steroid before challenge. The mean percentage of decrease in PNIF was significantly higher in the reactor group (-0.30 ± 0.29 vs -0.07 ± 0.16, P < .001). A cutoff value of 25% decrease in PNIF had the maximum sensitivity and specificity (56.1% and 94.1%). CONCLUSION: The high specificity of a 25% decrease in PNIF found in receiver operating characteristic curve analysis indicated that PNIF measurements can be useful for assessing nasal reactions during nasal ketorolac challenges in the diagnosis of aspirin-exacerbated respiratory disease.

The clinical dilemma of "silent desensitization" in aspirin-exacerbated respiratory disease.

Aspirin desensitization is a treatment option for patients with aspirin-exacerbated respiratory disease (AERD). Some patients with an excellent history of aspirin or nonsteroidal anti-inflammatory drug (NSAID) reactions have negative aspirin challenges/desensitization. This study discusses the clinical entity of silent desensitization in AERD and the dilemma that this presents to the practicing allergist/immunologist. We discuss a series of patients with a strong history of NSAID reactions who initially underwent a negative challenge/silent desensitization. These patients were subsequently proven to have AERD after a second positive aspirin challenge. Silent desensitization is an uncommon but important outcome to recognize in AERD. Clinicians performing aspirin desensitization should understand that this can occur and consider a second confirmatory aspirin challenge in some patients.

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.

Smoking, environmental tobacco smoke, and aspirin-exacerbated respiratory disease.

BACKGROUND: Tobacco smoke is a widely recognized environmental pollutant and is a major public health hazard worldwide. Although environmental tobacco smoke (ETS) has a clear link with many conditions, including asthma, ear infections, and sinus cancer, evidence related to aspirin-exacerbated respiratory disease (AERD) requires further investigation. OBJECTIVE: To investigate whether active smoke or ETS exposures are associated with an increased risk of developing AERD. METHODS: A total of 260 patients with AERD were enrolled in a case-control study with their respective asymptomatic spouses serving as matched controls. Multiple logistic regression analysis was used to examine the association of AERD with active smoking and ETS, adjusted for age, sex, and location of childhood residence. RESULTS: The AERD case patients were more likely to have ever smoked actively when compared with controls (odds ratio [OR], 1.54; 95% confidence interval [CI], 1.04-2.28). A significant association (OR, 3.46; 95% CI, 2.22-5.39) was found between childhood ETS exposure and AERD. If a patient was exposed to ETS during both childhood and adulthood, results showed an OR of 5.09 for developing AERD (95% CI, 2.75-9.43). However, no statistically significant association between AERD and ETS only during adulthood was found (OR, 1.60; 95% CI, 0.75-3.40), suggesting that the combined effect of childhood and adulthood ETS may be augmented by the prior childhood exposure. CONCLUSIONS: Active smoking and childhood ETS exposure are associated with increased odds of developing AERD. In particular, combined childhood and adulthood exposure had major effects. This study suggests that ETS is at least one contributor to the syndrome of AERD.

Aspirin-exacerbated respiratory disease: update on pathogenesis and desensitization.

Aspirin-exacerbated respiratory disease (AERD) is a unique syndrome of airway inflammation that frequently occurs in patients with nasal polyposis, chronic sinusitis, and asthma. These patients tend to have progressive and recalcitrant sinus disease requiring frequent surgical intervention and in many cases systemic corticosteroids. Much about the pathogenesis of AERD remains unclear, but environmental factors likely play a prominent role in its development. Avoidance of aspirin or nonsteroidal antiinflammatory drugs (NSAIDs) is imperative in the initial counseling of these patients. Because most of the exposure to these medications is available over the counter, most patients will experience a significant respiratory reaction to full therapeutic doses of seemingly innocent NSAIDs. Although the history of a reaction to aspirin or another NSAID is a very important part of making the diagnosis, the gold standard remains an observed aspirin challenge. Given the prevalence and usefulness of aspirin and NSAID therapy in primary care clinics, an accurate diagnosis should be made in all patients. Desensitization is an effective treatment option for many patients. Recent advances have made this procedure considerably safer and outpatient aspirin desensitization is now the standard of care.

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.

Methicillin-resistant Staphylococcus aureus pelvic abscesses in a female after gynecologic pelvic surgery.

Pelvic abscesses occurring after gynecologic pelvic surgery are uncommon. We describe the case of a woman who, after undergoing such a procedure, was found to have pelvic abscesses infected with methicillin-resistant Staphyloccocus aureus. The purpose of this report is to raise awareness of a life-threatening complication of gynecologic pelvic surgery.

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.

Aspirin sensitivity and desensitization for asthma and sinusitis.

NSAIDs-including aspirin (ASA)-that inhibit cyclooxygenase (COX)-1 induce nonallergic hypersensitivity reactions consisting of attacks of rhinitis and asthma. Such reactions occur exclusively in a subset of asthmatic patients who also have underlying nasal polyps and chronic hyperplastic eosinophilic sinusitis. We now refer to their underlying inflammatory disease of the entire respiratory tract as aspirin-exacerbated respiratory disease. This review focuses on descriptions of these patients; methods available to diagnose ASA-exacerbated respiratory disease; the unique ability of all NSAIDs that inhibit COX-1 to cross-react with ASA; lack of cross-reactivity with selective COX-2 inhibitors; an update on pathogenesis; and current thoughts about treatment, including ASA desensitization and daily ingestion of ASA itself.

A Tale of Two Knee Implants in the Same Person: Narcotics for the First and Anti-inflammatory Drugs for the Second.

Opioid addiction is a world-wide tragedy, with severe consequences for both the victims and the society that must care for them. The pathways to addiction are multiple but postoperative opioid prescriptions for pain management are a major contributor to this crisis. This case report describes the differences in pain management during 2 different arthroplasties of the knees in the same person. After the first arthroplasty of the right knee 10 years ago, postoperative opioids were used, but after the second arthroplasty of the left knee in 2007, anti-inflammatory drugs took the place of opioids. The first postoperative treatment with opioids was marked by addiction and a nasty withdrawal. The recovery of knee function, driving, and return to work were prolonged. After the second arthroplasty in 2007, a combination of meloxicam (COX-2 inhibitor), high-dose acetaminophen (COX-1 inhibitor at higher doses), and diclofenac topical gel (COX-1 inhibitor with local effects) produced excellent pain control and significant reduction in swelling of the operated knee. The clinical course was smooth and recovery was rapid. The patient was walking normally and driving a car at 2 weeks and took an airplane trip at 4 weeks. After arthroplasty, postoperative opioids may not be necessary for most people.