Matthew A. Rank

Ovalbumin content of influenza vaccines

Some 2009–2010 influenza vaccine package inserts indicate that each dose may contain up to 1 μg ovalbumin; others do not provide information on ovalbumin content. The ovalbumin content of influenza vaccines is important if these vaccines are administered to patients with egg allergy. In a previous publication (1) we (MAR and JTL) proposed a protocol for administration of influenza vaccine to patients with egg allergy when the ovalbumin content of the vaccine is unknown.

Safe administration of the seasonal trivalent influenza vaccine to children with severe egg allergy

BACKGROUND Anaphylaxis to egg or severe egg allergy has been considered a contraindication to receiving trivalent seasonal influenza vaccine (TIV). OBJECTIVE To evaluate the safety of TIV among severely egg allergic children. METHODS A 2-phase, multicenter study at 7 sites was conducted between October 2010 and March 2012. Inclusion criteria included a history of a severe reaction, including anaphylaxis, to the ingestion of egg and a positive skin test result or evidence of serum specific IgE antibody to egg. Phase 1 consisted of a randomized, prospective, double-blind, placebo controlled trial of TIV administration to egg allergic children, using a 2-step approach; group A received 0.1 mL of influenza vaccine, followed in 30 minutes if no reaction with the remainder of an age-appropriate dose, whereas group B received an injection of normal saline followed in 30 minutes if no reaction with the full 100% of the age-appropriate dose. Phase 2 was a retrospective analysis of single dose vs split-dose administration of TIV in eligible study participants who declined participation in the randomized controlled trial. RESULTS Thirty-one study participants were prospectively evaluated in the randomized controlled trial (group A, 14; group B, 17); 45.1% had a history of anaphylaxis after egg ingestion. A total of 112 participants were retrospectively evaluated (87 with the single dose and 25 with the split dose); 77.6% of participants had a history of anaphylaxis after egg ingestion. All participants in both phases received TIV without developing an allergic reaction. CONCLUSION TIV administration is safe even in children with histories of severe egg allergy. Use of 2-step split dosing appears unnecessary because a single dose was well tolerated.

Formulating an effective and efficient written asthma action plan.

Written asthma action plans (WAAPs) are recommended by national and international guidelines to help patients recognize and manage asthma exacerbations. Despite this recommendation, many patients with asthma do not have a WAAP. In addition, WAAPs vary widely in their readability and usability. To promote issuance and patient use, the WAAP should clearly define the decision (action) points, expected response, and expected time of response. The WAAP should also be easily integrated into a physicians busy practice. Herein, we describe the key elements of an effective WAAP, including concise, detailed recommendations regarding asthma exacerbation recognition (patient self-monitoring) and treatment.

Acute exacerbations of chronic rhinosinusitis occur in a distinct seasonal pattern

To the Editor: Chronic rhinosinusitis (CRS) is a common and debilitating problem that involves inflammation of the mucosal surfaces lining the nose and sinuses.1 Triggers leading to CRS disease exacerbation are not well characterized. Previous epidemiologic studies have focused on identification of risk factors for having a diagnosis of CRS rather than on risk factors that lead to disease exacerbation in those with an established CRS diagnosis.2 and 3 Given the insights gained from examining seasonal patterns of asthma exacerbations (a disease often linked to CRS),4 we performed a study that examined the seasonal pattern of CRS exacerbation visits using a unique database that electronically links residents of a single county in southeastern Minnesota (Olmsted County). We performed a retrospective cohort study following patients for up to 2 years (2003–2004) using existing medical records. Patients were identified by using the Rochester Epidemiology Project, an electronically linked medical record system that allows for examination of nearly all health care encounters in Olmsted County, Minnesota. Both sexes and all ages were included. Patients with a diagnosis of specific immune deficiency were excluded. A CRS exacerbation was defined as any visit with an International Classification of Diseases–Ninth Revisions (ICD-9) code of 473.xx and at least 1 of the following: a prescription for systemic antibiotics, systemic corticosteroid, plans for a semiurgent surgical intervention, emergency department or urgent care visit, or a hospitalization for CRS. Each medical record was reviewed to ensure subjects met inclusion criteria and that the prescribed medications were directly linked with the diagnosis of CRS. The study was approved by the Institutional Review Board of the Olmsted Medical Center and Mayo Clinic Rochester. Descriptive statistics were tabulated for subject demographics and visit frequencies. Seasonality was confirmed by defining 4 equal-length calendar seasons and comparing visit frequencies for equality across seasons with a χ2 test. For graphic displays, visit frequencies were smoothed by using a kernel smoother with a Parzen kernel and a bandwidth chosen empirically. One thousand one hundred four patients with a diagnosis of 473.xx were screened, and 800 patients had at least 1 visit that met our definition of a CRS exacerbation. Most subjects were female (65.6%) and white (94%). The mean age of the patients was 37 years, with 17.8% of the subjects defined as children (<18 years old). A total of 1217 CRS exacerbation visits were analyzed. The number of visits per subject over 2003–2004 ranged from 1 to 16, and 607 (75.9%) patients had only 1 CRS exacerbation visit. Primary care provider visits accounted for 55.7% of the visits, whereas allergy (13.7%), otolaryngology (13.1%), and emergency department/urgent care (13.1%) accounted for the nearly all of the remaining visits. Subjects were approximately twice as likely to present for a CRS exacerbation in winter months compared with spring, summer, or fall (P < .0001, Fig 1). The seasonal pattern of increased CRS exacerbation visits in winter was consistent between 2003 and 2004. Age and sex did not significantly affect the seasonal pattern of CRS exacerbation visits, although in both 2003 and 2004, the CRS exacerbation visit frequency of children began to increase earlier (more in fall than winter) compared with that seen in adults (Fig 2). Fig 1 Seasonal pattern of CRS exacerbation visits (n=1217). Each bar represents 1 weeks Fig 2 Seasonal pattern of CRS exacerbation visits by age and sex The findings from this study suggest that patients with CRS are most likely to present for disease exacerbation in the winter months in the upper Midwestern United States than in spring, summer, or fall seasons. Using the linked electronic medical record system in Olmsted County, Minnesota, we were able to use a definition of disease exacerbation that is based on health care use (escalating management, mostly prescriptions for systemic antibiotics or systemic corticosteroids) rather than billing data alone. There are important limitations when interpreting the data from this study. Screening patients based on ICD-9 codes relies on clinician billing diagnosis rather than an objective set of criteria. A risk for diagnostic misclassification exists, in particular that the increased winter visit frequency represented viral upper respiratory tract infections uncomplicated by sinusitis. The potential for this bias to occur is difficult to measure with our study design, and even if sinus computed tomographic scans were available from each visit, they might be difficult to interpret given that previous research has demonstrated that uncomplicated upper respiratory tract viral infections frequently result in significant sinus computed tomographic findings.5 A consensus definition of an acute exacerbation of CRS is not available. Therefore although we recognize that a surgical intervention and a prescription for antibiotics might represent different impressions of disease severity, we believed that evidence of management escalation was the best possible measurement that an exacerbation of CRS had occurred in our dataset. Another limitation of this study is that generalizing findings to other climates is difficult. Finally, the ethnic diversity in our sample might not represent other CRS populations well, and ethnic differences in the inflammatory characteristics of CRS have been demonstrated.6 Despite these limitations, we believe that these data uncovered a strong signal that patients with CRS exacerbations are more likely to visit for disease worsening during winter months. Several plausible hypotheses arise from these findings, including a potential relationship between CRS disease activity and viral infection, air quality, air temperature, air humidity, or indoor allergen/irritant exposure. These findings are important because they direct future research toward previously understudied explanations for CRS exacerbations. Data from this study also might help clinicians anticipate an increased need for CRS disease management during winter months.

The risk of asthma exacerbation after reducing inhaled corticosteroids: A systematic review and meta-analysis of randomized controlled trials

Asthma guidelines suggest reducing controller medications when asthma is stable.

The predictive value of skin testing in the diagnosis of local anesthetic allergy.

Local anesthetics are commonly used medications and can result in adverse reactions. The diagnostic workup of local anesthetic reactions remains controversial. This study was designed to determine the effectiveness of skin testing for local anesthetic allergy evaluation. A retrospective chart review was performed on patients undergoing local anesthetic skin testing. Patients were included if they underwent prick and intradermal skin testing followed by incremental subcutaneous challenge. Charts were further systematically reviewed to evaluate response to local anesthetics in the clinical setting after open subcutaneous challenge. One hundred seventy-eight patients underwent 227 local anesthetic skin tests. Two hundred twenty (97%) of the skin tests were negative. Of the negative skin tests results, 214 (97%) had negative challenge or probable non-IgE-mediated events during challenge. Three patients with six negative skin tests had a local reaction during the open subcutaneous challenge. Seven skin tests on five patients met the criteria for a positive skin test with local anesthetics. One patient had an equivocal local skin reaction with subcutaneous challenge without systemic effects. Three patients had a negative subcutaneous challenge and one patient did not undergo a challenge. Ninety-eight percent of patients receiving local anesthetics in the clinical setting after open subcutaneous challenge tolerated the medications. The negative predictive value of the local anesthetic skin test was 97% with few positive skin tests. Positive local anesthetic skin tests are uncommon and the local anesthetic skin tests have an excellent negative predictive value. Additional study with skin test-only protocols is warranted.

Antifungal therapy for chronic rhinosinusitis: The controversy persists

Purpose of reviewChronic rhinosinusitis is a debilitating disease seen frequently by allergist–immunologists. Recent research examining the pathophysiological mechanisms and treatment options for chronic rhinosinusitis have yielded contradicting results, particularly in regard to the role of fungi and antifungal therapies. Recent findingsRecent studies using antifungal therapies for chronic rhinosinusitis will be critically evaluated with careful attention to sample selection, length of the intervention, drug delivery system, drug stability and handling, assessment of compliance to study medications, and choice of outcome measures with attention to study power (both primary and secondary). Using this framework to evaluate currently available studies reveals limitations in studies showing a benefit for antifungal therapy and in studies showing no benefit (or harm). SummaryLimitations in studies that either support or refute the benefit of antifungal therapy for chronic rhinosinusitis prevent any firm conclusions about its efficacy.

Trigger recognition and management in poorly controlled asthmatics.

Previous studies using cross-sectional designs suggest that asthma trigger recognition and management are suboptimal in clinical practice. The objective of this study was to assess gaps between asthma guideline recommendations and clinical practice regarding asthma trigger recognition and management by tracking poorly controlled asthma patients over a 2-year period. A retrospective cohort study of a representative sample of 102 children and adult residents of Olmsted County, MN, with poor asthma control in 2003-2004 was performed. All medical records from each asthma-related visit were examined for documented asthma trigger inquiries, specific trigger avoidance advice, and for adherence to the trigger avoidance advice. One hundred two subjects made 686 asthma-related visits that were included for analysis. At least 1 trigger inquiry occurred in 83% of visits, with an average of 2.0 triggers queried per visit. The most common trigger inquiries were for infection (47%), environmental tobacco smoke (41%), and allergens (29%). The mean number of triggers queried was higher during exacerbation visits versus nonexacerbation visits (2.1 versus 1.8; p < 0.001) and in the emergency care settings compared with outpatient settings (2.4 versus 1.7; p < 0.001). Advice for managing asthma triggers was given in 30% of visits and adherence to trigger advice was evaluated at 6% of visits. Future interventions for improving asthma trigger management should be targeted to routine asthma outpatient visits, where trigger avoidance advice is infrequent and rarely addressed in follow-up visits.

Taming chronic cough

OBJECTIVE To review the available evidence on treating chronic cough to relay a thoughtful, evidence-based approach for the diagnosis and treatment of chronic cough. DATA SOURCES MEDLINE, PubMed, EMBASE, and CINAHL were searched using the following keywords: cough, asthma, gastroesophageal reflux, sinusitis, rhinitis (allergic, seasonal), postnasal drip, vocal cord dysfunction, lung disease (interstitial), bronchiectasis, and bronchoscopy. STUDY SELECTION Studies were selected based on their relevance to the diagnosis and treatment of chronic cough. Because of a lack of randomized prospective studies, nonrandomized and retrospective studies were considered, with their strengths and limitations noted. RESULTS Few randomized controlled trials have addressed the diagnosis and treatment of chronic cough. There are several prospective noncontrolled trials for adults with chronic cough that found a high percentage of cough resolution when using an approach that focused on the diagnosis and treatment of the most common causes: asthma, gastroesophageal reflux disease, and upper airway cough syndrome. Preliminary studies in children support an approach that distinguishes between a wet and dry cough, as well as an in-depth investigation of any specific symptoms that point to an underlying chronic illness. CONCLUSION Allergists, as experts in treating upper airway and lower airway disorders, are uniquely poised to diagnose and treat chronic cough.

Predicting which medication classes interfere with allergy skin testing.

Medications often interfere with allergy skin test interpretation. This study was performed to determine which medications interfere with allergy skin tests. We retrospectively reviewed skin-prick test results from patients who had discontinued H(1)-antagonists, tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), selective norepinephrine reuptake inhibitors (SNRIs), benzodiazepines, atypical antidepressants, antipsychotics, hypnotics, sedatives, proton pump inhibitors (PPIs), and H(2)-antagonists between 0 and 7 days before allergy skin testing. Ninety-seven subjects had taken second-generation H(1)-antihistamines within 7 days of skin testing; all patients who had stopped 3 days before testing had positive histamine controls. Two hundred sixty-eight skin tests performed on patients taking a single medication of interest showed that patients had the following percentages of a positive histamine control: TCAs, 56.5%; SNRIs, 100%; H(2)-blockers, 100%; SSRIs, 97%; PPIs, 97%; benzodiazepines, 85.7%; and atypical antidepressants/sedatives, 92.6%. The 580 patients taking multiple medications of interest showed that the odds ratio and 95% confidence intervals of a negative histamine test for patients taking TCAs were 6.33 (2.11-20.5), for H(1)-blockers were 4.95 (1.78-15.1), for benzodiazepines were 5.01 (1.72-15.80), for atypical antidepressants/sedatives were 3.11 (1.09-9.61), and for H(2)-blockers were 2.91 (0.97-9.37). The odds of a negative histamine test for SSRIs, SNRIs, or PPIs were not significantly increased. SSRIs, SNRIs, and PPIs are unlikely to interfere with skin testing. TCAs, H(1)-blockers, benzodiazepines, quetiapine, and mirtazapine should be discontinued temporarily if clinically able. H(2)-antagonists, bupropion, eszopiclone, trazodone, or zolpidem showed minimal interference with immediate hypersensitivity skin test histamine response.