Showing papers in "Annals of Allergy Asthma & Immunology in 2008"

Allergy diagnostic testing: An updated practice parameter

Abstract: I. Leonard Bernstein, MD; James T. Li, MD, PhD; David I. Bernstein, MD; Robert Hamilton, PhD, DABMLI; Sheldon L. Spector, MD; Ricardo Tan, MD; Scott Sicherer, MD; David B. K. Golden, MD; David A. Khan, MD; Richard A. Nicklas, MD; Jay M. Portnoy, MD; Joann Blessing-Moore, MD; Linda Cox, MD; David M. Lang, MD; John Oppenheimer, MD; Christopher C. Randolph, MD; Diane E. Schuller, MD; Stephen A. Tilles, MD; Dana V. Wallace, MD; Estelle Levetin, PhD; and Richard Weber, MD

Hereditary angiodema: a current state-of-the-art review, VII: Canadian Hungarian 2007 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema

Abstract: Background We published the Canadian 2003 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema (HAE; C1 inhibitor [C1-INH] deficiency) in 2004. Objective To ensure that this consensus remains current. Methods In collaboration with the Canadian Network of Rare Blood Disorder Organizations, we held the second Canadian Consensus discussion with our international colleagues in Toronto, Ontario, on February 3, 2006, and reviewed its content at the Fifth C1 Inhibitor Deficiency Workshop in Budapest on June 2, 2007. Papers were presented by international investigators, and this consensus algorithm approach resulted. Results This consensus algorithm outlines the approach recommended for the diagnosis, therapy, and management of HAE, which was agreed on by the authors of this report. This document is only a consensus algorithm approach and continues to require validation. As such, participants agreed to make this a living 2007 algorithm, a work in progress, and to review its content at future international HAE meetings. Conclusions There is a paucity of double-blind, placebo-controlled trials on the treatment of HAE, making levels of evidence to support the algorithm less than optimal. Controlled trials currently under way will provide further insight into the management of HAE. As with our Canadian 2003 Consensus, this 2007 International Consensus Algorithm for the Diagnosis, Therapy, and Management of HAE was formed through the meeting and agreement of patient care professionals along with patient group representatives and individual patients.

Preventive effects of sublingual immunotherapy in childhood: an open randomized controlled study.

Abstract: Background Sublingual immunotherapy (SLIT) has been proved to be effective in allergic rhinitis and asthma, but there are few data on its preventive effects, especially in children. Objective To evaluate the clinical and preventive effects of SLIT in children by assessing onset of persistent asthma and new sensitizations, clinical symptoms, and bronchial hyperreactivity. Methods A total of 216 children with allergic rhinitis, with or without intermittent asthma, were evaluated and then randomized to receive drugs alone or drugs plus SLIT openly for 3 years. The clinical score was assessed yearly during allergen exposure. Pulmonary function testing, methacholine challenge, and skin prick testing were performed at the beginning and end of the study. Results One hundred forty-four children received SLIT and 72 received drugs only. Dropouts were 9.7% in the SLIT group and 8.3% in the controls. New sensitizations appeared in 34.8% of controls and in 3.1% of SLIT patients (odds ratio, 16.85; 95% confidence interval, 5.73-49.13). Mild persistent asthma was less frequent in SLIT patients (odds ratio, 0.04; 95% confidence interval, 0.01-0.17). There was a significant decrease in clinical scores in the SLIT group vs the control group since the first year. The number of children with a positive methacholine challenge result decreased significantly after 3 years only in the SLIT group. Adherence was 80% or higher in 73.8% of patients. Only 1 patient reported systemic itching. Conclusions In everyday clinical practice, SLIT reduced the onset of new sensitizations and mild persistent asthma and decreased bronchial hyperreactivity in children with respiratory allergy.

Benefits and risks of danazol in hereditary angioedema: a long-term survey of 118 patients

Abstract: Background Hereditary angioedema (HAE) due to C1 inhibitor deficiency is clinically characterized by relapsing skin swellings, abdominal pain attacks, and life-threatening upper airway obstruction. Treatment with androgens prevents attacks for those with this condition. Objective To examine the benefits and risks of long-term treatment with danazol. Methods Data were generated retrospectively from 118 German and Danish patients who had HAE due to C1 inhibitor deficiency and were treated with danazol from 2 months to 30 years. The frequency and severity of acute attacks were registered before and during danazol treatment, and adverse effects to the treatment were noted. Data were collected by using standardized questionnaires. Results In all, 111 of 118 patients responded to danazol. During treatment, 54 of the 118 patients (45.8%) became symptom free or had 1 attack or less per year. In the other patients, hereditary angioedema ran a mild course. The frequency of acute attacks during danazol treatment was reduced to 16.2%, and the attacks were considerably milder than before treatment. Laryngeal edema was reduced to 4.8%. Adverse effects (weight gain, virilization, menstrual irregularities, headache, depression, and/or liver adenomas) occurred in 93 of the 118 patients and led to discontinuation of danazol therapy in 30 patients. Conclusions Danazol is highly beneficial in patients with frequent and severe attacks of HAE. Because the risk of adverse effects is high, close monitoring of patients is mandatory. However, many patients accept the adverse effects of prophylactic treatment to avoid the distressing and sometimes life-threatening attacks of this condition.

Increasing anaphylaxis hospitalizations in the first 2 decades of life: New York State, 1990 -2006.

Abstract: Background Although an increase in the occurrence of anaphylaxis has been reported in several parts of the world, this phenomenon has not been described in the United States. Objective To characterize anaphylaxis hospitalizations in New York State in patients younger than 20 years. Methods Using a statewide administrative database, hospital admissions of patients with an allergic disease (anaphylaxis, angioedema, urticaria, and allergy unspecified) as the primary diagnosis were analyzed from 1990 through 2006 in New York State. Admission rates were calculated for the allergic disease groups, as were hospitalization characteristics. Statistical modeling and group comparisons were performed with the use of negative binomial distribution analysis. Results For patients younger than 20 years, the anaphylaxis hospitalization rate increased by more than 4-fold during the study period and by 2002 exceeded the combined hospitalization rates for urticaria, angioedema, and unspecified allergy. After the widespread adoption of food anaphylaxis codes in 1994, food anaphylaxis predominated hospitalizations for anaphylaxis. Peanut was the most common food allergen in food anaphylaxis admissions. The anaphylaxis hospitalization rate for males was significantly greater than that of females (risk ratio, 1.45; 95% confidence interval, 1.26-1.66). Blacks were not disproportionately hospitalized for anaphylaxis. An overall bimodal age distribution showed peaks in the very young and in teens. Conclusion These data demonstrate that in a populous Northeastern state in the United States, anaphylaxis requiring hospitalization is increasing in the age group younger than 20 years.

Multicenter study of patients with angiotensin- converting enzyme inhibitor-induced angioedema who present to the emergency department

Abstract: Background Recent data are lacking about the number of patients with angiotensin-converting enzyme inhibitor (ACEI)-induced angioedema who present to the emergency department (ED). Current management of the condition and clinical outcomes also are not known. Objective To describe the clinical epidemiology of ACEI-induced angioedema in patients who present to the ED. Methods We performed a medical record review of ACEI-induced angioedema in patients who presented to 5 EDs in the Emergency Medicine Network. A structured data abstraction form was used to collect each patient's demographic factors, medical history, and details about the angioedema that prompted the ED visit. The medical record review also focused on treatment provided in the ED and subsequent need for hospitalization. Results We identified a total of 220 patients with ACEI-induced angioedema. The frequency of ACEI-induced angioedema among all patients with angioedema who presented to the ED was 30% (95% confidence interval, 26%-34%). The annual rate of visits for ACEI-induced angioedema was 0.7 per 10,000 ED visits. The most frequent presenting signs were shortness of breath, lip and tongue swelling, and laryngeal edema. Most patients (58%) were sent home directly from the ED, whereas 12% were regular inpatient admissions, 11% were admitted to the intensive care unit, and 18% were admitted under observation status ( Conclusion ACEI-induced angioedema accounted for almost one-third of angioedema treated in the ED, although it remains a rare ED presentation. A subgroup of these patients still needs inpatient hospitalization for management of upper airway angioedema.

Pearls and pitfalls of allergy diagnostic testing: report from the American College of Allergy, Asthma and Immunology/American Academy of Allergy, Asthma and Immunology Specific IgE Test Task Force.

Abstract: The intended purpose of this monograph is to provide a general overview of allergy diagnostics for health care professionals who care for patients with allergic disease. For a more comprehensive review of allergy diagnostic testing, readers can refer to the Allergy Diagnostic Practice Parameters. A key message is that a positive allergy test result (skin or blood) indicates only the presence of allergen specific IgE (called sensitization). It does not necessarily mean clinical allergy (ie, allergic symptoms with exposure). It is important for this reason that the allergy evaluation be based on the patient's history and directed by a health care professional with sufficient understanding of allergy diagnostic testing to use the information obtained from his/her evaluation of the patient to determine (1) what allergy diagnostic tests to order, (2) how to interpret the allergy diagnostic test results, and (3) how to use the information obtained from the allergy evaluation to develop an appropriate therapeutic treatment plan.

Probiotics for the treatment of allergic rhinitis and asthma: systematic review of randomized controlled trials

Abstract: Objective To evaluate the clinical evidence for the use of probiotics as a therapeutic modality for allergic rhinitis (AR) and asthma. Data Sources PubMed was searched to identify randomized controlled trials (RCTs) that studied the effects of probiotics on AR (n = 12) and asthma (n = 4). Study Selection RCTs that studied the effects of probiotics administration on the treatment but not the prevention of AR and asthma were selected for inclusion in this review. Results Nine of the 12 RCTs that evaluated clinical outcomes in AR showed an improvement due to the use of probiotics. All the RCTs that studied perennial AR showed lower symptom scoring and medication use with the use of probiotics compared with placebo. Also, 5 of the 8 RCTs that referred to seasonal AR suggested an improvement in clinical outcomes. Nine RCTs that reported various immunologic measurements of allergy found no significant probiotic effects. The RCTs that studied the effect of probiotic administration on the treatment of asthma showed no positive effects. Conclusions Probiotics may have a beneficial effect in AR by reducing symptom severity and medication use. Many more good-quality studies are needed to resolve this issue.

Epidemiologic and clinical features of anaphylaxis in Korea

Abstract: Background Little is known about the characteristics of anaphylaxis in Korea or even in Asia. Objective To evaluate the incidence of anaphylaxis and the clinical features of patients with anaphylaxis in a Korean tertiary care hospital. Methods We performed a retrospective review from January 1, 2000, through July 31, 2006, of 138 patients with anaphylaxis, including inpatients, outpatients, and emergency department visitors, in the Seoul National University Hospital. Results Among 978,146 patients, 138 (0.014%) had anaphylaxis. Two cardiopulmonary resuscitations were performed and 1 death occurred. The total mortality rate of anaphylactic patients was 0.0001%. The causes of anaphylaxes were drug (35.3%), food (21.3%), food-dependent exercise-induced (13.2%), idiopathic (13.2%), insect stings (11.8%), exercise induced (2.9%), blood products (1.5%), and latex (0.7%). Radiocontrast media and buckwheat were the leading causes of drug and food anaphylaxis, respectively. The organs most frequently involved in the anaphylaxis were cutaneous (95.7%), cardiovascular (76.8%), and respiratory (74.6%). The most common manifestations were dyspnea (71.3%), urticaria (81.9%), and angioedema (69.4%). Three of 138 patients (2.2%) had biphasic reactions. Conclusions The incidence, mortality rate, and clinical features of Korean patients with anaphylaxis were similar to rates for patients from other countries, despite some differences in causative agents.

Barriers to adherence to asthma management guidelines among inner-city primary care providers

Abstract: Background Health care provider adherence to national asthma guidelines is critical in translating evidence-based recommendations into improved outcomes. Unfortunately, provider adherence to the National Heart, Lung, and Blood Institute (NHLBI) guidelines remains low. Objective To identify barriers to guideline adherence among primary care professionals providing care to inner-city, minority patients with asthma. Methods We surveyed 202 providers from 4 major general medicine practices in East Harlem in New York, New York. The study outcome was self-reported adherence to 5 NHLBI guideline components: inhaled corticosteroid (ICS) use, peak flow (PF) monitoring, action plan use, allergy testing, and influenza vaccination. Potential barriers included lack of agreement with guideline, lack of self-efficacy, lack of outcome expectancy, and external barriers. Results Most providers reported adhering to the NHLBI guidelines for ICS use (62%) and for influenza vaccinations (73%). Self-reported adherence was 34% for PF monitoring, 9% for asthma action plan use, and 10% for allergy testing. Multivariate analyses showed that self-efficacy was associated with increased adherence to ICS use (odds ratio [OR], 2.8; P = .03), PF monitoring (OR, 2.3; P = .05), action plan use (OR, 4.9; P = .03), and influenza vaccinations (OR, 3.5; P = .05). Conversely, greater expected patient adherence was associated with increased adherence to PF monitoring (OR, 3.3; P = .03) and influenza vaccination (OR, 3.5; P = .01). Familiarity with specific guideline components and higher level of training were also predictors of adherence. Conclusions Lack of outcome expectancy and poor provider self-efficacy prevent providers from adhering to national asthma guidelines. Efforts to improve provider adherence should address these specific barriers.

Combination therapy with azelastine hydrochloride nasal spray and fluticasone propionate nasal spray in the treatment of patients with seasonal allergic rhinitis.

Abstract: Background To our knowledge, there are no published studies that evaluated the efficacy of azelastine hydrochloride nasal spray in combination with an intranasal corticosteroid, although anecdotal reports of the use of these agents in combination are common. Objective To determine if greater efficacy could be achieved with the intranasal antihistamine azelastine and the intranasal corticosteroid fluticasone propionate used concurrently compared with the efficacy of each agent alone. Methods This randomized, 2-week, multicenter, double-blind trial was conducted during the Texas mountain cedar season. After a 5-day placebo lead-in period, 151 patients with moderate to severe nasal symptoms were randomized to treatment with the following: (1) azelastine nasal spray, 2 sprays per nostril twice daily; (2) fluticasone nasal spray, 2 sprays per nostril once daily; or (3) azelastine nasal spray, 2 sprays per nostril twice daily, plus fluticasone nasal spray, 2 sprays per nostril once daily. The primary efficacy variable was the change from baseline in the total nasal symptom score (TNSS), consisting of sneezing, itchy nose, runny nose, and nasal congestion. Results All 3 groups had statistically significant ( P P Conclusions The significant improvement in the TNSS with combination therapy relative to the individual agents alone is in contrast to previously published studies that found no advantage with an oral antihistamine and an intranasal corticosteroid in combination. Azelastine nasal spray and fluticasone nasal spray in combination may provide a substantial therapeutic benefit for patients with seasonal allergic rhinitis compared with therapy with either agent alone.

Asthma : a syndrome composed of heterogeneous diseases

Abstract: Objective To review the concept that asthma comprises distinct heterogeneous inflammatory disorders characterized by patients showing different phenotypes with distinct genetic components, environmental causes, and immunopathologic signatures. Data Sources Ovid MEDLINE and PubMed databases from 1950 to the present time were searched for relevant articles and references regarding the heterogeneity of asthma. Study Selection Articles that described the various phenotypes of asthma were used for this review. Results Asthma is unlikely to be a single disease but rather a series of complex, overlapping individual diseases or phenotypes, each defined by its unique interaction between genetic and environmental factors. These conditions include syndromes characterized by allergen-exacerbated, nonallergic, and aspirin-exacerbated factors along with syndromes best distinguished by their pathologic findings (eosinophilic, neutrophilic, pauci-granulocytic), response to therapy (corticosteroid resistant), and natural history (remodeling prone). Additional phenotypes will almost certainly be identified as advances in genetics and other profiling methods are made and will be accompanied by the availability of clear biomarkers for distinguishing among them. Conclusions Responses to asthma medications vary considerably among patients, likely reflecting, at least in part, the differing sensitivities of the various asthma phenotypes. Selecting the best possible treatment course in individual patients will be aided by clearly identifying the different phenotypes. Physicians need to recognize this when making decisions to adjust treatment to improve asthma control.

Predicting outcomes of oral aspirin challengesin patients with asthma, nasal polyps, andchronic sinusitis

Abstract: Background A definitive diagnosis of aspirin-exacerbated respiratory disease (AERD) requires a positive oral aspirin challenge (OAC), but predicting which patients will have positive challenges is often difficult. Objective To analyze information about historical aspirin- and nonsteroidal anti-inflammatory drug (NSAID)-associated respiratory reactions and clinical characteristics as potential markers to predict positive OACs. Methods A total of 243 patients underwent OACs. Data related to previous reactions and clinical characteristics of patients were correlated with the result of the OACs. Results Without prior exposure to aspirin or NSAIDs, the chance of a positive OAC was 5 in 12 (42%) but was 198 in 231 (86%) for those with a history of aspirin- and NSAID-associated asthma attacks. Sex, atopy, number of sinus infections per year, and number of sinus surgical procedures were not associated with positive OACs. Patients with 2 or more prior aspirin- and NSAID-associated respiratory reactions had an 89% chance of having a positive OAC vs single reactors (80%; P = .04). Mild or moderate prior reactions were associated with 84% or 80% positive OACs, whereas 100% of the 45 patients with severe prior reactions had positive OACs (P = .007). Except for hospitalizations, treatment locations of prior reactions (home or emergency department) did not seem to make any difference. Logistic regression identified age, sense of smell, and multiple prior reactions as independent risk factors associated with positive OACs. Conclusions Age younger than 40 years, poor sense of smell, multiple prior respiratory reactions, and severe prior asthmatic reactions associated with aspirin and NSAIDs significantly increased the chances of a positive OAC.

Hereditary angiodema : a current state-of-the-art review, IV: short-and long-term treatment of hereditary angioedema: out with the old and in with the new?

Abstract: Objective To provide a context to understand the opportunity for novel therapeutic modalities to transform the treatment of hereditary angioedema (HAE). Data Sources MEDLINE and PubMed were searched to identify studies involving current treatment of HAE in the United States. Study Selection Studies were selected based on their relevance to the treatment of HAE. Results The current HAE treatment strategy is far from satisfactory, and its limitations create an unmet clinical need. Current prophylactic treatment exposes patients with HAE to significant risk of adverse effects, and the efficacy of prophylactic treatment, although generally good, is far from perfect. Conclusions No specific treatment is currently available in the United States for acute HAE attacks that will reliably work, resulting in a significant unmet clinical need. The emergence of several promising drugs for the treatment of HAE attacks is, thus, an extraordinarily important development in the management of these patients.

The logarithmic transformation and the geometric mean in reporting experimental IgE results: what are they and when and why to use them?

Abstract: Background Immunologic data, such as IgE and interleukin 4, tend to have positively skewed distributions with a long tail of larger values. This renders analyses based on normal distribution theory questionable (eg, t tests and analysis of variance) and distorts the sample mean as a measure of central tendency. These problems can be addressed through analysis of log-transformed data. Data analyzed in this fashion are summarized with the geometric mean. Objective To elucidate the use of the logarithmic transform and the geometric mean in the analysis of immunologic data. Methods The analysis may be conducted by transforming the data to a logarithmic scale to achieve a bell-shaped (approximately normal) distribution. The bell-shaped distribution needed to validate statistical inferences is only achieved in the transformed scale. In summarizing the research findings, the statistical analyst usually will transform means and confidence intervals from the logarithmic scale back to the original scale of measurement. Statistical inferences in the log scale remain valid for the data. The result of back transforming the mean of logarithmic values to the original scale is the geometric mean. This statistic is less subject to distortion by the unusually large values in the tail of the positively skewed distribution of the data. Results A brief example is used to illustrate this type of analysis. Conclusions Logarithmic transformation permits valid statistical inference for positively skewed immunologic data. A result of this analysis is the geometric mean, which is a better measure of central tendency of this data type than the usual sample mean.

Effect of mouse allergen and rodent environmental intervention on asthma in inner-city children

Abstract: Background Mouse allergens are prevalent in inner-city households, and increasing levels of exposure are associated with sensitization in children with asthma. Objectives To examine mouse allergen sensitization and exposure in inner-city children, mouse allergen as an independent risk factor for asthma morbidity, and the efficacy of a rodent environmental intervention. Methods We conducted a subanalysis of children with asthma aged 5 to 11 years enrolled in the Inner-City Asthma Study. After randomization, 150 participants received a home rodent-specific environmental intervention. Asthma morbidity measures were obtained bimonthly. Bedroom dust was collected and analyzed for Mus m 1 at baseline and every 6 months for 2 years. Results Twenty-two percent of children tested positive to mouse. Most bedrooms (80%) had detectable mouse allergen. Sensitization occurred at low levels of exposure. Sensitization and exposure were associated with increased asthma morbidity, including hospitalizations. Mouse allergen levels on the bedroom floor decreased 27.3% (95% confidence interval, −46.1% to −1.9%) in intervention homes. Mouse allergen reduction was associated with less missed school, sleep disruption, and caretaker burden but not symptoms or medical utilization. Conclusions Mouse allergen is prevalent in inner-city homes. Sensitization seems to occur at low levels of exposure. Mouse allergen is an independent risk factor for asthma morbidity. The described environmental intervention reduced mouse allergen levels and asthma-related sleep and activity disturbance.

Efficacy of probiotics in the treatment of pediatric atopic dermatitis: a meta-analysis of randomized controlled trials

Abstract: Background Several articles describing the efficacy of probiotics in atopic dermatitis (AD) have been published. However, not all studies support a similar outcome. Objective To determine whether probiotics are efficacious in treating AD and to explore whether type of probiotic used, duration of therapy, patient age, severity of disease, and IgE sensitization are factors in determining efficacy. Methods For this meta-analysis of randomized controlled trials describing the efficacy of probiotics in AD, a comprehensive search was performed of databases through January 2008. Three reviewers independently evaluated the studies for methodological qualities. All the data were analyzed, and forest plots were evaluated for the overall efficacy of probiotics in AD and the therapeutic benefit to subgroups of selected patient populations. Results Eleven studies were identified, and data from 10 studies (n = 678) were available to analyze. There was an overall statistically significant difference favoring probiotics compared with placebo in reducing the Scoring of Atopic Dermatitis Severity Index score (mean change from baseline, −3.01; 95% confidence interval, −5.36 to −0.66; P = .01). Children with moderately severe disease were more likely to benefit. Duration of probiotic administration, age, and type of probiotic used did not affect outcome. Conclusion Data from this meta-analysis suggest a modest role for probiotics in pediatric AD. The effect is seen in moderately severe rather than mild disease.

Prescriptions for self-injectable epinephrine and follow-up referral in emergency department patients presenting with anaphylaxis

Abstract: Background Anaphylaxis guidelines recommend that patients with a history of anaphylactic reaction should carry self-injectable epinephrine and should be referred to an allergist. Objective To evaluate how frequently patients dismissed from the emergency department after treatment for anaphylaxis received a prescription for self-injectable epinephrine or allergist referral. Methods A retrospective medical record review identified patients with anaphylaxis in a community-based study from 1990 through 2000. Records of patients with Hospital Adaptation of the International Classification of Diseases, Second Edition or International Classification of Diseases, Ninth Revision codes representing anaphylaxis were reviewed, and a random sample of patients with associated diagnoses was also reviewed. Patients who met the criteria for diagnosis of anaphylaxis were included in the study. Results Among 208 patients identified with anaphylaxis, 134 (64.4%) were seen in the emergency department and discharged home. On dismissal, 49 patients (36.6%; 95% confidence interval [CI], 28.4%-44.7%) were prescribed self-injectable epinephrine, and 42 patients (31.3%; 95% CI, 23.5%-39.2%) were referred to an allergist. Treatment with epinephrine in the emergency department (odds ratio, 3.6; 95% CI, 1.6-7.9; P = .001) and insect sting as the inciting allergen (odds ratio, 4.0; 95% CI, 1.6-10.5; P = .004) were significantly associated with receiving a prescription for self-injectable epinephrine. Patient age younger than 18 years was the only factor associated with referral to an allergist ( P = .007). Conclusions Most patients dismissed after treatment for anaphylaxis did not receive a self-injectable epinephrine prescription or allergist referral. Emergency physicians may be missing an important opportunity to ensure prompt treatment of future anaphylactic reactions and specialized follow-up care.

Risk of angioedema with angiotensin receptor blockers in patients with prior angioedema associated with angiotensin-converting enzyme inhibitors: a meta-analysis

Abstract: Background Patients who have angioedema after taking angiotensin-converting enzyme inhibitors (ACE-Is) have been reported to develop angioedema when taking an angiotensin receptor blocker (ARB), but few studies quantify the risk. Objective To perform a systematic review of the literature. Methods A literature search was performed in MEDLINE, EMBASE, BIOSIS, and Current Contents, with no limitations from January 1990 to May 2007. Any article that described a cohort of patients who had angioedema after taking an ACE-I, were subsequently exposed to an ARB, and were followed for a least 1 month were included. The percentage of patients who had angioedema was abstracted from each article, and confidence intervals were calculated using the exact binomial method. The pooled percentage was calculated with the inverse variance method. Results Two-hundred fifty-four unique articles were identified, and 3 articles met inclusion criteria, which described 71 patients with the outcome of interest. One was a randomized controlled trial and 2 were retrospective cohorts. These articles described both confirmed and possible cases of angioedema. The risk of angioedema was 9.4% (95% confidence interval, 1.6%-17%) for possible cases and 3.5% (95% confidence interval, 0.0%-9.2%) for confirmed cases. No fatal events were reported. No statistical heterogeneity was reported between trials ( P > .3). Conclusions Limited evidence suggests that for patients who develop angioedema when taking an ACE-I, the risk of development of any subsequent angioedema when taking an ARB is between 2% and 17%; for confirmed angioedema, the risk is 0% to 9.2%. This information will aid clinicians in counseling patients regarding therapy options after development of angioedema due to ACE-Is.

European allergen extract units and potency: review of available information

Abstract: Background There is considerable variability in how allergen extract potency is measured and reported worldwide. In Europe, where many sublingual immunotherapy studies have been conducted, manufacturers report allergen extract potency as units based on an in-house reference, making it difficult to understand the exact doses used and to compare studies. Objectives To describe the various methods of expressing extract potency that European allergen extract manufacturers use and to gather reports on the micrograms of major allergen of the in-house units of European allergen extract manufacturers. Methods Information was derived from 3 sources: data on extract potency in micrograms of major allergen in articles on sublingual immunotherapy found by PubMed (references through October 2005) and in reference articles, brochures on allergen extracts from the manufacturers, and information provided by structured questionnaires e-mailed to the manufacturers. Results All but 1 of the European allergen extract manufacturers use in-house reference standards that are based on titrated skin prick testing of allergic patients. Subsequently, in vitro tests compare the potency of commercial batches with the in-house reference and potency is assigned as arbitrary units. Most manufacturers measure major allergen content of their standardized products but do not release this information with the package insert. Diversity in major allergen content was found. Conclusions Micrograms of major allergens given in articles on sublingual immunotherapy to express the dose administered cannot be used to translate the dose to US extracts. Extract potency can only be compared if uniform test methods and reference extracts are used.

Acupuncture in patients with allergic rhinitis: a pragmatic randomized trial

Abstract: Background Acupuncture is widely used in patients with allergic rhinitis, but the available evidence of its effectiveness is insufficient. Objective To evaluate the effectiveness of acupuncture in addition to routine care in patients with allergic rhinitis compared with treatment with routine care alone. Methods In a randomized controlled trial, patients with allergic rhinitis were randomly allocated to receive up to 15 acupuncture sessions during a period of 3 months or to a control group receiving no acupuncture. Patients who did not consent to random assignment received acupuncture treatment. All patients were allowed to receive usual medical care. The Rhinitis Quality of Life Questionnaire (RQLQ) and general health-related quality of life (36-Item Short-Form Health Survey) were evaluated at baseline and after 3 and 6 months. Results Of 5,237 patients (mean [SD] age, 40 [12] years; 62% women), 487 were randomly assigned to acupuncture and 494 to control, and 4,256 were included in the nonrandomized acupuncture group. At 3 months, the RQLQ improved by a mean (SE) of 1.48 (0.06) in the acupuncture group and by 0.50 (0.06) in the control group (3-month scores, 1.44 [0.06] and 2.42 [0.06], respectively; difference in improvement, 0.98 [0.08]; P P Conclusions The results of this trial suggest that treating patients with allergic rhinitis in routine care with additional acupuncture leads to clinically relevant and persistent benefits. In addition, it seems that physician characteristics play a minor role in the effectiveness of acupuncture treatment, although this idea needs further investigation.

Clinical benefits of combination treatment with mometasone furoate nasal spray and loratadine vs monotherapy with mometasone furoate in the treatment of seasonal allergic rhinitis

Abstract: Background Intranasal corticosteroids and nonsedating antihistamines are the drug classes most often prescribed to treat allergic rhinitis (AR). Treatment guidelines recommend a combination of these agents for moderate-to-severe AR. However, clinical studies have found that combining an antihistamine with an intranasal corticosteroid provides few or no advantages over monotherapy with an intranasal corticosteroid. Objective To compare the efficacy of mometasone furoate nasal spray (NS) plus loratadine with that of monotherapy with the individual agents in patients 12 years and older with at least a 2-year history of seasonal AR. Methods In a multicenter, randomized, double-blind, parallel-group, placebo-controlled clinical study, 702 patients were randomized to receive mometasone furoate NS, 200 μg, plus loratadine, 10 mg (n = 169); mometasone furoate NS, 200 μg (n = 176); loratadine, 10 mg (n = 181); or placebo (n = 176) once daily for 15 days. Primary efficacy variables were total nasal symptom score (TNSS) and total symptom score (TSS) as recorded on diary cards. Results No statistically significant differences were observed between mometasone furoate NS plus loratadine and mometasone furoate NS monotherapy for the primary efficacy variables. For TNSS and TSS, all 3 active drug therapies were more effective than placebo ( P ≤ .02). Both mometasone furoate NS treatment regimens were more effective than loratadine or placebo for TNSS ( P P ≤ .03 for both), whereas loratadine was more effective than placebo for TNSS only ( P = .02). Conclusions Combination therapy with mometasone furoate NS and loratadine provided benefits similar to monotherapy with mometasone furoate NS for the symptoms of seasonal AR. Therefore, mometasone furoate NS monotherapy was shown to be an effective treatment for seasonal AR.

Asthma control during pregnancy and the risk of preterm delivery or impaired fetal growth

Abstract: Background Concerns regarding potential harmful effect of medications on fetuses often result in inadequate treatment of asthma in pregnancy, whereas risks posed by poorly controlled maternal asthma are often underestimated. Objective To evaluate the effect of maternal asthma on preterm delivery and fetal growth. Methods Study participants were individuals enrolled in the Organization of Teratology Information Specialists Asthma Medications in Pregnancy Study between February 1, 1998, and December 31, 2003. Pregnant women with physician-diagnosed asthma (n = 719) evaluated their asthma control repeatedly during pregnancy based on symptom frequency and interference with daily activities and sleep and reported hospitalizations and unscheduled clinic visits for asthma exacerbations. The incidence of preterm delivery, the incidence of intrauterine growth restriction, and mean birth weight were evaluated relative to asthma symptom control and exacerbation measures. Results The incidence of preterm delivery was significantly higher among patients with inadequate asthma symptom control during the first part of pregnancy (11.4%) compared with patients with adequate asthma control (6.3%; P = .02). Similarly, patients who were hospitalized for asthma during pregnancy had a higher incidence of preterm delivery (16.4%) compared with asthmatic women without a history of hospitalization (7.6%; P = .02). The effect seemed independent from use of systemic corticosteroids and other covariates. Neither the incidence of intrauterine growth restriction nor mean birth weight varied by any measures of asthma symptom control or exacerbations. Conclusions This study demonstrates a substantial risk for preterm delivery posed by poorly controlled maternal asthma and provides additional evidence regarding the importance of adequate treatment of asthma in pregnancy to maintain optimal asthma control.

Skin testing and oral penicillin challenge in patients with a history of remote penicillin allergy

Abstract: Background Penicillin administration is usually contraindicated in penicillin-allergic patients with positive skin test results. Objective To examine whether penicillin oral challenge for patients with a history of remote non-life-threatening allergic reaction to penicillin can be well tolerated irrespective of skin test results. Methods In a prospective open-label trial, 8,702 individuals were screened between November 1998 and January 2000. Of 687 patients with a non-life-threatening allergic reaction to penicillin, occurring longer than 3 years earlier, 169 were enrolled. Regardless of the response to penicillin skin testing, patients received the usual 1-day dosage of penicillin and amoxicillin, on 2 separate occasions. Two to 6 years later, a follow-up was conducted to assess the outcomes of further penicillin administration. Results A total of 272 combined skin tests and oral challenges were performed on 169 patients. Among 137 challenges with a positive skin test result and 135 patients with a negative skin test result, 9 (6.6%) and 5 (3.7%) ( P = .29), respectively, developed a mild rash to oral challenge. At follow-up, 2 to 6 years afterward, 3 of 55 patients (5.5%) who were given a full treatment course of penicillin developed a mild skin eruption. Conclusions Positive penicillin skin test results for patients with a remote history of non-life-threatening allergic reaction to penicillin were not associated with a greater prevalence of adverse reactions to oral challenge with penicillin than negative results. Because skin testing is considered the gold standard and the safest method for predicting tolerance to penicillin administration, oral penicillin challenge may be used as a diagnostic method only in these specific patients when skin testing is not feasible.

Discrepancy between clinical asthma control assessment tools and fractional exhaled nitric oxide.

Abstract: Background Asthma is an inflammatory disease, yet clinical tools that evaluate asthma control do not include measures of inflammation. Objective To determine the correlation between fractional exhaled nitric oxide (FeNO) and each of 5 asthma control evaluation tools, namely, the Asthma Control Questionnaire (ACQ), the Asthma Control Test (ACT), the National Asthma Education and Prevention Program (NAEPP) goals of therapy, the Joint Task Force Practice Parameter (JTFPP) on attaining optimal asthma control, and the Global Initiative for Asthma (GINA) guidelines. Methods Patients 6 years or older who had asthma were clinically evaluated by an asthma specialist. Patients completed the ACT and ACQ and underwent spirometry and FeNO measurement. The physician was blinded to FeNO results until asthma control assessments were concluded. Correlations between FeNO level and each clinical evaluation tool were calculated. Results One hundred patients 6 to 86 years old were enrolled. No significant association was found between FeNO level and asthma control based on ACQ ( P > .99), ACT ( P = .53), NAEPP ( P = .53), JTFPP ( P = .30), or GINA ( P = .86) criteria. Agreement was high among the NAEPP, the JTFPP, and GINA; moderate between the ACQ and the ACT; and poor to fair between the ACT or the ACQ and the other 3 tools. Conclusions In addition to clinical evaluation, the incorporation of FeNO measurement in evaluating asthma is likely to lead to a more optimal pharmacotherapy, guidance in adjusting the dosage of anti-inflammatory agents, and positive long-term disease outcome.

Incremental prognostic factors associated with cow's milk allergy outcomes in infant and child referrals: the Milan Cow's Milk Allergy Cohort study

Abstract: Background The prognosis for many children with cow's milk allergy (CMA) is remission within 3 years, and the clinical parameters that predict duration of disease have not been measured incrementally. Objective To prospectively determine prognostic predictors of tolerance in a random cohort of referrals using CMA workup outcomes as covariates and tolerance as the status variable in a duration model of CMA. Methods The 2001-2006 Milan Cow's Milk Allergy Cohort (MiCMAC) enrolled children referrals using double-blind, placebo-controlled food challenges (DBPCFCs) as study end points (confirmation of CMA; onset of tolerance). The Cox regression model was used to analyze all clinical factors that contributed to tolerance. Covariates analyzed were skin, gastrointestinal, and respiratory symptoms; history and demographics at presentation; age at diagnosis and DBPCFC outcomes; sensitization (skin and serum) by cow's milk protein fractions; sensitization to other food and inhalant allergens; total IgE levels; specific IgE concentrations for cow's milk protein fractions, other ingestants, and aeroallergens; and threshold doses at DBPCFC. Sensitization and DBPCFC were performed at 6-month intervals. Results A total of 112 infants were enrolled (mean [SD] age, 13.85 [9.84] months), and 59 achieved tolerance (mean [SD] age when tolerance was achieved, 27.58 [11.81] months). On univariate analysis, asthma and/or rhinitis at presentation was an independent predictor of persistence (hazard ratio [HR], 2.19; 95% confidence interval [CI], 1.26-3.82). On multivariate analysis, predictors of persistence were a fresh milk wheal diameter increment of 1 mm (HR, 1.18; 95% CI, 1.07-1.31) and a positive skin prick test result with soy (HR, 6.99; 95% CI, 1.56-31.25). Conclusions This is the first study, to our knowledge, to identify incremental biological predictors of delayed tolerance to cow's milk in children that should be integrated into DBPCFC schedules for CMA in infants.

Allergies to sulfonamide antibiotics and sulfur-containing drugs

Abstract: Objective To provide a literature review and clinical summary of the evaluation and management of sulfonamide drug reactions. Data Sources Published English-language medical literature. Study Selection Selected trials of drug desensitization protocols. Results Obtaining a detailed history is invaluable in assessing a history of reactions to sulfonamide medications, because allergy to these drugs remains a clinical diagnosis at present. Numerous efficacious drug desensitization protocols for management have been published and are reviewed in detail. Conclusions The term sulfa allergy is imprecise and misleading and therefore should be discouraged. There are important distinctions between sulfonylarylamines (antimicrobial sulfonamides), nonarylamine (nonantimicrobial) sulfonamides, and sulfones, with regard to allergic and other adverse drug reactions. Most reactions to sulfonylarylamines probably result from multifactorial immunologic and toxic metabolic mechanisms, whereas less is known about the precise mechanisms of reactions to other sulfur-containing drugs.

Ocular symptom reduction in patients with seasonal allergic rhinitis treated with the intranasal corticosteroid mometasone furoate.

Abstract: Background Allergic rhinitis (AR) is more appropriately termed allergic rhinoconjunctivitis owing to the equally bothersome nasal and ocular symptoms. Extensive evidence supports the ability of intranasal corticosteroids to reduce nasal symptoms of AR, although less evidence is available to define clearly their impact on allergic conjunctivitis. Objective To determine the effect of the intranasal corticosteroid mometasone furoate nasal spray (NS) on the ocular symptoms of seasonal AR. Methods This retrospective pooled analysis of 4 placebo-controlled clinical studies randomized patients 12 years and older with symptomatic seasonal AR to receive mometasone furoate NS, 200 μg once daily (n = 491), or placebo (n = 492). Ocular symptom (eye tearing [epiphora], itching [pruritus], and redness [erythema]) severity was rated by patients twice daily on a 4-point scale (0 = none to 3=severe) in the morning and evening, with scores averaged to obtain a daily mean score. Efficacy variables were the pooled mean change from baseline in the averaged morning and evening total ocular symptom score (TOSS) and the individual ocular symptom scores. Results The change in mean TOSS from baseline to days 1 to 15 was −1.33 (−19.8%) with mometasone furoate NS and −0.93 (−5.6%) with placebo ( P Conclusions This detailed analysis of an intranasal corticosteroid on individual ocular symptoms supports the positive impact of mometasone furoate NS on ocular symptoms.

Atopic irritable bowel syndrome: a novel subgroup of irritable bowel syndrome with allergic manifestations

Abstract: Background Mast cells have a primary role in atopy. Mast cells may play a unique role in a subgroup of patients with irritable bowel syndrome (IBS). This observation suggests a link between atopic disorders and IBS. Objective To determine whether there is an association between atopic disorders and IBS. Methods We undertook a prospective study using structured questionnaires. We administered questionnaires to 125 consecutive patients seen in the following clinics from July 1 through October 31, 2001: allergy/immunology (AI) (n = 39), gastroenterology (n = 36), and general medicine (n = 50). The survey included questions detailing gastrointestinal and allergic symptoms. Diagnosis of IBS was based on Rome II criteria. Diagnosis of atopy was based on clinical parameters. Results The AI clinic reported a significantly ( P = .015) higher rate of IBS than the general medicine clinic. The IBS incidence reported in the AI clinic was similar to that reported in the gastroenterology clinic. The likelihood of IBS was significantly higher in patients with seasonal allergic rhinitis (2.67 times; 95% confidence interval [CI], 1.10-6.49; P = .03), patients with allergic eczema (3.85 times; 95% CI, 1.72-8.60; P = .001), and patients with depression (2.56 times; 95% CI, 1.05-6.14; P = .04). Patients reporting atopic symptoms (seasonal allergic rhinitis, allergic eczema, and asthma) were 3.20 times (95% CI, 1.20-8.50) ( P = .02) more likely to fulfill the criteria for IBS. Conclusions Adults with atopic symptoms report a high incidence of IBS, suggesting a link between atopy and IBS. We proposed a subgroup of patients with IBS (atopic IBS) who have typical IBS symptoms in association with atopic manifestations. Identifying atopic vs nonatopic IBS may help in identifying the underlying pathophysiologic mechanisms and therapeutic options.

Relationship of the Asthma Control Test with pulmonary function and exhaled nitric oxide

Abstract: Background The Asthma Control Test (ACT) is a short, simple, patient-based tool for identifying patients with poorly controlled asthma; however, its value in practice has yet to be demonstrated. Objective To clarify the relationship of ACT scores and clinical parameters, including pulmonary function tests, peak expiratory flow (PEF) indices, and exhaled nitric oxide (eNO) levels. Methods The study included 105 patients with asthma who underwent routine checkups by asthma specialists since September 1, 2006, through January 31, 2007. All patients had been taking inhaled corticosteroids with or without other medications for asthma for at least 3 months. The patients completed the ACT questionnaire and underwent testing for eNO and spirometry. PEF indices, including PEF percentage of predicted value (%PEF), lowest PEF during 1 week expressed as a percentage of the highest PEF (Min%Max PEF), and PEF variability, were also analyzed in patients undergoing PEF monitoring. Results The ACT scores ranged from 8 to 25 (median, 24), and total control was obtained in 45 patients (42.8%). The PEF indices and eNO values in the total control group were significantly better than those in the less controlled groups. However, the ACT scores were weakly correlated with percentage of predicted forced expiratory volume in 1 second ( r = 0.219), %PEF ( r = 0.387), Min%Max PEF ( r = 0.354), PEF variability ( r = −0.351), and eNO values ( r = −0.310). Total control of ACT included uncontrolled conditions in physiologic and inflammatory parameters. Conclusion ACT should be used in combination with pulmonary function tests and/or eNO measurements.