Sandra C. Christiansen

Aspirin desensitization treatment of aspirin-sensitive patients with rhinosinusitis-asthma : Long-term outcomes

BACKGROUND Aspirin-sensitive patients with asthma experience continuous inflammation of their nasal and sinus tissues, complicated by recurrent sinusitis, which frequently leads to asthma attacks. Systemic corticosteroid therapy and sinus or polyp surgery are currently required to control underlying rhinosinusitis, and bursts of corticosteroids are used for asthma control. OBJECTIVE After aspirin desensitization therapy, objective measures of respiratory disease activity, linked to the need for systemic corticosteroids and sinus surgery, were studied to determine whether any changes occurred. METHODS Sixty-five aspirin-sensitive patients with asthma underwent aspirin challenge, followed by aspirin desensitization and daily treatment with aspirin over 1 to 6 years (mean, 3.1 years). Clinical outcome measurements before aspirin desensitization treatment and during follow-up were analyzed for the larger group of 65 patients and subgroups (29 patients receiving therapy for 1 to 3 years and 36 patients receiving therapy for 3 to 6 years). RESULTS In the larger group of 65 patients, there were significant reductions in numbers of sinus infections per year (median, 6 to 2), hospitalizations for treatment of asthma per year (median, 0.2 to 0), improvement in olfaction (median, 0 to 2), and reduction in use of systematic corticosteroids (mean, 10.2 to 2.5 mg) with p values less than 0.0001. Numbers of sinus and polyp operations per year were significantly reduced (median, 0.2 to 0; p = 0.004), and doses of nasal corticosteroids (in micrograms) were significantly reduced (mean dose, 139 to 106 micrograms, p = 0.01). Emergency department visits and use of inhaled corticosteroids were unchanged. CONCLUSIONS The results support a role for aspirin desensitization treatment of aspirin-sensitive patients with rhinosinusitis-asthma.

Prevalence of cross-sensitivity with acetaminophen in aspirin-sensitive asthmatic subjects

OBJECTIVE Cross-sensitivity between aspirin and acetaminophen in aspirin-sensitive asthmatic patients has been reported with frequencies ranging from 0% to 29%. The relationship is dose-dependent for acetaminophen challenges, ranging between 300 and 100 mg. METHODS To determine the prevalence of cross-sensitivity to high-dose acetaminophen, we performed single-blind acetaminophen oral challenges with 1000 mg and 1500 mg in 50 aspirin-sensitive asthmatic patients and in 20 non-aspirin-sensitive asthmatic control subjects. RESULTS Overall, 17 of 50 (34%) of aspirin-sensitive asthmatic patients reacted to acetaminophen in doses of 1000 to 1500 mg (95% confidence interval: 20% to 49%). By contrast, none of the 20 non-aspirin-sensitive asthmatic patients reacted to acetaminophen (95% confidence interval: 0% to 14%). This difference was highly significant (p = 0.0013), supporting the hypothesis that cross-sensitivity between aspirin and acetaminophen is unique in aspirin-sensitive asthmatic patients. CONCLUSION Although high-dose ( > 1000 mg) acetaminophen cross-reactions with aspirin were significant with respect to frequency (34%), such reactions included easily reversed bronchospasm in only 22%, and were generally mild. We recommended that high doses of acetaminophen (1000 mg or greater) should be avoided in aspirin-sensitive asthmatic patients.

Hereditary angioedema with normal C1 inhibitor function: consensus of an international expert panel.

A new form of hereditary angioedema (HAE) with normal C1 inhibitor (C1INH) was first described in 2000. The lack of clear diagnostic criteria, the heterogeneity among affected patients, and the varying names given to this disease have led to substantial confusion among both physicians and patients. This study was designed to bring more clarity to the diagnosis and potential treatment of HAE with normal C1INH. An international symposium of experts was convened to review the field and develop consensus opinions that could help clinicians who evaluate and manage these patients. Criteria were developed for the diagnosis of HAE with normal C1INH in patients with recurrent angioedema in the absence of concurrent urticaria. In addition, potential therapeutic strategies are discussed. The consensus criteria developed during this symposium will allow physicians to better diagnose and treat patients with HAE with normal C1INH.

The association of obesity and asthma severity and control in children

BACKGROUND The association between obesity and asthma severity and control in children is not well understood. OBJECTIVE The objective of this study was to examine the association of childhood body mass index (BMI) percentile for age of 85% or greater with the number of β-agonist canisters dispensed, corticosteroid courses, emergency department visits, and hospitalizations for asthma. METHODS A retrospective cohort of 32,321 children aged 5 to 17 years and given a diagnosis of asthma who received at least 1 asthma (controller or rescue) medication and were enrolled in Kaiser Permanente from 2004-2008 was identified. Outcomes from electronic medical records included β-agonist canister and nebulizer units dispensed per year, hospitalizations and emergency department visits for asthma exacerbations, and oral corticosteroid courses. Potential confounding factors known to influence asthma outcomes were also collected: demographics, parental education level, asthma controller use, gastroesophageal reflux disease diagnosis, and diabetes mellitus diagnosis. Multiple logistic regression models were used to measure the independent association of BMI status with outcomes. RESULTS Even after adjusting for demographics, parental education level, asthma controller use, and gastroesophageal reflux disease and diabetes mellitus diagnoses, overweight (BMI percentile for age, 85% to 94%) and obese (BMI percentile for age, ≥ 95%) children were more likely to have increased β-agonists dispensed (odds ratio of 1.15 [95% CI, 1.02-1.27] and odds ratio of 1.17 [95% CI, 1.06-1.29], respectively) and increased risk for oral corticosteroids dispensed (odds ratio of 1.21 [95% CI, 1.13-1.29] and odds ratio of 1.28 [95% CI, 1.21-1.36], respectively) compared with normal-weight (BMI percentile for age, 16% to 84%) children. CONCLUSIONS Our findings suggest that childhood obesity is associated with an increased risk of worse asthma control and exacerbations.

Montelukast is only partially effective in inhibiting aspirin responses in aspirin-sensitive asthmatics

BACKGROUND Leukotrienes have been implicated as major mediators of ASA-induced respiratory reactions. In several prior studies, pretreatment of ASA-sensitive respiratory disease (ASRD) patients with leukotriene modifiers have sometimes allowed subjects to tolerate previously established provoking doses of oral ASA or inhalation ASA-lysine, without respiratory reactions. OBJECTIVE The purpose of this study was to examine whether ASA-provoked respiratory reactions would be blocked or attenuated by pretreatment with a cystLT1 receptor antagonist, montelukast, particularly if ASA doses were increased above their threshold doses. METHODS Baseline ASA oral challenges were performed. Eight to 12 days later, following pretreatment with montelukast 10 mg daily, threshold and then escalating doses of ASA were used during repeat oral ASA challenges. The differences in responses between baseline and montelukast protected ASA oral challenges were then compared. RESULTS Nine of 10 patients, despite pretreatment with montelukast, experienced at least naso-ocular reactions during their second oral ASA challenges. In four of nine patients, asthmatic reactions also occurred. In comparing baseline and montelukast protected ASA challenges, there were no statistically significant differences in their responses. CONCLUSIONS Pretreatment with montelukast allowed only one patient to proceed through all challenge doses of ASA without any reactions. The remaining nine patients enjoyed only partial protection from respiratory reactions. Montelukast pretreatment was generally not effective in altering upper airway reactions and only partly effective in altering lower airway reactions.

Evaluation of a school-based asthma education program for inner-city children

BACKGROUND We have previously reported a high prevalence of current asthma-related symptoms affecting predominantly Hispanic, socioeconomically disadvantaged schoolchildren in Southeast San Diego. OBJECTIVE We sought to assess the impact of a school-based education program on asthma outcomes. METHODS In cooperation with the San Diego Unified Schools, we developed and implemented a school-based asthma education program. Based on the National Heart, Lung, and Blood Institute consensus guidelines for asthma, the five-session bilingual, interactive curriculum was conducted in 20-minute segments. Asthma knowledge was tested before and after the education program, and asthma severity was prospectively assessed at monthly intervals. Outcome parameters were compared in educated and control (noneducated) fourth grade students with asthma by using nonparametric techniques. RESULTS After asthma education, students demonstrated improvement with increases in mean scores for: asthma knowledge quiz from 9.9 (SEM = 0.44, n = 34) to 13.7 (SEM = 0.30); peak flowmeter technique from 3.9 (SEM = 0.33, n = 32) to 6.4 (SEM = 0.29); and inhaler technique from 2.3 (SEM = 0.26, n = 32) to 4.3 (SEM = 0.26). All changes were highly significant (p < or = 0.00001 as determined by Wilcoxon matched-pairs signed-rank test). Mean score comparisons for asthmatic control students given paired examinations after a time interval matched with the educated students, did not reach statistical significance: quiz score of 11.3 (SEM = 0.80, n = 11) versus 10.9 (SEM = 0.68), peak flowmeter technique score of 2.6 (SEM = 0.50, n = 18) versus 3.1 (SEM = 0.37) , and inhaler technique score of 2.5 (SEM = 0.37, n = 18) versus 2.2 (SEM = 0.31). Prospective monthly data were collected on 27 educated and 15 control asthmatic subjects. Severity of asthma was not significantly different between groups at entry to the study. Symptom questionnaires, validated for functional asthma severity, revealed a significant reduction in mean symptom scores at 180 days for the educated (2.87, SEM = 0.447) versus the control (4.36, SEM = 0.573) groups (p = 0.0188 as determined by the Mann-Whitney U test). CONCLUSION Child-centered asthma education can be successfully conducted in the school setting, resulting in increased asthma knowledge, improved skills for peak flowmeter and inhaler use, and a reduction in the severity of asthma symptoms.

A short goal-pursuit intervention to improve physical capacity: A randomized clinical trial in chronic back pain patients

&NA; The present study tested a short intervention using goal‐pursuit strategies to increase physical capacity in pain patients. Sixty chronic back pain patients were randomly assigned to intervention or control conditions. Both groups followed a 3‐week conventional back pain program at an outpatient back pain center. Instead of routine treatment, the intervention group received a one‐hour intervention consisting of a combination of (a) a goal‐setting strategy (i.e., mental contrasting, MC) aimed at commitment to improved physical capacity, (b) a short cognitive behavioral therapy‐oriented problem‐solving approach (CBT) to help patients overcome the obstacles associated with improving physical capacity, and (c) a goal‐pursuit strategy, i.e., implementation intentions (II) aimed at performing physical exercise regularly. At two follow‐ups (3 weeks after discharge and 3 months after returning home) the MCII‐CBT group had increased its physical capacity significantly more than the control group as measured by both behavioral measures (ergometer, lifting) and subjective ratings. Findings are discussed with relation to the use of the intervention as a specific treatment to increase chronic pain patients’ motivation to be physically active.

US Hereditary Angioedema Association Medical Advisory Board 2013 Recommendations for the Management of Hereditary Angioedema Due to C1 Inhibitor Deficiency

BACKGROUND The treatment of hereditary angioedema (HAE) has undergone dramatic changes as newer medicines have become available in recent years. Optimal care of these patients requires a comprehensive management plan. Although several consensus papers have been published concerning the diagnosis and treatment of HAE, guidelines for a comprehensive management plan have not been developed. OBJECTIVE To develop state-of-the-art recommendations for the treatment and management of HAE due to C1 inhibitor (C1INH) deficiency in the United States. METHODS Members of the US Hereditary Angioedema Association Medical Advisory Board began by reviewing the literature concerning treatment of HAE. Preliminary recommendations were developed based on the literature review, discussions in a face-to-face meeting, and refinements in a series of drafts. Final recommendations reflect the unanimous consensus of the medical advisory board and the US Hereditary Angioedema Association leadership. RESULTS Recommendations are provided regarding a comprehensive care plan for HAE, including the following: development of an overall management plan, treatment of angioedema attacks, prophylactic treatment, and patient monitoring. CONCLUSION A comprehensive individualized management plan developed between an expert HAE physician and the patient, in collaboration with local medical providers and emergency departments, can provide patients with the best opportunity to lead a normal life.

Up-Regulation of Functional Kinin B1 Receptors in Allergic Airway Inflammation

B1 receptors are known to be induced during allergic airway inflammation in animal models. However, little is known regarding in vivo B1 receptor expression in humans. We examined B1 receptor mRNA expression in nasal tissue samples from allergic rhinitis and normal subjects. Allergic rhinitis subjects displayed significantly higher expression of B1 receptor mRNA than did the normal subjects, and nasal allergen challenge increased B1 receptor mRNA expression at 8 to 24 h time points in allergic rhinitis subjects. No significant difference was found in B2 receptor expression. To confirm B2 and B1 receptor functional activity, subjects were challenged with kinin agonists. Nasal challenge with the B1 receptor ligand, Lys-des-Arg-bradykinin (BK), activated extracellular signal-regulated kinase in allergic rhinitis, but not normal, subjects. Nasal challenge with the B2 receptor ligand, BK, activated extracellular signal-regulated kinase in both allergic rhinitis and normal subjects. The consequences of B1 receptor activation were investigated using the human airway epithelial cell lines A549 and BEAS-2B. We demonstrated that Lys-des-Arg-BK activates the transcription factor AP-1. Taken together, these results show that functional B1 receptors are induced in the airway during allergic inflammation and suggest that they participate in the regulation of gene expression.

Inhibition of monocyte leukotriene B4 production after aspirin desensitization.

Aspirin-sensitive patients may be desensitized through a graded series of exposures to aspirin. We investigated the underlying mechanism of aspirin desensitization by measuring the release of leukotrienes B4 and C4 from calcium ionophore-stimulated peripheral blood monocytes. Compared with monocytes from normal volunteers (n = 5), monocytes from patients with aspirin-sensitive asthma (n = 10) released increased amounts of thromboxane B2 (1060 +/- 245 pg/ml vs 456 +/- 62 pg/ml), leukotriene B4 (861 +/- 139 pg/ml vs 341 +/- 44 pg/ml), and leukotriene C4 (147 +/- 31 pg/ml vs 56 +/- 6 pg/ml) at baseline. After aspirin desensitization, thromboxane B2 release was almost completely suppressed in both groups. Leukotriene B4 release was significantly decreased in the aspirin-sensitive group (484 +/- 85 pg/ml) but not in the normal subject group (466 +/- 55 pg/ml). The need for prednisone decreased significantly after patients were desensitized to aspirin (10.4 +/- 2.2 mg/day to 1.6 +/- 2.8 mg/day). These results demonstrate that desensitization to aspirin results in decreased monocyte leukotriene B4 release. On the basis of the bronchospastic and inflammatory potential of leukotrienes, the decrease in leukotriene release may contribute to the clinical improvement seen after aspirin desensitization.