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This comprehensive practice parameter for allergic rhinitis (AR) and nonallergic rhinitis (NAR) provides updated guidance on diagnosis, assessment, selection of monotherapy and combination pharmacologic options, and allergen immunotherapy for AR. Newer information about local AR is reviewed. Cough is emphasized as a common symptom in both AR and NAR. Food allergy testing is not recommended in the routine evaluation of rhinitis. Intranasal corticosteroids (INCS) remain the preferred monotherapy for persistent AR, but additional studies support the additive benefit of combination treatment with INCS and intranasal antihistamines in both AR and NAR. Either intranasal antihistamines or INCS may be offered as first-line monotherapy for NAR. Montelukast should only be used for AR if there has been an inadequate response or intolerance to alternative therapies. Depot parenteral corticosteroids are not recommended for treatment of AR due to potential risks. While intranasal decongestants generally should be limited to short-term use to prevent rebound congestion, in limited circumstances, patients receiving regimens that include an INCS may be offered, in addition, an intranasal decongestant for up to 4 weeks. Neither acupuncture nor herbal products have adequate studies to support their use for AR. Oral decongestants should be avoided during the first trimester of pregnancy. Recommendations for use of subcutaneous and sublingual tablet allergen immunotherapy in AR are provided. Algorithms based on a combination of evidence and expert opinion are provided to guide in the selection of pharmacologic options for intermittent and persistent AR and NAR. [ABSTRACT FROM AUTHOR]

Deformation within the downgoing oceanic lithosphere seawards of subduction zones is typically characterised by regimes of shallow extension and deeper compression, due to the bending of the oceanic plate as it dips into the subduction zone. However, offshore Sumatra there are shallow compressional earthquakes within the downgoing oceanic plate outboard of the region of high slip in the 2004 Aceh–Andaman earthquake, occurring at the same depth as extensional faulting further seaward from the trench. A clear separation is seen in the location of intraplate earthquakes, with extensional earthquakes occurring further seawards than compressional earthquakes at the same depth within the plate. The adjacent section of the forearc prism west of Aceh is also anomalous in its morphology, characterised by a wide prism with a steep bathymetric front and broad, gradually-sloping top. This shape is in contrast to the narrower and more smoothly-sloping prism to the south, and along other subduction zones. The anomalous near-trench intraplate earthquakes and prism morphology are likely to be the result of the geologically-rapid gravitational collapse of the forearc, which leads to induced bending within the subducting plate, and the distinctive plateau-like morphology of the forearc. Such collapse of the forearc could be caused by changes through time of the material properties of the forearc rocks, or of the thickness of the sediments entering the subduction zone. [ABSTRACT FROM AUTHOR]

Extension at slow- and intermediate-spreading mid-ocean ridges is commonly accommodated through slip on long-lived faults called oceanic detachments. These curved, convex-upward faults consist of a steeply-dipping section thought to be rooted in the lower crust or upper mantle which rotates to progressively shallower dip-angles at shallower depths. The commonly-observed result is a domed, sub-horizontal oceanic core complex at the seabed. Although it is accepted that detachment faults can accumulate kilometre-scale offsets over millions of years, the mechanism of slip, and their capacity to sustain the shear stresses necessary to produce large earthquakes, remains subject to debate. Here we present a comprehensive seismological study of an active oceanic detachment fault system on the Mid-Atlantic Ridge near 13°20′N, combining the results from a local ocean-bottom seismograph deployment with waveform inversion of a series of larger teleseismically-observed earthquakes. The unique coincidence of these two datasets provides a comprehensive definition of rupture on the fault, from the uppermost mantle to the seabed. Our results demonstrate that although slip on the deep, steeply-dipping portion of detachment faults is accommodated by failure in numerous microearthquakes, the shallow, gently-dipping section of the fault within the upper few kilometres is relatively strong, and is capable of producing large-magnitude earthquakes. This result brings into question the current paradigm that the shallow sections of oceanic detachment faults are dominated by low-friction mineralogies and therefore slip aseismically, but is consistent with observations from continental detachment faults. Slip on the shallow portion of active detachment faults at relatively low angles may therefore account for many more large-magnitude earthquakes at mid-ocean ridges than previously thought, and suggests that the lithospheric strength at slow-spreading mid-ocean ridges may be concentrated at shallow depths. [ABSTRACT FROM AUTHOR]

Background MicroRNAs (miRNAs) are emerging as important regulatory molecules that might be involved in the pathogenesis of various diseases. Circulating miRNAs might be noninvasive biomarkers to diagnose and characterize asthma and allergic rhinitis (AR). Objective We sought to determine whether miRNAs are differentially expressed in the blood of asthmatic patients compared with those in the blood of nonasthmatic patients with AR and nonallergic nonasthmatic subjects. Furthermore, we sought to establish whether miRNAs could be used to characterize or subtype asthmatic patients. Methods Expression of plasma miRNAs was measured by using real-time quantitative PCR in 35 asthmatic patients, 25 nonasthmatic patients with AR, and 19 nonallergic nonasthmatic subjects. Differentially expressed miRNAs were identified by using Kruskal-Wallis 1-way ANOVA with Bonferroni P value adjustment to correct for multiple comparisons. A random forest classification algorithm combined with a leave-one-out cross-validation approach was implemented to assess the predictive capacities of the profiled miRNAs. Results We identified 30 miRNAs that were differentially expressed among healthy, allergic, and asthmatic subjects. These miRNAs fit into 5 different expression pattern groups. Among asthmatic patients, miRNA expression profiles identified 2 subtypes that differed by high or low peripheral eosinophil levels. Circulating miR-125b, miR-16, miR-299-5p, miR-126, miR-206, and miR-133b levels were most predictive of allergic and asthmatic status. Conclusions Subsets of circulating miRNAs are uniquely expressed in patients with AR and asthmatic patients and have potential for use as noninvasive biomarkers to diagnose and characterize these diseases. [ABSTRACT FROM AUTHOR]

Background: PCR studies have demonstrated evidence of Mycoplasma pneumoniae and Chlamydophila pneumoniae in the lower airways of patients with asthma. Objective: To test the hypothesis that clarithromycin would improve asthma control in individuals with mild-to-moderate persistent asthma that was not well controlled despite treatment with low-dose inhaled corticosteroids. Methods: Adults with an Asthma Control Questionnaire score ≥1.5 after a 4-week period of treatment with fluticasone propionate were entered into a PCR-stratified randomized, controlled trial to evaluate the effect of 16 weeks of either clarithromycin or placebo, added to fluticasone, on asthma control in individuals with or without lower airway PCR evidence of M pneumoniae or C pneumoniae. Results: A total of 92 participants were randomized. Twelve (13%) subjects demonstrated PCR evidence of M pneumoniae or C pneumoniae in endobronchial biopsies; 80 were PCR-negative for both organisms. In PCR-positive participants, clarithromycin yielded a 0.4 ± 0.4 unit improvement in the Asthma Control Questionnaire score, with a 0.1 ± 0.3 unit improvement in those allocated to placebo. This between-group difference of 0.3 ± 0.5 (P = .6) was neither clinically nor statistically significant. In PCR-negative participants, a nonsignificant between-group difference of 0.2 ± 0.2 units (P = .3) was observed. Clarithromycin did not improve lung function or airway inflammation but did improve airway hyperresponsiveness, increasing the methacholine PC20 by 1.2 ± 0.5 doubling doses (P = .02) in the study population. Conclusion: Adding clarithromycin to fluticasone in adults with mild-to-moderate persistent asthma that was suboptimally controlled by low-dose inhaled corticosteroids alone did not further improve asthma control. Although there was an improvement in airway hyperresponsiveness with clarithromycin, this benefit was not accompanied by improvements in other secondary outcomes. [Copyright &y& Elsevier]

Background: Hereditary angioedema caused by C1 esterase inhibitor deficiency is a rare disorder. Objective: To compare the efficacy of pasteurized C1 esterase inhibitor concentrate (Berinert, CSL Behring) at intravenous doses of 10 or 20 U/kg body weight with placebo in the treatment of single, acute abdominal or facial attacks in patients with hereditary angioedema. Methods: This was a randomized, double-blind, placebo-controlled study in 125 patients with type I or II hereditary angioedema. The primary outcome was time from start of treatment to onset of symptom relief. Secondary outcomes were time to complete resolution, proportion of patients with worsened intensity of angioedema symptoms between 2 and 4hours after treatment, and number of vomiting episodes within 4 hours. Results: Median time to onset of relief was significantly shorter with C1 esterase inhibitor concentrate at a dose of 20 U/kg than with placebo (0.5 vs 1.5 hours; P = .0025), whereas with 10 U/kg, the time to onset of relief was only slightly shorter than with placebo (1.2 vs 1.5 hours; P = .2731). Compared with placebo, the reduction in time to onset of relief was greatest for severe attacks (0.5 vs 13.5 hours). The secondary outcomes consistently supported the efficacy of the 20 U/kg dose. C1 esterase inhibitor concentrate was safe and well tolerated. No seroconversions were observed for HIV, hepatitis virus, or human B19 virus. Conclusion: C1 esterase inhibitor concentrate given intravenously at a dose of 20 U/kg is an effective and safe treatment for acute abdominal and facial attacks in patients with hereditary angioedema, with a rapid onset of relief. [Copyright &y& Elsevier]

Background: Large local reactions to insect stings cause significant morbidity and impair quality of life. Venom immunotherapy is not recommended because of a low risk for future systemic reaction and unproven efficacy in preventing large local reactions. Objective: To determine the feasibility of performing a controlled trial to examine the efficacy of venom immunotherapy in reducing the size and duration of large local reactions. Methods: Sting challenge in 41 patients with previous large local reactions and positive venom skin tests caused large local reactions 16 cm or larger in 34 patients, and 29 consented to treatment. Venom immunotherapy was initiated in 19, and 10 were untreated controls. Sting challenge was repeated after 7 to 11 weeks (control patients then began venom immunotherapy), and annually for as long as 4 years. Results: After 7 to 11 weeks of treatment, the size and duration of large local reactions decreased 42% and 53%, respectively, in treated patients and 18% in controls (P < .01 for both). The response was similar after 1 year, and improved after 2 to 4 years to 60% and 70%, respectively. Conclusions: Venom immunotherapy significantly reduced the size and duration of the large local reactions, and the efficacy improved over a period of 2 to 4 years of treatment. Further studies are needed to establish the safety and efficacy of venom immunotherapy for large local reactions, the optimal duration of treatment, and the mechanism for the differences in degree and rate of clinical response compared with venom immunotherapy in systemic reactors. [Copyright &y& Elsevier]

Background: Aeroallergen sensitization in adult asthmatic patients from a wide geographic area has not been correlated with patients'' characteristics, markers of airways inflammation, and lung function. Objective: We assessed data obtained from the Asthma Clinical Research Network trials to determine the relationship of aeroallergen sensitization to age, sex, ethnicity, and markers of inflammation and airways function. Methods: Skin testing (14 epicutaneous) was performed on 1338 subjects with objectively diagnosed mild-to-moderate asthma from 11 Asthma Clinical Research Network studies. Skin testing used identical techniques and a quality assurance program to ensure uniformity across centers. Results: Ninety-five percent of the subjects had at least 1 positive skin test response. Of these, 14% had positive reactions to 1 or 2 allergens and 81% had positive reactions to 3 or more allergens, and 2% of subjects reacted only to seasonal allergens, 26% only to perennial allergens, and 67% to both. Increasing IgE and exhaled nitric oxide values, decreasing PC20 values, and minority ethnicity significantly correlated with the number of positive skin test responses. Subjects with late-onset asthma were less likely to be sensitized; nonetheless, 89% of subjects older than 60 years had positive responses. Conclusion: Ninety-five percent of patients with mild-to-moderate asthma might have an allergic component. Age does not significantly affect aeroallergen sensitization, but the pattern of allergic sensitization varies with ethnicity and geography. Measures used to characterize asthma, such as IgE, exhaled nitric oxide, and PC20 values, are correlated with aeroallergen sensitization. [Copyright &y& Elsevier]

Summary: Objective: The reduction of oral prednisone use by mometasone furoate (MF) delivered by HFA-227 metered dose inhaler (MDI) was examined in oral corticosteroid (OCS)-dependent patients with severe persistent asthma. Methods: A 3-month, double-blind, placebo-controlled clinical trial (), followed by a 9-month open-label phase (). The study was conducted at 26 medical centers in the United States. Patients were randomized to treatment with MF-MDI 400 or 800μg twice-daily (bid) doses, or placebo in the double-blind trial. All patients received MF in the open-label phase. Results: At the endpoint of the double-blind trial, MF-MDI 400 and 800μg bid reduced the daily OCS dose by 39.4% and 31.1%, respectively, while placebo increased the OCS dose by 107.2% (P<0.01). The OCS requirement was reduced by 50% or more in 63% and 60% of patients treated with MF-MDI 400 and 800μg bid, respectively, compared with 14% of patients receiving placebo. After 12 weeks, despite prednisone reductions, pulmonary function, asthma symptoms, albuterol use, nocturnal awakenings, and physician-evaluated response to therapy also showed significant improvement with MF-MDI treatment compared with placebo. Further reductions in OCS requirements were achieved with long-term MF-MDI treatment in the open-label phase, with an overall 67% reduction in prednisone usage and 51% of patients completely eliminating prednisone usage by the 1-year time point. Conclusion: MF delivered by HFA-227 MDI significantly reduces daily OCS use compared with placebo and facilitates elimination of OCS use in patients with severe persistent asthma. [Copyright &y& Elsevier]

Background: Although guidelines recommend anti-inflammatory therapy for persistent asthma, recent studies suggest that 25% to 35% of patients with asthma may not improve lung function with inhaled corticosteroids. Objective: To evaluate potential biomarkers of predicting short-term (6-week) response to inhaled corticosteroid with subsequent evaluation of responders and nonresponders to asthma control over a longer interval (16 additional weeks). Methods: Eighty-three subjects with asthma off steroid were enrolled in this multicenter study. Biomarkers and asthma characteristics were evaluated as predictors of inhaled corticosteroid response over a 6-week trial for changes in FEV1 and methacholine PC20. After this, an additional 4-month trial evaluated asthma control. Results: Although multiple baseline predictors had significant correlations with improvements for short-term inhaled steroid success, the only strong correlations (r ≥ ± 0.6) were albuterol reversibility (r = 0.83; P < .001), FEV1/forced vital capacity (r = −0.75; P < .001), and FEV1 % predicted (r = −0.71; P < .001). Dividing the subjects in the short-term inhaled steroid trial into responders (>5% FEV1 improvement) and nonresponders (≤5%) determined the longer-term need for steroids. For the nonresponders, asthma control remained unchanged whether inhaled corticosteroids were continued or were substituted with a placebo (P = .99). The good short-term responders maintained asthma control longer-term only if maintained on inhaled steroids (P = .007). Conclusion: The short-term response to inhaled corticosteroids with regard to FEV1 improvement predicts long-term asthma control. Clinical implications: The decision to use long-term inhaled steroids could be based on a short-term trial. Different therapeutic strategies would need to be established for nonresponders. [Copyright &y& Elsevier]

Background: The reported frequency of systemic reactions to challenge sting varies greatly. Objective: To evaluate the interaction of clinical and entomological factors that determine the outcome of a challenge sting. Methods: Patients allergic to yellow jacket were stung and monitored for systemic reaction. The frequency and severity of sting reactions were analyzed in relation to the species of insect used and patient characteristics. Results: Objective systemic reactions occurred in 21 of 69 patients (30%) stung with Vespula maculifrons and in 8 of 71 patients (11%) with Vespula germanica (P = .005). Systemic reactions were more frequent in patients with a severe history (9/30; 30%) than in those with a mild or moderate history (21/145; 14%; P = .04). In only 1 of 111 patients (0.9%) was the reaction to sting challenge more severe than previous reactions. The reaction rate was higher when venom skin tests were positive at <1.0 μg/mL (17/75 = 23%) than when sensitivity was milder (9/100 = 9%; P = .012). We compared sting outcome and venom-induced histamine release in relation to insects collected in July or in October, and found no difference. Conclusion: Allergic reactions to sting challenge are determined by the species of yellow jacket used, the severity of previous sting reactions, and the degree of skin test sensitivity, but not by the time of year. These factors are important to clinicians when they evaluate the chance of reaction to a future sting and to researchers when they design and report sting challenge studies. [Copyright &y& Elsevier]

Background: Although inhaled corticosteroids (ICSs) are effective in preventing deterioration in asthma control, at least half of subjects with mild-to-moderate asthma will remain stable when these agents are discontinued. Objective: We sought to determine whether noninvasive markers of inflammation predict which individuals maintain asthma control after discontinuation of ICSs. Methods: We analyzed data obtained from 164 subjects with mild-to-moderate asthma who participated in a 16-week trial comparing the effects of continued ICS use with the effects of a switch to salmeterol or placebo. Results: In comparison with continued ICS use, a switch to salmeterol or placebo was associated with increased rates of asthma deterioration over 16 weeks (9.3% vs 24.1% and 37.5%, respectively; P =.04 and P < .001, respectively). We found that neither exhaled nitric oxide nor methacholine PC20, when measured at randomization or 2 weeks after randomization, were significant predictors of subsequent asthma control in subjects who discontinued ICSs. However, both induced sputum eosinophil counts measured 2 weeks after a switch from ICS to placebo and changes in sputum eosinophil counts from before cessation of ICSs to after a switch to placebo predicted subsequent asthma deterioration (area under the receiver-operating characteristic curve, 0.771 [P < .001] and 0.825 [P < .001], respectively). Conclusion: On the basis of a model treatment strategy, we estimate that allocating subjects to ICS therapy on the basis of changes in sputum eosinophil counts after a trial discontinuation could allow 48% of subjects with mild-to-moderate asthma to discontinue ICS therapy without an increased risk of asthma deterioration over a period of at least 14 weeks. [ABSTRACT FROM AUTHOR]

The double-blind, placebo-controlled food challenge is a rigorous tool that has become popular for evaluating adverse reactions to foods. The standard use of the double-blind, placebo-controlled food challenge has been to document food allergies for individual patients, but it recently has been gaining acceptance as a procedure for investigating the effectiveness of therapies to prevent/minimize food-induced anaphylaxis. The purpose of this study was to describe the statistical design and analysis issues for clinical trials that use the double-blind, placebo-controlled food challenge in measuring sensitivity to food allergens. Nonparametric tests for within-group and between-group comparisons are described, as well as a discrete-time survival analysis. The statistical methods are applied to simulated data from a clinical trial that compares control therapy and experimental therapy groups. The results indicate that the experimental therapy is significantly better than control in improving the tolerance to peanut flour in patients with peanut allergy. Although simple nonparametric tests for within-group and between-group comparisons are easy to apply, a discrete-time survival analysis provides the best approach because of its flexibility in accounting for important independent variables (regressors) and longitudinal data. Statistical software packages can be adapted to perform such analyses. [ABSTRACT FROM AUTHOR]

Therapy for rhinitis improves sleep quality and symptoms of daytime sleepiness. This improvement with therapy may be secondary to anti-inflammatory effects, leading to a reduction of inflammatory mediators, or to a mechanical reduction of congestion directly leading to improvement in sleep disturbance. We combined our data from 3 placebo-controlled studies of intranasal corticosteroids in patients with perennial rhinitis to determine whether a correlation between the reduction of congestion and improved sleep and daytime somnolence existed. The pooled data of budesonide, flunisolide, and fluticasone demonstrated significantly decreased nasal congestion, sleep problems, and sleepiness in treated patients. The data demonstrated a correlation between a reduction in nasal congestion and an improvement of sleep (P < .01) and daytime somnolence (P = .01). Thus, topical intranasal corticosteroids should be used to decrease nasal congestion and to improve sleep and daytime somnolence in patients manifesting these symptoms. [Copyright &y& Elsevier]