The impact/role of asthma in otolaryngology.
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Asthma↗
Biomedical subjects
John H Krouse
Publications and source records attributed to John H Krouse.
Modulation of immune mediators with MQT-based immunotherapy.
OBJECTIVE: Assess immune and clinical changes with immunotherapy based on modified quantitative testing (MQT). BACKGROUND: Immunotherapy promotes immunomodulation that occurs over several years. Quantitative testing offers the advantage of initiating immunotherapy with robust antigen concentrations. This study assessed whether changes in immune mediators and allergy symptoms occur rapidly using quantitative techniques. METHODS: Sixteen allergic adults were tested using MQT. Subjects had serum drawn for immunoglobulins E and G4 (IgE, IgG4) to 3 antigens, Der p1, Der f1, and Fel d1, and for interleukins IL-1beta, IL-2, IL-4, IL-5, IL-10, IL-12, and IL-13, and IL-1 receptor antagonist (IL-1RA). Subjects also completed the Sino-Nasal Outcome Test-20 (SNOT-20), the Allergy Outcome Scale (AOS), and the Rhinosinusitis Disability Index (RSDI). They underwent MQT-based immunotherapy and completed outcome measures again at 6 and 12 weeks. RESULTS: Nine subjects completed the study. Analysis demonstrated significant increases in IgG4 levels to all antigens, significant decreases in serum levels of IL-1beta and IL-5, and significant increases in levels of IL-1RA. Improvement was also noted in AOS and RSDI subscales. CONCLUSION: Immunotherapy based on MQT demonstrates significant changes in immunoglobulin and cytokine levels by 12 weeks following initiation. In addition, improvement in symptom and quality-of-life measures occurs by 12 weeks. These findings support the rapid onset of clinical effects with MQT-based treatment of inhalant allergy. EBM RATING: C-4.
Adult↗
Intradermal positivity after negative prick testing for inhalants.
OBJECTIVE: Examine the incidence of positive intradermal tests after a negative skin prick test for 24 inhalant antigens. STUDY DESIGN AND SETTING: Retrospective study. Charts from patients who underwent modified quantitative testing (MQT) over a 3-year period were reviewed. Patients were initially tested with Multi-Test II. Subjects with negative wheals to a specific allergen were then tested with a 1:500 weight:volume intradermal injection of that allergen. RESULTS: One hundred thirty-three patients underwent MQT for 24 antigens. Allergens with the highest incidence of positive intradermal wheals after negative prick testing were Dermatophagoides pteronyssinus and Dermatophagoides farinae at 26.67%. Allergens with elevated incidence of positive intradermals included fusarium, cockroach, cocklebur, rough marsh elder, and ragweed, all with incidences of 16% to 19%. CONCLUSION: Positive intradermal responses after negative prick testing occur commonly. Future study is needed to determine the generalizability and clinical significance of these findings. EBM RATING: C-4.
Algorithms↗
Allergy and chronic rhinosinusitis.
The association between chronic rhinosinusitis (CRS) and allergy of the upper respiratory system has been discussed for many years,but much of this discussion has been anecdotal. Although epidemiologic evidence supports the increased prevalence of CRS among patients who have allergic rhinitis, and treatment of upper airway inflammation and allergy has been shown to decrease morbidity in patients who have CRS, but pathophysiologic mechanisms linking the two disease states have not been well elucidated. This article examines data supporting the link between upper airway allergic disease and CRS. It proposes a frame work for the treatment of CRS, with consideration of managing the allergic inflammation commonly noted in this disease. Finally, it discusses avenues for potential future research in evaluating the comorbidities of allergic inflammation and CRS.
Airway Obstruction↗
Optimal duration of allergic rhinitis clinical trials.
OBJECTIVE: Guidelines have been published by the Food and Drug Administration (FDA) and the European Agency for the Evaluation of Medicinal Products (EMEA) for the conduct of seasonal allergic rhinitis (SAR) and perennial allergic rhinitis (PAR) studies. These guidelines have differences regarding the duration of such trials: the FDA suggests 2 weeks for SAR and 4 weeks for PAR but the EMEA suggests 2 to 4 weeks for SAR and 6 to 12 weeks for PAR trials. In the interest of global harmonization, it would be desirable to have a uniform duration of such trials so that investigators, internationally, would be able to readily compare results for various types of treatments based on a single standard. Therefore, we performed an evidence-based review to answer the clinical question, What is the optimal duration for SAR and PAR clinical trials? METHODS: We performed a MEDLINE search of the published literature from 1995 to the present. We used appropriate search terms, such as allergic rhinitis, seasonal allergic rhinitis, perennial allergic rhinitis, SAR, and PAR, to identify pertinent articles. These articles were reviewed and graded according to the evidence quality. RESULTS: After an initial screening of more than 300 articles, 138 articles were analyzed thoroughly. No study specifically addressed the question of the optimal duration of SAR or PAR clinical trials. CONCLUSIONS: We conclude that the current FDA (draft) guidelines calling for a study length of 2 weeks for the assessment of drug efficacy for SAR and 4 weeks for the study of drug efficacy in PAR are appropriate and that longer study periods are not likely to add meaningfully to the assessment of drug efficacy.
Clinical Trials as Topic↗
Endoscopic ligation of the sphenopalatine artery as a primary management of severe posterior epistaxis in patients with coagulopathy.
We describe our experience with endoscopic ligation of the sphenopalatine artery in the treatment of severe posterior epistaxis in 2 patients with coagulopathy. Conservative treatment had failed in both cases. The key elements of this procedure are the identification of the branches of the sphenopalatine artery via an endoscopic endonasal approach and the application of two titanium clips under direct vision. This procedure was successful in both patients, and we recommend it in selected cases.
Blood Coagulation Disorders↗
Inflammatory sinonasal disease.
Inflammation of the nose and sinuses is a clinical problem frequently encountered in the practice of otolaryngology. The most common of these inflammatory illnesses are allergic rhinitis and acute and chronic rhinosinusitis. The recognition of inflammatory sinonasal diseases and an understanding of their pathophysiology are essential to successful management of these common illnesses.
Acute Disease↗
Sensitivity and specificity of prick and intradermal testing in predicting response to nasal provocation with timothy grass antigen.
OBJECTIVE: Examine the efficacy of epicutaneous and intradermal testing in predicting response to nasal provocation with timothy antigen. STUDY DESIGN AND SETTING: Prospective study. Subjects were tested with Multi-Test II (MT). Subjects with negative wheals were tested with a 1:500 intradermal injection of timothy. They had baseline assessment of nasal cross-sectional area (CSA) using acoustic rhinometry and underwent nasal provocation with increasing timothy concentrations. CSA was assessed and nasal visual analog scale (VAS) completed with each concentration. RESULTS: Sensitivity and specificity of MT in predicting nasal response to provocation were 87% and 86%. Intradermal testing increased sensitivity to 93%. Hierarchical linear modeling (HLM) demonstrated that subjects positive to skin testing had significant reductions in CSA and worsening VAS scores with increasing concentrations of nasally delivered antigen. CONCLUSION AND SIGNIFICANCE: Epicutaneous testing with the Multi-Test II offers 87% sensitivity and 86% specificity in assessing timothy grass reactivity.
Adult↗
Velopharyngeal dysfunction: speech characteristics, variable etiologies, evaluation techniques, and differential treatments.
This tutorial addresses the complex pathophysiology; various structural and neurologic causes; methods of clinical appraisal; and alternative behavioral prosthetic, and medicosurgical treatments of velopharyngeal dysfunction. To balance the primary focus of this review on hypernasal resonance and articulation disorders, discussions concerning hyponasal speech characteristics and underlying etiologies are also rendered.
Adolescent↗
Skin testing in predicting response to nasal provocation with alternaria.
OBJECTIVE: Examine the efficacy of epicutaneous and intradermal testing in predicting response to nasal provocation with Alternaria antigen. STUDY DESIGN AND SETTING: Prospective study. Subjects were tested with the Multi-Test II (MT) epicutaneous testing device. Subjects with negative wheals were then tested with a 1:500 weight:volume intradermal injection of Alternaria. They had baseline assessment of nasal cross-sectional area (CSA) using acoustic rhinometry and underwent nasal provocation with increasing Alternaria concentrations. CSA was assessed at each concentration. A nasal allergen provocation score (NAP) of nasal symptoms as well as a nasal visual analogue scale (VAS) were also completed with each concentration. RESULTS: Sensitivity and specificity of MT in predicting nasal response to Alternaria were poor at 42% and 44%, respectively. The addition of intradermal testing increased sensitivity only modestly to 58%. hierarchical linear modeling analysis demonstrated that subjects positive to Alternaria on skin testing did not show a significant reduction in nasal CSA on acoustic rhinometry or significant elevations in two nasal symptom scores with direct nasal provocation. CONCLUSION AND SIGNIFICANCE: Skin testing with either epicutaneous or intradermal testing may not be an accurate or sufficient technique in the assessment of Alternaria reactivity. These results suggest that mold allergies may involve more complex immune mechanisms than simply an immunoglobulin (Ig)E mediated type I immediate hypersensitivity response alone. An alternate model for mold sensitivity, as well as modifications in testing methods, may be required in the evaluation of mold allergy.
Adolescent↗
Pathology quiz case. Osteoma of the maxilla.
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Adult↗
Current in vivo and in vitro screens for inhalant allergy.
Screening for inhalant allergy requires the use of a rapid, accurate, cost-effective methodology for the detection of the presence or absence of allergic responsiveness. In vivo and in vitro methods have been demonstrated to be sensitive and specific in the diagnosis of inhalant allergy, even with panels as small as seven or eight antigens. There is good concurrence between skin testing techniques and various serum measures of specific IgE, and both methods can be used effectively for screening inhalant allergy, although per-test costs for in vitro methods remain higher than comparable costs for skin testing [28]. Although the rapidity of both methods is acceptable, skin testing allows immediate observation and interpretation of test results, whereas all in vitro methods involve serum processing that delays results for hours to days. In general, both in vitro methods and epicutaneous testing with a device such as the Multi-Test II offer the clinician effective techniques in screening for inhalant allergy. Each technique has benefit and can be used in both primary care practices and in specialists' offices. The choice of the primary technique to be used for screening depends on the type of practice, the practice's familiarity with skin testing, the geographic region, and the relevant payer mix. A review of the relevant research on allergy screening suggests that the number of antigens used should be in the range of 8 to 12 and should include representative allergens from all the significant classes for the specific geographic [table: see text] region. This screen would probably contain one or two grasses, weeds, and trees, two or three molds, cat allergen, and one dust mite allergen. A sample panel is demonstrated in Box 6. It is important to recognize that the diagnosis and treatment of inhalant allergy is a fluid process. In patients who have negative allergy screens but for whom suspicion of inhalant allergy remains high, additional testing with ID techniques is sometimes indicated. This procedure might be suggested in patients for whom there is a high suspicion of mold allergy or who have unusual inhalant exposures. These individuals may represent a failure of the screening process and require additional testing. In these unusual cases, the judgment of the otolaryngic allergist is critical in guiding this further diagnostic work-up. The use of screening procedures for the diagnosis of inhalant allergy provides a rapid, accurate, and cost-effective method for evaluating patients with a history suggestive of allergic disease. Research suggests that a screening panel has strong clinometric properties and has both sensitivity and specificity in excess of 95%. It is statistically unlikely that a patient with negative findings to an allergy screen will demonstrate clinically significant inhalant allergy.
Humans↗
The effects of montelukast on intradermal wheal and flare.
OBJECTIVE: We sought to determine the effect of montelukast, a leukotriene receptor antagonist, on intradermal skin testing. Study design and setting We conducted a prospective, randomized, double-blind, placebo-controlled study in a university setting. METHODS: After a 1-week washout of allergy pharmacotherapy, intradermal skin testing was performed on 23 atopic subjects. Whealing size was measured 20 minutes after injection. Subjects then began a 1-week regimen of daily loratadine, montelukast, or placebo. At 1 week, subjects again underwent intradermal skin testing. The change in wheal size was then calculated from baseline. RESULTS: A significant difference (P < 0.05) between the montelukast and loratadine groups in suppression of intradermal whealing at 1 week was observed. No significant difference was noted between the montelukast and placebo subjects. CONCLUSIONS: Montelukast demonstrated no significant suppression of skin whealing after antigen challenge over placebo. SIGNIFICANCE: Montelukast does not need to be discontinued before intradermal allergy testing.
Acetates↗
Skin testing for inhalant allergy 2003: current strategies.
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Algorithms↗
Laryngeal effects of antigen stimulation challenge with perennial allergen Dermatophagoides pteronyssinus.
OBJECTIVE: We conducted a pilot study to assess the effects of antigen stimulation on the appearance and function of the larynx. STUDY DESIGN AND SUBJECTS: The prospective, double-blind, randomized study included 9 adult patients with a skin-prick test positive for Dermatophagoides pteronyssinus. MAIN OUTCOME MEASURES: Subjects were blindly challenged via nebulizer with either an active antigenic suspension or placebo. Baseline and 30-minute evaluations of the larynx were performed. Assessments included subjective voice and videostroboscopic assessments, acoustic analysis of voice, speech aerodynamic testing, and allergy and voice handicap questionnaires. RESULTS: Although both inflammation and increased mucus were noted, there were no significant differences between the antigen- and placebo-exposed subjects on any of the measures obtained. CONCLUSIONS: Our preliminary investigation was not successful in demonstrating a direct causal relationship between antigen exposure and physical or functional changes in the larynx. Future studies will involve modifications to our current methodology, including increasing the concentration of antigen, prolonging the exposure time, and observing for late phase responses.
Adult↗
The role of allergy in chronic rhinosinusitis.
Issues surrounding the cause and pathogenesis of chronic rhinosinusitis (CRS) remain controversial. Various models involving physiologic factors and anatomic obstruction have been offered to explain the pathogenesis of this common disease. More recently, the role of chronic inflammatory processes has been demonstrated. These findings may modify the current paradigm of this disease and transform the diagnosis and management of patients with CRS. This review focuses on the role of allergy and inflammation in the pathogenesis of CRS.
Chronic Disease↗
Immune mediators in allergic rhinitis and sleep.
OBJECTIVE: Our study goal was to examine polysomnography, indices of sleep and allergy, and serum and nasal cytokines in allergic and nonallergic subjects. STUDY DESIGN AND SETTING: In this descriptive, exploratory study, 4 allergic and 4 nonallergic subjects underwent 2 nights of polysomnographic recording with serial measurements of cytokines and completed measures of sleep quality and allergic symptoms. RESULTS: Three serum cytokines (interleukin [IL]-1beta, IL-4, and IL-10) were higher in allergic subjects and were termed proallergic. Three serum cytokines (IL-1ra, IL-2, and IL-12) were higher in nonallergic subjects and were termed allergy inhibitory. Proallergic serum cytokines correlated with increased latency to rapid eye movement sleep, decreased time in rapid eye movement sleep, and decreased latency to sleep onset. Low levels of allergy-inhibitory serum cytokines were associated with increased allergic symptoms. CONCLUSIONS: Differences in serum cytokines between allergic and nonallergic individuals are associated with variations in polysomnography and allergic symptoms. SIGNIFICANCE: Understanding these mechanisms may suggest novel approaches to alleviating drowsiness and other symptoms in allergic patients.
Adult↗
The importance of glycerin-containing negative control tests in allergy research studies that use intradermal skin tests.
OBJECTIVE: We sought to assess skin whealing with glycerin-containing control injections for intradermal skin tests. DESIGN: Observational. METHODS: Wheal sizes were measured at 0, 10, and 15 minutes after intradermal injection of 0.01 and 0.02 mL of phenolated normal saline and 0.5% and 5% concentrations of glycerin in the same quantity of phenolated saline. RESULTS: Intradermal injection of 0.01 mL of phenolated saline produced an average 4.9-mm wheal, which expanded to 5.2 mm at 10 minutes and to 6.0 mm at 15 minutes. Intradermal injection of 0.02 mL of phenolated saline produced a 6.4-mm wheal, which expanded to 7.0 mm at 10 minutes and 8.0 mm at 15 minutes. The addition of glycerin produced proportionally larger wheals. CONCLUSIONS: Because glycerin increases whealing beyond that with phenolated saline, skin tests containing glycerin must be compared with glycerin-containing negative controls. Intradermal skin tests that fail to compare findings in this manner contain an inherent methodologic flaw and are uninterpretable.
Bias↗