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Objective To review the role of nitric oxide production in anaphylaxis. Data Sources We performed MEDLINE searches of the literature. In addition, some references known to the authors but not listed in MEDLINE, such as abstracts and a CD-ROM, were included. Finally, additional clinical details of the cases were provided by one of the authors. Study Selection Primary reports were preferentially selected for inclusion. However, some secondary publications are also cited. Results Histamine along with other mediators, such as leukotrienes, tumor necrosis factor, and platelet-activating factor, induce the production of nitric oxide. Nitric oxide can inhibit the release and effects of catecholamines. Sympathetic amines may inhibit production of nitric oxide. Studies in animals have demonstrated the generation of nitric oxide during anaphylaxis. Inhibition of nitric oxide synthase improves survival in an animal model of anaphylaxis. Nitric oxide causes vasodilation indirectly by increasing the activation of guanylyl cyclase, which then causes smooth muscle relaxation by increasing the concentration of smooth muscle cyclic guanosine monophosphate. Methylene blue is an inhibitor of guanylyl cyclase, which increases systemic vascular resistance and reverses shock in animal studies. The previously reported successful treatment with methylene blue of 11 patients with anaphylactic hypotension is reviewed. Conclusion Nitric oxide plays a significant role in the pathophysiology of anaphylaxis. Treatment with methylene blue should be considered in patients with anaphylactic hypotension that has not responded to other interventions.

Background Vocal cord dysfunction can coexist with or masquerade as asthma. Vocal cord dysfunction, when coexistent with asthma, contributes substantially to the refractory nature of the respiratory problem. Objective To report a case of an asthmatic patient with vocal cord dysfunction and a previously unreported unique expiratory flow volume curve. Results A 16-year-old female, known to have asthma, developed increased frequency of her asthma exacerbations. Spirometry, during symptoms, showed an extrathoracic airway obstruction with a reproducible unique abrupt drop and rise in the expiratory flow volume loop. Laryngoscopy showed adduction of the vocal cords during inspiration and expiration. Conclusions We report a unique expiratory flow volume curve in an asthmatic with vocal cord dysfunction that resolved with panting maneuvers. Speech and psychological counseling helped prevent future attacks.

Background Oropharyngeal candidiasis is a well described side effect of inhaled corticosteroids. Nevertheless, few cases of esophageal candidiasis have been reported Objective To present a patient with esophageal candidiasis associated with inhaled corticosteroids. Methods Case report. Results Our patient is a 70-year-old white woman with a 20-year history of intrinsic asthma, well controlled on triamcinolone acetonide 400 micrograms, ipratropium bromide 36 micrograms, and pirbuterol acetate 400 micrograms, each inhaled four times daily. She reported no oral steroid use for >4 years and that she always rinsed her mouth following tramcinolone acetonide inhalation. The patient had gastritis with peptic ulcer disease in the past and developed worsening dyspeptic pain and heartburn. Following discontinuation of cimetidine and initiation of ranitidine without improvement, esophagogastroduodenoscopy was performed. Several small white patches in the mid and distal esophagus could not be removed with pressure. A biopsy confirmed the diagnosis of candidal esophagitis. Following a 4-week course of fluconazole, the patient was clinically improved and follow-up esophagogastroduodenoscopy was normal. There was no evidence of underlying cellular immunosuppression, malignancy, or diabetes mellitus and no history of recent antibiotic usage. Delayed skin tests revealed 5 × 5 mm induration to dermatophytin. Delayed hypersensitivity to Candida and mumps tests was absent. There was strong in vitro lymphocyte transformation and a positive immediate skin test response to Candida. ELISA for human immunodeficiency virus was negative. T and B cell counts were normal with CD4=630/mm 3 , CD8=520/mm 3 , and absolute B cell=120/mm 3 . It is possible that this patient's immediate hypersensitivity response to Candida suppressed her delayed response. Candidal esophagitis is a rare, yet important, complication of inhaled corticosteroid use. Conclusion Immunocompetent patients on inhaled corticosteroids with medically unresponsive symptoms of esophagitis should be investigated for esophageal candidiasis.

Background Previous population-based analyses of emergency department (ED) visits for anaphylaxis have been limited to small populations in limited geographic areas and focused on children or have included patients who had allergic conditions other than anaphylaxis. Objective We sought to describe the epidemiology and risk factors among patients with anaphylaxis presenting to Florida EDs. Methods Two thousand seven hundred fifty-one patients with anaphylaxis were identified for 2005-2006 within ED records by using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM), and a validated ICD-9-CM–based algorithm. Age- and sex-specific rates were calculated. Regression analyses were used to determine relative risks for anaphylaxis caused by various triggers (food, venom, and medication) and risk factors (age, sex, race, and ethnicity). Results The highest observed rates were among the youngest male subjects (8.2/100,000 Floridians aged 0-4 years) and among adult female subjects (15-54 years) grouped in 10-year age categories (9.9-10.9/100,000 Floridians). Male and black subjects were 20% and 25%, respectively, more likely to have a food trigger than female and white subjects. White, male, and older subjects were more likely to have an anaphylaxis-related ED visit caused by insect stings. Venom-induced anaphylaxis was more likely in August through October. Children were less likely than those older than 70 years (referent) to have medication-induced anaphylaxis ( P Conclusion This is the only ED-based population study in a US lower-latitude state. The overall rate is considerably lower than other US ED-based population studies. The rates of anaphylaxis by age group differed by sex. Male and black subjects were more likely to have a food trigger.

Epidemiologic studies of anaphylaxis have been limited by significant underdiagnosis.The purpose of this study was to develop and validate a method for capturing previously unidentified anaphylaxis cases by using International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) based datasets.Florida emergency department data for the years 2005 and 2006 from the Florida Agency for Health Care Administration were used. Patients with anaphylaxis were identified by using ICD-9-CM codes specifically indicating anaphylaxis or an ICD-9-CM algorithm based on the definition of anaphylaxis proposed at the 2005 National Institute of Allergy and Infectious Disease and the Food Allergy and Anaphylaxis Network symposium. Cases ascertained with the algorithm were compared with the traditional case-ascertainment method. Comparisons included demographic and clinical risk factors, proportion of monthly visits, and age/sex-specific rates. Cases ascertained with anaphylaxis ICD-9-CM codes were excluded from those ascertained with the algorithm.One thousand one hundred forty-nine patients were identified by using anaphylaxis ICD-9-CM codes, and 1,602 patients were identified with the algorithm. The clinical risk factors and demographics of cases were consistent between the 2 methods. However, the algorithm was more likely to identify older subjects (P.0001), those with hypertension or heart disease (P.0001), and subjects with venom-induced anaphylaxis (P.0001).This study introduces and validates an ICD-9-CM-based diagnostic algorithm for the diagnosis of anaphylaxis to capture subjects missed by using the ICD-9-CM anaphylaxis codes. Fifty-eight percent of anaphylaxis cases would be missed without the use of the algorithm, including 88% of venom-induced cases.

Rationale It is commonly assumed that aeroallergen sensitization in children persists. Two previous studies suggest that a proportion of school-age children spontaneously loose their sensitization. This phenomenon was examined further in younger children in a prospectively studied birth cohort. Methods The Childhood Allergy Study in suburban southeast Michigan was the source of these data. Testing for IgE to D. farinae , D. pteronyssinus , dog, cat, short ragweed, and timothy grass antigens was performed using a biotin-avidin amplified ELISA. Sensitization as determined by measurement of aeroallergen-specific circulating IgE to any of these 6 aeroallergens was assessed in children at ages 2 and 4 years. Results Of the 339 children tested at ages 2 and 4 years, 165 initially had at least one positive allergen-specific IgE test. At age 4 years, 61 children (37%) who had had a positive test became negative to all tests upon retesting. 104 were positive and 109 were negative on both occasions. 65 of 174 (37%) who were initially negative, became positive. Conclusion Many children who were initially sensitized to an aeroallergen at age 2 years had lost their sensitization at age 4 years. This finding has significant implications for the longitudinal assessment of clinical allergy in young children as well as for the study of the immunological effects of allergen-injection immunotherapy.

VOLUME 109, NUMBER 1 7' Prevalence of Positive Skin Prick Tests to Aeroallergens in | Children Without Symptoms of Allergic Disease: Analysis of the NHANES III Data Jenny M Montejo*, Michael R Simon§, Merlin Hamre*, Ronald Thomas*, Abdul H Bahrainwala* *Children's Hospital of Michigan, Wayne State University, Detroit, MI §Wayne State University, Children's Hospital of Michigan, Detroit, MI Positive skin prick tests to aeroallergens do not necessarily indicate the presence of allergy symptoms. The prevalence of positive skin prick tests for common aeroallergens in children with absence of rhinitis and asthma symptoms has not been studied. The aim of this study was to determine the prevalence of positive skin tests to aeroallergens and absence of allergic rhinitis and asthma symptoms in children ages 7 to 16 years. METHODS: The Third National Health and Nutrition Examination Survey (NHANES III), conducted from 1988 to 1994, was the source of data for this study. NHANES III is a cross-sectional, random household survey of the civilian, non-institutionalized population that used a complex, multistage probability sampling design. The survey included an extensive questionnaire regarding asthma and allergic rhinitis symptoms, spirometry, and epicutaneous skin test performed using 9 common aeroallergens: dust mite, German cockroach, cat, ragweed, Bermuda grass, rye grass, Russian thistle, white oak and Alternaria. Analyses were conducted using SUDANN software (Research Triangle Park Institute, NC) to account for the complex, multistage sampling design of the survey. Sample weights were used to produce national estimates by adjusting for the oversampling of young children and minority groups. Differences in the proportions of African-American and White children with positive skin tests, no symptoms and normal spirometry were examined using crosstabs procedure, with statistical significance set at a p-value 0.8, 18.9% had positive skin tests to at least one of the 9 aeroallergens tested. Among 4610 White and African-American children with no such symptoms and FEV 1/FVC >0.8, 17.2% of whites and 24.1% of African-Americans had positive skin tests, chi square 15.4, p 20% of FVC and FEV 1 from baseline) and laboratory responses (marked leukocytosis and hypoxemia) was observed 6 hours after pulmonary inhalation provocation test. Bronchoalveolar lavage performed 24 hours after PIPT showed a total cell count of 220.000 with marked lymphocitosis. Histopathologic examination of a transbrochial biopsy specimen revealed intersticial alveolitis. DISCUSSION: Our case gathers sufficient criteria to be considered as hypersensitivity pneumonitis caused by the dust derived from corn. We were able to detect IgG antibodies against our corn extract, and within 6 hours after PIPT with corn extract, the patient had a systemic picture closely resembling the ones he had with corn harvest. 7 -~B~ Sinus CT and Markers of Inflammation in Vocal Cord DysfuncJF~ I tion and Asthma Tina Hatley, Edward Peters, Scott Crater, Timothy McLaughlin, Thomas AE Platts-Mills, Larry Borish University of Virginia, Charlottesville, VA The paradoxical inspiratory closure of the vocal cords is characteristic of vocal cord dysfunction (VCD). These patients present with wheezing and frequently receive a misdiagnosis of asthma. Treatment with beta agonists and corticosteroids tends to be unsuccessful, and these patients therefore develop refractory disease. Our purpose was to evaluate the presence and extent of sinus disease using computed tomography (CT) and compare the findings with other aspects of airway inflammation, and markers of atopy in a series of patients with vocal cord dysfunction, acute asthma and controls. Twenty patients presenting to the University of Virginia ER or Asthma Clinic were diagnosed with clinical obstructive airway symptoms consistent with vocal cord dysfunction. Diagnosis was confirmed by a combination of history, lung function and laryngoscopy. Comparisons were made between 71 patients presenting to the university ER with acute asthma, 27 non-acute asthmatics and 56 non-asthmatic controls. Evaluation consisted of spirometry with flow-volume loops, exhaled nitric oxide gas (eNO), cell blood count for eosinophils, total serum IgE and specific IgE, as well as sinus CT scan. Sinus CT's were scored using our validated system on the basis of the opacity in each of the sinus cavities and the osteomeatal complex (max score 30). Extensive sinus CT changes (score > 12) were present in 23/71 acute asthmatic patients, 4/27 non-acute asthmatics and 2/56 nonasthmatic controls. In addition, absolute eosinophil counts, eNO, and total IgE were significantly elevated among the asthmatics. Patients with extensive sinus disease had elevated total IgE (500 IU -+ 104). Sinus symptoms reported by questionnaire did not predict sinus CT findings and were equally common among controls. Among the 20 patients with VCD, none had extensive sinus disease (mean score 2). They also had normal eNO (

Using morphological criteria, patients with Crohn's disease have higher in vitro spontaneous peripheral blood lymphocyte blast transformation than control subjects (P < 0.01). The rate of spontaneous thymidine uptake did not differ between the two groups. The immune mechanism responsible for this phenomenon is unknown.

A patient had infection with Mycobacterium intracellulare and anergy. Antituberculous chemotherapy proved ineffective. Repeated administration of dialyzable leukocyte extract (DLE) produced a sequential appearance of delayed type hypersensitivity in response to several antigens, as well as definitive clinical improvement. Unfortunately, the patient died from an Aspergillus fumigatus brain abscess. At autopsy, no evidence of active mycobacterial infection was found. DLE therapy may be indicated for the treatment of M. intracellulare infections which are unresponsive to chemotherapy. The disparity between the onset and course of skin test reactivities to different antigens suggests that DLE enhanced cellular immunity on an antigen-specific basis.