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Co-administration of human secretory IgA (sIgA) together with subtherapeutic vancomycin significantly enhanced survival in the Clostridioides difficile infection (CDI) hamster model . Vancomycin (5 or 10 mg/kgx5 days) + healthy donor plasma sIgA/monomeric IgA (TIDx21 days) or hyperimmune sIgA/monomeric IgA (BIDx13 days) enhanced survival of CDI hamsters. Survival curves were significantly improved compared to vancomycin alone (p=0.018 and 0.039 by log-rank (Mantel-Cox) for healthy, and hyperimmune, sIgA, respectively. Passive immunization with sIgA made with recombinant human secretory component and IgA dimer/polymer from pooled human plasma can be administered orally, and prevents lethal infection in a partially treated CDI hamster model.

Background: Patients with chronic kidney disease have been reported to have increased concentrations of blood tryptase. Detection of tryptase in the urine of healthy subjects has been reported. Objective: The objective is to determine whether tryptase is indeed cleared by the kidneys. Methods: Blood and urine collections were performed in healthy and systemic mastocytosis subjects. Total and mature tryptase concentrations in blood and total tryptase concentrations in urine were determined. Results: Total tryptase levels in urine were below the limit of detection in both healthy subjects and those with systemic mastocytosis, even after concentrating the urine 10-fold. Thus, both mature and protryptase levels in urine are Conclusion: Tryptase is not cleared by the kidneys into the urine.

Transient wheezing in young children has been reported to be independent of atopy. Although persistence of early wheezing has been associated with factors related to allergy in multiple studies, transient wheezing has not been similarly studied. The Childhood Allergy Study birth cohort was the source of these data. Transient wheezing was defined as history of wheezing in the past 12 months at ages 1, 2, and/or 4 years, but not at 6 years, and evaluated in relationship to aeroallergen-specific circulating IgE and positive skin testing as markers of an atopic profile. Testing for IgE and skin-prick testing to dust mites, dogs, cats, ragweed, and timothy were performed at the age of 6 years. Other variables in logistic regression analyses were sex; breast-feeding; birth order; parental allergy and smoking history; and household pets, daycare, fever, and antibiotic use in the 1st year of life. Of 372 children, 128 (34.4%) experienced transient wheezing and 175 (47.0%) never wheezed. Atopy was not associated with transient wheezing (adjusted odds ratio for a positive allergen-specific IgE test = 1.2, p = 0.66; skin-prick test = 0.8, p = 0.47). Boys were more likely to be transient wheezers (adjusted relative risk [RR] = 1.7; 95% confidence interval [CI], 1.1-2.8; p = 0.018). Transient wheeze was associated with antibiotic treatment in the first 6 months of life (adjusted RR = 1.6; 95% CI, 1.0-2.6; p = 0.048). We confirm previous observations that transient wheezing in young children is not associated with an atopic predisposition.

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: High osmolal ionic radiocontrast media (RCM) cause vascular release of endothelin-1 (ET-1) and activate mast cells. Iomeprol, a nonionic RCM, has recently been reported not to activate cardiac mast cells. This coronary angiography study was performed to extend those findings using another nonionic RCM, iopromide, and to further determine whether iopromide causes release of ET-1. Methods: Pulmonary artery plasma ET-1, histamine and serum tryptase were determined before and 30 min following angiography with iopromide in 11 subjects. ET-1, histamine and tryptase were measured using immunoassays. Results: The concentrations of ET-1 (1.36 ± 0.66 pg/ml), histamine (2.63 ± 1.15 nM), and β (M), and β (Conclusions: This study demonstrates the lack of release of ET-1 by iopromide. The lack of cardiac mast cell activation by iopromide is consistent with the report that iomeprol also does not activate cardiac mast cells.

Clostridium difficile infection has emerged as a growing worldwide health problem. The colitis of Clostridium difficile infection results from the synergistic action of C. difficile secreted toxins A and B upon the colon mucosa. A human monoclonal IgG anti-toxin has demonstrated the ability in combination therapy to reduce mortality in C. difficile challenged hamsters. This antibody is currently in a clinical trial for the treatment of human Clostridium difficile infection. More than one group of investigators has considered using polyclonal bovine colostral antibodies to toxins A and B as an oral passive immunization. A significant proportion of the healthy human population possesses polyclonal antibodies to the Clostridium difficile toxins. We have demonstrated that polyclonal IgA derived from the pooled plasma of healthy donors possesses specificity to toxins A and B and can neutralize these toxins in a cell-based assay. This suggests that secretory IgA prepared from such pooled plasma IgA may be able to be used as an oral treatment for Clostridium difficile infection.

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.

Anaphylaxis incidence rates and time trends in the United States have been reported using different data sources and selection methods. Larger studies using diagnostic coding have inherent limitations in sensitivity and specificity. In contrast, smaller studies using chart reviews, including reports from single institutions, have better case characterization but suffer from reduced external validity due to their restricted nature. Increasing anaphylaxis hospitalization rates since the 1990s have been reported abroad. However, we report no significant overall increase in the United States. There have been several reports of increasing anaphylaxis rates in northern populations in the United States, especially in younger people, lending support to the suggestion that higher anaphylaxis rates occur at higher latitudes. We analyzed anaphylaxis hospitalization rates in comparably sized northern (New York) and southern (Florida) states and found significant time trend differences based on age. This suggests that the relationship of latitude to anaphylaxis incidence is complex.

Background The assumption that the assessment of forced expiratory flow between 25% and 75% of vital capacity (FEF 25-75 ) does not provide additional information in asthmatic children with normal FEV 1 percent predicted has not been adequately tested. Objective We sought to determine whether the measurement of FEF 25-75 percent predicted offers advantages over FEV 1 percent predicted and FEV 1 /forced vital capacity (FVC) percent predicted for the evaluation of childhood asthma. Methods This is a secondary analysis of data from the Pediatric Asthma Controller Trial and the Characterizing the Response to a Leukotriene Receptor Antagonist and Inhaled Corticosteroid trials. Pearson correlation coefficients, Pearson partial correlation coefficients, canonical correlations, and receiver operating characteristic (ROC) curves were constructed. Results Among 437 children with normal FEV 1 percent predicted, FEF 25-75 percent predicted, and FEV 1 /FVC percent predicted were (1) positively correlated with log 2 methacholine PC 20 , (2) positively correlated with morning and evening peak expiratory flow percent predicted, and (3) negatively correlated with log 10 fraction of exhaled nitric oxide and bronchodilator responsiveness. Pearson partial correlations and canonical correlations indicated that FEF 25-75 percent predicted was better correlated with bronchodilator responsiveness and log 2 methacholine PC 20 than were FEV 1 percent predicted or FEV 1 /FVC percent predicted. In the ROC curve analysis, FEF 25-75 at 65% of predicted value had a 90% sensitivity and a 67% specificity for detecting a 20% increase in FEV 1 after albuterol inhalation. Conclusion FEF 25-75 percent predicted was well correlated with bronchodilator responsiveness in asthmatic children with normal FEV 1 . FEF 25-75 percent predicted should be evaluated in clinical studies of asthma in children and might be of use in predicting the presence of clinically relevant reversible airflow obstruction.

The authors wish to add the following to the acknowledgments of [1]: “The authors acknowledge the contribution of Dr. Ricky Malhotra to our research efforts. Dr. Malhotra introduced the cell culture techniques into our lab and helped to establish the cell based assay. He also helped to prepare Figure 4.”

Dystonia-associated features of anaphylaxis, including tongue swelling, and chest and throat tightness, have been rarely reported with selective serotonin reuptake inhibitor (SSRI) use. The patient is a 44-year-old woman who presented with palpitations, diaphoresis, dyspnea, swelling of the lips and tongue, and fixed upward deviation of her right eye following inadvertent ingestion of 20 mg of escitalopram in addition to her usual 10-mg dose. She reported transient resolution of all symptoms after autoinjector aqueous epinephrine administration (0.3 mg), with recurrence of symptoms after 35 min. The patient presented with one prior episode of anaphylactic symptoms and dystonia. She also reported one episode with purely anaphylactic features of swelling of lips and tongue, difficulty breathing and syncope. This case represents a unique dose-dependent episode of escitalopram-associated oculogyric dystonia with anaphylactic features. The transient resolution of the associated features of dystonia with intramuscular epinephrine administration is unique and suggests a common pathophysiology of the dystonic and anaphylactic symptoms.

OBJECTIVE To test the effects of written emotional disclosure on the health of adolescents with asthma and to examine how language in disclosures predicts outcomes. METHODS We randomized 50 adolescents with asthma to write for 3 days at home about stressful events (disclosure) or control topics. At baseline and 2 months after writing, we assessed symptoms, affect, disability, internalizing behavior problems, and lung function; parents independently rated internalizing behavior and disability. RESULTS Compared with control writing, disclosure writing led to improved positive affect and internalizing problems. Disclosure also decreased asthma symptoms and functional disability among adolescents with baseline elevations of these difficulties. Lung function was not changed. Disclosures with more negative emotion, insight, and causal words--and increased causal or insight words over days--predicted improved health. CONCLUSIONS Written emotional disclosure improves emotional and behavioral functioning among adolescents with asthma, particularly those whose writings suggest emotional processing and cognitive restructuring.

Volume production immersion lithography scanners will require new light sources offering increased output power while delivering improved dose stability over a shorter exposure window. Scaling the light source repetition rate from 4 to 6 kHz is the logical step toward meeting those combined requirements. We will present the results of the latest progress towards developing a 193 nm, 6 kHz light-source using Cymer’s proprietary MOPA technology. We will discuss how the design of critical core technology elements, such as the discharge chamber, the solid-state-pulsed-power modules and opto-electronic detectors within the system are modified to handle the higher average power, thermal demands, and speed to support reliable operation up to 6kHz. The XLA platform, which is already used on three generations of 193 nm MOPA light source, allows seamless integration of these improved technology elements into a reliable, proven product platform. We will also report results of the characterization of the optical parameters critical to the lithography process, such as spectral bandwidth and its stability, energy stability and dose stability, up to 6 kHz.

HISTORY OF PRESENT ILLNESS A 28-month-old male presented in September 1999 to our allergy/immunology clinic for followup of asthma and recurrent infections. Swelling and redness of the left suborbital area was noted that morning. However, the patient was still afebrile and playful. A review of his available medical records revealed that the patient was seen once at our clinic at the age of 10 months. He had been referred for recurrent otitis media (six episodes) and a periorbital cellulitis requiring hospitalization at 8 months of age. The infant’s poor growth had heightened the pediatrician’s suspicion of an immune deficiency. The patient was born at term with a birth weight of 2.93 kg. At 9 months of age, his weight plotted at the 5th percentile and his length was slightly below the 5th percentile. He had a history of five emergency room visits for wheezing and was started on nebulized cromolyn sodium. He had just been evaluated by an otorhinolaryngologist for persistent nasal congestion, snoring, and recurrent otitis media. A tympanostomy had been scheduled and the patient was started on mometasone furoate nasal spray and cefpodoxime proxetil for otitis media prophylaxis. The initial work-up obtained by the pediatrician showed the following: immunoglobulin (Ig)G 5.63 g/L (normal range is 5.76 to 14.03), IgA 260 mg/L (normal 140 to 1,590), IgM 690 mg/L (normal 470 to 2,280), and IgE 17 kIU/L (normal 0.8 to 15). White blood cell count was 5.8 109/L with 17% neutrophils, 49% lymphocytes, and 29% atypical reactive lymphocytes. Hemoglobin 1.78 mmol/L (normal 1.78 to 2.40), mean corpuscular volume 88 fL (normal 82 to 96), mean corpuscular hemoglobin 0.44 fmol (normal 0.37 to 0.47), mean corpuscular hemoglobin concentration 5.17 mmol/L (normal 4.96 to 5.58), platelets 237 109/L. A sweat chloride test was within normal range. Skin prick tests to common indoor allergens done in our clinic at 10 months of age were negative. The evaluation, at that time, was asthma, moderate in severity, and rhinitis. Discontinuation of cefpodoxime proxetil after 3 weeks was suggested. A followup appointment in 2 months was scheduled, but the patient returned 18 months later, because his asthma was poorly controlled.

Vocal cord dysfunction (VCD) is a respiratory disorder characterized by paradoxical closure of the vocal cords during the respiratory cycle leading to obstructive airway symptoms. The presenting symptoms vary from stridor to wheezing. VCD may coexist with asthma or masquerade as asthma. Misdiagnosis of VCD as asthma leads to inappropriate use of systemic steroids with its adverse effects, frequent emergency department visits, hospitalization, and, rarely, intubation and tracheostomy. Attenuation of the inspiratory flow volume loop on spirometry is suggestive of VCD. Laryngoscopic demonstration of the paradoxical vocal cord movements during an acute attack is the gold standard for the diagnosis of VCD. Patient education, speech therapy, and psychologic counseling are the therapeutic tools for treatment.

Atopic dermatitis is characterized by elevated serum IgE concentrations and dysregulation of T-lymphocyte function. To examine the pattern of cytokine production associated with elevated IgE levels, phorbol ester plus ionomycin-stimulated production of interleukin (IL)-4, IL-5, and interferon-gamma (IFN-gamma) by blood mononuclear cells from 16 patients with atopic dermatitis was compared with that of 18 healthy subjects. Spontaneous in vitro IgE production was also studied longitudinally in patients receiving placebo or daily treatment with 0.05 mg/m2 IFN-gamma. Spontaneous in vitro IgE production and mitogen-driven IL-4 and IFN-gamma synthesis did not differ when patients were receiving interferon treatment compared with no treatment. Furthermore, ionomycin plus phorbol ester-stimulated mononuclear cells from patients with atopic dermatitis produced less IL-4 and more IFN-gamma than did cells from healthy subjects. IL-5 production by cells from patients with atopic dermatitis did not differ from that of cells from healthy subjects. The ratio of IL-4 to IFN-gamma produced in vitro was significantly lower (p = 0.04) in the cells of patients with atopic dermatitis (0.9) as compared with those of healthy subjects (2.7). The findings suggest that when circulating T cells are stimulated under antigen presenting cell-independent conditions, atopic dermatitis is not characterized by the shift in the reciprocal relationship between IL-4 and IFN-gamma production, which has been postulated to explain the pathogenesis of IgE elevation and the therapeutic action of IFN-gamma in patients with atopic dermatitis.

RATIONALE AND OBJECTIVES The author evaluated the hypothesis that the incidence of allergic-type adverse events among atopic and asthmatic cardiac angiography patients would be lower in patients randomized to receive nonionic versus ionic lower osmolal contrast medium. METHODS Enrollment criteria included a history of food allergy, asthma, atopic dermatitis or pollinosis but not prior contrast media-induced adverse events. One hundred forty-two patients enrolled were randomized to receive either the ionic agent ioxaglate or nonionic iopamidol. Patients and investigators were masked. Sixty-eight patients received iopamidol, and 74 received ioxaglate. Group means were compared using the unpaired Student's t test. Contingency tables were analyzed using chi-square or Fisher's exact test. RESULTS Allergic-type adverse events (excluding flushing, warmth, and cardiac events) were recorded in 8 of 68 patients in the iopamidol group versus 19 of 74 in the ioxaglate group. Ioxaglate was more likely to be associated with a reaction than iopamidol (P < 0.05, chi-square test). Iopamidol was more likely to be associated with flushing when considered independently (38 of 68) than use ioxaglate (24 of 74)(P < 0.005, chi-square test). There was no difference in the incidence of cardiac events, or any combination of allergic-type adverse events, cardiac events, and flushing in patients who received iopamidol or ioxaglate. CONCLUSION In this double-masked study, iopamidol caused fewer allergic-type adverse events (excluding flushing and cardiac events) but more flushing than ioxaglate in patients with a history of asthma or atopic disease. When cardiac events also were considered, there was no difference in the incidence of reactions after iopamidol and ioxaglate.

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.

The relationship of angiotensin converting enzyme activity and angiotensin II to the inflammatory process in diseases such as sarcoidosis remains unclear. We hypothesize that granuloma macrophages regulate inflammation by release of angiotensin converting enzyme, which produces angiotensin II, and that angiotensin II in turn modulates monocyte/macrophage activity. Since tyrosine kinase catalyzes phosphorylation of tyrosine residues in proteins and is important in signal transduction and cellular activation, we further postulated that monocyte tyrosine kinases may play a role in the regulation of this process. Mononuclear cells from 11 healthy subjects were assayed for tyrosine kinase activity in the presence and absence of angiotensin II. In addition, tyrosine-specific phosphorylation of cellular proteins was also determined. Angiotensin II increased tyrosine kinase activity in a concentration-dependent manner. The maximal stimulation, which varied from 31 to 506%, was achieved following incubation of cells with 10−4 m angiotensin II. Angiotensin II also increased the tyrosyl-phosphorylation of three proteins with molecular weights of 57, 62, and 63 kDa. We conclude that tyrosine kinase activity of adherent mononuclear cells and tyrosine phosphorylation of certain protein(s) may be involved in angiotensin II regulation of inflammatory processes.

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.

Serum angiotensin converting enzyme activity is elevated in certain human granulomatous diseases. Angiotensin II modestly suppresses thymidine incorporation and augments gamma interferon production from human blood mononuclear cells. This suggests that angiotensin II may play an immunoregulatory role in human granulomatous inflammation. For this reason, the binding of angiotensin II to human peripheral blood mixed mononuclear cells, and to the human monocyte-like cell line, U-937, was studied. Angiotensin II binding to U-937 cells reveals a low level of saturable specific binding (Kd = 3 x 10(-10) M). However, binding to human cells is not easily reversible and is poorly inhibited in a competitive manner. In addition, the molecular integrity of the radioligand is not maintained following binding. Therefore, the definition of classical receptor binding cannot be fulfilled. Since binding is decreased by low temperatures and various metabolic inhibitors, it appears likely that endocytosis occurs, perhaps along with receptor binding. Angiotensin II or its breakdown products modulate the production of monocyte cAMP in spite of the inability to demonstrate classical cell surface receptors.

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.

Recent evidence suggests that anglotens in II may participate in the regulation of Inflammation. We previously reported that anglotens in II in bits its human peripheral blood mononuclear cell reactivity and acts directly on lymphocytes. These observations are again confirmed. In addition, purified OKT8+ but not OKT4+ T cell suspensions stimulated with phytohemagg uniting revealed Increased thymidine incorporation when simultaneously cultured for 48 hours with angictensin II. These findings suggest that anglotens in II may Inhibit mononuclear cell thymidlne uptake through stimulator of suppresser lymphocytes contained within the OKTE+ subpopulation.

The relationship between serum angiotensin-converting enzyme activity and inflammatory bowel disease was investigated in 37 patients who had Crohn's disease, 31 patients who had ulcerative colitis, and 104 control subjects. The enzyme activity tended to be depressed in Crohn's ileitis (P less than 0.05) and colitis, but not in Crohn's ileocolitis and ulcerative colitis. No increase in enzyme activity was observed in Crohn's disease ileum or colon or in ulcerative colitis colon. The granulomatous inflammation in Crohn's disease differs from that in sarcoidosis, in which striking elevation of angiotensin-converting enzyme is present in granulomatous tissue and frequently in serum.

Excerpt To the editor: In the recently published paper "Cimetidine as an Immunomodulator: Chronic Mucocutaneous Candidiasis as a Model" (1), the authors report that their patients with chronic muco...

Angiotensin-converting enzyme activity is present in human sarcoid as well as murine schistosome granulomas. Inhibition of angiotensin-converting enzyme by captopril results in decreased granuloma size in animals. Since captopril is used clinically to treat hypertension, its effect on human lymphocyte thymidine incorporation was determined. It was found that 5 X 10(-5) M and 10(-4) M captopril enhances lymphocyte thymidine uptake induced by 25 micrograms/ml phytohaemagglutinin-P. This suggests that captopril can alter immunological reactivity in man and that angiotensin-converting enzyme may have an immunological function.

Human allergic disease is mediated by antigen-specific IgE which fixes to a high-affinity receptor on the surfaces of mast cells and basophils. Antigen bridging of adjacent IgE molecules results in the release of mediators of Type I hypersensitivity. These include histamine, neutrophil chemotactic factors, eosinophil chemotactic factor of anaphylaxis (ECF-A), and platelet-activating factor (PAF) (Plaut and Lichtenstein, 1978). In turn, these substances affect various other leukocytes.

Recent evidence suggests that angiotensin II may participate in the regulation of inflammation. We therefore studied the effects of angiotension II on human peripheral blood mononuclear cell reactivity. Peripheral blood mononuclear cell suspensions stimulated with PHA-P revealed decreased thymidine incorporation when simultaneously cultured for 48 or 72 hours with angiotensin II. Experiments were next conducted to determine whether angiotensin II acted directly on lymphocytes. Complete monocyte depletion (greater than 99.5%) resulted in low PHA-P-induced reactivity which was still inhibited by the addition of angiotensin II. Purified (greater than 99.5%) lymphocytes incubated with angiotensin II prior to reconstitution of mixed mononuclear cell suspensions led to reduced PHA-P-stimulated thymidine incorporation. These findings suggest that angiotensin II can effect mononuclear cell uptake possibly through actions on the lymphocyte population.