Assessment of serum allergen-specific IgE levels in horses with seasonal allergic dermatitis and recurrent airway obstruction in Spain.

Allergic conditions are prevalent equine diseases that can be diagnosed by clinical examination alone, but definitive diagnosis is more likely with laboratory testing. The ELISA Allercept© test was used to analyse the serum samples of 73 horses with allergic diseases. Sixty-one horses (83.5%) had allergen-specific IgE levels ≥ 150 ELISA Units (EU), the cut-off defined by the assay. Fifty-four horses had allergic dermatitis (AD) with high IgE levels to Tyrophagus putrescentiae (51.9%), Rumex crispus (48.1%), Tabanus (46.3%) and Dermatophagoides farinae/ D. pteronyssinus (40.7%). Seven horses with recurrent airway obstruction (RAO) had a high prevalence of T. putrescentiae (85.7%), followed by that of Acarus siro (57.1%) and D. farinae/D. pteronyssinus (57.1%). Horses affected with RAO had more positive reactions to mites (2.22 ± 0.84) than did horses with AD (1.51 ± 0.61, P < 0.05). A strong correlation of serum allergen-specific IgE level was found between Culex tarsalis and Stomoxys (r = 0.943) and between Dactylis glomerata and both Secale cereale (r = 0.79) and R. crispus (r = 0.696). These results indicate that among horses with allergic diseases in Spain, ELISA tests demonstrated a high prevalence of serum allergen-specific IgE in response to mites. Our study emphasises the importance of laboratory testing and updating allergy panels to improve the likelihood of a definitive diagnosis and the identification of allergens that should be included in allergic disease treatment.

Analysis of soluble CD14 and its use as a biomarker in neonatal foals with septicemia and horses with recurrent airway obstruction.

Soluble CD14 (sCD14) binds bacterial lipopolysaccharide (LPS) and acts as an anti-inflammatory LPS-inhibitor in vivo. In humans, sCD14 is one of the soluble biomarkers used for various inflammatory diseases and conditions, however, sCD14 assays have not yet been evaluated in horses. Here, we developed and optimized a bead-based assay for the quantification of sCD14 in horses. The assay was then used to determine native sCD14 concentrations in serum from healthy and septic foals, in the colostrum of healthy mares and in plasma from adult horses with recurrent airway obstruction (RAO) and control horses. Healthy foals and adult horses had sCD14 concentrations in serum or plasma in the high ng/ml range. The concentration of sCD14 in colostrum samples from healthy mares was in the µg/ml range. Foals with septicemia and adult horses with RAO had significantly higher sCD14 concentrations in their circulation than the respective control groups. The findings suggest that sCD14 can become a valuable biomarker for neonatal septicemia, RAO and possibly also for other inflammatory diseases in horses. Further studies and larger samples numbers are required to determine normal sCD14 concentration ranges and those that are indicative of disease progression, severity or prognosis.

Blood eosinophils in workers with aluminum potroom asthma are increased to higher levels in non-smokers than in smokers.

BACKGROUND: Aluminum potroom asthma (PA) has been described in several reports. This study aimed to investigate the association between blood eosinophils and PA. METHODS: In a cross-sectional study, 338 workers were examined as follows: spirometry, blood eosinophils, skin prick test, and work exposure measurements. They also completed a questionnaire on respiratory symptoms, smoking, allergy, and duration of work exposure. RESULTS: The odds ratio for PA was 4.2 (95% confidence interval 1.5-9.7) for workers with eosinophils > or =400 x 10(6) cells/L compared with workers with eosinophils <200 x 10(6) cells/L. In non-smokers, the number of eosinophils was 177 x 10(6) cells/L (P < 0.001) higher among workers with PA than asymptomatic workers, whereas the corresponding difference among current smokers was only 63 x 10(6) cells/L (P = 0.03). CONCLUSIONS: The prevalence of PA was positively associated with blood eosinophils. An attenuation of the blood eosinophil increase was observed in smoking asthmatics, suggesting an immune-modulating effect of smoking.

Temporal clinical exacerbation of summer pasture-associated recurrent airway obstruction and relationship with climate and aeroallergens in horses.

OBJECTIVE: To describe the seasonal pattern of clinical exacerbation of summer pasture-associated recurrent airway obstruction (SPA-RAO) in relation to climate and aeroallergens in horses. ANIMALS: 19 horses with SPA-RAO and 10 nonaffected horses. PROCEDURES: Daily examinations were performed on all horses while they were kept on pasture for 3 years. Onset and progression of clinical exacerbation based on a clinical score of respiratory effort were evaluated in relation to changes in maximum temperature, minimum temperature, mean temperature, maximum dew-point temperature, minimum dew-point temperature, and delta dew-point temperature. Seasonal pattern of clinical exacerbation was evaluated in relation to aeroallergen counts (20 types of fungal spores and 28 types of pollen). RESULTS: Seasonal pattern of clinical exacerbation of SPA-RAO was associated with increases in temperature (heat) and dew-point temperature (humidity), counts of fungal spores, and counts of grass pollen grains. Seasonal pattern of clinical exacerbation paralleled and was associated with increases in counts of specific types of fungal spores, particularly Basidiospore, Nigrospora, and Curvularia spp. CONCLUSIONS AND CLINICAL RELEVANCE: Although a causal relationship could not be determined, the seasonal pattern of clinical exacerbation of SPA-RAO was associated with hot and humid conditions and high environmental counts for fungal spores and grass pollen grains. It is not known yet whether these are aeroallergens that cause clinical exacerbation of the disease.

Para-Bromophenacyl bromide alleviates airway hyperresponsiveness and modulates cytokines, IgE and eosinophil levels in ovalbumin-sensitized and -challenged mice.

Airway hyperresponsiveness, airway eosinophilia and increased IgE levels in serum are the important characteristic features of asthma. We evaluated the potential of para-Bromophenacyl bromide (PBPB), a known phospholipase A(2) inhibitor, on allergen-induced airway hyperresponsiveness in a mouse model. We sensitized and challenged mice with ovalbumin (OVA) to develop airway hyperresponsiveness as assessed by airway constriction and airway hyperreactivity (AHR) to methacholine (MCh) induced by allergen. The mice were orally treated with PBPB (0.1, 1 and 10 mg/kg) during or after OVA-sensitization and OVA-challenge to evaluate its protective or reversal effect on airway constriction and AHR to MCh. Determination of OVA-induced airway constriction and AHR to MCh were performed by measuring specific airway conductance (SGaw) using non-invasive dual-chamber whole body-plethysmography. We observed that PBPB (1 mg/kg) significantly reduced OVA-induced airway constriction and AHR to MCh (p<0.01). PBPB (1 mg/kg) treatment significantly inhibited PLA(2) activity in the BAL fluid. Cytokine analysis of the BAL fluid revealed that PBPB caused an increase in interferon-gamma (IFN-gamma) (p<0.02) and a decrease in interleukin-4 (IL-4) (p<0.05) and interleukin-5 (IL-5) (p<0.05) levels. The OVA-specific serum IgE levels (p<0.01) and the BAL eosinophils (p<0.001) were also reduced significantly. Thus, PBPB is capable of modulating allergen induced cytokine levels and serum IgE levels, and alleviating allergen induced airway hyperresponsiveness and eosinophils in mice. These data suggest that PBPB could be useful in the development of novel agents for the treatment of allergen induced airway hyperresponsiveness.

7-Oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridines as novel inhibitors of human eosinophil phosphodiesterase.

High-throughput file screening against inhibition of human lung PDE4 led to the discovery of 3-ethyl-1-(4-fluorophenyl)-6-phenyl-7-oxo-4, 5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine (11) as a novel PDE4 inhibitor. Subsequent SAR development, using an eosinophil PDE assay, led to analogues up to 50-fold more potent than 11 with IC50 values of 0.03-1.6 microM. One such compound, CP-220,629 (22) (IC50 = 0.44 microM), was efficacious in the guinea pig aerosolized antigen induced airway obstruction assay (ED50 2.0 mg/kg, po) and demonstrated a significant reduction in eosinophil (55%), neutrophil (65%), and IL-1beta (82%) responses to antigen challenge in atopic monkeys (10 mg/kg, po).

The effect of of glucocorticoids on grain dust-induced airway disease.

STUDY OBJECTIVES: To determine the effect of glucocorticoids on grain dust-induced airflow obstruction and airway inflammation. DESIGN: Randomized controlled trial. SETTING: University hospital. PARTICIPANTS: Health volunteers. INTERVENTIONS: Two randomized, placebo-controlled trials, each studying 10 healthy volunteers who were pretreated with either triamcinolone acetonide (Azmacort) oral inhaler 4 puffs twice daily (800 microg daily) for 7 consecutive days or IV hydrocortisone (3 microg/kg/min) as a 14-h continuous infusion, then subjected to a controlled inhalation exposure to corn dust extract (CDE) (endotoxin exposure dose of 3 microg/kg). A single-blind, crossover study design was performed for each trial enrolling 10 healthy, lifetime nonsmokers, with no history of lung disease or environmental exposure to grain dust. MEASUREMENTS AND RESULTS: Following each inhalation exposure to CDE, spirometry was performed at regular intervals and BAL was performed at 4 h. Both treatment and placebo groups demonstrated significant decrements in spirometry and increments in BAL cellularity following CDE inhalation compared with placebo. Inhaled steroid treatment resulted in a significantly higher FEV1 only at the 2-h time point following CDE inhalation with no significant differences observed in the BAL total cell concentration or cellular differential compared with placebo. IV hydrocortisone treatment resulted in a significantly higher FEV1 and FVC between 2 and 4 h after CDE inhalation, as well as significant reductions in the BAL total cell, macrophage, and eosinophil concentrations. Interestingly, the concentration of tumor necrosis factor-alpha and interleukin-8 in the BAL fluid was also decreased following treatment with IV glucocorticoids. CONCLUSIONS: These results demonstrate that glucocorticoids, administered IV and perhaps by inhalation, have a mildly protective effect on airflow obstruction and airway inflammation induced by inhalation of grain dust.

Modification of allergen-induced airway obstruction and airway hyperresponsiveness in an allergic rabbit model by the selective platelet-activating factor antagonist, BN 52021.

Allergen challenge of eight ragweed-immunized rabbits elicited a prolonged airway obstruction that was evident during the 6-hour study period. Airway responsiveness to histamine was enhanced 24 hours after allergen exposure (geometric mean of the 50% reduction in effective dose [ED50] of dynamic compliance [Cdyn] before challenge, 3.46 mg/ml, decreased to 0.52 mg/ml after challenge, p less than 0.01; pulmonary resistance ED50 geometric mean before challenge, 3.50 mg/ml, decreased to 0.65 mg/ml after challenge, p less than 0.05). In a random crossover study, the selective platelet-activating factor antagonist, BN 52021 (60 mg/kg, orally, 1 hour before allergen challenge), significantly reduced the allergen-induced airway obstruction (p less than 0.005). In addition, pretreatment with BN 52021 reduced the associated increased airway responsiveness induced by allergen exposure (prechallenge Cdyn ED50, 1.93; after challenge, 2.13 mg/ml; pulmonary resistance ED50, 1.91 mg/ml before challenge and 1.69 mg/ml after challenge). These present observations suggest a role for platelet-activating factor in the pathogenesis of allergen-induced airway obstruction and in the development of airway hyperresponsiveness in an allergic rabbit model.

Prevention of allergen-induced bronchial obstruction in sensitized guinea pigs by crude alcoholic onion extract.

Thirteen guinea pigs, sensitized to ovalbumin, were pretreated with either 1 ml alcoholic onion extract (= 12% v/v ethanol) or 1 ml 12% ethanol solution (control) according to a randomized crossover protocol. Thirty minutes later the animals were challenged twice for 30 sec (n = 5), respectively 60 sec (n = 8), by the inhalation of ovalbumin (1 ml 1% ovalbumin solution nebulized in 10 l air). The intensity of bronchial obstruction was measured by whole body plethysmography using as parameter the amount of 'compressed air'. Oral pretreatment of guinea pigs with onion extract markedly reduced the asthmatic response (p less than 0.02). After onion pretreatment near normal values were obtained after 30 sec challenge (0.04 +/- 0.06 ml compared to 0.24 +/- 0.15 ml in the control) and only slightly increased values after 60 sec challenge (0.16 +/- 0.07 ml compared to 0.33 +/- 0.25 ml in the control).