Pulmonary function in horses with recurrent airway obstruction after aerosol and parenteral administration of beclomethasone dipropionate and dexamethasone, respectively

OBJECTIVE: To determine changes in clinical signs of disease and response to pulmonary function testing in horses with recurrent airway obstruction (heaves) after aerosol and parenteral administration of beclomethasone dipropionate and dexamethasone, respectively. ANIMALS: 6 horses with inducible and reversible heaves. PROCEDURE: Episodes of heaves were induced by exposure (challenge) to moldy hay and straw for 7 days. Horses were assigned to treatment groups (aerosolized beclomethasone dipropionate, parenterally administered dexamethasone, aerosolized propellant [control]), and respiratory frequency and subjective assessment of respiratory effect were determined twice daily. Maximal change in pleural pressure (delta-Pplmax), pulmonary resistance (RL), and dynamic compliance (Cdyn) was determined on days 0, 7, 10, 14, and 21. RESULTS: The RL and delta Pplmax were increased, and Cdyn was decreased in all horses in response to natural challenge. Beclomethasone reduced RL on day 10, reduced delta Pplmax on days 14 and 21 and increased Cdyn on day 14. Dexamethasone reduced RL and delta Pplmax on days 10, 14, and 21 and increased Cdyn on days 10 and 14. Respiratory effort (subjective assessment) improved after 2 and 3 days of beclomethasone and dexamethasone administration but rebounded to pretreatment values 1 and 3 days after discontinuation of drugs. CONCLUSIONS: Pulmonary function testing responses and clinical signs of airway obstruction were improved by administration of beclomethasone. The magnitude of response to aerosolized beclomethasone generally was less marked than the response to parenterally administered dexamethasone. Higher or more frequent dosing of aerosolized beclomethasone may be necessary to achieve the anti-inflammatory response to parenterally administered dexamethasone.     

Alteration in adrenocortical function in horses with recurrent airway obstruction after aerosol and parenteral administration of beclomethasone dipropionate and dexamethasone, respectively

OBJECTIVE: To determine alteration in adrenocortical function in horses with recurrent airway obstruction (heaves) after aerosol and parenteral administration of beclomethasone dipropionate and dexamethasone, respectively. ANIMALS: 6 horses with inducible and reversible heaves. PROCEDURE: Episodes of heaves were induced by exposure to moldy hay and straw for 7 days (natural challenge). Horses then underwent treatment (aerosolized beclomethasone, parenterally administered dexamethasone, and aerosolized propellant) for 7 days. Horses remained in the mold-contaminated environment for 7 days after discontinuation of drugs. Adrenocortical function was determine by serial evaluation of cortisol concentration in serum obtained on days 0, 7, 9, 12, 14, 16, 19, and 21. Adrenocorticotropic hormone stimulation testing was performed in 4 horses/treatment group on days 0, 7, 14, and 21. RESULTS: Endogenous cortisol production was suppressed in beclomethasone- and dexamethasone-treated horses within 2 days of treatment but recovered to values similar to those in propellant-treated horses approximately 2 and 4 days after discontinuation of drugs. Serum cortisol concentration in propellant-treated horses gradually decreased during the study and was significantly lower than baseline on days 14, 16, 19, and 21. Mean increase in serum cortisol concentration in response to ACTH stimulation testing after beclomethasone and dexamethasone administration did not differ significantly from the response observed in propellant-treated horses. CONCLUSIONS: Aerosol and parenteral administration of beclomethasone and dexamethasone, respectively, suppressed adrenocortical function; however, endogenous cortisol production resumed approximately 2 and 4 days after discontinuation of drugs. Responsiveness to ACTH stimulation testing was not affected by the 7-day treatment period.     

Cytologic evaluation of bronchoalveolar lavage fluid from horses with recurrent airway obstruction after aerosol and parenteral administration of beclomethasone dipropionate and dexamethasone, respectively

OBJECTIVE: To determine cytologic changes in horses with recurrent airway obstruction (heaves) after administration of aerosolized beclomethasone dipropionate and dexamethasone parenterally. ANIMALS: 6 horses with inducible and reversible heaves. PROCEDURE: Episodes of heaves were induced by exposure to moldy hay and straw for 7 days. Horses were assigned to treatment groups (aerosolized beclomethasone, parenterally administered dexamethasone, aerosolized propellant), and pulmonary inflammation was evaluated by serial cytologic examination of bronchoalveolar lavage (BAL) fluid samples obtained on days 0, 7, 10, 14, and 21. Total and differential cell counting and phenotypic analysis of lymphocyte subpopulations in BAL fluid were performed. RESULTS: 7 days of natural challenge induced neutrophilic inflammation. Neutrophil counts in BAL fluid were reduced in beclomethasone- and dexamethasone-treated horses on days 10 and 14 but rebounded to pretreatment values on day 21. The proportion of proinflammatory lymphocyte subpopulations (CD4+ and B+) and MHC class-II antigen expression were increased on days 14 and 21 in propellant-treated horses, compared with beclomethasone- and dexamethasone-treated horses. CONCLUSIONS: Aerosolized beclomethasone attenuated neutrophilic pulmonary inflammation and prevented alteration in lymphocyte subpopulations in horses with heaves. Results were similar to the response associated with parenterally administered dexamethasone. Short-term administration of aerosolized beclomethasone without minimizing environmental allergen exposure is not expected to provide prolonged anti-inflammatory benefit for horses with heaves.     

Onset of action of aqueous beclomethasone dipropionate nasal spray in seasonal allergic rhinitis

Beclomethasone dipropionate nasal spray is widely used in the treatment of seasonal allergic rhinitis; however, the time of onset of action has not been determined. This study assessed the onset of action, level of relief, and efficacy of beclomethasone nasal spray in patients with seasonal allergic rhinitis. In a double-blind, randomized, placebo-controlled, parallel-group, multicenter, 7-day study, symptomatic patients were administered two inhalations of beclomethasone dipropionate (n = 80) or placebo (n = 81) into each nostril twice daily. Patients assessed the onset of action and level of relief at 6, 24, and 48 hours and at days 3 and 7. Investigators evaluated symptoms at days 0, 3, and 7 and response to therapy at days 3 and 7. The difference in the cumulative number of patients reporting relief of symptoms was statistically significant in favor of beclomethasone dipropionate by hour 24 (P = 0.05). Patients in the beclomethasone dipropionate group experienced a greater level of relief than patients receiving placebo at hour 24, and improvement increased over the 7-day study compared with a decrease in relief in the placebo group. Beclomethasone dipropionate was significantly more effective than placebo in reducing symptoms (P < or = 0.02), and patients in the beclomethasone dipropionate group showed a more favorable response to treatment than did patients in the placebo group (P < 0.01). Adverse events were minor in both groups. Beclomethasone dipropionate nasal spray produced significant onset of relief of symptoms the first day of treatment; improvement was sustained and increased over the course of the study.     

Slowing the deterioration of asthma and chronic obstructive pulmonary disease observed during bronchodilator therapy by adding inhaled corticosteroids. A 4-year prospective study

OBJECTIVE: To determine if deterioration in patients with asthma or chronic obstructive pulmonary disease (COPD) during bronchodilator therapy could be slowed by additional treatment with an inhaled corticosteroid. DESIGN: A 4-year prospective study. SETTING: Twenty-nine general practices in the catchment area of the University of Nijmegen, Nijmegen, the Netherlands. PATIENTS: The study included 56 patients (28 with asthma and 28 with COPD) who showed an annual decrease in the forced expiratory volume in 1 second (FEV1) of at least 80 mL in combination with at least two exacerbations per year during bronchodilator therapy alone. Forty-eight patients completed the study. INTERVENTION: During the first 2 years of treatment, patients received only bronchodilator therapy (salbutamol, 400 micrograms, or ipratropium bromide, 40 micrograms). During years 3 and 4, they received additional treatment with beclomethasone dipropionate, 400 micrograms two times daily. RESULTS: Prebronchodilator FEV1 increased 458 mL/y (95% CI, 233 to 683 mL/y) during the first 6 months of beclomethasone treatment; FEV1 then decreased 102 mL/y (CI, 57 to 147 mL/y) during months 7 to 24. The annual decline in FEV1 during beclomethasone treatment was less than the decline of 160 mL/y seen before beclomethasone therapy (difference, 58 mL/y; 95% CI, 2 to 87 mL/y). Only in patients with asthma did beclomethasone treatment improve bronchial hyperresponsiveness (assessed by determining the concentration of histamine that provoked a 20% decrease in FEV1 [PC20]) by 3.0 doubling doses per year (95% CI, 0.8 to 5.2 doses per year). Beclomethasone treatment was associated with improvement in peak expiratory flow rate, alleviation of symptoms, and a decrease in the number of exacerbations in both patient groups. CONCLUSIONS: Adding beclomethasone, 800 micrograms daily, slowed the unfavorable course of asthma or COPD seen with bronchodilator therapy alone. This effect was most evident in asthmatic patients.     

Maternal malignant melanoma metastatic to the products of conception. Report of a case

Beclomethasone dipropionate aerosol at a dose of 100 mug four times a day was administered to 32 patients suffering from chronic perennial asthma. Twenty-three of these patients had previously received prolonged treatment with corticosteroids, causing various degrees of adrenal suppression in some patients. Almost complete recovery of adrenal function was observed within a period of six months in most patients. Treatment with beclomethasone dipropionate did not affect the hypothalamic-pituitary-adrenal axis in the other nine asthmatic patients who had not received prolonged corticosteroid therapy previously and who served as a control group.     

Anti-inflammatory effects of inhaled beclomethasone dipropionate in nonatopic asthmatics

The effects of inhaled beclomethasone dipropionate (BDP) on asthma symptoms and infiltration of the bronchial mucosa by inflammatory cells were investigated in an open study of 10 patients with mild-to-moderate nonatopic bronchial asthma. Asthma scores were recorded in an asthma diary. Peak expiratory flow (PEF), PEF diurnal variation (PEF%), forced expiratory volume in one second (FEV1%), methacholine airway hypersensitivity (minimum dose of methacholine) (Dmin) were measured. Biopsy of the bronchial mucosa was performed before and after 8 weeks of treatment with BDP (400 micrograms.day-1). The following inflammatory cells were immunostained: eosinophils with anti-EG2; mast cells with AA1; neutrophils with NP57; T-lymphocytes with anti-CD3, CD4, and CD8; and activated T-lymphocytes with anti-CD25. There was a significant improvement in the asthma symptom score, PEF%, FEV1%, and Dmin after BDP therapy and the number of EG2-, AA1-, CD3-, CD4-, and CD25-positive cells decreased significantly. We conclude that inhaled beclomethasone dipropionate inhibited inflammatory cell infiltration of airway tissue and that associated with this there was an improvement of symptoms in this open study of inhaled beclomethasone dipropionate in a group of nonatopic asthmatic subjects.     

Beclomethasone dipropionate use in chronic asthmatic patients. Effect on adrenal function after substitution for oral glucocorticosteroids

The clinical effectiveness of beclomethasone dipropionate (BDP) aerosol and adrenal function after withdrawal of oral corticosteroid therapy were evaluated in 32 severely steroid-dependent asthmatic patients. Twenty-four of 28 patients were able to discontinue oral glucocorticosteroid therapy, while four failed to do so. Ventilatory studies showed no substantial changes at the end of six months' BDP treatment. In 24 patients, adrenal insufficiency was present before BDP therapy was started. In 20 of those patients, the response of cosyntropin returned to normal two months after discontinuation of systemic steroid treatment and administration of BDP.     

Beclomethasone given after the early asthmatic response inhibits the late response and the increased methacholine responsiveness and cromolyn does not

BACKGROUND: Single doses of inhaled beclomethasone or inhaled cromolyn, given before allergen inhalation, inhibit allergen-induced late asthmatic responses (LARs) and increased airway responsiveness (delta log methacholine PC20). We hypothesized that when given 2 hours after allergen, beclomethasone might work better than cromolyn. METHODS: In 10 patients with mild, stable, atopic asthma with LARs or delta log PC20 or both, we performed a double-blind, double-dummy, random-order trial comparing a single dose of inhaled beclomethasone (500 micrograms), cromolyn (20 mg), and placebo, administered 2 hours after allergen challenge on LAR and delta log PC20. RESULTS: The treatment effect on LAR was significant (p < 0.001). The LAR after beclomethasone (7.3% +/- 6.1%) was significantly less than after cromolyn (20.4% +/- 15.2%) or placebo (26.4% +/- 8.2%); cromolyn was not different from placebo. There was a borderline treatment effect on delta log PC20 (p = 0.056) with beclomethasone (0.12 +/- 0.31) less than placebo (0.37 +/- 0.39) but not less than cromolyn (0.34 +/- 0.18). CONCLUSION: Beclomethasone (500 micrograms) administered 2 hours after allergen challenge markedly inhibited the LAR and had a small effect on allergen-induced airway responsiveness. Cromolyn (20 mg) was not effective on maximal LAR; a small effect on the early part of the LAR was suggested.     

Pulmonary function measurements during repeated environmental challenge of horses with recurrent airway obstruction (heaves)

OBJECTIVES: To evaluate the degree of reproducibility in clinical variables, blood gas measurements, and lung function variables, and the changes in these variables caused by exposure to moldy hay in naturally sensitized and control horses. PROCEDURE: The magnitude of variation in arterial blood gas and pulmonary function measurements were evaluated in a model of naturally acquired heaves. Horses with heaves and similarly aged control horses were studied prior to moldy hay challenge and again after the horses with heaves manifested clinical signs of airway obstruction. This cycle of testing was repeated 3 times to determine the variation of the before and after challenge measurements. Variables evaluated for repeatability included: clinical score; arterial O2 and CO2 tensions; pulmonary function variables, such as breathing rate (f), tidal volumes, and flow rates; lung resistance (RL); dynamic compliance; and work of breathing (Wb). RESULTS: Before challenge, significant differences observed between control horses and horses with heaves included clinical score, expiratory flow rate at near-end expiration, RL, and Wb. After exposure to moldy hay, variables measured in control horses were largely unchanged. However, in the afflicted horses, significant changes were observed for clinical score, arterial O2 and CO2 tensions, breathing rate, peak tidal inspiratory and expiratory flow rates, dynamic compliance, RL, and Wb, compared with prechallenge values and with control horses' postchallenge values. Analysis of the data revealed few statistically significant differences between repeats of challenges. CONCLUSION: Horses afflicted with heaves manifest airway obstruction that can be measured in repeatable fashion.     

A clinical comparison of intranasal budesonide with beclomethasone dipropionate for perennial non-allergic rhinitis: a 12 month study

To evaluate possible differences in efficacy and safety between budesonide and beclomethasone dipropionate when used intranasally in the treatment of perennial non-allergic rhinitis, a 12-month open study was undertaken in 24 patients suffering from perennial non-allergic rhinitis. Both drugs were applied intranasally from pressurised aerosols at a daily dosage of 400 micrograms. On entry and at visits after 1, 2, 4, 6, 9 and 12 months, rhinoscopy was performed and the severity of nasal symptoms graded according to a four-point rating scale. All nasal symptoms were reduced from baseline during the treatment period in both groups. Tachyphylaxis was not observed. No clinically significant changes in haematology or blood chemistry parameters were observed in either group, and analysis of plasma cortisol levels revealed no influence of either drug on the hypothalamic-pituitary-adrenal axis. Local adverse reactions were uncommon and mild. Budesonide and beclomethasone dipropionate used intranasally at 400 micrograms per day were found to be safe, and budesonide was found to have a significantly higher (p < 0.05) efficacy than beclomethasone dipropionate in alleviating symptoms of perennial non-allergic rhinitis.     

Effects of glucocorticoids and beta-adrenoceptor agonists on the proliferation of airway smooth muscle

An increase in airway smooth muscle is a characteristic feature of asthma. Because beta-adrenoceptor agonists and corticosteroids are commonly used in the treatment of asthma we have studied the effects of these medicines on the growth of airway smooth muscle. These agents were incubated with bovine airway smooth muscle cells for 40 h for measurement of thymidine incorporation and 64 h for measurement of cell counts. Salbutamol inhibited thymidine incorporation (IC50 = 60 nM) and led to a reduction in cell number (IC50 = 10 nM). At 10 microM there was a 14.6 +/- 2.6% reduction in cell number. Salmeterol also inhibited the growth of the airway smooth muscle cells but the effect did not plateau at 10 microM. At this concentration there was an 89.5 +/- 3.6% reduction in thymidine incorporation and a 44.1 +/- 5.2% reduction in cell number. Cortisol and beclomethasone dipropionate were more potent than salbutamol in inhibiting thymidine incorporation with IC50 values of 5 nM and 0.2 nM respectively. Cortisol 100 nM led to a 16.6 +/- 6.5% reduction and beclomethasone dipropionate 3 nM led to a 17.8 +/- 5.8% reduction in cell number. If similar effects occur in man and in vivo, these medicines could act directly on airway smooth muscle to inhibit the development of hyperplasia.     

Interferon-alpha treatment of chronic hepatitis C virus infection in children

The leukotrienes (LT) LTD4 and LTB4 have been shown to cause bronchoconstriction and neutrophil accumulation, respectively, in horse lungs. Such changes are characteristic of the equine allergic respiratory disease, chronic obstructive pulmonary disease (COPD). To further investigate the role of these putative mediators in the pathogenesis of equine COPD the effect of a 5-lipoxygenase inhibitor, fenleuton, on antigen-induced changes in horses with this condition has been examined. Six horses with COPD underwent a series of four antigen challenges, one month apart, with placebo pre-treatment on three occasions and fenleuton (4 days oral dosing 5 mg/kg) pre-treatment on one occasion. Three horses received fenleuton prior to the second challenge and three horses received the drug prior to the fourth antigen challenge. Changes in radiolabelled neutrophil distribution, lung function and peripheral leucocyte counts were monitored on each occasion for 7 h following the start of antigen challenge. Antigen challenge caused an increase in radioactive counts over the lungs and a decrease in peripheral leucocyte count. Neither response was affected by fenleuton pre-treatment. Mean maximal changes in pleural pressure (delta Pplmax) and respiratory rate were also unaffected by fenleuton pre-treatment. However, in the two horses which responded to antigen-challenge with a particularly marked increase in delta Pplmax (> 15 cm H2O), prior administration of fenleuton reduced the response by 64 and 63%. These results suggest that 5-lipoxygenase inhibitors warrant further investigation as bronchodilators in equine COPD.     

Beclomethasone dipropionate aerosol in the treatment of chronic bronchial asthma

In a double-blind, randomized study, 93 corticosteroid-independent patients with chronic bronchial asthma were treated with either beclomethasone dipropionate aerosol at 400 mug per day of its vehicle for 4 wk to determine and compare the effectiveness and safety of the preparations. Evaluations made before, at weekly intervals during, and 1 wk after treatment indicated that beclomethasone dipropionate aerosol was superior to its vehicle is improving FVC, FEV1, FEF25%--75%, and clinical signs and symptoms, and in the overall evaluations by both the investigators and the patients. Plasma cortisol levels measured at the end of the second and fourth weeks were not substantially different from those before treatment in either group. No significant side effects or abnormalities in laboratory results were noted.     

Variations in systemic and pulmonary endothelin-1 in horses with recurrent airway obstruction (heaves)

Recurrent airway obstruction (RAO) is an asthma-like condition of the horse that represents a major cause of morbidity and loss of performance. The exact pathogenesis of asthma in man is unclear but the role of endothelin (ET) is currently under investigation, thus sparking interest in the bronchoconstrictive and vasoconstrictive properties of endothelin in the equine-specific disease entity. In this study, we investigated the levels of ET-1 in systemic blood, as well as in bronchoalveolar lavage (BAL) from horses with RAO. We also studied how these values might correlate with those of lung function tests and pulmonary artery pressure. Five horses with RAO were evaluated both in remission and in crisis and compared to five control horses. RAO horses had significantly (P<0.05) higher systemic ET-1 levels than control horses. They also had a negative arteriovenous ET-1 difference that may correspond to a net uptake of ET-1 in the lung. RAO horses in crisis had increased amounts of immunoreactive ET in BAL fluid compared to normal control subjects. Additionally, the reduction in lung function seen in RAO horses in crisis was significantly correlated with lower epithelial lining fluid ET-1 levels. Our results demonstrate that endothelin may contribute to the pathogenesis of asthma.     

Effects of airway obstruction on transmural pulmonary artery pressure in exercising horses

OBJECTIVE: To determine whether laryngeal hemiplegia would increase transmural pulmonary artery pressure (TPAP). ANIMALS: 6 horses. DESIGN: Horses were studied under 5 conditions: control conditions, after induction of left laryngeal hemiplegia, during obstruction of the left nostril, after placement of an instrumented tracheostomy, and after placement of an open tracheostomy. Horses were evaluated after being given saline solution and after being given furosemide. PROCEDURES: Horses were exercised on a high speed treadmill, using a maximum speed of 13 m/s. During each exercise, airway pressures, airflow, esophageal and pulmonary artery pressures, and blood gas partial pressures were measured. RESULTS: When adjusted for horse, speed, and obstruction condition, mean TPAP (pulmonary artery pressure-esophageal pressure) and minimum TPAP were significantly lower after administration of furosemide than after administration of saline solution. In horses given saline solution, respiratory obstruction that increased intrapleural pressure significantly increased mean TPAP, and respiratory obstruction that decreased intrapleural pressure significantly decreased minimum TPAP. CONCLUSIONS: Changes in intrapleural pressure appear to play an important role in pulmonary artery pressure and TPAP. CLINICAL RELEVANCE: Because induction of laryngeal hemiplegia did not increase TPAP, laryngeal hemiplegia is unlikely to contribute to development of exercise-induced pulmonary hemorrhage.     

Mometasone furoate. A review of its intranasal use in allergic rhinitis

Mometasone furoate is a synthetic corticosteroid which has been evaluated for intranasal use in the treatment of adults and children with allergic rhinitis. In several large, well-controlled clinical trials, mometasone furoate 200 micrograms administered once daily as an aqueous intranasal spray was significantly more effective than placebo in controlling the symptoms associated with moderate to severe seasonal or perennial allergic rhinitis. Mometasone furoate was as effective as twice-daily beclomethasone dipropionate or once-daily fluticasone propionate in the treatment of perennial allergic rhinitis, and was as effective as twice-daily beclomethasone dipropionate and slightly more effective than once-daily oral loratadine in the treatment of seasonal allergic rhinitis. Mometasone furoate was also as effective as twice-daily beclomethasone dipropionate or once-daily budesonide, and significantly more effective than placebo in the prophylaxis of seasonal allergic rhinitis. The onset of action of mometasone furoate was approximately 7 hours in patients with seasonal allergic rhinitis. Mometasone furoate was as well tolerated as beclomethasone dipropionate, fluticasone propionate and budesonide in clinical trials, with an overall incidence of adverse events similar to placebo. Adverse events were generally mild to moderate and of limited duration. The most common adverse events associated with mometasone furoate therapy were nasal irritation and/or burning, headache, epistaxis and pharyngitis. Intranasal or oral mometasone furoate had no detectable effect on hypothalamic-pituitary-adrenal axis function in studies of < or = 1 year in duration. CONCLUSIONS: Mometasone furoate is a well tolerated intranasal corticosteroid with minimal systemic activity and an onset of action of < or = 7 hours. It is effective in the prophylaxis and treatment of seasonal allergic rhinitis and the treatment of perennial allergic rhinitis in patients with moderate to severe symptoms.     

One year follow-up study of endocrine and lung function of asthmatic children on inhaled budesonide

Inhaled corticosteroids have become a mainstay in the management of chronic asthma. Their use had been considered safe, although some degree of adrenal suppression has been demonstrated after 2 and 4 weeks of treatment with either 400 microg x day(-1) of beclomethasone dipropionate or budesonide. To weigh the benefits and risks of long-term treatment, 12 children with moderately severe asthma were assessed in a follow-up study on budesonide 200 microg b.i.d. After 1 yr, the nocturnal cortisol production was significantly reduced by 19%, but no greater compared to 2 and 4 weeks of treatment. Growth and growth hormone levels were normal. Lung function tests were significantly better, not only versus baseline values but also versus 2 and 4 weeks of treatment. We conclude that systemic effects of inhaled corticosteroids in conventionally low doses do not accumulate with length of treatment, whilst lung function parameters will continue to improve. Therefore, inhaled corticosteroids once started in asthmatic children not controlled on other medications should be continued, but their use should be carefully considered and the minimal dose required to control the asthma employed.     

Effect of aluminum hydroxide/magnesium hydroxide antacid and bismuth subsalicylate on gastric pH in horses

OBJECTIVE: To assess the effect of aluminum hydroxide/magnesium hydroxide antacid and bismuth subsalicylate on gastric pH in clinically normal horses and to develop guidelines on the use of these agents for treatment of peptic ulcer disease in horses. DESIGN: Prospective, randomized, controlled trial. ANIMALS: 5 clinically normal adult horses with chronically implanted gastric cannulas. PROCEDURE: Each horse received all 5 treatments (30 g of aluminum hydroxide/15 g of magnesium hydroxide, 12 g of aluminum hydroxide/6 g of magnesium hydroxide, 10.5 g of bismuth subsalicylate, 26.25 g of bismuth subsalicylate, and 5% methylcellulose control) with only 1 experiment performed each day. Gastric pH was measured via a glass electrode inserted through the gastric cannula for 1 hour before treatment and continued for 2 hours after treatment. Food or water was not given to the horses during the experiment. Measurements of gastric pH obtained during posttreatment hours were compared with pretreatment gastric pH values. RESULTS: Only a dose of 30 g of aluminum hydroxide/ 15 g of magnesium hydroxide resulted in a significant increase in gastric pH over baseline or control values. Mean pH was 5.2 +/- 0.62 and 4.59 +/- 0.48 for posttreatment hours 1 and 2, respectively. CLINICAL IMPLICATIONS: Oral administration of 30 g of aluminum hydroxide/15 g of magnesium hydroxide to adult horses should result in a mean hourly gastric pH > or = 4.0 for at least 2 hours.     

Inhaled steroids modify bronchial responses to hyperosmolar saline

We investigated the effects of inhaled beclomethasone dipropionate (BDP) on airway sensitivity (provocative dose producing a 20% fall in forced expiratory volume in one second (FEV1) from baseline (PD20)) and reactivity (slope of the dose-response curve) to inhaled aerosols of hyperosmolar (4.5%) saline, and histamine or methacholine. This was an open study on 13 patients referred to the laboratory by their respiratory physician for investigation of their asthma. These challenges were performed on separate days before (initial visit) and 8.8 +/- 0.8 (SD) weeks (range 5.6-12.4 weeks) after (visit 1) a treatment period with BDP (dose range 600-1,500 micrograms.day-1). At visit 1 there was a significant reduction in sensitivity to 4.5% NaCl and histamine/methacholine and in reactivity. The PD20 increased 5.6 fold for 4.5% NaCl and 4.1 fold for histamine/methacholine. All patients remained responsive to histamine/methacholine and a fall in FEV1 > 20% to 4.5% saline was documented in 10 of the 13 patients. We conclude that treatment with BDP reduces sensitivity and reactivity to both osmotic and pharmacological challenge.