(9R)-9-chloro-11-17-dihydroxy-17-(2-hydroxy-1-oxoethyl)-10-13-16-trimethyl-6-7-8-11-12-14-15-16-octahydrocyclopenta[a]phenanthren-3-one and Hypersensitivity

From the experience above, it may be concluded that corticosteroid therapy in allergic disease has become more effective than ever before. The expected variations in usage of new important pharmacologic agents is seen with special clarity in the use of corticosteroids. The wide acclaim for the "miracle drug of the 1950's", which followed penicillin of the 1940's, soon gave away to anguish about side-effects that threatened to abolish its use entirely in the late 1950's. The 1960's brought alternate day therapy for chronic usage and recognition that short term usage was relatively safe. The 1970's saw proliferation of topically active steroids similar to those so important to the practice of Dermatology in the previous decade. Results in treating asthma and nasal diseases have been excellent and extensive research for adverse effects has been largely unrevealing.

Topics: Administration, Intranasal; Adrenal Cortex Hormones; Asthma; Beclomethasone; Cataract; Cushing Syndrome; Humans; Hypersensitivity; Hypersensitivity, Immediate; Long-Term Care; Nasal Polyps; Osteonecrosis; Osteoporosis; Prednisone; Rhinitis; Sleep Initiation and Maintenance Disorders; Stress, Physiological

Allergen avoidance is important in allergic asthma management. Nocturnal treatment with Temperature-controlled Laminar Airflow (TLA; Airsonett. Asthma Quality of Life Questionnaire (AQLQ) scores were collected in a previous study. TTO of improvements in Quality of Life was analysed for difference (TLA-placebo) in Area-under-Curve using backwards deletion from 12, 9, 6, 3 down to 1 month for the AQLQ total score, the four individual domains and specifically the sleep question.. Patients with uncontrolled asthma on GINA step 4 (n = 87)) reported a statistically significant and clinically relevant (≥0.5 point) improvement in total AQLQ score (0.57; p = 0.009) after 3 months treatment for TLA over placebo. The shortest TTO was within 1 month for the environmental domain (0.68; p = 0.016) and the sleep question (0.771; p = 0.037). TTO for the emotional and symptom domains was 3 months (0.66; p = 0.020 and 0.64; p = 0.014 respectively) and for the activity domain 6 months (0.47; p = 0.036).. Nocturnal avoidance of allergens using TLA provided a statistically significant and clinically relevant improvement in total AQLQ score within 3 months in patients in the GINA 4 + ACT<18 group. Questions related to sleep quality may provide the first signal of response already within a month after commencing treatment.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Air Movements; Allergens; Asthma; Beclomethasone; Environment, Controlled; Exhalation; Female; Humans; Hypersensitivity; Inflammation; Male; Nitric Oxide; Quality of Life; Severity of Illness Index; Sleep; Temperature; Time Factors

The ability of omalizumab, an anti-immnoglobulin-E agent, to maintain long-term disease control in patients with moderate-to-severe allergic asthma was investigated in a 24-week double-blind extension to a 28-week core trial. During the extension, 483 of the initial 546 patients were maintained on randomised treatment and the lowest sustainable dose of beclomethasone dipropionate (BDP) as established during the steroid-reduction phase of the core trial. The use of concomitant asthma medication was permitted and investigators were allowed to adjust the BDP dose or switch patients from BDP to other asthma medications if deemed necessary. More omalizumab-treated patients (33.5%) than placebo-treated patients (13.5%) were able to complete the extension period without requiring inhaled corticosteroid treatment. The mean BDP equivalent dose throughout the extension was lower in the omalizumab group (25 microg x day(-1)) than in the placebo group (43 microg x day(-1)). Disease control was sustained in 76% of omalizumab patients compared with 59.4% of placebo patients free from an asthma exacerbation during the extension period. Compared with placebo, fewer patients in the omalizumab group used other concomitant asthma medication during the extension. Treatment with omalizumab was well tolerated and the incidence of adverse events was similar between groups. In conclusion, these results suggest that omalizumab is a promising new agent for the long-term control of allergic asthma.

Topics: Adolescent; Adult; Aged; Anti-Asthmatic Agents; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Asthma; Beclomethasone; Child; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Humans; Hypersensitivity; Male; Middle Aged; Omalizumab; Severity of Illness Index; Time Factors; Treatment Outcome

We have demonstrated the detection of proallergic cytokines in the nasal secretions after antigen challenges. Our aim was to determine the secretion kinetics of chemokines (interleukin [IL]-8, macrophage inflammatory protein-1 alpha [MIP-1 alpha], and RANTES) and other cytokines (IL-1 beta and granulocyte/macrophage colony-stimulating factor [GM-CSF] after allergen challenges and their inhibition by steroid therapy. Ten allergic patients were given either beclomethasone dipropionate (BDP) or placebo in a double-blind, randomized, crossover manner. Allergen challenges were performed after 1 wk of treatment. Nasal secretions were collected serially for 11 h after allergen challenge by a matrix method. Subjects maintained symptom scores at each time point of nasal secretion recovery. Cytokines were measured by specific enzyme-linked immunosorbent assays. The mean peak values for each cytokine and total symptom scores during the early (ER) and/or late-phase reactions (LPR) were significantly reduced during the BDP treatment period (p < 0.05). The levels of cytokine correlated (p < 0.05) with corresponding total symptom scores during ER (IL-1 beta and MIP-1 alpha) and LPR (all cytokines). Our findings document local elevations of IL-1 beta, GM-CSF, and chemokines in the nasal secretions after allergen challenges and their inhibition by steroids. We speculate that the inhibition of cytokine production and secretion in the nasal mucosa may contribute to the clinical efficacy of topical steroids.

Topics: Beclomethasone; Chemokine CCL4; Chemokine CCL5; Cross-Over Studies; Cytokines; Double-Blind Method; Enzyme-Linked Immunosorbent Assay; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Hypersensitivity; Interleukin-1; Interleukin-8; Kinetics; Lymphokines; Macrophage Inflammatory Proteins; Monokines; Nasal Lavage Fluid; Nasal Mucosa; Nasal Provocation Tests

Formoterol is a new long-acting beta 2-agonist. We compared the protective effect of 24 micrograms formoterol with 200 micrograms beclomethasone and placebo on inhaled allergen-induced asthmatic responses in mild stable asthmatic subjects. We measured airflow rates, histamine airway responsiveness, cell counts from sputum and peripheral blood, and markers of lymphocyte and eosinophil activation. Adjustments were made for the confounding effect of bronchodilatation produced by formoterol in comparisons using a control inhalation of normal saline. Formoterol caused bronchodilation and inhibition of histamine airway responsiveness for at least 24 h. It completely inhibited the early asthmatic responses when beclomethasone had no effect. Control comparisons of the effect of formoterol and beclomethasone on the allergen-induced late asthmatic response and increase in histamine responsiveness showed each to be equally effective but not to inhibit the responses completely. Formoterol caused bronchodilation in addition to preventing bronchoconstriction. Both drugs inhibited the rise in serum eosinophil cationic protein 24 h after allergen, but neither inhibited the allergen-induced increases in sputum or blood eosinophils or CD25+ lymphocytes. These results suggest that formoterol modifies allergen-induced airway responses through functional antagonism rather than the inhibition of inflammatory cell infiltration.

Topics: Adult; Airway Resistance; Asthma; Beclomethasone; Blood Cell Count; Blood Proteins; Bronchial Provocation Tests; Bronchoconstriction; Bronchodilator Agents; Confounding Factors, Epidemiologic; Eosinophil Granule Proteins; Eosinophils; Ethanolamines; Female; Forced Expiratory Volume; Formoterol Fumarate; Histamine; Humans; Hypersensitivity; Lymphocyte Activation; Male; Receptors, Interleukin-2; Ribonucleases; Sputum

From the start of the Astemizole clinical investigations, until now the results of 39 trials including more than 2300 patients are available. These results show that Astemizole is an effective and safe Histamine-H1-antagonist for the therapy of hayfever, chronic allergic rhinitis, allergic conjunctivitis, chronic urticaria and allergic bronchitis in adults and children. Astemizole was superior to placebo and the classical antihistamines like Clemastine, Terfenadine, Ketotifen, Mequitazine, pheniramine and Chlorphenamine.

Topics: Astemizole; Beclomethasone; Benzimidazoles; Bronchitis; Clinical Trials as Topic; Conjunctivitis; Double-Blind Method; Drug Therapy, Combination; Histamine H1 Antagonists; Humans; Hypersensitivity; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Urticaria

Topics: Administration, Intranasal; Adolescent; Aerosols; Airway Resistance; Beclomethasone; Child; Female; Humans; Hypersensitivity; Male; Methylprednisolone; Mites; Nose; Placebos; Pollen; Rhinitis; Rhinitis, Allergic, Seasonal

SUMMARY. Airway nitric oxide (NO) production can be measured by chemiluminescence analyzer in children able to perform a single low exhalation. The aim of the present study was to evaluate whether exhaled NO (e-NO) peaks (first part of the exhalation) were as useful as e-NO plateaus (last part of the exhalation) in evaluating e-NO production in asthmatic children and in detecting responses to inhaled steroid treatment. E-NO peak, plateau, and rate of production values were measured in 100 atopic asthmatic children using a chemiluminescence analyser. Thirty-seven patients (mean age, 11.1 +/- 0.7 years) were receiving inhaled steroids (flunisolide, 0.8-1 mg daily) or beclomethasone (0.2-0.4 mg daily), while the remaining 63 (mean age, 12.0 +/- 0.4 yrs) were-steroid naive and treated only with inhaled beta(2)-agonists on an as-needed basis. Fifteen out of the 63 steroid-naive patients were reevaluated after a short course (3 weeks) of inhaled corticosteroid treatment (flunisolide, 0.8-1 mg daily, or beclomethasone, 0.2-0.4 mg daily). Regardless of the type of data analysis (peak, plateau, or rate of production), the e-NO values of the steroid-naive patients were significantly higher than those of inhaled steroid-treated patients (P < 0.01, each comparison). Similarly, in the subgroup of steroid-naive patients, the three methods were able to detect a decrease in e-NO levels by inhaled steroid therapy (P < 0.001, each comparison). Plotting the difference between e-NO peak and e-NO plateau values against their average, the peak e-NO concentrations were higher than e-NO plateau values. This difference was independent of the absolute e-NO concentration. The results of the two types of data analysis seems to agree more closely in steroid-naive patients than in steroid treated patients, or in the subgroup of steroid-naive patients who received a short course treatment with inhaled steroids. In steroid-treated subjects, the differences were up to five times higher for peak than plateau e-NO values. These data suggest that both e-NO plateau and e-NO peak values are useful in detecting airway NO production in atopic asthmatic children, but they cannot be used interchangeably. Because of possible nasal contamination in e-NO peak measurement, we prefer e-NO plateau levels for evaluating lower airway e-NO production.

Topics: Administration, Inhalation; Adolescent; Adrenergic beta-Agonists; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Child; Child, Preschool; Female; Fluocinolone Acetonide; Forced Expiratory Volume; Humans; Hypersensitivity; Luminescent Measurements; Lung; Male; Maximal Midexpiratory Flow Rate; Nitric Oxide; Peak Expiratory Flow Rate; Pulmonary Ventilation; Reproducibility of Results; Statistics as Topic; Vital Capacity

There is an increase in vascularity in the asthmatic airway. Although inhaled corticosteroids (ICS) are an effective anti-inflammatory treatment in asthma, there are few data on any effects on structural changes.. Endobronchial biopsy specimens from seven asthmatic subjects not receiving ICS and 15 receiving 200-1500 microg/day beclomethasone dipropionate (BDP) were immunohistochemically stained with an anti-collagen type IV antibody to outline the endothelial basement membrane of the vessels. These were compared with biopsy tissue from 11 non-asthmatic controls (four atopic and seven non-atopic).. There was a significant increase in the density of vessels (number of vessels/mm2 of lamina propria) in the asthmatic subjects not on ICS compared with non-asthmatic controls (mean 485 (interquartile range (IQR) 390-597) versus 329 (IQR 248-376) vessels/mm2, p<0.05; 95% CI for the difference 48 to 286). There was no significant difference between asthmatic subjects on ICS and those not on ICS or control subjects in the number of vessels/mm2 (mean 421 (IQR 281-534)). However, patients who received >/=800 microg/day BDP tended to have a reduced number of vessels/mm2 compared with patients not on ICS and those receiving

Topics: Administration, Inhalation; Adult; Asthma; Basement Membrane; Beclomethasone; Bronchi; Bronchoconstrictor Agents; Bronchoscopy; Case-Control Studies; Collagen; Drug Administration Schedule; Female; Glucocorticoids; Humans; Hypersensitivity; Immunohistochemistry; Male; Methacholine Chloride; Middle Aged; Neovascularization, Pathologic

The ability of four drugs with anti-allergic action to modulate the uptake of bystander protein, lactulose/rhamnose permeability ratios and mast cell activation was studied in rats presensitized with egg albumin in alum and challenged intraduodenally with the same antigen. Beclomethasone dipropionate (BDP) and nedocromil both significantly reduced the uptake of the bystander protein, bovine serum albumin (P < 0.002 and P > 0.02 respectively). BDP also significantly reduced sugar permeability (P < 0.01). In animals with elevated lactulose/rhamnose permeability ratios we confirmed our earlier observation of a significant correlation between levels of the specific mucosal mast cell protease Rat Chymase II (RChyII-previously known as RMCPII) and the sugar ratios. None of the drugs had any influence on the levels of mast cell protease II released following challenge and there was no correlation between the histological light microscopic appearance of the mast cells and the experimental treatment administered. Our results suggest that in the gut the pharmacological effect of anti-allergic drugs may be complex. Some, such as nedocromil, appear to act only on the mechanisms underlying increased protein uptake whereas others, such as BDP, appear to abrogate both increased protein uptake and increased sugar permeability.

Topics: Animals; Anti-Inflammatory Agents; Beclomethasone; Bronchodilator Agents; Cell Membrane Permeability; Chymases; Cromolyn Sodium; Duodenum; Hypersensitivity; Intestinal Absorption; Intestinal Diseases; Intestinal Mucosa; Jejunum; Lactulose; Mast Cells; Nedocromil; Rats; Rats, Sprague-Dawley; Rhamnose; Serine Endopeptidases; Serum Albumin, Bovine; Thioxanthenes; Xanthones

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Allergy and Immunology; Beclomethasone; Drug Labeling; Humans; Hypersensitivity; Respiration Disorders; Societies, Medical; United States; United States Food and Drug Administration; Virus Diseases

It has long been recognized that these drugs may be decisive in allowing patients to function. Now, with recently developed strategies, reasonably safe treatment is practical. Guidelines for clinical application of these strategies are offered.

Topics: Adrenal Cortex Hormones; Adult; Beclomethasone; Child; Female; Humans; Hypersensitivity; Pregnancy; Pregnancy Complications; Respiratory Hypersensitivity; Respiratory Tract Diseases

Topics: Asthma; Basophils; Beclomethasone; Cromolyn Sodium; Humans; Hypersensitivity; Rhinitis

Topics: Administration, Intranasal; Beclomethasone; Child; Child, Preschool; Drug Therapy, Combination; Female; Humans; Hypersensitivity; Infant; Male; Otitis Media; Sulfisoxazole; Time Factors

Immediate (IgE-mediated) skin tests are widely used in the diagnosis of allergic diseases. Skin tests correlate well with more specialized studies (RAST, histamine release and provocation tests) in the diagnosis of allergic disease. Lack of standardization and quantitation of biologic potency of allergens make critical comparison of skin test results impossible. A survey of practicing allergists yielded widely divergent opinions concerning the effect of anti-allergic drugs on skin tests. The results of published studies indicate that only antihistamines cause significant depression of skin reactivity. Therefore, therapy for asthma may be continued while diagnostic skin testing is in progress, avoiding the possible morbidity associated with discontinuing pharmacologic therapy.

Topics: Adrenergic beta-Agonists; Allergens; Beclomethasone; Health Surveys; Histamine H1 Antagonists; Histamine Release; Humans; Hypersensitivity; Hypersensitivity, Immediate; Immunoglobulin E; Prednisone; Radioallergosorbent Test; Skin Tests

Topics: Acari; Adolescent; Adult; Aerosols; Animals; Asthma; Beclomethasone; Dust; Feathers; Female; Humans; Hypersensitivity; Male; Middle Aged; Pollen; Skin Tests; Vaccines

Topics: Asthma; Beclomethasone; Bronchi; Female; Humans; Hypersensitivity; Male

Topics: Adolescent; Adult; Aerosols; Asthma; Beclomethasone; Desensitization, Immunologic; Humans; Hypersensitivity; Respiratory Insufficiency; Rhinitis, Allergic, Seasonal; Tracheitis

Orally inhaled and nasally exhaled beclomethasone diproprionate (b.d.) under increased nasopharyngeal pressure was found beneficial in ameliorating symptoms of allergic nasopharyngitis. The most spectacular help was obtained by patients suffering from sinus headache. This treatment also was found to avert the flaring up of rhinitis, an occasional "unmasking" effect of orally inhaled b.d.

Topics: Adolescent; Adult; Aged; Beclomethasone; Child; Child, Preschool; Drug Evaluation; Female; Humans; Hypersensitivity; Male; Middle Aged; Nasopharyngitis; Pharyngitis

Topics: Asthma; Beclomethasone; Humans; Hypersensitivity