pulmicort and Respiratory-Tract-Diseases

Acute wheezing illnesses in preschoolers require better management strategies to reduce morbidity.. We sought to examine the effectiveness of episodic use of an inhaled corticosteroid and a leukotriene receptor antagonist in preschoolers with intermittent wheezing.. In a randomized, double-blind, placebo-controlled 12-month trial, 238 children aged 12 to 59 months with moderate-to-severe intermittent wheezing received 7 days of either budesonide inhalation suspension (1 mg twice daily), montelukast (4 mg daily), or placebo in addition to albuterol with each identified respiratory tract illness (RTI). Proportion of episode-free days (EFDs) during the 12-month trial was the primary outcome.. The 3 treatment groups did not differ in proportions of EFDs, with adjusted mean EFDs of 76% (95% CI, 70% to 81%) for budesonide, 73% (95% CI, 66% to 79%) for montelukast, and 74% (95% CI, 65% to 81%) for conventional therapy (P = .66). The 3 groups did not differ in oral corticosteroid use, health care use, quality of life, or linear growth. However, during RTIs, budesonide and montelukast therapy led to modest reductions in trouble breathing (38% [P = .003] and 37% [P = .003], respectively) and interference with activity scores (32% [P = .01] and 40% [P = .001], respectively) that were most evident in those with positive asthma predictive indices.. In preschool children with moderate-to-severe intermittent wheezing, episodic use of either budesonide or montelukast early in RTIs, when added to albuterol, did not increase the proportion of EFDs or decrease oral corticosteroid use over a 12-month period. However, indicators of severity of acute illnesses were reduced, particularly in children with positive asthma predictive indices.

Topics: Acetates; Administration, Inhalation; Albuterol; Bronchodilator Agents; Budesonide; Child, Preschool; Cyclopropanes; Double-Blind Method; Female; Glucocorticoids; Humans; Infant; Leukotriene Antagonists; Male; Quinolines; Respiratory Sounds; Respiratory Tract Diseases; Sulfides

Asthma is a chronic inflammatory disease that persists even during adequate therapy and asymptomatic episodes. We questioned whether "silent" chronic allergen exposure can induce and maintain airway inflammation and whether this still occurs during regular treatment with inhaled steroids. Twenty-six patients with house dust mite allergy and mild asthma (dual responders) participated in a parallel, double-blind study. All patients inhaled a low-dose of allergen on 10 subsequent working days (Days 1-5, 8-12). They were treated with 400 micro g budesonide once daily (n = 13) or placebo (n = 13) from Days -3 to 19. At baseline (Day -6) and on Days 5, 12, and 19 we measured the provocative concentration of methacholine causing a 20% fall in FEV(1) (PC(20)), and percent eosinophils, interleukin (IL)-5/interferon-gamma messenger RNA ratio (in sputum cells by real-time reverse transcription-polymerase chain reaction [RT-PCR]), and eosinophilic cationic protein (ECP) in induced sputum. Symptoms, peak expiratory flow (PEF), FEV(1), and exhaled nitric oxide (NO) were recorded repeatedly during the study. In the placebo group, repeated low-dose allergen exposure resulted in a significant increase in sputum eosinophils (p = 0.043), ECP (p = 0.011), IL-5/IFN-gamma messenger RNA ratio (p = 0.04), and in exhaled NO (p = 0.001), without worsening of symptoms, PEF, or baseline FEV(1) (p > 0.07). In the budesonide group, the changes in PC(20), sputum ECP, and exhaled NO were significantly different as compared with the placebo group (p < 0.03). We conclude that repeated low-dose allergen exposure in asthma can lead to airway inflammation without worsening of symptoms, which can be prevented by inhaled steroid treatment. This suggests that antiinflammatory therapy is beneficial during allergen exposure, even during asymptomatic episodes.

Topics: Administration, Inhalation; Adolescent; Adult; Allergens; Anti-Inflammatory Agents; Asthma; Budesonide; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Inflammation; Male; Respiratory Function Tests; Respiratory Tract Diseases; Severity of Illness Index

Phosphodiesterase 4 (PDE4) is a key cAMP-metabolizing enzyme involved in the pathogenesis of inflammatory disease, and its pharmacological inhibition has been shown to exert therapeutic efficacy in chronic obstructive pulmonary disease (COPD). Herein, we describe a drug discovery program aiming at the identification of novel classes of potent PDE4 inhibitors suitable for pulmonary administration. Starting from a previous series of benzoic acid esters, we explored the chemical space in the solvent-exposed region of the enzyme catalytic binding pocket. Extensive structural modifications led to the discovery of a number of heterocycloalkyl esters as potent in vitro PDE4 inhibitors. (S*,S**)-18e and (S*,S**)-22e, in particular, exhibited optimal in vitro ADME and pharmacokinetics properties and dose-dependently counteracted acute lung eosinophilia in an experimental animal model. The optimal biological profile as well as the excellent solid-state properties suggest that both compounds have the potential to be effective topical agents for treating respiratory inflammatory diseases.

Topics: Administration, Inhalation; Animals; Binding Sites; Cyclic Nucleotide Phosphodiesterases, Type 4; Dose-Response Relationship, Drug; Drug Discovery; Drug Evaluation, Preclinical; Drug Stability; Humans; Male; Phosphodiesterase 4 Inhibitors; Pulmonary Eosinophilia; Pyrrolidines; Rats, Inbred BN; Respiratory Tract Diseases; Structure-Activity Relationship; Thiazoles

OBJECTIVE To evaluate the influence of respiratory tract disease (ie, recurrent airway obstruction [RAO]) and mode of inhalation on detectability of inhaled budesonide in equine plasma and urine samples. ANIMALS 16 horses (8 healthy control horses and 8 horses affected by RAO, as determined by results of clinical examination, blood gas analysis, bronchoscopy, and cytologic examination of bronchoalveolar lavage fluid). PROCEDURES 4 horses of each group inhaled budesonide (3 μg/kg) twice daily for 10 days while at rest, and the remaining 4 horses of each group inhaled budesonide during lunging exercise. Plasma and urine samples were obtained 4 to 96 hours after inhalation and evaluated for budesonide and, in urine samples, the metabolites 6β-hydroxybudesonide and 16α-hydroxyprednisolone. RESULTS Detected concentrations of budesonide were significantly higher at all time points for RAO-affected horses, compared with concentrations for the control horses. All samples of RAO-affected horses contained budesonide concentrations above the limit of detection at 96 hours after inhalation, whereas this was found for only 2 control horses. Detected concentrations of budesonide were higher, but not significantly so, at all time points in horses that inhaled budesonide during exercise, compared with concentrations for inhalation at rest. CONCLUSIONS AND CLINICAL RELEVANCE Results of this study indicated that the time interval between inhalation of a glucocorticoid and participation in sporting events should be increased when inhalation treatment is administered during exercise to horses affected by respiratory tract disease.

Topics: Administration, Inhalation; Airway Obstruction; Animals; Anti-Inflammatory Agents; Bronchoalveolar Lavage Fluid; Budesonide; Case-Control Studies; Horse Diseases; Horses; Physical Conditioning, Animal; Respiratory Tract Diseases; Treatment Outcome

Chronic respiratory disease and inhaled corticosteroid (ICS) therapy for chronic obstructive pulmonary disease (COPD) increase the risk of pneumonia. Few data are available on the association of these risk factors with non-tuberculous mycobacterial (NTM) pulmonary disease.. This study examined chronic respiratory diseases and ICS use as risk factors in a population-based case-control study encompassing all adults in Denmark with microbiologically confirmed NTM pulmonary disease between 1997 and 2008. The study included 10 matched population controls per case. Conditional logistic regression was used to compute adjusted ORs for NTM pulmonary disease with regard to chronic respiratory disease history.. Overall, chronic respiratory disease was associated with a 16.5-fold (95% CI 12.2 to 22.2) increased risk of NTM pulmonary disease. The adjusted OR for NTM disease was 15.7 (95% CI 11.4 to 21.5) for COPD, 7.8 (95% CI 5.2 to 11.6) for asthma, 9.8 (95% CI 2.03 to 52.8) for pneumoconiosis, 187.5 (95% CI 24.8 to 1417.4) for bronchiectasis, and 178.3 (95% CI 55.4 to 574.3) for tuberculosis history. ORs were 29.1 (95% CI 13.3 to 63.8) for patients with COPD on current ICS therapy and 7.6 (95% CI 3.4 to 16.8) for patients with COPD who had never received ICS therapy. Among patients with COPD, ORs increased according to ICS dose, from 28.1 for low-dose intake to 47.5 for high-dose intake (more than 800 μg/day). The OR was higher for fluticasone than for budesonide.. Chronic respiratory disease, particularly COPD treated with ICS therapy, is a strong risk factor for NTM pulmonary disease.

Topics: Administration, Inhalation; Aged; Androstadienes; Anti-Inflammatory Agents; Asthma; Bronchiectasis; Budesonide; Case-Control Studies; Chronic Disease; Confidence Intervals; Denmark; Female; Fluticasone; Humans; Male; Middle Aged; Mycobacterium Infections, Nontuberculous; Odds Ratio; Pneumoconiosis; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Diseases; Risk Factors; Tuberculosis, Pulmonary

Inhaled corticosteroids, anticholinergics and β₂-adrenoceptor agonists are frequently combined for treating chronic respiratory diseases. We examine the corticosteroid, budesonide, and novel NO-donating derivative, TPI 1020, against histamine- and methacholine-induced bronchoconstriction and whether they enhance the β₂-adrenoceptor agonist formoterol or muscarinic antagonist tiotropium in conscious guinea pigs.. Dunkin-Hartley guinea pigs received inhaled histamine (3 mM) or methacholine (1.5 mM) and specific airway conductance (sG(aw)) was measured before and 15 or 75 min after treatment with budesonide, TPI 1020, tiotropium or formoterol alone or in combinations.. Formoterol (0.7-10 µM) and budesonide (0.11-0.7 mM) inhibited histamine-induced bronchoconstriction and tiotropium (2-20 µM) inhibited methacholine-induced bronchoconstriction by up to 70.8 ± 16.6%, 34.9 ± 4.4% and 85.1 ± 14.3%, respectively. Formoterol (2.5 µM) or tiotropium (2 µM) alone exerted small non-significant bronchoprotection. However, when co-administered with TPI 1020 0.11 mM, which alone had no significant effect, there was significant inhibition of the bronchoconstriction (45.7 ± 12.2% and 79.7 ± 21.4%, respectively). Co-administering budesonide (0.11 mM) with tiotropium (2 µM), which alone had no effect, also significantly inhibited the methacholine bronchoconstriction (36.5 ± 13.0%), but there was no potentiation of formoterol against histamine. The NO scavenger, CPTIO, prevented the bronchoprotection by SNAPand TPI 1020.. TPI 1020 potentiated the bronchoprotection by formoterol and tiotropium. Budesonide also enhanced the effects of tiotropium but not formoterol. Combination of TPI 1020 with a long-acting β₂-adrenoceptor agonist or muscarinic receptor antagonist may therefore be a more potent therapeutic approach for treatment of chronic respiratory diseases.

Topics: Administration, Inhalation; Animals; Bronchoconstriction; Bronchodilator Agents; Budesonide; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Synergism; Drug Therapy, Combination; Ethanolamines; Formoterol Fumarate; Guinea Pigs; Histamine; Male; Methacholine Chloride; Respiratory Tract Diseases; Scopolamine Derivatives; Time Factors; Tiotropium Bromide

Adverse drug reactions is an important healthcare issue, it causes excess morbidity and mortality. The aim of this study was to determine the adverse drug reactions in patients who admitted to the outpatient clinic of respiratory diseases and to improve some clinical strategies if they are preventable.. This study is a prospective observational study which was performed to determine adverse drug reaction in patients who admitted to the outpatient clinic of respiratory diseases.. During the 15 months of study period a total of 114 adverse reactions were reported in 92 out of 18.130 patients. Most of the adverse reactions were related with gastrointestinal system, central nervous system and cardiovascular system. The most of the adverse events were associated with fixed inhaled formoterol-budesonide combination and inhaled tiotropium. The most frequently reported reactions were hoarseness, xerostomia, headache and dizziness. Poliuri and cough were less frequently reported reactions.. Most of the adverse reactions were of limited intensity but some of these side effects might effect patients compliance. Serious adverse events were not detected.

Topics: Administration, Inhalation; Bronchodilator Agents; Budesonide; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Ethanolamines; Female; Formoterol Fumarate; Humans; Male; Middle Aged; Outpatient Clinics, Hospital; Patient Compliance; Pharmacovigilance; Respiratory Tract Diseases; Scopolamine Derivatives; Tiotropium Bromide

Acute asthma is the third commonest cause of pediatric emergency visits at PGIMER. Typically, it presents with acute onset respiratory distress and wheeze in a patient with past or family history of similar episodes. The severity of the acute episode of asthma is judged clinically and categorized as mild, moderate and severe. The initial therapy consists of oxygen, inhaled beta-2 agonists (salbutamol or terbutaline), inhaled budesonide (three doses over 1 h, at 20 min interval) in all and ipratropium bromide and systemic steroids (hydrocortisone or methylprednisolone) in acute severe asthma. Other causes of acute onset wheeze and breathing difficulty such as pneumonia, foreign body, cardiac failure etc. should be ruled out with help of chest radiography and appropriate laboratory investigations in first time wheezers and those not responding to 1 h of inhaled therapy. In case of inadequate response or worsening, intravenous infusion of magnesium sulphate, terbutaline or aminophylline may be used. Magnesium sulphate is the safest and most effective alternative among these. Severe cases may need ICU care and rarely, ventilatory support.

Topics: Albuterol; Algorithms; Anti-Asthmatic Agents; Budesonide; Child; Child, Preschool; Diagnosis, Differential; Emergencies; Humans; Magnesium Sulfate; Respiratory Tract Diseases; Severity of Illness Index; Software Design; Status Asthmaticus; Terbutaline

Allergic asthma is characterized by airway inflammation in response to chronic allergen exposure, resulting in remodeling of the airway wall accompanied by dysfunctional airway physiology. However, a link between the immune-inflammatory response to allergen and changes to airway structure and physiology has not yet been fully elucidated. Moreover, the impact of inhaled corticosteroids and beta(2)-agonists, the primary pharmacotherapy for asthma, on this process has not been completely evaluated. In this study, we employed a murine model of chronic exposure to a common environmental aeroallergen, house dust mite, to recapitulate the phenotype of clinical asthma. By examining the therapeutic effects of corticosteroid/beta(2)-agonist combination therapy with budesonide/formoterol (BUD/FORM) in this model of airway disease, we endeavored to determine the impact of BUD/FORM on lung inflammation, structure, and physiology. BUD/FORM was delivered either while allergen exposure was ongoing (concurrent therapy) or following the cessation of allergen exposure (postexposure therapy). Our results show that airway inflammation was substantially reduced in BUD/FORM-treated mice in the concurrent therapy group, whereas in the postexposure therapy group airway inflammation spontaneously resolved. In contrast, BUD/FORM was most effective in resolving several aspects of airway remodeling and bronchial hyperreactivity when delivered in conjunction with allergen withdrawal. This study demonstrates that although both BUD/FORM therapy and allergen avoidance independently reduce airway inflammation, only BUD/FORM therapy in conjunction with allergen avoidance can effectively reverse airway remodeling and bronchial hyperreactivity induced by chronic allergen exposure.

Topics: Actins; Allergens; Animals; Bronchial Hyperreactivity; Bronchodilator Agents; Budesonide; Collagen; Drug Therapy, Combination; Epithelial Cells; Epithelium; Ethanolamines; Female; Formoterol Fumarate; Methacholine Chloride; Mice; Mice, Inbred BALB C; Mucus; Pneumonia; Pyroglyphidae; Respiratory Tract Diseases

Topics: Acetates; Administration, Inhalation; Albuterol; Bronchodilator Agents; Budesonide; Child, Preschool; Cyclopropanes; Double-Blind Method; Female; Glucocorticoids; Humans; Infant; Leukotriene Antagonists; Male; Quinolines; Respiratory Sounds; Respiratory Tract Diseases; Sulfides

This Society for Medicines Research symposium, sponsored by UCB, was held on September 11, 2007, at the Wellcome Trust Conference Centre, Hinxton, Cambridge, United Kingdom. The meeting, organized by Ruth Lock, Steve Collingwood and Andrew Ratcliffe, reviewed current thinking in the area of airway drug delivery and the challenges and progress made in the discovery and development of novel medicines to treat respiratory diseases, such as chronic obstructive pulmonary disease, asthma, allergic rhinitis and cystic fibrosis.

Topics: Acetates; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Albuterol; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Cyclopropanes; Drug Combinations; Drug Therapy; Ethanolamines; Humans; Leukotriene Antagonists; Molecular Structure; Quinolines; Respiratory Tract Diseases; Sulfides

The purpose of this study was to compare efficacy on fetal lung maturation of intra-amniotic betamethasone or budesonide with the efficacy of maternal intramuscular betamethasone.. Pregnant ewes received intra-amniotic betamethasone (0.5 mg/kg or 2 mg/kg fetal weight), intra-amniotic budesonide (0.5 mg/kg or 2 mg/kg), maternal intramuscular betamethasone (0.5 mg/kg maternal weight), intra-amniotic saline solution, or maternal saline solution. Lambs were delivered 2 or 7 days later, at 124 days of gestation for measurement of respiratory system compliance, ventilatory efficiency index, and surfactant levels.. Lung function increased 2 days after maternal betamethasone, intra-amniotic betamethasone (2 mg/kg), and intra-amniotic budesonide (2 mg/kg) administration and 7 days after maternal betamethasone or intra-amniotic budesonide (2.0 mg/kg) administration. Lung function was not improved 7 days after intra-amniotic betamethasone (2.0 mg/kg) administration or 2 days after intra-amniotic betamethasone (0.5 mg/kg) or intra-amniotic budesonide (0.5 mg/kg) administration. Intra-amniotic corticosteroid administration increased fetal death and respiratory morbidity.. Intra-amniotic corticosteroid administration improved preterm lung function, but the associated morbidity and mortality rates suggest that they are not suitable for clinical use.

Topics: Amnion; Animals; Animals, Newborn; Betamethasone; Budesonide; Female; Fetal Death; Fetal Organ Maturity; Fetus; Glucocorticoids; Incidence; Injections, Intramuscular; Lung; Lung Injury; Mothers; Pregnancy; Pulmonary Emphysema; Pulmonary Surfactants; Respiratory Tract Diseases; Rupture; Sheep; Treatment Outcome

An ultrasonic spray system was tested for the production of aerosols for ultimate use in the respiratory delivery of drug to animals. A Sono-Tek ultrasonic spray system was mounted on top of a baffle to entrain aerosol particles within the carrier gas. Solvent was removed from the aerosol cloud by passing the droplets through drying columns composed of either charcoal or silica. The efficiency of removing ethanol and water were determined by measuring the outflow concentrations. Sodium fluorescein and sodium cromolyn dissolved in water were tested, and the effect of the liquid flow rate and drug concentration entering the atomizer on the output, and particle size distribution, were determined by the filter capture method, and by cascade impactor, respectively. Similar studies were conducted with budesonide and indomethacin dissolved in ethanol. The theoretical count median size distribution was calculated and compared with the experimental values calculated from the observed mass median aerodynamic diameter. The output rate expressed as the mass of aerosol collected in unit time increased nearly proportionately with the liquid flow rate (0.18-0.7 ml/min) and with the concentration of drug (0.19-12 mg/ml) entering the nebulizer. The mean particle size increased with solute concentration, but not by liquid flow rate. The calculated count median diameters were dependent on the type of solvent, but were independent of solute. At the high dose of cromolyn, there was very good agreement between the theoretical and observed. At lower doses, the observed size was larger than predicted, which was also true for the ethanol soluble solutes. The system has the potential of providing a wide range of dose levels for testing of drug delivery to animals including high doses with a controlled and relatively narrow particle size distribution.

Topics: Administration, Inhalation; Aerosols; Bronchodilator Agents; Budesonide; Cromolyn Sodium; Equipment Design; Ethanol; Fluorescein; Indomethacin; Nebulizers and Vaporizers; Particle Size; Respiratory Tract Diseases; Solvents; Ultrasonics

Groups of guinea pigs sensitized with ovalbumin were treated with budesonide and beclomethasone dipropionate, respectively, in an intraperitoneal dose of 50 mg/kg. 20 h later, the anaphylactic release of histamine and slow reacting substance of anaphylaxis (SRS-A) from chopped lung tissue was studied. Whereas the corticosteroids studied had no effect on the tissue content of histamine or on the amount of antigen-induced release of this autacoid, budesonide and beclomethasone dipropionate to a great extent inhibited the release of SRS-A. The anti-anaphylactic effect of budesonide and beclomethasone was also shown in sensitized guinea pigs pretreated with mepyramine, 2.5 mg/kg intraperitoneally, and challenged with nebulized ovalbumin. We suggest that the partial protection given by the corticosteroids budesonide and beclomethasone dipropionate is due to the inhibiton of SRS-A release.

Topics: Anaphylaxis; Animals; Beclomethasone; Bronchial Spasm; Budesonide; Female; Glucocorticoids; Guinea Pigs; Histamine Release; Immunization; Male; Pregnenediones; Respiratory Tract Diseases; SRS-A