pulmicort and Airway-Obstruction

Asthma is characterised by variable airflow obstruction, airway inflammation and hyper-responsiveness. Persistent inflammation is thought to lead to 'remodelling' of the airway, which in turn leads to the progressive loss of lung function seen in asthmatics. It would appear logical that anti-inflammatory drugs such as inhaled corticosteroids (ICS) would influence the natural history of asthma by reducing inflammation, subsequent remodelling, and thus preventing the decline in lung function. This review will summarise the effects of ICS on the secondary prevention of asthma, lung function and remodelling.. Many published studies show a reduction in airway inflammation, improvement in clinical symptoms and prebronchodilator lung function whilst taking ICS. Few studies, however, examine their effect on the natural history of asthma. Several recent studies have targeted very young children with asthma using ICS, and despite their differing target populations and treatment strategies, have failed to show any difference in lung function. Studies in adults with mild persistent asthma show similar findings. ICS appear to reverse some of the processes involved in airway remodelling, but not all.. Although ICS are effective in controlling symptoms they do not appear to alter the natural history of asthma.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Age Factors; Airway Obstruction; Asthma; Budesonide; Child; Humans; Infant; Respiratory Physiological Phenomena

Asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous disorders encompassing different phenotypes of airflow obstruction, which might differ in their response to treatment.. The aim of this study was to determine distinct phenotypes comprising the syndromes of asthma and COPD and the treatment responsiveness of these phenotypes to inhaled β-agonist, antimuscarinic, and corticosteroid therapy.. We undertook a cross-sectional study with 3 phases. In phase 1, 1,264 participants aged 18 to 75 years with self-reported current wheeze and breathlessness were identified from a random population sample of 16,459. In phase 2, 451 participants attended for detailed assessment, including responsiveness to inhaled salbutamol and ipratropium bromide. In phase 3, 168 steroid-naive participants were enrolled in a 12-week trial of inhaled budesonide. Cluster analysis was performed in 389 participants who completed phase 2 with full data. Treatment responsiveness was compared between phenotypes.. Cluster analysis identified 5 phenotypes: moderate-to-severe childhood-onset atopic asthma, asthma-COPD overlap, obese-comorbid, mild childhood-onset atopic asthma, and mild intermittent. Bronchodilation after salbutamol was equal to or greater than that after ipratropium for all phenotypes. The moderate-to-severe childhood-onset atopic asthma, asthma-COPD overlap, and obese-comorbid phenotypes had greater efficacy with inhaled corticosteroid treatment than the mild intermittent group.. Cluster analysis of adults with symptomatic airflow obstruction identifies 5 disease phenotypes, including asthma-COPD overlap and obese-comorbid phenotypes, and provides evidence that patients with the asthma-COPD overlap syndrome might benefit from inhaled corticosteroid therapy.

Topics: Adolescent; Adrenergic beta-2 Receptor Agonists; Adult; Aged; Airway Obstruction; Albuterol; Anti-Asthmatic Agents; Asthma; Budesonide; Cluster Analysis; Female; Glucocorticoids; Humans; Ipratropium; Male; Middle Aged; Muscarinic Antagonists; Obesity; Phenotype; Pulmonary Disease, Chronic Obstructive; Severity of Illness Index; Surveys and Questionnaires; Treatment Outcome

The role of fixed airflow obstruction (FAO) in asthma is unclear.. To assess the relationship between FAO and clinical features of asthma and the effect of FAO on treatment response.. Post hoc descriptive analysis of data stratified by FAO category (screening post-albuterol FEV1/FVC

Topics: Adolescent; Adult; Airway Obstruction; Albuterol; Asthma; Bronchodilator Agents; Budesonide; Child; Double-Blind Method; Ethanolamines; Formoterol Fumarate; Humans; Middle Aged; Respiratory Function Tests; Severity of Illness Index; Sex Factors; Time Factors; Young Adult

Although it has not been evaluated prospectively, the usual treatment for obstructive airway disease after allogeneic hematopoietic stem cell transplantation, which is related to graft versus host disease, consists of intensification of systemic immunosuppressive therapy. However, this treatment has a limited efficacy and is associated with a significant number of serious adverse effects, particularly infectious. Alternative treatments are therefore required. Recently, clinical and functional improvement in patients with obstructive airway disease following allogenic hematopoietic stem cell transplantation treated with inhaled combined Budesonide/Formoterol has been retrospectively reported.. The present prospective multi-centered, randomised double-blind trial is designed to evaluate the efficacy of the combination of budesonide/formoterol (400/12 microg 2 inhalations bid) versus placebo in patients with moderate to severe obstructive airway disease, not requiring initiation or intensification of systemic immunosuppressive therapy for extra thoracic graft versus host disease. The primary outcome will be the improvement of FEV1 at 1 month of treatment. The secondary outcomes will be the clinical and functional pulmonary improvements at 6 months.. The leading hypothesis is that patients treated with inhaled combined Budesonide/Formoterol will show significant improvement of their clinical symptoms and pulmonary functional testing.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Airway Obstruction; Anti-Asthmatic Agents; Bronchodilator Agents; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Drug Combinations; Dyspnea; Ethanolamines; Follow-Up Studies; Formoterol Fumarate; Glucocorticoids; Hematopoietic Stem Cell Transplantation; Humans; Lung Diseases, Obstructive; Placebos; Prospective Studies; Respiratory Function Tests; Statistics, Nonparametric; Time Factors; Transplantation, Homologous; Treatment Outcome

Data on the onset of action of COPD medications are lacking. This study compared the onset of bronchodilation following different inhaled therapies in patients with moderate-to-severe COPD and reversible airway obstruction.. In this double-blind, double-dummy, crossover study, 90 patients (aged >or=40 years; FEV(1) 30-70% predicted) were randomized to a single dose (two inhalations) of budesonide/formoterol 160/4.5 microg, salmeterol/fluticasone 25/250 microg, salbutamol 100 microg or placebo (via pressurized metered-dose inhalers) on four visits. The primary end-point was change in FEV(1) 5 min after drug inhalation; secondary end-points included inspiratory capacity (IC) and perception of onset of effect.. Budesonide/formoterol significantly improved FEV(1) at 5 min compared with placebo (P < 0.0001) and salmeterol/fluticasone (P = 0.0001). Significant differences were first observed at 3 min. Onset of effect was similar with budesonide/formoterol and salbutamol. Improvements in FEV(1) following active treatments were superior to placebo after 180 min (all P < 0.0001); both combinations were better than salbutamol at maintaining FEV(1) improvements (P

Topics: Adrenal Cortex Hormones; Adult; Aged; Airway Obstruction; Albuterol; Androstadienes; Anti-Asthmatic Agents; Bronchodilator Agents; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Cross-Over Studies; Double-Blind Method; Drug Combinations; Ethanolamines; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Spirometry; Time Factors

Guidelines for asthma management focus on treatment with inhaled corticosteroids and on home recording of peak expiratory flow (PEF). The effect of maintenance treatment with inhaled corticosteroids on PEF variation and its relation to other parameters of disease activity were examined in 102 asthmatic children aged 7-14 years.. During 20 months of treatment with inhaled salbutamol, with or without inhaled budesonide (600 micrograms daily), forced expiratory volume in one second (FEV1), the dose of histamine required to provoke a fall in FEV1 of more than 20% (PD20), the percentage of symptom free days, and PEF variation were assessed bimonthly. PEF variation was computed as the lowest PEF as a percentage of the highest PEF occurring over 14 days, the usual way of expressing PEF variation in asthma self-management plans. For each patient using inhaled corticosteroids within subject correlation coefficients (rho) were computed of PEF variation to the percentage of symptom free days, FEV1, and PD20.. PEF variation decreased significantly during the first two months of treatment with inhaled corticosteroids and then remained stable. The same pattern was observed for symptoms and FEV1. In contrast, PD20 histamine continued to improve throughout the whole follow up period. In individual patients predominantly positive associations of PEF variation with symptoms, FEV1, and PD20 were found, but the ranges of these associations were wide.. During treatment with inhaled corticosteroids the changes in PEF variation over time show poor concordance with changes in other parameters of asthma severity. When only PEF is monitored, clinically relevant deteriorations in symptoms, FEV1, or PD20 may be missed. This suggests that home recording of PEF alone may not be sufficient to monitor asthma severity reliably in children.

Topics: Administration, Inhalation; Administration, Topical; Adolescent; Airway Obstruction; Albuterol; Anti-Inflammatory Agents; Asthma; Bronchial Hyperreactivity; Bronchodilator Agents; Budesonide; Child; Female; Follow-Up Studies; Forced Expiratory Volume; Glucocorticoids; Humans; Long-Term Care; Male; Peak Expiratory Flow Rate

Previous reports suggest that regular use of beta-agonists does not lead to tolerance to their bronchodilator effects. However, most studies have been conducted in stable asthma. This study investigates whether bronchodilator tolerance can be demonstrated during acute bronchoconstriction. Thirty-four asthmatic subjects were treated with 6 weeks inhaled terbutaline (1 mg q.i.d.), budesonide (400 microg, b.i.d.), both drugs or placebo in a randomized, double-blind, cross-over study. After each treatment methacholine was administered to induce a 20% fall in the forced expiratory volume in one second (FEV1). The response to inhaled salbutamol 100, 100, 200 microg at 5 min intervals) was then measured. Dose-response curves were compared using an analysis of covariance. Pre-methacholine FEV1, the highest pre-methacholine FEV1, the fall in FEV1 induced by methacholine and the logarithm of the provocative dose of methacholine required to induce the 20% fall in FEV1 (PD20) were used as covariates. There was a significantly reduced response to salbutamol after 6 weeks terbutaline treatment: the mean (95% confidence intervals (CI)) area under the dose-response curve was reduced by 36% (24, 47) compared to placebo (p<0.0001). The reduction in bronchodilator response was not affected by concomitant treatment with budesonide. Significant tolerance to the bronchodilator effect of inhaled beta-agonists may be demonstrated when tested during acute bronchoconstriction. Continuous treatment with inhaled beta-agonists may lead to a reduced response to emergency beta-agonist treatment during asthma exacerbations.

Topics: Acute Disease; Adolescent; Adrenergic beta-Agonists; Adult; Airway Obstruction; Albuterol; Asthma; Bronchial Provocation Tests; Bronchoconstriction; Bronchodilator Agents; Budesonide; Cross-Over Studies; Double-Blind Method; Drug Therapy, Combination; Drug Tolerance; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Terbutaline

Nebulized budesonide and nebulized adrenaline have been shown to be effective in the treatment of moderately severe croup. However, there has been no direct comparison of these therapies. We undertook a multicenter, randomized, double-blind, parallel group study in 66 hospitalized children with viral or spasmodic croup.. Children 0.5 to 6 years of age were assessed using a validated croup symptom score (stridor, 0 through 4; cough, 0 through 3; retractions, 0 through 3; dyspnea, 0 through 3; and color, 0 through 4) at 0.5, 1, 1.5, 2, 12, and 24 hours after nebulization. Patients received either budesonide (2 mg/4 mL) or L-adrenaline (4 mg/4 mL) via nebulization. The primary outcome measure was change in the total croup symptom score.. Thirty-five children received budesonide and 31 received adrenaline. There was no significant difference in baseline features, including croup score (mean [95% confidence interval]: budesonide, 7.1 [6.7-7.5]; adrenaline, 7.7 [7.3-8.1]). All patients had significant improvement from baseline, and there was not significant difference between the two treatments, as measured by change in croup scores, change in oxygen saturation, duration of hospitalization, number of subsequent treatments with systemic steroids or adrenaline, and adverse events. No child required intubation.. This study does not show any difference in efficacy and safety between nebulized budesonide and nebulized adrenaline in the treatment of acute upper airway obstruction in patients with moderately severe croup.

Topics: Administration, Topical; Adrenergic Agonists; Aerosols; Airway Obstruction; Anti-Inflammatory Agents; Bronchial Spasm; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Croup; Double-Blind Method; Epinephrine; Glucocorticoids; Hospitalization; Humans; Infant; Intubation, Intratracheal; Length of Stay; Nebulizers and Vaporizers; Oxygen; Pregnenediones; Treatment Outcome

We have investigated separate and interactive effects of corticosteroids and bronchodilators on airflow obstruction and airway hyperresponsiveness. Twelve allergic subjects with asthma were treated in a double-blind, crossover, randomized study with budesonide, 1.6 mg daily for 3 weeks, prednisone, 40 mg daily, for 8 days, and placebo. After each period, dose-response curves were measured on 4 study days with doubling doses of salbutamol, ipratropium, a combination of salbutamol and ipratropium, and placebo until a plateau in FEV1 was reached. A histamine challenge was then performed, and the provocation concentration causing a 20% fall in FEV1 (PC20) was calculated. The budesonide and prednisone regimens were equipotent. FEV1 was 81.2% of predicted after budesonide, 81.0% predicted after prednisone, and 67.5% predicted after placebo, bronchodilatation thus being 13.7% predicted (budesonide) and 13.5% predicted (prednisone). PC20 improved with 2.17 doubling concentrations (DCs) after budesonide, and 1.86 DCs after prednisone, compared with that of placebo. Salbutamol caused stronger bronchodilatation than ipratropium (26.2% versus 14.7% predicted) and a better protection against histamine challenge (3.95 versus 1.12 DC). The effects of corticosteroids and bronchodilators on FEV1 and PC20 were, in general, additive. This study emphasizes different modes of action on both airflow obstruction and airway hyperresponsiveness by corticosteroids and bronchodilators, and it demonstrates no enhancement of bronchodilator action by corticosteroids.

Topics: Adrenal Cortex Hormones; Adult; Airway Obstruction; Airway Resistance; Albuterol; Asthma; Bronchial Hyperreactivity; Bronchodilator Agents; Budesonide; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Forced Expiratory Volume; Humans; Ipratropium; Male; Prednisone; Pregnenediones

The effect of intranasally administered corticosteroid (budesonide) on nasal symptoms, mode of respiration (nasal versus mouth breathing), and asthma was investigated in 37 asthmatic children who were mouth breathers because of chronic nasal obstruction. After a 2-wk run-in period, the children were allocated randomly to 4 wk of intranasal therapy with either budesonide (400 micrograms/day) or placebo spray. A double-blind, parallel design was used. Diaries for peak expiratory flow, asthma, and rhinitis symptom scores and degree of mouth breathing were recorded at home. Nasal eosinophilia, nasal airway resistance at a flow of 0.2 L/s (NAR0.2), and lung function at rest and after exercise challenge were assessed at the clinic immediately before and at end of the 4-wk treatment. Budesonide, when compared with placebo, significantly decreased nasal obstruction (p less than 0.05), secretion (p less than 0.01), and eosinophilia (p less than 0.02), as well as NAR0.2 (p less than 0.05) and mouth breathing (p less than 0.01). The improvement in nasal obstruction correlated closely to the changes in mouth breathing (r = 0.80, n = 17, p less than 0.001). Furthermore, intranasally administered budesonide resulted in less exercise-induced asthma (EIA) (p less than 0.02) and decreased cough and asthma severity significantly. Pulmonary mechanics were only marginally improved. The present study showed that intranasally administered budesonide is effective in the treatment of perennial allergic rhinitis. An attenuation of EIA and a tendency to less asthma after budesonide therapy suggest a decrease in bronchial reactivity, but the results gave no clear evidence of an association between nasal airway function and asthma.

Topics: Administration, Intranasal; Adolescent; Airway Obstruction; Airway Resistance; Asthma; Asthma, Exercise-Induced; Budesonide; Child; Double-Blind Method; Eosinophilia; Female; Humans; Male; Mouth Breathing; Nose; Nose Diseases; Peak Expiratory Flow Rate; Pregnenediones; Respiratory Function Tests

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

Although continuous or frequent stimuli in tracheostomized patients may cause tracheal granulomas, little is known about management of patients with translaryngeal intubation.. A 1-month-old Japanese boy, weighing 3.5kg, was admitted to our hospital owing to cardiac failure caused by an atrial septal defect and intractable arrhythmia. To treat his unstable cardiovascular status, surgery was performed to close his atrial septal defect. After the operation, stenosis was detected by auscultation and flow limitation worsened. A bronchoscopy revealed granulomas completely obstructing his right bronchus and partially obstructing his left bronchus. Dexamethasone infusion partially reduced the mass, after which removal by yttrium aluminium garnet laser was tried. The airway obstruction was not resolved, however, because of granuloma reproliferation. Budesonide (aerosol liquid) inhalation was started, and tissue was reduced using an yttrium aluminium garnet laser and physically removed using forceps. After continued budesonide inhalation, he was successfully liberated from the ventilator.. Life-threatening airway obstruction by granulomas developed in a translaryngeally intubated paediatric patient. The granuloma was detected after a couple of weeks of intubation. A bronchial granuloma is rare in paediatric patients. It should be suspected with evidence of bronchial obstruction. Treatment with corticosteroids and surgery using a laser maybe indicated.

Topics: Administration, Inhalation; Airway Obstruction; Anti-Inflammatory Agents; Bronchial Diseases; Bronchoscopy; Budesonide; Combined Modality Therapy; Granuloma; Humans; Infant; Intubation, Intratracheal; Lasers, Solid-State; Male

Inhaled glucocorticosteroids reduce airway inflammation in asthma patients, thereby improving lung function and reducing airway hyperresponsiveness and symptoms. The response to glucocorticosteroids can be measured with the glucocorticosteroid skin-blanching test. We investigated if asthmatics have a lower skin-blanching response to glucocorticosteroids than non-asthmatic subjects and if asthmatics with airway obstruction have lower skin-blanching response than those without obstruction. Finally, we assessed which clinical and inflammatory parameters influence the variability in skin-blanching response.. We evaluated the skin-blanching response to topical budesonide in a large group of 315 well-characterized asthmatics and their relatives (asthma n = 114, healthy n = 140, other = 61).. The skin-blanching scores of the asthma probands and their healthy spouses were not significantly different. The skin-blanching score of patients with FEV(1) < 80% predicted was lower than of patients without obstruction. Lower skin-blanching score was significantly associated with lower FEV(1) %predicted, higher age, female gender, absence of allergy and summer season, but not with use of inhaled or oral glucocorticosteroids or packyears smoking.. Asthmatics do not have lower skin-blanching response to glucocorticosteroids than healthy subjects. Furthermore, lower skin-blanching response to glucocorticosteroids is associated with lower FEV(1), female gender, higher age and the absence of allergy.

Topics: Adolescent; Adult; Age Factors; Airway Obstruction; Asthma; Budesonide; Child; Cohort Studies; Family; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Hypersensitivity; Male; Middle Aged; Pigmentation; Sex Factors; Skin Tests; Young Adult

To characterize physical and inflammatory injury that may result from repeated intubation, independent of positive-pressure ventilation; and to determine whether corticosteroids can attenuate injury and or inflammation that may result from repeated intubation.. A 4-hr animal protocol.. All work was done in the animal laboratory at the Alfred I. DuPont Hospital for Children.. Neonatal piglets (2-8 days old; 2.5 ± 0.4 kg) were intubated and randomized to four groups (n = 8 each) to be followed over 4 hrs. Groups were control (not reintubated), injured (reintubated every 0.5 hr), intratracheal pretreatment with 1 mg of nebulized budesonide (intratracheal pretreated), or intravenous pretreatment with 0.3 mg/kg of dexamethasone (intravenous pretreated).. Each pig was sedated for the duration of study and had a 3.5F catheter inserted in the femoral artery for blood sampling and blood pressure measurement every hour. After 4 hrs, each pig was killed, and tissue was harvested for histology and interleukin-6 assays.. Laryngeal tissue interleukin-6 content was greater in the injured group compared with the control group (p < .05). In the intratracheal pretreated group, the interleukin-6 content of laryngeal tissue was greater compared with the control group (p < .05), whereas the intravenous pretreated group was not different from the control group. The reintubation injury resulted in plasma interleukin-6 levels that, compared with control, were greater in the injured and intratracheal pretreated groups (p < .05). Quantitative histology showed that the degree of tracheal injury was higher in injured and intratracheal pretreated groups compared with the control group (p < .05).. Repeated intubation alone results in significant tracheal trauma and systemic inflammation. Intravenous but not inhaled steroids attenuated the injury.

Topics: Airway Obstruction; Analysis of Variance; Animals; Animals, Newborn; Biomarkers; Budesonide; Dexamethasone; Disease Models, Animal; Inflammation; Injury Severity Score; Interleukin-6; Intubation, Intratracheal; Larynx; Random Allocation; Swine

Topics: Airway Obstruction; Animals; Animals, Newborn; Biomarkers; Budesonide; Dexamethasone; Disease Models, Animal; Humans; Inflammation; Interleukin-6; Intubation, Intratracheal; Larynx; Randomized Controlled Trials as Topic; Swine

Previously, we found pulmonary gas trapping to be a rapid, simple and objective measure of methacholine-induced airway obstruction in naïve mice. In this study we extended that finding by using methacholine-induced pulmonary gas trapping to differentiate airway responses of ovalbumin-sensitized, ovalbumin-exposed (Positive Control) and ovalbumin-sensitized, sodium chloride-exposed (Negative Control) mice. Additionally, pulmonary gas trapping and enhanced pause were compared following methacholine exposure in sensitized and nonsensitized mice. Finally, we examined by nose-only inhalation the ability of the glucocorticosteroid budesonide and the peroxisome proliferator-activated receptor-gamma agonist ciglitazone to modify methacholine-induced airway responses in ovalbumin-sensitized mice. Positive Controls exhibited a 7.8-fold increase in sensitivity and a 2.4-fold enhancement in the maximal airway obstruction to methacholine versus Negative Controls. Following methacholine, individual Positive and Negative Control mouse enhanced pause values overlapped in 9 of 9 studies, whereas individual Positive and Negative Control mouse excised lung gas volume values overlapped in only 1 of 9 studies, and log[excised lung gas volume] correlated (P=0.023) with in vivo log[enhanced pause] in nonsensitized mice. Finally, budesonide (100.0 or 1000.0 microg/kg) reduced methacholine-mediated airway responses and eosinophils and neutrophils, whereas ciglitazone (1000.0 microg/kg) had no effect on methacholine-induced pulmonary gas trapping, but reduced eosinophils. In conclusion, pulmonary gas trapping is a more reproducible measure of methacholine-mediated airway responses in ovalbumin-sensitized mice than enhanced pause. Also, excised lung gas volume changes can be used to monitor drug interventions like budesonide. Finally, this study highlights the importance of running a positive comparator when examining novel treatments like ciglitazone.

Topics: Administration, Inhalation; Airway Obstruction; Animals; Anti-Asthmatic Agents; Asthma; Bronchial Hyperreactivity; Bronchodilator Agents; Budesonide; Disease Models, Animal; Dose-Response Relationship, Drug; Eosinophils; Male; Methacholine Chloride; Mice; Mice, Inbred BALB C; Neutrophils; Ovalbumin; PPAR gamma; Thiazolidinediones

The dry-powder inhaler (DPI) Turbuhaler((R)) has been on the market for nearly two decades. Products containing terbutaline, formoterol, budesonide, and the combination budesonide/formoterol are widely used by patients with asthma and COPD. Most patients and physicians find Turbuhaler((R)) easy to use, and local side effects are rare. This is thought to arise from the lack of additives or only small amounts in the formulation, in addition to minimal deposition of the drug in the oropharynx and on the vocal cords during inspiration.The function of Turbuhaler((R)) has frequently been questioned. This article aims to review and clarify some key issues that have been challenged in the literature (e.g. the effectiveness of Turbuhaler((R)) in patients with more restricting conditions), to discuss the importance of lung deposition, and to explain the low in vivo variability associated with Turbuhaler((R)) and the lack of correlation with the higher in vitro variability.Turbuhaler((R)), like other DPIs, is flow dependent to some degree. However, a peak inspiratory flow (PIF) through Turbuhaler((R)) of 30 L/min gives a good clinical effect. These PIF values can be obtained by patients with conditions thought to be difficult to manage with inhalational agents, such as asthmatic children and adult patients with acute severe airway obstruction and COPD. Excellent clinical results with Turbuhaler((R)) in large controlled studies in patients with COPD and acute severe airway obstruction provide indirect evidence that medication delivered via Turbuhaler((R)) reaches the target organ.Due to the large amount of small particles and the moderate inbuilt resistance in Turbuhaler((R)), which opens up the vocal cords during inhalation, Turbuhaler((R)) is associated with a high lung deposition (25-40% of the delivered dose) compared with pressurized metered-dose inhalers (pMDIs) and other DPIs. A good correlation has been found between lung deposition and clinical efficacy. A high lung deposition always results in the best ratio between clinical efficacy and risk of unwanted systemic activity. Studies with Turbuhaler((R)) also show that the in vivo variation in lung deposition is significantly lower compared with a pMDI or, for example, the Diskus((R)) inhaler, and much lower than the in vitro dose variability seen in laboratory tests. Turbuhaler((R)) appears to be a reliable DPI which can be used with confidence by patients with airway diseases, including those with clinical c

Topics: Administration, Inhalation; Airway Obstruction; Asthma; Budesonide; Child; Humans; Lung; Nebulizers and Vaporizers; Pulmonary Disease, Chronic Obstructive

Eosinophilic bronchitis is an important cause of chronic cough. Treatment with inhaled corticosteroids is associated with a short-term improvement in cough and reduced sputum eosinophil count but the long-term outcome is uncertain.. To determine the long-term outcome in patients diagnosed with and treated for eosinophilic bronchitis.. We have performed a longitudinal study of symptoms, eosinophilic airway inflammation, spirometry and airway hyper-responsiveness in all patients diagnosed with eosinophilic bronchitis over 7 years.. We identified 52 patients with eosinophilic bronchitis and longitudinal data of greater than 1 year (mean 3.1 years) was available in 32 patients, all of whom were treated with inhaled steroids. Three (9%) patients developed symptoms consistent with asthma and a methacholine PC20<8 mg/mL on one or more occasion. Five (16%) patients developed fixed airflow obstruction defined by a persistent post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity<70%. One (3%) patient had complete resolution of symptoms and eosinophilic airway inflammation off treatment. The remaining patients had ongoing eosinophilic airway inflammation and/or continuing symptoms. Multiple linear regression identified smoking, female gender and area under the curve of sputum eosinophil count over time as the most important predictors of decline in FEV1.. The most common outcome in eosinophilic bronchitis is continuing disease and complete resolution is rare. Asthma and fixed airflow obstruction developed in relatively few patients. The most important factors associated with a more rapid decline in FEV1 were female gender, smoking and prolonged eosinophilic airway inflammation.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Aged, 80 and over; Airway Obstruction; Asthma; Bronchitis; Bronchodilator Agents; Budesonide; Cough; Eosinophilia; Female; Forced Expiratory Volume; Humans; Longitudinal Studies; Male; Middle Aged; Prognosis; Sex Factors; Smoking; Time Factors; Treatment Outcome

Many children with asthma go into long-term clinical remission at adolescence, but bronchial hyperresponsiveness (BHR) persists in some of these subjects. BHR in asthma is characterized by an increase in sensitivity and in maximal airway response to bronchoconstrictor stimuli.. The aims of this study were to compare the profiles of maximal airway response between adolescents with asthma remission and adolescents with symptomatic asthma to a similar degree of airway hypersensitivity, and to determine whether maximal airway response in adolescents with asthma remission is reduced by prolonged treatment with inhaled corticosteroids.. A high-dose methacholine inhalation test was performed in 46 adolescents with long-term asthma remission (remission group) and 44 adolescents with symptomatic asthma (symptomatic group). Subjects exhibiting a maximal response plateau in the remission group were administered inhaled budesonide (400 microg bid, budesonide/remission group, n = 15) or identical placebo (placebo/remission group, n = 15) for 6 months, and the subjects in the symptomatic group were administered the same regimen of budesonide (budesonide/symptomatic group, n = 17). The plateau level was measured after 3 months and 6 months of treatment.. Thirty-four subjects (73.9%) in the remission group featured a maximal response plateau on the dose-response curve to methacholine, whereas 19 subjects (43.2%) in the symptomatic group had a plateau (p = 0.003). In neither the placebo/remission group nor the budesonide/remission group did the plateau level change significantly over the 6-month period, whereas budesonide markedly decreased the level in the budesonide/symptomatic group.. The difference in frequency of detection of a plateau between the remission group and the symptomatic group, as well as the difference in its response to treatment with budesonide between the two groups, suggests that inflammatory changes impact the maximal airway response in symptomatic asthmatic adolescents but not in adolescents with asthma remission.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Airway Obstruction; Asthma; Bronchial Hyperreactivity; Bronchial Provocation Tests; Budesonide; Case-Control Studies; Dose-Response Relationship, Drug; Female; Forced Expiratory Volume; Humans; Male; Methacholine Chloride; Probability; Prognosis; Reference Values; Remission, Spontaneous; Respiratory Function Tests; Sampling Studies; Sensitivity and Specificity; Severity of Illness Index; Statistics, Nonparametric

The diagnoses, transfer, management and outcome of patients with upper airway obstruction (UAO) admitted from district general hospitals (DGH) to a regional paediatric intensive care unit were retrospectively reviewed over a 3.5-year period. Sixty-seven patient episodes were analysed. Fifty-two cases (78%) underwent tracheal intubation prior to transport with a low morbidity for both procedures. The most common diagnosis was viral croup (n = 34, 51%) with a median duration of intubation of 5 days, with subglottic stenosis being the next most common category (n = 10, 15%), median duration of intubation 7 days. Inhaled budesonide was used prior to intubation in 12 (35%) of those with croup, and inhaled bronchodilators in 28%, possibly reflecting diagnostic uncertainty. Patients with croup treated with budesonide were significantly less likely to require intubation (P = 0.04). The re-intubation rate for patients with viral croup was uncomfortably high at 16% (4/25) despite the routine use of prednisolone throughout the intubation period. Successful extubation of patients with viral croup could not be predicted by age (P = 0.31), length of intubation (P = 0.94), endotracheal tube size, (P = 0.60) abnormalities on the chest X-ray (P = 1.0), or presence of secondary bacterial infection (P = 0.23).. Although viral croup remains the most common diagnostic category presenting at the DGH level with severe UAO, a wide range of other diagnoses is seen. Despite clear evidence of benefit, steroid administration to children presenting at the DGH with viral croup has not become routine practice. Once intubated, no reliable predictors of successful extubation were found amongst this patient group.

Topics: Airway Obstruction; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Critical Care; Croup; Hospitals, District; Hospitals, General; Humans; Infant; Infant, Newborn; Intensive Care Units, Pediatric; Intubation, Intratracheal; London; Patient Transfer; Retrospective Studies; Treatment Outcome

1. In this study, an attempt was made to distinguish between local and systemic effects of low doses of the topical glucocorticoid, budesonide. The effect of aerosolized budesonide administered to the lower airways versus intravenously administered budesonide on the acute and late response to nebulized Ascaris suum extract in the lung, was evaluated in the minipig after active sensitization with purified A. suum antigen. Budesonide was administered once, 1 h prior to A. suum challenge and airway reactions and mediator release were observed for 8 h after allergen challenge. 2. In the budesonide aerosol group (n = 6), 10.2 +/- 1.2 micrograms kg-1 budesonide was given locally and in the budesonide infusion group (n = 5), 5 micrograms kg-1 was given intravenously. The area under the plasma concentration curve for budesonide during the experiment was 11.4 +/- 1.2 and 10.3 +/- 1.2 nM h in the budesonide aerosol and budesonide infusion group, respectively (no significant difference). The lung tissue content of budesonide in the two groups was 45.2 +/- 4.9 and 18.4 +/- 3.5 nmol kg-1 dry tissue, respectively, 8 h after allergen challenge (P < 0.05). For comparison, 6 pigs were given budesonide vehicle as an infusion prior to A. suum challenge. 3. Total lung resistance (RL) increased acutely (maximal response within 15 min) in the budesonide aerosol, budesonide infusion and budesonide vehicle groups (by 91 +/- 40, 150 +/- 86 and 80 +/- 27%, respectively). The acute reaction partially resolved at about 1 h and was followed by a late increase in RL in the budesonide infusion and budesonide vehicle groups (by 251 +/- 148 and 281 +/- 136% at 8 h, respectively). However, no late change in RL was seen in the budesonide aerosol group (7 +/- 24%). 4. Aerosolized budesonide had a protective effect in that it attenuated the late changes in arterial blood gas and pH as well as the late elevation of plasma catecholamines. Budesonide given as an infusion did not protect against the late changes in these parameters. However, budesonide aerosol or infusion did not inhibit the late vasodilation in the bronchial circulation. 5. Histamine and cysteinyl-leukotrienes were released during the acute reaction as measured by urinary concentration of methylhistamine and leukotriene E4 respectively. There was no release of histamine during the late reaction. A late increase in leukotriene E4 was observed in 2 of the budesonide infusion and 3 of the budesonide vehicle pigs, whereas no such i

Topics: Administration, Inhalation; Administration, Topical; Airway Obstruction; Allergens; Analysis of Variance; Animals; Anti-Inflammatory Agents; Antigens, Helminth; Ascaris suum; Blood Pressure; Budesonide; Glucocorticoids; Heart Rate; Histamine; Injections, Intravenous; Leukotriene E4; Lung; Male; Pregnenediones; Swine; Swine, Miniature; Vascular Resistance

Late airways obstruction and eosinophil infiltration after allergen challenge are often seen in human asthma and animal models of allergy. This inflammatory reaction, which may be a link between acute and chronic asthma, is blocked by glucocorticoid pretreatment. However, the role of eosinophils in late airways obstruction and the primary site of action of glucocorticoids, i.e. locally or systemically, have not been fully determined.. This study was initiated to find out the role of eosinophils and neutrophils in allergen-induced late airways obstruction in the pig. The effect of pretreatment with budesonide (BUD) given locally or systemically on cellular responses seen within 8 h after allergen challenge was also studied.. Twenty-five minipigs were actively sensitized with Ascaris suum antigen and challenged under anaesthesia with antigen in the lower airways. Pigs were given BUD as an aerosol (10 micrograms/kg) or an intravenous infusion (5 micrograms/kg) 1 h before allergen challenge. In one group, high doses of BUD (50 micrograms/kg) were infused twice with a 3-h interval before allergen challenge. As a positive control, one group was given the BUD vehicle as an infusion and as a negative control, one group not treated with BUD was given the irrelevant antigen ovalbumin. Eosinophils and neutrophils in lung tissue specimens were detected and levels of eosinophil peroxidase (EPO) and myeloperoxidase (MPO) in bronchoalveolar lavage (BAL) fluid were measured using specific antibodies against porcine EPO and MPO.. The number of eosinophils in lung tissue and BAL fluid and the level of EPO in BAL fluid were significantly increased 8 h after A. suum challenge in pigs not treated with BUD. With regard to possible recruitment and activation of neutrophils the only significant finding was an increase in the number of cells in BAL fluid. The eosinophil numbers and the level of EPO in BAL fluid were shown to be decreased by all BUD treatments in all the compartments studied compared to the positive control. However, the number of eosinophils in lung tissue and EPO levels in BAL fluid did not correlate with the magnitude of the late airways obstruction.. Although eosinophils are present in the bronchial wall and lumen and are apparently activated, a causative relationship between this granulocyte and the late bronchial obstruction could not be established in this model.

Topics: Administration, Inhalation; Aerosols; Airway Obstruction; Allergens; Animals; Anti-Inflammatory Agents; Ascaris suum; Bronchoalveolar Lavage Fluid; Budesonide; Eosinophil Peroxidase; Eosinophils; Infusions, Intravenous; Leukocyte Count; Lung; Male; Neutrophils; Peroxidase; Peroxidases; Pregnenediones; Rabbits; Swine; Swine, Miniature

The aim of the study was to find out whether asthma patients whose airways obstruction is sensitive (CS) or resistant (CR) to corticosteroid treatment also differ in their cutaneous vasoconstrictor response to a potent topical glucocorticoid. Corticosteroid resistance was defined by failure of forced expiratory volume in 1 s (FEV1) and peak expiratory flow rate to improve by at least 15% after a 2-week trial of corticosteroids (prednisolone 20 mg daily for 1 week, then 40 mg daily for 1 week) despite more than 15% improvement with inhaled beta agonists. Beclomethasone dipropionate in concentrations of 3 micrograms/ml, 10 micrograms/ml, 30 micrograms/ml, and 100 micrograms/ml was applied to forearm skin; the site was occluded under plastic and the degree of blanching assessed after 18 h. CS asthmatic subjects (n = 31), asthma patients with mild airways obstruction (n = 26), asthma patients taking long-term prednisolone (n = 13), and healthy volunteers showed similar vasoconstrictor responses. In CR asthmatic subjects (n = 15), the response (expressed in terms of either blanching intensity or the proportion of patients showing a positive response) was significantly lower than that in the CS group at concentrations of 3 micrograms/ml (p less than 0.01), 10 micrograms/ml (p less than 0.01), and 30 micrograms/ml (p less than 0.05), but not at 100 micrograms/ml. This resistance to glucocorticoids in the skin, together with reported evidence of glucocorticoid resistance in peripheral blood leucocytes, suggests a general defect in the ability of tissues to respond to glucocorticoids in CR asthma.

Topics: Administration, Oral; Administration, Topical; Adult; Aged; Airway Obstruction; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Drug Administration Schedule; Female; Glucocorticoids; Humans; Male; Middle Aged; Prednisolone; Pregnenediones; Skin; Vasoconstriction

Acute reversible airways obstruction in children, especially those aged under one year, who may respond poorly to inhaled beta 2-stimulants, is difficult to treat in general practice. In an open study, 48 episodes in 29 children, half aged under one year, were treated with budesonide (Pulmicort) 0.1-2.09 mg used to charge a Nebuhaler fitted with a facemask. In 45 instances, clinical improvement was observed, and with doses of 0.8 mg and above, this usually occurred within 10 minutes. This study suggests that budesonide via a suitable delivery system can evoke rapid improvement in reversible airways obstruction in young children.

Topics: Administration, Inhalation; Airway Obstruction; Asthma; Budesonide; Child; Child, Preschool; Humans; Infant; Infant, Newborn; Masks; Pregnenediones; Respiratory Distress Syndrome, Newborn

Topics: Adrenergic beta-Agonists; Aerosols; Airway Obstruction; Aspirin; Asthma; Bronchi; Bronchodilator Agents; Budesonide; Calcium Channel Blockers; Cromolyn Sodium; Drug Administration Schedule; Epinephrine; Glucocorticoids; Gold; Humans; Inflammation; Mucous Membrane; Osteoporosis; Parasympatholytics; Patient Education as Topic; Prednisone; Pregnenediones; Theophylline

Topics: Adult; Airway Obstruction; Allergens; Asthma; Bronchial Provocation Tests; Budesonide; Female; Glucocorticoids; Humans; Male; Pregnenediones