fluticasone and Lung-Diseases--Obstructive

Seretide (Advair [North America], GlaxoSmithKline) is an inhaler combination formulation intended for the maintenance therapy of obstructive airways disease. Seretide was developed and made available initially as three multi-dose, dry powder inhaler formulations delivering 50 microg/puff of the long acting beta(2) agonist salmeterol and either 100, 250 or 500 microg/puff of the inhaled corticosteroid fluticasone propionate. In addition to the initial multi-dose dry powder inhaler system (Diskus or Accuhaler), a chlorofluorocarbon (CFC)-free pressurised aerosol formulation has become available. Studied mostly extensively as a maintenance therapy for patients with persistent asthma, the combination inhaler is at least equivalent to its components administered separately and is superior to monotherapy with salmeterol or inhaled corticosteroid in both paediatric and adult populations. The combination has a logical role in the treatment of moderate-to-severe asthma, offering the advantage of increased convenience and possibly improved compliance. In addition to improvements in lung function, symptom scores and quality of life, the combination therapy reduces exacerbation rates, an outcome that contributes to favourable cost-effectiveness. A role as initial maintenance therapy in all forms of persistent asthma is also plausible but there are fewer data concerning the impact of Seretide in milder forms of persistent asthma. Clinical trials are underway to examine the potential role of Seretide in patients with chronic obstructive pulmonary disease (COPD). Salmeterol has been shown to be an effective first-line bronchodilator in COPD and fluticasone has been shown to reduce the frequency and or severity of exacerbations in COPD patients in two key trials. At a time when the prevalence of both asthma and COPD is increasing, Seretide is a valuable step in the management of these common obstructive lung diseases.

Topics: Administration, Inhalation; Albuterol; Androstadienes; Anti-Inflammatory Agents; Clinical Trials as Topic; Drug Combinations; Fluticasone; Fluticasone-Salmeterol Drug Combination; Humans; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Salmeterol Xinafoate

Topics: Administration, Inhalation; Administration, Topical; Androstadienes; Anti-Inflammatory Agents; Fluticasone; Forced Expiratory Volume; Glucocorticoids; Humans; Lung Diseases, Obstructive; Prednisolone; Randomized Controlled Trials as Topic

Triamcinolone is a commonly used synthetic corticosteroid that has recently been tested in a large clinical trial for chronic obstructive pulmonary disease and shown to have some benefits. To our knowledge, there are no reviews of the pharmacotherapy of triamcinolone. This review has a brief overview of the pharmacology of triamcinolone, followed by a discussion of the clinical trials with triamcinolone. Triamcinolone is used in the treatment of respiratory inflammation, rheumatoid arthritis and a variety of other inflammatory conditions.

Topics: Administration, Intranasal; Adult; Aerosols; Androstadienes; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Astemizole; Asthma; Child; Clinical Trials as Topic; Conjunctivitis, Allergic; Dose-Response Relationship, Drug; Fluticasone; Humans; Injections, Intramuscular; Loratadine; Lung Diseases, Obstructive; Macular Degeneration; Molecular Structure; Nasal Mucosa; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Structure-Activity Relationship; Triamcinolone

Chronic obstructive pulmonary disease (COPD) remains difficult to manage. Patients with COPD present with progressive dyspnea; difficulty in stopping smoking; recurrent exacerbations; and, ultimately, respiratory failure. Because of the lack of proven treatments for COPD and because inhaled corticosteroids can prevent airway inflammation and permanent lung damage in patients with asthma, it has become common practice to prescribe inhaled corticosteroids for patients with COPD despite a lack of data suggesting that these agents have any long-term benefit in these patients. In the past 12 months, three randomized, double-blind, placebo-controlled clinical trials (the European Respiratory Society Study on Chronic Obstructive Pulmonary Disease, the Copenhagen City Lung Study, and the Inhaled Steroids in Obstructive Lung Disease study) designed to assess the long-term effect of inhaled corticosteroids in patients with varying severity of airway obstruction have been presented. The results of these studies have been disappointing; they show little to suggest that any long-term benefit is gained from using inhaled corticosteroids in most patients with COPD, whether they continue to smoke or not.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Androstadienes; Budesonide; Fluticasone; Forced Expiratory Volume; Glucocorticoids; Humans; Lung Diseases, Obstructive; Predictive Value of Tests; Quality of Life; Severity of Illness Index

BASIS OF TREATMENT: Chronic obstructive pulmonary disease (COPD) is a common condition. Medical, and particularly drug, therapy still provides insufficiently effective relief. Corticosteroid treatment relies on the effect of these drugs on the underlying inflammatory mechanisms. Their efficacy has been demonstrated in asthma which exhibits certain features common with COPD.. Short-term corticosteroid regimens are generally well tolerated. Clinical data favor their use in certain cases of acute decompensation. Long-term systemic regimens are not warranted due to the risk of adverse effects and the difficulty in maintaining appropriate dosages. Inhaled corticosteroids are widely used although the efficacy remains controversial.. Clear evidence of efficacy from large controlled trials is still lacking. The difficulty encountered in obtaining such evidence is an indication of the minimal impact of such treatment and raises the question of its clinical pertinence. Patients exhibiting features similar to those observed in asthma (atopy, eosinophilia, improvement with bronchodilatation, non-smokers...) should be able to benefit from corticosteroids. For others a therapeutic test would be advisable to identify responders who could benefit from a preventive effect on the progression of COPD or associated asthma. A test lasting a few weeks at sufficient dosage is needed for subjective and objective (respiratory function tests) assessment. This costly therapy would not be warranted in non-responders, particularly in light of the expected secondary effects. Current evidence does not point to corticosteroid therapy as the much needed fully effective treatment for COPD.

Topics: Administration, Inhalation; Administration, Oral; Administration, Topical; Adrenal Cortex Hormones; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Beclomethasone; Bronchodilator Agents; Clinical Trials as Topic; Fluticasone; Glucocorticoids; Humans; Lung Diseases, Obstructive; Maximal Expiratory Flow-Volume Curves; Placebos; Risk Factors; Smoking; Sympathomimetics; Time Factors

Asthma is a chronic inflammatory disorder of the airways characterized by variable airflow limitation and airway hyperresponsiveness. The type of inflammatory response in asthma is compatible with a major contribution of professional antigen-presenting cells. The airways in chronic obstructive pulmonary disease (COPD) are also markedly inflamed; however, the predominant types of inflammatory cells and the main anatomical site of the lesion appear to differ from those in asthma. COPD is characterized by reduced maximum expiratory flow and slow forced emptying of the lungs. Steroids are the most prominent medication used in the treatment of asthma and COPD; however, the beneficial effect of steroid treatment in COPD is subject of debate. We investigated the efficacy of fluticasone propionate (FP) treatment in atopic asthmatics and in COPD patients with bronchial hyperreactivity who smoke. The effect of the treatment on bronchial hyperreactivity and indices of the methacholine dose-response curve were analysed, as well as indices of inflammation of the airway mucosa with special emphasis on the antigen presenting dendritic cell. Treatment of allergic asthmatic patients resulted in improvement of lung function (FEV1), a decrease in bronchial hyperresponsiveness and a decrease of maximal airway narrowing. During the FP-treatment of COPD patients, FEV1 remained stable, while FEV1 deteriorated significantly in the placebo group. Therefore, steroid treatment may have a beneficial effect in COPD patients with bronchial hyperresponsiveness (BHR). Since immunohistochemical analysis of bronchial biopsy specimens from asthma and COPD patients show disease-specific aspects of inflammation, the anti-inflammatory effect of FP is obtained through modulation of different cell populations in asthma and COPD.

Topics: Androstadienes; Animals; Anti-Asthmatic Agents; Asthma; Bronchial Hyperreactivity; Bronchial Provocation Tests; Dendritic Cells; Dose-Response Relationship, Drug; Fluticasone; Forced Expiratory Volume; Humans; Lung Diseases, Obstructive; Methacholine Chloride

Recently, a step-by-step pharmacologic therapy for chronic obstructive pulmonary disease (COPD) has been recommended by several principal organizations. The characteristic of this therapy is that it is a stepwise approach organized according to the severity of disease and is mainly composed of bronchodilators including beta 2-agonists and anticholinergic agents, theophylline, and oral corticosteroids, and the goal of this therapy is to induce bronchodilation, decrease the inflammatory reaction, and facilitate expectoration. Since the effectiveness of one of the inhaled corticosteroids has been also indicated by the multicentre randomised trial in a few years, they may have an important role in the long-term treatment of COPD.

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Androstadienes; Bronchodilator Agents; Cholinergic Antagonists; Fluticasone; Humans; Lung Diseases, Obstructive; Multicenter Studies as Topic; Prednisolone; Randomized Controlled Trials as Topic; Theophylline

In smoking COPD patients the bronchoalveolar lavage (BAL) fluid contains high numbers of inflammatory cells. These cells might produce arachidonic acid (AA) metabolites, which contribute to inflammation and an increased bronchomotor tone.. To investigate levels of AA metabolites in BAL fluid, before and after inhaled glucocorticoid therapy: fluticasone propionate (FP) 1 mg per day, or placebo.. A double-blind placebo controlled trial lasting six months. COPD patients were selected by clinical criteria and the presence of bronchial hyper-responsiveness (BHR). Lung function was recorded and in BAL fluid we counted cell numbers and measured LTB4, LTC4/D4/E4, PGE2, 6kPGF1alpha, PGF2alpha and TxB2. A control group consisted of asymptomatic smokers (n=6).. Paired data were obtained from 9 FP treated and 11 placebo patients. BAL cells were almost exclusively alveolar macrophages. In patients and controls both cellularity and levels of AA metabolites were equal Cell numbers did not change after treatment. Statistically significant decreases after FP therapy were noticed for PGE2 (30%), 6kPGF1alpha (41%) and PGF2alpha (54%).. In COPD, the capability of inflammatory cells to produce certain AA metabolites was decreased after inhaled FP treatment. This result is discussed in its relation to clinical effects, the influence of smoking, and the results of an earlier, similar study in asthma patients.

Topics: Adult; Androstadienes; Anti-Inflammatory Agents; Arachidonic Acid; Bronchoalveolar Lavage Fluid; Double-Blind Method; Fluticasone; Humans; Lung Diseases, Obstructive; Middle Aged; Respiratory Function Tests; Smoking

Although both inhaled and oral corticosteroids have anti-inflammatory effects causing improvement in clinical symptoms and spirometry in the treatment of asthma, the role of corticosteroids in the management of chronic obstructive pulmonary disease (COPD) is controversial.. To evaluate the effects of inhaled corticosteroids on sputum neutrophilia in clinically stable COPD patients.. In total, 18 patients were enrolled in the study. During 2 months, 9 patients in group A inhaled fluticasone propionate (FP) 500 microg 3 times daily. In group B 9 patients received placebo. All of the patients continued to inhale both salbutamol and ipratropium bromide. In 9 patients, sustained-released theophylline was also administered. Blood samples, spirometric tests, blood gas analyses, and either spontaneous or induced sputum cultures were evaluated on entry into the study, after a 2 months of treatment and following the 6-week washout period.. After the 2-month FP treatment, no significant changes in the number of peripheral blood neutrophils, blood gas and spirometry data were observed in both groups. In group A, the total cell number and the number of neutrophils decreased from a mean of 3. 4 +/- 1.3 x 10(6) cells/g and 0.6 +/- 0.3 x 10(6) neutrophils/g on entry into study to 1.9 +/- 0.6 x 10(6) cells/g and 0.02 +/- 0.01 x 10(6) neutrophils/g after 8-week treatment with FP, returning to 3.3 +/- 1.1 x 10(6) cells/g and 0.5 +/- 0.3 x 10(6) neutrophils/g following the washout period. The percentages of neutrophils were 55. 6 and 77.9% in groups A and B after 2 months of FP treatment. There was no significant change in group B values during the study.. These data suggest that neutrophilic inflammation in sputum may be decreased by inhaled corticosteroids in clinically stable COPD patients.

Topics: Administration, Inhalation; Aged; Androstadienes; Anti-Inflammatory Agents; Blood Gas Analysis; Female; Fluticasone; Humans; Inflammation; Lung Diseases, Obstructive; Male; Middle Aged; Neutrophils; Spirometry; Sputum

To determine the effect of long term inhaled corticosteroids on lung function, exacerbations, and health status in patients with moderate to severe chronic obstructive pulmonary disease.. Double blind, placebo controlled study.. Eighteen UK hospitals.. 751 men and women aged between 40 and 75 years with mean forced expiratory volume in one second (FEV(1)) 50% of predicted normal.. Inhaled fluticasone propionate 500 microgram twice daily from a metered dose inhaler or identical placebo.. Efficacy measures: rate of decline in FEV(1) after the bronchodilator and in health status, frequency of exacerbations, respiratory withdrawals. Safety measures: morning serum cortisol concentration, incidence of adverse events.. There was no significant difference in the annual rate of decline in FEV(1 )(P=0.16). Mean FEV(1) after bronchodilator remained significantly higher throughout the study with fluticasone propionate compared with placebo (P<0.001). Median exacerbation rate was reduced by 25% from 1.32 a year on placebo to 0.99 a year on with fluticasone propionate (P=0.026). Health status deteriorated by 3.2 units a year on placebo and 2.0 units a year on fluticasone propionate (P=0.0043). Withdrawals because of respiratory disease not related to malignancy were higher in the placebo group (25% v 19%, P=0.034).. Fluticasone propionate 500 microgram twice daily did not affect the rate of decline in FEV(1) but did produce a small increase in FEV(1). Patients on fluticasone propionate had fewer exacerbations and a slower decline in health status. These improvements in clinical outcomes support the use of this treatment in patients with moderate to severe chronic obstructive pulmonary disease.

Topics: Administration, Inhalation; Adult; Aged; Algorithms; Androstadienes; Anti-Inflammatory Agents; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Health Status; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Treatment Outcome

In a prospective study, we investigated the long-term compliance to fluticasone propionate (FP) by dry powder inhalation (Rotadisk) in subjects with early signs of asthma and chronic obstructive pulmonary disease (COPD) without an established diagnosis. Subjects were selected from a large screening program on early stages of asthma and COPD (Detection, Intervention, and Monitoring Program of COPD and Asthma [DIMCA] program) in the general practice. Forty-eight adult subjects with "early signs of COPD" (slightly increased forced expiratory volume in 1 sec [FEV1] decline of >0.04L/year) and 29 adult subjects with "early signs of asthma" (signs of bronchial hyperresponsiveness or reversibility) participated in a randomized placebo-controlled trial with FP (Flixotide 500 microg daily) versus placebo with a duration of 2 years or 1 year, respectively. Compliance was measured by counting Rotadisks returned. By means of a questionnaire, participants were asked about perceived effects and/or side effects of the trial drug. The mean overall individual compliance rates of 72% (range 7%-102%) in the early COPD trial and 71% (range 8%-99%) in the early asthma trial were maintained throughout the study. Perceived effectiveness (12% of the participants) or side effects (30% of the participants) of the trial drug were not related to compliance. The willingness of patients to use the trial drug in daily practice if efficacy would be proved was statistically significantly related to compliance during the trial (p = 0.017). It was concluded that the compliance rates found were relatively high in patients with symptoms of mild asthma or COPD without an established diagnosis. Conviction of the importance of treatment influenced compliance more positively than perceived (side) effects. These results again emphasize the importance of patient education in establishing early treatment with inhaled corticosteroids.

Topics: Administration, Inhalation; Androstadienes; Anti-Inflammatory Agents; Asthma; Double-Blind Method; Female; Fluticasone; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Nebulizers and Vaporizers; Patient Compliance; Powders; Time Factors

Oxidative stress in the lung is important in the pathogenesis of COPD. Published data indicate that glucocorticoids inhibit blood cells in their capacity to produce reactive oxygen species (ROS). We investigated the effect of Fluticasone propionate (FP) on the ROS production capabilities of pulmonary cells. Bronchoalveolar lavage (BAL) was performed in smoking COPD patients, before and after a six month, placebo-controlled treatment with FP. BAL cells were stimulated with phorbol myristrate acetate (PMA) alone, and together with superoxide dismutase (SOD). From kinetic plots of ferricytochrome-c conversion we calculated the maximal rate of superoxide production: V(max). We also examined BAL cell subsets and performed correlation analyses on ROS production and relevant clinical determinants. Paired results were obtained from 6 FP- and 9 placebo-treated patients. No significant change of V(max) was found in both patient groups. Also BAL cellularity was unchanged. Correlation analyses showed a significant (inverse) association of V(max) with the number of cigarettes smoked per day. We concluded that a potent inhaled glucocorticoid had no effect on the ROS production capability of BAL cells from smoking COPD patients. Apparently, heavy smoking impaired the ability of alveolar macrophages to produce ROS, which was not further decreased by FP.

Topics: Administration, Inhalation; Administration, Topical; Adult; Aged; Androstadienes; Anti-Inflammatory Agents; Bronchial Hyperreactivity; Bronchoalveolar Lavage Fluid; Double-Blind Method; Fluticasone; Glucocorticoids; Humans; Lung Diseases, Obstructive; Middle Aged; Reactive Oxygen Species; Smoking; Superoxides

There is no agreement about the efficacy of systemic corticosteroids in patients with COPD, but corticosteroids often are employed during exacerbations of the disease. The use of systemic or inhaled corticosteroids in patients in stable condition is even more controversial, even though the more severely affected patients seem to respond better. Unfortunately, in this subset of patients, the use of forced expiratory maneuvers frequently fails to detect significant functional response.. We evaluated the short-term effects of an inhaled corticosteroid, fluticasone propionate (FP), on FEV(1) and on the mechanical properties of patients in stable condition with severe COPD and chronic hypercapnic respiratory failure who were receiving long-term ventilatory support. This allowed us to measure respiratory mechanics (RM) passively, thereby avoiding any problems linked with voluntary maneuvers.. Randomized, placebo-controlled, crossover study.. A respiratory ICU.. Twelve hypercapnic COPD patients (mean [+/- SD] PaCO(2), 60+/-11 mm Hg; mean FEV(1), 13+/-5% predicted; and mean FEV(1)/FVC, 31 +/- 7%) were enrolled.. A daily dose of 2,000 microg FP or placebo was administered via metered-dose inhaler during mechanical ventilation for 5 consecutive days. A washout of 72 h was allowed between regimens.. End-expiratory and end-inspiratory airway occlusions were performed to assess static intrinsic positive end-expiratory pressure (PEEPi,st), static compliance of the respiratory system (Cst,rs), maximal respiratory resistance (Rmax, rs), and minimal respiratory resistance (Rmin,rs). The bronchodilator response also was assessed by FEV(1) level.. No significant changes were found in RM after administration of the placebo. By day 6, FP had induced the following significant decreases: PEEPi,st, 4.3+/-2.4 to 3.1+/-1.7 cm H(2)O (p<0.01); Rmax,rs, 19.0+/-6.5 to 14.6+/-6 cm H(2)O/L/s (p<0.001); and Rmin,rs, 14.8+/-4.2 to 10.5+/-3.4 cm H(2)O/L/s (p<0.001). The Cst,rs and the effective additional resistance of the respiratory system did not change significantly, the latter suggesting that the major effect of FP was on the airway caliber (Rmin,rs). FEV(1) changes significantly (p<0.01) underestimated the bronchodilator response, as compared with changes in Rmin,rs.. We conclude that in patients in stable condition with severe COPD and chronic hypercapnic respiratory failure, a brief trial of FP may induce a bronchodilator response, mainly related to a reduction in airway resistances, that is not detected by the usual pulmonary function tests.

Topics: Administration, Inhalation; Administration, Topical; Adult; Aged; Airway Resistance; Androstadienes; Anti-Inflammatory Agents; Blood Gas Analysis; Cross-Over Studies; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Glucocorticoids; Humans; Lung Compliance; Lung Diseases, Obstructive; Male; Middle Aged; Nebulizers and Vaporizers; Positive-Pressure Respiration; Treatment Outcome

Topics: Administration, Inhalation; Administration, Topical; Androstadienes; Anti-Inflammatory Agents; Bronchodilator Agents; Double-Blind Method; Fluticasone; Follow-Up Studies; Humans; Hydrocortisone; Lung Diseases, Obstructive; Maximal Expiratory Flow-Volume Curves; Multicenter Studies as Topic; Placebos; Prospective Studies; Retrospective Studies; Surveys and Questionnaires; Time Factors

ss(2)-Agonists and corticosteroids or theophylline can interact to produce beneficial effects on airway function in asthma, but this has not been established in COPD.. Eighty patients with well-controlled COPD were randomized to receive 3 months of treatment in one of four treatment groups: (1) salmeterol, 50 microg bid; (2) salmeterol, 50 microg, plus fluticasone propionate, 250 microg bid; (3) salmeterol, 50 microg, plus fluticasone propionate, 500 microg bid; and (4) salmeterol, 50 microg, plus titrated theophylline bid. At each visit, a dose-response curve to inhaled salbutamol was constructed using a total cumulative dose of 800 microg.. A gradual increase in FEV(1) was observed with each of the four treatments. Maximum significant increases in FEV(1) over baseline values that were observed after 3 months of treatment were as follows: salmeterol, 50 microg bid, 0.163 L (95% confidence interval [CI], 0.080 to 0.245 L); salmeterol, 50 microg, plus fluticasone propionate, 250 microg bid, 0.188 L (95% CI, 0.089 to 0. 287 L); salmeterol, 50 microg, plus fluticasone propionate, 500 microg bid, 0.239 L (95% CI, 0.183 to 0.296 L); and salmeterol, 50 microg, plus titrated theophylline bid, 0.157 L (95% CI, 0.027 to 0. 288 L). Salbutamol always caused a significant dose-dependent increase in FEV(1) (p < 0.001), although the 800-microg dose never induced further significant benefit when compared with the 400-microg dose. The mean differences between the highest salbutamol FEV(1) after salmeterol, 50 microg, plus fluticasone propionate, 500 microg bid, and that after salmeterol, 50 microg, plus titrated theophylline bid or salmeterol, 50 microg bid, were statistically significant (p < 0.05).. These data show that both long-acting ss(2)-agonists and inhaled corticosteroids have a role in COPD. The data also show that fluticasone propionate and salmeterol given together are more effective than salmeterol alone. Moreover, it suggests that the addition of fluticasone propionate to salmeterol allows a greater improvement in lung function after salbutamol, although regular salmeterol is able to improve lung function in COPD patients without development of a true subsensitivity to its bronchodilator effect. In any case, patients must be treated for at least 3 months before a real improvement in lung function is achieved.

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Aged; Albuterol; Androstadienes; Bronchodilator Agents; Dose-Response Relationship, Drug; Drug Synergism; Drug Therapy, Combination; Female; Fluticasone; Forced Expiratory Volume; Glucocorticoids; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Salmeterol Xinafoate; Theophylline

Topics: Administration, Inhalation; Administration, Topical; Androstadienes; Anti-Inflammatory Agents; Bronchiectasis; Double-Blind Method; Fluticasone; Glucocorticoids; Humans; Leukocyte Count; Lung Diseases, Obstructive; Neutrophils

Asthma is a chronic inflammatory disorder of the airways characterized by variable airflow limitation and airway hyperresponsiveness. The type of inflammatory response in asthma is compatible with a major contribution of professional antigen-presenting cells. The airways in chronic obstructive pulmonary disease (COPD) are also markedly inflamed; however, the predominant types of inflammatory cells and the main anatomical site of the lesion appear to differ from those in asthma. COPD is characterized by reduced maximum expiratory flow and slow forced emptying of the lungs. Steroids are the most prominent medication used in the treatment of asthma and COPD; however, the beneficial effect of steroid treatment in COPD is subject of debate. We investigated the efficacy of fluticasone propionate (FP) treatment in atopic asthmatics and in COPD patients with bronchial hyperreactivity who smoke. The effect of the treatment on bronchial hyperreactivity and indices of the methacholine dose-response curve were analysed, as well as indices of inflammation of the airway mucosa with special emphasis on the antigen presenting dendritic cell. Treatment of allergic asthmatic patients resulted in improvement of lung function (FEV1), a decrease in bronchial hyperresponsiveness and a decrease of maximal airway narrowing. During the FP-treatment of COPD patients, FEV1 remained stable, while FEV1 deteriorated significantly in the placebo group. Therefore, steroid treatment may have a beneficial effect in COPD patients with bronchial hyperresponsiveness (BHR). Since immunohistochemical analysis of bronchial biopsy specimens from asthma and COPD patients show disease-specific aspects of inflammation, the anti-inflammatory effect of FP is obtained through modulation of different cell populations in asthma and COPD.

Topics: Androstadienes; Animals; Anti-Asthmatic Agents; Asthma; Bronchial Hyperreactivity; Bronchial Provocation Tests; Dendritic Cells; Dose-Response Relationship, Drug; Fluticasone; Forced Expiratory Volume; Humans; Lung Diseases, Obstructive; Methacholine Chloride

Inhaled corticosteroids are widely prescribed for the treatment of stable chronic obstructive pulmonary disease (COPD), despite lack of proven efficacy. Because COPD involves airway inflammation and probable protease-antiprotease imbalance, we examined the effect of high dose fluticasone propionate on markers of activity of both pathogenetic mechanisms. Thirteen patients with COPD were treated with fluticasone propionate (500 microg twice a day) for 4 wk, delivered via MDI and spacer, in a double-blind crossover study. There was no clinical benefit in terms of lung function or symptom scores, and induced sputum inflammatory cells, percentage neutrophils, and IL-8 levels were unchanged. Sputum supernatant elastase activity, matrix metalloproteinase (MMP)-1, MMP-9, and the antiproteases secretory leukoprotease inhibitor (SLPI) and tissue inhibitor of metalloproteinase (TIMP)-1 were similarly unaffected by treatment. These results add to previous evidence that inhaled steroids have no anti-inflammatory action in stable COPD. Furthermore, inhaled steroids do not appear to redress the protease-antiprotease imbalance that is thought to be important in the pathogenesis of airway obstruction.

Topics: Administration, Inhalation; Administration, Topical; Adult; Aerosols; Aged; Androstadienes; Anti-Inflammatory Agents; Cross-Over Studies; Cytokines; Double-Blind Method; Endopeptidases; Female; Fluticasone; Glucocorticoids; Humans; Inflammation; Interleukin-8; Lung Diseases, Obstructive; Male; Matrix Metalloproteinases; Middle Aged; Pancreatic Elastase; Proteinase Inhibitory Proteins, Secretory; Proteins; Secretory Leukocyte Peptidase Inhibitor; Serine Proteinase Inhibitors; Sputum; Tissue Inhibitor of Metalloproteinase-1

The efficacy of inhaled corticosteroids in the treatment of chronic obstructive pulmonary disease (COPD) remains controversial because of a lack of placebo-controlled studies. We compared the effect of inhaled fluticasone propionate with placebo in the treatment of patients with COPD.. We used a randomised, double-blind, placebo-controlled design. We enrolled from 13 European countries, New Zealand, and South Africa, 281 outpatient current or ex-smokers, aged between 50 and 75 years. They had a forced expiratory volume in 1 s (FEV1) of between 35% and 90% of predicted normal values, a ratio of FEV1 to forced vital capacity of 70% or less and bronchodilator reversibility of less than 15%, as well as a history of chronic bronchitis. Patients were randomly assigned fluticasone propionate 500 microg (n=142) or placebo (n=139) twice daily via a metered-dose inhaler for 6 months. The main outcome measures were the number of patients who had at least one exacerbation by the end of treatment, the number and severity of exacerbations, clinic lung function, diary card symptoms and peak expiratory flow and 6 min walking distance.. 51 (37%) patients in the placebo group compared with 45 (32%) in the fluticasone propionate group had had at least one exacerbation by the end of treatment (p=0.449). Significantly more patients had moderate or severe exacerbations in the placebo group than in the fluticasone propionate group (86% vs 60%, p<0.001). Diary-card and clinic morning peak expiratory flows improved significantly in the fluticasone propionate group (p<0.001, p=0.048, respectively), as did clinic FEV1 (p<0.001), forced vital capacity (p<0.001), and mid-expiratory flow (p=0.01). Symptom scores for median daily cough and sputum volume were significantly lower with fluticasone propionate treatment than with placebo (p=0.004 and p=0.016, respectively). At the end of treatment, patients on fluticasone propionate had increased their 6 min walking distance significantly more than those on placebo (p=0.032). Fluticasone propionate was tolerated as well as placebo, with few adverse effects and without a clinically important effect on mean serum cortisol concentration.. Fluticasone propionate may be of clinical benefit in patients with COPD over at least 6 months. Inhaled corticosteroids may have an important role in the long-term treatment of COPD.

Topics: Administration, Inhalation; Administration, Topical; Androstadienes; Anti-Inflammatory Agents; Double-Blind Method; Female; Fluticasone; Glucocorticoids; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Respiratory Function Tests; Time Factors; Treatment Outcome

Inhaled corticosteroid (ICS) use is associated with an increased risk of pneumonia. This study was performed to determine if ICS use is associated with an increased risk of nontuberculous mycobacterial pulmonary disease (NTM-PD) or tuberculosis (TB).We conducted a population-based nested case-control study using linked laboratory and health administrative databases in Ontario, Canada, including adults aged ≥66 years with treated obstructive lung disease (

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Aged; Aged, 80 and over; Budesonide; Case-Control Studies; Female; Fluticasone; Humans; Logistic Models; Lung Diseases, Obstructive; Male; Mycobacterium Infections, Nontuberculous; Ontario; Risk Factors; Tuberculosis

Beta-agonists have been shown to display anti-inflammatory properties in several experimental models. The aim of this study was to investigate the anti-inflammatory properties of clenbuterol (CB), administered either intravenously or by aerosol, in comparison with fluticasone propionate (FP) in recurrent airway obstruction (RAO)-susceptible horses. Eight horses, of which five were known to be susceptible to RAO, underwent an inhalation challenge with Aspergillus fumigatus (AF) antigen and were treated with CB intravenously, CB by aerosol, or FP by aerosol. Twenty-four hours after the challenge, bronchoalveolar lavage was performed, the total and differential cell counts were assessed, and cytokines were measured in isolated alveolar macrophages. After challenge with AF, RAO-susceptible horses showed an increase in total cell count, based on an increase in macrophages and lymphocytes, which was inhibited by treatment with intravenous CB, aerosolized CB and aerosolized FP. Neutrophil ratios were decreased when treated with aerosolized CB and FP. Expression of interleukin (IL)-1beta and IL -8 was significantly increased after AF challenge . Interleukin -1beta was significantly decreased following treatment with intravenous CB, aerosolized CB and aerosolized FP, whereas only FP decreased the expression of IL-8. These data suggest that the anti-inflammatory property of CB provide new opportunities in the therapeutic intervention of early inflammation in RAO.

Topics: Administration, Inhalation; Androstadienes; Animals; Antigens, Fungal; Aspergillus fumigatus; Bronchoalveolar Lavage Fluid; Bronchodilator Agents; Clenbuterol; Cytokines; Female; Fluticasone; Horse Diseases; Horses; Injections, Intravenous; Lung Diseases, Obstructive; Macrophages, Alveolar; Random Allocation; Treatment Outcome

Topics: Androstadienes; Anti-Inflammatory Agents; Clinical Trials as Topic; Fluticasone; Follow-Up Studies; Humans; Lung Diseases, Obstructive; Quality of Life

Topics: Adrenergic beta-Agonists; Albuterol; Androstadienes; Bronchitis; Bronchodilator Agents; Cholinergic Antagonists; Critical Pathways; Drug Therapy, Combination; Fluticasone; Humans; Lung Diseases, Obstructive; Salmeterol Xinafoate

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Androstadienes; Dose-Response Relationship, Drug; Double-Blind Method; Fluticasone; Forced Expiratory Volume; Humans; Long-Term Care; Lung Diseases, Obstructive; Randomized Controlled Trials as Topic; Treatment Outcome

Topics: Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Diagnosis, Differential; Fluticasone; Humans; Lung Diseases, Obstructive; Methacholine Compounds; Prednisolone; Sensitivity and Specificity

Topics: Administration, Inhalation; Androstadienes; Anti-Inflammatory Agents; Female; Fluticasone; Forced Expiratory Volume; Health Status; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Recurrence; Treatment Outcome

Topics: Administration, Inhalation; Adult; Aged; Androstadienes; Anti-Inflammatory Agents; Double-Blind Method; Fluticasone; Forced Expiratory Volume; Health Status; Humans; Lung Diseases, Obstructive; Middle Aged; Nebulizers and Vaporizers; Randomized Controlled Trials as Topic; Reproducibility of Results

Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow obstruction and a neutrophilic inflammation. Exhaled nitric oxide (NO) may be a marker of disease activity in a variety of lung diseases. We measured exhaled NO in patients with documented COPD and investigated whether the concentration of exhaled NO is related to the severity of disease as defined by lung function. We also investigated whether concentration of exhaled NO was different in COPD patients who received inhaled steroids compared with steroid-naive patients. We studied 13 current smokers with COPD, eight exsmokers with COPD, 12 patients with unstable COPD (exacerbation or severe disease), and 10 smokers with chronic bronchitis without airflow limitation. Exhaled NO levels were significantly higher in patients with unstable COPD (12.7 +/- 1.5 ppb) than in other groups (p < 0.01). Exhaled NO levels were significantly higher in smokers with COPD than in smokers with chronic bronchitis (4.3 +/- 0.5 versus 2.5 +/- 0.5 ppb, p < 0.05), and were even higher in patients with COPD who had stopped smoking (6.3 +/- 0.6 ppb, p < 0.01). Exhaled NO levels showed a significant negative correlation with their lung function assessed by % predicted FEV1 values (r = -0.6, p < 0.001). Exhaled NO levels in patients treated with inhaled steroids were significantly higher compared with steroid-naive patients (8.2 +/- 1.2 ppb versus 5 +/- 0.4 ppb, p < 0.05), but the first group included more severe patients as assessed by lung function. We conclude that exhaled NO could serve as a useful, practical marker for monitoring disease activity in COPD.

Topics: Administration, Inhalation; Administration, Topical; Analysis of Variance; Androstadienes; Anti-Inflammatory Agents; Biomarkers; Bronchitis; Chronic Disease; Female; Fluticasone; Forced Expiratory Volume; Glucocorticoids; Humans; Lung; Lung Diseases, Obstructive; Male; Middle Aged; Nitric Oxide; Regression Analysis; Respiration; Severity of Illness Index; Smoking; Smoking Cessation

Topics: Administration, Inhalation; Administration, Topical; Aged; Androstadienes; Anti-Inflammatory Agents; Asthma; Female; Fluticasone; Glucocorticoids; Humans; Lung Diseases, Obstructive; Male; United Kingdom

The purpose of this open multicentre study was to evaluate prospectively the efficacy and safety of a combination of fluticasone (250 micrograms b.i.d.) and salmeterol (50 micrograms b.i.d.), both given by a metered dose inhaler, in 413 patients (mean age [+/- SEM] 46.9 +/- 0.7 years) suffering from obstructive airways disease (FEV1 % predicted 73 +/- 1.1%) for 10 +/- 0.5 years. 8 weeks of therapy with both drugs improved FEV1 and peak expiratory flow by 24 +/- 3.1% and 27 +/- 2.7%, respectively. Daytime and nocturnal symptoms, rescue beta 2 agonist use, days off work, and symptoms during working hours decreased. Similarly, the quality of sleep improved (p < 0.001, all comparisons to baseline). More than 80% of patients and physicians independently classified the study medication as superior to their previous therapy. Adverse events possibly, likely or definitely related to the study medication were seen in 9% of patients. In conclusion, an inhaled corticosteroid (fluticasone) together with an inhaled long-acting beta 2 agonist (salmeterol) is an effective and well tolerated therapy in patients with obstructive airways disease.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Albuterol; Androstadienes; Anti-Asthmatic Agents; Bronchodilator Agents; Drug Therapy, Combination; Female; Fluticasone; Forced Expiratory Volume; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Prospective Studies; Salmeterol Xinafoate; Treatment Outcome

Treatment of chronic airflow obstruction with inhaled corticosteroids at an early stage has been shown to preserve the lung function. We tested the hypothesis that "fear of corticosteroids" may be an important reason for nonparticipation in the Detection, early Intervention and Monitoring programme on Chronic obstruction pulmonary disease (COPD) and Asthma ("DIMCA") project. One thousand seven hundred and forty nine adult subjects from 10 general practices were invited to participate in the several parts of the "DIMCA" programme. Refusers were questioned about the reason(s) for nonparticipation. Together the screening, monitoring and three drug interventions of the study showed on average 25-35% refusers. The most frequent reasons for nonparticipation were absence of pulmonary symptoms and lack of time. For those invited to take part in one of the three drug interventions, "dislike of medication" was the most important reason for nonparticipation (33, 45 and 67% of the refusers). "Fear of corticosteroids" specifically was the reason for nonparticipation in 8% of the refusers on the basis of "dislike of medication". We concluded that a specific fear of corticosteroids was not a major obstacle for early intervention with inhaled corticosteroids.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Double-Blind Method; Family Practice; Fear; Female; Fluticasone; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Randomized Controlled Trials as Topic; Surveys and Questionnaires; Treatment Refusal

Topics: Administration, Inhalation; Androstadienes; Anti-Inflammatory Agents; Fluticasone; Forced Expiratory Volume; Humans; Hydrocortisone; Lung Diseases, Obstructive; Research Design

Corticosteroids are widely used in the treatment of many inflammatory conditions but the exact mode of action on neutrophil function is uncertain. Fluticasone propionate is a new topically active synthetic steroid which can be measured in body fluids and which undergoes first pass metabolism.. The effects of fluticasone propionate on the function of neutrophils isolated from normal, healthy control subjects and on the chemotactic activity of sputum sol phase were assessed.. Preincubation of neutrophils with fluticasone propionate reduced the chemotactic response to 10(-8) mol/l F-Met-Leu-Phe (FMLP) and to a 1:5 dilution of sputum sol phase in a dose dependent manner. Furthermore, when fluticasone propionate was added to sputum from eight patients with stable chronic obstructive bronchitis the chemotactic activity of a 1:5 dilution of the sol phase fell from a mean (SE) value of 22.2 (1.21) cells/field to 19.6 (0.89), 17.1 (0.74), and 11.9 (0.6) cells field at 1 mumol/l, 10 mumol/l, and 100 mumol/l, respectively. In further experiments fluticasone propionate preincubated with neutrophils inhibited fibronectin degradation by resting cells and by cells stimulated by FMLP (15.2% inhibition of resting cells, 5.1% inhibition of stimulated cells with 1 mumol/l fluticasone propionate, 24% and 18.7% inhibition respectively at 100 mumol/l fluticasone propionate. Fluticasone propionate had no effect on generation of superoxide anion by resting or stimulated cells.. These results indicate that fluticasone propionate has a direct suppressive effect on several aspects of neutrophil function and may suggest a role for this agent in the modulation of neutrophil mediated damage to connective tissue.

Topics: Administration, Topical; Androstadienes; Anti-Inflammatory Agents; Chemotaxis, Leukocyte; Dose-Response Relationship, Drug; Fibronectins; Fluticasone; Glucocorticoids; Humans; Lung Diseases, Obstructive; N-Formylmethionine Leucyl-Phenylalanine; Neutrophils; Sputum; Superoxides