fluticasone and Bronchitis

Airway inflammation in chronic obstructive pulmonary disease (COPD) is characterised by infiltration of CD8+ T cells and CD68+ macrophages and an increased number of neutrophils, whereas few studies have described the presence of eosinophils. Although the anti-inflammatory effects of corticosteroids in stable COPD are unclear, recent studies suggest that combination therapy could be beneficial. A study was therefore undertaken to evaluate combined salmeterol/fluticasone propionate (SFC) and fluticasone propionate (FP) alone on inflammatory cells in the airways of patients with COPD.. Patients were treated in a randomised, double blind, parallel group, placebo-controlled trial with either a combination of 50 microg salmeterol and 500 microg FP twice daily (SFC, n = 19, 19 men, mean age 62 years), 500 microg FP twice daily (n = 20, 15 men, mean age 64 years) or placebo (n = 21, 17 men, mean age 66 years) for 3 months. At the start and end of treatment bronchoscopy with bronchial biopsies was performed and the numbers of CD8+ T lymphocytes, CD68+ macrophages, neutrophils and eosinophils were measured.. CD8+ cells were significantly reduced by SFC compared with placebo (difference -98.05 cells/mm(2); 95% CI -143.14 to -52.9; p<0.001). Such a marked effect was not seen with FP alone (-44.67 cells/mm(2); 95% CI -90.92 to 1.57; p = 0.06). CD68+ macrophages were also reduced by SFC compared with placebo (difference -31.68 cells/mm(2); 95% CI -61.07 to -2.29; p = 0.03) but not by FP. SFC did not significantly change neutrophils and eosinophils compared with placebo.. SFC has airway anti-inflammatory effects not seen with inhaled corticosteroids alone.

Topics: Administration, Inhalation; Aged; Albuterol; Androstadienes; Bronchitis; Bronchodilator Agents; CD8-Positive T-Lymphocytes; Double-Blind Method; Drug Therapy, Combination; Female; Fluticasone; Forced Expiratory Volume; Humans; Immunohistochemistry; Lymphopenia; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Salmeterol Xinafoate; Treatment Outcome; Vital Capacity

Addition of the long acting beta2 agonist salmeterol to inhaled corticosteroids leads to better symptomatic asthma control than increasing the dose of inhaled corticosteroids. However, little is known about the long term effects of adding salmeterol on the asthmatic inflammatory process, control of which is considered important for the long term outcome of asthma.. After a 4 week fluticasone run-in period, 54 patients with allergic asthma were randomised to receive twice daily treatment with fluticasone 250 microg with or without salmeterol 50 microg for 1 year in a double blind, parallel group design (total daily dose of fluticasone 500 microg in both treatment groups). Primary outcomes were sputum eosinophil numbers and eosinophil cationic protein concentrations. Secondary outcomes were neutrophil associated sputum parameters and a respiratory membrane permeability marker. The effects on allergen induced changes were determined before and at the end of the treatment period.. Adding salmeterol to fluticasone resulted in improved peak expiratory flow, symptom scores, rescue medication usage, and bronchial hyperresponsiveness (p < 0.05 for all). There was no sustained effect on sputum cell differential counts and cytokine concentrations during the treatment period or on changes induced by allergen challenge at the end of treatment (p > 0.05). However, adding salmeterol significantly reduced sputum ratios of alpha2-macroglobulin and albumin during the treatment period (p = 0.001).. The addition of salmeterol to fluticasone produces no sustained effect on allergen induced cellular bronchial inflammation but leads to a significant improvement in size selectivity of plasma protein permeation across the respiratory membrane. This may contribute to the improved clinical outcome seen in patients with allergic asthma when a long acting beta2 agonist is combined with inhaled corticosteroids.

Topics: Administration, Inhalation; Adult; Albuterol; Analysis of Variance; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchitis; Bronchodilator Agents; Double-Blind Method; Drug Combinations; Female; Fluticasone; Humans; Male; Middle Aged; Salmeterol Xinafoate; Treatment Outcome

Newer generations and formulations of inhaled corticosteroids have necessitated the development of a clinically relevant model to compare their clinical potency.. We evaluated whether sputum eosinophil counts could demonstrate a dose-response to inhaled corticosteroids, and compared the response with other inflammatory markers.. Fourteen steroid-naive patients with asthma with an initial sputum eosinophilia of > or = 2.5% entered a 6-week sequential, placebo-controlled, patient-blinded, cumulative dose-response study. After 7 days of placebo, they received incremental doses of fluticasone propionate (FP), 50, 100, 200, and 400 microg/d, each for 7 days. Measurements were made of sputum and blood eosinophils, exhaled nitric oxide, spirometry, airway responsiveness to methacholine (methacholine PC20), and symptom scores before and after each dose.. Sputum eosinophils and exhaled nitric oxide were extremely sensitive to the effects of FP, and exhibited significant dose-dependent reductions of 99.4% and 99.8 parts per billion, respectively, where each variable was expressed per 100 microg/d FP. This compared with a 0.5 doubling dose increase of airway responsiveness to methacholine and a 0.3 decrease in symptom scores. Airway responsiveness to methacholine was the only variable that increased throughout the study.. These results suggest that the model of eosinophilic bronchitis could be used to compare the effect of cumulative doses of an inhaled corticosteroid delivered by different types of delivery systems or preparations using a relatively small number of patients.. Future clinical studies based on this model will allow clinicians to make informed decisions regarding the relative potencies of different inhaled corticosteroids.

Topics: Administration, Inhalation; Adult; Androstadienes; Asthma; Biomarkers; Bronchitis; Dose-Response Relationship, Drug; Eosinophil Cationic Protein; Eosinophilia; Fibrinogen; Fluticasone; Humans; Nitric Oxide; Serine Endopeptidases; Single-Blind Method; Sputum; Tryptases

Chronic obstructive pulmonary disease (COPD) is accompanied by both airway and systemic inflammation and by oxidative stress. This study aimed to characterise the relationship between oxidative stress and inflammatory components in induced sputum and blood.. We studied blood and sputum samples from stable COPD patients (mean FEV1 60.5+/-7.5% predicted) at baseline (no treatment) and after 10 weeks treatment with either inhaled steroid, fluticasone propionate (FP) (1000 microg/d) or 10 weeks treatment with N-acetylcysteine (600mg/d) (NAC). We assessed the inflammatory markers (IL-8, ECP, sICAM-1, NE) in sputum and serum and we compared them with blood markers of oxidative stress (SOD, GPx, TEAC, albumin, vitamin E and A).. At baseline blood sICAM-1 correlated with IL-8 levels (P<0.01, r = 0.62) and negatively with GPx (P<0.01, r = -0.63) and with TEAC (P<0.05, r = -0.53). TEAC correlated positively with GPx (P<0.01, r = 0.70). Correlation between sICAM and IL-8 disappeared after NAC treatment. The correlation between sICAM and GPx disappeared after FP treatment. The correlation between TEAC and GPx was maintained after both NAC and FP.. The relationship between markers of inflammation, adhesion and antioxidant capacity is significantly modulated by treatment with N-acetylcysteine or inhaled corticosteroids.

Topics: Administration, Inhalation; Aged; Androstadienes; Anti-Inflammatory Agents; Antioxidants; Biomarkers; Bronchitis; Cross-Over Studies; Female; Fluticasone; Forced Expiratory Volume; Humans; Interleukin-8; Male; Middle Aged; Oxidative Stress; Pulmonary Disease, Chronic Obstructive; Spirometry; Sputum; Vital Capacity

To determine the effect of prophylactic treatment with an inhaled bronchodilator and anti-inflammatory on arterial saturation (SaO2) in trained non-asthmatic male athletes with exercise induced arterial hypoxaemia (EIAH).. Nine male athletes (mean (SD) age 26.3 (6.7) years, height 182.6 (7.9) cm, weight 79.3 (10.5) kg, VO2MAX 62.3 (6.3) ml/kg/min, SaO2MIN 92.5 (1.1)%) with no history of asthma were tested in two experimental conditions. A combination of a therapeutic dose of salbutamol and fluticasone or an inert placebo was administered in a randomised crossover design for seven days before maximal cycling exercise. Oxygen consumption (VO2), ventilation (VE), heart rate (HR), power output, and SaO2 were monitored during the exercise tests.. There were no significant differences between the drug (D) and placebo (P) conditions for minimal SaO2 (D = 93.6 (1.4), P = 93.0 (1.1)%; p = 0.93) VO2MAX (D = 61.5 (7.2), P = 61.9 (6.3) ml/kg/min; p = 0.91), peak power (D = 444.4 (48.3), P = 449.4 (43.9) W; p = 0.90), peak VE (D = 147.8 (19.1), P = 149.2 (15.5) litres/min; p = 0.82), or peak heart rate (D = 182.3 (10.0), P = 180.8 (5.5) beats/min; p = 0.76).. A therapeutic dose of salbutamol and fluticasone did not attenuate EIAH during maximal cycling in a group of trained male non-asthmatic athletes.

Topics: Administration, Inhalation; Adult; Albuterol; Androstadienes; Bronchitis; Bronchodilator Agents; Cross-Over Studies; Double-Blind Method; Drug Therapy, Combination; Exercise Test; Fluticasone; Heart Rate; Humans; Hypoxia; Male; Oxygen Consumption; Sports

Inhaled corticosteroids (ICS) markedly reduce bronchial mucosal inflammation in asthma but whether they have an anti-inflammatory effect in airway tissue in chronic obstructive pulmonary disease (COPD) is unknown.. A study of endobronchial biopsy samples was conducted as part of a double blind, placebo controlled, randomised trial of parallel design. Patients had mild to moderately severe COPD (FEV(1) 25-80% of predicted) and were given 3 months treatment with ICS, fluticasone propionate (FP; 500 micro g twice daily, n=14) or placebo (n=10). Biopsy tissue taken at baseline and after treatment was examined by transmission electron microscopy to count the numbers of all ultrastructurally distinct inflammatory cells.. Compared with their baseline values, FP resulted in a significant decrease (on average 65%) in the numbers of mucosal mast cells (median 7.8 (range 1-33) v 2.8 (1-14), p<0.05). The reductive effect of FP held true when the post-treatment values of the placebo and FP groups were compared: 8.8 (1-24) v 2.8 (1-14) (p<0.05). Unexpectedly, there were significantly more neutrophils in the FP than in the placebo group: 4.0 (0-23) v 1.7 (0-8), respectively (p<0.05). There were no alterations to other cell types including mononuclear cells. Symptoms markedly improved in the patients treated with FP for 3 months.. Fluticasone propionate given for 3 months to patients with COPD has selective effects on the inflammatory cells in the bronchial mucosa: the reduction in mast cell numbers may account for the improvement in symptoms over this time.

Topics: Aged; Androstadienes; Biopsy; Bronchi; Bronchitis; Bronchodilator Agents; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Pulmonary Disease, Chronic Obstructive; Vital Capacity

There are few data in asthma relating airway physiology, inflammation and remodelling and the relative effects of inhaled corticosteroid (ICS) treatment on these parameters. A study of the relationships between spirometric indices, airway inflammation, airway remodelling, and bronchial hyperreactivity (BHR) before and after treatment with high dose inhaled fluticasone propionate (FP 750 microg bd) was performed in a group of patients with relatively mild but symptomatic asthma.. A double blind, randomised, placebo controlled, parallel group study of inhaled FP was performed in 35 asthmatic patients. Bronchoalveolar lavage (BAL) and airway biopsy studies were carried out at baseline and after 3 and 12 months of treatment. Twenty two normal healthy non-asthmatic subjects acted as controls.. BAL fluid eosinophils, mast cells, and epithelial cells were significantly higher in asthmatic patients than in controls at baseline (p<0.01). Subepithelial reticular basement membrane (rbm) thickness was variable, but overall was increased in asthmatic patients compared with controls (p<0.01). Multiple regression analysis explained 40% of the variability in BHR, 21% related to rbm thickness, 11% to BAL epithelial cells, and 8% to BAL eosinophils. The longitudinal data corroborated the cross sectional model. Forced expiratory volume in 1 second improved after 3 months of treatment with FP with no further improvement at 12 months. PD(20) improved throughout the study. BAL inflammatory cells decreased following 3 months of treatment with no further improvement at 12 months (p<0.05 v placebo). Rbm thickness decreased in the FP group, but only after 12 months of treatment (mean change -1.9, 95% CI -3 to -0.7 microm; p<0.01 v. baseline, p<0.05 v. placebo). A third of the improvement in BHR with FP was associated with early changes in inflammation, but the more progressive and larger improvement was associated with the later improvement in airway remodelling.. Physiology, airway inflammation and remodelling in asthma are interrelated and improve with ICS. Changes are not temporally concordant, with prolonged treatment necessary for maximal benefit in remodelling and PD(20). Determining the appropriate dose of inhaled steroids only by reference to symptoms and lung function, as specified in current international guidelines, and even against indices of inflammation may be over simplistic. The results of this study support the need for early and long term intervention with ICS, even in patients with relatively mild asthma.

Topics: Administration, Topical; Adult; Aged; Androstadienes; Anti-Inflammatory Agents; Asthma; Basement Membrane; Biopsy; Bronchial Hyperreactivity; Bronchitis; Bronchoalveolar Lavage Fluid; Bronchodilator Agents; Bronchoscopy; Collagen; Cross-Sectional Studies; Double-Blind Method; Fluticasone; Forced Expiratory Volume; Glucocorticoids; Humans; Longitudinal Studies; Mast Cells; Middle Aged; Observer Variation; Regression Analysis

Inhaled corticosteroids (ICS) are effective in the treatment of asthma and markedly reduce the numbers of inflammatory cells in bronchial biopsies. However, the effect of ICS on the inflammatory profile of biopsies in smokers with chronic obstructive pulmonary disease (COPD) is unknown. We have performed a double-blind, placebo-controlled, randomized study to compare fluticasone propionate (FP) 500 microg twice daily via a dry powder inhaler and placebo (P) over a 3-month period in subjects with COPD. Fiberoptic bronchoscopy and bronchial biopsy was carried out at baseline and after the 3 months of treatment. Thirty-one subjects completed the trial and 30 paired biopsies were available for analysis. Compared with P (n = 14), subjects on inhaled FP (n = 16) had no significant reductions in the primary endpoints: CD8+, CD68+ cells, or neutrophils, considered to be of importance in COPD. However, there was a reduction in the CD8:CD4 ratio in the epithelium and of the numbers of subepithelial mast cells in the FP group. CD4+ cells were significantly raised in the P group in both subepithelium and epithelium. Symptoms significantly improved, and there were significantly fewer exacerbations in subjects on FP, compared to subjects on P. The data indicate that inhaled fluticasone does affect selected aspects of airway inflammation in COPD, and this may explain, in part, the decrease in exacerbations seen in long-term studies with fluticasone propionate.

Topics: Administration, Inhalation; Adult; Aged; Androstadienes; Anti-Inflammatory Agents; Biopsy; Bronchitis; Double-Blind Method; Female; Fluticasone; Follow-Up Studies; Forced Expiratory Volume; Glucocorticoids; Humans; Immunohistochemistry; London; Lung; Male; Mast Cells; Middle Aged; Predictive Value of Tests; Pulmonary Disease, Chronic Obstructive; Respiratory Mucosa; Severity of Illness Index; Treatment Outcome

Systemic corticosteroids have been recommended as a therapeutic option in patients with moderate to severe COPD. In an early stage of the disease, i.e. chronic bronchitis with mild or no airflow obstruction, a trial with inhaled steroids could reveal potential benefits, particularly in terms of a modulation of airway inflammation. We therefore investigated the effect of inhaled fluticasone (1000 microg day(-1)) on markers of airway inflammation in 19 patients with chronic bronchitis (mean+/-SEM FEV1, 83.4+/-3.0% predicted; FEV1/VC, 67.5+/-2.4%) in a double-blind, cross-over, placebo-controlled manner. Visits were performed before and after two 4-week treatment periods. separated by a 4-week washout period. Lung function, the concentration of exhaled nitric oxide, differential cell counts in induced sputum and the number of cells positive for iNOS, as well as the levels of LDH, ECP, neutrophil elastase and IL-8 in sputum supernatants were determined. Although the total cell number decreased significantly after fluticasone (geometric mean 12.3 vs. 7.7 x 10(6)/ml; P<0.05) it was not significantly different from the change observed after placebo (14.2 vs. 10.6 x 10(6)/ml; n.s.). None of the other parameters showed statistically significant changes after fluticasone or placebo and the results did not depend on the presence of airway hyperresponsiveness. We conclude that in patients with chronic bronchitis short-term treatment with inhaled corticosterids did not improve lung function or inflammatory parameters to an extent which was statistically significant as compared to spontaneous variability.

Topics: Administration, Inhalation; Adult; Aged; Analysis of Variance; Androstadienes; Anti-Inflammatory Agents; Biomarkers; Breath Tests; Bronchitis; Cell Count; Chronic Disease; Cross-Over Studies; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Sputum; Time Factors; Treatment Failure; Vital Capacity

Acute exacerbations of chronic bronchitis are common and the presenting symptoms vary, although it is not clear how this should influence management. From a health care perspective, an understanding of the speed of symptom resolution is of importance to determine the success of treatment or when a change is indicated because of treatment failure.. The response of 63 patients treated at home for exacerbations of chronic bronchitis was assessed using a patient directed diary card incorporating sputum characteristics and symptoms. Treatment was given according to the nature of the sputum at presentation; patients with purulent sputum received an antibiotic for 5 or 10 days (randomised, double blind) whereas patients with mucoid sputum received high dose inhaled steroid or placebo for 14 days (randomised, double blind).. The mean (SE) total diary card score at presentation was significantly higher in the purulent group than in the mucoid group (19.7 (0.9) v 16.3 (0.9); mean difference -3.4 (95% CI -6.1 to -0.7), p<0.05). In the purulent group sputum colour and volume improved rapidly and in both groups the mean (SE) total diary card score had improved by the fifth day of treatment to 13.0 (0.7) in the purulent group (mean difference -6.6 (95% CI -8.8 to -4.4), p<0.001) and 14.6 (0.8) in the mucoid group (mean difference -1.7 (95% CI -4.0 to 0.8), p<0.05), which was no longer significantly different from the stable state. Diary card scores did not differ significantly between patients who received antibiotics for 5 or 10 days in the purulent group or between patients who received inhaled fluticasone or placebo in the mucoid group.. Exacerbations of chronic bronchitis associated with purulent sputum have significantly worse symptoms at presentation than those with mucoid sputum. In both groups these symptoms resolve rapidly so that by the fifth day of treatment they are no different from the stable state. No significant effect was found on symptom resolution of antibiotic duration (5 v 10 days) in the purulent group or of inhaled fluticasone in the mucoid group, which resolved without antibiotics. Larger numbers may be required to demonstrate a statistically (if not clinically) significant difference.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Analysis of Variance; Androstadienes; Anti-Inflammatory Agents; Bronchitis; Cefuroxime; Cephalosporins; Chronic Disease; Double-Blind Method; Female; Fluticasone; Humans; Male; Medical Records; Middle Aged; Statistics, Nonparametric; Time Factors; Treatment Outcome

In a double-blind, parallel-group study, we examined the effect of short-term treatment with inhaled fluticasone propionate (FP) in a group of 20 nonsmoking asthmatic patients who required only beta2-agonists to control their symptoms. We administered FP (250 microg twice daily) or matched placebo for 6 wk. Methacholine challenge was performed before treatment, after 3 wk, and at the end of treatment. Each patient underwent bronchoscopy with bronchoalveolar lavage (BAL) and bronchial biopsy before and after treatment. Eight patients in the placebo group and nine patients in the FP group completed the study. Bronchial responsiveness to methacholine decreased significantly only after 6 wk of treatment with FP (p < 0.05). When we compared the FP group with the placebo group, we observed a significant decrease only in the number of cells expressing intracellular adhesion molecule-1 (ICAM-1) and MAC-1 (p < 0.04 and p < 0.03, respectively). Moreover, we saw that the tryptase level in BAL decreased (p < 0.001), whereas the eosinophil cationic protein (ECP) level did not change significantly. Additionally, the number of eosinophils and mast cells in the lamina propria in bronchial biopsies specimens was significantly smaller in the FP group than in the placebo group (p < 0.02 and p < 0.01, respectively). Additionally, in the FP group, we found that basement-membrane thickness was significantly decreased when compared with that of the placebo group (p < 0.05). In conclusion, our results show that short-term treatment with low-dose FP reduces inflammatory cell infiltration into the lamina propria in bronchial biopsy specimens. Moreover, short-term low-dose FP treatment might control the intensity of airway remodeling in mild asthma.

Topics: Administration, Inhalation; Adolescent; Adult; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Bronchi; Bronchitis; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluticasone; Humans; Lung; Male; Methacholine Chloride; Middle Aged; Placebos; Time Factors

The effects of fluticasone propionate (FP) on sputum chemotactic activity, elastase inhibitory potential, albumin concentrations, and peripheral neutrophil function were studied in a group of patients with clinically stable, smoking-related chronic bronchitis and emphysema. Seventeen patients (50 to 75 yr of age) were entered into a double-blind, placebo-controlled study of 1.5 mg inhaled FP/d for 8 wk. Following treatment with FP the chemotactic activity of the sputum sol phase was lower than the corresponding values for the placebo group (p < 0.01). Values fell from a mean of 21.75 (+/- 1.58) during the run-in period to 18.37 (+/- 1.46; p < 0.01) after 4 wk and 17.63 (+/- 1.86; p < 0.05) after 8 wk treatment returning to 22.08 (+/- 1.26) cell/field after the washout period. The neutrophil elastase inhibitory capacity of the sputum sol phase increased (p < 0.025) with treatment from a mean of 0.177 microM elastase inhibited/L (+/- 0.05) pretreatment to 0.413 microM (+/- 0.054) after 4 wk and 0.415 microM (+/- 0.054) after 8 wk returning to 0.270 microM (+/- 0.07) after the washout period. Treatment with FP did not result in a change in the peripheral neutrophil functions studied or sputum albumin and myeloperoxidase concentrations. The results suggest that FP may play a protective role in these patients through a reduction in the chemotactic activity of lung secretions and potentially a reduction in the recruitment of neutrophils to the lung, and also by directly affecting the proteinase/antiproteinase balance, in favor of antiproteinases, within lung secretions.

Topics: Administration, Inhalation; Aged; Albumins; Androstadienes; Bronchitis; Chemotaxis, Leukocyte; Chronic Disease; Double-Blind Method; Female; Fibronectins; Fluticasone; Glucocorticoids; Humans; Leukocyte Elastase; Male; Middle Aged; Neutrophils; Pancreatic Elastase; Peroxidase; Pulmonary Emphysema; Sputum; Superoxides

Topics: Administration, Inhalation; Administration, Intravenous; Administration, Oral; Adult; Aftercare; Anti-Inflammatory Agents; Benzyl Alcohols; Bronchitis; Bronchoscopy; Chlorobenzenes; Dermatitis, Allergic Contact; Emergency Service, Hospital; Fluticasone; Humans; Hydrocortisone; Inhalation Exposure; Male; Prednisolone; Tear Gases; Tracheitis; Treatment Outcome

A 52-year-old man with well-controlled HIV infection taking ritonavir and increasing doses of inhaled fluticasone for chronic bronchitis developed thrush. Within days of discontinuing fluticasone and initiating fluconazole, he presented with fatigue, malaise, lower-extremity oedema and orthostasis. Testing confirmed exogenous Cushing's syndrome and secondary adrenal insufficiency. Although ritonavir-fluticasone interactions have been previously reported as a cause for adrenal insufficiency, we propose that fluconazole increased the rapidity of onset and severity of symptoms through synergistic inhibition of the adrenal axis.

Topics: Adrenal Insufficiency; Androstadienes; Anti-HIV Agents; Anti-Inflammatory Agents; Bronchitis; Drug Interactions; Fluconazole; Fluticasone; HIV Infections; Humans; Male; Middle Aged; Ritonavir

A 56-year-old woman was referred to our hospital because of dyspnea, wheezing, and a productive cough. Eight years before presentation, bronchial asthma was diagnosed and the patient received inhaled corticosteroids plus antiasthmatic agents (a long-acting inhaled beta2-agonist, leukotriene modifiers, and theophylline). Chest radiography showed small diffuse nodular shadows, and a computed tomographic scan showed thickening of the bronchi and bronchioles, with diffuse centrilobular nodules in both lung fields. A blood test and microscopic examination of the bronchoalveolar fluid revealed marked eosinophilia. Transbronchial lung biopsy and transbronchial biopsy showed eosinophilic bronchitis and bronchiolitis. After treatment with oral prednisolone (40 mg daily) and inhaled corticosteroids, the symptoms, blood eosinophilia, and radiographic findings improved. Recently, several similar cases of eosinophilic bronchiolitis have been reported. Studies of further cases and elucidation of the pathophysiology of eosinophilic bronchiolitis are necessary to establish a concept for this disease and to determine whether it should be classified as a subtype of bronchial asthma or as a distinct entity.

Topics: Androstadienes; Asthma; Bronchiolitis; Bronchitis; Bronchoalveolar Lavage Fluid; Bronchoscopy; Cough; Diagnosis, Differential; Dyspnea; Eosinophilia; Female; Fluticasone; Hematologic Tests; Humans; Middle Aged; Prednisolone; Radiography, Thoracic; Respiratory Function Tests; Respiratory Sounds

To compare risk of hospitalization or emergency department (ED) visit and healthcare costs in patients with chronic bronchitis initiating inhaled maintenance therapy with fluticasone propionate/salmeterol 250/50 mcg combination (FSC) versus other inhaled maintenance therapies.. This retrospective cohort study assessed 9,217 patients from the PharMetrics administrative claims database enrolled from July 1997 to January 2005. Study subjects were persons with medical claims with diagnoses of chronic bronchitis (ICD-9-CM 491.xx) who also had pharmacy claims for FSC, salmeterol (SAL), inhaled corticosteroid (ICS), ipratropium (IPR), or ipratropium/albuterol combination (IAC). Persons with <12 months of continuous eligibility after the first prescription for initial maintenance therapy ("index date") were excluded as were those receiving fluticasone propionate/salmeterol 100/50 mcg or 500/50 mcg (not indicated for patients with chronic bronchitis). For remaining persons, time to first hospitalization or ED visit during follow-up was compared for those receiving FSC versus other therapies using Cox proportional hazards regression. Healthcare costs during the first 12 months of follow-up were analyzed using generalized linear model regression.. Receipt of FSC as initial inhaled maintenance therapy for chronic bronchitis (n = 1361) was associated with 41% lower risk of COPD-related hospitalization or ED visit compared with IPR (n < 1316) (p < 0.001). Adjusted costs of COPD-related hospitalization/ED visit were $507 (95% CI $218-$1083) less with FSC than IPR. However, patients receiving FSC had $261 (95% CI $205-$322) higher COPD-related pharmacy costs than those receiving IPR. Total COPD-related costs were $90 lower with FSC than IPR although this difference was not significant (95% CI $330-$443). Compliance, as measured by medication possession ratio, was 12% greater with FSC compared with IPR (p < 0.05). Comparisons of FSC with IAC yielded generally similar results. The limitations of the study are similar to those of other observational studies of secondary data regarding potential misclassification and omitted variable bias and residual confounding.. In persons with chronic bronchitis, initial maintenance therapy with FSC 250/50 mcg was associated with improved outcomes versus ipratropium-based therapy and although FSC was associated with greater pharmacy costs, it did not significantly increase total costs of COPD-related care.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Aged; Albuterol; Androstadienes; Bronchitis; Bronchodilator Agents; Chronic Disease; Cohort Studies; Drug Therapy, Combination; Female; Fluticasone; Health Care Costs; Health Services; Humans; Ipratropium; Male; Middle Aged; Salmeterol Xinafoate; Treatment Outcome

Current guidelines generally recommend a combination of inhaled corticosteroids and a Beta2-agonist for persistent asthma. The adjustment of anti-inflammatory therapy in persistent asthma is advised to be guided mainly by the presence of symptoms.. To investigate whether clinically masked increases in bronchial inflammation occur in guideline-treated, persistent asthma following allergen exposure.. After a 4-week steroid-run-in period (fluticasone 250 microg twice daily) 48 allergic patients with persistent asthma underwent a bronchial challenge with a single dose of allergen, after inhalation of salbutamol (400 microg, nebulized dose). FEV1 and sputum markers of bronchial inflammation were measured before and after allergen challenge. Furthermore, additional rescue-salbutamol usage was recorded following allergen challenge.. After allergen challenge there was a significant increase in sputum eosinophil numbers (geometric mean number x 10(4)/g [95% CI]: 0.5 [0.3; 1.0] before, and 2.4 [1.3; 4.2] after challenge, p=0.01). The mean change in FEV1 between 4 and 8h after challenge relative to baseline was -0.04% [95% CI-2.3; 2.2], p>0.9. None of the patients took additional rescue salbutamol over 8 h after allergen challenge.. Clinically masked increases in bronchial inflammation occur in guideline-treated, persistent asthma following allergen exposure. This finding underscores the need for additional guides for the adjustment of anti-inflammatory therapy in persistent asthma.

Topics: Adolescent; Adult; Albuterol; Allergens; Androstadienes; Asthma; Bronchitis; Bronchodilator Agents; Dermatophagoides pteronyssinus; Dose-Response Relationship, Drug; Eosinophils; Female; Fluticasone; Forced Expiratory Volume; Guidelines as Topic; Humans; Male; Middle Aged; Prospective Studies; Radioallergosorbent Test; Respiratory Function Tests

Topics: Androstadienes; Anti-Inflammatory Agents; Bronchitis; Colitis, Ulcerative; Fluticasone; Humans; Male; Middle Aged; Prednisone; Respiratory Sounds; Tracheitis

To determine the value of inhaled corticosteroids in the management of chronic inflammatory airway disease in dogs.. Medical records of dogs that were presented for the investigation of respiratory disease were reviewed retrospectively. Criteria for inclusion were knowledge of previous medical treatment including side effects, diagnosis of the underlying disease, use of inhaled corticosteroids and at least two-months follow-up data.. Thirteen dogs that fulfilled the criteria were identified. Ten dogs were diagnosed with chronic bronchitis and three with eosinophilic bronchopneumopathy. Four dogs had not previously received corticosteroid treatment for their respiratory disease, and all these showed a reduction or a resolution of clinical signs without obvious side effects after inhaled corticosteroid therapy. Nine dogs had previously received oral or parenteral corticosteroids for treatment of their respiratory disease, and all had exhibited side effects. Five of these dogs were treated with inhaled corticosteroids alone, and all exhibited an improvement in clinical signs without observable side effects. The remaining four dogs were treated with a combination of inhaled and oral corticosteroids, and all showed improvement in clinical signs and reduction in side effects. Inhaled medication was well tolerated in all dogs.. Inhaled corticosteroids were used for the management of chronic bronchitis and eosinophilic bronchopneumopathy in 13 dogs, and these may have the advantage of reducing side effects associated with oral corticosteroids.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Androstadienes; Animals; Anti-Inflammatory Agents; Beclomethasone; Bronchitis; Bronchopneumonia; Chronic Disease; Dog Diseases; Dogs; Female; Fluticasone; Male; Pulmonary Eosinophilia; Respiratory Tract Diseases; Retrospective Studies; Treatment Outcome

Topics: Androstadienes; Anti-Inflammatory Agents; Bronchitis; Cough; Eosinophilia; Female; Fluticasone; Humans; Male; Prognosis; Treatment Outcome

We report a case of tracheo-bronchitis in Crohn's disease. A 23-year-old Japanese woman who had been diagnosed with Crohn's disease three years previously was hospitalized. She had been suffering from dry cough for one month. Computed tomography of the chest revealed marked thickening of the tracheal wall. Bronchoscopy showed erythematous and edematous mucosa with diffuse whitish granular lesions in the trachea and bronchi. The bronchial biopsy specimens showed non-specific inflammatory infiltrates consisting of lymphocytes and plasma cells, and hyperplasia of bronchial glands. Inhaled corticotherapy, fluticasone propionate 800 microg/day, was effective for both the inflammatory mucosa and thickened tracheal wall.

Topics: Administration, Inhalation; Adult; Androstadienes; Anti-Inflammatory Agents; Bronchitis; Bronchoscopy; Crohn Disease; Female; Fluticasone; Humans; Tomography, X-Ray Computed; Tracheitis

We studied 223 outpatients who presented between October 2001 and June 2003 with persistent cough of more than 3 weeks' duration. Eosinophilic airway disorders (EAD), including atopic cough and cough variant asthma, were clinically diagnosed in 119 patients, on the basis of the following factors: history of atopic disease, duration of cough, history of previous prolonged cough, or presence of forced expiration wheeze. Since eosinophils are frequently found in the sputum of patients with EAD, a positive test strongly suggests the presence of EAD. In this study, the test was positive in 86% of the patients with EAD. The patients with clinically diagnosed EAD, including those with no eosinophils in the sputum, were treated with inhaled fluticasone 400 or 800 microg/day. Fluticasone was effective in 97% of the patients with EAD and was more effective than bronchodilators or antiallergic drugs. When we compared the results of fluticasone 400 microg/day with those of 800 microg/day doses, the cough disappeared within 1 week in 28% of the patients who received 400 microg/day, whereas in 76% with 800 microg/day. Among the patients with diagnosed EAD, bronchial asthma developed in 6 patients during the observation period. Most of these patients had forced expiration wheeze and lower FEV 1 at the initial visit. This study showed that EAD could be diagnosed in the early stage on the basis of thorough history-taking, the presence of forced expiration wheeze and detection of eosinophils in the sputum. It is important to diagnose and treat EAD as early as possible since inhaled steroid is highly effective.

Topics: Administration, Inhalation; Adult; Androstadienes; Anti-Inflammatory Agents; Asthma; Bronchitis; Cough; Eosinophilia; Female; Fluticasone; Gastroesophageal Reflux; Humans; Male; Retrospective Studies

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

This study aimed at documenting airway inflammation and subepithelial collagen deposition in patients using only inhaled beta(2)-agonists with either recently diagnosed asthma (RDA: /= 13 yr, n = 16) and at the influence of an intense inhaled corticosteroid (ICS) treatment on these parameters, in relation to changes in airway responsiveness. Patients had a methacholine inhalation test and a bronchoscopy with bronchial biopsies before and after an 8-wk treatment with inhaled fluticasone propionate (FP), 1,000 microgram/day. Baseline FEV(1) (mean +/- SEM) was normal and similar in both groups (RDA: 98.1 +/- 2.7, LSA: 94.5 +/- 4.6%). Geometric mean methacholine PC(20) was lower in LSA than in RDA (0.44 versus 3.37 mg/ml) at baseline and improved similarly by 1.85 and 1.86 double concentrations with FP treatment. PC(20) normalized (>/= 16 mg/ml) in five patients with RDA and two patients with LSA. Baseline mean bronchial cell counts (per mm(2) connective tissue surface) for CD3(+), CD4(+), CD8(+), CD25(+), EG1(+), CD45ro(+), and AA1(+) cells were similar in both groups. With FP, EG1(+) (p < 0.001), EG2(+) (p = 0.018), and AA1(+) counts (p = 0.009) decreased significantly in both groups while CD45ro(+) (p = 0.02) counts decreased only in LSA. Baseline type 1 and type 3 collagen deposition underneath the basement membrane was similar in RDA and LSA and did not change significantly after FP. This study shows that recent compared to long-standing mild asthma is associated with a similar degree of airway inflammation and subepithelial fibrosis, and a similar improvement in airway hyperresponsiveness after 8 wk on high-dose ICS. It also indicates that once asthma becomes symptomatic, airway responsiveness cannot normalize in most subjects over such a time period, even with a high dose of ICS.

Topics: Administration, Inhalation; Adolescent; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Basement Membrane; Biopsy; Bronchi; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchitis; Bronchoscopy; Collagen; Epithelium; Female; Fluticasone; Forced Expiratory Volume; Humans; Immunoenzyme Techniques; Male

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

Airway inflammation is important in the development and progression of many lung diseases, including bronchiectasis. Activation of inflammatory cells such as neutrophils, eosinophils, and macrophages induces a respiratory burst resulting in the production of reactive oxygen species such as hydrogen peroxide (H2O2). We have measured exhaled H2O2 in patients with documented bronchiectasis and investigated whether the concentration of H2O2 is related to the disease severity, as defined by lung function. We also investigated whether the concentrations of expired H2O2 were different in bronchiectatic patients who received inhaled corticosteroids compared with steroid-naïve patients. In 37 patients with bronchiectasis (mean age, 45 +/- 2.5 yr; FEV1, 59 +/- 3% pred), mean H2O2 concentration in exhaled breath condensate was significantly elevated as compared with the values in 25 age-matched (mean age, 42 +/- 2 yr) normal subjects (0.87 +/- 0.01 versus 0.26 +/- 0.04 microM, p < 0.001). There was a significant negative correlation between H2O2 and FEV1 (r = -0.76, p < 0.0001). Patients treated with inhaled corticosteroids had values of H2O2 similar to those of steroid-naïve patients (0.8 +/- 0.1 versus 0.9 +/- 0.1, p > 0.05). We conclude that H2O2 is elevated in exhaled air condensate of patients with bronchiectasis and is correlated with disease severity. Measurement of H2O2 may be used as a simple noninvasive method to monitor airway inflammation and oxidative stress.

Topics: Administration, Inhalation; Administration, Topical; Adult; Androstadienes; Anti-Inflammatory Agents; Bronchiectasis; Bronchitis; Case-Control Studies; Disease Progression; Eosinophils; Female; Fluticasone; Forced Expiratory Volume; Glucocorticoids; Humans; Hydrogen Peroxide; Lung; Macrophages, Alveolar; Male; Middle Aged; Neutrophils; Oxidative Stress; Reactive Oxygen Species; Respiration; Respiratory Burst

The purpose of the study is to investigate the relationship between inhaled or intranasal adrenergic agonists and corticosteroids and the development of central serous chorioretinopathy (CSC).. The medical records of three patients with CSC who were found to use inhaled adrenergic agents or corticosteroids or both were identified prospectively. A survey of members of the Retina, Macula, and Vitreous societies and the National Registry of Drug-Induced Ocular Side Effects identified three additional cases.. Six patients with CSC were found to be chronic users of corticosteroid (four patients) or both beta adrenergic agonist and corticosteroid (two patients) metered dose inhalers or nasal sprays. In three cases, there was a close temporal correlation between the use of a corticosteroid nasal spray and the development of CSC.. These findings suggest that, in patients who are susceptible, the periocular or systemic absorption of inhaled corticosteroids may be sufficient to produce CSC in humans, supporting previous hypotheses regarding the pathogenesis of the disorder. Further studies are needed to confirm this association and to determine whether inhaled adrenergic agents also contribute to the development of this disorder. Patients in whom CSC develops while using corticosteroid inhalers or nasal sprays should be alerted to the possible relationship between CSC and these agents.

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Adult; Albuterol; Androstadienes; Asthma; Beclomethasone; Bronchitis; Choroid Diseases; Exudates and Transudates; Female; Fluorescein Angiography; Fluticasone; Fundus Oculi; Glucocorticoids; Humans; Male; Middle Aged; Pigment Epithelium of Eye; Prospective Studies; Retinal Detachment; Retinal Diseases; Rhinitis; Risk Factors; Triamcinolone Acetonide; Visual Acuity