fluticasone and Bronchiectasis

Bronchiectasis is being increasingly diagnosed and recognised as an important contributor to chronic lung disease in both adults and children in high- and low-income countries. It is characterised by irreversible dilatation of airways and is generally associated with airway inflammation and chronic bacterial infection. Medical management largely aims to reduce morbidity by controlling the symptoms, reduce exacerbation frequency, improve quality of life and prevent the progression of bronchiectasis. This is an update of a review first published in 2000.. To evaluate the efficacy and safety of inhaled corticosteroids (ICS) in children and adults with stable state bronchiectasis, specifically to assess whether the use of ICS: (1) reduces the severity and frequency of acute respiratory exacerbations; or (2) affects long-term pulmonary function decline.. We searched the Cochrane Register of Controlled Trials (CENTRAL), the Cochrane Airways Group Register of trials, MEDLINE and Embase databases. We ran the latest literature search in June 2017.. All randomised controlled trials (RCTs) comparing ICS with a placebo or no medication. We included children and adults with clinical or radiographic evidence of bronchiectasis, but excluded people with cystic fibrosis.. We reviewed search results against predetermined criteria for inclusion. In this update, two independent review authors assessed methodological quality and risk of bias in trials using established criteria and extracted data using standard pro forma. We analysed treatment as 'treatment received' and performed sensitivity analyses.. The review included seven studies, involving 380 adults. Of the 380 randomised participants, 348 completed the studies.Due to differences in outcomes reported among the seven studies, we could only perform limited meta-analysis for both the short-term ICS use (6 months or less) and the longer-term ICS use (> 6 months).During stable state in the short-term group (ICS for 6 months or less), based on the two studies from which data could be included, there were no significant differences from baseline values in the forced expiratory volume in the first second (FEV. This updated review indicates that there is insufficient evidence to support the routine use of ICS in adults with stable state bronchiectasis. Further, we cannot draw any conclusion for the use of ICS in adults during an acute exacerbation or in children (for any state), as there were no studies.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Androstadienes; Anti-Bacterial Agents; Beclomethasone; Bronchiectasis; Disease Progression; Fluticasone; Forced Expiratory Volume; Humans; Randomized Controlled Trials as Topic; Respiratory Function Tests; Vital Capacity

Bronchiectasis is increasingly recognized as a major cause of respiratory morbidity especially in developing countries and in some ethnic populations of affluent countries. It is characterized by irreversible dilatation of airways, generally associated with chronic bacterial infection. Medical management largely aims to reduce morbidity by controlling the symptoms and by preventing the progression of bronchiectasis.. To evaluate the efficacy of inhaled corticosteroids (ICS) in children and adults with bronchiectasis (a) during stable bronchiectasis; and for reducing; (b) the severity and frequency of acute respiratory exacerbations and (c) long term pulmonary decline.. The Cochrane Register of Controlled Trials (CENTRAL), the Cochrane Airways Group Specialized Register Collaboration and Cochrane Airways Group, MEDLINE and EMBASE databases were searched by the Cochrane Airways Group. The latest searches were performed in September 2007.. All randomised controlled trials comparing ICS with a placebo or no medication. Children and adults with clinical or radiographic evidence of bronchiectasis were included, but patients with cystic fibrosis (CF) were excluded.. Results of searches were reviewed against pre-determined criteria for inclusion.. There were no paediatric studies. Six adult studies fulfilled the inclusion criteria. Of the 303 randomised, 278 subjects completed the trials. In the short term group (ICS for less then 6 months duration), adults on huge doses of ICS (2g per day of budesonide equivalent) had significantly improved forced expiratory volume in the first second (FEV(1)), forced vital capacity (FVC), Quality of life (QOL) score and sputum volume but no significant difference in peak flow, exacerbations, cough or wheeze, when compared to adults in the control arm (no ICS). When only placebo-controlled studies were included, there were no significant difference between groups in all outcomes examined (spirometry, clinical outcomes of exacerbation or sputum volume etc). The single study on long term outcomes showed no significant effect of inhaled steroids in any of the outcomes.. The present review indicates that there is insufficient evidence to recommend the routine use of inhaled steroids in adults with stable state bronchiectasis. While a therapeutic trial may be justified in adults with difficult to control symptoms and in certain subgroups, this has to be balanced with adverse events especially if high doses are used. No recommendation can be made for the use of ICS in adults during an acute exacerbation or in children (for any state) as there were no studies.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Androstadienes; Anti-Bacterial Agents; Beclomethasone; Bronchiectasis; Fluticasone; Humans; Randomized Controlled Trials as Topic; Respiratory Function Tests

The effects of inhaled steroids upon the quality of life of patients with bronchiectasis remain unknown.. To analyze the effect of inhaled fluticasone propionate (FP) for 6 months upon the clinical, functional, microbiological and outcome parameters of patients with steady-state bronchiectasis not due to cystic fibrosis, and its repercussions for patient health-related quality of life (HRQoL).. Prospective, randomized, double-blind (for effective doses) study.. The diagnosis of bronchiectasis was made by high-resolution computed tomography. Ninety-three patients (mean age: 68.5 [8.4]) were randomized to receive 250 microg bid, 500 microg bid or no treatment with inhaled FP for 6 months. Data were collected at baseline and at 1, 3 and 6 months after the start of treatment. HRQoL was assessed using the validated Spanish version of the St. George's Respiratory Questionnaire.. The group administered FP 1000 microg daily showed significant improvement in dyspnea (1.03 [2.1]-1.24 [2.2] points; P = 0.01-0.04), sputum production (P = 0.001), days without cough (P = 0.02) and short-acting beta-2 agonists used (P = 0.01) from the first month of treatment, with no changes in pulmonary function, number or severity of exacerbations, or microbiological profile of the sputum. As a result, an improvement in HRQoL was seen in this group after 3 months of treatment (45.4 [14.2] vs. 40.5 [13.9]; P = 0.01).. Inhalatory FP 500 microg bid is effective from the first month of treatment for controlling the symptoms of patients with steady-state bronchiectasis-thus ensuring a significant improvement in HRQoL.

Topics: Administration, Inhalation; Aged; Androstadienes; Bronchiectasis; Bronchodilator Agents; Cough; Double-Blind Method; Dyspnea; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Prospective Studies; Quality of Life; Respiratory Sounds; Vital Capacity

The clinical efficacy of inhaled corticosteroid (ICS) treatment has not been evaluated in bronchiectasis, despite the presence of chronic airway inflammation.. After three consecutive weekly visits, 86 patients were randomised to receive either fluticasone 500 mug twice daily (n = 43, 23F, mean (SD) age 57.7 (14.4) years) or matched placebo (n = 43, 34F, 59.2 (14.2) years) and reviewed regularly for 52 weeks in a double blind fashion.. 35 and 38 patients in the fluticasone and placebo groups completed the study. Significantly more patients on ICS than on placebo showed improvement in 24 hour sputum volume (OR 2.5, 95% CI 1.1 to 6.0, p = 0.03) but not in exacerbation frequency, forced expiratory volume in 1 second, forced vital capacity, or sputum purulence score. Significantly more patients with Pseudomonas aeruginosa infection receiving fluticasone showed improvement in 24 hour sputum volume (OR 13.5, 95% CI 1.8 to 100.2, p = 0.03) and exacerbation frequency (OR 13.3, 95% CI 1.8 to 100.2, p = 0.01) than those given placebo. Logistic regression models revealed a significantly better response in sputum volume with fluticasone treatment than with placebo among subgroups of patients with 24 hour sputum volume <30 ml (p = 0.04), exacerbation frequency 5 (p = 0.03).. ICS treatment is beneficial to patients with bronchiectasis, particularly those with P. aerurginosa infection.

Topics: Administration, Inhalation; Androstadienes; Bronchiectasis; Bronchodilator Agents; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Sputum; Treatment Outcome; Vital Capacity

While exhaled nitric oxide (eNO) levels are reduced by inhaled corticosteroid therapy in asthma, such treatment effect is unclear in bronchiectasis.. Stable non-smoking bronchiectasis patients were randomised to receive either fluticasone (1 mg/daily) or identical placebo via the Accuhaler device.. Sixty non-smoking patients (38 women; mean age 56.4 +/- 12.7 years) were recruited. Of these, half received inhaled fluticasone and half placebo therapy. eNO was measured using a chemiluminescence analyser at 0, 4, 12, 24, 36 and 52 weeks. There was no significant difference in eNO levels between fluticasone and placebo patients over the study period. There was no correlation between baseline eNO with age, FEV1, FVC, 24 h sputum volume or number of bronchiectatic segments. Patients with Pseudomonas aeruginosa (PA) infection, but not their counterparts, displayed a correlation between 0- and 52-week eNO levels. PA infection was associated with significantly lower eNO levels among the patients.. Inhaled fluticasone therapy, despite being an effective anti-inflammatory agent, has no significant effect on eNO production, either at individual time points or over the entire 52-week profile, in bronchiectasis. It appears that eNO might not reflect the extent of airway inflammation in bronchiectasis.

Topics: Administration, Inhalation; Adult; Aged; Androstadienes; Anti-Inflammatory Agents; Breath Tests; Bronchiectasis; Double-Blind Method; Drug Administration Schedule; Exhalation; Female; Fluticasone; Humans; Longitudinal Studies; Male; Middle Aged; Nitric Oxide

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

Although corticosteroid therapy might be clinically beneficial for bronchiectasis, very little is known of its effects on the inflammatory and infective markers in bronchiectasis. We have therefore performed a double-blind, placebo-controlled study to evaluate the effects of a 4-wk administration of inhaled fluticasone in bronchiectasis. Twenty-four patients (12 female; mean age 51 yr) were randomized into receiving either inhaled fluticasone (500 microgram twice daily) via the Accuhaler device (n = 12) or placebo. At each visit, spirometry, 24-h sputum volume, sputum leukocyte density, bacterial densities, and concentrations of interleukin (IL)-1beta, IL-8, tumor necrosis factor-alpha (TNF-alpha), and leukotriene B4 (LTB4) were determined. There was a significant (p < 0.05) decrease in sputum leukocyte density and IL-1beta, IL-8, and LTB4 after fluticasone treatment. The fluticasone group had one and the placebo group three episodes of exacerbation. There were no significant changes in spirometry (p > 0.05) or any reported adverse reactions in either group. The results of this study show that high-dose fluticasone is effective in reducing the sputum inflammatory indices in bronchiectasis. Large-scale and long-term studies are indicated to evaluate the effects of inhaled steroid therapy on the inflammatory components in bronchiectasis.

Topics: Administration, Inhalation; Administration, Topical; Adult; Androstadienes; Anti-Inflammatory Agents; Bronchiectasis; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Glucocorticoids; Humans; Inflammation; Interleukin-1; Interleukin-8; Leukocyte Count; Leukotriene B4; Male; Middle Aged; Nebulizers and Vaporizers; Peak Expiratory Flow Rate; Placebos; Pseudomonas aeruginosa; Sputum; Tumor Necrosis Factor-alpha; Vital Capacity

Few studies have reported the association between the radiographic characteristics and the development of pneumonia in patients with chronic obstructive pulmonary disease (COPD) treated with inhaled corticosteroids (ICSs). Our study aimed to assess the effect of radiographic phenotypes on the risk of pneumonia in patients treated with ICSs.. This study retrospectively analysed all patients with COPD treated with ICSs in a subset of the Korea Chronic Obstructive Pulmonary Disorders Subgroup Study registry between January 2017 and December 2019. The association between radiographic phenotypes including the presence and severity of emphysema, airway wall thickening, or bronchiectasis on chest computed tomography were determined visually/qualitatively and the risk of pneumonia was analyzed using the Cox regression model.. Among the 90 patients with COPD treated with ICSs, 41 experienced pneumonia more than once during the median follow-up of 29 (interquartile range, 8-35) months. In univariate Cox regression analysis, older age, longer use of ICSs, use of fluticasone propionate or metered dose inhaler, and severe exacerbation events increased the risk of pneumonia. In multivariate analysis, the presence of emphysema (adjusted hazard ratio [aHR]=3.73, P=0.033), severity measured using the visual sum score (mild-to-moderate, aHR=8.58, P=0.016; severe, aHR=3.58, P=0.042), Goddard sum score (mild-to-moderate, aHR=3.31, P=0.058; severe, aHR=5.38, P=0.014), and the upper lobe distribution of emphysema (aHR=3.76, P=0.032) were associated with a higher risk of pneumonia. Subtypes of centrilobular and panlobular emphysema had a higher risk of pneumonia compared with paraseptal emphysema (aHR=3.98, P=0.033; HR=3.91, P=0.041 vs HR=2.74, P=0.304). The presence of bronchiectasis (aHR=2.41, P=0.02) and emphysema/bronchiectasis overlap phenotype (aHR=2.19, P=0.053) on chest CT was a risk factor for pneumonia in this population. However, severity of bronchiectasis and the presence or severity of bronchial wall thickening according to the visual sum score were not associated with the risk of pneumonia.. Among patients with COPD treated with ICSs, radiographic phenotypes including the presence of emphysema, bronchiectasis or emphysema/bronchiectasis overlap phenotype, severity with emphysema, subtypes of centrilobular or panlobular emphysema, and upper lobe distribution of emphysema may help predict the risk of pneumonia.

Topics: Adrenal Cortex Hormones; Bronchiectasis; Emphysema; Fluticasone; Humans; Phenotype; Pneumonia; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Retrospective Studies

Topics: Administration, Inhalation; Androstadienes; Bronchiectasis; Eosinophils; Fluticasone; Humans

Topics: Androstadienes; Bronchiectasis; Bronchodilator Agents; Eosinophils; Fluticasone; Humans

Topics: Bronchiectasis; Bronchodilator Agents; Budesonide; Eosinophils; Fluticasone; Humans

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

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

Increased concentrations of exhaled nitric oxide (NO) have been detected in inflammatory lung diseases including asthma and have been attributed to increased expression and activity of inducible nitric oxide synthase (iNOS) within the airways. However, previous studies of exhaled NO in patients with bronchiectasis have yielded conflicting results, with reports of both increased and normal NO values. Recent evidence from animal models suggests that chronic airway infection reduces NO production within the lung, despite causing increased iNOS expression. We tested the hypothesis that, in human subjects with bronchiectasis, chronic airway infection reduces NO output from the conducting airways.. Using a recently described two-compartment model, we measured separately the contributions of the conducting airways and the alveoli to exhaled NO in nine patients with stable bronchiectasis and eight control subjects before and after inhaled glucocorticoid therapy.. We found that airway NO output was significantly lower in bronchiectasis than in normal airways whereas NO output from the alveoli was similar to that of control subjects. High-dose inhaled glucocorticoid therapy did not alter airway or alveolar NO production.. These findings demonstrate that, in patients with bronchiectasis, airway NO output is reduced and that iNOS does not contribute significantly to airway NO production.

Topics: Adult; Androstadienes; Breath Tests; Bronchiectasis; Bronchodilator Agents; Female; Fluticasone; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Middle Aged; Nitric Oxide; Nitric Oxide Synthase Type II; Pulmonary Alveoli; Vital Capacity

Topics: Administration, Inhalation; Androstadienes; Anti-Allergic Agents; Antifungal Agents; Aspergillosis, Allergic Bronchopulmonary; Asthma; Bronchiectasis; Cushing Syndrome; Drug Interactions; Fluticasone; Humans; Hydrocortisone; Itraconazole; Male; Middle Aged

To determine the concentration of exhaled H(2)O(2) in patients with bronchiectasis, and to study the relationship between levels of exhaled H(2)O(2), extent of disease, symptoms score, spirometry, and cellular composition obtained from induced sputum; furthermore, to account for possible confounding effects of inhaled corticosteroids (ICS) usage, long-term oral antibiotic treatment, and chronic colonization with Pseudomonas aeruginosa.. Cross-sectional study.. Thirty patients with steady-state bronchiectasis.. Mean (95% confidence interval [CI]) exhaled H(2)O(2) levels were significantly elevated in patients with bronchiectasis compared to normal subjects: 1.1 (0.87 to 1.29) microM vs 0.3 (0.19 to 0.36) microM, respectively (p < 0.0001). Patients treated with ICS had similar values as steroid-naïve patients. The group of patients with P aeruginosa colonization showed a significantly increased concentration of H(2)O(2) compared to the group without P aeruginosa colonization. Patients receiving long-term oral antibiotic treatment had significantly higher values of H(2)O(2) compared to those not receiving antibiotics. There was a significant positive correlation between H(2)O(2) and either the percentage of neutrophils in induced sputum or the extent of the disease as defined by high-resolution CT. A significant negative correlation was found between H(2)O(2) and FEV(1) percent predicted. Finally, there was a significant positive correlation between H(2)O(2) and the symptoms score.. Patients with bronchiectasis in stable condition showed increased levels of exhaled H(2)O(2). The above-mentioned levels were not decreased either by ICS or long-term oral antibiotic treatment, but were significantly affected by chronic colonization with P aeruginosa. H(2)O(2) levels could be an indirect index of neutrophilic inflammation, impairment of lung function, and extension and severity of the disease.

Topics: Administration, Inhalation; Administration, Oral; Adrenal Cortex Hormones; Adult; Androstadienes; Anti-Bacterial Agents; Breath Tests; Bronchiectasis; Budesonide; Confidence Intervals; Female; Fluticasone; Forced Expiratory Volume; Humans; Hydrogen Peroxide; Leukocyte Count; Long-Term Care; Male; Middle Aged; Pneumonia, Bacterial; Pseudomonas aeruginosa; Pseudomonas Infections; Risk Factors; Spirometry; Sputum; Vital Capacity

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

Bronchiectasis is a chronic inflammatory lung disease associated with increased production of oxidants due mostly to neutrophilic inflammation. Induction of heme oxygenase (HO-1) by reactive oxygen species is a general cytoprotective mechanism against oxidative stress. HO-1 catabolises heme to bilirubin, free iron and carbon monoxide (CO). Exhaled CO measurements may therefore reflect an oxidative stress and be clinically useful in the detection and management of inflammatory lung disorders.. The levels of exhaled CO of 42 non-smoking patients with bronchiectasis treated or not treated with inhaled corticosteroids were compared with CO levels in 37 normal non-smoking subjects.. Levels of exhaled CO were raised in patients with bronchiectasis, both those treated with inhaled corticosteroids (n = 27, median 5.5 ppm, 95% CI 5.16 to 7.76) and those not treated with inhaled corticosteroids (n = 15, median 6.0 ppm. 95% CI 4.74 to 11.8), compared with normal subjects (n = 37, median 3.0 ppm, 95% CI 2.79 to 3.81, p = 0.0024). There was no correlation between exhaled CO and HbCO levels (r = 0.42, p = 0.12) in normal subjects (n = 7), nor between the urine cotinine concentration and exhaled CO levels (r = 0.2, p = 0.12).. Increased levels of exhaled CO may reflect induction of HO-1 and oxidative stress in bronchiectasis. Measurement of exhaled CO may be useful in the management of bronchiectasis and possibly other chronic inflammatory lung disorders.

Topics: Androstadienes; Anti-Inflammatory Agents; Biomarkers; Breath Tests; Bronchiectasis; Carbon Monoxide; Case-Control Studies; Female; Fluticasone; Heme Oxygenase (Decyclizing); Humans; Male; Middle Aged; Oxidative Stress; Statistics, Nonparametric