(9R)-9-chloro-11-17-dihydroxy-17-(2-hydroxy-1-oxoethyl)-10-13-16-trimethyl-6-7-8-11-12-14-15-16-octahydrocyclopenta[a]phenanthren-3-one and Pneumonia

Bronchopulmonary dysplasia (BPD), defined as oxygen dependence at 36 weeks postmenstrual age (PMA), remains an important complication of prematurity. Pulmonary inflammation plays a central role in the pathogenesis of BPD. Attenuating pulmonary inflammation with postnatal systemic corticosteroids reduces the incidence of BPD in preterm infants but may be associated with an increased risk of adverse neurodevelopmental outcomes. Local administration of corticosteroids via inhalation might be an effective and safe alternative.. To determine if administration of inhalation corticosteroids after the first week of life until 36 weeks PMA to preterm infants at high risk of developing BPD is effective and safe in reducing the incidence of death and BPD as separate or combined outcomes.. We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2017, Issue 4), MEDLINE via PubMed (1966 to 19 May 2017), Embase (1980 to 19 May 2017), and CINAHL (1982 to 19 May 2017). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials.. We included randomised controlled trials comparing inhalation corticosteroids, started ≥ 7 days postnatal age (PNA) but before 36 weeks PMA, to placebo in ventilated and non-ventilated infants at risk of BPD. We excluded trials investigating systemic corticosteroids versus inhalation corticosteroids.. We collected data on participant characteristics, trial methodology, and inhalation regimens. The primary outcome was death or BPD at 36 weeks PMA. Secondary outcomes were the combined outcome death or BPD at 28 days PNA, the seperate outcomes of death and BPD at both 28 days PNA, and at 36 weeks PMA, and short-term respiratory outcomes, such as failure to extubate; total days of mechanical ventilation and oxygen use; and the need for systemic corticosteroids. We contacted the original trialists to verify the validity of extracted data and to provide missing data. We analysed all data using Review Manager 5. When possible, we performed meta-analysis using typical risk ratio (RR) for dichotomous outcomes and weighted mean difference (WMD) for continuous outcomes along with their 95% confidence intervals (CI). We analysed ventilated and non-ventilated participants separately.We used the GRADE approach to assess the quality of the evidence.. We included eight trials randomising 232 preterm infants in this review. Inhalation corticosteroids did not reduce the separate or combined outcomes of death or BPD. The meta-analyses of the studies showed a reduced risk in favor of inhalation steroids regarding failure to extubate at seven days (typical RR (TRR) 0.80, 95% CI 0.66 to 0.98; 5 studies, 79 infants) and at the latest reported time point after treatment onset (TRR 0.60, 95% CI 0.45 to 0.80; 6 studies, 90 infants). However, both analyses showed increased statistical heterogeneity (I. Based on the results of the currently available evidence, inhalation corticosteroids initiated at ≥ 7 days of life for preterm infants at high risk of developing BPD cannot be recommended at this point in time. More and larger randomised, placebo-controlled trials are needed to establish the efficacy and safety of inhalation corticosteroids.

Topics: Administration, Inhalation; Anti-Inflammatory Agents; Beclomethasone; Bronchopulmonary Dysplasia; Budesonide; Dexamethasone; Fluocinolone Acetonide; Fluticasone; Glucocorticoids; Humans; Infant, Newborn; Infant, Premature; Pneumonia; Randomized Controlled Trials as Topic

Bronchopulmonary dysplasia (BPD), defined as oxygen dependence at 36 weeks postmenstrual age (PMA), remains an important complication of prematurity. Pulmonary inflammation plays a central role in the pathogenesis of BPD. Attenuating pulmonary inflammation with postnatal systemic corticosteroids reduces the incidence of BPD in preterm infants but may be associated with an increased risk of adverse neurodevelopmental outcomes. Local administration of corticosteroids via inhalation might be an effective and safe alternative.. To determine if administration of inhalation corticosteroids after the first week of life to preterm infants at high risk of developing BPD is effective and safe in reducing the incidence of death and BPD as separate or combined outcomes.. We identified randomised, controlled trials by searching the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), PubMed (from 1966), EMBASE (from 1974), CINAHL (from 1982), references from retrieved trials and handsearches of journals, all assessed to February 2012.. Randomised controlled trials comparing inhalation corticosteroids, started ≥ 7 days postnatal age (PNA) but before 36 weeks PMA, to placebo in ventilated and non-ventilated infants at risk of BPD were included. Trials investigating systemic corticosteroids versus inhalation corticosteroids were excluded.. Data on patient characteristics, trial methodology, and inhalation regimens were collected. The primary outcomes were death or BPD, or both, at 28 days PNA or 36 weeks PMA. Secondary outcomes were short-term respiratory outcomes, such as failure to extubate, total days of mechanical ventilation and oxygen use, and the need for systemic corticosteroids. The original trialists were contacted to verify the validity of extracted data and to provide missing data. All data were analysed using RevMan 5.0.24. When possible, meta-analysis was performed using typical risk ratio (TRR) for dichotomous outcomes and weighted mean difference (WMD) for continuous outcomes along with their 95% confidence intervals (CI). Ventilated and non-ventilated participants were analysed separately.. Eight trials randomising 232 preterm infants were included in this review. Inhalation corticosteroids did not reduce the separate or combined outcomes of death or BPD. Furthermore, inhalation steroids did not impact short-term respiratory outcomes such as failure to extubate and total duration of mechanical ventilation or oxygen dependency. There was a trend to a reduced use of systemic corticosteroids in favour of inhalation corticosteroids (TRR 0.51; 95% CI 0.26 to 1.00). There was a paucity of data on short-term and long-term adverse effects. These results should be interpreted with caution because the total number of randomised patients is relatively small and most trials differed considerably in patient characteristics, inhalation therapy and outcome definitions.. Based on the results of the currently available evidence, inhalation corticosteroids initiated at ≥ 7 days of life for preterm infants at high risk of developing BPD cannot be recommended at this point in time. More and larger randomised, placebo-controlled trials are needed to establish the efficacy and safety of inhalation corticosteroids.

Topics: Administration, Inhalation; Androstadienes; Anti-Inflammatory Agents; Beclomethasone; Bronchopulmonary Dysplasia; Budesonide; Dexamethasone; Fluocinolone Acetonide; Fluticasone; Glucocorticoids; Humans; Infant, Newborn; Infant, Premature; Pneumonia; Randomized Controlled Trials as Topic

Chronic lung disease (CLD) is one of the most severely disabling conditions of extremely low-birth-weight infants. Systemic corticosteroids are effective but cause many adverse effects. Targeted therapy with inhaled corticosteroids may be an effective and less toxic alternative.. To evaluate the additive effect of inhaled corticosteroids on markers of lung inflammation in infants receiving a 7-day course of systemic steroids.. Preterm neonates weighing 1 kg or less and aged 12 to 28 days who were prescribed a 7-day course of systemic corticosteroids for evolving CLD were studied prospectively and randomized to receive either a tapering 4-week course of beclomethasone metered-dose inhaler (MDI) (n = 5) or placebo MDI (n = 6). Primary outcome variables were the levels of pro- and anti-inflammatory cytokines, IL-8, TNF-alpha, IL-1alpha, and sIL-2R.. This study was terminated early following literature reports of the adverse neurodevelopmental effects of dexamethasone. Measurements of respiratory and serum IL-8, IL-1alpha and TNF-alpha were similar between the study group taking inhaled and systemic corticosteroids and the study group taking systemic steroids alone. No differences were found between the two groups in relation to dynamic compliance or resistance.. The addition of inhaled corticosteroids to a 7-day systemic course of corticosteroids did not alter cytokine response or improve pulmonary function.

Topics: Administration, Inhalation; Anti-Inflammatory Agents; Beclomethasone; Biomarkers; Chronic Disease; Cytokines; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Lung; Lung Diseases; Pneumonia

Inhaled corticosteroids have become a key element in the maintenance treatment of bronchial asthma. Recent studies have shown that administration of inhaled corticosteroids is associated with evidence of derangement in bone turnover. Therefore, we studied the bone mineral density (BMD) of asthmatic women receiving long-term inhaled corticosteroids and compared them with healthy individuals matched for age, sex, menopausal status and body mass index.. Thirty-two female patients with bronchial asthma, who had been using inhaled corticosteroids (beclomethasone dipropionate 750-1500 microg/day) regularly for at least 3 months, were included in the study. Bone mineral density measurements were done with dual X-ray absorptiometry in the lumbar area of the spine and the hip. Detailed laboratory examination was also done for the patients and 26 controls.. There was a significant decrease in BMD of the patient group at the lumbar region and femur as compared with normal controls. In the patients there was a significant negative correlation between the duration of therapy, daily and cumulative doses, and BMD at the lumbar region but not BMD at the femur.. These results indicate that long-term use of inhaled corticosteroids is associated with significant bone loss in asthmatic women and is especially related to the duration of therapy. Therefore, it is necessary to appropriately screen and give prophylactic treatment to those who are likely to develop osteoporosis from inhaled corticosteroid treatment.

Topics: Absorptiometry, Photon; Administration, Inhalation; Anti-Asthmatic Agents; Asthma; Beclomethasone; Body Mass Index; Bone Density; Calcium, Dietary; Cross-Sectional Studies; Female; Glucocorticoids; Humans; Middle Aged; Pneumonia; Time Factors; Women

A double blind controlled trial of Becotide (beclomethasone diproprionate) inhalations was carried out for treating cystic fibrosis patients with chronic P. aeruginosa lung infection to determine its efficacy and safety. The aim of the treatment was to diminish the inflammatory response in the lungs of these patients, a response which is initiated by an allergic type III reaction. Pulmonary inflammation was evaluated by measurements of proteolytic activity, albumin concentration and immune complex activity in the sputum sol-phase before, during, and after the 16 weeks the trial lasted. 26 cystic fibrosis patients participated (13 received Becotide and 13 placebo) and the results showed that local steroids have no effect on the inflammatory response in the lungs of cystic fibrosis patients with chronic P. aeruginosa lung infection. No adverse effects were demonstrated. There was, however, a significant increase in the inflammatory parameters for all 26 cystic fibrosis patients when the trial period was over, compared to the insidious pulmonary destruction which takes place in the lungs of these patients, and it corresponded to a significant decrease (p less than 0.05) in forced vital capacity which took place at the same time. Therefore, chronic P. aeruginosa lung infection in these patients should be treated as efficiently as possible.

Topics: Adolescent; Adult; Beclomethasone; Child; Child, Preschool; Clinical Trials as Topic; Cystic Fibrosis; Double-Blind Method; Female; Humans; Longitudinal Studies; Male; Pneumonia; Pseudomonas Infections; Sputum

Despite multiple available fixed-dose combinations (FDCs) of inhaled long-acting β. Can comparative effectiveness and safety of LABA plus LAMA (LABA/LAMA) and LABA plus ICS (LABA/ICS) FDCs vary by different individual components of the dual combinations in COPD?. We conducted a new user, propensity score-inverse probability of treatment weighting cohort study to compare the effectiveness and safety of two frequently used LABA/LAMA FDCs (indacaterol plus glycopyrronium [IND/GLY] and vilanterol plus umeclidinium [VI/UMEC]) vs three commonly prescribed LABA/ICS FDCs (salmeterol plus fluticasone propionate [SAL/FP], formoterol fumarate plus budesonide [FF/BUD], and formoterol fumarate plus beclomethasone dipropionate [FF/BDP]) using the Taiwanese nationwide health care claims from 2014 through 2017. The primary effectiveness outcome was the annual moderate to severe exacerbation rate, and safety outcomes included risks of severe pneumonia and cardiovascular disease requiring hospitalization. Weighted generalized linear mixed models and Cox proportional hazard models were used to assess the effectiveness and safety outcomes, respectively.. Patients with COPD initiating IND/GLY and VI/UMEC showed an 11% (incidence rate ratio [IRR], 0.89; 95% CI, 0.80-0.98) and 20% (IRR, 0.80; 95% CI, 0.71-0.90) reduced annual rate of moderate to severe exacerbations, respectively, than those initiating SAL/FP, but showed a similar rate as those initiating FF/BUD or FF/BDP. Both LABA/LAMA FDCs, compared with SAL/FP and VI/UMEC vs FF/BDP, were associated with a 27% (hazard ratio [HR], 0.73; 95% CI, 0.59-0.90) to 42% (HR, 0.58; 95% CI, 0.48-0.70) reduced pneumonia risk. Cardiovascular risk was comparable in five groups. An intraclass difference existed in rates of moderate to severe COPD exacerbation and risks of pneumonia among LABA/ICS FDCs, but not between LABA/LAMA FDCs.. Both LABA/LAMAs vs SAL/FP are associated with a lower exacerbation rate and pneumonia risk, but exhibit similar effectiveness and safety outcomes compared with FF/BDP or FF/BUD, suggesting that comparative effects may differ by individual components of the dual therapies in COPD.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Aged; Beclomethasone; Benzyl Alcohols; Budesonide, Formoterol Fumarate Drug Combination; Chlorobenzenes; Cohort Studies; Comparative Effectiveness Research; Disease Progression; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Glucocorticoids; Glycopyrrolate; Humans; Indans; Male; Muscarinic Antagonists; Pneumonia; Propensity Score; Proportional Hazards Models; Pulmonary Disease, Chronic Obstructive; Quinolones; Quinuclidines

The differential risk of pneumonia among inhaled corticosteroid (ICS) use in patients with COPD requires more investigation, especially regarding beclomethasone-containing inhalers. The goal of this study was to compare the risk and benefit profile of different ICS/long-acting β. This retrospective cohort study was conducted by using national health insurance claims data from the years 2009 to 2015 in Taiwan and included patients with COPD with new ICS/LABA use. Propensity score matching and Cox regression models were used to estimate the hazard ratios of severe pneumonia and acute exacerbation for different ICS/LABA users.. Both budesonide/formoterol (BUD/FOR) dry-powder inhalers and beclomethasone/formoterol (BEC/FOR) metered-dose inhalers, compared with fluticasone propionate/salmeterol (FLU/SAL) delivered via the same device type, were associated with a lower risk of severe pneumonia (BUD/FOR hazard ratio [HR], 0.83 [95% CI, 0.70-0.98]; BEC/FOR HR, 0.69 [95% CI, 0.58-0.81]) and severe acute exacerbation (BUD/FOR HR, 0.88 [95% CI, 0.78-0.99]; BEC/FOR HR, 0.82 [95% CI, 0.72-0.93]). After additionally adjusting for the average daily ICS dose, BUD/FOR dry-powder inhaler users continued to have a significantly decreased risk of severe pneumonia (18%), although BEC/FOR metered-dose inhaler users did not. The results were consistent in most of the prespecified subgroups and across all the sensitivity analyses.. This study augments the existing evidence concerning the different safety and effectiveness outcomes of ICS/LABA combinations in patients with COPD, which may be considered when making clinical treatment decisions.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Aged; Beclomethasone; Bronchodilator Agents; Budesonide; Drug Combinations; Drug Therapy, Combination; Female; Fluticasone; Formoterol Fumarate; Glucocorticoids; Humans; Male; Metered Dose Inhalers; Middle Aged; Pneumonia; Propensity Score; Pulmonary Disease, Chronic Obstructive; Retrospective Studies; Salmeterol Xinafoate; Taiwan

Despite advances in vaccination and antimicrobial therapy, community-acquired pneumonia (CAP) remains as a leading cause of morbidity and mortality worldwide. As the severity of CAP has been linked to the extent of inflammation in the body, adjunctive therapeutic measures aimed at modulating the immune response have therefore become increasingly attractive in recent years. In particular, for CAP patients with underlying medical conditions such as chronic obstructive pulmonary disease (COPD), a steroid-antibiotic combination will no doubt be a useful and timely therapeutic intervention. Unfortunately, no combined steroid-antibiotic dry powder formulation is available commercially or has been reported in the academic literature. The aim of this work was hence to develop a novel steroid-antibiotic dry powder inhaler formulation [ciprofloxacin hydrochloride (CIP) and beclomethasone dipropionate (BP)] for inhaled anti-infective therapy. The spray-dried powder was of respirable size (d50 of ∼2.3 μm), partially crystalline and had BP preferentially deposited on the particle surface. Favorably, when formulated as a binary mix, both CIP and BP showed much higher drug release and fine particle fractions (of the loaded dose) over their singly delivered counterparts, and had robust activity against the respiratory tract infection-causing bacteria Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus.

Topics: Administration, Inhalation; Anti-Bacterial Agents; Bacterial Infections; Beclomethasone; Ciprofloxacin; Dry Powder Inhalers; Glucocorticoids; Humans; Klebsiella pneumoniae; Pneumonia; Powders; Pseudomonas aeruginosa; Pulmonary Disease, Chronic Obstructive; Staphylococcus aureus

Natural surfactant combined with beclomethasone decreases pulmonary oxidative stress in preterm lambs with respiratory distress syndrome (RDS).. To test the hypothesis that this occurs through a decrease in pulmonary inflammation.. Preterm lambs received 200 mg/kg of natural surfactant or 200 mg/kg of natural surfactant combined with 400 or 800 μg/kg of beclomethasone. Interleukin 8 (IL-8) and macrophage migration inhibitory factor (MIF) were assayed in bronchial aspirate samples and lung mechanics were evaluated.. IL-8 increased in all the groups, but the increase was lower in the groups treated with surfactant plus 400 and 800 μg/kg of beclomethasone. MIF decreased in the surfactant group, did not vary in the surfactant plus 400 μg/kg beclomethasone group, and decreased in the surfactant plus 800 μg/kg beclomethasone group. MIF concentration was higher in the surfactant plus 800 μg/kg beclomethasone group than in the other groups.. Natural surfactant combined with beclomethasone at 800 μg/kg is effective in reducing lung inflammation in an animal model of RDS, thus explaining the associated decrease in lung oxidative stress. The increase in MIF in animals treated with surfactant plus 800 μg/kg of beclomethasone might be an important maturative and protective factor for neonatal lungs.

Topics: Animals; Animals, Newborn; Anti-Inflammatory Agents; Beclomethasone; Disease Models, Animal; Female; Humans; Infant, Newborn; Interleukin-8; Macrophage Migration-Inhibitory Factors; Oxidative Stress; Pneumonia; Pregnancy; Pulmonary Surfactants; Respiratory Distress Syndrome, Newborn; Sheep

To study the alteration of thymus matrix lymphocyte generator (TSLP) and change of the Th factor in the course of disease development, and to analyze the curative effect of inhalation of Vitamin A (VA) with corticosteroid for the treatment of asthmatic pneumonia.. Asthmatic pneumonia models were prepared by challenging rats with inhalation of ovalbumin for 4 weeks, and rested for 1 week. The treatment with VA and corticosteroid inhalation for 1 week was followed. The rat thymus and lung specimen were examen by histochemical and immunofluorescence staining.. After 4 - 5 weeks of stimulation, there were more TSLP-positive cells and alveolar macrophages (AM) found in thymus and lung tissue of asthmatic group, the cell proliferation in spleen and thymus was obvious, and blood Th factors elevated. The inflammation within the lung tissue aggravated gradually. In VA group, the expression of TSLP and Th2 factors were all lowered at the 4th week. The TSLP expression slightly increased at the 5th week, and the cell proliferation within T-cell zone of spleen and thymus was strong at first and weakened later. Alveolar microphages (AM) increased significantly and the inflammation in the lung subsided gradually at the 5th week. In the hormone group, TSLP and Th2 factors expression in both thymus and lung were decreased at the 5th week, while the cell proliferation in thymus and lung was gradually increased. The quantity of AM was decreased, whereas the inflammation of the lung was increased gradually at the 5th week.. During asthmatic period elevated TSLP expression was accompanied by Th2 type responses while VA and corticosteroid both suppressed TSLP and Th2 factors expression. VA alone promoted T lymphocyte proliferation as well as the antigen elimination function by AM, after ceasing the usage, the lung inflammation abated gradually. In contrast, after ceasing the use of corticosteroid, inflammation aggravated.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Animals; Asthma; Beclomethasone; Cytokines; Pneumonia; Rats; Rats, Sprague-Dawley; Thymic Stromal Lymphopoietin; Vitamin A