Inhaled Glucocorticoids Research Articles

Level of Compliance with Spanish Guideline Recommendations in the Management of Asthma.

To describe the clinical management of asthmatic patients and the level of compliance with the Guía Española para el Manejo del Asma (GEMA, Spanish Guidelines for Asthma Management) in the influential al area of Virgen de la Victoria University Hospital, Málaga (Spain). Descriptive, cross-sectional study in asthma patients from the Virgen de la Victoria University Hospital influential area, Málaga (Spain). Asthma Control Test (ACT) results, demographic and clinical characteristics, and GEMA indicators of quality asthma care were obtained from each participating patient. Two hundred and eighty-eight patients (64.2% woman, mean age 48.6 years) were included in the study. The evaluation of the level of compliance with the GEMA quality indicators showed that in 20.8% of the patients the diagnosis of asthma was confirmed by spirometry and bronchodilator test, and 52.5% of the patients with suspicion of allergic asthma performed a sensitization test. Among the smoker patients, 76.3% were recommended to stop smoking; 14.2% of the patients received a paper-based educational plan. Regarding asthma treatment, 92.3% of patients with persistent asthma received inhaled glucocorticoids (IGC). IGC and LABA were the most common treatments for asthma, used in combination (ICG + LABA) in 139 (48.3%) patients; 32.6% discontinued SABA treatment during the study period. Asthma was well controlled in 54.9% of the patients (ACT score ≥20), and 13.9% of the patients registered exacerbations during the previous year with a mean (SD) of 1.38 (0.74) events. Most of the GEMA quality indicators of asthma care are not followed in real-world clinical practice. Specialists select the best option among the available treatments but there is an unmet need for training plans in other relevant aspects, such as diagnosis and/or disease monitoring.

Chronic obstructive pulmonary disease (COPD) and COPD-like phenotypes.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease. Historically, two COPD phenotypes have been described: chronic bronchitis and emphysema. Although these phenotypes may provide additional characterization of the pathophysiology of the disease, they are not extensive enough to reflect the heterogeneity of COPD and do not provide granular categorization that indicates specific treatment, perhaps with the exception of adding inhaled glucocorticoids (ICS) in patients with chronic bronchitis. In this review, we describe COPD phenotypes that provide prognostication and/or indicate specific treatment. We also describe COPD-like phenotypes that do not necessarily meet the current diagnostic criteria for COPD but provide additional prognostication and may be the targets for future clinical trials.

The Relationship of Fractional Exhaled Nitric Oxide in Patients with AECOPD.

To identify the relationship between patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and their fractional-exhaled nitric oxide (FeNO) levels. Patients diagnosed with AECOPD in the respiratory department of Beijing Chaoyang Hospital from June 2017 to August 2019 were recorded. The demographic data, FeNO value, peripheral blood eosinophil count, number of acute exacerbations in the past year, pulmonary function test, use of inhaled glucocorticoids (ICS) and other data were collected and analyzed. FeNO was measured again three months after discharge, the participants were assessed to determine if the stable period criteria were met. A total of 214 patients met the requirements of this study. 25ppb for FeNO was used as the cutoff for further analysis. The proportion of males, number of acute exacerbations in the past year, number of ICS users, leukocyte count and eosinophil count in the high FeNO-level group was significantly higher than that in the low-level group (P < 0.05). The results showed that the number of acute exacerbations in the past year, number of ICS users, and eosinophil count were statistically significant in the model (P < 0.05). The study also showed that the level of FeNO in the acute exacerbation phase was significantly higher than that in the stable phase. The ROC curve that the area under the curve used by FeNO to predict ICS used is 0.631 (95% CI: 0.526-0.736), and the corresponding P value is 0.022. FeNO is closely related to activated T2 inflammation and eosinophil count in COPD patients. The FeNO levels can be used as an index to evaluate the severity of COPD and predict the recovery of activity after ICS treatment. FeNO can predict the use of ICS and is a beneficial supplement to eosinophils.

Identification of study populations in the clinical study of chronic obstructive pulmonary disease: Surface-based or essence-based

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disorder characterized by chronic bronchitis, emphysema, or both. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) has had a tremendous impact on the diagnosis and treatment of COPD. This article reviewed the evolution of the definition of COPD in GOLD and the change of its treatment strategy. In addition, in light of relevant clinical studies, the paper attempted to illustrate the importance of understanding the heterogeneous nature of COPD, and analyzed the possible consequences of ignoring this nature, including confusion with bronchial asthma caused by lung function as the "gold standard" and excessive use of inhaled glucocorticoids (ICS). It is suggested that in clinical practice, the essential characteristics of COPD patients should be clarified by collecting a variety of information in order to provide personalized treatment for patients' assessment, therapy and rehabilitation. At the same time, more basic and clinical research on COPD should be conducted, based on the nature of the disease, to explore new treatment methods.

Increased expression of IL1-RL1 is associated with type 2 and type 1 immune pathways in asthma

BackgroundAsthma is a common chronic airway disease in the world. The purpose of this study was to explore the expression of IL1-RL1 in sputum and its correlation with Th1 and Th2 cytokines in asthma.MethodsWe recruited 132 subjects, detected IL1-RL1 protein level in sputum supernatant by ELISA, and analyzed the correlation between the expression level of IL1-RL1 and fraction of exhaled nitric oxide (FeNO), IgE, peripheral blood eosinophil count (EOS#), and Th2 cytokines (IL-4, IL-5, IL-10, IL-13, IL-33 and TSLP) and Th1 cytokines (IFN-γ, IL-2, IL-8). The diagnostic value of IL1-RL1 was evaluated by ROC curve. The expression of IL1-RL1 was further confirmed by BEAS-2B cell in vitro.ResultsCompared with the healthy control group, the expression of IL1-RL1 in sputum supernatant, sputum cells and serum of patients with asthma increased. The AUC of ROC curve of IL1-RL1 in sputum supernatant and serum were 0.6840 (p = 0.0034), and 0.7009 (p = 0.0233), respectively. IL1-RL1 was positively correlated with FeNO, IgE, EOS#, Th2 cytokines (IL-4, IL-5, IL-10, IL-13, IL-33 and TSLP) and Th1 cytokines (IFN-γ, IL-2, IL-8) in induced sputum supernatant. Four weeks after inhaled glucocorticoids (ICS) treatment, the expression of IL1-RL1 in sputum supernatant and serum was increased. In vitro, the expression of IL1-RL1 in BEAS-2B was increased after stimulated by IL-4 or IL-13 for 24 h.ConclusionThe expression of IL1-RL1 in sputum supernatant, sputum cells and serum of patients with asthma was increased, and was positively correlated with some inflammatory markers in patients with asthma. IL1-RL1 may be used as a potential biomarker for the diagnosis and treatment of asthma.

Microbiome Analysis and Pharmacovigilance After Inhaled Glucocorticoid: Oral Dysbiosis With the Isolation of Three Rothia Species and Subsequent Sjögren's Syndrome.

Background: Treatment of respiratory tract diseases with inhaled glucocorticoids is a form of therapy that has been used for many years. It shows lower potency of side effects; nevertheless, microbiome change, sinopulmonary dysbiosis, secondary immunodeficiency, and immunomodulatory effects are underestimated. The latest guideline recommendations introduce the use of empirical antibiotic and/or multiplying inhaled glucocorticoids in therapeutic intervention of asthma and chronic pulmonary obstructive disease. Aims and objectives: The aim of the study was to describe a simple, universal, and cost-effective method of microbiome analysis for clinical trials. Such a general method for monitoring pharmacovigilance should be widely available and reliable. Methods: The study material included two kinds of swabs, taken from the same mouth ulcerations of patients with asthma treated with a temporary quadruple dose of fluticasone. The microbiological investigation was performed, and identification of the isolates was carried out using the matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF-MS) Biotyper. Results: The analysis of dry swab demonstrated the presence of typical oral bacteria (Neisseria spp. and Streptococcus spp.), alongside with the potentially pathogenic Actinomyces spp. and three different Rothia species, identified simultaneously: R. aeria, R. dentocariosa, and R. mucilaginosa. Although quadrupled dose of corticoids was discontinued and ulcer healing was observed, the patients required topical therapy for maintained xerostomia. Progressive systemic autoimmunity (seronegative Sjögren’s syndrome with major organ involvement) was observed later. Conclusion: Topical steroids (especially in quadruple dose) require attention to safety, immunomodulation, and microbiological outcome. They showed systemic side effects: microbiome alteration, humoral (IgG) immunodeficiency, and systemic autoimmunity. Isolation of three species of Rothia from a patient with mouth ulcers after steroid therapy suggests their participation in infectious and inflammatory processes. The proposed a methodology using MALDI-TOF-MS may be a prototype approach for microbial diagnostics in clinical trials of immunomodulatory drugs.

Comparison of CRP, Procalcitonin, Neutrophil Counts, Eosinophil Counts, sTREM-1, and OPN between Pneumonic and Nonpneumonic Exacerbations in COPD Patients.

Introduction The patients with community-acquired pneumonia (CAP) and acute exacerbations of COPD (AECOPD) could have a higher risk of acute and severe respiratory illness than those without CAP in AECOPD. Consequently, early identification of pneumonia in AECOPD is quite important. Methods. 52 subjects with AECOPD + CAP and 93 subjects with AECOPD from two clinical centers were enrolled in this prospective observational study. The values of osteopontin (OPN), soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), C-reactive protein (CRP), procalcitonin (PCT), eosinophil (EOS) counts, and neutrophil (Neu) counts in blood on the first day of admission and clinical symptoms were compared in AECOPD and AECOPD + CAP. In addition, subgroup analyses of biomarker difference were conducted based on the current use of inhaled glucocorticoids (ICS) or systemic corticosteroids (SCS). Results Patients with AECOPD + CAP had increased sputum volume, sputum purulence, diabetes mellitus, and longer hospital stays than AECOPD patients (p < 0.05). A clinical logistic regression model showed among the common clinical symptoms, purulent sputum can independently predict pneumonia in AECOPD patients after adjusting for a history of diabetes. At day 1, AECOPD + CAP patients had higher values of Neu, CRP, PCT, and OPN, while serum sTREM-1 levels and EOS counts were similar in the two groups. CRP fared best at predicting AECOPD with CAP (p < 0.05 for the test of difference), while OPN had similar accuracy with Neu, PCT, and purulent sputum (p > 0.05 for the test of difference). Multivariate analysis, including clinical symptoms and biomarkers, suggested that CRP ≥15.8 mg/dL at day 1 was a only promising predictor of pneumonia in AECOPD. CRP and OPN were not affected by ICS or SCS. Conclusions CRP ≥15.8 mg/dL is an ideal promising predictor of pneumonia in AECOPD, and its plasma level is not affected by ICS or SCS. The diagnostic performance of CRP is not significantly improved when combined with clinical symptoms or other markers (OPN, PCT, and Neu).

Phenotypes of bronchial asthma during the health resort period and personalized programs of medical rehabilitation

Bronchial asthma (BA) is a relevant social and medical problem in our country and around the world. Currently, phenotypes of the disease are distinguished. One of the original decisions in phenotypes distinguishing is the use of cluster analysis. However, the concept of BA phenotypes at the health resort period of rehabilitation has not yet been formed. To determine the BA phenotypes upon admission of patients to a health resort medical rehabilitation (HRMR) using cluster analysis and to offer personalized rehabilitation programs. 518 patients with asthma who underwent HRMR on the southern coast of Crimea were examined. Each patient received clinical, functional and laboratory examination. HRMR included correction of long-term treatment according to the severity of asthma, climate therapy, respiratory therapy, educational programs, and physiotherapeutic procedures. We applied cluster analysis in order to identify BA phenotypes. Description statistics methods were used for phenotype-cluster characterization, comparative analysis - for determination of reliable phenotypic characteristics and relation of the effectiveness of HRMR and phenotypes. A model of three phenotype-clusters was developed. The first cluster included patients with BA of moderate severity, uncontrolled course, frequent exacerbations, history of atopy, a tendency to obesity, moderately reduced external respiration function, fixed airway obstruction, high adherence to long-term therapy with medium doses of inhaled glucocorticoids (ICS) combined with long-acting β-2 agonists (LABA). Cluster 2 included patients with mild asthma, controlled or partially controlled course of the disease, with rare short exacerbations, late onset, preserved external respiration function and exercise tolerance, but low adherence to long-term therapy with medium and low doses of ICS. Cluster 3 included patients with moderate to severe BA, uncontrolled course, with early onset, frequent and prolonged exacerbations, severe symptoms, significantly reduced external respiration function with fixed obstruction, decreased exercise tolerance, but low adherence to long-term therapy (4th stage) with high doses of ICS in combination with LABA and long-acting anticholinergics. A close relationship was found between phenotypes-clusters and the achieved effects: a significant increase in the control of BA and a high efficiency of rehabilitation in patients of the 1st and especially 3rd clusters and low in the 2nd cluster. The optimal rehabilitation programs for each of the selected cluster phenotypes were determined. The cluster model developed with the help of artificial intelligence has demonstrated high prognostic value in the determination of the effectiveness and change of control over the course of asthma as a result of HRMR. Personalized HRMR programs are suggested.

Mild bronchial asthma: a modern treatment concept

Mild bronchial asthma (BA) occurs in 50–75% of patients with this disease. It is characterized by clinical symptoms that are controlled by low doses of inhaled glucocorticoids (IGCS) or anti-leukotriene drugs. Mild BA reduces the quality of life of patients, is accompanied by the development of severe, in some cases fatal exacerbations, and is characterized by a significant cost of treatment. One of the main problems in the management of patients with this disease is their low adherence to IGCS treatment and the excessive use of short-acting 2-adrenomimetic agents. Several clinical studies have shown that the use of a combination of budesonide/formoterol (Symbicort® Turbuhaler®) in an «as needed» mode reduces the incidence of severe exacerbations of mild BA as well as low doses of budesonide, and is characterized by a lower cumulative dose of this glucocorticoid. The results obtained were the basis for the creation of a new treatment concept, which gives preference to the combination of IGCS / formoterol «as needed» in mild BA as a supporting therapy, and for the management of symptoms of the disease.

Abnormal microarchitecture and stiffness in postmenopausal women using chronic inhaled glucocorticoids.

While oral glucocorticoids are well recognized to have destructive skeletal effects, less is known about the effects of IGCs. The detrimental skeletal effects of IGCs may be greatest in PM women, in whom they compound negative effects of estrogen loss and aging. The goal of this study was to evaluate microarchitecture and stiffness in PM women using chronic IGCs. This case-control study compared PM women using IGCs for ≥ 6months (n = 20) and controls matched for age and race/ethnicity (n = 60). Skeletal parameters assessed included areal BMD (aBMD) by DXA, trabecular and cortical vBMD and microarchitecture by HRpQCT of the radius and tibia, and whole bone stiffness by finite element analysis. By DXA, mean values in both groups were in the osteopenic range; hip aBMD was lower in IGC users (P < 0.04). By HRpQCT, IGC users had lower total, cortical, and trabecular vBMD at both radius and tibia (all P < 0.05). IGC users had lower cortical thickness, lower trabecular number, greater trabecular separation and heterogeneity at the radius (all P < 0.03), and greater heterogeneity at the tibia (P < 0.04). Whole bone stiffness was lower in IGC users at radius (P < 0.03) and tended to be lower at the tibia (P = 0.09). PM women using IGCs had substantial abnormalities in vBMD, microarchitecture, and stiffness compared to controls. These abnormalities were most severe at the radius. These preliminary results suggest that there may be major, heretofore unrecognized, skeletal deficits in PM women using IGCs.

CLINICAL-GENETIC PHENOTYPING BRONCHIAL ASTHMA

Objective – to determine BA phenotypes using cluster analysis based on clinical and genetic traits in the Ukrainian population. Materials and methods. The study involved 195 patients with asthma. The diagnosis of asthma was made on the basis of the recommendations of GINA (2016) and order № 868 of 08.10.2013 of the Ministry of Health of Ukraine. To assess the control of asthma, an ACQ-5 questionnaire was used. The function of external respiration (FVD) was studied by means of the diagnostic complex Cardioplus (Ukraine) and the results were evaluated according to national recommendations. All patients underwent a reversibility test using 4 inhalations of salbutamol (400 μg). For the cluster analysis, 24 variables were used – clinical and instrumental, anamnestic and genetic parameters. For the cluster analysis, the SPSS-21 program was used. Gln27Glu (rs1042714) polymorphism of the ADRB2 gene was determined using the polymerase chain reaction method. The control group for the genetic study was 95 practically healthy persons without allergopathology. Results. Using the cluster analysis, we identified 3 phenotypes of BA: the 1-st phenotype (cluster A, n=81) − allergic asthma which occurs at a young age with a partially controlled course and a good response to inhaled glucocorticoids (IGCC) and β2-agonists long-acting (LABA); the 2-nd phenotype (cluster B, n=38) − non-allergic asthma, most of the women with overweight are characterized by an onset of BA at young age with uncontrolled course and inadequate response to medium doses of IGCC and LABA; the 3-d phenotype (cluster C, n=76) − non-allergic asthma which is associated with obesity diagnosed predominantly in women and has a partially controlled course. Conclusions. Carriers of the Glu27Glu genotype were more frequent among BA patients from cluster B, Gln27Glu genotype − in BA patients from cluster A and C, and Gln27Gln genotype − in BA patients from cluster A. The risk of BA was 5.5 times higher in carriers of Glu allele in comparison with carriers of the Gln allele of Gln27Glu polymorphism of ADRB2.

Inhaled glucocorticoids are associated with vertebral fractures in COPD patients.

Chronic obstructive pulmonary disease (COPD) is an independent risk factor for osteoporosis. Oral glucocorticoids are deleterious to bone; however, the impact of inhaled glucocorticoids (ICS) remains unclear. Our objective was to determine whether ICS contribute to osteoporosis and fragility fractures. Sixty-one COPD patients, 35 current users of ICS and 26 who had never received glucocorticoids, were evaluated for bone mineral density (BMD) and body composition and underwent vertebral fracture assessment (VFA). The risk factors for bone disease considered for analysis were age, gender, ICS use, body mass index (BMI), muscle mass index (MMI), and the Global Initiative for Chronic Obstructive Lung Disease (GOLD) category. The Fracture Risk Assessment Tool (FRAX) calculation tool for the Brazilian population was also employed. The groups did not differ regarding gender, BMI, MMI, GOLD class, lowest values of the BMD T-score and Z-score, prevalence of osteoporosis, or low BMD for age. Vertebral fractures were identified via VFA in seven patients using ICS and in none of those not receiving glucocorticoids (p=0.02). There was a trend for an association between MMI and osteoporosis (p=0.05) and for a progressive decrease in the BMD Z-score according to the COPD severity assessed via the GOLD score (p=0.08). Vertebral fractures were not associated with osteoporosis (p=0.69) or low MMI (p=0.12). The fracture risk was not estimated by FRAX. ICS may lead to bone fragility before a significant decrease in BMD. Low muscle mass and COPD severity may contribute to bone disease.

Clinical effectiveness of anticholinergic tiotropium bromide as an add-on therapy in patients with severe bronchial asthma: A randomized controlled trial

Background and Objectives: Severe asthma seen in substantial proportion of patients has been a poorly controlled disease, with recurring symptoms and exacerbations despite the use of inhaled glucocorticoids (ICS), long-acting beta-agonists (LABAs-2), leukotriene receptor antagonist (LTRA), and theophyllines. A potential alternative approach is addition of a second bronchodilator with an alternative mode of action, the anticholinergic tiotropium bromide. Hence, the present study was undertaken to evaluate clinical effectiveness of tiotropium bromide 18 mcg as add-on therapy in severe asthma patients. Methodology: A single-blinded randomized study was carried in patients with severe asthma. The patients were randomized into two groups. The study group received an addition of 18 mcg of tiotropium while both groups were continued on LABA and high dose ICS combination, theophyllines, and LTRA. Improvement in lung function (forced expiratory volume in 1 s [FEV1], forced vital capacity [FVC], and peak expiratory flow rate [PEFR]), clinical symptoms, and quality of life were assessed by mini asthma quality of life questionnaire (mini-AQLQ) at 4, 8, and 12 weeks. Results: Seventy patients were included in the study, of which 63 completed the study period. Baseline characteristics were well matched between the groups. At the end of 12 weeks, the tiotropium group showed a mean improvement in FEV1 and FVC of 450 ml and 560 ml, respectively, as compared to the control group (P Conclusions: The addition of once-daily tiotropium to severe asthma treatment regimen including high-dose ICS plus LABA, theophyllines, and LTRA significantly improves lung functions and quality of life over 12 weeks of therapy.

The effect of inhaled glucocorticoid therapy on serum proteomics of asthmatic patients

To screen the biomarkers which may play important roles in the pathogenesis and therapy of asthma by using serum comparative proteomics. From June 2011 to September 2012, 30 chronic persistent asthmatic patients (asthma group) and 30 healthy controls (control group) were selected for study in our hospital. All the asthmatic patients were given 8 week-treatment with inhaled glucocorticoids (ICS). Then comparative proteomics were employed to identify differential proteins in serum samples from the control group, the asthma pre-treatment group and the asthma post-treatment group. The differential proteins which had significant differences before and after ICS therapy were selected for Western blot analysis and ELISA detection. Besides, the correlation between the differential proteins and IgE, eosinophils (EOS), neutrophil percentage(NEUT%), and FEV1% were analyzed. Eleven differential proteins were identified. Among them, heat shock protein 70 (HSP70), eosinophil chemotactic protein (Eotaxin) and vitamin D binding protein (VDBP) had significant differences in protein abundance before and after treatment. The differential expression of the 3 proteins in each group was confirmed by Western blot. ELISA data showed that the serum levels of HSP70 and Eotaxin were significantly higher in the asthma pre-treatment group [(439 ± 103)ng/L, (183 ± 79)ng/L] than those in the control group [(209 ± 58)ng/L, (91 ± 46)ng/L] (t = 5.281, 4.972, all P < 0.01), but significantly lower in the asthma post-treatment group[(247 ± 96) ng/L, (105 ± 58)ng/L] than those in the pre-treatment group (t = 4.157, 3.892, all P < 0.01). However, the serum level of VDBP was significantly lower in the asthmatics pre-treatment group [(318 ± 115)mg/L] than that in the control group [(541 ± 98)mg/L] (t = 3.878, P < 0.01), but significantly higher in the asthma post-treatment group[(479 ± 132)mg/L] than that in the pre-treatment group(t = 3.572, P < 0.01). The correlation analysis showed that HSP70 was correlated positively with IgE and NEUT%, but negatively with FEV1% (r = 0.568, 0.613, -0.516, all P < 0.01). Eotaxin was correlated positively with IgE and EOS, but negatively with FEV1% (r = 0.752, 0.826, -0.618, all P < 0.01). VDBP was correlated negatively with NEUT%, but positively with FEV1% (r = -0.537, 0.426, all P < 0.05). HSP70, Eotaxin, and VDBP may participate in the pathogenesis of asthma, and may become the potential targets for ICS therapy.

CP-021 Economic impact of transfer of omalizumab to hospital dispensing and check of appropriate prescribing practice

BackgroundAsthma treatment with omalizumab is very expensive. The transfer of omalizumab dispensing from community to hospital pharmacy in April 2012 increased spending. This turned the spotlight on prescription practice.PurposeTo assess...

Asthma diagnosis and treatment – 1012. The efficacy of budesonide in the treatmetn of acute asthma in children: a double-blind, randomized, controlled trial

Background Current evidence suggests that inhaled glucocorticoids (IGC) have a more profound topical none genomic effect on bronchial airways as compared to systemic glucocorticoids. The value of adding IGC to current therapy of acute asthma is not well established. Methods We conducted a double-blind, randomized, two-arm, parallel groups, controlled clinical trial to compare the addition of budesonide 1500 mcg or placebo (normal saline) to standard acute asthma treatment (albuterol and ipratropium bromide) administered in 3 divided mixed doses within 1 hour in the emergency department (ED). Children 2-12 years of age with moderate or severe acute asthma, scoring 8-15/15 on a well-validated scoring system were included. Both groups received a single dose of prednisone 2 mg/kg/day (max. 60 mg) at the beginning of therapy. The primary outcome was admission rate within 2-4 hours from starting therapy. Results A total of 723 children were enrolled in the study over 17 months duration, of whom 139 were allowed to re-enroll and be randomized to constitute 906 randomization assignments (458 on the treatment group and 448 on the control group); with baseline mean + SD asthma score of 10.63 + 1.73; age 5.52 + 2.76 years; 35% girls; 30.8% (16.5%) with baseline severe asthma score of ≥12 (≥ 13). Statistical Analysis plan allowed for the potential dependency in response due to reenrollments of a subset of children, using Generalized Linear Mixed Modeling (GLMM) techniques. Baseline demographic and clinical characteristics were not significantly different between the two randomized groups. Seventy-five out of 458 (16.4%) of the treatment group vs. 82/448 (18.3%) of the control group were admitted, (OR 0.85, CI: 0.59-1.23, p-value=0.39). Among the severe asthmatics with baseline score ≥13, treatment vs. placebo group, GLMM adjusted admission rate was 30% vs. 47%, indicating a 17% difference in admission rate in favor of the treatment group (adjusted OR of 0.49, CI: 0.25-0.95; p-value= 0.035) that indicated a 51% reduction in the risk of admission for the treatment vs. control group. Conclusions Children with baseline severe asthma score ≥13 who were treated with budesonide had a significant reduction in their admission rate.

Use of anti-asthmatic medications as a proxy for prevalence of asthma in children and adolescents in Norway:a nationwide prescription database analysis

The validity of using self-reported or parental reported asthma symptoms and/or doctor-diagnosed asthma in the estimation of asthma prevalence among children has been questioned. The aim of this study was to assess the prevalence of dispensed anti-asthmatic medications as a proxy of asthma among children and adolescents aged 0-19 years in Norway. Prescription data on subjects aged 0-19 years receiving at least one prescription for an anti-asthmatic during 2004 were retrieved from the nationwide Norwegian Prescription Database. Overall, 108,719 (9.1% of the Norwegian population aged 0-19 years) individuals received at least one prescription for medication(s) for obstructive airway diseases. The application of criteria that restricted the study population to those receiving inhaled anti-asthmatic medications and those receiving medications reimbursed by the Norwegian health care system for asthma resulted in the identification of 64,458 (5.4%) individuals (4.6% of girls and 6.2% of boys). The prevalence varied by age, with a maximum in both genders at about 2 years of age (7.0% of girls and 10.1% of boys) and a minimum in girls at about 10 years of age (3.3%) and in boys at about 19 years of age (3.5%). Anti-asthmatic inhalants were more frequently prescribed among boys than among girls during the first 15 years of life. Of the children treated, 75% received inhaled glucocorticoids (ICS) in combination with beta2-agonists, of whom 38% received a fixed combination in one inhaler. In 2004, about 1 in 20 Norwegians aged 0-19 years were in need of medical treatment for asthma for at least 3 months, reflecting ongoing and clinically important asthma. A rather high proportion of children received fixed combinations of ICS and long-acting beta2-agonists, which may indicate moderate to severe asthma.

Adrenal Function in Children with Severe Asthma Treated with High-Dose Inhaled Glucocorticoids: Recommended Screening Tests in Outpatient Conditions

A number of previous studies have suggested that adrenal suppression occurs in asthmatic children treated with high-doses of inhaled glucocorticoids (IGC). This study was designed to determine the frequency of adrenal suppression in children with severe asthma treated with recommended doses of IGC: namely 500-1,000 microg/day of fluticasone propionate or the equivalent of budesonide (1,000-2,000 microg/day) for a period of at least 12 months. Early morning cortisol (F) and ACTH serum levels were measured in 27 severe asthmatics aged 6-16 years old. The children underwent a low dose ACTH test (1 microg/1.73 m2) with a parallel glucose measurement. Twenty-four hour urine collection was performed before examination for free F (UfF) and creatinine levels. There were no clinical manifestations of adrenal hypofunction in the analyzed children. Of the 27 patients, 22 had normal basal and post-stimulatory levels of F and normal UfF, and the other five (18.5%) had basal serum F levels of <400 nmol/l. Four of the five also had normal post-stimulatory levels of F and normal UfF. One child had a subnormal peak F value of 484 nmol/l during the ACTH test. None of the patients had a suppressed serum ACTH level, but an elevated ACTH level was found in four children. This study provided biochemical evidence of suboptimal adrenal function in one child in the examined group (3.7%) and a good response to stimulation in all the others, even in those with slightly reduced basal cortisol levels. This study showed that the use of fluticasone in doses of up to 1,000 microg/day (or the equivalent of budesonide) as long-term treatment of children with severe asthma did not substantially affect their adrenal function.

Calcitriol does not prevent bone loss in patients with asthma receiving corticosteroid therapy: a double-blind placebo-controlled trial

Oral glucocorticoid therapy reduces bone mineral density (BMD) and increases fracture risk. It is uncertain whether inhaled glucocorticoids, the most commonly used long-term therapy for asthma, have a similar effect. If bone loss does occur, it is unclear whether this is preventable by calcitriol. Patients with asthma receiving inhalational plus intermittent oral glucocorticoids lose bone, and treatment with 0.5 microg/day of calcitriol will prevent bone loss. A 2-year randomized double-blind placebo-controlled trial. One hundred eight patients with asthma were stratified by gender, age, and inhaled glucocorticoid dose and treated with calcitriol (n=55) or placebo (n=53). There were 41 men (mean age 53.2+/-1.7 years) and 67 women (mean age 49.1+/-1 years) with moderate to severe asthma (requiring >/=800 microg/day of beclomethasone dipropionate or equivalent maintenance therapy). BMD values at the lumbar spine (LS) and femoral neck (FN) were measured at baseline and at 6, 12, and 24 months using dual x-ray absorptiometry. Changes in LS and FN BMD. Bone loss occurred in both groups at the FN (both p<0.03) and at the LS in the calcitriol (p<0.001), but not the control, group. Bone loss was not less in the calcitriol group at either site. Patients with asthma receiving inhalational plus intermittent short courses of oral glucocorticoids lose bone. Calcitriol is unlikely to be appropriate therapy against this bone loss.

COPDX: an update of guidelines for the management of chronic obstructive pulmonary disease with a review of recent evidence

Long-acting beta(2) agonists are an effective and convenient treatment for chronic obstructive pulmonary disease (COPD), but do not significantly improve lung function. The long-acting anticholinergic tiotropium, which can be taken once daily, decreases exertional dyspnoea and increases endurance by reducing hyperinflation. The role in COPD of the combination of a long-acting beta(2) agonist and a glucocorticoid in a single inhaler remains unclear. The minimum duration of an effective pulmonary rehabilitation program that includes exercise training is 6 weeks. Long-term treatment with inhaled glucocorticoids may reduce the rate of decline in lung function, but the effect is small. Aminophylline should no longer be routinely used in acute exacerbations of COPD. Non-invasive positive pressure ventilation (NPPV) reduces mortality and hospital stay in patients with acute hypercapnic ventilatory failure; it is also an effective weaning strategy for patients who require intubation. Further studies are required to clarify the role of NPPV in the long-term management of stable COPD.