One-year treatment with mometasone furoate in chronic obstructive pulmonary disease

Many patients with chronic obstructive pulmonary disease (COPD) are treated with twice daily (BID) inhaled corticosteroids (ICS). This study evaluated whether daily PM mometasone furoate administered via a dry powder inhaler (MF-DPI) was equally effective compared to twice daily dosing

Budesonide/formoterol as effective as prednisolone plus formoterol in acute exacerbations of COPD A double-blind, randomised, non-inferiority, parallel-group, multicentre study

<p>Abstract</p> <p>Background</p> <p>Oral corticosteroids and inhaled bronchodilators with or without antibiotics represent standard treatment of COPD exacerbations of moderate severity. Frequent courses of oral steroids may be a safety issue. We wanted to evaluate in an out-patient setting whether a 2-week course of inhaled budesonide/formoterol would be equally effective for treatment of acute COPD exacerbations as standard therapy in patients judged by the investigator not to require hospitalisation.</p> <p>Methods</p> <p>This was a double-blind, randomised, non-inferiority, parallel-group, multicentre study comparing two treatment strategies; two weeks' treatment with inhaled budesonide/formoterol (320/9 μg, qid) was compared with prednisolone (30 mg once daily) plus inhaled formoterol (9 μg bid) in patients with acute exacerbations of COPD attending a primary health care centre. Inclusion criteria were progressive dyspnoea for less than one week, FEV₁30–60% of predicted normal after acute treatment with a single dose of oral corticosteroid plus nebulised salbutamol/ipratropium bromide and no requirement for subsequent immediate hospitalisation, i.e the clinical status after the acute treatment allowed for sending the patient home.</p> <p>A total of 109 patients (mean age 67 years, 33 pack-years, mean FEV₁45% of predicted) were randomized to two weeks' double-blind treatment with budesonide/formoterol or prednisolone plus formoterol and subsequent open-label budesonide/formoterol (320/9 μg bid) for another 12 weeks. Change in FEV₁was the primary efficacy variable. Non-inferiority was predefined.</p> <p>Results</p> <p>Non-inferiority of budesonide/formoterol was proven because the lower limit of FEV₁-change (97.5% CI) was above 90% of the efficacy of the alternative treatment. Symptoms, quality of life, treatment failures, need for reliever medication (and exacerbations during follow-up) did not differ between the groups. No safety concerns were identified.</p> <p>Conclusion</p> <p>High dose budesonide/formoterol was as effective as prednisolone plus formoterol for the ambulatory treatment of acute exacerbations in non-hospitalized COPD patients. An early increase in budesonide/formoterol dose may therefore be tried before oral corticosteroids are used.</p> <p>Clinical trial registration</p> <p>NCT00259779</p

Spirometric changes in obstructive disease: after all, how much is significant?

OBJECTIVE: To establish the upper limits for changes in FEV1, slow vital capacity (SVC), FVC, and inspiratory capacity (IC) after placebo administration in patients with airflow obstruction. METHODS: One hundred and two adults with airflow obstruction (FEV1 = 62 ± 19% of predicted) were included in the study. All of the participants performed SVC and FVC maneuvers before and after the administration of placebo spray. The changes in FEV1, SVC, FVC, and IC were expressed as absolute values, percentage of change from baseline values, and percentage of predicted values, 95% CIs and 95th percentiles being calculated. Factor analysis was performed in order to determine how those changes clustered. RESULTS: Considering the 95% CIs and 95th percentiles and after rounding the values, we found that the upper limits for a significant response were as follows: FEV1 = 0.20 L, FVC = 0.20 L, SVC = 0.25 L, and IC = 0.30 L (expressed as absolute values); FEV1 = 12%, FVC = 7%, SVC = 10%, and IC = 15% (expressed as percentage of change from baseline values); and FEV1 = 7%, FVC = 6%, SVC = 7%, and IC = 12% (expressed as percentage of predicted values). CONCLUSIONS: In patients with airflow obstruction, IC varies more widely than do FVC and SVC. For IC, values greater than 0.30 L and 15% of change from the baseline value can be considered significant. For FVC, values greater than 0.20 L and 7% of change from the baseline value are significant. Alternatively, changes exceeding 0.20 L and 7% of the predicted value can be considered significant for FEV1 and FVC. On factor analysis, spirometric parameters clustered into three dimensions, expressing changes in flows, volumes, and dynamic hyperinflation.OBJETIVO: Estabelecer os limites superiores para mudanças em VEF1, capacidade vital lenta (CVL), CVF e capacidade inspiratória (CI) após o uso de placebo em pacientes com obstrução ao fluxo aéreo. MÉTODOS: Cento e dois adultos com obstrução ao fluxo aéreo (VEF1 = 62 ± 19% do previsto) foram incluídos neste estudo. Todos os participantes realizaram manobras de CVL e CVF antes e depois do uso de spray de placebo. As mudanças em VEF1, CVL, CVF e CI foram expressas em valores absolutos, porcentagem de variação em relação aos valores basais e porcentagem dos valores previstos, e foram calculados os IC95% e os percentis 95. A análise fatorial foi realizada a fim de determinar como essas alterações se agrupavam. RESULTADOS: Considerando os IC95% e percentis 95 e após o arredondamento dos valores, obtivemos os seguintes limites superiores para resposta significante: VEF1 = 0,20 L, CVF = 0,20 L, CVL = 0,25 L e CI = 0,30 L (em valores absolutos); VEF1 = 12%, CVF = 7%, CVL = 10% e CI = 15% (em porcentagem de variação em relação aos valores basais) e VEF1 = 7%, CVF = 6%, CVL = 7% e CI = 12% (em porcentagem dos valores previstos). CONCLUSÕES: Em pacientes com obstrução ao fluxo aéreo, a CI apresenta maior variabilidade do que a CVF e a CVL. Para a CI, valores maiores que 0,30 L e 15% de variação em relação ao valor basal devem ser considerados significantes. Para CVF, valores maiores que 0,20L e 7% de variação em relação ao valor basal são significantes. Alternativamente, alterações de mais de 0,20 L e 7% do previsto no VEF1 e na CVF devem ser consideradas significantes. Na análise fatorial, os parâmetros espirométricos se agruparam em três dimensões, expressando mudanças no fluxo, volume e hiperinsuflação dinâmica.Universidade Federal do Rio Grande do NorteUniversidade Federal de São Paulo (UNIFESP)Hospital do Servidor Público Estadual de São PauloUNIFESPSciEL

Risk factors for exacerbations and pneumonia in patients with chronic obstructive pulmonary disease: a pooled analysis.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) are at risk of exacerbations and pneumonia; how the risk factors interact is unclear. METHODS: This post-hoc, pooled analysis included studies of COPD patients treated with inhaled corticosteroid (ICS)/long-acting β2 agonist (LABA) combinations and comparator arms of ICS, LABA, and/or placebo. Backward elimination via Cox's proportional hazards regression modelling evaluated which combination of risk factors best predicts time to first (a) pneumonia, and (b) moderate/severe COPD exacerbation. RESULTS: Five studies contributed: NCT01009463, NCT01017952, NCT00144911, NCT00115492, and NCT00268216. Low body mass index (BMI), exacerbation history, worsening lung function (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage), and ICS treatment were identified as factors increasing pneumonia risk. BMI was the only pneumonia risk factor influenced by ICS treatment, with ICS further increasing risk for those with BMI <25 kg/m2. The modelled probability of pneumonia varied between 3 and 12% during the first year. Higher exacerbation risk was associated with a history of exacerbations, poorer lung function (GOLD stage), female sex and absence of ICS treatment. The influence of the other exacerbation risk factors was not modified by ICS treatment. Modelled probabilities of an exacerbation varied between 31 and 82% during the first year. CONCLUSIONS: The probability of an exacerbation was considerably higher than for pneumonia. ICS reduced exacerbations but did not influence the effect of risks associated with prior exacerbation history, GOLD stage, or female sex. The only identified risk factor for ICS-induced pneumonia was BMI <25 kg/m2. Analyses of this type may help the development of COPD risk equations

Quantifying the real life risk profile of inhaled corticosteroids in COPD by record linkage analysis

BACKGROUND: Inhaled corticosteroids (ICS), especially when prescribed in combination with long-acting β(2) agonists have been shown to improve COPD outcomes. Although there is consistent evidence linking ICS with adverse effects such as pneumonia, the complete risk profile is unclear with conflicting evidence on any association between ICS and the incidence or worsening of existing diabetes, cataracts and fractures. We investigated this using record linkage in a Dundee COPD population. METHODS: A record linkage study linking COPD and diabetes datasets with prescription, hospitalisation and mortality data via a unique Community Health Index (CHI) number. A Cox regression model was used to determine the association between ICS use and new diabetes or worsening of existing diabetes and hospitalisations for pneumonia, fractures or cataracts after adjusting for potential confounders. A time dependent analysis of exposure comparing time on versus off ICS was used to take into account patients changing their exposure status during follow-up and to prevent immortal time bias. RESULTS: 4305 subjects (3243 exposed to ICS, total of 17,229 person-years of exposure and 1062 non exposed, with a follow-up of 4,508 patient-years) were eligible for the study. There were 239 cases of new diabetes (DM) and 265 cases of worsening DM, 550 admissions for pneumonia, 288 hospitalisations for fracture and 505 cataract related admissions. The hazard ratio for the association between cumulative ICS and outcomes were 0.70 (0.43-1.12), 0.57 (0.24-1.37), 1.38 (1.09-1.74), 1.08 (0.73-1.59) and 1.42 (1.07-1.88) after multivariate analysis respectively. CONCLUSION: The use of ICS in our cohort was not associated with new onset of diabetes, worsening of existing diabetes or fracture hospitalisation. There was however an association with increased cataracts and pneumonia hospitalisations

Effects of different antibiotic classes on airway bacteria in stable COPD using culture and molecular techniques: a randomised controlled trial

Long-term antibiotic therapy is used to prevent exacerbations of COPD but there is uncertainty over whether this reduces airway bacteria. The optimum antibiotic choice remains unknown. We conducted an exploratory trial in stable patients with COPD comparing three antibiotic regimens against placebo

Comparison of resource use by COPD patients on inhaled therapies with long-acting bronchodilators: a database study

<p>Abstract</p> <p>Background</p> <p>The purpose of this analysis was to compare health care costs and utilization among COPD patients who had long-acting beta-2 agonist (LABA) OR long-acting muscarinic antagonist (LAMA); LABA AND LAMA; or LABA, LAMA, AND inhaled corticosteroid (ICS) prescription claims.</p> <p>Methods</p> <p>This was a 12 month pre-post, retrospective analysis using COPD patients in a national administrative insurance database. Propensity score and exact matching were used to match patients 1:1:1 between the LABA or LAMA (formoterol, salmeterol, or tiotropium), LABA and LAMA (tiotropium/formoterol or tiotropium/salmeterol), and LABA, LAMA and ICS (bronchodilators plus steroid) groups. Post-period comparisons were evaluated with analysis of covariance. Costs were evaluated from a commercial payer perspective.</p> <p>Results</p> <p>A total of 523 patients were matched using 29 pre-period variables (e.g., demographics, medication exposure). Post-match assessments indicated balance among the cohorts. COPD-related costs differed among groups (LABA or LAMA $2,051 SE = 91; LABA and LAMA$2,823 SE = 62; LABA, LAMA and ICS $3,546 SE = 89; all p < .0001) with the differences driven by study medication costs. However, non-study COPD medication costs were higher for the LABA or LAMA therapy group ($911 SE = 91) compared to the LABA and LAMA therapy group ($668 SE = 58; p = 0.0238) and non-study respiratory medications were approximately$100 greater for the LABA or LAMA therapy group relative to both LABA and LAMA (p = .0018) and LABA, LAMA, and ICS (p = .0071) therapy groups. While there was no observed difference in outpatient costs, there was a slightly higher number of outpatient visits per patient in the LABA and LAMA (25.5 SE = 0.9, p = 0.0070) relative to the LABA or LAMA therapy group (22.3 SE = 0.8) and higher utilization (89.7% of patients) with COPD visits in the LABA and LAMA therapy group relative to both the LABA or LAMA (73.8%; p < .0001) and LABA, LAMA and ICS therapy groups (85.3; p = 0.0305).</p> <p>Conclusions</p> <p>Significant cost differences driven mainly by pharmaceuticals were observed among LABA or LAMA, LABA and LAMA and LABA, LAMA and ICS therapies. A COPD-related cost offset was observed from single bronchodilator to two bronchodilators. Addition of an ICS with two bronchodilators resulted in higher treatment costs without reduction in other COPD-related costs compared with two bronchodilators.</p