Unmet needs in the treatment of idiopathic pulmonary fibrosis-insights from patient chart review in five European countries.

BACKGROUND: Two antifibrotic drugs, pirfenidone and nintedanib, are approved by the European Medicines Agency and the US Food and Drug Administration for the treatment of idiopathic pulmonary fibrosis (IPF). In this analysis, treatment patterns of European patients with IPF were investigated to understand antifibrotic prescribing and identify unmet needs in IPF treatment practice. METHODS: Between February and March 2016, respiratory physicians from France, Germany, Italy, Spain, and the UK participated in an online questionnaire designed to collect information on IPF treatment patterns in patients under their care. Patients were categorized as treated (received approved antifibrotics) or untreated (did not receive approved antifibrotics, but may have received other unapproved therapies). Classification of IPF diagnosis (confirmed/suspected) and severity ('mild'/'moderate'/'severe') for each patient was based on the individual physician's report. Patients' perspectives were not recorded in this study. RESULTS: In total, 290 physicians responded to the questionnaire. Overall, 54% of patients with IPF did not receive treatment with an approved antifibrotic. More patients had a confirmed IPF diagnosis in the treated (84%) versus the untreated (51%) population. Of patients with a confirmed diagnosis, 40% did not receive treatment. The treated population was younger than the untreated population (67 vs 70 years, respectively; p ≤ 0.01), with more frequent multidisciplinary team evaluation (83% vs 57%, respectively; p ≤ 0.01). A higher proportion of untreated patients had forced vital capacity > 80% at diagnosis versus treated patients. Of patients with 'mild' IPF, 71% did not receive an approved antifibrotic versus 41% and 60% of patients with 'moderate' and 'severe' IPF, respectively. CONCLUSIONS: Despite the availability of antifibrotic therapies, many European patients with confirmed IPF do not receive approved antifibrotic treatment. Importantly, there appears to be a reluctance to treat patients with 'mild' or 'stable' disease, and instead adopt a 'watch and wait' approach. More education is required to address diagnostic uncertainty, poor understanding of IPF and its treatments, and issues of treatment access. There is a need to increase physician awareness of the benefits associated with antifibrotic treatment across the spectrum of IPF severity.

Self-assessment of Allergic Rhinitis and Asthma (SACRA) Questionnaire-based Allergic Rhinitis Treatment Improves Asthma Control in Asthmatic Patients with Allergic Rhinitis.

Objective This study was conducted to investigate whether the add-on treatment of allergic rhinitis (AR) based on the Self-assessment of Allergic Rhinitis and Asthma (SACRA) questionnaire for assessing AR control improves both AR and asthma control in asthmatic patients with AR. Methods This multi-center prospective study was performed in Nagano prefecture, Japan. Two hundred five asthmatic patients and 23 respiratory physicians participated in the study. We administered add-on AR treatments based on the results of the SACRA questionnaire. After the first SACRA questionnaire, 67 asthmatic patients agreed to receive an add-on AR treatment. Three months after the AR treatment, a secondary SACRA questionnaire, asthma control test (ACT), and pulmonary function tests were performed. Results After the add-on AR treatment, the visual analogue scales (VASs) for AR and asthma, as assessed by the SACRA questionnaire and ACT score, were significantly improved in the patients of the AR+ group. With regard to the pulmonary function tests, the percent predicted vital capacity, and percent predicted forced expiratory volume in one second were also significantly improved. Regardless of whether the patients had previously undergone leukotriene receptor antagonists (LTRA) treatment, the VASs for AR and asthma and the ACT score were significantly improved in the AR+ group. However, the vital capacity (VC), forced vital capacity (FVC) and forced expiratory volume (FEV1) were only significantly improved in the AR+ group that had previously undergone LTRA treatment. Conclusion SACRA questionnaire-based add-on AR treatment would be convenient for the detection of AR by respiratory physicians and would offer improved asthma control. This questionnaire can also be used to assess the therapeutic effects.

Relationship between pulmonary function and indoor air pollution from coal combustion among adult residents in an inner-city area of southwest China

Few studies evaluate the amount of particulate matter less than 2.5 mm in diameter (PM2.5) in relation to a change in lung function among adults in a population. The aim of this study was to assess the association of coal as a domestic energy source to pulmonary function in an adult population in inner-city areas of Zunyi city in China where coal use is common. In a cross-sectional study of 104 households, pulmonary function measurements were assessed and compared in 110 coal users and 121 non-coal users (≥18 years old) who were all nonsmokers. Several sociodemographic factors were assessed by questionnaire, and ventilatory function measurements including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), the FEV1/FVC ratio, and peak expiratory flow rate (PEFR) were compared between the 2 groups. The amount of PM2.5 was also measured in all residences. There was a significant increase in the relative concentration of PM2.5 in the indoor kitchens and living rooms of the coal-exposed group compared to the non-coal-exposed group. In multivariate analysis, current exposure to coal smoke was associated with a 31.7% decrease in FVC, a 42.0% decrease in FEV1, a 7.46% decrease in the FEV1/FVC ratio, and a 23.1% decrease in PEFR in adult residents. The slope of lung function decrease for Chinese adults is approximately a 2-L decrease in FVC, a 3-L decrease in FEV1, and an 8 L/s decrease in PEFR per count per minute of PM2.5 exposure. These results demonstrate the harmful effects of indoor air pollution from coal smoke on the lung function of adult residents and emphasize the need for public health efforts to decrease exposure to coal smoke.

Relationship between pulmonary function and indoor air pollution from coal combustion among adult residents in an inner-city area of southwest China.

Few studies evaluate the amount of particulate matter less than 2.5 mm in diameter (PM2.5) in relation to a change in lung function among adults in a population. The aim of this study was to assess the association of coal as a domestic energy source to pulmonary function in an adult population in inner-city areas of Zunyi city in China where coal use is common. In a cross-sectional study of 104 households, pulmonary function measurements were assessed and compared in 110 coal users and 121 non-coal users (≥18 years old) who were all nonsmokers. Several sociodemographic factors were assessed by questionnaire, and ventilatory function measurements including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), the FEV1/FVC ratio, and peak expiratory flow rate (PEFR) were compared between the 2 groups. The amount of PM2.5 was also measured in all residences. There was a significant increase in the relative concentration of PM2.5 in the indoor kitchens and living rooms of the coal-exposed group compared to the non-coal-exposed group. In multivariate analysis, current exposure to coal smoke was associated with a 31.7% decrease in FVC, a 42.0% decrease in FEV1, a 7.46% decrease in the FEV1/FVC ratio, and a 23.1% decrease in PEFR in adult residents. The slope of lung function decrease for Chinese adults is approximately a 2-L decrease in FVC, a 3-L decrease in FEV1, and an 8 L/s decrease in PEFR per count per minute of PM2.5 exposure. These results demonstrate the harmful effects of indoor air pollution from coal smoke on the lung function of adult residents and emphasize the need for public health efforts to decrease exposure to coal smoke.

Aldehyde dehydrogenase 2-a potential genetic risk factor for lung function among southern Chinese: evidence from the Guangzhou Biobank Cohort Study.

PURPOSE: In Asia, moderate alcohol users have better lung function. Never users have more inactive aldehyde dehydrogenase 2 (ALDH2) alleles (A) potentially generating confounding because inactive alleles may increase acetaldehyde exposure and reduce lung function. METHODS: We examined the association of ALDH2 genotypes with percentage predicted lung function (forced expiratory volume in 1 second; forced vital capacity) for age, sex, and height among 5641 older Chinese using multivariable linear regression. RESULTS: ALDH2 genotypes were associated with alcohol use and height but not other attributes. Inactive alleles were inversely associated with lung function (percentage predicted forced expiratory volume in 1 second -1.52%, 95% confidence interval [CI], -2.52% to -0.51% for one inactive allele and -2.05%, 95% CI, -3.85% to -0.26% for two inactive alleles compared with two active alleles; and for percentage predicted forced vital capacity -1.25%, 95% CI -2.15% to -0.35% and -1.65%, 95% CI, -3.25% to -0.04%). The association of moderate use with lung function was attenuated after adjusting for ALDH2, in addition to other potential confounders. CONCLUSIONS: Previous findings in Chinese may be confounded by ALDH2. High frequency of inactive ALDH2 alleles in East Asia may exacerbate the effect of environmental acetaldehyde exposure on lung function and potentially on chronic obstructive pulmonary disease.

Influence of salmeterol/fluticasone via single versus separate inhalers on exacerbations in severe/very severe COPD.

BACKGROUND: Patients with severe or very severe chronic obstructive pulmonary disease (COPD) frequently suffer repeated exacerbations generating high health care utilization costs. Combined corticosteroid and bronchodilator treatment using a single inhaler might - via improved compliance - reduce exacerbation rates. OBJECTIVES: Our aim was to obtain descriptive data on exacerbation rates in patients with severe or very severe COPD (GOLD Stages III and IV as per GOLD 2009 classification) receiving salmeterol xinafoate/fluticasone propionate via a single inhaler (SFC) or via separate inhalers (Sal/FP) in addition to individual existing therapy in order to investigate the potential benefit of a fixed combination device as compared with two separate devices due to potentially improved patients' compliance. METHODS: This prospective, randomized, open-label, parallel-group, multi-center, exploratory study was conducted in Germany in 2007-2009. Patients were required to have suffered ≥ 2 moderate/severe exacerbations in the preceding year. RESULTS: 213 patients (SFC: 108 patients, Sal/FP: 105 patients) from 23 centers were evaluated. Approximately 25% of patients showed COPD Stage IV. On average patients had suffered 2.3 ± 0.6 moderate/severe exacerbations in the preceding year. The annual rate of moderate/severe exacerbations observed in the study was similar in both treatment groups (SFC: 0.86 ± 0.13; Sal/FP: 0.86 ± 0.14; exacerbation rate ratio SFC/Sal/FP: 1.00; p = 0.73; negative binomial model). Compliance was high and comparable in both groups. Besides COPD exacerbations, pneumonia (5.6%) and nasopharyngitis (5.2%) were the most common adverse events. CONCLUSION: Observed exacerbation rates were lower than those reported at baseline. No substantial difference was observed between administration of salmeterol xinafoate/fluticasone propionate via a single inhaler and separate inhalers. Treatment was safe and well tolerated. ClinicalTrials.gov Identifier: NCT00527826.

Clinical management and outcome of refractory asthma in the UK from the British Thoracic Society Difficult Asthma Registry.

Refractory asthma represents a significant unmet clinical need. Data from a national online registry audited clinical outcome in 349 adults with refractory asthma from four UK specialist centres in the British Thoracic Society Difficult Asthma Network. At follow-up, lung function improved, with a reduction in important healthcare outcomes, specifically hospital admission, unscheduled healthcare visits and rescue courses of oral steroids. The most frequent therapeutic intervention was maintenance oral corticosteroids and most steroid sparing agents (apart from omalizumab) demonstrated minimal steroid sparing benefit. A significant unmet clinical need remains in this group, specifically a requirement for therapies which reduce systemic steroid exposure.

Quantitative texture-based assessment of one-year changes in fibrotic reticular patterns on HRCT in scleroderma lung disease treated with oral cyclophosphamide.

OBJECTIVES: The Scleroderma Lung Study showed the efficacy of cyclophosphamide in modestly improving the forced vital capacity (FVC) compared with placebo over 1 year. Using changes in texture-based scores that quantify lung fibrosis as the percentage involvement of reticulation patterns, the effectiveness of cyclophosphamide was re-assessed by examining its impact on quantitative lung fibrosis (QLF). METHODS: Axial HRCT images were acquired (1-mm slice thickness, 10-mm increments) in the prone position at inspiration. A validated model for quantifying interstitial disease patterns was applied to images from 83 subjects at baseline and 12 months. Scores were calculated for six zones (upper, mid, lower of the right/left lung) and the whole lung. Average changes were compared. Correlations were performed between QLF and physiological and clinical scores. RESULTS: From the most severe zones identified at baseline, QLF scores decreased by 2.6% in the cyclophosphamide group, whereas they increased by 9.1% in the placebo group, leading to ~12% difference (p = 0.0027). Between-treatment difference in whole lung QLF was ~5% (p = 0.0190). Significant associations were observed between changes in QLF and FVC (r = -0.33), dyspnea score (r = -0.29), and consensus visual score (p = 0.0001). CONCLUSIONS: QLF scores provide an objective quantitative tool for assessing treatment efficacy in scleroderma-related interstitial lung disease.

The beneficial effects of preperitoneal catheter analgesia following colon and rectal resections: a prospective, randomized, double-blind, placebo-controlled study.

BACKGROUND: Preperitoneal catheter analgesia following abdominal surgery has attracted interest in the last decade. We conducted this study to evaluate the benefits of preperitoneal catheter analgesia in managing pain after abdominal colon and rectal resections. METHODS: A total of 50 patients undergoing colon and rectal resections for benign and malignant diseases received analgesic medicines via an epidural catheter placed just prior to surgery and a preperitoneal catheter placed at the end of the surgical procedure. Patients were instructed to use the epidural patient-controlled analgesia (PCA) device freely and were randomized into two groups after obtaining the approval of the Institutional Review Board: Group A received 10 ml of levobupivacaine twice a day postoperatively via preperitoneal catheter and group B received only 10 ml of saline. Demographics, surgical characteristics, pain scores recorded four days following surgery, analgesic volume used from the epidural PCA, clinical outcomes (length of stay, time to first bowel movement, time to first passage of gas or stool, time to first oral intake) and respiratory function test results (preoperative vs. postoperative) were compared. RESULTS: There were no significant differences in demographics or surgical characteristics between both groups. Pain scores were similar. Clinical outcomes and respiratory functions were comparable. The use of analgesic volume via epidural catheter was significantly lower in group A than in group B (P = 0.032). CONCLUSIONS: Preperitoneal catheter analgesia significantly decreased the need for epidural drug consumption and proved to be a beneficial adjunct for postoperative pain management of patients who underwent colon and rectal resections.

Is the EQ-5D responsive to recovery from a moderate COPD exacerbation?

BACKGROUND: To correctly estimate the cost-effectiveness of treatments that reduce COPD exacerbations, the utility gains from preventing exacerbations need to be measured. This requires utility measurement during exacerbations. AIM: To assess the ability of the EQ-5D to detect the recovery from moderate COPD exacerbations. METHODS: In the US, 65 COPD and/or chronic bronchitis patients (≥40 years old smokers or ex-smokers with a history of 10 pack-years) were enrolled within 48 h of symptom onset of the exacerbation. Patients completed the EQ-5D at enrollment and after 7, 14 and 42 days. Symptoms and medication use were recorded in diaries. Change over time and loss of quality-adjusted life years (QALYs) due to the exacerbation was estimated. Using standardized response mean (SRM) as the metric of responsiveness, we compared the responsiveness of the EQ-5D to the responsiveness of morning peak expiratory flow rate, rescue medication use and symptom scores. SRMs were also used to assess whether patients with greater improvements in peak expiratory flow rate, rescue medication use, symptom scores, clinician global impression of change, and patient global impression of change had a greater improvement in EQ-5D than patients with smaller improvement. RESULTS: Mean utility index scores (standard deviation) using the US value set were 0.683 (0.209), 0.726 (0.216), 0.768 (0.169) and 0.760 (0.181) at days 1, 7, 14 and 42, respectively. The mean of each patient's lowest index score, either at visit 1 or visit 2, was 0.651 (0.213). Over the course of 6 weeks there was a highly significant improvement in mean utility. The greatest improvement was seen between day 7 and day 14. Patients lost on average 0.00896 QALY (0.0086) or 3.27 (3.13) quality-adjusted life days during the exacerbation. The EQ-5D (SRM: 0.653) was more responsive to change than peak expiratory flow (0.269), rescue medication use (0.343) and sputum symptom scores (0.322) and equally responsive as cough (0.587) and dyspnea (0.638) symptom scores. CONCLUSION: The EQ-5D is responsive to the recovery from a moderate COPD exacerbation.

Effect of oral magnesium supplementation on measures of airway resistance and subjective assessment of asthma control and quality of life in men and women with mild to moderate asthma: a randomized placebo controlled trial.

BACKGROUND: Epidemiological data shows low dietary magnesium(Mg) may be related to incidence and progression of asthma. OBJECTIVE: To determine if long term(6.5 month) treatment with oral Mg would improve asthma control and increase serum measures of Mg status in men and women with mild-to-moderate asthma. SUBJECTS: 55 males and females aged 21 to 55 years with mild to moderate asthma according to the 2002 National Heart, Lung, and Blood Institute(NHLBI) and Asthma Education and Prevention Program(NAEPP) guidelines and who used only beta-agonists or inhaled corticosteroids(ICS) as asthma medications were enrolled. DESIGN: Subjects were randomly assigned to consume 340 mg(170 mg twice a day) of Mg or a placebo for 6.5 months. MEASUREMENTS: Multiple measures of Mg status including serum, erythrocyte, urine, dietary, ionized and IV Mg were measured. OBJECTIVE: markers of asthma control were: methacholine challenge test(MCCT) and pulmonary function test(PFT) results. Subjective validated questionnaires on asthma quality of life(AQLQ) and control(ACQ) were completed by participants. Markers of inflammation, including c-reactive protein(CRP) and exhaled nitric oxide(eNO) were determined. RESULTS: The concentration of methacholine required to cause a 20% drop in forced expiratory volume in in minute(FEV(1)) increased significantly from baseline to month 6 within the Mg group. Peak expiratory flow rate(PEFR) showed a 5.8% predicted improvement over time(P = 0.03) in those consuming the Mg. There was significant improvement in AQLQ mean score units(P < 0.01) and in overall ACQ score only in the Mg group(P = 0.05) after 6.5 months of supplementation. Despite these improvements, there were no significant changes in any of the markers of Mg status. CONCLUSION: Adults who received oral Mg supplements showed improvement in objective measures of bronchial reactivity to methacholine and PEFR and in subjective measures of asthma control and quality of life.

Permutation test following covariate-adaptive randomization in randomized controlled trials.

In randomized controlled trials, patients are recruited and randomly allocated to treatments. Patients are never randomly sampled from large population of patients on treatments under study. Therefore, it is important to consider the design and statistical analysis based on the randomization model. In this article, we show theoretically that a permutation test based on the difference in means is identical to analysis of covariance if marginal covariate balance is completely attained. Our theoretical results and Monte Carlo simulation study suggest that the permutation test following Pocock-Simon's covariate-adaptive randomization can be a useful alternative to traditional population-based tests in a confirmatory randomized controlled trial with important prognostic factors. The proposed procedure is illustrated with modified data from the randomized placebo-controlled trial of pirfenidone.

Assessing uncertainty in spatial exposure models for air pollution health effects assessment.

BACKGROUND: Although numerous epidemiologic studies now use models of intraurban exposure, there has been little systematic evaluation of the performance of different models. OBJECTIVES: In this present article we proposed a modeling framework for assessing exposure model performance and the role of spatial autocorrelation in the estimation of health effects. METHODS: We obtained data from an exposure measurement substudy of subjects from the Southern California Children's Health Study. We examined how the addition of spatial correlations to a previously described unified exposure and health outcome modeling framework affects estimates of exposure-response relationships using the substudy data. The methods proposed build upon the previous work, which developed measurement-error techniques to estimate long-term nitrogen dioxide exposure and its effect on lung function in children. In this present article, we further develop these methods by introducing between- and within-community spatial autocorrelation error terms to evaluate effects of air pollution on forced vital capacity. The analytical methods developed are set in a Bayesian framework where multistage models are fitted jointly, properly incorporating parameter estimation uncertainty at all levels of the modeling process. RESULTS: Results suggest that the inclusion of residual spatial error terms improves the prediction of adverse health effects. These findings also demonstrate how residual spatial error may be used as a diagnostic for comparing exposure model performance.

Asthma prevention in urbanites.

OBJECTIVES: The purpose of this intervention was to evaluate the efficacy of low-literacy asthma education and the provision of free asthma controller medications to persons living in the urban inner-city. METHODS: The intervention was conducted as a series of three studies. A health educator from the Johnson Health Center (JHC) performed chart reviews in the first two studies to identify urban asthma patients with frequent emergency department (ED) visits. The third study evaluated participants from the community-at-large who came to the ED for episodic asthma care. Free controller medications and education were provided to participants in all three studies. RESULTS: Emergency department utilization, inpatient admissions, and consumer medical costs were greatly reduced in all three studies during the 5-year intervention period. Lung function improved, and participants reported an improved quality of life. CONCLUSION: The provision of free asthma controller medications resulted in greatly improved asthma management and reduced costs. There was no evidence that an asthma education component per se produced any of the changes.

Sequential testing for efficacy in clinical trials with non-transient effects.

This paper describes a new type of sequential testing for clinical trials. The sequential nature of the data is not from additional patients, but rather from longer follow-up times. At each analysis, the null hypothesis that all treatments are equivalent in effect on the outcome after that amount of time is tested. The trial might still have staggered entry or not, but the key feature is that a different statistical hypothesis is tested at each analysis. It is assumed that any effect of treatment is non-transient, allowing a conclusion to be drawn in favour of one treatment or the other based on a difference at a single follow-up time. It is shown that a general method based on the Bonferroni inequality can be used to obtain critical cutpoints for sequential testing, that controls the chance of a type I error for the clinical decision. This method is applicable regardless of the test used at each analysis. In the case of a two-armed trial with a Gaussian outcome variable, it is shown how simulation can be used to obtain critical cutpoints that maintain the chance of a type I error for the clinical decision. The methods are compared by Monte-Carlo simulation, and it is seen that in most practical cases the Bonferroni method is not very conservative. The Bonferroni procedure is illustrated on the results of a real clinical trial of Pirfenidone on pulmonary fibrosis in Hermansky-Pudlak Syndrome.

Pharmacological approaches to stable chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) causes disabling, slowly progressive breathlessness on exertion, chronic cough and sputum production. Its natural history is punctuated by increasingly frequent exacerbations which in turn accelerate disease progression and reduce a patient's quality of life. COPD has previously been ignored in the mistaken belief that nothing could be done. There are now a number of therapies that can be used to reduce symptoms and prevent exacerbations. In turn this reduces disability, improves the patient's health-related quality of life and has the potential to reduce costs to the health service and to society.

[Assessment of reversibility in airway obstruction]. / Analiza sposobów interpretacji próby rozkurczowej.

In the medical literature there have been described some methods to determine bronchodilator response. They are different because of the required percentage increase in FEV1 and /or FVC and the way of expressing results -as the percent of predicted or initial value. This study on 38 subjects evaluated that there is better bronchodilator responses when the results are presented as the percentage of the initial value compared with the predicted value. The intensity of improvement in FEV1 depends on the baseline airway obstruction. There are more meaningful responses in subjects with 'poor' initial value when using the criteria of change in FEV1 as a percentage of initial value. About 10% of positive responses are misunderstood as 'poor' when it was considered improvement only in FEV1 (they are positive with reference only to FVC).

Helium/oxygen mixture reduces the work of breathing at the end of the weaning process in patients with severe chronic obstructive pulmonary disease.

OBJECTIVE: To test the hypothesis that helium/oxygen mixture can reduce the work of breathing at the end of the weaning process in patients with chronic obstructive pulmonary disease. DESIGN: Prospective, randomized, crossover study. SETTING: Two medical intensive care units at two university tertiary care centers. PATIENTS: Thirteen patients with chronic obstructive pulmonary disease evaluated just before and after extubation. INTERVENTIONS: Helium/oxygen and air/oxygen mixtures were administered sequentially, for 20 mins each, in a randomized order, just before extubation. It was possible to repeat the study after extubation in five patients. MEASUREMENTS AND MAIN RESULTS: Before extubation, the helium/oxygen mixture induced no significant variation in the breathing pattern. By contrast, it reduced the work of breathing from 1.442 +/- 0.718 J/L (mean +/- sd) to 1.133 +/- 0.500 J/L (p <.05). This reduction was explained mainly by a reduction in the resistive component of the work of breathing from 0.662 +/- 0.376 to 0.459 +/- 0.256 J/L (p <.01). We also observed a slight reduction in the intrinsic positive end-expiratory pressure from 2.9 +/- 2.1 cm H(2)O to 2.1 +/- 1.8 cm H(2)O (p <.05). Similar results were also observed after extubation in five patients in whom the repetition of the study was possible. CONCLUSIONS: In spontaneously breathing intubated patients with chronic obstructive pulmonary disease recovering from an acute exacerbation, helium/oxygen mixture reduces the work of breathing as well as intrinsic positive end-expiratory pressure without modifying the breathing pattern.

Cost-effectiveness of fluticasone propionate in the treatment of chronic obstructive pulmonary disease: a double-blind randomized, placebo-controlled trial.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a debilitating disease and places a large financial burden on health-care systems and society. We prospectively evaluated the cost-effectiveness offluticasone propionate (FP) treatment in patients with moderate-to-severe COPD, who were symptomatic on regular bronchodilator therapy. METHODS: An economic analysis was performed in a 6-month, randomized, double-blind clinical trial comparing FP 1,000 microg/day with placebo in 281 patients aged 45-79 years with symptomatic moderate-to-severe COPD. Data on clinical efficacy, health-care resource use and productivity loss associated with the management of COPD were prospectively collected. The main outcome measures were the incremental cost-effectiveness of achieving a > or = 10% improvement in FEV1 and of remaining exacerbation-free throughout the study. The economic evaluation was costed from the perspective of the NHS (direct costs) and of society (direct and indirect costs). RESULTS: FP was significantly more effective than placebo in terms of the proportions of patients demonstrating a > or = 10% improvement in FEV1 (32 vs. 19%; P = 0.02) and remaining free of moderate/severe exacerbations (75 vs. 63%; P = 0.02). The difference between the groups in total costs was not significantly different. Incremental cost-effectiveness analyses showed that the additional clinical benefits of FP relativeto placebo, in terms of a > or = 10% improvement in FEV1 or an increased number of patients free of moderate/severe exacerbations, were achieved at minimal additional costs from an NHS perspective (additional 0.25 pounds per day for bath) or at a net saving from a societal perspective. Sensitivity analysis showed that these results were robust to changes in the underlying assumptions. CONCLUSIONS: Treatment with FP was associated with statistically significant clinical benefits in patients with moderate-to-severe COPD currently symptomatic on regular bronchodilator therapy. As the differences in direct and total costs compared with placebo were small and non-significant, this treatment can be considered cost-effective in this patient population.