Biomedical subjects

Job van der Palen

Publications and source records attributed to Job van der Palen.

17 recordsLinked to original sources

PubMed2026

Developing low-carbon metered-dose inhalers: effects of propellant HFA-152a on mucociliary clearance and bronchoconstriction in two Phase 1 randomised trials.

BACKGROUND: To reduce the impact of respiratory care on climate change, metered-dose inhalers (MDIs) are being reformulated with low-global warming potential (GWP) propellants. Next-generation propellant hydrofluoroalkane (HFA)-152a has >90% lower GWP than HFA-134a. As part of the safety evaluation for HFA-152a, mucociliary clearance (MCC), bronchoconstriction and safety were compared with HFA-134a. METHODS: Two Phase 1, randomised, two-way crossover studies (NCT06506266/NCT06702462) were conducted. MCC study: healthy participants inhaled HFA-152a and HFA-134a in two 7-day sequences. MCC was quantified as area under radiolabelled particle retention time curve over 4 h (AUC0-4h) after nebulised 99mTc sulphur colloid, following each propellant. Bronchoconstriction study: patients with mild asthma inhaled single doses of HFA-152a and HFA-134a. Non-inferiority of HFA-152a versus HFA-134a was defined as percent change in FEV1 (litres), 15 min post dose (95% confidence intervals [CI]: lower limit >-10%, upper limit >0%). Both studies assessed safety. RESULTS: In 22 healthy participants, the impact on MCC did not differ between HFA-134a and HFA-152a (AUC0-4h geometric mean ratio [90% CI]: 1.00 [0.99, 1.01]). In 19 patients with mild asthma, neither HFA-152a nor HFA-134a induced bronchoconstriction (percent change in FEV1 at 15 min: -0.37% [HFA-152a] vs -0.60% [HFA-134a]); HFA-152a was non-inferior to HFA-134a (mean difference [95% CI]: 0.23% [-3.61, 4.07]). Adverse event (AE) rates were low and similar for both propellants in both studies; all AEs were mild, with no serious AEs or deaths. CONCLUSION: HFA-152a and HFA-134a had almost identical effects on MCC, neither induced bronchoconstriction, supporting MDI reformulation with the low-GWP propellant HFA-152a.

Humans↗

PubMed2006

Prospective determinants of smoking cessation in COPD patients within a high intensity or a brief counseling intervention.

OBJECTIVES: The aims of this study were to identify prospective determinants of smoking cessation in COPD patients, and to assess whether prospective determinants vary between two different cessation interventions. METHODS: Two hundred and twenty-five moderate to severe COPD patients were randomly allocated to two smoking cessation interventions. One-year cotinine-validated continuous abstinence rates were 9% for the minimal intervention strategy for lung patients (LMIS) and 19% for the SmokeStopTherapy (SST). The baseline characteristics that showed a significant univariate relationship with 1-year continuous abstinence (p<.20) were included in the logistic regression model. This procedure was performed for each intervention separately. Variables that did not remain independent predictors were removed. RESULTS: For the SST separately, no independent significant predictor remained. For the LMIS, attitude towards smoking cessation (OR: 11.8; 95% CI: 1.7-81.5; p=.013) and cotinine level (OR: 2.1; 95% CI: 1.08-3.93; p=.028) remained significant predictors. Within the LMIS, 31% of the variance in continuous abstinence was explained by these variables (p=.003). CONCLUSION: This study suggests that a moderately intensive intervention (LMIS) is primarily suitable for COPD patients with a positive attitude regarding smoking cessation. The more intensive SST can be an alternative for patients without such baseline characteristic. PRACTICE IMPLICATIONS: This stepped-care approach in smoking cessation counseling may be useful in clinical practice and will enable health care providers to match interventions to individual needs and increase efficiency.

Adult↗

PubMed2006

Relation between lipoprotein(a) and fibrinogen and serial intravascular ultrasound plaque progression in left main coronary arteries.

OBJECTIVES: Patients with elevated lipoprotein(a) [Lp(a)] and fibrinogen levels have an increased risk of coronary heart disease and adverse cardiovascular events. There is evidence that coronary plaque progression is linked to a higher risk for future cardiovascular events. BACKGROUND: There are no data demonstrating a relation between Lp(a), fibrinogen, and directly measured coronary plaque progression over time. METHODS: We performed a retrospective analysis of serial intravascular ultrasound (IVUS) studies of 60 left main stems (18 +/- 9 months apart) to evaluate plaque progression in relation to Lp(a) and fibrinogen levels and association with adverse cardiovascular events. RESULTS: There was a positive correlation between Lp(a) (r = 0.58; p < 0.0001), fibrinogen (r = 0.48; p < 0.0001), and changes in plaque-plus-media area. Patients with plaque progression (n = 41) had higher Lp(a) (30 +/- 26 mg/dl vs. 14 +/- 9 mg/dl; p < 0.0012) and fibrinogen (295 +/- 88 mg/dl vs. 240 +/- 72 mg/dl; p = 0.019) levels than patients with plaque regression (n = 19). Multivariate linear regression analysis showed Log Lp(a) (regression coefficient = 9.45; p = 0.0008) but not fibrinogen to be independently associated with plaque progression. A total of 19 patients suffered from adverse cardiovascular events; they had higher Lp(a) (44 +/- 30 mg/dl vs. 16 +/- 12 mg/dl; p < 0.0001) and fibrinogen (342 +/- 73 mg/dl vs. 248 +/- 76 mg/dl; p < 0.0001) levels. Multivariate logistic regression analysis showed Log Lp(a) (odds ratio 10.20, 95% confidence interval 2.36 to 44.13; p = 0.0019) and fibrinogen (odds ratio 1.01, 95% confidence interval 1.00 to 1.03; p = 0.018) were independently associated with adverse cardiovascular events. CONCLUSIONS: Serial IVUS showed a positive correlation between Lp(a) and fibrinogen levels and plaque progression. Lp(a), but not fibrinogen, remains independently associated with plaque progression. In addition, the present data suggest a considerable incremental value of Lp(a) in predicting cardiovascular risk.

Aged↗

PubMed2006

Timing of radiotherapy and survival benefit in breast cancer.

PURPOSE: To look at the optimum timing of radiotherapy in breast-conserving therapy (BCT) in relation to outcome in breast cancer. METHODS: We analyzed 1473 BCT on 1446 breast cancer patients from our prospective cohort, stage I or II, node-negative, and without adjuvant systemic therapy. Timing was defined as time from lumpectomy till radiotherapy. Patients were categorized into three timing tertiles: 1-36 days, 37-53 days, and 54-112 days. RESULTS: The 10-year local relapse-free survival rates did not show significant differences between the three groups. The 10-year Distant Metastasis-Free Survival (DMFS) was 78.9% for the first tertile, versus 86.1% (HR 0.6; P = 0.009) for the second, and 90.7% (HR 0.3; P < 0.001) for the third. The 10-year Disease-specific Survival (DSS) was 83.8% for the first tertile, versus 90.6% (HR 0.5; P = 0.007) for the second, and 97.2% (HR 02; P < 0.001) for the third. Also in multivariate Cox regression analysis the second (HR 0.6; P = 0.053) and the third tertile (HR 0.3; P = 0.002) had significantly better DSS. CONCLUSION: Timing of radiotherapy in BCT for breast cancer seems to be highly important in relation to survival. This study shows a 40-70% relative survival benefit with timing after 36 days.

Adult↗

PubMed2006

Allele variants of the cytochrome P450 2C9 genotype in white subjects from The Netherlands with serious gastroduodenal ulcers attributable to the use of NSAIDs.

BACKGROUND: The most common serious adverse effects (AEs) associated with NSAID therapy are bleeding and perforated gastroduodenal ulcers. These AEs are dose related, and reduced oral clearance of NSAIDs associated with polymorphisms of cytochrome P450 (CYP) would, theoretically, increase the risk for AEs. OBJECTIVE: The purpose of this study was to determine whether polymorphisms of the CYP2C9 genotype are associated with the development of serious complications of NSAID-related ulcers. METHODS: We examined the records of patients with complications of serious NSAID-related ulcers who were hospitalized from November 2001 to December 2003. Diagnosis was confirmed by endoscopy or abdominal surgery, and a group of consecutive subjects was identified for genetic analysis. CYP2C9 allele frequencies were determined and compared with those in a matched cohort of subjects receiving stable weekly maintenance doses of oral coumarin anticoagulants. Allele frequencies also were compared with those in matched cohorts from earlier studies. RESULTS: All 26 subjects with serious NSAID-related ulcers were white, 15 (58%) were female, and the median age was 74.5 years (range, 32-96 years). All 87 subjects in the reference group were white, 24 (28%) were female, and the median age was 69 years (range, 48-81 years). CYP2C9 genotype frequencies did not differ significantly between subjects with serious complications of NSAID-related ulcers and subjects using oral coumarin anticoagulants. The genotype frequencies in both groups were similar to those reported in previous studies in white subjects. CONCLUSION: The CYP2C9 genotype was not a significant or clinically relevant risk factor in the development of serious NSAID-related ulcers in this group of subjects.

Adult↗

PubMed2006

Consistency in endovascular aneurysm repair suitability assessment requires group decision audit.

INTRODUCTION: Proper selection of patient and stent-graft combinations in endovascular aneurysm repair (EVAR) depends on knowledge and experience with the different types of stents that have to be adapted to the patient's unique abdominal aortoiliac anatomy. The aim of this study was to analyze the consistency and variance in EVAR suitability assessment between clinicians. METHODS: Worksheets that contained anatomic data derived from computed tomography scans and angiography were compiled for 202 patients. Five clinicians, all experienced in EVAR surgery, assessed the anatomic data on the worksheets for suitability for three types of stent-grafts. The obtained 3030 assessments represented a quantification of the likelihood of success the clinician expected for effective and durable sealing and fixation of the stent-graft in EVAR. The Delphi method was used to determine consensus in the thinking process among clinicians, and kappa analysis was used to determine the proportion of variances in the assessment result between clinicians. RESULTS: With the Delphi method, Cronbach alpha values of 0.87, 0.87, and 0.90 were reached for the three types of stent-grafts in the second assessment round. The individual clinician-group correlation in round two was between 0.69 and 0.86 for clinicians 1, 2, 3, and 4. Between clinician 5 and the others, correlation varied between 0.43 and 0.64. The kappa values ranged between 0.32 and 0.51 among clinicians 1, 2, and 3. Between clinician 5 and the others, kappa values between 0.08 and 0.29 were reached. CONCLUSION: EVAR suitability estimation in a cohort of patients is highly consistent in a group of experienced clinicians. The EVAR suitability estimation at the individual patient level varies substantially between clinicians, however. Aggregating expert opinions in abdominal aortic aneurysm anatomic suitability assessment for EVAR had the opportunity to replace individual clinician decision diversification in a more solid and consistent group decision process.

Aged↗

PubMed2005

The effect of the initiation of renal replacement therapy on lipid profile and oxidative stress during the first 6 months of treatment.

BACKGROUND: Disturbed lipoproteins and increased oxidative stress are two of the "non-traditional" cardiovascular risk factors in chronic renal failure. There are very few prospective data of the influence of dialysis on these two factors. In the present study we investigated the effects of the initiation of both hemo- and peritoneal dialysis therapy on lipoproteins and parameters of LDL oxidation. METHODS: In this prospective cohort study, we assessed lipoproteins, plasma lipid peroxides and in vitro copper-induced LDL oxidation in 46 patients with end-stage renal disease prior to the start of dialysis and after 6 months of treatment with either hemodialysis (n=33) or peritoneal dialysis (n=13). RESULTS: After 6 months of treatment with hemodialysis there was an increase in total cholesterol (4.6+/-1.1 vs. 5.0+/-1.3 mmol/l; p<0.05) and triglycerides (2.0+/-0.9 vs. 2.8+/-1.6 mmol/l; p<0.03). In the peritoneal dialysis group the lipoproteins did not change. Regarding lipid peroxides and in vitro copper-induced LDL oxidation, also no changes were observed after 6 months of treatment in both groups. CONCLUSION: Dyslipidemia aggravates after 6 months of hemodialysis but not after 6 months of peritoneal dialysis. During this period, no net effects on oxidative stress were demonstrated.

Female↗

PubMed2004

What general practitioners and paediatricians think about their patients' asthma.

The Asthma Insight and Reality in Europe (AIRE) study showed that the current management and treatment of asthma in Europe falls short of the goals set in the GINA guidelines. Patient care may be negatively influenced by the physicians' underestimation of their patients' disease state, and overestimation of their patients' knowledge of asthma management. We interviewed 118 paediatricians and 152 general practitioners (response rate 70 and 86%, respectively) in order to get an insight into the physicians view on his patients' asthma management. A questionnaire containing similar items to those used in the AIRE study was used. Dutch physicians believe that the asthma of the majority of their patients is well controlled and underestimate the prevalence of daytime symptoms. They believe that their patients are aware of the differences between reliever medication and maintenance medication and overestimate the number of patients in possession of a written action plan. Dutch paediatricians and general practitioners underestimate the severity of their patients' disease state and overestimate their patients' knowledge of disease management.

Absenteeism↗

PubMed2004

Clinical predictors of bacterial involvement in exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: The wide use of antibiotics for treatment of exacerbations of chronic obstructive pulmonary disease (COPD) lacks evidence. The efficacy is debatable, and bacterial involvement in exacerbation is difficult to verify. The aim of this prospective study was to identify factors that can help to estimate the probability that a microorganism is involved in exacerbation of COPD and, therefore, predict the success of antibiotic treatment. METHODS: Clinical data and sputum samples were obtained from 116 patients during exacerbation of COPD. Bacterial infection was defined by the abundant presence of >or=1 potential pathological microorganism in relation to the normal flora in sputum. RESULTS: Of 116 exacerbations, 22 (19%) had bacterial involvement. The combination of a negative result of a sputum Gram stain, a relevant nonclinical decrease in lung function (compared with baseline measurements), and occurrence of <2 exacerbations in the previous year were 100% predictive of a nonbacterial origin of the exacerbation. The presence of all 3 of these clinical characteristics yielded a positive predictive value of 67% for a bacterial exacerbation. CONCLUSIONS: Patients presenting with an exacerbation who have a negative result of sputum Gram stain, do not have a clinically relevant decrease in lung function, and have experienced <2 exacerbations of COPD in the previous year do not require antibiotic treatment [corrected]. A treatment protocol taking into account these variables might lead to a 5%-24% reduction in unnecessary treatment with antibiotics, depending on actual prescription rates.

Administration, Inhalation↗

PubMed2004

A qualitative evaluation of a comprehensive self-management programme for COPD patients: effectiveness from the patients' perspective.

The COPE self-management programme, including a self-management education course, self-treatment of exacerbations and a fitness programme, appeared to have no significant effect on health related quality of life (HRQoL) as measured by the St. George's Respiratory Questionnaire (SGRQ). This is in contrast to our hypothesis and despite expressions of satisfaction of patients to healthcare workers. To understand this discrepancy, a qualitative study was performed. A purposive sample of 20 participants of the COPE self-management programme were interviewed at home using in-depth, semi-structured interviews. Interviews were audio taped and transcribed verbatim and analysed according grounded theory. The fitness programme was most positively evaluated by patients due to the perceived increase of exercise capacity and the social aspect of the group training. Major effects gained by the self-management education course reported by patients were the skills to evenly distribute their energy and to listen to their body signals. Most patients thought favourable about self-treatment of exacerbations. The possibility to start early, not having to call a doctor and autonomy were raised as important advantages. Furthermore, several patients reported increased self-confidence and coping behaviour as important effects of the COPE programme. Finally, many patients reported feeling safe due to the frequent follow-up visits and 24h access to the hospital, and this aspect elicited to be very important. In this study, the qualitative interviews suggest that the SGRQ and possibly other existing HRQoL instruments might fail to capture the full experience of patients in self-management studies. The need for more elaborate qualitative research on this subject is indicated.

Adaptation, Psychological↗

PubMed2004

Incremental cost-effectiveness of cyclooxygenase 2-selective versus nonselective nonsteroidal anti-inflammatory drugs in a cohort of coumarin users: a pharmacoeconomic analysis linked to a case-control study.

BACKGROUND: A previous case-control study involving concomitant users of coumarin and nonsteroidal anti-inflammatory drugs (NSAIDs) found that cyclooxygenase 2 (COX-2)-selective NSAIDs were associated with fewer bleeding complications than nonselective NSAIDs. OBJECTIVE: The goal of this study was to determine the incremental cost-effectiveness of COX-2-selective versus nonselective NSAIDs in relation to the occurrence of bleeding complications in a cohort of concomitant coumarin users. METHODS: The pharmacoeconomic evaluation was linked to a case-control analysis (patients with and without bleeding complications) based on data from the earlier study in users of concomitant coumarin and NSAIDs. Medical costs associated with NSAID use and bleeding complications were estimated according to Dutch guidelines for pharmacoeconomic analyses, based on Dutch drug prices and national averages for health care costs. Rofecoxib, meloxicam, and nabumetone were considered COX-2 selective. Total costs were calculated and compared for 2 hypothetical scenarios in which patients used either COX-2-selective or nonselective NSAIDs. Sensitivity analyses were performed in which both the odds ratios (ORs) and the costs of NSAIDs and bleeding episodes were varied. RESULTS: A total of 1,491 bleeding complications occurred in 4400 coumarin users: among the 221 (15%) NSAID users with a bleeding episode, 96% used a nonselective NSAID and 4% used a COX-2-selective NSAID. The adjusted OR of a bleeding episode for nonselective compared with COX-2-selective NSAIDs was 3.07 (95% CI, 1.18-8.03). The estimated mean cost of a bleeding episode was 478 per patient. Factoring in the excess cost of a COX-2-selective NSAID compared with a nonselective NSAID, as well as the cost savings in averted bleeding episodes, it was determined that there would be net medical cost savings of 53,800 and 162 averted bleeding episodes if the entire patient group received COX-2-selective NSAIDs rather than nonselective NSAIDs. The sensitivity analysis showed these results to be robust. CONCLUSION: In this study population of concomitant coumarin and NSAID users, the reduction in bleeding complications with the use of more expensive COX-2-selective inhibitors was associated with net medical cost savings compared with nonselective NSAIDs.

Aged↗

PubMed2004

Managing COPD: no more nihilism!

This special issue of Patient Education and Counseling is long overdue. During most of the last two decades asthma, and notably asthma self-management has been in the spotlight, while COPD has had to endure a nihilistic approach. The first sign that interest was shifting to the treatment of COPD came from a few large randomized trials on the use of inhaled corticosteroids (ICS) in COPD. Although these studies demonstrated a moderate effect of ICS in COPD, it has become clear that true improvements in the management of this chronic disease will have to come from behavioral interventions. This special issue of Patient Education and Counseling is dedicated solely to the non-pharmaceutical management of COPD. It addresses many issues related to behavioral therapy, such as smoking cessation, exercise training, nutritional aspects, and self-management programs, including action plans to self-treat exacerbations. With the availability of all the treatment and management options, described in this special issue, a nihilistic attitude toward the patient with COPD is no longer justified.

Adrenal Cortex Hormones↗

PubMed2004

Management of stable COPD.

Chronic obstructive pulmonary disease (COPD) is a systemic disease with major impact worldwide. In the treatment of COPD a holistic approach should be taken. In order to reach this, an individual treatment plan should be made which includes at least elements of smoking cessation, optimisation of pulmonary status by pharmacotherapy and exercise embedded in a new lifestyle. Furthermore, more research on nutritional and metabolic intervention strategies for COPD patients is needed. With the availability of all these treatment options, a nihilistic attitude toward the patient with COPD is no longer justified.

Adrenal Cortex Hormones↗

PubMed2004

The effect of a minimal contact smoking cessation programme in out-patients with chronic obstructive pulmonary disease: a pre-post-test study.

This study assessed the efficacy of an individual, minimal contact, smoking cessation programme in chronic obstructive pulmonary disease (COPD) patients, using a pre-post-test design. The study was part of a large ongoing investigation into the efficacy of self-management in patients with COPD (the COPE-study). In total, the participants received three 15-30 min home-based counselling sessions. Additionally, patients were provided with a written self-help manual. On the patient's request, the chest physician prescribed bupropion or nicotine replacement therapy (NRT). Cessation rates after nine months were based on self-report, and afterwards confirmed by salivary cotinine analysis. Patients were biochemically classified as smoker if their cotinine levels exceeded 20 ng/ml. At baseline, one third of the 269 patients in the COPE-study were active smokers (according to self-report). Almost 70% (n=64) of these patients were willing to participate in the smoking cessation program. After nine months follow-up, 23 (36.5%) patients self-reported abstinence. However, the cotinine validated abstinence rate was much lower: 12.7% (n=8), implying that the actual abstinence rate is severely overestimated by self-report in this study. The results suggest that the (validated) effectiveness of this intervention is probably in line with that of comparable programmes for "healthy" persons. However, considering the urgent need for quitting in COPD patients, a more intensive programme resulting in higher quit rates, seems to be required for this high-risk population.

Adult↗

PubMed2004

Oxidative stress in patients with end-stage renal disease prior to the start of renal replacement therapy.

BACKGROUND/AIM: In patients with end-stage renal disease (ESRD), cardiovascular complications are the main cause of death. Increased oxidative stress is one of the risk factors for enhanced atherosclerosis in this population. Literature data vary partially dependent on differences in methodology. The present study compares three different methods: plasma lipid peroxides, the newly developed measurement of circulating oxidized LDL (Ox-LDL) particles and the frequently used copper-induced LDL oxidation lag time. METHODS: We assessed plasma lipid peroxides, circulating Ox-LDL and in vitro copper-induced LDL oxidation lag time in 47 non-diabetic patients with ESRD, at the start of renal replacement therapy, and compared these with 41 age- and sex-matched controls. RESULTS: In ESRD, total cholesterol (4.6 +/- 1.1 vs. 5.6 +/- 0.9 mmol/l; p < 0.001), LDL cholesterol (2.8 +/- 0.8 vs. 3.5 +/- 0.7 mmol/l; p < 0.001) and HDL cholesterol (1.0 +/- 0.3 vs. 1.4 +/- 0.4 mmol/l; p < 0.001) were lower compared to controls. Plasma lipid peroxides were higher (1.1 +/- 0.5 vs. 0.8 +/- 0.5 micromol/l; p = 0.003) in ESRD. No differences were observed in plasma Ox-LDL (63.1 +/- 62.0 vs. 55.3 +/- 48.0 mg/l). However, due to the lower plasma LDL cholesterol in ESRD, LDL oxidation level was increased in ESRD (7.1 +/- 0.1 vs. 4.2 +/- 0.3%; p = 0.03). LDL lag time was slightly longer (89 +/- 11 vs. 84 +/- 11 min; p = 0.04) in ESRD. There were no significant differences regarding the amount and rate of dienes produced. CONCLUSIONS: Elevated levels of lipid peroxides and higher LDL oxidation levels support the theory that ESRD is associated with increased oxidative stress, which may explain the accelerated atherosclerosis. The measured amount of oxidative stress is not reflected by in vitro oxidizability of LDL.

Biomarkers↗

PubMed2003

The value of a positive margin for invasive carcinoma in breast-conservative treatment in relation to local recurrence is limited to young women only.

PURPOSE: To identify the importance of positive margins for invasive carcinoma on local control in patients treated with breast-conservative treatment (BCT). METHODS AND MATERIALS: A total of 1752 BCT with known margins were analyzed. Fifty-five patients had a second BCT, leaving 1697 patients for analysis. The margins were positive in 193/1752 BCT (11%). The median follow-up was 78 months. RESULTS: The 5- and 10-year local recurrence rates (LRR) were 3.1% and 6.9%, respectively, for negative margins vs. 5.6% and 12.2% for positive margins. A statistical interaction between age category and margin status was noted in relation to disease-free survival (DFS) and local relapse-free survival. The 5-year LRR for women < or =40 years was 8.4% for negative margins and 36.9% for positive margins (p = 0.005). In a multivariate analysis, a positive margin was significant. The 5-year LRR for women >40 years was 2.6% for negative and 2.2% for positive margins. The 5-year DFS for women </=40 years was 27.4% for positive and 74.5% for negative margins (p = 0.001). The 5-year DFS for women >40 years was 84.3% for positive and 87.2% for negative margins. CONCLUSION: Women < or =40 years are a special category of patients in breast cancer. Women < or =40 years must have negative margins for invasive carcinoma when treated with BCT. Minimum surgery for an optimal cosmetic result followed by irradiation, even with microscopic positive margins for invasive carcinoma, yields excellent results with regard to local control in patients older than 40 years.

Adult↗

PubMed2002

Effect of discontinuation of inhaled corticosteroids in patients with chronic obstructive pulmonary disease: the COPE study.

The aim of this double-blind single center study (the COPE study) was to investigate the effect of discontinuation of the inhaled corticosteroid fluticasone propionate (FP) on exacerbations and health-related quality of life in patients with chronic obstructive pulmonary disease. After 4 months of treatment with FP (1,000 microg/day), 244 patients were randomized to either continue FP or to receive placebo for 6 months: 123 patients continued FP (FP group), and 121 received placebo (placebo group). In the FP group, 58 (47%) patients developed at least one exacerbation compared with 69 (57%) in the placebo group. The hazard ratio of a first exacerbation in the placebo group compared with the FP group was 1.5 (95% confidence interval [CI] 1.1-2.1). In the placebo group 26 patients (21.5%) experienced rapid recurrent exacerbations and were subsequently unblinded and prescribed FP compared with 6 patients (4.9%) in the FP group (relative risk = 4.4; 95% CI 1.9-10.3). Over a 6-month period, a significant difference in favor of the FP group was observed in the total score (+2.48 95% CI 0.37-4.58), activity domain (+4.64 95% CI 1.60-7.68), and symptom domain (+4.58 95% CI 1.05-8.10) of the St. George's Respiratory Questionnaire. This study indicates that discontinuation of FP in patients with chronic obstructive pulmonary disease is associated with a more rapid onset and higher recurrence-risk of exacerbations and a significant deterioration in aspects of Health-Related Quality of Life.

Administration, Inhalation↗