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Marc Decramer

Publications and source records attributed to Marc Decramer.

29 records · Page 2Linked to original sources
PubMed2004

Clinical trial design considerations in assessing long-term functional impacts of tiotropium in COPD: the UPLIFT trial.

An accelerated loss of lung function is one of the defining characteristics of chronic obstructive pulmonary disease (COPD). To date, the only successful intervention shown to conclusively attenuate the loss of lung function over time is smoking cessation. Pharmacological interventions including inhaled corticosteroids and ipratropium bromide have not altered the rate of decline of lung function. Tiotropium is an inhaled anticholinergic that provides 24-hour bronchodilation with once-daily dosing due to prolonged muscarinic M3 receptor blockade. Controlled clinical trials have suggested sustained efficacy for periods of up to one year. We therefore initiated a four-year, controlled clinical trial (UPLIFT, Understanding the Potential Long-Term Impacts on Function with Tiotropium) in patients with COPD to evaluate the long-term effects of tiotropium on the rate of decline in lung function and health status as well as the frequency of exacerbations. The design of such large, long-term clinical trials presents unique methodological challenges including the definition of endpoints, the quality and variability of spirometric measurements and premature patient discontinuations from the trial. The present manuscript outlines the rationale for the UPLIFT study, and reviews the study design and the steps taken to address methodological challenges experienced in other long term studies. Careful design and implementation of the UPLIFT trial is anticipated to yield high quality results that will help in increasing our understanding of the long term natural history of COPD in a global population as well as to elucidate the role that tiotropium can play in affecting the course of this debilitating disease.

Administration, Inhalation↗
PubMed2004

Office spirometry significantly improves early detection of COPD in general practice: the DIDASCO Study.

STUDY OBJECTIVES: To determine if spirometry is essential for the early detection of COPD in general practice, compared to the screening value of a short questionnaire. METHODS: A prospective survey of the population aged 35 to 70 years visiting their general practitioner (GP) during a 12-week period, using a questionnaire on symptoms of obstructive lung disease (OLD). Spirometry was performed in all participants with positive answers and in a 10% random sample from the group without complaints. Twenty GPs were provided with a hand-held spirometer, and received training in performance and interpretation of lung function tests. All 35- to 70-year-old patients (n = 3,408) were screened for current use of bronchodilators. The subgroup receiving bronchodilators (n = 250, 7%) was assumed to have OLD, and was excluded. Airflow obstruction was defined according to the European Respiratory Society standards. RESULTS: The positive predictive power of the questionnaire was low (sensitivity, 58%; specificity, 78%; likelihood ratio, 2.6). One hundred twenty-six cases of formerly unknown OLD were detected in the group of patients with complaints, vs an extrapolated number of 90 in the group without complaints. Despite a negative predictive value of 95% for the questionnaire used, 42% of the newly diagnosed cases of OLD would not have been detected without spirometry. CONCLUSIONS: The use of a spirometer is mandatory if early stages of OLD are to be detected in general practice. Screening for airflow obstruction almost doubles the number of known patients with OLD.

Adult↗
PubMed2004

Mechanisms of improvement in exercise capacity using a rollator in patients with COPD.

STUDY OBJECTIVE: We analyzed the effects of the use of a rollator on walking distance and physiologic variables: pulmonary gas exchange, heart rate, minute ventilation (Ve), oxygen saturation, and symptoms during the 6-min walk test (6MWT) in patients with COPD. SETTING: Outpatient clinic at university hospital. PATIENTS: Fourteen patients with COPD in stable clinical condition. One patient had mild COPD, five patients had moderate COPD, six patients had severe COPD, and two patients had very severe COPD. INTERVENTIONS: Two 6MWTs were performed with a portable metabolic system (VmaxST 1.0; Viasys Healthcare; MEDA; Aartselaar, Belgium) with a rollator and without a rollator, in random order. In addition, maximal voluntary ventilation (MVV) was measured with and without a rollator, randomly. RESULTS: The median 6MWT distance increased significantly with a rollator: 416 m without a rollator (interquartile range [IQR], 396 to 435 m), vs 462 m with a rollator (IQR, 424 to 477 m) [p = 0.04]. Significant increases were also seen in oxygen uptake (0.04 L/min [IQR, - 0.002 to 0.09 L/min]); tidal volume (0.06 L/min [IQR, - 0.001 to 0.11 L/min]); and Ve (0.95 L/min [IQR, - 0.67 to 7.1 L/min]), recorded in the last minute of the 6MWT; as well as in MVV (3 L/min [IQR, 0 to 12 L/min]) [p < 0.05 for all]. Borg dyspnea scores tended to be lower with a rollator: 6 (IQR, 4 to 7) without a rollator, vs 5 (IQR, 4 to 7) with a rollator (p = 0.10). The variation in the 6MWT was explained by individual changes in walking efficiency (partial R(2) = 0.31) and changes in Ve (partial R(2) = 0.36) [p model < 0.04]. CONCLUSION: The use of a rollator improves walking distance of patients with COPD through an increased ventilatory capacity and/or better walking efficiency.

Aged↗
PubMed2003

Early changes in rat diaphragm biology with mechanical ventilation.

To better characterize the effects of 24-hour mechanical ventilation on diaphragm, the expression of myogenic transcription factors, myosin heavy chains, and sarcoplasmic/endoplasmic reticulum calcium-ATPase pumps was examined in rats. In the diaphragm of mechanically ventilated animals, the mRNA of MyoD, myosin heavy chain-2a and -2b, and sarcoplasmic/endoplasmic reticulum calcium-ATPase-1a decreased, whereas myogenin mRNA increased. In the diaphragm of anesthetized and spontaneously breathing rats, only the mRNA of MyoD and myosin heavy chain-2a decreased. MyoD and myogenin protein expression followed the changes at the mRNA, whereas the myosin heavy chain isoforms did not change. Parallel experiments involving the gastrocnemius were performed to assess the relative contribution of muscle shortening versus immobilization-induced deconditioning on muscle regulatory factor expression. Passive shortening produced no additional effects compared with immobilization-induced deconditioning. The overall changes followed a remarkably similar pattern except for MyoD protein expression, which increased in the gastrocnemius and decreased in the diaphragm while its mRNA diminished in both muscles. The early alterations in the expression of muscle protein and regulatory factors may serve as underlying molecular basis for the impaired diaphragm function seen after 24 hours of mechanical ventilation. Whether immobilization-induced deconditioning and/or passive shortening play a role in these alterations could not be fully unraveled.

Animals↗
PubMed2003

Detrimental effects of short-term mechanical ventilation on diaphragm function and IGF-I mRNA in rats.

OBJECTIVES: Because respiratory muscle weakness appears to play an important role in weaning from mechanical ventilation, we developed an animal model of mechanical ventilation with appropriate controls in order to determine whether 24 h of mechanical ventilation already affected diaphragmatic function. DESIGN AND INTERVENTIONS: Fifty-two male Wistar rats were randomized into three groups: a non-anesthetized control group (C, n=10), an anesthetized spontaneously breathing group (SB, n=9 out of 26), and an anesthetized and mechanically ventilated group (MV, n=12 out of 16). RESULTS: After 24 h, in vitro diaphragmatic force was decreased in SB group but even more so in MV group (i.e., 80 Hz: -15% in SB, P<0.005 vs C and -34% in MV group, P<0.005 vs C and SB). This was associated with a significant decrease in the diaphragm type I and type IIa dimensions in the SB group, which was more pronounced in the MV group. Interestingly, diaphragm IGF-I mRNA was decreased in the SB group (-14%, P<0.05 vs C), but more so in MV group (-29%, P<0.001 vs C and P<0.01 vs SB). Moreover, there was a significant correlation between diaphragm force and IGF-I mRNA (at 80 Hz r=0.51, P=0.0056). CONCLUSIONS: We conclude that 24 h of mechanical ventilation in rats, independently of anesthesia, already significantly reduced diaphragm force, fiber dimensions, and its IGF-I mRNA levels.

Animals↗
PubMedDate not supplied

Effects of N-acetylcysteine on outcomes in chronic obstructive pulmonary disease (Bronchitis Randomized on NAC Cost-Utility Study, BRONCUS): a randomised placebo-controlled trial.

BACKGROUND: Increased oxidative stress is important in the pathogenesis of chronic obstructive pulmonary disease (COPD). We postulated that treatment with the antioxidant N-acetylcysteine would reduce the rate of lung-function decline, reduce yearly exacerbation rate, and improve outcomes. METHODS: In a randomised placebo-controlled study in 50 centres, 523 patients with COPD were randomly assigned to 600 mg daily N-acetylcysteine or placebo. Patients were followed for 3 years. Primary outcomes were yearly reduction in forced expiratory volume in 1 s (FEV1) and the number of exacerbations per year. Analysis was by intention to treat. FINDINGS: The yearly rate of decline in FEV1 did not differ between patients assigned N-acetylcysteine and those assigned placebo (54 mL [SE 6] vs 47 mL [6]; difference in slope between groups 8 mL [9]; 95% CI -25 to 10). The number of exacerbations per year did not differ between groups (1.25 [SD 1.35] vs 1.29 [SD 1.46]; hazard ratio 0.99 [95% CI 0.89-1.10, p=0.85]). Subgroup analysis suggested that the exacerbation rate might be reduced with N acetylcysteine in patients not treated with inhaled corticosteroids and secondary analysis was suggestive of an effect on hyperinflation. INTERPRETATION: N-acetylcysteine is ineffective at prevention of deterioration in lung function and prevention of exacerbations in patients with COPD.

Acetylcysteine↗
PubMedDate not supplied

Chronic obstructive pulmonary disease and chronic heart failure: two muscle diseases?

Chronic obstructive pulmonary disease and congestive heart failure are two increasingly prevalent chronic diseases. Although care for these patients often is provided by different clinical teams, both disease conditions have much in common. In recent decades, more knowledge about the systemic impact of both diseases has become available, highlighting remarkable similarities in terms of prognostic factors and disease management. Rehabilitation programs deal with the systemic consequences of both diseases. Although clinical research also is conducted by various researchers investigating chronic obstructive pulmonary disease and chronic heart failure, it is worthwhile to compare the progress in relation to these two diseases over recent decades. Such comparison, the purpose of the current review, may help clinicians and scientists to learn about progress made in different, yet related, fields. The current review focuses on the similarities observed in the clinical impact of muscle weakness, the mechanisms of muscle dysfunction, the strategies to improve muscle function, and the effects of exercise training on chronic obstructive pulmonary disease and chronic heart failure.

Aged↗