Necessity of amoxicillin clavulanic acid in addition to prednisolone in mild-to-moderate COPD exacerbations

Background: The effectiveness of antibiotics in chronic obstructive pulmonary disease (COPD) exacerbations is still a matter of debate, especially in outpatients with an intermediate probability of bacterial infection. Methods: In this study, 35 COPD outpatients diagnosed by their chest physician with moderately severe COPD exacerbation, but without pneumonia, were randomised in a double blind, placebo-controlled study. Patients had one or two of the following characteristics: a positive Gram's stain of the sputum, 2 or more exacerbations in the previous year, a decrease in lung function of >200 mL and >12%. Patients received amoxicillin clavulanic acid (500/125 mg three times daily) or placebo for 7 days, always combined with a course of prednisolone (30 mg/day) for 7 days. Primary outcome was duration of the exacerbation. Additionally, we measured severity of the exacerbation, health-related quality of life, sputum parameters, number of relapses within 28 days and the number of re-exacerbations within 4 months after the study. Results: There was no difference observed in time to resolution of the exacerbation between the two groups (HR=1.12; (95% CI 0.5 to 2.3; p=0.77)), nor in any other treatment parameter. Conclusions: We detected no evidence for the effectiveness of addition of antibiotics to prednisolone for COPD exacerbations of moderate severity and with intermediate probability of bacterial infection in this underpowered study. More placebo-controlled studies are needed to properly define subgroups of COPD outpatients in which antibiotics are of additional value

The influence of type of inhalation device on adherence of COPD patients to inhaled medication

Objective: To study the influence of type of inhalation device on medication adherence of COPD patients. Methods: Adherence to inhalation medication of 795 patients was recorded from pharmacy records over 3 years. It was expressed as percentage and deemed good at ≥75–≤125%, sub-optimal ≥50–<75%, and poor <50% (underuse) or >125% (overuse). Since most patients used more than one device, 1379 medication periods were analyzed. Results: Patients using a Metered Dose Inhaler (MDI) or Diskus had a 2.3-fold and 2.2-fold increased risk, respectively, of suboptimal adherence versus good adherence, compared to Handihaler and a 2.1-fold and 2.2-fold increased risk, respectively, of underuse versus good adherence compared to Handihaler. Turbuhaler, MDI, Respimat had a 7.9-fold, 3.5-fold, and 2.0-fold increased risk, of overuse versus good adherence compared to Handihaler. Conclusions: In COPD, adherence to inhalation medication is device-related. Overuse was most pronounced for devices without a dose counter, devices with the ability to load a dosage without actual inhalation, or devices lacking feedback of correct inhalation. The design of the device seems to be related to underuse and overuse of inhaled medication. Future research might investigate whether prescribing a different device with similar medication improves therapy adherence

Differences in adherence to common inhaled medications in COPD

Objective: To study differences in adherence to common inhaled medications in COPD. Methods: Adherence of 795 patients was recorded from pharmacy records over 3 years in the COMIC cohort. It was expressed as percentage and deemed good at ≥75–≤125%, sub-optimal ≥50–<75%, and poor <50% (underuse) or >125% (overuse). Most patients used more than one medication, so we present 1379 medication periods. Results: The percentages of patients with good therapy adherence ranged from 43.2 (beclomethasone) –75.8% (tiotropium); suboptimal from 2.3 (budesonide) –23.3% (fluticasone); underuse from 4.4 (formoterol/budesonide) –18.2% (beclomethasone); and overuse from 5.1 (salmeterol) –38.6% (budesonide). Patients using fluticasone or salmeterol/fluticasone have a 2.3 and 2.0-fold increased risk of suboptimal versus good adherence compared to tiotropium. Patients using salmeterol/fluticasone or beclomethasone have a 2.3- and 4.6-fold increased risk of underuse versus good adherence compared to tiotropium. Patients using budesonide, salmeterol/fluticasone, formoterol/budesonide, ciclesonide and beclomethasone have an increased risk of overuse versus good adherence compared to tiotropium. Adherence to inhalation medication is inversely related to lung function. Conclusion: Therapy adherence to inhalation medication for the treatment of COPD is in our study related to the medication prescribed. Tiotropium showed the highest percentage of patients with good adherence, followed by ciclesonide, both dosed once daily. The idea of improving adherence by using combined preparations cannot be confirmed in this study. Further research is needed to investigate the possibilities of improving adherence by changing inhalation medication

Stability in eosinophil categorisation during subsequent severe exacerbations of COPD

BACKGROUND: The blood eosinophil count has been shown to be a promising biomarker for establishing personalised treatment strategies to reduce corticosteroid use, either inhaled or systemic, in chronic obstructive pulmonary disease (COPD). Eosinophil levels seem relatively stable over time in stable state, but little is known whether this is also true in subsequent severe acute exacerbations of COPD (AECOPD). AIMS AND OBJECTIVES: To determine the stability in eosinophil categorisation between two subsequent severe AECOPDs employing frequently used cut-off levels. METHODS: During two subsequent severe AECOPDs, blood eosinophil counts were determined at admission to the hospital in 237 patients in the Cohort of Mortality and Inflammation in COPD Study. The following four cut-off levels were analysed: absolute counts of eosinophils ≥0.2×10⁹/L (200 cells/µL) and ≥0.3×10⁹/L (300 cells/µL) and relative eosinophil percentage of ≥2% and ≥3% of total leucocyte count. Categorisations were considered stable if during the second AECOPD their blood eosinophil status led to the same classification: eosinophilic or not. RESULTS: Depending on the used cut-off, the overall stability in eosinophil categorisation varied between 70% and 85% during two subsequent AECOPDs. From patients who were eosinophilic at the first AECOPD, 34%–45% remained eosinophilic at the subsequent AECOPD, while 9%–21% of patients being non-eosinophilic at the first AECOPD became eosinophilic at the subsequent AECOPD. CONCLUSIONS: The eosinophil variability leads to category changes in subsequent AECOPDs, which limits the eosinophil categorisation stability. Therefore, measurement of eosinophils at each new exacerbation seems warranted

Amoxicillin concentrations in relation to beta-lactamase activity in sputum during exacerbations of chronic obstructive pulmonary disease

Background: Acute exacerbations of chronic obstructive pulmonary disease (COPD) are often treated with antibiotics. Theoretically, to be maximally effective, the antibiotic concentration at sites of infection should exceed the minimum inhibitory concentration at which 90% of the growth of potential pathogens is inhibited (MIC90). A previous study showed that most hospitalized COPD patients had sputum amoxicillin concentrations <MIC90 when treated with amoxicillin/clavulanic acid. Those with adequate sputum concentrations had better clinical outcomes. Low amoxicillin concentrations can be caused by beta-lactamase activity in the lungs. This study investigated whether patients with sputum amoxicillin concentrations <MIC90 had higher beta-lactamase activity in sputum than patients with a concentration ≥MIC90. Methods: In total, 23 patients hospitalized for acute exacerbations of COPD and treated with amoxicillin/clavulanic acid were included. Sputum and serum samples were collected at day 3 of treatment to determine beta-lactamase activity in sputum and amoxicillin concentrations in both sputum and serum. Results: We found no difference in beta-lactamase activity between patients with sputum amoxicillin concentrations <MIC90 and ≥MIC90 (P=0.79). Multivariate logistic regression analysis showed no significant relationship between beta-lactamase activity and sputum amoxicillin concentrations <MIC90 or ≥MIC90 (odds ratio 0.53; 95% confidence interval 0.23–1.2; P=0.13). Amoxicillin concentrations were <MIC90 in 78% of sputum samples and in 30% of serum samples. Conclusion: In patients treated with amoxicillin/clavulanic acid for an acute exacerbation of COPD, sputum beta-lactamase activity did not differ between those with sputum amoxicillin concentrations <MIC90 or ≥MIC90. The finding that the majority of patients had sputum amoxicillin concentrations <MIC90 suggests that current treatment with antibiotics for acute exacerbations of COPD should be optimized

A telehealth programme for self-management of COPD exacerbations and promotion of an active lifestyle: a pilot randomized controlled trial

The objective of this pilot study was to investigate the use of and satisfaction with a chronic obstructive pulmonary disease (COPD) telehealth program applied in both primary and secondary care. The program consisted of four modules: 1) activity coach for ambulant activity monitoring and real-time coaching of daily activity behavior, 2) web-based exercise program for home exercising, 3) self-management of COPD exacerbations via a triage diary on the web portal, including self-treatment of exacerbations, and 4) teleconsultation. Twenty-nine COPD patients were randomly assigned to either the intervention group (telehealth program for 9 months) or the control group (usual care). Page hits on the web portal showed the use of the program, and the Client Satisfaction Questionnaire showed satisfaction with received care. The telehealth program with decision support showed good satisfaction (mean 26.4, maximum score 32). The program was accessed on 86% of the treatment days, especially the diary. Patient adherence with the exercise scheme was low (21%). Health care providers seem to play an important role in patients’ adherence to telehealth in usual care. Future research should focus on full-scale implementation in daily care and investigating technological advances, like gaming, to increase adherence

Tissue micro array analysis of ganglioside N-glycolyl GM3 expression and signal transducer and activator of transcription (STAT)-3 activation in relation to dendritic cell infiltration and microvessel density in non-small cell lung cancer

Background: Tumor immune escape and angiogenesis contribute to tumor progression, and gangliosides and activation of signal transducer and activator of transcription (STAT)-3 are implicated in these processes. As both are considered as novel therapeutic targets, we assessed the possible association of ganglioside GM3 expression and STAT3 activation with suppression of dendritic cell (DC) activation and angiogenesis in non-small cell lung cancer (NSCLC). Methods: Immunohistochemistry was performed on a tissue array to determine N-glycolyl GM3 (GM3) and phosphorylated STAT3 (pSTAT3) expression in 176 primary NSCLC resections. Median values of GM3 and pSTAT3 expression were used as cut off. Microvessel density (MVD) was determined by CD34 staining and morphology. CD1a and CD83 were used to determine infiltrating immature and mature dendritic cells, respectively. Results: 94% and 71% of the NSCLC samples expressed GM3 and nuclear pSTAT3, respectively. Median overall survival was 40.0 months. Both low GM3 expression and high pSTAT3 expression were associated with a worse survival, which reached near significance for GM3 (P = 0.08). Microvessel density (MVD), determined by CD34 staining and morphology, was lower in NSCLC samples with high GM3 expression. CD1a(+) cells (immature DCs) were more frequent in NSCLC tissues as compared to peritumoral lung tissue, while CD83(+) cells (mature DCs) were more frequent in peritumoral lung tissue. CD83(+) DCs were less frequent in NSCLC tissues with high GM3 expression. Conclusion: GM3 and pSTAT3 are widely expressed in NSCLC. Based on CD83 expression, GM3, but not pSTAT3, appeared to be involved in tumor-induced DC suppression. pSTAT3 expression was not associated with MVD, while GM3 might play an anti-angiogenic rol

Excellent adherence and no contamination by physiotherapists involved in a randomized controlled trial on reactivation of COPD patients: a qualitative process evaluation study

Contains fulltext : 107813.pdf (publisher's version ) (Open Access)OBJECTIVE: To assess the adherence of physiotherapists to the study protocol and the occurrence of contamination bias during the course of a randomized controlled trial with a recruitment period of 2 years and a 1-year follow-up (COPE-II study). STUDY DESIGN AND SETTING: In the COPE-II study, intervention patients received a standardized physiotherapeutic reactivation intervention (COPE-active) and control patients received usual care. The latter could include regular physiotherapy treatment. Information about the adherence of physiotherapists with the study protocol was collected by performing a single interview with both intervention and control patients. Patients were only interviewed when they were currently receiving physiotherapy. Interviews were performed during two separate time periods, 10 months apart. Nine characteristics of the COPE-active intervention were scored. Scores were converted into percentages (0%, no aspects of COPE-active; 100%, full implementation of COPE-active). RESULTS: Fifty-one patients were interviewed (first period: intervention n = 14 and control n = 10; second period: intervention n = 18 and control n = 9). Adherence with the COPE-active protocol was high (median scores: period 1, 96.8%; period 2, 92.1%), and large contrasts in scores between the intervention and control group were found (period 1: 96.8% versus 22.7%; period 2: 92.1% versus 25.0%). The scores of patients treated by seven physiotherapists who trained patients of both study groups were similar to the scores of patients treated by physiotherapists who only trained patients of one study group. CONCLUSION: The adherence of physiotherapists with the COPE-active protocol was high, remained unchanged over time, and no obvious contamination bias occurred