Paul VanderValk

Stable-State Midrange-Proadrenomedullin Level Is a Strong Predictor of Mortality in Patients With COPD

ABSTRACT BACKGROUND Midrange-proadrenomedullin (MR-proADM) has been shown to be elevated in patients hospitalized for an acute exacerbation of COPD (AECOPD) and in patients with community acquired pneumonia. MR-proADM when measured during AECOPD has also been shown to be a predictor for mortality, we hypothesized that MR-proADM levels measured in a stable state could also predict mortality. METHODS We included 181 patients in whom we had paired plasma samples for MR-proADM determinations during stable state and at hospitalization for AECOPD when they also produced sputum. Time to death or censoring was compared between patients with MR-proADM above or below the median of 0.71 nmol/L. The predictive value of MR-proADM for survival was determined by calculating the C statistic. RESULTS COPD patients with MR-proADM levels > 0.71 nmol/L in stable state had a 3-fold higher risk of dying than patients with MR-proADM levels < 0.71 nmol/L (HR 2.98 (95% CI 1.51-5.90); C statistic 0.76). The corrected Odds Ratio for one year mortality was 8.90 (95% CI 1.94 - 44.6) in patients with high MR-proADM levels measured in stable state, compared to patients with low levels. CONCLUSIONS MR-proADM measured in stable state showed to be a strong predictor for mortality in COPD patients. MR-proADM is far more convenient to measure than other predictors for mortality in COPD such as the BODE score.BACKGROUND Midrange-proadrenomedullin (MR-proADM) has been shown to be elevated in patients hospitalized for an acute exacerbation of COPD (AECOPD) and in patients with community-acquired pneumonia. When measured during AECOPDs, MR-proADM has also been shown to be a predictor of mortality. We hypothesized that MR-proADM levels measured in a stable state could also predict mortality. METHODS We included 181 patients in whom we had paired plasma samples for MR-proADM determinations during a stable state and at hospitalization for an AECOPD when they also produced sputum. Time to death or censoring was compared between patients with MR-proADM above or below the median of 0.71 nmol/L. The predictive value of MR-proADM for survival was determined by calculating the C statistic. RESULTS Patients with COPD and MR-proADM levels > 0.71 nmol/L in the stable state had a threefold-higher risk of dying than did patients with MR-proADM levels < 0.71 nmol/L (hazard ratio, 2.98 [95% CI, 1.51-5.90]; C statistic, 0.76). The corrected OR for 1-year mortality was 8.90 (95% CI, 1.94-44.6) in patients with high MR-proADM levels measured in the stable state, compared with patients with low levels measured in the stable state. CONCLUSIONS MR-proADM measured in the stable state appeared to be a strong predictor of mortality in patients with COPD. MR-proADM is far easier to measure than other predictors of mortality in COPD, such as BMI, airflow obstruction, dyspnea, and exercise capacity score.

Stable state MR-proadrenomedullin level is a strong predictor for mortality in COPD patients.

ABSTRACT BACKGROUND Midrange-proadrenomedullin (MR-proADM) has been shown to be elevated in patients hospitalized for an acute exacerbation of COPD (AECOPD) and in patients with community acquired pneumonia. MR-proADM when measured during AECOPD has also been shown to be a predictor for mortality, we hypothesized that MR-proADM levels measured in a stable state could also predict mortality. METHODS We included 181 patients in whom we had paired plasma samples for MR-proADM determinations during stable state and at hospitalization for AECOPD when they also produced sputum. Time to death or censoring was compared between patients with MR-proADM above or below the median of 0.71 nmol/L. The predictive value of MR-proADM for survival was determined by calculating the C statistic. RESULTS COPD patients with MR-proADM levels > 0.71 nmol/L in stable state had a 3-fold higher risk of dying than patients with MR-proADM levels < 0.71 nmol/L (HR 2.98 (95% CI 1.51-5.90); C statistic 0.76). The corrected Odds Ratio for one year mortality was 8.90 (95% CI 1.94 - 44.6) in patients with high MR-proADM levels measured in stable state, compared to patients with low levels. CONCLUSIONS MR-proADM measured in stable state showed to be a strong predictor for mortality in COPD patients. MR-proADM is far more convenient to measure than other predictors for mortality in COPD such as the BODE score.BACKGROUND Midrange-proadrenomedullin (MR-proADM) has been shown to be elevated in patients hospitalized for an acute exacerbation of COPD (AECOPD) and in patients with community-acquired pneumonia. When measured during AECOPDs, MR-proADM has also been shown to be a predictor of mortality. We hypothesized that MR-proADM levels measured in a stable state could also predict mortality. METHODS We included 181 patients in whom we had paired plasma samples for MR-proADM determinations during a stable state and at hospitalization for an AECOPD when they also produced sputum. Time to death or censoring was compared between patients with MR-proADM above or below the median of 0.71 nmol/L. The predictive value of MR-proADM for survival was determined by calculating the C statistic. RESULTS Patients with COPD and MR-proADM levels > 0.71 nmol/L in the stable state had a threefold-higher risk of dying than did patients with MR-proADM levels < 0.71 nmol/L (hazard ratio, 2.98 [95% CI, 1.51-5.90]; C statistic, 0.76). The corrected OR for 1-year mortality was 8.90 (95% CI, 1.94-44.6) in patients with high MR-proADM levels measured in the stable state, compared with patients with low levels measured in the stable state. CONCLUSIONS MR-proADM measured in the stable state appeared to be a strong predictor of mortality in patients with COPD. MR-proADM is far easier to measure than other predictors of mortality in COPD, such as BMI, airflow obstruction, dyspnea, and exercise capacity score.

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 Grams 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. Trials registration number clinical trial registered with http://www.trialregister.nl/(NTR351).

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 <LMIC90 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.

Association between poor therapy adherence to inhaled corticosteroids and tiotropium and morbidity and mortality in patients with COPD

Aim The aim of this study was to analyze the association between therapy adherence to inhaled corticosteroids (ICSs) and tiotropium on the one hand and morbidity and mortality in COPD on the other hand. Methods Therapy adherence to ICSs and tiotropium over a 3-year period of, respectively, 635 and 505 patients was collected from pharmacy records. It was expressed as percentage and deemed optimal at ≥75–≤125%, suboptimal at ≥50%–<75%, and poor at <50% (underuse) or >125% (overuse). The association between adherence and time to first hospital admission for an acute exacerbation of chronic obstructive pulmonary disease (AECOPD), community acquired pneumonia (CAP), and mortality was analyzed, with optimal use as the reference category. Results Suboptimal use and underuse of ICSs and tiotropium were associated with a substantial increase in mortality risk: hazard ratio (HR) of ICSs was 2.9 (95% CI 1.7–5.1) and 5.3 (95% CI 3.3–8.5) and HR of tiotropium was 3.9 (95% CI 2.1–7.5) and 6.4 (95% CI 3.8–10.8) for suboptimal use and underuse, respectively. Suboptimal use and overuse of tiotropium were also associated with an increased risk of CAP, HR 2.2 (95% CI 1.2–4.0) and HR 2.3 (95% CI 1.2–4.7), respectively. Nonadherence to tiotropium was also associated with an increased risk of severe AECOPD: suboptimal use HR 3.0 (95% CI 2.01–4.5), underuse HR 1.9 (95% CI 1.2–3.1), and overuse HR 1.84 (95% CI 1.1–3.1). Nonadherence to ICSs was not related to time to first AECOPD or first CAP. Conclusion Poor adherence to ICSs and tiotropium was associated with a higher mortality risk. Furthermore, nonadherence to tiotropium was associated with a higher morbidity. The question remains whether improving adherence can reduce morbidity and mortality.

Stable State Proadrenomedullin Level in COPD Patients: A Validation Study

ABSTRACT In patients with stable COPD, proadrenomedullin (MR-proADM) has been shown to be a good predictor for mortality. This study aims to provide an external validation of earlier observed cut-off values used by Zuur-Telgen et al. and Stolz.et al. in COPD patients in stable state and at hospitalization for an acute exacerbation of COPD (AECOPD). From the COMIC cohort study we included 545 COPD patients with a blood sample obtained in stable state (n = 490) and/or at hospitalization for an AECOPD (n = 101). Time to death was compared between patients with MR-proADM cut-off scores 0.71 and 0.75 nmol/L for stable state or 0.79 and 0.84 nmol/l for AECOPD. The predictive value of MR-proADM for survival was represented by the C statistic. Risk ratios were corrected for sex, age, BMI, presence of heart failure, and GOLD stage. Patients above the cut-off of 0.75 nmol/l had a 2-fold higher risk of dying than patient below this cut-off (95% CI: 1.20–3.41). The cut-off of 0.71 nmol/l showed only a borderline significantly higher risk of 1.67 (95% CI: 0.98–2.85). The corrected odds ratios for one-year mortality were 3.15 (95% CI 1.15–8.64) and 3.70 (95% CI 1.18–11.6) in patients with MR-proADM levels above versus below the cut-off of respectively 0.75 and 0.71 nmol/l measured in stable state. MR-proADM levels in samples at hospitalization for an AECOPD were not predictive for mortality in this validation cohort. MR-proADM in stable state is a powerful predictor for mortality.

Original Research: COPDStable-State Midrange-Proadrenomedullin Level Is a Strong Predictor of Mortality in Patients With COPD

ABSTRACT BACKGROUND Midrange-proadrenomedullin (MR-proADM) has been shown to be elevated in patients hospitalized for an acute exacerbation of COPD (AECOPD) and in patients with community acquired pneumonia. MR-proADM when measured during AECOPD has also been shown to be a predictor for mortality, we hypothesized that MR-proADM levels measured in a stable state could also predict mortality. METHODS We included 181 patients in whom we had paired plasma samples for MR-proADM determinations during stable state and at hospitalization for AECOPD when they also produced sputum. Time to death or censoring was compared between patients with MR-proADM above or below the median of 0.71 nmol/L. The predictive value of MR-proADM for survival was determined by calculating the C statistic. RESULTS COPD patients with MR-proADM levels > 0.71 nmol/L in stable state had a 3-fold higher risk of dying than patients with MR-proADM levels < 0.71 nmol/L (HR 2.98 (95% CI 1.51-5.90); C statistic 0.76). The corrected Odds Ratio for one year mortality was 8.90 (95% CI 1.94 - 44.6) in patients with high MR-proADM levels measured in stable state, compared to patients with low levels. CONCLUSIONS MR-proADM measured in stable state showed to be a strong predictor for mortality in COPD patients. MR-proADM is far more convenient to measure than other predictors for mortality in COPD such as the BODE score.BACKGROUND Midrange-proadrenomedullin (MR-proADM) has been shown to be elevated in patients hospitalized for an acute exacerbation of COPD (AECOPD) and in patients with community-acquired pneumonia. When measured during AECOPDs, MR-proADM has also been shown to be a predictor of mortality. We hypothesized that MR-proADM levels measured in a stable state could also predict mortality. METHODS We included 181 patients in whom we had paired plasma samples for MR-proADM determinations during a stable state and at hospitalization for an AECOPD when they also produced sputum. Time to death or censoring was compared between patients with MR-proADM above or below the median of 0.71 nmol/L. The predictive value of MR-proADM for survival was determined by calculating the C statistic. RESULTS Patients with COPD and MR-proADM levels > 0.71 nmol/L in the stable state had a threefold-higher risk of dying than did patients with MR-proADM levels < 0.71 nmol/L (hazard ratio, 2.98 [95% CI, 1.51-5.90]; C statistic, 0.76). The corrected OR for 1-year mortality was 8.90 (95% CI, 1.94-44.6) in patients with high MR-proADM levels measured in the stable state, compared with patients with low levels measured in the stable state. CONCLUSIONS MR-proADM measured in the stable state appeared to be a strong predictor of mortality in patients with COPD. MR-proADM is far easier to measure than other predictors of mortality in COPD, such as BMI, airflow obstruction, dyspnea, and exercise capacity score.