Relationship between biomarkers and findings on low-dose computed tomography in hospitalised patients with acute exacerbation of COPD.

Background: Acute exacerbations of COPD (AECOPD) and community acquired pneumonia (CAP) often coexist. Although chest radiographs may differentiate between these diagnoses, chest radiography is known to underestimate the incidence of CAP in AECOPD. In this exploratory study, we prospectively investigated the incidence of infiltrative changes using low-dose computed tomography (LDCT). Additionally, we investigated whether clinical biomarkers of CAP differed between patients with and without infiltrative changes. Methods: Patients with AECOPD in which pneumonia was excluded using chest radiography underwent additional LDCT-thorax. The images were read independently by two radiologists; a third radiologist was consulted as adjudicator. C-reactive protein (CRP), procalcitonin (PCT), and serum amyloid A (SAA) at admission were assessed. Results: Out of the 100 patients included, 24 had one or more radiographic abnormalities suggestive of pneumonia. The interobserver agreement between two readers (Cohen's κ) was 0.562 (95% CI 0.371-0.752; p<0.001). Biomarkers were elevated in the group with radiological abnormalities compared to the group without abnormalities. Median (interquartile range (IQR)) CRP was 76 (21.5-148.0) mg·L-1 compared to 20.5 (8.8-81.5) mg·L -1 (p=0.018); median (IQR) PCT was 0.09 (0.06-0.15) µg·L-1 compared to 0.06 (0.04-0.08) µg·L-1 (p=0.007); median (IQR) SAA was 95 (7-160) µg·mL-1 compared to 16 (3-89) µg·mL-1 (p=0.019). Sensitivity and specificity for all three biomarkers were moderate for detecting radiographic abnormalities by LDCT in this population. The area under the receiver operating characteristic curve was 0.66 (95% CI 0.52-0.80) for CRP, 0.66 (95% CI 0.53-0.80) for PCT and 0.69 (95% CI 0.57-0.81) for SAA. Conclusion: LDCT can detect additional radiological abnormalities that may indicate acute-phase lung involvement in patients with AECOPD without infiltrate(s) on the chest radiograph. Despite CRP, PCT and SAA being significantly higher in the group with radiological abnormalities on LDCT, they proved unable to reliably detect or exclude CAP. Further research is warranted.

Blood eosinophilia as a marker of early and late treatment failure in severe acute exacerbations of COPD.

BACKGROUND: Blood eosinophilia is frequently encountered in patients with AECOPD. However the impact of blood eosinophilia at admission in patients with AECOPD on outcome on the short and long term has not been extensively studied which was the objective of the present study. METHODS: We used data of 207 exacerbations from a randomized clinical trial on antibiotic prescription based upon CRP-levels versus GOLD guided strategy and analyzed the impact of blood eosinophils (≥2% of total white cell count and eosinophil count ≥300 cell/microliter) on clinical outcome. RESULTS: 207 patients were included of whom 39 (18·8%) had eosinophilia ≥2%, 23 patients (11.1%) had blood eosinophil ≥300 cell/microliter. Eosinophilia was associated with shorter median length of stay in the eosinophilic groups(≥2% and ≥300 cell/microliter) compared to the non-eosinophilic groups. Early treatment failure was reduced in the both the eosinophilic groups (≥2% and ≥300 cell/microliter). Late treatment failure (day 11-30) did not differ between the groups. Relapse, was more frequent the eosinophilic groups (≥2% and ≥300 cell/microliter), however in the latter group this did not reach statistical significance. Eosinophilia ≥2% was a risk factor for having relapse (eosinophilia ≥2%: HR = 2·351; 95%CI 1·335-4·139), whereas eosinophilia <2% was associated with a lower risk factor for having early treatment failure (HR = 0·339 95%CI 0·122-0·943). CONCLUSION: We showed that blood eosinophilia at admission in patients with an AECOPD is associated with higher short-term treatment success rate. However, blood eosinophilia ≥2% predicts a less favorable outcome due to an increased risk of relapse. CLINICAL TRIAL REGISTRATION: NCT01232140.

Effects of daily vitamin D supplementation on respiratory muscle strength and physical performance in vitamin D-deficient COPD patients: a pilot trial.

BACKGROUND: Although vitamin D is well known for its function in calcium homeostasis and bone mineralization, several studies have shown positive effects on muscle strength and physical function. In addition, vitamin D has been associated with pulmonary function and the incidence of airway infections. As vitamin D deficiency is highly prevalent in chronic obstructive pulmonary disease (COPD) patients, supplementation might have a beneficial effect in these patients. OBJECTIVE: To assess the effect of vitamin D supplementation on respiratory muscle strength and physical performance in vitamin D-deficient COPD patients. Secondary outcomes are pulmonary function, handgrip strength, exacerbation rate, and quality of life. METHODS: We performed a randomized, double-blind, placebo-controlled pilot trial. Participants were randomly allocated to receive 1,200 IU vitamin D3 per day (n=24) or placebo (n=26) during 6 months. Study visits were conducted at baseline, and at 3 and 6 months after randomization. During the visits, blood was collected, respiratory muscle strength was measured (maximum inspiratory and expiratory pressure), physical performance and 6-minute walking tests were performed, and handgrip strength and pulmonary function were assessed. In addition, participants kept a diary card in which they registered respiratory symptoms. RESULTS: At baseline, the mean (standard deviation [SD]) serum 25-hydroxyvitamin D (25(OH)D) concentration (nmol/L) was 42.3 (15.2) in the vitamin D group and 40.6 (17.0) in the placebo group. Participants with vitamin D supplementation had a larger increase in serum 25(OH)D compared to the placebo group after 6 months (mean difference (SD): +52.8 (29.8) vs +12.3 (25.1), P<0.001). Primary outcomes, respiratory muscle strength and physical performance, did not differ between the groups after 6 months. In addition, no differences were found in the 6-minute walking test results, handgrip strength, pulmonary function, exacerbation rate, or quality of life. CONCLUSION: Vitamin D supplementation did not affect (respiratory) muscle strength or physical performance in this pilot trial in vitamin D-deficient COPD patients.

Effects of doxycycline on local and systemic inflammation in stable COPD patients, a randomized clinical trial.

UNLABELLED: Neutrophilic inflammation plays a causal role in Chronic Obstructive Pulmonary Disease (COPD). Neutrophil derived myeloperoxidase(MPO) matrix metalloproteinases(MMP's), and elastases are thought to contribute to the perpetuation of the disease. The tetracycline analogue doxycycline has been shown to inhibit neutrophil-mediated inflammation. It was thus reasoned that doxycycline may attenuate neutrophil-mediated inflammation in COPD. METHODS: In this double blind randomized controlled trial the effect of a 3-week course of doxycycline on sputum and systemic inflammatory parameters was evaluated in stable COPD patients. In order to exclude inflammation by bacterial colonisation patients must have 2 negative sputum cultures in the previous year. The effect of doxycycline treatment on inflammatory markers (TNF-α, IL-1ß and IL-6) and neutrophil specific markers in sputum (MPO, MMP's, and IL-8) and serum C-reactive protein was evaluated. Sputum was obtained by sputum induction with hypertonic saline. RESULTS: A total of 41 patients were included. Ten patients were excluded as they were not able to produce sputum at the first or second visit. Baseline characteristics were similar in the two groups. In the remaining patients doxycycline did not influence sputum MPO concentrations. Also MMP-8 and 9, IL-6 and IL-8 concentrations as well as lung function parameters were not affected by doxycycline. Systemic inflammation by means of CRP was also not influenced by doxycycline. CONCLUSION: A three week course of doxycycline did not influence MPO sputum levels nor any of the other inflammatory sputum and systemic markers. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00857038 URL: clinicaltrials.gov.

The value of 3.0-tesla MRI in diagnosing scapholunate ligament injury.

Objective To determine the sensitivity and specificity of 3.0-tesla (T) magnetic resonance imaging (MRI) and a dedicated hand coil in diagnosing scapholunate ligament (SLL) injury compared with intraoperative findings. Methods From January 2006 until September 2010, 3.0-T MRI scans were performed on 38 wrists (37 patients) with clinically unclear but suspected lesions of the SLL. These scans were evaluated by two experienced radiologists. Radiological findings were compared with intraoperative findings during arthrotomy. Sensitivity, specificity, accuracy, and positive and negative predictive value were calculated. Results An SLL lesion was identified during arthrotomy in 37 wrists. The first radiologist identified an SLL lesion on MRI in 26 wrists, all of which were confirmed intraoperatively. The second radiologist identified SLL lesions in 31 patients; however, intraoperatively it was found that there was no lesion of the ligament in one patient. Sensitivity ranged from 70 to 81% with a specificity of 100% and a positive predictive value of 97 to 100%. Accuracy measured 71 to 79%. Conclusions 3.0-T MRI of the wrist is moderately sensitive and very specific for detection of SLL lesions. However, if there is a high clinical suspicion of an SLL rupture, a 3.0-T MRI does not often have an additional value. Level of Evidence Diagnostic, level II.