Chronic Obstructive Pulmonary Disease Pneumonia Research Articles

Cause-specific mortality adjudication in the UPLIFT® COPD trial: Findings and recommendations

Mortality is an important endpoint in chronic obstructive pulmonary disease (COPD) trials, although accurately determining cause of death is difficult. In the Understanding the Potential Long-term Impacts on Function with Tiotropium (UPLIFT®) trial, a mortality adjudication committee (MAC) provided systematic, independent and blinded assessment of cause-specific mortality of all 981 reported deaths. Here we describe this process of mortality adjudication and methodological revisions introduced to help standardise the adjudication of two areas recognised to pose particular difficulty; firstly, the classification of fatal COPD exacerbations that occur in the setting of pneumonia and secondly, the categorisation of sudden death. In addition MAC determined cause of death was compared with that reported by site investigators (SIs). MAC-assigned causes of death were: respiratory, 35%; cancer, 25%; cardiovascular, 11%; sudden cardiac death, 4.4%; sudden death, 3.4%; other, 8.8%; unknown, 12.4%. Cancer/cardiac deaths were more common in Global Initiative for Chronic Obstructive Lung Disease stage II, respiratory deaths in stages III and IV. Agreement between MAC and SI regarding cause of death was complete (50.2%), incomplete (18.5%) or none (31.3%). The SI classified deaths as cardiac three-fold more frequently than MAC (incidence rate [IR]/100 patient-years 0.797 vs. 0.257), although IR ratios for cardiac deaths for tiotropium vs. control were similar between SI and MAC. Discrepancies between MAC- and SI-adjudicated causes of death are common, especially increased reporting of cardiac deaths by the SI. Future multicentre COPD trials should plan appropriate infrastructure before study initiation to ensure collection and interpretation of fatal events data.

The aspiration pneumonia in COPD

The aspiration pneumonia in COPD

Infection as a comorbidity of COPD

The normal lung has several defence mechanisms to deal with microorganisms. Lower respiratory infections in the absence of lung disease are therefore relatively infrequent as compared with upper respiratory tract infections in healthy adults. In the setting of chronic obstructive pulmonary disease (COPD), lower respiratory tract infections, both acute and chronic, occur with increased frequency. As these infections contribute considerably to the clinical course of the patient with COPD, they constitute a significant comorbidity in COPD. Recurrent acute infections by bacterial and/or viral pathogens are now clearly linked with the occurrence of exacerbations of COPD. In addition, the occurrence of pneumonia in COPD has received considerable recent attention as it appears to be increased by the use of inhaled corticosteroids. The role of chronic infection in the pathogenesis of COPD is an active area of research with several different types of pathogens potentially implicated. Additionally, COPD patients with HIV infection have a more rapidly progressive decline in lung function than non-HIV-infected patients. Enhanced understanding of the host-pathogen interaction is needed to better prevent and treat respiratory tract infection in COPD.

Review: inhaled corticosteroids do not reduce mortality but increase pneumonia in COPD

Review: inhaled corticosteroids do not reduce mortality but increase pneumonia in COPD

Inhaled Corticosteroids and Pneumonia in COPD: An Association Looking for Evidence

Inhaled Corticosteroids and Pneumonia in COPD: An Association Looking for Evidence

Inhaled Corticosteroids and Pneumonia in COPD: An Association Looking for Evidence

Inhaled Corticosteroids and Pneumonia in COPD: An Association Looking for Evidence

Value of liver tissue dosimetry data to design and interpret in vitro (hepatocyte) gap junction studies with peroxisomal proliferating agents

COPD patients have increased risk of pneumonia when treated with fluticasone propionate (FP), whereas this is generally not the case with budesonide (BUD) treatment. We hypothesized that BUD and FP differentially affect the expression of immune defense genes.Human bronchial epithelial 16HBE cells and air-liquid interface (ALI)-cultured primary bronchial epithelial cells (PBECs) were pre-treated with clinically equipotent concentrations of BUD or FP (0.16–16 nM BUD and 0.1–10 nM FP), and the expression of immune defense genes was studied at baseline and after exposure to rhinovirus (RV16).Using microfluidic cards, we observed that both BUD and FP significantly suppressed CXCL8, IFNB1 and S100A8 mRNA expression in unstimulated 16HBE cells. Interestingly, BUD, but not FP, significantly increased lactotransferrin (LTF) expression. The difference between the effect of BUD and FP on LTF expression was statistically significant and confirmed by qPCR and at the protein level by western blotting. RV16 infection of ALI-cultured PBECs significantly increased the expression of CCL20, IFNB1 and S100A8, but not of LTF or CAMP/LL-37. In these RV16-exposed cells, LTF expression was again significantly higher upon pre-treatment with BUD than with FP. The same was observed for S100A8, but not for CCL20, IFNB1 or CAMP/LL-37 expression.Treatment of human bronchial epithelial cells with BUD results in significantly higher expression of specific immune defense genes than treatment with FP. The differential regulation of these immune defense genes may help to explain the clinical observation that BUD and FP treatment differ with respect to the risk of developing pneumonia in COPD.