Azithromycin and cough-specific health status in patients with chronic obstructive pulmonary disease and chronic cough: a randomised controlled trial

Background

Macrolides reduce exacerbations in patients with COPD. Their effects on health status has not been assessed as primary outcome and is less clear. This study assessed the effects of prophylactic azithromycin on cough-specific health status in COPD-patients with chronic productive cough.

Methods

In this randomised controlled trial 84 patients met the eligibility criteria: age of ≥40 years, COPD GOLD stage ≥2 and chronic productive cough. The intervention-group (n = 42) received azithromycin 250 mg 3 times a week and the control-group (n = 42) received a placebo. Primary outcome was cough-specific health status at 12 weeks, measured with the Leicester Cough Questionnaire (LCQ). Secondary outcomes included generic and COPD-specific health status and exacerbations. Changes in adverse events and microbiology were monitored.

Results

Mean age of participants was 68 ± 10 years and mean FEV1 was 1.36 ± 0.47 L. The improvement in LCQ total score at 12 weeks was significantly greater with azithromycin (difference 1.3 ± 0.5, 95% CI 0.3;2.3, p = 0.01) and met the minimal clinically important difference. Similar results were found for the domain scores, and COPD-specific and generic health status questionnaires. Other secondary endpoints were non-significant. No imbalances in adverse events were found.

Conclusions

Prophylactic azithromycin improved cough-specific health status in COPD-patients with chronic productive cough to a clinically relevant degree.

Trial registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01071161","term_id":"NCT01071161"}}NCT01071161     

Large oncosomes mediate intercellular transfer of functional microRNA

Prostate cancer cells release atypically large extracellular vesicles (EVs), termed large oncosomes, which may play a role in the tumor microenvironment by transporting bioactive molecules across tissue spaces and through the blood stream. In this study, we applied a novel method for selective isolation of large oncosomes applicable to human platelet-poor plasma, where the presence of caveolin-1-positive large oncosomes identified patients with metastatic disease. This procedure was also used to validate results of a miRNA array performed on heterogeneous populations of EVs isolated from tumorigenic RWPE-2 prostate cells and from isogenic non-tumorigenic RWPE-1 cells. The results showed that distinct classes of miRNAs are expressed at higher levels in EVs derived from the tumorigenic cells in comparison to their non-tumorigenic counterpart. Large oncosomes enhanced migration of cancer-associated fibroblasts (CAFs), an effect that was increased by miR-1227, a miRNA abundant in large oncosomes produced by RWPE-2 cells. Our findings suggest that large oncosomes in the circulation report metastatic disease in patients with prostate cancer, and that this class of EV harbors functional molecules that may play a role in conditioning the tumor microenvironment.     

The Use of a Mathematical Model for the Analysis of Manurial and Weather Effects on the Growth of Carrots

A model for the study of yearly and other variation in cropyields, based on a generalized form of the logistic equationof growth, was applied to three years' growth analysis dataon carrot crops from 16 plots of a long-term manurial experiment.In the ideal case, it is postulated that the growth in differentyears of carrot leaves or taproots on soil receiving a givenmanurial treatment could be described by a single curve if timein days was replaced by a scale based on one or more meteorologicalelements which affect relative growth-rates. The equation fitted the data on the growth of the leaves butnot that on the taproots. For leaf growth, the use of the sumsof solar radiation, day degrees or evaporation from an openwater surface did not give curves that fitted the growth databetter than those obtained with time in days. Yearly differencesin leaf (but not taproot) growth appeared to be related to correspondingdifferences in rainfall amounts, and it is suggested that ascale taking account of soil moisture tension might have givena better fit to the model. It appeared that whereas the relative leaf growth-rate was afunction of leaf but not taproot weight, relative taproot growth-ratewas a function of taproot weight and leaf weight. A furthermodel for the growth of carrots, based on this hypothesis isdescribed.