COPD exacerbation phenotypes in a real-world five year hospitalisation cohort.

INTRODUCTION: COPD exacerbation phenotypes have been defined in research populations by predominantly infective or inflammatory aetiology. We sought to characterise this in patients admitted to our centre. MATERIALS AND METHODS: Case-notes of consecutive patients discharged alive after treatment for acute COPD exacerbations between December 2012 and January 2017 were analysed. Data were collected on treatment, length of stay, C-reactive protein (CRP), eosinophil count and bacterial sputum culture positivity for potentially pathogenic microorganisms (PPM). RESULTS: 1029 exacerbations were included. There was an inverse correlation between CRP and eosinophil count (rho = -0.277, p < 0.01). The proportion of eosinophilic exacerbations (eosinophils ≥0.3 × 109/L) was low (157, 15%). Median length of stay was longer in patients with a CRP >100 mg/L (4d [3,8] vs 4d [2,7], p < 0.01) or when given antibiotics (4d [2,8] vs 3d [1,6], p < 0.001) and shorter if receiving corticosteroids (4d [2,6] vs 6d [3,7], p < 0.001). Being sputum culture positive on first exacerbation was associated with sputum culture positivity in subsequent exacerbations. Patients with PPM in sputum culture had a significantly higher median CRP than culture negative patients (38 mg/L [18.75, 57] v 18 mg/L [8.5,45.5] p < 0.05). Length of stay, eosinophil count and CRP were significantly correlated between exacerbation pairs. CONCLUSIONS: This real-world population found eosinophilic and high CRP exacerbations to be distinct and significantly stereotyped within individual patients across recurrent exacerbations. High CRP exacerbations are associated with greater healthcare utilisation and chance of sputum positivity with PPM. Eosinophilic exacerbations were associated with lower rate of readmission. Phenotype-driven treatment warrants further investigation in this population.

Sea urchin embryos exposed to thalidomide during early cleavage exhibit abnormal morphogenesis later in development.

BACKGROUND: Clinical use of thalidomide has increased drastically, pushing the questions concerning the teratogenic mechanisms of this drug back to the forefront. Progress in understanding the teratogenic mechanisms has been slow, with the lack of non-primate vertebrate animal models susceptible to the classic reduction deformities remaining a concern. Sea urchin embryos have been used as model organisms for developmental studies for the last century. Like vertebrates, they are deuterostomes and share similar developmental and signaling pathways suggesting they may be an effective system for thalidomide studies. Therefore, we tested sea urchin embryos to see if they were sensitive to the effects of thalidomide. METHODS: Sea urchin embryos were obtained using standard spawning and fertilization techniques. Thalidomide dissolved in DMSO was added to embryo cultures either at fertilization or during early cleavage. Samples of the embryos were evaluated during specific development stages. RESULTS: Lytechinus pictus embryos exposed to 400 microM thalidomide at fertilization or within a window during early cleavage (2-6 hours post-fertilization) exhibit significant levels of abnormal embryos (60-82%) at the pluteus stage, compared to controls levels (< or =10%). Strongylocentrotus purpuratus embryos exposed at initial fertilization or during early cleavage (2-6 hours post-fertilization) exhibit similar responses with significant abnormal levels ranging from (55-70%) at pluteus stage. CONCLUSIONS: Both species of sea urchin tested were susceptible to thalidomide-induced teratogenesis during cleavage (4-16 cell stages). This response during cleavage stages warrants further study and indicates that sea urchin embryos may prove to be a useful tool for studying thalidomide effects early in development.