Lung ultrasound allows for earlier diagnosis of bronchiolitis than auscultation: an animal experiment and human case series.

PURPOSE: Early diagnosis of bronchiolitis in infants allows for risk stratification for central apnea, and, when available, the timely initiation of antiviral treatment. An animal model could demonstrate if earlier diagnosis is possible with ultrasound than with clinical exam. Even if possible, translating this to pediatrics would require observations from undifferentiated human infants. METHODS: We used serial daily clinical and lung ultrasound exams in a bovine calf model (Bos taurus) of respiratory syncytial virus bronchiolitis. Ultrasound and clinical examiners were blinded to each other's findings and the treatments used in 24 calves. Time to diagnosis was compared using Kaplan-Meier curves. A case series of human infants with upper respiratory tract infections, without clinical signs of bronchiolitis, and in whom lung ultrasound was performed, was extracted from hospital records. RESULTS: In the bovine model, lung ultrasound findings emerged earlier and lasted later than auscultatory findings. Relying on auscultation, 5/24 (21%) of animals were diagnosed by post-inoculation day 5 whereas 24/24 (100%) were diagnosed by ultrasound. We identified seven infants in whom lung ultrasound was used to diagnose bronchiolitis before adventitial lung sounds emerged. Three of these subsequently developed typical clinical findings of bronchiolitis in the hospital. Two had alternative explanations for their abnormal lung ultrasounds (both required surgical intervention). Two were discharged and required no further medical attention. CONCLUSION: Lung ultrasound allowed earlier diagnosis of bronchiolitis than clinical exam in the bovine model. In the human case series this was also true, but alternative causes of abnormal ultrasound were frequent.

Validating a bovine model for lung ultrasound of bronchiolitis.

PURPOSE: Bronchiolitis is a very common acute lung disease in infants caused commonly by respiratory syncytial virus (RSV). Point-of-care lung ultrasound is increasingly used in clinical care but proof that ultrasound reflects histological disease is lacking. Bovine calves are a good model for RSV bronchiolitis. We answered the following two questions: (1) does point-of-care lung ultrasound reflect lung pathology at the histological level in a bovine calf model of bronchiolitis? and (2) are point-of-care lung ultrasound images in human infants similar to those obtained in calves? METHODS: We experimentally infected 24 five to six-week-old bovine calves with RSV and compared six window lung ultrasound with lung histology10 days after inoculation. The calves were treated with antivirals and antipyretics leading to variable severity of illness. We used canonical discriminant analysis to determine if abnormal lung ultrasound findings reflected different histological findings. We compared the ultrasounds obtained from the calves with ultrasounds obtained from 10 human infants who were diagnosed clinically with bronchiolitis. RESULTS: Canonical discriminant analysis generally demonstrated good class separation based on the maximal severity of ultrasound finding in each acoustic window. Lung ultrasound performed poorly at detecting bronchopneumonia. Bovine ultrasounds looked similar to human infant lung ultrasounds. CONCLUSION: Point-of-care lung ultrasound abnormalities reflect lung pathology at the histological level in a bovine calf model of bronchiolitis. Point-of-care lung ultrasound images in human infants are similar to those obtained in calves.

Cytokine production and the effects of oclacitinib in three canine mast cell tumour cell lines.

BACKGROUND: Cytokines are capable of manipulating the tumour microenvironment supporting tumour growth. Interleukin (IL)-8 and monocyte chemoattractant protein (MCP)-1, shown to be produced by various tumours, can negatively affect prognosis. The production of cytokines by canine mast cell tumours (MCT) has not been reported. HYPOTHESIS/OBJECTIVES: We hypothesise that MCT cell lines produce IL-8 and/or MCP-1 in addition to other cytokines, and that their production can be modulated by the Janus kinase (JAK) inhibitor oclacitinib. This pilot study aims to investigate the production of IL-8, MCP-1 and nine additional cytokines in three canine MCT cell lines, and determine the effects of oclacitinib on their production. METHODS AND MATERIALS: Reverse transcriptase-PCR was used to detect the expression of IL-8 and MCP-1 mRNA in three MCT cell lines (CoMS, CM-MC1 and VI-MC1). The supernatant of the cell lines was evaluated for the presence of 11 cytokines [IL-2, -6, -7, -8, -10, -15 and -18, and MCP-1, granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon (IFN)γ and tumour necrosis factor (TNF)α] by enzyme-linked immunosorbent assay (ELISA). The IC50 of oclacitinib was identified for each cell line. ELISA was performed again to compare changes in IL-8 and MCP-1 in treated cell lines versus untreated controls. RESULTS: Interleukin-8 and MCP-1 were produced by all MCT cell lines tested. Oclacitinib significantly decreased the release of IL-8 in the CoMS cell line and of MCP-1 in CoMS and VI-MC1 in clinically relevant concentrations. Furthermore, oclacitinib significantly decreased the proliferation of all three cell lines. CONCLUSIONS: Interleukin-8 and MCP-1 are produced by canine MCT cell lines. Modulation of their production is possible with oclacitinib.

Corexit, oil and marine microgels.

Corexit, an EPA-approved chemical dispersant, was intensively used during the 2010 Deepwater Horizon Oil Spill in the Gulf of Mexico. Current studies surrounding Corexit have mainly focused on its toxicity and oil removal capacity. The potential impact of Corexit on the surface ocean carbon dynamics has remained largely unknown. The spontaneous assembly of DOM (dissolved organic matter) polymers into microgels (POM, particulate organic matter) was demonstrated previously that it can influence various critical processes, such as colloidal pump, microbial loops, and nutrition availability in the surface ocean. Here, we report that Corexit alone can significantly inhibit DOM microgel formation and reduce the stability of pre-existing microgels. However, Corexit and oil, Chemically Enhanced Water Accommodated Fraction (CEWAF), could effectively facilitate DOM microgel formation. The unanticipated disturbance of Corexit and oil spills on the critical DOM-POM continuum warrant particular caution and thus should be considered for future application of Corexit during oil spills.