Lung function,symptoms and inflammation during exacerbations of non-cystic fibrosis bronchiectasis: a prospective observational cohort study

Background

Exacerbations of non-cystic fibrosis bronchiectasis cause significant morbidity but there are few detailed data on their clinical course and associated physiological changes. The biology of an exacerbation has not been previously described.The purpose of this study was to describe changes in lung function, symptoms, health status and inflammation during the development and recovery from community-treated exacerbations.

Methods

This was a prospective observational cohort study of 32 outpatients with non-cystic fibrosis bronchiectasis conducted between August 2010 and August 2012. Patients completed a symptom diary card and measured their peak expiratory flow rate (PEFR) daily. Exacerbations were defined as oral antibiotic treatment taken for a worsening of respiratory symptoms. Symptoms and peak flow at exacerbation were analysed, and further measurements including the COPD Assessment Test (CAT) and inflammatory markers were also compared to baseline values.

Results

At baseline, health status was significantly related to lung function, prognostic severity and systemic inflammation. 51 exacerbations occurred in 22 patients. Exacerbation symptoms began a median (interquartile range) of 4 (2, 7) days before treatment started and the median exacerbation duration was 16 (10, 29) days. 16% had not recovered by 35 days. At exacerbation, mean PEFR dropped by 10.6% (95% confidence interval 6.9-14.2, p < 0.001) and mean CAT score increased by 6.3 units (3.6-9.1, p = 0.001), median symptom count by 4 (2.25, 6, p < 0.001), and mean CRP by 9.0mg/L (2.3-15.8, p = 0.011). Exacerbations where PEFR fell by ≥10% were longer with more symptoms at onset.

Conclusion

Exacerbations of non-CF bronchiectasis are inflammatory events, with worsened symptoms, lung function and health status, and a prolonged recovery period. Symptom diary cards, PEFR and CAT scores are responsive to changes at exacerbation and may be useful tools for their detection and monitoring.

Electronic supplementary material

The online version of this article (doi:10.1186/s12931-015-0167-9) contains supplementary material, which is available to authorized users.     

A tetravalent dengue nanoparticle stimulates antibody production in mice

Background

Dengue is a major public health problem worldwide, especially in the tropical and subtropical regions of the world. Infection with a single Dengue virus (DENV) serotype causes a mild, self-limiting febrile illness called dengue fever. However, a subset of patients experiencing secondary infection with a different serotype progresses to the severe form of the disease, dengue hemorrhagic fever/dengue shock syndrome. Currently, there are no licensed vaccines or antiviral drugs to prevent or treat dengue infections. Biodegradable nanoparticles coated with proteins represent a promising method for in vivo delivery of vaccines.

Findings

Here, we used a murine model to evaluate the IgG production after administration of inactivated DENV corresponding to all four serotypes adsorbed to bovine serum albumin nanoparticles. This formulation induced a production of anti-DENV IgG antibodies (p < 0.001). However, plaque reduction neutralization assays with the four DENV serotypes revealed that these antibodies have no neutralizing activity in the dilutions tested.

Conclusions

Our results show that while the nanoparticle system induces humoral responses against DENV, further investigation with different DENV antigens will be required to improve immunogenicity, epitope specicity, and functional activity to make this platform a viable option for DENV vaccines.     

Treatment of pulmonary acariasis in rhesus macaques with ivermectin

Rhesus monkeys were treated for pulmonary acariasis with single injections of ivermectin (200 micrograms/kg). Monkeys were killed and complete necropsies performed. Control monkeys had numerous live mites, while treated monkeys had only dead, frequently fragmented mites. Histopathologically, inflammatory lesions were most severe in control monkeys and monkeys killed one week after treatment. Inflammatory changes progressively decreased with increasing time post treatment.     

Hemosiderosis in lemurs

In the late 1960s, pathologists at the San Diego Zoo began to notice iron storage in the internal organs of captive lemurs. Hemosiderin was found in liver, spleen, lymph nodes, duodenum, and occasionally other organs. This was most pronounced in Lemur macaco, least pronounced in Lemur catta, with the severity in Lemur variegatus variegatus and Lemur variegatus ruber falling somewhere in between. Since 1968, 20 of 29 necropsied lemurs had hemosiderosis, three with hepatomas, three with cholangiomas, and one with a metastatic pheochromocytoma. In a preliminary attempt to compare their iron absorption, five black-and-white ruffed lemur (Lemur variegatus variegatus) weanlings and five rhesus monkey weanlings were each given ～500 nmol/kg FeCI₃ (27.9 μg iron/kg) containing 5 μCi of ⁵⁹Fe in 0.1 M HCl via a nasogastric tube. Retained ⁵⁹Fe was measured by whole body gamma counting and found to be roughly the same in the two groups, possibly because insufficient quantities of iron were administered and/or excessive iron absorption becomes apparent only in older animals. Our conclusions were the following: (1) Hemosiderosis in lemurs is associated with tissue damage similar to that seen in humans with idiopathic hemochromatosis. (2) Because iron deposits occur both in parenchymal cells and reticuloendothelial cells, hemosiderosis in lemurs is probably not a model for idiopathic hemochromatosis in a pure sense.     

Cryptosporidial infections in captive wild animals

Neonatal diarrhea was an important cause of morbidity and mortality in a hand-rearing facility for exotic ruminants at the San Diego Wild Animal Park. Studies undertaken to determine the causes of the problem revealed that oocysts of Cryptosporidium sp. were demonstrable in auramine O stained fecal smears from 52 of 183 (28.4%) animals examined. Cryptosporidial infection was identified in 21 of 40 species of exotic ruminants with diarrhea. In addition, cryptosporidia were associated with gastroenteric disease in two primates and two reptiles. It was observed also that auramine O stained coccidial oocysts of the genus Eimeria, which were present in five of 183 (2.7%) of the specimens examined.     

Chromosome studies in the superfamily Bovoidea

The chromosome morphology of about 50 species of Bovoidea has now been investigated. Although the diploid number varies from 30 to 60 among these species, the fundamental number (NF) varies only (with but three exceptions) from 58 to 62. This indicates an almost exclusive use of the Robertsonian fusion mechanism of karyotype evolution in this group of species which represent 30 different genera. All known cytogenetic information on the Bovoidea has been summarized and a complete bibliography is presented for each species. Karyotypes and data on a number of previously unstudied species are presented.     

Cytogenetics of extragonadal tumors.

Tissue from six human extragonadal teratomas was obtained for cytogenetic study. These included two gluteal lesions in infant females, and one each of thyroid, mediastinal, sacral and gastric teratomas in males. Tissue culture characteristics indicated tumor growth. All tumors, except the mediastinal lesion showed the presumed karyotype of its host, XX or XY. The mediastinal mass was tetraploid XXYY and contained an X chromatin body and double Y bodies. Our data support the concept that extragonadal teratomas in males and females arise mitotically from diploid cells and are more similar to identical twins. No heterosexual (XX) tumors were seen in males which would be expected in parthenogenetic tumors. The sex chromatin positive tumors seen in earlier studies may have resulted from polyploidy. Thus, male and female extragonadal teratomas have a different origin from the postmeiotic ovarian teratomas.     

Prenatal diagnosis of trisomy 9.

A male karyotype with trisomy 9 (47,XY,+9) was identified in amniotic fluid cells from a 40-year-old pregnant woman. After termination of the pregnancy by saline abortion, the cytogenetic diagnosis was confirmed in a cell line grown from placental tissue. Microscopic and gross pathological findings in the fetus were compared to 1 case with trisomy 9 and 3 with trisomy 9 mosaicism reported in the literature. A distinct clinical syndrome appears to be associated with this rare autosomal trisomy.