Anaerobic bacteria have been identified in abundance in the airways of cystic fibrosis (CF) subjects. The impact their presence and abundance has on lung function and inflammation is unclear. The aim of this study was to investigate the relationship between the colony count of aerobic and anaerobic bacteria, lung clearance index (LCI), spirometry and C-Reactive Protein (CRP) in patients with CF. Sputum and blood were collected from CF patients at a single cross-sectional visit when clinically stable. Community composition and bacterial colony counts were analysed using extended aerobic and anaerobic culture. Patients completed spirometry and a multiple breath washout (MBW) test to obtain LCI. An inverse correlation between colony count of aerobic bacteria (n = 41, r = -0.35; p = 0.02), anaerobic bacteria (n = 41, r = -0.44, p = 0.004) and LCI was observed. There was an inverse correlation between colony count of anaerobic bacteria and CRP (n = 25, r = -0.44, p = 0.03) only. The results of this study demonstrate that a lower colony count of aerobic and anaerobic bacteria correlated with a worse LCI. A lower colony count of anaerobic bacteria also correlated with higher CRP levels. These results indicate that lower abundance of aerobic and anaerobic bacteria may reflect microbiota disruption and disease progression in the CF lung.
Recently we have presented an electrophoretic comparison of genetically determined human serum albumin variants from diverse populations, distinguishing 20 different types of 'monomeric' variants as well as three 'dimeric' variants (Weitkamp et al. 1973; Weitkamp & Neel, 1972). A t this time we compare the 20 previously described types of monomeric variants with 30 more variants, generally rare, and extend our data and conclusions on the population distribution of albumin variants. MATERIALS AND METHODS Each albumin variant, its source, and ethnic origin are listed in the Appendix. Many of the new variants were found in several individuals in a single family. In other cases the variants were found in one or more individuals in a single village. The electrophoretic comparisons were made in the three starch-gel systems, acetate-EDTA a t pH 5.0, tris-lithium-succinate-citrate a t pH 6.0 and tris-EDTA-borate a t pH 6.9, used previously (Weitkamp et al. 1973). RESULTS The results of the comparison of 30 new or recently described serum albumin variants with 20 variants previously distinguished using three starch-gel electrophoretic systems are presented in Table 1. Although the amount of separation reported here for the 20 variants previously described differs slightly from the earlier results, due to minor variations in electrophoretic conditions, the conclusions regarding their mobility relative to normal albumin and to each other remain the same. Three new variants, RS I, Xavante, and Yanomama-2, all slowly migrating, have been identified. Electropherograms showing these variants adjacent to variants with similar mobility are presented in Fig. 1. Albumin RS I, found in an indigene from Somali, has been mentioned in two previous reports. Porta et al. (1972) found it (identified as R.s.) indistinguishable from SO/BS on cellulose acetate electrophoresis a t pH 9-25. The sample available a t the time of our prior comparison (Weitkamp et al. 1973) was sufficiently degraded, as determined by the smeared patterns in the pH 6.0 and 6.9 systems and the altered mobility of normal albumin in the pH 5.0 system, to preclude determination of its mobility. In the present sample, both the normal and variant albumin bands stain less intensely with Amido Black 1OB than the albumin bands
These data support the use of LCI as a surrogate outcome measure in CF clinical trials in adults as well as in children.
Lung disease is the main cause of morbidity and mortality in cystic fibrosis (CF), and involves chronic infection and perturbed immune responses. Tissue damage is mediated mostly by extracellular proteases, but other cellular proteins may also contribute to damage through their effect on cell activities and/or release into sputum fluid by means of active secretion or cell death.We employed MudPIT (multidimensional protein identification technology) to identify sputum cellular proteins with consistently altered abundance in adults with CF, chronically infected with , compared with healthy controls. Ingenuity Pathway Analysis, Gene Ontology, protein abundance and correlation with lung function were used to infer their potential clinical significance.Differentially abundant proteins relate to Rho family small GTPase activity, immune cell movement/activation, generation of reactive oxygen species, and dysregulation of cell death and proliferation. Compositional breakdown identified high abundance of proteins previously associated with neutrophil extracellular traps. Furthermore, negative correlations with lung function were detected for 17 proteins, many of which have previously been associated with lung injury.These findings expand our current understanding of the mechanisms driving CF lung disease and identify sputum cellular proteins with potential for use as indicators of disease status/prognosis, stratification determinants for treatment prescription or therapeutic targets.
Background: Alterations in the lung microbiota may drive disease development and progression in patients with chronic respiratory diseases. Following lung transplantation (LTx), azithromycin is used to both treat and prevent chronic lung allograft dysfunction (CLAD). The objective of this study was to determine the association between azithromycin use, CLAD, acute rejection, airway inflammation and bacterial microbiota composition and structure after LTx. Methods: Bronchoalveolar lavage (BAL) samples (n=219) from 69 LTx recipients (azithromycin, n=32; placebo, n=37) from a previously conducted randomized placebocontrolled trial with azithromycin were analysed. Samples were collected at discharge, 1 and 2 years following randomization and at CLAD diagnosis. Bacterial microbial community composition and structure was determined using 16S rRNA gene sequencing and associated with clinically important variables. Results: At discharge and following 1 and 2 years of azithromycin therapy, no clear differences in microbial community composition or overall diversity were observed. Moreover, no changes in microbiota composition were observed in CLAD phenotypes. However, acute rejection was associated with a reduction in community diversity (p = 0.0009). Significant correlations were observed between microbiota composition, overall diversity and levels of inflammatory cytokines in BAL, particularly CXCL8. Conclusions: Chronic azithromycin usage did not disturb the bacterial microbiota. However, acute rejection episodes were associated with bacterial dysbiosis.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.