OBJECTIVES: The aim of this study is to assess the role of Granulocyte Macrophage-Colony Stimulating Factor (GMCSF) in asthmatic airway hyper-responsiveness associated with RSV infections.
MATERIALS AND METHODS: Forty five asthmatic cases and 45 healthy individuals were studied in a cross-sectional design. All asthmatics underwent symptom score assessment.GMCSF concentrations in sputum and RSV-IgM/IgG in serum samples were measured for all participants by Enzyme Linked Immuno-Sorbent Assay (ELISA).
RESULTS: The GM-CSF concentration level was significantly higher in asthmatics (270.27± 194.87pg/mL) especially among moderate and severe disease with mean concentration of 197.33±98.47 and 521.08± 310.04 respectively, compared to healthy controls (22.20±21.27 pg/ mL) (p =0.0001). The sputum level of GM-CSF in asthmatics is highly significant associated with positive anti-RSV IgG sera which represents 35/45(77.8%) with mean GM-CSF concentration of (276.99± 86.42) compared with controls at about 31/45 (68.9%) with GM-CSF mean concentration of (22.84±23.47). On the other hand, positive anti-RSV IgM in asthma cases was 8 out of 45(17.8 %) with GM-CSF mean concentration of (307.25± 306.65). Furthermore, GM-CSF sputum level was significantly correlated with eosinophil count especially in moderate and severe asthma.
CONCLUSIONS: This study revealed that GM-CSF level is associated with eosinophilia and indicates asthma severity that might be evident during RSV infection .The distinctive GM-CSF features observed in the sputum from asthmatics with RSV may be useful as a diagnostic methods to help match patients with antibody therapy.
METHODS: In this study, we generated whole genome sequences of eight clinical strains of Mtb that were isolated from the cerebrospinal fluid (CSF) of patients presenting with tuberculous meningitis (TBM) in Malaysia, and compared them to the genomes of H37Rv and other respiratory Mtb genomes either downloaded from public databases or extracted from local sputum isolates. We aimed to find genomic features that might be distinctly different between CSF-derived and respiratory Mtb.
RESULTS: Genome-wide comparisons revealed rearrangements (translocations, inversions, insertions and deletions) and non-synonymous SNPs in our CSF-derived strains that were not observed in the respiratory Mtb genomes used for comparison. These rearranged segments were rich in genes for PE (proline-glutamate)/PPE (proline-proline-glutamate), transcriptional and membrane proteins. Similarly, most of the ns SNPs common in CSF strains were noted in genes encoding PE/PPE proteins. Protein globularity differences were observed among mycobacteria from CSF and respiratory sources and in proteins previously reported to be associated with TB meningitis. Transcription factors and other transcription regulators featured prominently in these proteins. Homologs of proteins associated with Streptococcus pneumoniae meningitis and Neisseria meningitidis virulence were identified in neuropathogenic as well as respiratory mycobacterial spp. examined in this study.
DISCUSSION: The occurrence of in silico genetic differences in CSF-derived but not respiratory Mtb suggests their possible involvement in the pathogenesis of TBM. However, overall findings in this comparative analysis support the postulation that TB meningeal infection is more likely to be related to the expression of multiple virulence factors on interaction with host defences than to CNS tropism associated with specific genetic traits.
Objective: To compare the real-world effectiveness of EHRZ and FDC treatment groups on a cohort registry by investigating the sputum conversion rate and treatment outcomes of both groups.
Methods: A total of 11,489 patients' data were extracted from the Sabah TB registry between January 2012 and June 2016, including EHRZ (n = 4188) and FDC (n = 7301) patients. Then, 1:1 propensity score matching was adopted to reduce the baseline bias. Caliper matching was conducted with maximum tolerance score set at 0.001. Confounders included in the propensity score matching were gender, nationality, diabetes, HIV status, smoking status, and chest X-ray status. Successful matching provided 4188 matched pairs (n = 8376) for final analysis.
Results: In this matched cohort of 4188 pairs, the 2-month sputum conversion rate of FDC group was significantly higher than the EHRZ group (96.3% vs. 94.3%; P < 0.001) whereas 6-month sputum conversion of both groups showed no significant difference. Treatment outcomes such as noncompliance rate, failure rate, and success rate have no significant difference (P > 0.05) in both the treatment groups. There was an incidental finding of reduced death rate among FDC group compared to the EHRZ group (0.2% vs. 0.5%; P = 0.034).
Conclusion: The FDC formulation has better sputum conversion rate at 2 months compared to conventional EHRZ regime as separate-drug formulation. It was also observed that FDC has a slight protective effect against all-cause death among TB patients. This protective effect of FDC, however, still needs to be proven further.