Mechanism of impaired monocyte responses in patients with Chronic Obstructive Pulmonary Disease (COPD)

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Synat Keam^1,2, Dino B.A Tan^1,2, Jesse David Armitage^1,2, Dave Singh³, Yuben Moodley^1,2,4

¹Center for Respiratory Health, School of Biomedical Sciences, University of Western Australia, WA, Australia

²Stem Cell Unit, Institute for Respiratory Health, University of Western Australia, WA, Australia
³Respiratory Research Group, University of Manchester, United Kingdom

Abstract

Background
COPD is a chronic respiratory inflammatory disease and patients are highly susceptible to respiratory infections. This suggests a faulty host-immune system such as impaired phagocytic function and increases the risk of acute exacerbation events, which can be life‑threatening.

Aim(s)
To understand the underlying mechanisms, we aimed to determine:

1. The level of phagocytosis and TLR2 / 4 expression by monocytes.

2. The level of CTLA-4 and PD-1 on T cell subsets.

3. If phagocytosis can be improved by CTLA-4 or PD-1 blockade.

Method(s)
Cryopreserved cells of excised lung samples from COPD patients (n=10) and non-COPD controls (n=10) were cultured with NTHi pre-labelled with pHrodo™ with or without CTLA-4 or PD-1 blockade for two hours and phagocytosis was assessed by flow cytometry. Cells were also immunophenotyped for the expression of TLR-2 / 4 and inhibitory receptors (PD-1 and CTLA-4) on CD4+ T cells, and regulatory T cells (Tregs) using flow cytometry.

Result(s)
Phagocytosis of pHrodo™-NTHi by monocytes was lower in COPD patients than non‑COPD controls (p=0.01). TLR-4 expression on monocytes was significantly reduced in COPD patients than non‑COPD controls (p=0.01). Additionally, TLR‑2 expression on monocytes positively correlated with phagocytosis of NTHi by monocytes (r=0.76, p=0.01). Frequencies of CD4+ T cells and Tregs expressing intracellular CTLA-4 and PD-1 did not differ between COPD patients and non‑COPD controls. Interestingly, intracellular CTLA-4 on CD4+ T cell and Tregs negatively correlated with phagocytosis of NTHi by monocytes (r=-0.89, p=0.001 and r=-0.64, p=0.04). Increased phagocytosis of NTHi by monocyte after CTLA-4 and PD-1 blockade was seen only in a proportion of COPD and non-COPD subjects.

Summary and conclusions

Overall, CTLA-4 blockade increased phagocytosis in a proportion of COPD patients. Impaired TLR-2 / 4 expression on monocytes may present a more direct cause of impaired phagocytosis and thus provide a therapeutic target to improve anti-bacterial responses in COPD.

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Retrospective analysis of Internal Quality Control of Biochemistry Tests in the National Public Health Laboratory between 2015 and 2016

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Tous Chansamrach¹, Chau Darapheak², Ly Vanthy³

1. International Training and Education Center for Health-Cambodia, Phnom Penh, Cambodia.

2. National Public Health Laboratory, and Lecturer of School of Public Health, Phnom Penh, Cambodia.

3. US-CDC in Cambodia, and Lecturer of School of Public Health, Phnom Penh, Cambodia.

Abstract

Introduction
Internal quality control (IQC) is a fundamental technique to detect errors in the analytical phase and ensure that the results produced from any assay are reliable for patient result in order to improve the quality of patient care. The study aims to determine the potential error of current internal quality control practice in biochemistry section at NPHL, identify preferable IQC rules based on Sigma Metrics, and identify the root cause of problems and provide recommendation.

Methods
Retrospective analysis was conducted by using the existing biochemistry IQC data of Humatrol N and Humatrol P in Lot 002 and Lot 003 of NPHL from 02 June, 2015 to 27 June, 2016. IQC of thirteen tests including Triglyceride (TRI), Glucose (GLU), Total Cholesterol (CHO), Creatinine (CREA), Uric acid (UA), Protein Total (PT), Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Urea (URE), Calcium (CAL), Albumin (ALB), Amylase (AMY), and Gama Glutamyl Transferase (GGT) were measured in this study. The potential errors of these tests were detected when value of Total Error (TE) was smaller than value of Total Allowable Error (TEa) defined by the Clinical Laboratory Improvement Amendments (CLIA) Requirements. Sigma Metrics was calculated and plotted on Sigma Scale to identify the preferable IQC rules. The focus group discussion were conducted to identify the root cause of problems and provide recommendation.

Results
Potential errors for IQC of Humatrol N in Lot 002 were detected in CHO, CREA, URE, CAL, and ALB (TE: 11.9%, 20.3%, 15.5%, 0.28 mmol/l, and 14.1%, respectively). Potential errors for IQC of Humatrol P in Lot 002 were detected in CHO, CREA, URE, CAL, and ALB (TE: 10.8%, 17.4%, 14.2%, 0.47 mmol/l, and 13.2%, respectively).  Potential errors for IQC of Humatrol N in Lot 003 were detected in GLU, CHO, CREA, AST, ALT, URE, CAL, and ALB (TE: 14.2%, 18.4%, 24.5%, 24.0%, 27.9%, 12.7%, 0.3 mmol/l, and 16%, respectively). Potential errors for IQC of Humatrol P in Lot 003 were detected in GLU, CHO, TP, URE, CAL, and ALB (TE: 17.4%, 12.2%, 25.2%, 10.4%, 0.49 mmol/l, and 16%, respectively). Multi rules was suggested to monitor IQC performance (Sigma scale ranged from 3 to 5). The four keys finding of problems relate to policy/regulation on reagent and supply, staff, Monitor/supervise were revealed and the recommendations have been provided to laboratory are include establish Stock Inventory Information System, IQC Information Management System, conduct advance staff training on IQC interpretation and troubleshooting, provide enough spare part and stabilizer, and regular maintenance on material and equipment.

Conclusion
When evaluated on the Total Error and the sigma metric, potential errors of IQC performance in NPHL were detected include five tests in IQC Humatrol N and P including CHO, CREA, URE, CAL, and ALB were outside desirable limits of TEa. The problems were identified by conducted focus group discussion, and the four priority actions were recommended to solve.

Key words
Internal Quality Control (IQC), Total Error (TE), Total Allowable Error (TEa), and Sigma Metric.

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Implementation research: a mentoring program to improve laboratory quality in Cambodia

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Lucy A Perrone¹, Vireak Voeurng², Sophat Sek², Sophanna Song², Nora Vong², Chansamrach Tous², Jean-Frederic Flandin¹, Deborah Confer¹, Alexandre Costa³ & Robert Martin³

1. International Training and Education Center for Health, Department of Global Health, School of Public Health, University of Washington, 901 Boren Ave, Suite 1100, Seattle, WA 98104, United States of America.
2. International Training and Education Center for Health-Cambodia, Phnom Penh, Cambodia.
3. World Health Organization, Phnom Penh, Cambodia.

Abstract

Objective

To implement a mentored laboratory quality stepwise implementation (LQSI) program to strengthen the quality and capacity of Cambodian hospital laboratories.

Methods

We recruited four laboratory technicians to be mentors and trained them in mentoring skills, laboratory quality management practices and international standard organization (ISO) 15189 requirements for medical laboratories. Separately, we trained staff from 12 referral hospital laboratories in laboratory quality management systems followed by tri-weekly in-person mentoring on quality management systems implementation using the LQSI tool, which is aligned with the ISO 15189 standard. The tool was adapted from a web-based resource into a software-based spreadsheet checklist, which includes a detailed action plan and can be used to qualitatively monitor each laboratory’s progress. The tool – translated into Khmer – included a set of quality improvement activities grouped into four phases for implementation with increasing complexity. Project staff reviewed the laboratories’ progress and challenges in weekly conference calls and bi-monthly meetings with focal points of the health ministry, participating laboratories and local partners. We present the achievements in implementation from September 2014 to March 2016.

Findings

As of March 2016, the 12 laboratories have completed 74–90% of the 104 activities in phase 1, 53–78% of the 178 activities in phase 2, and 18–26% of the 129 activities in phase 3.

Conclusion

Regular on-site mentoring of laboratories using a detailed action plan in the local language allows staff to learn concepts of quality management system and learn on the job without disruption to laboratory service provision.

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