Determining Bacterial Communities in the Lungs of HIV-infected Individuals With COPD in Uganda.
LMB
Investigating the Association Between Altered Lung MicroBiome and HIV-associated Chronic Obstructive Pulmonary Disease in a Ugandan Cohort
3 other identifiers
observational
200
1 country
1
Brief Summary
Research question Is there any association between altered lung bacterial communities and HIV-associated Chronic Obstructive Pulmonary Disease (COPD)? Rationale Sub-Saharan Africa has experienced dramatic increases in COPD related-morbidity and mortality. Longitudinal studies have shown that people living with HIV develop worsening airflow obstruction with a prevalence higher than that of the general population (i.e 3.4 to 21% compared to 0.4 to 12.2%). It is still unknown why HIV-infected individuals develop COPD at a prevalence higher than their HIV-negative counterparts. It's been hypothesized that a change in the lung bacterial communities in the setting of HIV drives inflammation leading to lung damage. There is a need to explore the dynamics of lung bacterial communities and elucidate mechanisms responsible for irreversible lung damage that may follow lung disturbances in bacterial richness and diversity. In addition, understanding the bacterial communities of the lung in normal subjects is an essential step in providing negative controls to interpret lung microbe in disease states for-example COPD. Insights from this research will inform efforts to design optimal screening and treatment strategies for COPD in the HIV-infected population in sub Saharan Africa. Methods A cross sectional study will be conducted in which lung bacterial communities in 63 HIV infected participants ≥ 35 years with and without COPD will be compared with 63 HIV negative participants with and without COPD. Participants will be recruited from COPD/HIV and LINK Nakaseke cohorts, which were population based studies conducted in the same study setting. Sputum samples will be collected using sputum DNA collection, preservation and isolation Kits. Extracted bacterial DNA will be sequenced and used to determine all bacterial species in the processed samples using available online metagenomics databases. Analysis plan A histogram will be used to display the frequencies of the identified bacterial species in the processed samples. Bacterial richness and diversity of samples in the 4 groups will be compared to determine any differences.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for all trials
Started Jan 2019
Typical duration for all trials
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
January 11, 2019
CompletedFirst Submitted
Initial submission to the registry
August 24, 2019
CompletedFirst Posted
Study publicly available on registry
August 28, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 1, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
February 1, 2021
CompletedAugust 30, 2019
August 1, 2019
1.1 years
August 24, 2019
August 28, 2019
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Operational taxanomical units
Operational taxonomic units (OTUs) of the four study groups determined from the bacterial genomic sequences.
By Febraury 2020
Study Arms (4)
Group 1
50 HIV-seropositive with spirometry confirmed COPD
Group 2
50 HIV-seropositive without COPD
Group 3
50 HIV-seronegative with spirometry confirmed COPD
Group 4
50 HIV-seronegative without COPD
Interventions
Eligibility Criteria
The study population will include HIV-infected individuals ≥35 years attending rural ART clinics in Nakaseke diagnosed with and without COPD following ERS/ATS guidelines and HIV-negative individuals ≥ 35 years from LiNK cohort in Nakaseke with and without COPD following ERS/ATS guidelines.
You may qualify if:
- Male and female individuals atleast 35 years of age
- Both HIV seropositive and seronegative.
- Spirometry confirmed COPD and no COPD
You may not qualify if:
- Participants with asthma
- Participants with significant respiratory disease other than COPD
- Failure to perform spirometry
- Pulse rate greater than 120 beats per minute
- Blood pressure greater than 140(systolic)/90( diastolic)
- History of headaches in the past 6 months
- History of eye, chest or abdominal surgery
- History of hernia or chest trauma
- Pregnant women
- Bed ridden patients
- Mentally incapacitated patients
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Makerere University Lung Institute
Kampala, 256, Uganda
Related Publications (13)
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PMID: 21074260BACKGROUNDvan Zyl Smit RN, Pai M, Yew WW, Leung CC, Zumla A, Bateman ED, Dheda K. Global lung health: the colliding epidemics of tuberculosis, tobacco smoking, HIV and COPD. Eur Respir J. 2010 Jan;35(1):27-33. doi: 10.1183/09031936.00072909.
PMID: 20044459BACKGROUNDDrummond MB, Kunisaki KM, Huang L. Obstructive Lung Diseases in HIV: A Clinical Review and Identification of Key Future Research Needs. Semin Respir Crit Care Med. 2016 Apr;37(2):277-88. doi: 10.1055/s-0036-1578801. Epub 2016 Mar 14.
PMID: 26974304BACKGROUNDWang Z, Bafadhel M, Haldar K, Spivak A, Mayhew D, Miller BE, Tal-Singer R, Johnston SL, Ramsheh MY, Barer MR, Brightling CE, Brown JR. Lung microbiome dynamics in COPD exacerbations. Eur Respir J. 2016 Apr;47(4):1082-92. doi: 10.1183/13993003.01406-2015. Epub 2016 Feb 25.
PMID: 26917613BACKGROUNDCui L, Morris A, Huang L, Beck JM, Twigg HL 3rd, von Mutius E, Ghedin E. The microbiome and the lung. Ann Am Thorac Soc. 2014 Aug;11 Suppl 4(Suppl 4):S227-32. doi: 10.1513/AnnalsATS.201402-052PL.
PMID: 25148429BACKGROUNDVlahos R, Bozinovski S. Role of alveolar macrophages in chronic obstructive pulmonary disease. Front Immunol. 2014 Sep 10;5:435. doi: 10.3389/fimmu.2014.00435. eCollection 2014.
PMID: 25309536BACKGROUNDMorris A, George MP, Crothers K, Huang L, Lucht L, Kessinger C, Kleerup EC; Lung HIV Study. HIV and chronic obstructive pulmonary disease: is it worse and why? Proc Am Thorac Soc. 2011 Jun;8(3):320-5. doi: 10.1513/pats.201006-045WR.
PMID: 21653535BACKGROUNDCassol E, Cassetta L, Alfano M, Poli G. Macrophage polarization and HIV-1 infection. J Leukoc Biol. 2010 Apr;87(4):599-608. doi: 10.1189/jlb.1009673. Epub 2009 Dec 30.
PMID: 20042468BACKGROUNDSze MA, Hogg JC, Sin DD. Bacterial microbiome of lungs in COPD. Int J Chron Obstruct Pulmon Dis. 2014 Feb 21;9:229-38. doi: 10.2147/COPD.S38932. eCollection 2014.
PMID: 24591822BACKGROUNDCurtis JL, Freeman CM, Hogg JC. The immunopathogenesis of chronic obstructive pulmonary disease: insights from recent research. Proc Am Thorac Soc. 2007 Oct 1;4(7):512-21. doi: 10.1513/pats.200701-002FM.
PMID: 17878463BACKGROUNDBafadhel M, McKenna S, Terry S, Mistry V, Reid C, Haldar P, McCormick M, Haldar K, Kebadze T, Duvoix A, Lindblad K, Patel H, Rugman P, Dodson P, Jenkins M, Saunders M, Newbold P, Green RH, Venge P, Lomas DA, Barer MR, Johnston SL, Pavord ID, Brightling CE. Acute exacerbations of chronic obstructive pulmonary disease: identification of biologic clusters and their biomarkers. Am J Respir Crit Care Med. 2011 Sep 15;184(6):662-71. doi: 10.1164/rccm.201104-0597OC.
PMID: 21680942BACKGROUNDLa Rosa PS, Brooks JP, Deych E, Boone EL, Edwards DJ, Wang Q, Sodergren E, Weinstock G, Shannon WD. Hypothesis testing and power calculations for taxonomic-based human microbiome data. PLoS One. 2012;7(12):e52078. doi: 10.1371/journal.pone.0052078. Epub 2012 Dec 20.
PMID: 23284876BACKGROUND
Biospecimen
Induced sputum specimens
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Alex Kayongo, MBChB,Msc
Makerere University Lung Institute
Central Study Contacts
Study Design
- Study Type
- observational
- Observational Model
- OTHER
- Time Perspective
- CROSS SECTIONAL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 24, 2019
First Posted
August 28, 2019
Study Start
January 11, 2019
Primary Completion
February 1, 2020
Study Completion
February 1, 2021
Last Updated
August 30, 2019
Record last verified: 2019-08
Data Sharing
- IPD Sharing
- Will not share
Individual participant data will remain at Makerere Lung Institute, However, we will submit genomic sequence data to the genomic databases during publication. Use of the data by other researchers will require approval from the Institutional reveiw board.