Yeonsoo Baik

Lung function and collagen 1a levels are associated with changes in six-minute walk test distance during treatment of TB among HIV-infected adults: a prospective cohort study

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Presenter

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Dr. Yeonsoo Baik is a Research Associate in the Department of Biostatistics, Epidemiology, and Informatics at the Perelman School of Medicine with a primary research interest in introducing new TB diagnostics within an innovative self-testing approach to encourage more potential patients to engage with the care system. Dr. Baik has received extensive training in advanced epidemiological methods and statistics. 

Authors

Y Baik1, Y Li1, S Auld2, G Bisson1

  1. Department of Biostatistics, Epidemiology, and Informatics, Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia
  2. Departments of Medicine and Epidemiology, School of Medicine and Rollins School of Public Health, Emory University, Atlanta, GA, USA

Abstract

Background

Tuberculosis (TB) survivors often suffer from post-TB sequelae that affect the overall functional decline. We evaluated the functional capacity over the treatment course and identified which immunological pathways are associated.

Methods

Adults with HIV/TB who initiated antiretroviral therapy (ART) and anti-TB treatment at the time of enrollment were recruited for the study at a primary health center in South Africa. They were followed up at week 4, week 12, and month 6, and underwent clinical evaluations of lung function, inflammatory biomarker serum levels, and six-minute walk distances (6MWDs) – which reflect functional capacity. We examined the association of 6MWDs at month 6 with changes in biomarker levels. We repeated the examination using a minimum clinically important difference (MCID).

Results

Of 128 patients, 89 (70%) were successfully followed up. The average 6MWD was 393 (±69) meters at baseline and increased by 9% (430 ±70 meters) at month 6. Patients who experienced MCID in 6MWD had more severe conditions at baseline but improved 6MWDs by 28%. The substantial increases in 6MWDs were associated with changes in biomarker levels, such as collagen I alpha (9.5 meters increased per 1000pg/L, 95% Confidence Interval [CI]=0.4-18.6) and VCAM1 (16.0 meters decreased per 1000000pg/L, 95%CI=-29.2,-2.8). Despite the improvement, patients’ 6MWDs and biomarker levels did not reach the normal range. 

Conclusion

Our findings highlight biomarkers, involved in tissue repair, were associated with an improved functional capacity among the advanced HIV/TB cohort. This reflects the restorative capacity of ART and anti-TB treatment and suggests dynamics for inflammatory and tissue remodeling processes during and after treatment. 

Keywords

HIV/TB, six-minute walk test, inflammatory biomarkers

Comments

Really interesting results! Do you have a biological hypothesis regarding why collagen would increase for those with increases in walking? Would it be related to increases in muscular growth more generally?
Great work!

Dr. Baik sent this reply: We actually expected Collagen 1a would be negatively associated with a six-minute walk distance as seen in other inflammatory biomarkers. We are interpreting this result as 1) perhaps increases in Collagen 1a reflect the extent of recovery during the treatment from a greater initial injury; and 2) greater muscle mass (as you said!) or other extrapulmonary characteristics could manifest as greater exercise capacity. Certainly, our findings are pretty robust and the relationship is opposite from our expectation or other literature exploring Collagen 1a in other respiratory diseases.

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