Elevated Plasma Matrix Metalloproteinase 8 Associates With Sputum Culture Positivity in Pulmonary Tuberculosis

Walker, Naomi F.; Karim, Farina; Moosa, Mohamed Y. S.; Moodley, Sashen; Mazibuko, Matilda; Khan, Khadija; Heijden, Yuri F. van der; Grant, Alison D.; Elkington, Paul; Pym, Alexander S.; Leslie, Al

doi:10.1093/infdis/jiac160

Cited by 5 publications

(7 citation statements)

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“…Elevated plasma MMP-8, together with MMP-3, -7, -10 and PIIINP associated with Mtb -BSI and mortality at 12 weeks, suggesting that MMP upregulation and matrix turnover are features of TB disease severity. This is in keeping with our recently reported finding that elevated plasma MMP-8 concentrations at the end of TB treatment are associated with persistent Mtb culture positivity (7). In the clustering analysis, MMP-8 was most closely associated with procalcitonin (an acute phase reactant) and the matrix degradation product, PIIINP (released during Type III collagen turnover), suggesting that MMP-8 activity, collagen turnover and acute inflammation are closely related processes in HIV-TB (5, 8).…”

Section: Discussionsupporting

confidence: 93%

Elevated plasma matrix metalloproteinases associate withMycobacterium tuberculosisblood stream infection and mortality in HIV-associated tuberculosis

Walker,

Schutz,

Ward

et al. 2023

Preprint

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Mortality from HIV-associated tuberculosis (HIV-TB) is high, particularly among hospitalised patients. In 433 people living with HIV admitted to hospital with symptoms of TB, we investigated plasma matrix metalloproteinases (MMP) and matrix-derived biomarkers in relation to TB diagnosis, mortality andMycobacterium tuberculosis(Mtb)blood stream infection (BSI). Compared to other diagnoses, MMP-8 was elevated in confirmed TB and inMtb-BSI, positively correlating with extracellular matrix breakdown products. Baseline MMP- 3, -7, -8, -10 and procollagen III N-terminal propeptide (PIIINP) associated withMtb-BSI and 12-week mortality. These findings implicate MMP dysregulation in pathophysiology of advanced HIV-TB and support MMP inhibition as a host-directed therapeutic strategy for HIV- TB.

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Section: Discussionsupporting

confidence: 93%

Elevated plasma matrix metalloproteinases associate withMycobacterium tuberculosisblood stream infection and mortality in HIV-associated tuberculosis

Walker,

Schutz,

Ward

et al. 2023

Preprint

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“…This indicates that changes in the levels of these inflammatory mediators are linked with the early bactericidal effect during the first two months of intensive TB treatment. Similar results were observed in previous studies [ 18 , 19 , 23 , 29 , 31 , 32 ]. Neutrophil levels in blood correlated negatively with MMP-2 at baseline and month 6, and they also declined during TB treatment, with the opposite effect observed for MMP-2 levels.…”

Section: Discussionsupporting

confidence: 92%

“…Muefong and Sutherland (2020) described that levels of pro-inflammatory neutrophil-derived mediators in blood, such as MMP-1, -2, -3, -8 and -9, are linked to lung damage at baseline and lung recovery [ 18 , 22 ]. Consistent with these results, another study also showed that levels of certain neutrophil mediators decreased upon TB treatment initiation in a cohort of TB patients living with HIV; hence, such MMPs can be potential biomarkers for monitoring TB treatment regardless of HIV coinfection [ 23 ].…”

Section: Introductionmentioning

confidence: 58%

Effect of TB Treatment on Neutrophil-Derived Soluble Inflammatory Mediators in TB Patients with and without HIV Coinfection

Sitoe,

Chelene,

Ligeiro

et al. 2023

Pathogens

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The mycobacteriological analysis of sputum samples is the gold standard for tuberculosis diagnosis and treatment monitoring. However, sputum production can be challenging after the initiation of TB treatment. As a possible alternative, we therefore investigated the dynamics of neutrophil-derived soluble inflammatory mediators during TB treatment in relation to HIV ART status and the severity of lung impairment. Plasma samples of TB patients with (N = 47) and without HIV (N = 21) were analyzed at baseline, month 2, month 6 (end of TB treatment) and month 12. Plasma levels of MMP-1, MMP-8, MPO and S100A8 markedly decreased over the course of TB treatment and remained at similar levels thereafter. Post-TB treatment initiation, significantly elevated plasma levels of MMP-8 were detected in TB patients living with HIV, especially if they were not receiving ART treatment at baseline. Our data confirm that the plasma levels of neutrophil-based biomarkers can be used as candidate surrogate markers for TB treatment outcome and HIV-infection influenced MMP-8 and S100A8 levels. Future studies to validate our results and to understand the dynamics of neutrophils-based biomarkers post-TB treatment are needed.

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“…In this study, the prevalence of malnutrition in patients with bacterial positivity was significantly higher than bacteria negative, and bacterial positivity was a risk factor for malnutrition. Walker et al ( 78 ) observed that patients with bacterial positivity had significantly higher levels of inflammatory factors, such as matrix metalloproteinase 1 and matrix metalloproteinase 8, than negative patients, and the stronger the inflammatory response, the more active the catabolism, the greater the energy expenditure, and the greater the risk for malnutrition. Moreover, malnutrition can also lead to delayed sputum conversion ( 16 ).…”

Section: Discussionmentioning

confidence: 99%

Prevalence and risk factors of malnutrition in patients with pulmonary tuberculosis: a systematic review and meta-analysis

Li,

Yuan,

et al. 2023

Front. Med.

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BackgroundMalnutrition is prevalent in patients with pulmonary tuberculosis (PTB) and is associated with a poor prognosis.ObjectiveThis study aims to assess the prevalence and risk factors of malnutrition in patients with PTB.MethodsStudies related to the prevalence and risk factors of malnutrition in patients with PTB were searched through PubMed, Embase, Web of Science, and Cochrane Library databases from January 1990 to August 2022, and two researchers screened the literature, evaluated the quality, and extracted data independently. A random-effects model was used to pool the effect sizes and 95% confidence intervals. Subgroup analysis, meta-regression analysis, and sensitivity analysis were further performed to identify sources of heterogeneity and evaluate the stability of the results. Publication bias was assessed by Doi plot, Luis Furuya-Kanamori (LFK) asymmetry index, funnel plot, and Egger's tests.ResultsA total of 53 studies involving 48, 598 participants were identified in this study. The prevalence of malnutrition was 48.0% (95% CI, 40.9–55.2%). Subgroup analysis revealed that malnutrition was more common among male gender (52.3%), bacterial positivity (55.9%), family size over 4 (54.5%), drug resistance (44.1%), residing in rural areas (51.2%), HIV infection (51.5%), Asian (51.5%), and African (54.5%) background. The prevalence of mild, moderate, and severe malnutrition was 21.4%, 14.0%, and 29.4%, respectively. Bacterial positivity (OR = 2.08, 95% CI 1.26–3.41), low income (OR = 1.44, 95% CI 1.11–1.86), and residing in rural areas (OR = 1.51, 95% CI 1.20–1.89) were risk factors of malnutrition in patients with PTB. However, male (OR = 1.04, 95% CI 0.85–1.26) and drinking (OR = 1.17, 95% CI 0.81–1.69) were not risk factors for malnutrition in patients with PTB. Due to the instability of sensitivity analysis, HIV infection, age, family size, smoking, and pulmonary cavity need to be reevaluated. Meta-regression suggested that sample size was a source of heterogeneity of prevalence. The Doi plot and LFK asymmetry index (LFK = 3.87) indicated the presence of publication bias for prevalence, and the funnel plot and Egger's test showed no publication bias for risk factors.ConclusionThis meta-analysis indicated that malnutrition was prevalent in patients with PTB, and bacterial positivity, low income, and those residing in rural areas were risk factors for malnutrition. Therefore, clinical workers should pay attention to screening the nutritional status of patients with PTB and identifying the risk factors to reduce the incidence of malnutrition and provide nutritional interventions early to improve the prognosis in patients with PTB.

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Elevated Plasma Matrix Metalloproteinase 8 Associates With Sputum Culture Positivity in Pulmonary Tuberculosis

Cited by 5 publications

References 12 publications

Elevated plasma matrix metalloproteinases associate withMycobacterium tuberculosisblood stream infection and mortality in HIV-associated tuberculosis

Elevated plasma matrix metalloproteinases associate withMycobacterium tuberculosisblood stream infection and mortality in HIV-associated tuberculosis

Effect of TB Treatment on Neutrophil-Derived Soluble Inflammatory Mediators in TB Patients with and without HIV Coinfection

Prevalence and risk factors of malnutrition in patients with pulmonary tuberculosis: a systematic review and meta-analysis

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