Neutrophil-to-Lymphocyte Ratio and Post-Tuberculosis Pulmonary Function: A Potential Marker for Reduced Function

Abstract RATIONALE: Pulmonary tuberculosis (PTB) causes long-term pulmonary function impairment in up to 50% of cases; however, risk factors for post-tuberculosis lung disease (PTLD) are not well-established. Neutrophilic inflammation has been implicated in the pathogenesis of PTLD, and neutrophil-to-lymphocyte ratio (NLR), a marker of neutrophilic inflammation, is associated with disease severity and mortality in sepsis, pneumonia, and bronchiectasis with NLR ≥6.0 considered significantly elevated. We sought to determine if NLR is associated with spirometry defects after successful PTB treatment. METHODS: We enrolled adults (age≥18) in Chennai and Pune, India, with newly diagnosed drug-sensitive PTB within one week of initiating tuberculosis treatment. Complete blood counts with differential were performed at enrollment using fluorescence flow cytometry. Spirometry was performed at any time point during 12 months of post-PTB treatment follow-up. We evaluated the association of baseline absolute neutrophil counts (ANC) and NLR with forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and FEV1/FVC ratio z-scores using linear regression. Multivariable models adjusted for age, sex, HIV, diabetes, ever-smoking, body mass index (BMI), and Timika chest X-ray score. RESULTS: Of 120 participants included in this analysis, 64 (53%) were male, 25 (21%) ever-smoked, 14 (12%) had diabetes, and 15 (13%) had HIV. The median age and BMI were 32 (IQR 23 – 40) years and 18.16 (IQR 16.56 – 20.56) kg/m2, respectively. The median Timika chest x-ray score was 55 (IQR 25 – 75), and median NLR was 3.36 (IQR 2.42 – 5.01) at enrollment. Eighteen (15%) had NLR ≥6.0. Up to 12 months after PTB treatment, the median FEV1 and FVC z-scores were -2.02 (IQR -4.09 to -0.37) and -1.39 (IQR -3.46 to -0.06), respectively; 29 (24%) had airflow obstruction, and 39 (33%) had restrictive spirometry. Higher baseline NLR was independently associated with reduced FEV1 (-0.37 z-score per unit higher NLR; 95% CI [-0.71, -0.02]; p=0.038) and FVC (-0.32 z-score per unit higher NLR; 95% CI [-0.61, -0.03]; p=0.033). NLR ≥6.0 had a stronger negative association with FEV1 (-3.08 z-score; 95% CI [-5.21, -0.97]; p=0.005) and FVC (-2.52 z-score; 95% CI [-4.34, -0.71]; p=0.007). ANC was also associated with reduced FEV1 and FVC z-scores; however, these results were not statistically significant. CONCLUSIONS: Our study suggests NLR could be used as a point-of-care biomarker to identify those at higher risk of developing PTLD. Future studies should validate its use in larger cohorts and with spirometry obtained beyond 12 months following PTB treatment.