INTRODUCTION Despite the exalted status of sputum mycobacterial load for gauging pulmonary tuberculosis treatment and progress, Chest X-rays supplement valuable information for taking instantaneous therapeutic decisions, especially during the COVID-19 pandemic. Even though literature on individual parameters is overwhelming, few studies have explored the interaction between radiographic parameters denoting severity with mycobacterial burden signifying infectivity. By using a sophisticated approach of integrating Chest X-ray parameters with sputum mycobacterial characteristics, evaluated at all the three crucial time points of TB treatment namely pre-treatment, end of intensive phase and completion of treatment, utilizing the interactive Cox Proportional Hazards model, we aimed to precisely deduce predictors of unfavorable response to TB treatment. MATERIALS AND METHOD We extracted de-identified data from well characterized clinical trial cohorts that recruited rifampicin-sensitive Pulmonary TB patients without any comorbidities, taking their first spell of anti-tuberculosis therapy under supervision and meticulous follow up for 24 months post treatment completion, to accurately predict TB outcomes. Radiographic data independently obtained, interpreted by two experienced pulmonologists was collated with demographic details and, sputum smear and culture grades of participants by an independent statistician and analyzed using the Cox Proportional Hazards model, to not only adjust for confounding factors including treatment effect, but also explore the interaction between radiological and bacteriological parameters for better therapeutic application. RESULTS Of 667 TB patients with data available, cavitation, extent of involvement, lower zone involvement, smear and culture grade at baseline were significant parameters predisposing to an unfavorable TB treatment outcome in the univariate analysis. Reduction in radiological lesions in Chest X-ray by at least 50% at 2 months and 75% at the end of treatment helped in averting unfavorable responses. Smear and Culture conversion at the end of 2 months was highly significant as a predictor (p<0.001). In the multivariate analysis, the adjusted hazards ratios (HR) for an unfavorable response to TB therapy for extent of involvement, baseline cavitation and persistence (post treatment) were 1.21 (95% CI: 1.01-1.44), 1.73 (95% CI: 1.05-2.84) and 2.68 (95% CI: 1.4-5.12) respectively. A 3+ smear had an HR of 1.94 (95% CI: 0.81-4.64). Further probing into the interaction, among patients with 3+ and 2+ smears, HRs for cavitation were 3.26 (95% CI: 1.33-8.00) and 1.92 (95% CI: 0.80-4.60) while for >2 zones, were 3.05 (95% CI: 1.12-8.23) and 1.92 (95% CI: 0.72-5.08) respectively. Patients without cavitation, zonal involvement <2, and a smear grade less than 2+ had a better prognosis and constituted minimal disease. CONCLUSION Baseline Cavitation, Opacities occupying >2 zones and 3+ smear grade individually and independently forecasted a poorer TB outcome. The interaction model revealed that Zonal involvement confined to 2 zones, without a cavity and smear grade up to 2+, constituting "minimal disease", had a better prognosis. Radiological clearance >50% along with smear conversion at the end of intensive phase of treatment, observed to be a reasonable alternative to culture conversion in predicting a successful outcome. These parameters may potentially take up key positions as stratification factors for future trials contemplating on shorter TB regimens.

中文翻译：

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使用放射学表现和痰分枝杆菌负荷的综合方法预测对利福平敏感的肺结核治疗的不利反应。

简介 尽管痰分枝杆菌负荷在衡量肺结核治疗和进展方面的地位很高，但胸部 X 光片为做出即时治疗决定提供了有价值的信息，尤其是在 COVID-19 大流行期间。尽管关于个别参数的文献是压倒性的，但很少有研究探讨表示严重程度的放射学参数与表示感染性的分枝杆菌负担之间的相互作用。通过使用将胸部 X 射线参数与痰分枝杆菌特征相结合的复杂方法，利用交互式 Cox 比例危险模型，在结核病治疗的所有三个关键时间点（即治疗前、强化期结束和治疗完成）进行评估，我们旨在准确推断出对结核病治疗不利的预测因子。材料和方法 我们从特征明确的临床试验队列中提取了去识别的数据，这些队列招募了对利福平敏感且没有任何合并症的肺结核患者，在监督下接受了他们的第一次抗结核治疗，并在治疗完成后进行了 24 个月的细致随访，以准确预测结核病结局。由两名经验丰富的肺科医师独立获得并解读的放射影像数据与人口统计细节以及参与者的痰涂片和培养等级由独立统计学家进行比较，并使用 Cox 比例风险模型进行分析，不仅调整混杂因素，包括治疗效果，而且探索放射学和细菌学参数之间的相互作用，以更好地应用治疗。结果 在有可用数据的 667 名 TB 患者中，空洞、受累程度、较低区域受累、涂片和基线时的培养等级是单变量分析中导致不利 TB 治疗结果的重要参数。2 个月时胸部 X 光检查中的放射损伤减少至少 50%，治疗结束时减少 75%，这有助于避免不良反应。2 个月末的涂片和培养转化作为预测指标非常显着（p<0.001）。在多变量分析中，对结核病治疗的不利反应在受累程度、基线空化和持续性（治疗后）的调整后风险比（HR）分别为 1.21（95% CI：1.01-1.44）、1.73（95% CI： 1.05-2.84) 和 2.68 (95% CI: 1.4-5.12)。3+ 涂片的 HR 为 1.94（95% CI：0.81-4.64）。进一步探讨相互作用，在涂片 3+ 和 2+ 的患者中，气蚀的 HR 分别为 3.26（95% CI：1.33-8.00）和 1.92（95% CI：0.80-4.60），而对于 >2 个区域，为 3.05（ 95% CI: 1.12-8.23) 和 1.92 (95% CI: 0.72-5.08)。无空洞、区域受累<2、涂片分级低于2+的患者预后较好，属于最小病灶。结论 基线空化、占据>2 个区域的不透明度和3+ 涂片等级单独和独立地预测较差的结核病结果。交互作用模型显示，区域受累局限于2个区域，无空洞，涂片分级达2+，构成“最小病变”，预后较好。放射学清除率 > 50% 以及在强化治疗阶段结束时涂片转化，观察到在预测成功结果方面是文化转换的合理替代方案。这些参数可能会成为未来考虑较短结核病治疗方案试验的分层因素的关键位置。