Abstract Rationale Approximately half of all tuberculosis (TB) survivors develop post-TB lung disease (PTLD), defined as persistent respiratory abnormalities despite a microbiological cure. Fibrosis, which typically presents as a restrictive ventilatory impairment on pulmonary function testing (PFT), is common in PTLD. Despite the substantial global burden of PTLD, no guidelines exist for screening TB survivors using PFTs. In this study, we evaluated the utility of spirometry at the end of TB treatment for detecting restrictive lung disease as compared to the gold standard definition with lung volume measurements. Methods In an ongoing observational cohort study in Johannesburg, South Africa, adults with and without HIV were enrolled at the time of drug-susceptible pulmonary TB diagnosis. At TB treatment completion, participants underwent comprehensive PFTs (spirometry, lung volumes by multiple breath washout, diffusion capacity) with standardized z-scores calculated using ATS/ERS-recommended GLI-Global reference equations. Restriction, defined as a total lung capacity (TLC) less than the lower limit of normal (LLN, z-score -1.65), was compared to two definitions of restrictive spirometric patterns: (1) forced vital capacity (FVC) LLN and (2) FVC LLN and forced expiratory volume in one second (FEV1)/FVC ≥ LLN. Receiver operating characteristic (ROC) analyses compared diagnostic performance across continuous values of these two definitions. Results Among 109 adults who completed TB treatment, (median age 36 years IQR: 30-46, 72% male, 62% ever-smokers, 62% HIV-negative), restriction was prevalent (21%) and did not differ by HIV status (HIV-positive: 29% vs. HIV-negative: 16%, p = 0.10). The sensitivities of “FVC LLN” with and without “FEV1/FVC ≥ LLN” were 0.78 (95% CI: 0.56-0.93) and 0.57 (95% CI: 0.34-0.77), with corresponding specificities of 0.94 (95% CI: 0.87-0.98), and 0.94 (95% CI: 0.87-0.98), respectively (Table 1). ROC analyses showed no significant difference in the continuous measures of FVC with and without FEV1/FVC for detecting restriction across all participants and within HIV strata (data not shown). Threshold analysis identified an FVC z-score of -1.26 as achieving a 90% sensitivity for restriction. Conclusions Restrictive spirometric patterns showed poor-to-moderate sensitivity in detecting restrictive lung disease after TB treatment, and the inclusion of the FEV1/FVC criterion offered no additional diagnostic benefit. The FVC z-score threshold corresponding to an acceptable sensitivity for restriction fell within the expected normal range, underscoring the limitations of spirometry in capturing the full spectrum of pulmonary abnormalities. Incorporating lung volume measurements into post-treatment assessments may substantially improve the accurate diagnosis of restrictive lung disease in PTLD. This abstract is funded by: R01AI166988-04, T32AI157855-04
Marll et al. (Fri,) studied this question.