Abstract Rationale The bronchiectasis severity index (BSI) and FACED scores have helped characterize complex bronchiectasis cohorts but they score highly for Pseudomonas positivity. We developed a composite Chest CT score (NECTAR score) to better characterize radiological severity in NTM+ bronchiectasis. After validating the score for a clinical outcome, we delineated various microbiome and host transcriptome characteristics that are pertinent to radiological damage in NTM+ bronchiectasis. Methods BALF samples were collected from 200 bronchiectasis subjects undergoing clinically indicated testing (46% NTM+). All samples underwent 16S rRNA, metatranscriptome and bulk host RNA sequencing and a neutrophil extracellular trap (NET) immunoassay. EdgeR and Ingenuity Pathway Analysis (IPA) were used for comparative analyses. All Chest CT scans were scored based on Nodules, Extent of Cavities, Count of Cavities, Tree-in-Bud and Airway Dilatation by Reiff score (NECTAR score). Range for NECTAR score was 1-42, median 13. IQR 12-16. Subjects with a median/median score were labelled as high-CT-group and the rest as low-CT-group. Results 114/200 subjects had a high NECTAR score, with 59% NTM positivity. The high-CT-group had both significantly higher NET levels and history of exacerbations (p = 0.00000023 and 0.00075, Fig. 1A and 1B), thus validating the score for clinical outcomes. Alpha diversity was lower in the high-CT-group (p = 0.007, Fig. 1C) but beta diversity was not significantly different. EdgeR analysis of 16SrRNA and metatranscriptome sequencing showed enrichment with Proteus, Nocardia, Mycoplasma, Staphylococcus and Mycobacterium, Nocardia, Streptococcus and Influenza A virus (Fig. 1D). Analysis of the host transcriptome identified 3759 differentially enriched genes (DEGs) in the high-CT-group. IPA showed up-regulation of canonical pathways such as IL-10, antimicrobial peptides, and TNFR in the high-CT-group (Fig 1E). Next, specifically in NTM+ subjects, alpha diversity was lower (p = 0.0083) and beta diversity was significantly different (p = 0.047). EdgeR analysis of 16SrRNA and metatranscriptome sequencing showed enrichment with Achromobacter, Stenotrophomonas, Staphylococcus, Mycobacterium and Haemophilus, Achromobacter and Influenza A virus (Fig. 1F). Analysis of the host transcriptome identified 2244 DEGs in the NTM+ high-CT-group. IPA showed up-regulation of phospholipases, p38 MAPK, granzyme A, and IFN signaling in NTM+ high-CT-group (Fig 1G). Conclusions In this study, we show that a composite chest CT score (NECTAR) can be used to predict specific microbiome, host transcriptome and immunological signatures. We envision that this score can be used more reliably than the BSI/FACED in NTM+ subjects who have a higher burden of lung damage than NTM- subjects. This abstract is funded by: American Thoracic Society, NIH
Atandi et al. (2026) studied this question.