Work continues on novel endpoint analysis resulting from the iABC clinical studies and will appear in this section in due course.

Some initial findings:

Novel quantitative bronchiectasis scoring technique for chest computed tomography

Abstract from European Respiratory Journal 2019 54: PA4817; DOI: 10.1183/13993003.congress-2019.PA4817

Objectives: To develop a sensitive CT outcome measure to phenotype and quantify lung disease in bronchiectasis (BE) patients.

Methods: Collection of the most recent CT scan of BE patients with chronic Pseudomonas aeruginosa infection enrolled in the iBEST-1 study, an RCT of inhaled tobramycin. Volumetric CT scans with a slice thickness ≤ 3 mm were included. In the BE scoring technique for CT (BEST-CT), grid cells were annotated on 10 axial slices. Scoring items in hierarchical order: consolidation/ atelectasis, BE with mucus plugging (MP), BE without MP, airway wall thickening (AWT), MP, ground-glass opacities (GGO), emphysema/ bullae, healthy airways, and healthy parenchyma. Low attenuation regions were scored on expiratory scans. Subscores are expressed as median [IQR] as % of total lung volume. CT scans were also scored using the Hartmann method developed for immunodeficiency patients, and 20 scans were rescored for agreement analyses.

Results: We collected 99 CT scans, and included 85 CT scans. Median BE was 3.0% [1.4-5.1], MP 2.7% [1.5-6.1], AWT 0.1 [0-0.2], total airway disease (BE + MP + AWT) 6.2% [3.4-11.8], consolidation/ atelectasis 1.5% [0.6-3.2], GGO 0.3% [0.1-1.1], and emphysema/ bullae 0% [0-0] of total lung volume. Besides BE, atelectasis/ consolidation (84/85), MP (83/85), GGO (68/85), and AWT (55/85) were most frequent annotated abnormalities. Emphysema/ bullae were annotated the least often (13/85). To be performed: inter-and intra-observer agreement analyses and comparison with the Hartmann method.

Conclusion: BEST-CT is a quantitative scoring method for BE. Subscores can be used for phenotyping and as outcome measures in clinical trials.

Multiple-Breath Washout Outcome Measures in Adults with Bronchiectasis

Abstract from Annals of The American Thoracic Society https://doi.org/10.1513/AnnalsATS.202006-584OC

Rationale: Lung clearance index (LCI) has good intravisit repeatability with better sensitivity in detecting lung disease on computed tomography scan compared with forced expiratory volume in 1 second (FEV₁) in adults with bronchiectasis. Alternative multiple-breath washout parameters have not been systematically studied in bronchiectasis.

Objectives: To determine the validity, repeatability, sensitivity, specificity, and feasibility of standard LCI (LCI^2.5), shortened LCI (LCI^5.0), ventilation heterogeneity arising within proximal conducting airways (S_condVT), and ventilation heterogeneity arising within the acinar airways (S_acinVT) in a cross-sectional observational cohort of adults with bronchiectasis.

Methods: Cross-sectional multiple-breath nitrogen washout data (Exhalyzer D; Eco Medics AG) from 132 patients with bronchiectasis across five United Kingdom centers (BronchUK Clinimetrics study) and 88 healthy control subjects were analyzed.

Results: Within-test repeatability (mean coefficient of variation) was <5% for both LCI^2.5 and LCI^5.0 in patients with bronchiectasis, and there was no difference in mean coefficient of variation for LCI^2.5 and LCI^5.0 in patients with bronchiectasis compared with healthy volunteers. Moderate-strength correlations were seen between FEV₁ and LCI^2.5 (r = −0.54), LCI^5.0 (r = −0.53), S_condVT (r = −0.35), and S_acinVT (r = −0.38) z-scores. The proportion of subjects with abnormal multiple-breath washout (z-score > 2) but in normal FEV₁ (z-score < −2) was 42% (LCI^2.5) and 36% (LCI^5.0). Overall results from the receiver operating characteristic curve analysis indicated that LCI^2.5 had the greatest combined sensitivity and specificity to discriminate between bronchiectasis and control subjects, followed by LCI^5.0, FEV₁, and S_condVT z-scores. There was a 57% time saving with LCI^5.0.

Conclusions: LCI^2.5 and LCI^5.0 had good within-test repeatability and superior sensitivity compared with spirometry measures in differentiating between health and bronchiectasis disease. LCI^5.0 is quicker and more feasible than LCI^2.5.