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Inhaled Antibiotics in Bronchiectasis and Cystic Fibrosis (iABC)

Novel Endpoints

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

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 (LCI2.5), shortened LCI (LCI5.0), ventilation heterogeneity arising within proximal conducting airways (ScondVT), and ventilation heterogeneity arising within the acinar airways (SacinVT) 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 LCI2.5 and LCI5.0 in patients with bronchiectasis, and there was no difference in mean coefficient of variation for LCI2.5 and LCI5.0 in patients with bronchiectasis compared with healthy volunteers. Moderate-strength correlations were seen between FEV1 and LCI2.5 (r = −0.54), LCI5.0 (r = −0.53), ScondVT (r = −0.35), and SacinVT (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% (LCI2.5) and 36% (LCI5.0). Overall results from the receiver operating characteristic curve analysis indicated that LCI2.5 had the greatest combined sensitivity and specificity to discriminate between bronchiectasis and control subjects, followed by LCI5.0, FEV1, and ScondVT z-scores. There was a 57% time saving with LCI5.0.

Conclusions: LCI2.5 and LCI5.0 had good within-test repeatability and superior sensitivity compared with spirometry measures in differentiating between health and bronchiectasis disease. LCI5.0 is quicker and more feasible than LCI2.5.