Multiple-Breath Washout Outcome Measures in Adults with Bronchiectasis

Abstract

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. Clinical trial registered with www.clinicaltrials.gov (NCT02468271).

Keywords: bronchiectasis; lung function; multiple breath washout.

Figure 1.

(A) Relationship between forced expiratory volume in 1 second (FEV₁) and standard lung clearance index (LCI 2.5) z-scores. Dotted lines indicate FEV₁ LLN and LCI 2.5 ULN. Percentage indicates proportion in each quadrant. (B) Relationship between FEV₁ and shortened lung clearance index (LCI 5.0) z-scores. Dotted lines indicate FEV₁ LLN and LCI 5.0 ULN. Percentage indicates proportion in each quadrant. CI = confidence interval; LLN = lower limit of normal; ULN = upper limit of normal.

Figure 2.

(A) Relationship between forced expiratory volume in 1 second (FEV₁) and ventilation heterogeneity arising within proximal conducting airways (ScondVT) z-scores. Dotted lines indicate FEV₁ LLN and ScondVT ULN. Percentage indicates proportion in each quadrant. (B) Relationship between FEV₁ and ventilation heterogeneity arising within the acinar airways (SacinVT) z-scores. Dotted lines indicate FEV₁ LLN and SacinVT ULN. Percentage indicates proportion in each quadrant. CI = confidence interval; LLN = lower limit of normal; ULN = upper limit of normal.

Figure 3.

(A) Relationship between forced expiratory flow at 25–75% (FEF_25–75) and standard lung clearance index (LCI 2.5) z-scores. Dotted lines indicate FEF_25–75 LLN and LCI 2.5 ULN. Percentage indicates proportion in each quadrant. (B) Relationship between FEF_25–75 and shortened lung clearance index (LCI 5.0) z-scores. Dotted lines indicate FEF_25–75 LLN and LCI 5.0 ULN. Percentage indicates proportion in each quadrant. CI = confidence interval; LLN = lower limit of normal; ULN = upper limit of normal.

Figure 4.

ROC curves showing the sensitivity of multiple-breath washout and spirometry z-score parameters between healthy control subjects and subjects with bronchiectasis. FEF = forced expiratory flow; FEV₁ = forced expiratory volume in 1 second; FVC = forced vital capacity; LCI2.5 = standard lung clearance index; LCI5.0 = shortened lung clearance index; ROC = receiver operating characteristic.