Maximal mid-expiratory flow is a surrogate marker of lung clearance index for assessment of adults with bronchiectasis

Wei-Jie Guan, Jing-Jing Yuan, Yong-Hua Gao, Hui-Min Li, Jin-Ping Zheng, Rong-Chang Chen, Nan-Shan Zhong, Wei-Jie Guan, Jing-Jing Yuan, Yong-Hua Gao, Hui-Min Li, Jin-Ping Zheng, Rong-Chang Chen, Nan-Shan Zhong

Abstract

Little is known about the comparative diagnostic value of lung clearance index (LCI) and maximal mid-expiratory flow (MMEF) in bronchiectasis. We compared the diagnostic performance, correlation and concordance with clinical variables, and changes of LCI and MMEF% predicted during bronchiectasis exacerbations (BEs). Patients with stable bronchiectasis underwent history inquiry, chest high-resolution computed tomography (HRCT), multiple-breath nitrogen wash-out test, spirometry and sputum culture. Patients who experienced BEs underwent these measurements during onset of BEs and 1 week following antibiotics therapy. Sensitivity analyses were performed in mild, moderate and severe bronchiectasis. We recruited 110 bronchiectasis patients between March 2014 and September 2015. LCI demonstrated similar diagnostic value with MMEF% predicted in discriminating moderate-to-severe from mild bronchiectasis. LCI negatively correlated with MMEF% predicted. Both parameters had similar concordance in reflecting clinical characteristics of bronchiectasis and correlated significantly with forced expiratory flow in one second, age, HRCT score, Pseudomonas aeruginosa colonization, cystic bronchiectasis, ventilation heterogeneity and bilateral bronchiectasis. In exacerbation cohort (n = 22), changes in LCI and MMEF% predicted were equally minimal during BEs and following antibiotics therapy. In sensitivity analyses, both parameters had similar diagnostic value and correlation with clinical variables. MMEF% predicted is a surrogate of LCI for assessing bronchiectasis severity.

Trial registration: ClinicalTrials.gov NCT01761214.

Conflict of interest statement

Profs. Zhong and Chen declared that they had received Changjiang Scholars and Innovative Research Team in University ITR0961, The National Key Technology R&D Program of the 12th National Five-year Development Plan 2012BAI05B01 and National Key Scientific & Technology Support Program: Collaborative innovation of Clinical Research for chronic obstructive pulmonary disease and lung cancer No. 2013BAI09B09. Dr. Guan declared that he has received National Natural Science Foundation No. 81400010 and 2014 Scientific Research Projects for Medical Doctors and Researchers from Overseas, Guangzhou Medical University No. 2014C21. All other authors declared no potential conflict of interest. None of the funding sources had any role on the study.

Figures

Figure 1. Patient recruitment flowchart Of 146…
Figure 1. Patient recruitment flowchart Of 146 patients who underwent screening, 115 successfully participated in baseline measurements.
Of these patients, 39 experienced Exacerbations and 22 accomplished exacerbation visits.
Figure 2. Diagnostic performance of LCI and…
Figure 2. Diagnostic performance of LCI and MMEF predicted% in clinically stable bronchiectasis.
(A), Diagnostic performance of LCI and MMEF% predicted in patients with Bronchiectasis Severity Index of 5 or greater; AUC: 0.672, 95% CI: (0.57, 0.78) for LCI; AUC: 0.63, 95% CI: (0.52, 0.74) for MMEF% predicted. (B), Diagnostic performance of LCI and MMEF% predicted in patients with Bronchiectasis Severity Index of 9 or greater; AUC: 0.71, 95% CI: (0.60, 0.81) for LCI; AUC: 0.67, 95% CI: (0.56, 0.78) for MMEF% predicted. (C), Diagnostic performance of LCI and MMEF% predicted in bronchiectasis patients with HRCT score of 7 or greater; AUC: 0.83, 95% CI: (0.76, 0.91) for LCI; AUC: 0.82, 95% CI: (0.75, 0.90) for MMEF% predicted (D), Diagnostic performance of LCI and MMEF% predicted in bronchiectasis patients with HRCT score of 13 or greater. AUC: 0.92, 95% CI: (0.87, 0.98) for LCI; AUC: 0.81, 95% CI: (0.71, 0.92) for MMEF% predicted AUC: area under curve The bold black line indicated the LCI, whereas the grey dotted line represented the minus MMEF% predicted (for direct comparison purposes).
Figure 3. Association between LCI and MMEF%…
Figure 3. Association between LCI and MMEF% predicted and disease severity.
(A), Association between LCI and the Bronchiectasis Severity Index; Thirty-eight patients had a Bronchiectasis Severity Index of 4 or lower, 39 patients had a Bronchiectasis Severity Index of 5 or greater and 8 or lower, and 33 patients had a Bronchiectasis Severity Index of 9 or greater. (B), Association between MMEF% predicted and the Bronchiectasis Severity Index; Thirty-eight patients had a Bronchiectasis Severity Index of 4 or lower, 39 patients had a Bronchiectasis Severity Index of 5 or greater and 8 or lower, and 33 patients had a Bronchiectasis Severity Index of 9 or greater. (C), Association between LCI and the HRCT total score; Forty-four patients had an HRCT total score of 6 or lower, 46 patients had an HRCT total score of 7 or greater and 12 or lower, and 20 patients had an HRCT total score of 13 or greater. (D), Association between MMEF% predicted and the HRCT total score. Forty-four patients had an HRCT total score of 6 or lower, 46 patients had an HRCT total score of 7 or greater and 12 or lower, and 20 patients had an HRCT total score of 13 or greater.
Figure 4. Changes in LCI and MMEF%…
Figure 4. Changes in LCI and MMEF% predicted from baseline to acute exacerbation and post-antibiotic treatment visit
(A). Changes in LCI predicted from baseline to acute exacerbation and post-antibiotic treatment visit in all bronchiectasis patients; (B). Changes in MMEF% predicted from baseline to acute exacerbation and post-antibiotic treatment visit in all bronchiectasis patients.

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