Multiple-Breath Inert Gas Washout to Assess Ventilation Inhomogeneity in Chronic Obstructive Pulmonary Disease

  • Alan Bell

Student thesis: Master of Philosophy


Background: COPD is a hetergeneous condition with increased morbidity and mortality. Clinical hallmarks include dyspnoea, cough, sputum production, and non-reversible airflow obstruction. It is also associated with exacerbations that become more prevalent as severity increases, leading to further deterioration in health status and accelerated disease progression. Exacerbations are poorly understood and subjective measures are relied upon for diagnosis and monitoring recovery. There is a large amount of current evidence to suggest that increased resistance and VI manifest in mild disease prior to symptoms developing. Recently MBW has been shown to effectively measure VI using LCI in cystic fibrosis. Aims: The aim of this thesis was to evaluate the sensitivity of LCI as a clinical measure of airways disease in COPD. The following were investigated: 1) LCI comparison between COPD and HC's. 2) COPD LCIN2 comparison to other physiological tests. 3) LCIN2 pre and post salbutamol. 4) The intra-test and inter-test variability of LCI. 5) Comparison of LCI measured on 2 different systems. 6) Practicalities of MBW in COPD. 7) Impact of exacerbations on MBW parameters. Methods: Fifty-four COPD and 12 HC's were recruited and performed LCIN2, LCISF6 and spirometry, with a repeatability visit separated by greater than or equal to24 hrs. The COPD subjects (n = 54) also completed IOS, DLCO, plethysmography, with LCIN2 reversibility collected in a sub-set (n = 25). Subjects who exacerbated and perfomred LCIN2 (n = 9) were tested on day of onset, 2 weeks post treatment and after 6 weeks. Results and Conclusions: LCIN2 was able to differentiate between COPD and HC group. Twenty % of COPD subjects with an FEV1 within normal range were found to have abnormal VI. LCIN2 did not differ after treatment with salbutamol (p> 0.05) but did correlate with R5-R20, X5, RV/TLC, Raw and Gaw.Both MBWN2 and MBWSF6 had low intra and inter test variability but MBWN2 produced significantly greater LCI and FRC% values. The difference between the two FRC% methods became disproportionatly greater with disease severity. FRCN2 % produced values greater than FRCpleth % with mean 156% (45) and 137% (36) respectively. Test time was greatly extended for both methods in moderate to severe subjects which may limit testing in clinical practice. In the exacerbation cohort LCIN2 was not found to signifcantly change at the onset of an exacerbation nor throughout recovery. Data suggestes that LCI is best used in mild COPD patients and the N2 system may be erronous and requires more research in a COPD population.
Date of Award31 Dec 2016
Original languageEnglish
Awarding Institution
  • The University of Manchester
SupervisorAlexander Horsley (Supervisor) & Sukh Singh (Supervisor)


  • Ventilation Inhomogeneity
  • COPD
  • Lung Clearance Index
  • FRC
  • Phase III Slope Analysis

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