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Role of Lung Clearance Index in the Early Detection of Pulmonary Changes in Children with Sickle Cell DiseaseChaung, Monica 30 March 2018 (has links)
A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine. / Pulmonary complications including acute chest syndrome are
leading causes of sickle cell disease related morbidity and
mortality. Studies have shown that pulmonary changes can be
detected during childhood. Spirometry is the current standard
for measuring lung function. Growing evidence suggests that
lung clearance index (LCI) is as sensitive as spirometry in
identifying pulmonary changes in pediatric patients.
Our cross-sectional study compared the sensitivity of LCI to
spirometry in the detection of early pulmonary changes in
children with sickle cell disease. Our results show that LCI
significantly correlates to FEV1% predicted (Spearman’s
coefficient -0.44, p = 0.003), FVC % predicted (Spearman’s
coefficient -0.44, p = 0.006) and FEF25-75 (Spearman’s
coefficient -0.49, p <0.001).
Using receiver operating characteristic (ROC) curves, LCI was
found to be more sensitive than spirometry, but less specific.
The data support LCI’s use as a test to screen for pulmonary
changes in children with sickle cell disease. Earlier monitoring
of lung function will allow for preventative therapies and delayed progression of pulmonary dysfunction.
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Non-invasive assessment of ventilation maldistribution in lung disease using multiple breath inert gas washoutsHorsley, Alex January 2009 (has links)
Clinical research in cystic fibrosis (CF) requires study endpoints that are sensitive to airways disease, repeatable and non-invasive. Despite significant advances in the treatment of CF, lung function assessments continue to rely on the forced expiratory volume in 1 second (FEV1). Although simple to perform, it lacks sensitivity, is difficult for younger subjects, and changes over time. An alternative method of assessing lung physiology is to derive measures of ventilation heterogeneity from inert gas washout tests. In early lung disease, measures of gas mixing appear to be more sensitive than spirometry. In addition, since only tidal breathing is required, they are more physiological and are more straightforward for younger subjects. Widespread use has been impaired by the lack of a robust and cost effective gas analyser technology. The work presented in this thesis concerns the adaptation, validation and then use of a novel gas analyser (Innocor) in a clinical system for the performance of multiple breath washouts. Lung clearance index (LCI), a simple measure of ventilation heterogeneity, has been calculated from washouts in 52 adults with CF and 50 healthy controls. LCI was more sensitive to disease than FEV1 in CF, being elevated in 11 of the 12 CF patients with normal spirometry. In healthy subjects, LCI has been shown to be repeatable and reproducible, with a narrow range of normal that is stable over a wide age range. In a separate study of 19 patients, LCI has also been shown to improve with treatment of an exacerbation in CF. Correlation with changes in other biochemical (serum CRP, peripheral blood white cell count, sputum IL-8, sputum neutrophil) clinical (symptom score) or structural (computed tomography) markers was poor. Short term change in LCI has also been demonstrated in CF patients in response to chest physiotherapy, although there was considerable heterogeneity of response in terms of both LCI and volume of lung ventilated by tidal breathing (as measured by washout functional residual capacity). In addition to LCI, multiple breath phase III slope analysis has been performed on washouts of CF patients and healthy controls, and this has been compared to other measures of lung physiology. Proposed measures of convective and diffusive gas mixing have been shown to be unreliable in CF. These studies have also been the first to demonstrate multi-centre use of washout tests as endpoints. The technology described here offers the possibility of a simple and reliable system for performing multiple breath washouts, though at present it is not available commercially. The studies have added to the understanding of the utility and reliability of washout tests, as well as some of their limitations. It is hoped that in future LCI will be an important clinical endpoint in therapeutic intervention studies in CF, and that it will also offer new ways to follow changes in lung physiology in other diseases.
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Lung Clearance Index as a Marker of Ventilation Inhomogeneity in Early Childhood with Health and DiseaseBrown, Meghan 05 December 2011 (has links)
Rationale: Ventilation inhomogeneity (VI) may be an early sign of obstructive airway disease. The lung clearance index (LCI) has been suggested as a sensitive marker of VI, although it has not been well characterized in young children in health and in those with CF and asthma.
Objective: To determine if LCI can detect VI in asymptomatic infants and preschool-age subjects with CF or wheeze/asthma compared to healthy controls.
Methods: Sulphur hexafluoride (SF6) multiple breath washout (MBW) testing was completed in all subjects.
Results: LCI was found to be dependent on age in a large healthy cohort. Accounting for age, LCI was significantly elevated in disease groups compared to healthy controls in early childhood, illustrating early presence of VI in wheezy infants and the progression of disease in CF. Furthermore, the effects of breathing pattern and the variability of MBW parameters showed positive associations with age and VI.
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Lung Clearance Index as a Marker of Ventilation Inhomogeneity in Early Childhood with Health and DiseaseBrown, Meghan 05 December 2011 (has links)
Rationale: Ventilation inhomogeneity (VI) may be an early sign of obstructive airway disease. The lung clearance index (LCI) has been suggested as a sensitive marker of VI, although it has not been well characterized in young children in health and in those with CF and asthma.
Objective: To determine if LCI can detect VI in asymptomatic infants and preschool-age subjects with CF or wheeze/asthma compared to healthy controls.
Methods: Sulphur hexafluoride (SF6) multiple breath washout (MBW) testing was completed in all subjects.
Results: LCI was found to be dependent on age in a large healthy cohort. Accounting for age, LCI was significantly elevated in disease groups compared to healthy controls in early childhood, illustrating early presence of VI in wheezy infants and the progression of disease in CF. Furthermore, the effects of breathing pattern and the variability of MBW parameters showed positive associations with age and VI.
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The practical use of the Multiple Breath Washout test in children : biological variability in health and diseaseSheridan, Helen Sarah January 2017 (has links)
The Multiple Breath Washout (MBW) test is increasingly being recognised as a sensitive method of detecting early small airways lung disease. Indices of MBW include lung clearance index (LCI), Scond and Sacin. Factors that affect MBW variability have not been fully established. This thesis presents five studies which examine MBW repeatability in children with and without cystic fibrosis (CF) or asthma. MBW was performed using 0.2% sulphur hexafluoride and the modified Innocor (Innovision). Testing was performed at the Clinical Research Facility of the Royal Hospital for Sick Children in Edinburgh. (1) MBW and spirometry were performed in children with and without CF (n=20 in each group), initially while sitting and then 30 minutes after assuming a supine posture. LCI was found to significantly rise on lying supine in healthy children (p < 0.01) and children with CF (p=0.03). (2) Thirty two children with CF performed MBW and spirometry on four study visits, results were correlated with findings from high resolution chest computed tomography scans taken on the first visit. LCI showed the strongest correlation with extent and severity of bronchiectasis (r=0.66, p < 0.01 and r=0.69, p < 0.01 respectively). Variability of LCI was similar to FEV1 over the 4 visits. (3) MBW and spirometry of 66 healthy children were compared to 63 children with stable asthma; lung function of asthmatic children was related to symptoms and medication use. LCI was higher in the asthmatic group (6.7 vs 6.3, p < 0.01); within the asthmatic group LCI was significantly higher if asthma was less well controlled (p=0.02). (4) Children with and without asthma (n=21 in each group) performed MBW and spirometry before and after exercise and again after salbutamol, symptom data was collected from asthmatic children. Baseline LCI was abnormal in the asthmatic group who had severe exercise induced bronchospasm during testing. (5) Asthmatic children admitted to hospital due to exacerbation performed MBW and spirometry. Mean (SD) LCI was abnormally high at 8.5 (1.7) in the nine patients recruited and returned to normal 6.7 (0.6) in three patients who attended follow up. I have presented evidence that LCI is repeatable and sensitive to early disease in CF and asthma. I have described for the first time the effects of exercise and exacerbation on MBW indices in asthmatic children. MBW is potentially a very useful tool in paediatrics; standardisation of testing and equipment may enable clinical use.
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