Abnormal Lung Clearance Index Research Articles

Slow and fast lung compartments in cystic fibrosis measured by nitrogen multiple-breath washout.

Imaging studies describe significant ventilation defects across a wide range of cystic fibrosis (CF) related lung disease severity. These are unfortunately poorly reflected by phase III slope analysis-derived Scond and Sacin from multiple-breath washout (MBW). Methodology extending previous two-lung compartment model-based analysis is presented describing size and function of fast- and slow-ventilating lung compartments from nitrogen (N2) MBW and correlation to obstructive lung disease severity. In 37 CF subjects (forced expiratory volume in 1 s [FEV1] mean [SD] 84.8 [19.9] % predicted; abnormal lung clearance index [LCI] in 36/37, range 7.28-18.9) and 74 matched healthy controls, volume and specific ventilation of both fast and slowly ventilated lung compartments were derived from N2-based MBW with commercial equipment. In healthy controls lung emptying was characterized by a large compartment constituting 75.6 (8.4)% of functional residual capacity (FRC) with a specific ventilation (regional alveolar tidal volume/regional lung volume) of 13.9 (3.7)% and a small compartment with high specific ventilation (48.4 [15.7]%). In CF the slowly ventilated lung compartment constituted 51.9(9.1)% of FRC, with low specific ventilation of 5.3 (2.4)%. Specific ventilation of the slowly ventilated lung compartment showed stronger correlation with LCI (r2 = 0.70, P < 0.001) vs. Sacin (r2 = 0.44, P < 0.001) or Scond (no significant correlation). Overventilation of the fast lung compartment was no longer seen in severe CF lung disease. Magnitude and function of under- and overventilated lung volumes can be derived from routine N2 MBW in CF. Reported values agree with previous modelling-derived estimates of impaired ventilation and offer improved correlation to disease severity, compared with SnIII analysis.

Tracking Lung Clearance Index and chest CT in mild cystic fibrosis lung disease over a period of three years

Lung disease remains the main cause of morbidity and mortality in patients with Cystic Fibrosis (CF). To detect lung disease before clinical symptoms become apparent, sensitive tools are essential. Spirometry is used for monitoring, but the FEV1 remains frequently normal throughout childhood. The Lung Clearance Index (LCI) calculated from Multiple Breath Washout (MBW) was introduced at the CF centre Innsbruck in 2007 for assessing ventilation inhomogeneity in patients with mild lung disease. We hypothesized that LCIs in 2007 are of prognostic value for the presence or absence of structural lung changes in later years. Between 2007 and 2010 MBW, spirometry and ultra-low-dose HR-CT were prospectively tracked in 36 patients (6-53 years) with a mean FEV1 ≥ 80% predicted in 2007. At study start the majority of patients had abnormal CT scores and LCI results. While CT and spirometry remained largely stable throughout the study, LCI results slightly improved but still correlated with CT scores in 2010. LCI results in 2007 correlated with CT scores in 2010 while FEV1 did not. In 86% the LCI value in 2007 was indicative for the presence or absence of structural lung changes in 2010. The LCI is a sensitive tool for detecting and tracking pulmonary changes. Extended structural changes are unlikely if the LCI is normal. The LCI has the potential to be used for monitoring the progression of early CF lung disease and assessing the effect of treatment in both clinical care and research settings.

Acinar and conductive ventilation heterogeneity in severe CF lung disease: Back to the model

Severe convective ventilation heterogeneity occurring in CF lung disease requires a modified method to determine acinar and conductive components of ventilation heterogeneity from normalized phase III slope (Sn) curves. Modified Sacin* and Scond* (as opposed to standard Sacin and Scond) are proposed and interpreted on the basis of 2 conceptual mechanisms: (a) flow asynchrony between two convection-dependent units with a different specific ventilation, but with an identical acinus inside each unit (generating an identical diffusion-convection-dependent portion of Sn); (b) different specific ventilation (without any flow asynchrony) between two convection-dependent units with the worst ventilated unit containing an abnormal acinus generating the greatest diffusion-convection-dependent portion of Sn. In CF patients with an abnormal lung clearance index (LCI), Scond* (but not Scond) and Sacin* were significant contributors to LCI (β(Scond*)=0.70; β(Sacin*)=0.49; P<0.001 for both). Mechanism (a) can entirely account for experimental Scond* values, while mechanism (b) implies that experimental Sacin* values are likely dominated by peripheral ventilation heterogeneity in the best ventilated portions of the lung.

Lung clearance index in adult cystic fibrosis patients: the role of convection-dependent lung units

We investigated the extent of convective ventilation heterogeneity contributing to the observed lung clearance index values in adult cystic fibrosis patients, as the result of two simulated scenarios, either 1) a fixed part of the lungs becoming increasingly less compliant, or 2) an increasingly greater part of the lung being less compliant. In 25 cystic fibrosis patients and 25 matched controls, we computed the lung clearance index and also quantified curvilinearity of the washout concentration curve, where curvilinearity is equal to 0 (linear in semilog plot) reflects homogeneous ventilation and curvilinearity equal to 1 corresponds to the presence of an infinitesimally slowly emptying lung unit. In the cystic fibrosis group (forced expiratory volume in 1 s 27-100% predicted), lung clearance index and curvilinearity average±sd values were 10.3±2.3 and 0.57±0.13, respectively, and were significantly different from control values (6.2±0.4 and 0.18±0.07; both p<0.001); lung clearance index and curvilinearity were also correlated (R = 0.67; p<0.001). The average curvilinearity value in the cystic fibrosis group was found to be compatible with a cumulative volume of underventilated lung of 40-50%, depending on the simulation scenario considered. The degree of washout curvilinearity observed here indicates that a major determinant of the abnormal lung clearance index values observed in adult cystic fibrosis patients is ventilation heterogeneity generated between convection-dependent lung units, while the remainder of lung clearance index abnormality with respect to normal controls potentially represents the small airways within these lung zones.

Lung Clearance Index and HRCT are complementary markers of lung abnormalities in young children with CF

RationaleHigh resolution computed tomography (HRCT) is a more sensitive tool for detecting early cystic fibrosis (CF) lung disease than either spirometry or plain radiography, but its relationship to other measures...

Lung Clearance Index at 4 Years Predicts Subsequent Lung Function in Children with Cystic Fibrosis

The markedly improved life expectancy of children with cystic fibrosis (CF) has created a new challenge, as traditional markers of lung disease are frequently normal in young children. This prevents identification of individuals who may benefit from more aggressive therapy and also obliges large study numbers and prolonged duration for intervention studies. There is an urgent need for alternative surrogates that detect early lung disease and track through early childhood. This study aimed to determine whether multiple-breath washout (MBW) results at preschool age can predict subsequent abnormal lung function. Preschool children (3-5 yr) with CF and healthy control subjects underwent spirometry and MBW with testing repeated during early school age (6-10 yr). Primary outcomes were FEV1 from spirometry and lung clearance index (LCI) from MBW. Forty-eight children with CF and 45 healthy children completed testing. Thirty-five (73%) children with CF had abnormal LCI at preschool age, whereas only five had abnormal FEV1. The positive predictive value of preschool LCI for predicting any abnormal school-age result was 94%, with a negative predictive value of 62%. Only one child with abnormal FEV1 at school age had had a normal preschool LCI. In contrast, for preschool FEV1 the positive predictive value was 100%, but negative predictive value was only 25%. This study demonstrates that an abnormal preschool LCI predicts subsequent lung function abnormalities, whereas a normal preschool LCI usually remains normal. MBW has potential as a clinical and research outcome in young children with CF.

Multiple-breath inert gas washout and spirometry versus structural lung disease in cystic fibrosis

Background: A sensitive and valid non-invasive marker of early cystic fibrosis (CF) lung disease is sought. The lung clearance index (LCI) from multiple-breath washout (MBW) is known to detect abnormal...

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Lung disease remains the main cause of morbidity and mortality in patients with Cystic Fibrosis (CF). To detect lung disease before clinical symptoms become apparent, sensitive tools are essential. Spirometry is used for monitoring, but the FEV1 remains frequently normal throughout childhood. The Lung Clearance Index (LCI) calculated from Multiple Breath Washout (MBW) was introduced at the CF centre Innsbruck in 2007 for assessing ventilation inhomogeneity in patients with mild lung disease.We hypothesized that LCIs in 2007 are of prognostic value for the presence or absence of structural lung changes in later years.Between 2007 and 2010 MBW, spirometry and ultra-low-dose HR-CT were prospectively tracked in 36 patients (6–53 years) with a mean FEV1 ≥80% predicted in 2007.At study start the majority of patients had abnormal CT scores and LCI results. While CT and spirometry remained largely stable throughout the study, LCI results slightly improved but still correlated with CT scores in 2010. LCI results in 2007 correlated with CT scores in 2010 while FEV1 did not. In 86% the LCI value in 2007 was indicative for the presence or absence of structural lung changes in 2010.The LCI is a sensitive tool for detecting and tracking pulmonary changes. Extended structural changes are unlikely if the LCI is normal. The LCI has the potential to be used for monitoring the progression of early CF lung disease and assessing the effect of treatment in both clinical care and research settings.

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<b>Introduction: </b>We have previously reported increased respiratory symptoms in adult survivors of bronchopulmonary dysplasia (BPD) compared with very low birth weight (VLBW) (&lt;1500g) and term controls. Here we report preliminary findings from spirometric and Lung Clearance Index (LCI) measurements. <b>Objective: </b>To investigate whether adult survivors of BPD have greater impairment of lung function and LCI than age and gender matched VLBW and term controls. <b>Methods: </b>Spirometry measurements (MicroLab ML3500 Mk8™) were obtained in 16 BPD [8male; mean (SD) age 24.9 (3.9) y]<b>,</b> 9 VLBW [Mean (SD) age 25.8 (3.73) y] and 55 term controls [30 male; mean (SD) age 26.0 (4.0) y]. LCI measurements (Innocor™ device) obtained in BPD and VLBW participants were compared to 17 healthy controls [6M, mean (SD) age 30.5 (7.5) y]. <b>Results: </b>For all spirometry end points (FEV₁, FVC, FEV₁/FVC and FEF_25-75), BPD adults had significantly lower values than term controls (p&lt;0.001). Mean FEV₁and FEV₁/FVC measurements were lower in BPD adults than VLBW (p&lt;0.05)). Mean LCI measurements were higher (more impaired) in BPD [mean (SD) 6.99 (0.78)] versus healthy controls [mean (SD) 6.36 (0.362)] (p=0.006). LCI measurements were also higher in BPD than VLBW but this was not statistically significant. Three BPD subjects had entirely normal spirometry but abnormal LCI values (value &gt; healthy control mean +2SD). <b>Conclusions:</b> Our preliminary findings suggest persisting lung function impairment in adult survivors of BPD. LCI may be a useful tool in detecting early small airways disease in adult survivors of preterm birth.