Novel volumetric capnography indices measure ventilation inhomogeneity in cystic fibrosis

BackgroundVolumetric capnography (VCap) is a simpler alternative of multiple-breath washout (MBW) to detect ventilation inhomogeneity (VI) in patients with cystic fibrosis (CF). However, its diagnostic performance is influenced by breathing dynamics. We introduce two novel VCap indices, the Capnographic Inhomogeneity Indices (CIIs) that may overcome this limitation and explore their diagnostic characteristics in a cohort of CF patients.MethodsWe analysed 320 N2-MBW trials from 50 CF patients and 65 controls (age 4-18 years) and calculated classical VCap indices, such as slope III (SIII) and the capnographic index (KPIv). We introduced novel CIIs based on a theoretical lung model, and assessed their diagnostic performance compared to classical VCap indices and the lung clearance index (LCI).ResultsBoth CIIs were significantly higher in CF patients compared with controls (mean±SD CII1 5.9±1.4% versus 5.1±1.0%, p=0.002; CII2 7.7±1.8% versus 6.8±1.4%, p=0.002) and presented strong correlation with LCI (CII1 R2=0.47 and CII2 R2=0.44 in CF patients). Classical VCap indices showed inferior discriminative ability (SIII 2.3±1.0%/L versus 1.9±0.7%/L, P=0.013; KPIv 3.9±1.3% versus 3.5±1.2%, P=0.071), while the correlation with LCI was weak (SIII R2=0.03; KPIv R2=0.08 in CF patients). CIIs showed lower intra-subject inter-trial variability, calculated as coefficient of variation for three and relative difference for two trials, than classical VCap indices, but higher than LCI (CII1 11.1±8.2% and CII2 11.0±8.0% versus SIII 16.3±13.5%; KPIv 15.9±12.8%; LCI 5.9%±4.2%).ConclusionCIIs detect VI better than classical VCap indices and correlate well with LCI. However, further studies on their diagnostic performance and clinical utility are required.

Spatial Ventilation Inhomogeneity Determined by Electrical Impedance Tomography in Patients With Chronic Obstructive Lung Disease

The aim of this study was to examine whether electrical impedance tomography (EIT) could determine the presence of ventilation inhomogeneity in patients with chronic obstructive lung disease (COPD) from measurements carried out not only during conventional forced full expiration maneuvers but also from forced inspiration maneuvers and quiet tidal breathing and whether the inhomogeneity levels were comparable among the phases and higher than in healthy subjects. EIT data were acquired in 52 patients with exacerbated COPD (11 women, 41 men, 68 ± 11 years) and 14 healthy subjects (6 women, 8 men, 38 ± 8 years). Regional lung function parameters of forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), forced inspiratory vital capacity (FIVC), forced inspiratory volume in 1 s (FIV1), and tidal volume (VT) were determined in 912 image pixels. The spatial inhomogeneity of the pixel parameters was characterized by the coefficients of variation (CV) and the global inhomogeneity (GI) index. CV and GI values of pixel FVC, FEV1, FIVC, FIV1, and VT were significantly higher in patients than in healthy subjects (p ≤ 0.0001). The ventilation distribution was affected by the analyzed lung function parameter in patients (CV: p = 0.0024, GI: p = 0.006) but not in healthy subjects. Receiver operating characteristic curves showed that CV and GI discriminated patients from healthy subjects with an area under the curve (AUC) of 0.835 and 0.852 (FVC), 0.845 and 0.867 (FEV1), 0.903 and 0.903 (FIVC), 0.891 and 0.882 (FIV1), and 0.821 and 0.843 (VT), respectively. These findings confirm the ability of EIT to identify increased ventilation inhomogeneity in patients with COPD.

Lung clearance index: a new measure of ventilation inhomogeneity in childhood respiratory diseases

: Conventional spirometry has long been considered the primary test for assessing respiratory function deficits in children and adults. However, the need to perform forced breathing maneuvers can make it challenging to perform these examinations in an uncooperative child. For these reasons, techniques such as gas dilutions and the multiple-breath-washout (MBW) method have been implemented because they allow for early assessment of damage to the small airways. These methods permit the determination of the possible presence of ventilatory inhomogeneity in the lungs by analyzing the clearance of an inert gas used as a tracer. The equipment consists of a mass spectrometer combined with a flow meter. The Lung Clearance Index (LCI) is most often used to evaluate ventilatory inhomogeneity. This narrative review aimed to review the literature on technical and practical aspects of the MBW test and evaluate the clinical implications of the LCI in pediatric respiratory disease.

Four-week daily airway clearance using oscillating positive-end expiratory pressure versus autogenic drainage in bronchiectasis patients: a randomised controlled trial

BackgroundAirway clearance (AC) is a fundamental component of bronchiectasis care. Lung clearance index (LCI) is a measurement of ventilation inhomogeneity. Its responsiveness to long-term AC is unknown. We aimed to compare two methods of daily AC over four weeks: autogenic drainage (AD) and oscillating positive airway pressure (oPEP), and to to determine effects of AC on LCI and clinical outcomes.MethodsAdults with bronchiectasis naive to airway clearance were randomised to daily AC with either AD or oPEP. Difference in LCI as primary outcome, spirometry, sputum volume and purulence, and quality of life were evaluated at randomisation and after four weeks of AC.ResultsFifty-one patients (32 women, 19 men, mean age 66.2±12.8 years) were randomised and 49 completed the study (25 AD, 24 oPEP). The LCI and forced expiratory volume in the first second (FEV1) did not change between visits between groups (difference between groups 0.02), nor between visits in either group. Sputum quantity decreased in 12/24 (50%) of the oPEP group, and in 6/25 (24%) of the AD group (p=0.044). The “treatment burden” worsened or was unchanged in 70% of participants randomised to AD and 55% randomised to oPEP (p=0.038).ConclusionSputum quantity decreased in more participants randomised to oPEP group after one month of daily AC, with a better treatment burden. The effects of four weeks of AC on LCI were not significant in either treatment group.

Association of lung clearance index with survival in individuals with cystic fibrosis

BackgroundThe lung clearance index (LCI) assesses global ventilation inhomogeneity and is a sensitive biomarker of airway function in cystic fibrosis (CF) lung disease.ObjectivesWe examined the association of LCI with the risk of death or lung transplantation (LTX) in individuals with CF.MethodsWe performed a retrospective analysis in a cohort of individuals with CF aged≥5 years with LCI and FEV1 measurements performed between 1980 and 2006. The outcome was time until death or LTX. We used the earliest available LCI and FEV1 values in a Cox proportional hazard regression adjusted for demographic and clinical variables. For sensitivity analyses, we used the mean of the first three LCI and FEV1 measurements, stratified the cohort based on age, and investigated individuals with normal FEV1.ResultsIn total, 237 individuals with CF with a mean (range) age of 13.9 (5.6–41.0) years were included. The time-to-event analysis accrued 3813 person-years and 94 (40%) individuals died or received LTX. Crude hazard ratios [95% CI] were 1.04 [1.01–1.06] per one z-score increase in LCI and 1.25 [1.11–1.41] per one z-score decrease in FEV1. After adjusting LCI and FEV1 mutually in addition to sex, age, BMI and the number of hospitalisations, hazard ratios were 1.04 [1.01–1.07] for LCI, and 1.12 [0.95–1.33] for FEV1. Sensitivity analyses yielded similar results and using the mean LCI strengthened the associations.ConclusionsIncreased ventilation inhomogeneity is associated with greater risk of death or LTX. Our data support LCI as novel surrogate of survival in individuals with CF.

Association of lung clearance index with survival in individuals with cystic fibrosis

Background: Lung clearance index (LCI) quantifies global ventilation inhomogeneity, a sensitive biomarker of airway function in cystic fibrosis (CF) lung disease. Objectives: We examined the association of LCI with the risk of death or lung transplantation (LTX) in individuals with CF. Methods: We performed a retrospective analysis in a cohort of individuals with CF aged ≥ five years with available LCI and FEV1 measurements between 1980 and 2006. Outcome was time until death or LTX. We applied Cox proportional hazard regressions using the earliest available LCI and FEV1 values and adjusted for demographic and clinical variables. For sensitivity analyses, we used the mean of the first three LCI and FEV1 measurements, stratified the cohort based on age, and investigated individuals with normal FEV1. Results: In total, 237 individuals with CF aged mean (range) 13.9 (5.6-41.0) years were included. This time-to-event analysis accrued 3813 person-years, 94 (40%) individuals died or received LTX. Crude hazard ratios [95% CI] were 1.04 [1.01-1.06] per one z-score increase in LCI and 1.25 [1.11-1.41] per one z-score decrease in FEV1. After adjusting LCI and FEV1 mutually in addition to sex, age, BMI and the number of hospitalisations, hazard ratios were 1.04 [1.01-1.07] for LCI, and 1.12 [0.95-1.33] for FEV1. Sensitivity analyses yielded similar results and using the mean LCI strengthened the associations. Conclusions: Increased ventilation inhomogeneity is associated with greater risk of death or LTX. Our data support LCI as novel surrogate of survival in individuals with CF.

Volumetric capnography pre- and post-surfactant during initial resuscitation of premature infants

Background Volumetric capnography allows for continuous monitoring of expired tidal volume and carbon dioxide. The slope of the alveolar plateau of the capnogram (SIII) could provide information regarding ventilation homogeneity. We aimed to assess the feasibility of measuring SIII during newborn resuscitation and determine if SIII decreased after surfactant indicating ventilation inhomogeneity improvement. Methods Respiratory function traces of preterm infants resuscitated at birth were analysed. Ten capnograms were constructed for each infant: five pre- and post-surfactant. If a plateau was present SIII was calculated by regression analysis. Results Thirty-six infants were included, median gestational age of 28.7 weeks and birth weight of 1055 g. Average time between pre- and post-surfactant was 3.2 min. Three hundred and sixty capnograms (180 pre and post) were evaluated. There was adequate slope in 134 (74.4%) capnograms pre and in 100 (55.6%) capnograms post-surfactant (p = 0.004). Normalised for tidal volume SIII pre-surfactant was 18.89 mmHg and post-surfactant was 24.86 mmHg (p = 0.006). An increase in SIII produced an up-slanting appearance to the plateau indicating regional obstruction. Conclusion It was feasible to evaluate the alveolar plateau pre-surfactant in preterm infants. Ventilation inhomogeneity increased post-surfactant likely due to airway obstruction caused by liquid surfactant present in the airways. Impact Volumetric capnography can be used to assess homogeneity of ventilation by SIII analysis. Ventilation inhomogeneity increased immediately post-surfactant administration during the resuscitation of preterm infants, producing a characteristic up-slanting appearance to the alveolar plateau. The best determinant of alveolar plateau presence in preterm infants was the expired tidal volume.

Multiple Breath Wash-out for early assessment of pulmonary complications in patients with Primary Antibody Deficiencies: an observational study in pediatric age

Purpose. In Primary Antibody Deficiencies (PADs), pulmonary complications are the main cause of morbidity, despite immunoglobulin substitutive therapy, antibiotic treatment of exacerbations and respiratory physiotherapy. Current recommendations for surveillance of PADs respiratory complications include the annual assessment of spirometry and the execution of chest High Resolution Computed Tomography (HRCT) every four years.This study aims to evaluate the effectiveness of Lung Clearance Index (LCI) as early marker of lung damage in patients with PADs. LCI is measured by Multiple Breath Wash-out, a non-invasive and highly specific test widely used in Cystic Fibrosis patients.Methods. Pediatric patients with PADs (n=17, 10, M, 7, F, age range 5-15 years) underwent baseline assessment of lung involvement with chest HRCT, Spirometry and Multiple Breath nitrogen Wash-out. Among them, 13 patients were followed up to repeat HRCT after four years, while performing Pulmonary Function Tests annually. Their baseline and control LCI and FEV1 values were compared, taking HRCT as gold standard, using logistic regression analysis.Results. LCI (OR 2.43 at baseline, OR 14.95 at control) has a stronger discriminating power between altered and normal HRCT rather than FEV1 (OR 0.82 at baseline, OR 1.91 at control).Conclusion. Within the context of a limited sample size, LCI seems to be more predictive of HRCT alterations than FEV1 and more sensitive than HRCT in detecting ventilation inhomogeneity, in absence of bronchiectasis. A study of a larger cohort of pediatric patients followed longitudinally in adulthood is needed to challenge these findings.