Defining the Clinical Utility of the Lung Clearance Index. Are We There Yet?
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ABSTRACT:
SUBMITTER: Spano J
PROVIDER: S-EPMC8048751 | biostudies-literature | 2021 Apr
REPOSITORIES: biostudies-literature
Publications
Defining the Clinical Utility of the Lung Clearance Index. Are We There Yet?
Spano Jacquelyn J Milla Carlos E CE
American journal of respiratory and critical care medicine 20210401 8
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Project description:BackgroundLung clearance index (LCI) is accepted as an early marker of lung disease in cystic fibrosis (CF), however the utility of LCI to identify subgroups of CF disease in the paediatric age group has never been explored. The aim of the study was to characterize phenotypes of children with CF using LCI as a marker of ventilation inhomogeneity and to investigate whether these phenotypes distinguished patients based on time to pulmonary exacerbation (PE).MethodsData were collected on patients with CF aged < 18 years old, attending the CF Center of Milan during outpatient follow-up visits between October 2014 and September 2019. Cluster analysis using agglomerative nesting hierarchical method was performed to generate distinct phenotypes. Time-to-recurrent event analysis investigated association of phenotypes with PE.ResultsWe collected 313 multiple breath washout tests on 125 children aged 5.5-16.8 years. Cluster analysis identified two divergent phenotypes in children and adolescents of same age, presenting with almost normal FEV1 but with substantial difference in markers of ventilation inhomogeneity (mean LCI difference of 3.4, 95% Confidence Interval [CI] 2.6-4.2). A less severe phenotype was associated with a lower risk of PE relapse (Hazard Ratio 0.45, 95% CI 0.34-0.62).ConclusionsLCI is useful in clinical practice to characterize distinct phenotypes of children and adolescents with mild/normal FEV1. A less severe phenotype translates into a lower risk of PE relapse.
| S-EPMC8976307 | biostudies-literature
Project description:Lung clearance index (LCI) is a measure of abnormal ventilation distribution derived from the multiple breath inert gas washout (MBW) technique. We aimed to determine the clinical utility of LCI in non-CF bronchiectasis, and to assess two novel MBW parameters that distinguish between increases in LCI due to specific ventilation inequality (LCIvent) and increased respiratory dead space (LCIds).Forty-three patients with non-CF bronchiectasis and 18 healthy control subjects underwent MBW using the sulphur hexafluoride wash-in technique, and data from 40 adults with CF were re-analysed. LCIvent and LCIds were calculated using a theoretical two-compartment lung model, and represent the proportional increase in LCI above its ideal value due to specific ventilation inequality and increased respiratory dead space, respectively.LCI was significantly raised in patients with non-CF bronchiectasis compared to healthy controls (9.99 versus 7.28, p?<?0.01), and discriminated well between these two groups (area under receiver operating curve?=?0.90, versus 0.83 for forced expiratory volume in one second [% predicted]). LCI, LCIvent and LCIds were repeatable (intraclass correlation coefficient?>?0.75), and correlated significantly with measures of spirometric airflow obstruction.LCI is repeatable, discriminatory, and is associated with spirometric airflow obstruction in patients with non-CF bronchiectasis. LCIvent and LCIds are a practical and repeatable alternative to phase III slope analysis and may allow a further level of mechanistic information to be extracted from the MBW test in patients with severe ventilation heterogeneity.
| S-EPMC4035904 | biostudies-other
Project description: Not available
| S-EPMC9148690 | biostudies-literature
Project description:BackgroundPrognostic factors have yet to be established for patients with interstitial lung disease (ILD). We aimed to clarify whether the Charlson Comorbidity Index score (CCIS) could help predict disease prognosis in patients with ILD.MethodsAmong ILD patients treated between April 2013 and April 2017, we retrospectively assessed the relationship between baseline clinical parameters including age, sex, CCIS, ILD diagnosis, pulmonary function test results, and 3-year ILD-related events including cause-specific death and first acute exacerbation (AE).ResultsWe assessed 180 patients (mean age, 74 years), all of whom underwent pulmonary function testing including percentage predicted diffusion capacity for carbon monoxide (%DLco). Underlying pathologies included idiopathic pulmonary fibrosis (IPF) in 57 cases, idiopathic nonspecific interstitial pneumonia (iNSIP) and collagen vascular disease-related interstitial pneumonia in 117 cases, and chronic hypersensitivity pneumonia (CHP) in 6 cases. A composite scoring system comprising IPF diagnosis, CCIS, and %DLco provided a favorable C-index (0.825) for predicting 3-year ILD-related events. The nomogram for 3-year prognosis revealed the largest contributions from CCIS, %DLco and IPF diagnosis.ConclusionsThis composite scoring system accounting for IPF diagnosis, CCIS, and %DLco could provide a useful tool for predicting prognosis in relatively mild ILD patients tolerated to pulmonary diffusion capacity testing.
| S-EPMC7656418 | biostudies-literature
Project description:Purpose:Targeted therapy is the cornerstone of treatment of advanced EGFR-mutant non-small-cell lung cancer (NSCLC). Next-generation sequencing (NGS), the preferred method for genotyping, typically requires several weeks. Here, we assessed workflows designed to rapidly identify patients with actionable EGFR mutations and reduce time to initiation (TTI) of epidermal growth factor receptor (EGFR)-directed therapy. Patients and Methods:We performed rapid testing for EGFR L858R mutations and exon 19 deletions on paraffin-embedded or frozen section biopsy specimens from newly diagnosed patients with metastatic NSCLC by using an EGFR-specific assay (rapid test). To determine clinical utility, we assessed concordance with NGS results, turnaround time, and TTI of EGFR therapy, and we evaluated reimbursement data. Results:Between January 2015 and September 2017, we performed 243 rapid EGFR tests and identified EGFR mutations in 43 patients (18%). With NGS results as a reference, sensitivity and specificity of the rapid EGFR polymerase chain reaction assay were 98% and 100%, respectively. The median turnaround time for NGS was 14 days, compared with 7 days for rapid testing (P < .001). In the rapid group, 95% of patients received an EGFR inhibitor in the first-line setting. The median TTI of EGFR therapy was significantly shorter in the rapid cohort when compared with 121 historical cases (22 v 37 days; P = .01). Escalation of the initiative into an interdisciplinary ultra-rapid next-day frozen-section workflow for highly symptomatic patients (n = 8) resulted in a reduction in the median (± standard deviation) turnaround time to 1 ± 0.4 days and allowed several patients to initiate therapy within 1 week of biopsy. An extended 9-month clinical evaluation phase confirmed operational sustainability (turnaround times: ultra-rapid, 0.81 ± 0.4 days; rapid, 3 ± 1.5 days), and a 63% reimbursement rate indicated financial sustainability. Conclusion:Rapid genotyping facilitates earlier initiation of EGFR-directed therapies without compromising NGS workflows.
| S-EPMC6200882 | biostudies-other
Project description:PURPOSE:Primary ciliary dyskinesia (PCD) is characterised by repeated upper and lower respiratory tract infections, neutrophilic airway inflammation and obstructive airway disease. Different ultrastructural ciliary defects may affect lung function decline to different degrees. Lung clearance index (LCI) is a marker of ventilation inhomogeneity that is raised in some but not all patients with PCD. We hypothesised that PCD patients with microtubular defects would have worse (higher) LCI than other PCD patients. METHODS:Spirometry and LCI were measured in 69 stable patients with PCD. Age at testing, age at diagnosis, ethnicity, ciliary ultrastructure, genetic screening result and any growth of Pseudomonas aeruginosa was recorded. RESULTS:Lung clearance index was more abnormal in PCD patients with microtubular defects (median 10.24) than those with dynein arm defects (median 8.3, p = 0.004) or normal ultrastructure (median 7.63, p = 0.0004). Age is correlated with LCI, with older patients having worse LCI values (p = 0.03, r = 0.3). CONCLUSION:This study shows that cilia microtubular defects are associated with worse LCI in PCD than dynein arm defects or normal ultrastructure. The patient's age at testing is also associated with a higher LCI. Patients at greater risk of obstructive lung disease should be considered for more aggressive management. Differences between patient groups may potentially open avenues for novel treatments.
| S-EPMC5854730 | biostudies-literature
Project description:Post-infectious bronchiolitis obliterans (BO) could be diagnosed via spirometry and chest computed tomography (CT); however, these tests are limited in infants. We aimed to evaluate the utility of lung clearance index (LCI) and air-trapping lung volume from chest CT in infants. This prospective study included 20 infants (mean age, 10.9 ± 6.3 months) diagnosed with post-infectious BO between 2009 and 2016. All subjects underwent multiple breath washout tests. For quantitative analysis of chest CT, the mean lung area attenuation value was used as an individual cutoff to determine the air-trapping lung volume. The mean cutoff lung attenuation value was -659 Hounsfield units, the mean total lung volume was 265 ml, and the mean air-trapping lung volume percentage was 22.9%. Functional residual capacity correlated with total lung volume and normal attenuation lung volume (p < 0.02). LCI (p < 0.02) and moment ratio (MR) 1 (p < 0.05) correlated with the air-trapping lung volume percentage. The concordance indices of LCI (0.659, p = 0.025) and MR1 (0.642, p = 0.046) were significantly correlated with the air-trapping lung volume percentage from CT. LCI and quantitative air-trapping lung volume from chest CT are feasible, complimentary tools for assessing infants with post-infectious BO.
| S-EPMC5680196 | biostudies-literature
Project description:RationaleLung clearance index (LCI), measured by multiple breath washout (MBW), is a noninvasive measure of ventilation inhomogeneity that holds promise as an objective physiologic endpoint for clinical trials in infants and preschool children with cystic fibrosis (CF).ObjectivesTo study the feasibility of using LCI to assess treatment effect outcomes in CF trials of infants and preschoolers.MethodsThe Infant Study of Inhaled Saline trial was a multicenter, randomized, controlled trial of hypertonic (7%) versus isotonic (0.9%) saline inhaled twice daily for 48 weeks in children with CF under 6 years of age. LCI measurements were performed in a single-center pilot substudy at baseline and 48 weeks using a respiratory mass spectrometer and sulfur hexafluoride as the tracer gas. LCI measurements were standardized using published normative data (zLCI) to account for height-related changes in LCI during early childhood. A generalized estimating equation model with an interaction between treatment group and test occasion was used to estimate a treatment effect.Measurements and main resultsA total of 27 participants were randomized; 25 participants, aged (median [range]) 2.6 (0.34-4.95) years, had acceptable baseline and follow-up LCI measures. On average, LCI decreased in the hypertonic saline group (n = 12) by 1.19 z-scores units (95% confidence interval [CI] = -2.46 to 0.06), and remained stable in the isotonic saline group (n = 13) at 0.81 (95% CI = -0.40 to 2.02). A significant treatment effect was observed for zLCI (2.01; 95% CI = 0.26 to 3.76; P = 0.025).ConclusionsMBW testing is feasible in an interventional study in infants and preschool children with CF. These pilot findings support the development of MBW and LCI as an objective outcome measure in interventional trials in young children with CF, and provide estimates for sample size calculations for future studies.
| S-EPMC3778738 | biostudies-literature
Project description:BackgroundSubtle neurodegenerative motor and cognitive impairments accumulate over a prodromal period several years before clinical diagnosis of Huntington's disease (HD). The inclusion of prodromal individuals in therapeutic trials would facilitate testing of therapies early in the disease course and the development of treatments intended to prevent or delay disability.ObjectivesWe evaluate the normalized prognostic index (PIN) score as a tool to select participants for a perimanifest trial. We explore anticipated PIN-based inclusion rates from the preHD screening population and estimate sample-size requirements based on PIN threshold, trial duration, and outcome measure.MethodsIndividual participant data from ENROLL-HD were used to fit mixed effect linear models to assess longitudinal changes in clinical metrics for participants with early-manifest HD and PIN-stratified preHD subcohorts.ResultsA PIN threshold of 0.0 was met by 40% of the preHD participants in ENROLL-HD; 39.4% and 55.2% progressed to new diagnoses of early-manifest HD within 2 and 3 years, respectively. Various PIN thresholds also enabled the selection of specified ratios of prodromal preHD to early manifest HD participants for a perimanifest trial. Estimated sample sizes for a trial enrolling prodromal preHD (PIN > 0.0) and stage 1 and 2 motor-diagnosed participants varied depending on the composition of the screening pool, the length of follow-up (1, 2, or 3 years), and outcome measure.ConclusionsThe composition of a perimanifest clinical trial population can be defined using preselected PIN thresholds, facilitating the assessment of potential disease-modifying therapies in HD. © 2022 Voyager Therapeutics, Inc. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.
| S-EPMC9306552 | biostudies-literature
Project description:Liquid biopsy is a blood test that detects evidence of cancer cells or tumor DNA in the circulation. Despite complicated collection methods and the requirement for technique-dependent platforms, it has generated substantial interest due, in part, to its potential to detect driver oncogenes such as epidermal growth factor receptor (EGFR) mutants in lung cancer. This technology is advancing rapidly and is being incorporated into numerous EGFR tyrosine kinase inhibitor (EGFR-TKI) development programs. It appears ready for integration into clinical care. Recent studies have demonstrated that biological fluids such as saliva and urine can also be used for detecting EGFR mutant DNA through application other user-friendly techniques. This review focuses on the clinical application of liquid biopsies to lung cancer genotyping, including EGFR and other targets of genotype-directed therapy and compares multiple platforms used for liquid biopsy.
| S-EPMC5392351 | biostudies-literature