Lung Clearance Index Research Articles

Prenatal Exposure to Oxidative Potential and Lung Function in Infants and Preschool- Age Children: A Prospective Study.

Fine particulate matter () has been found to be detrimental to respiratory health of children, but few studies have examined the effects of prenatal oxidative potential (OP) on lung function in infants and preschool children. We estimated the associations of personal exposure to and OP during pregnancy on offspring objective lung function parameters and compared the strengths of associations between both exposure metrics. We used data from 356 mother-child pairs from the SEPAGES cohort. PM filters collected twice during a week were analyzed for OP, using the dithiothreitol (DTT) and the ascorbic acid (AA) assays, quantifying the exposure of each pregnant woman. Lung function was assessed with tidal breathing analysis (TBFVL) and nitrogen multiple-breath washout () test, performed at 6 wk, and airwave oscillometry (AOS) performed at 3 y. Associations of prenatal mass and OP with lung function parameters were estimated using multiple linear regressions. In neonates, an interquartile (IQR) increase in () was associated with a decrease in functional residual capacity (FRC) measured by [; 95% confidence interval (CI): , 0.15]. Associations with showed similar patterns in comparison with but of smaller magnitude. Lung clearance index (LCI) and TBFVL parameters did not show any clear association with the exposures considered. At 3 y, increased frequency-dependent resistance of the lungs () from AOS tended to be associated with higher (; 95% CI: , 0.24) and (; ; 95% CI: , 0.27) but not with (; ; 95% CI: , 0.16). Results for FRC and remained similar in OP models adjusted on . Prenatal exposure to was associated with several offspring lung function parameters over time, all related to lung volumes. https://doi.org/10.1289/EHP11155.

Using electrical impedance tomography to characterize lung impairment of children with primary ciliary dyskinesia: A pilot cross-sectional study.

In children with primary ciliary dyskinesia (PCD), measures more sensitive than spirometry are needed to characterize underlying pulmonary impairment. Electrical impedance tomography (EIT) is a promising noninvasive method for monitoring the distribution of lung ventilation, and it does not require patient collaboration. We aimed to provide an assessment of the feasibility and clinical usefulness of EIT in characterizing lung impairment in children with PCD, compared to spirometry and multiple breath nitrogen washout (MBWN2 ) test. Children and adolescents with PCD underwent MBWN2 test as first respiratory assessment, followed by EIT monitoring and spirometry during outpatient follow-up. We included 12 out of 16 individuals regularly followed at our clinic. A total of 41.7% (5/12) showed abnormalforced expiratory volume in 1 s (FEV1 ), whereas 11/12 (91.7%) had abnormal ventilation inhomogeneity measured with MBWN2 test. Using EIT, the global inhomogeneity (GITOT ) index showed moderate to strong correlation with FEV1 (ρ = -0.55, 95% confidence interval [CI]: -0.87 to 0.02) and ranged from 37 to 44, with the highest inhomogeneity detected in the dorsal right quadrant. GITOT was moderately correlated with RV/TLC %predicted (ρ = 0.38, 95%CI: -0.17 to 0.74), while we detected a weak correlation between GITOT and lung clearance index(ρ = 0.29, 95%CI: -0.45 to 0.82). EIT appears promising as a noninvasive technique to characterize ventilation distribution in children with PCD, thus providing a complementary assessment to static and dynamic lung function measures of PCD disease.

Turning lung clearance index on its head. Reference data for SF6 multiple-breath washout derived ventilation distribution efficiency.

Cystic fibrosis (CF) lung disease is characterized by increased ventilation inhomogeneity (VI), as measured by multiple-breath washout (MBW). Lung clearance index (LCI) is the most reported VI outcome. This study aimed to evaluate historically published reference equations for sulfur hexafluoride (SF6) MBW outcomes, to data collected using updated commercial SF6MBW equipment, and to produce device-specific equations if necessary. SF6MBW was performed in 327 healthy children aged 0.1-18.4 yr [151 (46%) girls], 191 (58.4%) <3 yr. z-Scores were calculated from published reference equations (FRC and LCI) and multivariate linear regression was performed to produce device-specific reference equations. Due to increasing residual standard deviations with increasing LCI values, investigation of methods for improvement were investigated, based on the relationship between VI and dead space ventilation (VD/VT; dead space volume/tidal volume) in a cohort of 59 healthy children, 26 children with CF (n = 138 test occasions), and 49 adults with lung disease. Historical SF6MBW reference equations were unsuitable for EXHALYZER D data. In contrast to LCI and log10(LCI), 1/LCI (ventilation distribution efficiency; VDE) was linearly related to VD/VT, with z-scores linearly related to its absolute values. Reference equations were reported for VDE and log10(FRC). Significant predictors for VDE and log10(FRC), respectively, were log10(age) and sex, and log10(height), sex, and posture. VDE is potentially a better index of VI than LCI, particularly in more advanced CF lung disease and also for longitudinal monitoring. Further confirmatory clinical studies, particularly longitudinal imaging studies of structural or ventilatory changes, are warranted.NEW & NOTEWORTHY Lung clearance index (LCI) is the most used outcome from the multiple-breath washout test. As known for decades, the LCI is not linearly related to dead space ventilation, giving difficulties interpreting changes over time and in clinical trials. We present a new and improved outcome based on LCI, the ventilation distribution efficiency (VDE), which solves this problem by being linearly related to dead space ventilation. A pediatric age range reference equation for VDE is presented.

Clinimetric Properties of Outcome Measures in Bronchiectasis.

Rationale: There is a lack of outcome measures with robust clinimetric properties in bronchiectasis. Objectives: To determine the clinimetric properties (reliability over 1 year during clinical stability and responsiveness over the course of antibiotics for pulmonary exacerbation) of objective and patient-reported outcome measures. Methods: This multicenter cohort study included adults with bronchiectasis from seven hospitals in the United Kingdom. Participants attended four visits, 4 months apart over 1 year while clinically stable and at the beginning and end of exacerbation and completed lung function (spirometry and multiple breath washout), provided a blood sample for C-reactive protein (CRP) measurement, and completed health-related quality of life (HRQoL) questionnaires (Quality of Life-Bronchiectasis, St. George's Respiratory Questionnaire, and EuroQoL 5-Dimensions 5-Levels). Results: Participants (n = 132) had a mean (standard deviation) age of 66 (11) years, and 64% were female. Lung function parameters (forced expiratory volume in one second [FEV1], standard lung clearance index [LCI2.5]) were reliable over time [coefficient of variation (CV): <10%]). Regarding responsiveness, FEV1 demonstrated better properties than LCI2.5; therefore, a clear justification for the use of LCI2.5 in future trials is needed. CRP was less reliable (CV > 20%) over time than FEV1 and LCI2.5, and whereas CRP had a large mean change between the start and end of an exacerbation, this may have been driven by a small number of patients having a large change in CRP. Reliability of HRQoL questionnaires and questionnaire domains ranged from acceptable (CV: 20-30%) to good (CV: 10-20%), and HRQoL were responsive to treatment of exacerbations. Considering the specific questionnaire domain relevant to the intervention and its associated clinimetric properties is important. Additional statistics will support future power and/or sample size analysis. Conclusions: This information on the clinimetric properties of lung function parameters, CRP, and HRQoL parameters should be used to inform the choice of outcome measures used in future bronchiectasis trials.

Effect of Trikafta on bone density, body composition and exercise capacity in CF: A pilot study.

While the positive effect of Trikafta on cystic fibrosis (CF) pulmonary disease is well established, there is limited data about its effect on bone mineral density (BMD), body composition and exercise capacity. A pilot single center study. BMD and body composition were measured three months after the initiation of Trikafta (study group) and compared to values obtained 2 years earlier. CF patients not treated with Trikafta, for whom BMD was measured 2 years apart, served as controls. Spirometry, lung clearance index (LCI), sweat test, six-minwalk test (6MWT) and cardio-pulmonary exercise test (CPET) were performed before and three months after the initiation of Trikafta. Nine study patients, aged 18.6 ± 4.7 years, and nine controls. For the study group, BMI and hip and spine BMD increased significantly (19.4 ± 2.6 to 20.3 ± 2.19 BMI, p = 0.05; 0.73 ± 0.098 to 0.81 ± 0.12 gr/cm2 hip, p = 0.017; 0.76 ± 0.14 to 0.82 ± 0.14 gr/cm2 spine, p = 0.025). For the control group, there was no difference in hip or spine BMD. Lean body mass, %fat z-score and fat mass/height2 z-score increased significantly (34770.23 ± 10521.21 to 37430.16 ± 10330.09gr, p = 0.017; -0.8 ± 0.75 to 0.46 ± 0.58, p = 0.012; and -0.98 ± 0.66 to -0.04 ± 0.51, p = 0.025, respectively). 6MWT improved from 541.1 ± 48.9 to 592.9 ± 54.5 m (p = 0.046). As expected, FEV1%pred increased (p = 0.008) and sweat chloride decreased significantly (p = 0.017). In CPET, VE/VCO2 improved, indicating better ventilatory efficiency. To the best of our knowledge, this is the first study evaluating the metabolic effects of Trikafta. The results are encouraging and offer hope beyond the well-established effect on pulmonary disease. Larger long-term studies are warranted to unpin the underlying physiological mechanisms.

Estimating the minimum sample size for interventional and observational studies using the lung clearance index as an endpoint✰

BackgroundWith the increasing availability of highly effective modulators for people living with cystic fibrosis (CF), there is a need to re-design research studies to reflect the changing epidemiology of the CF population. The lung clearance index (LCI), a sensitive physiological measure of lung function, may be ideally suited as an endpoint in the era of CF modulator therapies. In this study we describe study design considerations for implementing LCI into interventional and observational research. MethodsSimulations were used to estimate the required sample size to detect a range of treatment effects for interventional studies (including cross-over trials) and to track lung disease progression in observational studies. ResultsUsing published treatment effects to inform the design of prospective studies can lead to inefficient study designs. Large improvements in LCI for a few individuals can skew results and can influence interpretations of treatment effects. Adjusting for baseline LCI can help to improve the efficiency of a study. Compared to the forced expiratory volume in 1 second (FEV1), analysis using LCI as an endpoint requires as little as one third of the total sample size. ConclusionsPlanning of prospective studies that include LCI as an endpoint need to consider baseline LCI and disease severity of the study population; whereas interpretation of results needs to consider whether a few individuals skew the overall treatment effect.

Variability of clinically measured lung clearance index in children with cystic fibrosis.

The lung clearance index (LCI) is increasingly being used in the clinical surveillance of patients with cystic fibrosis (CF). However, there are limited data on long-term variability and physiologically relevant changes in LCI during routine clinical surveillance. To evaluate the long-term variability of LCI and propose a threshold for a physiologically relevant change. In children aged 4-18 years with CF, LCIwas measuredevery 3 months as part of routine clinical surveillance during 2011-2020 in two centers. The variability of LCI during periods of clinical stability was assessed using mixed-effects models and was used to identify thresholds for physiologically relevant changes. Repeated LCI measurements of acceptable quality (N = 858) were available in 100 patients with CF; for 74 patients, 399 visits at clinical stability were available. The variability of repeated LCI measurements over time expressed as the coefficient of variation (CV%) was 7.4%. The upper limit of normal (ULN) for relative changes in LCI between visits was 19%. We report the variability of LCI in children and adolescents with CF during routine clinical surveillance. According to our data, a change in LCI beyond 19% may be considered physiologically relevant. These findings will help guide clinical decisions according to LCI changes.

In children with primary ciliary dyskinesia, which type of lung function test is the earliest determinant of decline in lung health: A systematic review.

Primary ciliary dyskinesia is a rare genetic disorder characterized by recurrent sinopulmonary infections and worsening obstructive lung disease. Kidney and brain involvement is less common and is associated with overlapping ciliopathies/syndromes. The lungs are impacted early in the course of the disease, so it is vital to monitor lung function and recognize any decline by doing appropriate lung function tests. This systematic review compares different lung function tests and analyzes which one becomes abnormal earlier in the disease. A systematic review was conducted following the methodology in the "Cochrane Handbook on Systematic Reviews for diagnostic tests." The Preferred Reporting Items for Systematic Review and Meta-Analyses were used to report the results. The risk of bias assessment was done using "The Cochrane Handbook for Systematic Reviews tool for interventional studies." A meta-analysis was not performed due to the small sample size. All studies were analyzed by using Joanna Briggs Institute's critical appraisal tool. After screening for the duplication of results and applying inclusion and exclusion criteria, 14 studies were assessed by reading the full texts. Out of these, eight were finally included in this systematic review. The total sample size from all studies was 165, including 80 males. All the studies used spirometry as a lung function test, whereas multiple breath washout was used in five studies. Other tests used for comparison were computed tomography(CT),magnetic resonance imaging(MRI), cardiopulmonary exercise testing,6-min walk test, DLCO,maximal inspiratory pressure,maximal expiratory pressure, and PaO2 .Lung clearance index(LCI)by multiple breath washout had a stronger association with the structural changes on CT/MRI than spirometry indices like forced expiratory volumein 1 s (FEV1)and forced expiratory flowat 25% to 75% of lung volume(FEF 25-75). Based on the evidence from this systematic review, LCI becomes abnormal earlier than FEV1 or FEF 25-75 and positively correlates with the findings on high-resolutionCT. It has limitations like the lack of reference values and a complex technique to perform the test.

Effect of Dornase Alfa on the Lung Clearance Index in Children with Cystic Fibrosis: A Lesson from a Case Series.

Dornase alfa (DNase) is the only mucus-degrading agent that has proven efficacy in cystic fibrosis (CF). Few studies have evaluated the effects of DNase on the lung clearance index (LCI). We report the experience of two CF centers in which LCI monitoring was used to evaluate the efficacy of DNase therapy. This is a prospective and observational study, evaluating the effects of DNase therapy on LCI values in three CF children followed at CF centers in Florence and Catania, Italy. In both centers, LCI was performed routinely, every 3-6 months, based on the clinical picture and severity of the lung disease. In this study, we evaluated the LCI before and after long-term DNase therapy. DNase improved LCI values in the absence of respiratory exacerbations: in case n. 1 LCI decreased by 39% in 16 months (from 11.1 to 6.8); in case n. 2 by 20% in 12 months (from 9.3 to 7.4); in case n. 3 by 24% in 16 months (from 9.3 to 7.0). This case series confirms the efficacy of DNase therapy in CF children, as demonstrated by the LCI reduction in treated patients. Furthermore, our results suggest that LCI is a sensitive marker of disease and can be used for the evaluation of response to treatment.

92 Confirmatory genetic testing for all CF screen positive newborns: a 12-year analysis

Abstract Background Cystic fibrosis (CF) is an autosomal recessive disease that can present with multisystem manifestations based on mutations in the CF transmembrane regulator (CFTR) gene. Screening for CF was added to the Newborn Screening Ontario (NSO) program in 2008 using immunoreactive trypsinogen and genetic testing with a panel of 39 + 3 polymorphisms. From 2008-2020, our centre had all referred screen positive individuals undergo confirmatory genetic testing with an expanded panel of 70 + 4 polymorphisms, occasionally identifying a second mutation of varying clinical consequence. If an individual had a second mutation identified on our panel, prospective follow-up was offered. Objectives The aim of the study is to evaluate the utility of our expanded panel and subsequent identification of individuals with possible CFTR dysfunction. Design/Methods We conducted a retrospective descriptive analysis of our database of screen positive individuals, focusing on the subset who had a second mutation identified through expanded panel and whom we have offered clinical follow-up for 12 years. Results From 2008 to 2020, 718 screen positive individuals were referred to our CF Canada-accredited centre. 566 had one mutation identified by NSO. 94 of these had a second mutation identified on expanded panel. Of these, 13 had a sweat chloride between 30-60 mmol/L and 7 had a positive sweat test. Of those with borderline or negative sweats, 9 individuals continued to be followed. Two have converted to positive sweats, with 1 of these individuals requiring antibiotics for pulmonary exacerbations and the other remaining asymptomatic. Another 2 individuals are trending toward positive sweats (&amp;gt; 50 mmol/L). All spirometry values (FEV1, FVC) have been normal to date, and none have grown Pseudomonas aeruginosa. Conclusion Use of a confirmatory expanded panel identified a second mutation in 94 newborns referred with a positive screen. Offering follow-up has allowed us to monitor clinical progression, including conversion to positive sweats in 2 individuals. While spirometry and cultures have been unremarkable, more sensitive measures such as lung clearance index could be considered for future study. As of 2020, NSO moved to the use of extended sequencing and analysis of this change is ongoing.

Dynamic Perfluorinated Gas MRI Shows Improved Lung Ventilation in People with Cystic Fibrosis after Elexacaftor/Tezacaftor/Ivacaftor: An Observational Study.

The availability of highly effective CFTR modulators is revolutionizing the treatment of cystic fibrosis (CF) and drastically improving outcomes. MRI-based imaging modalities are now emerging as highly sensitive endpoints, particularly in the setting of mild lung disease. Adult CF patients were recruited from a single center prior to starting treatment with E/T/I. The following studies were obtained before and after one month on treatment: spirometry, multiple breath nitrogen washout (MBW), 1H UTE MRI (structural images) and 19F MRI (ventilation images). Changes between visits were calculated, as were correlations between FEV1, lung clearance index (LCI), MRI structural scores, and MRI-based ventilation descriptors. Eight subjects had complete datasets for evaluation. Consistent with prior clinical trials, FEV1 and LCI improved after 28 days of E/T/I use. 1H UTE MRI detected improvements in bronchiectasis/airway wall thickening score and mucus plugging score after 28 days of therapy. 19F MRI demonstrated improvements in fractional lung volume with slow gas washout time (FLV↑tau2) and ventilation defect percentage (VDP). Improvements in FLV↑tau2 and VDP correlated with improvement in FEV1 (r = 0.81 and 0.86, respectively, p < 0.05). This observational study establishes the ability of 19F MRI and 1H UTE MRI to detect improvements in lung structure and function after E/T/I treatment. This study supports further development of 19F MRI and 1H UTE MRI as outcome measures for cystic fibrosis research and drug development.

Breath detection algorithms affect multiple-breath washout outcomes in pre-school and school age children.

BackgroundAccurate breath detection is essential for the computation of outcomes in the multiple-breath washout (MBW) technique. This is particularly important in young children, where irregular breathing is common, and the designation of inspirations and expirations can be challenging.AimTo investigate differences between a commercial and a novel breath-detection algorithm and to characterize effects on MBW outcomes in children.MethodsWe replicated the signal processing and algorithms used in Spiroware software (v3.3.1, Eco Medics AG). We developed a novel breath detection algorithm (custom) and compared it to Spiroware using 2,455 nitrogen (N2) and 325 sulfur hexafluoride (SF6) trials collected in infants, children, and adolescents.ResultsIn 83% of N2 and 32% of SF6 trials, the Spiroware breath detection algorithm rejected breaths and did not use them for the calculation of MBW outcomes. Our custom breath detection algorithm determines inspirations and expirations based on flow reversal and corresponding CO2 elevations, and uses all breaths for data analysis. In trials with regular tidal breathing, there were no differences in outcomes between algorithms. However, in 10% of pre-school children tests the number of breaths detected differed by more than 10% and the commercial algorithm underestimated the lung clearance index by up to 21%.ConclusionAccurate breath detection is challenging in young children. As the MBW technique relies on the cumulative analysis of all washout breaths, the rejection of breaths should be limited. We provide an improved algorithm that accurately detects breaths based on both flow reversal and CO2 concentration.

Pulmonary function in children with persistent tachypnea of infancy.

Data on the prevalence and type of lung function impairment in preschool and school-aged children previously diagnosed with persistent tachypnea of infancy (PTI) are scarce. Therefore, this study aims to assess pulmonary function in this age group. Children diagnosed with PTI over 3 years old were admitted for follow-up visits and healthy controls were enrolled. The study group included children who were able to complete pulmonary function tests (PFTs). Medical history, physical examination, and pulmonary function (spirometry, body plethysmography, impulse oscillometry, nitrogen multiple breath washout test, diffusing capacity for carbon monoxide [DLCO ]) were assessed. Thirty-seven children (26 boys, 11 girls; median age: 5.6 years) diagnosed with PTI and 37 healthy controls were recruited. Forced expiratory volume in 1 sand forced vital capacity were significantly lower (-1.12 vs. 0.48, p = 0.002 and -0.83 vs. 0.31, p = 0.009, respectively); respiratory resistance at 5 Hz (0.06 vs. -0.62, p = 0.003), resonant frequency (1.86 vs. 1.36, p = 0.04), residual volume(RV) (2.34 vs. -1.2, p < 0.0001), RV%TLC (total lung capacity) (2.63 vs. -0.72, p < 0.0001), and specific airway resistance (5.4 vs. 2.59, p = 0.04) were significantly higher in PTI patients as compared with controls (data were presented as median z-score). Air trapping was found in 60.0%, and abnormally high lung clearance index and DLCO were found in 73.3% and 90.9% of PTI patients, respectively. This study demonstrated that lung function is affected in most children with PTI. PFTs showed that peripheral airways are the major zone of functional impairment.

122 Changes in lung clearance index in newborns who screened positive for cystic fibrosis with an inconclusive diagnosis

122 Changes in lung clearance index in newborns who screened positive for cystic fibrosis with an inconclusive diagnosis

184 Effects of elexacaftor/tezacaftor/ivacaftor therapy on lung clearance index and magnetic resonance imaging in patients with cystic fibrosis and one or two F508del alleles

184 Effects of elexacaftor/tezacaftor/ivacaftor therapy on lung clearance index and magnetic resonance imaging in patients with cystic fibrosis and one or two F508del alleles

134 Effect of hypertonic saline therapy on lung clearance index in preschool children with cystic fibrosis

134 Effect of hypertonic saline therapy on lung clearance index in preschool children with cystic fibrosis

176 How frequently should the lung clearance index be measured in children with cystic fibrosis?

176 How frequently should the lung clearance index be measured in children with cystic fibrosis?

Influence of bronchopulmonary dysplasia on lung function in adolescents who were born extremely prematurely.

To assess if a previous diagnosis of bronchopulmonary dysplasia(BPD) was associated with poorer lung function at 16 to 19 years of age, regardless of whether postnatal corticosteroids had been administered. Infants with BPD will have poorer lung function at 16 to 19 years of age. Prospective follow-up study. One hundred and sixty-one participants aged between 16 and 19 years who were born at less than 29 weeks of gestation; 87 had had BPD. Lung function was assessed by spirometry (FEV1 , FVC, FEV1 /FVC, FEF75 , FEF50 , FEF25 , FEF25 -75 , PEF), impulse oscillometry (R5Hz and R20Hz), plethysmography (FRCpleth , TLCpleth , RVpleth ), diffusion capacity of the lungs for carbon monoxide (DL CO, DL CO/VA) and lung clearance index (LCI). Questionnaires were used to quantify respiratory symptoms and a shuttle sprint test to assess exercise capacity. At 16 to 19 years, those who had had a diagnosis of BPD had poorer airway function (FEV1 , FEF75 , FEF50 , FEF25 -75 ) compared to those without. FVC and DL CO were also poorer in those who had BPD. Those differences remained significant after adjusting for sex, gestational age, and maternal smoking. When excluding those who had received postnatal corticosteroids, differences remained significant in FEV1 , FVC, and FEF75 . There were no significant differences in exercise capacity or respiratory symptoms between those with and without BPD. In adolescents and young adults born prematurely, those who had BPD had poorer lung function compared to those without, regardless of whether they had received postnatal corticosteroids.

Progress and challenges in fungal lung disease in cystic fibrosis.

This review is an overview of the recent progress made for the diagnosis and understanding of fungal lung disease in people with cystic fibrosis (CF), with a focus on Aspergillus fumigatus , the most common filamentous fungus in the CF airway. Currently, the longstanding question of the clinical significance of Aspergillus fumigatus and other fungi in CF respiratory cultures, in the absence of allergy, remains. Clinical criteria and biomarkers are needed to classify fungal lung disease and determine who may warrant therapy. Several retrospective and prospective studies have described the prevalence of A. fumigatus and other fungi in the CF lung and factors contributing to the changes in fungal epidemiology. Selective fungus culture testing for the detection of fungi in CF sputa has been well studied, yet a standardized fungus culture protocol has yet to be defined. Culture-independent molecular studies and other fungal diagnostic testing have been conducted in the CF population, leading to efforts to better understand the clinical role of these tests. Recent works have aimed to determine whether chronic A. fumigatus colonization is associated with lung disease progression measured by FEV 1 percentage predicted, structural lung disease, lung clearance index and respiratory quality-of-life. However, the existing knowledge gaps remain: definition of a fungal respiratory infection, the association between fungal infection and clinical outcomes, and indications for antifungal therapy. Significant progress has been made for the detection and diagnosis of fungal lung disease. Yet, the role and impact of A. fumigatus and other fungal infections on respiratory health in people with CF remains to be determined.

Pulmonary exacerbations, airway pathogens, and long-term course of lung clearance index in children and young adults with cystic fibrosis.

Pulmonary exacerbations (PEx), pathogens colonizing the respiratory tract, and patients' age are associated with progressive worsening of lung function among patients with cystic fibrosis (CF). However, the effect of these factors on longitudinal changes of Lung Clearance Index(LCI) remains unclear. To assess the role of age, different types of bronchial infection, and PEx on LCI deterioration. We conducted a retrospective study assessing multiple-breath washout(MBW) and spirometry changes among CF patients evaluated at quarterly outpatient clinic visits over 8 years. MBW and spirometry were performed at each visit, sputum samples and/or cough swabs were obtained for culture, whereas respiratory symptoms and clinical examination findings were recorded. Patients who had ≥5 serial MBW measurements, one of which coincided with a pulmonary exacerbation, were reviewed. Seventy-six patients were included in the study: mean age of 10.61 years (range 1.75-23.75). A total of 1152 MBW tests and 1047 spirometry tests were performed. LCI was significantly higher among CF patients aged 11-15, 16-20, and over 20 years than those under 5 years of age; ΔLCI: 1.16 (confidence interval [CI] 0.43-1.90) and 3.25 (CI 2.33-4.17), respectively. Furthermore, LCI was significantly elevated in CF patients with positive cultures for Pseudomonas aeruginosa (0.52 LCI [CI -0.12 to 0.71]) and Stenotrophomonas Maltophilia (1.41 LCI [CI 0.61-2.21]). Moreover, increased values of LCI in CF patients were significantly associated with increased risk of PEx (odds ratio [OR] 1.19, CI [1.14-1.25], p < 0.001). LCI demonstrates a progression of lung disease and corresponds to changes in bacterial infections and PEx among patients with CF. LCI may be a valuable marker for tracking disease deterioration and may have a role in the routine clinical care of patients with CF.