Risk factors for poorer respiratory outcomes in adolescents and young adults born preterm.

RATIONALE: The respiratory outcomes for adult survivors of preterm birth in the postsurfactant era are wide-ranging with prognostic factors, especially those encountered after the neonatal period, poorly understood. OBJECTIVES: To obtain comprehensive 'peak' lung health data from survivors of very preterm birth and identify neonatal and life-course risk factors for poorer respiratory outcomes in adulthood. METHODS: 127 participants born ≤32 weeks gestation (64%, n=81 with bronchopulmonary dysplasia (BPD), initially recruited according to a 2 with-BPD:1 without-BPD strategy), and 41 term-born controls completed a lung health assessment at 16-23 years, including lung function, imaging and symptom review. Risk factors assessed against poor lung health included neonatal treatments, respiratory hospitalisation in childhood, atopy and tobacco smoke exposure. MEASUREMENTS AND MAIN RESULTS: Young adults born prematurely had greater airflow obstruction, gas trapping and ventilation inhomogeneity, in addition to abnormalities in gas transfer and respiratory mechanics, compared with term. Beyond lung function, we observed greater structural abnormalities, respiratory symptoms and inhaled medication use. A previous respiratory admission was associated with airway obstruction; mean forced expiratory volume in 1 s/forced vital capacity z-score was -0.561 lower after neonatal confounders were accounted for (95% CI -0.998 to -0.125; p=0.012). Similarly, respiratory symptom burden was increased in the preterm group with a respiratory admission, as was peribronchial thickening (6% vs 23%, p=0.010) and bronchodilator responsiveness (17% vs 35%, p=0.025). Atopy, maternal asthma and tobacco smoke exposure did not influence lung function or structure at 16-23 years in our preterm cohort. CONCLUSIONS: Even after accounting for the neonatal course, a respiratory admission during childhood remained significantly associated with reduced peak lung function in the preterm-born cohort, with the largest difference seen in those with BPD. A respiratory admission during childhood should, therefore, be considered a risk factor for long-term respiratory morbidity in those born preterm, especially for individuals with BPD.

Pleural Plaques and the Risk of Lung Cancer in Asbestos-exposed Subjects.

Rationale: Asbestos exposure is associated with a dose-dependent risk of lung cancer. The association between lung cancer and the presence of pleural plaques remains controversial.Objectives: To define the relationship between pleural plaques and lung cancer risk.Methods: Subjects were from two cohorts: 1) crocidolite mine and mill workers and Wittenoom Township residents and 2) a mixed-asbestos-fiber, mixed-occupation group. All subjects underwent annual review since 1990, chest X-ray or low-dose computed tomography scan, and outcome linkage to national cancer and mortality registry data. Cox regression, with adjustment for age (as the underlying matching time variable), was used to estimate hazard ratios (HRs) for lung cancer incidence by sex, tobacco smoking, asbestos exposure, presence of asbestosis, and pleural plaques.Measurements and Main Results: For all 4,240 subjects, mean age at follow up was 65.4 years, 3,486 (82.0%) were male, 1,315 (31.0%) had pleural plaques, and 1,353 (32.0%) had radiographic asbestosis. Overall, 3,042 (71.7%) were ever-smokers with mean tobacco exposure of 33 pack-years. In total, 200 lung cancers were recorded. Risk of lung cancer increased with cumulative exposure to cigarettes, asbestos, and presence of asbestosis. Pleural plaques did not confer any additional lung cancer risk in either cohort (cohort 1: HR, 1.03; 95% confidence interval, 0.64-1.67; P = 0.89; cohort 2: HR, 0.75; 95% confidence interval, 0.45-1.25; P = 0.28).Conclusions: The presence of pleural plaques on radiologic imaging does not confer additional increase in the risk of lung cancer. This result is consistent across two cohorts with differing asbestos fiber exposures and intensity.

Aspergillus Infections and Progression of Structural Lung Disease in Children with Cystic Fibrosis.

Rationale: Recent data show that Aspergillus species are prevalent respiratory infections in children with cystic fibrosis (CF). The biological significance of these infections is unknown.Objectives: We aimed to evaluate longitudinal associations between Aspergillus infections and lung disease in young children with CF.Methods: Longitudinal data on 330 children participating in the Australian Respiratory Early Surveillance Team for Cystic Fibrosis surveillance program between 2000 and 2018 who underwent annual chest computed tomography (CT) imaging and BAL were used to determine the association between Aspergillus infections and the progression of structural lung disease. Results were adjusted for the effects of other common infections, associated variables, and repeated visits. Secondary outcomes included inflammatory markers in BAL, respiratory symptoms, and admissions for exacerbations.Measurements and Main Results:Haemophilus influenzae, Staphylococcus aureus, Pseudomonas aeruginosa, and Aspergillus infections were all associated with worse CT scores in the same year (Poverall < 0.05). Only P. aeruginosa and Aspergillus were associated with progression in CT scores in the year after an infection and worse CT scores at the end of the observation period. P. aeruginosa was most significantly associated with development of bronchiectasis (difference, 0.9; 95% confidence interval, 0.3-1.6; P = 0.003) and Aspergillus with trapped air (difference, 3.2; 95% confidence interval, 1.0-5.4; P = 0.004). Aspergillus infections were also associated with markers of neutrophilic inflammation (P < 0.001) and respiratory admissions risk (P = 0.008).Conclusions: Lower respiratory Aspergillus infections are associated with the progression of structural lung disease in young children with CF. This study highlights the need to further evaluate early Aspergillus species infections and the feasibility, risk, and benefit of eradication regimens.

Low dose CT detected interstitial lung abnormalities in a population with low asbestos exposure.

BACKGROUND: The use of low dose CT (LDCT) chest is becoming more widespread in occupationally exposed populations. There is a knowledge gap as to heterogeneity in severity and the natural course of asbestosis after low levels of exposure. This study reports the characteristics of LDCT-detected interstitial lung abnormalities (ILA). METHODS: The Asbestos Review Program offers annual LDCT, health assessments, and pulmonary function tests to an asbestos-exposed cohort. Asbestosis was defined using the Helsinki Consensus statement and the presence of ILA defined using a protocol for occupational CT reports. At least two of three pulmonary function tests: forced expiratory volume in 1 s (FEV1 );​ forced vital capacity (FVC); and diffusion capacity for carbon monoxide (DLco) were required for analysis of physiological decline. RESULTS: From 1513 cases, radiological ILA was present in 485 (32%). The cohort was 83.5% male with a median age of 68.3 years and a median (IQR) asbestos exposure of 0.7 (0.09-2.32) fiber/ml-year. A mixed occupation, mixed asbestos fiber cohort comprised the majority of the cohort (65.8%). Of those with ILA, 40 (8.2%) had an FVC decline of ≥10% and 30 (6.2%) had a DLco decline of ≥15% per year. Time since first exposure, increasing tobacco exposure and reported dyspnea were independently associated with the presence of ILA. CONCLUSIONS: In this population with relatively low asbestos exposure, LDCT-detected ILA that fits criteria for asbestosis is common, but physiological decline is not. This mild chronic stable phenotype of asbestos-associated ILA contrasts with the traditionally accepted views that asbestosis requires high exposures.

Initial acquisition and succession of the cystic fibrosis lung microbiome is associated with disease progression in infants and preschool children.

The cystic fibrosis (CF) lung microbiome has been studied in children and adults; however, little is known about its relationship to early disease progression. To better understand the relationship between the lung microbiome and early respiratory disease, we characterized the lower airways microbiome using bronchoalveolar lavage (BAL) samples obtained from clinically stable CF infants and preschoolers who underwent bronchoscopy and chest computed tomography (CT). Cross-sectional samples suggested a progression of the lower airways microbiome with age, beginning with relatively sterile airways in infancy. By age two, bacterial sequences typically associated with the oral cavity dominated lower airways samples in many CF subjects. The presence of an oral-like lower airways microbiome correlated with a significant increase in bacterial density and inflammation. These early changes occurred in many patients, despite the use of antibiotic prophylaxis in our cohort during the first two years of life. The majority of CF subjects older than four harbored a pathogen dominated airway microbiome, which was associated with a further increase in inflammation and the onset of structural lung disease, despite a negligible increase in bacterial density compared to younger patients with an oral-like airway microbiome. Our findings suggest that changes within the CF lower airways microbiome occur during the first years of life and that distinct microbial signatures are associated with the progression of early CF lung disease.

The arterial supply of the nipple areola complex (NAC) and its relations: an analysis of angiographic CT imaging for breast pedicle design.

PURPOSE: To investigate the blood supply to the nipple areola complex (NAC) on thoracic CT angiograms (CTA) to improve breast pedicle design in reduction mammoplasty. METHODS: In a single centre, CT scans of the thorax were retrospectively reviewed for suitability by a cardiothoracic radiologist. Suitable scans had one or both breasts visible in extended fields, with contrast enhancement of breast vasculature in a female patient. The arterial sources, intercostal space perforated, glandular/subcutaneous course, vessel entry point, and the presence of periareolar anastomoses were recorded for the NAC of each breast. RESULTS: From 69 patients, 132 breasts were suitable for inclusion. The most reproducible arterial contribution to the NAC was perforating branches arising from the internal thoracic artery (ITA) (n = 108, 81.8%), followed by the long thoracic artery (LTA) (n = 31, 23.5%) and anterior intercostal arteries (AI) (n = 21, 15.9%). Blood supply was superficial versus deep in (n = 86, 79.6%) of ITA sources, (n = 28, 90.3%) of LTA sources, and 10 (47.6%) of AI sources. The most vascularly reliable breast pedicle would be asymmetrical in 7.9% as a conservative estimate. CONCLUSION: We suggest that breast CT angiography can provide valuable information about NAC blood supply to aid customised pedicle design, especially in high-risk, large-volume breast reductions where the risk of vascular-dependent complications is the greatest and asymmetrical dominant vasculature may be present. Superficial ITA perforator supplies are predominant in a majority of women, followed by LTA- and AIA-based sources, respectively.

Risk factors for bronchiectasis in children with cystic fibrosis.

BACKGROUND: Bronchiectasis develops early in the course of cystic fibrosis, being detectable in infants as young as 10 weeks of age, and is persistent and progressive. We sought to determine risk factors for the onset of bronchiectasis, using data collected by the Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST CF) intensive surveillance program. METHODS: We examined data from 127 consecutive infants who received a diagnosis of cystic fibrosis after newborn screening. Chest computed tomography (CT) and bronchoalveolar lavage (BAL) were performed, while the children were in stable clinical condition, at 3 months and 1, 2, and 3 years of age. Longitudinal data were used to determine risk factors associated with the detection of bronchiectasis from 3 months to 3 years of age. RESULTS: The point prevalence of bronchiectasis at each visit increased from 29.3% at 3 months of age to 61.5% at 3 years of age. In multivariate analyses, risk factors for bronchiectasis were presentation with meconium ileus (odds ratio, 3.17; 95% confidence interval [CI], 1.51 to 6.66; P=0.002), respiratory symptoms at the time of CT and BAL (odds ratio, 2.27; 95% CI, 1.24 to 4.14; P=0.008), free neutrophil elastase activity in BAL fluid (odds ratio, 3.02; 95% CI, 1.70 to 5.35; P<0.001), and gas trapping on expiratory CT (odds ratio, 2.05; 95% CI, 1.17 to 3.59; P=0.01). Free neutrophil elastase activity in BAL fluid at 3 months of age was associated with persistent bronchiectasis (present on two or more sequential scans), with the odds seven times as high at 12 months of age and four times as high at 3 years of age. CONCLUSIONS: Neutrophil elastase activity in BAL fluid in early life was associated with early bronchiectasis in children with cystic fibrosis. (Funded by the National Health and Medical Research Council of Australia and Cystic Fibrosis Foundation Therapeutics.)

Ultra low dose CT screen-detected non-malignant incidental findings in the Western Australian Asbestos Review Programme.

BACKGROUND AND OBJECTIVE: Computed tomography (CT)-based studies of asbestos-exposed individuals report a high prevalence of lung cancer, but the utility of low dose CT (LDCT) to screen asbestos-exposed populations is not established. We aimed to describe the prevalence of indeterminate pulmonary nodules and incidental findings on chest LDCT of asbestos-exposed subjects in Western Australia. METHODS: A total of 906 subjects from the Western Australian Asbestos Review Programme underwent LDCT of the chest as part of regular annual review. An indeterminate (solid) nodule was defined as >50 mm3 and part-solid/non-solid nodules >5 mm. The presence of asbestos-related diseases was recorded with a standardized report. RESULTS: Subjects were mostly (81%) men with a median age of 70 years. Fifty-eight (6.5%) participants were current smokers, 511 (56.4%) ex-smokers and 325 (36.4%) never-smokers. One hundred and four indeterminate nodules were detected in 77 subjects (8.5%); of these, eight cases had confirmed lung cancer (0.88%). Eighty-seven subjects (9.6%) had incidental findings that required further investigation, 42 (4.6%) from lower airways inflammation. The majority of nodules were solid, 4-6 mm and more common with age. Five hundred and eighty (64%) subjects had pleural plaques, and 364 (40.2%) had evidence of interstitial lung disease. CONCLUSION: The prevalence of LDCT-detected indeterminate lung nodules in 906 individuals with significant asbestos exposure was 8.5%, lower than many other CT studies. Clinically important incidental findings were found in 9.4%, predominantly related to lower respiratory tract inflammation. LDCT appears to effectively describe asbestos-related diseases and is likely to be an acceptable modality to monitor asbestos-exposed individuals.

PRAGMA-CF. A Quantitative Structural Lung Disease Computed Tomography Outcome in Young Children with Cystic Fibrosis.

RATIONALE: Chest computed tomography (CT) is the gold standard for demonstrating cystic fibrosis (CF) airway disease. However, there are no standardized outcome measures appropriate for children younger than 6 years. OBJECTIVES: We developed the Perth-Rotterdam Annotated Grid Morphometric Analysis for CF (PRAGMA-CF), a quantitative measure of airway disease, and compared it with the commonly used CF-CT scoring method. METHODS: CT scans from the Australian Respiratory Early Surveillance Team for CF (AREST CF) cohort in Western Australia were included. PRAGMA-CF was performed by annotating a grid overlaid on 10 axial slices for the presence of bronchiectasis, mucous plugging, or other airway abnormalities (inspiratory scans) and trapped air (expiratory scans). The separate proportions of total disease (%Dis), bronchiectasis (%Bx), and trapped air (%TA) were determined. Thirty scans were used for observer reliability, and 30 paired scans obtained at 1 and 3 years old were used for comparison with a validated standard and biologic plausibility. MEASUREMENTS AND MAIN RESULTS: Intraobserver, intraclass correlation coefficients (95% confidence interval) for %Dis, %Bx, and %TA were 0.93 (0.86-0.97), 0.93 (0.85-0.96), and 0.96 (0.91-0.98), respectively. The change in %Dis (P = 0.004) and %Bx (P = 0.001) with PRAGMA-CF was related to neutrophil elastase presence at age 3, whereas only the change in bronchiectasis score was related to neutrophil elastase (P < 0.001) with CF-CT. Sample-size calculations for various effect sizes are presented. CONCLUSIONS: PRAGMA-CF is a sensitive and reproducible outcome measure for assessing the extent of lung disease in very young children with CF.

Distribution of early structural lung changes due to cystic fibrosis detected with chest computed tomography.

OBJECTIVE: To examine the distribution of early structural lung changes in clinically stable infants and young children with cystic fibrosis using chest computed tomography (CT). STUDY DESIGN: This cross-sectional study included 62 children aged 1-6 years with volume-controlled volumetric chest CT scans performed under general anesthesia as part of an early surveillance program. Each lobe was scored for presence and extent of bronchiectasis, mucus plugging, and air trapping using a semiquantitative score. The topographic distribution of structural abnormalities was evaluated by comparing the presence and extent of abnormalities in different lung regions and examining relationships between components. RESULTS: Although bronchiectasis was most common in the right upper lobe, overall changes in lung structure were not more common or more extensive in the upper lobes. Rather, bronchiectasis was more common in the right lung (right lung 0.95, left lung 0.68, P = .003), and mucus plugging (upper 0.41, middle 0.41, lower 0.72, P = .028) and air trapping (upper 0.79, middle 0.48, lower 0.96, P < .001) were more common in the lower lobes. The extents of bronchiectasis (P < .001) and air trapping (P = .011) were greater in the right lung. Scans with bronchiectasis were also more likely to have coexisting mucus plugging (P = .008) and air trapping (P < .001). CONCLUSION: Early structural lung disease is heterogeneously distributed in the lung. Quantitative scoring tools for studies using chest CT as an end point, and mechanistic studies that seek to better understand the pathogenesis of early cystic fibrosis lung disease, should take account of this differential topographic expression of disease early in life.

Cinematic versus volume rendered imaging for the depiction of complex congenital heart disease.

INTRODUCTION: Planning for surgical intervention for patients with complex congenital heart disease requires a comprehensive understanding of the individual's anatomy. Cinematic rendering (CR) is a novel technique that purportedly builds on traditional volume rendering (VR) by converting CT image data into clearly defined 3D reconstructions through the stimulation and propagation of light rays. The purpose of this study was to compare CR to VR for the understanding of critical anatomy in unoperated complex congenital heart disease. METHODS: In this retrospective study, CT data sets from 20 sequential scanned cases of unoperated paediatric patients with complex congenital heart disease were included. 3D images were produced at standardised and selected orientations, matched for both VR and CR. The images were then independently reviewed by two cardiologists, two radiologists and two surgeons for overall image quality, depth perception and the visualisation of surgically relevant anatomy, the coronary arteries and the pulmonary veins. RESULTS: Cinematic rendering demonstrated significantly superior image quality, depth perception and visualisation of surgically relevant anatomy than VR. CONCLUSION: Cinematic rendering is a novel 3D CT-rendering technique that may surpass the traditionally used volumetric rendering technique in the provision of actionable pre-operative anatomical detail for complex congenital heart disease.

Progression of early structural lung disease in young children with cystic fibrosis assessed using CT.

BACKGROUND: Cross-sectional studies implicate neutrophilic inflammation and pulmonary infection as risk factors for early structural lung disease in infants and young children with cystic fibrosis (CF). However, the longitudinal progression in a newborn screened population has not been investigated. AIM: To determine whether early CF structural lung disease persists and progresses over 1 year and to identify factors associated with radiological persistence and progression. METHODS: 143 children aged 0.2-6.5 years with CF from a newborn screened population contributed 444 limited slice annual chest CT scans for analysis that were scored for bronchiectasis and air trapping and analysed as paired scans 1 year apart. Logistic and linear regression models, using generalised estimating equations to account for multiple measures, determined associations between persistence and progression over 1 year and age, sex, severe cystic fibrosis transmembrane regulator (CFTR) genotype, pancreatic sufficiency, current respiratory symptoms, and neutrophilic inflammation and infection measured by bronchoalveolar lavage. RESULTS: Once detected, bronchiectasis persisted in 98/133 paired scans (74%) and air trapping in 178/220 (81%). The extent of bronchiectasis increased in 139/227 (63%) of paired scans and air trapping in 121/264 (47%). Radiological progression of bronchiectasis and air trapping was associated with severe CFTR genotype, worsening neutrophilic inflammation and pulmonary infection. DISCUSSION: CT-detected structural lung disease identified in infants and young children with CF persists and progresses over 1 year in most cases, with deteriorating structural lung disease associated with worsening inflammation and pulmonary infection. Early intervention is required to prevent or arrest the progression of structural lung disease in young children with CF.

Sabre-sheath trachea: An underused diagnostic weapon in the thoracic armoury.

INTRODUCTION: A sabre-sheath trachea is a highly specific sign for chronic obstructive pulmonary disease. It also correlates well with the degree of disease. We hypothesized that the term is vastly under-utilized in radiologic reporting, despite its high diagnostic value. METHODS: We interrogated our multisite metropolitan-wide radiology information system to find the number of CT reports containing the phrase 'sabre-sheath trachea' and conceivable variants thereof, over the 10 years to present. We compared this with the entire number of CT chest reports in the same time period in order to estimate the utilization of the sign. RESULTS: The results confirmed our hypothesis that the sign is rarely invoked, likely around 1 in 41 times relative to opportunity. CONCLUSIONS: This highly specific sign of chronic obstructive small airway disease should be reinforced in training and utilized by radiologists.

A screening tool to identify risk for bronchiectasis progression in children with cystic fibrosis.

BACKGROUND: The marked heterogeneity in cystic fibrosis (CF) disease complicates the selection of those most likely to benefit from existing or emergent treatments. OBJECTIVE: We aimed to predict the progression of bronchiectasis in preschool children with CF. METHODS: Using data collected up to 3 years of age, in the Australian Respiratory Early Surveillance Team for CF cohort study, clinical information, chest computed tomography (CT) scores, and biomarkers from bronchoalveolar lavage were assessed in a multivariable linear regression model as predictors for CT bronchiectasis at age 5-6. RESULTS: Follow-up at 5-6 years was available in 171 children. Bronchiectasis prevalence at 5-6 was 134/171 (78%) and median bronchiectasis score was 3 (range 0-12). The internally validated multivariate model retained eight independent predictors accounting for 37% (adjusted R2 ) of the variance in bronchiectasis score. The strongest predictors of future bronchiectasis were: pancreatic insufficiency, repeated intravenous treatment courses, recurrent lower respiratory infections in the first 3 years of life, and lower airway inflammation. Dichotomizing the resulting prediction score at a bronchiectasis score of above the median resulted in a diagnostic odds ratio of 13 (95% confidence interval [CI], 6.3-27) with positive and negative predictive values of 80% (95% CI, 72%-86%) and 77% (95% CI, 69%-83%), respectively. CONCLUSION: Early assessment of bronchiectasis risk in children with CF is feasible with reasonable precision at a group level, which can assist in high-risk patient selection for interventional trials. The unexplained variability in disease progression at individual patient levels remains high, limiting the use of this model as a clinical prediction tool.

A prospective randomised longitudinal MRI study of left ventricular adaptation to endurance and resistance exercise training in humans.

The principle that 'concentric' cardiac hypertrophy occurs in response to strength training, whilst 'eccentric' hypertrophy results from endurance exercise has been a fundamental tenet of exercise science. This notion is largely based on cross-sectional comparisons of athletes using echocardiography. In this study, young (27.4 ± 1.1 years) untrained subjects were randomly assigned to supervised, intensive, endurance (END, n = 10) or resistance (RES, n = 13) exercise and cardiac MRI scans and myocardial speckle tracking echocardiography were performed at baseline, after 6 months of training and after a subsequent 6 weeks of detraining. Aerobic fitness increased significantly in END (3.5 to 3.8 l min(-1), P < 0.05) but was unchanged in RES. Muscular strength significantly improved compared to baseline in both RES and END ( = 53.0 ± 1.1 versus 36.4 ± 4.5 kg, both P < 0.001) as did lean body mass (2.3 ± 0.4 kg, P < 0.001 versus 1.4 ± 0.6 kg P < 0.05). MRI derived left ventricular (LV) mass increased significantly following END (112.5 ± 7.3 to 121.8 ± 6.6 g, P < 0.01) but not RES, whilst training increased end-diastolic volume (LVEDV, END: +9.0 ± 5.0 versus RES +3.1 ± 3.6 ml, P = 0.05). Interventricular wall thickness significantly increased with training in END (1.06 ± 0.0 to 1.14 ± 0.06, P < 0.05) but not RES. Longitudinal strain and strain rates did not change following exercise training. Detraining reduced aerobic fitness, LV mass and wall thickness in END (P < 0.05), whereas LVEDV remained elevated. This study is the first to use MRI to compare LV adaptation in response to intensive supervised endurance and resistance training. Our findings provide some support for the 'Morganroth hypothesis', as it pertains to LV remodelling in response to endurance training, but cast some doubt over the proposal that remodelling occurs in response to resistance training.

Air trapping in early cystic fibrosis lung disease-Does CT tell the full story?

INTRODUCTION: Mosaic attenuation on expiratory chest computed tomography (CT) is common in early life cystic fibrosis (CF) and often referred to as "air trapping". It is presumed to be localized hyperinflation due to small airway obstruction. In order to test this assumption, we compared air trapping extent to lung volumes measured on CT in young children with CF. MATERIALS AND METHODS: Children aged below 7 years undergoing inspiratory/expiratory CT were recruited from the Australian Respiratory Early Surveillance Team for Cystic Fibrosis cohort. Automated lung segmentation was used to determine functional residual capacity (FRC), total lung capacity (TLC), and their ratio (FRC/TLC). Structural lung disease (%Disease) and air trapping (%TrappedAir) extent were assessed using PRAGMA-CF. Lung clearance index (LCI), an index of ventilation heterogeneity, was measured. Linear mixed model analysis was used to determine associations. RESULTS: Seventy-three scans from 55 patients were obtained. %TrappedAir was associated with %Disease (0.19 [0.07, 0.31]; P = 0.003) and LCI (0.22 [0.04, 0.39]; P = 0.016), but not FRC/TLC (0.00 [-0.02, 0.02]; P = 0.931). DISCUSSION: CT mosaic attenuation is associated with CF lung disease, however it is not always accompanied by physiologic hyperinflation. Other pathologies may contribute to mosaic attenuation. A better understanding of these factors could guide future therapies.