MRI Shows Lung Perfusion Changes after Vaping and Smoking.

Background Evidence regarding short-term effects of electronic nicotine delivery systems (ENDS) and tobacco smoke on lung ventilation and perfusion is limited. Purpose To examine the immediate effect of ENDS exposure and tobacco smoke on lung ventilation and perfusion by functional MRI and lung function tests. Materials and Methods This prospective observational pilot study was conducted from November 2019 to September 2021 (substudy of randomized controlled trial NCT03589989). Included were 44 healthy adult participants (10 control participants, nine former tobacco smokers, 13 ENDS users, and 12 active tobacco smokers; mean age, 41 years ± 12 [SD]; 28 men) who underwent noncontrast-enhanced matrix pencil MRI and lung function tests before and immediately after the exposure to ENDS products or tobacco smoke. Baseline measurements were acquired after 2 hours of substance abstinence. Postexposure measurements were performed immediately after the exposure. MRI showed semiquantitative measured impairment of lung perfusion (RQ) and fractional ventilation (RFV) impairment as percentages of affected lung volume. Lung clearance index (LCI) was assessed by nitrogen multiple-breath washout to capture ventilation inhomogeneity and spirometry to assess airflow limitation. Absolute differences were calculated with paired Wilcoxon signed-rank test and differences between groups with unpaired Mann-Whitney test. Healthy control participants underwent two consecutive MRI measurements to assess MRI reproducibility. Results MRI was performed and lung function measurement was acquired in tobacco smokers and ENDS users before and after exposure. MRI showed a decrease of perfusion after exposure (RQ, 8.6% [IQR, 7.2%-10.0%] to 9.1% [IQR, 7.8%-10.7%]; P = .03) and no systematic change in RFV (P = .31) among tobacco smokers. Perfusion increased in participants who used ENDS after exposure (RQ, 9.7% [IQR, 7.1%-10.9%] to 9.0% [IQR, 6.9%-10.0%]; P = .01). RFV did not change (P = .38). Only in tobacco smokers was LCI elevated after smoking (P = .02). Spirometry indexes did not change in any participants. Conclusion MRI showed a decrease of lung perfusion after exposure to tobacco smoke and an increase of lung perfusion after use of electronic nicotine delivery systems. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Kligerman in this issue.

MRI lung lobe segmentation in pediatric cystic fibrosis patients using a recurrent neural network trained with publicly accessible CT datasets.

PURPOSE: To introduce a widely applicable workflow for pulmonary lobe segmentation of MR images using a recurrent neural network (RNN) trained with chest CT datasets. The feasibility is demonstrated for 2D coronal ultrafast balanced SSFP (ufSSFP) MRI. METHODS: Lung lobes of 250 publicly accessible CT datasets of adults were segmented with an open-source CT-specific algorithm. To match 2D ufSSFP MRI data of pediatric patients, both CT data and segmentations were translated into pseudo-MR images that were masked to suppress anatomy outside the lung. Network-1 was trained with pseudo-MR images and lobe segmentations and then applied to 1000 masked ufSSFP images to predict lobe segmentations. These outputs were directly used as targets to train Network-2 and Network-3 with non-masked ufSSFP data as inputs, as well as an additional whole-lung mask as input for Network-2. Network predictions were compared to reference manual lobe segmentations of ufSSFP data in 20 pediatric cystic fibrosis patients. Manual lobe segmentations were performed by splitting available whole-lung segmentations into lobes. RESULTS: Network-1 was able to segment the lobes of ufSSFP images, and Network-2 and Network-3 further increased segmentation accuracy and robustness. The average all-lobe Dice similarity coefficients were 95.0 ± 2.8 (mean ± pooled SD [%]) and 96.4 ± 2.5, 93.0 ± 2.0; and the average median Hausdorff distances were 6.1 ± 0.9 (mean ± SD [mm]), 5.3 ± 1.1, 7.1 ± 1.3 for Network-1, Network-2, and Network-3, respectively. CONCLUSION: Recurrent neural network lung lobe segmentation of 2D ufSSFP imaging is feasible, in good agreement with manual segmentations. The proposed workflow might provide access to automated lobe segmentations for various lung MRI examinations and quantitative analyses.

Influence of ventilation inhomogeneity on diffusing capacity of carbon monoxide in smokers without COPD.

In smokers with preserved spirometry, D LCO is associated with ventilation inhomogeneity arising from peripheral airways. Measurement of D LCO to screen for early lung function abnormalities in smokers may be suboptimal and could be replaced by MBW. https://bit.ly/3nLmgg1.

Lung clearance index predicts pulmonary exacerbations in individuals with primary ciliary dyskinesia: a multicentre cohort study.

BACKGROUND: Lung clearance index (LCI) is a promising lung function outcome in individuals with primary ciliary dyskinesia (PCD). The impact of events clinically important for individuals with PCD, such as pulmonary exacerbations, on LCI is unknown. METHODS: We conducted an international, multicentre, observational cohort study to assess the association of LCI and risk of pulmonary exacerbation, specific changes in LCI during pulmonary exacerbation and global variability of LCI across four visits every 4 months. Ninety individuals with PCD, aged 3-41 years, underwent nitrogen multiple-breath washout (MBW) and spirometry measurements. The association of LCI and pulmonary exacerbations was assessed by Cox proportional hazards and random-effects regression models. RESULTS: We obtained 430 MBW and 427 spirometry measurements. In total, 379 person-years at risk contributed to the analysis. Per one unit increase (deterioration) in LCI, the risk of future pulmonary exacerbation increased by 13%: HR (95% CI), 1.13 (1.04 to 1.23). If LCI changed from a range of values considered normal to abnormal, the risk of future pulmonary exacerbations increased by 87%: 1.87 (1.08 to 3.23). During pulmonary exacerbations, LCI increased by 1.22 units (14.5%). After pulmonary exacerbations, LCI tended to decline. Estimates of variability in LCI suggested lower variation within individuals compared with variation between individuals. Findings were comparable for forced expiratory volume in 1 s. CONCLUSION: On a visit-to-visit basis, LCI measurement may add to the prediction of pulmonary exacerbations, the assessment of lung function decline and the potential lung function response to treatment of pulmonary exacerbations.

Penetrating chest trauma after attempted suicide: An extraordinary behavior of a posttraumatic pulmonary artery pseudoaneurysm.

Posttraumatic pulmonary artery pseudoaneurysm is a very rare, yet potentially lethal complication after thoracic trauma. Pulmonary artery pseudoaneurysm is associated with high mortality. Still literature highlights that untreated, lesions can enlarge, rupture, and lead to exsanguination and death. We present a case of a posttraumatic peripheral pulmonary artery pseudoaneurysm with complete disappearance after one year. This case confirms that conservative treatment can be an effective option in asymptomatic and stable patients.

[Assessment of lung impairment in patients with cystic fibrosis : Novel magnetic resonance imaging methods]. / Detektion von Lungenveränderungen bei Patienten mit Mukoviszidose : Innovationen der Magnetresonanztomographie des Thorax.

CLINICAL/METHODOLOGICAL ISSUE: The differentiated assessment of respiratory mechanics, gas exchange and pulmonary circulation, as well as structural impairment of the lung are essential for the treatment of patients with cystic fibrosis (CF). Clinical lung function measurements are often not sufficiently specific and are often difficult to perform. STANDARD RADIOLOGICAL METHODS: The standard procedures for pulmonary imaging are chest X­ray and computed tomography (CT) for assessing lung morphology. In more recent studies, an increasing number of centers are using magnetic resonance imaging (MRI) to assess lung structure and function. However, functional imaging is currently limited to specialized centers. METHODOLOGICAL INNOVATIONS: In patients with CF, studies showed that MRI with hyperpolarized gases and Fourier decomposition/matrix pencil MRI (FD/MP-MRI) are feasible for assessing pulmonary ventilation. For pulmonary perfusion, dynamic contrast-enhanced MRI (DCE-MRI) or contrast-free methods, e.g., FD-MRI, can be used. PERFORMANCE: Functional MRI provides more accurate insight into the pathophysiology of pulmonary function at the regional level. Advantages of MRI over X­ray are its lack of ionizing radiation, the large number of lung function parameters that can be extracted using different contrast mechanisms, and ability to be used repeatedly over time. ACHIEVEMENTS: Early assessment of lung function impairment is needed as the structural changes usually occur later in the course of the disease. However, sufficient experience in clinical application exist only for certain functional lung MRI procedures. PRACTICAL RECOMMENDATIONS: Clinical application of the aforementioned techniques, except for DCE-MRI, should be restricted to scientific studies.

Postinfectious Bronchiolitis Obliterans in Children: Diagnostic Workup and Therapeutic Options: A Workshop Report.

Bronchiolitis obliterans (BO) is a rare, chronic form of obstructive lung disease, often initiated with injury of the bronchiolar epithelium followed by an inflammatory response and progressive fibrosis of small airways resulting in nonuniform luminal obliteration or narrowing. The term BO comprises a group of diseases with different underlying etiologies, courses, and characteristics. Among the better recognized inciting stimuli leading to BO are airway pathogens such as adenovirus and mycoplasma, which, in a small percentage of infected children, will result in progressive fixed airflow obstruction, an entity referred to as postinfectious bronchiolitis obliterans (PIBO). The present knowledge on BO in general is reasonably well developed, in part because of the relatively high incidence in patients who have undergone lung transplantation or bone marrow transplant recipients who have had graft-versus-host disease in the posttransplant period. The cellular and molecular pathways involved in PIBO, while assumed to be similar, have not been adequately elucidated. Since 2016, an international consortium of experts with an interest in PIBO assembles on a regular basis in Geisenheim, Germany, to discuss key areas in PIBO which include diagnostic workup, treatment strategies, and research fields.

A multi-scale model of gas transport in the lung to study heterogeneous lung ventilation during the multiple-breath washout test.

The multiple-breath washout (MBW) is a lung function test that measures the degree of ventilation inhomogeneity (VI). The test is used to identify small airway impairment in patients with lung diseases like cystic fibrosis. However, the physical and physiological factors that influence the test outcomes and differentiate health from disease are not well understood. Computational models have been used to better understand the interaction between anatomical structure and physiological properties of the lung, but none of them has dealt in depth with the tracer gas washout test in a whole. Thus, our aim was to create a lung model that simulates the entire MBW and investigate the role of lung morphology and tissue mechanics on the tracer gas washout procedure. To this end, we developed a multi-scale lung model to simulate the inert gas transport in airways of all size. We then applied systematically different modifications to geometrical and mechanical properties of the lung model (compliance, residual airway volume and flow resistance) which have been associated with VI. The modifications were applied to distinct parts of the model, and their effects on the gas distribution within the lung and on the gas concentration profile were assessed. We found that variability in compliance and residual volume of the airways, as well as the spatial distribution of this variability in the lung had a direct influence on gas distribution among airways and on the MBW pattern (washout duration, characteristic concentration profile during each expiration), while the effects of variable flow resistance were negligible. Based on these findings, it is possible to classify different types of inhomogeneities in the lung and relate them to specific features of the MBW pattern, which builds the basis for a more detailed association of lung function and structure.

Spirometric indices in primary ciliary dyskinesia: systematic review and meta-analysis.

Primary ciliary dyskinesia (PCD) is a genetic, heterogeneous disease caused by dysfunction of cilia. Evidence is sparse and reports of lung function in PCD patients range from normal to severe impairment. This systematic review and meta-analysis of studies of lung function in PCD patients examines the spirometric indices of PCD patients and differences by age group and sex. We searched PubMed, Embase and Scopus for studies that described lung function in 10 or more patients with PCD. We performed meta-analyses and meta-regression to explain heterogeneity. We included 24 studies, ranging from 13 to 158 patients per study. The most commonly reported spirometric indices were forced expiratory volume in 1 s (FEV1) and forced vital capacity presented as mean and standard deviation of percent predicted values. We found considerable heterogeneity for both parameters (I 2=94-96%). The heterogeneity remained when we stratified the analysis by age; however, FEV1 in adult patients was lower. Even after taking into account explanatory factors, the largest part of the between-studies variance remained unexplained. Heterogeneity could be explained by genetic differences between study populations, methodological factors related to the variability of study inclusion criteria or details on the performance and evaluation of lung function measurements that we could not account for. Prospective studies therefore need to use standardised protocols and international reference values. These results underline the possibility of distinct PCD phenotypes as in other chronic respiratory diseases. Detailed characterisation of these phenotypes and related genotypes is needed in order to better understand the natural history of PCD.

Within-breath changes in respiratory system impedance in children with cystic fibrosis.

BACKGROUND: The aim of this study was to assess within-breath respiratory system impedance by the forced oscillation technique (FOT) in children with cystic fibrosis (CF) and relate it to the underlying lung disease. METHODS: Thirty-three children with CF (median [range] age 12.0 [6-17] years) underwent FOT at 8 Hz during tidal breathing, multiple breath nitrogen washout (LCI), spirometry (FEV1), body plethysmography (RV/TLC), and magnetic resonance imaging (MRI). FOT outcomes included: mean inspiratory, expiratory, and whole breath resistance (R8INSP , R8EXP , R8TOT ) and reactance (X8INSP , X8EXP , X8TOT ), and the differences between X8INSP and X8EXP (ΔX8). Morphological changes were evaluated by MRI using CF-specific morphological scores. Spearman correlation was performed to examine the correlation between FOT indices and other parameters. RESULTS: FEV1 was negatively correlated with R8EXP (r = -0.52, P = 0.002) and ΔX8 (r = -0.55, P = 0.001), and positively correlated with and X8EXP (r = 0.56, P < 0.001). RV/TLC was positively correlated with R8EXP (r = 0.43, P = 0.013), and ΔX8 (r = 0.54, P = 0.001) and negatively correlated with X8EXP (r = -0.54, P = 0.001). We found poor correlation between FOT parameters and LCI and no correlation between FOT parameters and MRI scores. CONCLUSION: In children with CF, changes in within-breath FOT parameters are consistent with peripheral obstruction and dynamic airway compression, while they are not associated with ventilation heterogeneities and morphological alterations.

Respiratory rate in infants with cystic fibrosis throughout the first year of life and association with lung clearance index measured shortly after birth.

BACKGROUND: Lung impairment in cystic fibrosis (CF) starts in infancy. However, tools to monitor early lung disease are limited. Respiratory rate (RR) as a key vital sign is easy to assess during sleep and is elevated during acute respiratory disease. Thus, elevated RR could indicate early lung impairment and potentially serve as a diagnostic tool in disease monitoring. METHODS: In a prospective cohort of infants with CF diagnosed by newborn screening and healthy controls RR was measured and respiratory symptoms reported weekly throughout infancy. Infants performed a lung function measurement within the first weeks of life. RESULTS: The analyses included 5656 measurements from 153 infants (43 with CF). RR declined from 43.2 (40.5)/min at 6 weeks of age to 28.3 (24.6)/min at 50 weeks in infants with CF (healthy controls). Infants with CF had consistently higher RR than controls (mean difference: 4.15/min; (95% CI 2.86-5.44); p < .001). In both study groups, RR was increased throughout the study period in infants with higher lung clearance indices (LCI) and during episodes of respiratory infections. CONCLUSIONS: Infants with CF have a higher RR compared to healthy controls during the first year of life. The association with early LCI measurements, the current gold standard to assess physiology of peripheral airways persisted throughout the study period. This may indicate tracking of lung function by RR. It might thus be an early subtle sign of functional respiratory deficit. Further studies will show if RR can be used as a sensitive and promising marker to monitor early CF lung disease.

Ventilation and perfusion assessed by functional MRI in children with CF: reproducibility in comparison to lung function.

BACKGROUND: Chronic lung diseases such as cystic fibrosis (CF) can be monitored by imaging and lung function modalities. Magnetic resonance imaging (MRI) techniques such as matrix pencil (MP) decomposition allows for evaluation of regional impairment of fractional ventilation (RFV) and relative perfusion (RQ). However, reproducibility of MP MRI outcomes in children with CF is unknown. We examined short-term variability of ventilation and perfusion impairment from MP MRI and compared this to lung function outcomes. METHOD: Twenty-threeCF and 12 healthy school-aged children underwent MRI and lung function tests on the same day on two occasions 24 h apart. Global ventilation inhomogeneity was assessed by the lung clearance index (LCI) from nitrogen-multiple breath washout (N2-MBW) technique. Intra-class-coefficient (ICC), percentage change, and Bland-Altman limits of agreement were evaluated to assess reproducibility. RESULTS: Sixty-nine measurements from MP MRI and N2-MBW were performed. The ICC between two visits for RFV, RQ and LCI ranged between 0.60 and 0.90 in individuals with CF and healthy controls. In individuals with CF, percentage of change between the visits was 0.02% for RFV, -1.11% for RQ and 2.91% for LCI and limits of agreement between visits were - 4.3% and 3.9% for RFV, -4.4% and 3.7% for RQ, and -2.6 and 3.0 for LCI. CONCLUSIONS: Functional imaging is reproducible and short-term changes in RFV and RQ greater than ±4.4% can be considered clinical meaningful. Very good short-term reproducibility, and easy application without the need for breathing maneuvers or contrast agent, makes MP MRI a promising surveillance method for CF.

Structural and Functional Lung Impairment in Primary Ciliary Dyskinesia. Assessment with Magnetic Resonance Imaging and Multiple Breath Washout in Comparison to Spirometry.

RATIONALE: Primary ciliary dyskinesia (PCD) is an inherited disorder characterized by heterogeneous airway disease. Traditional lung function techniques (e.g., spirometry) may underestimate severity and complexity of PCD. OBJECTIVES: We assessed lung impairment in individuals with PCD using structural and functional magnetic resonance imaging (MRI) and different lung function techniques. METHODS: A total of 30 study participants with PCD (median, 13.4 yr; range, 5-28 yr) underwent structural and functional MRI, spirometry, and multiple breath washout (MBW) on the same day. Primary endpoints included structural MRI morphology scores, relative ventilation, and perfusion impairment from functional MRI, forced expiratory volume in 1 second (FEV1) from spirometry, and lung clearance index (LCI) from MBW. RESULTS: Severity and complexity of PCD lung disease varied significantly between individuals. Structural lung disease was detected in all subjects with a median (interquartile range) extent score of 10.3 (7-19; maximum score = 60). Functional MRI ventilation impairment was present in 52% of subjects, affecting 24.2% (21.1 to 25.2%) of the lung. Relative perfusion impairment was detected in 78% of individuals affecting 21.1% (19.4 to 25.9%) of the lung. LCI was abnormal in 83% (median, 8.3 [2.6 to 13.2] z-scores) and FEV1 was abnormal in 27% (-0.5 [-1.6 to 0.3] z-scores) of individuals. Concordance between spirometry and imaging outcomes was poor, with 52% of patients showing both abnormal MRI and LCI values, but normal FEV1. CONCLUSIONS: Discordance between lung function and imaging outcomes in patients with PCD supports the use of both imaging and lung function, such as MBW, for surveillance of this heterogeneous disease.

Alternate gas washout indices: Assessment of ventilation inhomogeneity in mild to moderate pediatric cystic fibrosis lung disease.

INTRODUCTION: Normalized phase III slope (SnIII ) indices from multiple breath washout (MBW) estimate ventilation inhomogeneity. Alternate (*) protocols for SnIII indices exist, however the utility of these outcomes in children with mild-to-moderate cystic fibrosis (CF) is unknown. METHODS: We measured nitrogen MBW and spirometry in 135 children (43 controls) aged 4-18 years. We assessed validity, practicability, and reliability of SnIII protocols. Outcomes included the ability to detect abnormal lung function, test agreement, measurement duration, intra-test repeatability, and quality. RESULTS: Lung clearance index (LCI) was abnormal in 80 (87%), Scond in 55 (60%), Scond* in 17 (19%), Sacin in 10 (11%), Sacin* in 11 (12%), and FEV1 in 28 (30%). Alternate protocols reduced measurement duration. Agreement of indices to detect abnormal lung function was poor. The quality of analysis and repeatability deteriorated with the alternate technique compared to standard. CONCLUSION: In children with mild-to-moderate CF lung disease, alternate protocols seem practical but clinimetric properties of standard SnIII protocols are preferable.

Short-Term Effects of Elastic Chest Wall Restriction on Pulmonary Function in Children with Cystic Fibrosis.

BACKGROUND: Elastic chest wall restriction introduced by Chevaillier is thought to reduce existing hyperinflation and improve mucus clearance from peripheral airways. In healthy adults, restriction decreases the functional residual capacity (FRC) and forced vital capacity (FVC), while ventilation inhomogeneity (lung clearance index [LCI]) increases. Pulmonary function response to restriction is unknown in individuals with cystic fibrosis (CF). OBJECTIVES: To examine short-term effects of elastic chest wall restriction on pulmonary function in children with CF. METHODS: Pulmonary function was first assessed twice 15 min apart at baseline and then again following 15 min of elastic chest wall restriction in 20 school-aged children with CF (12.3 ± 3.4 years). Primary outcomes were LCI from nitrogen multiple-breath washout, residual volume (RV), and FRC from plethysmography. Secondary outcomes were FVC and end-expiratory lung impedance (EELI) from electrical impedance tomography. Endpoints were test-retest reliability at baseline and lung function response to restriction, both on group and individual levels. RESULTS: Test-retest reliability was excellent (intra-class correlation coefficients range 0.84-0.99). Following restriction, FRC significantly declined on average (95% CI) by -0.09 (-0.17 to -0.02) L. Similarly, FVC declined while LCI did not change. RV and EELI declined, but this did not reach statistical significance. On the individuals' level, heterogeneous changes in pulmonary function occurred following elastic chest wall restriction. CONCLUSIONS: These findings indicate that the application of elastic chest wall restriction is safe, induces the intended decline in resting lung volume but does not systematically alter ventilation inhomogeneity in children with CF.

Comparison of different analysis algorithms to calculate multiple-breath washout outcomes.

Lung clearance index (LCI) is the main outcome of the multiple-breath washout (MBW) test. Current recommendations for LCI acquisition are based on low-grade evidence. The aim of this study was to challenge those recommendations using alternative methods for LCI analysis. Nitrogen MBW measurements from school-aged children, 20 healthy controls, 20 with cystic fibrosis (CF) and 17 with primary ciliary dyskinesia (PCD), were analysed using 1) current algorithms (standard), 2) three alternative algorithms to detect with higher precision the end of MBW testing and 3) two alternative algorithms to determine exhaled tracer gas concentrations. LCI values, intra-test repeatability, and ability to discriminate between health and lung disease were compared between these methods. The analysis methods strongly influenced LCI (mean±sd overall differences (%) between standard and alternative analysis methods: -4.9±5.7%; range: -66-19%), but did not improve intra-test variability. Discrimination between health and disease was comparable as areas under the receiver operator curves were not greater than that from standard analysis. This study supports current recommendations for LCI calculation in children. Alternative methods influence LCI estimates and hamper comparability between MBW setups. Alternative algorithms, whenever used, should be carefully reported.

The Swiss Cystic Fibrosis Infant Lung Development (SCILD) cohort.

The Swiss Cystic Fibrosis Infant Lung Development (SCILD) cohort is a prospective birth cohort study investigating the initiating events of cystic fibrosis lung disease during infancy, and their influence on the trajectory of disease progression throughout early childhood. Infants with cystic fibrosis are recruited throughout Switzerland after diagnosis by new-born screening. It is the first European population-based prospective cohort study of infants with cystic fibrosis taking advantage of a nationwide new-born screening programme. The study was established in 2011 and recruitment is ongoing. The cohort study is currently divided into three study phases (phase 1: diagnosis to age 1 year; phase 2: age 1 to 3 years; and phase 3: age 3 to 6 years). Study participants have weekly telephone interviews, weekly anterior nasal swab collection and two study visits in the first year of life. They also complete follow-up study visits at 3 and 6 years of age. Data for this study are derived from questionnaires, lung function measurements, telephone interviews, nasal swab material and magnetic resonance imaging. To date, 70 infants have been recruited into the study and 56 have completed phase 1, including a baseline study visit at 6 weeks of age, weekly surveillance and a study visit at one year of age. More than 2500 data points on respiratory health and almost 2000 nasal samples have been collected. Phases 2 and 3 will commence in 2018. The dataset of the SCILD cohort combines lung function data, the collection of environmental and sociodemographic factors, documentation of respiratory symptoms, and microbiological analyses. The design not only allows tracking of the cystic fibrosis lung disease independent of clinical status, but also surveillance of early disease prior to severe clinical symptoms. This cohort profile provides details on the study design and summarizes the first published results of the SCILD cohort.

Multiple breath washout: A new and promising lung function test for patients with idiopathic pulmonary fibrosis.

BACKGROUND AND OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) is a devastating progressive lung disease affecting the parenchyma. Nitrogen multiple-breath washout (N2 -MBW) is a lung function test that measures ventilation inhomogeneity, a biomarker of small airway disease. We assessed clinical properties of N2 -MBW in IPF. METHODS: In this prospective cohort pilot study, 25 IPF patients and 25 healthy controls were assessed at baseline and 10 patients at median 6.2 months later. Outcomes included the lung clearance index (LCI) from N2 -MBW, forced vital capacity (FVC) from spirometry, diffusion capacity of the lungs for carbon monoxide (DLCO ), bronchiectasis score from computed tomography scans, the Gender-Age-Physiology (GAP score for IPF) stage and death or lung transplantation (LTx). Study end points were feasibility, repeatability, discriminative capacity and correlation with disease severity and structural lung damage. RESULTS: All patients were able to perform N2 -MBW. LCI was repeatable and reproducible. Median (interquartile range (IQR)) LCI in IPF was 11.6 (10.1-13.8) in IPF versus 7.3 (6.9-8.4) in controls (P < 0.0001). LCI correlated with DLCO corrected for haemoglobin (corrDLCO ; r = -0.49, P = 0.016), bronchiectasis score (r = 0.45, P = 0.024) and the GAP stage (r = 0.59, P = 0.002), but not with FVC. FVC was not related to bronchiectasis. During follow-up, six patients died and one received LTx. LCI correlated with the latter compound outcome: hazard ratio (95% CI) was 2.43 (1.26; 4.69) per one LCI SD from the patient population. CONCLUSION: N2 -MBW is a feasible, reliable and valid lung function test in IPF. LCI correlates with diffusion impairment, structural airway damage and clinical disease severity. LCI is a promising surveillance tool in IPF that may predict mortality.

Inert Gas Washout in Bronchiolitis Obliterans Following Hematopoietic Cell Transplantation.

BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is a leading cause of chronic graft-vs-host disease (cGvHD) and is associated with mortality after allogeneic hematopoietic stem cell transplantation (alloHSCT). The nitrogen multiple breath washout test (N2-MBW) measures ventilation inhomogeneity, a biomarker of central and peripheral airway obstruction. The aim of this study was to examine ventilation inhomogeneity according to cGvHD score and histologically defined bronchiolitis obliterans (BO). METHODS: This single-center prospective cross-sectional study included 225 adults (mean age, 52.8 years; median, 5.4 years [interquartile range, 2.0-11 years]) after alloHSCT. Outcomes were global (lung clearance index [LCI]) and acinar ventilation inhomogeneity index (SACIN) from N2-MBW. Patients were categorized into five groups: (1) no cGvHD and no obstruction (cGvHD overall score 0 and FEV1/FVC ≥ 70) (2) cGvHD and no obstruction (cGvHD overall score 1-3 and FEV1/FVC ≥ 70), (3) BOS with or without cGvHD (if available, no BO on histologic examination, and FEV1/FVC < 70), (4) histologically proven BO, and (5) diffuse parenchymal lung disease other than BO. RESULTS: The LCI and SACIN differed significantly between groups (P < .001) and increased progressively according to cGvHD score. In BO, the LCI and SACIN were elevated in 95.5% and 81.8% of patients, respectively, whereas FEV1/FVC was abnormal in only 56.5% of patients, respectively. CONCLUSIONS: N2-MBW is highly sensitive for detecting abnormal lung function in patients following alloHSCT. LCI and SACIN seem to be promising biomarkers of lung involvement in cGvHD.

Novel magnetic resonance technique for functional imaging of cystic fibrosis lung disease.

Lung function tests are commonly used to monitor lung disease in cystic fibrosis (CF). While practical, they cannot locate the exact origin of functional impairment. Contemporary magnetic resonance imaging (MRI) techniques provide information on the location of disease but the need for contrast agents constrains their repeated application. We examined the correlation between functional MRI, performed without administration of contrast agent, and lung clearance index (LCI) from nitrogen multiple-breath washout (N2-MBW).40 children with CF (median (range) age 12.0 (6-18) years) and 12 healthy age-matched controls underwent functional and structural MRI and lung function tests on the same day. Functional MRI provided semiquantitative measures of perfusion (RQ) and ventilation (RFV) impairment as percentages of affected lung volume. Morphological MRI was evaluated using CF-specific scores. LCI measured global ventilation inhomogeneity.MRI detected functional impairment in CF: RFV 19-38% and RQ 16-35%. RFV and RQ correlated strongly with LCI (r=0.76, p<0.0001 and r=0.85, p<0.0001, respectively), as did total morphology score (r=0.81, p<0.0001). All indices differed significantly between patients with CF and healthy controls (p<0.001).Noninvasive functional MRI is a promising method to detect and visualise perfusion and ventilation impairment in CF without the need for contrast agents.