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The forced oscillation technique can identify a surrogate of closing volume (CVFOT). We investigated its relationship with the one measured by single-breath washout (CVSBW). CVFOT weakly correlates with CVSBW. The respective closing capacities were correlated, but their increases after methacholine challenge in asthmatics did not. Our results suggest that CVFOT is less sensitive than CVSBW to few flow-limited/closed airways but more specific in detecting increases in flow-limited/closed airways involving the majority of the lung.

FEV1 increase usually observed after tHe inhalation of short-acting β2-agonists in asthma patients tends to involve peripheral airways. This study shows that the heterogeneity of responses to short-acting β2-agonists in asthma not only involves distinct sites of bronchodilation, but also distinct sequences between these sites. This indicates that a detailed understanding of the bronchodilator effect of β2-agonists in asthma should not be limited to studying its early impact on FEV1.

Objectives: To estimate the variability of CT diagnostic reference levels (DRLs) according to the methods used for computing collected data. Methods: Dose-length products (DLP) were collected by our national nuclear control agency from the 250 devices installed in 140 medical centers in the country. In 2015, the number of head, thorax, abdomen, and lumbar spine examinations collected in these centers ranged from approximately 20,000 to 42,000. The impact on DRLs of the number of devices considered, as well as the differences in descriptive statistics (mean vs. median DLP) or methods of pooling DLP data (all devices vs. all patients), was investigated. Variability in DRLs was investigated using a bootstrapping method as a function of the numbers of devices and examinations per device. Results: As expected, DRLs derived from means were higher than those from medians, with substantial differences between device- and patient-related DRLs. Depending on the numbers of devices and DLP data per device, the variability ranged from 10 to 40% but was stabilized at a level of 10–20% if the number of devices was higher than 50 to 60, regardless of the number of DLP data per device. Conclusion: Number of devices and of DLP data per device, descriptive statistics, and pooling data influence DRLs. As differences in methods of computing survey data can artificially influence DRLs, harmonization among national authorities should be recommended. Key Points: • Due to CT dose variability, that of DRLs is at least of 10%. • DRLs derived from medians are lower than from means and differ from those obtained by pooling all patient data. • Fifty to 60 devices should be sufficient for estimating national DRLs, regardless of the number of data collected per device., SCOPUS: ar.j, info:eu-repo/semantics/published

To determine the variabilities of dose-area-products (DAP) of frequent X-ray examinations collected for comparison with diagnostic reference levels (DRLs). DAP values of chest, abdomen, and lumbar spine examinations obtained on devices from two manufacturers were collected in three centers over 1 to 2 years. The variability of the average DAP results defined as the 95% confidence interval in percentage of their median value was calculated for increasing sample sizes, each examination and center. We computed the sample sizes yielding variabilities lower or equal to 25% and 10%. The effect of narrowing patient selection based on body weight was also investigated (ranges of 67–73 Kg, or 60–80 Kg). DAP variabilities ranged from 75 to 170% of the median value when collecting small samples (10 to 20 DAP). To reduce this variability, larger samples are needed, collected over up to 2 years, regardless of the examination and center. A variability ≤ 10% could only be reached for chest X-rays, requiring up to 800 data. For the abdomen and lumbar spine, the lowest achievable variability was 25%, regardless of the body weight selection, requiring up to 400 data. Variabilities in DAP collected through small samples of ten data as recommended by authorities are very high, but can be reduced down to 25% (abdomen and lumbar spine) or even 10% (chest) through a substantial increase in sample sizes. Our findings could assist radiologists and regulatory authorities in estimating the reliability of the data obtained when performing X-ray dose surveys. • Low but reasonable variabilities cannot be reached with samples sized as recommended by regulatory authorities. Higher numbers of DAP values are required to reduce the variability. • Variabilities of 10% for the chest and 25% for abdomen and lumbar spine examinations are achievable, provided large samples of data are collected over 1 year. • Our results could help radiologists and authorities interpret X-rays dose surveys.

SCOPUS: le.j, info:eu-repo/semantics/published

We previously documented, in patients with asthma, three different profiles of bronchodilation induced by short-acting β-2 mimetics (SABA), characterized by dilation up to central, preacinar, and intra-acinar airways assessed by ventilation distribution tests and associated with no change, increase, and decrease of fractional exhaled nitric oxide concentration (FENO), respectively. To investigate the dynamics of these profiles over the entire SABA action period, assuming that bronchodilation of proximal and peripheral airways could exhibit varying kinetics due to differences in the distribution of β-2 receptors in both the central and peripheral human airways. FENO, forced expired volume in one second (FEV

Over the years, various studies have been dedicated to the mathematical modeling of gas transport and exchange in the lungs. Indeed, the access to the distal region of the lungs with direct measurements is limited and, therefore, models are valuable tools to interpret clinical data and to give more insights into the phenomena taking place in the deepest part of the lungs. In this work, a new computational model of the transport and exchange of a gas species in the human lungs is proposed. It includes (i) a method to generate a lung geometry characterized by an asymmetric branching pattern, based on the values of several parameters that have to be given by the model user, and a method to possibly alter this geometry to mimic lung diseases, (ii) the calculation of the gas flow distribution in this geometry during inspiration or expiration (taking into account the increased resistance to the flow in airways where the flow is non-established), (iii) the evaluation of the exchange fluxes of the gaseous species of interest between the tissues composing the lungs and the lumen, and (iv) the computation of the concentration profile of the exchanged species in the lumen of the tracheobronchial tree. Even if the model is developed in a general framework, a particular attention is given to nitric oxide, as it is not only a gas species of clinical interest, but also a gas species that is both produced in the walls of the airways and consumed within the alveolar region of the lungs. First, the model is presented. Then, several features of the model, applied to lung geometry, gas flow and NO exchange and transport, are discussed, compared to existing works and notably used to give new insights into experimental data available in the literature, regarding diseases, such as asthma, cystic fibrosis, and chronic obstructive pulmonary disease.

Objectives: To estimate the variability of X-ray diagnostic reference levels (DRLs) depending on the number of X-ray devices and data per device. Methods: Dose-area products (DAP) were collected by the national nuclear control agency from the 590 devices installed in 345 medical centers in the country. From 2015 to 2017, the number of chest (postero-anterior (PA) view alone, and both postero-anterior and lateral views (PA/LAT)), abdomen, pelvis, and lumbar spine examinations collected in these centers ranged from 23,000 to 77,000. The impact of the number of devices and DAP data per device on DRLs’ variabilities (95th confidence intervals divided by medians) is estimated using a bootstrapping method as a function of the number of devices and DAP per device. Results: The DRLs’ variabilities ranged from 30 to 200% depending on the number of devices and DAP data per device but stabilized at 30% when the number of devices was higher than 200 for chest PA and abdomen examinations, 300 for lumbar spine and pelvis examinations, and 400 for chest PA/LAT examinations, regardless of the number of DAP data per device. Extrapolations of our results suggest that thousands of devices are necessary to reduce DRLs’ variabilities to 10%. Conclusion: DAP-related DRL variabilities are high but only moderately influenced by the number of DAP data per device and of devices provided this number is higher than 200 to 400 devices according to the type of examination. Harmonization of methods of data collection between the authorities of the EU states should be recommended. Key Points: • DAP-related DRLs are not fixed values but ranges of values with at least 30% variability. • DAP-related DRLs strongly depend on the number of devices included when lower than 100. • If the number of devices included exceeds 200 to 400, the DRLs’ variabilities do not depend on the number of DAP per device and should not exceed 30%., SCOPUS: ar.j, info:eu-repo/semantics/published

To prospectively compare the prevalence and frequency of subchondral bone marrow edema (BME) in the lumbar facet joints of low back pain patients and healthy subjects. Lumbar magnetic resonance imaging (MRI) examinations were performed on 55 asymptomatic participants (18 men; age range 21–63; mean 36 ± 12 years; body mass index (BMI) range 16–31; mean 22.6 ± 3.2 kg/m2) and 79 low back pain patients (36 men; age range 18–77; mean 47 ± 14 years; BMI range 18–40; mean 27.8 ± 4.4 kg/m2). In both groups, facet joint subchondral BME signal was evaluated using T2-weighted STIR imaging, and facet joint osteoarthritis was characterized as mild, moderate, and severe. The BME signal was found in seven asymptomatic participants (12.7%) and 28 low back pain patients (35.4%) (P = 0.003). A significant portion of the patients (15.2%) presented more than one BME signal (P = 0.011). By pooling the ten facet joints of all subjects in each group, a significant difference in osteoarthritis grade distribution was observed between the two groups (P

Background: Propylene glycol and glycerol are e-cigarette constituents that facilitate liquid vaporization and nicotine transport. As these small hydrophilic molecules quickly cross the lung epithelium, we hypothesized that short-term cessation of vaping in regular users would completely clear aerosol deposit from the lungs and reverse vaping-induced cardio-respiratory toxicity. Aims: To assess the acute effects of vaping and their reversibility on biological/clinical cardio-respiratory parameters (serum/urine pneumoproteins, hemodynamic parameters, lung-function test and diffusing capacities, transcutaneous gas tensions (primary outcome) and skin microcirculatory blood flow). Methods: Regular e-cigarette users were enrolled in this randomized, investigator-blinded, three-period crossover-study. The periods consisted of nicotine-vaping (nicotine-session), nicotine-free vaping (nicotine-free-session), and complete cessation of vaping (stop-session), all maintained for five days before the session began. Multiparametric metabolomic analyses were used to verify subjects' protocol compliance. Biological/clinical cardio-respiratory parameters were assessed at the beginning of each session (baseline) and after acute vaping exposure. Results: Compared to the nicotine- and nicotine-free-sessions, a specific metabolomic signature characterized the stop-session. Baseline serum club-cell protein-16 was higher during the stop-session than the other sessions ( p, info:eu-repo/semantics/published

Rationale and Objectives Computed tomography (CT) airways measurements can be used as surrogates to spirometric measurements for assessing bronchodilation in a particular patient with chronic obstructive pulmonary disease. Although spirometric measurements show variations within the opening hours of a hospital department, we aimed to compare the variability of CT airways measurements between morning and afternoon in patients with chronic obstructive pulmonary disease to that of spirometric measurements. Materials and Methods Twenty patients had pulmonary function tests and CT around 8 am and 4 pm . Luminal area (LA) and wall thickness (WT) of third and fourth generation airways were measured twice by three readers. The percentage of airway area occupied by the wall (WA%) and the square root of wall area at an internal perimeter of 10 mm (√WAPi10) were calculated. The effects of examination time, reader, and measurement session on CT airways measurements were assessed, and the variability of these measurements was compared to that of spirometric measurements. Results Variability of LA3rd and LA4th was greater than that of spirometric measurements (P values ranging from .999). There was no effect of measurement session on any CT airway measurement (P values ranging from .535 to >.999). Conclusion As the variability of LA3rd and LA4th is greater than that of spirometric measurements, clinical studies should include cohorts with larger numbers of patients when considering LA than when considering spirometric measurements as end points.

The purpose of this study is to investigate the magnitude of differences between attenuation values measured on virtual unenhanced images and true unenhanced images obtained using third-generation dual-source dual-energy CT (DECT).A total of 83 patients requiring thoracoabdominal CT for cancer workup were included in this prospective study. CT examinations included true unenhanced acquisitions (tube potential, 120 kVp) and arterial and portal phase dual-energy CT (DECT) acquisitions (tube potential, 100 kVp and Sn 150 kVp [where Sn denotes the interposition of a tin filter in the high-energy beam]; tube current-exposure time product, 190 and 95 mAs). Virtual unenhanced images were created using two commercially available DECT postprocessing algorithms, one of which was designed to create liver images (hereafter referred to as VNC1 images) and the other of which was designed to create images of organs containing minor amounts of fat (hereafter referred to as VNC2 images). Attenuation values on the liver, spleen, paraspinal muscles, retroperitoneal fat, renal cortex and medulla, and gallbladder and bladder lumens were measured.The attenuation values of all tissues were significantly different between virtual unenhanced and true unenhanced images (p =0.001-0.042), except for the liver and spleen in the portal phase and muscles in both phases. When statistically significant, correlations between these differences and body mass index (weight in kilograms divided by the square of height in meters) depended on the tissue imaged and algorithm used. The percentage of cases in which these differences were 10 HU or greater was 1% for the liver and approximately 5% for the spleen and muscles, regardless of the algorithm and phase, but on VNC1 images it reached approximately 30% for the kidney, 70% for the gallbladder and bladder, and depending on the phase, 40-70% for fat. On VNC2 images, the percentage of cases in which these differences were 20 HU or greater was approximately 90% for fat.Abdominal virtual unenhanced images obtained with third-generation dual-source DECT still should not replace true unenhanced images because of substantial differences in attenuation measurements for fluid, fat, and renal tissues.

To test the hypothesis that referral guidelines are not sufficiently known by prescribers and that medico-legal concerns could influence the prescription of radiographs in minor chest trauma. We submitted a questionnaire including a typical clinical history and questions on reasons for prescribing radiographs of the ribs in minor chest trauma to 112 prescriptors (33 residents, 18 surgeons, 7 internists, 24 general practitioners and 30 ER physicians). All accepted to participate. Comparisons were performed by Fisher's exact test followed by a post-hoc analysis and by a McNemar test. Fifty-eight percent of prescriptors proposed rib radiographs, most (89%) being unaware of the guidelines. Only 11% of them changed their intention to order radiographs after information on referral guidelines and radiation dose (P=0.057). The mean dose delivered by rib radiographs was 38 times higher than that of a chest X-ray. Legal and medico-legal concerns (requirements from insurance policies and avoidance of lawsuits) were the main reasons for requesting radiographs. Unsharpness of guidelines in addition to social and medico-legal issues, rather than medical reasons or the lack of knowledge of the guidelines, strongly influence the prescription of radiographs of the ribs in minor chest trauma. • Most prescriptors order radiographs of the ribs in minor chest trauma. • Only few prescriptors are aware of referral guidelines. • Information on guidelines does not change their need for radiographs. • Motivations for ordering radiographs are rather legal than medical, but poor compliance to guidelines could also be explained by their unsharpness. • Radiation dose of rib radiographs was 38 times that of a PA chest radiograph.

Background: Exhaled nitric oxide (FENO) is a rather reliable marker of asthma control. Its ability is influenced by airway caliber variation (Michils et al. 2017) and should also be impacted by the type of airway inflammation (i.e. type 2- high vs low). Aim: To assess FENO as a marker of control in patients suffering from type 2-high vs type 2-low asthma, defined by FENO level, taking lung function into account. Methods: At each visit at the outpatient clinic, FEV1, asthma control questionnaire score (ACQ) and FENO were assessed. From patients with at least 4 visits, low (L-NO, 29 patients) and high (H-NO, 21 patients) FENO groups were constituted as having a mean FENO 60ppb. Between consecutive visits (pairs), an improvement or a worsening of control were defined as ΔACQ 0.5. An index β was 0 or 1 if ΔFEV1*ΔFENO =0 (same directions). Ability of FENO to reflect control change was assessed by the area under ROC curve (AUC [95% CI]). Results: AUC significantly differed from 0.5 in H-NO for improvement (0.63 [0.55-0.72]) and worsening (0.60 [0.52-0.70]) and never in L-NO. Considering only pairs with β=0 improved AUC in H-NO for improvement (0.78 [0.67-0.87]) and for worsening (0.81 [0.70-0.91]) and not in L-NO. Discussion: In type 2-low asthma patients, FENO never reflects asthma control. In contrast, FENO predicts control changes in type 2-high asthma patients and its ability is significantly improved when FENO and FEV1 change in opposite directions. Conclusion: FENO utility in asthma management appears maximal in a subgroup of type 2-high asthma patients easily identified by lung function in clinical practice.

Introduction: Conditioning of air during respiration occurs in the upper airways, but also in the bronchi (McFadden et al., 1985). Because it is related to the evaporation of the water contained in the mucus (Karamaoun et al., 2018), it could affect its dynamics, but also the body water and thermal balance.Aim and objectives: To assess theoretically the influence of the bronchial evaporation on the mucus dynamics and on the body water and thermal balance. Then, to issue recommendations for the management of airway pathologies. Methods: A theoretical model, previously developed (Karamaoun et al., 2018), is used with parameterssimulating resting and exercise respiration in room conditions. Heat and water losses are computed forevery bronchial generation. Results:At rest:power loss is 5 W and water loss is 150 mL/day. Air saturation occurs in generation 10; peak of heat dissipation in generation 4.Exercise: power loss rises to 45 W and water loss is 1.4 L/day. Air saturation occurs in generation 15; peak of heat dissipation in generation 8. Discussion: The magnitude of thermal and hydric losses in the bronchi suggests that evaporation can modify the dynamics of bronchial mucus. This could influence its properties, such as its viscosity, which is critical in several pathologies, as in cystic fibrosis (CF). Body water and thermal balance are likely to be impacted too, especially during exercise. Conclusion: Our results confirm that bronchial evaporation is critical regarding mucus dynamics, and body water and thermal balance. They highlight the importance of inspired air conditions for the management of sensitive subjects, such as CF patients or athletes with exercise-induced asthma.

International audience; Lining the bronchi in the lung, the mucus constitutes a protective layer from harmful pathogens and particles. Its displacement due to the coordinated beating of the bronchial epithelium cilia contributes to its clearance from the lung. As this mucociliary clearance is impaired in numerous pathologies, a comprehensive understanding of this process is critical. A simple mass balance over the mucus layer in an airway suggests that the cilia beating, on its own, is not sufficient enough for controlling the bronchial mucus balance in the entire lung. In this article, we show through a mathematical modeling approach that the evaporation of the water contained in the mucus layer could act as a control mechanism of the mucus balance. Furthermore, we suggest that other control mechanisms act in parallel to evaporation to maintain the mucus balance. Our model and results could be useful in the study and management of several mucus-related airway diseases , such as cystic fibrosis or exercise-induced asthma.

When heated by an electronic cigarette, propylene glycol and glycerol produce a nicotine-carrying-aerosol. This hygroscopic/hyperosmolar aerosol can deposit deep within the lung. Whether these deposits trigger local inflammation and disturb pulmonary gas exchanges is not known. The aim of this study was to assess the acute effects of high-wattage electronic cigarette vaping with or without nicotine on lung inflammation biomarkers, transcutaneous gas tensions, and pulmonary function tests in young and healthy tobacco smokers. Acute effects of vaping without nicotine on arterial blood gas tensions were also assessed in heavy smokers suspected of coronary artery disease. Using a single-blind within-subjects study design, 25 young tobacco smokers underwent three experimental sessions in random order: sham-vaping and vaping with and without nicotine at 60 W. Twenty heavy smokers were also exposed to sham-vaping (n = 10) or vaping without nicotine (n = 10) in an open-label, randomized parallel study. In the young tobacco smokers, compared with sham-vaping: 1) serum club cell protein-16 increased after vaping without nicotine (mean ± SE, -0.5 ± 0.2 vs. +1.1 ± 0.3 µg/l, P = 0.013) and vaping with nicotine (+1.2 ± 0.3 µg/l, P = 0.009); 2) transcutaneous oxygen tension decreased for 60 min after vaping without nicotine (nadir, -0.3 ± 1 vs. -15.3 ± 2.3 mmHg, P < 0.001) and for 80-min after vaping with nicotine (nadir, -19.6 ± 2.8 mmHg, P < 0.001). Compared with sham vaping, vaping without nicotine decreased arterial oxygen tension for 5 min in heavy-smoking patients (+5.4 ± 3.3 vs. -5.4 ± 1.9 mmHg, P = 0.012). Acute vaping of propylene glycol/glycerol aerosol at high wattage with or without nicotine induces airway epithelial injury and sustained decrement in transcutaneous oxygen tension in young tobacco smokers. Intense vaping conditions also transiently impair arterial oxygen tension in heavy smokers., SCOPUS: ar.j, info:eu-repo/semantics/published

To determine variability of volume computed tomographic dose index (CTDIvol) and dose–length product (DLP) data, and propose a minimum sample size to achieve an expected precision. CTDIvol and DLP values of 19,875 consecutive CT acquisitions of abdomen (7268), thorax (3805), lumbar spine (3161), cervical spine (1515) and head (4106) were collected in two centers. Their variabilities were investigated according to sample size (10 to 1000 acquisitions) and patient body weight categories (no weight selection, 67–73 kg and 60–80 kg). The 95 % confidence interval in percentage of their median (CI95/med) value was calculated for increasing sample sizes. We deduced the sample size that set a 95 % CI lower than 10 % of the median (CI95/med ≤ 10 %). Sample size ensuring CI95/med ≤ 10 %, ranged from 15 to 900 depending on the body region and the dose descriptor considered. In sample sizes recommended by regulatory authorities (i.e., from 10–20 patients), mean CTDIvol and DLP of one sample ranged from 0.50 to 2.00 times its actual value extracted from 2000 samples. The sampling error in CTDIvol and DLP means is high in dose surveys based on small samples of patients. Sample size should be increased at least tenfold to decrease this variability. • Variability of dose descriptors is high regardless of the body region. • Variability of dose descriptors depends on weight selection and the region scanned. • Larger samples would reduce sampling errors of radiation dose data in surveys. • Totally or partially disabling AEC reduces dose variability and increases patient dose. • Median values of dose descriptors depend on the body weight selection.

PURPOSE The aim of the study was to compare radiation dose and image quality between the "average" and the "very strong" automatic exposure control (AEC) strength curves. MATERIALS AND METHODS Images reconstructed with filtered back-projection techniques and radiation dose data of unenhanced helical chest computed tomography (CT) examinations obtained at 2 hospitals (hospital A, hospital B) using the same scanner devices and acquisition protocols but different AEC strength curves were evaluated over a 3-month period. The selected AEC strength curve applied to "slim" patients (diameter

The relationship between cognitive function and breath-holding time is in need of further investigation. We aim to determine whether cognitive mobile games (CMG) are sensitive enough to assess the link between cognition and breath-holding time in non-trained subjects. Thirty-one healthy subjects participated in this study. A set of 3 short CMG: Must Sort (response control), Rush Back (attention, working memory) and True Color (mental flexibility, inhibition) was used. Apneic time was recorded in three different conditions: Total Lung Capacity (TLC): 88 ± 35 s, Functional Residual Capacity (FRC): 49 ± 17 s, and Residual Volume (RV): 32 ± 14 s. In males, breath-holding time at RV was correlated with True Color (r = 0.48) and Rush Back (r = 0.65) and at TLC with True Color (r = 0.45). In women, breath-holding time at TLC and FRC was inversely correlated with Must Sort (r = -0.59 and r = -0.49 respectively). Males and females appeared to differ in their use of cognitive resources during different breath-holding conditions., info:eu-repo/semantics/published

Background: Few data are available on the long-term effect of pulmonary rehabilitation (PR) and on long PR programs in interstitial lung diseases (ILD). We aimed to evaluate the effects of PR on exercise capacity (6-Minute Walking Distance, 6MWD; Peak Work Rate, Wmax), quality of life (St George's Respiratory Questionnaire, SGRQ), quadriceps force (QF) and objectively measured physical activity in ILD after the 6-month PR-program and after 1 year. Methods: 60 patients (64 ± 11 years; 62% males; 23% with IPF) were randomly assigned to receive a 6 month-PR program or usual medical care. Results: Exercise capacity, quality of life and muscle force increased significantly after the program as compared to control (mean,95%CI[ll to ul]; 6MWD + 72,[36 to 108] m; Wmax 19, [8 to 29]%pred; SGRQ - 12,[- 19 to - 6] points; QF 10, [1 to 18] %pred). The gain was sustained after 1 year (6MWD 73,[28 to 118] m; Wmax 23, [10 to 35]%pred; SGRQ - 11,[- 18 to - 4] points; QF 9.5, [1 to 18] %pred). Physical activity did not change. Conclusions: PR improves exercise tolerance, health status and muscle force in ILD. The benefits are maintained at 1-year follow-up. The intervention did not change physical activity. Trial registration: Clinicaltrials.gov NCT00882817., SCOPUS: ar.j, info:eu-repo/semantics/published

In this work, we aim to analyze and compare the mechanisms controlling the volume of mucus in the bronchial region of the lungs of a healthy human adult, at rest and in usual atmospheric conditions. This analysis is based on a balance equation for the mucus in an airway, completed by a computational tool aiming at characterizing the evaporation, during respiration, of the water contained in the bronchial mucus. An idealized representation of the lungs, based on Weibel's morphometric model, is used. The results indicate that the mechanisms controlling the volume of mucus in an airway depend on the localization of the airway in the bronchial region of the lungs. In the proximal generations, the volume of mucus in an airway is mainly controlled by the evaporation of the water it contains and the replenishment, with water, of the mucus layer by epithelial cells or the submucosal glands. Nevertheless, cilia beating in this part of the bronchial region remains of fundamental importance to transport the mucus and hence to eliminate dust and pathogens trapped in it. On the other hand, in the distal generations of the bronchial region, the volume of mucus in an airway is mainly controlled by the mucociliary transport and by the absorption of liquid by the epithelium. This absorption is a consequence of the mucus displacement by the cilia along generations with an interface between the epithelium and the airway surface layer of decreasing area. The numerical results obtained are in good agreement with previously published experimental data, thus validating our approach. We also briefly discuss how our results can improve the understanding and, possibly, the treatment of pulmonary diseases., SCOPUS: ar.j, info:eu-repo/semantics/published

Although considered as an inflammation marker, exhaled nitric oxide (FENO) was shown to be sensitive to airway caliber changes to such an extent that it might be considered as a marker of them. It is thus important to understand how these changes and their localization mechanically affect the total NO flux penetrating the airway lumen ( JawNO), and hence FENO, independently from any inflammatory status change. In this work, a new model was used. It simulates NO production, consumption, and diffusion inside the airway epithelium, NO excretion from the epithelial wall into the airway lumen and, finally, its axial transport by diffusion and convection in the airway lumen. This model may also consider the possible presence of a fluid layer coating the epithelial wall. Simulations were performed. They show the great sensitivity of JawNO to peripheral airway caliber changes. Moreover, FENO shows distinct behaviors, depending on the location of the caliber change. Considering a bronchodilation, absence of FENO change was associated with dilation of central airways, FENO increase with dilation down to pre-acinar small airways, and FENO decrease with intra-acinar dilation due to the amplification of the back diffusion flux. The presence of a fluid layer was also shown to play a significant role in FENO changes. Altogether, the present work theoretically supports that specific FENO changes in acute situations are linked to specifically located airway caliber changes in the lung periphery. This opens the way for a new role for FENO as a functional marker of peripheral airway caliber change. NEW & NOTEWORTHY Using a new model of nitric oxide production and transport, allowing realistic simulation of airway caliber change, the present work theoretically supports that specific changes of the molar fraction of nitric oxide in the exhaled air, occurring without any change in the inflammatory status, are linked to specifically located airway caliber changes in the lung periphery. This opens the way for a new role for FENO as a functional marker of peripheral airway caliber change.

The objective of our study was to evaluate in vivo urinary calculus characterization with third-generation dual-source dual-energy CT (DECT) at reduced versus standard radiation dose.One hundred fifty-three patients requiring unenhanced CT for suspected or known urolithiasis were prospectively included in our study. They underwent two acquisitions at reduced-dose CT (90 kV and 50 mAsThe radiologist visualized 279 calculi on standard-dose CT and 262 on reduced-dose CT; 17 calculi were missed on reduced-dose CT, all of which were ≤ 3 mm. Among the 262 calculi visualized at both doses, the CT number ratio was obtained with the software for 227 calculi and was not different between the doses (p = 0.093). Among these 262 calculi, 197 were labeled at both doses; 194 of the 197 labeled calculi were labeled with the same color code. Among the 65 remaining calculi, 48 and 61 (all ≤ 5 mm) were not labeled at standard-dose and reduced-dose CT (p = 0.005), respectively. At reduced-dose CT, the mean CTDIWith third-generation dual-source DECT, a larger proportion of calculi ≤ 5 mm are not characterized as UA or non-UA at a reduced dose.

Computed tomography (CT) airways measurements can be used as surrogates to spirometric measurements for assessing bronchodilation in a particular patient with chronic obstructive pulmonary disease. Although spirometric measurements show variations within the opening hours of a hospital department, we aimed to compare the variability of CT airways measurements between morning and afternoon in patients with chronic obstructive pulmonary disease to that of spirometric measurements.Twenty patients had pulmonary function tests and CT around 8 am and 4 pm. Luminal area (LA) and wall thickness (WT) of third and fourth generation airways were measured twice by three readers. The percentage of airway area occupied by the wall (WA%) and the square root of wall area at an internal perimeter of 10 mm (√WAPi10) were calculated. The effects of examination time, reader, and measurement session on CT airways measurements were assessed, and the variability of these measurements was compared to that of spirometric measurements.Variability of LAAs the variability of LA

Abnormal airway reactivity and overproduction of nitric oxide (NO) occurring in small airways have been found in asthma. If the “one airway, one disease” concept is consistent, such dysfunctions should also be detected in the peripheral airways of patients suffering from allergic rhinitis.We investigated whether peripheral airway reactivity and NO overproduction could be documented in distal airways in patients with allergic rhinitis. Exhaled NO fraction (FeNO) and the slope (S) of phase III of the single-breath washout test (SBWT) of helium (He) and sulfur hexafluoride (SF6) were measured in 31 patients with allergic asthma, 23 allergic rhinitis patients and 24 controls, before and after sputum induction. SBWT is sensitive to airway calibre change occurring in the lung periphery.The FeNO decrease was more significant in asthma and rhinitis than in controls (−55.1% and −50.0%, respectively, versus −40.8%) (p=0.007 and p=0.029, respectively). SSF6 and SHe increased in all groups. Change in SHe (ΔSHe) > ΔSSF6 was observed in rhinitis (p=0.004) and asthma (pSF6 = ΔSHe in controls (p=0.431).This study provides evidence of peripheral airway dysfunction in patients with allergic rhinitis quite similar to that described in asthma. Furthermore, a large proportion of the increased NO production reported in allergic rhinitis appears to originate in the peripheral airways.

Changes in airway calibre have the potential to modify exhaled nitric oxide fraction (FENO) values and could hamper how FENO captures changes in asthma control. Here, our objective was to assess whether forced expiratory volume in 1 s (FEV1) variations alter the ability of FENO to reflect asthma control. FENO, asthma control (Asthma Control Questionnaire (ACQ)) and FEV1 were measured at least two times in 527 patients during 1819 pairs of visits. Determinants of FENO–ACQ discordance probability were evaluated through a logistic regression analysis. The effectiveness of FENO at capturing either asthma control worsening or improvement between two visits was then assessed by undertaking a stratified receiver operating characteristic curves analysis. When FEV1 and FENO change in the same direction, the odds of FENO–ACQ being discordant are multiplied by 3 (p, Clinicians must take into account FEV1 changes when using FENO as a marker of asthma control http://ow.ly/XFmp30c4emj

Objective:Testing the hypothesis that CT airway measurements could be influenced by total lung capacity (TLC), gender and height in normal individuals.Methods:In this ethics committee-approved prospective trial, 87 healthy never-smoking volunteers who provided written informed consent were included. From a helical CT scan of the chest, the wall thickness (WT) and the lumen area were twice measured in the third- and fourth-generation airways by three readers using a dedicated software. In addition, the TLC was also measured using CT (TLCCT). The percentage of airway area occupied by the wall (WA%) and the square root of wall area at an internal perimeter of 10 mm (√WAPi10) were calculated. CT airway measurements were compared between genders by using a mixed linear model. The correlations between height, TLCCT and CT airway measurements were tested by using a Pearson correlation analysis. These correlations were arbitrarily considered as significant if there was a significant correlation observed for each ...

Breath tests cover the fraction of nitric oxide in expired gas (FENO), volatile organic compounds (VOCs), variables in exhaled breath condensate (EBC) and other measurements. For EBC and for FENO, official recommendations for standardised procedures are more than 10 years old and there is none for exhaled VOCs and particles. The aim of this document is to provide technical standards and recommendations for sample collection and analytic approaches and to highlight future research priorities in the field. For EBC and FENO, new developments and advances in technology have been evaluated in the current document. This report is not intended to provide clinical guidance on disease diagnosis and management.Clinicians and researchers with expertise in exhaled biomarkers were invited to participate. Published studies regarding methodology of breath tests were selected, discussed and evaluated in a consensus-based manner by the Task Force members.Recommendations for standardisation of sampling, analysing and reporting of data and suggestions for research to cover gaps in the evidence have been created and summarised.Application of breath biomarker measurement in a standardised manner will provide comparable results, thereby facilitating the potential use of these biomarkers in clinical practice.

The increased fraction of exhaled nitric oxide (Feno) values observed in asthmatic patients are thought to reflect increased airway inflammation. However, Feno values can be affected by airway caliber reduction, representing a bias when using Feno values to assess asthma control.We sought to determine the effect of changes in both airway caliber and inflammation on Feno values using the allergen challenge model.FEV1 and Feno values were measured during early airway responses (EARs) and late airway responses after challenge with house dust mite allergens in 15 patients with mild allergic asthma. Helium and sulfur hexafluoride (SF6) phase III expired concentration slopes (SHe and SSF6, respectively) from single-breath washout tests were measured to identify sites of airway constriction.In EARs, FEV1 and Feno value decreases reached 36.8% and 22%, respectively (P.001). ΔSHe was greater than ΔSSF6 (+189.4% vs +82.2%, P = .001). In late airway responses FEV1 and Feno value decreases reached 31.7% and 28.7%, respectively (P.001), with the same ΔSHe and ΔSSF6 pattern (+155.8% vs +76%, P = .001). Eight hours after the EAR, FEV1 was still decreased (P.001), whereas Feno values had returned to baseline. At 24 hours, FEV1 had returned to baseline, with Feno values increased by 38.7% (P = .04).In patients with mild allergic asthma, airway caliber changes modulate changes in Feno values resulting from airway inflammation. Therefore Feno should no longer be considered solely an inflammation biomarker but rather a biomarker that integrates both airway inflammation and lung function changes. Furthermore, early and late phases resulting from allergen exposure were shown to involve similar lung regions.

The fraction of NO in exhaled air (FeNO) is a marker of inflammation in asthma. The aim of the present study was to assess, in a real-world setting, whether only high (⩾50 ppb) FeNO levels predict improvement in asthma control when being treated with inhaled corticosteroids (ICS), as suggested by current guidelines on the clinical use of FeNO.FeNO and asthma control were assessed in a retrospective observational study in 153 non-smoking, steroid-naïve, adult subjects with asthma with a mean age of 40 years both before and after 6 weeks (median follow-up time) of treatment with 500 μg beclomethasone (median).Having at the initial visit intermediate FeNO (⩾25 and50 ppb) and high FeNO (⩾50 ppb), compared to normal FeNO (25 ppb), were associated with a larger proportion of subjects achieving an improvement of Asthma Control Questionnaire (ACQ) score with ⩾1 (78% and 67% vs 43%, p0.05) or both ⩾1 improvement and asthma control at follow-up (31% and 37% vs 4%, p0.05). These associations were consistent in multiple logistic regression models after adjustments for confounders.It is not only high but also intermediate FeNO levels that are associated with a significant improvement in asthma control after starting ICS treatment. This challenges current clinical guidelines stating that only high FeNO levels predict response to ICS treatment.

RATIONALE Besides its role as an inflammatory marker in asthma, fractional exhaled nitric oxide (FENO) provides information on the extent of the airway obstruction process through evaluating its change after bronchodilation. OBJECTIVE To investigate whether FENO change after bronchodilation can identify different sites of airway obstruction in COPD patients. METHODS FENO, FEV1 and the slopes (S) of the alveolar plateau of the single breath washout test (SBWT) were measured in 61 stable COPD patients (FEV1 34.5% predicted) before and after the inhalation of 400 μg salbutamol. SBWT used Helium (He), and sulfur-hexafluoride (SF6). Obstruction relief occurring in pre-acinar and intra-acinar small airways is expected to decrease SHe and SSF6, respectively. Indices changes (Δ) after bronchodilation were expressed as a percentage of pre-bronchodilation values. RESULTS FENO stability (∣ΔFENO∣ ≤ 11%) was observed in 19 patients [-2.7(6.7)%] [mean (SD)] (NO = group); ΔFENO > 11% [+37.4(27.7)%] in 20 patients (NO+ group) and ΔFENO

Background: We showed that FENO remains stable, increases or decreases in asthma patients 209 min after salbutamol (SABA) inhalation depending on the site of bronchoconstriction relief: up to central, pre-acinar and intra-acinar airways respectively (A. Michils JACI-In press). This may impact the use of FENO in asthma management if these effects are prolonged all over the period of SABA action. Aim: To evaluate the FENO changes induced by SABA in asthma patients over 4 hours. Methods: FENO, FEV 1 , and the slope (S) of phase III of He, and SF 6 from a single-breath test were measured in stable asthma patients (n=17)before and up to 4 hours after SABA (400µg). S He and S SF6 decrease reflects pre- and intra-acinar obstruction relief respectively. Results: Patients (4F/13M, age: 51±18 years) were divided in groups with positive (FENO+, n=9) and negative (FENO-, n=8) FENO change at 209 after SABA inhalation, compared to baseline. Discussion: At 209, we confirm a dilation up to pre- and intra acinar airways in the FENO+ and FENO-, respectively. After 4 hrs, FENO still slightly increased for both groups, indicating that SABA use should be stopped 4 hrs prior FENO measurement. The results also suggest that, in the FENO- group, the early dilation of acinar airways fades away in favour of a late dilation of pre-acinar airways indicating a different duration of the proximal and peripheral SABA effects.

Background: We have shown that the change of exhaled nitric oxide (FENO) after bronchodilation allows to identify the site of airway obstruction in asthma: FENO stability, increase, or decrease reflects obstruction relief by bronchodilation up to central, pre-acinar and intra-acinar airways (1). Aim: To investigate whether FENO change after bronchodilation is able to identify different sites of airway obstruction in COPD patients. Methods: FENO, FEV 1 , and the slope (S) of phase III of He, and SF 6 from a single-breath test were measured in 41 stable COPD patients with median(range) FEV1 of 48(20-78)%predicted before and 20 minutes after inhalation of 400 µg salbutamol. S He and S SF6 decrease reflects pre- and intra-acinar obstruction relief respectively. Changes (Δ) were expressed as a percentage of baseline. Results: No FENO change (|ΔFENO|≤10%) was found in 8 patients [-1.7 (7.7)%] [mean (SD)] (FENO=); ΔFENO>10% [+44 (38)%] was found in 18 patients (FENO+) and ΔFENO 1 (p=0.445; [+10 (8)%]). In FENO= and FENO+ groups, neither S He nor S SF6 changed, whereas in FENO- both S He [-25(25)%, p SF6 [-26 (23)%, p Conclusion: Three FENO behaviours were observed in response to β2-agonists in COPD patients: a decrease likely due to relief of an intra-acinar airway obstruction; an increase or a stability associated with a more proximal dilation. These preliminary results suggest that FENO might be useful to assess the sites of obstruction that appear to differ among COPD patients. (1) Michils A et al. J Allergy Clin Immunol (In press).

BACKGROUND: Nitrogen (N2) single breath washout (SBW) and Forced Oscillation Technique (FOT) are sensitive to airway closures and choke points by different physical mechanisms. AIM: to characterize SBW and FOT in healthy and asthmatics pre and post methacholine challenge (Mch) and to compare the information provided by the two approaches. METHODS: Lung function was evaluated in 13 healthy subjects (9F/4M, 46±13years) and 12 stable asthmatics (7F/3M, 37±13years) by SBW and within-breath FOT at 5, 11 and 19Hz. Closing volume (CV N2 ) and the slope of phaseIII (SIII) from SBW were identified by a blinded expert. Resistance (R 5 ), reactance (X 5 ) and frequency dependence of resistance (R 5 -R 19 ) were measured during quiet breathing and during a slow vital capacity maneuver (SVC). CV FOT was defined as the volume corresponding to X 5 =-7 cmH2O*s/l during SVC. Asthmatics were studied also post Mch at 20% fall in FEV 1 . RESULTS: No differences in FOT and SBW parameters were found between healthy and asthmatics pre-Mch. However, all of them changed significantly in asthmatics after Mch, with CV FOT showing the biggest change for all the patients (minimal change=103% vs -3% in CV N2 ; 8% in SIII; 22% in R 5 ; 48% in X 5 and 75% in R 5 -R 19 ). pIII N2 correlates with all FOT parameters while CV N2 showed only a weak correlation with CV FOT (Spearman, p=0.04). CONCLUSION: CV FOT might be useful to assess in a more accurate and sensitive way the response to bronchial challenge.

To prospectively investigate the effect of submaximal inspiration on computed tomographic (CT) indexes used to quantify emphysema and to discriminate between effects of lung tissue loss and increase in total lung capacity (TLC) on these indexes.In this ethical committee-approved study, 20 control subjects and 16 patients with chronic obstructive pulmonary disease (COPD) who provided written informed consent were included. Three 1-mm-thick sections were obtained from each participant at 100%, 90%, 80%, 70%, and 50% of vital capacity (VC). At each volume, eight percentiles of attenuation distribution, as well as relative area (RA) of lung occupied by attenuation coefficients lower than nine thresholds, were calculated. A linear regression line between TLC and each CT index was plotted for control subjects. Mean distance from data points measured in patients with COPD to the normal regression line was used to reflect the effect of lung tissue loss, regardless of TLC.The RA of lung occupied by attenuation coefficients lower than -950 HU (RA(950)) at any percentage of VC lower than 100% decreased significantly from that at 100% VC (P ≤ .002) in control subjects and patients with COPD; however, between 100% VC and 90% VC, the average difference in RA(950) was only 3% and 2% in control subjects and patients with COPD, respectively. The 1st percentile at any percentage of VC lower than 100% increased from that at 100% VC (P.001) in control subjects. This percentile did not significantly differ from 100% VC at 90% VC or 80% VC (P = .176 and P = 0.077, respectively), but it did significantly differ from 100% VC at 70% VC and 50% VC (P ≤ .002 for both) in patients with COPD. Slope and mean distance were different from zero for all RAs and percentiles except for mean distance for RAs between RA(900) and RA(920).Submaximal inspiration induces underestimation of pulmonary emphysema. Both lung tissue loss and TLC influence CT indexes, suggesting the need to establish normal CT values.

Alveolar (CA(NO)) and exhaled nitric oxide (FE(NO)) concentrations, mainly regarded as inflammation surrogates, may also be affected by perfusion redistribution changing alveolar transfer factor (DA(NO)). A model of blood redistribution is hypergravity, Karlsson et al. (2009b) found, at 2G, increases of 22% and 70%, for FE(NO), and CA(NO), respectively. The present study aimed at theoretically estimating the amplitude of DA(NO) changes that mimic these experimental data. An equation describing convection, diffusion and NO sources was solved in a 2-trumpet model (parallel dependent and non-dependent lung units). Acinar airways lumen reduction was also simulated. A reduction of 33% of the overall DA(NO) (-51% in the non-dependent unit) along with a 36% reduction of acinar airways lumen reproduced experimental findings. In conclusion, substantial FE(NO) and CA(NO) increases may be accounted for by a decrease of the alveolo-capillaries contact surface, here hypergravity-induced. Acinar airway constriction may also have a part in the overall FE(NO) increase.