Improvements of the shape and strength of the diaphragm after endoscopic lung volume reduction.

RATIONALE: Endoscopic lung volume reduction improves lung function, quality of life and exercise capacity in severe emphysema patients. However, its effect on the diaphragm function is not well understood. We hypothesised that endoscopic lung volume reduction increases its strength by modifying its shape. OBJECTIVES: To investigate changes in both diaphragm shape and strength induced by the insertion of endobronchial valves. METHODS: In 19 patients, both the diaphragm shape and strength were investigated respectively by 3D Slicer software applied on CT scans acquired at functional residual capacity and by transdiaphragmatic pressure measurements by bilateral magnetic stimulation of the phrenic nerves before and 3 months after unilateral valves insertion. MEASUREMENTS AND MAIN RESULTS: After lung volume reduction (median (IQR), 434 mL (-597 to -156], p<0.0001), diaphragm strength increased (transdiaphragmatic pressure: 3 cmH2O (2.3 to 4.2), p<0.0001). On the treated side, this increase was associated with an increase in the coronal (16 mm (13 to 24), p<0.0001) and sagittal (26 mm (21 to 30), p<0.0001) lengths as well as in the area of the zone of apposition (62 cm2 (3 to 100), p<0.0001) with a decrease in the coronal (8 mm (-12 to -4), p<0.0001) and sagittal (9 mm (-18 to -2), p=0.0029) radii of curvature. CONCLUSIONS: Endoscopic lung volume reduction modifies the diaphragm shape by increasing its length and its zone of apposition and by decreasing its radius of curvature on the treated side, resulting in an increase in its strength. TRIAL REGISTRATION NUMBER: NCT05799352.

Short halt in vaping modifies cardiorespiratory parameters and urine metabolome: a randomized trial.

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 cardiorespiratory toxicity. We aimed to assess the acute effects of vaping and their reversibility on biological/clinical cardiorespiratory parameters [serum/urine pneumoproteins, hemodynamic parameters, lung-function test and diffusing capacities, transcutaneous gas tensions (primary outcome), and skin microcirculatory blood flow]. 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 5 days before the session began. Multiparametric metabolomic analyses were used to verify subjects' protocol compliance. Biological/clinical cardiorespiratory parameters were assessed at the beginning of each session (baseline) and after acute vaping exposure. Compared with 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 < 0.01), and heart rate was higher in the nicotine-session (P < 0.001). Compared with acute sham-vaping in the stop-session, acute nicotine-vaping (nicotine-session) and acute nicotine-free vaping (nicotine-free-session) slightly decreased skin oxygen tension (P < 0.05). In regular e-cigarette-users, short-term vaping cessation seemed to shift baseline urine metabolome and increased serum club cell protein-16 concentration, suggesting a decrease in lung inflammation. Additionally, acute vaping with and without nicotine decreased slightly transcutaneous oxygen tension, likely as a result of lung gas exchanges disturbances.

Variabilities in X-ray diagnostic reference levels.

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%.

Fourth generation e-cigarette vaping induces transient lung inflammation and gas exchange disturbances: results from two randomized clinical trials.

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.

CT diagnostic reference levels: are they appropriately computed?

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.

X-ray examination dose surveys: how accurate are my results?

OBJECTIVES: To determine the variabilities of dose-area-products (DAP) of frequent X-ray examinations collected for comparison with diagnostic reference levels (DRLs). METHODS: 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). RESULTS: 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. CONCLUSION: 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. KEY POINTS: • 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.

Small airways dysfunction: the link between allergic rhinitis and allergic asthma.

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 (p<0.001), whereas ΔSSF6 = 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.

Short and long-term effects of pulmonary rehabilitation in interstitial lung diseases: a randomised controlled trial.

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 .

Radiation protection: Factors influencing compliance to referral guidelines in minor chest trauma.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. KEY POINTS: • 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.

Airway calibre variation is a major determinant of exhaled nitric oxide's ability to capture asthma control.

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<0.001). The area under the curve values were 0.765 (95% CI 0.713-0.805) (improvement; p<0.001) and 0.769 (95% 0.706-0.810) (worsening; p<0.001) or 0.590 (95% 0.531-0.653) (improvement; p=0.001) and 0.498 (95% 0.416-0.567) (worsening; p=0.482) when FEV1 and FENO changed in the opposite or same direction, respectively.The manner in which FENO and FEV1 vary concomitantly when asthma control changes determines the ability of FENO to capture this change: parallel or opposite changes in FEV1 and FENO either decrease or increase this ability to capture asthma control changes.

A European Respiratory Society technical standard: exhaled biomarkers in lung disease.

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.

CT dose survey in adults: what sample size for what precision?

OBJECTIVES: 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. METHODS: 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 %). RESULTS: 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. CONCLUSIONS: 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. KEY POINTS: • 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.

Different patterns of exhaled nitric oxide response to ß2-agonists in asthmatic patients according to the site of bronchodilation.

BACKGROUND: In asthmatic patients undergoing airway challenge, fraction of exhaled nitric oxide (FENO) levels decrease after bronchoconstriction. In contrast, model simulations have predicted both decreased and increased FENO levels after bronchodilation, depending on the site of airway obstruction relief. OBJECTIVE: We sought to investigate whether ß2-agonists might induce divergent effects on FENO values in asthmatic patients as a result of airway obstruction relief occurring at different lung depths. METHODS: FENO, FEV1, and the slope of phase III of the single-breath washout test (S) of He (S(He)) and sulfur hexafluoride (S(SF6)) were measured in 68 asthmatic patients before and after salbutamol inhalation. S(He) and S(SF6) decreases reflected preacinar and intra-acinar obstruction relief, respectively. Changes (Δ) were expressed as a percentage from the baseline. RESULTS: No FENO change (|ΔFENO| ≤ 10%) was found in 16 patients (mean [SD]: 2.5% [5.2%]; ie, FENO= group); a ΔFENO value of greater than 10% was found in 23 patients (31.7% [20.3%]; ie, the FENO+ group); and a ΔFENO value of less than -10% was found in 29 patients (-31.5% [17.3%]; ie, the FENO- group). All groups had similar ΔFEV1 values. In the FENO= group neither S(He) nor S(SF6) changed, in the FENO+ group only S(He) decreased significantly (-21.8% [SD 28.5%], P = .03), and in the FENO- group both S(He) (-29.8% [24.0%], P < .001) and S(SF6) (-27.2% [23.3%], P < .001) decreased. DISCUSSION: Three FENO behaviors were observed in response to ß2-agonists: a decrease likely caused by relief of an intra-acinar airway obstruction that we propose reflects amplification of nitric oxide back-diffusion, an increase likely associated with a predominant dilation up to the preacinar airways, and FENO stability when obstruction relief involved predominantly the central airways. In combination, these results suggest a new role for FENO in identifying the site of airway obstruction in asthmatic patients.

Transfer factor, lung volumes, resistance and ventilation distribution in healthy adults.

Monitoring of chronic lung disease requires reference values of lung function indices, including putative markers of small airway function, spanning a wide age range.We measured spirometry, transfer factor of the lung for carbon monoxide (TLCO), static lung volume, resistance and ventilation distribution in a healthy population, studying at least 20 subjects per sex and per decade between the ages of 20 and 80 years.With respect to the Global Lung Function Initiative reference data, our subjects had average z-scores for forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC of -0.12, 0.04 and -0.32, respectively. Reference equations were obtained which could account for a potential dependence of index variability on age and height. This was done for (but not limited to) indices that are pertinent to asthma and chronic obstructive pulmonary disease studies: forced expired volume in 6 s, forced expiratory flow, TLCO, specific airway conductance, residual volume (RV)/total lung capacity (TLC), and ventilation heterogeneity in acinar and conductive lung zones.Deterioration in acinar ventilation heterogeneity and lung clearance index with age were more marked beyond 60 years, and conductive ventilation heterogeneity showed the greatest increase in variability with age. The most clinically relevant deviation from published reference values concerned RV/TLC values, which were considerably smaller than American Thoracic Society/European Respiratory Society-endorsed reference values.

Chronic Obstructive Pulmonary Disease: CT Quantification of Airway Dimensions, Numbers of Airways to Measure, and Effect of Bronchodilation.

PURPOSE: To determine the effect of bronchodilation on airway indexes reflecting airway disease in patients with chronic obstructive pulmonary disease (COPD) and to determine the minimum number of segmental and subsegmental airways required. MATERIALS AND METHODS: This study was approved by the local ethical committee, and written informed consent was obtained from all subjects. Twenty patients with COPD who had undergone pre- and postbronchodilator pulmonary function tests and computed tomographic (CT) examinations were prospectively included. Eight healthy volunteers underwent two CT examinations. Luminal area and wall thickness (WT) of third- and fourth-generation airways were measured twice by three readers. The percentage of total airway area occupied by the wall and the square root of wall area at an internal perimeter of 10 mm (√WAPi10) were calculated. The effects of pathologic status, session, reader, bronchodilation, and CT examination were assessed by using mixed linear model analyses. The number of airways to measure for a definite percentage error of √WAPi10 was computed by using a bootstrap method. RESULTS: There were no significant session, reader, or bronchodilation effects on WT in third-generation airways and √WAPi10 in patients with COPD (P values ranging from .187 to >.999). WT in third-generation airways and √WAPi10 were significantly different in patients with COPD and control subjects (P = .018 and <.001, respectively). Measuring 12 third- or fourth-generation airways ensured a maximal 10% error of √WAPi10. CONCLUSION: WT in third-generation airways and √WAPi10 are not significantly different before and after bronchodilation and are different in patients with COPD and control subjects. Twelve is the minimum number of third- or fourth-generation airways required to ensure a maximal 10% error of √WAPi10. (©) RSNA, 2015 Clinical trial registration no. NCT01142531 Online supplemental material is available for this article.

Exhaled nitric oxide: a biomarker integrating both lung function and airway inflammation changes.

BACKGROUND: 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. OBJECTIVE: We sought to determine the effect of changes in both airway caliber and inflammation on Feno values using the allergen challenge model. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

FeNO as a predictor of asthma control improvement after starting inhaled steroid treatment.

INTRODUCTION: 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. METHODS: 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). RESULTS: Having at the initial visit intermediate FeNO (⩾25 and <50 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%, p<0.05) or both ⩾1 improvement and asthma control at follow-up (31% and 37% vs 4%, p<0.05). These associations were consistent in multiple logistic regression models after adjustments for confounders. CONCLUSIONS: 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.

CT-Based Evaluation of the Shape of the Diaphragm Using 3D Slicer.

The diaphragm is the main inspiratory muscle and separates the thorax and the abdomen. In COPD, the evaluation of the diaphragm shape is clinically important, especially in the case of hyperinflation. However, delineating the diaphragm remains a challenge as it cannot be seen entirely on CT scans. Therefore, the lungs, ribs, sternum, and lumbar vertebrae are used as surrogate landmarks to delineate the diaphragm. We herein describe a CT-based method for evaluating the shape of the diaphragm using 3D Slicer-a free software that allows delineation of the diaphragm landmarks-in ten COPD patients. Using the segmentation performed with 3D Slicer, the diaphragm shape was reconstructed with open-source Free Pascal Compiler. From this graduated model, the length of the muscle fibers, the radius of curvature, and the area of the diaphragm-the main determinants of its function-can be measured. Inter- and intra-user variabilities were evaluated with Bland and Altman plots and linear mixed models. Except for the coronal length (p = 0.049), there were not statistically significant inter- or intra-user differences (p values ranging from 0.326 to 0.910) suggesting that this method is reproducible and repeatable. In conclusion, 3D Slicer can be applied to CT scans for determining the shape of the diaphragm in COPD patients.