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Introduction When performing computerized tomography chest imaging in children, obtaining high quality, motion-free images is important in the accurate diagnosis of underlying pathology. General anesthesia is associated with the development of atelectasis, which can impair accurate diagnosis by obscuring or altering the appearance of the lung parenchyma or airways. Recruitment maneuvers, performed by anesthesiologists, can be used to effectively re-expand atelectatic lung. Methods The computerized tomography chest imaging in 44 children aged between 2 months and 7 years, undergoing serial imaging for monitoring of cystic fibrosis, were reviewed and graded for atelectasis. The first scan performed on each child was performed with a supraglottic airway device and a non-standardized recruitment maneuver. The second scan on each child was performed with a cuffed endotracheal tube and a standardized recruitment maneuver. Results When a supraglottic airway device and a non-standardized recruitment maneuver were used, 77% of patients demonstrated atelectasis of any degree on their computerized tomography chest imaging, compared with only 39% when a cuffed endotracheal tube and standardized recruitment maneuver were used. The percentage of computerized tomography chest scans that were scored acceptable (with either a total combined lung atelectasis score of 0 or 1) improved from 37% to 75% when a cuffed endotracheal tube and standardized recruitment maneuver where used. In particular, the mean atelectasis score for both lungs improved from 2.91 (SD ± 2.6) to 1.11 (SD ± 1.9), with a mean difference of 1.8 (95% CI 0.82-2.77) (p 0.0004). Conclusion The use of a cuffed endotracheal tube and a standardized recruitment maneuver is an effective way to reduce atelectasis as a result of general anesthesia. Anesthesiologists can actively contribute towards improved image quality through their choice of airway and recruitment maneuver.

New findings What is the central question of this study? Does endogenous testosterone modulate the consequences of IH in the lungs of male mice ? What is the main finding and its importance? Orchiectomized mice exposed to IH develop a pattern that is similar to emphysema or obstructive lung disease with elevated lung volumes, low pulmonary elastance during a methacholine challenge test and high counts of lymphocytes in bronchoalveolar lavages. Since low testosterone levels and other respiratory diseases are common in sleep apnea there is a clear clinical relevance to these results. Abstract We tested the hypothesis that low testosterone levels modulate the pulmonary responses to intermittent hypoxia (IH - used as a model of sleep apnoea) in male mice. We used intact (SHAM) or orchiectomised (ORX) mice exposed to IH for 14 days (12h/day, 10cycles/h, 6% oxygen) or to normoxia (Nx). We first measured ventilation and metabolic rates in freely behaving mice (whole body plethysmography) and then respiratory mechanics in tracheotomised mice (flexiVent). We assessed the respiratory system resistance (Rrs) and elastance (Ers), Newtonian resistance (Rn: resistance of the large airways), tissue damping (G) and tissue elastance (H) under baseline conditions and during a methacholine challenge test. We also measured the quasi-static compliance (Cst) and inspiratory capacity with partial pressure-volume loops. Finally, inflammatory cells were counted in the broncho-alveolar lavage (BAL) and we measured lung volume by water displacement. ORX-IH mice had higher tidal volume, inspiratory capacity, and lung volume compared to the other groups, but showed signs of low efficiency of O2 exchange rate relative to minute ventilation. During the methacholine challenge, orchiectomy decreased the values of most mechanical parameters and IH reduced Ers and H leading to very low values in ORX-IH mice. Finally, the total number of cells and the number of lymphocytes in BAL were both increased by IH in ORX mice. Since reduced lung elasticity, low O2 extraction, increased lung volumes, and inflammation are signs of emphysematous lung disease, we conclude that testosterone might prevent lung emphysema during IH exposures. This article is protected by copyright. All rights reserved.

NEW FINDINGS: What is the central question of this study? Are chronotropic responses to a 6-minute walk test different in women with post-acute coronavirus disease 2019 (COVID-19) syndrome compared with control subjects? What is the main finding and its importance? Compared with control subjects, the increase in heart rate was attenuated and recovery delayed after a 6-minute walk test in participants after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Women reporting specific symptoms at time of testing had greater impairments compared with control subjects and SARS-CoV-2 participants not actively experiencing these symptoms. Such alterations have potential to constrain not only exercise tolerance but also participation in free-living physical activity in women during post-acute recovery from COVID-19. ABSTRACT: The short-term cardiopulmonary manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are well defined. However, the implications of cardiopulmonary sequelae, persisting beyond acute illness, on physical function are largely unknown. Herein, we characterized heart rate responses to and recovery from a 6-minute walk test (6MWT) in women ∼3 months after mild-to-moderate SARS-CoV-2 infection compared with non-infected control subjects. Forty-five women (n = 29 SARS-CoV-2; n = 16 controls; age = 56 ± 11 years; body mass index = 25.8 ± 6.0 kg/m2 ) completed pulmonary function testing and a 6MWT. The SARS-CoV-2 participants demonstrated reduced total lung capacity (84 ± 8 vs. 93 ± 13%; P = 0.006), vital capacity (87 ± 10 vs. 93 ± 10%; P = 0.040), functional residual capacity (75 ± 16 vs. 88 ± 16%; P = 0.006) and residual volume (76 ± 18 vs. 93 ± 22%; P = 0.001) compared with control subjects. No between-group differences were observed in 6MWT distance (P = 0.194); however, the increase in heart rate with exertion was attenuated among SARS-CoV-2 participants compared with control subjects (+52 ± 20 vs. +65 ± 18 beats/min; P = 0.029). The decrease in heart rate was also delayed for minutes 1-5 of recovery among SARS-CoV-2 participants (all P

Objectives The full range of long‐term health consequences in intensive care unit (ICU) survivors with COVID‐19 is unclear. This study aims to investigate the role of ventilatory support for long‐term pulmonary impairment in critically ill patients and further to identify risk factors for prolonged radiological recovery. Methods A prospective observational study from a single general hospital, including all with COVID‐19 admitted to ICU between March and August 2020, investigating the association between ventilatory support and the extent of residual parenchymal changes on chest computed tomography (CT) scan and measurement of lung volumes at follow‐up comparing high‐flow nasal oxygen (HFNO) or non‐invasive ventilation (NIV) with invasive ventilation. A semi‐quantitative score (CT involvement score) based on lobar involvement and a total score for all five lobes was used to estimate residual parenchymal changes. The association was calculated with logistic regression and adjusted for age, sex, smoking, and severity of illness. Results Among the 187 eligible, 86 had a chest CT scan and 76 a pulmonary function test at the follow‐up with a median time of 6 months after ICU discharge. Residual lung changes were seen in 74%. The extent of pulmonary changes was similar regardless of ventilatory support, but patients with invasive ventilation had a lower total lung capacity 84% versus 92% of predicted (p

Introduction/aims In this study, researchers evaluated the effects of lung volume recruitment treatment (LVR) - a low-tech, low-cost, manual 'breath stacking' technique used to help people cough with enough force to clear their airways, thereby reducing the risk of aspiration and choking - on five volitional airway clearance and protection behaviors used by people living with amyotrophic lateral sclerosis (PwALS). Methods Using a repeated-measures cross-over design, 29 PwALS performed five volitional airway clearance and protection behaviors in LVR treatment and in no-treatment, control conditions. Peak cough flow (PCF) was used to measure maximum expiratory rate during forced expiration, throat clearing, hawking, post-swallow coughing and the supraglottic swallowing maneuver. Comparisons were made as a function of condition (treatment or control) and three time-points (pre-treatment, and 15- and 30-minutes post-treatment). Results LVR treatment had a significant positive effect on maximum expiratory rates during all tested airway clearance and protection behaviors. Increased PCF values lasted for up to 30 minutes post-LVR for all tested behaviors in the treatment condition. Discussion Findings demonstrate that LVR treatment can increase control over airway clearance in PwALS, as well as provide improved airway protection for up to 30 minutes, the duration of a typical meal. This study has implications for patient care. These include offering patients control over some of the most feared symptoms of ALS, particularly choking during activities of daily living, and enhanced ALS respiratory care in low-resource settings. Findings may have implications for other neurodegenerative disorders in which dysphagia occurs with retained sensory function. This article is protected by copyright. All rights reserved.

BACKGROUND Persistent tachypnea of infancy (PTI) is the most common interstitial lung disease in young children. As no standardized therapeutic guidelines exist, different pharmaceuticals are used to treat PTI; inhaled corticosteroids (ICS) and bronchodilators being mostly used. This observation assessed the effectiveness of bronchodilators and ICS in children with PTI enrolled in the children's interstitial lung diseases (chILD)-EU Register. METHODS Symptomatic children with PTI were observed according to a predetermined stepwise protocol including bronchodilators as the first choice treatment (6 weeks). In patients with incomplete response, additionally, ICS was given (12 weeks). Signs, symptoms, and pulmonary function were evaluated at three time points: at baseline, 6 (±1) weeks after initiation of bronchodilators, and 12 (±1) weeks after bronchodilators/ICS. RESULTS Thirty-one children (median age: 44 months, interquartile range [IQR]: 15-67) were included. The therapy was associated with a significant reduction of tachypnea (53.3% of patients, p = 0.02), exercise intolerance (52.2% of patients, p

Key points Multibreath imaging to estimate regional gas mixing efficiency is superior to intensity-based single-breath ventilation markers, as it is capable of revealing minute but essential measures of ventilation heterogeneity which may be sensitive to subclinical alterations in the early stages of both obstructive and restrictive respiratory disorders. Large-scale convective stratification of ventilation in central-to-peripheral directions is the dominant feature of observed ventilation heterogeneity when imaging a heavy/less diffusive xenon gas mixture; smaller-scale patchiness, probably originating from asymmetric lung function at bronchial airway branching due to the interaction of convective and diffusive flows, is the dominant feature when imaging a lighter/more diffusive helium gas mixture. Since detecting low regional ventilation is crucial for characterizing diseased lungs, our results suggest that dilution with natural abundance helium and imaging at higher lung volumes seem advisable when imaging with hyperpolarized 129 Xe; this will allow the imaging gas to reach slow-filling and/or non-dependent lung regions, which might otherwise be impossible to distinguish from total ventilation shunt regions. The ability to differentiate these regions from those of total shunt is worse with typical single-breath imaging techniques. Abstract The mixing of freshly inhaled gas with gas already present in the lung can be directly assessed with heretofore unachievable precision via magnetic resonance imaging of signal build-up resulting from multiple wash-ins of a hyperpolarized (HP) gas. Here, we used normoxic HP 3 He and 129 Xe mixtures to study regional ventilation at different spatial scales in five healthy mechanically ventilated supine rabbits at two different inspired volumes. To decouple the respective effects of density and diffusion rates on ventilation heterogeneity, two additional studies were performed: one in which 3 He was diluted with an equal fraction of natural abundance xenon, and one in which 129 Xe was diluted with an equal fraction of 4 He. We observed systematic differences in the spatial scale of specific ventilation heterogeneity between HP 3 He and 129 Xe. We found that large-scale, central-to-peripheral convective ventilation inhomogeneity is the dominant cause of observed heterogeneity when breathing a normoxic xenon gas mixture. In contrast, small-scale ventilation heterogeneity in the form of patchiness, probably originating from asymmetric lung function at bronchial airway branching due to interactions between convective and diffusive flows, is the dominant feature when breathing a normoxic helium gas mixture, for which the critical zone occurs more proximally and at an imageable spatial scale. We also showed that the existence of particular underventilated non-dependent lung regions when breathing a heavy gas mixture is the result of the density of that mixture - rather than, for example, its diffusion rate or viscosity. Finally, we showed that gravity-dependent ventilation heterogeneity becomes substantially more uniform at higher inspired volumes for xenon gas mixtures compared to helium mixtures.

The morphology of the rib cage affects both the biomechanics of the upper body's musculoskeletal structure and the respiratory mechanics. This becomes particularly important when evaluating skeletal deformities, as in adolescent idiopathic scoliosis (AIS). The aim of this study was to identify morphological characteristics of the rib cage in relation to the lung in patients with non‐deformed and scoliotic spines. Computed tomography data of 40 patients without any visible spinal abnormalities (healthy group) and 21 patients with AIS were obtained retrospectively. All bony structures as well as the right and left lung were reconstructed using image segmentation. Morphological parameters were calculated based on the distances between characteristic morphological landmarks. These parameters included the rib position, length, and area, the rib cage depth and width, and the rib inclination angle on either side, as well as the spinal height and length. Furthermore, we determined the left and right lung volumes, and the area of contact between the rib cage and lung. Differences between healthy and scoliotic spines were statistically analysed using the t‐test for unpaired data. The rib cage of the AIS group was significantly deformed in the dorso‐ventral and medio‐lateral directions. The anatomical proximity of the lung to the ribs was nearly symmetrical in the healthy group. By contrast, within the AIS group, the lung covered a significantly greater area on the left side of the rib cage at large thoracic deformities. Within the levels T1–T6, no significant difference in the rib length, depth to width relationship, or area was observed between the healthy and AIS groups. Inferior to the lung (T7–T12), these parameters exhibited greater variability. The ratio between the width of the rib cage at T6 and the thoracic spinal height (T1–T12) was significantly increased within the thoracic AIS group (1.1 ± 0.08) compared with the healthy group (1.0 ± 0.05). No statistical differences were found between the lung volumes among all the groups. While the rib cage was frequently strongly deformed in the AIS group, the lung and its surrounding ribs appeared to be normally developed. The observed rib hump in AIS appeared to be formed particularly by a more ventral position of the ribs on the concave side. Furthermore, the rib cage width to spinal height ratio suggested that the spinal height of the thoracic AIS‐spine is reduced. This indicates that the spine would gain its growth‐related height after correcting the spinal deformity. These are the important aspects to consider in the aetiology research and orthopaedic treatment of AIS.

PURPOSE The potential to compute volume metrics of emphysema from planar scout images was investigated in this study. The successful implementation of this concept will have a wide impact in different fields, and specifically, maximize the diagnostic potential of the planar medical images. METHODS We investigated our premise using a well-characterized chronic obstructive pulmonary disease (COPD) cohort. In this cohort, planar scout images from computed tomography (CT) scans were used to compute lung volume and percentage of emphysema. Lung volume and percentage of emphysema were quantified on the volumetric CT images and used as the "ground truth" for developing the models to compute the variables from the corresponding scout images. We trained two classical convolutional neural networks (CNNs), including VGG19 and InceptionV3, to compute lung volume and the percentage of emphysema from the scout images. The scout images (n = 1,446) were split into three subgroups: (1) training (n = 1,235), (2) internal validation (n = 99), and (3) independent test (n = 112) at the subject level in a ratio of 8:1:1. The mean absolute difference (MAD) and R-square (R2) were the performance metrics to evaluate the prediction performance of the developed models. RESULTS The lung volumes and percentages of emphysema computed from a single planar scout image were significantly linear correlated with the measures quantified using volumetric CT images (VGG19: R2 = 0.934 for lung volume and R2 = 0.751 for emphysema percentage, and InceptionV3: R2 = 0.977 for lung volume and R2 = 0.775 for emphysema percentage). The mean absolute differences (MADs) for lung volume and percentage of emphysema were 0.302 ± 0.247L and 2.89 ± 2.58%, respectively, for VGG19, and 0.366 ± 0.287L and 3.19 ± 2.14, respectively, for InceptionV3. CONCLUSIONS Our promising results demonstrated the feasibility of inferring volume metrics from planar images using CNNs.

Introduction Conventionally computed tomography (CT) has been used to delineate target volumes in radiotherapy; however, magnetic resonance imaging (MRI) is being continually integrated into clinical practice; therefore, the investigation into targets derived from MRI is warranted. The purpose of this study was to evaluate the impact of imaging modality (MRI vs. CT) and patient positioning (supine vs. prone) on planning target volumes (PTVs) and organs at risk (OARs) for partial breast irradiation (PBI). Methods A retrospective data set, of 35 patients, was accessed where each patient had undergone MRI and CT imaging for tangential whole breast radiotherapy in both the supine and prone position. PTVs were defined from seroma cavity (SC) volumes delineated on each respective image, resulting in 4 PTVs per patient. PBI plans were generated with 6MV external beam radiotherapy (EBRT) using the TROG 06.02 protocol guidelines. A prescription of 38.5Gy in 10 fractions was used for all cases. The impact analysis of imaging modality and patient positioning included dose to PTVs, and OARs based on agreed criteria. Statistical analysis was conducted though Mann–Whitey U, Fisher’s exact and chi‐squared testing (P, This study investigates how image modality (magnetic resonance imaging (MRI) vs computed tomography (CT)) and patient positioning (supine vs. prone) affects partial breast irradiation (PBI) planning. There was no proven superiority of MRI‐derived target volumes, although notably, positioning influenced dose to organs at risk (OARs). MRI has the potential to be integrated into future practice to replace the need for CT based planning.

Background Multiple-breath inert gas washout (MBW) is a sensitive technique to assess lung volumes and ventilation inhomogeneity in infancy. Poor agreement amongst commercially available setups and a lack of transparency in the underlying algorithms for the computation of infant MBW outcomes currently limit the widespread application of MBW as a surveillance tool in early lung disease. Methods We determined all computational steps in signal processing and the calculation of MBW outcomes in the current infant WBreath/Exhalyzer D setup (Exhalyzer D device, Eco Medics AG; WBreath software version 3.28.0, ndd Medizintechnik AG; Switzerland). We developed a revised WBreath version based on current consensus guidelines and compared outcomes between the current (3.28.0) and revised (3.52.3) WBreath version. We analyzed 60 visits from 40 infants with cystic fibrosis (CF) and 20 healthy controls at six weeks and one year of age. Results Investigation into the algorithms in WBreath 3.28.0 revealed discrepancies from current consensus guidelines, which resulted in a potential overestimation of functional residual capacity (FRC) and underestimation of lung clearance index (LCI). We developed a revised WBreath version (3.52.3), which overall resulted in 6.7% lower FRC (mean (SD) -1.78 (0.99) mL/kg) and 14.1% higher LCI (1.11 (0.57) TO) than WBreath version 3.28.0. Conclusion Comprehensive investigation into the signal processing and algorithms used for analysis of MBW measurements improves the transparency and robustness of infant MBW data. The revised software version calculates outcomes according to consensus guidelines. Future work is needed to validate and compare outcomes between infant MBW setups. This article is protected by copyright. All rights reserved.

Purpose Helical tomotherapy (HT) is a form of intensity‐modulated radiation therapy that is employed in total body irradiation (TBI). Because TBI targets the whole body, accurate setup positioning at the edge of the treatment volume is made difficult by the whole‐body rotational posture. The purpose of this study is to clarify the tolerance for rotational setup error (SE) in the vertical direction. In addition, we perform a retrospective analysis of actually irradiated dose distributions using previous patients’ irradiation data. Methods To clarify the effects of rotational SE on the dose distribution, the planned CT images of 10 patients were rotated by 1–5° in the vertical (pitch) direction to create a pseudo‐rotational SE image. Then, the effect of the magnitude of the rotational SE on the dose distribution was simulated. In addition, the irradiated dose to the patients was analyzed by obtaining recalculated dose distributions using megavoltage CT images acquired before treatment. Results The simulation results showed that the average value of the lung volume receiving at least 10 Gy did not exceed the allowable value when the SE value was ≤2°. When the rotational SE was ≤3°, it was possible to maintain the clinical target volume dose heterogeneity within ±10% of the prescribed dose, which is acceptable according to the guidelines. A retrospective analysis of previous patients’ irradiation data showed their daily irradiation dose distribution. The dose to the clinical target volume was reduced by up to 3.4% as a result of the residual rotational SE. Although whole‐course retrospective analyses showed a statistically significant increase in high‐dose areas, the increase was only approximately 1.0%. Conclusions Dose errors induced by rotational SEs of ≤2° were acceptable in this study.

OBJECTIVES/HYPOTHESIS To investigate the effects of acute vocal exertion on individuals with vocal fatigue and to determine whether semi-occluded vocal tract exercises (SOVTEs) are more effective than vocal rest in mitigating acute effects. STUDY DESIGN Prospective, repeated-measures design. METHODS On consecutive days, 10 individuals (6 males, 4 females) with scores indicating vocal fatigue on the Vocal Fatigue Index completed two 10-minute vocal exertion tasks. Vocal rest or SOVTEs were interspersed in counterbalanced order between exertion tasks. Respiratory kinematic, acoustic, aerodynamic, and self-perceptual measures were collected at baseline, following vocal exertion, following SOVTE/vocal rest, and following the second exertion task. RESULTS Acute vocal exertion worsened phonation threshold pressure (P

OBJECTIVE To quantify the effect of age on two-dimensional (2D) radiographic lung and diaphragm morphology and determine if 2D radiographic lung measurements can be used to estimate computer tomography (CT)-derived lung volume in normative pediatric subjects. MATERIALS AND METHODS Digitally reconstructed radiographs (DRRs) were created using retrospective chest CT scans from 77 pediatric male and female subjects aged birth to 19 years. 2D lung and diaphragm measurements were made on the DRRs using custom MATLAB code, and Spearman correlations and exponential regression equations were used to relate 2D measurements with age. In addition, 3D lung volumes were segmented using CT scans, and power regression equations were fitted to predict each lung's CT-derived volume from 2D lung measurements. The coefficient of determination (R2 ) and standard error of the estimate (SEE) were used to assess the precision of the predictive equations with p

Early postnatal lung development (1-25 days) in the eastern quoll (Dasyurus viverrinus) was investigated to assess the morphofunctional status of one of the most immature marsupial neonates. Lung volume, surface density, surface area, and parenchymal and nonparenchymal volume proportions were determined using light microscopic morphometry. The lungs of the neonate were at the canalicular stage and consisted of two "balloon-like" airways with few septal ridges. The absolute volume of the lung was only 0.0009 cm3 with an air space surface density of 108.83 cm-1 and a surface area of 0.082 cm2 . The increase in lung volume in the first three postnatal days was mainly due to airspace expansion. The rapid postnatal development of the lung was indicated by an increase in the septal proportion of the parenchyma around day 4, which was reflected by an increase in the airspace surface density and surface area. By day 5, the lung entered the saccular stage of development with a reduction in septal thickness, expansion of the tubules into saccules and development of a double capillary system. The subsequent saccular period was characterized by repetitive septation steps, which increased the number of airway generations. The lungs of the newborn Dasyurus viverrinus must be considered as structurally and quantitatively insufficient to meet the respiratory requirements at birth. Hence, cutaneous gas exchange might be crucial for the first three postnatal days. The lung has to mature rapidly in the early postnatal period to support the increased metabolic requirements of the developing young.

INTRODUCTION COPD has multiple extrapulmonary manifestations and the latest studies have focused on cognitive dysfunction effects on sleep quality. The purpose of this study is to assess if there is a relationship between sleep quality and cognitive decline in COPD patients with severe airflow limitation. METHODS We performed an observational study to determine if there is a link between cognitive function and sleep quality. The included patients were divided into two groups: a group with COPD patients and control group. We evaluated lung volumes, cognitive function, sleep quality and disease impact on the quality of life. RESULTS Most of the COPD patients presented mild cognitive impairment (MCI) (95.7%), compared with only 24.1% in the control group (Pearson chi-square χ2 (1) = 42.560, p

Objective Galectin-10 (Gal-10) is a key molecule involved in eosinophil-mediated suppression of T-cell immune response. Systemic sclerosis (SSc) is characterized by T helper (Th) 2/Th17 immune response and impaired function of regulatory T cells, but the pathological role of Gal-10 has not been studied so far. Therefore, we investigated the clinical correlation of serum Gal-10 levels in SSc patients. Methods Serum Gal-10 levels were determined by enzyme-linked immunosorbent assay in 38 patients with diffuse cutaneous SSc (dcSSc), 30 with limited cutaneous SSc and 20 healthy controls. Clinical correlations of serum Gal-10 levels were examined. Results Serum Gal-10 levels were significantly lower in SSc patients than in healthy controls, especially in dcSSc patients, and inversely correlated with skin score, the percentage of predicted diffusion lung capacity for carbon monoxide and estimated right ventricular systolic pressure (RVSP). Furthermore, serum Gal-10 levels had negative correlations with leucocyte counts and inflammatory parameters. Multivariate regression analysis identified C-reactive protein and RVSP as explanatory parameters for serum Gal-10 levels. Conclusion Decreased serum Gal-10 levels may reflect the impairment of eosinophil-mediated regulatory system for T-cell immune response in SSc, possibly contributing to pulmonary vascular involvement leading to pulmonary arterial hypertension.

Background Hyperpolarized gas with helium (HHe-3) MR (magnetic resonance) is a noninvasive imaging method which maps and quantifies regions of ventilation heterogeneity (VH) in the lung. VH is an important feature of asthma, but little is known as to how VH informs patient phenotypes. Purpose To determine if VH indicators quantified by HHe-3 MR imaging (MRI) predict phenotypic characteristics and map to regions of inflammation in children with problematic wheeze or asthma. Methods Sixty children with poorly-controlled wheeze or asthma underwent HHe-3 MRI, including 22 with bronchoalveolar lavage (BAL). The HHe-3 signal intensity defined four ventilation compartments. The non-ventilated and hypoventilated compartments divided by the total lung volume defined a VH index (VHI %). Results Children with VHI % in the upper quartile had significantly greater airflow limitation, bronchodilator responsiveness, blood eosinophils, expired nitric oxide (FeNO), and BAL eosinophilic or neutrophilic granulocyte patterns compared to children with VHI % in the lower quartile. Lavage return from hypoventilated bronchial segments had greater eosinophil % than from ventilated segments. Conclusion In children with asthma, greater VHI % as measured by HHe-3 MRI identifies a severe phenotype with higher type 2 inflammatory markers, and maps to regions of lung eosinophilia. Listed on ClinicalTrials. gov (NCT02577497).

BACKGROUND Pediatric emergency front of neck airway guidelines recommend oxygenation via cannula cricothyroidotomy or tracheotomy. AIM The primary aim was to measure test lung pressures and volumes generated by cannula insufflation devices recommended for emergency front of neck airway compared with a pressure limit of 50 cm H2 O and volume limit of 20 ml/kg. The secondary aim was to calculate pressure and volume variability. The primary end point was test lung expansion. METHOD Adult, child, and infant airway models, each with three degrees of upper airway obstruction, were oxygenated using six cannula insufflation devices: 3-way stopcock, Rapid-O2 , Manujet, Enk oxygen flow modulator, Ventrain, and self-inflating bags. Test lung pressures and volumes were recorded. RESULTS Pressures and volumes from all devices were highly variable, despite oxygen flow calibration and strict adherence to oxygen insufflation protocols. With upper airway occlusion, pressures >50 cm H2 0 were produced by Rapid-O2 and Enk oxygen flow meter in adult and infant lungs, 3-way stopcock in adult and child lungs, and Manujet in all lung sizes. Ventrain produced acceptable pressures 20 ml/kg were recorded in airway models with fully obstructed proximal airways using Rapid-O2 and Enk oxygen flow meter in infant lungs, and Manujet in all lung sizes. Rapid-O2 produced lung volumes >20 ml/kg in the infant model with partially obstructed and open upper airways. Test lung volumes >20 ml/kg were produced by the 3-way stopcock in adult, child, and infant models. Insufflation was unsuccessful with the self-inflating bag. Ventrain produced acceptable volumes

BACKGROUND AND OBJECTIVE Late-onset non-allergic asthma in obesity is characterized by an abnormally compliant, collapsible lung periphery; it is not known whether this abnormality exists in proximal airways. We sought to compare collapsibility of central airways between lean and obese individuals with and without asthma. METHODS A cross-sectional study comparing luminal area and shape (circularity) of the trachea, left mainstem bronchus, right bronchus intermedius and right inferior lobar bronchus at RV and TLC by CT was conducted. RESULTS In 11 lean controls (BMI: 22.4 (21.5, 23.8) kg/m2 ), 10 lean individuals with asthma (23.6 (22.0, 24.8) kg/m2 ), 10 obese controls (45.5 (40.3, 48.5) kg/m2 ) and 21 obese individuals with asthma (39.2 (35.8, 42.9) kg/m2 ), lumen area and circularity increased significantly with an increase in lung volume from RV to TLC for all four airways (P

Introduction Failure to expectorate mucus resulting in progressive airway damage is the hallmark of bronchiectasis. Therefore effective airway clearance techniques (ACT) is the key step in its management. The aim of this study was to evaluate the efficacy of 3% hypertonic saline (HS) pre-medication in ACT in children with non cystic fibrosis (non-CF) bronchiectasis. Methods In this randomized crossover control trial five to 15 year old children, diagnosed with non-CF bronchiectasis were randomized either to receive 200 µg of inhaled salbutamol followed by HS nebulization (test) or only 200 µg of inhaled salbutamol, before chest physiotherapy which is the conventional ACT (controls) for 8 weeks. Inhaled salbutamol was administered via a pressurized metered dosed inhaler with a valved holding chamber. After completion of first phase both groups went through one month washout period, before being crossed over to the opposite arms in the second phase. Spirometric parameters and number of exacerbations were recorded at the end of phase I, washout period and phase II. Results Fifty two out of 63 enrolled completed the study. Baseline characteristics of the two groups were similar. A significantly higher mean improvement was seen in predicted forced expiratory volume in 1 s in the HS arm during phase 1 (HS = 14.15 ± 5.50 vs. conventional = 5.04 ± 5.55, p = .001) and phase II (HS = 10.81 ± 5.51 vs. conventional = 3.54 ± 5.13, p = .001) compared to conventional ACT arm. HS group showed a significantly higher mean improvement in predicted forced vital capacity in phase I (HS = 13.77 ± 5.73 vs. conventional = 7.54 ± 4.90, p = .001) and phase II, (HS = 9.42 ± 7.00 vs. conventional = 4.42 ± 4.00, p = .003). Mean number of exacerbations experienced by a single child during phase I (2 months) were significantly less (p = .001) in HS arm (0.42 ± 0.64) compared to that of conventional arm (1.30 ± 1.05) butthis difference was not significant in phase II (HS = 0.65 ± 0.74 and conventional = 1.03 ± 0.77, p = .074). Conclusion Incorporating HS nebulization into ACT is an effective strategy to improve dynamic lung volumes and morbidity in children with non-CF bronchiectasis.

BACKGROUND AND PURPOSE Respiratory dysfunction in Parkinson's disease (PD) is often an underdiagnosed and untreated impairment associated with the disease. Clinically, a reactive approach to respiratory morbidity is taken, rather than preventative approaches that address underlying impairment/s. This systematic review identifies the current evidence to support nonpharmacological interventions to improve respiratory impairments in individuals with PD. METHODS The relevant literature was searched using a customised and systematic strategy. Randomised and nonrandomised control trials of nonpharmacological interventions targeting respiratory outcome measures in PD were included. Outcomes of interest were respiratory morbidity and mortality, respiratory muscle strength, spirometry measures, lung volumes, peak cough flow, and perception of dyspnoea. RESULTS Nonpharmacological interventions included: functional training, generalised strength training, respiratory muscle strength training, aerobic exercise, qigong, yoga, breath stacking, incentive spirometry and singing. Methodological quality of included studies varied. Meta-analyses of nonpharmacological interventions demonstrated significant effects for inspiratory muscle strength (mean difference [MD] 19.68; confidence interval [CI] 8.49, 30.87; z = 3.45; p = 0.0006; I2 = 2%), expiratory muscle strength (MD 18.97; CI 7.79, 30.14; z = 3.33; p = 0.0009; I2 = 23%) and peak expiratory flow (MD 72.21; CI 31.19, 113.24; z = 3.45; p = 0.0006; I2 = 0%). Best-evidence synthesis identified level 1 evidence supporting nonpharmacological interventions for improving peak cough flow and perceived dyspnoea. No studies were identified reporting outcomes of respiratory rate, inspiration:expiration ratio or respiratory morbidity or mortality in PD. CONCLUSIONS Nonpharmacological interventions improved respiratory muscle strength and peak expiratory flow in PD. Additional trials targeting respiratory dysfunction and longitudinal studies examining the relationship between respiratory dysfunction and morbidity and mortality rates in PD are required.

Nitrogen mustard (NM) causes acute lung injury, which progresses to fibrosis. This is associated with a macrophage-dominant inflammatory response and the production of proinflammatory/profibrotic mediators, including tumor necrosis factor alpha (TNF-α). Herein, we refined magnetic resonance imaging (MRI) and computed tomography (CT) imaging methodologies to track the progression of NM-induced lung injury in rodents and assess the efficacy of anti-TNF-α antibody in mitigating toxicity. Anti-TNF-α antibody was administered to rats (15 mg/kg, every 8 days, intravenously) beginning 30 min after treatment with phosphate-buffered saline control or NM (0.125 mg/kg, intratracheally). Animals were imaged by MRI and CT prior to exposure and 1-28 days postexposure. Using MRI, we characterized acute lung injury and fibrosis by quantifying high-signal lung volume, which represents edema, inflammation, and tissue consolidation; these pathologies were found to persist for 28 days following NM exposure. CT scans were used to assess structural components of the lung and to register changes in tissue radiodensities. CT scans showed that in control animals, total lung volume increased with time. Treatment of rats with NM caused loss of lung volume; anti-TNF-α antibody mitigated this decrease. These studies demonstrate that MRI and CT can be used to monitor lung disease and the impact of therapeutic intervention.

Objectives The relationship between marijuana use and markers of chronic lung disease in people living with HIV (PLWH) is poorly understood. Methods We performed a cross-sectional analysis of the Examinations of HIV-Associated Lung Emphysema (EXHALE) study, including 162 HIV-positive patients and 138 participants without HIV. We modelled marijuana exposure as: (i) current daily or weekly marijuana smoking vs. monthly or less often; or (ii) cumulative marijuana smoking (joint-years). Linear and logistic regression estimated associations between marijuana exposure and markers of lung disease, adjusted for tobacco smoking and other factors. Results In PLWH, current daily or weekly marijuana use was associated with a larger forced vital capacity (FVC), larger total lung capacity and increased odds of radiographic emphysema compared with marijuana non-smokers in adjusted models; these associations were not statistically significant in participants without HIV. Marijuana joint-years were associated with higher forced expiratory volume in 1 s and FVC in PLWH but not with emphysema. Conclusions In PLWH, marijuana smoking was associated with higher lung volumes and potentially with radiographic emphysema. No consistently negative associations were observed between marijuana and measures of chronic lung health.

Slight changes in lung volume have previously been reported in ducks. We studied the functional structure of the lung of the domestic duck using classical anatomical techniques as well as ultrasound monitoring to unravel the causes of such changes. Later dorsal and medioventral secondary bronchi were superficially positioned and covered with a thin transparent and collapsible membrane, internally lined with a cuboidal to squamous epithelium. The lung parenchyma was rigid, with atria well supported by septa containing smooth muscles, interparabronchial septa reinforced by collagen fibres, and blood capillaries supported by epithelial plates. On ultrasound monitoring, an outward and inward movement of the lung surface during inspiration and expiration, respectively, was evident at the region where the airways were covered by the thin membranes. The movements plausibly facilitated air movement in the lung just like the air sacs. We conclude that volume changes in the duck lung occur due to a slight morphological adaptation rather than a change in the archetypical design of the avian lung parenchyma.

PURPOSE To measure the transverse relaxation time ( T2∗ ) and apparent diffusion coefficient (ADC) of 19 F-C3 F8 gas in vivo in human lungs at 1.5T and 3T, and to determine the representative distribution of values of these parameters in a cohort of healthy volunteers. METHODS Mapping of ADC at lung inflation levels of functional residual capacity (FRC) and total lung capacity (TLC) was performed with inhaled 19 F-C3 F8 (eight subjects) and 129 Xe (six subjects) at 1.5T. T2∗ mapping with 19 F-C3 F8 was performed at 1.5T (at FRC and TLC) for 8 subjects and at 3T (at TLC for seven subjects). RESULTS At both FRC and TLC, the 19 F-C3 F8 ADC was smaller than the free diffusion coefficient demonstrating airway microstructural diffusion restriction. From FRC to TLC, the mean ADC significantly increased from 1.56 mm2 /s to 1.83 mm2 /s (P = .0017) for 19 F-C3 F8, and from 2.49 mm2 /s to 3.38 mm2 /s (P = .0015) for 129 Xe. The posterior-to-anterior gradient in ADC for FRC versus TLC in the superior half of the lungs was measured as 0.0308 mm2 /s per cm versus 0.0168 mm2 /s per cm for 19 F-C3 F8 and 0.0871 mm2 /s per cm versus 0.0326 mm2 /s per cm for 129 Xe. A consistent distribution of 19 F-C3 F8T2∗ values was observed in the lungs, with low values observed near the diaphragm and large pulmonary vessels. The mean T2∗ across volunteers was 4.48 ms at FRC and 5.33 ms at TLC for 1.5T, and 3.78 ms at TLC for 3T. CONCLUSION In this feasibility study, values of physiologically relevant parameters of lung microstructure measurable by MRI ( T2∗ , and ADC) were established for C3 F8 in vivo lung imaging in healthy volunteers.

PURPOSE To test the feasibility of 3D phase-resolved functional lung (PREFUL) MRI in healthy volunteers and patients with chronic pulmonary disease, to compare 3D to 2D PREFUL, and to investigate the required temporal resolution to obtain stable 3D PREFUL measurement. METHODS Sixteen participants underwent MRI using 2D and 3D PREFUL. Retrospectively, the spatial resolution of 3D PREFUL (4 × 4 × 4 mm3 ) was decreased to match the spatial resolution of 2D PREFUL (4 × 4 × 15 mm3 ), abbreviated as 3Dlowres . In addition to regional ventilation (RVent), flow-volume loops were computed and rated by a cross-correlation (CC). Ventilation defect percentage (VDP) maps were obtained. RVent, CC, VDPRVent , and VDPCC were compared for systematic differences between 2D, 3Dlowres , and 3D PREFUL. Dividing the 3D PREFUL data into 4- (≈ 20 phases), 8- (≈ 40 phases), and 12-min (≈ 60 phases) acquisition pieces, the ventilation parameter maps, including the heterogeneity of ventilation time to peak, were tested regarding the required temporal resolution. RESULTS RVent, CC, VDPRVent , and VDPCC presented significant correlations between 2D and 3D PREFUL (r = 0.64-0.94). CC and VDPCC of 2D and 3Dlowres PREFUL were significantly different (P < .0113). Comparing 3Dlowres and 3D PREFUL, all parameters were found to be statistically different (P < .0045). CONCLUSION 3D PREFUL MRI depicts the whole lung volume and breathing cycle with superior image resolution and with likely more precision compared to 2D PREFUL. Furthermore, 3D PREFUL is more sensitive to detect regions of hypoventilation and ventilation heterogeneity compared to 3Dlowres PREFUL, which is important for early detection and improved monitoring of patients with chronic lung disease.

Objective Myocardial involvement may occur during systemic sclerosis (SSc) and can lead to impaired myocardial contraction and/or arrhythmia. Cardiac magnetic resonance imaging (MRI) is used for noninvasive characterization of the myocardium. The aim of this study was to evaluate the utility of cardiac MRI with intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) and longitudinal relaxation time (T1) sequence mapping for assessment of myocardial microvascular and interstitium impairment in SSc. Methods In this single-center prospective cohort study, 40 consecutive patients with SSc and 20 healthy controls were assessed by cardiac MRI with IVIM DWI and T1 mapping sequences on a 3T scanning system. Images were analyzed independently by 2 assessors, and Bland-Altman plots were used to assess interreader concordance and reproducibility. Characteristics of the patients were compared according to quartiles of T1 and perfusion fraction (f-coefficient) values, using exact Cochran-Ermitage trend tests for qualitative variables and analysis of variance for quantitative variables. Kaplan-Meier cardiac events-free survival curves were plotted and compared with a log-rank test for trend. Results T1 values were higher in SSc patients than in healthy controls, and were higher in the diffuse cutaneous SSc (dcSSc) subset (P = 0.02). Higher T1 values were associated with the immunologic pattern seen in patients with the dcSSc form (P = 0.0001), a higher modified Rodnan skin thickness score (MRSS) (P = 0.003), and a higher frequency of interstitial lung disease (P = 0.03). Moreover, higher T1 values were correlated with higher MRSS scores (r = +0.32, P = 0.04) and reduced forced vital capacity (r = -0.34, P = 0.048), and tended to be correlated with reduced total lung capacity (r = -0.30, P = 0.07). Lower f-coefficient values, as a measure of decreased tissue perfusion, were associated with less frequent use of vasodilators (P = 0.02 for angiotensin-converting enzyme inhibitors and P = 0.06 for calcium-channel blockers) and more frequent use of glucocorticoids (P = 0.02). The f-coefficients were inversely correlated with the T1 values (r = -0.31, P = 0.02). Furthermore, higher T1 values were associated with higher incidence of cardiac events (log-rank test for trend P = 0.03). Conclusion Increased T1 values, potentially suggesting microscopic fibrosis, were observed more frequently in patients with dcSSc, and higher T1 values were associated with interstitial lung disease and more frequent cardiac events during follow-up. The results of this study show that cardiac MRI with T1 mapping sequences and IVIM DWI may be useful in assessing myocardial involvement in patients with SSc.

Objective Respiratory compromise in congenital muscular dystrophy (CMD) occurs, in part, from chest wall contractures. Passive stretch with hyperinsufflation therapy could reduce related costo-vertebral joint contractures. We sought to examine the impact of hyperinsufflation use on lung function and quality of life in children with CMD. Study design We conducted a randomized controlled trial on hyperinsufflation therapy in children with CMD at two centers. An individualized hyperinsufflation regimen of 15 minutes twice daily using a cough assist device over a 12 months period was prescribed. We measured lung function, quality of life, and adherence. To demonstrate reproducibility, pulmonary function was measured twice on the same day. A mixed-effects regression model adjusting for confounders was used to assess the effects of hyperinsufflation. Results We enrolled 34 participants in the study; 31 completed the trial (n = 17 treatment group and n = 14 controls). Participants in the treatment group demonstrated a relative gain in lung volume measured at 4 and 8 months, but not at 12 months. The control group required increases in the maximum insufflation pressures to achieve maximum lung volumes while the treatment group did not. Adherence was best early in the study, peaking at the first visit and decreasing at subsequent visits. Caregiver-reported quality of life was higher in the treatment group. Conclusion Hyperinsufflation therapy is effective in increasing and sustaining lung volume over time. Adherence, however, was inconsistent and difficult to maintain. Further research should determine if improved adherence leads to sustained benefits of hyperinsufflation.

Introduction Deep inspiration breath hold (DIBH) has been proven to reduce cardiac dose for women receiving left breast and chest wall radiation therapy. However, it utilises extra departmental resources and patient exertion. The aim of this exploratory study was to investigate if any factors existed that could identify breast cancer patients who may benefit most from DIBH, to facilitate appropriate utilisation of departmental resources. Methods Left‐sided breast cancer patients aged 18–70 years, and right‐sided breast cancer patients with internal mammary nodes included, were recruited. DIBH and free breathing (FB) plans were created for all patients. Patient demographic and clinical history were recorded. Variables including lung threshold value, lung volume, patient separation, maximum heart in field, volume of planning target volume (PTV), heart dose, ipsilateral lung dose were compared between plans. Results Plans for 31 patients were analysed. No correlations were found between lung threshold value or patient separation and cardiac dose. Moderate to strong correlations were found with BMI, PTV volume and lung volume change however no definitive thresholds were determined. A significant difference was found in the maximum heart in field between DIBH and FB (P, The aim of this study was to investigate factors that could help identify breast cancer patients who may benefit most from DIBH, to facilitate appropriate utilisation of departmental resources. Only factors that could be evaluated after CT simulation were found to have a significant relationship with reduction in heart dose. The only possible threshold identified was the maximum heart in field in free breathing, with those patients with >0.7 cm heart in field experiencing greater reductions in mean heart dose.

Background Radiation pneumonitis (RP) is a major pulmonary adverse event of chest radiotherapy. The PACIFIC trial that identified durvalumab as an effective subsequent‐line therapy after concurrent chemoradiotherapy (CCRT) found that patients with grade 2 or higher RP may have to be excluded from treatment under certain criteria. The purpose of this study was to investigate the relationship between grade ≥2 RP and the parameters of dose‐volume histograms after CCRT with cisplatin/docetaxel for stage III non‐small cell lung cancer and conduct a subset analysis of severe RP that can lead to the permanent discontinuation of treatment per the PACIFIC trial criteria to help determine treatment strategy. Methods We calculated the percentage of the lung volume received at least 5 Gy (V5) and 20 Gy (V20), the mean lung dose (MLD), and the lung volume spared from a 5 Gy dose (VS5) to the total lung volume. Factors affecting the incidence of grade ≥2 RP were identified; severe RP was defined as grade ≥3 as well as grade 2 RP that required ≥10 mg prednisolone for at least 12 weeks. Results This study included 45 patients. On univariate analysis, all parameters and total lung volume were found to be significant predictors of grade ≥2 RP (P = .001, .003, .03, .004, and .02, respectively). On multivariate analysis, V20 was a significant predictive factor of grade ≥2 RP (P = .007). Severe RP developed in 6 of 37 patients (16.2%) whose V20 values were 35% or lower. On univariate analysis, only V20 was a significant predictor of severe RP in these patients (P = .01). Conclusions The best approach to reduce the rate of grade ≥2 RP is to maintain the V5, V20, MLD, and VS5 as low as possible during radiotherapy planning in patients receiving definitive CCRT with cisplatin/docetaxel., V20 was a significant predictor of grade ≥2 radiation pneumonitis after chemoradiotherapy with cisplatin/docetaxel for stage III non‐small cell lung cancer. Severe radiation pneumonitis that would lead to the permanent discontinuation of treatment per the PACIFIC trial criteria developed in 6 of 37 patients (16.2%) whose V20 values were 35% or lower. Only the V20 was a significant predictor of severe radiation pneumonitis.

Background Body position might affect the coordination between respiration and swallowing. This study was carried out to test the hypothesis that during swallowing, coordinated movements of muscle groups such as the diaphragm and rectus abdominis muscles are important to control normal swallowing apnea. Objective To investigate this hypothesis, respiratory parameters, swallowing apnea and muscle activity were measured in each of four body positions: sitting position with feet on the floor, 30° reclining position, lateral position, and standing position. Methods All measurements were performed in nine healthy subjects. Nasal airflow was measured using a pneumotachometer and muscle activity was measured using an electromyograph. All lung volume fraction parameters were measured using spirometer and swallowing apnea time was calculated. Results The maximum inspiratory volume was 2.76 ± 0.83 L in the 30° reclining position, which was significantly larger than that in the other positions (p = .0001). The preliminary expiratory volume was 1.05 ± 0.42 L in the 30° reclining position, which was significantly smaller than that in the other positions (p < .0001). The swallowing apnea time during water swallowing was 1.17 ± 0.35 sec in the lateral position and 0.87 ± 0.28 sec in the 30° reclining position, which tended to be longer than the 0.78 sec in the sitting position. Conclusion We conclude that both lateral and reclining positions require a longer period of swallowing apnea compared to the sitting and standing positions. Differences in body position may significantly influence the coordination between respiration and swallowing.

Introduction The multiple breath nitrogen washout (MBW) test offers a sensitive measure of airway function. In this study we aim to (a) assess the validity of the EasyOne Pro LAB (MBWndd) in an in vitro lung model, (b) assess the feasibility, repeatability, and reproducibility of MBWndd and (c) compare outcomes with the Exhalyzer D (MBWEM) and body plethysmography.Methods In vitro, functional residual capacity (FRC) measurements were assessed using a lung model under quasi-physiological conditions and compared to measured FRC. In vivo plethysmography and MBW were performed in a prospective study of children at two visits (n = 45 healthy; n = 41 cystic fibrosis [CF]). Bland-Altman plots were used to compare agreement between FRC and lung clearance index (LCI) measurements.Results In vitro FRCndd measurements were repeatable but lung volumes were underestimated (mean relative difference -5.4% (limits of agreement [LA] -9.6%; -1.1%), 95% confidence interval (CI) -6.27; -4.45). In vivo, compared to plethysmography, FRCndd was consistently lower (-19.3% [-40.5; 1.9], 95% CI [-23.9; -14.7]), and showed a volume dependency. LCIndd values were also higher in children with smaller lung volumes. The within-test coefficient of variation of the FRCndd and LCIndd were 4.9% in health, and 5.6% and 6.9% in CF respectively. LCIndd was reproducible between-visits (mean relative difference [LA] -3.7% [-14.8, -7.5; 95% CI -6.6; -0.73] in health [n = 17] and 0.34% [-13.2, 22.8; 95% CI -5.0; 5.69] in CF [n = 23]). When calculated using the same algorithm, LCIndd was similar to LCIEM in health.Conclusions MBWndd measurements are feasible, repeatable, and reproducible, however, MBW-derived outcomes are not interchangeable with MBWEM.

BACKGROUND Capnoperitoneum during laparoscopy leads to cranial shift of the diaphragm, loss in lung volume, and risk of impaired gas exchange. Infants are susceptible to these changes and bedside assessment of lung volume during laparoscopy might assist with optimizing the ventilation. Thus, the primary aim was to investigate the monitoring value of a continuous end-expiratory lung volume (EELV) assessment method based on CO2 dynamics ( EELVCO2 ) in a pediatric capnoperitoneum model by evaluating the correlation and trending ability against helium washout (EELVHe ). METHODS Intra-abdominal pressure (IAP) was randomly varied between 0, 6, and 12 mm Hg with CO2 insufflation, while positive end-expiratory pressure (PEEP) levels of 3, 6, and 9 cm H2 O were randomly applied in eight anesthetized and mechanically ventilated chinchilla rabbits. Concomitant EELVCO2 and EELVHe and lung clearance index (LCI) were obtained under each experimental condition. RESULTS Significant correlations were found between EELVCO2 and EELVHe before capnoperitoneum (r = .85, P

Introduction Lung protective ventilation can decrease post-operative pulmonary complications. The aim of this study was to evaluate a capnodynamic method estimating effective lung volume (ELV) as a proxy for end-expiratory lung volume in response to PEEP changes in patients, healthy subjects and a porcine model. Methods Agreement and trending ability for ELV in anaesthetized patients and agreement in awake subjects were evaluated using nitrogen multiple breath wash-out/in and plethysmography as a reference respectively. Agreement and trending ability were evaluated in pigs during PEEP elevations with inert gas wash-out as reference. Results In anaesthetized patients bias (95% limits of agreement [LoA]) and percentage error (PE) at PEEP 0 cm H2O were 133 mL (-1049 to 1315) and 71%, at PEEP 5 cm H2O 161 mL (-1291 to 1613 mL) and 66%. In healthy subjects: 21 mL (-755 to 796 mL) and 26%. In porcines, at PEEP 5-20 cm H2O bias decreased from 223 mL to 136 mL LoA (34-412) to (-30 to 902) and PE 29%-49%. Trending abilities in anaesthetized patients and porcines were 100% concordant. Conclusion The ELV-method showed low bias but high PE in anaesthetized patients. Agreement was good in awake subjects. In porcines, agreement was good at lower PEEP levels. Concordance related to PEEP changes reached 100% in all settings. This method may become a useful trending tool for monitoring lung function during mechanical ventilation, if findings are confirmed in other clinical contexts.

Objectives In this study, we assessed the clinical effect of inhaled verapamil on hospitalized COPD patients in a randomized and double-blind study. Method COPD patients randomly received 10 mg of inhaled verapamil or 4 cc nebulized distilled water (DW) as placebo. Results Twenty patients enrolled in each group with no difference in baseline characteristics. Mean age was 64.95 ± 8.9 and 66.9 ± 10.74 years in verapamil and control group; respectively, (P > 0.05). The mean dyspnea score was 6.4 ± 1.2 and 6.2 ± 1.8 in the verapamil and control group, respectively and decreased to 4.9 ± 1.3 and 5.7 ± 1.8 after the intervention. The mean change in the verapamil group was significantly higher, (22.43% ± 10.6% vs 8.7% ± 12.1%), P = 0.00. Unlike the control group, the FEV1 value in the verapamil group significantly increased and reached to 1.17 ± 0.4 L from 1.03 ± 0.4. There was a significant decrease in airway resistance in both groups after intervention. However, neither total lung capacity and residual volume nor forced vital capacity changed significantly. Moreover, oxygen saturation in the verapamil group changed 4.8% ± 2.5% and this improvement in the control group was 1.8 ± 1 (P = 0.00). Smoker subjects, ones with PAP more than 35 mm Hg and obese patients benefit from verapamil. Conclusion The beneficial impact of inhaled verapamil on the diminishing of dyspnea score along with its bronchodilatory effect would make this selective calcium blocker agent a therapeutic option in COPD.

Objective Although both obesity and body posture are important factors affecting end‐expiratory lung volume (EELV) and upper airway patency, the influence of those factors on EELV and the association between EELV and upper airway calibers are still unknown in mice. This study examined such interaction effects in obese mice to test the hypothesis that obese mice have decreased EELV accompanied by structural alterations of the upper airway. Methods A high‐resolution in vivo micro‐computed tomography was utilized to scan anesthetized lean and diet‐induced obese mice in the prone and supine positions, followed by quantifying lung volume and analyzing upper airway morphology. Results There was a statistically significant interaction between the effects of body weight and posture on both EELV (p = 0.0049, η 2 = 0.1041) and upper airway calibers (p = 0.0215, η 2 = 0.6304). In lean mice, EELV in the prone position was significantly larger than in the supine position (prone EELV = 193.22 ± 9.10 µl vs. supine EELV = 176.01 ± 10.91 µl; p = 0.0072), whereas obese mice did not have such an improvement in EELV in the prone position (prone EELV = 174.37 ± 20.23 µl vs. supine EELV = 183.39 ± 17.49 µl; p = 0.0981) and tended to have a smaller upper airway when EELV was low based on Spearman's correlation analysis. Conclusions These data indicate that obesity is an important factor compromising both EELV and upper airway calibers in a posture‐dependent manner even in mice, which should be taken into consideration in future studies regarding upper airway collapse and lung mechanical properties using mice., This study examined effects of obesity and body posture on end‐expiratory lung volume and upper airway calibers in mice. The reduced chest wall compliance secondary to obesity diminished the advantageous effect of the prone position on lung mechanical properties. Obese mice had a smaller upper airway compared to lean mice when EELV was low.

We examined the morphology of the lungs of five species of high‐altitude resident ducks from Lake Titicaca in the Peruvian Andes (yellow‐billed pintail [Anas georgica], cinnamon teal [Anas cyanoptera orinomus], puna teal [Anas puna], speckled teal [Anas flavirostris oxyptera], and ruddy duck [Oxyura jamaicensis ferruginea]) and compared them with those of the high‐altitude migratory bar‐headed goose (Anser indicus) and the low‐altitude migratory barnacle goose (Branta leucopsis). We then determined the relationship between mass‐specific lung volume, the volume densities of the component parts of the lung, and previously reported hypoxia‐induced increases in pulmonary O(2) extraction. We found that the mass‐specific lung volumes and the mass‐specific volume of the exchange tissue were larger in the lungs of high‐altitude resident birds. The bar‐headed goose had a mass‐specific lung volume that fell between those of the low‐altitude species and the high‐altitude residents, but a mass‐specific volume of exchange tissue that was not significantly different than that of the high‐altitude residents. The data suggest that the mass‐specific volume of the lung may increase with evolutionary time spent at altitude. We found an inverse relationship between the percentage increase in pulmonary O(2) extraction and the percentage increase in ventilation across species that was independent of the volume density of the exchange tissue, at least for the resident Andean birds.

Background Ultrasound imaging has been widely used for imaging of the diaphragm thickness (Tdi) and thickening. Few studies assessed the Tdi using ultrasonography in patients with chronic obstructive pulmonary disease (COPD). We measured the Tdi and thickening in patients with COPD compared with healthy younger and healthy older adults to reveal the influence of ageing and/or COPD. Methods Thirty-eight male patients with COPD (age 72 ± 8 years), 15 healthy younger (age 22 ± 1 years) and 15 healthy older (age 72 ± 5 years) male volunteers were recruited. We measured Tdi at total lung capacity (TdiTLC ), functional residual capacity (TdiFRC ) and residual volume (TdiRV ) using B-mode ultrasonography. We calculated the change ratio of TdiTLC and TdiRV (ΔTdi%). We used a one-way analysis of variance and multiple comparison test for the comparison analysis. Results The TdiTLC and the ΔTdi% were significantly lower in patients with COPD compared to the healthy adults. There was no significant difference in these values with age. There was no between group difference in the TdiFRC or TdiRV . Conclusions Our results indicate significant differences in TdiTLC and ΔTdi% between patients with COPD and healthy adults. Therefore, diaphragm ultrasonography can assess diaphragm dysfunction associated with COPD. We suggest that it is better to use TdiTLC and ΔTdi% (not only Tdi at rest) to assess diaphragm function.

Dyspnea is an under-recognized and debilitating symptom that is reported in up to 40% of patients with Parkinson's disease and may have multiple origins. Despite its frequency, it is poorly researched, and there is a general lack of understanding of the pathophysiology of dyspnea and respiratory dysfunction in PD. Consequently, a number of PD patients are labelled as having "unexplained dyspnea." Studies to date have focused mainly on evaluating ventilatory capacity and lung volumes, and little is known about the effects of the disease on the medullary and pontine ventilatory control centers within the brainstem. This is of particular relevance in view of neuropathological studies demonstrating early involvement of the dorsal medulla and other brainstem structures by the disease process. The possibility that impaired brainstem ventilatory control is a contributory mechanism for dyspnea and could be a premotor manifestation in some PD patients therefore warrants further attention. This review focuses on clinical, pathological, and experimental evidence for the involvement of brainstem respiratory centers in PD. We highlight the need for further research, particularly in PD patients with unexplained dyspnea. © 2020 International Parkinson and Movement Disorder Society.

BACKGROUND Mannitol inhalation testing is specific for asthmatics with eosinophilic airway inflammation, a factor that has been negatively correlated with the development of deep inhalation bronchoprotection. OBJECTIVE To evaluate the effect of deep inhalations on responsiveness to inhaled mannitol in correlation with the degree of airway inflammation. METHODS Twenty participants with stable asthma completed this randomized, crossover study. A screening visit assessed responsiveness to methacholine and airway inflammation through fractional exhaled nitric oxide (FeNO) measures and sputum induction. Participants next completed two mannitol challenges, one with deep inhalations (standard method) and one with inhalations to half of total lung capacity, and two methacholine challenges, one with tidal breathing (standard method) and one with deep inhalations. Only the inhalation technique for dose administration differed between repeat mannitol or methacholine challenges. RESULTS Deep inhalations did not significantly influence the provocative dose of mannitol causing a 15% fall in forced expiratory volume in 1 second ((P = .73; n = 7) or the mannitol dose-response slope (P = .26; n = 20). Deep inhalations produced significant bronchoprotection against methacholine (P = .03; n = 20). FeNO levels were significantly correlated to sputum eosinophilia (P = .02; n = 15), responsiveness to deep inhalation methacholine (P = .005; n = 20), the dose-response slopes from deep inhalation mannitol (P = .01; n = 20), and the dose-response slope from non-deep inhalation mannitol (P = .005; n = 20). CONCLUSIONS AND CLINICAL RELEVANCE Deep inhalations did not produce significant bronchoprotection against inhaled mannitol. This result is in agreement with past findings linking airway inflammation with loss of deep inhalation bronchoprotection. CLINICAL TRIAL REGISTRATION This study was prospectively registered on clinicaltrials.gov (NCT03505489).

OBJECTIVE To determine reference values of sniff nasal inspiratory pressure (SNIP) in healthy children. METHODS This cross-sectional observational study included healthy children aged 6 to 11 years of both sexes. The volunteers underwent a pulmonary function test to rule out respiratory disorders. Respiratory muscle strength was measured using maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP), respectively, with MIP close to functional residual capacity (FRC) and residual volume, while MEP to total lung capacity. SNIP was performed through the nostril contralateral to the occlusion, close to FRC. Two 6-minute walk tests were performed to assess functional exercise capacity. RESULTS The sample comprised 121 healthy children (62 girls); 54% presented body mass index (BMI) percentile less than 85th and 46% more than equal to 85th percentile, higher than expected. SNIP values were similar between sexes (91.1 ± 21.0 cmH2 O in girls and 87.7 ± 19.4 cmH2 O in boys; P = .36) as well as the means of lower limits of normal (56.88 cmH2 O for girls and 56.66 cmH2 O for boys). Girls presented SNIP measurements larger than those of the MIP of FRC (P

Background and objective Idiopathic interstitial pneumonia (IIP) with autoimmune features that does not fulfil connective tissue disease (CTD) criteria has been recently defined as interstitial pneumonia with autoimmune features (IPAF). However, its long-term clinical course and outcome are poorly understood. Methods We included consecutive patients diagnosed with IIP (n = 586) or CTD-related interstitial lung disease (CTD-ILD, n = 149). Some patients with IIP were reclassified as IPAF based on recent guidelines. Results The median follow-up period was 45 months. Among the IIP patients, 109 (18.6%) were reclassified as IPAF. Compared to the non-IPAF-IIP group, the IPAF group had slower diffusing capacity of the lung for carbon monoxide (DLCO ) and total lung capacity declines, and more frequent CTD development during follow-up periods. The prognosis of the IPAF was better than that of the non-IPAF-IIP and similar to that of the CTD-ILD. IPAF was associated with better prognosis in the IIP cohort on univariate but not on multivariate analysis. Usual interstitial pneumonia (UIP) pattern, old age and low DLCO independently predicted mortality in the IPAF group. Conclusion Compared to the non-IPAF-IIP group, the IPAF group had slower lung function declines and more frequent CTD development during follow-up. Although the prognosis of IPAF group was better than that of non-IPAF-IIP group and similar to that of CTD-ILD group, it showed poor prognosis in patients with old age, UIP pattern, and low DLCO .

KEY POINTS The effect of combined inspiratory and expiratory muscle training on resting and reflexive cardiac function, as well as exercise capacity, in individuals with cervical spinal cord injury (SCI) is presently unknown. Six weeks of combined inspiratory and expiratory muscle training enhances both inspiratory and expiratory muscle strength in highly-trained athletes with cervical SCI with no significant effect on lung function. There was a significant decrease in left-ventricular filling and stroke volume at rest in response to 45° head-up tilt, which is irreversible by respiratory muscle training. Combined inspiratory and expiratory muscle training increased peak aerobic work rate and reduced end-expiratory lung volumes during exercise, which may have implications for left-ventricular filling during exercise. ABSTRACT To investigate the pulmonary, cardiovascular and exercise responses to combined inspiratory and expiratory respiratory muscle training (RMT) in athletes with tetraplegia, six wheelchair rugby athletes (five males and one female, aged 33 ± 5 years) completed 6 weeks of pressure threshold RMT, 2 sessions day-1 on 5 days week-1 . Resting pulmonary and cardiac function, exercise capacity, exercising lung volumes and field-based exercise performance were assessed at pre-RMT, post-RMT and after a 6-week no RMT period. RMT enhanced maximal inspiratory (pre- vs. post-RMT: -76 ± 15 to -106 ± 23 cmH2 O, P = 0.002) and expiratory (59 ± 26 to 73 ± 32 cmH2 O, P = 0.007) mouth pressures, as well as peak expiratory flow (6.74 ± 1.51 vs. 7.32 ± 1.60 L/s, P

New Findings What is the central question of this study? To what extent are the mechanical‐ventilatory responses to upper‐body exercise influenced by task‐specific locomotor mechanics? What is the main finding and its importance? When compared with lower‐body exercise performed at similar ventilations, upper‐body exercise was characterized by tidal volume constraint, dynamic lung hyperinflation and an increased propensity towards neuromechanical uncoupling of the respiratory system. Importantly, these responses were independent of respiratory dysfunction and flow limitation. Thus, the mechanical ventilatory responses to upper‐body exercise are attributable, in part, to task‐specific locomotor mechanics (i.e. non‐respiratory loading of the thorax). Abstract The aim of this study was to determine the extent to which the mechanical ventilatory responses to upper‐body exercise are influenced by task‐specific locomotor mechanics. Eight healthy men (mean ± SD: age, 24 ± 5 years; mass, 74 ± 11 kg; and stature, 1.79 ± 0.07 m) completed two maximal exercise tests, on separate days, comprising 4 min stepwise increments of 15 W during upper‐body exercise (arm‐cranking) or 30 W during lower‐body exercise (leg‐cycling). The tests were repeated at work rates calculated to elicit 20, 40, 60, 80 and 100% of the peak ventilation achieved during arm‐cranking (V˙E, UBE ). Exercise measures included pulmonary ventilation and gas exchange, oesophageal pressure‐derived indices of respiratory mechanics, operating lung volumes and expiratory flow limitation. Subjects exhibited normal resting pulmonary function. Arm‐crank exercise elicited significantly lower peak values for work rate, O2 uptake, CO2 output, minute ventilation and tidal volume (p

Background MRI of hyperpolarized 129 Xenon (HP 129 Xe) is increasingly utilized for investigating pulmonary function. The solubility of HP 129 Xe in lung tissue, blood plasma (Barrier), and red blood cells (RBC), with unique chemical shifts, enables spectroscopic imaging of potential imaging biomarkers of gas exchange and microstructural pulmonary physiology. Purpose To quantify global average and regional repeatability of Barrier:gas, RBC:gas, and RBC:Barrier ratios derived from dissolved-phase 129 Xe imaging and their dependence on intervisit changes in lung inflation volume. Study type Prospective. Population Fourteen healthy volunteers. One subject was unable to complete the study resulting in 13 subjects for analysis (eight female, five male, ages 24-69, 53.8 ± 13.9). Field strength 1.5T. Assessment Subjects were imaged using a 3D radial 1-point Dixon method to separate Barrier and RBC component signals, at two different timepoints, with ~1 month between visits. RBC:Gas, Barrier:Gas, and RBC:Barrier measures were compared across time and with pulmonary function tests (PFTs). Statistical tests Repeatablilty was quantified using Bland-Altman plots, coefficient of repeatability, coefficient of variation (CV), and intraclass correlation coefficients (ICCs). Dependence of imaging measures on PFTs and lung volume was evaluated using Spearman and Pearson correlation coefficients, respectively. Statistical significance was determined by F-test for intraclass correlations, and t-test for Spearman correlations and regression. Results Mean RBC:Gas, Barrier:Gas, and RBC:Barrier had CVs of 19.2%, 20.0%, and 11.5%, respectively, and had significant ICCs, equal to 0.78, 0.79, and 0.92, respectively. Intervisit differences in RBC:Barrier were significantly correlated with intervisit differences in DLCO (r = 0.93, P = 0.007). Significant correlations with intervisit lung volume differences and intervisit differences in mean RBC:Gas (r = -0.73, P = 0.005) and Barrier:Gas (r = -0.69, P = 0.009) were found. Data conclusion Three commonly used 129 Xe MRI-based measures of gas-exchange show good repeatability, particularly the Barrier:RBC ratio, which did not depend on lung inflation volume and was strongly associated with intervisit changes in DLCO . Level of evidence 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;50:1182-1190.

Purpose To improve the accuracy of computed tomography (CT) number mapping inside the lung in deformable image registration with large differences in lung volume for applications in vertical CT imaging and adaptive radiotherapy. Methods The deep inspiration breath hold (DIBH) CT image and the end of exhalation (EE) phase image in four-dimensional CT of 14 thoracic cancer patients were used in this study. Lung volumes were manually delineated. A Demons-based deformable registration was first applied to register the EE CT to the DIBH CT for each patient, and the resulting deformation vector field deformed the EE CT image to the DIBH CT space. Given that the mass of the lung remains the same during respiration, we created a mass-preserving model to correlate lung density variations with volumetric changes, which were characterized by the Jacobian derived from the deformation field. The Jacobian determinant was used to correct the lung CT numbers transferred from the EE CT image. The absolute intensity differences created by subtracting the deformed EE CT from the DIBH CT with and without density correction were compared. Results The ratio of DIBH CT to EE CT lung volumes was 1.6 on average. The deformable registration registered the lung shape well, but the appearance of voxel intensities inside the lung was different, demonstrating the need for density correction. Without density correction, the mean and standard deviation of the absolute intensity difference between the deformed EE CT and the DIBH CT inside the lung were 54.5 ± 45.5 for all cases. After density correction, these numbers decreased to 18.1 ± 34.9, demonstrating greater accuracy. The cumulative histogram of the intensity difference also showed that density correction improved CT number mapping greatly. Conclusion Density correction improves CT number mapping inside the lung in deformable image registration for difficult cases with large lung volume differences.