Larger Lung Volumes Research Articles

Lung volumes are increased in fetuses with transposition of the great arteries on intrauterine MRI.

Fetal brain size is decreased in some children with complex CHDs, and the distribution of blood and accompanying oxygen and nutrients is regionally skewed from early fetal life dependent on the CHD. In transposition of the great arteries, deoxygenated blood preferentially runs to the brain, whereas the more oxygenated blood is directed towards the lungs and the abdomen. Knowledge of whether this impactsintrauterine organ development is limited. We investigated lung, liver, and total intracranial volume in fetuses with transposition of the great arteries using MRI.Eight fetuses with dextro-transposition and without concomitant disease or chromosomal abnormalities and 42 fetuses without CHD or other known diseases were scanned once or twice at gestational age 30 through 39 weeks. The MRI scans were conducted on a 1.5T system, using a 2D balanced steady-state free precession sequence. Slices acquired covered the entire fetus, slice thickness was 10 mm, pixel size 1.5 × 1.5 mm, and scan duration was 30 sec.The mean lung z score was significantly larger in fetuses with transposition compared with those without a CHD; mean difference is 1.24, 95% CI:(0.59;1.89), p < 0.001. The lung size, corrected for estimated fetal weight, was larger than in the fetuses without transposition; mean difference is 8.1 cm3/kg, 95% CI:(2.5;13.7 cm3/kg), p = 0.004.In summary, fetuses with dextro-transposition of the great arteries had both absolute and relatively larger lung volumes than those without CHD. No differences were seen in liver and total intracranial volume. Despite the small number of cases, the results are interesting and warrant further investigation.

Evidence of Alveolar Macrophage Metabolic Shift Following Stereotactic Body Radiation Therapy -Induced Lung Fibrosis in Mice

Radiation-induced pneumopathy is the main dose-limiting factor in cases of chest radiation therapy. Macrophage infiltration is frequently observed in irradiated lung tissues and may participate in lung damage development. Radiation-induced lung fibrosis can be reproduced in rodent models using whole thorax irradiation but suffers from limits concerning the role played by unexposed lung volumes in damage development. Here, we used an accurate stereotactic body radiation therapy preclinical model irradiating 4% of the mouse lung. Tissue damage development and macrophage populations were followed by histology, flow cytometry, and single-cell RNA sequencing. Wild-type and CCR2 KO mice, in which monocyte recruitment is abrogated, were exposed to single doses of radiation, inducing progressive (60 Gy) or rapid (80 Gy) lung fibrosis. Numerous clusters of macrophages were observed around the injured area, during progressive as well as rapid fibrosis. The results indicate that probably CCR2-independent recruitment and/or in situ proliferation may be responsible for macrophage invasion. Alveolar macrophages experience a metabolic shift from fatty acid metabolism to cholesterol biosynthesis, directing them through a possible profibrotic phenotype. Depicted data revealed that the origin and phenotype of macrophages present in the injured area may differ from what has been previously described in preclinical models exposing large lung volumes, representing a potentially interesting trail in the deciphering of radiation-induced lung damage processes. Our study brings new possible clues to the understanding of macrophage implications in radiation-induced lung damage, representing an interesting area for exploration in future studies.

A dive into the physiological responses to maximal apneas, O2 and CO2 tables in apnea novices.

Apnea duration is dependent on three factors: oxygen storage, oxygen consumption, hypoxia and hypercapnia tolerance. While current literature focuses on maximal apneas to improve apnea duration, apnea trained individuals use timed-repeated submaximal apneas, called "O2 and CO2 tables". These tables claim to accommodate the body to cope with hypoxia and hypercapnia, respectively. The aim of this study was twofold. First, to investigate the determinants of maximal apnea duration in apnea novices. Second, to compare physiologic responses to maximal apneas, O2 and CO2 tables. After medical screening, lung function test and hemoglobin mass measurement, twenty-eight apnea novices performed three apnea protocols in random order: maximal apneas, O2 table and CO2 table. During apnea, peripheral oxygen saturation (SpO2), heart rate (HR), muscle (mTOI) and cerebral (cTOI) tissue oxygenation index were measured continuously. End-tidal carbon dioxide (EtCO2) was measured before and after apneas. Larger lung volumes, higher resting cTOI and lower resting EtCO2 levels correlated with longer apnea durations. Maximal apneas induced greater decreases in SpO2 (- 16%) and cTOI (- 13%) than O2 (- 8%; - 8%) and CO2 tables (- 6%; - 6%), whereas changes in EtCO2, HR and mTOI did not differ between protocols. These results suggest that, in apnea novices, O2 and CO2 tables did not induce a more profound hypoxia and hypercapnia, but a similar reduction in oxygen consumption than maximal apneas. Therefore, apnea novices should mainly focus on maximal apneas to improve hypoxia and hypercapnia tolerance. The use of specific lung training protocols can help to increase oxygen storage capacity.

Spatiotemporal analysis of SARS-CoV-2 infection reveals an expansive wave of monocyte-derived macrophages associated with vascular damage and virus clearance in hamster lungs.

We present the first study of the 3D kinetics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the early host response in a large lung volume using a combination of tissue imaging and transcriptomics. This approach allowed us to make a number of important findings: Spatially restricted antiviral response is shown, including the formation of monocytic macrophage clusters and upregulation of the major histocompatibility complex II in infected epithelial cells. The monocyte-derived macrophages are linked to SARS-CoV-2 clearance, and the appearance of these cells is associated with post-infection endothelial damage; thus, we shed light on the role of these cells in infected tissue. An early onset of tissue repair occurring simultaneously with inflammatory and necrotizing processes provides the basis for longer-term alterations in the lungs.

Changes in Lung Volumes with Spirometric Disease Progression in COPD.

Abnormal lung volumes representing air trapping identify the subset of smokers with preserved spirometry who develop spirometric chronic obstructive pulmonary disease (COPD) and adverse outcomes. However, how lung volumes evolve in early COPD as airflow obstruction develops remains unclear. To establish how lung volumes change with the development of spirometric COPD, we examined lung volumes from the pulmonary function data (seated posture) available in the U.S. Department of Veterans Affairs electronic health records (n=71,356) and lung volumes measured by computed tomography (supine posture) available from the COPD Genetic Epidemiology (COPDGene®) study (n=7969) and the SubPopulations and InterMediate Outcome Measures In COPD Study (SPIROMICS) (n=2552) cohorts, and studied their cross-sectional distributions and longitudinal changes across the airflow obstruction spectrum. Patients with preserved ratio-impaired spirometry (PRISm) were excluded from this analysis. Lung volumes from all 3 cohorts showed similar patterns of distributions and longitudinal changes with worsening airflow obstruction. The distributions for total lung capacity (TLC), vital capacity (VC), and inspiratory capacity (IC) and their patterns of change were nonlinear and included different phases. When stratified by airflow obstruction using Global initiative for chronic Obstructive Lung Disease (GOLD) stages, patients with GOLD 1 (mild) COPD had larger lung volumes (TLC, VC, IC) compared to patients with GOLD 0 (smokers with preserved spirometry) or GOLD 2 (moderate) disease. In longitudinal follow-up of baseline GOLD 0 patients who progressed to spirometric COPD, those with an initially higher TLC and VC developed mild obstruction (GOLD 1) while those with an initially lower TLC and VC developed moderate obstruction (GOLD 2). In COPD, TLC, and VC have biphasic distributions, change in nonlinear fashions as obstruction worsens, and could differentiate those GOLD 0 patients at risk for more rapid spirometric disease progression.

Radiation and immune checkpoint inhibitor-mediated pneumonitis risk stratification in patients with locally advanced non-small cell lung cancer: role of functional lung radiomics?

BackgroundPatients undergoing chemoradiation and immune checkpoint inhibitor (ICI) therapy for locally advanced non-small cell lung cancer (NSCLC) experience pulmonary toxicity at higher rates than historical reports. Identifying biomarkers beyond conventional clinical factors and radiation dosimetry is especially relevant in the modern cancer immunotherapy era. We investigated the role of novel functional lung radiomics, relative to functional lung dosimetry and clinical characteristics, for pneumonitis risk stratification in locally advanced NSCLC.MethodsPatients with locally advanced NSCLC were prospectively enrolled on the FLARE-RT trial (NCT02773238). All received concurrent chemoradiation using functional lung avoidance planning, while approximately half received consolidation durvalumab ICI. Within tumour-subtracted lung regions, 110 radiomics features (size, shape, intensity, texture) were extracted on pre-treatment [99mTc]MAA SPECT/CT perfusion images using fixed-bin-width discretization. The performance of functional lung radiomics for pneumonitis (CTCAE v4 grade 2 or higher) risk stratification was benchmarked against previously reported lung dosimetric parameters and clinical risk factors. Multivariate least absolute shrinkage and selection operator Cox models of time-varying pneumonitis risk were constructed, and prediction performance was evaluated using optimism-adjusted concordance index (c-index) with 95% confidence interval reporting throughout.ResultsThirty-nine patients were included in the study and pneumonitis occurred in 16/39 (41%) patients. Among clinical characteristics and anatomic/functional lung dosimetry variables, only the presence of baseline chronic obstructive pulmonary disease (COPD) was significantly associated with the development of pneumonitis (HR 4.59 [1.69–12.49]) and served as the primary prediction benchmark model (c-index 0.69 [0.59–0.80]). Discrimination of time-varying pneumonitis risk was numerically higher when combining COPD with perfused lung radiomics size (c-index 0.77 [0.65–0.88]) or shape feature classes (c-index 0.79 [0.66–0.91]) but did not reach statistical significance compared to benchmark models (p > 0.26). COPD was associated with perfused lung radiomics size features, including patients with larger lung volumes (AUC 0.75 [0.59–0.91]). Perfused lung radiomic texture features were correlated with lung volume (adj R2 = 0.84–1.00), representing surrogates rather than independent predictors of pneumonitis risk.ConclusionsIn patients undergoing chemoradiation with functional lung avoidance therapy and optional consolidative immune checkpoint inhibitor therapy for locally advanced NSCLC, the strongest predictor of pneumonitis was the presence of baseline chronic obstructive pulmonary disease. Results from this novel functional lung radiomics exploratory study can inform future validation studies to refine pneumonitis risk models following combinations of radiation and immunotherapy. Our results support functional lung radiomics as surrogates of COPD for non-invasive monitoring during and after treatment. Further study of clinical, dosimetric, and radiomic feature combinations for radiation and immune-mediated pneumonitis risk stratification in a larger patient population is warranted.

Large lungs may predict increased air trapping in navy divers.

Navy divers tend to have large lungs and low expiratory flow rates in the terminal portion of a spirogram. We examined Finnish Navy divers for the presence of air trapping, airway obstruction, and functional airway compression, and their association with lung volumes. Divers (n = 57) and non‐diving men (n = 10) underwent a variety of pulmonary function tests. The amount of trapped air was calculated as the subtraction of the total lung capacity (TLC) measured in a single‐breath helium dilution test from the TLC in body plethysmography (TLCb). Mean vital capacity (VC) was 6.4 L in the divers versus 5.8 L in the controls (p = 0.006) and TLCb 8.9 L in the divers versus 8.1 L in the controls (p = 0.002). No difference existed between them in the amount of trapped air. However, we found break points in a linear regression model (Davies test) between trapped air and several pulmonary parameters. Those individuals above the break points had lower ratio of forced expiratory volume in first second to forced vital capacity, lower resistance of airways, and higher reactance than those below the break points. In conclusion, navy divers had larger lungs than controls. Large lung volumes (VC >7.31 L or >122% of predicted value) were associated with air trapping. Furthermore, large volumes of air trapping (>1.1 L) were associated with increased residual volume (RV) and RV/TLCb. Despite no concurrent obstruction, functional airway compression, or reduced diffusing capacity, this slowly ventilated trapped air might remain disadvantageous for divers.

Large Lung Volumes Delay the Onset of the Physiological Breaking Point During Simulated Diving.

During breath holding after face immersion there develops an urge to breathe. The point that would initiate the termination of the breath hold, the “physiological breaking point,” is thought to be primarily due to changes in blood gases. However, we theorized that other factors, such as lung volume, also contributes significantly to terminating breath holds during face immersion. Accordingly, nine naïve subjects (controls) and seven underwater hockey players (divers) voluntarily initiated face immersions in room temperature water at Total Lung Capacity (TLC) and Functional Residual Capacity (FRC) after pre-breathing air, 100% O2, 15% O2 / 85% N2, or 5% CO2 / 95% O2. Heart rate (HR), arterial blood pressure (BP), end-tidal CO2 (etCO2), and breath hold durations (BHD) were monitored during all face immersions. The decrease in HR and increase in BP were not significantly different at the two lung volumes, although the increase in BP was usually greater at FRC. BHD was significantly longer at TLC (54 ± 2 s) than at FRC (30 ± 2 s). Also, with each pre-breathed gas BHD was always longer at TLC. We found no consistent etCO2 at which the breath holding terminated. BDHs were significantly longer in divers than in controls. We suggest that during breath holding with face immersion high lung volume acts directly within the brainstem to actively delay the attainment of the physiological breaking point, rather than acting indirectly as a sink to produce a slower build-up of PCO2.

NOTA SUI LIMITI FISIOLOGICI DELLE IMMERSIONI PROFONDE IN APNEA

This article discusses the limits of deep breath-hold diving in humans. After a short historical introduction and a discussion of the evolution of depth records, the classical theories of breath-hold diving limits are presented and discussed, namely that of the ratio between total lung capacity and residual volume and that of blood shift, implying an increase in central blood volume. Then the current vision is introduced, based on the principles of the energetics of muscular exercise. The new vision has turned the classical vision upside down, moving the discussion to a different level. A direct consequence of the new theory is the importance of having large lung volumes at the start of a dive, in order to increase body oxygen stores. I finally discuss the role of anaerobic lactic metabolism as a possible mechanism of oxygen preservation, thus prolonging breath-hold duration.

Prone positioning redistributes gravitational stress in the lung in normal conditions and in simulations of oedema.

What is the central question of this study? How does the interaction between posture and gravity affect the stresses on the lung, particularly in highly inflated gravitationally non-dependent regions, which are potentially vulnerable to increased mechanical stress and injury? What is the main finding and its importance? Changes in stress attributable to gravity are not well characterized between postures. Using a new metric of gravitational stress, we show that regions of the lung near maximal inflation have the greatest gravitational stresses while supine, but not while prone. In simulations of increased lung weight consistent with severe pulmonary oedema, the prone lung has lower gravitational stress in vulnerable, non-dependent regions, potentially protecting them from overinflation and injury. Prone posture changes the gravitational vector, and potentially the stress induced by tissue deformation, because a larger lung volume is gravitationally dependent when supine, but non-dependent when prone. To evaluate this, 10 normal subjects (six male and four female; age, means ± SD = 27±6years; height, 171±9cm; weight, 69± 13kg; forced expiratory volume in the first second/forced expiratory volume as a percentage of predicted, 93 ± 6%) were imaged at functional residual capacity, supine and prone, using magnetic resonance imaging, to quantify regional lung density. We defined regional gravitational stress as the cumulative weight, per unit area, of the column of lung tissue below each point. Gravitational stress was compared between regions of differing inflation to evaluate differences between highly stretched, and thus potentially vulnerable, regions and less stretched lung. Using reference density values for normal lungs at total lung capacity (0.10±0.03g/ml), regions were classified as highly inflated (density< 0.13g/ml, i.e., close to total lung capacity), intermediate (0.13≤density< 0.16g/ml) or normally inflated (density ≥ 0.16g/ml). Gravitational stress differed between inflation categories while supine (-1.6±0.3cmH2 O highly inflated; -1.4±0.3cmH2 O intermediate; -1.1±0.1cmH2 O normally inflated; P=0.05) but not while prone (-1.4±0.2cmH2 O highly inflated; -1.3±0.2cmH2 O intermediate; -1.3±0.1cmH2 O normally inflated; P=0.39), and increased more with height from dependent lung while supine (-0.24±0.02cmH2 O/cm supine; -0.18±0.04cmH2 O/cm prone; P=0.05). In simulated severe pulmonary oedema, the gradient in gravitational stress increased in both postures (all P<0.0001), was greater in the supine posture than when prone (-0.57±0.21cmH2 O/cm supine; -0.34±0.16cmH2 O/cm prone; P=0.0004) and was similar to the gradient calculated from supine computed tomography images in a patient with acute respiratory distress syndrome (-0.51cmH2 O/cm). The non-dependent lung has greater gravitational stress while supine and might be protected while prone, particularly in the presence of oedema.

Effect of tumor and normal lung volumes on the lung volume–dose parameters of IMRT in non–small-cell lung cancer

OBJECTIVES:To explore the effect of tumor and normal lung volumes on lung volume-dose parameters in patients with non-small-cell lung cancer (NSCLC) who had undergone intensity-modulated radiation therapy (IMRT).METHODS:The clinical data of 208 patients with NSCLC who underwent radical IMRT between June 2014 and June 2018 were retrospectively analyzed. A regression model curve was used to evaluate the effect of tumor and normal lung volumes on normal lung relative volumes receiving greater than 5 and 20 Gy (V5, V20), on mean lung dose (MLD), and on absolute volumes spared from greater than 5 and 20 Gy (AVS5, AVS20).RESULTS:The V5, V20, and MLD of the bilateral lung were fitted to a quadratic equation curve with the change in tumor volume, which increased initially and then decreased when the tumor volume increased. The V5, V20, and MLD of the lung reached their apex when the tumor volumes were 288.07, 341.69, and 326.83 cm3, respectively. AVS5 and AVS20 decreased in a logarithmic curve with an increase in tumor volume. The V5, V20, and MLD of the small normal lung volume group were all significantly higher than those of the large normal lung volume group (p<0.001, p=0.004, p=0.002). However, the AVS5 and AVS20 of the small normal lung volume group were all significantly lower than those of the large normal lung volume group (p<0.001).CONCLUSION:The effects of tumor volume and normal lung volume on dose-volume parameters should be considered. AVS5 is an important supplementary dose limitation parameter for patients whose tumor volume exceeds a certain boundary value (approximately 300 cm3).

Contrast media volume is significantly related to patient lung volume during CT pulmonary angiography when employing a patient-specific contrast protocol

Aim: The purpose of this study is to investigate the relationship between contrast media volume and patient lung volume when employing a patient-specific contrast media formula during pulmonary computed tomography angiography (CTA).&#x0D; Materials and methods: IRB approved this retrospective study. CTA of the pulmonary arteries was performed on 200 patients with suspected pulmonary embolism (PE). The contrast media volume (CMV) was calculted by employing a patient-specific contrast formula. Lung volume was quantified employing semi-automated lung software that calculated lung volumes (intellispace -Philips). The mean cross-sectional opacification profile of central and peripheral pulmonary arteries and veins were measured for each patient and arteriovenous contrast ratio (AVCR) calculated for each lung segment. Mean body mass index (BMI) and lung volume were quantified. Receiver operating (ROC) and visual grading characteristics (VGC) measured reader confidence in emboli detection and image quality respectively. Inter and intra-observer variations were investigated employing Cohen’s kappa methodology.&#x0D; Results: Results showed that the mean pulmonary arterial opacification of the main pulmonary circulation (343.88±73HU), right lung; upper (316.51±23HU), middle (312.5±39HU) and lower (315.23±65HU) lobes and left; upper (318.76±83HU), and lower (321.91±12HU) lobes. The mean venous opacification of all pulmonary veins was below 182±72HU. AVCR was observed at all anatomic locations (p&lt;0.0002) where this ratio was calculated. Moreover, larger volumes of contrast significantly correlated with larger lung volumes (r=0.89, p&lt;0.03) and radiation dose (p&lt;0.03). VGC and ROC analysis demonstrated increased area under the curve: 0.831 and 0.99 respectively (p&lt;0.02). Inter-observer variation was observed as excellent (κ = 0.71).&#x0D; Conclusion: We conclude that increased CMV is significantly correlated to increased patient lung volume and radiation dose when employing a patient-specific contrast formula. The effects patient habitus is highlighted.

Should We Consider the Resected Lung Volume in Primary Spontaneous Pneumothorax?

Although bullectomy is the most curative treatment in primary spontaneous pneumothorax (PSP), postoperative recurrence is not uncommon. New bulla formation at the staple line is the most common cause of recurrence. However, the mechanism is not known. We believe that the pressure gradient plays the main role in new bulla formation. A large resection amount induces a prolonged pressure gradient for obliteration of the residual space. This study aimed to identify the association between resected lung volume and recurrence. The medical records of patients who underwent video-assisted thoracoscopic surgery (VATS) bullectomy were reviewed between October 2010 and December 2017. A total of 396 patients underwent surgery for spontaneous pneumothorax. The electronic medical records (EMRs) of the patients were reviewed. Patients with secondary spontaneous pneumothorax were excluded. Patients who were diagnosed with emphysema on CT were excluded. Patients with PSP were excluded from the study if the bulla was not located in the apex or if there was no ruptured bulla at the time of the operation. Patients who lacked EMRs were also excluded. We reviewed the medical records of 276 patients. The apical resected lung volume was estimated using a conical volumetric formula with the use of the specimen size. The risk factors for postoperative recurrence were analyzed. The median age was 19years old (range 13-36). A total of 261 patients were male (94.6%). The median body weight and body mass index (BMI) were 58kg (range 40-82) and 18.92 (range 15.21-26.47), respectively. In 24 patients, both sides were operated on simultaneously. The resected lung volume was obtained by using a conical volumetric formula, and the value was divided by the BMI value. The median value was 1.43 (0.03-5.67). The median operative time was 35min (range 15-120). The median postoperative day was 4 (range 2-12). Age (p = 0.006), the value of the resected lung volume divided by BMI (p = 0.003), bilateral bullectomy (p = 0.013) and transverse diameter (p = 0.034) were associated with postoperative recurrence according to the univariate analysis. According to the multivariate analysis, age and the value of the lung volume divided by BMI were significant risk factors for postoperative recurrence. Younger age and a large resected lung volume and a low BMI are associated with postoperative recurrence after VATS bullectomy for PSP.

Technical Note: Density correction to improve CT number mapping in thoracic deformable image registration.

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. 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. 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. Density correction improves CT number mapping inside the lung in deformable image registration for difficult cases with large lung volume differences.

Human Genetic Adaptation to High Altitude: Evidence from the Andes.

Whether Andean populations are genetically adapted to high altitudes has long been of interest. Initial studies focused on physiological changes in the O2 transport system that occur with acclimatization in newcomers and their comparison with those of long-resident Andeans. These as well as more recent studies indicate that Andeans have somewhat larger lung volumes, narrower alveolar to arterial O2 gradients, slightly less hypoxic pulmonary vasoconstrictor response, greater uterine artery blood flow during pregnancy, and increased cardiac O2 utilization, which overall suggests greater efficiency of O2 transfer and utilization. More recent single nucleotide polymorphism and whole-genome sequencing studies indicate that multiple gene regions have undergone recent positive selection in Andeans. These include genes involved in the regulation of vascular control, metabolic hemostasis, and erythropoiesis. However, fundamental questions remain regarding the functional links between these adaptive genomic signals and the unique physiological attributes of highland Andeans. Well-designed physiological and genome association studies are needed to address such questions. It will be especially important to incorporate the role of epigenetic processes (i.e., non-sequence-based features of the genome) that are vital for transcriptional responses to hypoxia and are potentially heritable across generations. In short, further exploration of the interaction among genetic, epigenetic, and environmental factors in shaping patterns of adaptation to high altitude promises to improve the understanding of the mechanisms underlying human adaptive potential and clarify its implications for human health.

Prestrain and cholinergic receptor-dependent differential recruitment of mechanosensitive energy loss and energy release elements in airway smooth muscle.

We tested the hypothesis that oscillatory airway smooth muscle (ASM) mechanics is governed by mechanosensitive energy loss and energy release elements that can be recruited by prestrain and cholinergic stimulation. We measured mechanical energy loss and mechanical energy release in unstimulated and carbachol-stimulated bovine ASM held at prestrains ranging from 0.3 to 1.0 Lo (reference length) and subjected to sinusoidal length oscillation at 1 hz with oscillatory strain amplitudes ranging from 0.1 to 1.5% Lo. We found that oscillatory ASM mechanics during sinusoidal length oscillation is governed predominantly by one class of nonlinear mechanosensitive energy loss element and one class of nonlinear mechanosensitive energy release element with differential mechanosensitivities to oscillatory strain amplitude. The greater mechanosensitivity of the energy loss element than energy release element may explain the bronchodilatory effect of deep inspiration. Prestrain, an important determinant of ASM responsiveness, differentially increased energy loss and energy release in unstimulated and carbachol-stimulated ASM. Cholinergic stimulation, an important cause of bronchoconstriction and airway inflammation, also differentially increased energy loss and energy release. When prestrain and cholinergic stimulation were combined, we found that prestrain and cholinergic stimulation synergistically increased energy loss and energy release by ASM. The relationship between recruitment of energy loss elements and recruitment of energy release elements was nonlinear, suggesting that energy loss and energy release elements are not coupled in ASM cells. These findings imply that large lung volume and cholinergic ASM activation would synergistically increase mechanical energy expenditure during inspiration and mechanical recoil of ASM during expiration. NEW & NOTEWORTHY We report for the first time that oscillatory airway smooth muscle mechanics is governed predominantly by one class of nonlinear mechanosensitive energy loss element and one class of nonlinear mechanosensitive energy release element with differential mechanosensitivities to oscillatory strain amplitude. Prestrain and cholinergic stimulation synergistically and differentially recruit energy loss and energy release elements. The greater mechanosensitivity of the energy loss element than the energy release element may explain the bronchodilatory effect of deep inspiration.

Singing for adults with chronic obstructive pulmonary disease (COPD).

Singing is a complex physical activity dependent on the use of the lungs for air supply to regulate airflow and create large lung volumes. In singing, exhalation is active and requires active diaphragm contraction and good posture. Chronic obstructive pulmonary disease (COPD) is a progressive, chronic lung disease characterised by airflow obstruction. Singing is an activity with potential to improve health outcomes in people with COPD. To determine the effect of singing on health-related quality of life and dyspnoea in people with COPD. We identified trials from the Cochrane Airways Specialised Register, ClinicalTrials.gov, the World Health Organization trials portal and PEDro, from their inception to August 2017. We also reviewed reference lists of all primary studies and review articles for additional references. We included randomised controlled trials in people with stable COPD, in which structured supervised singing training of at least four sessions over four weeks' total duration was performed. The singing could be performed individually or as part of a group (choir) facilitated by a singing leader. Studies were included if they compared: 1) singing versus no intervention (usual care) or another control intervention; or 2) singing plus pulmonary rehabilitation versus pulmonary rehabilitation alone. Two review authors independently screened and selected trials for inclusion, extracted outcome data and assessed risk of bias. We contacted authors of trials for missing data. We calculated mean differences (MDs) using a random-effects model. We were only able to analyse data for the comparison of singing versus no intervention or a control group. Three studies (a total of 112 participants) were included. All studies randomised participants to a singing group or a control group. The comparison groups included a film workshop, handcraft work, and no intervention. The frequency of the singing intervention in the studies ranged from 1 to 2 times a week over a 6 to 24 week period. The duration of each singing session was 60 minutes.All studies included participants diagnosed with COPD with a mean age ranging from 67 to 72 years and a mean forced expiratory volume in one second (FEV1) ranging from 37% to 64% of predicted values. The sample size of included studies was small (33 to 43 participants) and overall study quality was low to very low. Blinding of personnel and participants was not possible due to the physical nature of the intervention, and selection and reporting bias was present in two studies.For the primary outcome of health-related quality of life, there was no statistically significant improvement in the St George's Respiratory Questionnaire total score (mean difference (MD) -0.82, 95% confidence interval (CI) -4.67 to 3.02, 2 studies, n = 58, low-quality evidence). However, there was a statistically significant improvement in the SF-36 Physical Component Summary (PCS) score favouring the singing group (MD 12.64, 95% CI 5.50 to 19.77, 2 studies, n = 52, low-quality evidence). Only one study reported results for the other primary outcome of dyspnoea, in which the mean improvement in Baseline Dyspnoea Index (BDI) score favouring the singing group was not statistically significant (MD 0.40, 95% CI -0.65 to 1.45, 1 study, n = 30, very low-quality evidence).No studies examined any long-term outcomes and no adverse events or side effects were reported. There is low to very low-quality evidence that singing is safe for people with COPD and improves physical health (as measured by the SF-36 physical component score), but not dyspnoea or respiratory-specific quality of life. The evidence is limited due to the low number of studies and the small sample size of each study. No evidence exists examining the long-term effect of singing for people with COPD. The absence of studies examining singing performed in conjunction with pulmonary rehabilitation precludes the formulation of conclusions about the effects of singing in this context. More randomised controlled trials with larger sample sizes and long-term follow-up, and trials examining the effect of singing in addition to pulmonary rehabilitation, are required to determine the effect of singing on health-related quality of life and dyspnoea in people with COPD.

Correlation between heart size and emphysema in patients with chronic obstructive pulmonary disease: CT-based analysis using inspiratory and expiratory scans.

The objective of this study was to investigate the relationship between the extent of emphysema and heart size in patients with chronic obstructive pulmonary disease (COPD) using inspiratory and expiratory chest computed tomography (CT). This retrospective study was approved by the institutional review board and informed consent was waived. We measured lung volume (LV), low attenuation area percent (%LAA; less than or equal to −950 HU), maximum cardiac area, and maximum transverse cardiac diameter on inspiratory/expiratory chest CT in 60 patients with COPD. Spearman rank correlation analysis was used to determine the correlations between the heart and lung CT measurements, and the correlations between these measurements and spirometric values. On inspiratory CT, the maximum transverse cardiac diameter was negatively correlated with LV (ρ = −0.42; p < 0.01) and %LAA (ρ = −0.43; p < 0.001). Furthermore, on expiratory CT, the maximum cardiac area was negatively correlated with LV (ρ = −0.35; p < 0.01) and %LAA (ρ = −0.37; p < 0.01), and there was a negative correlation between transverse cardiac diameter and %LAA (ρ = −0.34; p < 0.01). Although inspiratory cardiac size was not correlated with any of the spirometric values, the maximum cardiac area and transverse diameter on expiratory scans were significantly correlated with the reduced airflow values on spirometry (p < 0.01). In patients with COPD, the transverse cardiac diameter decreased as the emphysema progressed. A smaller cardiac area on expiratory CT suggested the presence of large LVs, emphysema, and airflow limitation in COPD.

Patterns of Oxygen Pulse Curve in Response to Incremental Exercise in Patients with Chronic Obstructive Pulmonary Disease \u2013 An Observational Study

In COPD, pulmonary hyperinflation causes decreased stroke volume thereby decreased oxygen pulse (O2P). While O2P flattening is related to myocardial ischemia in cardiac patients, O2P patterns have seldom been explored in COPD. The aims of the study were to investigate O2P-curve patterns and associated factors in COPD. Seventy-five patients with stable COPD were enrolled. The demographics, cardiac size, physiological measurements and stress EKG were compared among O2P-curve pattern groups. An algorithm to identify O2P-curve patterns was developed in 28 patients. In the remaining 45 patients after excluding two with poor effort, this algorithm revealed 20 (44%) flattening, 16 (36%) increasing, and nine (20%) decreasing patterns. The flattening-type group had lower body mass, cardiac size, and diffusing capacity, and larger lung volumes (p = 0.05–<0.0001) compared to the increasing-type group. During exercise, the flattening-type group had a lower operable O2P and more hyperventilation and dyspnea (p = 0.02–<0.01). None had ST-T changes. Most differences were related to body mass and mildly to inspiratory fraction. The decreasing-type group performed higher effort than the increasing-type group (p < 0.05). In conclusion, O2P flattening was common and was associated with reduced body mass and pulmonary hyperinflation rather than with myocardial ischemia. The decreasing-type may be caused by motivation to exercise.

Rural-urban disparity in lung function parameters of Nigerian children: effects of socio-economic, nutritional and housing factors

IntroductionThe effect of socio-demographic and nutritional factors on lung functions of African children is poorly studied. This study set out to determine the effects of these factors on lung functions of Nigerian school children.MethodsRural and urban secondary schools students in Ilesa, Nigeria were selected by multistage sampling. The socio-demographic, nutritional status as well as lung function parameters measured using incentive Spirometry (MIR Spirolab III srl, Italy) of the children were obtained and compared among the rural and urban children.ResultsA total of 250 children (128 rural and 122 urban) aged 9 to 17 years participated in the study over a 12 month period. Mean (SD) age was 12.6 (1.9) years and Male: Female 1:1.1. The urban children were heavier, taller and have larger lung volumes than their age and sex matched rural counterpart. Stunted rural males [Mean (SD) FVC 1.8 (0.3) L vs. 2.2 (0.6) L t-test = 2.360; p = 0.022], underweight females [Mean (SD) FVC 1.8 (0.4) L vs. 2.2 (0.6) L; t-test = 2.855; p = 0.006] and those exposed to unclean fuel [Mean (SD) FVC 2.1 (0.6) L vs. 2.4 (0.5) L; t-test = 2.079; p = 0.041] had significantly lower lung volumes compared to their counterparts without these conditions.ConclusionUndernutrition, low socio-economic class and use of unclean fuels adversely affect the lung functions of Nigerian children. Improved standard of living, use of clean fuel and adequate nutrition may ensure better lung health among these children.