Control Of Breathing Research Articles

Phox2b-expressing neurons contribute to breathing problems in Kcnq2 loss- and gain-of-function encephalopathy models

Loss- and gain-of-function variants in the gene encoding KCNQ2 channels are a common cause of developmental and epileptic encephalopathy, a condition characterized by seizures, developmental delays, breathing problems, and early mortality. To understand how KCNQ2 dysfunction impacts behavior in a mouse model, we focus on the control of breathing by neurons expressing the transcription factor Phox2b which includes respiratory neurons in the ventral parafacial region. We find Phox2b-expressing ventral parafacial neurons express Kcnq2 in the absence of other Kcnq isoforms, thus clarifying why disruption of Kcnq2 but not other channel isoforms results in breathing problems. We also find that Kcnq2 deletion or expression of a recurrent gain-of-function variant R201C in Phox2b-expressing neurons increases baseline breathing or decreases the central chemoreflex, respectively, in mice during the light/inactive state. These results uncover mechanisms underlying breathing abnormalities in KCNQ2 encephalopathy and highlight an unappreciated vulnerability of Phox2b-expressing ventral parafacial neurons to KCNQ2 pathogenic variants.

Obstructive sleep apneas and cardiovascular diseases

Obstructive sleep apneas (OSA) are a breathing disorder characterized by recurrent apneas and hypopneas associated with complete or partial obstruction of the upper airways during sleep, resulting in disturbed sleep architecture, repeated hypoxemia and awakenings, and daytime sleepiness. OSA syndrome affects up to 34% of men and 17% of women in Western countries. Abnormalities in upper airway anatomy (frequently due to obesity), muscle tone, or neural control of breathing are the main causes. OSA is associated with impaired cognitive function and favors the onset of hypertension, being a major determinant of resistant hypertension, and may favor cardiovascular diseases (e.g., coronary artery disease and heart failure), thereby increasing mortality. Polysomnography and (cardio)-respiratory portable systems are used to diagnose and determine the severity of OSA. Management of OSA includes lifestyle modifications, such as weight loss and avoidance of supine sleep position, and continuous positive airway pressure. Mandibular advancement devices and upper airway surgery may also be appropriate for some patients. Hypoglossal nerve stimulation and pharmacological interventions are currently investigated to improve symptoms and outcomes.

Lung function is related to salivary cytokines and hormones in healthy children. An exploratory cross‐sectional study

AbstractPulmonary mechanics has been traditionally viewed as determined by lung size and physical factors such as frictional forces and tissue viscoelastic properties, but few information exists regarding potential influences of cytokines and hormones on lung function. Concentrations of 28 cytokines and hormones were measured in saliva from clinically healthy scholar children, purposely selected to include a wide range of body mass index (BMI). Lung function was assessed by impulse oscillometry, spirometry, and diffusing capacity for carbon monoxide, and expressed as z‐score or percent predicted. Ninety‐six scholar children (55.2% female) were enrolled. Bivariate analysis showed that almost all lung function variables correlated with one or more cytokine or hormone, mainly in boys, but only some of them remained statistically significant in the multiple regression analyses. Thus, after adjusting by height, age, and BMI, salivary concentrations of granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) in boys were associated with zR5‐R20 and reactance parameters (zX20, zFres, and zAX), while glucagon inversely correlated with resistances (zR5 and zR20). Thus, in physiological conditions, part of the mechanics of breathing might be influenced by some cytokines and hormones, including glucagon and GM‐CSF. This endogenous influence is a novel concept that warrants in‐depth characterization.

Failure to breathe persists without air hunger or alarm following amygdala seizures.

Postictal apnea is thought to be a major cause of sudden unexpected death in epilepsy (SUDEP). However, the mechanisms underlying postictal apnea are unknown. To understand causes of postictal apnea, we used a multimodal approach to study brain mechanisms of breathing control in 20 patients (ranging from pediatric to adult) undergoing intracranial electroencephalography for intractable epilepsy. Our results indicate that amygdala seizures can cause postictal apnea. Moreover, we identified a distinct region within the amygdala where electrical stimulation was sufficient to reproduce prolonged breathing loss persisting well beyond the end of stimulation. The persistent apnea was resistant to rising CO2 levels, and air hunger failed to occur, suggesting impaired CO2 chemosensitivity. Using es-fMRI, a potentially novel approach combining electrical stimulation with functional MRI, we found that amygdala stimulation altered blood oxygen level-dependent (BOLD) activity in the pons/medulla and ventral insula. Together, these findings suggest that seizure activity in a focal subregion of the amygdala is sufficient to suppress breathing and air hunger for prolonged periods of time in the postictal period, likely via brainstem and insula sites involved in chemosensation and interoception. They further provide insights into SUDEP, may help identify those at greatest risk, and may lead to treatments to prevent SUDEP.

The role of the peripheral chemoreceptor reflex in non-hospitalised patients with post-COVID-19 syndrome

Abstract Background Long COVID (post COVID-19 syndrome) is a common debilitating illness. Little is known regarding the underlying mechanisms driving ongoing symptoms, which include lethargy, breathlessness, dysregulated breathing, and exercise intolerance. The carotid body is important in the control of breathing, is abundant in ACE2 (cell entry mechanism for SARS-CoV-2) and is known to drive similar symptoms in patients with heart failure (HF). We hypothesised that the carotid chemoreflex becomes hyperreactive in patients with long COVID-19 syndrome, which could be important in driving several ongoing symptoms. Purpose We aimed to examine whether carotid chemoreflex sensitivity was elevated in patients with long COVID (with initial mild-moderate symptoms) versus an age-matched control group and whether this could help to explain dysregulated breathing and poor exercise tolerance in long COVID. Methods Long COVID participants (n=14; 12F) were prospectively recruited from a tertiary cardiology long COVID clinic (after being cleared for cardiac conditions) and from advertising publicly. Patients were non-hospitalised and had received a diagnosis of long COVID via their GP or long COVID clinic. Participants had a positive PCR or sero-positive antibody test for their initial infection. Controls were healthy with no diagnosed comorbidities (n=14; 11F). Eight controls had a confirmed previous infection and did not develop ongoing symptoms. Participants completed baseline spirometry, a resting 12-lead electrocardiogram, and an incremental cardiopulmonary exercise test (CPET) to volitional exhaustion on a cycle ergometer. On a separate day, the carotid chemoreflex sensitivity was measured using the hypoxic ventilatory response (HVR) [1]. Averaged group data were compared using statistical software (GraphPad, Prism). Data are mean ± SD unless stated otherwise. Results Age and body mass index were similar between groups (Table 1). Resting spirometry indicated that lung function was similar between groups (Table 1). The long COVID group had a lower maximum volume of inspired oxygen (VO2 peak) and a similar maximum heart rate (as a % of predicted) vs. controls (Table 1). Ventilatory efficiency (VE/VCO2) slope, VE/VCO2 ratio at anaerobic threshold (AT), and VE/VCO2 nadir were higher in the long COVID group, indicating poor breathing efficiency, similar to the level observed in HF (Table 1) [2]. Finally, the HVR was elevated in the long COVID group (-0.45±0.23 l/min/SpO2%) versus the control group (-0.18±0.13 l/min/SpO2%, Figure 1, P=0.0007). The HVR correlated with the VE/VCO2 slope (r=0.54, P=0.0012). Conclusions These data suggest that the carotid chemoreflex is sensitised in people with long COVID and may help to explain dysregulated breathing in these patients. The carotid chemoreflex could be a viable target to help improve symptoms in people suffering with ongoing symptoms following even a mild original SARS-CoV-2 infection, but more research is needed.Table 1Figure 1

Effect of yoga training on body shape based on principal component analysis approach

Abstract This paper analyzes the practical strategy and significance of integrating form training in yoga training teaching and constructs an evaluation index system for yoga training teaching based on it. Secondly, a principal component analysis was used to introduce the covariance to calculate the comprehensive score of the indexes. Finally, an empirical analysis was conducted to verify the specific effects of yoga training on body shape. The research revealed that yoga asana teaching and breathing control method introduction were the primary components of yoga training, with factor loadings of 0.845 and 0.623, respectively. Yoga training significantly affected cardiorespiratory function, body fat and circumference, and flexibility, p<0.05. According to the statement, yoga training has the potential to enhance body shape and reduce body fat.

Effect and mechanical mechanism of spontaneous breathing on oxygenation and lung injury in mild or moderate animal ARDS

ObjectiveThe present study aimed to determine the effect and mechanical mechanism of spontaneous breathing during mechanical ventilation on oxygenation and lung injury using Beagles dogs mild or moderate acute respiratory distress syndrome (ARDS) model.MethodsAfter inducing mild or moderate ARDS by infusion of oleic acid, Eighteen Beagles dogs were randomly split into Spontaneous breathing group (BIPAPSB, n = 6), and Complete muscle paralysis group (BIPAPPC, n = 6),Six Beagles without ventilator support comprised the control group. Both groups were ventilated for 8 h under BIPAP mode. High-pressure was titrated TV to 6 ml/kg. A multi-pair esophageal balloon electrode catheter was used to measure respiratory mechanics and electromyogram. End-expiratory lung volume (EELV), gas exchange and respiratory variables were recorded in the process of mechanical ventilation. The contents of Interleukin (IL)-6 and IL-8 in lung tissue were measure using qRT-PCR. Besides, lung injury score was calculated in the end of mechanical ventilation.ResultsBased on the comparable setting of ventilator, BIPAPSB group exhibited higher safety peak transpulmonary pressure, abdominal pressure, EELV and P/F(PaO2/FiO2) than BIPAPPC group, whereas mean transpulmonary pressure, the mRNA levels of the IL-6 and IL-8 in the lung tissues and lung injury score in BIPAPSB group were lower than those in BIPAPPC group.ConclusionIn mild to moderate ARDS animal models, during mechanical ventilation, SB may improve respiratory function and reduce ventilator-induced lung injury. The mechanism may be that spontaneous inspiration up-regulates peak transpulmonary pressure and EELV; Spontaneous expiration decreases mean transpulmonary pressure by up-regulating intra-abdominal pressure, thereby reducing stress and strain.

Sleep Apnea and Dental Implications -A Review

Obstructive sleep apnea (OSA) is an increasingly common, chronic, sleep-related breathing disorder.The prevalence of obstructive sleep apnea (OSA) continues to rise due to change in life patterns.The most common presenting symptom of OSA is excessive sleepiness and is associated with a 2- to 3-fold increased risk of cardiovascular and metabolic disease. The key contributors to OSA pathogenesis include a narrow, crowded, or collapsible upper airway “anatomical compromise” and “non-anatomical” contributors such as ineffective pharyngeal dilator muscle function during sleep, a low threshold for arousal to airway narrowing during sleep, and unstable control of breathing. Effective treatments include weight loss and exercise, positive airway pressure, oral appliances that hold the jaw forward during sleep, and surgical modification of the pharyngeal soft tissues or facial skeleton to enlarge the upper airway. This review summarizes the latest knowledge ondifferent contributors to OSA with a focus on emerging clinical tools.

Respiratory disorders and their association with clinical outcomes in COVID-19: a narrative review of current literature.

The coronavirus disease 2019, also known as COVID-19, has caused significant worldwide morbidity and mortality. Given the direct effect of severe acute respiratory syndrome virus-2 (SARS-CoV-2) on the respiratory system, it is important that clinicians who manage chronic respiratory conditions are familiar with the pathophysiology and impact of COVID-19 on pre-existing respiratory disease. Literature review relating to COVID-19 and respiratory disorders from PubMed and Google Scholar was conducted, with aim to encompass all publications relating to the most commonly encountered respiratory diseases in clinical practice, namely chronic obstructive lung disease (COPD), asthma, interstitial lung disease (ILD), obstructive sleep apnea (OSA), as well as obesity given it's known effect on both gas exchange and mechanistic aspects of respiration. The publications were analyzed for relevance to clinical implications and pathophysiologic mechanisms. Additional manual literature review was conducted based on citations from large review articles and society guidelines/statement papers. Certain respiratory disorders such as COPD, ILD, OSA, and obesity carry higher burden of morbidity and mortality associated with COVID-19. Surprisingly, and in contrast to previously studied viral epidemics, asthma does not carry increased associated risk of contracting the virus or worse clinical outcomes. A thorough understanding of the mechanisms responsible for control of breathing and the effect of COVID-19 on pulmonary pathophysiology will allow clinicians who manage chronic respiratory disease to effectively predict associated clinical outcomes as well as improve management strategies.

Neuromotor control of spontaneous quiet breathing in awake rats evaluated by assessments of diaphragm EMG stationarity.

The neuromotor control of the diaphragm muscle (DIAm) is dynamic. The activity of the DIAm can be recorded via electromyography (EMG), which represents the temporal summation of motor unit action potentials. Our goal in the present study was to investigate DIAm neuromotor control during quiet spontaneous breathing (eupnea) in awake rats by evaluating DIAm EMG at specific temporal locations defined by motor unit recruitment and derecruitment. We evaluated the nonstationarity of DIAm EMG activity to identify DIAm motor unit recruitment and derecruitment durations. Combined with assessments of root mean square (RMS) and sum of squares (SS) EMG, the durations of these phases provide physiological information about the temporal aspects of motor control. During eupnea in awake rats (n = 10), the duration of motor unit recruitment comprised 61 ± 19 ms of the onset-to-peak duration (214 ± 62 ms) of the DIAm RMS EMG. The peak-to-offset duration of DIAm EMG activity was 453 ± 96 ms, with a terminating period of derecruitment of 161 ± 44 ms. The burst duration was 673 ± 128 ms. Both the RMS EMG amplitude and the SS EMG were higher at the completion of motor unit recruitment than at the start of motor unit derecruitment, suggesting that offset discharge rates were lower than onset discharge rates. Our analyses provide novel insights into the time domain aspects of DIAm neuromotor control and allow indirect estimates of the contribution of recruitment and frequency to RMS EMG amplitude during eupnea in awake rats.NEW & NOTEWORTHY We characterized three phases of neuromotor control-motor unit recruitment, sustained activity, and derecruitment-based on statistical assessments of stationarity of the diaphragm muscle (DIAm) EMG activity in awake rats. Our findings may allow indirect estimates of the contribution of motor unit recruitment and frequency coding toward generating force and provide novel insights about the temporal aspects of DIAm neuromotor control and descending respiratory drive in unanesthetized animals.

Effects of the antipsychotic quetiapine on sleep and breathing: a review of clinical findings and potential mechanisms.

Quetiapine is an antipsychotic medication indicated for schizophrenia and bipolar disorder. However, quetiapine also has hypnotic properties and as such is increasingly being prescribed at low doses 'off-label' in people with insomnia symptoms. Pharmacologically, in addition to its dopaminergic properties, quetiapine also modulates multiple other transmitter systems involved in sleep/wake modulation and potentially breathing. However, very little is known about the impact of quetiapine on obstructive sleep apnoea (OSA), OSA endotypes including chemosensitivity, and control of breathing. Given that many people with insomnia also have undiagnosed OSA, it is important to understand the effects of quetiapine on OSA and its mechanisms. Accordingly, this concise review covers the existing knowledge on the effects of quetiapine on sleep and breathing. Further, we highlight the pharmacodynamics of quetiapine and its potential to alter key OSA endotypes to provide potential mechanistic insight. Finally, an agenda for future research priorities is proposed to fill the current key knowledge gaps.

Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) and Sudden Infant Death Syndrome: A Potential Model for Investigation.

Sudden infant death syndrome (SIDS) represents a significant cause of post-neonatal mortality, yet its underlying mechanisms remain unclear. The triple-risk model of SIDS proposes that intrinsic vulnerability, exogenous triggers, and a critical developmental period are required for SIDS to occur. Although case-control studies have identified potential risk factors, no in vivo model fully reflects the complexities observed in human studies. Pituitary adenylate cyclase-activating polypeptide (PACAP), a highly conserved neuropeptide with diverse physiological functions, including metabolic and thermal regulation, cardiovascular adaptation, breathing control, stress responses, sleep-wake regulation and immunohomeostasis, has been subject to early animal studies, which revealed that the absence of PACAP or its specific receptor (PAC1 receptor: PAC1R) correlates with increased neonatal mortality similar to the susceptible period for SIDS in humans. Recent human investigations have further implicated PACAP and PAC1R genes as plausible contributors to the pathomechanism of SIDS. This mini-review comprehensively synthesizes all PACAP-related research from the perspective of SIDS and proposes that PACAP deficiency might offer a promising avenue for studying SIDS.

Sleep Disordered Breathing in Children with Neuromuscular Disease.

Sleep disordered breathing (SDB) in children with neuromuscular disease (NMD) is more prevalent compared to the general population, and often manifests as sleep-related hypoventilation, sleep-related hypoxemia, obstructive sleep apnea, central sleep apnea, and/or disordered control of breathing. Other sleep problems include, sleep fragmentation, abnormal sleep architecture, and nocturnal seizures in certain neuromuscular diseases. The manifestation of sleep disordered breathing in children depends on the extent, type, and progression of neuromuscular weakness, and in some instances, may be the first sign of a neuromuscular weakness leading to diagnosis of an NMD. In-lab diagnostic polysomnography (PSG) remains the gold standard for the diagnosis of sleep disordered breathing in children, but poses several challenges, including access to many children with neuromuscular disease who are non-ambulatory. If SDB is untreated, it can result in significant morbidity and mortality. Hence, we aimed to perform a comprehensive review of the literature of SDB in children with NMD. This review includes pathophysiological changes during sleep, clinical evaluation, diagnosis, challenges in interpreting PSG data using American Academy of Sleep (AASM) diagnostic criteria, management of SDB, and suggests areas for future research.

Physical exercise-intervention can be valuable therapy for COVID-19 confinement and post-COVID-19 periods.

The COVID-19 pandemic and its transition into an endemic phase have profoundly impacted physical health, well-being, mental health, education, and various aspects of society, including the economy and social networks. Home confinement, social distancing, and physical inactivity have exacerbated numerous health issues, including obesity, diabetes mellitus, hypertension, hyperlipidemia, cardiovascular diseases, depression, and poor sleep quality. A systematic review has revealed significant findings: Regular aerobic programs (such as cycling or walking at an intensity of 60-80% of HR max for 20-60 minutes per session, repeated 2-3 times a week) have proven effective in improving both physical and mental health, as well as immune function. This type of physical activity has been shown to increase immunological markers, including lymphocytes, leukocytes, neutrophils, monocytes, and interleukin-6 (IL-6), while reducing low-grade inflammation. Therefore, in this study we aimed to assess the impact of tailored exercise interventions on the physical and mental health of COVID-19 patients. Based on the results, we can establish exercise intervention strategies to mitigate the negative health consequences during and after the COVID-19 pandemic. We conducted a search of the PubMed database from January 2020 to August 2023 using predefined search terms such as "COVID-19 and post-COVID-19," "exercise intervention and immunity," and "mental health." By examining references, we explored the links between exercise interventions and the mental and physical health of COVID-19 patients. A tailored, multifaceted exercise intervention should be developed and implemented to address the existing mental challenges and enhance mental health during both the pandemic and the post-COVID-19 periods. Breathing exercises and respiratory support techniques, including yoga, thoracic expansion exercises, airway clearance methods, and breathing control, are likely to be beneficial.

Reducing Racial Disparities in Breast Cancer Treatment

Racial disparities in breast cancer screening, treatment, and outcomes are well established. A recent multi-institutional paper showed a higher mean heart dose (MHD) in Black women and other minorities compared to White women who underwent left-sided breast or chest wall irradiation. We evaluated the MHD of women treated in our institution and investigated whether institution-wide measures can mitigate disparities. We identified 509 consecutively treated female patients from 2012 to 2021 who received left-sided breast or chest wall irradiation (with or without regional nodal irradiation). Medical records were queried to report cardiac dosimetry across various racial groups. Details regarding the use of active breathing control (ABC), breast size, internal mammary nodal irradiation, and whether the patient's treatment plan met the departmental boarding pass requirement and was prospectively presented at departmental peer review were noted. MHD were noted in absolute values and 2-Gy equivalent doses (EQD2). Kruskal-Wallis test was used to analyze differences in MHD between racial groups. Univariate and multivariable Cox regression analyses were performed to determine association of MHD with other factors. MHD was similar across racial groups; 1.38 Gy (1.12, 2.02) in Black women, 1.35 Gy (1.02, 1.97) in White women, and 1.39 Gy (1.07, 2.01) in others with an EQD2 of 0.71, 0.70 and 0.72 (P = 0.6). Rates of the use of hypofractionation, a cavity boost, regional nodal irradiation, internal mammary nodal irradiation, meeting departmental boarding pass requirement, and peer review of treatment plan before starting treatment were similar across all racial groups. The use of ABC was 83% in White women, 75% in Black women and 62% in other races (P = 0.005). The difference in ABC use was attributed to a higher rate of volumetric modulated arc therapy treatment in other races (33%). Median breast size was 1904 cc in Black women, 1504 cc in White women, and 1331 cc in other racial groups (P = 0.001). On univariate and multivariate analysis, MHD differed with IMN treatment, boost and use of ABC but remained similar across racial groups and varying breast size. Despite anatomical differences such as breast size, achieving similar cardiac dose is feasible across racial groups by uniformly utilizing ABC for left sided breast or chest wall irradiation, applying standardized boarding pass constraints and peer review of all cases. Further studies to identify factors that may lead to differences in the rates of cardiac morbidity among racial groups are warranted.

Assessment of Daily Target Motion to Optimize ITV Margins in Online Adaptive Plan for Liver and Pancreatic SBRT on MR-LINAC

Accurate measurement of daily target motion on online plan adaptation is essential for re-optimizing the internal target volume (ITV) margins. In this study, by analyzing 2D cine MR images acquired in a 1.5T MR-Linac, we assessed daily target motion and its inter-fractional variations, which is then used to customize ITV margins for MR-based online adaptive plan of liver and pancreatic stereotactic body radiotherapy (SBRT). Twenty-threepatients, enrolled in this study, underwent MR-guided online adaptive SBRT on 1.5 T MR-Linac: liver (n = 12 without compression belt (CB), n = 2 with CB) and pancreas (n = 9 with CB). Target motion in a 2D coronal and sagittal MR images (> 200 cine images to cover multiple breathing cycles), as well as a set of 4D-CT images during the simulation, was analyzed to determine patient specific ITV margins for a reference plan. On every fraction of online adaptive SBRT, the 2D MR images were exported to commercially available software along with a planning MR images: a T1-wighted MR image set for pancreas and or a navigated T2-wighted MR image set for liver. Daily target motion was then measured by overlaying the orthogonal cine image set on the T1- or T2-wighted image set. The ITV margin was adjusted when required prior to online plan optimization RESULTS: Thisstudy successfully assessed the daily target motion and inter-fractional variations in 23 liver or pancreatic cancer patients. We found a discrepancy of daily target motion of orthogonal 2D cine MR images from that of 4D-CT, required to adjust the ITV margin for online plan adaptation. In liver SBRT without CB, 15 out of 45 fractions from 12 patients (33.3 %) went through adjusted ITV margin. The tumor motion was large up to a 2.2 cm along the inferior direction in a patient without CB and thus the patient was treated on a conventional Linac with the active breathing control (ABC) unit for breath-hold. On the other hand, no adjustments were necessary for 2 liver patients with CB. In 9 patients with pancreatic cancers, we found the inter-fractional ITV variations in 3 out of 45 fractions (6.7 %) adjusted the ITV margin. The daily target motion in the pancreatic patients with CB was more stable and relatively smaller than that of the liver patients. Theorthogonal 2D cine MR images are evidently essential for assessing daily target motion to evaluate the inter-fractional variation and achieve daily ITV-customized liver and pancreatic SBRT in the 1.5 T MR-Linac. The customized ITV approach will improve the treatment outcome of the MR-guided online adaptive therapy.

Preoperative pulmonary rehabilitation in medical inoperable patients with early stage non-small cell lung cancer and postoperative results

Aims: The impact of postoperative complications after surgery for lung cancer is substantial, with the increasing age of patients and the presence of comorbidities. Impairment in exercise capacity is a potential modifiable risk factor for postoperative complications. This study aimed to assess the contribution of preoperative pulmonary rehabilitation (PR) for increasing operability conditions in non-small cell lung cancer (NSCLC) for patients with limited pulmonary functions and postoperative results.
 Methods: The patients with NSCLC who had preoperative pulmonary rehabilitation and underwent surgical resection in our clinics between 2010-2019 were evaluated retrospectively. The patients enrolled in a comprehensive, multidisciplinary, supervised outpatient 10-day duration PR program preoperatively, consisting of bronchial hygiene, breathing control, energy conservation techniques, exercise training (endurance and strength), psychological support, and nutritional support. Exercise capacity and VO2 peak were evaluated by using an incremental shuttle walk test (ISWT).
 Results: Eighteen patients who underwent surgery due to NSCLC and had a pre-operative pulmonary rehabilitation program were evaluated. All the cases were male; the mean age was 66.2 (53-77) years. The squamous cell/adenocarcinoma ratio was 2.6 (13:5), and the mean tumor size was 4.6 (8-18) cm. The postoperative hospital stay was 12.7 (4-42) days, and they were followed up for an average of 30.2 (2-83) months. 
 Conclusion: Complete surgical resection is the most effective curative treatment for lung cancer. However, many patients with lung cancer also have severe COPD, increasing their risk of postoperative complications and their likelihood of being considered "inoperable." Preoperative pulmonary rehabilitation (PR) has been proposed as an intervention for risk modification and to decrease surgical morbidity and mortality. The results of our study also revealed the importance of preoperative pulmonary rehabilitation in centers where lung cancer surgery was performed.

Ventilatory limitations in patients with HFpEF and obesity

Heart failure with preserved ejection fraction (HFpEF) patients have an increased ventilatory demand. Whether their ventilatory capacity can meet this increased demand is unknown, especially in those with obesity. Body composition (DXA) and pulmonary function were measured in 20 patients with HFpEF (69 ± 6 yr;9 M/11 W). Cardiorespiratory responses, breathing mechanics, and ratings of perceived breathlessness (RPB, 0–10) were measured at rest, 20 W, and peak exercise. FVC correlated with %body fat (R2 =0.51,P = 0.0006), V̇O2peak (%predicted,R2 =0.32,P = 0.001), and RPB (R2 =0.58,P = 0.0004). %Body fat correlated with end-expiratory lung volume at rest (R2 =0.76,P < 0.001), 20 W (R2 =0.72,P < 0.001), and peak exercise (R2 =0.74,P < 0.001). Patients were then divided into two groups: those with lower ventilatory reserve (FVC<3 L,2 M/10 W) and those with higher ventilatory reserve (FVC>3.8 L,7 M/1 W). V̇O2peak was ∼22% less (p < 0.05) and RPB was twice as high at 20 W (p < 0.01) in patients with lower ventilatory reserve. Ventilatory reserves are limited in patients with HFpEF and obesity; indeed, the margin between ventilatory demand and capacity is so narrow that exercise capacity could be ventilatory limited in many patients.

Progressive tauopathy disrupts breathing stability and chemoreflexes during presumptive sleep in mice.

Rationale: Although sleep apnea occurs in over 50% of individuals with Alzheimer's Disease (AD) or related tauopathies, little is known concerning the potential role of tauopathy in the pathogenesis of sleep apnea. Here, we tested the hypotheses that, during presumptive sleep, a murine model of tauopathy (rTg4510) exhibits: 1) increased breathing instability; 2) impaired chemoreflex function; and 3) exacerbation of these effects with tauopathy progression. Methods: rTg4510 mice initially develop robust tauopathy in the hippocampus and cortex, and eventually progresses to the brainstem. Type I and II post-sigh apnea, Type III (spontaneous) apnea, sigh, and hypopnea incidence were measured in young adult (5-6months; n = 10-14/group) and aged (13-15months; n = 22-24/group) non-transgenic (nTg), monogenic control tetracycline transactivator, and bigenic rTg4510 mice using whole-body plethysmography during presumptive sleep (i.e., eyes closed, curled/laying posture, stable breathing for >200 breaths) while breathing room air (21% O2). Peripheral and central chemoreceptor sensitivity were assessed with transient exposures (5min) to hyperoxia (100% O2) or hypercapnia (3% and 5% CO2 in 21% O2), respectively. Results: We report significant increases in Type I, II, and III apneas (all p < 0.001), sighs (p = 0.002) and hypopneas (p < 0.001) in aged rTg4510 mice, but only Type III apneas in young adult rTg4510 mice (p < 0.001) versus age-matched nTg controls. Aged rTg4510 mice exhibited profound chemoreflex impairment versus age matched nTg and tTA mice. In rTg4510 mice, breathing frequency, tidal volume and minute ventilation were not affected by hyperoxic or hypercapnic challenges, in striking contrast to controls. Histological examination revealed hyperphosphorylated tau in brainstem regions involved in the control of breathing (e.g., pons, medullary respiratory column, retrotrapezoid nucleus) in aged rTg4510 mice. Neither breathing instability nor hyperphosphorylated tau in brainstem tissues were observed in young adult rTg4510 mice. Conclusion: Older rTg4510 mice exhibit profound impairment in the neural control of breathing, with greater breathing instability and near absence of oxygen and carbon-dioxide chemoreflexes. Breathing impairments paralleled tauopathy progression into brainstem regions that control breathing. These findings are consistent with the idea that tauopathy per se undermines chemoreflexes and promotes breathing instability during sleep.

Liver stereotactic body radiation therapy without fiducial or retained ethiodized oil guidance warrants greater than 5 mm planning target volumes.

For liver stereotactic body radiation therapy (SBRT), the placement of fiducial markers or retained ethiodized oil by transarterial chemoembolisation (TACE) provides a landmark for consistent target localisation. TACE and fiducial markers are invasive procedures that harbour additional risks. We hypothesise that liver SBRT can be accurately delivered without the use of these invasive surrogate markers. We retrospectively identified 50 consecutive patients who underwent liver SBRT with respiratory motion management to a single lesion which exhibited retained ethiodized oil per prior TACE delivery. For each SBRT fraction, two manual rigid image registrations were performed by the treating physician. One using the liver contour as a surrogate for the target and second aligning only to the radio-opaque retained ethiodized oil of the treated lesion. The magnitude of the displacement vector between the two registration methods was used to assess the accuracy of target localisation if ethiodized oil was not present. For the 50 patients, a total of 244 analysable cone-beam CTs (CBCTs) were included (six CBCTs excluded due to poor ethiodized oil visualisation). Respiratory motion management techniques consisted of active breathing control for 13 and abdominal compression for 37 patients. Forty-two patients had peripheral lesions and eight had central lesions (<2 cm from left and right portal veins). The average target localisation offset between the two registration methods (i.e. liver contour vs. retained ethiodized oil alignment) for patients with a single peripheral or central liver lesion was 5.8 and 5.3 mm, respectively. Across all patients, the average change in target position exceeded 5 mm for image registration methods based on the liver contour alone versus the retained ethiodized oil region. This suggests that margins greater than 5 mm may be required for respiratory motion-managed liver SBRT treatments in patients who do not undergo prior TACE or fiducial placement.