Ventilation Output Research Articles

Ethanol abolishes ventilatory long-term facilitation and blunts the ventilatory response to hypoxia in female rats

Obstructive sleep apnea (OSA) is a breathing disorder in which airway obstruction during sleep leads to periodic bouts of inadequate (hypopneic) or absent (apneic) ventilation despite neurorespiratory effort. Repetitive apneic and hypopneic exposures can induce intermittent hypoxemia and lead to a host of maladaptive behavioral and physiological outcomes. Intermittent hypoxia treatment (IH), which consists of alternating exposure to hypoxic and normal air, can induce a long-lasting increase in breathing motor outputs called long term facilitation (LTF). IH models key aspects of the hypoxemia experienced during OSA and LTF might serve to prevent OSA or ameliorate its severity by stimulating ventilatory output during or after apnea/hypopnea. Ethanol consumption prior to sleep exacerbates existing OSA, but it is unknown how ethanol affects LTF expression. Thus, we hypothesized that ethanol treatment would attenuate LTF expression and the magnitude of the ventilatory response during acute hypoxic exposure. We administered either low-dose (0.8g/kg) or high-dose (3g/kg) ethanol or saline to adult female Sprague-Dawley rats through intraperitoneal injection and then measured subjects’ ventilatory output by whole-body plethysmography during baseline, a 5 by 3-minute moderate IH protocol (hypoxia: FiO2 = 0.11, Normoxia: room air), and for one hour following the end of IH. Results indicate that low-dose ethanol abolishes LTF of respiratory rate and minute ventilation and trends suggest that low-dose ethanol might attenuate respiratory rate and minute ventilation during acute hypoxic exposure. While high-dose ethanol significantly diminished subjects’ respiratory rate and minute ventilation during hypoxia, LTF expression was not significantly different between high-dose ethanol and saline-treated subjects. Overall, data indicate that ethanol exposure dramatically attenuates LTF expression following IH treatment and impairs ventilatory responses to hypoxia in a dose-dependent manner. Such findings inspire further consideration of ethanol’s negative effects upon endogenous compensatory mechanisms for repeated hypoxic exposure, both in the context of OSA and beyond.

Ethanol pre-exposure attenuates the hypoxic ventilatory response and may attenuate expression of long term facilitation following intermittent hypoxia treatment in adult rats

Obstructive sleep apnea (OSA) is a highly prevalent breathing disorder in which airway collapse or obstruction during sleep leads to periodic bouts of inadequate (hypopneic) or absent (apneic) ventilation despite neurorespiratory effort. Repetitive apneic and hypopneic exposures during sleep can induce intermittent hypoxemia, sympathetic activation, and sleep fragmentation which can lead to a host of maladaptive behavioral and physiological outcomes. Intermittent hypoxia, which consists of alternating exposure to hypoxia and normal oxygen levels (normoxia), can induce a long-lasting increase in breathing motor output called long term facilitation (LTF) and is currently being investigated as a therapeutic treatment. Interestingly, experts in the field of LTF have noted how IH models some key aspects of OSA. It has been well established through clinical studies that ethanol consumption prior to sleep exacerbates existing OSA, increasing the apnea/hypopnea index and worsening arterial blood oxygen desaturations during the night. However, it is unknown whether ethanol affects expression of LTF following IH treatment. If LTF might serve as a means of increasing ventilatory output to compensate for periods of apnea and hypopnea during OSA, ethanol might not only worsen the severity of OSA, but impede individuals’ compensatory response. Thus, for this study we hypothesized that ethanol treatment would attenuate LTF expression and the magnitude of the hypoxic ventilatory response during IH treatment. Using adult female Sprague-Dawley rats, we administered either low-dose (0.8 g/kg) or high-dose (3 g/kg) ethanol through intraperitoneal injection to model a 2-drink nightcap or binge drinking-type ethanol exposure, respectively. Immediately afterwards, we measured subjects’ ventilatory output during baseline, then during a 5 by 3-minute moderate IH protocol, and for one hour following the end of IH using whole-body plethysmography. Finally, we took venous blood samples to assay serum ethanol concentration at the end of the approximately 2.5 hour plethysmography measurement. Results from the high-dose ethanol group indicate that ethanol pre-exposure might attenuate respiratory rate and minute volume LTF in comparison to saline-treated control. Furthermore, high-dose ethanol attenuated the hypoxic ventilatory response with respect to respiratory rate and minute volume. Low dosage of ethanol attenuated subjects’ HVR of respiratory rate and minute volume, but conflictingly trends towards increasing LTF of tidal volume while diminishing LTF of respiratory rate when compared to saline control. Overall, our findings indicate that high levels of ethanol exposure dramatically diminish the acute ventilatory response to hypoxic exposure and may impede long-term increases in ventilatory output following IH treatment. On the other hand, lower doses of ethanol have a subtler effect on the ventilatory response to hypoxia. Future directions will include analysis of additional parameters of ventilatory function to gain a more detailed understanding of how ethanol effects respiratory plasticity in the context of intermittent hypoxic exposure. NIH 5T32 AA027488 to ALSUniversity of Kentucky Endowment to WJA. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effect of Ventilator Settings on Mechanical Power During Simulated Mechanical Ventilation of Patients With ARDS.

In recent years, mechanical power (MP) has emerged as an important concept that can significantly impact outcomes from mechanical ventilation. Several individual components of ventilatory support such as tidal volume (VT), breathing frequency, and PEEP have been shown to contribute to the extent of MP delivered from a mechanical ventilator to patients in respiratory distress/failure. The aim of this study was to identify which common individual setting of mechanical ventilation is more efficient in maintaining safe and protective levels of MP using different modes of ventilation in simulated subjects with ARDS. We used an interactive mathematical model of ventilator output during volume control ventilation (VCV) with either constant inspiratory flow (VCV-CF) or descending ramp inspiratory flow, as well as pressure control ventilation (PCV). MP values were determined for simulated subjects with mild, moderate, and severe ARDS; and whenever MP > 17 J/min, VT, breathing frequency, or PEEP was manipulated independently to bring back MP to ≤ 17 J/min. Finally, the optimum VT-breathing frequency combinations for MP = 17 J/min were determined with all 3 modes of ventilation. VCV-CF always resulted in the lowest MPs while PCV resulted in highest MPs. Reductions in VT were the most efficient for maintaining safer and protective MP. At targeted MPs of 17 J/min and maximized minute ventilation, the optimum VT-breathing frequency combinations were 250-350 mL for VT and 32-35 breaths/min for breathing frequency in mild ARDS, 200-350 mL for VT and 34-40 breaths/min for breathing frequency in moderate ARDS, and 200-300 mL for VT and 37-45 breaths/min for breathing frequency for severe ARDS. VCV-CF resulted in the lowest MP. VT was the most efficient for maintaining safe and protective MP in a mathematical simulation of subjects with ARDS. In the context of maintaining low and safe MPs, ventilatory strategies with lower-than-normal VT and higher-than-normal breathing frequency will need to be implemented in patients with ARDS.

Estimation of airway resistance throughout the bronchial tree from mechanical ventilation output data

Estimation of airway resistance throughout the bronchial tree from mechanical ventilation output data

Design and Build a Ventalitor Tester With PIP and PIF Waveform Displays As Validation (PIP)

PIP (Peak Inspiratory Pressure) is the highest level of pressure exerted into the lungs by the ventilator during inhalation. This PIP parameter is important for monitoring because inappropriate PIP values ​​can lead to fatal errors in patients. PIP should be kept below 20 to 25 cm H2O each time ventilation. This PIP control can be a value as well as a waveform. This waveform display is also used to validate the ventilator output. Checking the output on this ventilator is used using a ventilator tester. The purpose of this research is to get the accuracy and precision of the sensor to display the waveform and PIP value of the ventilator output. The procedure of this research is to use MPX5010GP to detect the pressure value on the ventilator and then display the value and waveform of the PIP. From this study, the results of the measurement of accuracy and precision from the MPX5010 sensor to detect PIP and display a waveform graph are said to be good. This is because the highest error value is ±6.27% at the 15 CmH20 setting. While the value of the largest standard deviation at the 15 CmH20 setting is 0.837 and the greatest uncertainty value at the 15 CmH20 setting is 0.033. Then, the largest correction value is found in the 25 CmH20 setting, which is 1.56. PIF monitoring is carried out to maximize service to patients and maximize ventilator care.

Hypoxic ventilatory response and respiratory chemosensitivity in differing rat models of female sex hormone loss

Respiratory function is modulated by circulating sex steroids. Specifically, concentrations of circulating 17β-estradiol and progesterone regulate the responsiveness of the respiratory system in adult female rats. Progesterone was first noted to influence breathing following the observation that pregnancy impacted blood gasses. 17β-estradiol is the most abundant and neuroactive form of estrogen, and female respiratory neuroplasticity is dependent on its presence. Circulating sex hormone levels fluctuate across the normal estrus cycle and gradually decline as part of the natural aging process. The specific influences of sex hormones on hypoxic ventilatory response (HVR) and chemosensitivity are slowly emerging in the literature. A developing pattern is that short-term hormone fluctuations, such as estrus cycle, do not appear to significantly change basic respiratory responsiveness. However, less is known about larger hormone shifts, such as those following the loss of gonads or with natural aging. We hypothesized that the loss of sex hormones would differentially impact HVR and chemosensitivity in an ovariectomy (OVX) model versus a naturally aged female rat. Specifically, we theorized that aged rats would demonstrate reduced sensitivity to hypoxia and reduced dynamic range within ventilatory output, as compared to OVX and intact female rats. Three experimental groups of female rats were used: young rats (3 mos old; n=4), young OVX rats (n=5), and aged rats (>24 mos old; n=5). Chemosensitivity was measured during progressive hypoxic challenges at 15%, 12%, and 9% oxygen (O 2 ) using unrestrained barometric plethysmography. Serum samples were taken for measurement of estrogen (E 2 ) and progesterone (P) using ELISA assays. At the highest level of hypoxia (9% O 2 ), all groups exhibited intact chemosensitivity as demonstrated by significant changes in minute ventilation (V E ; < 0.05), V E controlling for metabolism (V E / VCO 2 ; < 0.05), and respiratory neural drive (calculated as the ratio of tidal volume (T V ) to inspiratory time (Ti), controlling for metabolism; T V /T i /VCO 2 ; < 0.05). Further analysis showed that young and OVX groups demonstrated greater sensitivity to hypoxia as compared to the aged group. Using analyses targeting rate of change, the young and OVX groups had a faster rate of change in V E , V E / VCO 2 , and T V /T i /VCO 2 (< 0.05) as the hypoxia intensity increased. ELISA analyses suggest that E 2 , but not P, concentration is significantly correlated with these results (< 0.05). Collectively, these data indicate that aging impacts respiratory function in complex and unique ways that differ from OVX in female rats. This may be significant since OVX is commonly used as a model of age-related physiological changes. University of Minnesota BIRCWH/Women's Health Research Program Seed Grant, National Heart Lungs Brain Institute R01HL146477, Rehabilitation Science Graduate Program, UMN Medical School This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Identification of Breathing Pattern Disorder in Athletes With Exercise-Induced Laryngeal Obstruction: A Novel Assessment Tool

To report the diagnostic utility of the novel, high-ventilatory task assessment tool called the Milstein Breathing Pattern Assessment Index (M-BPAI) for evaluation of Breathing Pattern Disorder (BPD) in athletes with and without breathing difficulty, and to evaluate the prevalence of BPD in athletes referred for Exercise Induced Laryngeal Obstruction (EILO). BPD is an abnormal respiratory biomechanical pattern caused from functional or structural factors. The presence of BPD in athletes with EILO is unknown. The current clinical evaluations of dysfunctional breathing patterns are limiting for evaluation of BPD in patients with EILO, as these only evaluate the patients in low ventilatory output tasks of rest breathing. In this prospective study, a total of 77 athletes referred to the clinic for suspected EILO and 58 athletes without any respiratory difficulty underwent M-BPAI assessment. Data collection from the experimental group also included the Dyspnea Index, and laryngeal video endoscopic provocation test. The M-BPAI score was significantly larger in the patient group compared to the control group. An overall M-BPAI score of ≥8 corresponds to the AUC of 0.87 (95% CI: 0.81-0.93) with a sensitivity of 0.862 and specificity of 0.792. A total of 60 (78%) patients had an overall M-BPAI score of ≥8. The M-BPAI has the potential to be a valuable clinical diagnostic marker for identifying BPD in patients with suspected EILO with further research and validation.

Design and Build a Ventilator Tester with a Peak Inspiratory Flow Waveform Display as Validation using the F1031V Sensor

The ventilator is a supporter of respiratory needs which is very important for the patient so that there are several parameters that must be monitored specifically, such as the measurement of pressure and flow rate used in the ventilator system, the accuracy of which must be in accordance with the accuracy of the respirator. One of the important parameters to monitor is PIF (Peak Inspiratory Flow) which is the peak inspiratory flow rate given through the ventilator. PIF that is too high or too low can cause adverse effects on the patient. PIF monitoring can be seen through the PIF value and waveform on the PIF. Monitoring the waveform of the PIF will be very useful to improve the results of using the ventilator. The purpose of this research is to get the accuracy and precision of the sensor to display the waveform of the ventilator output. The procedure carried out is to use the F1031V sensor to detect the flow generated by the ventilator and then detect the PIF value and PIF waveform. From this research, the measurement of accuracy and precision of the F1031V sensor to detect PIF and generate a waveform graph is said to be good. This is because the highest error value is ±2.04% at the 20 LPM setting. While the value of the largest standard deviation at the 30 LPM setting is 1.517 and the greatest uncertainty value at the 30 LPM setting is 0.061. Then, the largest correction value is found in the setting of 20 LPM and 30 LPM, namely 0.4. PIF monitoring is carried out to maximize patient care and reduce the breakdown time on the ventilator.

Periodic Modulation and Functional Demonstrations of Mechanically Operated Reciprocating Ventilator

Abstract: During this period of COVID-19 pandemic, the lack of medical equipment (like ventilators) leads to complications arising in the medical field. A low-cost ventilator seems to be an alternative substitute to fill the lacking. This paper presents a numerical analysis for predicting the delivered parameters of a low-cost mechanical ventilator. Based on several manufactured mechanical ventilators, two proposed designs are investigated in this study. Fluid-structure interaction (FSI) analysis is used for solving any problems with the first design, and computational fluid dynamic (CFD) analysis with moving boundary is used for solving any issues with the second design. For this purpose, ANSYS Workbench platform is used to solve the set of equations. The results showed that the Ambu-bag-based mechanical ventilator exhibited difficulties in controlling ventilation variables, which certainly will cause serious health problems such as barotrauma. The mechanical ventilator based on piston-cylinder is more satisfactory with regards to delivered parameters to the patient. The ways to obtain pressure control mode (PCM) and volume control mode (VCM) are identified. Finally, the ventilator output is highly affected by inlet flow, length of the cylinder, and piston diameter.

Compensatory responses to increased mechanical abnormalities in COPD during sleep.

To assess whether night-time increases in mechanical loading negatively impact respiratory muscle function in COPD and whether compensatory increases in inspiratory neural drive (IND) are adequate to stabilize ventilatory output and arterial oxygen saturation, especially during sleep when wakefulness drive is withdrawn. 21 patients with moderate-to-severe COPD and 20 age-/sex-matched healthy controls (CTRL) participated in a prospective, cross-sectional, one-night study to assess the impact of COPD on serial awake, supine inspiratory capacity (IC) measurements and continuous dynamic respiratory muscle function (esophageal manometry) and IND (diaphragm electromyography, EMGdi) in supine sleep. Supine inspiratory effort and EMGdi were consistently twice as high in COPD versus CTRL (p < 0.05). Despite overnight increases in awake total airways resistance and dynamic lung hyperinflation in COPD (p < 0.05; not in CTRL), elevated awake EMGdi and respiratory effort were unaltered in COPD overnight. At sleep onset (non-rapid eye movement sleep, N2), EMGdi was decreased versus wakefulness in COPD (-43 ± 36%; p < 0.05) while unaffected in CTRL (p = 0.11); however, respiratory effort and arterial oxygen saturation (SpO2) were unchanged. Similarly, in rapid eye movement (stage R), sleep EMGdi was decreased (-38 ± 32%, p < 0.05) versus wakefulness in COPD, with preserved respiratory effort and minor (2%) reduction in SpO2. Despite progressive mechanical loading overnight and marked decreases in wakefulness drive, inspiratory effort and SpO2 were well maintained during sleep in COPD. Preserved high inspiratory effort during sleep, despite reduced EMGdi, suggests continued (or increased) efferent activation of extra-diaphragmatic muscles, even in stage R sleep. The COPD data reported herein were secondary data (Placebo arm only) obtained through the following Clinical Trial: "Effect of Aclidinium/Formoterol on Nighttime Lung Function and Morning Symptoms in Chronic Obstructive Pulmonary Disease" ( https://clinicaltrials.gov/ct2/show/NCT02429765 ; NCT02429765).

Ventilator output splitting interface 'ACRA': Description and evaluation in lung simulators and in an experimental ARDS animal model.

The current COVID-19 pandemic has led the world to an unprecedented global shortage of ventilators, and its sharing has been proposed as an alternative to meet the surge. This study outlines the performance of a preformed novel interface called 'ACRA', designed to split ventilator outflow into two breathing systems. The 'ACRA' interface was built using medical use approved components. It consists of four unidirectional valves, two adjustable flow-restrictor valves placed on the inspiratory limbs of each unit, and one adjustable PEEP valve placed on the expiratory limb of the unit that would require a greater PEEP. The interface was interposed between a ventilator and two lung units (phase I), two breathing simulators (phase II) and two live pigs with heterogeneous lung conditions (phase III). The interface and ventilator adjustments tested the ability to regulate individual pressures and the resulting tidal volumes. Data were analyzed using Friedman and Wilcoxon tests test (p < 0.05). Ventilator outflow splitting, independent pressure adjustments and individual tidal volume monitoring were feasible in all phases. In all experimental measurements, dual ventilation allowed for individual and tight adjustments of the pressure, and thus volume delivered to each paired lung unit without affecting the other unit's ventilation-all the modifications performed on the ventilator equally affected both paired lung units. Although only suggested during a dire crisis, this experiment supports dual ventilation as an alternative worth to be considered.

Obesity Blunts the Ventilatory Response to Exercise in Men and Women.

Rationale: Obesity presents a mechanical load to the thorax, which could perturb the generation of minute ventilation (V̇e) during exercise. Because the respiratory effects of obesity are not homogenous among all individuals with obesity and obesity-related effects could vary depending on the magnitude of obesity, we hypothesized that the exercise ventilatory response (slope of the V̇e and carbon dioxide elimination [V̇co2] relationship) would manifest itself differently as the magnitude of obesity increases.Objectives: To investigate the V̇e/V̇co2 slope in an obese population that spanned across a wide body mass index (BMI) range.Methods: A total of 533 patients who presented to a surgical weight loss center for pre-bariatric surgery testing performed an incremental maximal cycling test and were studied retrospectively. The V̇e/V̇co2 slope was calculated up to the ventilatory threshold. Patients were examined in groups based on BMI (category 1: 30-39.9 kg/m2, category 2: 40-49.9 kg/m2, and category 3: ≥50 kg/m2). Because the respiratory effects of obesity could be sex and/or age specific, we further examined patients in groups by sex and age (younger: <50 yr and older: ≥50 yr). Differences in the V̇e/V̇co2 slope were then compared between BMI category, age, and sex using a three-way ANOVA.Results: No significant BMI category by sex by age interactions was detected (P = 0.75). The V̇e/V̇co2 slope decreased with increases in BMI (category 1, 29.1 ± 4.0; category 2, 28.4 ± 4.1; and category 3, 27.1 ± 3.3) and was elevated in women (28.9 ± 4.1) compared with men (26.7 ± 3.2) (BMI category by sex interaction, P < 0.05). No age-related differences were observed (BMI category by age interaction, P = 0.55). The partial pressure for end-tidal CO2 was elevated at the ventilatory threshold in BMI category 3 compared with BMI categories 1 and 2 (both P < 0.01).Conclusions: These findings suggest that obesity presents a unique challenge to augmenting ventilatory output relative to CO2 elimination, such that the increase in the exercise ventilatory response becomes blunted as the magnitude of obesity increases. Further studies are required to investigate the clinical consequences and the mechanisms that may explain the attenuation of exercise ventilatory response with increasing BMI in men and women with obesity.

Design and simulation of mechanical ventilators.

During this period of COVID-19 pandemic, the lack of medical equipment (like ventilators) leads to complications arising in the medical field. A low-cost ventilator seems to be an alternative substitute to fill the lacking. This paper presents a numerical analysis for predicting the delivered parameters of a low-cost mechanical ventilator. Based on several manufactured mechanical ventilators, two proposed designs are investigated in this study. Fluid-structure interaction (FSI) analysis is used for solving any problems with the first design, and computational fluid dynamic (CFD) analysis with moving boundary is used for solving any issues with the second design. For this purpose, ANSYS Workbench platform is used to solve the set of equations. The results showed that the Ambu-bag-based mechanical ventilator exhibited difficulties in controlling ventilation variables, which certainly will cause serious health problems such as barotrauma. The mechanical ventilator based on piston-cylinder is more satisfactory with regards to delivered parameters to the patient. The ways to obtain pressure control mode (PCM) and volume control mode (VCM) are identified. Finally, the ventilator output is highly affected by inlet flow, length of the cylinder, and piston diameter.

Comparative study of intravenous butorphanol versus intravenous clonidine for prevention of intraoperative shivering under spinal anaesthesia

Background: Shivering is a common problem during the perioperative period, in surgeries done under regional anesthesia. Shivering is a potentially serious complication, resulting in increased metabolic rate; increased oxygen consumption along with raised carbon dioxide production; ventilation and cardiac output; adverse postoperative outcomes, such as wound infection; increased surgical bleeding; and morbid cardiac events.4,5 Present study aimed to compare the efficacy of butorphanol versus clonidine for control of shivering in patients undergoing surgeries under spinal anaesthesia. Material and Methods: Present study was conducted patients aged between 18-60 years, of either sex, ASA physical status I/II, scheduled for elective lower abdominal surgeries under subarachnoid block. 60 Patients were randomly allocated using a computer generated table of random numbers. Group B (n= 30) received intravenous bolus butorphanol 1 mg while group C (n= 30) received an intravenous bolus of 150 μg (1 mL) clonidine. Results: In present study, 60 patients were randomly allocated into group B (n= 30, received butorphanol) and group C (n= 30, received clonidine). Age (years), weight (Kg), BMI(Kg/m2), Gender (Male/Female), ASA grade, duration of surgery (min) and baseline axillary temperature were comparable between both groups and no statistically significant difference was noted among them. In butorphanol group an earlier onset of sensory as well as motor block and prolonged duration of sensory as well as motor block was noted as compared to clonidine group and difference was statistically significant. In present study, higher incidence of shivering was noted in clonidine group as compared to butorphanol group and difference was statistically significant. Side effects, such as hypotension, nausea and vomiting werer more in clonidine group as compared to butorphanol group and difference was statistically significant. Bradycardia was noted in both groups in 3 patients. Conclusion: Intravenous butorphanol is a safe and effective for prevention of shivering as well as had early onset and prolonged duration of sensory/motor block.

Mechanisms underlying the sensation of dyspnea.

Dyspnea is defined as a subjective experience of breathing discomfort that consists of qualitatively distinct sensations that vary in intensity. It is a common symptom among patients with respiratory diseases that reduces daily activities, induces deconditioning, and is self-perpetuating. Although clinical interventions are needed to reduce dyspnea, its underlying mechanism is poorly understood depending on the intertwined peripheral and central neural mechanisms as well as emotional factors. Nonetheless, experimental and clinical observations suggest that dyspnea results from dissociation or a mismatch between the intended respiratory motor output set caused by the respiratory neuronal network in the lower brainstem and the ventilatory output accomplished. The brain regions responsible for detecting the mismatch between the two are not established. The mechanism underlying the transmission of neural signals for dyspnea to higher sensory brain centers is not known. Further, information from central and peripheral chemoreceptors that control the milieu of body fluids is summated at higher brain centers, which modify dyspneic sensations. The mental status also affects the sensitivity to and the threshold of dyspnea perception. The currently used methods for relieving dyspnea are not necessarily fully effective. The search for more effective therapy requires further insights into the pathophysiology of dyspnea.

Inhaled Albuterol Increases Forced Mid-expiratory Flows In Non-asthmatic Children With And Without Obesity

PURPOSE: The effect of albuterol on β2-adrenoceptor activation is usually assessed by a significant increase in forced expiratory volume in one second (FEV1). However, even without a significant increase in FEV1, an increase in isovolume forced expiratory flow between 25% and 75% (isoFEF25-75) of forced vital capacity (FVC) would allow for greater exercise tidal flow rates thus increasing ventilatory capacity (V̇Ecap). This could be particularly important in children with obesity, who breathe at low lung volumes and have limited expiratory reserves. We examined if isoFEF25-75 and V̇Ecap increase with albuterol in non-asthmatic prepubescent children with and without obesity. METHODS: A total of 46 obese (n=29 boys) and 29 nonobese (n=14 boys) children, ages 8-12yr, performed spirometry according to the American Thoracic Society guidelines before and after 360μg of albuterol. Subjects who displayed ≥12% and ≥200mL increase in FEV1 after albuterol were excluded. For each individual, V̇Ecap was determined using an estimated tidal volume at maximal exercise (‘VTmax’ = FVC/2) and forced expiratory time between 25% and 75% of FVC (FET25-75) to estimate an individualized maximum breathing frequency (fbmax), where V̇Ecap = VTmax*fbmax. A two-way ANOVA with repeated measures (obese x nonobese; pre- x post-inhaler) was conducted. RESULTS: No significant group by treatment interaction was detected. No significant differences were detected in spirometry parameters between children with and those without obesity. From pre- to post-inhaler in the total cohort of children (n=75), FVC significantly decreased (-0.70%, p = 0.04). While there was a statistically significant increase in peak expiratory flow (+3.0%, p = 0.02), FEV1 (+2.6%, p < 0.01) and FEV1/FVC (+3.0%, p < 0.01), there were more meaningful increases in isoFEF25-75 (+17.1%, p < 0.01) and V̇Ecap (+15.5%, p < 0.01).CONCLUSIONS: Administration of albuterol can increase isoFEF25-75 despite a relatively small nonclinical increase in FEV1. The remarkable increase in flow rates along the effort-independent portion of a forced expiration yields a large increase in V̇Ecap, which could potentially change breathing mechanics and ventilatory output during heavy exercise in non-asthmatic prepubescent children with and without obesity.

19 Y/o Male Marine Experiencing Exercise-induced Laryngeal Obstruction (eilo) During Military Training.

HISTORY: 19 year old male with a long history of shortness of breath on exertion. States that since childhood he has had inspiratory wheezing and tightness in chest with exertion, but he was told he would outgrow it. More recently, he has noted that it has worsened with maximal exertion during military training. He states that he is unable to run all out once around the track without experiencing inspiratory difficulty with gasping. It takes about 10 minutes for him to recover. If he resumes exercise it will recur. Asthma inhalers have not helped. Episodes are associated with pain and dysphagia. PHYSICAL EXAMINATION: Laryngeal examination shows that there is reduced abduction of the vocal folds, with a maximum glottic space of about 6 mm. During high ventilatory output tasks there is evidence of paradoxical movement of the vocal folds, most prominently on inspiration, resulting in shortness of breath, and loud stridor on inspiration. Cardiac: RRR, without murmur Lungs: Clear to Auscultation bilaterally"at rest", Loud inspiratory stridor during “high ventilation”.MSK: Significant muscle tension dyspnea, an inefficient breathing pattern with an upper torso / clavicular breathing, and hyperfunction of strap muscles. DIFFERENTIAL DIAGNOSIS:- Hypertrophic Obstructive Cardiomyopathy (HOCM)- Asthma- Exercise-Induced Bronchoconstricion (EIB)- Exercise-Induced Laryngeal Obstruction (EILO)- Exercise-Induced Anaphylaxis (EIA) TEST AND RESULTS: Cardiopulmonary Exercist Test (CPET): negative. Spirometry with methacholine challenge: negative. Laryngeal function Study: videoendoscopy with stroboscopy revealed reduced abduction of the vocal folds. During high ventilatory provocative challenge, there was evidence of paradoxical movement of the vocal folds, most prominently on inspiration, resulting in shortness of breath, and loud stridor on inspiration. FINAL/WORKING DIAGNOSIS: Exercise-Induced Laryngeal Obstruction (EILO) Patient has developed poor breathing patterns with reduced bilateral vocal fold abduction. TREATMENT AND OUTCOMES: Breathing Retraining Therapy (4-6 sessions). Patient report significant improvement in symptoms after 2nd session, and complete resolution of symptoms following the 5th session. Remaining symptom free for 4 months.

Assessment of spontaneous breathing during pressure controlled ventilation with superimposed spontaneous breathing using respiratory flow signal analysis

Integrating spontaneous breathing into mechanical ventilation (MV) can speed up liberation from it and reduce its invasiveness. On the other hand, inadequate and asynchronous spontaneous breathing has the potential to aggravate lung injury. During use of airway-pressure-release-ventilation (APRV), the assisted breaths are difficult to measure. We developed an algorithm to differentiate the breaths in a setting of lung injury in spontaneously breathing ewes. We hypothesized that differentiation of breaths into spontaneous, mechanical and assisted is feasible using a specially developed for this purpose algorithm. Ventilation parameters were recorded by software that integrated ventilator output variables. The flow signal, measured by the EVITA® XL (Lübeck, Germany), was measured every 2 ms by a custom Java-based computerized algorithm (Breath-Sep). By integrating the flow signal, tidal volume (VT) of each breath was calculated. By using the flow curve the algorithm separated the different breaths and numbered them for each time point. Breaths were separated into mechanical, assisted and spontaneous. Bland Altman analysis was used to compare parameters. Comparing the values calculated by Breath-Sep with the data from the EVITA® using Bland–Altman analyses showed a mean bias of − 2.85% and 95% limits of agreement from − 25.76 to 20.06% for MVtotal. For respiratory rate (RR) RRset a bias of 0.84% with a SD of 1.21% and 95% limits of agreement from − 1.53 to 3.21% were found. In the cluster analysis of the 25th highest breaths of each group RRtotal was higher using the EVITA®. In the mechanical subgroup the values for RRspont and MVspont the EVITA® showed higher values compared to Breath-Sep. We developed a computerized method for respiratory flow-curve based differentiation of breathing cycle components during mechanical ventilation with superimposed spontaneous breathing. Further studies in humans and optimizing of this technique is necessary to allow for real-time use at the bedside.

Dyspnea in COPD: New Mechanistic Insights and Management Implications.

Dyspnea is the most common symptom experienced by patients with chronic obstructive pulmonary disease (COPD). To avoid exertional dyspnea, many patients adopt a sedentary lifestyle which predictably leads to extensive skeletal muscle deconditioning, social isolation, and its negative psychological sequalae. This “dyspnea spiral” is well documented and it is no surprise that alleviation of this distressing symptom has become a key objective highlighted across COPD guidelines. In reality, this important goal is often difficult to achieve, and successful symptom management awaits a clearer understanding of the underlying mechanisms of dyspnea and how these can be therapeutically manipulated for the patients’ benefit. Current theoretical constructs of the origins of activity-related dyspnea generally endorse the classical demand–capacity imbalance theory. Thus, it is believed that disruption of the normally harmonious relationship between inspiratory neural drive (IND) to breathe and the simultaneous dynamic response of the respiratory system fundamentally shapes the expression of respiratory discomfort in COPD. Sadly, the symptom of dyspnea cannot be eliminated in patients with advanced COPD with relatively fixed pathophysiological impairment. However, there is evidence that effective symptom palliation is possible for many. Interventions that reduce IND, without compromising alveolar ventilation (VA), or that improve respiratory mechanics and muscle function, or that address the affective dimension, achieve measurable benefits. A common final pathway of dyspnea relief and improved exercise tolerance across the range of therapeutic interventions (bronchodilators, exercise training, ambulatory oxygen, inspiratory muscle training, and opiate medications) is reduced neuromechanical dissociation of the respiratory system. These interventions, singly and in combination, partially restore more harmonious matching of excessive IND to ventilatory output achieved. In this review we propose, on the basis of a thorough review of the recent literature, that effective dyspnea amelioration requires combined interventions and a structured multidisciplinary approach, carefully tailored to meet the specific needs of the individual.

Cardiopulmonary exercise testing may not predict appropriate implantable cardioverter defibrillator therapies in heart failure patients

Background: The prognostic value of cardiopulmonary exercise testing (CPET) variables for major cardiovascular events in patients with heart failure (HF) is widely established. However, the prognostic value of these variables as predictors of appropriate implantable cardioverter-defibrillator (ICD) therapies has not been sufficiently well addressed. This study aimed to evaluate CPET variables such as peak oxygen uptake (VO2 peak), relationship between change in minute ventilation (VE) and carbon dioxide output (VCO2) during incremental exercise (VE/VCO2 slope) and exercise-related periodic breathing (EPB) as appropriate ICD therapy predictors in HF patients.Methods: We retrospectively assessed 61 HF patients who underwent CPET and had ICD implanted for primary prevention. Patients were followed for 767 ± 601 days. Primary outcome was appropriate ICD-delivered therapy, either anti-tachycardia pacing (ATP) or shock.Results: The sample consisted mostly of male patients (65.6%), with severe ventricular dysfunction (mean left ventricular ejection fraction (LVEF) 27 ± 6%). The primary outcome occurred in 20 patients (32%). There were no significant differences in VO2 peak (17.7 ± 4.1 and 16.9 ± 4.5 mL/kg/min), VE/VCO2 slope (39.7 ± 8.4 and 39.6 ± 10.2) or EPB prevalence (20% and 19.5%) in patients with or without appropriate ICD therapy. According to Cox regression analysis, none of the CPET variables were significant predictors of appropriate ICD therapy.Conclusions: In this cohort study of HF patients, CPET variables did not predict appropriate ICD therapies. Further studies with large number of patients are warranted to address this issue.