Inspiratory Resistance Research Articles

Reliability of Tidal Volume in Average Volume Assured Pressure Support Mode.

Remote monitoring is increasingly used in patients who receive home mechanical ventilation. The average volume assured pressure support mode is a target volume pressure preset mode that delivers a given tidal volume (VT) within a range of controlled inspiratory pressures. In a mode such as this, it is important to verify that the VT value retrieved from the ventilator SD card is accurate. A lung model was set with C (Compliance) 0.075 L/cm H2O and RI (Inspiratory resistance)-RE (Expiratory resistance) 15-25 cm H2O/L/s (model 1) or with C 0.050 L/cm H2O and RI 6 cm H2O/L/s (model 2) and 6 cm H2O effort. Three home-care ventilators (A40, PrismaST30, and Vivo40) were set to average volume assured pressure support mode with 0.3 and 0.6 L VT each at PEEP 5 and 10 cm H2O, and were connected to the lung model with and without nonintentional leak. The reference airway pressure and flow were measured by a data logger. VT was expressed in body temperature and pressure saturated. We assessed the difference in VT between the ventilator SD card and a data logger relative to set VT and factors associated with its magnitude. For A40, PrismaST30, and Vivo40, the adjusted mean VT differences between the ventilator SD card and the data logger were -0.053 L (95% CI -0.067 to -0.039 L) (P < .001), -0.002 L (95%CI -0.022 to 0.019 L) (P = .86), and -0.067 L (95% CI -0.007 to 0.127 L) (P = .03), respectively. The partial Spearman correlation coefficients between the ventilator SD card and a data logger were 0.89 (P < .001), 0.59 (P < .001), and 0.78 (P < .001), respectively to the ventilators. The relative variations in measured VT from the set VT were 16.0, -12.0, and 6.7% for the ventilator SD card, and were -2.5, -7.5, and -27.2% for the data logger, respectively. The discrepancy in ventilator between SD card and data logger were influenced by PEEP for the PrismaST30 ventilator, nonintentional leak for the Vivo40 ventilator and PEEP, nonintentional leak, and underlying disease, the effect of each depending on the levels of the other factors, for the A40 ventilator. In the 3 home-care ventilators, the ventilator SD card underestimated VT. Factors involved in this difference differed among the ventilators.

Sex differences in diaphragmatic fatigue: the cardiovascular response to inspiratory resistance.

Diaphragmatic fatigue (DF) elicits a sympathetically mediated metaboreflex resulting in increased heart rate, blood pressure and limb vascular resistance. Women may be more resistant to DF compared to men, and therefore it was hypothesised that women would experience an attenuated inspiratory muscle metaboreflex during inspiratory pressure-threshold loading (PTL) performed to task failure. At the time of PTL task failure, the severity of DF was not different between sexes; however, inspiratory muscle endurance time was significantly longer in women than in men. For a given cumulative diaphragmatic force output, the severity of DF was less in women than in men. Women exhibited a blunted cardiovascular response to inspiratory resistance (i.e. metaboreflex) that may have implications for exercise tolerance. Diaphragmatic fatigue (DF) elicits reflexive increases in sympathetic vasomotor outflow (i.e. metaboreflex). There is some evidence suggesting women may be more resistant to DF compared to men, and therefore may experience an attenuated inspiratory muscle metaboreflex. To this end, we sought to examine the cardiovascular response to inspiratory resistance in healthy young men (n=9, age=24±3years) and women (n=9, age=24±3years). Subjects performed isocapnic inspiratory pressure-threshold loading (PTL, 60% maximal inspiratory mouth pressure) to task failure. Diaphragmatic fatigue was assessed by measuring transdiaphragmatic twitch pressure (Pdi,tw ) using cervical magnetic stimulation. Heart rate (HR) and mean arterial pressure (MAP) were measured beat-by-beat throughout PTL via photoplethysmography, and low-frequency systolic pressure (LFSBP ; a surrogate for sympathetic vasomotor tone) calculated from arterial waveforms using power spectrum analysis. At PTL task failure, the degree of DF was similar between sexes (∼23% reduction in Pdi,tw ; P=0.33). However, time to task failure was significantly longer in women than in men (27±11vs. 16±11min, respectively; P=0.02). Women exhibited less of an increase in HR (13±8vs. 19±12bpm; P=0.02) and MAP (10±8vs. 14±9mmHg; P=0.01), and significantly lower LFSBP (23±11vs. 34±8mmHg2 ; P=0.04) during PTL compared to men. An attenuation of the inspiratory muscle metaboreflex may influence limb and respiratory muscle haemodynamics with implications for exercise performance.

Inspiratory and expiratory resistance cause right-to-left bubble passage through the foramen ovale.

A patent foramen ovale (PFO) is linked to increased risk of decompression illness in divers. One theory is that venous gas emboli crossing the PFO can be minimized by avoiding lifting, straining and Valsalva maneuvers. Alternatively, we hypothesized that mild increases in external inspiratory and expiratory resistance, similar to that provided by a SCUBA regulator, recruit the PFO. Nine healthy adults with a Valsalva‐proven PFO completed three randomized trials (inspiratory, expiratory, and combined external loading) with six levels of increasing external resistance (2–20 cmH2O/L/sec). An agitated saline contrast echocardiogram was performed at each level to determine foramen ovale patency. Contrary to our hypothesis, there was no relationship between the number of subjects recruiting their PFO and the level of external resistance. In fact, at least 50% of participants recruited their PFO during 14 of 18 trials and there was no difference between the combined inspiratory, expiratory, or combined external resistance trials (P > 0.05). We further examined the relationship between PFO recruitment and intrathoracic pressure, estimated from esophageal pressure. Esophageal pressure was not different between participants with and without a recruited PFO. Intrasubject variability was the most important predictor of PFO patency, suggesting that some individuals are more likely to recruit their PFO in the face of even mild external resistance. Right‐to‐left bubble passage through the PFO occurs in conditions that are physiologically relevant to divers. Transthoracic echocardiography with mild external breathing resistance may be a tool to identify divers that are at risk of PFO‐related decompression illness.

PULMONARY GAS EXCHANGE AND ACID-BASE STATUS OF BLOOD UNDER THE USE OF MEANS FOR INDIVIDUAL PROTECTION OF RESPIRATORY ORGANS

The aim of the study was to evaluate the effect of the duration of training on the use of personal respiratory protective equipment on indices of pulmonary gas exchange. Simulation of conditions for the use of personal respiratory protective equipment was carried out at the inspiratory resistance of 40, 60, 70 and 80% Pmmax. The study included 38 healthy male subjects aged 20 to 36 years. According to the results of the study, under the use of personal protective equipment for the respiratory system, preliminary training was shown to be essential. In the subjects without preliminary training, the use of personal protective equipment was followed by a weak change in the nature of the respiratory pattern. After the preliminary training subjects had an adaptive rearrangement of the respiratory pattern, consisted of the decline in breathing movements as the respiratory resistance increased. Preliminary training to the exposure of additional resistance to breathing, altered pulmonary gas exchange and acid-base state of blood. The trained subjects had higher pCO2 blood values and lower values of pO2. They showed a greater deficit of buffer bases of plasma compared to untrained ones. This fact testified the preliminary training for the use of personal respiratory protective equipment (long-term adaptation) changed the gas composition and acid-base state of the blood to be a more economical mode of the discharge of buffer systems. On the basis of the data obtained, the preliminary training for increased respiratory resistance was suggested to be advisable before the using personal respiratory protective equipment.

The Effects of Experimental Sleep Fragmentation and Sleep Deprivation on the Response of the Genioglossus Muscle to Inspiratory Resistive Loads.

Poor upper airway dilator muscle function may contribute to obstructive sleep apnea (OSA). Sleep deprivation reduces dilator muscle responsiveness, but sleep fragmentation, which is most characteristic of OSA, has not been assessed. This study compared the effects of sleep deprivation and fragmentation on dilator muscle responsiveness during wakefulness. Twenty-four healthy individuals (10 female) participated in two consecutive overnight polysomnography (PSG) sessions. The first was an adaptation PSG of normal sleep. The second was an experimental PSG, where participants were allocated to groups of either normal sleep, no sleep, or fragmented sleep. Inspiratory resistive loading assessment occurred the morning following each PSG. Four 10 cmH2O and four 20 cmH2O loads were presented in random order for 60 seconds while participants were awake and supine. Sleep (electroencephalogram, electrooculogram, electromyogram [EMG]), intramuscular genioglossus activity (EMGGG), and ventilation were measured throughout the loading sessions. Five controls, seven sleep deprivation participants, and seven sleep fragmentation participants provided data. Contrary to expectations, neither EMGGG nor ventilation showed significant interaction effects (group × session × load) during resistive loading. There was a main effect of load, with peak EMGGG (mean % max ± standard error) significantly higher for the 20 cmH2O load (4.1 ± 0.6) than the 10 cmH2O load (3.3 ± 0.6) across both sessions and all groups. Similar results were observed for peak inspiratory flow, duty cycle, and mask pressure. Upper airway function was not affected by 1 night of no sleep or poor-quality sleep. This raises doubt as to whether fragmented sleep in OSA increases disorder severity via reduced upper airway dilator responses.

Blunted Sympathetic Vasomotor Outflow To Inspiratory Resistive Breathing During Exercise In Women Compared to Men

It has been reported that in young men high inspiratory muscle work at rest and during exercise reflexively increases muscle sympathetic nerve activity (MSNA), with corresponding increases in arterial blood pressure (ABP). This sympathoexcitation occurs through an inspiratory muscle-induced metaboreflex. Young women have attenuated inspiratory muscle metaboreflex-induced increases in ABP compared to age-matched men. One potential mechanism is less sympathetic vasomotor output in women compared to men. PURPOSE: We compared changes in MSNA and cardiovascular variables during leg cycle exercise with increased inspiratory muscle resistance in men and women. METHODS: Eight young women (19.5±0.2) and seven men (20.3±0.3) completed the study. The subjects performed two 10-min submaximal cycle ergometer exercises in a semirecumbent position. The first 5-min was spontaneous breathing, and latter 5-min half was voluntary hyperventilation with or without inspiratory resistive breathing. Mean arterial blood pressure (MAP) was measured using finger photoplethysmography and MSNA was recorded via microneurography of the arm at the elbow. RESULTS: During exercise with inspiratory resistive breathing, MSNA burst frequency was significantly increased accompanied by an increase (p<0.05) in MAP in both men and women. Women had significantly less of an increase in MSNA (Women: +9.6±1.0 vs. Men: +14.6±2.4 bursts/min) and MAP (Women: +22.8±5.7 vs. Men: +32.2±2.0 mmHg) as compared to men. CONCLUSION: These results suggest that lesser sympathetic vasomotor outflow partially contributes the attenuated inspiratory muscle-induced metaboreflex during exercise in young women. Supported by JSPS KAKENHI Grant Number 15H3079.

Experimentally Manipulating Mechanical Ventilatory Constraint During Exercise Does Not Influence Dyspnea in Older Men and Women

During exercise at a standardized metabolic work load, the perception of dyspnea is higher in older women than older men, which is thought to be related to sex-differences in mechanical ventilatory constraint; however, this hypothesis has yet to be experimentally tested. PURPOSE: To determine the effect of manipulating the magnitude of mechanical ventilatory constraint during submaximal exercise on dyspnea in older men and women. METHODS: Thirteen healthy subjects (60-80 y; n=7 women) completed two days of testing. On Day 1, subjects performed pulmonary function testing and a maximal incremental cycle exercise test. On Day 2, esophageal pressure (Pes) and diaphragm electromyography (EMGdi) were recorded during three constant load cycle exercise tests (6 min each) at ventilatory threshold (VTh). Constant load exercise tests were performed under three conditions in a single blind, randomized, counterbalanced fashion: i) breathing normoxic helium-oxygen gas (HeO2) to reduce the work of breathing (W b ) and alleviate expiratory flow limitation (EFL); ii) inspiratory resistance (RES) of 5 cmH2O·l-1·s-1 to increase W b ; and iii) control (CON) breathing room air. During exercise on Day 2, Pes-derived measures of Wb, EMGdi, and EFL were assessed. RESULTS: During the HeO2 condition, there was a significant decrease in Wb (men=-20±4%, women= -16±5%) and EMGdi (men= -11±7%, women= -9±7%) relative to CON (both p<0.01). Moreover, if EFL was present during the CON condition (n=3 men, n=5 women), it was alleviated during HeO2. Conversely, during the RES condition, there was a significant increase in Wb (men= 34±11%, women= 50±12%) and EMGdi (men=32±15%, women= 23±12%) relative to CON (both p<0.01). The effect of condition on Wb and EMGdi was not significantly different between the sexes (both p>0.05). Across conditions, women reported significantly higher levels of dyspnea than men (3.3±0.4 vs. 1.9±0.4 Borg units, p<0.05). However, despite significant differences in the degree of mechanical ventilatory constraint between conditions, there was no effect of condition on the perception of dyspnea intensity, regardless of sex (p=0.46). CONCLUSION: Our results suggest that during short bouts of exercise at VTh, sex-differences in dyspnea in older adults are not related to sex-differences in mechanical ventilatory constraint.

Thoracoabdominal asynchrony correlates with peripheral vascular resistance changes in a cohort of obese children.

Objective:&nbsp;The purpose of this study was to assess the relationship between the thoracoabdominal asynchrony (phase angle), as an index of inspiratory airflow resistance, pulse transit time arousal index (PTT Ar/I), as changes in peripheral vascular resistance and intrathoracic pressure, and obstructive apnea index (OA), Oxygen Desaturation Index (ODI), snoring (% estimated Total Sleep Time - eTST) and apnea-hypopnea index (AHI) in a cohort of exogenous obese children. Material and Methods:&nbsp;Body mass index (BMI) and BMI z-scores were calculated according to age and sex in 36 consecutive obese children. Nasal patency, tonsil size, Friedman palate position scoring were also recorded. An overnight sleep respiratory recording was performed using an polygraphic ambulatory device. Results:&nbsp;&nbsp;Subjects studies had normal to mild sleep respiratory involvement (assessed by respiratory polysomnographic scoring). Phase angle correlated significantly with PTT Ar/I, but not with AHI (n/hr), OA (n/hr), ODI (n/hr) and snoring (% eTST), even adjusting for nasal patency, tonsil hypertrophy, palate position and BMI (z-score). Conclusion:&nbsp;Thoracoabdominal asynchrony (phase angle) is correlated with peripheral vascular resistance changes (PTT Ar/I), suggesting a subclinical upper respiratory airflow anomaly with autonomic activation in obese subjects

Evaluation of a clinical implementation of a respiratory muscle training group during spinal cord injury rehabilitation.

Retrospective cohort study. To evaluate the clinical implementation of a respiratory muscle training group during rehabilitation of individuals with spinal cord injury. Spinal cord injury rehabilitation center. Individuals with complete or incomplete lesions during inpatient rehabilitation, level C4-T12.Ten or more training sessions of either an inspiratory or a combined in- and expiratory muscle training were performed in a group setting with respiratory function measurements before and after the training period. Analysis of 79 persons. Inspiratory muscle training was performed for 7 weeks with a median of 3.1 training sessions per week. Median training intensity was at 33% of baseline PImax and 58 repetitions were performed per training session. Respiratory mucle strength parameters improved by 18-68% of baseline values and lung function parameters by 11-31% after inspiratory muscle training.The combined respiratory muscle training was performed for 13 weeks with a median of 2.8 sessions per week and 88 repetitions per training session. Median inspiratory training resistance was at 39% of baseline PImax and median expiratory training resistance was at 27% of baseline PEmax. Respiratory muscle strength parameters improved by 14-51% of baseline values and lung function parameters improved by 15-34% after the combined in- and expiratory muscle training. Respiratory resistance training improved respiratory function of individuals with acute spinal cord injury. Even if the combined respiratory muscle training was performed with more repetitions per training and nearly twice as long, relative improvements of respiratory function parameters were comparable with isolated inspiratory muscle training.

Modelling nasal high flow therapy effects on upper airway resistance and resistive work of breathing

AimThe goal of this paper is to quantify upper airway resistance with and without nasal high flow (NHF) therapy. For adults, NHF therapy feeds 30–60 L/min of warm humidified air into the nose through short cannulas which do not seal the nostril. NHF therapy has been reported to increase airway pressure, increase tidal volume (Vt) and decrease respiratory rate (RR), but it is unclear how these findings affect the work done to overcome airway resistance to air flow during expiration. Also, there is little information on how the choice of nasal cannula size may affect work of breathing. In this paper, estimates of airway resistance without and with different NHF flow (applied via different cannula sizes) were made. The breathing efforts required to overcome airway resistance under these conditions were quantified. MethodNHF was applied via three different cannula sizes to a 3-D printed human upper airway. Pressure drop and flow rate were measured and used to estimate inspiratory and expiratory upper airway resistances. The resistance information was used to compute the muscular work required to overcome the resistance of the upper airway to flow. ResultsNHF raises expiratory resistance relative to spontaneous breathing if the breathing pattern does not change but reduces work of breathing if peak expiratory flow falls. Of the cannula sizes used, the large cannula produced the greatest resistance and the small cannula produced the least. The work required to cause tracheal flow through the upper airway was reduced if the RR and minute volume are reduced by NHF. NHF has been observed to do so in COPD patients (Bräunlich et al., 2013). A reduction in I:E ratio due to therapy was found to reduce work of breathing if the peak inspiratory flow is less than the flow below which no inspiratory effort is required to overcome upper airway resistance. ConclusionNHF raises expiratory resistance but it can reduce the work required to overcome upper airway resistance via a fall in inspiratory work of breathing, RR and minute volume.

Inspiratory Resistive (R) Load Endurance Testing in Normal Healthy Adults: Load compensation, effort sensation and affective perception.

Increased respiratory load is a key feature in various respiratory diseases, accompanied by ventilatory compensation, cognitive awareness and affective perception. Loaded breathing can occur from minutes to days requiring the individual to modulate their breathing pattern to maintain alveolar ventilation, minimize work of breathing and minimize aversive load sensations. Increased inspiratory load is associated with cognitive sensation of the load magnitude and affective escape behavior to reduce the aversive perception of loaded breathing. During exacerbations of lung diseases, an individual often must compensate for increased loads that exceed their ability to sustain alveolar ventilation. Yet it is difficult to assess the capacity of an individual to adapt to an increased respiratory load. The aim of this study was to determine the ventilatory and perceptual endurance response to a high magnitude inspiratory R load applied for 10 minutes. It was hypothesized that some individuals would be able to complete the task and other individuals would terminate the task early. It was further hypothesized that early termination of the task would be due to increased aversive affective awareness. Healthy participants were tested while breathing through a non‐rebreathing circuit with an inspiratory load R=50 cmH20/L/s. The individual respired with no‐load for 1 minute, then the load was applied for 10 minutes, followed by 1 minute of no‐load breathing. The subject was instructed that they could terminate the task at any time by removing the mouthpiece. Subjects estimated their perceived load intensity (MEInt) and unpleasantness (MEUn) every minute. Fear (MEF) was estimated before and after the load trial. Two of six subjects terminated the trial early. The ventilatory load pattern for all subjects was a load dependent increased maximum inspiratory pressure, decreased airflow, increased inspiratory duration and unchanged expiratory duration, increased total breath time, increased inspiratory volume, unchanged minute ventilation, PCO2 and PO2. The MEInt increased with the onset of the load, was constant throughout the task and was the same for individuals that completed and stopped the task. MEUn increased with the load onset with greater MEUn for subjects that stopped early. The individuals that stopped early had equal MEF at task onset but much greater MEF when the task stopped. The results suggest that inspiratory R50 endurance capacity is decreased in individuals with greater negative affective responses to high magnitude loaded breathing.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The immediate effects of a single autogenic drainage session on ventilatory mechanics in adult subjects with cystic fibrosis.

IntroductionThe aim of this study was to gain insight into the physiological changes occurring in subjects with cystic fibrosis (CF) after autogenic drainage (AD). Changes in respiratory system resistance (Rrs), reactance (Xrs), and spirometry were analyzed in adult CF subjects after a single AD physiotherapy session.MethodsThis prospective observational study was conducted during the annual check-up of adult CF subjects in stable condition. Spirometry and Rrs and Xrs measurements using the forced oscillations technique at 5, 11, and 19 hertz (Hz) were performed before and 30 min after a 20-min AD session. Control CF subjects were tested at baseline and 50 min without AD. Results are expressed as mean ± standard deviation or median [interquartile range].ResultsThirty subjects were included in the physiotherapy group (age 29 [25–34] years, forced expiratory volume in 1 s (FEV1) 40.3 [30.1–57.9]% predicted) and 11 in the control group (age 31 [28.5–36.5] years, FEV1 43.6 [31.1–51.9] % predicted). No significant changes in any parameter were observed in the control group. AD modestly but significantly increased the forced vital capacity (FVC) and FEV1 (p<0.001). Inspiratory resistance was also significantly improved by AD: Rrs5 from 5.74±2.39 to 5.24±2.17 cmH2O/L/s, p<0.05; Rrs11 from 4.83±1.98 to 4.32±1.7 cmH2O/L/s, p = 0.003; and Rrs19 from 4.18 [3.46–5.07] to 3.86 [2.76–4.98] cmH2O/L/s, p<0.001. In contrast, AD had no significant effects on frequency dependence of resistance (Rrs5–Rrs19) or expiratory resistance. Inspiratory Xrs5, but not ΔXrs5 (expiratory—inspiratory Xrs), was improved by AD (p<0.05). Moderate correlations were detected between the improvement in FEV1 and FVC and inspiratory resistance (r = 0.53, p = 0.005 and r = 0.44, p = 0.02, respectively).ConclusionA single session of AD improved inspiratory airway resistance, except in the distal airways. The forced oscillations technique provides a new tool for understanding the pathophysiological effects of airway clearance physiotherapy in CF.

Elevated sympathetic vasomotor outflow in response to increased inspiratory muscle activity during exercise is less in young women compared with men.

What is the central question of this study? Premenopausal women have an attenuated inspiratory muscle metaboreflex-induced increase in arterial blood pressure compared with men. It is unclear whether sympathetic vasomotor outflow during dynamic exercise with increased inspiratory muscle activation is less in young women than in men. What is the main finding and its importance? The magnitude of increased sympathetic vasomotor outflow during leg cycling with inspiratory resistance was smaller in women than in men. Less sympathetic vasomotor outflow with inspiratory muscle metaboreflex activation could be one of the mechanisms for the attenuated inspiratory muscle-induced metaboreflex during exercise in young women. We compared changes in muscle sympathetic nerve activity (MSNA) and cardiovascular variables during leg cycle exercise with increased inspiratory muscle resistance in men and women. We hypothesized that sympathetic vasomotor outflow during exercise with increased inspiratory resistance would be attenuated in young women compared with age-matched men. Eight women and seven men completed the study. The subjects performed two 10min exercise bouts at 40% peak oxygen uptake using a cycle ergometer in a semirecumbent position [spontaneous breathing for 5min and voluntary hyperventilation with or without inspiratory resistive breathing for 5min (breathing frequency 50breathsmin-1 with a 50% duty cycle; inspiratory resistance 30% of maximal inspiratory pressure)]. Mean arterial blood pressure (MAP) was acquired using finger photoplethysmography. The MSNA was recorded via microneurography of the right median nerve at the cubital fossa. During leg cycle exercise with inspiratory resistive breathing, MSNA burst frequency was increased, accompanied by an increase in MAP in both men and women. Women, compared with men, had less of an increase in MAP (women +22.8±12.3mmHg versus men +32.2±5.4mmHg; P<0.05) and MSNA burst frequency (women +9.6±2.9burstsmin-1 versus men +14.6±6.4burstsmin-1 ; P<0.05). These results suggest that the attenuated inspiratory muscle-induced metaboreflex during exercise in young women is attributable, in part, to a lesser sympathetic vasomotor outflow compared with men.

A Rapid, Handheld Device to Assess Respiratory Resistance: Clinical and Normative Evidence.

Following reports of respiratory symptoms among service members returning from deployment to South West Asia (SWA), an expert panel recommended pre-deployment spirometry be used to assess disease burden. Unfortunately, testing with spirometry is high cost and time-consuming. The airflow perturbation device (APD) is a handheld monitor that rapidly measures respiratory resistance (APD-Rr) and has promising but limited clinical data. Its speed and portability make it ideally suited for large volume pre-deployment screening. We conducted a pilot study to assess APD performance characteristics and develop normative values. We prospectively enrolled subjects and derived reference equations for the APD from those without respiratory symptoms, pulmonary disease, or tobacco exposure. APD testing was conducted by medical technicians who received a 10-min in-service on its use. A subset of subjects performed spirometry and impulse oscillometry (iOS), administered by trained respiratory therapists. APD measures were compared with spirometry and iOS. The total study population included 199 subjects (55.8% males, body mass index 27.7 ± 6.0 kg/m2, age 49.9 ± 18.7 yr). Across the three APD trials, mean inspiratory (APD-Ri), expiratory (APD-Re), and average (APD-Ravg) resistances were 3.30 ± 1.0, 3.69 ± 1.2, and 3.50 ± 1.1 cm H2O/L/s. Reference equations were derived from 142 clinically normal volunteers. Height, weight, and body mass index were independently associated with APD-Ri, APD-Re, and APD-Ravg and were combined with age and gender in linear regression models. APD-Ri, APD-Re, and APD-Ravg were significantly inversely correlated with FEV1 (r = -0.39 to -0.42), FVC (r = -0.37 to -0.40), and FEF25-75 (r = -0.31 to -0.35) and positively correlated with R5 (r = 0.61-0.62), R20 (r = 0.50-0.52), X5 (r = -0.57 to -0.59), and FRES (r = 0.42-0.43). Bland-Altman plots showed that the APD-Rr closely approximates iOS when resistance is normal. Rapid testing was achieved with minimal training required, and reference equations were constructed. APD-Rr correlated moderately with iOS and weakly with spirometry. More testing is required to determine whether the APD has value for pre- and post-deployment respiratory assessment.

Randomized Trials of Nasal Patency and Dermal Tolerability With External Nasal Dilators in Healthy Volunteers.

BackgroundExternal nasal dilator strips are used as nonpharmacological therapy to reduce snoring and daytime sleepiness. In a product improvement initiative, a marketed strip (BRNS) and 2 prototype nasal strips were evaluated.ObjectiveTo compare the nasal patency and multiple-use dermal tolerability of the BRNS and prototype nasal strips using both objective and subject-reported outcome measures.MethodsTwo studies were conducted separately in healthy volunteers ≥18 years of age. A single-day nasal patency randomized crossover study assessed minimal cross-sectional area (MCA; second restriction) and nasal volume (using acoustic rhinometry); nasal inspiratory flow and resistance (using posterior rhinomanometry); and subject-reported evaluations of the BRNS compared with the butterfly strip and teardrop strip prototypes. A single-center, randomized, controlled, parallel-group, evaluator-blinded study assessed dermal tolerability of the BRNS and the butterfly strip over 7 consecutive nights of use, using the Dermal Response Scale (DRS) and subject-reported comfort and ease of removal.ResultsIn the Patency study (N = 50), all 3 strips demonstrated significant improvement from baseline in MCA, nasal volume, and nasal flow parameters (resistance and peak flow). The prototype strips demonstrated significantly more improvement in nasal volume than the BRNS, and the butterfly strip showed significantly more improvement in MCA than the BRNS; all strips were similar with respect to nasal flow and subject-reported nasal breathing outcomes. In the Dermal Tolerability study (N = 82), all subjects scored 0 (no evidence of irritation) on the DRS at all 7 morning assessments; the BRNS was numerically, but not significantly, superior to the butterfly strip on subject-reported outcomes.ConclusionThe Patency study demonstrated significant improvement from baseline in nasal dimensions and flow for all 3 evaluated strips; between-strip differences were confined to nasal dimensions. Both the BRNS and butterfly strip were generally well tolerated, with no evidence of dermal response over 7 consecutive nights of use.ClinicalTrials.gov identifiers: NCT01105949 and NCT01495494

Characteristics of respiratory muscle activity due to load pressure difference in inspiratory resistance load breathing

Characteristics of respiratory muscle activity due to load pressure difference in inspiratory resistance load breathing

Effects of High-Flow Nasal Cannula on the Work of Breathing in Patients Recovering From Acute Respiratory Failure.

High-flow nasal cannula is increasingly used in the management of respiratory failure. However, little is known about its impact on respiratory effort, which could explain part of the benefits in terms of comfort and efficiency. This study was designed to assess the effects of high-flow nasal cannula on indexes of respiratory effort (i.e., esophageal pressure variations, esophageal pressure-time product/min, and work of breathing/min) in adults. A randomized controlled crossover study was conducted in 12 patients with moderate respiratory distress (i.e., after partial recovery from an acute episode, allowing physiologic measurements). Institut Universitaire de Cardiologie et de Pneumologie de Québec, QC, Canada. Twelve adult patients with respiratory distress symptoms were enrolled in this study. Four experimental conditions were evaluated: baseline with conventional oxygen therapy and high-flow nasal cannula at 20, 40, and 60 L/min. The primary outcomes were the indexes of respiratory effort (i.e., esophageal pressure variations, esophageal pressure-time product/min, and work of breathing/min). Secondary outcomes included tidal volume, respiratory rate, minute volume, dynamic lung compliance, inspiratory resistance, and blood gases. Esophageal pressure variations decreased from 9.8 (5.8-14.6) cm H2O at baseline to 4.9 (2.1-9.1) cm H2O at 60 L/min (p = 0.035). Esophageal pressure-time product/min decreased from 165 (126-179) to 72 (54-137) cm H2O • s/min, respectively (p = 0.033). Work of breathing/min decreased from 4.3 (3.5-6.3) to 2.1 (1.5-5.0) J/min, respectively (p = 0.031). Respiratory pattern variables and capillary blood gases were not significantly modified between experimental conditions. Dynamic lung compliance increased from 38 (24-64) mL/cm H2O at baseline to 59 (43-175) mL/cm H2O at 60 L/min (p = 0.007), and inspiratory resistance decreased from 9.6 (5.5-13.4) to 5.0 (1.0-9.1) cm H2O/L/s, respectively (p = 0.07). High-flow nasal cannula, when set at 60 L/min, significantly reduces the indexes of respiratory effort in adult patients recovering from acute respiratory failure. This effect is associated with an improvement in respiratory mechanics.

Alteration in upper airway dilator muscle coactivation during sleep: comparison of patients with obstructive sleep apnea and healthy subjects.

In patients with obstructive sleep apnea (OSA), substantial increases in genioglossus (GG) activity during hypopneas/apneas usually fail to restore normal airflow. We have previously suggested that sleep-induced alteration in tongue muscle coordination may explain this finding, as retractor muscle coactivation was reduced during sleep compared with wakefulness. The present study was undertaken to evaluate whether these alterations in dilator muscle activation during sleep play a role in the pathogenesis of OSA and whether coactivation of additional peripharyngeal muscles (non-GG muscles: styloglossus, geniohyoid, sternohyoid, and sternocleidomastoid) is also impaired during sleep. We compared GG and non-GG muscle electromyographic (EMG) activity in 8 patients with OSA and 12 healthy subjects during wakefulness while breathing through inspiratory resistors with the activity observed during sleep toward the end of flow limitation, before arousal, at equivalent esophageal pressures. During wakefulness, resistive breathing triggered increases in both GG and non-GG muscle activity. During sleep, flow limitation was associated with increases in GG-EMG that reached, on average, >2-fold the level observed while awake. In contrast, EMGs of the non-GG muscles, recorded simultaneously, reached, on average, only ~2/3 the wakefulness level. We conclude that during sleep GG activity may increase to levels that substantially exceed those sufficient to prevent pharyngeal collapse during wakefulness, whereas other peripharyngeal muscles do not coactivate during sleep in both patients with OSA and healthy subjects. We speculate that upper airway muscle dyssynchrony during sleep may explain why GG-EMG activation fails to alleviate flow limitation and stabilize airway patency during sleep. NEW & NOTEWORTHY Pharyngeal obstruction during sleep may trigger genioglossus activity to levels substantially exceeding those observed during wakefulness, without ameliorating flow limitation. In contrast, other peripharyngeal muscles exhibit a much lower activity during sleep in both patients with obstructive sleep apnea and healthy subjects. Coordinated muscular synergy stabilizes the pharynx despite relatively low activity while awake, yet even higher genioglossal activity allows the pharynx to obstruct when simultaneous activity of other dilator muscles is inadequate during sleep.

Efficacy of salmeterol and formoterol combination treatment in mice with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a severe lung disease characterized by progressive airflow limitation. Salmeterol and formoterol are two commonly used drugs in COPD therapy, which act as β2-receptor agonists. In the current study, a mouse model of COPD induced by airway lipopolysaccharide inhalation was established. The therapeutic efficacy of salmeterol and formoterol co-treatment was investigated in this model over a 56-day-long observation period. It was also identified that functional residual capacity and inspiratory resistance were significantly improved after salmeterol and/or formoterol treatment compared with the control group (all P<0.01). Furthermore, histological staining of lung tissue samples indicated that inflammation, thickening of the smooth muscle, goblet cell hyperplasia and pulmonary small vessel obstruction were reduced in the mice treated with salmeterol and/or formoterol, suggesting that salmeterol and formoterol were beneficial for ongoing airway and blood vessel remodeling in mice with COPD. The most common treatment-associated adverse events were hypertension and proteinuria. In conclusion, combined salmeterol and formoterol treatment was more effective compared with either single agent, suggesting that salmeterol and formoterol combined treatment has therapeutic value for the clinical treatment of patients with COPD.

Correlation between upper and lower airway inflammations in patients with combined allergic rhinitis and asthma syndrome: A comparison of patients initially presenting with allergic rhinitis and those initially presenting with asthma.

Allergic rhinitis (AR) and asthma often coexist. The terminology combined allergic rhinitis and asthma syndrome (CARAS) was introduced to describe patients with combined AR and asthma. The aim of the present study was to evaluate the correlation between eosinophilic inflammation in the upper and lower airways of patients with CARAS. Stable patients with CARAS initially presenting with AR or asthma were recruited. Healthy subjects and patients with AR alone were recruited as controls. Clinical characteristics, including disease history, lung function, nasal airway inspiratory resistance and upper and lower airway eosinophilic inflammation were evaluated and compared. A total of 73 subjects (22 patients with CARAS initially presenting with AR, 15 patients with CARAS initially presenting with asthma, 25 patients with AR alone and 11 healthy subjects) were studied. The nasal symptoms visual analogue scale scores at the week prior to enrollment and nasal airway inspiratory resistances were comparable among the groups. The percentage of predicted forced expiratory volume in 1 sec and percentage of predicted maximal middle expiratory flow in patients with CARAS initially presenting with asthma were significantly lower compared with the other three groups (P<0.05). No significant different in the percentage of eosinophils in the nasal lavage was observed between patients with CARAS and those with AR only; however, it was significantly increased compared with healthy subjects (P<0.05). The fractional concentration of exhaled nitric oxide and percentage of eosinophils in the sputum were significantly increased in patients with CARAS compared with those in the AR only and healthy subject groups (P<0.05). The difference in the percentage of eosinophils in the nasal lavage and sputum between patients with CARAS initially presenting with AR and initially presenting with asthma was not significant; however, a positive correlation between the percentage of eosinophils in the upper and lower airways was present in patients with CARAS initially presenting with AR only (r=0.526, P=0.030).