Expiratory Resistance Research Articles

The motor pattern of tracheobronchial cough is affected by inspiratory resistance and expiratory occlusion – The evidence for volume feedback during cough expiration

The role of pulmonary stretch receptor discharge and volume feedback in modulation of tracheobronchial cough is not fully understood. The current study investigates the effect of expiratory occlusion with or without preceding inspiratory resistance (delivery of tidal or cough volume by the ventilator lasting over the active cough expiratory period) on the cough motor pattern.Experiments on 9 male cats under pentobarbital sodium anesthesia have shown that inspiratory resistance followed by expiratory occlusion increased cough inspiratory and expiratory efforts and prolonged several time intervals (phases) related to muscle activation during cough. Expiratory occlusion (at regular cough volume) decreased number of coughs, increased amplitudes of abdominal electromyographic activity, inspiratory and expiratory esophageal pressure during cough and significantly prolonged cough temporal features. Correlation analysis supported major changes in cough expiratory effort and timing due to the occlusion.Our results support a high importance of volume feedback, including that during cough expulsion, for generation and modulation of cough motor pattern with obstruction or expiratory airway resistances, the conditions present during various pulmonary diseases.

Positive end-expiratory pressure improves elastic working pressure in anesthetized children

BackgroundPositive end-expiratory pressure (PEEP) has been demonstrated to decrease ventilator-induced lung injury in patients under mechanical ventilation (MV) for acute respiratory failure. Recently, some studies have proposed some beneficial effects of PEEP in ventilated patients without lung injury. The influence of PEEP on respiratory mechanics in children is not well known. Our aim was to determine the effects on respiratory mechanics of setting PEEP at 5 cmH2O in anesthetized healthy children.MethodsPatients younger than 15 years old without history of lung injury scheduled for elective surgery gave informed consent and were enrolled in the study. After usual care for general anesthesia, patients were placed on volume controlled MV. Two sets of respiratory mechanics studies were performed using inspiratory and expiratory breath hold, with PEEP 0 and 5 cmH2O. The maximum inspiratory and expiratory flow (QI and QE) as well as peak inspiratory pressure (PIP), plateau pressure (PPL) and total PEEP (tPEEP) were measured. Respiratory system compliance (CRS), inspiratory and expiratory resistances (RawI and RawE) and time constants (KTI and KTE) were calculated. Data were expressed as median and interquartile range (IQR). Wilcoxon sign test and Spearman’s analysis were used. Significance was set at P < 0.05.ResultsWe included 30 patients, median age 39 (15–61.3) months old, 60% male. When PEEP increased, PIP increased from 12 (11,14) to 15.5 (14,18), and CRS increased from 0.9 (0.9,1.2) to 1.2 (0.9,1.4) mL·kg− 1·cmH2O− 1; additionally, when PEEP increased, driving pressure decreased from 6.8 (5.9,8.1) to 5.8 (4.7,7.1) cmH2O, and QE decreased from 13.8 (11.8,18.7) to 11.7 (9.1,13.5) L·min− 1 (all P < 0.01). There were no significant changes in resistance and QI.ConclusionsAnalysis of respiratory mechanics in anesthetized healthy children shows that PEEP at 5 cmH2O places the respiratory system in a better position in the P/V curve. A better understanding of lung mechanics may lead to changes in the traditional ventilatory approach, limiting injury associated with MV.

Effect of Liuzijue Qigong on patients with chronic obstructive pulmonary disease: Protocol for a systematic review and meta-analysis.

Background:Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide with a substantial and increasing social and economic burden. Liuzijue Qigong is a kind of traditional Chinese Qigong exercises that Traditional Chinese Medicine practitioners prescribe to individuals with COPD to strengthen the internal organs’ function. Liuzijue Qigong was recommended for use in COPD rehabilitation, and some clinical trials indicate that Liuzijue Qigong would produce better functional capacity and quality of life of individuals with COPD. The objective of this study is to conduct a systematic review of the existing studies to assess effectiveness and safety of Liuzijue Qigong for the prevention or treatment of COPD in patients.Methods:We will perform the comprehensive literature search in English and Chinese electronic database. The publication period will be from inception to the search date. In addition, the clinical trial registries, dissertations, informal publication, grey literature, reference lists of studies, systematic reviews, and conference abstracts will also be collected. Two reviewers will identify relevant studies, extract data information, and then assess the methodical quality by the Cochrane risk of bias assessment tool. Only randomized controlled trials comparing Liuzijue Qigong against other intervention or nonintervention will be included. Data will be synthesized by either fixed-effect or random-effect model regarding to a heterogeneity test. The routine lung function, arterial blood gas tensions, partial pressure of carbon dioxide, functional capacity, 30 seconds sit-to-stand test, respiratory function, maximal inspiration pressure, maximal expiratory pressure, airway resistance, and specific airway conductance will be assessed as primary outcomes. The secondary outcomes involved dyspnea, and fatigue levels, respiratory muscle strength, upper and lower limb muscle strength, handgrip strength test, and health-related quality of life and safety. Meta-analysis will be performed by using Cochrane's Review Manager software (version 5.3.5).Results:This systematic review and meta-analysis will provide a high-quality synthesis and evaluate the efficacy and safety based on current relevant literature evidence of Liuzijue Qigong intervention for COPD patient.Conclusion:Our systematic review will provide evidence to determine whether Liuzijue Qigong is an effective and safe approach to prevention and treatment of COPD patients.

GAS5 promotes airway smooth muscle cell proliferation in asthma via controlling miR-10a/BDNF signaling pathway

AimsTo explore the role of long non-coding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5) in the cell proliferation of airway smooth muscle cells (ASMCs) in asthma. Materials and methodsAn asthma rat model was established by ovalbumin sensitization and challenge. The expression of GAS5, miR-10a and BDNF mRNA and protein was determined with qRT-PCR and western blot, separately. The targeting relationship between GAS5 and miR-10a was examined with RNA immunoprecipitation and RNA pull-down assay; the interaction between miR-10a and BDNF was evaluated by luciferase reporter assay. Cell Proliferation Assay (MTS) was used for ASMC proliferation detection. Knock-down of GAS5 was performed in asthmatic rats to determine the effects of GAS5 in vivo. Key findingsCompared with control group, the inspiratory resistance and expiratory resistance were increased in asthma group; and the expression of GAS5, miR-10a and BDNF was higher, lower and higher, respectively. The expression of GAS5 and miR-10a was elevated and repressed, respectively, by platelet-derived growth factor-BB (PDGF-BB). GAS5 functioned as a bait of miR-10a. GAS5 regulates BDNF expression through miR-10a. PDGF-BB promotes the cell proliferation of ASMCs through miR-10a/BDNF. Knock-down of GAS5 significantly decreased airway hyperresponsiveness in asthmatic rats. SignificanceThe lncRNA GAS5/miR-10a/BDNF regulatory axis played an important role in promoting ASMCs proliferation, thus contributing to asthma.

Respiratory waveform variation can prevent pulsus paradoxus measurement by sphygmomanometry

Background: Pulsus paradoxus (PP) represents increased fluctuation of systolic pressure during the respiratory cycle. PP increases in pathologic conditions, including asthma and other obstructive airways diseases. Respiratory waveform variation (RWV) represents arterial-waveform baseline variability resulting from intra-pleural pressure changes during the respiratory cycle in the presence of airway obstruction. It is not known whether RWV influences manual PP measurement using a sphygmomanometer and stethoscope. Methods: We performed an observational study in six healthy adults. Participants performed tidal-breathing through a breathing apparatus with pre-determined inspiratory (0–45.6 cm H2O) and expiratory (0–24.4 cm H2O) resistance levels for a total of 23 data sets per participant. PP was measured from continuous radial artery pressure recordings as the absolute difference between maximum and minimum systolic pressure levels during a complete respiratory cycle. Results: In this study, PP values measured without applied airway resistance exceeded 10 mmHg, the traditional definition of PP, in five of the six participants. Manual measurement of PP would not be possible at greater RWV because the maximum diastolic pressure exceeded minimum systolic pressure during RWV. Conclusions: PP in normal adults may exceed 10 mmHg, and RWV may be of sufficient magnitude to preclude manual PP measurement.

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.

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.

Resveratrol treatment alters lung microbiome in the murine ovalbumin-induced asthma model by increasing mucus-degrading Akkermansia muciniphila.

Abstract Asthma is a chronic inflammatory disease that involves the narrowing of the lung airways and excessive mucus production. Resveratrol (RES), a polyphenolic stilbene, is known to control asthmatic attacks via different molecular mechanisms. However, no studies have examined the effect of resveratrol on the microbiome in the ovalbumin (OVA)-induced asthma mouse model. In this study, we induced asthma in BALB/c mice by injecting OVA followed by 7 days treatment with RES. Plethysmography showed that the expiratory resistance in the lung tissue was significantly reduced in the RES treated group, while mean volume, peak expiratory flow, and frequency of respiration was increased. Histopathological examination of the lungs of the RES-treated group showed significant reduction in inflammatory cell infiltration and led to restoration of normal lung tissue architecture. In addition, there were significant increases in the expression of the genes encoding tight-junction molecules (claudin-1 and cadherin-18) in the RES-treated group. We performed 16S rRNA microbial analysis of cecal flushes and pulmonary tissues, which showed that RES treatment alters the gut microbiome by significantly increasing the level of Bacteroides acidifaciens spp. compared to disease controls. In addition, there was a significant increase in Akkermansia muciniphila (AM) species within the lungs after RES treatment. AM is a gram-negative, non-spore-forming bacterium known to induce mucus degradation. Since asthma is characterized by an increase in mucus in the lungs, we concluded that RES improves asthma in OVA-induced mouse model by significantly increasing AM and preventing mucus build-up in the lungs.

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.

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.

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.

Palatal prolapse as a signature of expiratory flow limitation and inspiratory palatal collapse in patients with obstructive sleep apnoea

In some individuals with obstructive sleep apnoea (OSA), the palate prolapses into the velopharynx during expiration, limiting airflow through the nose or shunting it out of the mouth. We hypothesised that this phenomenon causes expiratory flow limitation (EFL) and is associated with inspiratory "isolated" palatal collapse. We also wanted to provide a robust noninvasive means to identify this mechanism of obstruction.Using natural sleep endoscopy, 1211 breaths from 22 OSA patients were scored as having or not having palatal prolapse. The patient-level site of collapse (tongue-related, isolated palate, pharyngeal lateral walls and epiglottis) was also characterised. EFL was quantified using expiratory resistance at maximal epiglottic pressure. A noninvasive EFL index (EFLI) was developed to detect the presence of palatal prolapse and EFL using the flow signal alone. In addition, the validity of using nasal pressure was assessed.A cut-off value of EFLI >0.8 detected the presence of palatal prolapse and EFL with an accuracy of >95% and 82%, respectively. The proportion of breaths with palatal prolapse predicted isolated inspiratory palatal collapse with 90% accuracy.This study demonstrates that expiratory palatal prolapse can be quantified noninvasively, is associated with EFL and predicts the presence of inspiratory isolated palatal collapse.

Exhaled breath condensate as an alternative sample for drug monitoring.

Exhaled breath condensate as an alternative sample for drug monitoring.

Respiratory mechanics in infants with severe bronchiolitis on controlled mechanical ventilation

BackgroundAnalysis of respiratory mechanics during mechanical ventilation (MV) is able to estimate resistive, elastic and inertial components of the working pressure of the respiratory system. Our aim was to discriminate the components of the working pressure of the respiratory system in infants on MV with severe bronchiolitis admitted to two PICU’s.MethodsInfants younger than 1 year old with acute respiratory failure caused by severe bronchiolitis underwent neuromuscular blockade, tracheal intubation and volume controlled MV. Shortly after intubation studies of pulmonary mechanics were performed using inspiratory and expiratory breath hold. The maximum inspiratory and expiratory flow (QI and QE) as well as peak inspiratory (PIP), plateau (PPL) and total expiratory pressures (tPEEP) were measured. Inspiratory and expiratory resistances (RawI and RawE) and Time Constants (KTI and KTE) were calculated.ResultsWe included 16 patients, of median age 2.5 (1–5.8) months. Bronchiolitis due to respiratory syncytial virus was the main etiology (93.8%) and 31.3% had comorbidities. Measured respiratory pressures were PIP 29 (26–31), PPL 24 (20–26), tPEEP 9 [8–11] cmH2O. Elastic component of the working pressure was significantly higher than resistive and both higher than threshold (tPEEP – PEEP) (P < 0.01). QI was significantly lower than QE [5 (4.27–6.75) v/s 16.5 (12–23.8) L/min. RawI and RawE were 38.8 (32–53) and 40.5 (22–55) cmH2O/L/s; KTI and KTE [0.18 (0.12–0.30) v/s 0.18 (0.13–0.22) s], and KTI:KTE ratio was 1:1.04 (1:0.59–1.42).ConclusionsAnalysis of respiratory mechanics of infants with severe bronchiolitis receiving MV shows that the elastic component of the working pressure of the respiratory system is the most important. The elastic and resistive components in conjunction with flow profile are characteristic of restrictive diseases. A better understanding of lung mechanics in this group of patients may lead to change the traditional ventilatory approach to severe bronchiolitis.

Application of the Novel Ventilation Mode FLow-Controlled EXpiration (FLEX): A Crossover Proof-of-Principle Study in Lung-Healthy Patients.

Traditionally, mechanical ventilation is achieved via active lung inflation during inspiration and passive lung emptying during expiration. By contrast, the novel FLEX (FLow-controlled EXpiration) ventilator mode actively decreases the rate of lung emptying. We investigated whether FLEX can be used during intraoperative mechanical ventilation of lung-healthy patients. In 30 adult patients scheduled for neurosurgical procedures, we studied respiratory system mechanics, regional ventilation, oxygenation, and hemodynamics during ventilation with and without FLEX at positive end-expiratory pressure (PEEP) of 5 and 7 cm H2O. The FLEX system was integrated into the expiratory limb and modified the expiratory flow profile by continuously changing expiratory resistance according to a computer-controlled algorithm. Mean airway pressure increased with PEEP by 1.9 cm H2O and with FLEX by 1 cm H2O (all P < .001). The expiratory peak flow was 42% lower with FLEX than without FLEX (P < .001). FLEX caused significant shifts in aeration from ventral to the dorsal lung regions. Respiratory mechanics, end-tidal carbon dioxide partial pressure, oxygenation, and hemodynamics were independent from FLEX and PEEP. We observed no critical incidents or FLEX malfunctions in any measurement that would have required an intervention or termination of the FLEX mode. FLEX can be used in lung-healthy patients who are mechanically ventilated during general anesthesia. FLEX improves the homogeneous distribution of ventilation in the lungs.

The effect of closed septorhinoplasty on nasal functions and on external and internal nasal valves: A prospective study.

Because nasal function and shape are so closely intertwined, quantitative assessments can better define their relationship and how they are affected by septorhinoplasty. The aim of this prospective study was to perform an analysis of the nasal airflow resistances and a three-dimensional (3D) evaluation of the soft-tissue changes after closed septorhinoplasty. Before surgery (T0) and 6 months after closed septorhinoplasty (T1), 30 patients underwent symptoms evaluation by means of the Italian version of the Nasal Obstruction Symptom Evaluation scale, endoscopic fiberoptic nasal examination, and visual analog scale for subjective assessment of nasal obstruction. Nasal airflow resistances were investigated with active anterior active rhinomanometry. A 3D laser scanner was used to evaluate facial soft-tissues, with specific nasal points and angles. Subjective nasal obstruction decreased. Anterior active rhinomanometry demonstrated a reduction in total inspiratory and expiratory resistances between T0 and T1 but without statistical significance. The significance was still absent after decongestion, excluding turbinate hypertrophy as a cause of failed objective amelioration of nasal resistance. Facial laser scanning showed statistically significant reduction of the superior nasal width and superior alar angle, and a weak negative correlation between the superior alar angle and nasal resistances. The absence of objective reduction of nasal airflow resistances could be the result of concurrent surgery on nasal septum and nasal valve. In particular, the ameliorating effect on nasal airflow resistances is counterbalanced by the worsening effect of the narrowing of nasal valve.

Acute volume loading exacerbates direct ventricular interaction in a model of COPD

Volume loading increases left ventricular (LV) stroke volume (LVSV) through series interaction, but may paradoxically reduce LVSV in the presence of large increases in right ventricular (RV) afterload because of direct ventricular interaction (DVI). RV afterload is often increased in chronic obstructive pulmonary disease (COPD) as a result of pathological changes to respiratory mechanics, namely increased negative intrathoracic pressure (nITP), dynamic lung hyperinflation (DH), and increased pulmonary vascular resistance (PVR). These hallmarks of COPD negatively impact LV hemodynamics in normovolemia. However, it is unknown how these heart-lung interactions are impacted by acute volume loading. Twenty healthy subjects (23 ± 2 yr) completed the study protocol, involving acute volume loading via 20° head-down tilt (HDT) in isolation and with 1) inspiratory resistance of -20 cmH2O (HDT+nITP) and 2) nITP, expiratory resistance to induce DH and hypoxic-mediated increases in PVR (HDT+COPD model). LV volumes and geometry were assessed using triplane echocardiography. HDT significantly increased LVSV by 10 ± 10% through an 8 ± 6% increase in LV end-diastolic volume (LVEDV). HDT+nITP paradoxically decreased LVSV by 11 ± 12% and LVEDV by 6 ± 9% from supine baseline, or -14 ± 10% LVSV and -15 ± 13% LVEDV from HDT (P < 0.001). HDT+COPD model decreased LVSV (21 ± 10% and 28 ± 11%) and LVEDV (16 ± 10% and 22 ± 10%) from both supine and HDT, respectively (P < 0.001). Under all conditions, significant septal flattening (increased radius of septal curvature) occurred, indicating DVI. Thus, when RV afterload is increased and/or an external constraint to ventricular filling exists, acute volume loading appears to paradoxically reduce LVSV. These findings have important implications for understanding how volume status impacts cardiopulmonary interactions in COPD.NEW & NOTEWORTHY Volume loading may exacerbate adverse cardiopulmonary interaction in COPD; however, the mechanisms remain unclear. We found that when negative intrathoracic pressure is increased, acute volume loading paradoxically reduces stroke volume. This reduction in stroke volume is considerably greater in a model of COPD, owing to the effects of lung hyperinflation.

Development of an eosinophilic bronchitis mouse model and the effects of eosinophil activation on airway hyperresponsiveness in eosinophilic bronchitis mice

Objective: To develop a mouse model of eosinophilic bronchitis, and explore the effects of eosinophil activation on airway hyperresponsiveness. Methods: A total of 60 female specific pathogen free BALB/c female mice were divided randomly into four groups: polymyxin B group, normal saline group, polymyxin B+ N-methionine leucine phenylalanine (fMLP) group, normal saline+ fMLP group. All the groups were given corresponding nasal drops for 21 days. The former two groups were given 12 μl 0.5% polymyxin B or normal saline once a day by transnasal administration respectively. Besides the above, the latter two groups were given 10 μl fMLP (0.05 mg/ml, dissolved in acetic acid) once by transnasal administration 3 hours after polymyxin B or normal saline administration on the 21st day. Within 24 hours after the last transnasal administration, cells in bronchoalveolar lavage fluid (BALF) were collected and analyzed by absolute different cell counts. Airway responsiveness (inspiratory and expiratory airway resistance and lung compliance) to acetyl choline (Ach) were measured 3 hours after the last transnasal administration in the former two groups and 24 hours after the last transnasal administration in the latter two groups. Eosinophil peroxidase (EPX), eosinophil cationic protein (ECP) and eosinophil chemotactic factor (ECF) levels in serum, BALF and lung tissue were tested by emzyme linked immunosorbent assay (ELISA). HE and Chromotrope 2R staining of lung tissue were used to observe the infiltration of inflammatory cells. The morphology of low-density eosinophils was observed under electron microscope. Results: The total cell counts of BALF in polymyxin B group were significantly higher than the normal saline group [29.50 (3.25)×10(4)/ml vs 15.25 (2.25)×10(4)/ml, P<0.001], especially eosinophil counts [11.76 (6.02)×10(4)/ml vs 0.12 (1.08)×10(4)/ml, P<0.001]. However, no significant differences of inspiratory and expiratory airway resistance and lung compliance existed in the two groups. Inspiratory and expiratory airway resistance in polymyxin B+ fMLP group were significantly higher, lung compliance significantly lower than those in the other three groups (all P<0.001), and the EPX, ECP, ECF levels in serum, BALF and lung tissue of the polymyxin B+ fMLP group were significantly higher than the other three groups (all P<0.001). There were more inflammatory cells, especially eosinophils in lung tissue of polymyxin B and polymyxin B+ fMLP group. Meanwhile, more activated eosinophils in polymyxin B+ fMLP group were observed by electron microscopy. Conclusion: A mouse model of eosinophilic bronchitis can be successfully developed by transnasal administration of polymyxin B, and the eosinophil activation plays an important role in the occurrence of airway hyperresponsiveness.

Imposed expiratory resistance, hyperinflation, and dyspnea are dissociated from locomotor fatigue during moderate exercise

Expiratory flow resistance (e.g. asthma, chronic obstructive pulmonary disease) results in dyspnea, dynamic hyperinflation, and premature exercise intolerance during heavy intensity exercise. This cascade seems to be primarily precipitated by abnormal lung mechanics that result in exacerbated symptoms and reduced maximal evocable limb motor activity. We do not know whether this cascade behaves in the same way during moderate exercise where only modest locomotor fatigue is expected to develop.We hypothesized that expiratory flow resistance would result in dynamic hyperinflation, dyspnea, and exacerbated locomotor fatigue during moderate intensity exercise in a similar manner to that during heavy intensity exercise.Volunteers (N=10, 27±6 yr) completed constant power moderate exercise (50% peak ramp power) with 3 levels of imposed expiratory flow resistance (7, 9, 11 cm H2O·L·s−1) or control (no imposed flow resistance). We measured operating lung volumes during exercise with inspiratory capacity maneuvers. Participants reported dyspnea and leg effort using a Borg 10‐point scale. At the termination of exercise we used a rapid switch from hyperbolic to isokinetic cycling to measure the decline in peak isokinetic power (Piso).Decline in Piso was not different when expiratory flow resistance was imposed (p&gt;0.05). Inspiratory capacity was smaller at the end of exercise in the most severe resistance (11 cm H2O·L·s−1) as compared to control (2.31±1.52 vs. 3.15±0.71 L; p&lt;0.05). Similarly, inspiratory reserve volume was smaller at the end of exercise in the most severe resistance as compared to control (−0.07±1.28 vs. 0.82±0.43 L; p&lt;0.05). Dyspnea was greater at the end of exercise in both mild and severe resistance (7 and 11 cm H2O·L·s−1) as compared to control (5.7±2.5 and 5.2±1.9 vs. 3.7±1.6; p&lt;0.05). Piso was not related to inspiratory reserve volume, inspiratory capacity, or dyspnea (p&gt;0.05).Imposed severe expiratory flow resistance results in hyperinflation and exacerbated dyspnea in healthy volunteers. Unlike what we have found during heavy exercise, however, abnormal lung mechanics and dyspnea were not related to maximal locomotor power during moderate exercise.