High Inspiratory Flow Rates Research Articles

Application of computational fluid dynamics to investigate pathophysiological mechanisms in exercise-induced laryngeal obstruction.

The underlying pathophysiological mechanisms of exercise-induced laryngeal obstruction (EILO) remain to be fully established. It is hypothesized that high inspiratory flow rates can exert a force on laryngeal airway walls that contribute to its inward collapse causing obstruction. Computational fluid dynamics (CFD) presents an opportunity to explore the distribution of forces in a patient-specific upper airway geometry. The current study combined exercise physiological data and CFD simulation to explore differences in airflow and force distribution between a patient with EILO and a healthy matched control. Participants underwent incremental exercise testing with continuous recording of respiratory airflow and laryngoscopic video, followed by an MRI scan. The respiratory and MRI data were used to generate a subject-specific CFD model of upper respiratory airflow. In patient with EILO, the posterior supraglottis experiences an inwardly directed net force, whose magnitude increases nonlinearly with larger flow rates, with slight changes in the direction toward the center of the airway. The control demonstrated an outwardly directed force at all regions of the wall, with a magnitude that increases linearly with larger flow rates. A comparison is made between the CFD results and endoscopic visualization of supraglottic collapse, and a very good agreement is found. The current study presents the first hybrid physiological and computational approach to investigate the pathophysiological mechanisms of EILO, with preliminary findings showing great potential, but should be used in larger sample sizes to confirm findings.NEW & NOTEWORTHY The current study is the first to use a hybrid combined computational fluid dynamics (CFD) and exercise physiology approach to investigate pathophysiology in exercise-induced laryngeal obstruction (EILO). The hybrid methodology is a promising approach to explore the pathophysiological mechanisms underlying the condition. Notable differences occur in the distribution of airflow and wall forces between the EILO and control participants, which align with symptoms and visual observations.

Airflow through the supraglottis during inspiration

Exercise-induced laryngeal obstruction is a paradoxical laryngeal closure during inspiration at high-intensity exercise, with supraglottic closure being most common. This study develops a model based on the computational fluid dynamics to investigate airflow velocity and pressure and the air-induced loads on the supraglottis at various inspiratory flow rates. It is found that at high flow rates, positive wall pressure is formed in the hypopharynx localise towards its lower region, while posterior supraglottic wall pressures shift from positive to negative. These findings suggest that high inspiratory flow rates may increase supraglottic pressure differentials, ultimately contributing in the collapse.

Deposition of Inhaled Levofloxacin in Cystic Fibrosis Lungs Assessed by Functional Respiratory Imaging.

Pulmonary infections caused by Pseudomonas aeruginosa (PA) represent the leading cause of pulmonary morbidity in adults with cystic fibrosis (CF). In addition to tobramycin, colistin, and aztreonam, levofloxacin has been approved in Europe to treat PA infections. Nevertheless, no lung deposition data on inhaled levofloxacin are yet available. We conducted a Functional Respiratory Imaging (FRI) study to predict the lung deposition of levofloxacin in the lungs of patients with CF. Three-dimensional airway models were digitally reconstructed from twenty high-resolution computed tomography scans obtained from historical patients’ records. Levofloxacin aerosols generated with the corresponding approved nebuliser were characterised according to pharmacopeia. The obtained data were used to inform a computational fluid dynamics simulation of levofloxacin lung deposition using breathing patterns averaged from actual CF patients’ spirometry data. Levofloxacin deposition in the lung periphery was significantly reduced by breathing patterns with low inspiratory times and high inspiratory flow rates. The intrathoracic levofloxacin deposition percentages for moderate and mild CF lungs were, respectively, 37.0% ± 13.6 and 39.5% ± 12.9 of the nominal dose. A significant albeit modest correlation was found between the central-to-peripheral deposition (C/P) ratio of levofloxacin and FEV1. FRI analysis also detected structural differences between mild and moderate CF airways. FRI revealed a significant intrathoracic deposition of levofloxacin aerosols, which distributed preferentially to the lower lung lobes, with an influence of the deterioration of FEV1 on the C/P ratio. The three-dimensional rendering of CF airways also detected structural differences between the airways of patients with mild and moderate CF.

Factors DeterminingIn VitroLung Deposition of Albuterol Aerosol Delivered by Ventolin Metered-Dose Inhaler

The effectiveness of metered-dose inhalers (MDIs) in delivering medication to the lungs highly depends on its correct usage technique. Current guidelines state optimal technique for high lung deposition should include a slow inhalation (>5 seconds) at an inspiratory flow rate of 30 L/min and inhaler actuation at the start of inhalation. However, these recommendations were based on clinical studies using CFC (chlorofluorocarbon)-MDIs and in vitro studies of HFA (hydrofluoroalkane)-MDIs using idealized MDI techniques of uniform inhalation and actuation, disregarding the nonuniform techniques of actual patients. To better understand the effects of time-varying MDI usage parameters on lung deposition of aerosol delivered by an HFA-MDI, we conducted an in vitro study modeled on real-life variable inspiratory flow and actuation techniques recorded from 15 subjects with asthma/chronic obstructive pulmonary disease (COPD). We developed a model representing the time-varying inspiratory flow waveforms and actuation timings based on 43 MDI techniques recorded from patients. Furthermore, we constructed an in vitro experimental setup using a mouth-throat cast, programmable MDI actuator, and breath simulator to evaluate lung deposition for the MDI techniques derived from our model. High inspiratory flow rates, 60-90 L/min, consistently resulted in high in vitro lung deposition (>40%) of aerosol (albuterol delivered from Ventolin HFA-MDI) compared to 30 L/min when MDI actuation occurred in the first half of inhalation. Also, positive coordination resulted in higher in vitro lung deposition compared with negative or zero coordination (actuating before or at the start of inspiration). Furthermore, variation in coordination affected lung deposition more significantly (23%) than flow rate or duration of inspiration (≤5%). In an in vitro experimental model based on inhalation data from patients with asthma and COPD, we demonstrated that aerosol lung deposition emitted from Ventolin HFA-MDI is most optimal for MDI actuation in the first half of inspiration at high flow rates (60-90 L/min).

Validation of airway resistance models for predicting pressure loss through anatomically realistic conducting airway replicas of adults and children

This work describes in vitro measurement of the total pressure loss at varying flow rate through anatomically realistic conducting airway replicas of 10 children, 4 to 8 years old, and 5 adults. Experimental results were compared with analytical predictions made using published airway resistance models. For the adult replicas, the model proposed by van Ertbruggen et al. (2005. J. Appl. Physiol. 98, 970–980) most accurately predicted central conducting airway resistance for inspiratory flow rates ranging from 15 to 90L/min. Models proposed by Pedley et al. (1970. J. Respir. Physiol. 9, 371–386) and by Katz et al. (2011. J. Biomech. 44, 1137–1143) also provided reasonable estimates, but with a tendency to over predict measured pressure loss for both models. For child replicas, the Pedley and Katz models both provided good estimation of measured pressure loss at flow rates representative of resting tidal breathing, but under predicted measured values at high inspiratory flow rate (60L/min). The van Ertbruggen model, developed based on flow simulations performed in an adult airway model, tended to under predict measured pressure loss through the child replicas across the range of flow rates studied (2 to 60L/min). These results are intended to provide guidance for selection of analytical pressure loss models for use in predicting airway resistance and ventilation distribution in adults and children.

Effects of dynamic ventilatory factors on ventilator-induced lung injury in acute respiratory distress syndrome dogs.

Mechanical ventilation is a double-edged sword to acute respiratory distress syndrome (ARDS) including lung injury, and systemic inflammatory response high tidal volumes are thought to increase mortality. The objective of this study is to evaluate the effects of dynamic ventilatory factors on ventilator induced lung injury in a dog model of ARDS induced by hydrochloric acid instillation under volume controlled ventilation and to investigate the relationship between the dynamic factors and ventilator-induced lung injuries (VILI) and to explore its potential mechanisms. Thirty-six healthy dogs were randomly divided into a control group and an experimental group. Subjects in the experimental group were then further divided into four groups by different inspiratory stages of flow. Two mL of alveolar fluid was aspirated for detection of IL-8 and TNF-α. Lung tissue specimens were also extracted for total RNA, IL-8 by western blot and observed under an electronic microscope. IL-8 protein expression was significantly higher in group B than in groups A and D. Although the IL-8 protein expression was decreased in group C compared with group B, the difference was not statistically significant. The TNF-α ray degree of group B was significantly higher than that in the other groups (P<0.01), especially in group C (P>0.05). The alveolar volume of subjects in group B was significantly smaller, and cavity infiltration and cell autolysis were marked with a significant thicker alveolar septa, disorder of interval structures, and blurring of collagenous and elastic fiber structures. A large number of necrotic debris tissue was observed in group B. Mechanical ventilation with a large tidal volume, a high inspiratory flow and a high ventilation frequency can cause significant damage to lung tissue structure. It can significantly increase the expression of TNF-α and IL-8 as well as their mRNA expression. Furthermore, the results of our study showed that small tidal ventilation significantly reduces the release of pro-inflammatory media. This finding suggests that greater deterioration in lung injury during ARDS is associated with high inspiratory flow and high ventilation rate.

Aerosol Therapy in Patients Receiving Noninvasive Positive Pressure Ventilation

In selected patients, noninvasive positive pressure ventilation (NIPPV) with a facemask is now commonly employed as the first choice for providing mechanical ventilation in the intensive care unit (ICU). Aerosol therapy for treatment of acute or acute-on-chronic respiratory failure in this setting may be delivered by pressurized metered-dose inhaler (pMDI) with a chamber spacer and facemask or nebulizer and facemask. This article reviews the host of factors influencing aerosol delivery with these devices during NIPPV. These factors include (1) the type of ventilator, (2) mode of ventilation, (3) circuit conditions, (4) type of interface, (5) type of aerosol generator, (6) drug-related factors, (7) breathing parameters, and (8) patient-related factors. Despite the impediments to efficient aerosol delivery because of continuous gas flow, high inspiratory flow rates, air leaks, circuit humidity, and patient-ventilator asynchrony, significant therapeutic effects are achieved after inhaled bronchodilator administration to patients with asthma and chronic obstructive pulmonary disease. Similarly to invasive mechanical ventilation, careful attention to the technique of drug administration is required to optimize therapeutic effects of inhaled therapies during NIPPV. Assessment of the patient's ability to tolerate a facemask, the level of respiratory distress, hemodynamic status, and synchronization of aerosol generation with inspiratory airflow are important factors contributing to the success of aerosol delivery during NIPPV. Further research into novel delivery methods, such as the use of NIPPV with nasal cannulae, could enhance the efficiency, ease of use, and reproducibility of inhalation therapy during noninvasive ventilation.

Evaluation of a Humidified Nasal High-Flow Oxygen System, Using Oxygraphy, Capnography and Measurement of Upper Airway Pressures

In this study, we evaluated the performance of a humidified nasal high-flow system (Optiflow, Fisher and Paykel Healthcare) by measuring delivered FiO, and airway pressures. Oxygraphy, capnography and measurement of airway pressures were performed through a hypopharyngeal catheter in healthy volunteers receiving Optiflow humidified nasal high flow therapy at rest and with exercise. The study was conducted in a non-clinical experimental setting. Ten healthy volunteers completed the study after giving informed written consent. Participants received a delivered oxygen fraction of 0.60 with gas flow rates of 10, 20, 30, 40 and 50 l/minute in random order FiO2, F(E)O2, F(E)CO2 and airway pressures were measured. Calculation of FiO2 from F(E)O2 and F(E)CO2 was later performed. Calculated FiO2 approached 0.60 as gas flow rates increased above 30 l/minute during nose breathing at rest. High peak inspiratory flow rates with exercise were associated with increased air entrainment. Hypopharyngeal pressure increased with increasing delivered gas flow rate. At 50 l/minute the system delivered a mean airway pressure of up to 7.1 cm H20. We believe that the high gas flow rates delivered by this system enable an accurate inspired oxygen fraction to be delivered. The positive mean airway pressure created by the high flow increases the efficacy of this system and may serve as a bridge to formal positive pressure systems.

Advances in inhalation therapy in pediatrics

To review the most relevant articles regarding the technical aspects of inhalation therapy, inhalers currently available, and especially major advances in inhalation therapy in pediatrics. Articles of MEDLINE database from 1983 were reviewed, in addition to book chapters, and the most important studies were selected according to the criteria established for this article. Conventional nebulizers have a number of inconveniences, and breath-enhanced and breath-actuated inhalers are more attractive options. Among dry powder inhalers, we highlight those using passive and active powder dispersion mechanisms, which provide higher rates of drug deposition in the lung. Among pressurized metered-dose inhalers, we highlight breath-actuated, breath-coordinated, and velocity-modifying inhalers. These inhalers should be used preferably together with spacers, since the use of spacers produces a twofold increase in pulmonary drug deposition. For children younger than 8 years, pressurized metered-dose inhalers with spacers are the most appropriate devices, since they provide a practical approach associated with greater lung deposition. In children older than 8 years who can generate high inspiratory flow rates, dry powder devices are best suited.

Effects of inflammatory mediators and mechanism of dynamic factors on lung injury in a dog model of a-cute respiratory distress syndrome

Objective To evaluate the effect on inflammatory mediators and mechanism of dynamic factors on lung injury in a dog model of acute respiratory distress syndrome (ARDS). Method The ARDS dog model was duplicated by instillation hydrochloric acid. The dogs were randomly (random number) divided into six groups: (1) normal control group (N group); (2) ARDS group (M group); (3) low VT (6 mL/kg) at respiratory rate 30, low inspiratory flow 6 mL/(kg·s). (4) large VT (20 mL/kg) at respiratory rate 30, high inspiratory flow 20 mL/kg·s.(5) large VT (20 mL/kg) at respiratory rate 15, high inspiratory flow 17 mL/(kg·s). (6) large VT (20 mL/kg) at respiratory rate 15, low inspiratory flow 10 mL/(kg·s). All the dogs were killed after 4 h ventilation. TNF-α、IL-8, p38 MAPK and NF-κB activity in the lung were measured. Results The expression of IL-8 protein in B and C groups was much higher than that of other groups ( P 0.05). The gray scale ratio of B group was obviously higher than that of other groups (P 0.05). There was no significant changes among M, A and D groups in TNF-α protein contents. p38 MAPK value of positive staining of B group was the strongest, significantlyhigher than that of D group ( P < 0.01) .The expression of p38 MAPK in B and C groups was much higher than other groups (P <0.01). NF-κB activity in B group (33.56±2.85%) was significantly higher than that in A (10.35±0.6%)、D(7. 11 ± 0.47%)group, but there was no difference between B and C group (30.87 ± 1.16%). Conclusions Ventilation at high tidal volume, high inspiratory flow rate, high respiratory rate could activate p38 MAPK and increase the activity of NF-κB with the result of aggravating the release of inflammatory mediators. p38 MAPK and NF-κB activation are the major mechanisms in the development of VILI. Key words: Ventilator-induced lung injury; Acute respiratory distress syndrome; Dynamic factors; Inspiratory flow

The mouth-to-bag resuscitator during standard anaesthesia induction in apnoeic patients

Aim Ventilation of a non-intubated emergency patient by inexperienced rescuers with a standard bag-valve device may result in high inspiratory flow rates and subsequently high airway pressures with stomach inflation. Therefore, a self-inflating bag has been developed that requires lay rescuers to blow up a single-use balloon inside an adult bag-valve device, which, in turn, displaces air within the bag towards the patient. This concept has been compared to standard adult bag-valve devices earlier in bench models but not in patients. Methods An anaesthetist who was blinded to all monitor tracings ventilated the lungs of 40 apnoeic patients during routine anaesthesia induction either with a standard bag-valve device or with the mouth-to-bag resuscitator in a random order. Study endpoints were peak inspiratory flow rates, peak airway pressure, tidal volumes and inspiratory time. Results Peak inspiratory flow was 40 ± 10 l min −1 for the standard bag-valve device versus 33 ± 13 l min −1 for the mouth-to-bag resuscitator ( P < 0.0001); peak airway pressure was 17 ± 5 cmH 2O versus 14 ± 5 cmH 2O ( P < 0.0001); inspiratory tidal volume was 477 ± 133 ml versus 644 ± 248 ml ( P < 0.001) and inspiratory time was 1.1 ± 0.3 s versus 1.9 ± 0.6 s ( P < 0.0001). Conclusion Employing the mouth-to-bag resuscitator during simulated ventilation of a non-intubated patient in respiratory arrest significantly decreased peak inspiratory flow and peak airway pressure and increased inspiratory tidal volume and inspiratory times compared to a standard bag-valve device.

Assessing the performance of the Whisperflow® continuous positive airway pressure generator: a bench study

There are few data describing the performance of the Whisperflow continuous positive airway pressure (CPAP) generator. (i) (a) A static test of 11 Whisperflow devices examining maximum flow generation with no load and with 2.5, 5, 7.5, 10, 15, and 20 cm H2O valve loading, at varying Fi(O2). (b) CPAP valves (Accu-peep(R), Vital Signs, Totowa, NJ, USA) were tested by measuring mean upstream pressure at varying flows in five valves (2.5, 5, 7.5, 10, 15, and 20 cm H2O). (ii) We measured the mean and minimum inspiratory mask pressure generated by a representative Whisperflow device in a model of spontaneous respiration. Measurements were made with combinations of Fi(O2), ventilatory frequency, tidal volume, and valve loading similar to those encountered in clinical practice. (i) (a) The flow generated by the Whisperflow valves decreases with increasing valve load and increasing Fi(O2) (from 140 to 20 litre min(-1)). (b) The CPAP valves maintain the required pressure within acceptable limits against varying flow. (ii) At all permutations, the mean inspiratory mask pressure was significantly lower than that required. At high inspiratory flow rates, the minimum inspiratory pressure approached atmospheric pressure. The Whisperflow may not perform as expected. Clinicians should be cautious when using this device, particularly with high Fi(O2) and CPAP valve load. The flow setting should be set at maximum. Failure of CPAP therapy may be due to failure of the generator. Further in vivo data are required.

Nasal NPSH Depletion and Propylene Oxide Uptake in the Upper Respiratory Tract of the Mouse

Propylene oxide is a nasal toxicant and weak site-of-contact carcinogen in the mouse and rat. To aid in inhalation risk assessment of this vapor and to provide data for comparison to the rat, the current study was aimed at providing quantitative information on upper respiratory tract (URT) dosimetry of this vapor in the mouse. Toward this end, uptake efficiencies of propylene oxide were measured in the surgically isolated URT of the male B6C3F1 mouse under constant velocity inspiratory flow conditions at flow rates of 12 and 50 ml/min and exposure concentrations of 25, 50, 100, 300, or 500 ppm. URT uptake efficiencies were measured continuously during 1 h exposure; mice were terminated immediately after exposure and nasal respiratory and olfactory mucosal nonprotein sulfhydryl (NPSH) levels were determined. Propylene oxide was scrubbed with moderate efficiency in the URT, with uptake efficiencies of < or = 33 and < or = 16% at the low and high inspiratory flow rates, respectively. Uptake efficiencies were slightly (approximately 5%) higher at low (25 or 50 ppm) than high (300 or 500 ppm) exposure concentrations, suggesting that a saturable uptake pathway may exist. Nasal tissue NPSH levels were significantly depleted at exposure concentrations of 300 and 500 ppm but not at concentrations of 100 ppm or lower. Similar levels of NPSH depletion were observed in both nasal respiratory and olfactory mucosa. These data from mouse show some key differences when compared with those reported for the rat.

Imposed work of breathing during high-frequency oscillatory ventilation: a bench study

IntroductionThe ventilator and the endotracheal tube impose additional workload in mechanically ventilated patients breathing spontaneously. The total work of breathing (WOB) includes elastic and resistive work. In a bench test we assessed the imposed WOB using 3100 A/3100 B SensorMedics high-frequency oscillatory ventilators.MethodsA computer-controlled piston-driven test lung was used to simulate a spontaneously breathing patient. The test lung was connected to a high-frequency oscillatory ventilation (HFOV) ventilator by an endotracheal tube. The inspiratory and expiratory airway flows and pressures at various places were sampled. The spontaneous breath rate and volume, tube size and ventilator settings were simulated as representative of the newborn to adult range. The fresh gas flow rate was set at a low and a high level. The imposed WOB was calculated using the Campbell diagram.ResultsIn the simulations for newborns (assumed body weight 3.5 kg) and infants (assumed body weight 10 kg) the imposed WOB (mean ± standard deviation) was 0.22 ± 0.07 and 0.87 ± 0.25 J/l, respectively. Comparison of the imposed WOB in low and high fresh gas flow rate measurements yielded values of 1.63 ± 0.32 and 0.96 ± 0.24 J/l (P = 0.01) in small children (assumed body weight 25 kg), of 1.81 ± 0.30 and 1.10 ± 0.27 J/l (P < 0.001) in large children (assumed body weight 40 kg), and of 1.95 ± 0.31 and 1.12 ± 0.34 J/l (P < 0.01) in adults (assumed body weight 70 kg). High peak inspiratory flow and low fresh gas flow rate significantly increased the imposed WOB. Mean airway pressure in the breathing circuit decreased dramatically during spontaneous breathing, most markedly at the low fresh gas flow rate. This led to ventilator shut-off when the inspiratory flow exceeded the fresh gas flow.ConclusionSpontaneous breathing during HFOV resulted in considerable imposed WOB in pediatric and adult simulations, explaining the discomfort seen in those patients breathing spontaneously during HFOV. The level of imposed WOB was lower in the newborn and infant simulations, explaining why these patients tolerate spontaneous breathing during HFOV well. A high fresh gas flow rate reduced the imposed WOB. These findings suggest the need for a demand flow system based on patient need allowing spontaneous breathing during HFOV.

Optimizing bag-valve-mask ventilation with a new mouth-to-bag resuscitator

When ventilating an unintubated patient with a self-inflating bag, high peak inspiratory flow rates may result in high peak airway pressure with subsequent stomach inflation; this may occur frequently when rescuers without daily experience in bag-valve-mask ventilation need to perform advanced airway management. The purpose of this study was to assess the effects of a newly developed self-inflating bag (mouth-to-bag resuscitator; Ambu, Glostrup, Denmark) that limits peak inspiratory flow. A bench model simulating a patient with an unintubated airway was used, consisting of a face mask, manikin head, training lung (lung compliance, 100 ml/0.098 kPa (100 ml/cm H 2O)); airway resistance, 0.39 kPa/l per second (4 cm H 2O/l/s), oesophagus (LESP, 1.96 kPa (20 cm H 2O)) and simulated stomach. Twenty nurses were randomised to ventilate the manikin for 1 min (respiratory rate: 12 per minute) with either a standard self-inflating bag or the mouth-to-bag resuscitator, which requires the rescuer to blow up a single-use balloon inside the self-inflating bag, which in turns displaces air towards the patient. When supplemental oxygen is added, ventilation with up to 100% oxygen may be obtained, since expired air is only used as the driving gas. The mouth-to-bag resuscitator therefore allows two instead of one hand sealing the mask on the patient's face. The volunteers were blinded to the experimental design of the model until completion of the experimental protocol. The mouth-to-bag resuscitator versus standard self-inflating bag resulted in significantly ( P<0.05) higher mean±S.D. mask tidal volumes (1048±161 vs. 785±174 ml) and lung tidal volumes (911±148 vs. 678±157 ml), longer inspiratory times (1.7±0.4 vs. 1.4±0.4 s), but significantly lower peak inspiratory flow rates (50±9 vs. 62±13 l/min) and mask leakage (10±4 vs. 15±9%); peak inspiratory pressure (17±2 vs. 17±2 cm H 2O) and stomach tidal volumes (16±30 vs. 18±35 ml) were comparable. In conclusion, employing the mouth-to-bag resuscitator during simulated ventilation of an unintubated patient in respiratory arrest significantly decreased inspiratory flow rate and improved lung tidal volumes, while decreasing mask leakage.

Effects of decreasing inspiratory flow rate during simulated basic life support ventilation of a cardiac arrest patient on lung and stomach tidal volumes

If the airway of a cardiac arrest patient is unprotected, basic life support with low rather than high inspiratory flow rates may reduce stomach inflation. Further, if the inspiratory flow rate is fixed such as with a resuscitator performance may improve; especially when used by less experienced rescuers. The purpose of the present study was to assess the effect of limited flow ventilation on respiratory variables, and lung and stomach volumes, when compared with a bag valve device. After institutional review board approval, and written informed consent was obtained, 20 critical care unit registered nurses volunteered to ventilate a bench model simulating a cardiac arrest patient with an unprotected airway consisting of a face mask, manikin head, training lung [with lung compliance, 50 ml/0.098 kPa (50 ml/cmH2O); airway resistance, 0.39 kPa/l/s (4 cmH2O/l/s)] oesophagus [lower oesophageal sphincter pressure, 0.49 kPa (5 cmH2O)] and simulated stomach. Each volunteer ventilated the model with a self-inflating bag (Ambu, Glostrup, Denmark; max. volume, 1500 ml), and a resuscitator providing limited fixed flow (Oxylator EM 100, CPR Medical devices Inc., Toronto, Canada) for 2 min; study endpoints were measured with 2 pneumotachometers. The self-inflating bag vs. resuscitator resulted in comparable mean±SD mask tidal volumes (945±104 vs. 921±250 ml), significantly (P<0.05) higher peak inspiratory flow rates (111±27 vs. 45±21 l/min), and peak inspiratory pressure (1.2±0.47 vs. 78±0.07 kPa), but significantly shorter inspiratory times (1.1±0.29 vs. 1.6±0.35 s). Lung tidal volumes were comparable (337±120 vs. 309±61 ml), but stomach tidal volumes were significantly (P<0.05) higher (200±95 vs. 140±51 ml) with the self-inflating bag. In conclusion, simulated ventilation of an unintubated cardiac arrest patient using a resuscitator resulted in decreased peak flow rates and therefore, in decreased peak airway pressures when compared with a self-inflating bag. Limited flow ventilation using the resuscitator decreased stomach inflation, although lung tidal volumes were comparable between groups.

Subsecond Multisection CT of Regional Pulmonary Ventilation

Rationale and Objectives To evaluate the adequacy of multibreath and single-breath stable xenon gas techniques to measure regional ventilation during cardiac-gated, high-speed, multisection imaging, the authors carried out a series of studies using electron-beam computed tomography (CT) and a recently introduced subsecond multisection spiral CT scanner. Materials and Methods In four anesthetized pigs, the authors implemented single-breath and/or dynamic multibreath wash-in and washout protocols with respiratory- and cardiac-gated image acquisition. The effects of varying tidal volume and inspiratory flow rate were evaluated independently. Scanning was done at end expiration to avoid artifacts from partial volumed conducting airways, which are filled with inspired gas concentration during inspiration. Results A single breath of 100% xenon provides adequate enhancement in the lung parenchyma (mean, 32 HU ± 1.85 [standard error]) and should not cause unwanted side effects (mean xenon concentration in lung periphery, 21%). The single-breath method is suitable for studies requiring only short periods of apnea. Using the multibreath method, in dependent portions of the lung, there was close agreement between measured changes and predictions based on the xenon calibration data. More than 10 breaths were needed to clear tracer from poorly ventilated areas, and some nondependent regions demonstrated apparently “linear” rather than exponential clearance curves, possibly reflecting longer washout times. Analysis of wash-in and washout curves revealed vertical ventilation gradients and, at higher inspiratory flow rates, redistribution of ventilation to areas of the lung with greater pathway conductance. Conclusion With careful attention to lung volume and use of cardiac gating, it is now possible to correlate lung structure with function to a degree heretofore not possible.

Peak inspiratory flow rate and slope of the inhalation profiles in dry powder inhalers

Aerosol delivery depends on device design and inhalation technique. In vitro device evaluations have shown that the emitted dose and fine particle mass of dry powder inhalers (DPIs) increase at high peak inspiratory flow rates (PIFR). Since the PIFR is mostly achieved after the release of the powder, slope of the pressure profile is also described as an important determinant. The aim of the present study was to assess whether the PIFR while using Diskus it and Turbuhaler it inhalers could be used to predict the slope of the inhalation pressure profile. In a group of 10 stable asthma patients and three groups (mild, moderate and severe) of 16 chronic obstructive pulmonary disease (COPD) patients, lung function was measured, and for each device, 18 inhalation profiles were recorded with the inhalation profile recorder during six sessions over 10 weeks. The values for the pressure slope and PIFR of both Diskus and Turbuhaler, were significantly correlated. The r-values were 0.865 and 0.882, respectively (p<0.01). Percentage explained variance was 74.8% for Diskus and 77.8% for Turbuhaler. Significant correlations were found between peak inspiratory flow rates and slopes. It has been shown for two different dry powder inhalers that peak inspiratory flow rate and slope correlate well in a wide range of patient groups.

Fatiguing inspiratory muscle work causes reflex sympathetic activation in humans.

We tested the hypothesis that reflexes arising from working respiratory muscle can elicit increases in sympathetic vasoconstrictor outflow to limb skeletal muscle, in seven healthy human subjects at rest. We measured muscle sympathetic nerve activity (MSNA) with intraneural electrodes in the peroneal nerve while the subject inspired (primarily with the diaphragm) against resistance, with mouth pressure (PM) equal to 60 % of maximal, a prolonged duty cycle (TI/TTot) of 0.70, breathing frequency (fb) of 15 breaths min-1 and tidal volume (VT) equivalent to twice eupnoea. This protocol was known to reduce diaphragm blood flow and cause fatigue. MSNA was unchanged during the first 1-2 min but then increased over time, to 77 +/- 51 % (s.d.) greater than control at exhaustion (mean time, 7 +/- 3 min). Mean arterial blood pressure (+12 mmHg) and heart rate (+27 beats min-1) also increased. When the VT, fb and TI/TTot of these trials were mimicked with no added resistance, neither MSNA nor arterial blood pressure increased. MSNA and arterial blood pressure also did not change in response to two types of increased central respiratory motor output that did not produce fatigue: (a) high inspiratory flow rate and fb without added resistance; or (b) high inspiratory effort against resistance with PM of 95 % maximal, TI/TTot of 0.35 and fb of 12 breaths min-1. The heart rate increased by 5-16 beats min-1 during these trials. Thus, in the absence of any effect of increased central respiratory motor output per se on limb MSNA, we attributed the time-dependent increase in MSNA during high resistance, prolonged duty cycle breathing to a reflex arising from a diaphragm that was accumulating metabolic end products in the face of high force output plus compromised blood flow.

Efficacy of salbutamol via Easyhaler®unaffected by low inspiratory flow

The fine particle dose delivered via dry powder inhalers (DPIs) is often affected by the inspiratory flow rate generated during inhalation. This has clinical implications, since the fine particle dose determines the amount of drug reaching the lungs. With Easyhaler®DPI the fine particle dose remains relatively constant over the range of inspiratory flow rates from 30–60 l min−1. The aim of this study was to confirm that clinical efficacy is maintained even at low flow rates by comparing the bronchodilating effect of salbutamol (100 μ g) delivered via Easyhaler®at a target inspiratory flow of 30 l min−1with the same dose of salbutamol via pressurised metered-dose inhaler (pMDI) plus spacer.This was a double-blind, randomized, cross-over study with double-dummy technique. Twenty-one paediatric and adult asthmatic patients completed the study, which was conducted over 2 study days. The main outcome parameter was forced expiratory volume in 1 sec (FEV1). The patients were trained to generate a low peak inspiratory flow rate (PIFR) of 30 l min−1, and the actual PIFR through Easyhaler®was recorded.The average PIFR through Easyhaler®was 28·7 l min−1. The difference in the maximum value of FEV1(FEV1max) between the treatments after drug inhalation was 0·01 l. The mean of FEV1maxwas 2·67 l after pMDI plus spacer compared to 2·69 l after Easyhaler®. Improvements in FEV1were clinically significant. No significant differences between treatments were found.A reasonably low inspiratory flow rate through Easyhaler®produces an equivalent improvement in lung function to a correctly used pMDI plus spacer. Hence, Easyhaler®can be used with confidence in patients who may have difficulty in generating a high inspiratory flow rate, such as children and the elderly.