A Single-opening&closing Valve Tester for Direct Measurement of Closing Volume of the Heart Valve.

PURPOSE: The objective of this study was to develop a novel single opening&closing pulsatile flow in-vitro valve tester for direct measurement of closing volume of the heart valve. METHODS: A single opening&closing valve tester was composed of a piston pump, valve mounting chamber, reservoir, measurement and control system. The piston pump was used to drive a valve to open and close with dictated flow which comprised three phases of accelerated, constant, and decelerated flow with six slopes. A high speed camera was used to record valve opening and closing images. Two pressure transducers across the tested valve were used to capture the ending time of valve closing which was verified by the high-speed photography. The closing time was measured and closing volume was calculated with a piston displacement volume during valve closing. A tilting disc valve and porcine mitral valve were tested. RESULTS: There was a big difference in flowrate between the Transonic flowmeter and piston pump. The heart valve opened and closed under the dictated flow driven by the piston pump. The transvalvular pressure was minor during valve opening and then increased sharply during valve closing. The closing time varied approximately linearly with the slope of the decelerated flow and was comparable between the two methods by the transvalvular pressure and high-speed photography. The closing volumes did not change much with the slope of the decelerated flow and were 7.0 ± 1.0 and 14.0 ± 1.5 mL for the tilting disc valve and mitral valve, respectively. CONCLUSION: Pulsatile flow is challenging to the flowmeter. A novel single opening&closing pulsatile flow in-vitro valve tester for the heart valve has successfully been developed and can be used to simulate and evaluate the opening and closing hemodynamics of the heart valve. The tester can be used to measure valve closing volume and time accurately with a standardized testing protocol free from effect of other components such as the resistance, compliance units and auxiliary valve in the continuous pulsatile flow valve tester.

Closing volume detection by single-breath gas washout and forced oscillation technique.

Closing volume (CV) is commonly measured by single-breath nitrogen washout (CVSBW). A method based on the forced oscillation technique was recently introduced to detect a surrogate CV (CVFOT). As the two approaches are based on different physiological mechanisms, we aim to investigate CVFOT and CVSBW relationship at different degrees and patterns of airway obstruction. A mathematical model was developed to evaluate the CVSBW and CVFOT sensitivity to different patterns of airway obstruction, either located in a specific lung region or equally distributed throughout the lung. The two CVs were also assessed during slow vital capacity (VC) maneuvers in triplicate in 13 healthy subjects and pre- and postmethacholine challenge (Mch) in 12 subjects with mild-moderate asthma. Model simulations suggest that CVSBW is more sensitive than CVFOT to the presence of few flow-limited or closed airways that modify the contribution of tracer-poor and tracer-rich lung regions to the overall exhaled gas. Conversely, CVFOT occurs only when at least ∼65% of lung units are flow limited or closed, regardless of their regional distribution. CVSBW did not differ between healthy subjects and those with asthma (17 ± 9% VC vs. 22 ± 10% VC), whereas CVFOT did (16 ± 5% VC vs. 23 ± 6% VC, P < 0.01). In patients with asthma, both CVSBW and CVFOT increased post-Mch (33 ± 7% VC P < 0.001 and 43 ± 12% VC P < 0.001, respectively). CVSBW weakly correlated with CVFOT (r = 0.45, P < 0.01). The closing capacities (CV + residual volume) were correlated (r = 0.74, P < 0.001), but the changes with Mch in both CVs and closing capacities did not correlate. CVFOT is easy to measure and provides a reproducible parameter useful for describing airway impairment in obstructive respiratory diseases.NEW & NOTEWORTHY The forced oscillation technique can identify a surrogate of closing volume (CVFOT). We investigated its relationship with the one measured by single-breath washout (CVSBW). CVFOT weakly correlates with CVSBW. The respective closing capacities were correlated, but their increases after methacholine challenge in asthmatics did not. Our results suggest that CVFOT is less sensitive than CVSBW to few flow-limited/closed airways but more specific in detecting increases in flow-limited/closed airways involving the majority of the lung.

Airway occlusion assessed by single breath N2 test and lung P-V curve in healthy subjects and COPD patients.

PURPOSE: To determine whether the analysis of the slow expiratory transpulmonary pressure-volume (PL-V) curve provides an alternative to the single-breath nitrogen test (SBN) for the assessment of the closing volume (CV). METHODS: SBN test and slow deflation PL-V curve were simultaneously recorded in 40 healthy subjects and 43 COPD patients. Onset of phase IV identified CV in SBN test (CVSBN), whereas in the PL-V curve CV was identified by: a) deviation from the exponential fit (CVexp), and b) inflection point of the interpolating sigmoid function (CVsig). RESULTS: In the absence of phase IV, COPD patients exhibited a clearly discernible inflection in the PL-V curve. In the presence of phase IV, CVSBN and CVexp coincided (CVSBN/CVexp=1.04±0.04 SD), whereas CVsig was systematically larger (CVsig/CVexp=2.1±0.86). CONCLUSION: The coincidence between CVSBN and CVexp, and the presence of the inflection in the absence of phase IV indicate that the deviation of the PL-V curve from the exponential fit reliably assesses CV.

Techniques for assessing small airways function: Possible applications in asthma and COPD.

In recent years special interest has been expressed for the contribution of small airways in the pathophysiology, clinical manifestations and treatment of asthma and COPD. Small airways contribute little to the total respiratory resistance so that extensive damage of small airways may occur before the appearance of any symptoms, and this is the reason why they are characterized as the "silent zone" of airways. Furthermore, the peripheral localization of the small airways and their small diameter constitutes difficult their direct assessment. Thus, they are usually studied indirectly, taking advantage of the effects of their obstruction, such as premature closure, air trapping, heterogeneity of ventilation, and lung volume dependence of airflow limitation. Today, several heterogeneous methods for the assessment of small airways are available. These can be either functional (spirometry, plethysmography, resistance measurements, nitrogen washout, alveolar nitric oxide, frequency dependence of compliance, flow-volume curves breathing mixture of helium-oxygen) or imaging (mainly through high resolution computed tomography). The above-mentioned methods are summarized in Table 1. However, no method is currently considered as the "gold standard" and it seems that combinations of tests are needed. Furthermore, it is not clear whether the small airways are affected in all patients with asthma or COPD and their clinical significance remains under investigation. Well-designed future studies with large numbers of patients are expected to reveal which of the methods for assessing the small airways is the most accurate, reliable and reproducible, for which patients, and which can be used for the evaluation of the effects of treatment.

[A New Method of Analyzing the Closing Volume (CV) Curve: "N2 First Derivative Wave Method"].

Evaluation of the lung function involves the measurement of many factors. The closing volume (CV) curve is clinically important as an index of uneven alveolar ventilation and airway closure. Although conventional methods for CV measurement are usually based on the pattern of the exhaled nitrogen (N2) concentration curve with respect to the lung volume, it is often difficult to measure the steep pattern of patients with chronic obstructive pulmonary disease (COPD). In this paper, we proposed a new method called the "N2 first derivative (fdN) wave method" for measuring CV. The N2 concentration of the CV curve was transformed to a derivative with respect to the lung volume, which revealed the existence of cardiogenic oscillations. Discrimination between phases III and IV was straightforward based on the difference in the slope or in the amplitude of oscillations of the fdN wave. Our new method was able to distinguish phase IV from phase III using the difference in amplitude of the oscillation of the fdN wave even in the presence of COPD with steep patterns of the CV curve. Close relationships were seen among normal subjects including COPD patients in both the slope of the alveolar plateau (ΔN2) and the CV values measured with the conventional and new methods. In conclusion, the new method we propose in this paper was able to provide measurements of CV for all subjects including those with COPD. [Original]

Exhaled nitric oxide and lung function after moderate normobaric hyperoxic exposure.

INTRODUCTION: Pulmonary oxygen toxicity is associated with inflammatory responses in the airways and alveoli. The purpose of this study was to investigate whether the changes in exhaled nitric oxide (FE(NO)) after exposure to normobaric hyperoxia (NBO), 100% oxygen (O2) at 1 atmosphere absolute (atm abs) for 90 minutes, are associated with changes in lung function. METHODS: Eighteen healthy non-smoking subjects were exposed to NBO breathing 100% oxygen and to breathing ambient air, both for 90 minutes on separate days and in random order. Dynamic and static lung volumes, maximal expiratory flow rates, distribution of ventilation including closing volume and slope of phase III of the nitrogen washout curve (delta N2), diffusion capacity (D(L)CO) and FE(NO) were measured before and after the exposures. RESULTS: The mean reduction in FE(NO) was 20% (SD = 20) after the NBO exposure (p < 0.001). Static and dynamic lung volumes, maximal expiratory flow rates, DLCO and distribution of ventilation were unchanged. No association was found between the changes in the lung function variables and the change in FE(NO). DISCUSSION: Unchanged indices of distribution of ventilation and maximal expiratory flow rates indicate no small airways' dysfunction, and unchanged DLCO suggests preserved gas transfer in the lung despite a significant reduction in FE(NO). FE(NO) might be an index of oxygen exposure, but further studies over a wide range of oxygen exposures are necessary to establish the role of FE(NO) as a marker of pulmonary oxygen toxicity.

The mechanics of airway closure.

We describe how surface-tension-driven instabilities of the lung's liquid lining may lead to pulmonary airway closure via the formation of liquid bridges that occlude the airway lumen. Using simple theoretical models, we demonstrate that this process may occur via a purely fluid-mechanical "film collapse" or through a coupled, fluid-elastic "compliant collapse" mechanism. Both mechanisms can lead to airway closure in times comparable with the breathing cycle, suggesting that surface tension is the primary mechanical effect responsible for the closure observed in peripheral regions of the human lungs. We conclude by discussing the influence of additional effects not included in the simple models, such as gravity, the presence of pulmonary surfactant, respiratory flow and wall motion, the airways' geometry, and the mechanical structure of the airway walls.

A novel interpretation of closing volume based on single-breath nitrogen washout curve simulation.

Although closing volume is regarded as a clinical test for the early detection of peripheral airway closure, its grounds are not clear. There have been no simulation studies for phase IV in the single-breath nitrogen washout (SBNW) curve, even though several mathematical models for phase III have been proposed. We modeled the lung tissue deformation during slow expiration in which the tissue was regarded as a porous elastic body similar to a sponge. We assigned the maximum tissue density of lung parenchyma over which the lung tissue could not be contracted according to several experimental reports in literature. SBNW curves were then simulated by computing expired air volume and nitrogen concentration for respective acini in the lung model. The simulated SBNW curves well reproduced phase IV, cardiac oscillation, and its postural changes. We found that the higher lung compliance increased closing volume, but decreased residual volume. The smaller maximum tissue density generated larger closing volume and larger residual volume. It suggested that phase IV reflected the alveolar contractility, and the increase of closing volume in emphysema could be explained by an insufficient contraction of alveoli. We also found that the distribution of maximum tissue density affected the onset of Phase IV. A constant value of density generated a clear onset, but a wide distribution of it corresponding to peripheral airway closure obscured it. We suggest that the airway closure was not necessary for phase IV appearance in both normal and emphysematous lung.

Closing volume: a reappraisal (1967-2007).

Measurement of closing volume (CV) allows detection of presence or absence of tidal airway closure, i.e. cyclic opening and closure of peripheral airways with concurrent (1) inhomogeneity of distribution of ventilation and impaired gas exchange; and (2) risk of peripheral airway injury. Tidal airway closure, which can occur when the CV exceeds the end-expiratory lung volume (EELV), is commonly observed in diseases characterised by increased CV (e.g. chronic obstructive pulmonary disease, asthma) and/or decreased EELV (e.g. obesity, chronic heart failure). Risk of tidal airway closure is enhanced by ageing. In patients with tidal airway closure (CV > EELV) there is not only impairment of pulmonary gas exchange, but also peripheral airway disease due to injury of the peripheral airways. In view of this, the causes and consequences of tidal airway closure are reviewed, and further studies are suggested. In addition, assessment of the "open volume", as opposed to the "closing volume", is proposed because it is easier to perform and it requires less equipment.

Estudo funcional do acometimento das pequenas vias aéreas nas pneumopatias intersticiais fibrosantes / Physiological study of small airwayfunction in fibrosing interstitial lung disease

Apesar de bem estabelecido em termos morfológicos, a repercussão funcional do envolvimento das pequenas vias aéreas nas pneumopatias intersticiais fibrosantes (PIF) permanece controversa. O presente estudo avaliou de maneira invasiva e não-invasiva (espirometria, volume de fechamento, variação da complacência dinâmica com a freqüência respiratória) a função das pequenas vias aéreas em portadores de PIF, comparando com grupo controle e correlacionando com índices morfométricos de biópsias. Os testes funcionais não diferenciaram portadores da doença dos controles quanto ao acomentimento das pequenas via aéreas e não se correlacionaram com os dados morfométricos.

Although well known involvement of small airway in fibrosing interstitial lung disease based on morfologic issues, its functional consequences remains controversial. We present an invasive and non-invasive physiologic study for small airway function (pulmonary function tests, closing volume and frequency dependence of dynamic compliance) in patients with lung fibrosis. The physiological data were compared with normal controls and correlated with morfometric measurements from biopsies. Specific small airway function data could not show obstructive pattern when compared with normals, and did not correlate with morofmetric data.

Closing capacity and gas exchange in chronic heart failure.

BACKGROUND: Although it is commonly assumed that pulmonary congestion and edema in patients with chronic heart failure (CHF) promotes peripheral airway closure, closing capacity (CC) has not been measured in CHF patients. PURPOSES: To measure CC and the presence or absence of airway closure and expiratory flow limitation (FL) during resting breathing in CHF patients. METHODS: In 20 CHF patients and 20 control subjects, we assessed CC, FL, spirometry, blood gas levels, control of breathing, breathing pattern, and dyspnea. RESULTS: The patients exhibited a mild restrictive pattern, but the CC was not significantly different from that in control subjects. Nevertheless, airway closure during tidal breathing (ie, CC greater than functional residual capacity [FRC]) was present in most patients but was absent in all control subjects. As a result of the maldistribution of ventilation and the concurrent impairment of gas exchange, the mean (+/- SD) alveolar-arterial oxygen pressure difference increased significantly in CHF patients (4.3 +/- 1.2 vs 2.7 +/- 0.5 kPa, respectively; p < 0.001) and correlated with systolic pulmonary artery pressure (r = 0.49; p < 0.03). Tidal FL is absent in CHF patients. Mouth occlusion pressure 100 ms after onset of inspiratory effort (P0.1) as a percentage of maximal inspiratory pressure (Pimax) together with ventilation were increased in CHF patients (p < 0.01 and p < 0.005, respectively). The increase in ventilation was due entirely to increased respiratory frequency (fR) with a concurrent decrease in Paco2. Chronic dyspnea (scored with the Medical Research Council [MRC] scale) correlated (r2= 0.61; p < 0.001) with fR and P0.1/Pimax. CONCLUSIONS: In CHF patients at rest, CC is not increased, but, as a result of decreased FRC, airway closure during tidal breathing is present, promoting the maldistribution of ventilation, ventilation-perfusion mismatch, and impaired gas exchange. The ventilation is increased as result of increased fR, and Pimax is decreased with a concurrent increase in P0.1, implying that there is a proportionately greater inspiratory effort per breath (P0.1/Pimax). These, together with the increased fR, are the only significant contributors to increases in the MRC dyspnea score.

Contributions of lower limb and abdominal compression to ventilation inhomogeneity in hypergravity.

Gravito-inertial load in the head-to-foot direction (Gz) and compression of the lower body half by an anti-G suit (AGS) are both known to influence ventilation distribution in the lungs. To study the interaction of Gz and AGS and to asses the separate contributions from lower limbs and abdominal compressions to large and small-scale ventilation inhomogeneities nine males performed SF6/He vital capacity (VC) single-breath washouts at 1, 2, and 3 Gz in a centrifuge, with abdominal and/or lower limbs compressions. SF6/He and (SF6-He) phase III slopes were used for determination of overall and small-scale ventilation inhomogeneity. Closing volume and phase IV height were used as measures of large-scale inhomogeneity. VC decreased marginally with G-load but markedly with lower limbs compression. Small-scale ventilation inhomogeneity increased slightly with G-load, but substantially with AGS pressurization. Small-scale ventilation inhomogeneity increased with AGS pressurization. Large-scale inhomogeneity increased markedly with G-load. Translocation of blood to the lungs might be the key determinant for changes in small-scale ventilation inhomogeneity when pressurizing an AGS.

Airway closure in microgravity.

Recent single breath washout (SBW) studies in microgravity and on the ground have suggested an important effect of airway closure on gas mixing in the human lung, reflected particularly in the phase III slope of vital capacity SBW and bolus tests. In order to explore this effect, we designed a SBW in which subjects inspired 2-l from residual volume (RV) starting with a 150 ml bolus of He and SF6. In an attempt to vary the pattern of airways closure configuration before the test, the experiments were conducted in 1G and in microgravity during parabolic flight allowing the pre-test expiration to RV to be either in microgravity or at 1.8 G, with the actual test gas inhalation performed entirely in microgravity. Contrary to our expectations, the measured phase III slope and phase IV height and volume obtained from seven subjects in microgravity were essentially identical irrespective of the gravity level during the pre-test expiration to RV. The results suggest that airway closure configuration at RV before the test inspiration has no apparent impact on phases III and IV generation.

Contribution of body habitus and craniofacial characteristics to segmental closing pressures of the passive pharynx in patients with sleep-disordered breathing.

Obesity and craniofacial abnormalities may contribute to the pathogenesis of obstructive sleep apnea. The purpose of this study was to evaluate the influence of body habitus and craniofacial characteristics on types of pharyngeal closure. The types of pharyngeal closure were determined by endoscopic evaluations of closing pressures of the passive pharynx in 54 paralyzed and anesthetized patients with sleep-disordered breathing (SDB). Assessment of craniofacial characteristics of the SDB patients and 24 normal subjects were made by lateral cephalometry. As compared with normal subjects, SDB patients demonstrated receded mandibles and long lower faces with downward mandible development. SDB patients with positive closing pressures at both the velopharynx and oropharynx (VP + OP group) demonstrated smaller maxillas and mandibles than those with positive closing pressures at the velopharynx only (VP-only group). Obesity was more prominent in the VP-only group than in the VP + OP group. Our results suggest that obesity and craniofacial abnormalities contribute synergistically to increases in collapsibility of the passive pharyngeal airway in patients with SDB. Furthermore, the relative contribution of obesity and craniofacial anomaly appears to determine the type of pharyngeal closure in SDB.

Recurrent exacerbations in severe asthma are associated with enhanced airway closure during stable episodes.

Excessive airway narrowing is a cardinal feature of asthma, and results in closure of airways. Therefore, asthmatic patients in whom airway closure occurs relatively early during expiration might be prone to severe asthma attacks. To test this hypothesis, we compared closing volume (CV) and closing capacity (CC) in a group of asthmatic patients with recurrent exacerbations (more than two exacerbations in the previous year; difficult-to-control asthma), consisting of 11 males and two females, aged 20 to 51 yr, with those in a group of equally severely asthmatic controls without recurrent exacerbations (stable asthma) consisting of 13 males and two females aged 18 to 52 yr. Both groups used equivalent doses of inhaled corticosteroids and were matched for sex, age, atopy, postbronchodilator FEV(1), and provocative concentration of methacholine causing a 20% decrease in FEV(1). They were studied during a clinically stable period of their disease. The patients inhaled 400 microg salbutamol via a spacer device, after which TLC and RV were measured by multibreath helium equilibration, together with the slope of Phase 3 (dN(2)), CV, and CC, by single-breath nitrogen washout. CV and CC were expressed as ratios of VC and TLC, respectively, and all data are presented as % predicted (mean +/- SEM). There was no difference in TLC in patients with difficult-to-control asthma and those with stable asthma (106.7 +/- 4.0% predicted versus 101.7 +/- 4.3% predicted, p = 0.40), RV (113.1 +/- 7.8% predicted versus 100.9 +/- 7.1% predicted, p = 0.26), or dN(2) (142.7 +/- 16.3% predicted versus 116.0 +/- 20.2% predicted, p = 0.23). In contrast, CV and CC were increased in the patients with difficult-to-control asthma as compared with the group with stable asthma (CV: 159.5 +/- 26.8% predicted versus 98.8 +/- 12.5% predicted, p = 0.024; CC: 114.0 +/- 6.4% predicted versus 99.9 +/- 3. 6% predicted, p = 0.030). These findings show that asthmatic individuals with recurrent exacerbations have increased CV and CC as compared with equally severely asthmatic but stable controls, even after bronchodilation during well-controlled episodes. The findings imply that airway closure at relatively high lung volumes under clinically stable conditions might be a risk factor for severe exacerbations in asthmatic patients.

Closing volume influences the postural effect on oxygenation in unilateral lung disease.

In normal adults, both blood flow and ventilation are distributed preferentially to the dependent lung zones. In adults with unilateral lung disease, arterial oxygenation improves when they are positioned with their good lung down because of improved matching of ventilation and perfusion. When the closing volume is increased, dependent airways are closed during tidal breathing, so that reduced ventilation-perfusion ratio and hypoxia develops and ventilation is preferentially distributed to the upper lung zones. We undertook an observational study on the effects of lateral recumbency on arterial oxygenation in adult patients with unilateral lung disease and tested the hypothesis that oxygenation in lateral recumbency might be influenced by an increase in closing volume. Arterial blood gases were analyzed in the supine, right and left lateral decubitus positions and the AaPO(2) was calculated in 44 randomly selected patients 49.9 +/- 18.7 yr of age with unilateral pneumonia (23 cases) or pulmonary tuberculosis (21 cases). In 26 patients, individual Pa(O(2)) with the normal lung in the dependent position was higher than that with the diseased lung; the opposite was true for 18 patients. The difference in Pa(O(2)) and AaPO(2) between the two positions was statistically significant in both groups. In 16 patients (10 men and six women 49.2 +/- 18.2 yr of age), we measured closing volume and determined the fractional ventilation to each lung by (133)Xe lung scan in the three positions. In these 16 patients, the difference in Pa(O(2)) between the normal and the diseased lung in the dependent position was related significantly to the difference in the fractional ventilation going to the normal lung between the dependent and the supine position (r = 0.642, p = 0. 007). The latter was related significantly to the % predicted closing volume (CV/VC) (r = -0.597, p = 0.015). This study has shown that closing volume, as well as posture, might be involved in determining oxygenation in lateral recumbency in patients with unilateral lung disease.

Surfactant effects in model airway closure experiments.

The capillary instability that occurs on an annular film lining a tube is studied as a model of airway closure. Small waves in the film can amplify and form a plug across the tube. This dynamical behavior is studied using theoretical models and bench-top experiments. Our model predicts the initial growth rate of the instability and its dependence on surfactant effects. In experiments, an annular film is formed by infusion of water into an initially oil-filled glass capillary tube. The thickness of the oil film varies with the infusion flow rate. The instability growth rate and closure time are measured for a range of film thicknesses. Our theory predicts that a thinner film and higher surfactant activity enhance stability; surfactant can decrease the growth rate to 25% of its surfactant-free value. In experiments, we find that surfactant can decrease the growth rate to 20% and increase the closure time by a factor of 3.8. Functional values of a critical film thickness for closure support the theory that it increases in the presence of surfactant.