Effect of removal of bullae on airway conductance and conductance volume ratios

Airway conductance is known to increase with an increase in the lung volume at which it is measured, owing to a change in transpulmonary pressure and lung tissue tension. We investigated the effect of surgical resection of lung tissue on functional residual capacity and airway conductance in patients with localized lung disease (i.e., carcinoma or tuberculosis) and in patients with lung cysts or bullous emphysema. In four out of five of the patients who had resection of one or more lobes of the lung to remove localized disease there was a reduction both in the airway conductance and in the functional residual capacity with relatively little change in the conductance volume ratio.By contrast, in all patients who underwent bullectomy, there was a decrease in functional residual capacity but an increase in airway conductance, and an increase in the conductance/volume ratio. This change was sustained in patients who had had localized cysts removed. However, the measurements gradually reverted toward preoperative values in those patients who had generalized emphysema.The increase in airway conductance after resection of blebs and bullae presumably was due to improved lung elastic pressure causing the airways to increase in diameter and conductance. In addition, some patients may have experienced relief of compression of neighboring airways.     

Measurement of pulsatile tidal volume, pressure amplitude, and gas flow during high-frequency percussive ventilation, with and without partial cuff deflation

OBJECTIVE: With a high-frequency percussive ventilator and a mechanical lung model, to measure tidal volume (V(T)), pulsatile pressure amplitude (difference between peak and nadir pulsatile pressure [DeltaP];), and mean airway pressure (P (aw)) at various pulsatile frequencies, pulsatile inspiratory-expiratory ratios (I:E(p)), and pressures (measured at the interface between the pulse-generator and the endotracheal tube [P(vent)]). METHODS: With the endotracheal tube inside an artificial trachea, we manipulated the high-frequency percussive ventilation settings and adjuncts, including pulsatile frequency, I:E(p), and P(vent) by manipulating pulsatile flow. We also studied the effects of partially deflating the endotracheal tube cuff. We measured P (aw), pulsatile pressure amplitude at the carina (DeltaP(c)), and pulsatile V(T) at the carina. With the cuff partly deflated, we measured the fraction of inspired oxygen (F(IO(2))) in the gas efflux above and below the cuff. RESULTS: Increasing the pulsatile frequency from 300 cycles/min to 600 cycles/min and changing the I:E(p) from 1:3 to 1:1 significantly reduced V(T) (p < 0.001). P (aw) and DeltaP(c) were unaffected by the change in pulsatile frequency or I:E(p), except when we did not preserve the pulsatile flow. The measured V(T) range was from 19.1 mL (at 600 cycles/min) to 47.3 mL (at 300 cycles/min). Partial cuff deflation did not significantly reduce P (aw) or DeltaP(c), but it did significantly reduce V(T) and F(IO(2)). CONCLUSION: During high-frequency percussive ventilation, the pulsatile frequency is inversely related to V(T). Partial cuff deflation reduces the delivered F(IO(2)).     

Small Airways in Idiopathic Pulmonary Fibrosis: COMPARISON OF MORPHOLOGIC AND PHYSIOLOGIC OBSERVATIONS

18 patients with idiopathic pulmonary fibrosis were studied to determine if they had morphologic evidence of small airways disease and if physiologic testing could predict morphologic findings. In the presence of normal airway function by standard physiologic studies (forced expiratory volume in 1 s/forced vital capacity and airway resistance by plethysmography), dynamic compliance, maximum expiratory flow-volume curves, and maximum flowstatic recoil curves were measured to detect physiologic alterations consistent with small airways abnormalities. These physiologic data were then compared with estimates of small airways diameter made in lung biopsy specimens.     

Acute effects of inhaled isoproterenol on the mechanical characteristics of the lungs in normal man

We investigated the effects of isoproterenol on the pulmonary mechanics of eight healthy male subjects. We measured the flow-volume, pressure-volume, resistance-volume, and pressure-flow relationships of the lungs of our subjects in addition to the forced expiratory volume (FEV(1)). The results of this study confirm earlier observations that isoproterenol produces a considerable decrease in airway resistance but only small changes in maximum expiratory flow. Measurements of static pressure-volume curves showed that isoproterenol caused a temporary decrease in the elastic recoil pressure of the lungs. In five men there were mean falls in recoil pressure of 4.1 cm H(2)O at 85% total lung capacity (TLC), 2.6 cm H(2)O at 75% TLC, and 1.5 cm H(2)O at 50% TLC. We postulate that the reason for the relatively small increments in maximum expiratory flow after isoproterenol is primarily that the effects of airway dilatation are in large part negated by the reduction in lung recoil pressure, which results in a fall in the maximum effective driving force for expiratory air flow, and secondly that there is an increase in the compliance of the flow-limiting airways. These studies emphasize that tests of maximum flow and of airway resistance should not be regarded as invariably interchangeable in the assessment of airway reactions or mild disease of the airways.     

What does airway resistance tell us about lung function?

Spirometry is considered the primary method to detect the air flow limitation associated with obstructive lung disease. However, air flow limitation is the end-result of many factors that contribute to obstructive lung disease. One of these factors is increased airway resistance. Airway resistance is traditionally measured by relating air flow and driving pressure using body plethysmography, thus deriving airway resistance (R(aw)), specific airway resistance (sR(aw)), and specific airway conductance (sG(aw)). Other methods to measure airway resistance include the forced oscillation technique (FOT), which allows calculation of respiratory system resistance (R(RS)) and reactance (X(RS)), and the interrupter technique, which allows calculation of interrupter resistance (R(int)). An advantage of these other methods is that they may be easier to perform than spirometry, making them particularly suited to patients who cannot perform spirometry, such as young children, patients with neuromuscular disorders, or patients on mechanical ventilation. Since spirometry also requires a deep inhalation, which can alter airway resistance, these alternative methods may provide more sensitive measures of airway resistance. Furthermore, the FOT provides unique information about lung mechanics that is not available from analysis using spirometry, body plethysmography, or the interrupter technique. However, it is unclear whether any of these measures of airway resistance contribute clinically important information to the traditional measures derived from spirometry (FEV(1), FVC, and FEV(1)/FVC). The purpose of this paper is to review the physiology and methodology of these measures of airway resistance, and then focus on their clinical utility in relation to each other and to spirometry.     

Respiratory mechanics and dust exposure in byssinosis

Acute exposures to hemp dust, in healthy subjects as well as hemp workers with byssinosis, resulted in two different responses. Men with symptoms (chest tightness, coughing, and wheezing) after exposure showed decreases of forced expiratory volumes (FEV(1.0)), flow rates on maximum expiratory flow-volume (MEFV) curves, and of vital capacity (VC), while airway conductance (Gaw: TGV ratio) did not decrease significantly ("flow rate response"). Men without symptoms after exposure showed no changes of VC, FEV(1.0), and MEFV curves, but had a significantly decreased airway conductance ("conductance response"). The flow rate response is attributed to a pharmacological bronchoconstrictor effect of hemp dust on small airways, the conductance response to a mechanical or reflex effect of hemp dust on large airways. Both responses were abolished by a bronchodilator drug. The type of response reflects a difference between individuals and is not related to age, smoking habits, or prior exposure history. Men with normal control function data had either a flow rate or a conductance response. All men with abnormal control data had a flow rate response.Long-term hemp dust exposure causes irreversible obstructive lung disease, in particular among men who respond to acute dust exposure with symptoms and flow rate decreases. The detection of this response, with FEV(1.0) measurements and MEFV curves, is essential in the study of byssinosis. Decreases of airway conductance after dust exposure have no consistent relation to the development of clinical symptoms. The relative value of measurements of maximum expiratory flow rates and of airway conductance in other lung diseases needs to be reassessed.     

Maximum expiratory flow rates in induced bronchoconstriction in man

We evaluated changes of maximum expiratory flow-volume (MEFV) curves and of partial expiratory flow-volume (PEFV) curves caused by bronchoconstrictor drugs and dust, and compared these to the reverse changes induced by a bronchodilator drug in previously bronchoconstricted subjects. Measurements of maximum flow at constant lung inflation (i.e. liters thoracic gas volume) showed larger changes, both after constriction and after dilation, than measurements of peak expiratory flow rate, 1 sec forced expiratory volume and the slope of the effort-independent portion of MEFV curves. Changes of flow rates on PEFV curves (made after inspiration to mid-vital capacity) were usually larger than those of flow rates on MEFV curves (made after inspiration to total lung capacity). The decreased maximum flow rates after constrictor agents are not caused by changes in lung static recoil force and are attributed to narrowing of small airways, i.e., airways which are uncompressed during forced expirations. Changes of maximum expiratory flow rates at constant lung inflation (e.g. 60% of the control total lung capacity) provide an objective and sensitive measurement of changes in airway caliber which remains valid if total lung capacity is altered during treatment.     

The peak atrioventricular pressure gradient to transmitral flow relation: kinematic model prediction with in vivo validation.

Physiologists and cardiologists estimate peak transvalvular pressure gradients (DeltaP) by Doppler echocardiographic imaging of peak flow velocities using the simplified Bernoulli relationship: DeltaP (mm Hg) = 4V(2) (m/s). Because left ventricular filling is initiated by mechanical suction, V can be predicted by the motion of a simple harmonic oscillator by the parametrized diastolic filling formalism that characterizes E-wave contours by 3 unique simple harmonic oscillator parameters: initial displacement (x(o) cm); spring constant (k g/s(2)); and damping constant (c g/s). Parametrized diastolic filling predicts peak atrioventricular pressure gradient as kx(o), the peak simple harmonic oscillator force. For validation, simultaneous (micromanometric) left ventricular pressure and E-wave data from 19 patients were analyzed. Model-predicted peak gradient (kx(o)) was compared with actual gradient (DeltaP(cath)) and with 4V(2). Multiple linear regression results for all patients yielded highly significant relation between kx(o) and DeltaP(cath) (kx(o) = m(1)DeltaP(cath) + b(1), where m(1) = 40.7 +/- 8.0 dyne/mm Hg, b(1) = 1540 +/- 116 dyne, r(2) = 0.97, P <.001). Regression analysis showed no significant correlation between 4V(2) and DeltaP(cath) (4V(2) = m(2)DeltaP(cath) + b(2), where m(2) = 0.01 +/- 0.03, m(2)/s(2)/mm Hg and b(2) = 2.07 +/- 0.44 m(2)/s(2), P = nonsignificant). We conclude that E-wave analysis by parametrized diastolic filling predicts peak atrioventricular gradients reliably and more accurately than 4V(2).     

Effect of lung parenchyma on bronchial collapsibility during maximum expiratory flow in dogs.

Effect of peribronchial lung parenchyma on bronchial collapsibility during the maximum expiration was studied in the dog lung. Maximum expiratory flow volume curve (MEFVC) was obtained from dogs with intact parenchyma (I), parenchyma being dissected away from main lobar bronchi 1.5 cm in depth (II) and the dissected parenchyma glued to the bronchi with adhesive substance (III). Lung elastic pressure-volume curve and airway resistance were almost unchanged in the three conditions. Maximum expiratory flow (V max) in condition II was considerably decreased and the ratio of decrease to the control value was high at the lower lung volumes. V max in condition III was significantly higher than the control values except at the very low lung volumes. It was proved that even if the airway down to segmental bronchi was dessected from peribronchial lung parenchyma, V max was significantly limited. It was concluded that the radial traction of peribronchial parenchyma to the bronchi reduced bronchial collapsibility considerably, and in the dissected bronchi of condition II dynamic airway collapse would occur very easily.     

Positive end-expiratory pressure in COVID-19-related ARDS: Do not forget the airway closure

Airway closure is a physiological phenomenon in which the distal airways are obstructed when the airway pressure drops below the airway opening pressure. We assessed this phenomenon in 27 patients with coronavirus disease 2019-related acute respiratory distress syndrome. Twelve (44%) patients had an airway opening pressure above 5 cmH₂O. The median airway opening pressure was 8 cmH₂O (interquartile range, 7–10), with a maximum value of 17 cmH₂O. Three patients had a baseline positive end-expiratory pressure lower than the airway opening pressure.     

Lung Structure and Function with Age in Normal Rats and Rats With Papain Emphysema

Intrapulmonary deposition of the proteolytic enzyme papain produces a lesion resembling emphysema in experimental animals. The natural history of this lesion has not been well defined. The present study was performed to evaluate changes in lung structure and function with aging in normal rats and rats exposed to an aerosol of papain at 2 mo of age. Groups of control and papain-exposed animals were studied at 4, 8, and 18 mo of age. The parameters of lung function studied were specific airways' conductance (G(aw)/TGV), diffusing capacity per unit of alveolar volume (D(Lco)/V(A)), diffusing capacity (D(Lco)), and functional residual capacity (FRC). Morphometric parameters were the postfixation lung volume (V(L)) and mean chord length (L(M)); internal surface area (ISA) and ISA extrapolated to both the mean V(L) of the corresponding papain group and a V(L) of 10 ml (ISA(10)) were calculated.At 4 mo of age L(M) and FRC were significantly increased and ISA, D(Lco)/V(A), and D(Lco) were significantly reduced in the papain group. At 8 mo of age L(M) was significantly increased and ISA was significantly decreased in the papain group: physiologic studies were not performed in this group. At 18 mo of age L(M) was significantly increased and D(Lco)/V(A), D(Lco), and ISA were significantly decreased. Neither progression nor healing of the lesion was observed despite similar lung growth in both groups.This study demonstrates that a single proteolytic lung injury produces a fixed deficit of lung parenchyma. Progressive lung destruction may require repeated or continuous lung injury.     

Effect of atrial natriuretic factor on bronchomotor tone in the normal human airway

1. Asthmatic patients bronchodilate in response to infused atrial natriuretic factor. We wished to determine whether the airways of normal subjects responded in a similar way. 2. Changes in airway resistance, as determined by specific airway conductance, were measured in eight normal subjects in response to intravenous infusion of atrial natriuretic factor at doses of 0.5, 2 and 10 pmol min-1 kg-1. 3. No significant effect was observed on specific airway conductance at any rate of infusion despite maximum mean (SEM) plasma levels of 597 (62) pg of atrial natriuretic factor/ml in peripheral venous blood. 4. A second study was performed using six of the eight original subjects and employing a pharmacological dose of 50 pmol of atrial natriuretic factor min-1 kg-1. This produced mean plasma levels of 2056 pg/ml and a mean increase of 31% in specific airway conductance. 5. It is concluded that pharmacological, but not pathophysiological, elevations of plasma atrial natriuretic factor may significantly alter bronchomotor tone in normal subjects.     

States of low pulmonary blood flow can be detected non-invasively at the bedside measuring alveolar dead space

We tested whether the ratio of alveolar dead space to alveolar tidal volume (VD(alv)/VT(alv)) can detect states of low pulmonary blood flow (PBF) in a non-invasive way. Fifteen patients undergoing cardiovascular surgeries with cardiopulmonary bypass (CPB) were studied. CPB is a technique that excludes the lungs from the general circulation. The weaning of CPB is a model that manipulates PBF in vivo because each time blood flow through the CPB decreases, expected PBF (ePBF) increases. Patients were liberated from CPB in steps of 20 % every 2' starting from 100 % CPB (very low ePBF) to 0 % CPB (100 % ePBF). During constant ventilation, volumetric capnograms were recorded and Bohr's dead space ratio (VD(Bohr)/VT), VD(alv)/VT(alv) and the ratio of airway dead space to tidal volume (VD(aw)/VT) were calculated. Before CPB, VD(Bohr)/VT was 0.36 ± 0.05, VD(aw)/VT 0.21 ± 0.04 and VD(alv)/VT(alv) 0.18 ± 0.06 (mean ± SD). During weaning from CPB, VD(aw)/VT remained unchanged while VD(Bohr)/VT and VD(alv)/VT(alv) decreased with increasing ePBF. At CPB of 80, 60, 40 and 20 % VD(Bohr)/VT was 0.64 ± 0.06, 0.55 ± 0.06, 0.47 ± 0.05 and 0.40 ± 0.04, respectively; p < 0.001 and VD(alv)/VT(alv) 0.53 ± 0.07, 0.40 ± 0.07, 0.29 ± 0.06 and 0.25 ± 0.04, respectively; p < 0.001). After CPB, VD(Bohr)/VT and VD(alv)/VT(alv) reached values similar to baseline (0.37 ± 0.04 and 0.19 ± 0.06, respectively). At constant ventilation the alveolar component of VD(Bohr)/VT increased in proportion to the deficit in lung perfusion.     

Determinants of dynamic hyperinflation in a bench model

BACKGROUND: Previous in vivo data suggest that high airway resistance (R(aw)) promotes dynamic hyperinflation, especially when coupled to high minute ventilation (V(E)). However, no studies have systematically examined the relative effects of various mechanical parameters on dynamic hyperinflation. METHODS: Intrinsic positive end-expiratory pressure (PEEPi) was measured with a ventilator-lung model, over a range and various permutations of R(aw), V(E), respiratory system compliance (C(RS)), and duty cycles/flow regimes. RESULTS: Substantial dynamic hyperinflation (PEEPi > 5 cm H(2)O occurred at various V(E), even when R(aw) was low (4 cm H(2)O/L/s) or just above normal (18 cm H(2)O/L/s). A V(E) > or = 15 L/min was associated with increasing PEEPi in this model, across a broad range of mechanical permutations. PEEPi was significantly higher in all models during descending ramp flow than during constant flow, at equivalent peak flows (wherein duty cycle during descending ramp flow was twice that of constant flow). PEEPi was equivalent when duty cycles (and all other mechanical parameters) were equal. PEEPi was significantly greater, irrespective of duty cycle, R(aw), and C(RS), when delivered with lower tidal volume (0.6 L vs 1.0 L). The change in peak airway pressure associated with development of dynamic hyperinflation was consistently greater than the observed PEEPi. Higher V(E), resistance, compliance, and duty cycles were all independently associated with dynamic hyperinflation. CONCLUSIONS: In this bench model, dynamic hyperinflation occurred with high V(E), even at low R(aw). Since moderate R(aw) and V(E) frequently occur in vivo, even without obstructive lung disease, occult dynamic hyperinflation is likely to occur commonly. PEEPi was greater with high frequency and small tidal volume (0.6 L) than with equal V(E) of lower frequency and larger tidal volume (1.0 L).     

Setting positive end-expiratory pressure during jet ventilation to replicate the mean airway pressure of oscillatory ventilation

BACKGROUND: High-frequency ventilation can be delivered with either oscillatory ventilation (HFOV) or jet ventilation (HFJV). Traditional clinician biases may limit the range of function of these important ventilation modes. We hypothesized that (1) the jet ventilator can be an accurate monitor of mean airway pressure (P (aw)) during HFOV, and (2) a mathematical relationship can be used to determine the positive end-expiratory pressure (PEEP) setting required for HFJV to reproduce the P (aw) of HFOV. METHODS: In phase 1 of our experiment, we used a differential pressure pneumotachometer and a jet adapter in-line between an oscillator circuit and a pediatric lung model to measure P (aw), PEEP, and peak inspiratory pressure (PIP). Thirty-six HFOV setting combinations were studied, in random order. We analyzed the correlation between the pneumotachometer and HFJV measurements. In phase 2 we used the jet as the monitoring device during each of the same 36 combinations of HFOV settings, and recorded P (aw), PIP, and DeltaP. Then, for each combination of settings, the jet ventilator was placed in-line with a conventional ventilator and was set at the same rate and PIP as was monitored during HFOV. To determine the appropriate PEEP setting, we calculated the P (aw) contributed by the PIP, respiratory rate, and inspiratory time set for HFJV, and subtracted this from the goal P (aw). This value was the PEEP predicted for HFJV to match the HFOV P (aw). RESULTS: The correlation coefficient between the pneumotachometer and HFJV measurements was r = 0.99 (mean difference 0.62 +/- 0.30 cm H(2)O, p < 0.001). The predicted and actual PEEP required were highly correlated (r = 0.99, p < 0.001). The mean difference in these values is not statistically significantly different from zero (mean difference 0.25 +/- 1.02 cm H(2)O, p > 0.15). CONCLUSIONS: HFJV is an accurate monitor during HFOV. These measurements can be used to calculate the predicted PEEP necessary to match P (aw) on the 2 ventilators. Replicating the P (aw) with adequate PEEP on HFJV may help simplify transitioning between ventilators when clinically indicated.     

Superior vena caval collapsibility as a gauge of volume status in ventilated septic patients

OBJECTIVE: In mechanically ventilated patients inspiratory increase in pleural pressure during lung inflation may produce complete or partial collapse of the superior vena cava. Occurrence of this collapse suggests that at this time external pressure exerted by the thoracic cavity on the superior vena cava is greater than the venous pressure required to maintain the vessel fully open. We tested the hypothesis that measurement of superior vena caval collapsibility would reveal the need for volume expansion in a given septic patient. DESIGN AND SETTING: Prospective data collection for 66 successive patients in septic shock admitted in a medical intensive care unit and mechanically ventilated for an associated acute lung injury. MEASUREMENTS AND RESULTS: We simultaneously measured superior vena caval collapsibility by echocardiography and cardiac index by the Doppler technique at baseline and after a 10 ml/kg volume expansion by 6% hydroxyethyl starch in 30 min. The threshold superior vena caval collapsibility of 36%, calculated as (maximum diameter on expiration-minimum diameter on inspiration)/maximum diameter on expiration, allowed discrimination between responders (defined by an increase in cardiac index of at least 11% induced by volume expansion) and nonresponders, with a sensitivity of 90% and a specificity of 100%. CONCLUSIONS: Superior vena cava measurement should be systematically performed during routine echocardiography in septic shock as it gives an accurate index of fluid responsiveness.     

Roles of airway inflammation in chronic airflow obstruction]

Airway inflammation plays a vital role in the pathophysiology of chronic obstructive pulmonary disease (COPD). Chronic airflow obstruction, a hallmark of COPD, is a manifestation of an intricate combination of loss of elastic recoil of the lung, small airway disease, mucus hypersecretion, and airway wall thickening/contraction. Airway inflammation appears to contribute to all of these components.     

Comparison of different airway management strategies to ventilate apneic,nonpreoxygenated patients

OBJECTIVE: Endotracheal intubation is the gold standard for providing emergency ventilation, but acquiring and maintaining intubation skills may be difficult. Recent reports indicate that even in urban emergency medical services with a high call volume, esophageal intubations were observed, requiring either perfect intubation skills or development of alternatives for emergency ventilation. DESIGN: Simulated emergency ventilation in apneic patients employing four different airway devices that used small tidal volumes. SETTING: University hospital operating room. SUBJECTS: Forty-eight ASA I/II patients who signed written informed consent before being enrolled into the study. INTERVENTIONS: In healthy adult patients without underlying respiratory or cardiac disease who were breathing room air before undergoing routine induction of surgery, 12 experienced professional paramedics inserted either a laryngeal mask airway (n = 12), Combitube (n = 12), or cuffed oropharyngeal airway (n = 12) or placed a face mask (n = 12) before providing ventilation with a pediatric (maximum volume, 700 mL) self-inflating bag with 100% oxygen for 3 mins. MEASUREMENTS AND MAIN RESULTS: In three of 12 cuffed oropharyngeal airway patients, two of 12 laryngeal mask airway patients, and one of 12 Combitube patients, oxygen saturation fell below 90% during airway device insertion, and the experiment was terminated; no oxygenation failures occurred with the bag-valve-mask. Oxygen saturation decreased significantly (p <.05) during insertion of the Combitube and laryngeal mask but not with the bag-valve-mask and cuffed oropharyngeal airway; however, oxygen saturation increased after 1 min of ventilation with 100% oxygen. No differences in tidal lung volumes were observed between airway devices. CONCLUSIONS: Paramedics were able to employ the laryngeal mask airway, Combitube, and cuffed oropharyngeal airway in apneic patients with normal lung compliance and airways. In this population, bag-valve-mask ventilation was the most simple and successful strategy. Small tidal volumes applied with a pediatric self-inflating bag and 100% oxygen resulted in adequate oxygenation and ventilation.     

Expiratory flow limitation and the response to breathing a helium-oxygen gas mixture in a canine model of pulmonary emphysema

The pathophysiology of reduced maximum expiratory flow in a canine model of pulmonary emphysema was studied, and the results interpreted in terms of the wave-speed theory of flow limitation. According to this theory, maximum expiratory flow is related both to the cross-sectional area and compliance at an airway site where a critical gas velocity is first reached ("choke-point") and to gas density. Pulmonary emphysema was produced by the repeated instillations of the enzyme papain into the airways of six dogs. In five control dogs, a saline solution was instilled. During forced vital capacity deflation, in an open-chest preparation, maximum expiratory flow, choke-point locations, and the response to breathing an 80:20 helium/oxygen gas mixture were determined at multiple lung volumes. To locate choke-points, a pressure measuring device was positioned in the airway to measure lateral and end-on intrabronchial pressures, from which the relevant wave-speed parameters were obtained. In general, the reduced maximum expiratory flow in emphysema can be explained by diminished lung elastic recoil pressure and by altered bronchial pressure-area behavior, which results in a more peripheral location of choke-points that have smaller cross-sectional areas than controls. With respect to the density dependence of maximum expiratory flow, this response did not differ from control values in four dogs with emphysema in which frictional pressure losses upstream from choke-points did not differ on the two gas mixtures. In two dogs with emphysema, however, upstream frictional pressure losses were greater on helium/oxygen than on air, which resulted in a smaller cross-sectional area on helium/oxygen; hence density dependence decreased.     

The amiloride-inhibitable Na+ conductance is reduced by the cystic fibrosis transmembrane conductance regulator in normal but not in cystic fibrosis airways.

Cystic fibrosis (CF) airway cells, besides their well-known defect in cAMP-dependent Cl- conductance, are characterized by an enhanced Na+ conductance. In this study we have examined the Na+ conductance in human respiratory tract by measuring transepithelial voltage and resistance (Vte, Rte) and by assessing membrane voltages (Vm) of freshly isolated airway epithelial cells from CF and non-CF patients. Basal amiloride inhibitable (10 micromol/liter) equivalent short circuit current (Isc = Vte/Rte) was significantly increased in CF compared with non-CF tissues. After stimulation by forskolin (10 micromol/liter) a significant depolarization of Vm corresponding to the cAMP-dependent activation of a Cl- conductance was observed in non-CF but not in CF airway cells. In non-CF tissue but not in CF tissue the effects of amiloride and N-methyl-D-glucamine on Vm were attenuated in the presence of forskolin. Also the amiloride-inhibitable Isc was significantly reduced by forskolin (1 micromol/liter) and isobutylmethylxanthine (IBMX; 100 micromol/liter) only in non-CF tissue. We conclude that cystic fibrosis transmembrane conductance regulator acts as a downregulator of epithelial Na+ channels in human airways. This downregulation of epithelial Na+ channels is absent in CF airways, leading to hyperabsorption and to the characteristic increase in mucus viscosity.