ASTHMA,CHRONIC BRONCHITIS AND EMPHYSEMA—The Use of Intermittent Positive Pressure Breathing with Inspiratory Flow Rate Control: A Review of the Literature

In chronic obstructive lung disease (asthma, chronic bronchitis, obstructive emphysema) there is a segmental reduction in the caliber of the airways, which always results in obstruction to air-flow. Increased airway resistance is a physiological expression of airway obstruction.The addition of inspiratory flow rate control to an intermittent positive pressure breathing device permits slow filling of a lung with obstructed airways, and is presented as a simple means of reducing the high pulmonary flow resistance and increasing the tidal volume.     

Effect of lung volume on plateau response of airways and tissue to methacholine in dogs.

We have recently shown in dogs that much of the increase in lung resistance (RL) after induced constriction can be attributed to increases in tissue resistance, the pressure drop in phase with flow across the lung tissues (Rti). Rti is dependent on lung volume (VL) even after induced constriction. As maximal responses in RL to constrictor agonists can also be affected by changes in VL, we questioned whether changes in the plateau response with VL could be attributed in part to changes in the resistive properties of lung tissues. We studied the effect of changes in VL on RL, Rti, airway resistance (Raw), and lung elastance (EL) during maximal methacholine (MCh)-induced constriction in 8 anesthetized, paralyzed, open-chest mongrel dogs. We measured tracheal flow and pressure (Ptr) and alveolar pressure (PA), the latter using alveolar capsules, during tidal ventilation [positive end-expiratory pressure (PEEP) = 5.0 cmH2O, tidal volume = 15 ml/kg, frequency = 0.3 Hz]. Measurements were recorded at baseline and after the aerosolization of increasing concentrations of MCh until a clear plateau response had been achieved. VL was then altered by changing PEEP to 2.5, 7.5, and 10 cmH2O. RL changed only when PEEP was altered from 5 to 10 cmH2O (P < 0.01). EL changed when PEEP was changed from 5 to 7.5 and 5 to 10 cmH2O (P < 0.05). Rti and Raw varied significantly with all three maneuvers (P < 0.05). Our data demonstrate that the effects of VL on the plateau response reflect a complex combination of changes in tissue resistance, airway caliber, and lung recoil.     

Lung and chest wall impedances in the dog in normal range of breathing: effects of pulmonary edema.

We evaluated the effect of pulmonary edema on the frequency (f) and tidal volume (VT) dependences of respiratory system mechanical properties in the normal ranges of breathing. We measured resistance and elastance of the lungs (RL and EL) and chest wall of four anesthetized-paralyzed dogs during sinusoidal volume oscillations at the trachea (50-300 ml, 0.2-2 Hz), delivered at a constant mean airway pressure. Measurements were made before and after severe pulmonary edema was produced by injection of 0.06 ml/kg oleic acid into the right atrium. Chest wall properties were not changed by the injection. Before oleic acid, EL increased slightly with increasing f in each dog but was independent of VT. RL decreased slightly and was independent of VT from 0.2 to 0.4 Hz, but above 0.4 Hz it tended to increase with increasing flow, presumably due to the airway contribution. After oleic acid injection, EL and RL increased greatly. Large negative dependences of EL on VT and of RL on f were also evident, so that EL and RL after oleic acid changed two- and fivefold, respectively, within the ranges of f and VT studied. We conclude that severe pulmonary edema changes lung properties so as to make behavior VT dependent (i.e., nonlinear) and very frequency dependent in the normal range of breathing.     

Relationship between heterogeneous changes in airway morphometry and lung resistance and elastance

Lutchen, Kenneth R., and Heather Gillis. Relationshipbetween heterogeneous changes in airway morphometry and lung resistanceand elastance. J. Appl. Physiol.83(4): 1192-1201, 1997.We present a dog lung model to predictthe relation between inhomogeneous changes in airway morphometry andlung resistance (RL) andelastance (EL) for frequenciessurrounding typical breathing rates. TheRL andEL were sensitive in distinctways to two forms of peripheral constriction. First, when there is alarge and homogeneous constriction, theRL increases uniformly over thefrequency range. The EL israther unaffected below 1 Hz but then increases with frequencies up to5 Hz. This increase is caused by central airway wallshunting. Second, the RL andEL are extremely sensitive to mild inhomogeneous constriction in which a few highly constricted ornearly closed airways occur randomly throughout theperiphery. This results in extreme increases in the levelsand frequency dependence of RLand EL but predominantly attypical breathing rates (<1 Hz). Conversely, theRL andEL are insensitive to highly inhomogeneous airway constriction that does not produce any nearly closed airways. Similarly, alterations in theRL andEL due to central airway wallshunting are not likely until the preponderance of the peripheryconstricts substantially. The RLand EL spectra are far moresensitive to these two forms of peripheral constriction than toconstriction conditions known to occur in the central airways. On thebasis of these simulations, we derived a set of qualitative criteria toinfer airway constriction conditions from RL andEL spectra.

     

Inspiratory airway obstruction does not affect lung fluid balance in lambs

The purpose of this study was to examine the effects of inspiratory airway obstruction on lung fluid balance in newborn lambs. We studied seven 2- to 4-wk-old lambs that were sedated with chloral hydrate and allowed to breathe 30-40% O2 spontaneously through an endotracheal tube. We measured lung lymph flow, lymph and plasma protein concentrations, pulmonary arterial and left atrial pressures, mean and phasic pleural pressures and airway pressures, and cardiac output during a 2-h base-line period and then during a 2- to 3-h period of inspiratory airway obstruction produced by partially occluding the inspiratory limb of a nonrebreathing valve attached to the endotracheal tube. During inspiratory airway obstruction, both pleural and airway pressures decreased 5 Torr, whereas pulmonary arterial and left atrial pressures each decreased 4 Torr. As a result, calculated filtration pressure remained unchanged. Inspiratory airway obstruction had no effect on steady-state lung lymph flow or the lymph protein concentration relative to that of plasma. We conclude that in the spontaneously breathing lamb, any decrease in interstitial pressure resulting from inspiratory airway obstruction is offset by a decrease in microvascular hydrostatic pressure so that net fluid filtration remains unchanged.     

Site of airway obstruction in pulmonary disease: direct measurement of intrabronchial pressure.

To partition the central and peripheral airway resistance in awake humans, a catheter-tipped micromanometer sensing lateral pressure of the airway was wedged into the right lower lobe of a 3-mm-ID bronchus in 5 normal subjects, 7 patients with chronic bronchitis, 8 patients with emphysema, and 20 patients with bronchial asthma. We simultaneously measured mouth flow, transpulmonary pressure, and intra-airway lateral pressure during quiet tidal breathing. Total pulmonary resistance (RL) was calculated from transpulmonary pressure and mouth flow and central airway resistance (Rc) from intra-airway lateral pressure and mouth flow. Peripheral airway resistance (Rp) was obtained by the subtraction of Rc from RL. The technique permitted identification of the site of airway resistance changes. In normal subjects, RL was 3.2 +/- 0.2 (SE) cmH2O.l-1.s and the ratio of Rp to RL was 0.24 during inspiration. Patients with bronchial asthma without airflow obstruction showed values of Rc and Rp similar to those of normal subjects. Although Rc showed a tendency to increase, only Rp significantly increased in those patients with bronchial asthma with airflow obstruction and patients with chronic bronchitis and emphysema. The ratio of Rp to RL significantly increased in three groups of patients with airflow obstruction (P less than 0.01). These observations suggest that peripheral airways are the predominant site of airflow obstruction, irrespective of the different pathogenesis of chronic airflow obstruction.     

Vascular and airway effects of endogenous cyclooxygenase products during lung inflation

The influence of lung inflation on lung elasticity and pulmonary resistance (RL) and on pulmonary and bronchial hemodynamics was examined in five anesthetized, mechanically ventilated adult sheep before and after treatment with the cyclooxygenase inhibitor indomethacin (2 mg/kg). Lung inflation was accomplished by increasing levels of positive end-expiratory pressure (PEEP). Measurements of pulmonary vascular resistance (PVR), bronchial blood flow (Qbr), and RL were obtained with a Swan-Ganz catheter, with an electromagnetic flow probe placed around the carinal artery, and by relating airflow to transpulmonary pressure (Ptp), respectively. Before indomethacin, increasing PEEP from 5 to 15 cmH2O increased mean lung volume (VL) to 135% (P less than 0.01), Ptp to 165% (P less than 0.005), and PVR to 132% (P less than 0.05) of base line and decreased mean Qbr (normalized for cardiac output) to 53% (P less than 0.05) of base line. Mean RL showed a tendency to decrease with a mean value of 67% of base line at 15 cmH2O PEEP. After indomethacin the corresponding values were 121% for VL, 155% for Ptp, 124% for PVR, 35% for Qbr, and 31% for RL. The PEEP-dependent changes were not different before and after indomethacin except for mean VL, which increased less (P less than 0.05) after indomethacin. The failure of indomethacin to modify PEEP-induced changes in RL, PVR, and Qbr was also present when these parameters were expressed as a function of Ptp. These findings suggest that the cyclooxygenase products elaborated during lung inflation reduce lung elasticity but fail to influence airflow resistance and pulmonary and bronchial hemodynamics.     

Methacholine-induced bronchoconstriction in dogs: effects of lung volume and O3 exposure

The maximal effect induced by methacholine (MCh) aerosols on pulmonary resistance (RL), and the effects of altering lung volume and O3 exposure on these induced changes in RL, was studied in five anesthetized and paralyzed dogs. RL was measured at functional residual capacity (FRC), and lung volumes above and below FRC, after exposure to MCh aerosols generated from solutions of 0.1-300 mg MCh/ml. The relative site of response was examined by magnifying parenchymal [RL with large tidal volume (VT) at fast frequency (RLLS)] or airway effects [RL with small VT at fast frequency (RLSF)]. Measurements were performed on dogs before and after 2 h of exposure to 3 ppm O3. MCh concentration-response curves for both RLLS and RLSF were sigmoid shaped. Alterations in mean lung volume did not alter RLLS; however, RLSF was larger below FRC than at higher lung volumes. Although O3 exposure resulted in small leftward shifts of the concentration-response curve for RLLS, the airway dominated index of RL (RLSF) was not altered by O3 exposure, nor was the maximal response using either index of RL. These data suggest O3 exposure does not affect MCh responses in conducting airways; rather, it affects responses of peripheral contractile elements to MCh, without changing their maximal response.     

Effect of PEEP on respiratory mechanics in anesthetized paralyzed humans.

With the use of the technique of rapid airway occlusion during constant flow inflation, respiratory mechanics were studied in eight anesthetized paralyzed supine normal humans during zero (ZEEP) and positive end-expiratory pressure (PEEP) ventilation. PEEP increased the end-expiratory lung volume by 0.49 liter. The changes in transpulmonary and esophageal pressure after flow interruption were analyzed in terms of a seven-parameter "viscoelastic" model. This allowed assessment of static lung and chest wall elastance (Est,L and Est,W), partitioning of overall resistance into airway interrupter (Rint,L) and tissue resistances (delta RL and delta RW), and computation of lung and chest wall "viscoelastic constants." With increasing flow, Rint,L increased, whereas delta RL and delta RW decreased, as predicted by the model. Est,L, Est,W, and Rint,L decreased significantly with PEEP because of increased lung volume, whereas delta R and viscoelastic constants of lung and chest wall were independent of PEEP. The results indicate that PEEP caused a significant decrease in Rint,L, Est,L, and Est,W, whereas the dynamic tissue behavior, as reflected by delta RL and delta RW, did not change.     

Effects of lung volume on maximal methacholine-induced bronchoconstriction in normal humans

We examined the effects of lung volume on the bronchoconstriction induced by inhaled aerosolized methacholine (MCh) in seven normal subjects. We constructed dose-response curves to MCh, using measurements of inspiratory pulmonary resistance (RL) during tidal breathing at functional residual capacity (FRC) and after a change in end-expiratory lung volume (EEV) to either FRC -0.5 liter (n = 5) or FRC +0.5 liter (n = 2). Aerosols of MCh were generated using a nebulizer with an output of 0.12 ml/min and administered for 2 min in progressively doubling concentrations from 1 to 256 mg/ml. After MCh, RL rose from a base-line value of 2.1 +/- 0.3 cmH2O. 1-1 X s (mean +/- SE; n = 7) to a maximum of 13.9 +/- 1.8. In five of the seven subjects a plateau response to MCh was obtained at FRC. There was no correlation between the concentration of MCh required to double RL and the maximum value of RL. The dose-response relationship to MCh was markedly altered by changing lung volume. The bronchoconstrictor response was enhanced at FRC - 0.5 liter; RL reached a maximum of 39.0 +/- 4.0 cmH2O X 1-1 X s. Conversely, at FRC + 0.5 liter the maximum value of RL was reduced in both subjects from 8.2 and 16.6 to 6.0 and 7.7 cmH2O X 1-1 X s, respectively. We conclude that lung volume is a major determinant of the bronchoconstrictor response to MCh in normal subjects. We suggest that changes in lung volume act to alter the forces of interdependence between airways and parenchyma that oppose airway smooth muscle contraction.     

Impact of PEEP on lung mechanics and work of breathing in severe airflow obstruction

Positive end-expiratory pressure (PEEP) has generally been withheld from the treatment of patients with chronic airflow obstruction (CAO), in view of the risk of hyperinflation and lack of documented benefit. We studied 10 mechanically ventilated patients with exacerbated CAO and air trapping to determine the impact of PEEP on lung mechanics, alveolar pressure, and the work of breathing. PEEP levels of 5 and 10 cmH2O were applied to patients whose end-expiratory alveolar pressures were documented to be positive when breathing against ambient pressure (the auto-PEEP effect). All patients were studied under two conditions: every breath machine assisted (AMV) and every breath machine controlled (paralyzed, CMV). PEEP improved expiratory resistance without substantially increasing peak static pressure. Inspiratory resistance remained unchanged. The difference between the end-expiratory values of alveolar and central airway pressure narrowed as PEEP increased. Adding PEEP improved the effective triggering sensitivity of the ventilator, diminished ventilatory drive, and reduced the mechanical work of breathing during the machine-assisted ventilatory cycle. Our results indicate that low levels of PEEP may improve lung mechanics and reduce the effort required of mechanically ventilated patients with severe airflow obstruction, without substantially increasing the hazards of hyperinflation.     

Lung mechanics and end-expiratory lung volume during hypoxia in rats.

We investigated whether an hypoxia-induced increase in airway resistance mediated by vagal efferents participates in the increase in end-expiratory lung volume (EELV) observed in hypoxia. We also assessed the contribution of the end-expiratory activity of the diaphragm (DE) to this phenomenon. Therefore, we measured EELV, total lung resistance (RL), dynamic lung compliance (Cdyn), DE, and minute ventilation (VE) in anesthetized rats during normoxia and hypoxia (10% O(2)) before (control) and after administration of atropine or saline. In the control group, hypoxia increased EELV, Cdyn, DE, and VE but slightly decreased RL. These changes were unaffected by saline or atropine, except that, in the atropine-treated rats, hypoxia did not change RL. These results suggest that 1) the increase in EELV observed in hypoxia cannot result from an increase in airway resistance; 2) the increased and persistent activity of inspiratory muscles during expiration is the most likely cause of the increase in EELV during hypoxia; and 3) the decrease in RL induced by hypoxia could result from the increase in lung volume including EELV.     

Effects of mechanical ventilation at low lung volume on respiratory mechanics and nitric oxide exhalation in normal rabbits.

Lung mechanics, exhaled NO (NOe), and TNF-alpha in serum and bronchoalveolar lavage fluid were assessed in eight closed and eight open chest, normal anesthetized rabbits undergoing prolonged (3-4 h) mechanical ventilation (MV) at low volume with physiological tidal volumes (10 ml/kg). Relative to initial MV on positive end-expiratory pressure (PEEP), MV at low volume increased lung quasi-static elastance (+267 and +281%), airway (+471 and +382%) and viscolelastic resistance (+480 and +294%), and decreased NOe (-42 and -25%) in closed and open chest rabbits, respectively. After restoration of PEEP, viscoelastic resistance returned to control, whereas airway resistance remained elevated (+120 and +31%) and NOe low (-25 and -20%) in both groups of rabbits. Elastance remained elevated (+23%) only in closed-chest animals, being associated with interstitial pulmonary edema, as reflected by increased lung wet-to-dry weight ratio with normal albumin concentration in bronchoalveolar lavage fluid. In contrast, in 16 additional closed- and open-chest rabbits, there were no changes of lung mechanics or NOe after prolonged MV on PEEP only. At the end of prolonged MV, TNF-alpha was practically undetectable in serum, whereas its concentration in bronchoalveolar lavage fluid was low and similar in animals subjected or not subjected to ventilation at low volume (62 vs. 43 pg/ml). These results indicate that mechanical injury of peripheral airways due to their cyclic opening and closing during ventilation at low volume results in changes in lung mechanics and reduction in NOe and that these alterations are not mediated by a proinflammatory process, since this is expressed by TNF-alpha levels.     

Estimation of airway obstruction using oximeter plethysmograph waveform data

Background

Validated measures to assess the severity of airway obstruction in patients with obstructive airway disease are limited. Changes in the pulse oximeter plethysmograph waveform represent fluctuations in arterial flow. Analysis of these fluctuations might be useful clinically if they represent physiologic perturbations resulting from airway obstruction. We tested the hypothesis that the severity of airway obstruction could be estimated using plethysmograph waveform data.

Methods

Using a closed airway circuit with adjustable inspiratory and expiratory pressure relief valves, airway obstruction was induced in a prospective convenience sample of 31 healthy adult subjects. Maximal change in airway pressure at the mouthpiece was used as a surrogate measure of the degree of obstruction applied. Plethysmograph waveform data and mouthpiece airway pressure were acquired for 60 seconds at increasing levels of inspiratory and expiratory obstruction. At each level of applied obstruction, mean values for maximal change in waveform area under the curve and height as well as maximal change in mouth pressure were calculated for sequential 7.5 second intervals. Correlations of these waveform variables with mouth pressure values were then performed to determine if the magnitude of changes in these variables indicates the severity of airway obstruction.

Results

There were significant relationships between maximal change in area under the curve (P < .0001) or height (P < 0.0001) and mouth pressure.

Conclusion

The findings suggest that mathematic interpretation of plethysmograph waveform data may estimate the severity of airway obstruction and be of clinical utility in objective assessment of patients with obstructive airway diseases.     

Airway obstruction during exercise and isocapnic hyperventilation in asthmatic subjects.

We compared pulmonary mechanics measured during long-term exercise (LTX = 20 min) with long-term isocapnic hyperventilation (LTIH = 20 min) in the same asthmatic individuals (n = 6). Peak expiratory flow (PEF) and forced expiratory volume in 1 s (FEV(1)) decreased during LTX (-19.7 and -22.0%, respectively) and during LTIH (-6.66 and 10. 9%, respectively). In contrast, inspiratory pulmonary resistance (RL(I)) was elevated during LTX (57.6%) but not during LTIH (9.62%). As expected, airway function deteriorated post-LTX and post-LTIH (FEV(1) = -30.2 and -21.2%; RL(I) = 111.8 and 86.5%, respectively). We conclude that the degree of airway obstruction observed during LTX is of a greater magnitude than that observed during LTIH. Both modes of hyperpnea induced similar levels of airway obstruction in the posthyperpnea period. However, the greater airway obstruction during LTX suggests that a different process may be responsible for the changes in airway function during and after the two modes of hyperpnea. This finding raises questions about the equivalency of LTIH and LTX in the study of airway function during exercise-induced asthma.     

Effects of inspiratory resistance loading on lung fluid balance in awake sheep

Because pulmonary edema has been associated clinically with airway obstruction, we sought to determine whether decreased intrathoracic pressure, created by selective inspiratory obstruction, would affect lung fluid balance. We reasoned that if decreased intrathoracic pressure caused an increase in the transvascular hydrostatic pressure gradient, then lung lymph flow would increase and the lymph-to-plasma protein concentration ratio (L/P) would decrease. We performed experiments in six awake sheep with chronic lung lymph cannulas. After a base-line period, we added an inspiratory load (20 cmH2O) and allowed normal expiration at atmospheric pressure. Inspiratory loading was associated with a 12-cmH2O decrease in mean central airway pressure. Mean left atrial pressure fell 11 cmH2O, and mean pulmonary arterial pressure was unchanged; calculated microvascular pressure decreased 8 cmH2O. The changes that occurred in lung lymph were characteristic of those seen after other causes of increased transvascular hydrostatic gradient, such as increased intravascular pressure. Lung lymph flow increased twice base line, and L/P decreased. We conclude that inspiratory loading is associated with an increase in the pulmonary transvascular hydrostatic gradient, possibly by causing a greater fall in interstitial perimicrovascular pressure than in microvascular pressure.     

Small airway morphology and lung function in the transition from normality to chronic airway obstruction.

This study investigated the relationships between pathological changes in small airways (<6 mm perimeter) and lung function in 22 nonasthmatic subjects (20 smokers) undergoing lung resection for peripheral lesions. Preoperative pulmonary function tests revealed airway obstruction [ratio of forced expiratory volume in 1 s to forced vital capacity (FEV1/FVC) < 70%] in 12 subjects and normal lung function in 10. When all subjects were considered together, total airway wall thickness was significantly correlated with FEV1/FVC (r2 = 0.25), reactivity to methacholine (r2 = 0.26), and slope of linear regression of FVC against FEV1 values recorded during the methacholine challenge (r2 = 0.56). Loss of peribronchiolar alveolar attachments was significantly associated (r2 = 0.25) with a bronchoconstrictor effect of deep inhalation, as assessed from a maximal-to-partial expiratory flow ratio <1, but not with airway responses to methacholine. No significant correlation was found between airway smooth muscle thickness and lung function measurements. In conclusion, this study suggests that thickening of the airway wall is a major mechanism for airway closure, whereas loss of airway-to-lung interdependence may contribute to the bronchoconstrictor effect of deep inhalation in the transition from normal lung function to airway obstruction in nonasthmatic smokers.     

Tissue viscance during induced constriction in rabbit lungs: morphological-physiological correlations.

Tissue viscance (Vti), the pressure drop across the lung tissues in phase with flow, increases after induced constriction. To gain information about the possible site of response, we induced increases in Vti with methacholine (MCh) and attempted to correlate these changes with alterations in lung morphology. We measured tracheal (Ptr) and alveolar pressure (PA) in open-chest rabbits during mechanical ventilation [frequency = 1 Hz, tidal volume = 5 ml/kg, positive end-expiratory pressure (PEEP) = 5 cmH2O] under control conditions and after administration of saline or MCh (32 or 128 mg/ml) aerosols. We calculated lung elastance (EL), lung resistance (RL), Vti, and airway resistance (Raw) by fitting the equation of motion to changes in Ptr and PA. The lungs were then frozen in situ with liquid nitrogen (PEEP = 5 cmH2O), excised, and processed using freeze substitution techniques. Airway constriction was assessed by measuring the ratio of the airway lumen (A) to the ideally relaxed area (Ar). Tissue distortion was assessed by measuring the mean linear intercept between alveolar walls (Lm), the standard deviation of Lm (SDLm), and an atelectasis index (ATI) derived by calculating the ratio of tissue to air space using computer image analysis. RL, Vti, and EL were significantly increased after MCh, and Raw was unchanged. A/Ar, Lm, SDLm, and ATI all changed significantly with MCh. Log-normalized change (% of baseline) in Vti significantly correlated with A/Ar (r = -0.693), Lm (r = 0.691), SDLm (r = 0.648), and ATI (r = 0.656). Hence, changes in lung tissue mechanics correlated with changes in morphometric indexes of parenchymal distortion and airway constriction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Proteomic approaches for studying human parenchymal lung diseases

Parenchymal lung diseases comprise a wide variety of diseases, with different etiologies, pathogeneses and prognoses. This perspective provides an overview of two different disease types: chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. Chronic obstructive pulmonary disease, which is related to smoking, is one of the leading causes of chronic morbidity and mortality around the world, being characterized by airway obstruction and parenchymal lung damage (emphysema). Idiopathic pulmonary fibrosis of unknown etiology is classified as one of the most important idiopathic interstitial pneumonias and is connected to patchy but progressive lung fibrosis. Both diseases are generally diagnosed late and respond poorly to medical therapies. Although numerous biomarkers have been proposed for these diseases, they have not been validated or implemented into clinical practice. This perspective emphasizes some typical features of these diseases with different types of lung damage, how they are reflected in different samples, as well as potential advances and problems of current and future nonbiased proteomic approaches.     

Mechanisms of gas exchange response to lung volume reduction surgery in severe emphysema

Lung volume reduction surgery (LVRS) improves lung function, respiratory symptoms, and exercise tolerance in selected patients with chronic obstructive pulmonary disease, who have heterogeneous emphysema. However, the reported effects of LVRS on gas exchange are variable, even when lung function is improved. To clarify how LVRS affects gas exchange in chronic obstructive pulmonary disease, 23 patients were studied before LVRS, 14 of whom were again studied afterwards. We performed measurements of lung mechanics, pulmonary hemodynamics, and ventilation-perfusion (Va/Q) inequality using the multiple inert-gas elimination technique. LVRS improved arterial Po? (Pa(O?)) by a mean of 6 Torr (P = 0.04), with no significant effect on arterial Pco? (Pa(CO?)), but with great variability in both. Lung mechanical properties improved considerably more than did gas exchange. Post-LVRS Pa(O?) depended mostly on its pre-LVRS value, whereas improvement in Pa(O(2)) was explained mostly by improved Va/Q inequality, with lesser contributions from both increased ventilation and higher mixed venous Po(2). However, no index of lung mechanical properties correlated with Pa(O?). Conversely, post-LVRS Pa(CO?) bore no relationship to its pre-LVRS value, whereas changes in Pa(CO?) were tightly related (r2 = 0.96) to variables, reflecting decrease in static lung hyperinflation (intrinsic positive end-expiratory pressure and residual volume/total lung capacity) and increase in airflow potential (tidal volume and maximal inspiratory pressure), but not to Va/Q distribution changes. Individual gas exchange responses to LVRS vary greatly, but can be explained by changes in combinations of determining variables that are different for oxygen and carbon dioxide.