Ion transport by sheep distal airways in a miniature chamber.

Ion transport and the electric profile of distal airways of sheep lungs were studied in a miniature polypropylene chamber with a 1-mm aperture. Small airways with an inner diameter < 1 mm were isolated, opened longitudinally, and then mounted as a flat sheet onto the 1-mm aperture where it was glued and secured with an O-ring. Both sides of the tissue were bathed with identical physiological solutions at 37 degrees C and oxygenated. Pooled data from 27 distal airways showed an inner airway diameter of 854 +/- 22 (SE) microm and a transepithelial potential difference (PD) of 1.86 +/- 0.29 mV, lumen negative. Short-circuit current (I(sc)) was 25 +/- 3.5 microA/cm(2), tissue resistance was 96 +/- 14 Omega, and conductance was 15.2 +/- 1.7 mS/cm(2). At baseline, amiloride-sensitive Na transport accounted for 51% of I(sc) (change in I(sc) = 9.7 +/- 2.6 microA/cm(2); n = 8 airways), corresponding to 0.36 microeq. cm(-2). h(-1). Treatment with 0.1 mM bumetanide did not reduce the I(sc) (n = 5 airways). Exposure to 1 microM Ca ionophore A-23187 raised the I(sc) by 9 microA/cm(2) (47%; P < 0.03; n = 6 airways). The latter effect was blunted by bumetanide. Carbachol at 1 microM provoked a biphasic response, an initial rapid rise in I(sc) followed by a decline (n = 3 airways). There was no significant increase in PD or I(sc) in response to isoproterenol or dibutyryl cAMP. The data suggest that Na absorption constitutes at least 50% of baseline transport activity. Cl or other anion secretion such as HCO(3) appears to be present and could be stimulated by raising intracellular Ca.

Detection of Cl--HCO3- and Na+-H+ exchangers in human airways epithelium.

Molecular species of the Na(+)-H(+) exchanger (NHE) and anion exchanger (AE) gene families and their relative abundance in the human airway regions were assessed utilizing RT-PCR and the RNase protection assay, respectively. Organ donor lung epithelia from various bronchial regions (small, medium, and large bronchi and trachea) were harvested for RNA extraction. Gene-specific primers for the human NHE and AE isoforms were utilized for RT-PCR. Our results demonstrated that NHE1, AE2, and brain AE3 isoforms were expressed in all regions of the human airway, whereas NHE2, NHE3, AE1, and cardiac AE3 were not detected. RNase protection studies for NHE1 and AE2, utilizing glyceraldehyde-3-phosphate dehydrogenase as an internal standard, demonstrated that there were regional differences in the NHE1 mRNA levels in human airways. In contrast, the levels of AE2 mRNA remained unchanged. Differential regional expression of NHE1 isoform may be related to a higher acid load in the tracheal epithelial cells than in epithelia of distal airways. Fluctuations in PCO(2) during inspiration and expiration are probably larger in the tracheal lumen than in the lumen of distal airways with associated larger swings in intracellular pH with each respiratory cycle. Immunohistochemical staining for AE2 protein demonstrated localization to the epithelial cells of human bronchial mucosa.

Expression of the Na+/H+ and Cl-/HCO-3 exchanger isoforms in proximal and distal human airways.

Recent studies have indicated the presence of Na+/H+ and Cl-/HCO-3 exchange activities in lung alveolar and tracheal tissues of various species. To date, the identity of the Na+/H+ (NHE) and Cl-/HCO-3 (AE) exchanger isoforms and their regional distribution in human airways are not known. Molecular species of the NHE and AE gene families and their relative abundance in the human airway regions were assessed utilizing RT-PCR and the RNase protection assay, respectively. Organ donor lung epithelia from various bronchial regions (small, medium, and large bronchi and trachea) were harvested for RNA extraction. Gene-specific primers for the human NHE and AE isoforms were utilized for RT-PCR. Our results demonstrated that NHE1, AE2, and brain AE3 isoforms were expressed in all regions of the human airways, whereas NHE2, NHE3, AE1, and cardiac AE3 were not detected. RNase protection studies for NHE1 and AE2, utilizing glyceraldehyde-3-phosphate dehydrogenase as an internal standard, demonstrated that there were regional differences in the NHE1 mRNA levels in human airways. In contrast, the levels of AE2 mRNA remained unchanged. Differential expression of these isoforms in the human airways may have functional significance related to the airway absorption and secretion of electrolytes.

Regulation of Na and Cl transport in sheep distal airways.

To investigate ion transport function of distal airways mucosa we dissected and isolated segments of sheep bronchioles (outside diameter 664 +/- 10 microns, means +/- SE). Both ends of a segment were cannulated with glass micropipettes, and the preparation was placed in a bath and perfused with oxygenated Krebs-Henseleit solution at 37 degrees C. Luminal amiloride (0.1 mM) reduced potential difference (PD) from 3.06 +/- 0.68 mV to 1.08 +/- 0.24 mV (n = 5, P < 0.02). Submucosal ouabain (0.1 mM) decreased PD from 1.82 +/- 0.38 to 0.07 +/- 0.02 mV (n = 5, P < 0.009). Submucosal bumetanide (0.1 mM) caused a decline in PD from 3.44 +/- 0.98 to 2.75 +/- 0.71 mV (n = 19, P < 0.03). Exposure of the lumen to Cl channel blocker diphenylamine-2-carboxylate (1 mM) depolarized the bronchiole from a PD of 4.46 +/- 1.7 mV to 2.50 +/- 0.97 mV (n = 7, P < 0.03). Submucosal adenosine 3',5'-cyclic monophosphate (cAMP) analogue, 8-(4-chlorophenylthio)-cAMP (0.1 mM), raised PD from 3.45 +/- 1.08 to 3.82 +/- 1.24 mV (n = 10, P < 0.05). In eight experiments submucosal 0.1 mM carbachol, which elevates cytosolic Ca, resulted in rapid hyperpolarization (P < 0.02) followed by amiloride-inhibitable slow depolarization (P < 0.05). The data provide evidence for the presence in the sheep bronchiolar epithelium of active Na absorption that depends on a basolaterally located Na-K-ATPase ion pump. Increased cytosolic Ca probably inhibits Na absorption. The epithelium also has a Cl secretory process through apical Cl channels.

Microperfusion of sheep bronchioles.

We isolated segments of sheep bronchioles (length 406 +/- 46 microns, diameter 227 +/- 53 microns, n = 27). These segments were placed in a 37 degree C bath and cannulated at both ends with glass micropipettes. The proximal end was cannulated and held by three concentrically arranged micropipettes that delivered perfusion solution by gravity. The distal end was cannulated and held by two concentrically arranged micropipettes for fluid collection. When both the lumen and the bath contained oxygenated Krebs-Henseleit buffer (pH 7.40), spontaneous potential difference (PD) was 2.46 +/- 0.39 mV, lumen negative. KCN in the bath diminished PD by 1.48 +/- 0.29 mV (P = 0.00003, n = 25). The isolated bronchiole was depolarized when the luminal solution was Na free (delta PD -1.78 +/- 0.11 mV, P = 0.00007, n = 5) or when the submucosal bath was Cl free (delta PD -2.63 +/- 0.81, P = 0.018, n = 7). In preparations pretreated with 10 microM indomethacin, 1 microM isoproterenol raised PD by 0.75 +/- 0.29 mV (P = 0.03, n = 8), whereas 0.1 mM submucosal bumetanide reduced PD by 0.21 +/- 0.04 mV (P = 0.0005, n = 8). The data show that microperfusion technique is applicable for investigating ion transport by distal bronchioles and that the bronchiolar epithelium probably has both Na and Cl conductive pathways.

Collapse of intercellular spaces of canine tracheal mucosa by epinephrine.

Variations in the volume and width of lateral intercellular spaces (LICS) of dog tracheal mucosa in vitro were investigated by use of stereological and linear measurements of electron micrographs. Alterations in the volume or width of LICS were then correlated with physiological conditions and electrical parameters. LICS were quite narrow between the ciliated cells compared with those around the nonciliated dark cells (goblet, brush, and basal cells). LICS comprised 6.8 +/- 2.9% of tissue volume in preparations that were mounted in an Ussing chamber and short-circuited, whereas in unmounted and open-circuited tissues it occupied only 1 +/- 0.2% of the volume of the preparations (P less than 0.016, n = 5). The effects of stimulation of Cl secretion by 1 microM epinephrine were tested. In seven epinephrine-treated tissues LICS volume was 2.9 +/- 0.9% of total epithelial volume compared with 8.7 +/- 2.9% in control tissues (P less than 0.015). The width of LICS around dark cells in epinephrine-treated tissues was 0.42 +/- 0.06 micron compared with 0.98 +/- 0.13 micron in control tissues (P less than 0.001). The data suggest that LICS act as pliable fluid reservoirs that empty and collapse on stimulation of Cl secretion.

Effects of taurine-conjugated bile salts on ionic transport of the rabbit esophageal mucosa.

Bile salts have been implicated as a cause of esophageal injury. We examined in vitro the changes in ionic transport of the rabbit esophagus resulting from taurine-conjugated bile salts at neutral pH to define and characterize their actions independent of hydrogen ion. In an Ussing chamber changes in potential difference (PD, mV), short-circuit current (SCC, microA X cm-2) and resistance (R, omega X cm2) resulting from taurocholate (TC), taurodeoxycholate (TDC) and taurochenodeoxycholate (TCDC) were studied. Transport properties were unaffected by TC at 5 and 10 mM. With TDC (5 mM) there was an initial rise in SCC and PD. After 60 min PD and R declined in association with an increase in paracellular permeability as measured by [14C]sucrose flux. TCDC (5.0 and 7.5 mM) caused a sustained rise in PD and SCC with a greater rise seen at 7.5 mM. The rise in SCC after TCDC was secondary to an increase in net sodium absorption as basal net sodium absorption increased threefold from 0.15 +/- 0.03 to 0.44 +/- 0.10 mu eq X cm-2 X h-1. Increased net sodium absorption accounted for 73% of the TCDC-induced rise in SCC. Amiloride (10(-4) M) added to the mucosal solution significantly inhibited this bile salt-induced rise in SCC. We conclude that bile salts alter ionic transport in the esophageal mucosa independent of hydrogen ion. These changes are characterized by an early selective increase in apical membrane cation conductance and with longer exposure, particularly in the presence of more hydrophobic bile salts, there is a marked increase in paracellular conductance.

Regulation of salt and water transport across airway mucosa.

Effective mucociliary clearance of secretions by airway mucosa requires efficient ciliary beating. The structure of airway secretions provides for this requirement by having a viscous mucous layer touched underneath and propelled by ciliary tips, while the rest of the cilium is surrounded by a serous fluid layer. The regulation of the latter layer is thought to be a function of mucosal epithelial cells capable of active ion transport. Mammalian medium-sized bronchi actively absorb sodium, whereas the tracheal mucosae of several mammals are capable of sodium absorption as well as chloride secretion. By generating local osmotic gradients, these ion transport processes may regulate the depth of the periciliary sol layer. These transport processes generate an electrical PD across the mucosa such that the luminal side is negatively charged in reference to the submucosal side (electrogenic transport). Transport of sodium and chloride across the plasma membrane is against a steep electrochemical gradient, and cellular energy resources are utilized for this purpose (active transport). Chloride transport is coupled to sodium transport; therefore, inhibition of the sodium pump (Na-K-ATPase) with ouabain leads to inhibition of sodium as well as chloride transport. Several neurohumoral agents have been found to stimulate chloride secretion, such as PGs, beta-adrenergic agonists, VIP, substance P, and bradykinin. Mechanisms of regulation of sodium transport by airway epithelia are not clearly understood. Available evidence suggests that elevation of cellular PGs, cAMP, and calcium enhances apical cell-membrane conductance to chloride ion, with an opposite effect on sodium conductance. Therefore, it seems reasonable to suggest that neurohumoral control mechanisms may switch from sodium and fluid absorption to chloride and fluid secretion, and vice versa. Several lines of evidence support this proposal. First, the lung of fetal lamb secretes chloride and fluid in utero; this activity ceases at birth, when the catecholamine level is increased, causing a decrease in chloride secretion. In contrast, adult sheep trachea absorbs sodium. Second, agents that stimulate chloride secretion in bovine trachea concomitantly reduce sodium absorption, and vice versa. Similar observations were noted in some instances in dog trachea. Third, whereas unstimulated ferret and cat tracheas only absorb sodium, they secrete chloride upon exposure to beta agonists.(ABSTRACT TRUNCATED AT 400 WORDS)

Rapid estimation of total body clearance of theophylline in patients receiving intravenous aminophylline infusion.

The method of Chiou to rapidly estimate theophylline total body clearance using two serum concentration data during the early stage of intravenous aminophylline infusion was evaluated in 16 patients with acute exacerbation of asthma or chronic obstructive pulmonary disease. The observed serum concentrations at later times were compared with those predicted. The mean prediction error for serum concentrations was 4.93% with a standard deviation of 20.06%. These results indicate that this simple method of Chiou may offer a reliable rapid estimation of total body clearance for dosage individualization in patients receiving intravenous aminophylline infusion.

Calcium secretion in canine tracheal mucosa.

Calcium (Ca) affects many cellular functions of the respiratory tract mucosa and might alter the viscoelastic properties of mucus. To evaluate Ca homeostasis in a respiratory epithelium we investigated transport of Ca by the canine tracheal mucosa. Mucosal tissues were mounted in Ussing-type chambers and bathed with Krebs-Henseleit solution at 37 degrees C. Unidirectional fluxes of 45Ca were determined in tissues that were matched by conductance and short-circuit current (SCC). Under short-circuit conditions there was a significant net Ca secretion of 1.82 +/- 0.36 neq . cm-2 . h-1 (mean +/- SE). Under open-circuit conditions, where the spontaneous transepithelial potential difference could attract Ca toward the lumen, net Ca secretion increased significantly to 4.40 +/- 1.14 compared with 1.54 +/- 1.17 neq . cm-2 . h-1 when the preparation was short-circuited. Addition of a metabolic inhibitor, 2,4-dinitrophenol (2 mM in the mucosal bath), decreased tissue conductance and SCC and slightly decreased the unidirectional movement of Ca from submucosa to lumen. Submucosal epinephrine (10 microM) significantly enhanced Ca secretion by 2.0 +/- 0.63 neq . cm-2 . h-1. Submucosal ouabain (0.1 mM) failed to inhibit Ca secretion. The data suggest that canine tracheal mucosa secretes Ca; this secretory process is augmented by epinephrine or by the presence of a transepithelial potential difference as found under in vivo conditions.

Substance P stimulation of chloride secretion by canine tracheal mucosa.

We investigated the effect of a neuropeptide, substance P, on the electrical and ion transport properties of dog trachea. Posterior mucosal tissues were mounted in Ussing chambers and bathed with Krebs-Henseleit solution, pH 7.4, at 37 degrees C. The solution was gassed with 95% O2, 5% CO2. Substance P (10(-7)M) added to the mucosal bath elicited within seconds a rapid rise in short circuit current with a peak response of 23 microA.cm-2 and an increase in tissue conductance of 0.63 mS.cm-2 (p less than 0.001, n = 20). In 6 experiments, 36Cl and 22Na fluxes were measured under short circuit conditions and they revealed that net Cl secretion increased from 1.46 +/- 0.41 to 2.30 +/- 0.74 mueq.cm-2 X h-1 (mean +/- SE, p less than 0.05). This increase was brought about by enhancement of unidirectional submucosa to lumen flux. Net Na absorption of 0.63 +/- 0.09 did not change significantly (0.49 +/- 0.16). Short circuit current response to substance P was not modified by prior tissue incubation with atropine, phenoxybenzamine, propranolol, or naloxone. Removal of mucosal bath calcium and the presence of calcium channel blocker verapamil did not abolish tissue response to substance P. These findings suggest that nerve fibers containing substance P may play a role in regulation of ion transport across the trachea. This action does not appear to be related to the cholinergic, adrenergic, or oplate receptors.

Ion transport in dog tracheal mucosa: interaction between calcium and prostaglandins.

Prostaglandins E1 and F2 alpha (PGE1 and PGF2 alpha) stimulate short-circuit current (SCC), tissue conductance (G), and net Cl secretion by canine tracheal mucosa. To determine if these actions of prostaglandins require extracellular Ca we tested the effects of PGE1 and PGF2 alpha on tracheal mucosa mounted in Ussing chambers when one side of the preparation was exposed to 0.2 mM ethyleneglycol-bis(beta-aminoethylether)-N,N'-tetraacetic acid in Krebs-Henseleit solution without Ca. Lack of Ca from the mucosal bath was associated with increased G, lowered potential difference (PD), and severalfold increase of 22Na and 36Cl fluxes in both directions. Addition of 1 microM of PGE1 or PGF2 alpha to the Ca-free mucosal bath raised PD by 6 mV and SCC by 15 microA X cm-2 but decreased G by 1.4 mS X cm-2. Unidirectional 22Na and 36Cl fluxes decreased by 32-49% (n = 7, P less than 0.05). These findings suggest that the increase in G, most likely of the paracellular pathway and brought about by the lack of mucosal Ca, was partially reversible by PGE1 and PGF2 alpha. In contrast, when tissues were exposed to Ca-free solution on their submucosal side, PGE1 or PGF2 alpha were not able to reverse the progressive decline in PD and tissue resistance (n = 8). [14C]mannitol flux increased when Ca was absent from the mucosal bath; then addition of 1 microM PGF2 alpha caused a 37% decline in flux (n = 5). In contrast, the increase in the flux of [14C]mannitol found when the submucosal bath lacked calcium was not reversed by 1 microM PGE1.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of human saliva and serum on ion transport by dog tracheal mucosa. Comparison of normal subjects with cystic fibrosis patients.

It has been proposed that cystic fibrosis (CF) saliva or serum contains factors that alter ion transport in various tissues. Since CF frequently affects the lungs, and disturbances in epithelial ion transport has been proposed to contribute to the pathophysiology of pulmonary disease in CF, we investigated whether saliva or serum from CF patients could alter ion transport across airways epithelium. Canine tracheal mucosae were mounted in lucite chamber and perfused on both sides with Krebs-Henseleit solution at 37 degrees C and pH 7.4. Unidirectional fluxes of 22Na and 36Cl were measured in pairs of mucosal tissues under short circuit conditions. Saliva from 5 CF patients stimulated short circuit current (SCC) by 33 +/- 8 microA/cm2 and net Cl secretion by 1.10 +/- 0.33 muEq/cm2 X h (mean +/- SE; p less than 0.05). No change occurred in net Na absorption. Saliva from normal subjects raised SCC by 34 +/- 7 microA/cm2 and increased net Cl secretion by 1.29 +/- 0.46 muEq/cm2 X h (n = 9; p less than 0.02). Serum from both CF patients and control subjects briefly stimulated SCC. Exposure of tracheal mucosa to normal as well as CF saliva, such as by aspiration, or to serum, such as by transudation, stimulates Cl secretion, and therefore water secretion into airway lumen. There appears to be no difference in the effect exerted by CF saliva or serum and that of normal subjects. These findings argue against the presence of a specific circulating or secreted CF factor that could alter ion transport across respiratory epithelia in a way that might contribute to lung disease in CF.

Single breath nitrogen washout in pulmonary sarcoidosis.

In 35 patients with pulmonary sarcoidosis we explored the utility of single breath nitrogen washout as a means for detecting abnormalities in airway function and intrapulmonary distribution of air. Closing volume/vital capacity ratio (CV/VC) was 21% (predicted 12.5%) in patients with only hilar adenopathy (stage I). CV/VC was 21% (predicted 13%) in patients with hilar adenopathy and parenchymal infiltration (stage II). Abnormalities in CV/VC were less readily detectable in patients with parenchymal infiltrates only (stage III) or those with bullous lesions and lung retraction (stage IV). Closing capacity was abnormally high in 66% of the cases. The slope of the alveolar plateau (delta N2/L) increased with disease progression. Single breath nitrogen test provides useful information concerning the function of small airways and distribution of pulmonary ventilation in all stages of sarcoidosis.

Role of cyclic AMP in regulation of chloride secretion by canine tracheal mucosa.

Cyclic adenosine monophosphate (cyclic AMP) mediates the action of many hormones, and it affects ion transport in several different epithelia. The effect of the analogue dibutyryl cyclic AMP was tested in canine tracheal epithelium in vitro under short-circuit conditions. This agent raised short-circuit current and electrical conductance. Dibutyryl cyclic AMP at 1 mM concentration added to the submucosal bath increased net Cl secretion from 1.74 +/- 0.40 to 2.72 +/- 0.34 mu eq/cm2 . h (mean +/- SE, n = 6). Net Na absorption was slightly reduced. Dibutyryl cyclic AMP and theophylline decreased mannitol flux, suggesting that cyclic AMP acts on Cl transport by increasing its flow through cellular rather than through paracellular pathways. Epinephrine, which also stimulates Cl secretion, causes significant elevation in cyclic AMP in epithelial cells scraped from tracheal mucosa. Data suggest that cellular concentrations of cyclic AMP play an important role in the regulation of Cl transport by tracheal mucosa.

Measurement of airways closing pressure in man.

In 7 healthy males, lung static and quasi-static pressure-volume (QS-PV) curves were measured simultaneously with closing volume by the single breath N2 washout test. Comparison was made of four methods for estimation of the closing pressure (CP) at the onset of phase IV. In the first method the transpulmonary pressure (PL) that directly coincided on the tracing with onset of phase IV was measured, results varied widely with a mean of -1.3 +/- 2.2 cm H2O (X +/- SD). The second method was to identify on the QS-PV curve the point of transition in the shape of the curve from concavity to convexity. This method yielded a mean CP of 2.8 +/- 1.7 cm. H2O, bu did not correlate statistically with closing capacity (r = 0.07, p greater than 0.05). The third method was to treat the whole PV volume corresponding to the onset of phase IV, and calculate PL at this point. This method yielded CP of 2.1 +/- 0.76 cm H2O. When the same method was applied to static PV curve, CP was 2.0 +/- 0.7 cm H2O. Conformity of CP values obtained using extrapolation methods to those expected from theoretical considerations and from in vitro measurements suggests that the extrapolation methods most likely yield the true PL at the onset of airway closure.

Effect of catecholamines on ion transport in dog tracheal epithelium.

The action of adrenergic agonists on ion fluxes across the epithelium of the canine trachea was determined. Isolated sheets of tracheal mucosal membranes were mounted in Ussing-type chambers, bathed with Krebs-Henseleit solution at 37 degrees C, pH 7.4, and gassed with 5% CO2 Iin oxygen. Various adrenergic agents, when added to the bathing medium elevated short-circuit current (SCC) (isoproterenol greater than epinephrine greater than norepinephrine greater than phenylephrine). Propranolol (10(-6) M) decreased SCC response to epinephrine. Epinephrine (1mM) increased both unidirectional 36Cl fluxes; net 36Cl secretion toward the lumen increased from 2.01 +/- 0.52 to 3.20 +/- 0.46 mueg/cm2.h (P less than 0.05); 22Na flux did not change. In epinephrine-stimulated tissues, propranolol (1mM) abolished net 36Cl secretion. The SCC response to epinephrine was blunted in the absence of Na from the submucosal reservoir; this blunting suggests that Cl entry across the basal membrane is coupled with Na. Both the relative sensitivities of SCC to various adrenergic agonists and the effect of propranolol suggest that Cl-secretory process is highly sensitive to beta-adrenergic receptor stimulation. Epinephrine increased cell membrane permeability to Cl and probably stimulated a specific Cl pump.

Multiple granular cell tumors of the bronchi: treatment with laser.

Granular cell tumors involving multiple bronchial and extrapulmonary sites were found in a young man. Carbon dioxide laser ray was applied through a specially fitted rigid bronchoscope to a lesion at the left mainstem bronchus. Serial follow-up bronchoscopies revealed a white scarred plaque without evidence of regrowth. A partially obstructing lesion at the left lower lobe bronchus did not respond to one application of laser therapy. Laser treatment of proximal benign bronchial lesions is feasible; however, peripheral lesions may require several courses of laser therapy.

Single-breath nitrogen washout; effects of alterations of lung volumes and elastic recoil.

Strapping of the chest causes decreased lung volumes and increased elastic recoil pressure. Such strapping was used in conjunction with single-breath nitrogen washout to study the effects of changes in these factors on the dynamics of the small airways. Studies consisted of simultaneous measurements of the quasistatic lung pressure-volume curve and single-breath nitrogen washout. Strapping caused significant reductions in all lung volumes and in lung compliance at 50 percent of the total lung capacity (TLC). The volume of phase 4 was not changed; however, the ratio of closing capacity to control TLC decreased from 29.9 +/- 6 percent to 24.2 +/- 4 percent with strapping (P less than 0.02). This observation indicates that the onset of closing volumes occurred at a lower absolute lung volume during strapping, compared with control. The closing pressure of 2.1 +/- 0.8 cm H2O was not altered by strapping of the chest. The slope of phase 3 of the single-breath nitrogen-washout test and the average alveolar concentration of nitrogen were increased during strapping. A similar phenomenon occurred in three subjects who performed the single-breath nitrogen-washout test following partial vital capacities. A reduction of the onset of closure of the airways without a change in closing pressure suggests that restrictions of the chest wall caused no change in mechanical properties of the small airways. Elevation of the slope of the alveolar plateau is probably due to exaggeration of the apex-to-base nitrogen difference consequent to the strapping-associated decreased lung and alveolar compliance.