Effect of aerosolized uridine 5'-triphosphate on mucociliary clearance in mild chronic bronchitis.

Previous studies show that uridine 5'-triphosphate (UTP), a P2Y(2) receptor agonist, is effective at acutely enhancing mucociliary clearance in healthy, nonsmoking adults. UTP solution for inhalation is being developed by Inspire Pharmaceuticals under the compound number INS316. In a double-blind, randomized, crossover, placebo-controlled study we tested the single-dose effect of UTP in chronic smokers with mild chronic bronchitis (n = 15) by measuring the clearance of (99m)Tc-Fe(2)O(3) particles (4.0 microm mass median aerodynamic diameter [MMAD]) after inhalation of nebulized placebo (0.9% saline) and two doses of UTP (20 and 100 mg in the nebulizer). On each study day, gamma camera scanning was performed over a 2-h period. After an initial deposition scan, subjects inhaled placebo or UTP during the first 20 min of scanning. Analysis of whole lung clearance showed that the retention-time curves for each day were biphasic and that the earliest break point in the average curves occurred at 50 min. Mean particle clearance rate (Clr in %/min) through 50 min for placebo treatment was Clr = 0.65 +/- 0.27 whereas treatment with UTP showed Clr significantly increased to 0.95 +/- 0.48 and 0.93 +/- 0.44 for the 20-mg and 100-mg dose respectively, p < 0.005 for both as compared with placebo. These data show that mucociliary clearance associated with mild chronic bronchitis is acutely improved with minimal doses of aerosolized UTP, presumably because of its stimulation of ciliary beating and hydration of airway secretions.

Regional mucociliary clearance in patients with cystic fibrosis.

This paper reports on a large retrospective analysis of mucociliary clearance (MCC) studies in a group of 59 patients with cystic fibrosis (CF) and 17 age-matched healthy subjects. As many of the CF patients were studied on multiple occasions, a total of 184 patient studies are presented. MCC was measured using a radioaerosol and gamma camera technique. In addition to whole lung clearance, MCC was measured from the central, intermediate, peripheral, basal, mid and apical regions of the lung. MCC was markedly decreased in the CF patient group. Not only was whole lung clearance (14.2 +/- 1.4% vs. 28.0 +/- 3.7%) impaired, but also clearance from the central (19.1 +/- 1.9% vs. 35.6 +/- 4.3%), intermediate (10.7 +/- 1.6% vs. 25.5 +/- 3.7%), apical (12.4 +/- 2.6% vs. 31.6 +/- 4.6%) and mid (14.0 +/- 1.9% vs. 30.4 +/- 4.0%) regions. Attempts were made to identify factors that may have influenced MCC in both the normal subjects and CF patients. Age, gender, body mass index, patient genotype, penetration index, spontaneous cough, and various lung function parameters were entered into a stepwise multiple regression model, but none of the factors proved to be statistically important in determining MCC. Both intrasubject repeatability and intersubject variability estimates are presented for the patients and normal subjects that had multiple studies. The values were found to be remarkably similar for both CF patients and normal subjects and for both intra- and intersubject repeatability. With marked deviation from normal ranges and good repeatability, the measurement of MCC in CF patients would seem to be a valuable outcome measure for clinical trials involving new pharmaceuticals and physical therapy designed to improve removal of secretions from the airways.

The role of hypoventilation and ventilation-perfusion redistribution in oxygen-induced hypercapnia during acute exacerbations of chronic obstructive pulmonary disease.

The detailed mechanisms of oxygen-induced hypercapnia were examined in 22 patients during an acute exacerbation of chronic obstructive pulmonary disease. Ventilation, cardiac output, and the distribution of ventilation-perfusion (V A/Q ) ratios were measured using the multiple inert gas elimination technique breathing air and then 100% oxygen through a nose mask. Twelve patients were classified as retainers (R) when Pa(CO(2)) rose by more than 3 mm Hg (8.3 +/- 5.6; mean +/- SD) after breathing 100% oxygen for at least 20 min. The other 10 patients showed a change in Pa(CO(2)) of -1.3 +/- 2.2 mm Hg breathing oxygen and were classified as nonretainers (NR). Ventilation fell significantly from 9.0 +/- 1.5 to 7.2 +/- 1.2 L/min in the R group breathing oxygen (p = 0.007), whereas there was no change in ventilation in the NR group (9.8 +/- 1.8 to 9.9 +/- 1.8 L/min). The dispersion of V A/Q ratios as measured by log SD of blood flow (log SD Q) increased significantly in both R (0.96 +/- 0. 17 to 1.13 +/- 0.17) and NR (0.77 +/- 0.20 to 1.04 +/- 0.23, p < 0.05) groups breathing oxygen, whereas log SD of ventilation (log SD Q ) increased only in the R group (0.97 +/- 0.24 to 1.20 +/- 0.46, p < 0.05). This study suggests that an overall reduction in ventilation characterizes oxygen-induced hypercapnia, as an increased dispersion of blood flow from release of hypoxic vasoconstriction occurred to a significant and similar degree in both groups. The significant increase in wasted ventilation (alveolar dead space) in the R group only may be secondary to the higher carbon dioxide tension, perhaps related to bronchodilatation.

Prolonged airway retention of insoluble particles in cystic fibrosis versus primary ciliary dyskinesia.

Patients with cystic fibrosis (CF) and primary ciliary dyskinesia (PCD) have been shown to have impaired large airway clearance of radiolabelled particles as measured by external gamma camera scanning up to 6 hours post deposition. Recent studies suggest that 24-hour retention of particles may reflect some airway retention in addition to alveolar retention. In a retrospective study, we analyzed the relationship between the deposition pattern and 24-hour retention (Ret24 hr) of technetium 99-radiolabelled iron oxide (99Tc-Fe2O3) particles in 20 patients with CF, 12 patients with PCD, and 17 normal subjects. By gamma camera analysis, initial aerosol deposition was analyzed in terms of central-peripheral (C/P) activity within the lungs. Gamma camera scanning was performed immediately following deposition and again at 24 hours to assess residual retention (Ret24 hr) as a percent of initial deposition. C/P analysis was also performed on the 24-hour scan (C/P24). For all subjects, initial deposition pattern (C/P) was inversely related to lung function (forced expiratory volume in 1 second [FEV1]%pred vs. C/P, r = -.54). Ret24 hr was also inversely related to initial deposition pattern for all subjects (Ret24 hr vs. C/P ratio, r = -.42). Analysis of covariance showed that for a given C/P ratio, CF patients had significantly greater Ret24 hr compared to normal subjects (9.8 +/- 2.8 [SE]%). In addition, the CF patients had similar C/P24 as the normal subjects (1.35 +/- 0.40 [SD] vs. 1.10 +/- 0.39, respectively). These results suggest that small airway clearance is compromised in CF patients compared to normal subjects. On the other hand, PCD patients had C/P24 similar to their initial deposition C/P ratios (2.78 +/- 1.72 vs. 2.45 +/- 0.87, respectively), significantly greater than 1.0, and significantly greater than CF or normal subjects, suggesting that PCD patients have prolonged particle retention associated with their large bronchial airways.

Effect of aerosolized uridine-5'-triphosphate on airway clearance with cough in patients with primary ciliary dyskinesia.

Primary ciliary dyskinesia (PCD) is a genetic disease characterized by abnormal ciliary structure and function and impaired mucociliary clearance. Because patients with PCD use cough clearance as an airway defense mechanism, we tested the hypothesis that aerosolized uridine-5'-triphosphate (UTP) would improve clearance during cough by its actions to stimulate Cl- secretion and mucin release by goblet cells. We measured clearance during cough in 12 patients with PCD (ages 14 to 71 yr, FEV1 43% to 89% predicted) in a double blind, randomized, crossover study after aerosolization of a single dose of UTP (5 mg/ml, 3.5 ml) or vehicle (0.12% saline, 3.5 ml). Clearance during cough (whole lung) was quantified during and after a series of controlled coughs by measuring the clearance of [99mTc]Fe2O3 particles via gamma camera scanning over 120 min. Safety parameters were recorded during and after drug delivery. Aerosolized UTP improved whole-lung clearance during cough as compared with vehicle (from 0 to 60 min: 0.40 +/- 0.07%/min [UTP] versus 0.26 +/- 0. 04%/min [vehicle] [mean +/- SEM], p = 0.01), and from 0 to 120 min: 0.38 +/- 0.05%/min [UTP] versus 0.25 +/- 0.04%/ min [vehicle], p = 0. 02). Aerosolized UTP is safe, with no serious adverse effects. Whole-lung clearance during cough in patients with defective ciliary function is enhanced after inhalation of UTP.

End-expiratory lung volume during arm and leg exercise in normal subjects and patients with cystic fibrosis.

There are no reports concerning the regulation of end-expiratory lung volume (EELV) and flow-volume relationships during upper limb exercise in health and disease. We studied EELV during such exercise in 22 adults with cystic fibrosis (CF) and nine age-matched healthy control subjects. Subjects with CF were grouped according to the severity of their lung disease, as follows: mild = FEV1 > 80% predicted; moderate = FEV1 40 to 80% predicted, and severe = FEV1 < 40% predicted. EELV was calculated from measurements of inspiratory capacity (IC) made at each workload during an incremental arm and leg ergometer test to peak work capacity. In the control group, the decrease in EELV was significantly smaller for arm than for leg exercise at peak work (-0.13 L versus -0.53 L, p < 0.001) and for arm than for leg exercise at an equivalent submaximal ventilation (-0.13 L versus -0.46 L, p < 0.01). In the groups with moderate and severe CF, arm exercise resulted in an increase in EELV from resting levels (dynamic hyperinflation) that was not significantly different from the increase observed for leg exercise. For CF subjects there was a significant inverse relationship between FEV1 and changes in EELV from rest to peak arm exercise (r = -0.46, p < 0.05). In normal subjects, there was a difference in the EELV response for arm versus leg exercise. In CF subjects with airflow limitation, dynamic hyperinflation occurred with both forms of exercise.

Effect of increasing doses of hypertonic saline on mucociliary clearance in patients with cystic fibrosis.

BACKGROUND: Patients with cystic fibrosis are known to have decreased mucociliary clearance. It has previously been shown that inhalation of a 7.0% solution of hypertonic saline significantly improved mucociliary clearance in a group of adult patients with cystic fibrosis. The aim of this study was to measure the response to increasing concentrations of inhaled hypertonic saline. METHODS: Ten patients (seven men) of mean (SE) age 22 (4) years and mean forced expiratory volume in one second (FEV1) 52.0 (6.7)% predicted completed the study. Mucociliary clearance was measured using a radioaerosol technique for 90 minutes after the interventions which comprised 0.9% NaCl + voluntary cough (control), 3.0% NaCl, 7.0% NaCl, and 12% NaCl. RESULTS: There was a significant increase in the amount of activity cleared from the right lung with all concentrations of hypertonic saline (HS) compared with control. The amount cleared at 90 minutes on the control day was 12.7% (95% confidence interval (CI) 9.8 to 17.2) compared with 19.7% (95% CI 13.6 to 29.5) for 3% HS, 23.8% (95% CI 15.9 to 36.7) for 7% HS and 26.0% (95% CI 19.8 to 35.9) for 12% HS. The improvement in mucociliary clearance was not solely due to coughing as the number of coughs recorded on the control day exceeded that recorded on any other day. The hypertonic saline did not induce a clinically significant change in FEV1. CONCLUSIONS: Within the range of concentrations examined in this study, the effect of hypertonic saline appears to be dose dependent. Inhalation of hypertonic saline remains a potentially useful treatment for patients with cystic fibrosis.

Evaluation of supported upper limb exercise capacity in patients with cystic fibrosis.

Physiological responses to upper limb exercise have not been well documented in patients with cystic fibrosis (CF). This is the first study to quantify ventilatory responses to supported incremental upper limb exercise in this patient group. Twenty-four subjects with CF, with a wide range of pulmonary impairment, and ten normal control subjects were studied. Subjects performed pulmonary function tests and incremental arm and leg exercise to peak work capacity on an arm crank and bicycle ergometer. All subjects performed less work with the arms than legs. At an equivalent oxygen consumption, ventilation was higher for arm work than leg work. This higher ventilation was achieved mainly through a higher frequency of breathing. Only CF subjects with severe pulmonary impairment (FEV1 < 40% predicted, FEF25-75% < 20% predicted) had a reduced arm work capacity compared with control subjects. At peak arm work, these subjects had a mean ventilation to maximum voluntary ventilation ratio (VE/MVV) of 106% +/- 25, while maximum heart rate was less than 80% predicted. Despite the high ventilatory requirement for arm exercise, arm work capacity was well maintained in subjects with CF until severe lung disease impaired the ability to further increase ventilation.

Airway deposition and clearance and systemic pharmacokinetics of amiloride following aerosolization with an ultrasonic nebulizer to normal airways.

STUDY OBJECTIVES: Airway epithelial ion transport is an important component of the airway defense mechanism, and new therapies that target ion transport are being developed. Amiloride is an example of such a new drug, exerting a dose-dependent action to inhibit Na+ transport. Amiloride may be useful in cystic fibrosis, blocking the characteristic airway epithelial Na+ hyperabsorption that occurs in the disease. To evaluate airway and systemic delivery of amiloride via an ultrasonic nebulizer (Omron NE-UO7), we measured the airway surface concentrations of amiloride in normal volunteers via a novel approach, together with the systemic pharmacokinetics of amiloride. DESIGN: Direct measurement of airway surface liquid, plasma, and urine amiloride concentrations following ultrasonic nebulization. PARTICIPANTS/INTERVENTIONS: Seven normal subjects were studied in the General Clinical Research Center of the University of North Carolina. Following inhalation with amiloride (1 mg/mL, 4.5 mL) for approximately 12 min, a bronchoscopy was performed. Amiloride deposition and clearance from airway surfaces over 1 h were evaluated by transbronchoscopic sampling using preweighed filter papers. Pulmonary and systemic absorption was assessed by measuring drug concentrations in blood and urine. RESULTS: The mean volume aerosolized was 3.5+/-0.3 mL during 12 min of aerosolization time; the mean initial concentration of amiloride on airway surfaces after nebulization was 1.6 x 10(-4) mol/L, with an elimination half life of approximately 23 min. Peak plasma concentrations of amiloride (30 min, 3.36+/-0.70 ng/mL) suggest early absorption across lung surfaces, rather than via the GI route. Mean urinary excretion of amiloride over 72 h was 0.63+/-0.07 mg, with 87% excreted in the first 24 h. CONCLUSIONS: The ultrasonic nebulizer rapidly delivers amiloride to normal conducting airways as assessed by the transbronchoscopic sampling technique. Early blood concentrations of amiloride probably reflect initial absorption across lung surfaces and are a useful index of the efficiency of the machine.

Ventilatory mechanics at rest and during exercise in patients with cystic fibrosis.

Ventilatory mechanics were measured at rest and during steady-state (25%, 50%, 75%) and maximal exercise (W-Max) on a cycle-ergometer in eight adult patients (FEV1 22 to 114% of predicted) with cystic fibrosis (CF). Tidal flow-volume loops were measured at rest and during exercise and placed within the maximal pre- and postexercise flow-volume loops, based on measured end-expiratory lung volume (EELV). The degree of flow limitation was expressed as the percentage of the tidal flow-volume loop that met the expiratory boundary of the maximal loop (TFVL%). Pressure-volume relationships were assessed by measurement of transpulmonary pressure (PTP). Peak inspiratory PTP was compared with maximal inspiratory pressures at rest and during exercise (Pcap(i)) at the equivalent lung volume. The maximal effective expiratory pressure (Pmax(e)) was determined using the orifice technique. Three patients with milder disease (FEV1 114, 98, 89% of predicted) did not show any flow limitation at rest or 50% W-Max but two did show some flow limitation at W-Max (0, 3, 23 TFVL%) with a decrease in EELV (-400, -200, -300 ml). There was considerable reserve for inspiratory and expiratory pressure generation at W-Max. Flow limitation was noted at rest in three patients and at 50% W-Max in the five patients with more severe airways obstruction. The increased flow was achieved by an increase in EELV in all five patients (+400, +430, +330, +150, +700 ml at W-Max). Pcap(i) was reached in two patients (-28, -36 cm H2O), while Pmax(e) was exceeded by four patients suggesting inefficient pressure generation. Expiratory flow limitation, hyperinflation, and pressure swings approaching capacity severely compromised the capacity to generate ventilation in some patients with CF.

Effect of hypertonic saline, amiloride, and cough on mucociliary clearance in patients with cystic fibrosis.

In patients with cystic fibrosis (CF), dehydration of airway secretions leads to a decrease in mucociliary clearance (MCC). We examined the acute effect of MCC of a single administration by aerosolization of hypertonic saline (7%) (HS), amiloride (0.3% in 0.12% NaCl) (AML) and a combination of AML and HS (AML + HS) in 12 patients with CF using a radioaerosol technique. Isotonic saline [0.9%] (IS) was used as a control solution. As both the AML and HS solutions induced cough in some patients, the last nine patients studied also underwent a cough clearance day. This was to eliminate the possible confounding effect of cough on MCC measurement. Patients ranged from 18 to 28 yr (mean +/- SD, 22 +/- 3) with an FEV1 of 27 to 112% predicted (61 +/- 30%). Following deposition of the radioaerosol, baseline clearance was assessed for 30 min. This was followed by a 30-min intervention period. Assessment of post-intervention clearance for a further 30 min was then performed. Comparison of the amount of radioaerosol cleared from the right lung was made at 60 min (%C60) and 90 min (%C90) using repeated measures ANOVA. The percent cleared at 60 and 90 min was significantly increased with HS (%C60 = 26.5%, %C90 = 29.4%) and the combination of AML + HS (%C60 = 23.1%, %C90 = 27.4%) compared with both IS (%C60 = 14.7%, %C90 = 17.5%) and COUGH (%C60 = 18.0%, %C90 = 19.5%), p < 0.01. Inhalation of hypertonic saline is a potentially useful treatment in patients with cystic fibrosis.

Benefits of nocturnal nasal CPAP in patients with cystic fibrosis.

Patients with cystic fibrosis (CF) often hypoventilate during sleep with marked falls in oxygen saturation (SaO2%). This occurs most commonly during REM sleep, when there is a reduction in rib cage excursion and a fall in end-expiratory lung volume (EELV). The aim of this study was to examine the effect of nocturnal nasal continuous positive airway pressure (nCPAP) on SaO2 and the respiratory disturbance index (RDI) during sleep in patients with CF and severe lung disease. Seven patients (FEV1% pred, 23 +/- 5; range, 14 to 28%) were evaluated during sleep on two nights, control and nCPAP (11 +/- 2 cm H2O; range, 8 to 16 cm H2O), with four patients breathing room air and three patients breathing supplemental oxygen on both nights. Mean awake SaO2 was 91 +/- 1% (range, 89 to 93%). All patients showed significant oxyhemoglobin desaturation and respiratory disturbance in the control study. The maximal falls in SaO2 (15 +/- 10%) were most often associated with phasic eye movements, and a decline in rib cage excursion and the sum signal (Respitrace) during REM sleep. Nasal CPAP resulted in a significant improvement in the mean minimum oxygen saturation (MMOS) during both NREM (nCPAP 91 +/- 3% vs control 88 +/- 2%, p < 0.05) and REM sleep (nCPAP 89 +/- 6% vs control 83 +/- 6%, p < 0.05). Transcutaneous CO2 measurements were not significantly different between the control and the nCPAP studies. The RDI was also significantly reduced with nCPAP especially during REM sleep (9 +/- 7 events per hour vs control 25 +/- 11 events per hour, p < 0.05). Nasal CPAP caused no change in total sleep time or sleep efficiency yet significantly reduced the RDI and improved baseline SaO2 during both NREM and REM sleep.

Mucociliary clearance in patients with cystic fibrosis and in normal subjects.

The aim of this study was to examine baseline mucociliary clearance (MCC) in patients with cystic fibrosis (n = 30; mean +/- SEM age, 23 +/- 1 yr; FEV1, 68 +/- 5% pred; range, 14 to 126%) and a group of normal subjects (n = 12; mean age, 27 +/- 1 yr) after an aerosol deposition of 99mTc-sulphur colloid (mass median diameter, 4.8 microns; geometric standard deviation, 1.6). Dynamic geometric mean images were formed from gamma camera data, and the percent clearance of activity after 60 min (%C60) was calculated for the whole right lung. Initial deposition of the aerosol was determined in terms of the penetration index, the ratio of peripheral to central activity. For normal subjects, an increase in mean inspiratory flow rate (MIFR) (49 +/- 5 versus 21 +/- 3 L/min, p < 0.05) resulted in an increase in whole right lung MCC (%C60, 31 +/- 4 versus 18 +/- 2%; p < 0.05). When aerosol delivery was controlled (MIFR, 34 +/- 5 versus 36 +/- 5 L/min), there was excellent reproducibility between studies (whole lung %C60, 34 +/- 8 versus 31 +/- 7; NS). The measurement of MCC was highly reproducible in six patients studied on four occasions with a mean coefficient of variation of 3.3 +/- 1%. A breathing pattern to accentuate central deposition was utilized in the patient studies (MIFR, 49 +/- 4 L/min).(ABSTRACT TRUNCATED AT 250 WORDS)

Benefits of continuous positive airway pressure during exercise in cystic fibrosis and relationship to disease severity.

The aim of this study was to determine the benefits of CPAP applied during exercise in patients with cystic fibrosis (CF). A total of 33 CF patients with a wide range of lung function were studied. Pulmonary function tests were measured at rest. Endurance tests (80% of previously determined Wpeak) were performed on a bicycle ergometer with and without CPAP (5 cm H2O). Oxygen saturation (SaO2) was monitored by oximetry. Transdiaphragmatic pressure (Pdi) was measured in 7 patients. We found significant correlations between indices of disease severity (NIH score, FEV1, % of predicted, and RV/TLC) and the effects of CPAP on VO2, Pdi, and dyspnea score. CPAP reduced isotime (defined as the last common minute of exercise) VO2 and dyspnea in those patients with more severe lung disease, but these values tended to increase slightly in the patients with only mild lung disease. The change in dyspnea score related to changes in endurance time and VO2. In many patients isotime SaO2 was improved with CPAP, with the largest changes observed in those patients with severe disease. The decreases in VO2, Pdi, and dyspnea score with CPAP in patients with severe lung disease suggest that CPAP can reduce the work of breathing and increase exercise tolerance in patients with CF. These beneficial effects of CPAP during exercise in CF patients are related to disease severity.

Improvement in gas exchange with nasal continuous positive airway pressure in pulmonary alveolar microlithiasis.

A 37-yr-old man with pulmonary alveolar microlithiasis (PAM) presented with respiratory failure and cor pulmonale. The FEV1/FVC was 1.4/1.8 L with total lung capacity of 3.2 L using the helium dilution method (54% predicted) and 6.1 L using body plethysmography (102% predicted), indicating large noncommunicating regions. The KCO (transfer factor per liter lung volume) was 3.05 ml/min/mm Hg/L (47% predicted). Despite home oxygen (3 L/min) and diuretic therapy, the patient remained hypoxic (PaO2, 55 mm Hg) and incapacitated with dyspnea. Nasal continuous positive airway pressure (nCPAP) at 12 cm H2O and oxygen at 1 L/min improved his oxygenation (PaO2, 93 mm Hg), and introduction of this regimen at night resulted in subjective improvement in daytime function. A Grandjean right heart catheter was introduced at the bedside, and the multiple inert gas elimination technique (MIGET) was used to measure ventilation and blood flow distributions at ambient pressure and with the addition of 10 cm H2O nCPAP. The patient had severe pulmonary hypertension (mean Ppa, 57 mm Hg) and severe hypoxemia (PaO2 37 mm Hg), which was mainly due to shunt (16% of cardiac output) and a broadening of the main mode of the ventilation-perfusion (VA/Q) distribution (log SD Q, 0.94). There was a significant reduction in shunt during nCPAP to 6% of cardiac output without increasing Ppa, and this effect appeared to extend past the period of application. We conclude that nCPAP reduces intrapulmonary shunt in this rare condition and allows for correction of hypoxemia with a smaller oxygen flow rate.

Changes in end-expiratory lung volume during exercise in cystic fibrosis relate to severity of lung disease.

Changes in end-expiratory lung volume (EELV) during exercise in normal subjects and in patients with severe chronic obstructive lung disease have previously been examined. To date there are no studies that have examined the changes in EELV in patients with mild to moderate lung disease. We studied the changes in EELV during exercise in patients with cystic fibrosis (CF) with a wide range of pulmonary impairment to determine if changes in EELV were related to the severity of lung disease. Twenty-two patients with CF were studied (FEV1 17 to 112% of predicted) during progressive bicycle exercise, and changes in EELV were determined by repeat measures of inspiratory capacity. Changes in EELV at end exercise ranged from an increase of 0.67 L to a decrease of 0.61 L, and significant relationships were found between the changes in EELV and resting lung function (FEV1 percent predicted r = 0.79 and VR/TLC r = 0.58), indices of maximal expiratory flow (FEF50 r = -0.72 and FEF25-75 r = -0.71), and maximal work capacity (W-Max r = -0.76 and W-Max percent predicted r = -0.69). For subsequent analysis, patients were divided into two subgroups. Patients who were able to decrease EELV during exercise (Subgroup A) had significantly better resting lung function and SaO2 and significantly higher W-Max, peak oxygen consumption, and SaO2 at W-Max. Patients in Subgroup A also had a near normal ventilatory pattern during exercise. In contrast, the patients who increased EELV during exercise (Subgroup B) had severe lung disease (mean FEV1 29 +/- 4 percent predicted), limited work capacity, and desaturated during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)