Single Breath CO Research Articles

Airway resistance and reactance are affected in systemic sclerosis

BackgroundInterstitial lung disease often occurs as an early complication of systemic sclerosis (SSc). The aim was to investigate whether impulse oscillometry (IOS) could be used to evaluate lung impairment in SSc.MethodsSeventy-eight SSc patients, of which 65 had limited cutaneous SSc (lcSSc) and 13 had diffuse cutaneous SSc (dcSSc), were subjected to high-resolution computed tomography (HRCT) and pulmonary function tests (spirometry, IOS, and single breath CO diffusion capacity test). Twenty-six healthy individuals served as controls.ResultsPatients with lcSSc had higher levels of peripheral airway resistance, that is, R5–R20 (difference between resistance at 5 Hz and resistance at 20 Hz) showed a median (and interquartile range) of 0.05 (0.02–0.09) in lcSSc, 0.01 (0.00–0.04) in dcSSc and 0.04 (0.01–0.06) in healthy controls. They also had higher levels of reactance: reactance area was 0.26 (0.15–0.56) in lcSSc, 0.20 (0.11–0.29) in dcSSc and 0.18 (0.08–0.30) in healthy controls, and resonant frequency was 10.9 (8.8–14.8) in lcSSc, 9.0 (8.3–11.6) in dcSSc and 9.1 (8.0–13.1) in healthy controls. Airway reactance correlated to fibrotic findings on HRCT, such as ground glass opacities and reticulations.DiscussionThis implies that IOS parameters to some extent are related to fibrosis in patients with SSc.

AB0818 Nitric oxide diffusion and pulmonary capillary blood volume measurement in scleroderma patients

BackgroundCarbon monoxide diffusing capacity test (DLCO) is a non invasive diagnostic method for interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH), frequent and severe complications of systemic sclerosis (SSc)....

Comparison of volumetric capnography and mixed expired gas methods to calculate physiological dead space in mechanically ventilated ICU patients

Physiological dead space should be a routine measurement in ventilated patients but measuring dead space using the Douglas bag (DB) method is cumbersome and requires corrections for compressed ventilator gas. These factors make this method impractical in the critical care setting. Volumetric capnography (VCAP) offers a relatively simple solution to calculating dead space. Few studies have been conducted to directly compare dead space measured by VCAP and the DB method in critically unwell adults. Prospective observational study of 48 mechanically ventilated adults ICU patients. Dead space was calculated simultaneously using VCAP (CO(2)SMO) and the Bohr-Enghoff equation. In total, 168 paired readings were taken. Single-breath CO(2) waveform areas under the curve were computed automatically by software to calculate physiological dead space. The calculated value of P(Ē(CO(2))) was also recorded from the CO(2)SMO device. Exhaust ventilator gas was collected in a 10-l mixing chamber. P(Ē(CO(2))) was measured in the chamber following correction for compressed gas. The study demonstrated good agreement between physiological V(D)/V(T) calculated by VCAP and corrected (mean bias 0.03), and uncorrected (mean bias 0.02) Bohr-Enghoff method. There was good correlation between the two methods of measurement (VCAP vs corrected r(2) = 0.90 P < 0.001, VCAP vs uncorrected r(2) = 0.90, P < 0.001). There was good correlation between [Formula: see text] calculated by the CO(2)SMO and in the exhaust collected gas (mean bias 0.08). VCAP shows good agreement with Douglas Bag method in measuring physiological V(D)/V(T) over a wide range of dead space fractions.

Pneumoconiosis and emphysema in construction workers: results of HRCT and lung function findings

ObjectivesTo evaluate the prevalence of HRCT findings in construction workers previously surveyed by chest radiographs classified according to ILO guidelines. To examine the association between HRCT findings and exposure to...

Augmented peripheral chemoreflex in patients with heart failure and inspiratory muscle weakness

We hypothesized that heart failure patients with inspiratory muscle weakness (IMW) present greater peripheral chemoreflex responsiveness and augmented exercise ventilatory oscillation compared to patients with preserved inspiratory muscle strength. We studied 19 heart failure patients: 9 with IMW (maximal inspiratory pressure [PImax]<70% of predicted) and 10 with preserved inspiratory muscle strength. Inspiratory muscle strength was measured via pressure transducer. Peripheral chemoreflex was evaluated by the single-breath CO(2) test. Exercise ventilatory oscillation was determined as the ratio between amplitude and mean of each oscillation during incremental exercise. Patients with IMW had greater peripheral chemoreflex response (0.11+/-0.03 l min(-1) Torr(-1)) than those with preserved inspiratory muscle strength (0.07+/-0.03 l min(-1) Torr(-1), p=0.02). Moreover, there was a significant and inverse correlation between PImax and peripheral chemoreflex response (r=-0.57, p=0.01). Likewise, there was a significant and inverse correlation between PImax and ventilatory oscillations (r=-0.46, p=0.04). Our findings indicate that IMW is linked to increased peripheral chemoreflex and augmented exercise ventilatory oscillation in patients with chronic heart failure.

Effects of aging on peripheral chemoreceptor CO2 response during sleep and wakefulness in healthy men

Sleep-disordered breathing (SDB) prevalence multiplies with age and the mechanisms underlying this disorder are complex. Fifteen young and 13 elderly healthy male volunteers, ages ranging from 25 to 38 and from 55 to 76 years, were studied on three consecutive nights at the sleep laboratory. The peripheral chemoreceptor CO2 response was estimated by the single breath CO2 test (SBCO2T). The apnea-hypopnea index (AHI) was non-significantly higher in elderly men than in young men. During rapid eye movement (REM) sleep and non-REM sleep SBCO2T was similar in young and elderly subjects. During wakefulness, young had a tendency to higher SBCO2T than elderly (0.25+/-0.08 L/min/mmHg vs. 0.19+/-0.07 L/min/mmHg, respectively; p=0.054), but the five elderly subjects with AHI>5 had significantly higher SBCO2T than the remaining elderly subjects (0.24+/-0.07 L/min/mmHg vs. 0.16+/-0.04 L/min/mmHg, respectively; p=0.024). Aging seems to spare the SBCO2T during sleep. Investigation of SBCO2T during transition from wakefulness to sleep, as a factor in the pathogenesis of disordered breathing in elderly men, is justified.

Increased Exhaled H2O2 and Impaired Lung Function in Patients Undergoing Bioincompatible Hemodialysis

Chronic renal failure (CRF) and hemodialysis (HD) accumulate an inflammatory milieu, contributing to increased systemic and airway oxidative stress that may lead to lung damage. This study was designed to assess exhaled hydrogen peroxide (H2O2), lung function and whole blood chemiluminescence in HD and CRF patients and healthy controls. The study included 59 patients (Polyamide STM or Hemophan membranes--19, cuprophane--16, hemodiafiltration--14, continuous ambulatory peritoneal dialysis--10), 16 CRF and 16 healthy controls. The assessment of lung function included FVC (forced vital capacity), FEV1 (forced expiratory volume in the first second) and DLCOc (single breath CO diffusing capacity). Exhaled H2O2 was determined fluorometrically and resting and n-formyl-methionyl-leucyl-phenylalanine (fMLP) luminol-dependent whole blood chemiluminescence (LBCL) were measured simultaneously. Only cuprophane HD patients presented decreased lung function (FVC 63.8+/-17.4%, FEV1 55.9+/-20.3 and DLCOc 72.1+/- 9.3 % of predicted; p<0.05 vs. controls). These patients exhaled the highest H2O2 levels in comparison to CRF (p<0.01): median 0.36 microM (range R: 0.09-0.56 microM) and controls (p<0.05): 0.17 microM (0.2-17.8 microM). These levels were not decreased during the HD session: preHD 1.25 microM (0.2-16.5 microM) and postHD 1.3 microM (0.2-17.8 microM). As a marker of systemic oxidative stress, fMLP-induced LBCL (total light emission) was increased in these patients (1570.6 aUxs/10(4) phagocytes; R: 274.2-8598.9) and in the CRF group (2389.4 aUxs /10(4) phagocytes; R: 491.5- 6184; p<0.05 vs. controls). Other patient groups did not express elevated LBCL and revealed decreased exhaled H2O2 after a session. An increased oxidative burden in the lungs may contribute to functional lung impairment in patients dialyzed with a cellulose membrane. Biocompatible dialysis with other modalities might reduce airway-borne oxidative stress and is not related with lung damage.

Single breath CO measurements normalized to 5% CO2 in Coombs' test positive neonates

A portable, prototype instrument that measures peak CO, CO2 and H2 concentrations of breath samples was evaluated on 58 antibody positive, blood group incompatible infants. The reproducibility of 108 duplicate breath CO determinations improved when the result was normalized (COn) for the simultaneously measured CO2 concentration (r = 0.97 versus r = 0.87). The average COn for 18 antibody positive, ABO incompatible infants who received phototherapy was 1.2 ppm higher than the average for 32 who did not receive phototherapy (p < 0.001). There was a positive correlation between COn and the duration of phototherapy (r = 0.75). Sodium acetate infusion and breath H2 did not affect the COn results. In antibody positive infants, single breath CO to CO2 ratios provided more reproducible results than CO determinations that were not adjusted for the CO2 concentration. Therefore, a portable instrument that measures both gases on the same aliquot of exhaled air and that is not affected by H2 should have clinical utility as an indicator of heme catabolism and bilirubin production that is not distorted by hyper- or hypoventilation.

Serotonin regulation of the human stress response

Acute tryptophan depletion (ATD) is a technique that has been used to evaluate the effects on humans of acutely reducing serotonin neurotransmission. We have developed a model using a single breath of 35% CO(2) that activates the hormonal axis and produces autonomic and behavioural arousal, thus modelling a stress response. This study combines ATD and single breath 35% CO(2) inhalation to study stress responses in volunteers. A randomised, double-blinded, placebo-controlled, cross-over trial involving 14 healthy adult volunteers aged between 18 and 65 years was undertaken. Subjects underwent double-blind tryptophan depletion over 2 days and were then crossed over 1 week later. During each study day, at the time of peak depletion, participants were single blinded to receive a single breath of 35% CO(2) or air. This was followed 40 min later by the other gas. Psychological outcomes were assessed with the Spielberger State Anxiety Inventory (SSAI), Visual Analogue Scales (VAS), Panic Inventory (PI), Panic and Agoraphobia Scale (PSI) and Beck Depression Inventory (BDI). Physiological outcome was measured by serial plasma cortisol, prolactin and tryptophan levels, pulse and blood pressure. Tryptophan depletion did not exacerbate 35% CO(2) inhalation effects on anxiety symptoms. Single breath CO(2) robustly increased plasma cortisol levels in comparison to an air inhalation; this was less certain for prolactin levels. ATD influenced the HPA axis (associated with higher cortisol levels), apparently independent of CO(2) or air inhalation stressors. ATD and 35% CO(2) inhalation both induced a pressor response and bradycardia in these normal volunteers. Thirty-five percent CO(2) inhalation and ATD independently activate the human stress response, but do not appear to produce synergistic effects when combined, at least for the conditions produced in this study.

Adverse effects of asbestos exposure and smoking on lung function

Exposure to asbestos is a well-recognized cause of both malignant and nonmalignant diseases of lung parenchyma and pleura. This study was conducted to determine the adverse effects of exposure to asbestos and smoking on pulmonary function. Four hundred and sixty-eight workers who were occupationally exposed to asbestos for an average of 13 years were selected from an asbestos-product factory in China. Of them, 85 workers were diagnosed with asbestosis. Additionally, 282 workers who had no experience of exposure to industrial dust were included as a control group. A questionnaire was administered during a face-to-face interview and spirometric maneuvers and single-breath CO diffusing capacity (DL(CO)) were performed. Multivariate regression analysis showed that exposure to asbestos was more strongly associated with decreased forced vital capacity (FVC) and DL(CO), and asbestosis more strongly associated with decreased FVC, while smoking was a major contributing factor to reduced FEV1/FVC. The results were confirmed by a further analysis where the subjects were grouped exclusively by smoking, asbestos exposure, and chest radiographic changes. No interaction or joint effect was observed between asbestos exposure and smoking. This analysis suggested that asbestos and smoking might play independent roles, in which asbestos caused mainly a restrictive impairment, and smoking was a major causal factor for airway obstruction in the workers who were intensively exposed to asbestos.

Association of central sleep apnea and nocturnal CO 2 exhalation volume under oxygen inhalation in patients with chronic heart failure

We investigated impacts of O 2 on sleep apnea and nocturnal CO 2 exhalation volume in stable/severe CHF.Subjects were 7 patients with stable CHF (LVEF = 23.2 ± 7.6%, NYHA class = III). Nocturnal SaO 2 and sleep data were analyzed using PSG, with single breath CO 2 exhalation volume(SBCO 2) using a monitoring device.1. All of the patients had central sleep apnea (CSA). 2. SaO 24%ODI decreased with O 2 inhalation (7.9 ± 3.8 vs. 0.6 ± 0.5 times/hour, p < 0.01). 3. AHI was reduced with O 2 (19.7 ± 2.3 vs. 2.4 ± ;3.6 times/hour, p < 0.01). 4. SBCO 2 during sleep were: in room air, 44.0 ± 4.8ml during regular respiration and 119 ± 9.8ml at onset of CSA; in O 2, 90.8 ± 4.0ml during regular respiration. An increased level of the SBCO2 was attained with O 2.In CHF with CSA, a low level of SBCO 2 was observed. It was suggested that O 2 improved this low value and suppressed CSA.

Reproducibility of the respiratory dead space measurements in mechanically ventilated children using the CO2SMO monitor.

To assess the reproducibility of respiratory dead space measurements in ventilated children. Prospective study. University pediatric intensive care unit. Thirty-two mechanically ventilated children (0.13-15.4 years) who were clinically stable. The single-breath CO(2) test (SBT-CO(2)) was recorded using the CO(2)SMO Plus from the mean of 30 ventilatory cycles during 1 h (at T0, T15, T30, T45, and T60). Airway dead space was determined automatically (Novametrix Medical Systems, USA), and manually by Bohr- Enghoff equations using data obtained by SBT-CO(2). At the end of the study period, arterial blood gas was sampled in order to calculate alveolar and physiologic dead space. Intrasubject reproducibility of measurements was evaluated by the intraclass correlation coefficient. Two-way analysis of variance was used to evaluate the relationships between time and measurements. The two methods for calculating airway dead space were compared by using two-tailed Student's t-test and Bland-Altman analysis. Airway dead space measurement had a good reproducibility during the 1-h period, whatever the method used (intraclass correlation coefficient: 0.84 to 0.87). No significant difference was observed with time. Airway dead space values from the SBT-CO(2) method were smaller than those from Bohr-Enghoff equations. Physiologic dead space values from the SBT-CO2 method were similar to those from Bohr-Enghoff equations. The measurement of airway dead space by the CO(2)SMO Plus was reproducible over a 1-h period in children requiring mechanical ventilation, provided ventilatory parameters were constant throughout the study. SBT-CO(2) analysis may provide a bedside non-invasive monitoring of volumetric capnography.

Pulmonary involvement in type 1 Gaucher disease: functional and exercise findings in patients with and without clinical interstitial lung disease.

Pulmonary disease is a well-known complication of Type 1 Gaucher disease (GD), although its incidence is not well established and its severity varies. The purpose of this study was to determine the frequency and extent of pulmonary involvement in patients with GD. Pulmonary involvement was assessed by history, physical examination and chest radiograph in 150 consecutive patients with Type 1 GD presenting at a specialized center for genetic diseases. Five patients were noted to have clinical evidence of pulmonary involvement. Full pulmonary function tests were performed in these five patients and in an additional 13 patients randomly selected from the remaining 145. Many of the 18 patients also underwent radionuclide body imaging with 67 Gallium citrate and 111Indium-tagged leucocyte scans, as well as incremental cardiorespiratory exercise tests. Lung biopsies were available in two patients with lung disease, and a second examination of lung tissue was performed in one of these two patients post-mortem. Clinical lung disease was detected in five patients. All five had dyspnea, diffuse infiltrates, restrictive impairment and low single breath CO diffusing capacity (DLCOSB). Two of these patients underwent exercise testing and showed abnormalities consistent with lung disease (ventilatory limitation, excessive ventilation and increased dead space) as well as decreased VO2 max. and anaerobic threshold (AT). In contrast, in the other 13 patients, physical examination, chest radiographs and pulmonary function were normal (except for a low DLCOSB in one patient). Responses on exercise testing (performed in six of the 13 patients) were consistent with a circulatory impairment (decreased VO2 max. and AT). Our study found that <5% of patients with Type 1 GD have clinical interstitial lung disease. In addition, we found that some patients, without evident lung involvement, may experience limitations in physical exertion and are easily fatigued; this is attributable to impaired circulation.

Effect of an Intensive Chemotherapy Followed by Mediastinal Irradiation on Pulmonary and Cardiac Function in Advanced Hodgkin's Disease

Mediastinal irradiation combined with chemotherapy in patients with Hodgkin's disease have been associated with cardiopulmonary toxic effects that can last over the years.In this study we monitored pulmonary and cardiac function in 39 patients affected by advanced Hodgkin's disease (stage II B–III and IV) with mediastinal involvement and submitted to an intensive chemotherapy regimen (epirubicin, vincristine, ciclophosphamide, and etoposide) followed by involved field irradiation. Pulmonary function was verified with chest x-ray, spirometric parameters, arterial blood gas analysis, single breath CO transfer factor (DLCO), and its components Dm and Vc. Cardiac function was verified with electrocardiogram (EKG) and left ventricular ejection fraction (LVEF) by means of radionuclide angiocardiography. The median follow-up was 40 months. Spirometric parameters did no show modifications at the end of treatment, on the contrary they improved during the follow-up. Chest x-ray showed radiographic parenchimal damage in 51% of patients. DLCO remained constantly decreased. sEKG did not show significant modification, whereas LVEF significantly decreased at the end of treatment and remained persistently decreased during follow-up.None of the patients with reduction of DLCO or LVEF showed clinical symptoms of heart and pulmonary dysfunctions. One patient, 49 years old, suffered from myocardial infarction 25 months after the completion of radio-chemotherapy.These data indicate that this combined regimen can induce persistent pulmonary and cardiac damages at subclinical level.

Body mass, fat percentage, and fat free mass as reference variables for lung function: effects on terms for age and sex

BACKGROUNDSex specific cross sectional reference values for lung function indices usually employ a linear model with terms for age and stature. The effects of also matching for body mass index...

Changes in carbon monoxide transfer over 22 years in middle-aged men

We measured single breath CO transfer (TL co), single breath alveolar volume (VA), CO transfer coefficient (Kco) and forced expiratory volume in 1 sec (FEV1) in 84 men, mean age 40·5 years at recruitment, in 1975 and in 1997. At recruitment, 42 men were cigarette smokers and 42 were not smoking. Mean annual decline in FEV1was similar in never- (34·2 ml yr−1) and ex- (33·1 ml yr−1) smokers and faster (51·0 ml yr−1) in continuing smokers.In contrast to predictions from cross-sectional reference values, there was no fall in TL coor Kcoin men who did not smoke over the period of follow-up. In the 16 men who smoked throughout follow-up there was a 10% fall in TL co(P=0·043) but most of this was due to a significant fall in VA(P=0·017), presumably reflecting uneven gas mixing.These results indicate the need for population-based longitudinal studies of TL coand Kco. If single breath estimates of VAare used in subjects with even mild airflow obstruction, Kcorather than TLcoshould be used to assess alveolar function.

Late pulmonary effects in favorable stage I and IIA Hodgkin's disease treated with radiotherapy alone.

Radiotherapy (RT) in patients with favorable-stage Hodgkin's disease can induce clinical and subclinical evidence of pulmonary damage lasting over the years. In this study, we monitored 36 patients with stage IA-IIA Hodgkin's disease treated with subtotal nodal RT. The planned dose of RT was 40 Gy to 44 Gy to the involved areas and 36 Gy to the adjacent uninvolved areas. Pulmonary function was evaluated by chest radiograph, spirometric parameters, arterial blood gas analysis, and single-breath CO transfer factor (DLCO). The tests were performed before and at the end of irradiation, and during the follow-up 1 and 3 to 5 years after the treatment. At the end of RT, we found a significant decrease of total lung capacity, vital capacity, forced expiratory volume in 1 second, residual volume, and DLCO. Spirometric parameters improved during the follow-up period, whereas the decline of DLCO (-6.4%) was persistent. No correlation was found between mantle RT dose and DLCO changes. Four patients showed a decline of DLCO of >20% from pretreatment values but only one was symptomatic. Our study confirms that RT induces a pulmonary-restrictive disease at a subclinical level that seems to be reversible in the majority of patients.

Predictors of nocturnal oxygen desaturation in patients with COPD

The aim of this study was to identify factors which might predict nocturnal desaturation (defined as a fall of >4% from awake baseline level for ≥5 min) in normoxic or mildly hypoxic patients with stable COPD [arterial O 2 saturation ( SaO 2) ≥ 91%]. The study was prospective in nature, had full ethical approval and was performed in the Respiratory Department of a city teaching hospital. Thirty-three patients [mean ( sd) age 67·2 (9) years] with stable COPD [mean ( sd) FEV 1 36·8 (11·0) % pred.] were recruited via the respiratory outpatient clinics and through the respiratory wards. The following parameters were measured: daytime arterial blood gases; spirometry; lung volumes (helium dilution); single breath CO transfer factor ( T lCO and KCO); maximum inspiratory (IMP) and expiratory mouth pressures; pulse oximetry ( SpO 2) across a 6-min walk test, and SpO 2 during sleep. Seventeen patients who experienced nocturnal desaturation had significantly lower mean PaO 2 and SaO 2, and higher PaCO 2 values compared to non-desaturators. There was a positive correlation between mean nocturnal SpO 2 and daytime PaO 2, SaO 2, and minimum exercise SpO 2, and a negative correlation between mean nocturnal SpO 2 and PaCO 2, and FRC. Regression analysis revealed that daytime SaO 2 was the only independent predictor of mean nocturnal saturation (accounting for 61% of the variability in the mean nocturnal SpO 2). We observed nocturnal desaturation in all patients with a daytime SaO 2 ≤93% but in no patient with SaO 2 ≥95%. We conclude that daytime SaO 2 can be used to predict nocturnal desaturation in normoxic or mildly hypoxic patients with stable COPD. Nocturnal desaturation is likely in patients with COPD where daytime SaO 2 ≤93%, and unlikely where daytime SaO 2 ≥95%.

An epidemiological study of the health of Sri Lankan tea plantation workers associated with long term exposure to paraquat.

Pulmonary function tests (FVC, FEV1, FEV1/FVC%, TLCO, single breath CO diffusion), chest x ray film, renal function (serum creatinine and blood urea nitrogen), liver function (serum alanine aminotransferase, aspartate transferase, and alkaline phosphatase, bilirubin, total protein, and albumin), a haematological screen (haemoglobin and packed cell volume), and a general clinical examination were performed on 85 paraquat spraymen (mean spraying time 12 years) and on two control groups (76 factory workers and 79 general workers) frequency matched for age and years of occupational service. All the subjects were men. There were no clinically important differences in any of the measurements made between the study group and the two control groups. In particular the results of the lung function tests, appropriate for paraquat toxicity of the study group, were similar to those of the control groups. The same was true of blood tests for liver and kidney function. The incidence of skin damage, nose bleeds, and nail damage in the study group was slightly higher than in the control groups but lower than the incidence reported for paraquat workers in previous studies. The results of this study confirmed that long term spraying of paraquat, at the concentrations used, produced no adverse health effects, in particular no lung damage, attributable to the occupational use of the herbicide.

Effects of ventilation inhomogeneity on DLcoSB-3EQ in normal subjects.

In patients with airflow obstruction, we found that ventilation inhomogeneity during vital capacity single-breath maneuvers was associated with decreases in the three-equation single-breath CO diffusing capacity of the lung (DLcoSB-3EQ) when breath-hold time (tBH) decreased. We postulated that this was due to a significant resistance to diffusive gas mixing within the gas phase of the lung. In this study, we hypothesized that this phenomenon might also occur in normal subjects if the breathing cycle were altered from traditional vital capacity maneuvers to those that increase ventilation inhomogeneity. In 10 normal subjects, we examined the tBH dependence of both DLcoSB-3EQ and the distribution of ventilation, measured by the mixing efficiency and the normalized phase III slope for helium. Preinspiratory lung volume (V0) was increased by keeping the maximum end-inspiratory lung volume (Vmax) constant or by increasing V0 and Vmax. When V0 increased while Vmax was kept constant, we found that the tBH-independent and the tBH-dependent components of ventilation inhomogeneity increased, but DLcoSB-3EQ was independent of V0 and tBH. Increasing V0 and Vmax did not change ventilation inhomogeneity at a tBH of 0 s, but the tBH-dependent component decreased. DLcoSB-3EQ, although independent of tBH, increased slightly with increases in Vmax. We conclude that in normal subjects increases in ventilation inhomogeneity with increases in V0 do not result in DLcoSB-3EQ becoming tBH dependent.