Relationship between lung function, ventilation-perfusion inequality and extent of emphysema as assessed by high-resolution computed tomography.

UNLABELLED: The development of the high-resolution computed tomography (HRCT) has improved the ability to detect and quantify emphysema in various groups of patients with chronic airflow obstruction (COPD). Significant correlations have previously been found between indices of air flow obstruction, hyperinflation, reduced diffusing capacity for carbon monoxide (DLCO), and the extent of emphysema (emph.%) assessed by HRCT. However, the relationship between emph.% and ventilation-perfusion (V(A)/Q) inequality in COPD is unknown. Twenty COPD patients with a mean forced expiratory volume in 1 s (FEV1) of 38.2 (+/- 15.5)% in percent of predicted value (%P), a mean PaO2 value of 9.6 (+/- 1.3) kPa, and a mean diffusing capacity of 43.6 (+/- 23.0)%P, were subjected to measurements by the multiple elimination inert gas technique (MIGET). The extent of emphysema was determined by HRCT at both full inspiration, emph.I(%) and at full expiration, emph.E(%), with a cut-off limit of -910 Hounsfield Units (HU) using the "Density Mask" method. The ventilation directed towards high V(A)/Q areas was 73 (+/- 10.2)% and the mean ventilation (V-mean) was elevated about three times compared to normal. The mean emph.(I)% and emph.(E) was 45.6 (+/- 16.9) and 32.7 (+/- 190)%, respectively. Significant correlations were shown between the emphysema extent and several lung function parameters, but no correlation was found between the emphysema extent and the V(A)/Q relationships or the blood gas values. Reduced DLCO%P correlated with less high V(A)/Q ventilation (r=0.73, P < 0.05) for the subgroup of COPD patients with DLCO(%P) less than 50% (n=12). CONCLUSIONS: In COPD patients, suffering from moderate to severe emphysema without severe blood gas impairment, no correlation was shown between the extent of emphysema, as assessed by HRCT, and the severity of ventilation-perfusion inequality. A substantial collateral ventilation in severe emphysema may be a mechanism that prevents a deterioration in V(A)/Q relationships and in blood gas levels.

Effect of CO(2) pneumoperitoneum on ventilation-perfusion relationships during laparoscopic cholecystectomy.

BACKGROUND: Previous studies have shown that pneumoperitoneum transiently reduces venous admixture as assessed by a calculation based on the shunt formula, and increases arterial oxygen tension (PaO(2)) in patients without heart or lung disease. The aim of the present study was to further explore the relationship between ventilation-perfusion (V(A)/Q) before and during pneumoperitoneum by using the multiple inert gas technique. METHODS: Nine patients without heart or lung disease (ASA I), with a mean age of 42 years, scheduled for laparoscopic cholecystectomy were included. After premedication and induction of anaesthesia, radial artery and pulmonary artery catheters were introduced percutaneously. The V(A)Q relationships were evaluated by the multiple inert gas elimination technique before and during pneumoperitoneum to obtain a direct measure of the pulmonary shunt. RESULTS: Induction of pneumoperitoneum decreased the pulmonary shunt from 5.8 (4.5) to 4.1 (3.2)% (P<0.05) and increased PaO(2) from 21.7 (5.9) to 24.7 (4.8) kPa (P<0.01). During surgery, the shunt increased from 3.2 (2.8) to 5.2 (3.4)% to the same level as before pneumoperitoneum induction. No area with low V(A)Q was seen. Dead space ventilation amounted to 20.0 (1.2)% in the supine position and did not change during the investigation. CONCLUSIONS: In patients without heart or lung disease, pneumoperitoneum at an intra-abdominal pressure level of 11-13 mmHg causes a transient reduction of the pulmonary shunt. The mechanisms underlying the present finding remain to be elucidated.

Ventilation-perfusion inequality and carbon dioxide sensitivity in hypoxaemic chronic obstructive pulmonary disease (COPD) and effects of 6 months of long-term oxygen treatment (LTOT).

UNLABELLED: The aim of our study was to find out how blood gas disturbances in stable, eucapnic, severe chronic obstructive pulmonary disease (COPD) patients with an arterial oxygen tension (PaO(2)) value of 7.7 (6.1-8.4) kPa are affected by ventilation-perfusion (V(A)/Q) relationships and carbon dioxide (CO(2)) sensitivity and how these parameters are influenced by 6 months of long-term oxygen treatment (LTOT). V(A)/Q ratios were measured using the multiple inert gas elimination technique (MIGET). Mouth occlusion pressure 0.1 s after onset of inspiration (Pi0.1) and minute ventilation (V(E)) were measured to assess respiratory drive response (DeltaPi0.1/DeltaPCO(2)) and hypercapnic ventilatory response (HCVR) to CO(2) rebreathing. At the start of LTOT, a normal median respiratory drive response level of 1.2 (0.2-2.3) cm H2O/kPa and a low median HCVR as compared with healthy individuals (P<0.001) were found. However, 7.9 (0-29.8)% of the VE, was directed towards hypoperfused lung areas. The dispersion of ventilation (log SDV; 0.47-1.76), and the dispersion of perfusion (log SDQ; 0.66-1.07) were wider than normal. The PaO(2) level correlated inversely with mean V(A)/Q ratio for ventilation (V mean) and shunt. The PaCO(2) level correlated inversely with HCVR and vital capacity. After 6 months of LTOT, no significant changes in daytime blood gas levels, CO(2)-sensitivity or VA/Q ratios were found. VE tended to be reduced by 1.0 l min-1. CONCLUSIONS: An elevated V mean and probably shunting are important contributing factors for the reduced PaO(2) and hypercapnic ventilatory response is a major determinant of PaCO(2) in eucapnic stable hypoxaemic COPD. Six months of LTOT does not affect blood gases, CO(2) sensitivity or ventilation-perfusion relationships.

Effects on diffusing capacity and ventilation--perfusion relationships of budesonide inhalations for 2 months in chronic obstructive pulmonary disease (COPD).

Forced expiratory volumes are reduced in chronic obstructive pulmonary disease (COPD), mainly as a result of inflammatory and morphological changes in the small airways (with a diameter < 2 mm) and in the alveoli. However, it is difficult to detect minor changes in small airways by spirometry measurements. To study the effects on small airways of inhaled corticosteroids (ICS), 19 stable COPD patients were investigated; 15 were evaluated by ventilation-perfusion (V(A)/Q) relationships, assessed by the multiple inert gas elimination technique, and by diffusing capacity for carbon monoxide (DL(CO)), assessed by the single breath technique. Measurements were repeated after 2 months of budesonide inhalations (800 microg) twice daily. Before ICS treatment: mean forced expiratory volume in 1 sec (FEV1) as a percentage of predicted (% P) was 40.1 (+/- 16.0)%, DL(CO)% P was 45.7 (+/- 25.0)% and 6.0 (+/- 6.4)% of the ventilation was directed at high V(A)/Q areas. The mean of the V(A)/Q ratio for ventilation (V-mean) was 2.7 times higher than normal. After 2 months of ICS: the mean of DL(CO)% P increased by 8.6 (+/- 19.4)%, and FEV1/vital capacity decreased by 6.9 (+/- 11.3)%. Basal morning and ACTH-stimulated S-cortisol levels were significantly reduced. All the V(A)/Q relationships remained unchanged. In conclusion, a significant increase in diffusion capacity for carbon monoxide levels after treatment with corticosteroid inhalations for 2 months was shown, but no significant improvements were found in forced expiratory airflow, lung volumes, or V(A)/Q relationships.

Inspiratory muscle training in patients with prior polio who use part-time assisted ventilation.

OBJECTIVE: To evaluate whether inspiratory muscle training in patients with prior poliomyelitis (and with symptoms and signs of hypoventilation) who use part-time assisted ventilation could improve symptoms and respiratory muscle function without adverse effects. DESIGN: Intervention study with before-after trial. SETTING: Training was performed in the patients' homes; assessments were performed at the hospital. PATIENTS: Ten prior-polio patients were included. Three of them did not complete the trial, and their data were not included in results of training. INTERVENTION: Ten weeks of daily inspiratory muscle training. MAIN OUTCOME MEASURES: Spirometry, maximal inspiratory and expiratory pressures, inspiratory muscle endurance, and questions regarding activities of daily living were performed. RESULTS: Inspiratory endurance capacity over 5 minutes improved from 10.7 to 16.7cm H2O (p < .05) assessed at 15 on the Borg scale, and most patients improved in activities of daily living. The whole-body endurance capacity remained stable over the studied period. CONCLUSION: Inspiratory muscle training and close supervision can increase respiratory muscle endurance and improve well-being in patients with prior polio who use part-time assisted ventilation.

Pulmonary gas exchange in cystic fibrosis: basal status and the effect of i.v. antibiotics and inhaled amiloride.

In order to evaluate the degree and type of gas exchange impairment in cystic fibrosis, ventilation/perfusion relationships in ten patients (mean age 26 yrs, mean Shwachman score 86) were examined. Pulmonary gas exchange was studied using the multiple inert gas elimination technique. High-resolution computed tomography (HRCT) and spirometry, including diffusing capacity, were performed after each gas exchange study for comparison. Examinations were done before and after home i.v. antibiotic treatment (HIVAT, 14 days) and after inhaled amiloride and placebo (14 days), in crossover fashion, clinical status after HIVAT serving as the baseline for the crossover study. Before HIVAT, the mean residual volume was 182% of the predicted value, the mean vital capacity 72% pred and the mean forced expiratory volume in one second 53% pred (p<0.001). The dispersion of pulmonary blood flow at different ventilation/perfusion ratios (V'/Q') ((logarithmic SD of the perfusion distribution (log SDQ)), used as an index for gas exchange impairment, was increased to a mean of 0.72. No linear correlation was seen between ventilation/perfusion inequality, spirometry and HRCT (p>0.05). After HIVAT, log SDQ was significantly improved to 0.66 (p<0.05). After placebo, but not after amiloride, log SDQ, arterial oxygen tension, alveolar-arterial oxygen tension difference and maximal expiratory flows when 50% and 25% of the forced vital capacity tension remain to be exhaled were significantly worse (p<0.05, respectively). Areas with a low V'/Q' were significantly lower after amiloride compared to after the placebo period (p<0.05). Moderate ventilation/perfusion inequality was present in the majority of the studied cystic fibrosis patients. The degree of ventilation/perfusion inequality cannot be estimated from spirometry or high-resolution computed tomography. The low proportion of low ventilation/perfusion ratios indicates that the regular treatment directed towards mucus plugging of small airways is beneficial. An improvement in the ventilation/perfusion relationship was seen after home i.v. antibiotic treatment and inhaled amiloride may possibly have a further positive effect on gas exchange.

Sleep quality, carbon dioxide responsiveness and hypoxaemic patterns in nocturnal hypoxaemia due to chronic obstructive pulmonary disease (COPD) without daytime hypoxaemia.

In order to clarify whether nocturnal hypoxaemia (arterial oxygen saturation, SaO2 < 90%) may exist in the long-term before daytime hypoxaemia (PaO2 < 8.0 kPa) occurs in chronic obstructive pulmonary disease (COPD), 21 patients with stable severe COPD without daytime hypoxaemia (PaO2 > or = 8.0 kPa) were studied prospectively. Subjects were monitored twice by polysomnography (PSG) 12 months apart. Spirometry was performed, and diffusion capacity (DLCO) and hypercapnic respiratory drive response delta PI0.1 delta PCO2(-1)) were measured during the daytime in conjunction with polysomnography. At the start of the study our subjects had FEV1 %P (FEV1 as a percentage of predicted value) of 26.1 +/- 7.2%, a mean nocturnal nadir SaO2 of 83 +/- 5%, and a mean SaO2 during nocturnal hypoxaemic episodes of 88.0 +/- 0.7%. The patients' delta PI0.1 delta PCO2(-1) was 1.8 +/- 1.4 cm H2O kPa-1 (within the normal range). For the entire study group, no significant change in any lung function or blood gas parameter was noted during the year of observation, and nocturnal SaO2 remained unaltered. Stage I sleep decreased (P < 0.05) after 12 months. Prolonged stage I sleep was associated with nocturnal hypoxaemia at the second PSG. Five subjects developed daytime hypoxaemia and they showed poorer lung function but similar nocturnal hypoxaemia and delta PI0.1 delta PCO2(-1) level compared to the rest of the patients. Patients with sudden SaO2 dips had more pronounced nocturnal hypoxaemia and prolonged wakefulness than 'non-dippers'. In conclusion, the mean level of nocturnal hypoxaemia may persist unaltered for at least 1 yr. COPD patients with exclusively nocturnal hypoxaemia have a hypercapnic drive response within the normal range. Prolonged nocturnal hypoxaemia and reduced whole night oxygenation are associated with increased superficial sleep. Sleep fragmentation and high carbon dioxide sensitivity may be important defence mechanisms against sleep-related hypoxaemia. The appearance of daytime hypoxaemia is preceded by a substantial deterioration in lung function, but by only a minor deterioration of nocturnal hypoxaemia.

Nebulisation of hypertonic saline causes oedema of the airway wall.

The effect of aerosol challenge with distilled water, and with isotonic and hypertonic saline on the respiratory system of the anaesthetized rabbit was investigated. Nebulisation of hypertonic (3.6%) saline caused an increase in the extravascular lung water without altering the total body weight. Morphometrical investigations revealed an increase of the subepithelial tissue compartment (connective tissue and smooth muscle) of the airway wall. X-ray microanalysis showed higher content of Na, K, and Cl in this compartment already 10 min after nebulisation of hypertonic saline. The formation of oedema was associated with a significant decrease in both compliance and gas exchange.

Lung Function in Woodworking Teachers in Sweden.

Work-related airways symptoms are common in woodworkers. To study possible work-related effects on lung function, 40 exposed woodworking teachers and 31 controls were examined by spirometry, diffusion-capacity and nitrogen-washout determinations, and methacholine challenge. Measured levels of total and respirable dust and terpene concentrations in the shops were below the Swedish threshold-limit values. Lung-function values on Monday morning were similar in the two groups. Slight obstructive impairments during the working week were found in both groups. In the woodworking teachers, small changes in lung function were related to measured total dust, use of process ventilation, and use of a broom to clean the benches. Their methacholine reactivity was slightly more pronounced compared with that of the controls, but the numbers of hyperreactive individuals (PC&inf20; < 8 mg/m(3)) were equal in the two groups. These facts might indicate small work-related effects on lung function, but some contradictory findings disturb this interpretation. The results are therefore inconclusive.

Ventilation-perfusion inequality in nocturnal hypoxaemia due to chronic obstructive lung disease (COLD).

Nocturnal hypoxaemia is often noted in COLD patients with a daytime PaO2 above 8.0 kPa. It has been assumed that ventilation-perfusion inequality contributes to nocturnal hypoxaemia. 10 patients with advanced COLD [median FEV1 0.73 (range 0.50-1.32)l], but without daytime hypoxaemia [median PaO2 8.35 (range 8.0-12.2) kPa] were investigated with regard to possible nocturnal hypoxaemia using polysomnography. Daytime lung function was assessed by spirometry and carbon monoxide diffusion capacity (DLCO). Daytime ventilation-perfusion (VA/Q) relationships were measured by the multiple inert gas elimination technique. Dispersion of perfusion and ventilation distributions was increased [log SDQ 1.01 (range 0.80-1.35) and log SDV 0.91 (range 0.69-1.86) resp.]. Around 8% of the ventilation was directed towards high VA/Q areas (10 < VA/Q < 100). All subjects reached all sleep stages, and all but one had a nadir nocturnal oxygen saturation (SaO2) of below 90%. Their median lowest nocturnal SaO2 was 84.0 (range 70-93)% and their mean oxygen saturation in the course of desaturation episodes (MminSaO2) was 86.4 (range 83.6-91.5)%. An increased mean VA/Q ratio of ventilation distribution was associated with a reduced DLCO. Increased nocturnal episodes of wakefulness and of stage I sleep correlated with increased dead space ventilation and dispersion of the ventilation distribution. Patients with deep nocturnal desaturations had a low mean VA/Q ratio of the perfusion distribution (Q mean) (r = 0.87, P < 0.01) and increased perfusion of inferior VA/Q areas (0.1 VA/Q < 0.3). Low MminSaO2 was associated with low morning PaO2 and a low Q mean. COLD patient with solely nocturnal hypoxaemia have a high degree of pulmonary hyperinflation and emphysema. Increased sleep disruption is associated with more severe small airway disease. Increased perfusion of sparsely ventilated areas is associated with more pronounced nocturnal desaturations.

Spirometry and ventilation-perfusion inequality in patients with mild allergic asthma before and during the pollen season.

Several studies on asthma have shown a low correlation between gas exchange and spirometry, especially after treatment with bronchodilators. The aim of the present study was therefore to examine both spirometry results and gas exchange during a pollen-free period and at the end of the pollen season in patients with mild and well-controlled allergic asthma. Pulmonary gas exchange was studied using a modified form of the multiple inert gas elimination technique. Lung volumes and forced expiratory flows were measured by common spirometry. During the non-pollen season, spirometry and forced expiratory flows were within the reference values in all but one patient, who had decreased indices for airway flow. Three other patients showed signs of minor gas exchange impairment. During the pollen season, FRC was slightly increased (P < 0.05) and MEF50 was slightly decreased (P < 0.05) for the group. Two patients had an increased index for gas exchange impairment (log SDQ was 0.64 and 0.59) and four patients had borderline log SDQ (0.50 to 0.56). However, the mean log SDQ was not increased in the pollen season. The results show that, both in the pollen season and in the pollen-free season, low degrees of gas exchange impairment could be present in pollen allergic asthmatic patients despite normal spirometry. The low degree of gas exchange impairment in some patients indicates the presence of airway inflammation with oedema and/or secretion. However, high degrees of ventilation-perfusion inequality were not observed in these patients where air flow rates were mainly normal.

Variability in airway conductance and lung volume in subjects with asthma.

Variability in airway conductance (Gaw) and lung volume (TGV) was studied in 26 subjects with moderately severe asthma during a 9-week period. Specific airway conductance (SGaw) was calculated as Gaw:TGV. There was considerable inter-individual variability in airway conductance, and a smaller variability in TGV. Airway conductance (SGaw) showed an eight-fold difference and TGV a three-fold difference between smallest and largest values. The intra-individual variability was less, with a range of +/- 55% (SGaw) and +/- 12% (TGV) of the grand mean, respectively. The error of the method contributed only marginally to the variations in airway conductance. These data for spontaneous variability of conductance facilitate, for example, the assessment of the clinical importance of changes in lung function seen after exposure to air pollutants in chamber studies. Furthermore, the substantial inter-individual variability in conductance argues against comparing samples of asthmatic subjects in polluted and non-polluted areas, and in favour of prospective studies of cohorts of subjects with asthma.

Experimental evaluation of the effect of filtration of diesel exhaust by biologic exposure indicators.

The airway resistance, compliance of the respiratory system, transfer factor, and alveolar volume of 33 healthy rabbits were studied before and after exposure to diluted diesel exhaust generated in an experimental motor. Three diesel fuels and two particle traps were tested. Subsequent to the post-exposure lung function measurements, the animals were sacrificed and the lungs were processed for morphologic examination. The concentrations of particles, nitrogen dioxide, and formaldehyde were measured. The inflammatory airway changes were most pronounced in animals exposed to exhaust from standard fuel. Small changes were identified in animals exposed to exhaust filtered through the catalytic trap as well or exposed to unfiltered exhaust from fuels intended for densely built-up areas. Increase in compliance of the respiratory system was associated with the concentration of soot particles and formaldehyde. Compliance decreased significantly in animals exposed to exhaust from standard fuel filtered through the particle traps and increased almost significantly in animals exposed to unfiltered exhaust from the same fuel.

The bronchial response, but not the pulmonary response to inhaled methacholine is dependent on the aerosol deposition pattern.

The clinical effect of inhaled radio-labeled (Technetium-99m diethylenetriamine-pentaacetic acid) methacholine was studied in two separate experiments performed in eight symptom-free asthmatics with bronchial hyperresponsiveness. Aerosols were formed by two different nebulizers, producing either mainly small aerosol particles (2-microns mass median aerodynamic diameter [MMAD]) for peripheral, or mainly large aerosol particles (9-microns MMAD) for large airway deposition. The intended site of deposition was confirmed by gamma camera recordings. Changes in specific airway conductance (sGaw) were set as an index of central airway constriction, and functional alterations in the gas exchanging parts of the lung were estimated by multiple inert gas elimination technique (MIGET) and arterial blood gas analyses. The main finding was that the responses, as measured by the changes in arterial blood gases and by MIGET, were similar in the two experiments, while the fall in sGaw was significantly larger after deposition in the main bronchi than in the peripheral airways (p < 0.05). The time courses of the abnormalities in the gas exchanging elements were much longer than those of the responses of the central airways, and the abnormalities were recorded still at the end of the experiment 2 h after challenge in most patients. A discrepancy in dose dependency and time courses suggests differences in mechanism and/or dynamics of the responses exerted by the various target organs. Interaction in the process of clearance from the lung of inhaled methacholine by the bronchial circulation may have contributed to the observed discrepancies.

Ventilation-perfusion relationships and central haemodynamics in patients with cirrhosis. Effects of a somatostatin analogue.

The ventilation-perfusion relationships of the lung (VA/Q) and central haemodynamics were studied in seven patients with cirrhosis before and 30 min after a bolus injection of a somatostatin analogue, octreotide (Sandostatin, 50 micrograms i.v.), to elucidate the role of this substance in the hepatopulmonary syndrome. In the basal state all patients had normal spirometry but reduced diffusing capacity. Three patients had various degrees of hypoxaemia (6.9-8.3 kPa) and three had clubbing of the fingers. In the basal state VA/Q distributions, determined by inert gas elimination technique, showed an intrapulmonary shunt of 7.9 +/- 2.2% of cardiac output (range 1.5 to 17.1) and perfusion of lung regions with "low VA/Q" of 4.4 +/- 2.2% of cardiac output (range 0 to 15.4). After octreotide, the amount of shunting increased (10.9 +/- 4.4% of cardiac output; non-significant), while "low VAQ" was unchanged (3.7 +/- 1.3% of cardiac output). Arterial oxygen tension decreased from 10.2 +/- 1.1 to 9.7 +/- 1.1 kPa (non-significant). The mean pulmonary arterial pressure increased from 14.5 +/- 1.9 to 16.3 +/- 1.8 mmHg (p < 0.01). No alterations were seen in heart rate, stroke volume, cardiac output, central pressures or vascular resistances. The results of the present study do not support the hypothesis that octreotide improves hypoxaemia and ventilation-perfusion relationships in patients with hepatopulmonary syndrome.

Repeated measurements of transfer factor in rabbits: an animal model suitable for evaluation of short-term exposure.

Acute temporary changes in lung function may be of use as a biological exposure indicator. However, studies of humans occupationally exposed to complex airborne irritants are often expensive and time demanding. Therefore, an animal model could be a valuable complement. A rabbit model has been evaluated where transfer factor was measured twice during the same day, and with the rabbit awake and available for exposure, in between. Anaesthesia and intubation in 22 rabbits (2.6 [0.2] kg [Mean (SD)]) were immediately followed by two measurements of transfer factor and alveolar volume. Transfer factor was estimated by the single breath CO-technique used in humans. The samples were analysed for CO and He on a gas chromatograph. After one pair of measurements the rabbit was allowed to wake up and after 5 h the duplicate measurements were repeated. The mean values of transfer factor, alveolar volume and transfer constant were 0.50 (0.09) mmol min-1 kPa-1, 127 (8) ml and 3.9 (0.6) mmol min-1 kPa-1 l-1, respectively. The intraindividual coefficients of variation were 7.3%, 5.3% and 6.7%, respectively. Five hours later when the duplicate measurements were repeated, transfer factor, alveolar volume and transfer constant were unchanged still. The results suggest that relatively small changes in transfer factor may be detected without losing power, and thus that this model could be used as a biological exposure indicator.

Pulmonary gas exchange response following allergen challenge in patients with allergic asthma.

Pulmonary gas exchange was studied in 8 patients with allergic asthma before and after allergen challenge. Ventilation-perfusion relationships were assessed by the multiple inert gas elimination technique and forced expiratory flow by conventional spirometry. Measurements were made before, 7-8 minutes, and 0.5, 2.5 and 5 hours after challenge. During baseline conditions all patients showed normal forced expiratory flow (FEV1 3.9 +/- 0.77 (SD) l) and gas exchange expressed as the dispersion of pulmonary blood flow, log SDQ (0.35 +/- 0.08), (one of the common descriptors of ventilation-perfusion (VA/Q) inequality). Immediately after challenge there were significant decreases in FEV1 (to 2.3 +/- 0.75 l) and arterial PO2 (from 13.1 +/- 0.9 to 9.5 +/- 1.2 kPa). The developed ventilation-perfusion inequalities were similar to those found in other asthma studies, i.e. mainly a broad (log SDQ increased to 0.73 +/- 0.30) and sometimes bimodal distribution of the perfusion. Thirty minutes after challenge FEV1 significantly improved to 3.2 +/- 1.18 l while log SDQ remained high (0.71 +/- 0.32). Two and a half hours after challenge log SDQ was reduced and almost normalized to 0.38 +/- 0.07. Five patients developed a late phase reaction with decreasing flow rates after 5 hours. Three of these patients also showed increased log SDQ. There was no clear relationship between gas exchange mismatch and reduced forced expiratory flow. The results support the hypothesis that reduced expiratory flow and gas exchange impairment are caused by different pathophysiological mechanisms.

Gas exchange during simulated airway secretion in the anaesthetized rabbit.

We wished to study the effect of airways secretion on gas exchange. Peripheral airway secretion was simulated in 9 rabbits by the continuous inhalation of nebulized isotonic saline, at a droplet size of about 3 microns. Intrapulmonary deposition of saline in the peripheral airways (83% in airways smaller than 0.5 mm) did not alter total inspiratory resistance (mean 5.4 kPa.l-1.s), but led to a decrease in compliance of the total respiratory system from 45.9 to 21.8 ml.kPa-1 after one hour of nebulization. Arterial oxygen tension decreased from 17.8 kPa to 12.1 and 6.9 kPa after 5 and 60 min of nebulization, respectively. PaCO2 was unaffected after 5 min (4.5 kPa) but increased to 7.0 kPa after 60 min of nebulization. Ventilation-perfusion relationships (VA/Q) showed a significant increase in perfusion of areas with low VA/Q ratios (from 0.7 to 6.3% of cardiac output) and in shunt (from 1.4 to 4.3%) after 5 min of nebulization. At the end of the experiment shunt was increased markedly to 29.7% of cardiac output whereas perfusion of low VA/Q regions remained at the same level (7.3%). The results from this animal model indicate that all gas exchange abnormalities known to occur in asthma can be reproduced without measurably increasing the resistance of the respiratory system.

Relationships among gas exchange, spirometry and symptoms in asthma.

OBJECTIVES: The severity of asthma is usually evaluated by clinical examination and spirometry. In a small study of asthmatics considerable ventilation/perfusion (VA/Q) inequality was found, however, despite essentially normal flow rates. These findings prompted the current study. METHODS: We prospectively examined symptoms, spirometry and VA/Q inequality in 26 patients with chronic, symptomatic asthma once a week for 9 consecutive weeks. VA/Q measurements were made using a less invasive approach of the multiple inert gas elimination technique and symptoms were scored. RESULTS: Correlation coefficients between indices for VA/Q inequality (log SDQ), spirometry (FEV1.0/VC, MEF25) and symptom scores were only in the range 0.24-0.29. CONCLUSION: We conclude that even at the individual level, symptoms, spirometry and VA/Q inequality are so poorly correlated that one cannot evaluate any of these aspects of asthma without measuring each. The data support the notion that spirometric and gas exchange abnormalities in asthma are caused by different pathophysiologic events.

The sleep apnoea syndrome in obesity: risk of sudden death.

A total of 34 severely obese men with a history of heavy snoring and excessive daytime sleepiness indicative of obstructive sleep apnoea syndrome (OSAS) were studied prospectively. Their mean age was 46 years, and mean body mass index was 41.6 kg m-2. During a 4-year follow-up, 15% (5/34) of these subjects died (three cases of acute myocardial infarction and two cases of pulmonary oedema), all of them suddenly and unexpectedly, outside hospital. On autopsy the degree of atherosclerosis was found to be moderate in all cases. In 68% (15/22) of the men a pathological apnoea index (mean value 46 +/- 20) confirmed the OSAS diagnosis. Exercise tests and neurological examinations did not reveal any other causes of daytime sleepiness. Mean blood pressure at rest and during exercise was normal, and mean serum lipid and blood glucose levels were normal. Spirometry revealed intrapulmonary restrictive changes that could not be attributed to the heavy thoracic wall. Compliance was reduced to about 50% of reference values, and the mean pCO2 level (5.8 kPa) was close to the upper reference limit. Blood tests suggested that high alcohol consumption may be an important factor contributing to OSAS. These results demonstrate that morbidly obese men with a history of OSAS have a high risk of sudden cardiovascular death, despite the absence of other conventional risk factors.