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Biomedical subjects

R Rodriguez-Roisin

Publications and source records attributed to R Rodriguez-Roisin.

At least 55 records · Page 3Linked to original sources
PubMed1998

Pulmonary function tests and CT scan in the management of idiopathic pulmonary fibrosis.

Relationships between pulmonary function testing and high-resolution computed tomography (HRCT) were studied in 39 untreated patients with idiopathic pulmonary fibrosis (IPF) at diagnosis, 23 of whom were followed during 7.5 +/- 0.3 mo (mean +/- SEM). At diagnosis, the extent of overall lung involvement in the HRCT scans showed a moderate but significant correlation only with FVC (r = -0.46, p = 0. 003) and DLCO (r = -0.40, p = 0.03). The extent of ground glass pattern also correlated with FVC (r = -0.58, p = 0.0001). Arterial PO2 at peak exercise (n = 13 patients) showed a significant association with the extent of both ground-glass pattern and overall lung involvement in HRCT (r = -0.60, p = 0.02; and r = -0.64, p = 0. 01, respectively). On multivariate analysis a significant independent correlation between the global disease extent in HRCT and both FVC and DLCO was observed. Changes over time in the total extent of the disease evaluated with HRCT scans were also related to those observed in DLCO and in FVC (r = -0.57, p = 0.01, and r = -0. 51, p = 0.01, respectively). The present study suggests that FVC and DLCO are the physiological variables that best reflect the global extent of disease in IPF and thus may provide significant information for the assessment of the disease's progression.

Aged↗
PubMed1998

Effect of a platelet-activating factor (PAF) antagonist, SR 27417A, on PAF-induced gas exchange abnormalities in mild asthma.

Inhaled platelet-activating factor (PAF), both in normals and in asthmatic patients, provokes transient systemic effects, neutropenia, bronchoconstriction and arterial oxygenation abnormalities similar to those shown in spontaneous exacerbations of asthma. To investigate the efficacy of a new PAF-receptor antagonist, SR 27417A, on all these changes after PAF challenge, 12 nonsmoking patients (four females and eight males) (mean+/-SEM) age 24+/-1 yrs with mild asthma (forced expiratory volume in one second (FEV1) 93+/-3% predicted) were studied in a double-blind, placebo-controlled, cross-over fashion 2 weeks apart. PAF aerosol challenge (18 microg) was carried out 3 h after oral administration of either SR 27417A (20 mg) or placebo. Respiratory system resistance (Rrs) and arterial blood gases and neutrophil cell counts were measured at baseline, before compound/placebo administration, and at 5, 15 and 45 min after PAF. Compared to vehicle, SR 27417A brought about moderate attenuation of PAF-induced neutropenia at 5 min (by 140%; p<0.025), and rebound neutrophilia at 15 and 45 min (p<0.025), increases of Rrs (by 90-65%) (p<0.01) and of alveolar-arterial pressure difference for oxygen (PA-a,O2) at 5 min (by 68%) and 15 min (by 63%), and decreases of arterial oxygen tension (Pa,O2) at 5 min (by 57%; p<0.025, each). Furthermore, systemic effects and platelet aggregation tests (p<0.001) were abolished after the administration of the compound. We conclude that SR 27417A is effective in inhibiting systemic, cellular and pulmonary effects after platelet-activating factor challenge in patients with mild bronchial asthma.

Adult↗
PubMed1998

Forced oscillation technique for the evaluation of severe sleep apnoea/hypopnoea syndrome: a pilot study.

The forced oscillation technique (FOT) is a noninvasive method of potential clinical interest for quantitatively assessing airway mechanics during sleep. We investigated the applicability of FOT as a diagnostic tool for noninvasive assessment of airflow obstruction in patients with sleep apnoea/hypopnoea syndrome (SAHS) during sleep. In seven patients previously diagnosed with severe SAHS (mean+/-SD apnoea/ hypopnoea index (AHI) 67+/-14) we performed a full polysomnography (PSG) together with on-line measurement of respiratory impedance (IZI) using FOT. For each patient we determined: 1) number of respiratory events conventionally detected by full PSG, those obtained by FOT and their degree of concordance; and 2) the characteristics and values of IZI during the respiratory events. FOT was well tolerated and easily applied in conjunction with a conventional sleep setup. The mean number of respiratory events x h(-1) detected by PSG and FOT were 55+/-16 and 58+/-17, respectively, with a strong concordance. IZI increased from a baseline of 11+/-4 to 50+/-20 cmH2O x L(-1) x s during apnoea (mean+/-SD). In all but one patient intermittent increases of IZI occurred immediately before each obstructive apnoea. In four patients, the increases of IZI developed at end-expiration whereas in two others occurred during inspiration. During hypopnoea most of the patients showed decreases of IZI during expiration. In conclusion, forced oscillation technique can be used as a noninvasive and complementary tool for the diagnosis of respiratory events and provides an on-line quantitative approach for continuous monitoring of airflow obstruction during sleep in patients with sleep apnoea/hypopnoea syndrome.

Adult↗
PubMed1998

Effect of nitric oxide synthesis inhibition with nebulized L-NAME on ventilation-perfusion distributions in bronchial asthma.

Patients with clinically stable asthma may show ventilation-perfusion (V'A/Q') mismatch. Nitric oxide (NO), a potent endogenous vasodilator, is increased in exhaled air of asthmatics. Such an increased NO production may be detrimental for optimal V'A/Q' balance owing to the potential inhibition of hypoxic pulmonary vasoconstriction. This study was undertaken to investigate the relationship between the concentration of NO in exhaled air and the degree of gas-exchange impairment and to assess the effect of nebulized N(G)-nitro-L-arginine methyl ester (L-NAME), a competitive inhibitor of NO synthesis, on gas exchange in patients with asthma. Twelve patients (four females and eight males, aged 31+/-5 yrs) with clinically stable asthma (forced expiratory volume in one second (FEV1) 80+/-5%) not treated with glucocorticoids and increased exhaled NO (58+/-9 parts per billion (ppb)) were studied. Exhaled NO, respiratory system resistance (Rrs), arterial blood gases and V'A/Q' distributions were measured before and 30, 60, 90 and 120 min after placebo or L-NAME (10(-1) M) nebulization; in eight patients pulmonary haemodynamics were also measured. At baseline no relationships between exhaled NO and gas-exchange measurements were shown. Nebulized L-NAME induced a significant decrease in exhaled NO (p< 0.001), which was maximal at 90 min (-55+/-5%). However, after L-NAME no changes in Rrs, arterial oxygen tension, the alveolar-arterial pressure difference in oxygen or V'A/Q' distributions were shown and nebulized L-NAME did not modify pulmonary artery pressure. In conclusion, the degree of gas-exchange impairment in stable asthma is not related to nitric oxide concentration in exhaled air and nitric oxide synthesis inhibition with N(G)-nitro-L-arginine methyl ester does not alter gas exchange or pulmonary haemodynamics, such that ventilation-perfusion disturbances do not appear to be related to an increased synthesis of nitric oxide in the airways.

Administration, Inhalation↗
PubMed1998

Assessment of ventilation-perfusion mismatching in mechanically ventilated patients.

The multiple inert gas elimination technique (MIGET) is a robust tool to assess both ventilation-perfusion (V'A/Q') distributions and the role of extrapulmonary factors determining arterial oxygenation during spontaneous breathing and in mechanically ventilated patients. Mixed expired gas sampling used in the MIGET is most often obtained from a 10-L mixing box (10L-MB) placed in the expiratory side of the ventilator circuit. Consequently, a considerable increase in the compression volume (Vc) would be expected which, in turn, can give rise to potential errors in the estimation of the effective tidal volume delivered to the patient. The effects of the 10L-MB on the Vc were compared with those produced by a newly designed 1-L, mixing box (IL-MB). At a given peak pressure (Ppeak) within the ventilator circuit, the Vc generated by the 10L-MB was about six-times higher than that produced by the 1L-MB. At a Ppeak =50 cmH2O, the Vc were 377 mL (10L-MB) and 67 mL (1L-MB) (p<0.001). In six patients, the mixed expired partial pressures of the six inert gases simultaneously collected from the two mixing boxes fell on the identity line. V'A/Q' distributions recovered using each of the two mixing boxes were equivalent. With the IL-MB, the effects of different positive end-expiratory pressure levels (0, 6 and 12 cmH2O) on Vc and arterial carbon dioxide tension were negligible. In conclusion, the new 1-L mixing box provides efficient gas mixing and substantially decreases the compression volume. It is, therefore, recommended when studies requiring mixed expired gas are performed in ventilated patients.

Aged↗
PubMed1998

Invasive exercise testing in the evaluation of patients at high-risk for lung resection.

The aim of this study was to investigate whether invasive exercise testing with gas exchange and pulmonary haemodynamic measurements could contribute to the preoperative assessment of patients with lung cancer at a high-risk for lung resection. Sixty-five patients scheduled for thoracotomy (aged 66+/-8 yrs (mean+/-SD), 64 males, forced expiratory volume in one second (FEV1) 54+/-13% predicted) were studied prospectively. High risk was defined on the basis of predicted postpneumonectomy (PPN) FEV1 and/or carbon monoxide diffusing capacity of the lung (DL,CO) <40% pred. Arterial blood gas measurements were performed in all patients at rest and during exercise. In 46 patients, pulmonary haemodynamic measurements were also performed at rest and during exercise. Predicted postoperative (PPO) values for FEV1 and DL,CO were calculated according to quantitative lung scanning and the amount of resected parenchyma. There were four postoperative deaths (6.2% mortality rate) and postoperative cardiorespiratory complications developed in 31 (47.7%) patients. Patients with respiratory complications only differed from patients without or with minimal (arrhythmia) complications in FEV1,PPO. Peak O2 uptake and haemodynamic variables were similar in both groups. The four patients who died had a lower FEV1,PPO, a lower DL,CO,PPO and a greater decrease in arterial oxygen tension during exercise, compared with the remaining patients. In conclusion, the forced expiratory volume in one second, together with the extent of parenchymal resection and perfusion of the affected lung, are useful parameters to identify patients at greatest risk of postoperative complications among those at a high-risk for lung resection. In these patients, pulmonary haemodynamic measurements appear to have no discriminatory value, whereas gas exchange measurements during exercise may help to identify patients with higher mortality risk.

Adult↗
PubMed1997

Hepatopulmonary syndrome: the paradigm of liver-induced hypoxaemia.

The current chapter deals with the concept, clinical manifestations and diagnostic tools of the hepatopulmonary syndrome (HPS) and highlights its most salient pathophysiological, mechanistic and therapeutic aspects. Defined as a clinical triad, including a chronic liver disorder, pulmonary gas exchange abnormalities and generalized pulmonary vascular dilatations, in the absence of intrinsic cardiopulmonary disease, this entity is currently growing in interest with both clinicians and surgeons. The combination of arterial hypoxaemia, high cardiac output with normal or low pulmonary artery pressure, and finger clubbing in a patient with advanced liver disease should strongly suggest the diagnosis of HPS. Its potential high prevalence together with failure of numerous therapeutic approaches depicts a life-threatening unique clinical condition that may dramatically benefit with an elective indication of liver transplantation (LT). A better orchestration of the concepts of the pathophysiology of this lung-liver interplay may foster our knowledge and improve the clinical management and indications of LT.

Diagnosis, Differential↗
PubMed1997

Adjustment of DLCO for hemoglobin concentration.

The equation proposed by Cotes and coworkers is currently considered as the most acceptable to correct carbon monoxide diffusing capacity (DLCO) for hemoglobin concentration [Hb] by both the American Thoracic Society (ATS) and the European Respiratory Society (ERS) guidelines for standardization of DLCO. In a previous study on 24 anemic patients undergoing bone marrow transplantation (1), we found that DLCO is underestimated using the equation of Cotes and coworkers. To further explore this finding, 28 anemic patients ([Hb] = 8.2 +/- 1.0 (SD) g/dl) with chronic renal failure were prospectively studied during the recovery period of anemia (5.4 +/- 3.5 mo). In all 28 subjects, the slope deltaDLCO/delta[Hb] computed as ratio of overall change in DLCO to overall change in [Hb] throughout the study period was 1.40 +/- 0.72 ml CO/min/mm Hg/g/dl. The individual relationship between measured DLCO and [Hb] closely fitted a simple linear regression. The resulting equations for adjustment of DLCO (DLCOadj) to a standard [Hb] of 14.6 g/dl for men and 13.4 g/dl for women are: [equations: see text]. The present adjustment function for DLCO is linear and independent of the observed DLCO values, whereas the formulas previously proposed are curvilinear, DLCO correction varying with the measured DLCO values. For a measured DLCO of 15 ml CO/min/mm Hg and [Hb] ranging from 7 to 12 g/dl, the present DLCO adjustment is higher (by 2.7 ml CO/min/mm Hg, on average) than that proposed by Cotes and coworkers. This difference appears to be relevant for a precise interpretation of DLCO in patients with normocytic anemia in different clinical conditions.

Adult↗
PubMed1997

Inhibition of PAF-induced gas exchange defects by beta-adrenergic agonists in mild asthma is not due to bronchodilation.

Salbutamol inhibits neutropenia, increased airway resistance, and gas exchange abnormalities provoked by platelet-activating factor (PAF) challenge in normal persons. To further explore the intriguing dissociation between spirometric abnormalities and gas exchange defects shown in patients with asthma, we investigated whether the salbutamol-induced improvement in gas exchange disturbances after PAF is the result of bronchodilation by comparing this effect with that of ipratropium bromide. We hypothesized that ipratropium bromide, an anticholinergic agent without vascular effects, should block PAF-induced bronchoconstriction but not interfere with its systemic, neutropenic, and gas exchange effects. We studied eight nonsmokers with mild asthma (26 +/- 2.0 SE yr of age) who, prior to PAF challenge (18 micrograms), inhaled either ipratropium bromide (80 micrograms) or salbutamol (300 micrograms) in a randomized, double-blind, crossover fashion 1 wk apart. Peripheral blood neutrophils, respiratory system resistance (Rrs), arterial blood gases and ventilation-perfusion (VA/Q) inequalities were measured 5, 15, and 45 min after PAF. Compared with pretreatment with salbutamol, ipratropium bromide also blocked the increase of respiratory system resistance (Rrs) but did not prevent facial flushing and neutropenia (p < 0.03) at 5 min nor the decrease of PaO2 (p = 0.08 and 0.05), the increase of AaPO2 (p < 0.02 each), and the deterioration of VA/Q relationships (p < 0.05 each) at 5 and 15 min, respectively. This functional pattern was similar to that observed previously in normal subjects and in nonpremedicated asthmatic patients after PAF, with return to baseline values at 45 min. By contrast, salbutamol blocked PAF-induced increased Rrs, in addition to all the other PAF-induced abnormalities. These findings indicate that, in patients with mild asthma, salbutamol inhibits PAF-induced neutropenia and gas exchange abnormalities by mechanisms involving other than airway smooth muscle narrowing, possibly by acting on both the bronchial and pulmonary circulations.

Adrenergic beta-Agonists↗
PubMed1997

Increase in pulmonary ventilation-perfusion inequality with age in healthy individuals.

Arterial oxygen tension (PaO2) is known to decrease with age, and this is accompanied by a number of changes in mechanical properties of the lungs, including loss of elastic recoil and increase in closing volume. The changes in respiratory mechanics with age could induce greater ventilation/perfusion (VA/Q) mismatch and thus explain the decrease in PaO2. In 64 normal subjects aged 18 to 71 yr (lifetime nonsmokers with normal spirometry), we measured VA/Q inequality and arterial respiratory blood gases (PaO2 and PaCO2) at rest in the seated position. VA/Q mismatch, represented by the second moments of the blood flow and ventilation distributions (log SDQ and log SDV) increased with age, but only slightly (mean log SDQ was 0.36 at age 20 yr and 0.47 at age 70 yr). PaO2 fell by a correspondingly small amount of 6 mm Hg. Previously established upper 95% confidence limits for log SDQ (0.60) and log SDV (0.65) in subjects at age 20 yr were confirmed. At age 70 yr, the upper limits of reference for log SDQ are 0.70 and for log SDV 0.75. The study shows that an increased alveolar-arterial O2 gradient with age is due to VA/Q inequality rather than to shunting.

Adult↗
PubMed1997

Nebulized glutathione induces bronchoconstriction in patients with mild asthma.

To assess the effects on bronchial responsiveness of nebulized glutathione (GSH), one of the most efficient scavengers of oxidant substances in the airways, we studied eight patients with mild asthma (FEV1, 88 +/- 11% predicted [SD]) in a randomized, double-blind, cross-over, placebo-controlled fashion. Bronchial challenge was measured using both FEV1 and total pulmonary resistance (Rrs) by the forced oscillation technique. Patients received nebulized GSH (600 mg with 4 ml of 0.9% sodium chloride) or placebo (identical saline solution) over a period of 25 min, 1 wk apart. Placebo provoked subclinical mild bronchoconstriction (changes from baseline: FEV1, -1%; Rrs, +17%); by contrast, GSH caused major airway narrowing (changes from baseline: FEV1, -19%; Rrs, +61%) and induced cough (four patients) or breathlessness (three patients). Differences between placebo and GSH after challenge were also noticeable in both FEV1 (p = 0.03) and Rrs (p = 0.02). Neither osmolarity (660 mosm.kg-1) nor pH (3.0) of the GSH solution accounted for these effects. Nebulized salbutamol (5.0 mg) given before the GSH challenge blocked GSH-induced bronchoconstriction. Furthermore, GSH-induced FEV1 falls were inversely correlated with metabisulfite bronchoprovocation (provocative dose [PD20], 1.49 +/- 1.83 mumol) but not with methacholine challenge. The detrimental effects of nebulized GSH on the airway bronchial tone in patients with mild asthma strongly suggests bronchoconstriction provoked by sulfite formation.

Adult↗
PubMed1997

Nitric oxide inhalation during exercise in chronic obstructive pulmonary disease.

Patients with chronic obstructive pulmonary disease (COPD) may develop hypoxemia and pulmonary hypertension when exercising. To investigate whether inhaled nitric oxide (NO), a selective pulmonary vasodilator, modifies the changes induced by exercise in pulmonary hemodynamics and gas exchange in COPD, we studied nine patients (FEV1, = 39 +/- 2% predicted), at rest and at submaximal exercise, during breathing of room air and NO (40 ppm). NO inhalation decreased pulmonary artery pressure (Ppa) both at rest and during exercise (analysis of variance [ANOVA] p < 0.05). However, the effect of NO on PaO2 was different at rest than during exercise. At rest, NO decreased PaO2 from 72 +/- 3 mm Hg to 65 +/- 2 mm Hg, due to an increase in ventilation-perfusion (VA/Q) inequality (dispersion of blood flow distribution from 0.9 +/- 0.1 to 1.1 +/- 0.1). During exercise, PaO2 decreased during breathing of room air (-5 +/- 3 mm Hg), whereas it remained essentially unchanged during inhalation of NO (+2 +/- 3 mm Hg), with both changes being significantly different (p < 0.05). VA/Q relationships improved during exercise during breathing of both room air and NO, as a result of a reduction in the dispersion of ventilation distribution. Moreover, NO administered on exertion contributed to redistribute blood flow from alveolar units with low VA/Q ratios to units with normal ratios (p < 0.05). We conclude that in patients with COPD, the inhalation of NO during exercise moderately reduces pulmonary hypertension, and that in contrast with the effects of such inhalation at rest, it may prevent the exercise-associated decrease of PaO2. This effect is probably explained by a preferential distribution of inhaled NO during exercise to well-ventilated alveolar units with faster time constants and normal VA/Q ratios.

Administration, Inhalation↗
PubMed1997

Ventilation-perfusion mismatch in patients with pleural effusion: effects of thoracentesis.

Pleural effusion (PE) often causes abnormal pulmonary gas exchange. Thoracentesis is commonly used to relieve dyspnea in patients with PE, but its effect upon arterial oxygenation is varied and poorly understood. This investigation sought to: (1) characterize the distribution of ventilation-perfusion (VA/Q) ratios in patients with PE and (2) assess the effects of PE drainage by thoracentesis upon pulmonary gas exchange. We studied nine patients (two females) with a mean age of 39+/-20 (SD) yr. All of them had PE of recent clinical onset (< 2 wk of symptoms), without other apparent medical conditions. Before thoracentesis, PaO2 was 82.3+/-10.2 mm Hg and AaPO2 was 28.7+/-10.0 mm Hg. Patients had broadened unimodal VA/Q distributions with small amounts of blood flow perfusing lung units with low VA/Q ratios (< 0.1) (1.4+/-2.2%) and mild intrapulmonary shunt (6.9+/-6.7%). PaO2 was significantly related to the amount of shunt (rho = -0.82; p < 0.01) but not to the percentage of blood flow perfusing low VA/Q units. While thoracentesis drained 693+/-424 ml of fluid and caused a significant fall in mean pleural pressure (by -10.7 +/- 7.1 mm Hg; p < 0.01), PaO2, AaPO2, and shunt remained unchanged; only the amount of blood flow perfusing low VA/Q ratios increased slightly (2.4+/-2.6%; p < 0.05). This study shows that: (1) intrapulmonary shunt is the main mechanism underlying arterial hypoxemia in patients with PE and (2) effective thoracentesis has minor short-term effects upon pulmonary gas exchange. These findings are in accord with delayed (> 30 min) pulmonary volume re-expansion after thoracentesis with or without the coexistence of mild ex vacuo pulmonary edema.

Adolescent↗
PubMed1997

Effects of noninvasive ventilation on pulmonary gas exchange and hemodynamics during acute hypercapnic exacerbations of chronic obstructive pulmonary disease.

Noninvasive positive pressure ventilation (NIPPV) can replace tracheal intubation in acute exacerbations of chronic obstructive pulmonary disease (COPD) with severe hypercapnic respiratory failure. However, the underlying mechanisms by which NIPPV improves pulmonary gas exchange are not known. We studied 10 male COPD patients (68 +/- 8 [SD] yr) with acute severe hypercapnic respiratory failure within 36 h after hospital admission. Measurements of pulmonary gas exchange, hemodynamics, and respiratory mechanics were done: (I) breathing spontaneously (baseline); (2) after 15 and 30 min of NIPPV with pressure support (inspiratory pressure = 12 +/- 2 cm H20, PEEP = 3 +/- 2 cm H20); and (3) 15 min after NIPPV withdrawal. Patients were ventilated using a full face mask, keeping FIO2 constant (0.23 +/- 0.02) in all conditions. Compared with baseline, during NIPPV (15 min) we observed a moderate increase in Pa02 (from 50 +/- 6 to 57 +/- 9 mm Hg; p < 0.05), and a fall in PaCO2 (from 66 +/- 10 to 59 +/- 10 mm Hg; p < 0.0001), but AaPO2 increased (from 39 +/- 13 to 48 +/- 13 mm Hg; p < 0.001). Breathing frequency decreased (from 26 +/- 5 to 19 +/- 3 breaths/min; p < 0.0001), tidal volume increased (from 311 +/- 42 to 520 +/- 133 ml; p < 0.0001), and minute ventilation increased (from 8.0 to 1.7 to 9.6 +/- 2.0 L/min; p < 0.05). Cardiac output fell during NIPPV in all patients (from 6.7 +/- 1.6 to 5.8 +/- 1.3 L/min; p < 0.0025) with no impact on mixed venous PO2. No substantial changes in VA/Q mismatching (multiple inert gas elimination technique) were observed. While oxygen uptake showed a trend to decrease, the respiratory exchange ratio (R) increased (from 0.78 +/- 0.17 to 0.90 +/- 0.22; p < 0.001). The effects of NIPPV were unchanged at 30 min compared with 15 min and were reversed after 15 min of NIPPV withdrawal. We conclude that improvement in respiratory blood gases during NIPPV is essentially due to higher alveolar ventilation (p < 0.001) and not to improvement in VA/Q relationships. The increase in AaPO2 was explained by the rise in R due to an increased clearance of body stores of C02 during NIPPV. Our results indicate that attainment of an efficient breathing pattern rather than high inspiratory pressures should be the primary goal to improve arterial blood gases during NlPPV in this type of patient.

Acute Disease↗
PubMed1997

Mechanisms of worsening gas exchange during acute exacerbations of chronic obstructive pulmonary disease.

This study was undertaken to investigate the mechanisms that determine abnormal gas exchange during acute exacerbations of chronic obstructive pulmonary disease (COPD). Thirteen COPD patients, hospitalized because of an exacerbation, were studied after admission and 38+/-10 (+/-SD) days after discharge, once they were clinically stable. Measurements included forced spirometry, arterial blood gas values, minute ventilation (V'E), cardiac output (Q'), oxygen consumption (V'O2), and ventilation/perfusion (V'A/Q') relationships, assessed by the inert gas technique. Exacerbations were characterized by very severe airflow obstruction (forced expiratory volume in one second (FEV1) 0.74+/-0.17 vs 0.91+/-0.19 L, during exacerbation and stable conditions, respectively; p=0.01), severe hypoxaemia (ratio between arterial oxygen tension and inspired oxygen fraction (Pa,O2/FI,O2) 32.7+/-7.7 vs 37.6+/-6.9 kPa (245+/-58 vs 282+/-52 mmHg); p=0.01) and hypercapnia (arterial carbon dioxide tension (Pa,CO2) 6.8+/-1.6 vs 5.9+/-0.8 kPa (51+/-12 vs 44+/-6 mmHg); p=0.04). V'A/Q' inequality increased during exacerbation (log SD Q', 1.10+/-0.29 vs 0.96+/-0.27; normal < or = 0.6; p=0.04) as a result of greater perfusion in poorly-ventilated alveoli. Shunt was almost negligible on both measurements. V'E remained essentially unchanged during exacerbation (10.5+/-2.2 vs 9.2+/-1.8 L x min(-1); p=0.1), whereas both Q' (6.1+/-2.4 vs 5.1+/-1.7 L x min(-1); p=0.05) and V'O2 (300+/-49 vs 248+/-59 mL x min(-1); p=0.03) increased significantly. Worsening of hypoxaemia was explained mainly by the increase both in V'A/Q' inequality and V'O2, whereas the increase in Q' partially counterbalanced the effect of greater V'O2 on mixed venous oxygen tension (PV,O2). We conclude that worsening of gas exchange during exacerbations of chronic obstructive pulmonary disease is primarily produced by increased ventilation/perfusion inequality, and that this effect is amplified by the decrease of mixed venous oxygen tension that results from greater oxygen consumption, presumably because of increased work of the respiratory muscles.

Acute Disease↗
PubMed1997

Acute severe asthma: pathophysiology and pathobiology of gas exchange abnormalities.

Acute severe asthma, or "status asthmaticus", is a devastating clinical condition ultimately resulting in life-threatening hypoxaemia. The pivotal intrapulmonary mechanism of this condition is profound ventilation/perfusion (V'A/Q') mismatch, characterized by a predominant bimodal blood flow pattern reflecting a marked deterioration (increase) of the dispersion of pulmonary blood flow. This V'A/Q' profile is consistent with the presence of numerous alveolar units with low V'A/Q' ratios, in which ventilation is markedly reduced, although never abolished, but perfusion is maintained. Further V'A/Q' worsening whilst breathing 100% O2 suggests the presence of an underlying vigorous hypoxic vascular response. Of equal importance, gas exchange disturbances are poorly related to the severity of reduced maximal airflow rates. Inhaled platelet-activating factor (PAF), both in normal individuals and asthmatic patients, results in moderate-to-severe disturbance of V'A/Q' status, a finding that is probably related to altered microvascular permeability within the airway wall. Salbutamol, but not ipratropium bromide, prevented all PAF-induced systemic and lung function abnormalities, possibly because venoconstriction in the bronchial circulation was antagonized. Taken together, these findings support the hypothesis that platelet-activating factor may play a critical role in the pathobiology of severe acute exacerbations of asthma.

Acute Disease↗
PubMed1997

Effect of acetylsalicylic acid on pulmonary gas exchange in patients with severe pneumonia: a pilot study.

BACKGROUND: It has been hypothesized that local release of prostacyclin in acute pneumonia may ablate hypoxic pulmonary vasoconstriction, thus contributing to the impairment of pulmonary gas exchange in these patients. Inhibition of cyclooxygenase pathway could prevent this phenomenon by reducing the release of these metabolites. METHODS: A study was designed to assess the effect of I.V. acetylsalicylic acid (ASA) (2 g) on pulmonary gas exchange in seven patients (age, 64+/-11 [mean+/-SD] years) with unilateral severe pneumonia (PaO2/fraction of inspired oxygen, 168+/-67) needing mechanical ventilation. Respiratory gases, pulmonary and systemic hemodynamics, and ventilation-perfusion (VA/Q) distributions were studied before and 15 and 60 min after the infusion of ASA. RESULTS: At baseline, the amount of shunt (VA/Q ratios <0.005) was 28+/-17% of cardiac output, blood flow to areas with low VA/Q ratios (<0.1, excluding shunt) was 8+/-7%, and the dispersion of pulmonary blood flow distribution (second moment, log SD Q) was 1.45+/-0.49 (normal range, 0.3 to 0.6). Sixty minutes after the infusion of ASA, we observed a mild reduction of the amount of shunt, from 28+/-17% to 23.5+/-13% (p<0.05) without changes in arterial oxygenation. This was associated with a significant increase in mean pulmonary artery pressure (from 21.9+/-3.6 to 24.4+/-5.1 and 23.9+/-5.3 mm Hg, p<0.025 and p=0.1) and pulmonary vascular resistance (from 1.4+/-0.9 to 1.8+/-0.8 and 1.8+/-1.3 mm Hg x min x L(-1) , p<0.002 and p=0.11) 15 and 60 min after ASA, respectively. The ASA plasma levels were within the normal therapeutic range (120+/-7 microg/mL, 15 min, and 113+/-11 microg/mL, 60 min after ASA infusion). CONCLUSIONS: Although there was a modest improvement in intrapulmonary shunt, our results suggest that perfusion of ASA in this small sample of patients with severe pneumonia appears to be of little benefit as complementary treatment for severe hypoxemia.

Adult↗