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Biomedical subjects

J A Barberà

Publications and source records attributed to J A Barberà.

At least 19 recordsLinked to original sources
PubMed2006

Mitochondrial dysfunction in COPD patients with low body mass index.

Patients with chronic obstructive pulmonary disease (COPD) show abnormal adaptations of skeletal muscle redox status after exercise training. Increased skeletal muscle oxidative stress in COPD patients may prompt mitochondrial dysfunction. The present study explores the association between body composition and mitochondrial respiration in seven COPD patients with low body mass index (BMI(L)), eight COPD patients with normal body mass index (BMI(N)) and seven healthy controls. All of them underwent a vastus lateralis biopsy in which muscle structure, in vitro mitochondrial respiratory function, uncoupling protein 3 (UCP3) mRNA expression and glutathione levels in both isolated mitochondria and the whole muscle were determined. Mitochondrial respiratory function (assessed by acceptor control ratio (ACR)) was impaired in BMI(L) (2.2+/-0.6) compared with both BMI(N) (5.3+/-1.3) and controls (8.2+/-1.3). ACR significantly correlated with arterial oxygen tension and with muscle endurance but it showed a negative association with exercise-induced increase in blood lactate levels. UCP3 mRNA expression was reduced in BMI(L) patients. In conclusion, chronic obstructive pulmonary disease patients with low body mass index show electron transport chain dysfunction, which may contribute to low muscle endurance in the current subgroup of patients.

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PubMed2006

[Pulmonary varix inside a bulla].

Pulmonary varices are uncommon vascular abnormalities that are usually asymptomatic and so they are normally diagnosed by chance from a chest x-ray. They often present as a pulmonary nodule and can be either congenital or acquired. If acquired, they are associated with pulmonary venous hypertension, usually as a result of mitral valve disease. Pulmonary arteriography provides a definitive diagnosis, although the use of new noninvasive imaging techniques is spreading. Treatment is not normally required unless serious complications arise. We present the case of a pulmonary varix located within a pulmonary bulla. This form of presentation has not been previously reported.

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PubMed2005

Leukotriene D4-induced hypoxaemia in asthma is mediated by the cys-leukotriene1 receptor.

Bronchoprovocation with cysteinyl-leukotrienes (LTs) induces airflow obstruction and gas exchange abnormalities, namely ventilation-perfusion ratio (V'(A)/Q') imbalance. However, it is unknown which of the two different receptors for cysteinyl-LTs mediate these V'(A)/Q' disturbances. In a double-blinded, crossover design, 10 patients with mild asthma were randomised to receive an oral single dose of the selective cysteinyl-LT1 receptor antagonist montelukast (40 mg) or placebo before leukotriene (LT)D4 inhalation challenge. Gas exchange, including V'(A)/Q' descriptors were measured at baseline, 3 h after montelukast/placebo pretreatment and 5, 15 and 45 min after the LTD4 challenge. Compared with montelukast, inhalation of LTD(4) induced a marked fall in forced expiratory volume in one second (mean+/-se 33+/-2%) and profound V'(A)/Q' mismatching, reflected by a decreased arterial oxygen tension (from 100+/-4 to 75+/-3 mmHg) and an increased overall index of V'(A)/Q' heterogeneity dispersion of retention minus excretion inert gases corrected for dead space (from 4.9+/-1.2 to 8.4+/-1.1; normal< or =3.0; dimensionless), 5 min after placebo. Following montelukast, LTD4 produced no significant changes in any of the variables. In conclusion, these findings point to the view that leukotriene D4)-induced gas exchange disturbances and bronchoconstriction are both mediated by the cysteinyl-leukotriene1 receptor.

Acetates↗
PubMed2004

Formoterol protects against platelet-activating factor-induced effects in asthma.

Platelet-activating factor (PAF) is an inflammatory mediator that provokes neutropaenia, bronchoconstriction and gas exchange defects due to exudation of bulk plasma within the airways. While the inhibitory effects of short-acting beta2-agonists on PAF-induced disturbances have been consistently shown, those of long-acting beta2-agonists are less convincing. To further explore the mechanisms involved in PAF challenge in asthma, 12 patients (forced expiratory volume in one second, 90 +/- 4% predicted) were investigated 2 h after inhaled formoterol (18 microg), in a double-blind, placebo-controlled, crossover design following PAF (18 microg) inhalation. Compared with the placebo, at 5 min, premedication with formoterol reduced PAF-induced cough and dyspnoea, and attenuated increased respiratory system resistance (by 67%) and arterial deoxygenation (by 50%). Likewise, ventilation-perfusion (V'A/Q') inequality improved, as reflected by the dispersion of pulmonary blood flow (by 63%) and an overall index of V'A/Q' heterogeneity (by 71%). In contrast, PAF-induced facial flushing, neutropaenia and subsequent rebound neutrophilia remained unchanged. The improvement in gas exchange abnormalities shown after platelet-activating factor in patients with asthma pretreated with formoterol at the recommended clinical dose may reflect, in addition to its class effects, an anti-exudative effect of formoterol in the airways.

Administration, Inhalation↗
PubMed2003

Increased tumour necrosis factor-alpha plasma levels during moderate-intensity exercise in COPD patients.

Post-training downregulation of muscle tumour necrosis factor (TNF)-alpha messenger ribonucleic acid (mRNA) expression and decrease in cellular TNF-alpha levels have been reported in the elderly. It is hypothesised that chronic obstructive pulmonary disease (COPD) patients may not show these adaptations due to their reduced ability to increase muscle antioxidant capacity with training. Eleven COPD patients (forced expiratory volume in one second 40 +/- 4.4% of the predicted value) and six age-matched controls were studied. Pre- and post-training levels of TNF-alpha, soluble TNF receptors (sTNFRs: sTNFR55 and sTNFR75) and interleukin (IL)-6 in plasma at rest and during exercise and vastus lateralis TNF-alpha mRNA were examined. Moderate-intensity constant-work-rate exercise (11 min at 40% of pretraining peak work-rate) increased pretraining plasma TNF-alpha levels in COPD patients (from 17 +/- 3.2 to 23 +/- 2.7 pg x mL(-1); p<0.005) but not in controls (from 19 +/- 4.6 to 19 +/- 3.2 pg x mL(-1)). No changes were observed in sTNFRs or IL-6 levels. After 8 weeks' endurance training, moderate-intensity exercise increased plasma TNF-alpha levels similarly to pretraining (from 16 +/- 3 to 21 +/- 4 pg x mL(-1); p<0.01). Pretraining muscle TNF-alpha mRNA expression was significantly higher in COPD patients than in controls (29.3 +/- 13.9 versus 5.0 +/- 1.5 TNF-alpha/18S ribonucleic acid, respectively), but no changes were observed after exercise or training. It is concluded that moderate-intensity exercise abnormally increases plasma tumour necrosis factor-alpha levels in chronic obstructive pulmonary disease patients without exercise-induced upregulation of the tumour necrosis factor-alpha gene in skeletal muscle.

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PubMed2003

Pulmonary hypertension in chronic obstructive pulmonary disease.

Pulmonary hypertension is a common complication of chronic obstructive pulmonary disease (COPD). Its presence is associated with shorter survival and worse clinical evolution. In COPD, pulmonary hypertension tends to be of moderate severity and progresses slowly. However, transitory increases of pulmonary artery pressure may occur during exacerbations, exercise and sleep. Right ventricular function is only mildly impaired with preservation of the cardiac output. Structural and functional changes of pulmonary circulation are apparent at the initial stages of COPD. Recent investigations have shown endothelial dysfunction and changes in the expression of endothelium-derived mediators that regulate vascular tone and cell growth in the pulmonary arteries of patients with mild disease. Some of these changes are also present in smokers with normal lung function. Accordingly, it has been postulated that the initial event in the natural history of pulmonary hypertension in COPD could be the lesion of pulmonary endothelium by cigarette-smoke products. Long-term oxygen administration is the only treatment that slows down the progression of pulmonary hypertension in chronic obstructive pulmonary disease. Nevertheless, with this treatment pulmonary artery pressure rarely returns to normal values and the structural abnormalities of pulmonary vessels remain unaltered. Vasodilators are not recommended on the basis of their minimal clinical efficacy and because they impair pulmonary gas exchange. Recognition of the role of endothelial dysfunction in the physiopathology of pulmonary hypertension in chronic obstructive pulmonary disease opens new perspectives for the treatment of this complication.

Humans↗
PubMed2002

Characterization of pulmonary vascular remodelling in smokers and patients with mild COPD.

Intimal enlargement of pulmonary arteries is an early change in chronic obstructive pulmonary disease (COPD). The cellular and extracellular components that are involved in this enlargement are unknown. The present study was designed to characterize the structural changes occurring in pulmonary muscular arteries in the initial disease stages. Lung specimens from patients with moderate COPD (n=8; forced expiratory volume in one second (FEV1), 66 +/- 10% predicted) and smokers without airflow obstruction (n=7; FEV1, 86 +/- 6% pred), were investigated by histochemistry to characterize extracellular matrix proteins and by immunohistochemistry to identify intrinsic cells of the vascular wall. In both COPD patients and smokers, the majority of cells present in the enlarged intimas were stained by specific smooth muscle cell (SMC) markers. No staining with endothelial or fibroblast markers was shown. A proportion of SMCs did not stain with desmin, suggesting cellular heterogeneity in this population. Elastin was the most abundant extracellular matrix protein and collagen was seen in a lower proportion. The amount of collagen was related to the intimal thickness (p<0.001). The findings demonstrated smooth muscle cell proliferation, as well as elastin and collagen deposition, in the thickened intimas of pulmonary arteries in moderate chronic obstructive pulmonary disease patients and smokers, suggesting that these abnormalities may originate at an early stage in cigarette smoke-induced respiratory disease.

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PubMed2002

Fluticasone propionate attenuates platelet-activating factor-induced gas exchange defects in mild asthma.

Inhaled glucocorticosteroids may reduce airway mucosal oedema in acute asthma. Inhaled platelet-activating factor (PAF) provokes pulmonary gas exchange disturbances, similar to those shown in severe asthma, which may be due to increased airway plasma leakage. This randomized, double-blind, placebo-controlled, crossover study investigated the effects of high doses of inhaled fluticasone propionate (FP) in 12 patients with mild asthma before and after PAF inhalation. Patients were studied before and 12 h after inhaling FP (6 mg) or placebo (P), and then at 5, 15 and 45 min after PAF challenge. Compared with vehicle, FP inhaled before PAF improved forced expiratory volume in one second and respiratory system resistance (Rrs), increased peripheral blood neutrophils and reduced eosinophil counts. After PAF, FP enhanced transient neutropenia at 5 min and facilitated the recovery of oxygen tension in arterial blood (FP: 93+/-4 mmHg; P: 83+/-4 mmHg) at 45 min, without influencing the increases in Rrs. In conclusion, the improvement of platelet-activated factor-induced oxygen tension in arterial blood disturbances after fluticasone proprionate suggests that inhaled glucocorticosteroids may possess vasoconstrictor properties in the pulmonary circulation.

Administration, Inhalation↗
PubMed2002

Response to hypoxia of pulmonary arteries in chronic obstructive pulmonary disease: an in vitro study.

Patients with chronic obstructive pulmonary disease (COPD) show impaired hypoxic pulmonary vasoconstriction that might contribute to abnormal gas exchange and could be related to endothelial dysfunction in pulmonary arteries. The aim of the study was to investigate the response of PA to hypoxic stimulus in vitro in COPD, and the role of endothelium-derived nitric oxide (NO) in this response. The pulmonary arteries of 25 patients who underwent lung resection were studied. Patients were divided into controls, COPD+normoxaemia (COPDN) and COPD+ hypoxaemia (COPDH). Hypoxic vasoconstriction (HV) was evaluated before and after stimulation or inhibition of the endothelial release of NO, and in the presence of exogenous NO. Compared with the other groups, HV was reduced in COPDH. The magnitude of HV correlated with the oxygen tension in arterial blood. The hypoxic stimulus induced greater contraction after stimulating endothelial release of NO, whereas its inhibition practically abolished HV. Exogenous NO completely inhibited HV. Maximal relaxation induced by endothelium-dependent vasodilators correlated with the magnitude of HV. In conclusion, pulmonary arteries of patients with chronic obstructive pulmonary disease and hypoxaemia have an impaired response to hypoxic stimulus, and the endothelial release of nitric oxide modulates hypoxic vasoconstriction. The depressed response of pulmonary arteries to hypoxia may contribute to abnormal gas exchange in chronic obstructive pulmonary disease.

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PubMed2002

Physiological responses to the 6-min walk test in patients with chronic obstructive pulmonary disease.

The 6-min walking test (6MWT) is frequently used to assess functional capacity in chronic cardiopulmonary disorders because of its simplicity. The study examines the physiological responses during encouraged 6MWT in patients with chronic obstructive pulmonary disease. Pulmonary oxygen (O2) uptake (V'O2) was measured in 20 male patients (age 66+/-6 yrs, forced expiratory volume in one second 45+/-14% predicted) during 6MWT and incremental cycling, in random order. O2 tension in arterial blood, carbon dioxide tension in arterial blood and arterial lactate concentration ([La]art) were obtained in the last 10 patients. During the 6MWT, V'O2 showed a plateau after the 3rd min (1.39+/-0.28, 1.42+/-0.31, and 1.40+/-0.30 L x min(-1), 4th, 5th and 6th min, respectively), and minute ventilation (V'E) (42+/-8 L x min(-1)) was 91% maximal voluntary ventilation. No differences were shown between 6MWT (6th min) and peak cycling exercise in V'O2 (1.40+/-0.30 versus 1.41+/-0.28 L x min(-1), respectively), cardiac frequency (126+/-13 versus 130+/-12 beats x min(-1)), or arterial respiratory blood gases. The two tests were significantly different in V'E (42+/-8 versus 47+/-8 L x min(-1), 6MWT versus cycling, respectively), carbon dioxide production (1.30+/-0.31 versus 1.45+/-0.18 L x min(-1)) and [La]art (2.9+/-1.99 versus 5.9+/-1.51 M). The study demonstrates that an encouraged 6-min walking test generates a high but sustainable oxygen uptake. Since the oxygen uptake plateau reflects the integrated response of the system, it may explain the high prognostic value of the 6-min walking test.

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PubMed2001

Pulmonary hypertension associated with COPD.

Pulmonary hypertension is a common complication of chronic obstructive pulmonary disease (COPD). The increase in pulmonary artery pressures is often mild to moderate, but some patients may suffer from severe pulmonary hypertension, and present with a progressively downhill clinical course because of right-sided heart failure added to ventilatory handicap. The cause of pulmonary hypertension in COPD is generally assumed to be hypoxic pulmonary vasoconstriction leading to permanent medial hypertrophy. However, recent pathological studies point, rather, to extensive remodeling of the pulmonary arterial walls, with prominent intimal changes. These aspects account for minimal reversibility with supplemental oxygen. There may be a case for pharmacological treatment of pulmonary hypertension in selected patients with advanced COPD and right-sided heart failure. Candidate drugs include prostacyclin derivatives, endothelin antagonists and inhaled nitric oxide, all of which have been reported of clinical benefit in primary pulmonary hypertension. However, it will be a challenge for randomized controlled trials to overcome the difficulties of the diagnosis of right ventricular failure and the definition of a relevant primary endpoint in pulmonary hypertensive COPD patients.

Humans↗
PubMed2001

Mechanisms of pulmonary gas exchange improvement during a protective ventilatory strategy in acute respiratory distress syndrome.

To investigate the mechanisms underlying improvement of arterial oxygenation during a protective ventilatory strategy (PVS) in early acute respiratory distress syndrome (ARDS), we studied eight patients during volume-controlled mechanical ventilation, keeping respiratory rate and fraction of inspired oxygen (FI(O(2))) (0.82 +/- 0.20) unchanged: (1) at baseline (tidal volume [VT] 10 to 12 ml x kg(-1); positive end-expiratory pressure [PEEP] 8 to 10 cm H(2)O); (2) during PVS (PEEP 2 cm H(2)O above the low inflexion point (P(FLEX)) and VT of 5 to 7 ml x kg(-1)); and (3) post-PVS, back to baseline conditions. Inert gas measurements were done after 30 min in each ventilatory modality. During PVS, Pa(O(2)) increased significantly from 93 +/- 27 to 166 +/- 77 mm Hg (p < 0.008) and Pa(CO(2)) rose from 39 +/- 7 to 57 +/- 11 mm Hg (p < 0.0002) because of the decrease in minute ventilation (V E) (-3.6 L x min(-1)) (p < 0.005). Both heart rate (HR, +13 min(-1)) (p < 0.002) and cardiac output (Q, +1.2 L x min(-1)) (p < 0.05) increased. Static respiratory system linear compliance increased from 36 +/- 14 to 44 +/- 16 ml. cm H(2)O(-1) (p < 0.0002). PVS provoked recruitment of previously collapsed alveoli and redistribution of pulmonary blood flow from nonventilated alveoli to normal lung. Despite the increase in Q, intrapulmonary shunt fell from 39 +/- 15% to 31 +/- 11% (p < 0.04). We conclude that the decrease in intrapulmonary shunt owing to alveolar recruitment remains the pivotal mechanism to explain improvement of arterial oxygenation during this PVS.

Adult↗
PubMed2001

Reduced muscle redox capacity after endurance training in patients with chronic obstructive pulmonary disease.

The present study was undertaken to test whether endurance training in patients with COPD, along with enhancement of muscle bioenergetics, decreases muscle redox capacity as a result of recurrent episodes of cell hypoxia induced by high intensity exercise sessions. Seventeen patients with COPD (FEV(1), 38 +/- 4% pred; PaO2), 69 +/- 2.7 mm Hg; PaCO2, 42 +/- 1.7 mm Hg) and five age-matched control subjects (C) were studied pretraining and post-training. Reduced (GSH) and oxidized (GSSG) glutathione, lipid peroxidation, and gamma-glutamyl cysteine synthase heavy subunit chain mRNA expression (gammaGCS-HS mRNA) were measured in the vastus lateralis. Pretraining redox status at rest and after moderate (40% Wpeak) constant-work rate exercise were similar between groups. After training (DeltaWpeak, 27 +/- 7% and 37 +/- 18%, COPD and C, respectively) (p < 0.05 each), GSSG levels increased only in patients with COPD (from 0.7 +/- 0.08 to 1.0 +/- 0.15 nmol/ mg protein, p < 0.05) with maintenance of GSH levels, whereas GSH markedly increased in C (from 4.6 +/- 1.03 to 8.7 +/- 0.41 nmol/ mg protein, p < 0.01). Post-training gammaGCS-HS mRNA levels increased after submaximal exercise in patients with COPD. No evidence of lipid peroxidation was observed. We conclude that although endurance training increased muscle redox potential in healthy subjects, patients with COPD showed a reduced ability to adapt to endurance training reflected in lower capacity to synthesize GSH.

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PubMed2001

Reduced expression of endothelial nitric oxide synthase in pulmonary arteries of smokers.

Cigarette smoking has been associated with alterations in the structure and endothelial function of pulmonary arteries. Nitric oxide (NO) and endothelin-1 are endothelium-derived mediators with opposite effects on vascular tone and cell growth. To investigate whether cigarette smoking could induce changes in the synthesis of these mediators in pulmonary arteries, we compared the expression of both endothelial NO synthase (eNOS) and endothelin-1 in the lungs of smokers with that in nonsmokers. Lung tissue samples of 23 smokers and nine nonsmokers were studied. Expression of eNOS and endothelin-1 in pulmonary artery endothelium was evaluated by immunohistochemistry. In protein extracts of lung tissue, the content of eNOS protein was assessed by Western blot analysis and that of endothelin-1 by radioimmunoassay. The immunohistochemical expression of eNOS in arterial endothelium and the eNOS protein content in lung tissue were lower in the smokers than in the nonsmokers. No differences were shown in cell expression and protein content of endothelin-1 between both groups. We conclude that cigarette smoking is associated with reduced expression of eNOS in pulmonary arteries. The diminished synthesis of nitric oxide may contribute to the alterations in the structure and endothelial function of pulmonary vessels in cigarette-smoke-induced respiratory disease.

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PubMed2001

Pulmonary gas exchange and sputum cellular responses to inhaled leukotriene D(4) in asthma.

Inhalational challenges with inflammatory mediators may provoke lung function disturbances similar to those shown in spontaneous acute asthma. Cysteinyl leukotrienes (CysLTs) have recently been established as mediators of bronchoconstriction in asthma but their effects on pulmonary gas exchange in asthma have not been assessed. We therefore investigated the effects of leukotriene D(4) (LTD(4)) challenge resulting in a significant decrease in FEV(1) (mean +/- SE, by 32 +/- 3%) in 13 nonsmoking, mild asthmatics. Respiratory system resistance (Rrs), and respiratory and inert gases were measured before and immediately after, and at 15 and 45 min after challenge. After bronchoprovocation, Rrs increased (by 106 +/- 12%), Pa(O(2)) decreased (by 25 +/- 4 mm Hg), and ventilation-perfusion distributions moderately to severely deteriorated, as shown by increases in the dispersions of pulmonary blood flow (Log SDQ, by 59 +/- 12%) and alveolar ventilation (Log SDV, by 65 +/- 20%) (p < 0.05 each). Sputum eosinophils (p < 0.05) and urinary LTE(4) (p < 0.005) increased after challenge. Despite the lack of mathematical correlations between spirometric and Rrs changes and gas exchange indices, the pattern of improvement of the functional variables after challenge ran in parallel. These findings support the evidence that CysLTs, in addition to being potent bronchoconstrictors, also provoke profound disturbances of pulmonary gas exchange in asthma.

Administration, Inhalation↗
PubMed2001

Hepatopulmonary syndrome in candidates for liver transplantation.

BACKGROUND: Hepatopulmonary syndrome (HPS) has been defined as a clinical triad, including chronic liver disease, gas exchange defects (increased alveolar-arterial PO2 difference irrespective of the presence of arterial hypoxemia), and widespread intrapulmonary vascular dilatations. We determined the incidence and the clinical and pulmonary functional characteristics of HPS in candidates for orthotopic liver transplantation (OLT) and tested their predicted accuracy. METHODS: We studied 80 patients with cirrhosis prospectively, and carried out contrast-enhanced (CE) echocardiography and lung function tests, including ventilation-perfusion (V(A)/Q) distributions. RESULTS: Fourteen patients had HPS (incidence, 17.5%). Patients with HPS (49 +/- 12 (+/-SD) years) had more cutaneous spiders, finger clubbing and dyspnea (P < 0.05 each) and a lower diffusing capacity (DLCO, 56 +/- 18% predicted; P < 0.001) than non-HPS patients (n = 66). Mild to moderate V(A)/Q inequalities and increased intrapulmonary shunt were predominant in HPS patients, but oxygen diffusion impairment was observed in those with hypoxemia (n = 8) only. The DLCO showed a considerable area under the receiver operating characteristic curve (0.89). CONCLUSIONS: HPS in cirrhotic patient candidates for OLT shows a high incidence and these patients present with distinctive clinical and functional features compared with non-HPS individuals. The presence of a low DLCO may be of help for the diagnosis of HPS.

Adult↗