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Biomedical subjects

A G Agustí

Publications and source records attributed to A G Agustí.

At least 19 recordsLinked to original sources
PubMed2001

Treatment with continuous positive airway pressure is not effective in patients with sleep apnea but no daytime sleepiness. a randomized, controlled trial.

BACKGROUND: The sleep apnea-hypopnea syndrome is defined by a pathologic number of respiratory events during sleep (the apnea-hypopnea index, defined as the number of apnea and hypopnea episodes per hour) and daytime symptoms (mostly, excessive sleepiness). In patients with the sleep apnea syndrome, treatment with continuous positive airway pressure (CPAP) normalizes both the apnea-hypopnea index and diurnal symptoms. However, the effect of CPAP in persons with a pathologic apnea-hypopnea index without daytime sleepiness is unclear. OBJECTIVE: To investigate the short-term effects of CPAP on quality of life, objective sleepiness, cognitive function, and arterial blood pressure in nonsleepy patients with a pathologic apnea-hypopnea index. DESIGN: Multicenter randomized, placebo-controlled, parallel-group study. SETTING: Six teaching hospitals in Spain. PATIENTS: 55 patients with an apnea-hypopnea index of 30 or greater who did not have daytime sleepiness (Epworth Sleepiness Scale score </= 10). INTERVENTION: Patients were randomly assigned to receive optimal (n = 29) or sham (n = 25) CPAP and were observed for 6 weeks. MEASUREMENTS: Quality of life, objective sleepiness (Multiple Sleep Latency Test score), cognitive function, and arterial blood pressure. RESULTS: The intervention and control groups were similar in terms of mean (+/-SE) age (54 +/- 2 vs. 52 +/- 2 years), apnea-hypopnea index (54 +/- 3 vs. 57 +/- 4), Epworth Sleepiness Scale score (7.0 +/- 0.4 vs. 7.0 +/- 0.4) and adherence to CPAP treatment (5.0 +/- 0.4 vs. 4.0 +/- 0.5 hours/d). Other variables, such as quality of life, cognitive function, and arterial blood pressure, were also similar in both groups before treatment. After 6 weeks of CPAP or sham CPAP, none of these variables changed significantly. CONCLUSION: In patients with an apnea-hypopnea index of 30 or greater and no subjective daytime sleepiness, CPAP does not modify quality of life, objective sleepiness, vigilance, attention, memory, information processing, visuomotor coordination, or arterial blood pressure. Treatment with CPAP is therefore not indicated in nonsleepy patients with a pathologic apnea-hypopnea index.

Blood Pressure↗
PubMed2001

Enhanced neutrophil response in chronic obstructive pulmonary disease.

BACKGROUND: Neutrophils are likely to play a major role in the inflammatory response seen in chronic obstructive pulmonary disease (COPD). This study sought to address the hypothesis that an enhanced neutrophil response to proinflammatory agents in COPD may contribute to their recruitment and activation in the lungs. METHODS: Circulating neutrophils were obtained from 10 patients with COPD, eight long term smokers with normal lung function, and eight healthy never smoking controls. The in vitro production of reactive oxygen species (ROS) was measured by the NADPH oxidase method (respiratory burst) and the surface expression of several adhesion molecules (Mac-1, LFA-1 and L-selectin) was measured by flow cytometry. Measurements were obtained under basal conditions and after stimulation with phorbol myristate acetate (PMA) and tumour necrosis factor alpha (TNFalpha). mRNA levels of p22-phox (a subunit of NADPH oxidase) and Mac-1 (CD11b) were also determined by reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: Patients with COPD showed enhanced respiratory burst compared with smokers with normal lung function, both under basal conditions (mean (SE) fluorescence intensity (MFI) 15.1 (0.5) v 11.6 (0.5); mean difference -3.4 (95% CI of the difference -5.1 to -1.8), p<0.01) and after PMA stimulation (MFI 210 (7) v 133 (10); mean difference -77 (95% CI of the difference -102 to -52), p<0.01). Mac-1 surface expression was also enhanced in patients with COPD, both under basal conditions (MFI 91 (5) v 45 (3); mean difference -46 (95% CI of the difference -61 to -31), p<0.001) and after stimulation with TNFalpha (MFI 340 (15) v 263 (11); mean difference -77 (95% CI of the difference -119 to -34), p=0.001). These differences were also apparent when patients with COPD were compared with non-smokers (p<0.05). The mRNA levels of p22-phox and Mac-1 (CD11b) were similar in patients with COPD and smokers with normal lung function, suggesting that the observed differences were due to post-transcriptional regulation. CONCLUSIONS: These results demonstrate an enhanced neutrophil response to proinflammatory agents in patients with COPD which may contribute to their enhanced recruitment and activation in the lungs of these patients. These findings support those of other studies which have indicated that the neutrophil is likely to play a major role in the pathogenesis of this disease.

Aged↗
PubMed2001

Systemic effects of chronic obstructive pulmonary disease.

Traditionally, chronic obstructive pulmonary disease (COPD) has been understood as a disease of the lungs, characterized by irreversible airflow limitation due to chronic bronchitis and/or emphysema. The latter are thought mainly to be the consequence of an excessive inflammatory response to tobacco smoking. Recently, several studies have shown that this pulmonary inflammation may also be detected in the systemic circulation, and that this systemic inflammation may have important clinical consequences. Most prominent among them is the loss of skeletal muscle mass that a significant percentage of patients with COPD will show during the course of their disease. This limits considerably their exercise capacity, jeopardizes their health status, and has a negative impact on their prognosis. Importantly, such prognostic value is independent of the degree of airflow obstruction and potentially reversible with appropriate therapy. This chapter summarizes available evidence supporting the concept that COPD is more than a lung disease (the systemic effects of COPD), and speculates on potential cellular mechanisms as future therapeutic targets.

Humans↗
PubMed2000

Regulation of iNOS expression and glutathione levels in rat liver by oxygen tension.

Molecular oxygen (O(2)) regulates the expression of a variety of genes. We hypothesized that O(2) tension may regulate iNOS expression in rat liver through the production of reactive oxygen species (ROS) and the reduction of intracellular glutathione (GSH) levels. To investigate this hypothesis, we determined the effects of hyperoxia upon iNOS induction (both at the protein and mRNA level) and the intracellular concentration of GSH in an isolated in vitro perfused rat liver preparation. To study the potential involvement of ROS in the intracellular signaling pathway linking changes in oxygen tension to gene expression, we repeated these determinations in the presence of the thiol antioxidant N-acetyl-L-cysteine (NAC). We found that 95% O(2) tension caused a significant induction of the iNOS protein and mRNA levels paralleled by a significant fall in intracellular GSH concentration. The addition of NAC (1 mM) to the perfusate during hyperoxia blocked the induction of iNOS and restored GSH levels. These results indicate that molecular O(2) regulates the expression of iNOS in rat liver at the transcriptional level, most likely through the production of ROS and the reduction of intracellular GSH levels.

Acetylcysteine↗
PubMed2000

Abnormal lipid peroxidation in patients with sleep apnoea.

The prevalence of cardiovascular diseases is increased in patients with the obstructive sleep apnoea syndrome (OSAS). The fall and rise of arterial oxygenation that follows each apnoea may increase lipid peroxidation and contributes to explaining this association. In the present study, the authors determined lipid peroxidation in patients with OSAS and the effect of treatment with continuous positive airway pressure (CPAP). Fourteen male patients with severe OSAS (59+/-5 apnoea x h(-1)) (+/-SEM) and 13 healthy nonsmoking, male volunteers of similar age were studied. Patients were studied at diagnosis and after treatment with CPAP for more than 1 yr (>4 h x night(-1)). A venous blood sample was obtained early in the morning after fasting all night. In patients with OSAS, a sample before and during sleep was also obtained. Low density lipoprotein (LDL) particles were isolated by sequential ultracentrifugation. Their level of oxidation was determined by the thiobarbituric acid assay (TBARs), and their susceptibility to oxidation by the lag phase measurement. Patients with OSAS showed higher TBARs (28.1+/-2.8 versus 20.0+/-1.8 nmol x malondialdehyde x mgLDL protein(-1), p=0.02) and shorter lag phase values (83.8+/-3.4 versus 99.7+/-3.4 min, p=0.005) than controls. These differences were not due to the smoking status of the patient. Likewise, these values did not change significantly throughout the night yet, the lag phase value was significantly improved by treatment with CPAP (124.9+/-8.5 min; p<0.001). These results indicate that obstructive sleep apnoea syndrome is associated with abnormal lipid peroxidation and that this is improved by chronic use of Continuous positive airway pressure. These results can contribute towards explaining the high prevalence of cardiovascular diseases seen in Obstructive sleep apnoea syndrome.

Adult↗
PubMed2000

Changes induced by oxygen in rat liver proteins identified by high-resolution two-dimensional gel electrophoresis.

Molecular oxygen (O2) regulates the expression of a variety of genes. Several of the proteins that respond to changes in oxygen concentration have been identified in a variety of cell lines. We extend these previous studies by analyzing the effect of oxygen on the entire protein expression profile of an intact organ using high-resolution two-dimensional gel electrophoresis. To this end, we used an isolated, in vitro perfused organ preparation to produce two groups of rat livers perfused with high (95% O2, 5% CO2) or low (95% N2, 5% CO2) oxygen concentrations. Using two-dimensional gel electrophoresis we compared the protein expression profiles of both groups of livers. Computer analysis of the files obtained after laser densitometry of the two-dimensional gels revealed two spots that were strongly up-regulated in high PO2 perfused livers compared with low PO2 perfused livers. These spots were analyzed by peptide mass fingerprinting analysis. These spots were identified as arginase 1 (liver-type arginase; EC 3.5.3.1) and mitochondrial enoyl-CoA hydratase 1 (EC 4.2.1.17). The possible role of these proteins in its new context of oxygen availability is discussed.

Animals↗
PubMed2000

The activity of cytochrome oxidase is increased in circulating lymphocytes of patients with chronic obstructive pulmonary disease, asthma, and chronic arthritis.

We have previously shown that the activity of cytochrome oxidase (CytOx) in skeletal muscle of patients with chronic obstructive pulmonary disease (COPD) was higher than in healthy control subjects. The mechanisms and implications of this observation were unclear. In particular, it was not known if this abnormality can occur also in: (1) cell types other than muscle cells, and (2) other chronic inflammatory diseases. To obtain further insight into these questions, we measured the activity of CytOx in circulating lymphocytes in patients with stable COPD (n = 17), bronchial asthma (n = 6), or chronic arthritis (n = 5), and in healthy control subjects (n = 8). We found that, compared with healthy subjects (280 +/- 117 nKat/microg protein), patients with COPD showed increased CytOx activity (430 +/- 150 nKat/microg protein, p = 0.01) in lymphocytes. Further, this activity was negatively related to the degree of airflow obstruction present in these patients (r = -0.53, p < 0.05). We also found that the activity of CytOx in circulating lymphocytes was higher than normal in patients with chronic arthritis (411 +/- 130 nKat/microg protein, p < 0.05) and, particularly, in patients with bronchial asthma (1,667 +/- 1,027 nKat/microg protein, p < 0.001). These results show that the increased CytOx activity previously reported in skeletal muscle of patients with COPD is also detected in other cell types (such as circulating lymphocytes) and in other chronic inflammatory diseases (such as bronchial asthma and chronic arthritis). The mechanisms and implications of these findings deserve further investigation.

Arthritis↗
PubMed2000

The measurement of exhaled carbon monoxide is influenced by airflow obstruction.

The concentration of carboxyhaemoglobin (COHb) is often estimated from measurements of carbon monoxide in the exhaled air (COexh). This study investigates whether the presence of airflow obstruction significantly alters the relationship between COexh and COHb. Eighty-one regular smokers were prospectively studied and divided in four groups according to the presence and severity of airflow obstruction (none, mild, moderate, severe). In each subject, the authors measured in this order: 1) arterial blood gases; 2) haemoglobin concentration and COHb (by co-oxymetry); 3) COexh; 4) lung volumes; and 5) forced spirometry. The size of the measurement error (deltaCO) was calculated from the difference between COHb and COexh. Neither the smoking history nor COexh were different in the four groups of subjects studied. In contrast, deltaCO increased in parallel to the degree of airflow obstruction. DeltaCO was >2% (a threshold value normally used in the clinic to separate smokers from nonsmokers) only in patients with severe airflow obstruction. A stepwise multivariate analysis showed that both forced expiratory volume in one second (FEV1) (percentage reference) and COHb contributed significantly (p<0.0001) to predict deltaCO. This study shows that the estimation of carboxyhaemoglobin from exhaled carbon monoxide measurements can be inaccurate in patients with severe airflow obstruction. In these patients, the direct measurement of carboxyhaemoglobin seems advisable in clinical practice.

Adult↗
PubMed1999

Exhaled nitric oxide in patients with sleep apnea.

Cardiovascular diseases are frequent in patients with obstructive sleep apnea syndrome (OSAS), but the mechanisms underlying this association are largely unknown. Nitric oxide (NO) is a key regulatory element of vascular physiology. The concentration of NO in the exhaled air ([NOexh]) appears to be reduced in patients with systemic and pulmonary hypertension. This study sought to investigate whether [NOexh] is abnormal in patients with OSAS, and to explore potential relationships between [NOexh] and the severity of OSAS. We measured [NOexh] in 24 patients with OSAS (apnea-hypopnea index (AHI), 55 +/- 4 hour-1) (x +/- SEM), and in 7 healthy volunteers in whom OSAS was excluded clinically. [NOexh] was measured on line by a chemiluminescence analyzer (Dasibi Environmental Corporation, Glendale, Calif). Seven patients with OSAS (29%) had a positive history of cardiovascular disease. Mean [NOexh] was 19.7 +/- 3.2 ppb in healthy subjects, and 22.2 +/- 3.0 ppb in patients with OSAS (p = ns). [Noexh] was not significantly different in those patients with or without cardiovascular disease. [NOexh] was not significantly related to the AHI, the body mass index, or the arterial O2 saturation at night. These results show that [NOexh] is not abnormal in patients with OSAS, and that it does not relate to the presence of cardiovascular disease or to any of various common indices of disease severity.

Adult↗
PubMed1999

[The results of the operation of a monitoring unit for home oxygen therapy].

OBJECTIVE: This study aims to a) analyze the prevalence of domiciliary oxygen therapy (DOT) in Mallorca, b) evaluate the cost effectiveness of the DOT monitoring unit, and c) determine the survival of patients with chronic obstructive pulmonary disease who are presently receiving DOT. METHOD: When the DOT unit was created in April 1994, the situation of all patients receiving DOT in Mallorca was assessed in a transversal study. Over the next three years, these patients were reassessed regularly and all new prescriptions were evaluated (longitudinal study). RESULTS: Before the unit began work, DOT was prescribed for 71 out of 100,000 inhabitants. DOT was withdrawn from 31% of patients assessed in the transversal study. By the end of the longitudinal study, DOT was being prescribed at a rate of 56 times per 10,000 inhabitants. The activities of the DOT unit brought about annual savings of approximately 38 million pesetas. The number of patients with liquid oxygen and concentrators increased such that the latter has become the main delivery system. The survival of COPD patients with DOT in this study seems to be longer than report. CONCLUSIONS: a) The prevalence of DOT use in Mallorca before the DOT unit began operating was too high. b) The cost effectiveness of DOT monitoring is positive because DOT use has been optimized and significant savings have ensued (= 38 millions pesetas/year). c) The survival of COPD patients receiving DOT at present appears better than that reported in the literature, possibly related to the greater efficacy of modern treatment.

Aged↗
PubMed1999

Serial measurements of exhaled nitric oxide during exacerbations of chronic obstructive pulmonary disease.

Excessive inflammation seems important in chronic obstructive pulmonary disease (COPD), particularly during exacerbations of the disease. Exhaled nitric oxide concentration ([NOexh]) is a sensitive marker of bronchial inflammation in asthma; it is unclear if this is also the case in COPD. This study: 1) quantifies [NOexh] in patients with COPD (during an exacerbation and while clinically stable); 2) investigates the response of [NOexh] to i.v. steroid therapy, and its potential relationship with other relevant physiological variables; and 3) assesses the relative contributions of the central and peripheral airways to [NOexh] by collecting exhaled air in two different bags connected in series. Seventeen COPD patients (forced expiratory volume in one second (FEV1) 37.6+/-3.4% of the predicted value (+/-SEM)) hospitalized because of an exacerbation of the disease (arterial oxygen tension (Pa,O2) (7.46+/-0.72 kPa 56.1+/-5.4 mmHg), arterial carbon dioxide tension (Pa,CO2) 5.63+/-0.37 kPa 42.3+/-2.8 mmHg), pH 7.41+/-0.02) and 10 healthy subjects that served as controls were studied. On admission, [NOexh] in COPD was higher than normal (41.0+/-5.1 versus 13.3+/-0.8 parts per billion (ppb), respectively, p<0.001). Despite i.v. steroid therapy, [NOexh] remained elevated throughout recovery (37.9+/-4.8 ppb, p<0.001) until discharge (40.9+/-4.3 ppb, p<0.001). In contrast, when the patients were clinically stable (several months later), [NOexh] was significantly reduced (15.8+/-3.8 ppb, p<0.001), and no longer different from control values. [NOexh] was not related to any of the physiological variables measured during recovery (pulmonary gas exchange) or at discharge (forced spirometry, lung volumes, diffusing capacity). Finally, the contribution of the central and peripheral airways to [NOexh] was not different at any point in time. These results indicate that during exacerbations of chronic obstructive pulmonary disease, the exhaled nitric oxide concentration: 1) is higher than normal; 2) is not reduced acutely by i.v. steroids but is normalized several months after discharge; 3) is unrelated to several physiological indices of disease severity; and 4) appears to be produced homogeneously in central and peripheral airways. Overall, these results are different from those reported in asthma, suggesting that different inflammatory mechanisms are operating in both diseases.

Aged↗
PubMed1999

Oxygen therapy during exacerbations of chronic obstructive pulmonary disease.

Venturi masks (VMs) and nasal prongs (NPs) are widely used to treat acute respiratory failure (ARF) in chronic obstructive pulmonary disease (COPD). In this study, these devices were compared in terms of their potentiality to worsen respiratory acidosis and their capacity to maintain adequate (> 90%) arterial oxygenation (Sa,O2) through time (approximately 24 h). In a randomized cross-over study, 18 consecutive COPD patients who required hospitalization because of ARF were studied. After determining baseline arterial blood gas levels (on room air), patients were randomized to receive oxygen therapy through a VM or NPs at the lowest possible inspiratory oxygen fraction that resulted in an initial Sa,O2 of > or = 90%. Arterial blood gas levels were measured again 30 min later (on O2), and Sa,O2 recorded using a computer during the subsequent approximately 24 h. Patients were then crossed-over to receive O2 therapy by means of the alternative device (NPs or VM), and the same measurements obtained again in the same order. It was observed that both the VM and NPs improved arterial oxygen tension (p<0.0001) to the same extent (p=NS), without any significant effect upon arterial carbon dioxide tension or pH. However, despite this adequate initial oxygenation, Sa,O2 was < 90% for 3.7+/-3.8 h using the VM and for 5.4+/-5.9 h using NPs (p<0.05). Regression analysis showed that the degree of arterial hypoxaemia (p<0.05) and arterial hypercapnia (p<0.05) present before starting O2 therapy and, particularly, the initial Sa,O2 achieved after initiation of O2 therapy (p<0.0001) enabled the time (in h) that patients would be poorly oxygenated (Sa,O2 < 90%) on follow-up to be predicted. These findings suggest that, in order to maintain an adequate (> 90%) level of arterial oxygenation in patients with chronic obstructive pulmonary disease and moderate acute respiratory failure: 1) the initial arterial oxygen saturation on oxygen should be maximized whenever possible by increasing the inspiratory oxygen fraction; 2) this strategy seems feasible because neither the VM nor NPs worsen respiratory acidosis significantly; and 3) the Venturi mask (better than nasal prongs) should be recommended.

Acidosis, Respiratory↗
PubMed1999

Patients with obstructive sleep apnea exhibit genioglossus dysfunction that is normalized after treatment with continuous positive airway pressure.

Obstructive sleep apnea syndrome (OSAS) is characterized by repetitive episodes of pharyngeal closure during sleep. The pathogenesis of OSAS is unclear. We hypothesized that the genioglossus (GG), the most important pharyngeal dilator muscle, would be abnormal in patients with OSAS. Further, because treatment with continuous positive airway pressure (CPAP) is very effective clinically in these patients, we investigated the effects of CPAP upon the structure and function of the GG. We studied 16 patients with OSAS (nine of them at diagnosis and seven after having been under treatment with CPAP for at least 1 yr) and 11 control subjects in whom OSAS was excluded clinically. A biopsy of the GG was obtained in each subject, mounted in a tissue bath, and stimulated through platinum electrodes. The following measurements were obtained: maximal twitch tension, contraction time, half-relaxation time, the force-frequency relationship, and the response to a fatiguing protocol. The percentage of type I ("slow twitch") and type II ("fast twitch") fibers was also quantified. Patients with OSAS showed a greater GG fatigability than did control subjects (ANOVA, p < 0.001). Interestingly, this abnormality was entirely corrected by CPAP. Likewise, the percentage of type II fibers was significantly higher in patients with OSAS (59 +/- 4%) than in control subjects (39 +/- 4%, p < 0.001) and, again, these structural changes were corrected by CPAP (40 +/- 3%, p < 0.001). These results show that the function and structure of the GG is abnormal in patients with OSAS. Because these abnormalities are corrected by CPAP, we suggest that they are likely a consequence, not a cause, of the disease.

Humans↗