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Biomedical subjects

A G N Agustí

Publications and source records attributed to A G N Agustí.

15 recordsLinked to original sources
PubMed2006

Intracellular cytokine profile of T lymphocytes in patients with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is characterized by an excessive inflammatory response to inhaled particles, mainly tobacco smoking. T lymphocytes are important regulatory cells that secrete several cytokines and participate actively in this inflammatory response. According to the pattern of cytokines secreted, the immune response is classified as cytotoxic or type 1 [interferon (IFN)-gamma-, interleukin (IL)-2-dependent] and humoral or type 2 (IL-4-, IL-5-, IL-10- and IL-13-dependent). This paper sought to compare the intracellular profile of cytokine expression determined by flow cytometry in T lymphocytes harvested from bronchoalveolar lavage (BAL) and peripheral blood in patients with COPD, smokers with normal lung function and never smokers. We found that BAL T lymphocytes from COPD patients had a higher percentage of positive stained cells for most of the cytokines analysed when compared to never smokers or smokers with normal lung function. Differences reached statistical significance for IL-4, IL-10 and IL-13, particularly in CD8(+) T cells. Furthermore, the expression of most of these cytokines was related inversely to the degree of airflow obstruction present suggesting local activation and/or selective homing of T lymphocytes to the lungs in COPD patients. These observations were not reproduced in circulating T lymphocytes. These results suggest that BAL T lymphocytes in patients with COPD produce more cytokines than in controls and tend to show a type 2 pattern of intracellular cytokine expression, particularly a Tc-2 profile. This is related inversely to the degree of airflow obstruction present.

Bronchoalveolar Lavage Fluid↗
PubMed2006

Antioxidant status in patients with sleep apnoea and impact of continuous positive airway pressure treatment.

The episodes of hypoxia/re-oxygenation associated with the respiratory disturbances observed in patients with obstructive sleep apnoea syndrome (OSAS) may induce the generation of oxygen free radicals. Indeed, several studies suggest that OSAS is associated with oxidative stress. The present study tested the hypothesis that patients with OSAS have an alteration in antioxidant defences. The plasma levels of total antioxidant status (TAS), glutathione peroxidase (GPX), gamma-glutamyltransferase (GGT), vitamins A, E, B12 and folate, and homocysteine were determined in 47 patients with OSAS and 37 healthy subjects. Of these, 27 patients who used continuous positive airway pressure (CPAP) for >4 h.night-1 were re-examined 12 months later. Patients with OSAS had lower TAS (1.4+/-0.16 versus 1.50+/-0.10 mmol.L-1), vitamin A (64+/-19 versus 74+/-17 microg.dL-1) and vitamin E levels (1,525+/-499 versus 1,774+/-503 microg.dL-1), and increased values of GGT (42+/-22 versus 32+/-16 U.L-1) than controls. There was no difference between groups in GPX, homocysteine, vitamin B12 and folate plasma levels. CPAP treatment normalised the levels of TAS (1.50+/-0.13 mmol.L-1) and the activity of GGT (30+/-14 U.L-1) without any influence on vitamins levels. In conclusion, the results indicate that patients with obstructive sleep apnoea syndrome have a decreased antioxidant capacity that is partially reversed by continuous positive airway pressure treatment.

Adult↗
PubMed2006

Telomere shortening in smokers with and without COPD.

Telomeres are complex DNA-protein structures located at the end of eukaryotic chromosomes. Telomere length shortens with age in all replicating somatic cells. It has been shown that tobacco smoking enhances telomere shortening in circulating lymphocytes. The present study investigated whether this effect was further amplified in smokers who develop chronic obstructive pulmonary disease. Telomere length was determined by fluorescence in situ hybridisation in circulating lymphocytes harvested from 26 never-smokers, 24 smokers with normal lung function and 26 smokers with moderate-to-severe airflow obstruction (forced expiratory flow in one second 48+/-4% predicted). In contrast to never-smokers, telomere length significantly decreased with age in smokers. There was also a dose-effect relationship between the cumulative long-life exposure to tobacco smoking (pack-yrs) and telomere length. The presence and/or severity of chronic airflow obstruction did not modify this relationship. The results of the current study confirm that smoking exposure enhances telomere shortening in circulating lymphocytes. It also demonstrates a dose-effect relationship between exposure to tobacco smoking and telomere length, but failed to show that this effect is amplified in smokers who develop chronic obstructive pulmonary disease.

Adult↗
PubMed2005

Decreased macrophage release of TGF-beta and TIMP-1 in chronic obstructive pulmonary disease.

The present study tested the hypothesis that alveolar macrophages (AM) from patients with chronic obstructive pulmonary disease (COPD) release more pro-inflammatory and/or less anti-inflammatory mediators than those from smokers with normal lung function and never-smokers. AM were sorted by flow cytometry from bronchoalveolar lavage fluid in 13 patients with COPD (mean+/-SEM 67+/-2 yrs, forced expiratory volume in one second (FEV1) 61+/-4% reference), 16 smokers with normal lung function (55+/-2 yrs, FEV1 97+/-4% reference) and seven never-smokers (67+/-7 yrs, FEV1 94+/-4% reference). After sorting, AM were cultured (with and without lipopolysaccharide stimulation) after 4 h and 24 h, and the concentrations of leukotriene B4 (LTB4), transforming growth factor (TGF)-beta1 and tissue inhibitor of metalloproteinase (TIMP)-1 were quantified in the supernatant by ELISA. The production of reactive oxygen intermediates (ROI) in freshly isolated AM was determined by flow cytometry. LTB4 secretion and ROI production were not different between groups. In contrast, AM from COPD patients released significantly less TGF-beta1 and TIMP-1 than those from smokers with normal lung function and nonsmokers. In conclusion, these observations are compatible with reduced anti-inflammatory and anti-elastolytic capacity in chronic obstructive pulmonary disease, which is likely to contribute to the pathogenesis of the disease.

Aged↗
PubMed2005

Phenotypic characterisation of alveolar macrophages and peripheral blood monocytes in COPD.

Alveolar macrophages (AM) participate actively in the inflammatory response that characterises chronic obstructive pulmonary disease (COPD). The present study investigated potential changes in AM phenotypes in patients with COPD. Using flow cytometry, the surface expression of receptors implicated in phagocytosis (CD44, CD36, CD51, CD61, CD14), antigen-presenting capacity (human leukocyte antigen (HLA)-DR), costimulatory molecules (CD80, CD86, CD40) and complement receptor type 3 were assessed in AM from 18 patients with COPD, 14 smokers with normal lung function and nine nonsmokers. When compared to smokers with normal lung function and nonsmokers, the surface expression of HLA-DR and CD80 was lower in AM of patients with COPD. In addition, these patients had a higher percentage of AM with a low level surface expression of CD44. There did not appear to be any difference in the other receptors studied in AM between the three groups. The expression of all these receptors in peripheral blood monocytes also did not differ between groups. In conclusion, these observations suggest that the cell-mediated immune function of alveolar macrophages can be reduced in chronic obstructive pulmonary disease, and that this is a local rather than a systemic event.

Humans↗
PubMed2005

Blunted gamma delta T-lymphocyte response in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is characterised by an excessive inflammatory response to inhaled particles, mostly tobacco smoking. Although inflammation is present in all smokers, only a percentage of them develop COPD. T-lymphocytes are important effector and regulatory cells that participate actively in the inflammatory response of COPD. They comprise the T-cell receptor (TCR)-alpha beta (CD4+ and CD8+) and TCR-gamma delta T-lymphocytes. The latter represent a small percentage of the total T-cell population, but play a key role in tissue repair and mucosal homeostasis. To investigate TCR-alpha beta (CD4+ and CD8+) and TCR-gamma delta T-lymphocytes in COPD, the present authors determined, by flow cytometry, the distribution of both subpopulations in peripheral blood and bronchoalveolar lavage (BAL) samples obtained from patients with COPD, smokers with normal lung function and never-smokers. The present study found that: 1) the distribution of CD4+ and CD8+ lymphocytes in blood and BAL was similar in all three groups; 2) compared with nonsmokers, gamma delta T-lymphocytes were significantly increased in smokers with preserved lung function; and 3) this response was blunted in patients with COPD. These results highlight a novel, potentially relevant, pathogenic mechanism in chronic obstructive pulmonary disease.

Aged↗
PubMed2004

Effects of obesity upon genioglossus structure and function in obstructive sleep apnoea.

Obesity is a common feature of the obstructive sleep apnoea syndrome. It can influence the structure and function of skeletal muscles. However, its effects upon the upper airway muscles have not been explored directly. This study assessed the structure and function of the genioglossus in patients with obstructive sleep apnoea syndrome and in healthy subjects (with and without obesity, defined by a body mass index > 30 kg x m(-2)). Further, to investigate the effects of continuous positive airway pressure (CPAP) treatment, patients with obstructive sleep apnoea syndrome after at least 1 yr under CPAP were also studied. The study found that obese and nonobese patients showed different in vitro geniglossus endurance properties. In obese patients, geniglossus endurance was indistinguishable from normal while, nonobese patients, at diagnosis, showed increased genioglossus fatigability; this was not observed in patients treated with CPAP. By contrast, patients with obstructive sleep apnoea syndrome showed at diagnosis a higher percentage of type II fibres than controls and patients under CPAP treatment independently of obesity. This difference is mainly due to a predominance of subtype IIb fibre. This difference was not observed in the group of patients treated with CPAP. Genioglossus twitch force was normal in all patients. These results suggest that different pathogenic mechanisms may underlie the development of obstructive sleep apnoea syndrome in obese and nonobese patients. This observation may have potential clinical implications.

Adult↗
PubMed2003

[Steady car engine noise does not affect the cognitive abilities of sleep apnea syndrome patients].

Traffic accidents are more frequent for sleep apnea syndrome (SAS) patients than in the population at large. The mechanisms that underlie this observation are poorly defined. Our working hypothesis was that in SAS patients the steady noise of a car engine might alter cognitive capacities that may be involved in driving, thus increasing the risk of traffic accidents. To test this hypothesis we designed a prospective randomized controlled trial. Eighteen SAS patients (apnea-hypopnea index [SEM] 62 [6] h1) and 18 healthy controls were studied. All the participants were evaluated in random order both in basal conditions and after exposure to the steady noise of a car engine recorded on a compact disc. Their level of vigilance was evaluated (Steer-Clear) as well as their reaction time (PVT 192). Attention, coordination, and memory were measured using the following tests: Wechsler Memory Scale (digit span), the Wechsler Intelligence Scale (digit symbol), and Lezack's Trail Making tests A and B. The SAS patients were slightly younger than the control group (mean 50 [7] vs 57 [11] years, respectively; P=.05). The patients showed a lower level of vigilance than the controls both in basal and engine noise conditions (P<.05). No differences between groups were found for the other variables studied. Exposure to steady car engine noise had no effect on the tests of either group. In conclusion, the results of our study do not support the hypothesis that steady car engine noise significantly alters the cognitive ability of SAS patients.

Accidents, Traffic↗
PubMed2003

Systemic effects of chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is characterised by an inappropriate/excessive inflammatory response of the lungs to respiratory pollutants, mainly tobacco smoking. Recently, besides the typical pulmonary pathology of COPD (i.e. chronic bronchitis and emphysema), several effects occurring outside the lungs have been described, the so-called systemic effects of COPD. These effects are clinically relevant because they modify and can help in the classification and management of the disease. The present review discusses the following systemic effects of chronic obstructive pulmonary disease: 1) systemic inflammation; 2) nutritional abnormalities and weight loss; 3) skeletal muscle dysfunction; and 4) other potential systemic effects. For each of these, the potential mechanisms and clinical implications are discussed and areas requiring further research are highlighted.

Bone Diseases↗
PubMed2002

[Recovery of lung function after laparoscopic cholecystectomy: the role of postoperative pain].

OBJECTIVES: Lung function has been shown to deteriorate after laparoscopic cholecystectomy (LC). The present study evaluated 1) the rate of recovery after LC, and 2) the pathogenic role of postoperative pain in functional deterioration. DESIGN: Lung function was measured 24 hours before LC, upon hospital discharge (48-72 h after LC), and 10 days later. All patients received metamizol after LC until discharge (2 g every 6 h i.v.). Half the patients (analgesia group) received tramadol (150 mg i.m.) 30 minutes before lung function testing on the day of hospital discharge. The remaining patients constituted the control group. PATIENTS: Twenty healthy subjects (53 4 years old) undergoing LC for gall bladder removal. All signed informed consent forms. Measures and outcomes: Patient characteristics and preoperative lung function results were similar in both groups. LC duration and postoperative course were also similar in both groups. All were discharged without complications within 72 hours after LC. Lung function upon discharge (FVC, FEV1, TLC, PaO2 and AaPO2) had deteriorated in both groups (p<0.001). Deterioration was less marked in the analgesia group (p < 0.05). Ten days later, lung function had normalized for all subjects. CONCLUSIONS: These results indicate that after LC, 1) lung function is still abnormal when the patient is discharged from hospital, 2) lung function has fully recovered within 10 days, and 3) postoperative pain contributes significantly to temporary deterioration in lung function.

Adult↗
PubMed2002

Plasminogen activator inhibitor-I (PAI-I) polymorphisms in patients with obstructive sleep apnoea.

Cardiovascular diseases are frequent among patients with the obstructive sleep apnoea syndrome (OSAS), The aetiopathogenesis of this association is unclear. Type 1 plasminogen activator inhibitor (PAI-1) is one of the primary regulators of the fibrinolytic system. A reported association between PAI-1 activity and an insertion/deletion polymorphism (4G/5G) in the promoter region of the PAI-1 gene suggests a critical role for this genomic region in the pathogenesis of several cardiovascular diseases. In this study, we determined the prevalence of this polymorphism in patients with OSAS and in healthy control subjects. The 4G/5G polymorphism in the promoter region of the PAI-1 gene was determined in 78 male patients with severe OSAS (56 +/- 2 apnoeas per hour) and in 70 healthy male, non-smoker volunteers of similar age, without personal or familial history of cardiovascular disease. The frequency ofthe 4G/4G, 4G/5G and 5G/5G genotypes in patients with OSAS (18%, 62%, 19%, respectively) was not significantly different from that seen in healthy subjects (16%, 60%, 24% P=NS). These results show that the distribution of the 4G/5G polymorphism in the promoter region ofthe PAI-1 gene in patients with OSAS is similar to that observed in healthy subjects. This observation suggests that the PAI-1 polymorphism has no relationship with the increased risk of cardiovascular diseases seen in patients with OSAS.

Case-Control Studies↗
PubMed2002

[Systemic inflammation during exacerbations of chronic obstructive pulmonary disease].

OBJECTIVE: The circulating blood levels of several inflammatory cytokines and acute phase proteins are higher in patients with stable chronic obstructive pulmonary disease (COPD). However, whether or not these inflammatory markers increase during COPD exacerbation or are modified by corticosteroid treatment has not been investigated. The objective of this study was therefore 1) to describe changes in several inflammatory markers in systemic circulation during COPD exacerbation, and 2) to assess the potential effects of corticosteroid treatment during exacerbation. METHODS: Serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), interleukin 8 (IL-8) and C-reactive protein (CRP) were determined for 10 patients (65 2 years old) with severe COPD (FEV1 35 4% reference) who were hospitalized for acute respiratory failure (PaO2 57 2 mm Hg; PaCO2 48 3 mm Hg). Blood samples were obtained in the emergency room (before starting intravenous corticosteroid treatment), during the first 24 hours of admission, upon discharge and two months later. Eight healthy non-smokers of a similar age (54 3 years) were also studied as control subjects. RESULTS: The COPD patients had higher concentrations of IL-6 (5.1 1.6 vs. 1.8 0.5 pg/mL, p < 0.05) and CRP (2.2 0.4 vs. 0.6 0.2 mg/dL, p < 0.005) than did controls, but the concentrations of IL-8 were similar (29 11.3 vs. 34.7 10.3 pg/mL, p = ns). No statistically significant changes were seen either during recovery, in spite of intravenous corticosteroid treatment, or two months after discharge.The ELISA test used was unable to detect TNF-alpha in any of the samples obtained from either patients or controls. CONCLUSION: The results show that 1) there is evidence of systemic inflammation during exacerbation of COPD, and 2) such systemic inflammation does not appear to be influenced significantly by intravenous corticosteroid treatment.

Adrenal Cortex Hormones↗