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Biomedical subjects

C Agustí

Publications and source records attributed to C Agustí.

At least 37 records · Page 2Linked to original sources
PubMed2001

Pulmonary infiltrates in non-HIV immunocompromised patients: a diagnostic approach using non-invasive and bronchoscopic procedures.

BACKGROUND: The development of pulmonary infiltrates is a frequent life threatening complication in immunocompromised patients, requiring early diagnosis and specific treatment. In the present study non-invasive and bronchoscopic diagnostic techniques were applied in patients with different non-HIV immunocompromised conditions to determine the aetiology of the pulmonary infiltrates and to evaluate the impact of these methods on therapeutic decisions and outcome in this population. METHODS: The non-invasive diagnostic methods included serological tests, blood antigen detection, and blood, nasopharyngeal wash (NPW), sputum and tracheobronchial aspirate (TBAS) cultures. Bronchoscopic techniques included fibrobronchial aspirate (FBAS), protected specimen brush (PSB), and bronchoalveolar lavage (BAL). Two hundred consecutive episodes of pulmonary infiltrates were prospectively evaluated during a 30 month period in 52 solid organ transplant recipients, 53 haematopoietic stem cell transplant (HSCT) recipients, 68 patients with haematological malignancies, and 27 patients requiring chronic treatment with corticosteroids and/or immunosuppressive drugs. RESULTS: An aetiological diagnosis was obtained in 162 (81%) of the 200 patients. The aetiology of the pulmonary infiltrates was infectious in 125 (77%) and non-infectious in 37 (23%); 38 (19%) remained undiagnosed. The main infectious aetiologies were bacterial (48/125, 24%), fungal (33/125, 17%), and viral (20/125, 10%), and the most frequent pathogens were Aspergillus fumigatus (n=29), Staphylococcus aureus (n=17), and Pseudomonas aeruginosa (n=12). Among the non-infectious aetiologies, pulmonary oedema (16/37, 43%) and diffuse alveolar haemorrhage (10/37, 27%) were the most common causes. Non-invasive techniques led to the diagnosis of pulmonary infiltrates in 41% of the cases in which they were used; specifically, the diagnostic yield of blood cultures was 30/191 (16%); sputum cultures 27/88 (31%); NPW 9/50 (18%); and TBAS 35/55 (65%). Bronchoscopic techniques led to the diagnosis of pulmonary infiltrates in 59% of the cases in which they were used: FBAS 16/28 (57%), BAL 68/135 (51%), and PSB 30/125 (24%). The results obtained with the different techniques led to a change in antibiotic treatment in 93 cases (46%). Although changes in treatment did not have an impact on the overall mortality, patients with pulmonary infiltrates of an infectious aetiology in whom the change was made during the first 7 days had a better outcome (29% mortality) than those in whom treatment was changed later (71% mortality; p=0.001). CONCLUSIONS: Non-invasive and bronchoscopic procedures are useful techniques for the diagnosis of pulmonary infiltrates in immunocompromised patients. Bronchial aspirates (FBAS and TBAS) and BAL have the highest diagnostic yield and impact on therapeutic decisions.

AIDS-Related Opportunistic Infections↗
PubMed2001

Is it necessary to treat all patients with idiopathic pulmonary fibrosis?

BACKGROUND AND AIM OF THE WORK: To investigate the clinical course of untreated patients with idiopathic pulmonary fibrosis (usual interstitial pneumonia) (IPF/UIP). METHODS: Forty-three patients with IPF/UIP, divided into two groups. Group I consisted of 29 patients treated at diagnosis, while Group II comprised 14 patients who did not receive treatment. The indication of treatment was established whenever patients referred to a significant progression of the degree of dyspnea during the year prior to diagnosis. RESULTS: At diagnosis, patients from Group I had lower FVC (mean +/- SEM, 56+/-3% vs 73+/-3%) (p = 0.0004) and a greater extent of ground glass pattern in high resolution CT scan (18+/-4% vs 4+/-1%) (p = 0.004) than those from Group II. In group I, a follow-up study was carried out on 26 patients for 24+/-4 months. Thirteen of these 26 patients (50%) died 11+/-4 months after the initial assessment. Serial pulmonary functional tests were performed on 19 patients. Thirteen patients from Group II were followed up for 23+/-3 months. Seven of these 13 patients were treated 12+/-3 months after the diagnosis because of progression of the disease. The remaining 6 patients remained untreated and with the disease stable at the end of the follow-up, representing 15% (6 out of 39) of the whole study group. No patients from this group died during the follow-up. At the end of the follow-up, there were no differences in lung function changes between treated patients (19 from Group I and 7 from Group II), and the 6 untreated patients. CONCLUSIONS: Some patients with IPF/UIP remain stable for extended periods of time without treatment.

Aged↗
PubMed2001

Impact of BAL on the diagnosis and treatment of nosocomial pneumonia in ICU patients.

Nosocomial pneumonia and ventilator-associated pneumonia are currently the second leading cause of nosocomial infections and account for approximately 10-15% of all hospital-acquired infections. Crude mortality rates range from 24% to 76% depending on the population and clinical setting studied. During the last ten years, several diagnostic methods have been developed to microbiologically confirm the clinical diagnosis, especially in mechanically ventilated patients. This article seeks to clarify the issues surrounding the use of invasive fiberoptic bronchoscopic techniques in the diagnosis and treatment of nosocomial pneumonia.

Bronchoalveolar Lavage↗
PubMed2000

Nitric oxide-dependent neutrophil recruitment: role in nasal secretion.

Leukotriene B4 (LTB4), an inflammatory mediator, is a potent chemoattractant for neutrophils that plays an important role in nasal secretion via release of elastase. Nitric oxide (NO) is an important modulator of leucocyte-endothelial cell interactions, endogenously produced in large quantities in the paranasal sinuses. To examine the role of NO in LTB4-stimulated nasal secretion. A newly-developed method for isolating and superfusing a nasal segment in dogs was used. Instillation of LTB4 into the nasal segment caused a time-dependent increase in the volume of airway fluid and in the recruitment of neutrophils. N(G)-nitro-L-arginine-methylester (L-NAME), an inhibitor of NO synthase, prevented LTB4-induced neutrophil recruitment and nasal secretion. These studies show that NO modulates LTB4-induced neutrophil recruitment and subsequent fluid secretion in the nose, and they suggest a therapeutic role for NO inhibitors in modulating neutrophil-dependent nasal secretion.

Animals↗
PubMed2000

Nasal secretion in ragweed-sensitized dogs: effect of leukotriene synthesis inhibition.

Allergic rhinitis is an inflammatory disease associated with local leukotriene release during periods of symptoms. Zileuton, a leukotriene synthesis inhibitor, is known to inhibit the release of leukotriene B4. Because we previously showed that leukotriene B4 is a potent mediator of neutrophil-dependent nasal secretion, we investigated whether Zileuton inhibited allergen-induced nasal secretion. Using a newly developed method for isolating and superfusing a nasal segment, we examined the effect of Zileuton on nasal secretion and neutrophil recruitment in ragweed-sensitized dogs. Instillation of ragweed into the nasal segment caused time-dependent increases in the volume of airway fluid and the recruitment of neutrophils. Zileuton prevented ragweed-induced neutrophil recruitment and nasal secretion. These results indicate that leukotrienes are important mediators of allergy-induced nasal secretion in dogs. Future clinical studies in allergic patients will determine whether there is a therapeutic role for leukotriene synthesis inhibitors in modulating neutrophil recruitment and hypersecretion in the nose.

Animals↗
PubMed1999

Epidermal growth factor system regulates mucin production in airways.

Goblet-cell hyperplasia is a critical pathological feature in hypersecretory diseases of airways. However, the underlying mechanisms are unknown, and no effective therapy exists. Here we show that stimulation of epidermal growth factor receptors (EGF-R) by its ligands, EGF and transforming growth factor alpha (TGFalpha), causes MUC5AC expression in airway epithelial cells both in in vitro and in vivo. We found that a MUC5AC-inducing epithelial cell line, NCI-H292, expresses EGF-R constitutively; EGF-R gene expression was stimulated further by tumor necrosis factor alpha (TNFalpha). EGF-R ligands increased the expression of MUC5AC at both gene and protein levels, and this effect was potentiated by TNFalpha. Selective EGF-R tyrosine kinase inhibitors blocked MUC5AC expression induced by EGF-R ligands. Pathogen-free rats expressed little EGF-R protein in airway epithelial cells; intratracheal instillation of TNFalpha induced EGF-R in airway epithelial cells, and subsequent instillation of EGF-R ligands increased the number of goblet cells, Alcian blue-periodic acid-Schiff staining (reflecting mucous glycoconjugates), and MUC5AC gene expression, whereas TNFalpha, EGF, or TGFalpha alone was without effect. In sensitized rats, three intratracheal instillations of ovalbumin resulted in EGF-R expression and goblet-cell production in airway epithelium. Pretreatment with EGF-R tyrosine kinase inhibitor, BIBX1522, prevented goblet-cell production both in rats stimulated by TNFalpha-EGF-R ligands and in an asthma model. These findings suggest potential roles for inhibitors of the EGF-R cascade in hypersecretory diseases of airways.

Animals↗
PubMed1999

Role of neutrophil elastase in hypersecretion in asthma.

Goblet cell (GC) hyperplasia and mucous plugging are common in patients with acute asthma. These patients also show neutrophil recruitment into the airways. Neutrophils contain elastase, a potent secretagogue in airways. Therefore, it was reasoned that neutrophil recruitment, by releasing elastase, could result in GC hypersecretion. When neutrophil chemoattractants were instilled in the airways of guinea-pigs, time-dependent neutrophil recruitment and GC degranulation occurred. An inhibitor of leukocyte infiltration (NPC15669) prevented both responses, implicating neutrophils. An inhibitor of neutrophil elastase (ICI 200,355) abolished GC degranulation, implicating elastase. Further studies implicate movement of elastase from cytoplasmic granules to the neutrophil surface, and they suggest a role for adhesion molecules on neutrophils and on GCs in neutrophil-dependent GC degranulation. Similarly, instillation of ovalbumin (OVA) into airways of OVA-sensitized guinea-pigs caused early recruitment of neutrophils and GC degranulation. GC degranulation was prevented by pretreatment with NPC15669 or ICI 200,355. These results implicate neutrophil release of elastase in allergen-induced hypersecretion. The results suggest a mechanism for the mucous plugging that occurs in acute asthma; prevention of neutrophil recruitment, prevention of neutrophil-GC adhesion, or inhibition of elastase activity could provide effective therapy for this serious pathophysiological abnormality.

Animals↗
PubMed1999

LTB(4)-induced nasal gland serous cell secretion mediated by neutrophil elastase.

Local allergen challenge causes nasal hypersecretion and also causes local leukotriene (LT) release, including LTB(4). Because LTB(4) causes leukocyte recruitment, and because neutrophil elastase is a potent secretagogue, we examined the hypothesis that LTB(4) causes nasal hypersecretion via neutrophil elastase. We developed a method for isolating and superfusing a nasal segment in dogs. Instillation of LTB(4) into the nasal segment caused a time-dependent increase in the volume of airway fluid, in lysozyme secretion, and in the recruitment of neutrophils. ICI 200,355, a selective inhibitor of neutrophil elastase, prevented LTB(4)-induced nasal secretion and lysozyme secretion, but it had no effect on neutrophil recruitment. We conclude that LTB(4) causes potent nasal secretion via release of elastase, and therefore LTB(4) may play a major role in allergic nasal hypersecretion.

Animals↗
PubMed1998

Interleukin-8 expression in bronchoalveolar lavage cells in the evaluation of alveolitis in idiopathic pulmonary fibrosis.

Interleukin-8 (IL-8) is a neutrophilic chemotactic factor which may have a prominent role in the attraction of neutrophils to the lung in idiopathic pulmonary fibrosis (IPF). The objective of this study was to investigate the usefulness of IL-8 expression in bronchoalveolar lavage (BAL) cells in the evaluation of alveolitis in IPF. We analysed the BAL cell expression of IL-8 by immunocytochemistry in 19 patients with IPF (six smokers, three ex-smokers and ten non-smokers) and in a control group composed of 14 individuals (six smokers, eight non-smokers). In IPF, BAL was performed on both the pulmonary lobe with the most extensive involvement and the one less extensively involved on high-resolution computed tomography (HRCT) scans. The percentages and absolute numbers of BAL IL-8+ macrophages from lobes with the most extensive HRCT scan involvement (36 +/- 6% and (6 +/- 2 x 10(4) ml-1) (SE) and from those less extensively involved [26% +/- 4% and (6 +/- 1) x 10(4) ml-1] were significantly higher with respect to both those from healthy smokers [17% +/- 6% and (7 +/- 4) x 10(4) ml-1] and those from non-smokers [2% +/- 1% and (1 +/- 0.3) x 10(4) ml-1] (P = 0.005 and P = 0.001, respectively), without differences between the two lobes. In contrast, both the proportions and the absolute numbers of BAL neutrophils in IPF were significantly higher in lobes with the most extensively involved HRCT scan in comparison with lobes with the least extensive involvement [13% +/- 3%, (3 +/- 1) x 10(4) ml-1 vs. 8% +/- 2%, (1 +/- 0.3) x 10(4) ml-1, P = 0.05]. Moreover, the numbers of BAL neutrophils, but not those of IL-8+ macrophages, correlated with the extent of total pulmonary HRCT scan abnormalities in the most involved lobe (r = 0.64, P = 0.04). A correlation between neutrophils and IL-8+ cells was not observed. The results of this study suggest that, in IPF, BAL neutrophilia offers a better description of the disease inflammatory process than the expression of IL-8 in BAL cells.

Aged↗
PubMed1998

Neutrophil-dependent goblet cell degranulation: role of membrane-bound elastase and adhesion molecules.

We examined the effect of the neutrophil chemoattractants interleukin (IL)-8 and N-formyl-methionyl-leucyl-phenylalanine on goblet cell (GC) degranulation in guinea pigs. Chemoattractants caused time-dependent neutrophil recruitment and GC degranulation in vivo. NPC 15669 (an inhibitor of leukocyte infiltration) prevented both responses, implicating neutrophils. ICI 200,355 (an inhibitor of neutrophil elastase and proteinase-3) or secretory leukocyte protease inhibitor (an inhibitor of elastase but not of proteinase-3) abolished IL-8-induced GC degranulation, implicating elastase. Incubating tracheal segments with IL-8 plus neutrophils caused GC degranulation in vitro, an effect due to activation of the neutrophils themselves (and not an effect present in the supernatant). Chemoattractant increased surface staining of elastase and the cleavage of elastase-specific fluorogenic substrate by neutrophils. Pretreatment with anti-intercellular adhesion molecule-1, anti-CD18, or anti-CD11b antibody inhibited the chemoattractant-induced GC degranulation in vitro, implicating adhesion molecules. These studies suggest that chemoattractants cause neutrophil-dependent GC degranulation involving adhesive interactions between cells, with elastase activity occurring at the cell interface, causing GC secretion. The findings, reproduced in human airways, suggest novel methods of therapeutic intervention.

Animals↗
PubMed1998

Platelet-activating factor induces goblet cell hyperplasia and mucin gene expression in airways.

In patients dying from asthma, extensive mucous plugging occurs in the airways, associated with goblet cell hyperplasia. In this study, we examined the hypothesis that platelet-activating factor (PAF) induces goblet cell hyperplasia and mucin gene expression. After instilling PAF into the airways of guinea pigs and rats, we stained airway goblet cells with Alcian blue/periodic acid-Schiff and determined the number of goblet cells and percentage of stained area within the epithelium. In guinea pigs, one instillation of PAF (10(-)5 M, 100 microl) increased the goblet cell-stained area time-dependently, beginning at 24 h, maximum at 72 h. PAF also caused tracheal recruitment of eosinophils by 24 h, maximum at 48 h. In rats, which have few goblet cells in airways, PAF (3 instillations, 10(-)5 M, 200 microl) caused striking goblet cell hyperplasia, greatest in peripheral airways. Tumor necrosis factor alpha (TNFalpha) alone had no significant effect on goblet cells, but together with PAF, it caused exaggerated goblet cell hyperplasia. In rat tracheas studied by in situ hybridization, PAF induced mucin MUC5 gene expression in epithelial cells that stained for mucosubstances. In summary, PAF induces goblet cell hyperplasia and TNFalpha potentiates this effect.

Animals↗
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↗
PubMed1997

PACAP-induced plasma extravasation in rat skin.

The effects of pituitary adenylate cyclase activating peptide (PACAP) 38, PACAP 27 and vasoactive intestinal peptide (VIP) on plasma extravasation were investigated in vivo in rat skin. PACAP 38, PACAP 27 and VIP, caused concentration-dependent extravasation in rat skin. The order of potency was PACAP 38 > PACAP 27 = VIP, whereas the order of maximal induced extravasation was PACAP 38 = PACAP 27 > VIP, suggesting that PACAP 38 might be the most powerful inducer of plasma extravasation of the three tested members of the secretin-glucagon-VIP family. Substance P (SP) was about 5 times more potent than PACAP 38 and 15 times more potent than PACAP 27. These data indicate that PACAP 38 induced plasma extravasation in concentrations roughly equimolar to SP. Pyrilamine (H1 receptor antagonist) reduced the PACAP 38-induced plasma extravasation more than 50%; cimetidine (H2 receptor antagonist) was without effect. To investigate whether a cAMP-mediated process is involved in the induction of plasma extravasation, the synthetic adenosine 3',5'-cyclic monophosphate (cAMP), dibutyryl adenosine cyclic monophosphate (DBcAMP) and the cAMP-inducing drug, salbutamol, were each injected in the skin; neither of these drugs caused extravasation. We conclude that PACAP 38 and PACAP 27 cause potent plasma extravasation which, at least in part, involves histamine release.

Albuterol↗
PubMed1997

Bacterial colonization of distal airways in healthy subjects and chronic lung disease: a bronchoscopic study.

In contrast to the healthy population, distal airway bacterial colonization may occur in patients with chronic lung diseases, who often have altered pulmonary defences. However, the information dealing with this issue is insufficient and is based mainly on nonspecific samples, such as sputum cultures. Using quantitative cultures of bronchoscopic protected specimen brush (PSB) and bronchoalveolar lavage (BAL) samples, we studied the bacterial colonization of distal airways in 16 healthy subjects, 33 patients with bronchogenic carcinoma, 18 with chronic obstructive pulmonary disease (COPD), 17 with bronchiectasis, and 32 with a long-term tracheostomy due to laryngeal carcinoma. All patients were without exacerbation, and free from antibiotic treatment at least 1 month before the study protocol. Thresholds for quantitative cultures to define colonization were > or = 10(2) colony-forming units (cfu) x mL(-1) for PSB and > or = 10(3) cfu x mL(-1) for BAL. Only one healthy subject was colonized by a potential pathogenic microorganism (PPM) (Staphylococcus aureus 4x10(2) cfu x mL(-1) in a PSB culture). Colonization was observed in 14 (42%) bronchogenic carcinoma patients (19 non-PPMs, and 10 PPMs); in 15 (83%) COPD patients (22 non-PPMs and 7 PPMs); in 15 (88%) bronchiectasis patients (20 non-PPMs and 13 PPMs); and in 15 (47%) long-term tracheostomy patients (5 non-PPMs and 13 PPMs). The two most frequent non-PPMs isolated in all groups studied were Streptococcus viridans and Neisseria spp. Haemophilus spp., Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis were the most frequent PPMs isolated in bronchogenic carcinoma, COPD, bronchiectasis and long-term tracheostomized patients, respectively. Pseudomonas aeruginosa colonization was infrequent in all the groups. Our results show that distal airway bacterial colonization is a frequent feature in stable patients with chronic lung diseases and also in patients with long-term tracheostomy. However, the pattern of colonization differs among groups studied. The knowledge of different colonization patterns may be important for future antibiotic prophylactic strategies and for the empirical antibiotic regimens when exacerbations occur in these patients.

Adult↗
PubMed1995

Diffuse alveolar hemorrhage in allogeneic bone marrow transplantation. A postmortem study.

To define better the syndrome of diffuse alveolar hemorrhage (DAH), we conducted a postmortem study in 77 patients who died of pulmonary complications, distributed into three groups. Group A included 47 patients with hematologic diseases treated with allogeneic bone marrow transplant (BMT); Group B, 20 patients with hematologic diseases treated with conventional chemotherapy; and Group C, 10 patients without hematologic diseases. The diagnosis of DAH was established when there was blood in at least 30% of the lung tissue evaluated without evidence of infection or any other pathologic change that could account for its presence. The presence of an associated pulmonary complication was considered only when there was normal lung parenchyma between both blood and the specific lesions. Diffuse alveolar hemorrhage was shown in 11 patients in Group A (23%) compared with 1 patient in Group B (5%) (p < 0.05). Of the 11 patients with DAH in Group A, 10 had some associated pulmonary complication: 7 presented with diffuse alveolar damage (DAD), 2 with associated bacterial pneumonia and 1 with invasive aspergillosis, 2 others had an associated cytomegalovirus (CMV) pneumonitis, and the remaining patients had an associated herpes pneumonia. There were no clinical differences between patients with and without DAH. Of 8 patients with confirmed DAH in Group A, who had been submitted to a bronchoscopic examination within 1 wk of death, 4 had normal BAL fluid; by contrast, 7 of 13 patients without DAH had hemorrhagic BAL fluid.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Role of bronchoalveolar lavage in the diagnosis of fat embolism syndrome.

Fat embolism syndrome (FES) is a serious clinical disorder occurring in trauma patients. The diagnosis of fat embolism syndrome may be difficult to establish clinically. We therefore wanted to investigate the usefulness of bronchoalveolar lavage (BAL) in the diagnostic evaluation of fat embolism syndrome. We analysed the presence of fat droplets in BAL cells in 32 trauma patients (7 with full diagnostic criteria of fat embolism syndrome, 17 with incomplete diagnostic criteria, and 8 with no diagnostic criteria at the time of bronchoscopy), 9 nontrauma patients with acute respiratory failure and radiographic pulmonary infiltrates, and a control group composed of 10 individuals. An increased percentage of oil red O positive alveolar macrophages (cut-off point > 3%) in BAL was found in 6 out of 7 patients with definite clinical criteria of fat embolism syndrome, and in 6 out of 20 trauma patients without the clinical diagnosis of fat embolism syndrome. In two patients with fat embolism syndrome, sequential BAL showed that the percentage of positive macrophages decreased when the clinical manifestations disappeared. An increased number of BAL macrophages with fat droplets was also observed in two trauma patients without evidence of fat embolism syndrome after long-bone surgical intervention. By contrast, all non-trauma patients had a percentage of positive cells lower than 3%. Our findings suggest that BAL oil red O positive macrophages are frequently observed in trauma patients irrespective of the presence of fat embolism syndrome. Conceivably, a high number of oil red O positive macrophages could reflect clinically silent fat embolization.

Adult↗