[Inflammatory response in pneumonia: are glucocorticosteroids useful?].
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Anti-Bacterial Agents↗
Biomedical subjects
C Agustí
Publications and source records attributed to C Agustí.
Short-term effect of the application of selective decontamination of the digestive tract on different body site reservoir ICU patients colonized by multi-resistant Acinetobacter baumannii.
The effect of a selective decontamination of the digestive tract (SDD) regimen including polymyxin and tobramycin on several body site reservoirs was compared between a test group and a control group in intensive care unit (ICU) patients with faecal multi-resistant Acinetobacter baumannii colonization. SDD significantly reduced faecal and pharyngeal carriage when compared with the control group at the end of ICU stay (48% versus 91%, P = 0.001, and 38.5% versus 78%, P = 0.01, respectively), but failed to reduce axillary colonization (75% versus 78%, P = 0.6). In addition, the isolation of A. baumannii from new clinical samples was lower in patients with SDD (45.5% versus 81%, P = 0.05). No resistance to polymyxin was observed. We conclude that the digestive tract reservoir of A. baumannii in ICU patients may be decreased by a SDD regimen.
Acinetobacter↗
Bacterial colonisation in patients with bronchiectasis: microbiological pattern and risk factors.
BACKGROUND: A study was undertaken to investigate the incidence, diagnostic yield of non-invasive and bronchoscopic techniques, and risk factors of airway colonisation in patients with bronchiectasis in a stable clinical situation. METHODS: A 2 year prospective study of 77 patients with bronchiectasis in a stable clinical condition was performed in an 800 bed tertiary university hospital. The interventions used were pharyngeal swabs, sputum cultures and quantitative protected specimen brush (PSB) bacterial cultures (cut off point > or =10(2) cfu/ml) and bronchoalveolar lavage (BAL) (cut off point > or =10(3) cfu/ml). RESULTS: The incidence of bronchial colonisation with potential pathogenic microorganisms (PPMs) was 64%. The most frequent PPMs isolated were Haemophilus influenzae (55%) and Pseudomonas spp (26%). Resistance to antibiotics was found in 30% of the isolated pathogens. When the sample was appropriate, the operative characteristics of the sputum cultures were similar to those obtained with the PSB taken as a gold standard. Risk factors associated with bronchial colonisation by PPMs in the multivariate analysis were: (1) diagnosis of bronchiectasis before the age of 14 years (odds ratio (OR)=3.92, 95% CI 1.29 to 11.95), (2) forced expiratory volume in 1 second (FEV1) <80% predicted (OR=3.91, 95% CI 1.30 to 11.78), and (3) presence of varicose or cystic bronchiectasis (OR=4.80, 95% CI 1.11 to 21.46). CONCLUSIONS: Clinically stable patients with bronchiectasis have a high prevalence of bronchial colonisation by PPMs. Sputum culture is a good alternative to bronchoscopic procedures for evaluation of this colonisation. Early diagnosis of bronchiectasis, presence of varicose-cystic bronchiectasis, and FEV1 <80% predicted appear to be risk factors for bronchial colonisation with PPMs.
Adolescent↗
[Diagnosis of hemoptysis: is there a real argument?].
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Hemoptysis↗
Bronchial inflammation and colonization in patients with clinically stable bronchiectasis.
To evaluate the bronchial inflammatory response and its relationship to bacterial colonization in bronchiectasis, we performed a bronchoalveolar lavage (BAL) in 49 patients in stable clinical condition and in nine control subjects. BAL was processed for differential cell count, quantitative bacteriologic cultures, and measurement of inflammatory mediators. An increase was observed in the percentage of neutrophils (37 [0 to 98]) (median[range]) versus 1[0 to 4]%, p = 0.01), in the concentration of elastase (90.5 [8 to 2,930] versus 34 [9 to 44], p = 0.03), myeloperoxidase (9.1 [0 to 376] versus 0.3 [0.1 to 1.4], p = 0.01), and in the levels of TNF-alpha (4 [0 to 186] versus 0 [0 to 7], p = 0.03), IL-8 (195 [0 to 5,520] versus 3 [0 to 31], p = 0.001), and IL-6 (6 [0 to 115] versus 0 [0 to 3], p = 0.001) in patients with bronchiectasis compared with control subjects. Noncolonized patients showed a more intense bronchial inflammatory reaction than did control subjects. This inflammatory reaction was exaggerated in patients colonized by microorganisms with potential pathogenicity (MPP), with a clear relationship with the bronchial bacterial load. Patients with bronchiectasis showed a slight systemic inflammatory response, with poor correlations between systemic and bronchial inflammatory mediators, suggesting that the inflammatory process was mostly compartmentalized. We conclude that patients with bronchiectasis in a stable clinical condition present an active neutrophilic inflammation in the airways that is exaggerated by the presence of MPP, and the higher the bacterial load the more intense the inflammation.
Bacterial Infections↗
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↗
Pulmonary infiltrates in HIV-infected patients in the highly active antiretroviral therapy era in Spain.
OBJECTIVE: To study the incidence, etiology, and outcome of pulmonary infiltrates (PIs) in HIV-infected patients and to evaluate the yield of diagnostic procedures. DESIGN: Prospective observational study of consecutive hospital admissions. SETTING: Tertiary hospital. PATIENTS: HIV-infected patients with new-onset radiologic PIs from April 1998 to March 1999. METHODS: The study protocol included chest radiography, blood and sputum cultures, serologic testing for "atypical" causes of pneumonia, testing for Legionella urinary antigen, testing for cytomegalovirus antigenemia, and bronchoscopy in case of diffuse or progressive PIs. RESULTS: One hundred two episodes in 92 patients were recorded. The incidence of PIs was 18 episodes per 100 hospital admission-years (95% confidence interval [CI]: 15-21). An etiologic diagnosis was achieved in 62 cases (61%). Bacterial pneumonia (BP), Pneumocystis carinii pneumonia (PCP), and mycobacteriosis were the main diagnoses. The incidences of BP and mycobacteriosis were not statistically different in highly active antiretroviral therapy (HAART) versus non-HAART patients. The incidence of PCP was lower in those receiving HAART (p =.011), however. Nine patients died (10%). Independent factors associated with higher mortality were mechanical ventilation (odds ratio [OR] = 83; CI: 4.2-1,682), age >50 years (OR = 23; CI: 2-283), and not having an etiologic diagnosis (OR = 22; CI: 1.6-293). CONCLUSIONS: Pulmonary infiltrates are still a frequent cause of hospital admission in the HAART era, and BP is the main etiology. There was no difference in the rate of BP and mycobacteriosis in HAART and non-HAART patients. Not having an etiologic diagnosis is an independent factor associated with mortality.
Adult↗
Effects of bronchoalveolar lavage volume on arterial oxygenation in mechanically ventilated patients with pneumonia.
OBJECTIVE: To assess the effect of bronchoalveolar lavage (BAL) volume on arterial oxygenation in critically ill patients with pneumonia. DESIGN: Randomized clinical comparison. SETTING: Six-bed respiratory intensive care unit of a 850-bed tertiary care university hospital. PATIENTS: Thirty-seven intubated and mechanically ventilated patients with clinical suspicion of pneumonia. INTERVENTIONS: Bronchoscopically guided protected specimen brush (PSB) followed by either a "high volume" BAL (n = 16, protected catheter, mean volume: 131 +/- 14 ml) or a "low volume" BAL (n = 21, protected double-plugged catheter, 40 ml volume for all patients). MEASUREMENTS: Arterial oxygen tension/fractional inspired oxygen (PaO2/FIO2) and mean arterial pressure (MAP) before and up to 24 h after the intervention. Bacterial growth in quantitative cultures. Analysis of variance for repeated measurements with inter-subject factors. RESULTS: All patients showed a lower PaO2/FIO2 ratio and higher MAP after the diagnostic procedure, without differences between the study arms (p = 0.608 and p = 0.967, respectively). Patients with significant bacterial growth (p = 0.014) and patients without preemptive antibiotic (p = 0.042) therapy showed a more profound and longer decrease in arterial oxygenation after the diagnostic procedure. CONCLUSIONS: A decrease in the PaO2/FIO2 ratio was observed in all patients after a combined diagnostic procedure, independent of the BAL volume used. A significant bacterial burden recovered from the alveoli and no preemptive antibiotic therapy were associated with a larger and longer-lasting decrease in arterial oxygenation.
Analysis of Variance↗
Induced sputum in the diagnosis of peripheral lung cancer not visible endoscopically.
The diagnosis of small peripheral lung cancer is difficult to achieve by non-invasive methods. We hypothesized that in these patients induced sputum might ncrease the diagnostic yield over spontaneous sputum, representing a good diagnostic alternative in selected patients. We prospectively evaluated 60 patients with peripheral lung lesions and normal bronchoscopic evaluation. Six samples of sputum (three spontaneous and three induced with nebulization of hypertonic saline) before bronchoscopy and six samples of sputum after bronchoscopy (three spontaneous and three induced) were obtained in each subject. Forty-two out of the 60 patients included were finally diagnosed with lung cancer. Eighteen patients were diagnosed with different benign conditions of the lung. Overall, malignant cells in sputum were observed in 21 patients and in all but one, the final diagnosis of lung cancer was achieved. Only one patient with a pseudoinflammatory tumour of the lung had a false-positive result in one spontaneous sputum sample. The diagnosis of lung cancer was obtained in 18 patients with the induced sputum (43%) and in 14 patients with spontaneous sputum (31%) (P=NS). Samples of induced sputum were more adequate for cytological analysis than samples of spontaneous sputum (P < 0.001). Of 13 patients with peripheral lung neoplasms of 2 cm or less in diameter, five were diagnosed using induced sputum (38%) and only one using spontaneous sputum (8%) (P<0.05). In conclusion, induced sputum is a valuable technique for the diagnosis of peripheral lung cancer. Induced sputum gives better quality specimens and better diagnostic yield in small lesions than the spontaneous sputum and may be indicated in selected patients with disseminated disease, inoperability or severe co-morbities.
Adenocarcinoma↗
Bronchiectasis.
Bronchiectasis is a structural derangement of the bronchial wall that is characterized by airway dilatation and bronchial wall thickening. As a result of this abnormality, chronic inflammation and secondary microbial infections occur, which cause additional damage to the bronchi. Recent insights into the potential pathophysiological mechanisms of bronchiectasis, as well as improvements in computed tomography and the development of new pharmacological agents, might help to improve the clinical management of this chronic infective/inflammatory disorder.
Bronchiectasis↗
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↗
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↗
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↗
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↗
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↗
Bronchiolitis obliterans organizing pneumonia. Trying to answer an intriguing question.
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Cryptogenic Organizing Pneumonia↗
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↗
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↗