Julia Valls González

Airway inflammation and bronchial microbial patterns in patients with stable chronic obstructive pulmonary disease

The effect of bacterial colonization of the bronchi on the progress of airflow limitation is not well known. Therefore, the pattern of airway inflammation in smokers and patients with stable chronic obstructive pulmonary disease (COPD) and its relation to bronchial microbial colonization was assessed. Eight nonsmoking and 18 smoking controls as well as 52 patients with COPD (28 mild, 11 moderate and 13 severe) were studied. All subjects were investigated by means of flexible bronchoscopy including protected specimen brush and bronchoalveolar lavage (BAL) sampling. Differential cell counts, cytokine (interleukin (IL)-1beta, IL-6, IL-8, IL-10 and tumour necrosis factor-alpha(TNF-alpha) concentrations and microbial patterns were determined in BAL fluid. Forced expiratory volume in one second (FEV1) % of the predicted value was inversely correlated with pack-yrs of cigarette smoking (r=-0.47, p<0.0001), the percentage of neutrophil (p=-0.56, p<0.0001) and IL-6 (p=-0.37, p=0.01) and IL-8 concentration (p=-0.43, p=0.004) in BAL fluid. Accordingly, pk-yrs of cigarette smoking (p=0.39, p=0.01) and IL-8 (p=0.69, p<0.0001) and TNFalpha (p=0.4, p<0.005) were positively correlated with the percentage of neutrophils in BAL fluid. Smoking controls and COPD patients were mainly colonized in the bronchial tree (33%) by community endogenous potentially pathogenic micro-organisms (PPMs). Colonization rates and patterns of PPMs were not affected by severity of airflow obstruction. The presence of PPMs was significantly associated with higher percentages of neutrophils (33.2+/-10.4% versus 10.1+/-3.5%, p=0.02) and TNF-alpha concentration (29.9+/-10.8 versus 6.3+/-2.1 pg x mL(-1), p=0.01) in BAL fluid. In conclusion, bronchial neutrophilia is a key inflammatory pattern in chronic obstructive pulmonary disease patients. Bronchial colonization with potentially pathogenic micro-organisms may represent an independent stimulus for additional airway inflammation.

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.

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 ≥102 cfu/ml) and bronchoalveolar lavage (BAL) (cut off point ≥103 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.

Rapid urinary antigen test for diagnosis of pneumococcal community-acquired pneumonia in adults

Streptococcus pneumoniae is suspected to cause an important proportion of community-acquired pneumonia (CAP) whose aetiology cannot be detected with conventional tests. In this study, the authors evaluated the diagnostic yield of a new immunochromatographic membrane test (ICT) for the detection of the S. pneumoniae antigen in the urine of patients admitted with diagnosed CAP. ICT was performed in unconcentrated and concentrated urine from all the patients. ICT was repeated 1 month after discharge in a group initially testing positive. The authors also studied the ICT in clinically stable human immunodeficiency virus type 1 (HIV1)-infected patients. S. pneumoniae antigen was detected in all of the 68 (100%) patients tested with definitive pneumococcal pneumonia. In five of these cases ICT was only positive when it had been performed on the patients. The S. pneumoniae antigen was also detected in 36 (69.2%) of 52 patients with probable pneumococcal pneumonia and in 50 of 277 (18%) patients without pneumococcal pneumonia. ICT remained positive in 16 (69.5%) of 23 patients, 1 month after hospital discharge. Nasopharyngeal colonisation with S. pneumoniae was detected in 8 (12%) of 68 clinically stable HIV1 infected patients, but none tested ICT positive. The Binax NOW® immunochromatographic membrane test is a rapid, sensitive and specific test for detecting pneumococcal community-acquired pneumonia in adults. The test may remain positive for several weeks after pneumococcal pneumonia.

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), andPseudomonas 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.

Utility of Selective Digestive Decontamination in Mechanically Ventilated Patients

Nosocomial pneumonia is a frequent complication of prolonged mechanical ventilation [1-3]. Oropharyngeal and gastric colonization, because of potentially pathogenic microorganisms and their subsequent aspiration to the lower airways, play a substantial role in the pathogenesis of ventilator-associated nosocomial pneumonia [4, 5]. Selective digestive decontamination has been widely used as a prophylactic regimen for ventilator-associated nosocomial pneumonia. The first to describe this complication, Stoutenbeek and colleagues [6] suggested that the best combination for preventing nosocomial pneumonia was the use of topical nonabsorbable antibiotics in the oropharynx and stomach together with systemic antibiotics. Most studies have shown a substantial decrease in the carriage of gram-negative bacilli of the upper and lower airways and also in the incidence of nosocomial pneumonia [7, 8], and a few studies have shown a substantial decrease in the overall mortality rate [9-11]. Several important considerations in most of the studies still make selective digestive decontamination a controversial issue. First, several studies were not randomized or used historical controls [6, 12-19]. Second, most of the randomized studies used only nonspecific methods to diagnose nosocomial pneumonia [9, 11, 20-28]. Finally, despite the apparent decrease in the incidence of nosocomial pneumonia, mortality did not change in most of the studies [12-28], including two recent randomized and double-blind studies [29, 30] of a large population sample of patients in an intensive care unit. We did a randomized, double-blind study of selective digestive decontamination in a general population of patients requiring mechanical ventilation. The main end points of this study were to assess the effect of selective digestive decontamination in decreasing nosocomial pneumonia and mortality. Additional end points of this study were to determine the effect of selective digestive decontamination on the morbidity (length of stay and duration of mechanical ventilation) and the mortality rate. Methods Patients The study was done in the Respiratory Intensive Care Unit of the Hospital Clinic of Barcelona, Spain, a 1000-bed teaching hospital, during a period of 12 months. All mechanically ventilated patients admitted to the respiratory intensive care unit and expected to remain intubated for more than 3 days were included in the study. The only exclusion criterion was the presence of immunosuppression (human immunodeficiency virus [HIV] infection, HIV-related diseases, patients who received transplants, and patients treated with antineoplastic chemotherapy). Patients who were extubated or who died before receiving 72 hours of selective digestive decontamination or placebo were also excluded from the analysis. Study Design Patients were randomly allocated to either the selective digestive decontamination or the placebo group. The randomization was done using a computer-generated table, and the patients were enrolled consecutively. Severity of illness was evaluated by means of the Simplified Acute Physiologic Score after randomization. The authors of the study were blinded in the recovery of the results. The study ended after extubation or death of the patient in the intensive care unit. Administration of Antibiotics After samples for the bacteriologic assessment were obtained, antibiotics were administered for selective digestive decontamination. An aqueous suspension of 10 mL containing polymyxin E, 100 mg (Dumex; Dumex Limited, Denmark); tobramycin, 80 mg (Tobradistin; Dista SA, Madrid, Spain); and amphotericin B, 500 mg (Fungizona; Squibb Industria Farmaceutica SA, Madrid) was administered through a nasogastric tube to patients in the selective digestive decontamination group. Carboxymethyl-cellulose with pectin and with gelatin (0.5 mL, Orabase; Drogfesa, Mollet del Valles, Spain) containing polymyxin E, tobramycin, and amphotericin B, at 2% concentration, was applied four times a day. In the placebo group, an aqueous suspension of Maxipro (Scientific Hospital Supplies Limited, Liverpool, United Kingdom) and Orabase, both colored with tartrazine, were administered through the nasogastric tube and in the oropharynx at the same dosage as for patients who received selective digestive decontamination. Systemic Antibiotic and Stress Ulcer Prophylaxis Patients were treated with 2 g of intravenous cefotaxime four times a day (Primafen, Hoechst Iberica SA, Barcelona, Spain) for the first 4 days of mechanical ventilation if they did not have infection on admission. Infected patients who were admitted to the intensive care unit received other parenteral antibiotics according to clinical decisions. Prophylaxis for stress ulcers was done using 1 g of sucralfate every 4 hours (Urbal; Merck-Igoda SA, Mollet del Valles) through a nasogastric tube, except in patients with paralytic ileus or with upper gastrointestinal bleeding, who were treated with 50 mg of intravenous ranitidine, four times a day (Zantac; Glaxo SA-Allen Farmaceutica SA, Madrid). Bacteriologic Assessment Endotracheal aspirates, pharyngeal swabs, and gastric juice samples were obtained three times a week for quantitative cultures. Endotracheal aspirate samples were obtained by means of sterile tubes (Mocstrap; Productes Clinics, SA, La Llagosta, Barcelona). Samples obtained were diluted and homogenized in distilled water to 1/2 concentration using a vortex-style shaker (Reax 2000; Heidolph, Germany) and were rediluted in distilled water to 1/20 and 1/200 concentrations. Pharyngeal swabs were obtained using sterile swabs with Amies transport media (Eurotubo; Industrias Aulabor SA, Barcelona), were homogenized in 1 mL of distilled water, and were diluted to concentrations of 1/10, 1/102, and 1/103. Gastric juice samples were obtained by aspiration through a nasogastric tube using a sterile feeding syringe. The pH was determined in all the samples using paper indicators (Acilit, pH 0 to 6 and Spezialindikator, pH 6.5 to 10; Merck, Darmstadt, Germany). The samples were homogenized using a vortex-style shaker and were diluted in distilled water to concentrations of 1/10 and 1/100. All samples were plated on the following agar media: blood; chocolate; McConkey-2; buffered, charcoal, and yeast extract (BCYEa); Sabouraud-dextrose; Sabouraud with nalidixic acid; and blood with nalidixic acid. If negative, the plates were discarded after 5 days of testing for aerobic bacteria, after 10 days of testing for Legionella and anaerobic bacteria, and after 4 weeks of testing for fungi. If positive, counts of colony-forming units per milliliter and identification using standard methods [31] were done for the microorganisms. Definitions Potentially pathogenic microorganisms were defined [32] as those causing infection in a person with impaired defense mechanisms. They can be classified into community microorganisms, which cause infections in previously healthy persons with intact carriage defense, and nosocomial microorganisms, which cause infections in persons with impaired carriage defense. Colonization was defined as the isolation of the same strain of a potentially pathogenic microorganism from at least two consecutive surveillance samples in any concentration. The clinical diagnosis of pneumonia was based on the presence of all of the following criteria: new or progressive pulmonary radiologic infiltrate or both for 48 hours or more, purulent tracheal secretions, temperature of 38.5 C or more, and leukocytosis ( 12 109/L) or leukopenia ( 4 109/L). The diagnosis of pneumonia was confirmed by the isolation of a potentially pathogenic microorganism in a protected specimen brush sample in concentrations of 103 CFU/mL or more or in a bronchoalveolar lavage sampling in concentrations of 104 CFU/mL or more [33]. We defined definite pneumonia when all the clinical criteria and one bacteriologic criterion were present or by the presence of histologic signs of pneumonia at autopsy. Probable pneumonia was defined when only clinical criteria were present. Primary endogenous pneumonia was diagnosed when pneumonia developed within the first 4 days of mechanical ventilation and when etiologic microorganisms were isolated previously or concomitantly in pharyngeal swabs or in gastric juice. Secondary endogenous pneumonia was pneumonia that developed after the fourth day of mechanical ventilation. Exogenous pneumonia was diagnosed when the etiologic microorganism was not isolated in pharyngeal swabs or in gastric juice before the development of pneumonia. Community flora was defined as the isolation of normal buccal flora (Neisseria species, Streptococcus viridans, among others), Streptococcus pneumoniae, or Haemophilus influenzae. A catheter-related infection was diagnosed when inflammatory signs occurred in a catheterized blood vessel together with a temperature of 38.3 C or more, irrespective of the isolation of a potentially pathogenic microorganism in the culture of the removed catheter. Likewise, this diagnosis was considered if the fever improved within 12 hours after removing the catheter. A urinary tract infection was diagnosed after fresh-voided catheter urine containing five or more leukocytes per high-power light-microscopic field were identified and a potentially pathogenic microorganism was isolated in urine culture in concentrations of 105 CFU/mL or more. A wound infection was diagnosed if purulent secretions from wounds occurred with signs of inflammation and the isolation of a potentially pathogenic microorganism in concentrations of 105 CFU/mL or more from the purulent wound secretions. Septicemia was diagnosed if clinical signs of systemic infection occurred, such as fever, leukocytosis, increased percentage of band forms, and metabolic acidosis, combined with a positive blood culture. Multiple organ system failure was defined as three or more organ systems failing for more than 2 consecutive days. Infection-relat

Histopathologic and Microbiologic Aspects of Ventilator-associated Pneumonia

BackgroundThe relationship between microbiology and histology in patients with ventilator-associated pneumonia has been sparsely described.MethodsTwenty-five patients who died in the intensive care unit after their lungs had been mechanically ventilated for 72 h were studied. Twenty of the 25 died w

Value of intracellular bacteria detection in the diagnosis of ventilator associated pneumonia.

BACKGROUND: Markers of ventilator associated pneumonia are of interest for confirming the diagnosis and for guiding the initial management of this frequent complication of mechanical ventilation. The detection of intracellular organisms in the polymorphonuclear leucocytes (PMNLs) and/or macrophages of bronchoalveolar lavage (BAL) fluid has been suggested as a specific test for the early indication of an infectious pulmonary process. METHODS: The diagnostic value of detecting intracellular organisms in two types of BAL fluid--protected (P-BAL) and conventional (C-BAL)--in 25 patients who died in one unit was prospectively studied. Immediately after death both P-BAL and C-BAL were performed bilaterally. Through a minithoracotomy on both sides of the chest bilateral bronchoscopically guided open lung biopsy samples were obtained from the same area, and an average of eight open lung blind biopsy samples (not bronchoscopically guided) were taken from each lung for histological examination. BAL fluid was examined for quantitative cultures (threshold 10(4) cfu/ml) and for the presence of intracellular organisms and extracellular organisms, and differential cell counts were also performed. RESULTS: Using the histopathology of the bronchoscopically guided open lung biopsies as the gold standard, detection of intracellular organisms in P-BAL (> or = 5%) and C-BAL (> or = 5%) fluids yielded 75% and 57% positive predictive values, and 83% negative predictive values, respectively. Prior treatment with antibiotics decreased the positive and negative predictive values of intracellular organism detection for both types of BAL fluid. The presence of intracellular organisms was correlated with the quantitative cultures of P-BAL and C-BAL samples. Quantitative cultures from P-BAL fluid were less sensitive (22% versus 45%) and more specific (100% versus 55%) than those from C-BAL samples. The percentage of extracellular organisms and the differential cell count in P-BAL and C-BAL samples could not discriminate between the presence or absence of pneumonia. CONCLUSIONS: The presence of > or = 5% intracellular organisms infecting PMNLs or macrophages in P-BAL or C-BAL fluids is a specific marker of ventilator associated pneumonia.

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.

Bronchial bacterial colonization in patients with resectable lung carcinoma.

The pattern and clinical implications of bronchial bacterial colonization have been widely investigated in patients with chronic lung disease, particularly chronic obstructive pulmonary disease. The main aim of this study was to determine the frequency and risk factors for bronchial colonization in lung cancer patients who have undergone surgical resection. Forty-one patients with resectable lung cancer (22 (54%) active smokers, 52±23 pack-yrs) with a mean forced expiratory volume in one second of 80±16% predicted, were studied with bilateral protected specimen brush and lung tissue biopsy during the surgical procedure. Quantitative bacterial culture, susceptibility tests and histological examination of samples were performed. Bronchial colonization with ⩾1 potential pathogenic micro-organism was found in 17 of 41 (41%) patients. The most frequent strains isolated were: Haemophilus influenzae (35%), Streptococcus pneumoniae (13%) and Pseudomonas spp. (9%). The risk factors for bronchial colonization were central location of the tumour (odds ratio (OR)=9.2, confidence interval (CI) 95%=2.1–39.6, p=0.003) and increased body mass index (OR=1.6, CI 95%=1.2–2.2, p=0.005). The frequency of postoperative infectious pulmonary complications was low (five cases (12%)) and no relationship was observed with bronchial colonization. Patients with resectable lung carcinoma had a high rate of bronchial colonization (41%), mainly with potential pathogenic microorganisms. The independent risk factors for colonization in these patients were central location of the tumour and a high body mass index.