Search

Polymorphonuclear neutrophils (PMN) are involved in the pathogenesis of acute lung injury (ALI), secreting numerous mediators such as proteases, reactive oxygen species, and cytokines. Because we had recently observed the ability of normal human PMN to degranulate and synthesize oncostatin M (OSM), an IL-6-family cytokine, we quantified OSM production ex vivo by highly purified blood and alveolar PMN from 24 ventilated patients with ALI, including some patients with severe pneumonia. Most of the patients had no detectable OSM in plasma, and OSM production by cultured blood PMN was similar to that of healthy controls. However, OSM was present in bronchoalveolar lavage (BAL) fluid supernatant, with significantly higher levels during pneumonia. In addition, alveolar OSM levels correlated with the number of PMN obtained by BAL, suggesting that PMN are an important source of OSM within the alveoli. Indeed, purified alveolar PMN from all of the patients, especially those with pneumonia, strongly produced OSM. Interestingly, in the latter patients, alveolar PMN always produced more OSM than autologous blood PMN. These results document the functional duality of PMN in ALI by showing the participation of PMN in the modulation of lung inflammation.

To determine risk factors for ventilator-associated pneumonia (VAP) caused by potentially drug-resistant bacteria such as methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii, and/or Stenotrophomonas maltophilia, 135 consecutive episodes of VAP observed in a single ICU over a 25-mo period were prospectively studied. For all patients, VAP was diagnosed based on results of bronchoscopic protected specimen brush (> or = 10(3) cfu/ml) and bronchoalveolar lavage (> or = 10(4) cfu/ml) specimens. Seventy-seven episodes were caused by "potentially resistant" bacteria and 58 episodes were caused by "other" organisms. According to logistic regression analysis, three variables among potential factors remained significant: duration of mechanical ventilation (MV) > or = 7 d (odds ratio [OR] = 6.0), prior antibiotic use (OR = 13.5), and prior use of broad-spectrum drugs (third-generation cephalosporin, fluoroquinolone, and/or imipenem) (OR = 4.1). Distribution of the 245 causative bacteria was analyzed according to four groups defined by prior duration of MV (< 7 or > or = 7 d) and prior use or lack of use (within 15 d) of antibiotics. Although 22 episodes of early-onset VAP in patients receiving no prior antibiotics were caused by antibiotic-susceptible bacteria, 84 episodes of late-onset VAP in patients receiving prior antibiotics were mainly caused by potentially resistant bacteria. Differences in the potential efficacies (ranging from 100% to 11%) against microorganisms of 15 antimicrobial regimens were studied according to classification into these four groups. These findings may provide a more rational basis for selecting the initial therapy of patients suspected of having VAP.

Study Objective: To evaluate the role of quantitative cultures of BAL for diagnosing nosocomial pneumonia in mechanically ventilated patients., Design: Cohort study., Setting: Medical ICU, Hôpital Bichat, Paris, France, an academic tertiary care center., Patients: A total of 141 episodes of suspected lung infection in 84 consecutive patients mechanically ventilated for 48 h or more., Measurements and Results: Microbiologic findings obtained using BAL were compared with those obtained with protected specimen brush (PSB) samples and their operating characteristics were determined. The level of qualitative agreement between BAL and PSB specimen cultures was high, with 83% of the organisms isolated in PSB specimens being recovered simultaneously from BAL fluid. In addition, the results of quantitative BAL and PSB cultures were significantly correlated (rho = 0.46, p < 0.0001). Fifty-seven cases of pneumonia were diagnosed based on the following criteria: PSB sample yielding > or = 10(3) cfu/mL of at least one microorganism and/or > or = 5% of cells containing intracellular bacteria on direct examination of BAL. The operating characteristics of BAL fluid cultures were determined using different ways to report the results and over a range of values. The discriminative value of 10(4) cfu/mL was found to be an optimal threshold, with a sensitivity of 82% (95% confidence interval [CI], 76 to 88) and a specificity of 84.5% (95% CI, 79 to 90)., Conclusions: These results indicate that BAL fluid cultures can offer a sensitive and specific means to diagnose pneumonia in ventilated patients and may provide relevant information about the causative pathogens.

Although the pathogenesis of the acute respiratory distress syndrome (ARDS) is complex and poorly understood, several observations point to an important role of interactions between polymorphonuclear neutrophils (PMN) and cytokines in this process. We therefore studied certain parameters involved in PMN transendothelial migration (adhesion molecule expression and cytoskeletal organization) in patients with ARDS (n = 14) in comparison with other ventilated patients (n = 15). We found that in the basal state, both whole-blood PMN and alveolar PMN obtained by bronchoalveolar lavage (BAL) were activated, as shown by decreased L-selectin CD62L and increased beta 2 integrin CD11b expression, as well as decreased F-actin content. The degree of PMN activation increased with the degree of lung injury and with the levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-8 (IL-8). Moreover, the capacity of ex vivo stimulation of alveolar PMN by a bacterial peptide was low in ARDS and could partly account for the high susceptibility of these patients to lung infection. Therefore, ARDS-associated lung injury could be caused, at least in part, by inappropriate adhesion and transendothelial migration of proinflammatory cytokine-primed PMN.

There is ample experimental evidence that polymorphonuclear neutrophils (PMN) play a critical role in the pathogenesis of the adult respiratory distress syndrome (ARDS). Since interleukin-8 (IL-8) is a strong chemotactic factor for PMN, we measured IL-8 levels in plasma and bronchoalveolar lavage (BAL) fluid of 18 patients, 12 with ARDS and 6 with severe pneumonia uncomplicated by ARDS, all of whom had an increased number of PMN in BAL fluid. Seven healthy subjects served as controls. We found elevated levels of IL-8 in the alveolar spaces of all patients tested. Elevated BAL IL-8 levels were related to a fatal outcome and the presence of shock and correlated with a general clinical severity index (simplified acute physiological score). BAL fluid levels of IL-8 were significantly higher in patients with ARDS than in patients with pneumonia. In plasma, IL-8 levels were increased similarly in all patients and did not correlate with survival or the presence of shock. The BAL fluid-to-plasma ratio of IL-8 was significantly greater than that of tumor necrosis factor alpha, indicating higher local production of IL-8. Moreover, the presence of a primed subpopulation of blood PMN with respect to H2O2 production indicates that IL-8 may contribute to the neutrophil-mediated process in the pathogenesis of ARDS and pneumonia.

To gain further insight into the pathogenesis of the adult respiratory distress syndrome (ARDS), the authors studied possible relationships among the activation status of circulating polymorphonuclear neutrophils (PMN), cytokine levels, and the severity of lung injury in 31 patients: 15 with ARDS, 9 with severe pneumonia uncomplicated by ARDS, and 7 mechanically ventilated patients with neither ARDS nor pneumonia. Nine healthy subjects served as controls. Using flow cytometry, the authors identified a subpopulation of PMN with an increased capacity to generate hydrogen peroxide after stimulation ex vivo in all three patient groups; significantly higher values were found in those with ARDS. The PMN stimulation index, a reflection of the degree of hyperresponsiveness, correlated with elevated levels of tumor necrosis factor alpha (TNF-alpha) in plasma, and both spontaneous and lipopolysaccharide (LPS)-induced TNF-alpha production by cultured monocytes. These biological expressions of PMN activation and cytokine generation both correlated with indices of the severity of lung injury, but not with the overall clinical severity. In contrast, IL-6 and IL-1 beta showed little or no relationship with either the degree of lung injury or PMN hyperresponsiveness. We conclude that TNF alpha-primed PMN may play a major role in the pathogenesis of ARDS-associated lung injury.

Purpose: Although nosocomial pneumonia is a common problem in intubated and ventilated patients, previous studies have not clearly demonstrated that nosocomial pneumonia actually results in increased mortality or prolongs hospitalization of these patients. In an attempt to answer these questions, we have performed a cohort study in which patients who developed nosocomial pneumonia and control subjects were carefully matched for the severity of underlying illness and other important variables., Patients and Methods: Case patients were 48 ventilated patients with nosocomial pneumonia identified on the basis of results of protected specimen brush quantitative culture and identification of intracellular organisms in cells recovered by bronchoalveolar lavage. For matching cases and their respective controls, the following variables were used: age (+/- 5 years), Simplified Acute Physiologic Score (+/- 3 points), indication for ventilatory support, date of admission, and duration of exposure to risk., Results: Successful matching was achieved for 222 of 240 (92.5%) variables. The mortality rate in cases was 26 of 48 (54.2%) compared with 13 of 48 (27.1%) in controls. The attributable mortality was 27.1% (95% confidence interval [CI], 8.3% to 45.9%; p < 0.01) and the risk ratio for death was 2.0 (95% CI, 1.61 to 2.49). The mean length of stay was 34 days for cases and 21 days for controls (p < 0.02). In the case of pneumonia due to Pseudomonas or Acinetobacter species, the mortality rate was 71.4%, the attributable mortality was 42.8% (95% CI, 14.5% to 69.0%), and the risk ratio was 2.50 (95% CI, 1.31 to 4.61)., Conclusion: Pneumonias occurring in ventilated patients, especially those due to Pseudomonas or Acinetobacter species, are associated with considerable mortality in excess of that resulting from the underlying disease alone, and significantly prolong the length of stay in the intensive care unit.

To evaluate the accuracy of clinical judgment in the diagnosis and treatment of nosocomial pneumonia in ventilated patients, we studied 84 patients suspected of having nosocomial pneumonia because of the presence of a new pulmonary infiltrate and purulent tracheal secretions. We prospectively evaluated the accuracy of diagnostic predictions and therapeutic plans independently formulated by a team of physicians aware of all clinical, radiologic and laboratory data, including the results of Gram-stained bronchial aspirates. Definite (n = 51) or probable (n = 33) diagnoses could be established in all patients by strict histopathologic and/or bacteriologic criteria. Only 27/84 patients were diagnosed as having pneumonia. Organisms responsible for pneumonias were identified by quantitative cultures of samples obtained using a protected specimen brush or pleural fluid cultures. Four hundred eight predictions were made for the 84 studied patients. Clinical diagnoses for patients subsequently diagnosed as having pneumonia were accurate in 81/131 cases (62 percent). Furthermore, only 43/131 (33 percent) therapeutic plans proposed for these patients represented effective therapy. Common causes of inappropriate treatment included failure to diagnose pneumonia (50 plans), failure to effectively treat highly resistant organisms (21 plans), and failure to treat all organisms in cases of polymicrobial pneumonia (14 plans). Therapeutic plans formulated for patients without pneumonia included the unnecessary use of antibiotics in 45/277 cases (16 percent). These findings indicate that the use of clinical criteria alone does not permit the accurate diagnosis of nosocomial pneumonia in ventilated patients, and commonly results in inappropriate or inadequate antibiotic therapy for these patients.

To prospectively determine the bacteriologic and clinical efficacy of antimicrobial therapy for nosocomial bacterial pneumonia selected based upon information provided by cultures of protected specimen brush (PSB) samples obtained during bronchoscopy, 76 consecutive patients with ventilator-associated pneumonia were studied using follow-up quantitative PSB cultures obtained after 3 days of treatment. Of the 173 microorganisms initially present in the PSB samples, only 11 (6%) were not eradicated by antimicrobial therapy, including three recovered at high (> or = 10(3) cfu/ml) concentrations. Thirty-two emerging pathogens, including nine at high concentrations, were also detected; 26 of them (81%) were resistant to the initial antibiotics administered. Of the 76 patients included in the study, cultures of follow-up PSB samples identified 51 in whom the infection site in the lung was completely sterilized, 16 with low-grade infection, and only nine with persistent high-grade infection. Analysis of clinical outcome within the 15 days after the initiation of antimicrobial therapy demonstrated clinical improvement in 62 of 67 (93%) patients in whom the site of infection was contained by treatment as compared with four of 9 (44%) patients with persistent high-grade infection (p < 0.01). These data suggest that appropriate antimicrobial therapy for ventilator-associated pneumonia results in the control of the initial infection in 88% of the patients. However, an early superinfection caused by multiresistant pathogens can occur in a small subset of these patients. When follow-up PSB cultures were negative, an improved outcome was noted.

The optimal technique for diagnosing nosocomial bacterial pneumonia in critically ill patients cared for in the intensive care unit remains unclear, especially in the subgroup of patients requiring mechanical ventilation. An important advance has been the development of the protected specimen brush technique. We and others have demonstrated that secretions obtained using this technique and evaluated by quantitative cultures are useful in distinguishing patients with and without pneumonia. However, this procedure has important limitations in that results are not available immediately and in that a few false negative or false positive results may be observed. Recently, the use of bronchoalveolar lavage has been suggested to be of value in establishing the diagnosis of pneumonia, since the cells and liquid recovered can be examined microscopically immediately after the procedure and are also suitable for quantitative culture. We believe that microscopic identification of bacteria within cells recovered by lavage may provide a sensitive and specific means for early and rapid diagnosis of pneumonia in this setting and that the lavage technique can be conveniently incorporated into a protocol along with the quantitative culture of samples obtained using the protected specimen brush. This combination will probably improve the overall accuracy of diagnosis while allowing the administration of prompt empiric antimicrobial therapy in the majority of patients with pneumonia.

Purpose: To compare the usefulness of specimens recovered using a protected specimen brush and those recovered by bronchoalveolar lavage in the diagnosis of nosocomial pneumonia occurring in intubated patients undergoing ventilation, we performed both procedures in patients suspected of having pneumonia because of the presence of a new pulmonary infiltrate and purulent tracheal secretions., Patients and Methods: Twenty-one patients (16 men and five women) with an average age of 57 +/- 12 years were studied. They had been receiving mechanical ventilation for 8 +/- 6 days before inclusion in the trial. The clinical suspicion for nosocomial bacterial pneumonia was high in these patients. Fiberoptic bronchoscopy was performed in each patient. Bronchoscopy specimens were obtained by a protected specimen brush and by bronchoalveolar lavage, and were then processed for quantitative bacterial and fungal culture using standard methods. Total cell counts were performed on an aliquot of resuspended original lavage fluid. Differential cell counts were made on at least 500 cells. In addition, 300 cells were examined at high-power magnification and the percentage of cells containing intracellular microorganisms and the average number of extracellular organisms per oil-immersion field were determined., Results: Quantitative culture of specimens recovered using the protected specimen brush were positive (more than 10(3) colony-forming units [cfu]/ml) in five of five patients with subsequently confirmed pneumonia, and negative (less than 10(3) cfu/ml) in 13 of 13 patients without bacterial pneumonia, but results were not available until 24 to 48 hours after the procedure. Quantification of intracellular organisms in cells recovered by lavage was also useful in distinguishing patients with pneumonia (more than 25 percent of cells with intracellular organisms in five of five patients) from those without pneumonia (less than 15 percent of cells with intracellular organisms in all cases), and results were available immediately. In contrast, quantitative culture of lavage fluid and differential cell counts were of little value in identifying infected patients., Conclusion: The protected specimen brush and microscopic identification of intracellular organisms in cells recovered by lavage yield useful and complementary information, and together permit rapid and specific treatment of most patients with nosocomial pneumonia.

During a recent nosocomial outbreak, 20 critically ill patients with acute Legionnaires' disease were admitted to the intensive care unit of Hopital Bichat, Paris. Pulmonary specimens were obtained at surgery or immediately after death in 12 patients and were examined by light, immunofluorescent, and electron microscopy. Five of these 12 patients showed evidence of pulmonary fibrosis. In all of these five patients, infection with Legionella pneumophila was evidenced by bacteriologic methods, and other diseases known to cause fibrosis were excluded. The condition of four patients deteriorated rapidly with respiratory failure, and they died with pulmonary fibrosis. Only one patient finally recovered but was left with pulmonary sequelae. Two distinctive morphologic patterns were observed, one in which interstitial fibrosis was predominant and one in which intra-alveolar organization and fibrosis were also present. The alveolar epithelial lining and the basement membranes were disrupted in all patients, as evidenced by ultrastructural observations and by immunofluorescent studies showing gaps in the distribution of type 4 collagen and laminin. Types 1 and 3 collagen accumulated in areas corresponding to thickened interstitium and intra-alveolar fibrosis. Thus, some patients who survive the acute pneumonia of Legionnaires' disease may develop pulmonary fibrosis, and this process may lead to functional impairment or death despite prompt and appropriate treatment.

Epidemiologic studies of nosocomial bacterial pneumonia in patients requiring mechanical ventilation have been limited because of the poor reliability of diagnosis procedures in this setting. To determine prognostic and descriptive factors of ventilator-associated (V-A) pneumonia, we prospectively studied 567 patients who had been receiving mechanical ventilation for more than 3 days in our unit. Fiberoptic bronchoscopy using a protected specimen brush (PSB) was performed on each patient suspected of having pneumonia because of the presence of a new pulmonary infiltrate and purulent tracheal secretions. The diagnosis of V-A pneumonia was retained only if PSB specimens yielded greater than 10(3) cfu/ml of at least one microorganism, unless this result was established to be a false positive result on follow-up. V-A pneumonia developed in 49 patients for a total of 52 episodes (9%). The actuarial risk of V-A pneumonia was 6.5% at 10 days, 19% at 20 days, and 28% at 30 days of ventilation. Patients with pneumonia were significantly older (65 versus 57 yr of age, p less than 0.01) and more frequently had severe underlying illnesses (24 versus 10%, p less than 0.01) than did patients without pneumonia. A total of 84 microorganisms (51 gram-negative and 33 gram-positive) were isolated in significant concentrations from PSB specimens. Pseudomonas aeruginosa and Staphylococcus aureus were involved in 31 and 33% of these pneumonias, respectively. Forty percent of all specimens yielded a polymicrobial flora with more than one potential pathogen.(ABSTRACT TRUNCATED AT 250 WORDS)

To determine the relative cultural accuracy of the bronchoscopic protected specimen brush (PSB) in ventilated patients, we compared this method in the same area of the lung with histologic and bacteriologic examinations of pulmonary specimens. The procedures were concluded just after death when the ventilator was still functioning. Samples via the PSB were taken from a branch of the anterior basal bronchus of the left lower lobe, and immediate left thoracotomy was performed to obtain peripheral specimens from the corresponding segment for quantitative cultures. Twenty-six patients were studied; 6 had histologically proved pneumonia. Using quantitative cultures, a correlation was evidenced between PSB and lung cultures, especially in the subgroup of patients who received no antibiotic during the week preceding their death. No pneumonia was observed when PSB cultures isolated no organisms in concentrations greater than 10(3) colony-forming units (cfu) per ml. The PSB cultures at a level of 10(3) cfu/ml identified every patient with histologically proved pneumonia and every microorganism present in concentrations of 10(4) cfu/g or greater in the lungs. Moreover, in the subgroup of patients receiving no antibiotic, only 4 microorganisms were isolated by the PSB in concentrations greater than 10(3) cfu/ml and not found in the lung.(ABSTRACT TRUNCATED AT 250 WORDS)

We describe a patient who developed acute pulmonary distress with bilateral interstitial infiltrates and pleural effusion following talc pleurodesis. Talc particles, obtained by bronchoalveolar lavage, were identified by transmission electron microscopy and chemical analysis. The patient improved with corticosteroid therapy. Acute respiratory failure can be a potential hazard of talc pleurodesis.

To determine the usefulness of samples obtained by bronchoscopy using a protected specimen brush and evaluated by quantitative culture techniques in establishing the diagnosis of nosocomial pneumonia in patients requiring mechanical ventilation, we prospectively studied 147 ventilated patients suspected of having nosocomial pneumonia because of the presence of a new pulmonary infiltrate and purulent tracheal secretions. Positive cultures of protected brush specimens (greater than 10(3) cfu/ml) were found in only 45 patients (31%). Subsequent follow-up confirmed the diagnosis of pneumonia in 34 of 45 patients, and in only 4 of 45 patients was a positive culture firmly established to be a false positive result. No patient with less than 10(3) cfu/ml was subsequently shown to have had pneumonia, and the diagnosis was definitely excluded in 72 of 102 patients by the absence of pneumonia at autopsy or recovery without antibiotic therapy. In contrast, when 16 clinical variables were evaluated by stepwise logistic regression analysis, no combination could be identified that was useful in distinguishing patients with bacterial pneumonia. Furthermore, when the actual costs of evaluation and therapy of our patients were compared with the projected costs entailed in treating all patients suspected of having pneumonia with antibiotics, evaluation using the protected specimen brush and quantitative cultures was less expensive after only 6 days of treatment. These results suggest that the appearance of pulmonary infiltrates and purulent tracheal secretions does not result from bacterial pneumonia in a majority of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

We evaluated 13 transsexual men who were hospitalized for symptoms resulting from illicit subcutaneous injections of silicone. Patients with acute silicone pneumonitis were admitted because of fever, bilateral pulmonary infiltrates, and hypoxemia (mean PaO2, 58 +/- 14 mm Hg). Most patients in this group had received new silicone injections within hours of admission, but one presented with the same clinical syndrome a few hours after a brawl. The alveolitis of acute silicone pneumonitis was characterized by increased numbers of alveolar macrophages, neutrophils, and eosinophils (p less than 0.05 compared with those in normal persons with a similar smoking history). Evidence of alveolar hemorrhage was also present in some cases. Alveolar macrophages contained large, pleomorphic, cytoplasmic inclusions, which were identified as silicone by atomic absorption and infrared spectrometry. Patients with latent silicone pneumonitis underwent clinical study at much longer times after the silicone fluid injections because they developed local inflammatory phenomena at the sites of previous injections. Pulmonary function studies usually showed slight restrictive changes, and bronchoalveolar lavage disclosed abnormalities similar to those found in patients with acute silicone pneumonitis, although to a lesser degree. Thus, illicit silicone fluid injection carries a serious respiratory risk since it can induce pneumonitis, followed in some patients by respiratory failure.

We sought to determine the epidemiological characteristics of patients in an intensive care unit (ICU) who developed ventilator-associated pneumonia (VAP) caused by piperacillin-resistant Pseudomonas aeruginosa (PRPA; n = 34) or piperacillin-susceptible P. aeruginosa (PSPA; n = 101). According to univariate analysis, the factors associated with the development of PRPA VAP were presence of an underlying fatal medical condition, immunocompromised status, longer previous hospital stay, less-severe illness at the time of ICU admission, duration of mechanical ventilation before onset of VAP, number of classes of antibiotic received, and previous exposure to imipenem or fluoroquinolone. Multivariate logistic regression analysis identified the following significant independent factors: presence of an underlying fatal medical condition (odds ratio [OR], 5.6), previous fluoroquinolone use (OR, 4.6), and initial disease severity (OR, 0.8). We concluded that the clinical characteristics of patients who develop PRPA VAP differ from those of patients who develop PSPA VAP. Restricted fluoroquinolone use is the sole independent risk factor for PRPA VAP that is open to medical intervention. [ABSTRACT FROM AUTHOR]