Role of routine blood cultures in detecting unapparent infections during continuous renal replacement therapy.

OBJECTIVE: Continuous renal replacement therapy (CRRT) is frequently employed in the management of renal failure in unstable intensive care patients. At some centers, blood cultures are performed routinely while on CRRT to monitor for occult bacteremia. We questioned the role of routine blood cultures (RBC) in diagnosing underlying infections in these often afebrile patients. DESIGN: Retrospective cohort study (1998-2003). SETTING: Medical, surgical and pediatric intensive care units in a tertiary care teaching hospital. METHODS/MEASUREMENTS: We undertook a retrospective chart review of all 101 episodes of CRRT performed in our hospital since 1998. The primary endpoint of the study was the number of positive cultures that changed patient management. For each positive result, documented infection and parameters of sepsis were noted. RESULTS: There were 101 treatments of CRRT in 98 patients. A total of 698 routine RBC bottles were drawn, a mean of 7.2+/-7 per patient; of those, 29 (4%) were positive in 17patients, documenting 11 bacteremias. Six positive cultures represented contaminants. In all but one case, infection was known or signs of sepsis were present prior to receipt of the culture result. CONCLUSIONS: For patients on CRRT, RBC are rarely positive, and do not detect occult infection in the absence of clinical evidence of infection for the majority of patients. Because routine cultures utilize significant resources, and can result in false-positive results, RBC should not be performed in these patients. Careful clinical monitoring, with blood cultures performed at the first clinical suggestion of an infection, should detect all clinically relevant infections.

Silica-exposed macrophages release a growth-promoting activity for type II pneumocytes.

This study addresses the hypothesis that silica-activated alveolar macrophages could release soluble factors stimulating type II cell proliferation. Macrophages from control sheep were exposed or not in vitro to silica, aluminum-treated silica (Si-Al), or titanium dioxide (TiO2). In addition, macrophages from a model of chromic silica-exposed sheep were studied. Supernatants from unstimulated macrophages were found to double basal type II cell DNA synthesis. Alveolar macrophage-conditioned media (AMCM) collected from cells exposed in vitro to silica induced an additional growth-promoting activity for type II cells. Supernatants from Si-Al- or TiO2 dust-exposed alveolar macrophages had the same effects as unstimulated AMCM. In addition, AMCM from in vivo silicotic sheep cells also contained elevated levels of type II cell mitogenic activity. These results suggest that in vitro as in vivo, silica-activated macrophages produce a type II cell growth factor(s) for type II epithelial cells.

Partial characterization of the proliferative activity for fetal lung epithelial cells produced by silica-exposed alveolar macrophages.

The proliferation of lung epithelial cells is a prominent feature of lung tissue response following silica-induced lung injury and alveolar macrophages are recognized as a major contributing cell to the lung inflammatory processes. In previous studies, a growth-promoting activity for fetal rat lung epithelial cells was observed in silicotic alveolar fluids and in supernatants from in vitro and in vivo silica-exposed alveolar macrophages. In the present work, the biological and physicochemical properties of the macrophage-derived growth-promoting activity for fetal lung epithelial cells were explored. Four peaks of growth-promoting activity for lung epithelial cells ranging from 32 to 7 kDa were found in both in vitro and in vivo silica-exposed macrophage supernatants. The investigations were coupled with biochemical treatments of the mitogenic peaks and blocking antibodies or antisera were used to specify further the nature of the proliferative activities. Among the established growth factors, alveolar macrophage-derived growth fractions had characteristics consistent with platelet-derived growth factor-, insulin-like growth factor 1-, and fibroblast growth factor-like molecules. The cytokine production following in vitro exposure, which reflects very early events in the pathogenesis of silicosis, was more strongly related to the high-molecular-weight PDGF-like molecules, whereas the cytokine production following in vivo exposure, which reflects later events in the pathogenesis of silicosis, was more influenced by intermediate-molecular-weight FGF- and IGF-like molecules.

Dehydroepiandrosterone protects low density lipoproteins against peroxidation by free radicals produced by gamma-radiolysis of ethanol-water mixtures.

Oxidized low density lipoproteins (LDL) are believed to play a central role in the events that initiate atherosclerosis. Antioxidants have been shown to decrease the oxidation of LDL, leading to the diminution of atherosclerosis. Since it is well-known that decreased levels of dehydroepiandrosterone (DHEA) are linked to the development of atherosclerosis, we studied the modulation of the oxidation of LDL by DHEA. LDL were obtained from 10 healthy subjects and oxidized by free radicals produced by gamma-radiolysis of ethanol-water mixtures. The formation of conjugated dienes and thiobarbituric acid-reactive substances (TBARS), the vitamin E content, as well as the incorporation of 4-[14C]DHEA in LDL and the chemotactic effect of oxidized LDL in the presence of DHEA towards monocytes, were investigated. It was found that DHEA was able to inhibit the oxidation of LDL by reducing over 90% of the conjugated dienes and TBARS formation, as well as by reducing the vitamin E disappearance and significantly decreasing the chemotactic activity towards monocytes. Our results suggest that DHEA exerts its antioxidative effect by protecting the endogenous vitamin E of LDL.

Clara cell protein (CC-16) and surfactant-associated protein A (SP-A) in asbestos-exposed workers.

Asbestos-exposed workers (Asb) can sometimes develop lung impairments resembling idiopathic pulmonary fibrosis (IPF). Smoking is often a troubling confounder in the natural history of these lung diseases. Distal airspace epithelial cells, which are also altered in asbestosis, secrete Clara cell protein (CC-16, also designated CC-10) and surfactant-associated protein A (SP-A). By inhibiting phospholipase A2 (PLA2), CC-16 and SP-A are putative candidates for controlling lung inflammatory events. Both were measured with PLA2 activity in alveolar fluids (and sera for CC-16) of smoker and nonsmoker Asb and compared with smoking-matched normal subjects (N). CC-16 (in mg/L) was slightly increased in Asb and affected by smoking: nonsmoker Asb: 3.1 +/- 0.5 vs nonsmoker N: 1.9 +/- 0.2 (p < 0.05), smoker Asb: 1.7 +/- 0.3 vs smoker N: 0.6 +/- 0.1 (p < 0.05). SP-A (in microgram/mL) was enhanced in Asb but not affected by smoking: 5.4 +/- 1.5 in Asb vs 1.6 +/- 0.4 in N (p < 0.05), whereas SP-A to phosphorus ratio was increased in Asb but affected by smoking. CC-16 to albumin and CC-16 in serum to alveolar fluid ratios were altered by cigarette consumption in Asb (p < 0.05 vs N). Secretory PLA2 activity was slightly enhanced in Asb (p < 0.05 vs N). All data were similar between stages of disease. In summary, alveolar CC-16, SP-A, and secretory PLA2 activity were increased in Asb. Smoking affected several parameters. By this habit, Asb might reinforce lung profibrotic factors and increase their risk in developing lung alterations resembling IPF.

Interleukin-6, interferon-gamma, and phospholipid levels in the alveolar lining fluid of human lungs. Profiles in coal worker's pneumoconiosis and idiopathic pulmonary fibrosis.

Cytokines are widely involved in physiologic as well as immunoinflammatory and fibrosing processes of the lung. The aim of this work was to study, by bronchoalveolar lavage, two groups of human interstitial lung diseases (ILD) with fibrosing propensity (ie, idiopathic pulmonary fibrosis [IPF], n = 10; and coal worker's pneumoconiosis [CWP], n = 15). Patients were compared with nonsmoker control subjects (n = 20). Cellularity, proteins, and phospholipids were determined in the alveolar fluids. In addition, two cytokines (interleukin-6 [IL-6] and interferon-gamma [IFN-gamma]), which are presumed to possess respective antifibrotic and profibrotic activities, were measured in the respiratory tract. Compared with control subjects, IPF and simple CWP showed alveolar hypercellularity (p < 0.05) and relative lymphocytosis (p < 0.05). Both exhibited increased alveolar permeability (ie, increased albumin/urea ratio, p < 0.05), with enhanced IL-6 and decreased IFN-gamma in the alveolar spaces (p < 0.05). On the other hand, IPF displayed an associated polymorphonuclear alveolitis, enhanced alveolar epithelial lining fluid (AELF) volume and low surfactant phospholipid levels (p < 0.05 vs control), whereas simple CWP shared an exclusive lymphocytosis, normal AELF volume, and a surfactant lipid overflow (p < 0.05 vs control). Relationships among all of these parameters were found only between alveolar cellularity, neutrophils and IL-6 levels in the AELF of IPF (respectively, r = 0.85, p = 0.0009, and r = 0.89, p = 0.0006). In summary, common alterations of cellular and cytokine turnover were observed in IPF and simple CWP and may reflect activity of the antifibrotic fight in these diseased lungs. Surfactant phospholipid levels are likely to represent a specific disturbance among IPF and CWP, but no clear relationship with respect to the other parameters could be established for explaining the difference in time course outcome.

Computed tomography in the etiologic assessment of idiopathic spontaneous pneumothorax.

In an attempt to elucidate the origin of the so-called idiopathic spontaneous pneumothorax (ISP), clinical examination, pulmonary function tests, and computed tomography (CT) with visual quantification and density analysis were performed in 20 young patients two months after an ISP episode. Twenty controls were recruited for CT. The chest roentgenograms were normal in the two groups. The results indicated the presence of various types of emphysematous lesions (EL) in the ISP group located predominantly in the apical fields with subpleural location in 16 patients. Interestingly, diffuse but moderate centrilobular emphysema was noted in 12 of 20 patients. The EL visual quantification was always less than 5 percent of the CT slices' total areas. The lung mean density shifted significantly toward the air density in the patient group (patients: -743 +/- 57.5 HU vs controls -713 +/- 59.5 HU, p less than 0.01). These findings suggest that CT may be useful for early assessment of EL in patients with ISP.

Vasopressin and blood pressure support for pancreatitis-induced systemic inflammatory response syndrome with circulatory shock.

A 54-year-old patient, admitted to the intensive care unit with a diagnosis of severe pancreatitis, developed circulatory shock that failed to respond to standard vasopressor treatment: epinephrine and norepinephrine. Addition of vasopressin helped reduce standard catecholamine need while maintaining adequate arterial blood pressure. Vasopressin appears to be a promising agent for maintaining arterial pressure during septic shock or systemic inflammatory response syndrome, but due to limited data and potential side effects, its use as first-line treatment for these indications is not recommended.

Acute respiratory distress syndrome: 30 years later.

Acute respiratory distress syndrome (ARDS) was first described about 30 years ago. Modern definitions and statements have recently been proposed to describe ARDS accurately, but none is perfect. Diffuse alveolar damage is the basic pathological pattern most commonly observed in ARDS, and the term includes permeability edema. The alveolar epithelium of the alveolar-capillary barrier is clearly a key component requiring repair, given its multipotent functional activity. Lung inflammation and neutrophil accumulation are essential markers of disease in ARDS, and a wide variety of pro- and anti-inflammatory cytokines have been described in the alveolar fluid and blood of patients. These molecules still have to prove their value as diagnostic or prognostic biomarkers of ARDS. Supportive therapy in ARDS improved in the past decade; mechanical ventilation with lung protective strategies and patient positioning are gaining interest, but the indications for corticosteroids for ARDS are still debated. Nitric oxide may have a place in the treatment of one-third of patients. Novel approaches, such as surfactant replacement and liquid ventilation, may further improve supportive therapy. Innovative interventions may be on the horizon in treatments that help to resolve or modulate common pathways of ARDS, such as inflammation (eg, granulocyte-colony stimulating factor) or epithelial repair (eg, keratinocyte growth factor).

[Respiratory resuscitation in Quebec. General aspects and implications of pneumologists in intensive care units in "New France"]. / Réanimation respiratoire au Québec. Aspects généraux et implication des pneumologues aux soins intensifs en "Nouvelle France".

ICU set up is a complex framework in Québec. In this respect, quebecer and french systems are very different. Pulmonologists are one of the most committed sub-specialists in ICUs, either as consultant or as MD on duty. Amongst paramedics, respiratory therapists are essential members of the team. Invasive and noninvasive ventilations are commonly performed. Critical care teaching program and structures for developing and supporting clinical research activities are in place.

[Fibrosing pneumopathy induced by cyclothiazide. Apropos of a case]. / Pneumopathie fibrosante induite par le cyclothiazide. A propos d'un cas.

A diffuse interstitial pulmonary fibrosis associated with an idiopathic hepatic cirrhosis occurred in a 79 years old man treated during five years with cyclothiazide and triamterene for a mild systemic hypertension. The outcome was fatal. A provocation test was positive with BAL lymphocytic reaction. Cyclothiazide induced fibrosis is likely.

[Drug-induced pulmonary diseases: diagnostic, therapeutic and prognostic aspects. Apropos of 10 personal case reports]. / Pneumopathies médicamenteuses. Modalités diagnostiques, thérapeutiques et pronostiques. A propos de 10 observations personnelles.

The authors report ten cases of drug induced lung diseases, complicated by respiratory failure of whom five were attributed to cytotoxic drugs and five to non cytotoxic drugs. The drug induced lung disease presented as acute respiratory distress syndrome in two cases, alveolar interstitial lung disease in three cases, purely interstitial in five cases. There was acute respiratory failure (ARF) in eight cases and chronic respiratory failure (CRF) in two cases. Among the five patients admitted for cytotoxic drug induced lung disease and ARF, four recovered and one died of diffuse destructive pulmonary fibrosis. Among the five patients having non cytotoxic drug induced lung disease, three were in ARF and recovered. The other two had CRF and died of diffuse pulmonary fibrosis. The diagnostic of drug induced lung disease was established in each case with the chronology of the clinical events, the exclusion of other possible causes of the lung disease and the evolution after removal of the incriminated drug. Broncho-alveolar lavage (BAL) had a major diagnostic value. It was contraindicated by respiratory failure in five cases. The predominant alveolar cell type was lymphocyte (four cases), eosinophil (three cases) and neutrophil (one case), BAL was realized with a provocation test and demonstrated the pathogenic role of cyclothiazide in one case. No specific information was given by histology. The prognosis did not seem to be linked to the severity of the initial clinical picture, or to the nature of the underlying neoplastic disorder, but to the degree and evolution of the pulmonary fibrosis.

[Cystic fibrosis in adults]. / La mucoviscidose de l'adulte.

While fifty years ago 20 p. 100 of cystic fibrosis patients only reached the age of one year, more than 50 p. 100 of the patients now live more than twenty years. The clinical manifestations of cystic fibrosis are more diverse in adults than in children, so that the diagnosis might concern several specialties. In actual fact, only 3 to 7 p. 100 of cystic fibroses are diagnosed after thirteen to sixteen years, and in half the cases the symptoms had been present before the age of one year. In adults, the respiratory manifestations of cystic fibrosis are predominant, whereas the gastrointestinal manifestations tend to be blurred. Radiography of the chest shows interstitial lesions (opacities, cystic images, disorders of ventilation), principally located in the right side and the apex. The most common functional defect is an obstructive syndrome corresponding to a gradual involvement of the peripheral airways. A number of complications may develop, including recurrent Pseudomonas infection of the lung, pneumothorax, heart failure, malnutrition, liver cirrhosis, episodes of intestinal occlusion, etc. The longer life span of these patients raises the problems of diabetes with its vascular complications, infertility or pregnancy, social and professional insertion, and so forth. The prognosis of cystic fibrosis in adults depends on the date the diagnosis was made, on the therapeutic follow-up and on the creation of specialized centres. The control of Pseudomonas infections and the development of lung transplantation are the main advances to be expected.

Ventilator associated pneumonia and endotracheal tube repositioning: an underrated risk factor.

Aspiration of secretions toward lower airways potentially occurs during endotracheal tube (ETT) repositioning in mechanically ventilated patients in the intensive care unit and may be a risk factor for developing ventilator-associated pneumonia (VAP). This case-control study confirms that repositioning of the ETT is an independent risk factor for VAP.

Lung alveolar epithelial cell migration in vitro: modulators and regulation processes.

After acute lung injury, altered bronchioloalveolar epithelia must be repaired quickly in order to restore lung function. During reepithelialization, type II cells initially appear to migrate and spread over a remodeled matrix; then a secondary proliferative phase occurs. It was hypothesized that 1) type II cells can develop locomotion in vitro that is modulated by growth factors, proinflammatory cytokines, and substrate adhesion molecules and 2) migration and proliferation of type II cells can occur as distinctive processes. Chemotaxis assays were elaborated using short term cultures of rat type II pneumocytes. Epidermal growth factor (EGF), transforming growth factor-alpha, laminin, fibronectin were found to be the main attractants for type II cells with respective increases of approximately 8.5-, 10.5-, 8-, and 7-fold in cell migration (P<0.05 vs. control). Laminin induced gradient-dependent and random cell migration. Addition of laminin with EGF had a synergistic effect in promoting cell migration (approximately 30-fold increase over control, P<0.05). Interferon-gamma and interleukin-6 inhibited EGF-induced type II cell migration, whereas tumor necrosis factor-alpha and interleukin-1beta acted as primers for type II cell migration (approximately 1.5-fold increase over control, P<0.05. Type II cells did not need to be in a proliferative phase in order to exhibit motility. New insights regarding the regulatory processes for type II cell migration are especially relevant in our understanding of early events occurring during epithelial repair after acute lung injury.

Silica-exposed lung fluids have a proliferative activity for type II epithelial cells: a study on human and sheep alveolar fluids.

The type II pneumocyte changes in silicosis are characterized by hyperplasic and hypertrophic epithelial cells, and increased surfactant phospholipids in the bronchoalveolar lavage fluids (BALF). To assess the proliferative activity of alveolar lining fluids, BALF were applied on type II cell cultures. The growth-promoting activity was studied by tritiated thymidine incorporation for 24 h, and the cell number was measured by an electronic counting after a 48-h exposure time. Human BALF from 3 subsets of workers exposed to silica, staged according to ILO classification (silica exposed-workers without disease: hSWD n = 6; workers with simple silicosis: hSS n = 7; workers with confluent silicosis: hCS n = 5), were compared to healthy volunteers (hC n = 6). Sheep BALF from our model of silicosis and control animals (sS and sC) were studied at months 0, 6, and 24 of exposure. A clear enhancement was found in type II cell DNA synthesis under the effect of either normal and silicotic human or sheep BALF, in comparison to the negative control (p less than .05). In addition hSWD and hSS BALF as sS BALF at 20% dilution (peak activity) were significantly more stimulating than the normal alveolar fluids from the same species (p less than .05). The highest sheep BALF stimulatory activity was found at month 6 (170% of increase vs control, p less than .05) and clearly correlated with the high cellularity of BALF. The thymidine incorporation was supported by changes in cell counts. Sheep silicotic BALF run through G50 columns identified at least 3 molecular weight (MW) areas of mitogenic activity between 30 and 5 kDa. Biochemical characteristics of growth factors in the above MW range (PDGF, FGF, TGF alpha, EGF) were tested. Increased mitogenic activity of type II cells eluted from heparin sepharose columns loaded with silicotic sheep BALF, at 0.5 and 1 M NaCl, corresponded to the removal areas of PDGF- and acidic FGF-like heparin-binding molecules. The high proliferative activity on type II cells of the latter two molecules, alone or in combination with other growth factors, was demonstrated in vitro (greater than 9 x control). In conclusion, a stimulatory activity for type II cell growth was found in the normal human and sheep alveolar lining fluid. This activity was clearly enhanced in the early stages of human and sheep silicosis. The BALF type II cell growth factors had biochemical characteristics consistent with the PDGF- and FGF-like molecules.

Effect of contact avoidance or treatment with oral prednisolone on bronchoalveolar lavage surfactant protein A levels in subjects with farmer's lung.

BACKGROUND: Surfactant protein A (SP-A) acts as an immune system modulator in the lungs and may therefore be involved in the pathogenesis of hypersensitivity pneumonitis. METHODS: The levels of SP-A in bronchoalveolar lavage (BAL) fluid were measured in 20 subjects with acute farmer's lung, 16 asymptomatic dairy farmers, and 14 normal controls. Eight patients had a second evaluation after one month of treatment by either contact avoidance (n = 3) or oral prednisolone (20 or 25 mg/day, n = 5). Chest radiographs and lung function measurements were also obtained in all farmers, twice in those re-evaluated after treatment. RESULTS: Patients with acute farmer's lung had significantly higher levels of SP-A than asymptomatic farmers and normal controls (p = 0.005) with mean (SE) values of 1.43 (0.29) micrograms/ml, 0.62 (0.09) microgram/ml, and 0.68 (0.11) microgram/ml, respectively. In eight subjects tested after one month of treatment the level of SP-A was unchanged although all were clinically improved. No correlations were seen between levels of SP-A in BAL fluid and numbers of BAL cells, lung function measurements, or chest radiographic scores. CONCLUSION: Although the level of SP-A is increased in the BAL fluid of patients with acute farmer's lung, it is not correlated with clinical abnormalities of this disease.

Interleukin-2 involvement in early acute respiratory distress syndrome: relationship with polymorphonuclear neutrophil apoptosis and patient survival.

OBJECTIVE: To determine blood and lung alveolar concentrations of interleukin (IL)-2 in acute respiratory distress syndrome (ARDS) and their relationship with polymorphonuclear neutrophil (PMN) apoptosis and patient survival. DESIGN: Prospective cohort study. SETTING: Medical and surgical intensive care units (ICUs; Canada) and the intensive care department (Belgium). PATIENTS: Nineteen consecutive patients with ARDS, 14 non-ARDS ICU patients, and 20 healthy volunteers. INTERVENTIONS: Blood samples and bronchoalveolar lavages (BAL) obtained via venous puncture and by fiberoptic bronchoscopy in the first 72 hrs after the onset of ARDS. MEASUREMENTS AND MAIN RESULTS: One early point concentration of IL-2 was measured in both blood and BAL fluids of the three groups. In vivo alveolar PMN apoptotic index in BAL fluids and the influence of BAL fluid exposure on normal blood PMN spontaneous apoptosis in vitro were evaluated. Blood IL-2 was significantly lower in patients with ARDS compared with non-ARDS ICU patients and controls. In contrast, IL-2 in BAL fluids of patients with ARDS was dramatically elevated compared with non-ARDS ICU patients and controls. ARDS survivors exhibited lower early IL-2 blood levels than nonsurvivors and generally had a higher IL-2 lung content Lung alveolar PMN apoptosis in vivo was lower in patients with ARDS in comparison with controls. This apoptotic index was correlated with corresponding IL-2 alveolar levels in patients with ARDS. Exposure of normal blood PMN to BAL fluids from patients with ARDS delayed apoptosis in vitro. Immunodepletions of IL-2, granulocyte-macrophage colony stimulating factor, and a combination of both cytokines from BAL fluids of ARDS patients significantly restored PMN apoptosis. The recovery of PMN apoptosis was more effective when IL-2 was depleted in BAL fluids from ARDS survivors compared with nonsurvivors. CONCLUSIONS: Opposite and disproportional concentrations of IL-2 are observed in blood and lung fluids of patients with early ARDS. IL-2 significantly contributes (with granulocyte-macrophage colony stimulating factor) to the inhibition of PMN apoptosis in BAL fluids of patients with ARDS. Early low blood IL-2 and high IL-2-driven inhibition of PMN apoptosis are beneficial to survivors. Thus, IL-2 is a new candidate for monitoring in early ARDS and an interesting indicator of prognosis.

Alterations of surfactant lipid turnover in silicosis: evidence of a role for surfactant-associated protein A (SP-A).

Type II cell hypertrophy with surfactant accumulation in the lung is a common observation in silicosis. Mechanisms leading to these alterations are poorly understood. By using silica dusts and alveolar fluids from saline and silica exposed sheep, we explored four different pathways of surfactant turnover in vitro: (1) synthesis and (2) secretion of lipids by rat type II cells; and dipalmitoylphosphatidylcholine (DPPC) uptake/reuptake by (3) type II cells and (4) alveolar macrophages. Silica had no direct specific effect on type II cell lipid metabolism. Alveolar fluids from both saline and silica exposed animals induced several alterations compared to control medium: (a) an increase in lipid synthesis (60 to 130%, P < 0.05); (b) a decrease in lipid secretion (25 to 70%, P < 0.05); (c) a 50 to 75% increase in DPPC reuptake by type II cells (P < 0.05); (d) a 65 to 75% decrease in DPPC uptake by alveolar macrophages (P < 0.05). DPPC uptake by in vivo silica exposed alveolar macrophages was reduced. Alterations of surfactant lipid metabolism induced by alveolar fluids from silicotic animals was more pronounced than in those treated with control fluids. Anti SP-A antibodies significantly suppressed most of the alveolar fluid induced effects on surfactant turnover. From these in vitro data, silica-induced type II cell hypertrophy seems to result from an increase in lipid synthesis activity and an imbalance in the lipid secretion/reuptake ratio.