Type 3 procollagen peptide in bronchoalveolar lavage fluid. Poor indicator of course and prognosis in sarcoidosis

To investigate the role of bronchoalveolar lavage type 3 procollagen peptide as a prognostic indicator in sarcoidosis, we measured type 3 procollagen N-terminal peptide levels in lavage fluids from 84 sarcoidosis patients and monitored disease progress in these patients for a period of 12 months. Lavage procollagen peptide levels were significantly elevated in sarcoidosis patients compared to control subjects (p less than 0.001). No association was observed between lavage type 3 procollagen peptide and disease severity, as assessed by lung function tests. Follow-up monitoring of patients failed to demonstrate any relationship between subsequent functional deterioration and initial lavage type 3 procollagen peptide. These results suggest that elevated lavage type 3 procollagen peptide concentrations in sarcoidosis may reflect increased type 3 collagen synthesis associated with the inflammatory process rather than signal an early event in the development of chronic disease.     

Chronic nitrofurantoin reaction associated with T-lymphocyte alveolitis

Nitrofurantoin use was associated with the development of severe interstitial lung disease which was characterized by bronchoalveolar lavage with a marked increase in lymphocytes to 60 percent (compared to normal of 7 +/- 1 percent). Lymphocytes were predominantly of the T-helper subset. Lavage may prove useful in the assessment of the immune response in drug-induced lung disease.     

Chemotactic activity in bronchoalveolar lavage fluid from patients with adult respiratory distress syndrome

Recent studies have shown that an influx of polymorphonuclear neutrophils into distal air spaces occurs early in the adult respiratory distress syndrome (ARDS). To study the mechanism of cell accumulation in this syndrome, we have evaluated the chemotactic activity in bronchoalveolar lavage fluid from patients with ARDS. Lavage fluid was obtained from 16 patients with ARDS within 24 h of endotracheal intubation and from 5 normal nonsmoking subjects. Lavage fluid from patients with ARDS had an average of 85% neutrophils on differential counts of cytologic preparations compared to less than 3% neutrophils for the control subjects. After removal of cells and lipids, lavage fractions of molecular weight greater than 10,000 daltons were chemotactic for human neutrophils in 14 of 16 patients, but no activity was seen with the normal lavages. Preliminary studies to identify the chemotactic factor were performed.     

Failure of bronchial lavage to detect elevated levels of adrenocorticotropin (ACTH) in patients with ACTH-producing bronchial carcinoids

Saline lavage of the major bronchial segments was performed in five patients immediately preceding lobectomy to remove an ACTH-producing bronchial carcinoid. Lavage fluid from each bronchus was concentrated, and ACTH determinations were performed. Elevated concentrations of ACTH were not demonstrated in the aspirate from the bronchus containing the known tumor. Two additional patients with ectopic ACTH syndrome from an unknown primary source also underwent selective segmental bronchial lavage for ACTH determination. Neither patient demonstrated ACTH gradients in the lavage specimens. One was found to have an ACTH-producing bronchial carcinoid 18 months after negative lavage. Selective segmental bronchoscopic lavage with measurement of ACTH levels on the aspirate is not an effective technique for detecting ACTH-producing bronchial carcinoid tumor.     

Pulmonary alveolar proteinosis: analysis of airway and alveolar proteins.

Lavage effluents from the lungs of patients with pulmonary alveolar proteinosis were analyzed for soluble constitutents. Antiserums monospecific for normal plasma components, C-reactive protein, and secretory piece were used to investigate the presence of these proteins in lavage effluent, wheras 2-dimensional polyacrylamide gel electrophoresis provided a comprehensive map of the major proteins that were present. The proteins of lung washing obtained from normal subjects and of patient and normal serums were similarly analyzed. Most of the soluble-phase proteins from lavage of patients with pulmonary alveolar proteinosis were also found in patient serum, and were present in amounts consistent with a theory that they originate from the plasma by passage through channels of approximately normal size and selectivity. This findings suggests that the abundant soluble protein found in the alveoli of the lungs of these patients does not arise by leakage through a serverly damaged blood-air barrier. Patients had in their lung lavage effluents 2 soluble proteins of molecular weights 47,000 and 52,000 daltons not found in their serum and not present in lung washings from normal subjects. Uniformly increased concentrations of immunoglobulins in patient lavage effluent, abnormal immunoglobulin concentrations in patient serum, and the presence of C-reactive protein in the serum from 4 of 5 patients indicate a response of the immune system to the disease process and suggest that an atypical hypersensitivity reaction may be involved.     

Surfactant function affected by airway inflammation and cooling: possible impact on exercise-induced asthma.

Pulmonary surfactant maintains patency of narrow conducting airways. An inflammation, with a leakage of plasma proteins into the airway lumen, causes surfactant to lose some of this ability. Will a lowering of temperature aggravate the deteriorating effect of an inflammation? Calf lung surfactant extract (CLSE) with proteins added was studied with a capillary surfactometer (CS) at temperatures of 25-42 degrees C. BALB/c mice were infected with respiratory syncytial virus (RSV). Six days later the lungs were lavaged and the surfactant in the lavage fluid was studied with the CS at temperatures of 25-42 degrees C. Lavage fluid from allergen challenged asthmatics was examined for its content of surfactant inhibitors at reduced temperatures. It was shown that CLSE with proteins gradually lost its ability to maintain patency as the temperature was lowered. Lavage fluid from the RSV infected mice showed a similar dysfunction at low temperatures. Lavage fluid from the airways of human asthmatics, when challenged with antigen but not with saline, contained agents inhibiting surface activity, particularly at reduced temperatures. Airway inflammation causes surfactant to lose its ability to maintain patency, particularly as the temperature is reduced. That might be a reason for the increased airway resistance observed in asthma patients hyperventilating in cold weather.     

THE ROLE OF BRONCHOALVEOLAR LAVAGE IN THE ASSESSMENT OF DIFFUSE LUNG DISEASES

Bronchoalveolar lavage is a safe and simple technique for sampling the inflammatory cells of the lung. However, while its use in the evaluation of pulmonary pathogenic mechanisms is both well accepted and described, its clinical utility is more controversial. Marked variation in results may occur through variation in the lavage procedure. Standardisation of the lavage technique and laboratory processing of the specimen are essential for reliable results. This review examines the current clinical role of bronchoalveolar lavage in the assessment of patients with diffuse lung diseases, and immunocompromised patients with pulmonary infiltrates. In this latter category, for patients with Acquired Immunodeficiency Syndrome, lavage is of equal efficacy to lung biopsy and can establish the cause of pulmonary infiltrates in over 90% of cases. Bronchoalveolar lavage can detect abnormalities in patients with diffuse lung diseases prior to the development of irreversible fibrosis. Lavage features have been described for sarcoidosis, cryptogenic fibrosing alveolitis, extrinsic allergic alveolitis, connective tissue diseases, and asbestosis. In cryptogenic fibrosing alveolitis lavage data may be used to indicate a subsequent deterioration in the patient's condition, or predict a favourable response to therapy.     

Saline lavage: a rapid, effective, and acceptable method for cleansing the gastrointestinal tract.

The standard preparation for cleansing the gastrointestinal tract for diagnostic studies such as barium enema usually involves dietary restrictions, purgatives, and cleansing enemas. This preparation is time consuming, often uncomfortable for the patient, and frequently unsuccessful. In this study, we examined the efficacy of saline lavage (without dietary restrictions or cleansing enemas) as a gentle, alternative method for cleansing the bowel, and compared lavage to the standard castor oil method of bowel preparation. Lavage cleansing was preferred by 75% of patients who had previously experienced a castor oil preparation. Although 11% of patients could not consume an adequate (4-liter) lavage volume, there was no significant difference in preparation success rate between the remaining lavage patients and the castor oil patients. Total preparation time for lavage (3 +/- 1 hr) was 60% less than for castor oil. The anticipated dehydration produced by castor oil and the hydration produced by lavage were confirmed. No significant changes were noted, however, in serum electrolytes with either method of preparation. Additional early studies are promising for the lavage method when used in inflammatory bowel disease patients and as a cleansing preparation for colonoscopy.     

Treatment of meconium aspiration syndrome with surfactant lavage in an experimental rabbit model.

Meconium aspiration syndrome (MAS) is a frequent cause of respiratory distress in term infants. Recent reports suggested that surfactant dysfunction contributes to the pathophysiology of MAS. In the present study, we assessed the effect of three different concentrations of surfactant suspensions in the lavage fluid of a rabbit model of MAS. Young animals were given 5 mL/kg of a 20% slurry of human meconium into the endotracheal tube and were then mechanically ventilated. The animals were divided into four groups receiving lavage fluids with either saline or surfactant suspensions (2.5 mg/mL, 5 mg/mL, and 10 mg/mL). Lavage was performed an hour after meconium instillation with one of the four solutions at 10 mL/kg in three divided doses. After lavage, the total amount of meconium recovered was measured. The 10 mg/mL surfactant lavage group had the best improvement in gas exchange, whereas the saline group had no improvement. The amount of meconium recovered was the best in the 10 mg/mL surfactant group among the four groups studied. On histologic examination, alveolar inflammation was less evident in the surfactant lavage groups than in the saline lavage group. It was concluded that lavage with surfactant solution at a concentration of 10 mg/mL washed out meconium most effectively, and improved gas exchange and lung histology in the rabbit model of MAS more than saline lavage.     

Interlobar differences in bronchoalveolar lavage fluid from children with cystic fibrosis.

Bronchoalveolar lavage (BAL) performed in specialist centres has improved the understanding of infant cystic fibrosis (CF) lung disease. As most researchers sample from a single lobe, it was determined whether BAL results could be generalized to other lung segments. Thirty-three CF children, aged 1.5-57 months, underwent in random order sequential BAL of their right middle and lingula lobes. Specimens from each lobe had separate quantitative bacteriology, cytology and cytokine analysis. Bacterial counts > or = 1 x 10(5) colony forming units (cfu) x mL(-1) were observed in nine (27%) subjects, including six involving only the right middle lobe. These six children had similar inflammatory indices in their right middle and lingula lobes, and interleukin (IL)-8 concentrations in the latter were significantly higher than that observed within the lingula lobes of the 24 CF children with bacterial counts < 1 x 10(5) cfu x mL(-1). Lingula neutrophil and IL-8 levels correlated best with right middle lobe bacteria numbers. This observational study in cystic fibrosis children suggests that while inflammation is detected in both lungs, bacterial distribution may be more inhomogeneous. Bronchoalveolar lavage microbiological findings from a single lobe may therefore, not be generalized to other lung segments. When performing bronchoalveolar lavage in cystic fibrosis children, it is important to sample from multiple sites.     

The adult respiratory distress syndrome. Cell populations and soluble mediators in the air spaces of patients at high risk

In order to better understand the modulation of polymorphonuclear neutrophil influx into the lung during the development of the adult respiratory distress syndrome (ARDS), we evaluated bronchoalveolar lavage fluids from control subjects (n = 9), patients at high risk of developing ARDS (n = 12), and patients with ARDS (n = 11) for cellular and protein content and capacity to promote neutrophil adhesion to tissue culture plastic. Analysis of the lavage fluids from high risk patients and patients with ARDS showed an 8- to 10-fold increase in the total number of cells, an increase in the percentage of neutrophils present (control subjects = 1 +/- 0.4%, high risk = 53 +/- 8%, ARDS = 70 +/- 7%), and a 10- to 40-fold increase in protein content. The adherence of normal neutrophils to plastic surfaces after pretreatment with either concentrated lavage fluid, ultrafiltrates of BALF, or plasma samples was determined to evaluate the neutrophil adherence-promoting activity of each. Lavage fluid from high risk patients and patients with ARDS promoted an approximate 3-fold increase in neutrophil adherence when compared with control lavage fluid. Neutrophil adhesion-promoting activity of the plasma and lavage filtrates (mw less than 500 daltons) was not significantly different from that of control subjects. The adherence-promoting activity found in ARDS lavage was stable at 56 degrees C for 30 min.(ABSTRACT TRUNCATED AT 250 WORDS)     

Granulocytes and their secretory products, myeloperoxidase and eosinophil cationic protein, in bronchoalveolar lavage fluids from two lung lobes in normal subjects.

The interlobar variability of lavage neutrophils and eosinophils was studied in twelve healthy subjects. In addition, the interlobar variation of the neutrophil cell marker myeloperoxidase (MPO) and the eosinophil cell marker eosinophil cationic protein (ECP) was assessed. Bronchial washes (BW), as defined by the first aspirated lavage aliquot, and bronchoalveolar lavage (BAL) fluids were compared. One subsegment of the right middle lobe and one subsegment of the right lower lobe were lavaged in the same session. Interlobar consistency of neutrophil and eosinophil cell recoveries was observed but, in contrast, the levels of MPO or ECP did not correlate in lavage fluids aspirated from the two lobes. These results suggest that BAL cell content from a single lobe of the lung in healthy subjects does reflect the cell populations throughout the airways, while the levels of soluble proteins may differ between the lobes. Such a variation questions the correlation between cells and their secretory products or the correlation between levels of solutes in lavage fluid and in the underlying tissue. Further methodological studies appear warranted to elucidate whether cell and solute recoveries accurately reflect the underlying pathology.     

Altered epithelial lining fluid parameters in old normal individuals.

Pneumonia is a leading cause of morbidity and death in older patients, and immunosenescence is believed to contribute to their susceptibility. In order to investigate whether age-related changes occur on the epithelial surfaces of the lung, bronchoscopy and bronchoalveolar lavage (BAL) were performed without complication in 19 young (27.7 +/- 4.2 yrs), 6 middle-aged (49.8 +/- 3.5 yrs), and 8 old (74.1 +/- 4.3 yrs) normal, nonsmoking subjects. BAL was performed by instilling and retrieving five 20 ml aliquots of normal saline into three sites. The returns from the first aliquots (the bronchial sample) were analyzed separately from the returns from the subsequent aliquots (the distal sample). Lavage fluid cellularity was characterized and IgA, IgG, and albumin were measured by ELISA. Lavage fluid returns were lower in the elderly group and correlated with spirometric parameters. Significantly elevated numbers of neutrophils were recovered by the bronchial sample fluid from the old group. In contrast, no consistent difference in macrophage recovery by either the bronchial or distal sample was noted. In both the bronchial and distal samples, IgG, but not IgA or albumin, was elevated in the group of old subjects. Alterations occurring in BAL fluid with aging may reflect changes in local host defenses.     

Contributions of peritoneal lavage enzyme determinations to the management of isolated hollow visceral abdominal injuries.

STUDY OBJECTIVE: To determine the role of lavage amylase (LAM) and lavage alkaline phosphatase (LAP) in the identification of intraperitoneal hollow visceral injuries. DESIGN: Retrospective. SETTING: Level I trauma center, city/county institution. TYPE OF PARTICIPANTS: Patients with hollow visceral organ injury following major blunt or penetrating trauma whose diagnostic peritoneal lavage was negative by lavage red blood cell and lavage white blood cell were negative. MEASUREMENTS AND MAIN RESULTS: Fifty-one patients with injury isolated to one or more hollow visceral structures underwent diagnostic peritoneal lavage; 28 were positive based on aspirate, lavage red blood cell count (greater than 100,000/mm3), or lavage white blood cell count (greater than 500/mm3). Of the remaining 23 patients, each of 11 with isolated small bowel injury had LAM greater than or equal to 20 IU/L and six of these had LAP levels greater than or equal to 3 IU/L. All six patients with colon injury and two of the patients with gallbladder injury had LAM less than 20 IU/L and LAP less than 3 IU/L. CONCLUSIONS: In patients with hollow visceral injury and otherwise normal diagnostic peritoneal lavage, elevation in LAM is highly specific for isolated small bowel injury. Lavage enzyme determinations appear unhelpful in the detection of colonic injury. We recommend routine enzyme determinations of lavage effluent as a marker for isolated small bowel injury.     

Retropharyngeal abscess due to methicillin-resistant Staphylococcus aureus in a case of acute myeloid leukemia

We describe a case of acute myeloid leukemia (AML) complicated with retropharyngeal abscess (RPA) due to methicillin-resistant Staphylococcus aureus (MRSA) in a 56-year-old man. After administration of vancomycin and lavage of the retropharyngeal space with gentamicin, complete resolution of the RPA was observed. Despite their lower frequency, deep neck infections are associated with high mortality rates. The possibility of RPA should be considered in patients who present with fever, dysphagia and limitation of neck extension. Lavage of the retropharyngeal abscess with gentamicin may be optimal in cases of large RPA.     

支气管肺泡灌洗在高原地区老年肺部感染患者治疗中的应用

目的观察支气管肺泡灌洗在高原地区老年肺部感染患者治疗中的应用价值。方法对照组42例患者给于抗感染及综合治疗;灌洗组42例患者在抗感染及综合治疗的基础上给于支气管肺泡灌洗,每周2-3次,共2周。结果灌洗组42例中显效31例（73.8%）、有效7例（16.7%）、无效4例（9.5%）,总有效率90.5%;对照组42例中显效18例（42.9%）、有效9例（21.4%）、无效15例（35.7%）,总有效率64.3%,两组总有效率比较差异非常显著（χ^2=8.182,P〈0.01）。灌洗组肺泡灌洗细菌培养阳性率（90.5%）显著高于对照组痰液细菌培养阳性率（47.6%）,（χ^2=10.984,P〈0.01）。结论支气管肺泡灌洗在老年肺部感染中不仅能获得准确的病原菌,为临床选择敏感抗生素提供依据,是高原地区老年肺部感染治疗中一种安全、有效的辅助治疗方法。     

Exudation of plasma and production of thromboxane in human bronchi after local bradykinin challenge

Plasma exudation has been suggested to be an important component of the inflammatory response in asthma. Bradykinin elicits many of the features of asthma, including bronchoconstriction, cough, plasma exudation and mucus secretion. In an attempt to quantify local plasma exudation, we have employed a novel low-trauma technique with the aim of challenging and lavaging a central part of the bronchial tree, by selecting a medium sized bronchus. A fibreoptic bronchoscopy was performed in non-smoking healthy volunteers. The instrument was placed proximally in the right upper lobe bronchus. A plastic catheter, equipped with an inflatable latex balloon, was inflated with air (2-4 cmH2O). A solution (100 microl of either two different concentrations of bradykinin: 0.09 and 0.9 mg ml(-1) or normal saline) was instilled through the catheter and distal to the balloon. Eight minutes later a lavage procedure with 10 ml of saline was performed through the catheter. The procedure was then repeated twice, with the other solutions, but from the lingular and middle lobe bronchi. All solutions were given in a blinded fashion, and two different studies were performed. Lavage concentrations of albumin and IgG were quantified as measurements of plasma exudation. In our first study we found that bradykinin challenge significantly increased concentrations of albumin and IgG. In study two, there was no numeric increase in plasma proteins after local bradykinin challenge, but the concentration of thromboxane was significantly increased in lavages from bradykinin-challenged bronchi. Thus, local bronchial administration of bradykinin has the capacity to induce exudation of large plasma macromolecules into the bronchial lumen, as well as local thromboxane production.     

CLearance of calcium pyrophosphate dihydrate crystals in vivo. II. Studies using triclinic crystals doubly labeled with 45Ca and 85Sr.

The clearance rate of isotopically labeled synthetic triclinic calcium pyrophosphate dihydrate (CPPD) crystals injection into rabbit joints was estimated by serial counting. Kinetic analysis using a four compartment model showed that half of the injected dose was cleared from 4 rabbit knee joints in 19.1 +/- 0.42 (SEM) days. Profound hypomagnesemia, produced in 2 rabbits with a low magnesium diet, did not affect the rate of crystal clearance detectably. Lavage of joints with solutions known to promote CPPD crystal solubility failed to remove detectable radioactivity. The previous finding of CPPD crystals in synovial phagocytes by electron microscopy, together with the finding of nuclide activity in the synovium and the failure to remove such activity by joint lavage, suggests that endocytosis by synovial cells is an important, effective mechanism controlling the synovial fluid concentration of crystals in patients with CPPD crystal deposition disease.     

Diagnosis of Pneumocystis carinii pneumonia by multiple lobe, site-directed bronchoalveolar lavage with immunofluorescent monoclonal antibody staining in human immunodeficiency virus-infected patients receiving aerosolized pentamidine chemoprophylaxis.

The yields of both induced sputum examination and bronchoalveolar lavage (BAL) have been reported to be decreased for breakthrough episodes of Pneumocystis carinii pneumonia in human immunodeficiency virus-infected patients receiving aerosolized pentamidine chemoprophylaxis. This study assessed whether the yield of a single middle or lower lobe BAL could be increased by the utilization of two techniques: (1) indirect immunofluorescent staining with a combination of two murine monoclonal anti-Pneumocystis antibodies in addition to routine toluidine blue O and cytopathologic staining, and (2) the performance of multiple lobe, site-directed BAL (i.e., both upper lobe and middle or lower lobe lavage, including the lobe with the greatest radiographic abnormality). Results of 252 fiberoptic bronchoscopies performed at the National Institutes of Health and the Los Angeles County-University of Southern California Medical Center were analyzed. P. carinii pneumonia was documented in 21 episodes in patients who did not receive prior anti-Pneumocystis chemoprophylaxis and in 41 episodes in patients who received aerosolized pentamidine. Monoclonal antibody staining and multiple lobe, site-directed BAL resulted in similar diagnostic yields for P. carinii in the nonprophylaxis (100%) and aerosolized pentamidine (98%) groups. If BAL had been performed without monoclonal antibody staining and multiple lobe, site-directed lavage, then the yield would have decreased to 95% in the nonprophylaxis group and to 80% in the aerosolized pentamidine group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Direct evidence of secondary necrosis of neutrophils during intense lung inflammation.

Several pulmonary inflammatory conditions are characterised by infiltration of neutrophils. Normally, neutrophils are silently removed by apoptosis, followed by phagocytosis. However, if phagocytosis fails, apoptotic cells undergo secondary necrosis. Recent findings of increased levels of the pan-necrosis marker lactate dehydrogenase in bronchoalveolar lavage from lipopolysaccharide-exposed mice implies potential involvement of secondary necrosis. Using a similar model, this study aimed to identify the source of lactate dehydrogenase and to search for direct histological evidence of secondary necrosis. Lipopolysaccharide (LPS) was administered to the lungs of BALB/c mice, and bronchoalveolar lavage and tissue samples were collected 4, 12, 24, 36, 48, 60 and 72 h after administration. LPS induced a patchy neutrophil-rich lung inflammation, where the numbers of terminal deoxynucleotide transferase-mediated dUTP nick-end labelling-positive neutrophils were increased at 12 h and onwards. Lavage levels of neutrophils and lactate dehydrogenase increased significantly at 4 and 24 h, respectively. Detailed electron microscopic assessment of neutrophil activation and death modes revealed that up to 14% of the neutrophils were undergoing secondary necrosis, whereas apoptotic or primary necrotic structural cells were rarely found. In summary, this study provides direct evidence that secondary necrosis of neutrophils is a common process during intense lung inflammation. This implies that neutrophil apoptosis may cause rather than resolve airway inflammation.