Interstitial lung disease in scleroderma. Analysis by bronchoalveolar lavage

Interstitial pulmonary fibrosis is a common feature of scleroderma (systemic sclerosis) which may result in impairment of pulmonary function and may be a major determinant of morbidity and mortality. Clinicopathologic observations suggest that interstitial and alveolar inflammation may appear prior to fibrosis. Using the bronchoalveolar lavage (BAL) technique, we have characterized the nature of the inflammatory process in the lower respiratory tracts of 19 non-smoking scleroderma patients. Eleven of 19 patients (58%) had increased percentages of neutrophils and/or eosinophils in BAL fluid. Five of 10 patients (50%) had elevations of IgG in BAL fluid. The presence of neutrophils was associated with a decreased lung diffusing capacity for carbon monoxide (P less than 0.05) and with more advanced radiographic features of interstitial fibrosis in patients with disease of more than 1 year's duration. This study suggests that scleroderma lung involvement may be characterized by an inflammatory alveolitis and that the presence of such inflammation may relate to the severity of the pulmonary disease.     

Airway and alveolar inflammation assessments with bronchoalveolar lavage in various interstitial lung disorders]

Fractional analysis of bronchoalveolar lavage (FABAL) fluid was performed in 6 control patients and 41 patients with various interstitial lung disease. The cell differential counts in the first 30 ml fraction of BAL (FBAL-I), which is considered to be the bronchial lavage, differed from those of the 50 ml second and third fraction (FBAL-III). Hypersensitivity pneumonitis, pulmonary tuberculosis, and sarcoidosis showed a high recovery of lymphocytes (52%); however, the former two disorders were occasionally, associated with neutrophil airway inflammation, whereas sarcoidosis was not. The percentage recovery of neutrophils in total FBAL was considerably high in patients with diffuse panbronchiolitis, and relatively high in those with collagen vascular disease, idiopathic pulmonary fibrosis, pneumoconiosis, and control smokers. However, these neutrophils were largely recovered from FBAL-I, suggesting the presence of airway inflammation. Thus, it is valuable to apply the FBAL method to determine the topographic distribution of inflammatory cells in the lungs. It was also found that the lymphocyte morphology in the lavage fluid was of value in establishing the diagnosis of hypersensitivity pneumonitis, and it is critical whether or not mast cells and basophils are present in BALF since they indicate the pathologic state of allergy or fibrosis. Although present in various fibrotic lung diseases in a limit number, langerhans cells are a diagnostic marker for histiocytosis X.     

Bleomycin-induced lung injury in the rabbit. Analysis and correlation of bronchoalveolar lavage, morphometrics, and fibroblast stimulating activity

We have used a rabbit model of bleomycin-induced lung injury to evaluate the chronological changes in the bronchoalveolar lavage fluid (BALF) constituents. The correlation of these changes with morphologic alterations and measured soluble mediators of fibrosis has also been assessed. Three groups of 8 treated and 8 control New Zealand white rabbits received 10 U/kg bleomycin in normal saline, or equal volumes of saline intratracheally. The animals underwent bronchoalveolar lavage with a balloon tipped catheter localized to the right lower lobe at 3, 8, or 12 wk. Total cell counts and differentials were performed on the BALF. The lungs were examined histologically for inflammatory cells in the interstitium, alveoli, and airways by morphometric techniques. The lungs were also assayed for total hydroxyproline content. Bronchoalveolar lavage fluid supernatants and supernatants from lavaged macrophages cultured for 24 h were assayed for fibroblast stimulating activity (FSA) by 3H-thymidine incorporation into rabbit lung fibroblasts. There was a significant increase in macrophages and neutrophils in the BALF at 3 wk only, although the elevation of macrophages was sustained for longer than that of neutrophils. The numbers of BALF macrophages correlated with the morphometric assessment of the number of intra-alveolar macrophages (p less than 0.001) and interstitial mononuclear cells (p less than 0.001), as well as the extent of airway inflammation (p less than 0.001). The numbers of BALF neutrophils correlated with morphometrically assessed alveolar (p less than 0.01) and interstitial neutrophils (p less than 0.01) but not with any airway inflammation scores.(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of bronchoalveolar lavage in interstitial lung disease.

Bronchoalveolar lavage remains an important research tool in understanding ILD. It is still an important part of the clinical management of patients with ILD. It is most useful in detecting unusual forms of ILD. It helps the clinician narrow down the possible causes of the interstitial pattern. It also can confirm a clinical impression of certain conditions. Although rarely diagnostic, it is often supportive. In conjunction with high-resolution CT scan, most patients with ILD can be diagnosed using relatively noninvasive methods.     

肺泡灌洗液在肺癌早期诊断方面的研究进展

肺癌是全球癌症相关死亡的最常见原因。每年约有180万人被诊断出患有肺癌,其中约有160万人死于肺癌[1]。然而在我国约75%的肺癌患者在确诊时已属晚期,5年生存率仅为15.6%[2],有研究表明对于Ⅰ期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者早期手术切除,其5年生存率可提高至70%~90%[3]。这表明早期诊断和早期治疗在提高肺癌患者生存率、降低死亡率中起着至关重要的作用。目前世界范围公认的早期肺癌筛查手段为低剂量CT(low-dose computed tomographic,LDCT),美国国家肺癌筛查试验(National Lung Screening Trial,NLST)的随机对照研究结果显示LDCT筛查可使得肺癌死亡率相对降低20.0%,但其假阳性率高达96%[4],而对于其分辨率无法识别的早期肺癌又易漏诊,因此对于肺癌的筛查迫切需要一种创伤小、敏感性高、特异性好的标志物。肺癌是起源于支气管黏膜上皮及肺泡上皮的恶性肿瘤,脱落的肿瘤细胞及其代谢产物可直接进入肺泡腔内,所以支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)较其他液体标本更好的显示其中组分特异性,肺泡灌洗液中细胞学、分子生物学都可用于肺癌的早期诊断,本文就BALF中DNA甲基化、外泌体、端粒酶、非整倍体等在肺癌早期诊断方面的研究作一综述。     

Comparison between bronchial and alveolar samples of bronchoalveolar lavage fluid in asthma.

BACKGROUND: Cell content of BALF may vary according to the segment of the lung washed. It was proposed to separate BALF into several aliquots, the first sample being more related to bronchi. The present study compared bronchial and alveolar samples by fractionating aliquots of BALF in normal and asthmatic subjects. METHODS: One hundred asthmatic subjects (mean +/- SEM: 37 +/- 1.5 yr in age) were compared with 31 normal subjects (mean +/- SEM: 32 +/- 2.2 yr in age). None of the subjects was a smoker and none was taking drugs that might interfere with the results. The severity of asthma was defined by the clinical score of Aas examining the chronic severity of asthma and ranging from 1 to 5 (range: 1 to 4; mean +/- SEM: 2.2 +/- 0.1) and FEV1 (range: 45 to 130 percent; mean +/- SEM: 82 +/- 1.8 percent of predicted values). Bronchoscopy was done in a standardized manner. A first aliquot of 50 ml of saline each were instilled and the BALF recovered was pooled (alveolar sample). After centrifugation, total and differential cell counts (May Grünwald-Giemsa) were carried out on bronchial and alveolar samples. RESULTS: The alveolar sample contained significantly more cells per milliliter of BALF than the bronchial sample in normal (p less than 0.0077, Wilcoxon test) and in asthmatic subjects (p = 0.0001, Wilcoxon test). Both in normal and asthmatic subjects, bronchial samples contained significantly more neutrophils and epithelial cells and fewer macrophages and lymphocytes than alveolar samples. In asthmatic subjects, the bronchial sample contained a significantly greater percentage of eosinophils than the alveolar sample. Eosinophils were significantly increased in asthmatic subjects for both the bronchial and alveolar samples. Bronchial and alveolar eosinophilia both were correlated with the Aas score (r = 0.25, p = 0.024 and r = 0.38, p = 0.0006, respectively, by Spearman Rank test). CONCLUSIONS: This study shows in a large number of subjects that the cell content of bronchial and more distal segments of the lung is not comparable, indicating that studies should not give pooled data in asthmatic subjects. Moreover, it confirms the presence of BALF eosinophilia in asthmatic subjects.     

The effects of corticosteroid administration on the bronchoalveolar cells obtained from guinea pigs by lung lavage.

The effects of systemic administration of corticosteroids on the bronchoalveolar cell population obtained from guinea pigs by lung lavage were studied. The results of this study demonstrate that in contrast to the marked decrease in the percentage of T lymphocytes in the peripheral blood of animals treated with steroids, there was no significant decrease in the percentage of T lymphocytes in the bronchoalveolar cell population. In addition, corticosteroid administration did not significantly affect either the number of alveolar macrophages obtained by lavage or the Fc receptor activity of these cells. When considered in the context of previously reported data, these results emphasize that caution must be used in reaching conclusions about the integrity of the pulmonary immune response from the results of studies using a bronchoalveolar cell population obtained by lung lavage. This observation must be considered when evaluating the significance of studies of the human pulmonary immune response performed with cells obtained by segmental bronchopulmonary lavage.     

Bleomycin-induced lung injury in baboons: Alteration of cells and immunoglobulins recoverable by bronchoalveolar lavage

Bleomycin-induced lung injury in baboons was investigated by serial bronchoalveolar lavage. Nine juvenile baboons (Papio cynocephalus) were injected intramuscularly with bleomycin sulfate, 1. 5 U/kg body wt., twice weekly for 22 consecutive weeks. Six baboons of similar age served as untreated controls. During the treatment period, the amounts of immunoglobulin G and A and the numbers of eosinophils recovered by bronchoalveolar lavage were increased significantly. Fourteen of the 24 samples from treated animals had ratios of immunoglobulin G or A to albumin which were greater than any corresponding control ratio. After bleomycin was stopped, immunoglobulins G and A and eosinophils returned to control levels. However, during the recovery period lymphocytes were increased significantly in lavage fluids of treated animals for 10 weeks. Immunofluorescence of lung tissue biopsies from treated animals failed to detect immunoglobulins or complement deposition. Similarly, no binding of immunoglobulins present in lavage fluids to normal baboon lung was demonstrated by immunofluorescence. In the presence of collagen peptipes, alveolar macrophages from treated animals migrated shorter distances than did macrophages of control animals. Peripheral blood cells and immunoglobulins were unaffected by bleomycin treatment. These studies suggest that serial bronchoalveolar lavage may aid in the sequential evaluation of patients with diffuse interstitial pulmonary fibrosis, especially when it develops in conjunction with drug therapy.     

Fractional processing of sequential bronchoalveolar lavage to separate bronchial and alveolar samples

Bronchoalveolar lavage has been widely used to sample the lower respiratory tract. Most of the material recovered with this technique represents alveolar contents. A number of modifications have been suggested in order to obtain samples relatively enriched for bronchial material. In order to be able to use a standard technique for bronchoalveolar lavage to sample both airways and "routine" alveolar material, a simple modification of the technique as described by Reynolds and Newball was used: five sequential 20-ml aliquots were infused into the lower respiratory tract, and each aliquot was immediately aspirated. The return from the first aliquot was processed separately from the return from the subsequent four aliquots. These last four aliquots were pooled. Analysis of the first aliquot revealed it to be enriched for ciliated epithelial cells when compared with the subsequent aliquots. There were also differences in inflammatory cell composition with the bronchial sample containing relatively more neutrophils and relatively less lymphocytes. Aspiration during transoral bronchoscopy was documented by quantifying salivary amylase in the bronchial and alveolar lavage fluids. It was estimated, however, that the aspiration was not of quantitative significance in the vast majority of subjects studied. Finally, with the technique of fractional processing of bronchoalveolar lavage samples, it was possible to compare the protein concentrations in bronchial and alveolar lavages. Most prominent among the differences was a marked relative enrichment in the bronchial samples for immunoglobulin A. The technique of fractional processing of bronchoalveolar lavage samples provides a simple means to obtain samples enriched for bronchial and alveolar components. This should facilitate analysis of lower respiratory tract specimens in airway disease.     

Evaluation and management of scleroderma lung disease using bronchoalveolar lavage

PURPOSE: Bronchoalveolar lavage (BAL) was performed in 43 nonsmoking patients with scleroderma (systemic sclerosis) to determine the frequency of alveolitis, the status of BAL findings over time, and the relationship of such findings to pulmonary status initially and at follow-up. PATIENTS AND METHODS: Forty-three nonsmoking patients with systemic sclerosis underwent extensive pulmonary evaluation including pulmonary function tests, chest radiographs, and BAL with analysis of cells, IgG, albumin, immune complexes, and fibronectin. RESULTS: Alveolitis was detected on initial BAL evaluation in 21 patients (49%). Alveolitis was characterized by hypercellular lavage fluid, due to an absolute increase in alveolar macrophages and due to an increase in both the absolute number and percentage of granulocytes (neutrophils and eosinophils). Patients with systemic sclerosis had significantly higher levels of IgG and immune complexes in BAL fluid than did control subjects, and alveolar macrophages from patients with systemic sclerosis released higher amounts of fibronectin in vitro. In serial studies, alveolitis was found to persist. Patients with alveolitis had greater dyspnea than patients without alveolitis (p = 0.02), and they had greater reductions in lung volumes and carbon monoxide diffusing capacity (DLCO) (p = 0.004). Furthermore, patients with persistent alveolitis had significantly greater reductions in pulmonary function over time than patients without alveolitis (forced vital capacity [FVC]: -0.69 L versus -0.05 L, p less than 0.001; DLCO: -2.94 mL/minute/mm Hg versus +0.16 mL/minute/mm Hg, p = 0.03). BAL was used to select patients with alveolitis and at risk of pulmonary deterioration, and treatment was instituted with cyclophosphamide and prednisone, resulting in significant improvement in dyspnea (p less than 0.001) and the rate of change of FVC (p = 0.02) and DLCO (p less than 0.001). CONCLUSION: We conclude that alveolitis occurs frequently in systemic sclerosis and that BAL is useful in identifying such patients who are at risk for a further decline in pulmonary status. Preliminary observations suggest that treatment of patients with active alveolitis may result in improvement in pulmonary status.     

Quantitative culture of bronchoalveolar lavage from patients with anaerobic lung abscesses.

The study of anaerobic infections of the lung is usually limited to the use of invasive techniques such as transtracheal aspiration (TTA) to avoid contamination by oral flora. Bronchoalveolar lavage (BAL) has been used successfully in the study of the etiology of pneumonia in immunocompromised patients. This study evaluated the role of the quantitative culture of BAL in the diagnosis of lung abscess. Four episodes of lung abscess in three patients were studied, and the results of quantitative culture of BAL were compared with those of the standard technique of TTA. Nineteen anaerobic bacterial species were recovered from the BAL fluid, all but one at concentrations greater than 10(3) cfu/ml. Culture of BAL fluid yielded 18 of 22 of the isolates cultured from TTA, including 12 of 16 of the anaerobic bacteria. This study suggests that quantitative culture of BAL fluid may be useful in the bronchoscopic evaluation of lung abscess.     

Contribution of bronchoalveolar lavage to the management of interstitial lung disease

Bronchoalveolar lavage (BAL) is a minimally invasive method for exploring the distal lung. It enables collection of free cellular and acellular material present in the alveoli. Over the last two decades BAL has become a fundamental tool for positive diagnosis of interstitial lung disease and even more for differential diagnosis. It has contributed greatly to the diagnosis of lung infections, particularly in immunosuppressed patients. In the context of non-infectious infiltrative disease, the diagnostic contribution of BAL is limited due to the lack of a specific cell profile. It remains a fundamental tool for the differential diagnosis of idiopathic interstitial pneumonia. With BAL, a number of infectious or tumoral diseases can be ruled out with precision. It is also an important element for the evaluation of possible iatrogenic disease. BAL has transformed the diagnosis of interstitial lung disease and considerably reduced the indications for surgical biopsy.     

Nonfibrous mineral particles in bronchoalveolar lavage fluid and lung parenchyma from the general population.

It is recognized that bronchoalveolar lavage (BAL) gives access to particulate matter present at the surface of the peripheral airspace. The objective of the present study was to evaluate the ability of BAL fluid analysis to predict the lung parenchymal particulate content. A BAL fluid sample, the parenchyma sample having undergone BAL, and an adjacent parenchyma sample that had not undergone BAL were obtained at autopsy on 10 individuals without any known recent occupational exposure to mineral particles. The particles (larger than 0.1 micron) were analyzed using a transmission electron microscope equipped with a microanalysis system. Nineteen types of particles were distinguished. The distribution of particle types in the three samples was compared. No significant difference between the relative concentrations was found, except for two particle types: fly ash (excess in BAL fluid compared with lavaged lung) and kaolinite (excess in lavaged lung compared with adjacent area). Such differences may be due to limitations in methodology. Although no correlation could be found between the absolute concentrations of particles in BAL fluid and in lung tissue, analysis of particles in BAL fluid may provide information on the types of particles present in the lung parenchyma.     

Transbronchial biopsy of the lung and bronchoalveolar lavage in the diagnosis of sarcoidosis

The outcomes of a complex study of sarcoidosis and other interstitial pulmonary diseases in 1325 patients are presented. An important role of intrapulmonary biopsy and bronchoalveolar lavage methods in defining the diagnosis and the process activity, especially when they are used in combination, is demonstrated. Complications in the form of bleedings and pneumothorax were registered in a limited number of the patients, mainly as a result of rigid bronchoscope procedures. Differential and diagnostic signs of sarcoidosis and some other disseminations in the lung, obtained by means of biopsy, bronchoalveolar lavage and clinical data studies, are given.     

The role of bronchoalveolar lavage in patients considered for open lung biopsy.

In summary, BAL should be considered as a diagnostic alternative in many patients for whom open lung biopsy is considered. In the proper clinical setting, several disorders may be adequately confirmed or diagnosed by BAL, with or without transbronchial biopsy, avoiding the morbidity and mortality associated with open lung biopsy. Again in the immune-compromised host with diffuse pulmonary infiltrates, BAL is often the initial procedure of choice. In the future BAL will likely gain a more prominent role in the staging of interstitial and occupational lung diseases, as larger prospective studies are concluded.     

Glycosidases and proteases of alveolar macrophages obtained by bronchoalveolar lavage from smokers and non-smokers

Glycosidase and protease activities were characterized in alveolar macrophages obtained by bronchoalveolar lavage from two non-smokers, two light smokers, and two heavy smokers. These enzymatic activities were lower in non-smokers than in smokers.     

Pulmonary zygomycosis. A cause of positive lung scan diagnosed by bronchoalveolar lavage

The diagnosis of pulmonary zygomycosis usually depends on the detection of fungal hyphae in biopsied tissue specimens. We describe a patient with a high-probability lung scan and diffuse pulmonary infiltrates due to Zygomycetes diagnosed by the demonstration of nonseptate hyphae in bronchoalveolar lavage fluid.