Multinuclear giant cells in bronchoalveolar lavage in interstitial lung diseases

The presence of multinuclear giant cells (MGC) is a pathological feature of interstitial lung diseases produced either by some organic and inorganic dust or by granulomatous disorders. In order to assess the diagnostic significance of the presence of MGC in bronchoalveolar lavage (BAL), the percent of MGC in the BAL of 52 subjects exposed to asbestos (26 with asbestosis) as well as from 79 with several interstitial lung diseases (idiopathic pulmonary fibrosis, pulmonary fibrosis associated with collagen vascular disorders, hypersensitivity pneumonitis and sarcoidosis) was compared with that of a control group of 14 subjects with no evidence of diffuse pulmonary disease. The results of this study suggest that MGC are present in the BAL of subjects with no pulmonary disease, and the quantification of these cells does not aid in the diagnostic evaluation of interstitial lung diseases.     

Mast cells in bronchoalveolar lavage fluid of patients with interstitial lung diseases

Mast cells play an important role in tissue inflammation, fibrosis and remodelling. They are found in bronchoalveolar lavage fluid (BAL) of healthy persons only in small numbers. We investigated the number of mast cells in interstitial lung diseases and analysed our data for correlations with clinical parameters, cellular and non-cellular parameters of BAL. We found following counts of mast cells in % of total BAL cells: Sarcoidosis (n = 123); 0.22 +/- 0,04 %, idiopathic pulmonary fibrosis (IPF) (n = 35); 0.39 +/- 0.47 %, cryptogenic organising pneumonia (COP) (n = 27); 2.05 +/- 2.19 %, hypersensitivity pneumonitis (HP) (n = 24); 1.02 +/- 1.05 %, rheumatoid lung (n = 20); 0.21 +/- 0.21 %, respiratory bronchiolitis-associated interstitial lung disease (RBILD) (n = 11); 0.16 +/- 0.29 %) and control group (n = 16); 0.06 +/- 0.16 %. Compared to controls mast cells were increased in COP (p < 0.001) and HP (p < 0,01). Correlation analysis showed that an increased mast cell count correlated with: Higher age (sarcoidosis (p = 0.03); smaller vital capacity (sarcoidosis (p = 0.01)), smaller FEV 1 (sarcoidosis (p = 0.04), RBILD (p = 0.04)); higher alkaline phosphatase in BAL (sarcoidosis (p = 0.004), HP (p = 0.02), COP (p = 0.04); higher albumin level in BAL (sarcoidosis (p = 0.000), IPF (p = 0.003); higher cell counts in BAL (sarcoidosis (p = 0.013), COP (p = 0.04)); lower portion of macrophages in BAL cells (sarcoidosis (p = 0.001), HP (p = 0.02), COP (p = 0.02)); higher portion of lymphocytes in BAL cells (sarcoidosis (p = 0.03)); higher portion of neutrophils in BAL cells (sarcoidosis (p = 0.007)); higher portion of eosinophils in BAL cells (sarcoidosis (p = 0.001), HP (p = 0.006)). Correlations to smoking history in pack years and to lymphocyte surface markers CD3, CD4, CD8 were not found. In conclusion comparing different interstitial lung diseases we found significantly increased mast cell counts in COP and HP. Moreover there were correlations of increased mast cell counts with more intensive alveolitis and exudation.     

Integrated approach to bronchoalveolar lavage cytology to distinguish interstitial lung diseases

BackgroundBroncho-alveolar lavage (BAL) is a safe diagnostic procedure, useful for differentiating fibrotic lung disorders and for excluding malignancy and infection. A recent multicenter study demonstrated a new, relatively sensitive, and specific index called Bronchoalveolar Cytology Threshold (BCT), useful for distinguishing healthy individuals from patients with lung diseases.ObjectivesIn our study, BCT was applied for the first time to the analysis of interstitial lung diseases (ILDs), investigating its potential for differential diagnosis. Combinations of BAL cells that improve diagnostic accuracy for ILDs were studied and are proposed.MethodsA retrospective analysis of BAL samples was performed. We considered more than 1000 BAL samples from patients investigated for ILD, performed at Siena University Hospital.The samples enrolled for the study included 468 patients: 413 with and 55 without ILD. BAL was performed for diagnostic purposes in line with international guidelines. BCT were calculated according to available literature.ResultsAmong ILDs, patients with fibrotic hypersensitivity pneumonitis, idiopathic pulmonary fibrosis (IPF) and sarcoidosis showed significantly lower BCTs than unclassified ILD. Asbestosis patients showed significantly lower BCTs than nonspecific interstitial pneumonia (NSIP), cryptogenic organizing pneumonia (COP), connective tissue disease related ILD (CTD-ILD), sarcoidosis and unclassified ILD patients. COP patients showed significantly higher BCT than IPF, f-HP and sarcoidosis. Moreover, COP patients were best distinguished by BCT.ConclusionThe analysis of BAL features is currently included in the diagnostic algorithm of ILDs. BAL cell patterns and BCT index can provide useful information for distinguishing ILDs, reducing the need for invasive procedures. Integrated approaches to BAL analysis can improve the interpretation of results without further cost or loss of time.     

Changes in phospholipids in bronchoalveolar lavage fluid of patients with interstitial lung diseases

We analyzed phospholipids of human bronchoalveolar lavage (BAL) fluids from patients with interstitial lung diseases; idiopathic pulmonary fibrosis (IPF), sarcoidosis, and eosinophilic granuloma (EG) and compared them to those of normal subjects. The content of phospholipid/ml of BAL fluid was significantly decreased in IPF. There was a significant decrease in phosphatidylglycerol (PG) and an increase in phosphatidylinositol (PI) in IPF but not in sarcoidosis and EG. Thus, the PG to PI ratio was significantly decreased in IPF. The dipalmitoyl species of phosphatidylcholine (PC) was found to be significantly decreased in IPF and sarcoidosis by molecular species analysis using high performance liquid chromatography. In contrast, the unsaturated species were increased in these diseases. The decrease in dipalmitoyl PC appeared to be a common feature in interstitial lung diseases. The changes in phospholipids in BAL fluids, especially decreases in DPPC and PG to PI ratio in IPF, appear to indicate that damage of alveolar Type II cells and/or of metabolic disturbance in pulmonary surfactant occurs in IPF.     

Changes in phospholipids in bronchoalveolar lavage fluid of patients with interstitial lung diseases

We analyzed phospholipids of human bronchoalveolar lavage (BAL) fluids from patients with interstitial lung diseases; idiopathic pulmonary fibrosis (IPF), sarcoidosis, and eosinophilic granuloma (EG) and compared them to those of normal subjects. The content of phospholipid/ml of BAL fluid was significantly decreased in IPF. There was a significant decrease in phosphatidylglycerol (PG) and an increase in phosphatidylinositol (PI) in IPF but not in sarcoidosis and EG. Thus, the PG to PI ratio was significantly decreased in IPF. The dipalmitoyl species of phosphatidylcholine (PC) was found to be significantly decreased in IPF and sarcoidosis by molecular species analysis using high performance liquid chromatography. In contrast, the unsaturated species were increased in these diseases. The decrease in dipalmitoyl PC appeared to be a common feature in interstitial lung diseases. The changes in phospholipids in BAL fluids, especially decreases in DPPC and PG to PI ratio in IPF, appear to indicate that damage of alveolar Type II cells and/or of metabolic disturbance in pulmonary surfactant occurs in IPF.     

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.     

The role of bronchoalveolar lavage in interstitial lung disease

Considerable progress has been made in understanding the similarities and differences among the forms of the interstitial lung diseases (ILDs), particularly the forms of idiopathic interstitial pneumonia, now recognized as distinct clinicopathologic entities. Lung parenchymal evaluation by high-resolution CT scanning of the chest may provide images that are virtually diagnostic of certain forms of ILD, but other testing, including bronchoalveolar lavage (BAL) and lung biopsy, may be required for accurate diagnosis. The differential diagnosis of these disorders rests on the clinician's interpretation of the clinical presentation and physical examination findings, pulmonary function testing, radiographic imaging, and, if required, sampling of lung tissue. This discussion examines the usefulness of BAL in the diagnosis of specific forms of ILD.     

间质性肺疾病支气管肺泡灌洗液的酶活性研究

目的探讨支气管肺泡灌洗液（ＢＡＬＦ）多项酶活性与间质性肺疾病（ＩＬＤ）的关系。方法检测３０例ＩＬＤｓ：包括特发性肺纤维化（ＩＰＦ）１８例和结节病（Ｓａｒｃ）１２例与９例正常对照者的ＢＡＬＦ中超氧化歧化酶（ＳＯＤ）、谷胱甘肽过氧化物酶（ＧＳＨ－ＰＸ）、血管紧张素转换酶（ＡＣＥ）和乳酸脱氢酶（ＬＤＨ）活性，并分类计数ＢＡＬＦ细胞成份。结果（１）ＩＰＦ组ＢＡＬＦ中各项酶活性均与对照组间差异有显著性（ＳＯＤ和ＧＳＨ－ＰＸ降低，ＡＣＥ和ＬＤＨ升高）（Ｐ＜０．０５）；而Ｓａｒｃ组仅见ＡＣＥ明显增高（Ｐ＜０．０５）。（２）ＢＡＬＦ－ＡＣＥ与Ｓａｒｃ组淋巴细胞百分比及ＣＤ＋４／ＣＤ＋８比值均有显著线性相关（Ｐ＜０．０５）。结论ＢＡＬＦ中ＳＯＤ、ＧＳＨ－ＰＸ、ＡＣＥ和ＬＤＨ活性测定，有助于进一步探讨ＩＬＤ发病机理和提供辅助诊断依据，ＢＡＬＦ－ＡＣＥ对判断Ｓａｒｃ活动性有重要临床意义。     

Antiproteases are increased in bronchoalveolar lavage in interstitial lung disease

The present study evaluates different cellular and soluble components in the bronchoalveolar lavage (BAL) from patients with interstitial lung disease. We observed an increased T4/T8 lymphocyte ratio in BAL but not in blood from 24 patients with active pulmonary sarcoidosis compared to sixteen normal individuals and to eleven patients with inactive pulmonary sarcoidosis. Seven patients with hypersensitivity pneumonitis had a normal T4/T8 ratio. In the active sarcoidosis and hypersensitivity pneumonitis groups, alpha 1-Protease Inhibitor (alpha 1 PI) in BAL is significantly higher than in the normal group and a significant correlation between the two antiproteases (alpha 2-macroglobulin and alpha 1 PI) is observed. These data demonstrate that antiprotease levels (alpha 1 PI and alpha 2 M) are increased in the lower respiratory tract of patients with interstitial lung disease and that among cellular and soluble components of BAL, alpha 2 M represents a sensitive marker of the alveolitis.     

Bronchoalveolar lavage in other interstitial lung diseases

This article reviews the changes in bronchoalveolar lavage (BAL) cytology and cell differentials in some of the rarer interstitial lung diseases. In a few of these diseases BAL has a diagnostic value and can replace lung biopsy. In pulmonary Langerhans cell histiocytosis the characteristic diagnostic finding is an increase in CD1 + Langerhans cells greater than 4% of total cells. The sensitivity of this cutoff value is low because only approximately 50% of patients show this elevation. In pulmonary alveolar proteinosis, the sensitivity of a diagnostic BAL is almost 100%, and the characteristic finding of milky and turbid fluid on gross examination and the characteristic findings with acellular globules that stain pink with PAS (periodic-acid-Schiff), along with abnormal foamy macrophages and a characteristic dirty background obviates the need for lung biopsy. In diffuse alveolar hemorrhage, BAL is the method of choice to diagnose the alveolar bleeding by showing free red blood cells and hemosiderin-laden, iron-positive macrophages. The underlying disorder has to be identified by history and clinical and laboratory tests. In eosinophilic lung disease, the diagnosis can be made if the BAL cell differentials show 25% or more eosinophils. In collagen vascular disease-associated lung fibrosis, the precise role of BAL in assessment and monitoring disease remains unclear. In drug-induced interstitial lung disease BAL may support a certain clinical/pathological pattern of lung involvement and is helpful for exclusion of other diseases, such as malignancies with pulmonary metastasis, heart disease with pulmonary congestion, or infections. The same is true for radiation-induced lung injury.     

Bronchoalveolar lavage in idiopathic interstitial lung diseases

Bronchoalveolar lavage (BAL) is useful for diagnosing various interstitial lung diseases (ILDs) and monitoring ILD during treatment. The ability to detect specific agents or substances by using BAL is especially helpful in determining whether idiopathic ILD has a background causality. BAL in combination with other intensive examinations may enable the definitive diagnosis of an idiopathic ILD. Among the idiopathic ILDs of concern, this article focuses on idiopathic interstitial pneumonia (IIP) and cryptogenic organizing pneumonia (COP). IIP and COP are classified together as idiopathic interstitial pneumonia (IIP), an integrated clinicoradiographic pathological disease entity. BAL has identified two points important for differentiating the disease entity: a paucity of lymphocytes appears in the BAL fluid of patients with idiopathic pulmonary fibrosis (IPF), and lymphocytosis with a decreased CD4:CD8 ratio appears in patients with COP. These findings can be useful, in combination with high-resolution computed tomographic (HRCT) data, for selecting a favorable treatment option. On the other hand, these rules cannot be applied to IP associated with collagen vascular disease (CVD). Furthermore, some IIP patients may manifest features of CVD during the clinical course after the detection of IP (interstitial pneumonia). Thus the definite role of BAL cell profiles remains to be determined.     

Mast cells, atypical lymphocytes, and neutrophils in bronchoalveolar lavage in extrinsic allergic alveolitis. Comparison with other interstitial lung diseases

Bronchoalveolar lavage (BAL) samples from exposed patients with extrinsic allergic alveolitis (EAA) contained mast cells in increased numbers in addition to lymphocytes. The counts rarely exceeded 0.5% in sarcoidosis, cryptogenic fibrosing alveolitis, or asbestosis or in control samples, but they were as much as 10-fold higher in EAA (p less than 0.001). Higher concentrations of histamine were demonstrated in EAA BAL-cell lysates, and histamine was released from cells challenged with anti-IgE. Electron microscopic examination confirmed that the cells were mast cells that differed from mast cells in dermal connective tissue and alveolar interstitial tissue but resembled bronchial subepithelial tissue mast cells in showing more features suggestive of activation. However, they showed more marked degranulation, and many were young. By light microscopy, they also resembled "mucosal" rather than "connective" tissue mast cells since granule staining was prevented by formaldehyde. Mast cell counts fell to normal after removal of patients from exposure, but lymphocyte increases, including atypical "blast" forms, persisted despite clinical recovery. Neutrophils were also increased before, but rarely after, removal. We suggest that EAA may provide an example of a human disease to support recent evidence that some delayed hypersensitivity disorders involve mast cells as well as lymphocytes.     

Proteolytic activities in bronchoalveolar lavage fluid of interstitial lung diseases: correlation to stage and prognosis

In 18 patients with sarcoidosis, 10 patients with idiopathic pulmonary fibrosis (IPF), 6 patients with exogen allergic alveolitis (EAA), and 9 control persons we investigated proteolytic activities in bronchoalveolar lavage fluid (BALF). In lymphocyte-macrophage alveolitis (i.e. sarcoidosis and EAA) proteolytic activities in BALF were low, but the activities correlated with lung function deterioration within 1 year. In IPF (i.e. in neutrophil alveolitis) we found a striking correlation between proteolytic activities and stage of disease: high activities correlated with early stages, lower values with late stages of IPF. Measurement of proteolytic activity in BALF seems to be of interest to differential diagnosis and to prognosis of interstitial lung disease.     

Fractional analysis of bronchoalveolar lavage in systemic sclerosis-associated interstitial lung disease

BackgroundThe utility of bronchoalveolar lavage (BAL) in the evaluation of systemic sclerosis-associated interstitial lung disease (SSc-ILD) remains controversial. Fractional analysis of BAL (FBAL) is a technique that can analyze small airways and alveolar compartments separately and has proven informative in other ILDs. The aim of this study was to explore FBAL characteristics across the spectrum of SSc-ILD severity.MethodsWe retrospectively reviewed patients with SSc-ILD who underwent bronchoscopy with FBAL using three 50 mL aliquots of saline solution. These aliquots were analyzed separately for differential cell composition (FBAL-1, -2, and -3). We compared the FBAL cell composition to the progression of ILD and end-stages of ILD using Cox proportional hazards models.ResultsSixty-eight patients with SSc-ILD were enrolled in this study. The percentage of neutrophils and eosinophils was lower in FBAL-3 compared to FBAL-1. In contrast, the percentage of macrophages and lymphocytes was higher in FBAL-3. Neutrophils in FBAL-2, -3, and the estimated total FBAL cell fraction (FBAL-total) were negatively correlated with the forced vital capacity % predicted (r=−0.420, −0.362, −0.409, respectively). Although FBAL-total was not linked to the progression and end-stage of ILD, a high percentage of neutrophils in FBAL-3 was significantly associated with the development of end-stage ILD (HR 1.093, 95% CI: 1.003–1.190).ConclusionsA higher percentage of neutrophils in FBAL-3 is correlated with development of end-stage ILD in SSc-ILD as well as mortality.     

Lipid peroxidation in bronchoalveolar lavage fluid in interstitial lung diseases in relation to other components and smoking

We measured lipid peroxide (LPO) in bronchoalveolar lavage fluid (BALF) from patients with interstitial lung diseases (ILD, 45 cases) including sarcoidosis (22 cases) and idiopathic interstitial pneumonia (7 cases). LPO correlated negatively with the macrophage fraction, and positively with lymphocyte fraction, type III procollagen N terminal peptide (PIIIP), and total protein in all cases. In sarcoidosis, it correlated with PIIIP positively, and in IIP, with total cell count, macrophage count, PIIIP/protein and total protein. Comparison between the current smoker group (SM) and non-smoker group (NON/EX) showed that in all cases, SM had lower LPO, lymphocyte fraction, lymphocyte count and total protein whereas higher macrophage fraction than NON/EX. In sarcoidosis, SM had a lower lymphocyte fraction and total protein and higher macrophage fraction. We conclude that LPO in BALF reflects inflammation and fibrosis occurring in the lung with ILD and this process might be suppressed in smokers.     

Lipid-laden macrophages in bronchoalveolar lavage fluid as a marker for pulmonary aspiration.

An increased lipid content in alveolar macrophages of bronchoalveolar lavage (BAL) fluid is thought to be a useful indicator for recurrent pulmonary aspiration. To assess whether pulmonary diseases unrelated to aspiration can raise the lipid content in alveolar macrophages, we evaluated Oil-Red-O-stained smears of BAL fluid in 18 children aged 3-15 years undergoing elective surgery for nonpulmonary illnesses under general anesthesia and in 18 children aged 1-16 years who had pulmonary diseases without clinical evidence of aspiration (pneumonia, exogenous allergic alveolitis, or cystic fibrosis). A semiquantitative lipid-laden macrophage (LLM) index was determined for each patient. LLM indices in children without pulmonary disease were higher than those published for healthy adults. In children with pulmonary diseases but without evidence of aspiration, a significantly higher LLM index was observed compared to controls. The LLM indices of children with pulmonary diseases were similar to those published by other authors for children with pulmonary aspiration. We conclude that an elevated LLM index in alveolar macrophages of BAL can be found in a variety of pulmonary diseases in which there is no clinical evidence of aspiration and is therefore unlikely to be a specific parameter for silent pulmonary aspiration.     

Cytological examination of bronchoalveolar lavage fluid and its clinical significance in patients with diffuse interstitial lung diseases

Cytological examination of bronchoalveolar lavage fluid (BALF) was carried out in 48 patients with diffuse interstitial lung diseases based on chest roentgenography. 7 cases manifested with respiratory symptoms but without any abnormality on both chest roentgenogram and fibroptic bronchoscopy served as controls. The total cell counts of BALF in the study group were all higher than those of the control group (3.1 x 10(5)/ml) and the differential count of the cells showed that neutrophilic granulocytes was found in patients with fibrosing alveolitis, Neutrophilic granulocytes accounted for 21.3 +/- 2.4% of all the cells and the percentage was significantly higher than that of the control group (1.8 +/- 0.5% P less than 0.01). On the contrary, lymphocytosis was found in patients with allergic alveolitis and sarcoidosis; lymphocytes accounted for 30.8 +/- 5.3% and 29.0 +/- 1.1% of all the cells in these two diseases respectively and the percentage was also higher than that of the control group (3.0 +/- 0.6% P less than 0.01). However, the differential cell count of BALF in alveolar carcinoma showed no significant difference with that of the control group (P greater than 0.05). The factors influencing the quality control of both BAL and cytological examination were evaluated and the clinical significance of these results was discussed.