The response of alveolar lymphocytes induced by Propionibacterium acnes in pulmonary sarcoidosis: correlation with clinical studies, pulmonary function studies and bronchoalveolar lavage

Current concepts of the pathogenesis of sarcoidosis suggest that the alveolitis in this disorder is related to increased numbers of helper T-cells within the lungs. However, the mechanism of this accumulation of lymphocytes is not known. We have reported that proliferation of alveolar lymphocytes induced by P. acnes is increased in patients with active sarcoidosis. To determine whether the response of alveolar lymphocytes would be useful in staging the activity of pulmonary sarcoidosis, we studied 34 untreated patients with this disorder, and correlated the response of alveolar lymphocytes with clinical, roentgenographic, physiologic, and bronchoalveolar lavage findings in these non-smoking patients. There was a significant correlation of the response in the numbers of lymphocytes (p less than 0.05) and CD4 (+) T-cells (p less than 0.01) recovered from the lungs of these patients by bronchoalveolar lavage. Furthermore, the response correlated significantly with the activity of Interleukin-2 released by alveolar lymphocytes stimulated by P. acnes (p less than 0.05). In contrast, no correlation was found between the response and the clinical, roentgenographic, or physiologic data. However, in patients who showed abnormality in all three clinical examinations, i.e. serum angiotensin converting enzyme activity, number of alveolar lymphocytes, and 67Ga scintigraphy of the lung, the response was significantly higher than in controls (p less than 0.001) or in patients with none of these abnormalities (p less than 0.01). Also, the response in patients with an abnormality in two of these three examinations was significantly elevated compared to that in normals (p less than 0.025) or in patients without an abnormal examination (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)     

Latent pulmonary involvement in Crohn's disease: biological, functional, bronchoalveolar lavage and scintigraphic studies.

We have investigated the following pulmonary related parameters in 22 patients with Crohn's disease who were free of clinical pulmonary symptoms and had normal chest roentgenograms and in 25 controls: serum angiotensin converting enzyme, pulmonary function tests, bronchoalveolar lavage (lymphocyte count and subpopulations, macrophage viability and superoxide anion release by macrophages) and pulmonary scannings. Serum angiotensin converting enzyme was lower in Crohn's disease (14.1 +/- 5.1) than in controls (25.2 +/- 4.7) (p less than 0.001). Twelve of 22 Crohn's disease (54%) had a bronchoalveolar lavage lymphocytosis (greater than 18% alveolar lymphocytes). Bronchoalveolar lavage lymphocytes subpopulations were quite variable. Twelve of 17 Crohn's disease (71%) had an increase spontaneous and/or stimulated superoxide anion production by alveolar macrophages. Six of 12 Crohn's disease (50%) had an increase physiologic dead space in the upper part of their lung against one of 11 controls (9%). These data suggest that most patients with Crohn's disease have a latent pulmonary involvement.     

Amiodarone pulmonary toxicity. Assessment by bronchoalveolar lavage

Bronchoalveolar lavage was used to demonstrate morphologic changes in alveolar macrophages characteristic of amiodarone effect in lung tissue obtained by biopsy. This procedure may be useful in the assessment of abnormal chest x-ray findings in patients suspected to have amiodarone toxicity.     

Idiopathic pulmonary fibrosis. Pretreatment bronchoalveolar lavage cellular constituents and their relationships with lung histopathology and clinical response to therapy

Analysis of bronchoalveolar lavage cellular constituents has been recommended as a valuable method for the characterization of the inflammatory cellular population and for studying cellular interactions in the lower respiratory tract of patients with idiopathic pulmonary fibrosis (IPF). However, the clinical relevance of the enumeration of cells in bronchoalveolar lavage fluid (BALF) from patients with IPF remains controversial. We therefore examined the correlations between BALF cellular constituents and both the histopathologic abnormalities and the subsequent clinical response to corticosteroid therapy in 26 newly diagnosed, untreated patients with IPF. The BALF lymphocytosis was associated with moderate-to-severe alveolar septal inflammation (p less than 0.0005) and with a relative lack of histologic honeycombing (p less than 0.05). On the other hand, BALF neutrophil and eosinophil contents did not significantly correlate with any of eleven particular histopathologic abnormalities, and BALF neutrophil and lymphocyte contents did not correlate with the degree of clinical impairment (quantitated by a composite score based on dyspnea, radiographic abnormalities, and physiologic impairment) upon presentation. However, BALF eosinophil content correlated significantly with the severity of clinical impairment, higher eosinophil counts being associated with more severe initial clinical impairment (p less than 0.01). Neither pretreatment BALF neutrophil nor eosinophil content was related to the frequency or magnitude of subsequent clinical change in 20 patients evaluated before and after 1 yr of corticosteroid therapy. In contrast, pretreatment BALF lymphocytosis was associated with significant subsequent clinical improvement (p less than 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)     

Diagnosis of pulmonary strongyloidiasis by bronchoalveolar lavage

Bronchoalveolar lavage was performed on a patient with disseminated strongyloidiasis and 4.5 X 10(7) cells/65 ml of lavage fluid were recovered. Eighty-five percent of cells were polymorphonuclear leukocytes; 15 percent were pulmonary alveolar macrophages. Rhabditiform larvae (1 X 10(4)) were recovered in 65 ml of lavage fluid. This is the first report of bronchoalveolar lavage used in diagnosing disseminated strongyloidiasis.     

结节病患者肺功能与支气管肺泡灌洗液细胞学关系的研究

目的 探讨结节病患者不同影像分期之间肺功能指标、支气管肺泡灌洗液细胞学的改变以及两者的相关性.方法 回顾性调查71例结节病患者肺功能以及支气管肺泡灌洗液检查的资料.结果 在结节病患者不同影像分期之间肺功能指标用力肺活量(FVC)占预计值%、第1秒用力呼气容积(FEV1)占预计值%、肺总量(TLC)占预计值%以及肺一氧化...     

Detection of pulmonary lymphoma by bronchoalveolar lavage

A patient with bilateral interstitial infiltrates was evaluated by bronchoalveolar lavage prior to open lung biopsy. The patient was found to have lymphocytic alveolitis (34 percent lymphocytes) in which 43 percent of lymphocytes were B cells. A clonal proliferation of these B cells was suggested by the finding of monoclonal kappa light chain on the B lymphocytes. A suspected diagnosis of primary pulmonary non-Hodgkin's lymphoma was later confirmed by open lung biopsy.     

Amiodarone-induced pulmonary toxicity. Immunoallergologic tests and bronchoalveolar lavage phospholipid content

Amiodarone (A) is a widely-used antiarrhythmic drug. Pulmonary toxicity is the most serious adverse effect with an estimated mortality of 1 to 33 percent. In order to determine an element helpful for diagnosis, we examined four patients with amiodarone-induced pulmonary toxicity, three patients treated with A, without evidence of pulmonary toxicity but with a main underlying pulmonary disease, and four healthy volunteers. Daily and cumulative doses or duration of treatment were similar in the first two groups. Pulmonary function tests (spirometry, CO-diffusing capacity, arterial blood gases), roentgenographic examinations, pulmonary biopsies or immunoallergologic tests (skin reaction, lymphoblastic transformation test and human basophile degranulation test) did not provide any discriminatory element. In APT+, we observed an increased cellularity of the bronchoalveolar lavage. Neither the differential cell count nor the presence of foamy macrophages were distinguishable between APT+ and APT-. The phospholipid composition of BAL fluid showed a decreased total phospholipid and phospholipid/protein ratio in all patients compared to normal subjects. These changes reflect more the severity of pulmonary disease than the specificity of the causative agent. However, we observed that the unique PL which decreases in APT- and remains normal in APT+ is phosphatidyl-serine + phosphatidylinositol (PS + PI). This has to be confirmed and should be evaluated at different stages of the disease to determine an eventual specific element. We conclude that there are no data currently available to establish the diagnosis of APT except perhaps for the analysis of BAL PL content.     

Idiopathic pulmonary fibrosis. Abnormalities in bronchoalveolar lavage fluid phospholipids

Bronchoalveolar lavage has been used to sample cells and proteins in the distal lung. One of the major secretory products of the alveolar type II epithelial cells, pulmonary surfactant, can be recovered by lavage. Abnormalities in alveolar type II cells are found in biopsies of patients with idiopathic pulmonary fibrosis (IPF), and abnormalities of pulmonary surfactant phospholipids have been reported after diffuse lung injury in animals and in humans. Therefore, we questioned if abnormalities in lavage phospholipids might also occur in IPF, a chronic inflammatory disease of the alveolar epithelium and interstitium, and, if present, would these abnormalities reflect histopathologic changes or predict responsiveness to therapy. Fifteen untreated patients with IPF, diagnosed by open lung biopsy, were studied and were found to have less than half the amount of bronchoalveolar lavage phospholipid as that recovered from healthy volunteers (p less than 0.05). In addition, patients with IPF had a lower proportion of phosphatidylglycerol and a higher proportion of phosphatidylinositol in the recovered phospholipids than did healthy volunteers (p less than 0.05). The severity of these alterations in phospholipid composition correlated with more advanced fibrotic histopathologic changes. Patients with less depression of total phospholipids in lavage improved with corticosteroid therapy, whereas the patients with more severely decreased total phospholipid recovered in lavage did not.     

Correlation of chest roentgenograms with pulmonary function and bronchoalveolar lavage in interstitial lung disease

We used the ILO classification for occupational lung disease to determine whether there was any correlation between the type and/or severity of pulmonary infiltration on chest roentgenograms and either pulmonary function tests or the types of inflammatory cells present in BAL fluid in patients with interstitial lung disease. Of the 62 patients evaluated (27 with sarcoidosis, 18 with IPF, and 17 with a CV disease and lung involvement), 49 had irregular linear opacities and 13 had normal chest x-rays. There were no significant correlations between the types of cells present in BAL fluid and the various categories of infiltrate or profusion of the infiltrates within each disease group. In patients with sarcoidosis, more extensive infiltration (profusion) was associated with lower FEV, (p less than 0.01). In patients with IPE, linear opacity type, profusion, and the presence or absence of honeycombing were not related to the severity of pulmonary function abnormalities. We conclude that the ILO classification for analysis of chest roentgenograms can be applied to patients with interstitial lung disease not associated with an occupational exposure and that this approach is useful, especially for communication. However, these data provide no information regarding the inflammatory process in the lung and limited information regarding abnormalities in pulmonary function.     

Toxic-oil syndrome. Gallium-67 scanning and bronchoalveolar lavage studies in patients with abnormal lung function

The toxic-oil syndrome (TOS) is a multisystem disorder whose etiology and pathogenesis are as yet unknown. Lung alterations persist in a significant number of TOS patients due to the underlying vascular lesion. Computer-assisted 67Ga scanning and bronchoalveolar lavage (BAL) studies were performed in 14 TOS patients with sustained abnormal diffusing capacity for carbon monoxide (Dco). No significant difference was observed between the 67Ga uptake index of the TOS and control populations. Likewise, there was no significant difference in the number of effector cells recovered from the lungs of TOS patients and controls by bronchoalveolar lavage. However, a rise in IgA and IgG concentrations (p less than 0.002) and a fall in alpha 1-antitrypsin (p less than 0.05) and transferrin (p less than 0.01) were observed in the TOS group. Phospholipid and lecithin concentrations in the lavage fluid were similar for patients and controls. The alveolar macrophage function assayed in three TOS patients was normal. These observations raise new questions about the outcome of lung pathology in TOS and warrant further follow-up studies of the lung abnormalities observed.     

Idiopathic hypereosinophilic syndrome-related pulmonary involvement diagnosed by bronchoalveolar lavage.

Patients with HES and pulmonary infiltrates may pose certain diagnostic problems as the infiltrates may be attributed to infection, infarction, congestive heart failure, or HES itself. We report an 87-year-old woman with idiopathic HES presenting with bibasal alveolar infiltrates. Differential cell count in BAL fluid yielded a very high percentage (73 percent) of eosinophils. Other authors previously mentioned the absence of eosinophils in the lavage fluid despite an important peripheral eosinophilia in a patient with the idiopathic HES but without HES-related pulmonary involvement. Thus, BAL fluid eosinophilia may suggest HES-related pulmonary involvement. Therefore, BAL might be an important diagnostic tool in the management of pulmonary infiltrates in idiopathic HES.     

Diagnosis of pulmonary histoplasmosis and blastomycosis by detection of antigen in bronchoalveolar lavage fluid using an improved second-generation enzyme-linked immunoassay

Antigen detection is a useful adjunct for the diagnosis of histoplasmosis. The purpose of this study was to evaluate antigen detection in bronchoalveolar lavage (BAL) fluid using an improved second-generation Histoplasma antigen assay. Antigen was detected in 16 of 19 (84%) cases of histoplasmosis and 5 of 6 (83.3%) blastomycosis cases using the second-generation assay vs. 13 of 19 (68%) and 4 of 6 (66.7%), respectively, in the original assay. Ten-fold concentration permitted detection of antigen in an additional case of histoplasmosis and another with blastomycosis, for an overall sensitivity of 23 of 25 (92.0%). Specificity was 98.2% in both assays in controls with other pulmonary infections. These findings support the diagnostic utility of the second-generation assay in patients with pulmonary histoplasmosis and blastomycosis.     

Predictive value of bronchoalveolar lavage in pulmonary sarcoidosis

We investigated whether analysis of cellular composition (including lymphocyte subsets) in bronchoalveolar lavage (BAL) fluid at the start of follow-up in patients with untreated sarcoidosis has any predictive value for further evolution of the disease. The outcome was evaluated by the chest roentgenograms, the lung volumes, and the single breath diffusing capacity for CO (DCO) after 22 to 36 months. In contrast to the general belief, patients who improved radiologically had a significantly higher T4 cell count (as percentage of BAL lymphocytes) (p less than 0.02) and a higher T4-T8 ratio in the initial BAL sample (9.3 vs 3.2; p less than 0.05) than those whose chest roentgenogram showed deterioration or remained unchanged. Total cell count and the percentage of lymphocytes in BAL fluid were not different between both groups. The change in DCO at the end of the follow-up period correlated positively with the baseline BAL T4 cells (Rs = 0.44; p less than 0.05) and with the BAL T4-T8 ratio (Rs = 0.51; p less than 0.03) and negatively with the baseline BAL T8 cells (Rs = -0.48; p less than 0.04). In only three patients progression of the disease necessitated steroid therapy, and they all had a low to normal T4-T8 ratio in the initial BAL sample. Bronchoalveolar lavage was repeated at least once in ten patients. Improvement of the chest roentgenograms in these patients was accompanied by a decrease of the BAL T4 cell count (as percentage of lymphocytes) and of the T4-T8 ratio. We conclude that a high lymphocyte count, a high T4 cell count (as percentage of lymphocytes), and a high T4-T8 ratio in BAL fluid reflect an intense alveolitis at the time of the procedure, but they are not indicators of poor prognosis on which therapeutic decisions can be based.     

Bilateral bronchoalveolar lavage in the diagnosis of opportunistic pulmonary infections.

To further improve the diagnostic value of bronchoscopy in the immunosuppressed population presenting with diffuse pulmonary infiltrates, we prospectively investigated the utility of bilateral bronchoalveolar lavage (BAL). We performed 62 bronchoscopies on 52 immunosuppressed patients. Of the 52 patients, 33 had pulmonary infections. The yield for Pneumocystis carinii pneumonia on bilateral BAL was 94 percent (31/33), compared to the 84 percent (51/61) previously obtained with unilateral BAL in our institution. The recovery of P carinii was unilateral in four of five patients without AIDS and in four of 26 patients with AIDS. Transbronchial biopsy gave a yield of 85 percent (11/13). In ten patients with definitive cytomegalovirus (CMV) pneumonia, recovery of CMV by combined culture and cytology was 100 percent. Of nine bronchoscopies with positive cytology for CMV, five showed cytopathologic changes in the BAL from both sides and four in the BAL from one side only. No complications were seen in the 14 patients with thrombocytopenia or the five patients receiving mechanical ventilation. Our findings indicate that bilateral BAL significantly increases the yield for recovery of P carinii (p less than 0.02) and CMV (p less than 0.001) in immunosuppressed patients.     

Assessment of bleomycin-induced pulmonary fibrosis by bronchoalveolar lavage

To elucidate the pathogenesis of adult respiratory distress syndrome (ARDS), bleomycin is often used to induce lung injury because of is acute inflammatory and late fibrogenic effects on the lung. This study was undertaken to determine if fibroblast growth factors or suppressive factors might exist in bronchoalveolar lavage fluid (BALF) when acute lung injury is induced by bleomycin in rats. In the experimental group, 1.5 U of bleomycin was administered intratracheally, whereas in the control group, saline solution was given. In both groups, rats were sacrificed serially up to 4 wks. In each rat, bronchoalveolar lavage was done three times using an aliquot of 5 ml saline solution. BALF was centrifuged to obtain cells and supernatants which were further fractionated by gel-filtration. Fibroblast stimulatory and inhibitory activities were evaluated by [3H]-thymidine incorporation by fibroblasts. In the experimental group, the recovered cell count increased threefold compared with the control group and most of the increase was attributed to the increase of neutrophil. The fraction whose molecular weight is about 20,000 potentiated the [3H]-thymidine incorporation by fibroblast and its peak activity was found on the 5th day after BLM administration. On the other hand, the fraction of small molecular weight (less than 1,000) showed inhibitory activity which did not change throughout the study period. These results suggest that the imbalance between the fibroblast stimulatory and inhibitory activities after the acute lung injury may have a key role to develop pulmonary fibrosis.     

Acute myelomonocytic leukemia. Demonstration of pulmonary involvement by bronchoalveolar lavage

Massive pulmonary infiltration by leukemic cells resulting in respiratory symptoms is a rare complication of acute leukemia. We report the findings in a patient with acute myelomonocytic leukemia presenting with acute onset of fever, dyspnea, and nonproductive cough, in whom the diagnosis of pulmonary invasion by leukemic cells was made by cytochemical analysis of bronchoalveolar cells recovered by lavage.     

Sequential bronchoalveolar lavage in experimental extrinsic allergic alveolitis. The influence of cigarette smoking

We studied the alterations induced by acute experimental extrinsic allergic alveolitis (EAA) on bronchoalveolar cell population in smoking and nonsmoking guinea pigs. Sixty-two animals divided into 3 groups were studied: Group 1 (17 animals), controls; Group 2 (21 animals), extrinsic alveolitis; Group 3 (24 animals), cigarette smoking and alveolitis. Bronchoalveolar lavages (BAL) were performed on Days 1, 19, and 44 for all animals. Group 3 animals had a fourth lavage before starting cigarette smoking, that is, 28 days before the beginning of the antigen injections. The other lavages were as for the other groups. BAL results on Day 1 were similar for each group. Cigarette smoking per se did not modify BAL in Group 3. EAA induction resulted in a large increase in all BAL cells, especially neutrophils of recovered fluid, which increased from 38 x 10(3) to 1,474 x 10(3) ml-1 (p less than 0.01) in Group 2 and from 58 x 10(3) to 740 x 10(3) in Group 3 (p less than 0.01). After maintenance, BAL neutrophils.ml-1 decreased to 444 x 10(3) in Group 2 (p less than 0.01), but stayed the same in Group 3: 973 x 10(3). After EAA induction, BAL neutrophils.ml-1 were higher in Group 2 than in Group 3 (p = 0.039); however, Group 2 had less neutrophils.ml-1 than Group 3 (p = 0.035) after EAA maintenance. We conclude that EAA results in a neutrophilic alveolitis and which can be evaluated by sequential BAL, and that cigarette smoking decreases the initial neutrophilic response and retards the eventual recovery during maintenance injections.     

Influences of the cellular and humoral immune system in bronchoalveolar lavage on lung function in pulmonary sarcoidosis.

We investigated the changes in the cellular and humoral immune system in bronchoalveolar lavage (BAL) performed in 22 patients with pulmonary sarcoidosis and in 14 normal control subjects and their interactions with lung function parameters. Lymphocytosis, the increase in OKT4+ lymphocytes and OKT4+OKDR+ lymphocytes correlated with the increase in immunoglobulins, especially IgG, IgA and kappa chain assembled immunoglobulins. The transferrin levels obtained in BAL were found to be higher in patients with sarcoidosis, and they correlated with the cellular and, more closely, with other humoral findings. A negative correlation existed between the ventilatory parameters and the cell count and humoral findings. In addition, we found a negative correlation between the diffusing capacity for carbon monoxide and other cellular findings, which was most pronounced with reference to lymphocytes, OKT4+ lymphocytes and the OKT4+/OKT8+ ratio. These results underscore the role of OKT4+ lymphocytes, activated OKT4+OKDR+ lymphocytes and transferrin in the increase in immunoglobulins, mainly kappa chain isotypes. Because of the relationship between these changes and ventilatory parameters, and the diffusing capacity, the above results also reveal the clinical relevance of our findings.