Asbestos bodies in bronchoalveolar lavage fluid. A study of 20 asbestos-exposed individuals and comparison to patients with other chronic interstitial lung diseases

We studied the asbestos body (AB) content of bronchoalveolar lavage fluid from 20 patients with a history of occupational asbestos exposure, 31 patients with sarcoidosis and 5 patients with idiopathic pulmonary fibrosis. The cellular lavage pellet was digested in sodium hypochlorite and filtered onto Nuclepore filters for AB quantification by light microscopy. ABs were found in 15 of 20 asbestos-exposed individuals, 9 of 31 sarcoidosis cases and 2 of 5 patients with idiopathic pulmonary fibrosis. There was a statistically significant difference in the number of ABs per million cells recovered or per milliliter of recovered lavage fluid in the asbestos-exposed group as compared to the other categories of chronic interstitial lung disease. The highest levels occurred in patients with asbestosis. Large numbers of asbestos bodies in the lavage fluid (greater than 1 AB/10(6) cells) were indicative of considerable occupational asbestos exposure, whereas occasional bodies were a nonspecific finding.     

Sequential bronchoalveolar lavages by endotracheal intubation in guineapigs

We examined the feasibility of performing repeated bronchoalveolar lavage (BAL) on guineapigs. We also determined the influence of lavage volume on cell recovery in these animals, verified if the free cell populations were altered by repeated lavage, and compared the results with those obtained after euthanasia. Live animals were intubated orotracheally by direct vision laryngoscopy and lavaged, except for the last BAL which was done on isolated lungs after euthanasia. Each animal was lavaged weekly for 8 weeks: weeks 1-5 lavages were done with 5 aliquots of 2 ml of normal saline, week 6 with 3 aliquots of 1 ml, week 7 with 3 aliquots of 2 ml, and week 8 with 5 aliquots of 2 ml after euthanasia. The first 5 BAL gave similar results in volumes recovered, total number of cells, cell viability and differentials. The total cell yield of lavages 6 and 7 was less than that of the first 5 BAL and BAL 8; cell differentials with these smaller lavages were similar except for the percentage of neutrophils which was slightly higher than with the 10 ml lavage at week 3. The final lavage gave similar results as the first 5 BAL in terms of total cells recovered, cell viability, and differentials. We conclude that repeated BAL is feasible in live guineapigs, and that it gives a similar cells yield as lung lavage obtained after euthanasia.     

Macrophage derived chemokine (CCL22), thymus and activation-regulated chemokine (CCL17), and CCR4 in idiopathic pulmonary fibrosis

Background

Idiopathic pulmonary fibrosis (IPF) is a chronically progressive interstitial lung disease of unknown etiology. Previously, we have demonstrated the selective upregulation of the macrophage-derived chemokine CCL22 and the thymus activation-regulated chemokine CCL17 among chemokines, in a rat model of radiation pneumonitis/pulmonary fibrosis and preliminarily observed an increase in bronchoalveolar (BAL) fluid CCL22 levels of IPF patients.

Methods

We examined the expression of CCR4, a specific receptor for CCL22 and CCL17, in bronchoalveolar lavage (BAL) fluid cells, as well as the levels of CCL22 and CCL17, to elucidate their pathophysiological roles in pulmonary fibrosis. We also studied their immunohistochemical localization.

Results

BAL fluid CCL22 and CCL17 levels were significantly higher in patients with IPF than those with collagen vascular diseases and healthy volunteers, and there was a significant correlation between the levels of CCL22 and CCL17 in patients with IPF. CCL22 levels in the BAL fluid did not correlate with the total cell numbers, alveolar lymphocytes, or macrophages in BAL fluid. However, the CCL22 levels significantly correlated with the numbers of CCR4-expressing alveolar macrophages. By immunohistochemical and immunofluorescence analysis, localization of CCL22 and CCR4 to CD68-positive alveolar macrophages as well as that of CCL17 to hyperplastic epithelial cells were shown. Clinically, CCL22 BAL fluid levels inversely correlated with DLco/VA values in IPF patients.

Conclusion

We speculated that locally overexpressed CCL22 may induce lung dysfunction through recruitment and activation of CCR4-positive alveolar macrophages.     

Bronchoalveolar lavage fluid differential cell count. How many cells should be counted?

OBJECTIVE: To investigate the number of cells to be counted in cytocentrifuged bronchoalveolar lavage (BAL) fluid preparations in order to reach a reliable enumeration of each cell type. STUDY DESIGN: A total of 136 BAL fluid samples for patients with suspected pneumonia or interstitial lung disease were investigated. Differential cell counts were performed on May-Grünwald-Giemsa-stained cytocentrifuged preparations by 2 observers, each differentiating 500 cells. Reliability for the enumeration of each cell type was expressed as phi value, as calculated in generalizability theory. RESULTS: For polymorphonuclear neutrophils (PMNs), alveolar macrophages, lymphocytes and eosinophils, an acceptable phi value of > or = .95 was reached at a count of 300 cells by 1 observer. Mast cells reached a phi value of only .674 at a count of 500 cells by 1 observer, precluding a reliable count. At a count of 500 cells by 1 observer, squamous epithelial cells, bronchial epithelial cells and plasma cells displayed phi values of .868, .903 and .816, respectively. CONCLUSION: At a count of 300 cells, PMNs, alveolar macrophages, lymphocytes and eosinophils are reliably enumerated in cytocentrifuged BAL fluid samples.     

Multinucleated giant cells in bronchoalveolar lavage

OBJECTIVE: To determine the frequency, morphology and possible diagnostic significance of multinucleated giant cells (MGC) in bronchoalveolar lavage (BAL). STUDY DESIGN: Retrospectively we examined 671 BAL specimens. Enlarged cells having > or = 10 nuclei were defined as MGC. Cytomorphologic features were described. BAL specimens containing MGC were grouped according to clinicohistologic diagnosis into sarcoidosis, asbestosis, other interstitial lung diseases and different chronic, noninterstitial lung diseases. RESULTS: MGC were present in 10.7% of BAL specimens and occurred in low numbers. MGC were classified into Langhans' or foreign-body-type MGC (LF-MGC), alveolar macrophage-like MGC (AM-MGC) and nonspecific MGC (NS-MGC). LF-MGC were found most often in patients with sarcoidosis. AM-MGC were found in all groups of patients. NS-MGC were found most often in patients with asbestosis and other interstital lung diseases. CONCLUSION: MGC in BAL are not encountered frequently and are not numerous. Based on cytomorphologic features, three types of MGC can be distinguished.     

Pulmonary langerhans cell histiocytosis (histiocytosis X) on bronchoalveolar lavage: a report of 2 cases

BACKGROUND: Pulmonary Langerhans cell histiocytosis (PLCH) is an interstitial lung disease characterized by bilateral nodular and cystic lesions. Clinically it seems to be a reactive process related to cigarette smoking. CASES: In 2 cases of PLCH, cytologic and immunocytochemical evaluation of bronchoalveolar lavage (BAL) fluid was successfully used for the diagnosis of PLCH. Two heavy smokers complained of fever, cough and debilitation. Serologic and hematologic values were normal. In both cases radiography and computed tomography (CT) were similar, showing multiple bilateral nodular or cystic lesions in the middle and upper lung zones. Cytospins obtained from BAL were Papanicolaou and May-Grünwald-Giemsa stained; others were immunostained with cytokeratin cocktail, CD1a and S-100. Cytospins showed a monomorphous and dispersed cell population consisting ofmononucleated or binucleated and occasionally multinucleated histiocytes. Single cells showed wide, well-defined, acidophilic cytoplasm and oval or kidney-shaped, vesicular nuclei with irregular shapes, evident nucleoli and frequent grooves and indentations. Immunocytochemical staining showed diffuse cytoplasmic positivity for S-100 and CD1a and negativity for cytokeratin; only the few cylindrical cells present in the cytospins were positive for cytokeratin. In both cases the cytologic diagnosis of PLCH was confirmed by subsequent CT and clinical follow-up. CONCLUSION: Cytologic and immunocytochemical evaluation of BAL fluid permits a definitive diagnosis of PLCH. This cytologic diagnosis is clinically relevant because it permits surgical biopsy to be bypassed and allows waiting for a possible spontaneous or pharmacologic resolution.     

Bronchoalveolar eosinophilia in guinea pigs harboring inapparent infections of Paraspidodera uncinata

During the course of experiments examining the changes in cell populations in bronchoalveolar lavage (BAL) fluid in 3-11-wk-old guinea pigs, a marked increase in the numbers of eosinophils was observed in BAL fluid in untreated control animals from historical levels (observations made over the previous 2 yr) of 8.8 +/- 1.5% to levels greater than 16% and up to 44%. Repeated occurrence of this phenomenon in several different groups of guinea pigs that appeared clinically normal and the impact on our experimental studies led us to attempt to identify the cause of increased inflammatory cell numbers in these guinea pigs. Examination in 2 groups of animals of whole blood and lung tissue for the presence of bacteria or fungi revealed minor bacterial infections in one group but not the other, whereas both exhibited elevated eosinophil numbers. At necropsy, 41.7% and 60% of the animals in the 2 groups harbored the nematode Paraspidodera uncinata. Guinea pigs exhibiting eosinophil numbers in BAL fluid comparable to our historical levels were then inoculated with approximately 100 embryonated eggs of P. uncinata and developed elevated eosinophilia in BAL fluid compared to sham-inoculated animals (significant at 2 of the 3 examination times postinoculation). These findings suggest that P. uncinata is capable of causing changes in inflammatory cell populations in the lungs of guinea pigs and illustrate the importance of subclinical or inapparent infections in experimental design and interpretation.     

Isolation of the opioid peptide Leu-Val-Val-hemorphin-7 from bronchoalveolar lavage fluid of a patient with non-small cell lung cancer

The decapeptide Leu-Val-Val-Tyr-Pro-Trp-Thr-Gln-Arg-Phe was isolated in high yield (1.5 nmol/ml) from bronchoalveolar lavage (BAL) fluid from a patient with an adenocarcinoma of the lung. This peptide, termed LVV-hemorphin-7 represents residues 32-41 of the beta-chain of hemoglobin and has been shown to be an endogenous ligand for opioid receptors. The N-terminal flanking peptide of LVV-hemorphin-7 [residues (1-31) of hemoglobin beta-chain] was also isolated in high yield. Neither peptide was detected in BAL fluid from the tumor-free lung of the same patient or from patients with non-neoplastic inflammatory lung disease. LVV-hemorphin-7 was not identified in BAL fluid from seven additional patients with non-small cell lung cancer, indicating that the formation of the peptide is unlikely to be of any diagnostic significance. However, the ability of LVV-hemorphin-7 to inhibit angiotensin-converting enzyme suggests that its formation may be of pathophysiological significance in the regulation of tumor blood flow in certain patients.     

Leukocyte immunophenotypes in bronchoalveolar lavage fluid and peripheral blood of paracoccidioidomycosis, sarcoidosis and silicosis.

Leukocyte subsets in bronchoalveolar lavage (BAL) fluid and peripheral blood of patients with paraccoccidioidomycosis, sarcoidosis and silicosis were characterized using monoclonal antibodies and an immunoperoxidase technique. In paraccocidioidomycosis, the number of T-helper/inducer CD4-positive lymphocytes was lower in peripheral blood than in BAL fluid. Additional analysis showed that the expression of HLA-DR was very similar in alveolar macrophages, lung and blood T-cells. In sarcoidosis and silicosis there were higher proportions of T-helper/inducer cells in peripheral blood than in BAL fluid. The alterations in the T-helper/inducer/T-suppressor/cytoxic CD4/CD8 ratio in sarcoidosis and silicosis were more appreciable in peripheral blood than in BAL fluid, contrasting with the results in paracoccidioidomycosis. The expression of HLA-DR by alveolar macrophages in sarcoidosis was the highest of all the disease studied. No statistically significant differences were observed between chronic multifocal and chronic unifocal paracoccidioidomycosis disease, stage II and stage III sarcoidosis, and chronic and accelerated silicosis. The three granulomatous diseases analyzed had a few alveolar macrophages expressing the CD4 molecule on their surface. These findings and the technique of analyzing both peripheral blood and BAL leukocyte subsets may help to understand the pathogenesis of interstitial lung diseases.     

Familial pulmonary alveolar microlithiasis diagnosed by bronchoalveolar lavage. A case report

BACKGROUND: Familial alveolar microlithiasis is a rare lung disease. In this study we describe the cytologic features of this disease in bronchoalveolar lavage. CASE: A 10-year-old girl and her uncle, a 50-year-old man, had dyspnea and diffuse interstitial pattern on chest radiograph with no defined cause at a period of 10 years apart. Open lung biopsy in the girl and transbronchial lung biopsy plus bronchoalveolar lavage (BAL) in the man were per-formed to determine the diagnosis. In cyopen lung biopsy the diagnosis was alveolar microlithiasis. BAL revealed rehtypical microliths (calcospherites), and th transbronchial lung biopsy performed in the same patient failed to disclose superficially reset any significant pathology. In cytologic a smears, extracellular and intracellular concentrically layered purple-brown, round-to-oval microliths were clearly seen. Cyanophilic periodic acid-Schiff positive intracytoplasmic amorphous material was also frequently seen in alveolar macrophages. CONCLUSION: Familial alveolar microlithiasis is a rare interstitial lung disease that can be easily diagnosed by BAL. This procedure is a very useful tool in diagnosing and classifying some interstitial lung diseases.     

4-1BB enhances proliferation of beryllium-specific T cells in the lung of subjects with chronic beryllium disease

In contrast to naive T cells, reactivation of memory cells is less dependent on CD28-mediated costimulation. We have shown that circulating beryllium-specific CD4(+) T cells from chronic beryllium disease patients remain CD28-dependent, while those present in the lung no longer require CD28 for T cell activation. In the present study, we analyzed whether other costimulatory molecules are essential for beryllium-induced T cell function in the lung. Enhanced proliferation of a beryllium-responsive, HLA-DP2-restricted T cell line was seen after the induction of 4-1BB ligand expression on the surface of HLA-DP2-expressing fibroblasts. Following beryllium exposure, CD4(+) T cells from blood and bronchoalveolar lavage of chronic beryllium disease patients up-regulate 4-1BB expression, and the majority of beryllium-responsive, IFN-gamma-producing CD4(+) T cells in blood coexpress CD28 and 4-1BB. Conversely, a significant fraction of IFN-gamma-producing bronchoalveolar lavage (BAL) T cells express 4-1BB in the absence of CD28. In contrast to blood, inhibition of the 4-1BB ligand-4-1BB interaction partially blocked beryllium-induced proliferation of BAL CD4(+) T cells, and a lack of 4-1BB expression on BAL T cells was associated with increased beryllium-induced cell death. Taken together, these findings suggest an important role of 4-1BB in the costimulation of beryllium-responsive CD4(+) T cells in the target organ.     

Bronchoalveolar cell activation after inhalation of a bronchoconstricting agent

Airway inflammation is thought to be an important determinant of bronchoconstriction and bronchial hyperreactivity. We have recently demonstrated that bronchoconstriction induced by an aqueous extract of cotton bracts (CBE) is associated with bronchoalveolar complement activation, release of polymorphonuclear neutrophil (PMN) chemoattractants by pulmonary cells, and increased numbers of bronchoalveolar lavage PMN's. In the present study we performed bronchoalveolar lavage (BAL) on subjects after CBE or control (saline) challenge and examined whether BAL cells were activated in vitro to produce other inflammatory agonists. After CBE administration, cultured BAL cells released increased amounts of the reactive O2 species, superoxide (O2-.), and the cyclooxygenase products prostaglandin E2 and thromboxane B2. Although none of these in vitro parameters of BAL cell activation appeared to correlate with the degree of bronchoconstriction induced by CBE, BAL fluid levels of thromboxane B2 were also increased after CBE administration and in vivo amounts of this eicasanoid did correlate with the degree of bronchoconstriction induced by CBE (r = 0.50, P less than 0.04). Finally, although cell culture supernatants were highly chemotactic for PMN's, concentrations of leukotriene B4 were not increased, suggesting other chemotaxins were released by BAL cells in this setting. We conclude that CBE administration activates bronchoalveolar cells to release reactive O2 species and cyclooxygenase products that may be important in the bronchoconstricting response to CBE.     

Differential cell analysis of cytocentrifuged bronchoalveolar fluid samples affected by the area counted

OBJECTIVE: To investigate variations in the differential cell counts between the quadrants of cytocentrifuged bronchoalveolar lavage (BAL) fluid preparations and to evaluate the diagnostic impact of these differences in interstitial lung diseases (ILD). STUDY DESIGN: BAL fluid samples obtained from 30 patients suspected of having ILD or pneumonia were cytocentrifuged and additionally stained with May-Grünwald-Giemsa stain. Two observers differentiated 200 cells in each quadrant as well as in a circular pattern around the center of the cytocentrifuge spot. RESULTS: Lymphocytes and alveolar macrophages were not randomly distributed on the cytocentrifuge spot. Ten samples of patients with histologically confirmed ILD were selected to test the diagnostic impact using a validated computer program. The predicted diagnosis did not correspond to the histologic diagnosis for one quadrant from 1 of these 10 samples (sarcoidosis instead of idiopathic pulmonary fibrosis), whereas the differential cell counts performed around the center of the cytocentrifuge spot provided the correct diagnosis in all cases. CONCLUSION: BAL fluid differential cell counts varied between the quadrants of the cytocentrifuge spot. The center of the cytocentrifuge spot appeared to be the most reliable area. Therefore, cell counting is recommended in a circular pattern around the center of the cytocentrifuge spot.     

Determination of bronchoalveolar lavage leukocyte populations by flow cytometry in patients investigated for respiratory disease

BACKGROUND: Characteristic changes in the proportions of leukocyte populations in bronchoalveolar lavage (BAL) reflect different disease states in the lung. The standard method for examination of BAL leukocytes is by microscopy of cytospin preparations. This method may not be the optimum technique due to difficulties in distinguishing cell types morphologically and due to the low number of cells routinely counted. We hypothesized that flow cytometry (FCM) may be a more precise tool for investigating BAL. METHODS: 100 BALs were performed on 92 patients. All samples were stained using the pan-leukocyte marker (CD45) in combination with a granulocyte marker (CD15) and a cell viability marker (7-aminoactinomycin D). Selected samples were also stained with an eosinophil marker (CD23). These samples were run on an FCM and the results compared with leukocyte differentials obtained by light microscopy of parallel cytospin preparations. RESULTS: Close correlations between the two methods were demonstrated for the enumeration of all leukocyte subsets, but the coefficient of variation was considerably lower by FCM than by cytospin. CONCLUSIONS: These findings, combined with the speed of FCM and the ability to perform simple lymphocyte phenotyping, argue in favor of this becoming the method of choice for investigating BAL.     

Bronchoalveolar lavage fluid cytology in patients with Pneumocystis carinii pneumonia

OBJECTIVE: To evaluate bronchoalveolar lavage (BAL) cytology and organism burden in patients with Pneumocystis carinii pneumonia (PCP) who were infected with the human immunodeficiency virus (HIV) and in those with other immunodeficiencies. STUDY DESIGN: BAL fluid samples from patients with PCP were selected (HIV-infected patients, n = 15; patients with other immunodeficiencies, n = 11). May-Grünwald-Giemsa-stained cytocentrifuge preparations were evaluated. Foamy alveolar casts (FACs) and P carinii clusters were counted. RESULTS: The numbers of FACs and P carinii clusters in BAL fluid samples of HIV-infected patients were significantly higher as compared to those in samples from patients with other immunodeficiencies. Striking cytologic findings observed in half the samples from both patient groups included the presence of foamy alveolar macrophages, activated lymphocytes, plasma cells and reactive type II pneumocytes. Furthermore, a peculiar cell type, "nonidentified cell" (NIC), was observed almost exclusively in BAL fluid samples from HIV-infected patients. CONCLUSION: BAL fluid samples from HIV-infected patients with PCP displayed higher organism burdens as compared to those from patients with other immunodeficiencies. Moreover, cytologic findings suggestive of noninfectious lung conditions were common in BAL fluid samples obtained from patients with PCP. Further study is required to elucidate the identity of the NIC cell type.     

Shedding of soluble ICAM-1 into the alveolar space in murine models of acute lung injury

Intercellular adhesion molecule-1 (ICAM-1; CD54) is an adhesion molecule constitutively expressed in abundance on the cell surface of type I alveolar epithelial cells (AEC) in the normal lung and is a critical participant in pulmonary innate immunity. At many sites, ICAM-1 is shed from the cell surface as a soluble molecule (sICAM-1). Limited information is available regarding the presence, source, or significance of sICAM-1 in the alveolar lining fluid of normal or injured lungs. We found sICAM-1 in the bronchoalveolar lavage (BAL) fluid of normal mice (386 +/- 50 ng/ml). Additionally, sICAM-1 was spontaneously released by murine AEC in primary culture as type II cells spread and assumed characteristics of type I cells. Shedding of sICAM-1 increased significantly at later points in culture (5-7 days) compared with earlier time points (3-5 days). In contrast, treatment of AEC with inflammatory cytokines had limited effect on sICAM-1 shedding. BAL sICAM-1 was evaluated in in vivo models of acute lung injury. In hyperoxic lung injury, a reversible process with a major component of leak across the alveolar wall, BAL fluid sICAM-1 only increased in parallel with increased alveolar protein. However, in lung injury due to FITC, there were increased levels of sICAM-1 in BAL that were independent of changes in BAL total protein concentration. We speculate that after lung injury, changes in sICAM-1 in BAL fluid are associated with progressive injury and may be a reflection of type I cell differentiation during reepithelialization of the injured lung.     

Adoptive transfer of acute lung injury

In this study, we describe a novel adoptive transfer protocol to study acute lung injury in the rat. We show that bronchoalveolar lavage (BAL) cells isolated from rats 5 h after intratracheal administration of lipopolysaccharide (LPS) induce a lung injury when transferred to normal control recipient rats. This lung injury is characterized by increased alveolar-arterial oxygen difference and extravasation of Evans blue dye (EBD) into lungs of recipient rats. Recipient rats receiving similar numbers of donor cells isolated from healthy rats do not show adverse changes in the alveolar-arterial oxygen difference or in extravasation of EBD. The adoptive transfer-induced lung injury is associated with increased numbers of neutrophils in the BAL, the levels of which are similar to the numbers observed in BAL cells isolated from rats treated for 5 h with LPS. As an indicator of BAL cell activation, donor BAL cell inducible nitric oxide synthase (iNOS) expression was compared with BAL cell iNOS expression 48 h after adoptive transfer. BAL cells isolated 5 h after LPS administration expressed iNOS immediately after isolation. In contrast, BAL cells isolated 48 h after adoptive transfer did not express iNOS immediately after isolation but expressed iNOS following a 24-h ex vivo culture. These findings indicate that the activation state of donor BAL cells differs from BAL cells isolated 48 h after adoptive transfer, suggesting that donor BAL cells may stimulate migration of new inflammatory cells into the recipient rats lungs.     

Hyaluronate in bronchoalveolar lavage fluid: a new marker in sarcoidosis reflecting pulmonary disease.

Hyaluronate (hyaluronic acid) was not detectable in bronchoalveolar lavage fluid from smoking or nonsmoking healthy volunteers but was present in fluid from 23 patients with sarcoidosis; the mean concentration was 16 micrograms/1 returned fluid (range less than or equal to 5-430) or, expressed in relation to the amount of albumin recovered, 0.22 micrograms/mg albumin (range less than or equal to 0.05-3.6). The serum hyaluronate concentrations in the patients with sarcoidosis were normal. There was a significant inverse correlation between vital lung capacity and hyaluronate concentrations in bronchoalveolar lavage fluid (p less than 0.001), and patients with abnormal lung volumes had hyaluronate concentrations that were on average six times higher than those in patients with normal vital capacity. Duration of disease, pulmonary radiological findings, and markers for macrophage activation (angiotensin converting enzyme) and lymphocyte activation (beta 2 microglobulin) were not correlated with bronchoalveolar lavage fluid hyaluronate. It was concluded that in sarcoidosis release of hyaluronate into the airways is related to lung volume and therefore to the course of the disease. Increased synthesis of hyaluronate in lung parenchyma may reflect activation of fibroblasts, and measurements of hyaluronate may have clinical value for prognosis and treatment.     

Effects of fluticasone propionate inhalation on levels of arachidonic acid metabolites in patients with chronic obstructive pulmonary disease

BACKGROUND: In smoking COPD patients the bronchoalveolar lavage (BAL) fluid contains high numbers of inflammatory cells. These cells might produce arachidonic acid (AA) metabolites, which contribute to inflammation and an increased bronchomotor tone. AIMS: To investigate levels of AA metabolites in BAL fluid, before and after inhaled glucocorticoid therapy: fluticasone propionate (FP) 1 mg per day, or placebo. METHODS: A double-blind placebo controlled trial lasting six months. COPD patients were selected by clinical criteria and the presence of bronchial hyper-responsiveness (BHR). Lung function was recorded and in BAL fluid we counted cell numbers and measured LTB4, LTC4/D4/E4, PGE2, 6kPGF1alpha, PGF2alpha and TxB2. A control group consisted of asymptomatic smokers (n=6). RESULTS: Paired data were obtained from 9 FP treated and 11 placebo patients. BAL cells were almost exclusively alveolar macrophages. In patients and controls both cellularity and levels of AA metabolites were equal Cell numbers did not change after treatment. Statistically significant decreases after FP therapy were noticed for PGE2 (30%), 6kPGF1alpha (41%) and PGF2alpha (54%). CONCLUSIONS: In COPD, the capability of inflammatory cells to produce certain AA metabolites was decreased after inhaled FP treatment. This result is discussed in its relation to clinical effects, the influence of smoking, and the results of an earlier, similar study in asthma patients.