Arterial PCO2 as an index of activity in fibrosing alveolitis

Alveolar hyperventilation is a characteristic feature of the interstitial lung diseases, yet its pathogenesis remains unknown. We examined the relationship between inflammatory alveolar acinar cell counts and the steady state, resting arterial PCO2 in patients with fibrosing alveolitis. To eliminate the influence of overwhelming mechanical lung restriction or resting hypoxemia, we studied 20 patients who, despite having clinicopathologically confirmed fibrosing alveolitis, had vital capacities exceeding 50 percent of predicted, and arterial O2 saturations above 90 percent. There was a significant inverse relationship between the proportion of polymorphonuclear leukocytes (PMNs) in the recovered BAL fluid and the arterial PCO2 (r = -0.67; p less than 0.01). When PCO2 was above 35 mm Hg, the BAL PMN count was 8 percent or less (mean = 3.4; SD = 2.5), while the mean BAL PMN count among those patients whose PCO2 was less than 35 mm Hg was significantly higher (mean = 11.7; SD = 3.7; p less than 0.01). PCO2 levels were unrelated to arterial O2 saturation or PaO2. No relationship was found between the PCO2 and BAL lymphocyte counts. The findings suggest that in fibrosing alveolitis, the arterial PCO2 may be used as an indicator of the state of the inflammatory component of the alveolitis.     

Increased levels of oxidized methionine residues in bronchoalveolar lavage fluid proteins from patients with idiopathic pulmonary fibrosis

Phagocytic cells are believed to play a crucial role in the development of inflammatory lung diseases. We assumed that the oxidation of methionine (met) to methionine sulfoxide [met(O)] by oxygen-derived free radicals released from phagocytes is one parameter to identify the oxidative mechanisms of lung injury. To test this hypothesis we determined the molar ratio of met(O)/met in the soluble protein fraction of bronchoalveolar lavage (BAL) fluids from healthy nonsmokers and from nonsmoking patients with idiopathic pulmonary fibrosis (IPF) or sarcoidosis. The met(O)/met ratio of the healthy nonsmoker group (n = 11) was 0.046 +/- 0.008 (mean +/- SEM). In contrast, the met(O)/met ratio of the nonsmoking IPF group (n = 11) was significantly increased to 0.223 +/- 0.053 (p less than 0.0002). The BAL fluids of this group showed strongly increased numbers of neutrophils but normal numbers of alveolar macrophages (AM). In the sarcoidosis group (n = 10) the met(O)/met ratio (0.048 +/- 0.010) was not significantly different from control values. A close relationship was found between the met(O)/met ratios and the relative as well as the absolute neutrophil counts (r = 0.86; p less than 0.0002; n = 22). In contrast, no significant correlation was found between the met(O)/met ratios and the absolute AM counts (r = 0.22; p = 0.32; n = 22). We conclude that mechanisms of oxidative lung injury in IPF can be characterized by oxidation of met and that this oxidation may be mediated by neutrophils.     

Exhaled nitric oxide is increased in active fibrosing alveolitis.

STUDY OBJECTIVES: Interstitial inflammation is a major aggravating factor in fibrosing lung disease associated with scleroderma (FASSc) and cryptogenic fibrosing alveolitis (CFA). Exhaled nitric oxide (NO) production is increased in asthma and bronchiectasis and reflects the degree of inflammation. We investigated whether measuring levels of exhaled NO is valuable in assessing disease activity in patients with CFA and patients with FASSc. MEASUREMENTS AND RESULTS: NO levels were measured in 11 patients with CFA (mean age +/- SEM, 58 +/- 12 years old; 5 were male) and 17 patients with FASSc (mean age, 48 +/- 9 years old; 5 were male), and they were compared to BAL cell counts and lung function. Patients with CFA and FASSe had elevated NO levels (11.2 +/-1.0 parts per billion [ppb] and 9.8 +/- 1.0 ppb, respectively; p > 0.05), whereas in a group of 13 nonsmoking normal subjects, the NO levels were not elevated (6.9 +/- 0.5 ppb; p < 0.05). Patients with FASSc (n = 8) who had active BAL (defined as either lymphocytes > 14%, neutrophils > 4%, or eosinophils > 3%) had significantly higher NO levels (13.2 +/- 1.8 ppb), and neutrophil (16.5 +/- 4.0%) and lymphocyte (26.8 +/- 3.4%) BAL cell counts than did patients with FASSc who had inactive BAL (6.7 +/- 1.2 ppb; 1.3 +/- 1.0% and 7.5 +/- 1.3%, respectively; p < 0.05). There was a significant correlation between exhaled NO and lymphocyte cell count in patients with FASSc (r = 0.58; p < 0.05). All patients with CFA had active BAL; however, those treated with corticosteroids (12.9 +/- 1.0% ppb, p < 0.05) had lower NO levels (9.0 +/- 1 ppb) and higher BAL lymphocyte cell couits (16.6 +/- 2.0%) than did those not treated with corticosteroids (7.2 +/- 1.7%; p < 0.05). CONCLUSIONS: We conclude that exhaled NO may be a useful addition to BAL cell counts in disease monitoring.     

Alveolitis correlates with clinical pulmonary involvement in primary Sj?gren's syndrome

Bronchoalveolar lavage (BAL) was performed in 23 patients with primary Sj?gren's syndrome (1Ss) and ten healthy controls to evaluate alveolitis and correlate it with pulmonary and systemic manifestations. Patients with 1Ss had higher BAL total cell count (9.2 +/- 6.7 millions/ml vs 6.1 +/- 2.9 millions/ml) and higher percentage of lymphocytes 23.3 +/- 15.6 percent vs 6.5 +/- 2.9 percent, p less than 0.001) than controls. Twelve patients (group A) constituted the "high alveolitis" group (lymphocytes greater than 15.2 percent) and ten (group B) constituted the "low alveolitis" group (lymphocytes less than 15.2 percent). Group A had more frequent cough (6/12 vs 2/10, p = 0.07), dyspnea (4/12 vs 1/10), and roentgenologic evidence of interstitial lung disease (5/12 vs 0/10, p less than 0.05). They also had lower total lung capacity (85.6 +/- 14.2 percent pred vs 105.8 +/- 23.3 percent pred, p less than 0.05) and Dco (87.7 +/- 20.6 percent pred vs 103.6 +/- 21.0 percent pred). All patients with +3 or +4 grading or lymphocytic infiltrates in lip biopsy specimen belonged in group A (5/12). Finally, T-helper/T-suppressor ratio was lower in group A than in group B. The intensity of alveolitis was not correlated with clinical or serologic manifestations of systemic disease.     

Elevated bronchoalveolar lavage fluid histamine levels in allergic asthmatics are associated with increased airway obstruction

Bronchoalveolar lavage (BAL) fluid was evaluated for histamine and tryptase levels in 61 samples (46 samples from 24 atopic asthmatics, seven samples from seven patients with allergic rhinitis, and eight samples from eight normal volunteers). Asthmatics and patients with allergic rhinitis had significantly higher BAL histamine than did normal subjects (169 +/- 22, 141 +/- 23, 42 +/- 6 pg/ml, respectively; p less than 0.05, both comparisons). BAL fluid tryptase levels were also higher in asthmatics and patients with allergic rhinitis than in normal subjects (0.36 +/- 0.03, 0.38 +/- 0.05, 0.23 +/- 0.04 ng/ml, respectively; p less than 0.05, both comparisons); however, levels of tryptase and histamine in BAL were not correlated (r = -0.03 in the group as a whole, r = -0.12 in the asthmatic group). BAL concentration of histamine correlated inversely with FEV1 percent predicted in the asthmatic group (r = -0.44, p less than 0.005). Asthmatics with high BAL fluid histamine (greater than or equal to 100 pg/ml, n = 23) had lower FEV1 percent predicted (80 +/- 3% versus 96 +/- 3%, p = 0.0005), lower FEV1/FVC ratio (72 +/- 1% versus 77 +/- 2%, p less than 0.05), higher percentage of BAL eosinophils (2.2 +/- 0.4% versus 0.6 +/- 0.1%, p less than 0.002), and greater airway responsiveness (lower PD20 [13.1 +/- 3.4 versus 41.5 +/- 13.7 cumulative breath units, p less than 0.05]) compared with asthmatics with low BAL fluid histamine (less than 100 pg/ml, n = 23).(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum and bronchoalveolar lavage of N-terminal type III procollagen peptides in idiopathic pulmonary fibrosis.

Collagen deposition is a prime determinant of clinical course in idiopathic pulmonary fibrosis (IPF). Identification of a marker of connective tissue metabolism would significantly enhance the ability to stage the disease and monitor the course of these patients. Prior studies of IPF have indicated that N-terminal Type III procollagen peptide (N-PIIIP) levels in blood and bronchoalveolar lavage BAL fluid are elevated. We hypothesized that elevated levels of procollagen peptides are a marker of enhanced collagen deposition, which is associated with interstitial fibrosis characterizing active disease. The purpose of the present study was to explore the relationship between N-PIIIP recovery and physiologic parameters of lung function. N-PIIIP levels in sera and bronchoalveolar lavage (BAL) from 24 patients with IPF and 29 volunteers were measured by radioimmunoassay. The extent of disease in IPF was assessed by clinical history, physical examination, chest radiograph, pulmonary physiology evaluation, and confirmatory open-lung biopsy. The severity of disease was graded using a previously described clinical, radiologic, and physiologic (CRP) scoring system. N-PIIIP normalized to albumin was higher in BAL than in serum for both volunteers (1.6-fold; p less than 0.05) and IPF patients (24-fold; p less than 0.05), consistent with local pulmonary production. BAL N-PIIIP was significantly elevated in IPF patients, whether expressed as concentration (healthy volunteer 0.11 +/- 0.06 ng/ml; IPF, 5.0 +/- 14.4; mean +/- SD; p less than 0.05) or normalized to albumin (healthy volunteer, 2.8 +/- 1.2; IPF, 73 +/- 106; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Gallium-67 scanning in the staging of cryptogenetic fibrosing alveolitis and hypersensitivity pneumonitis

Gallium-67 citrate is known to localize within inflammatory sites. Gallium-67 scanning is used for the evaluation of lung inflammation (i.e. alveolitis) during interstitial lung diseases. We investigated 27 patients with cryptogenetic fibrosing alveolitis (n = 17) and hypersensitivity pneumonitis (n = 10) using gallium-67 lung scanning and lung function tests (forced vital capacity, diffusing capacity, resting and exercise blood gases). Investigations were performed before and after one year of methylprednisolone treatment. None of eight healthy volunteers had any abnormal gallium-67 uptake. In all patients with cryptogenetic fibrosing alveolitis an initial abnormal gallium-67 uptake was observed (mean fixation index: 163 +/- 18). In addition, analysis of lung function tests a year after initial evaluation showed that unchanged or improving patients presented initially with a lower gallium-67 index than patients with evidence of deterioration (153.9 +/- 23.7 vs 251.0 +/- 23.3.; p less than 0.01). Similarly, among patients with hypersensitivity pneumonitis the index was lower in unchanged or improving patients than in those with deterioration (74.9 +/- 22 vs 226.7 +/- 4.9; p less than 0.05). Thus gallium-67 scanning is useful in the management of cryptogenetic fibrosing alveolitis and hypersensitivity pneumonitis.     

Relationship of BAL and lung tissue CD4+ and CD8+ T lymphocytes, and their ratio in idiopathic pulmonary fibrosis

BACKGROUND: Surgical biopsy specimens have shown that T lymphocytes (TLs) infiltrate lung parenchyma in patients with idiopathic pulmonary fibrosis (IPF) and might play a pathogenetic role. BAL, a far less invasive technique, has also been used for the investigation of IPF pathogenesis. However, controversy exists whether the BAL fluid cellular profile reflects the cellular composition of the lung parenchyma. STUDY OBJECTIVE: To compare infiltrating TLs subpopulations (CD4+, CD8+, and CD4+/CD8+ ratio) in lung tissue and BAL fluid. PATIENTS AND METHODS: Immunohistochemistry was performed according to the streptavidin-biotin method on the surgical biopsy specimens of 12 untreated patients with IPF. The number of CD3+, CD4+, and CD8+ TLs was determined by observer-interactive computerized image analysis (SAMBA microscopic image processor; Meylan, France). In BAL fluid, the same TLs subpopulations were evaluated by flow cytometry. RESULTS: In lung tissue, CD3+ TLs accounted for a mean (+/- SEM) of 28.8 +/- 7% of total cells, CD4+ TLs accounted for 14.5 +/- 4% of total cells (50.1 +/- 4% of CD3+ TLs), and CD8+ TLs accounted for 13.8 +/- 4% of total cells (47.4 +/- 4% of CD3+ TLs). In BAL fluid, lymphocytes accounted for 9.8 +/- 2.5% of total cells, CD4+ TLs accounted for 51.8 +/- 4% of CD3+ TLs, and CD8+ TLs accounted for 42.2 +/- 4% of CD3+ TLs. Tissue CD4+ and CD8+ TLs (expressed as a percentage of CD3+ TLs) correlated significantly with the number of CD4+ and CD8+ TLs in BAL fluid (r = 0.846 and p = 0.001 vs r = 0.692 and p = 0.013, respectively). A significant positive correlation was also found between the mean CD4+/CD8+ ratio found in tissue and BAL fluid (1.05 +/- 0.21 and 1.5 +/- 0.27, respectively; r = 0.832; p = 0.01). CONCLUSION: The results suggest that in patients with IPF, the TL subpopulations in BAL fluid reflect the pattern of lymphocytic infiltration in pulmonary parenchyma.     

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.     

The influence of smoking on clinical manifestation and composition of bronchoalveolar lavage in sarcoidosis

Sarcoidosis is defined as an inflammatory systemic disease; the characteristic morphological feature is the noncaseating granuloma. Typical finding in bronchoalveolar lavage (BAL) is a lymphocytic alveolitis with an increased CD4/CD8-quotient. A higher frequency of sarcoidosis in non-smokers (NS) than in smokers (S) has been reported. The influence of inhalative smoking on demographical data, lung function and results of BAL in prospectively selected patients with sarcoidosis was investigated. 111 NS (Sarcoidosis stage I/II+III 48/63) and 44 S (23/21) were included in the study. 16 patients without provable pulmonary disease (9 NS, 7 S) served as controls. Patients with sarcoidosis ware less often S than NS (28 vs. 72%, p = 0,0001) Controls 44 vs. 56%, p = 0.6 [chi(2)]). Sarcoidosis S were younger than NS (40.4 +/- 11.9 vs. 45.6 +/- 14.7 years, p = 0.009). There were no differences in the IVC (in % predicted). There was a negative effect of smoking on the course of the IVC (% predicted) with incremental age, not seen in the non smoking group (S vs. NS: r = -0.54, p = 0.001 vs. r = -0.13, p = 0.22). In BAL of Sarcoidosis S there was a lower concentration of albumin than of NS (in mg/dl), S vs. NS: 9.5 +/- 5.9 vs. 14.5 +/- 13.4, p = 0.012 and a trend to a less intensive lymphocytic alveolitis (in % of BAL-cells, S vs. NS: 29.2 +/- 21.1 vs. 34.1 +/- 18.6, p = 0.099). Influences of the smoking on the populations of T-lymphocytes could not be seen. (CD4/CD8-ratio S vs. NS 10.0 +/- 11.4 vs. 7. 2 +/- 7.1, p = 0, 25). In conclusion patients with sarcoidosis were more often NS than S. S were younger than NS. A protective effect of smoking on the course of lung function in sarcoidosis could be excluded. In the BAL S demonstrated a lower content of albumin and a trend to a less pronounced lymphocytosis and therefore a less pronounced alveolitis than NS. Influences of smoking on the distribution of the lymphocytic populations were not seen.     

间质性肺疾病支气管肺泡灌洗液中性粒细胞趋化因子和肿瘤坏 …

OBJECTIVE: To investigate the relationship between the level of the neutrophil chemotactic factor(NCF), tumor necrosis factor-alpha(TNF-alpha) in patients with interstitial lung disease(ILD) and the activity of ILD. METHOD: The NCF activities in the BALF and in the serum from 11 patients with sarcoidosis, 7 with idiopathic pulmonary fibrosis (IPF) and 8 normal subjects were determined using the membrane filter and radio-immunoassay. The level of TNF-alpha was also detected. RESULT: In the 7 IPF patients, the level of NCF and TNF-alpha (203 +/- 44 cells/10 HP, 11.7 +/- 2.9 ng/L) in the BALF was higher than that in 8 control patients (83 +/- 45 cells/10 HP, 6.5 +/- 1.4 ng/L, P < 0.01). The level of NCF and TNF-alpha in the BALF from 11 patients with sarcoidosis (186 +/- 50 cells/10 HP, 12 +/- 3 ng/L) was highet than those in 8 control patients (P < 0.01). The level of NCF and TNF-alpha in the BALF from patients with IPF was positive correlated with the percentage of neutrophil (NCF: r = 0.89, P < 0.01; TNF-alpha: r = 0.86, P < 0.05). The level of NCF and TNF-alpha in the BALF of patients with sarcoidosis was positive correlated with the percentage of lymphocyte (NCF: r = 0.78, P < 0.01; TNF-alpha: r = 0.73, P < 0.01. CONCLUSION: The level of NCF and TNF-alpha in the BALF from patients with IPF and sarcoidosis can act as the marker of the activity of alveolitis of IPF and sarcoidosis.     

Subclinical pulmonary involvement in collagen-vascular diseases assessed by bronchoalveolar lavage. Relationship between alveolitis and subsequent changes in lung function

Collagen-vascular disorders (CVD) are commonly associated with chronic interstitial lung disease. Clinicopathologic observations suggest that inflammatory process of the lower respiratory tract may appear prior to fibrosis. Subclinical pulmonary involvement, as assessed by bronchoalveolar lavage (BAL) was evaluated in 61 patients with various CVD but free of clinical pulmonary symptoms and with normal chest roentgenograms. Eight of 61 had abnormal pulmonary function tests (PFT) at entry to the study. Total BAL cell yield from nonsmokers was greater in patients with abnormal than in those with normal PFT (p less than 0.05). Abnormal differential count of BAL cells was noted in 29 of 61 patients (48%). Lymphocyte alveolitis (lymphocytes greater than or equal to 18%) was a characteristic finding in patients with primary Sj?gren's syndrome (11 of 25) or Sj?gren's syndrome associated with another CVD (4 of 8). Neutrophil alveolitis (neutrophils greater than 4%) with or without increased percentage of lymphocytes occurred in patients with CVD classically associated with pulmonary fibrosis: progressive systemic sclerosis (6 of 10), rheumatoid arthritis (1 of 4), dermatopolymyositis (2 of 3), and mixed connective tissue disease (3 of 8). An increased percentage of eosinophils was detected in 1 patient with progressive systemic sclerosis. Bronchoalveolar lavage abnormalities were more frequently detected in patients with active and severe extrapulmonary disease. On follow-up PFT 12 months later, 11 patients with normal BAL and 10 patients with lymphocyte alveolitis had not deteriorated. In marked contrast, the presence of neutrophils in BAL was associated with a progressive deterioration of PFT in 6 of 7 untreated patients, whereas 4 corticosteroid-treated patients with neutrophil alveolitis had not deteriorated.(ABSTRACT TRUNCATED AT 250 WORDS)     

Alveolitis of pulmonary asbestosis. Bronchoalveolar lavage studies in crocidolite- and chrysotile-exposed individuals

Bronchoalveolar lavage (BAL) findings in 27 individuals with crocidolite- or chrysotile-induced asbestosis were compared to BAL findings in 29 unexposed control subjects. Alveolitis, defined as an increase in the proportions and/or absolute numbers of inflammatory cells present in BAL fluid compared to values in control subjects, was present in 26 (96 percent) subjects with asbestosis. Most exhibited a neutrophil-eosinophil alveolitis, with neutrophil proportions increased to 7.4 +/- 0.7 percent and eosinophil proportions increased to 2.2 +/- 0.4 percent, compared to 2 +/- 0.5 percent and 0.4 +/- 0.01 percent, respectively, in control subjects (p less than 0.01 for both neutrophils and eosinophils). An increase in the total number of neutrophils and eosinophils per ml of lavage fluid was also seen (neutrophils 23 +/- 5 and eosinophils 13 +/- 4 per ml; p less than 0.05 compared to control subjects). Severity of the alveolitis, defined by the neutrophil or eosinophil proportions, was independent of a history of exposure to cigarette smoke. The pattern and severity of alveolitis in crocidolite- and chrysotile-induced asbestosis were similar. There was a significant correlation between duration of exposure to asbestos and neutrophil proportions (p less than 0.01). No significant difference in the severity of the alveolitis was observed between individuals with radiologic and physiologic evidence of asbestosis compared to those with asbestos exposure and crackles alone, suggesting that, in asbestosis as in other chronic interstitial lung diseases, radiologic and physiologic parameters do not reflect the severity of the alveolitis. This study demonstrates that a neutrophil-eosinophil alveolitis is present in individuals with crocidolite- and chrysotile-induced asbestosis, that this alveolitis is independent of cigarette smoking, and that the severity of the BAL changes is not reflected in radiologic and physiologic changes.     

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.     

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.     

Increased oxidized methionine residues in BAL fluid proteins in acute or chronic bronchitis.

Phagocytic cells such as alveolar macrophages (AM) or polymorphonuclear neutrophils (PMN) in the bronchoalveolar tract are a potential source of the oxygen-derived free radicals which are presumed to be involved in lung tissue damage. Previous results have shown that the methionine sulphoxide (MET(O)) content of bronchoalveolar lavage fluid (BALF) protein is a reliable parameter to indicate oxidative processes in idiopathic pulmonary fibrosis (IPF). We measured the molar ratio between MET(O) and methionine (MET) in the BALF protein from healthy nonsmokers (control group), healthy smokers and patients with acute or chronic bronchitis (AB or CB). The MET(O)/MET ratio of the nonsmoking group (n = 11) was 0.046 +/- 0.008 (mean +/- SEM). Healthy smokers (n = 8) had similar values (0.042 +/- 0.008), even though they had strongly increased AM counts in BALF. Patients with AB (n = 12) showed an increased MET(O)/MET ratio (0.191 +/- 0.031) and had high PMN but normal AM counts in BALF. Patients with CB (n = 13) showed an increase in the MET(O)/MET ratio (0.086 +/- 0.010) and moderately increased PMN and markedly increased AM counts. Taking all results together, the MET(O)/MET ratio correlated positively with the relative PMN number (r = 0.70; p less than 0.0002) and inversely with the relative AM number (r = 0.67; p less than 0.0002). In the group with CB, the MET(O)/MET ratio correlated inversely with forced expiratory volume in one second (FEV1) % pred. (r = -0.77) and FEV1/inspiratory vital capacity (IVC) % pred. (r = -0.89).(ABSTRACT TRUNCATED AT 250 WORDS)     

Neutrophil chemotactic factor release and neutrophil alveolitis in asbestos-exposed individuals

Alveolar neutrophil accumulation occurs in asbestosis. To evaluate a possible role for release of neutrophil chemotactic factor (NCF) in the pathogenesis of asbestosis, spontaneous NCF release from alveolar macrophages obtained by bronchoalveolar lavage (BAL) in eight individuals with asbestosis, 13 asbestos-exposed individuals without asbestosis, and five control subjects has been studied. Alveolar macrophages were incubated in medium (four hours; 37 degrees C), and neutrophil responses to the supernatants were assayed in a microchemotaxis chamber. Alveolar macrophages from subjects with asbestosis released more NCF (97 +/- 19 neutrophils per high-power field [N/HPF]) than controls (3 +/- 1 N/HPF; p less than 0.01). Alveolar macrophages from individuals with asbestos exposure and increased BAL neutrophil proportions (n = 7) released more NCF (93 +/- 24 N/HPF) than individuals with asbestos exposure and normal BAL neutrophil proportions (n = 6; 11 +/- 6 N/HPF; p less than 0.02). The results show that spontaneous NCF release occurs in asbestosis and that NCF release is associated with neutrophil alveolitis in asbestos-exposed individuals without asbestosis, suggesting a pathogenic role for NCF in mediating this neutrophil alveolitis. The results of the study also suggest that the presence of crackles is a better predictor of the presence of neutrophil alveolitis than is an abnormal chest x-ray film.     

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.     

Elevated BAL fluid histamine levels and parenchymal pulmonary disease in rheumatoid arthritis

To determine the amount of histamine in BAL fluid in subjects with RA and to ascertain if elevated histamine levels were associated with parameters of active pulmonary disease, we measured BAL fluid histamine levels in 31 subjects with RA and 36 normal subjects. The subjects with RA had a significantly greater mean BAL histamine level than the normal subjects, (313 +/- 154 pg/ml vs 18 +/- 8 pg/ml; p less than 0.05). When the subjects with RA were divided into three groups based on chest radiograms (1 = normal; 2 = pleural disease only; 3 = interstitial or nodular disease), we found that subjects in group 3 had significantly lower values for TLC and D. Subjects in group 3 also had higher percentages of BAL neutrophils and eosinophils and higher BAL histamine levels (group 1, 115 +/- 52 pg/ml; group 2, 30 +/- 30 pg/ml; and group 3, 1,182 +/- 709 pg of histamine per milliliter). Moreover, BAL histamine levels were negatively correlated with TLC (r = -0.46; p = 0.01) and FVC (r = -0.45; p = 0.01) and positively correlated with BAL neutrophils (r = 0.6; p = 0.0003) and BAL eosinophils (r = 0.89; p = 0.0001). These data suggest that the BAL histamine level may be a useful marker to determine the activity of pulmonary disease in RA.     

Increased in CD8 T lymphocytes in the BAL fluid of patients with sulfur mustard gas-induced pulmonary fibrosis

OBJECTIVE: In an attempt to understand better the potential role of the T cell in the pathogenesis of pulmonary fibrosis (PF) due to sulfur mustard gas inhalation, this study was designed to analyze bronchoalveolar lavage (BAL) lymphocyte subsets and to determine the ratio of CD4 to CD8 lymphocytes in BAL fluid. SETTING: University hospital. PATIENTS: Twenty-one veterans with mustard gas-induced pulmonary fibrosis and 20 normal veterans as control group. INTERVENTION: Chest roentgenograms, pulmonary function tests (PFTs), tests for carbon monoxide diffusing capacity of the lung (DLCO), high-resolution CT scans of the chest, BAL via fiberoptic bronchoscopy, analyses of BAL fluids for cellular and Flow-cytometric analysis of the phenotype of bronchoalveolar cells were performed in all cases. A transbronchial lung biopsy was done in all patients following BAL. RESULTS: Neutrophilic alveolitis was the predominant feature. Neutrophils (P<0.0001) and eosinophils (P=0.0006) were the predominant cell types in the BAL fluid of patients with PF. CD8 lymphocytes expressed as percentage or absolute number were significantly higher in patients with PF than in healthy controls (22.96+/-7.48% vs. 14.16+/-7.73%, respectively; P=0.0006; and 2.28+/-0.84 vs. 1.10+/-0.55 x 10(3) cells/ml, respectively; P<0.0001). The CD4/CD8 ratio was significantly lower in patients with PF than in healthy controls (0.73+/-0.25 vs. 1.58+/-0.67; P<0.0001). Except for the percentage and the absolute number of the BAL fluid neutrophils (r=0.70, P=0.001: r=-0.62, P=0.005; respectively), no correlation was found between DLCO% and the other BAL cells. A significant negative correlation was observed between the percentage of DLCO and both the percentage and the absolute number of CD8 lymphocytes in BAL fluid in patients with PF (r=-0.81, P=0.0003; r=-0.61, P=0.006; respectively). A significant correlation was also seen between the percentage of DLCO and the CD4/CD8 ratio (r=-0.60, P=0.006) in our patients. CONCLUSION: CD8 T cells in BAL fluid were significantly elevated in patients with pulmonary fibrosis. Patients with higher grades of pulmonary fibrosis expressed as percentage of DLCO, revealed higher percentages and the absolute number of CD8 T cells and a lower CD4/CD8 ratio.