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Alveolitis is thought to precede permanent lung derangement in a variety of interstitial lung diseases (ILD). Bronchoalveolar lavage (BAL) cell differentials can be used to evaluate the intensity of alveolitis, whereas clinical, roentgenographic, and functional studies are insensitive monitors of lung inflammation. As ILD is generally diffuse, unilobar lavage is widely used and presumed to gauge overall lung inflammation. Consistency of lobe to lobe cell differential findings has not been systematically addressed. We analyzed 53 bilateral lobar lavages (right middle lobe and lingula) in 34 patients with sarcoidosis, idiopathic pulmonary fibrosis-collagen vascular disease (IPF-CV) and a group of mixed interstitial diseases. Cellular differentials from each lobe were independently assessed and compared. The sarcoid group, with predominantly T-lymphocytes in BAL, showed excellent interlobar correlation (r = 0.92, p less than 0.001), with only 17% showing a discrepancy of greater than 10% in percentage of T-lymphocytes. In contrast, the IPF-CV group, with predominantly neutrophils in BAL, showed good interlobar correlation (r = 0.79; p less than 0.01), but 35% had a greater than 10% discrepancy in percentage of neutrophils. Finally, the mixed group, with lymphocytes as the predominant cell in BAL, showed poor interlobar correlation (r = 0.58; p greater than 0.10), with 42% showing a greater than 10% discrepancy in percentage of lymphocytes. These results were not explicable on the basis of differences in volume of lavage fluid or total cells recovered, these parameters being remarkably consistent between lobes in the 3 patient groups and in a control group of 8 subjects without ILD. The chest roentgenogram was markedly insensitive to lavage interlobar variation.(ABSTRACT TRUNCATED AT 250 WORDS)

Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal disorder in which chronic accumulation of neutrophils within the alveolar structures occurs. These cells with their large stores of preformed mediators likely play a major role in subsequent lung derangement. To evaluate the adjunctive use of intermittent high dose "pulse" corticosteroid therapy as a means of inhibiting neutrophil accumulation in the IPF lung, 5 patients were treated in a single blind random fashion with "high dose" corticosteroids (2 g methylprednisolone given intravenously once a week plus 0.25 mg/kg prednisone given orally daily) and 8 patients were treated with "low dose" corticosteroids only (0.25 mg/kg prednisone given orally daily). All patients had biopsy-proved disease in midcourse, and the 2 groups were matched for clinical and physiologic criteria. To evaluate the effect of these therapies on the quantity of neutrophils in the lungs of these patients, both groups underwent bronchoalveolar lavage and 67Ga scanning at the beginning and end of the 6-month study period; both methods gave an estimate of the intensity of the neutrophil alveolitis in these patients. Low dose corticosteroids had little effect on neutrophil accumulation (% neutrophils in lavage, - 5 +/- 8% change from baseline; 67Ga uptake, + 27 +/- 14% change from baseline), whereas high dose corticosteroids significantly reduced neutrophil accumulation (% neutrophils in lavage, - 46 +/- 8% change from baseline, p less than 0.02 compared with that in the low dose group; 67 Ga uptake, - 23 +/- 11% change from baseline, p less than 0.05 compared with that in the low dose group). In addition, 2 patients in the high dose group were reevaluated 6 months after cessation of the intermittent high dose pulse corticosteroids. Both had marked increases in lavage neutrophils compared with when they were receiving the high dose therapy (10 to 22% and 18 to 52%, respectively). These findings suggest that massive doses of intermittent intravenously administered corticosteroids may help to suppress the neutrophil component of the alveolitis of IPF.

Although the etiology of rheumatoid interstitial lung disease (RILD) remains unknown, bronchoalveolar lavage (BAL) has been useful in studying potentially pathogenic mechanisms in this disorder. Previous investigations in patients with rheumatoid arthritis (RA) and RILD revealed abnormal BAL T-lymphocyte subpopulations and a significant elevation in BAL neutrophils. Because neutrophils have been implicated as important effector cells in inflammatory disorders such as ARDS and idiopathic pulmonary fibrosis, we evaluated BAL fluid in patients with RA for neutrophil chemotactic and activating properties and for evidence of neutrophil activation. The BAL fluid from patients with RILD contained significant neutrophil chemotactic activity derived from both lipid and nonlipid components. Evidence for neutrophil stimulation in the lower respiratory tract of patients with RILD was suggested by elevations in both myeloperoxidase activity and immunologically determined levels of human neutrophil elastase in BAL fluid. Free uninhibited elastolytic activity, however, was not demonstrated, suggesting that adequate protease inhibitor levels were present to inhibit active elastase activity. In addition to elevated myeloperoxidase activity, a potential role for neutrophil-derived oxidant injury was indirectly suggested by the enhanced release of superoxide anion (O2-) from resting normal human blood neutrophils challenged with concentrated BAL fluid from patients with RA and interstitial lung disease. Significant correlations were found between physiologic parameters and the percentage of BAL neutrophils, as well as levels of neutrophil-derived mediators. For example, levels of human neutrophil elastase were strongly correlated with diminished diffusion capacity (r = -0.73, p less than 0.001) and reduced forced vital capacity (r = -0.63, p less than 0.006).(ABSTRACT TRUNCATED AT 250 WORDS)

We evaluated 17 clinically unaffected members of three families with an autosomal dominant form of idiopathic pulmonary fibrosis for evidence of alveolar inflammation. Each person in the study was examined by gallium-67 scanning for a general estimate of pulmonary inflammation, and by bronchoalveolar lavage for characterization of the types of recovered cells and their state of activation. Eight of the 17 subjects had evidence of alveolar inflammation on the lavage studies. Supporting data included increased numbers of neutrophils and activated macrophages that released one or more neutrophil chemoattractants, and growth factors for lung fibroblasts--findings similar to those observed in patients with overt idiopathic pulmonary fibrosis. Four of these eight also had a positive gallium scan; in all the other clinically unaffected subjects the scan was normal. During a follow-up of two to four years in seven of the eight subjects who had evidence of inflammation, no clinical evidence of pulmonary fibrosis has appeared. These results indicate that alveolar inflammation occurs in approximately half the clinically unaffected family members at risk of inheriting autosomal dominant idiopathic pulmonary fibrosis. Whether these persons with evidence of pulmonary inflammation but no fibrosis will proceed to have clinically evident pulmonary fibrosis is not yet known.

Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease of unknown etiology characterized by inflammation of the lower respiratory tract and injury and fibrosis of the lung parenchyma. Neutrophils are a significant component of the alveolitis of IPF, and are known to have a potent armamentarium of mediators capable of damaging the lung parenchyma. To evaluate the ability of 2 pharmacologic agents, corticosteroids and cyclophosphamide, to suppress the neutrophil component of the inflammation of IPF, bronchoalveolar lavage was used to monitor those patients with active disease (greater than 10% neutrophils recovered by lavage). Those patients treated with corticosteroids alone showed no suppression in the neutrophil component of the alveolitis after 3 months and at 6 months of therapy (p greater than 0.8, both compared to before therapy). In marked contrast, patients treated with cyclophosphamide, alone or with corticosteroids, showed a significant reduction in the neutrophil alveolitis at 3 months (cyclophosphamide alone, p less than 0.01; cyclophosphamide and corticosteroids, p less than 0.02; both compared to before therapy) and at 6 months (cyclophosphamide alone, p less than 0.01; compared to before therapy). Pulmonary function tests at the beginning and end of the study were not different in any of the treatment groups. Thus, cyclophosphamide, alone or in combination with corticosteroids, is much more effective than corticosteroids alone in suppressing the neutrophil component of the inflammation of IPF. Whether or not this effect of cyclophosphamide will result in overall stabilization or improvement of the disease will require a larger, likely multicenter, trial.

Over a three-year period, 281 fiberoptic bronchoalveolar lavage procedures were performed on 119 individuals with interstitial lung disease and 22 normal volunteers. There were no major complications. Less than 5 percent of the procedures were associated with minor complications including (2.5 percent), pneumonitis (0.4 percent), bleeding (0.7 percent) and bronchospasm (0.7 percent); none of these complications required therapy. Those individuals developing complications had a wide range of physiologic findings; functional tests could not predict which subjects were more likely to develop minor complications associated with lavage. These findings suggest that bronchoalveolar lavage for interstitial disease is a safe procedure associated with minor risks.

Serum angiotensin-converting enzyme (ACE) is elevated in many patients with pulmonary sarcoidosis and has been proposed as a measure of disease activity. The present study was designed to evaluate the possible relationship between serum ACE and direct measures of the intensity of the alveolitis of pulmonary sarcoidosis as measured by bronchoalveolar lavage and gallium-67 (67Ga) scans. To accomplish this, 64 measurements of serum ACE, lavage T lymphocytes, and lung uptake of 67Ga were performed in 41 patients with biopsy-proven sarcoidosis. Elevations of serum ACE were found on at least one occasion in 17 patients (41%). However, serum ACE was found to be a poor predictor of the intensity of alveolitis in sarcoidosis as assessed by the quantitation of bronchoalveolar lavage cells that were T lymphocytes and by 67Ga scanning. Elevated serum ACE did not predict which patients would have elevated proportions of lavage T lymphocytes, which patients would demonstrate increased pulmonary uptake of 67Ga, or which patients would have high-intensity alveolitis as defined by a combination of these criteria. These observations suggest that while serum ACE may be useful in diagnosing sarcoidosis, it does not reflect accurately the intensity of the alveolitis of the pulmonary component of this disease. [ABSTRACT FROM AUTHOR]