Nasal and pharyngeal eosinophil peroxidase levels in adults with poorly controlled asthma correlate with sputum eosinophilia.

The objective of the study was to compare nasal, pharyngeal, and sputum eosinophil peroxidase (EPX) levels with induced sputum eosinophil percentage in 10 adults with poorly controlled asthma and 10 normal controls. EPX was measured using an ELISA and normalized for grams of protein for nasal and pharynx specimens and for mL-gram of protein for sputum. Sputum EPX levels were statistically different between asthma and control subjects (P = 0.024). EPX levels measured in the nasal and pharyngeal swab samples derived from the same patients were also different between asthma and control subjects, each displaying a high degree of significance (P = 0.002). Spearman's correlation coefficients for nasal EPX and pharyngeal EPX levels compared to induced sputum eosinophil percentage were 0.81 (P = 0.0007) and 0.78 (P = 0.0017), respectively. Thus, there is a strong association in a given patient between both nasal and pharyngeal EPX levels and the eosinophil percentage of induced sputum.

Pulmonary mucinous cystic tumor. Case report with review of the literature.

Mucinous cystic tumors of the lung are exceedingly rare. We describe the case of a 59-year-old white man with a left upper lobe mass documented on chest radiographs 11 years before thoracotomy. Grossly, the lobectomy specimen contained a 4.5 x 4.5 x 4.0 cm cystic gelatinous mass with complete occlusion of the anterior segmental bronchus by mucinous material. Although microscopically this pulmonary mucinous cystic tumor contained a focus of marked glandular atypia consistent with adenocarcinoma, the patient has remained free of recurrence or metastasis during 5 years of close postoperative follow-up. Pulmonary mucinous cystic tumors appear to have a remarkably favorable prognosis and should be distinguished from other common lung neoplasms.

Airway carcinoembryonic antigen concentrations in patients with central lung cancer or chronic bronchitis.

To determine the clinical utility of airway carcinoembryonic antigen (CEA) concentrations to distinguish malignant from inflammatory airway disease in patients undergoing bronchoscopy, we determined CEA concentrations by enzyme immunoassay in bronchial washings recovered in 48 subjects, including 20 patients with central lung cancer, 18 patients with chronic bronchitis, and ten nonsmoking patients with a diagnosis of pneumonia or peripheral granuloma. Concentrations of CEA in bronchial washings were standardized by using the total protein concentration in recovered fluid (CEA/TP). Concentrations of CEA were significantly increased in bronchial washings recovered from both patients with chronic bronchitis and lung cancer compared with patients with pneumonia or granuloma (252 +/- 47 ng/mg and 199 +/- 64 ng/ml vs 62 +/- 11 ng/mg, SEM, p less than 0.005). Airway CEA concentrations in patients with chronic bronchitis were somewhat increased compared with concentrations recovered from a cancer-involved airway (252 +/- 47 ng/ml vs 199 +/- 64 ng/mg, SEM, p less than 0.05). Measurement of airway CEA concentrations is not useful in distinguishing malignant from inflammatory airway disease as airway concentrations of CEA may be markedly increased in patients with both conditions.

Intrapulmonary cytokine accumulation following BAL and the role of endotoxin contamination.

STUDY OBJECTIVES: BAL induces alveolar inflammation, but its effects on intrapulmonary cytokines and the mechanisms causing inflammation are uncertain. The objectives of this study were: (1) to characterize cytokine response in the lungs to BAL, and (2) to determine whether endotoxin is introduced into the lungs during BAL, which could promote BAL-induced inflammation. DESIGN AND METHODS: We performed two BAL procedures in healthy volunteers separated by 4 (n=6), 24 (n=5), or 72 h (n=3). The initial BAL was performed in the right middle lobe (RML) and the second BAL was performed in the same location and the lingula. Concentrations of interleukin-8 (IL-8), interleukin-1 (IL-1beta), and transforming growth factor-beta were measured by enzyme-linked immunosorbent assay and tumor necrosis factor-alpha (TNF-alpha) bioactivity was determined. Endotoxin contents of saline (10 and 20 mL) infused through bronchoscopes as well as BAL fluids recovered from six subjects were assessed by limulus amebocyte assay. RESULTS: At 4 h after the initial lavage, but not at later times, BAL fluid recovered from the RML contained increased concentrations of IL-8 and IL-1beta, and increased TNF-alpha bioactivity. BAL fluid recovered from the lingula contained increased concentrations of TNF-alpha only at 4 h. All BAL samples tested contained detectable endotoxin as did all saline aliquots instilled through bronchoscopes. CONCLUSIONS: There is intrapulmonary accumulation of the cytokines TNF-alpha, IL-8, and IL-1beta in the lavaged lung within 4 h after BAL; this accumulation resolves by 24 h. Endotoxin contamination of the lungs during bronchoscopy may contribute to BAL-induced lung inflammation.

Increased lower respiratory tract iron concentrations in alkaloidal ("crack") cocaine users.

STUDY OBJECTIVE: We hypothesized that the use of inhaled alkaloidal ("crack") cocaine could increase lung content of iron, either by inducing alveolar hemorrhage or by other mechanisms. Intrapulmonary accumulation of iron could promote chronic lung diseases in crack users. The goal of this study was to determine whether iron and ferritin content of alveolar macrophages or fluid recovered by BAL was increased in subjects using crack, compared with nonsmokers. METHODS: BAL was performed in 31 volunteer subjects, including healthy nonsmokers (n = 7), subjects smoking crack alone (n = 7), as well as subjects smoking both crack and cigarettes (n = 7) or cigarettes alone (n = 10). Iron content of alveolar macrophages and BAL fluid was determined by a colorimetric method and ferritin content of alveolar macrophages, and BAL fluid was measured by a two-sided immunoradiometric method. RESULTS: Alveolar macrophages recovered from crack users contained more iron than did alveolar macrophages from nonsmokers (25.4 +/- 2.9 nmol/10(6) vs 5.5 +/- 0.6 nmol/10(6) [mean +/- SE]; p < 0.01). There were similar increases in alveolar macrophage ferritin as well as BAL fluid iron and ferritin in crack users, compared with nonsmokers. BAL fluid ferritin concentrations in subjects smoking both crack and cigarettes were increased, compared with subjects smoking crack alone or cigarettes alone (p < 0.05). CONCLUSIONS: Use of crack increases intrapulmonary concentrations of iron and ferritin. Effects of crack on extracellular ferritin concentrations may be additive with effects of cigarette smoking. Although the mechanism(s) causing pulmonary iron accumulation were not identified by this study, it may be a result of occult alveolar hemorrhage or increased vascular permeability. The increase in lung iron burden in habitual crack users could promote chronic lung diseases in these subjects.

Transferrin concentrations in serum and lower respiratory tract fluid of mechanically ventilated patients with COPD or ARDS.

Transferrin serves as the primary iron transport protein in serum, but it also is present in the lower respiratory tract where it has antioxidant and antibacterial properties. Prior studies indicate that patients with respiratory failure (RF) due to ARDS have increased concentrations of transferrin in the lower respiratory tract, which is attributed to increased lung vascular permeability. It is unclear whether mechanical ventilation contributes to increased lung transferrin content in patients with ARDS, although mechanical ventilation may increase lung microvascular permeability. To assess whether mechanical ventilation in patients with RF due to causes other than ARDS is also associated with increased respiratory tract concentrations of transferrin, we compared transferrin concentrations in serum and lung lavage fluid obtained from 12 mechanically ventilated patients with RF attributable to COPD, 6 patients with ARDS, and 15 healthy volunteers. Serum transferrin concentrations in patients with RF due to COPD were variable, but mean concentrations were similar to those in control subjects (336 +/- 58 vs 307 +/- 9 [SE] mg/dL), whereas serum transferrin concentrations were decreased in patients with ARDS (182 +/- 68 mg/dL; p < 0.05). Compared with control subjects, lavage fluid recovered from patients with RF due to COPD contained significantly decreased concentrations of transferrin (1.56 +/- 0.24 vs 4.27 +/- 0.44 micrograms/mL; p < 0.001), whereas transferrin concentrations in lavage fluid recovered from patients with ARDS were increased (15.72 +/- 2.01 micrograms/mL; p < 0.001). Transferrin concentrations of lavage fluid also were decreased in COPD patients when normalized for lavage fluid protein content (4.35 +/- 0.72 vs 19.96 +/- 3.13 micrograms/mg in control subjects, p < 0.001). These data indicate that mechanical ventilation of patients with COPD is associated with decreased lung transferrin concentrations, in contrast to an increased transferrin concentration found in patients with ARDS. Decreased transferrin concentrations in the lower respiratory tract may decrease defenses against oxidant injury and bacterial infection in patients with RF due to COPD.

Airway secretory IgA concentrations in patients with lung cancer. Evaluation of the uninvolved lung.

To determine whether concentrations of the primary airway immunoglobulins (SIgA, IgG) are altered in the uninvolved lung of patients with lung cancer, we determined concentrations of SIgA and IgG in bronchial washings recovered from a proximal airway of the uninvolved lung in 24 patients with lung cancer and in ten patients with benign lung disease. When standardized for the amount of total protein recovered (SIgA/TP, IgG/TP), bronchial washings recovered from the uninvolved lung of lung cancer patients demonstrated a significantly decreased SIgA/TP ratio compared to control subjects (.14 +/- .02 vs .31 +/- .05, SEM, p less than 0.05). There were no differences in the IgG/TP ratios. Lung cancer patients with a decreased serum albumin (less than 3.2 g/dl) had a significantly decreased SIgA/TP ratio in bronchial washings compared to patients with a higher serum albumin (.08 +/- .03 vs .18 +/- .04, SEM, p less than 0.05). The decreased relative concentration of airway SIgA in lung cancer patients may adversely affect airway defenses against bacterial colonization.

Increased iron and ferritin content of sputum from patients with cystic fibrosis or chronic bronchitis.

PURPOSE: Extracellular free iron, or iron bound to ferritin, may promote oxidative injury and bacterial growth in airways of patients with chronic airway inflammation due to cystic fibrosis (CF) or chronic bronchitis (CB). In this study, we assessed sputum content of total iron, ferritin, and transferrin in patients with CF or CB as well as sputum from normal subjects with acute airway inflammation caused by viral upper respiratory tract infections (URTIs). METHODS: Spontaneously produced sputum was obtained from 33 subjects, including 10 subjects with CF, 18 subjects with CB (10 acute exacerbations, 8 with stable CB), and 5 subjects with URTIs (control subjects). After lysing and dilution, total iron concentrations were determined by controlled coulometry, ferritin was measured by radioimmunoassay, and transferrin was measured by enzyme-linked immunosorbent assay. RESULTS: Iron was not present in detectable amounts in control sputums, but ferritin was present (6+/-2 ng/mg protein, mean+/-SE), as was transferrin (2.37+/-0.44 microg/mg). Compared with control subjects, concentrations of iron in sputum were increased in patient groups with higher amounts in CF patients (242+/-47 ng/mg, p<0.01) than CB patients with acute exacerbations or patients with stable CB (98+/-50 and 42+/-12 ng/mg, p<0.05 for both). Ferritin content of sputum was also increased in each group, with CF patients (113+/-22 ng/mg, p<0.001) higher than CB patients (acute, 45+/-10 ng/mg; stable, 87+/-24 ng/mg; p<0.01 for both). Compared with control subjects, sputum transferrin was decreased in CF patients (1.09+/-0.40 microg/mg, p<0.05), but not CB patients. CONCLUSIONS: These findings indicate there are increased airway concentrations of total iron and ferritin-bound iron in patients with CB and, to a greater extent, in patients with CF. Particularly in CF patients who also demonstrated decreased airway concentrations of transferrin, ferritin-bound iron in airways may promote oxidative injury and enhance bacterial growth.

Lymphocyte subsets in lung cancer.

Altered cellular immune function has been demonstrated in patients with lung cancer, including decreased numbers of circulating lymphocytes and changes in the percentage of lymphocytes in various functional subsets. We quantitated lymphocyte subsets in 54 patients with lung cancer including patients with limited (stages 1 and 2) nonsmall cell lung cancer (NSCLC, n = 23), advanced (stage 3) NSCLC (n = 16), and small cell cancer (SCLC, n = 15). Serum albumin was decreased in 15 lung cancer patients, and lymphocyte subsets were separately evaluated in these patients. Lymphocyte populations in cancer patients were compared to those of nonsmokers and a smoking patient population. No difference from smokers was noted in patients with limited NSCLC. Patients with SCLC and advanced NSCLC had significantly decreased numbers of T-helper and T-suppressor cells (p less than 0.05). Patients with lung cancer and hypoalbuminemia had the greatest decrease in number of circulating T-helper cells (p less than 0.001). B-lymphocytes were also decreased in patients with advanced NSCLC and patients with hypoalbuminemia (p less than 0.05). A decrease in population of T-lymphocytes subsets is frequent in patients with SCLC, advanced NSCLC, and lung cancer patients with hypoalbuminemia.

Effect of corticosteroid treatment on cell recovery by lung lavage in acute radiation-induced lung injury.

The purpose of this study was to quantitate cell populations recovered by lung lavage up to 6 weeks following thoracic irradiation (24 Gy) as an index of the acute inflammatory response within lung structures. Additionally, rats were treated five times weekly with intraperitoneal saline (0.3 cc) or methylprednisolone (7.5 mg/kg/week). Lung lavage of irradiated rats recovered increased numbers of total cells compared to controls beginning 3 weeks after irradiation (P less than 0.05). The initial increase in number of cells recovered was attributable to an influx of neutrophils (P less than 0.05), and further increases at 4 and 6 weeks were associated with increased numbers of recovered macrophages (P less than 0.05). Lung lavage of steroid-treated rats at 6 weeks after irradiation recovered increased numbers of all cell populations compared to controls (P less than 0.05); however, numbers of recovered total cells, macrophages, neutrophils, and lymphocytes were all significantly decreased compared to saline-treated rats (P less than 0.05). The number of inflammatory cells recovered by lung lavage during acute radiation-induced lung injury is significantly diminished by corticosteroid treatment. Changes in cells recovered by lung lavage can also be correlated with alteration in body weight and respiration rate subsequent to treatment with thoracic irradiation and/or corticosteroids.

Release of interleukin-1 by human alveolar macrophages after in vitro irradiation.

Therapeutic thoracic irradiation may induce two late pulmonary injury syndromes: radiation pneumonitis and subsequent pulmonary fibrosis. The alveolar macrophage has been considered a radioresistant cell and not a target cell involved in the pathogenesis of either type of radiation-induced lung injury. Alveolar macrophage-derived cytokines, including interleukin-1 (IL-1) and tumor necrosis factor (TNF), have been demonstrated to participate in inflammatory and fibrotic responses in the lung after various other types of lung injury. To evaluate whether the release of cytokines by alveolar macrophages is induced by radiation doses used clinically, alveolar macrophages recovered from nonsmoking volunteers were exposed in vitro to a single dose of 2 Gy and then maintained in culture for 18 h. Culture supernatants and cell lysates were then recovered and analyzed for IL-1 alpha and IL-1 beta by radioimmunoassay. Supernatants of irradiated alveolar macrophages contained significantly increased amounts of IL-1 alpha (P < 0.04) and IL-1 beta (P < 0.02) as well as total IL-1 (IL-1 alpha and IL-1 beta) (P < 0.02) compared to nonirradiated alveolar macrophages. Cell lysates of irradiated alveolar macrophages also contained increased amounts of IL-1 alpha and IL-1 beta, although differences from controls were not significant. The finding of increased release of IL-1 by alveolar macrophages after exposure to a single, clinically relevant dose of radiation suggests that the function of human alveolar macrophages is likely altered during therapeutic use of thoracic irradiation. Whether this release of IL-1 by alveolar macrophages contributes to early lung inflammation induced by thoracic irradiation is unclear.

Advances in interstitial lung disorders.

Interstitial lung disorders are a heterogeneous group of diseases that result in a similar clinical presentation and have similar physiologic consequences on lung function. Our current understanding of these disorders indicates that there is an inflammatory component of these diseases that is reversible and that precedes the development of interstitial pulmonary fibrosis, which is irreversible. Although conclusive clinical studies are still lacking, treatment of pulmonary disease in these patients is based on the concept that treatment of the inflammatory component of the disease with immunosuppressive agents will prevent or reduce the amount of pulmonary fibrosis that develops. Because of the significant side effects associated with immunosuppressive drugs, therapy should be used only when there is likely to be therapeutic benefit. The use of immunosuppressive agents is, therefore, indicated in selected groups of patients. If there is a known precipitating agent for the interstitial disorder, such as asbestos exposure, the primary therapy is to avoid further exposure to the agent. Sarcoidosis is one of the most common systemic disorders associated with interstitial lung disease, and in this disease, corticosteroids clearly are of benefit. In pulmonary sarcoidosis, patients who are symptomatic or patients who demonstrate progressive clinical deterioration of pulmonary function should be treated. Recent studies also suggest that patients with a high degree of pulmonary inflammation as demonstrated by a positive gallium scan and a high percentage (greater than 28%) of lymphocytes obtained on lung lavage may also benefit from corticosteroid therapy. Idiopathic pulmonary fibrosis is a progressive disease and is usually symptomatic at the time of presentation, so it is reasonable to give all patients a therapeutic trial with corticosteroids.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulmonary complications of cancer therapy.

Significant improvements in the result of cancer treatment have resulted in longer survival for many of these patients and increasing numbers of patients who are cured. Unfortunately, the toxic effect of cancer therapy on other organs, and particularly the lung, has become an increasingly recognized problem in these patients. There are no specific tests that are diagnostic for chemotherapy or radiation-induced lung injury so the clinician must keep this diagnosis in mind and attempt to evaluate other possibilities. If treatment induced lung injury is considered likely, whether radiation pneumonitis or drug-induced pneumonitis, corticosteroid therapy may be of benefit. Therapy should be initiated at high doses and then tapered slowly following the clinical response. Most of these patients will do well, however, pulmonary toxicity may lead to respiratory impairment or mortality in some patients. Hopefully, as we gain more understanding of the risk factors and mechanisms of treatment-induced lung toxicity, new methods will be developed to decrease lung impairment due to cancer treatment.

Pulmonary complications of cancer therapy.

The development of pulmonary disease as a result of cancer therapy is an increasingly recognized clinical problem. Chemotherapeutic drugs can induce an acute pneumonitis, pulmonary edema, and pulmonary fibrosis, as well as a variety of other pulmonary diseases in cancer patients.

Effect of bronchial brush size on cell recovery.

The effect of bronchial brush size on cell recovery during fiberoptic bronchoscopy was investigated. In 20 patients undergoing diagnostic bronchoscopy, 3 additional brushings in normal peripheral airways were performed using sheathed brushes of 1.0, 1.73, and 3.0 mm in diameter. Mean cell recovery was 5.7, 8.1, and 9.0 x 10(4) cells per brush, respectively. There were no significant differences in cell recovery between the 3 brushes. Brush size does not appear to significantly influence cell recovery in normal peripheral airways.

Alveolar macrophage proliferation in situ after thoracic irradiation of rats.

Saline lavage was performed on rat lungs at weekly intervals for as long as 6 wk after thoracic irradiation (24 Gy). The number of alveolar macrophages recovered by lavage was significantly increased compared with that in control animals beginning at 4 wk after irradiation (p less than 0.05). Autoradiographic analysis of macrophages recovered demonstrated an increased labeling index compared with that in control animals beginning 3 wk after irradiation (p less than 0.05). Macrophage proliferation in vivo was also assessed by injecting rats with vincristine and evaluating macrophages recovered by lung lavage for arrested mitoses. The number of arrested mitoses noted was significantly increased in rats at 4 wk after irradiation compared with that in control animals (p less than 0.05). These data indicate that after high dose thoracic irradiation there is an expansion of the alveolar macrophage population that is due at least in part to increased local proliferation of alveolar macrophages.

Alveolar macrophage content of isoferritins and transferrin. Comparison of nonsmokers and smokers with and without chronic airflow obstruction.

Alveolar macrophages (AM) contain iron and ferritin, and concentrations of both are increased in AM of smokers compared with nonsmokers. Ferritin stores iron in a nontoxic form but can release iron in the presence of reducing agents and thereby catalyze the generation of toxic hydroxyl radicals via the Haber-Weiss reaction. Two distinct isoferritins are found in peripheral monocytes, L ferritin and H ferritin. H ferritin is the predominant isoferritin in human monocytes and is more effective than L ferritin in detoxifying iron in vitro. In this study we quantitated content of H and L ferritins, transferrin, and iron in AM recovered by bronchoalveolar lavage (BAL) of 24 subjects, including eight nonsmokers, eight smokers with normal spirometry, and eight smokers with chronic airflow obstruction (CAO). Of total AM ferritin in nonsmokers 95% was composed of L ferritin. Smokers without CAO demonstrated a 6.5-fold increase in the AM content of L ferritin (1,886 +/- 266 versus 290 +/- 51 ng, mean +/- SEM; p less than 0.0001) and a 3.8-fold increase in H ferritin (61 +/- 18 versus 16 +/- 2 ng per 1 x 10(6) AM, p less than 0.01) compared with nonsmokers. Compared with smokers without CAO, AM recovered from smokers with CAO demonstrated a greater increase in L ferritin (5,059 +/- 493 versus 1,886 +/- 266 ng per 1 x 10(6) AM, p less than 0.002) but a similar increase in H ferritin (64 +/- 8 versus 61 +/- 18 per 1 x 10(6) AM).(ABSTRACT TRUNCATED AT 250 WORDS)

Increased release of ferritin and iron by iron-loaded alveolar macrophages in cigarette smokers.

The lower respiratory tract of cigarette smokers contains an increased amount of iron that is predominantly sequestered within alveolar macrophages (AM), but is also present in alveolar epithelial fluid. Extracellular ferritin-bound iron could potentially be released by reductants present in cigarette smoke and catalyze generation of highly reactive hydroxyl radicals capable of causing oxidant injury. To determine whether AM are a source of alveolar extracellular ferritin and iron, we assessed in vitro release of iron, ferritin, and transferrin by AM recovered by bronchoalveolar lavage (BAL) of 27 healthy subjects including nine nonsmokers (NS), nine light smokers (LS), and nine heavy smokers (HS). Release of iron in vitro over 20 h was increased in AM recovered from LS (2.24 +/- 0.21 nmol/10(6) AM/20 h, p < 0.001) and HS (3.11 +/- 0.32 nmol/10(6) AM, p < 0.001) compared with NS (1.28 +/- 0.08 nmol/10(6) AM). Release of ferritin in vitro over 20 h was also increased in AM recovered from LS (71 +/- 24 ng/10(6) AM, p < 0.05) and HS (176 +/- 35 ng/10(6), p < 0.001) compared with NS (18 +/- 3 ng/10(6) AM). AM recovered from 12 smokers (8 HS, 4 LS) contained greater than 10 nmol of iron per 10(6) cells. These iron-loaded AM released a greater percentage of cell ferritin stores in vitro over 4 h (8.4% +/- 1.1, p < 0.01) than did AM from NS (3.2% +/- 0.6). Release of lactate dehydrogenase (LDH) over 4 h was substantially less (2.9% +/- 0.3, p < 0.001) than ferritin release.(ABSTRACT TRUNCATED AT 250 WORDS)

Arterial oxygen desaturation during gastrointestinal endoscopy.

This prospective study evaluated the incidence and severity of arterial oxygen desaturation during gastrointestinal endoscopy. Following pulmonary function testing, 115 male patients underwent esophagogastroduodenoscopy (EGD), colonoscopy, or colonoscopy followed by EGD, with continuous recording of arterial oxygen saturation (SaO2). Most patients (80/115, 70%) showed arterial oxygen desaturation (greater than 4% decrease from baseline SaO2); severe arterial oxygen desaturation (SaO2 less than or equal to 85%) reflecting hypoxemia (PaO2 less than or equal to 50 mm Hg) was noted in one-third of patients overall (37/115, 32%). Severe arterial oxygen desaturation occurred in 9/62 EGD patients (15%), 23/46 colonoscopy patients (50%), and 4/7 patients having colonoscopy followed by EGD (57%). Arterial oxygen desaturation occurs frequently during gastrointestinal endoscopy and is often severe. These data support the concept that continuous monitoring of SaO2 should be standard procedure during all gastrointestinal endoscopic procedures.

Neutrophil chemotactic activity generation by alveolar macrophages after bleomycin injury.

Saline lavage was performed on rat lungs after the intratracheal injection of saline or bleomycin. An increase (p less than 0.025) in total cells recovered, an increase (p less than 0.001) in neutrophils, and an increase (p less than 0.001) in albumin concentration were noted in lavage fluid recovered from rats subsequent to bleomycin injury. At 5, 10, 15, and 20 days after injury, macrophages recovered from bleomycin-treated rats generated increased (p less than 0.05) amounts of neutrophil chemotactic activity in vitro compared with macrophages recovered from saline-treated rats. The chemotactic activity was attributable to a factor or factors of low molecular weight and hydrophobic in nature, characteristics similar to previously described alveolar macrophage-derived neutrophil chemotactic factors. The generation of neutrophil chemotactic activity was suppressed (p less than 0.025) by hydrocortisone and 5,8,11,14-eicosatetraynoic acid (ETYA), suggesting that the neutrophil chemotactic activity generation is dependent upon the lipoxygenase pathway of arachidonic acid metabolism.