Detection of IL-5 and IL-1 receptor antagonist in bronchoalveolar lavage fluid in acute eosinophilic pneumonia

BACKGROUND: Acute eosinophilic pneumonia is an idiopathic cause of respiratory failure, characterized by very high numbers of alveolar eosinophils without significant blood eosinophilia. OBJECTIVE: The purpose of this study was to determine which cytokines are associated with acute eosinophilic pneumonia. METHODS: Soluble IL-1 type II receptor and the cytokines IL-1β, IL-1ra, IL-3, IL-5, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor-α were measured in serum and in bronchoalveolar lavage fluid from two patients with acute eosinophilic pneumonia during both acute and convalescent phases. RESULTS: Compared with patients with adult respiratory distress syndrome, the patients with acute eosinophilic pneumonia had high bronchoalveolar lavage fluid levels of IL-5, IL-1ra, and soluble type II IL-1 receptor but not IL-1β, tumor necrosis factor-α>, IL-3, or granulocyte-macrophage colony-stimulating factor. Bronchoalveolar lavage fluid levels of IL-5 and IL-1ra fell after resolution of symptoms. In the serum of patients with acute eosinophilic pneumonia, IL-5 was not detectable, and IL-1ra was initially high but fell after corticosteroid treatment. CONCLUSION: Acute eosinophilic pneumonia is characterized by locally high levels of IL-5, IL-1ra, and soluble type II IL-1 receptor in the alveolar space. (J ALLERGY CLIN IMMUNOL 1996;97:1366-74.)     

Pulmonary eosinophilic syndromes

Acute eosinophilic pneumonia, chronic eosinophilia, Churg-Strauss syndrome, and the hypereosinophilic syndrome are pulmonary eosinophilic syndromes characterized by an increased number of eosinophils in peripheral blood, in lung tissue, in sputum, in bronchoalveolar lavage fluid, or in all of these. These pulmonary eosinophilic syndromes generally are characterized by increased respiratory symptoms, abnormal radiographic appearance, and the potential for systemic manifestations. It is critical to exclude other causes of eosinophilia in patients who have lung disease, to make a quick diagnosis, and to treat aggressively with corticosteroids and other therapies to prevent long-term sequelae.     

Cigarette smoking-induced acute eosinophilic pneumonia: a case report including a provocation test

The mechanism and cause of acute eosinophilic pneumonia are largely unknown. Many factors including the smoking of cigarettes have been suggested, but none have been proven to directly cause acute eosinophilic pneumonia. The authors report a case of acute eosinophilic pneumonia in a young Asian male who recently started smoking. The diagnosis was made based on his clinical course and results of chest radiography, lung spirometry, bronchoalveolar lavage, and transbronchial lung biopsies. After administration of methylprednisolone, his clinical course rapidly improved. A provocation test was designed to establish a connection between cigarette smoking and the development of acute eosinophilic pneumonia. After the provocation test, the patient showed identical symptoms, increase in sputum eosinophils, and worsening of pulmonary function. The results of the provocation test suggest that smoking may directly cause acute eosinophilic pneumonia, and support previous reports of cigarette smoking-induced acute eosinophilic pneumonia.     

Smoking-Induced Acute Eosinophilic Pneumonia in a 15-year-old Girl: A Case Report

Acute eosinophilic pneumonia is a very rare disease that is characterized by acute febrile respiratory failure, diffuse bilateral infiltrates on chest X-ray, and eosinophilia in bronchoalveolar lavage fluid in the absence of infection. We present the case of a 15-year-old girl diagnosed with smoking-induced acute eosinophilic pneumonia. A previously healthy young girl with a 1-day history of fever presented with cough, dyspnea, and diffuse bilateral infiltrates on chest X-ray. She had started smoking only 3 weeks before presentation. She was diagnosed by bronchoalveolar lavage fluid tests and lung biopsy and dramatically improved after steroid treatment. We emphasize that acute eosinophilic pneumonia must be considered when acute pneumonia does not respond to broad-spectrum antibiotics. Effective treatment and prompt institution of therapy can obviate unnecessary morbidity and mortality.     

Pulmonary Eosinophilia

Eosinophils may infiltrate the lung tissue, thus impairing gas exchange and causing several symptoms as dyspnea, fever, and cough. This process may be secondary to several factors, including drugs or parasite migration, or primary (idiopathic). Acute eosinophilic pneumonia is life-threatening and presents frequently in young smokers as an acute hypoxemic respiratory failure of generally less than a week with bilateral lung infiltrates, frequently misdiagnosed as severe community-acquired pneumonia. This patients present without peripheral eosinophilia but usually have more than 25% eosinophils on bronchoalveolar fluid. Chronic eosinophilic pneumonia is a protracted disease of usually more than a month before presentation, with a predilection for middle aged asthmatic patients. Hypoxemia is mild-moderate, and there are usually more than 1,000 eosinophils/mm3 of peripheral blood. Bronchoalveolar fluid has high eosinophil levels (usually more than 25%). Migratory peripheral infiltrates are seen in the chest x-ray film. Both acute and chronic eosinophilic pneumonia are treated by glucocorticoids and respiratory support as well as avoidance of any recognized trigger.     

Chronic eosinophilic pneumonia with subpleural curvilinear shadow

We report a rare case of chronic eosinophilic pneumonia with subpleural curvilinear shadow. CT scan showed a patchy consolidation in the bilateral upper lungs. In addition, subpleural curvilinear shadow was found in the bilateral upper lungs. A bronchoalveolar lavage obtained from the right middle lobe showed 25 % eosinophils. Although very rare, we should therefore keep in mind that patients, who have patchy consolidation with areas of subpleural curvilinear shadow in the bilateral upper lungs, may have chronic eosinophilic pneumonia.     

Eosinophilic airway inflammation in nasal polyposis.

BACKGROUND: Asthma and asymptomatic bronchial hyperresponsiveness (BHR) are frequent findings in patients with nasal polyposis (NP). OBJECTIVE: To elucidate mechanisms responsible for the development of BHR, we initiated a prospective study of bronchial inflammation as assessed by bronchial lavage (BL) and bronchial biopsy specimens in 35 patients with noninfectious NP. METHODS: BHR was determined with methacholine provocation testing. Differential cell count, ECP, and histamine and tryptase levels were determined in BLs. Pathologic examination of bronchial biopsy specimens was performed with May-Grünwald-Giemsa stain to assess the number of lymphocytes. Indirect immunoenzymatic methods were used to identify eosinophils and mast cells. RESULTS: Fourteen patients did not exhibit BHR (group A); 7 patients had asymptomatic BHR (group B); and 14 patients had BHR associated with asthma (group C). Patients of group C tended to have a longer duration of nasal symptoms than those of groups A and B. FEV1 (L) was significantly lower in group C than in groups A and B. The number and percentage of eosinophils were significantly higher in BLs in groups B and C than in group A (P <. 05). Patients of groups B and C had a significantly higher number of eosinophils in bronchial submucosa (14.0 +/- 1.5/mm2 and 19.0 +/- 1. 9/mm2, respectively) than patients of group A (0.1 +/- 0.1/mm2). The number of lymphocytes was also higher in groups B and C than in group A. FEV1 (percent of predicted value) and eosinophil number within bronchial mucosa correlated negatively. CONCLUSION: Our results demonstrate that patients with NP and asymptomatic BHR had an eosinophilic bronchial inflammation similar to that observed in asthmatic patients with NP, whereas patients with NP without BHR do not feature eosinophilic lower airways inflammation. The clinical relevance of these results requires careful follow-up to determine whether eosinophilic inflammation in these patients precedes and is responsible for the development of obvious asthma.     

Leukotrienes, LTC4 and LTB4, in bronchoalveolar lavage in bronchial asthma and other respiratory diseases

Leukotrienes (LTs) C4 and B4 are potent proinflammatory mediators with a wide variety of biologic activities, including smooth muscle contraction, mucus hypersecretion, and leukocyte activation, which may be of particular relevance to the pathology of asthma and other respiratory diseases. We measured the concentrations of LTC4 and LTB4 in bronchoalveolar lavage fluid from 16 atopic subjects with asthma (eight symptomatic and eight asymptomatic) and from 14 control subjects without asthma (six with hay fever and eight nonatopic). The amounts detected in symptomatic subjects with asthma were significantly higher than in control subjects (LTB4, 0.58 +/- 0.06 versus 0.36 +/- 0.05 pmol/ml, p less than 0.05; LTC4, 0.36 +/- 0.1 versus 0.12 +/- 0.02 pmol/ml, p less than 0.01). LTC4 and LTB4 were also measured in 17 patients: nine with interstitial lung disease of varying etiology (cryptogenic fibrosing alveolitis [CFA] or idiopathic pulmonary fibrosis), three with sarcoidosis, one with extrinsic allergic alveolitis, one with sulphonamide-induced pneumonia, and one patient with eosinophilic granuloma. The concentrations of LTB4 (but not LTC4) were significantly greater in patients with CFA compared with normal control subjects (0.69 +/- 0.3 versus 0.36 +/- 0.05 pmol/ml, p less than 0.01). There was a significant correlation (p less than 0.05) between the percentage of neutrophils and the concentration of LTB4 in the bronchoalveolar lavage fluid) of the group with interstitial lung disease as a whole. This study provides evidence for a role for LTs in the airways of subjects with day-to-day asthma and suggests that LTB4 may also be involved in the recruitment of granulocytes into the lung in patients with CFA.     

In vivo expression of CD69 on lung eosinophils in eosinophilic pneumonia: CD69 as a possible activation marker for eosinophils.

The antigen, CD69, has been demonstrated to be expressed on activated T cells and natural killer cells. There have been no studies concerning the expression of CD69 on eosinophils. In this article, we demonstrate that lung eosinophils obtained from the bronchoalveolar lavage fluid of patients with eosinophilic pneumonia expressed significant levels of CD69, whereas peripheral blood (PB) eosinophils did not express CD69. We also activated PB eosinophils in vitro using phorbol myristate acetate and cytokines to determine whether CD69 was expressed. PB eosinophils expressed CD69 after short-term culture with phorbol myristate acetate and eosinophil hemopoietic cytokines (interleukin-3, granulocyte-macrophage--colony-stimulating factor, and interleukin-5). These findings suggest that CD69 may be a useful marker for activated eosinophils at inflammatory sites.     

Pulmonary eosinophilic infiltrates

Pulmonary eosinophilic infiltrates include an heterogeneous group of disorders characterized by the presence of eosinophils in the lungs as detected by bronchoalveolar lavage or tissue biopsy, with or without blood eosinophilia. The disease can be idiopathic (simple pulmonary eosinophilia, acute and chronic eosinophilic pneumonia, hypereosinophilic syndrome), secondary (to drugs, parasites, fungal and mycobacterial infection, irradiation, toxic products) or associated with diffuse lung diseases (connective tissue diseases and some neoplasms). Pathologists faced with eosinophils in the lungs (either on cytology or biopsy) should keep in mind several possibilities, although a diagnosis of certainty is rarely based on morphology alone. Correlation with laboratory tests, imaging studies and clinical presentation has a key role, even if some pulmonary eosinophilic diseases are sufficiently characteristic on clinico-radiologic ground to not require a biopsy (e.g. some drug reactions, parasitic infections, idiopathic hypereosinophilic syndrome, allergic bronchopulmonary aspergillosis). Nevertheless, pathologists can play a central role because they can be the first to note eosinophils in the lungs of a very sick patient. Knowledge of histologic features and a striking collaboration with other physicians are necessary to achieve correct diagnosis and to establish adequate treatments.     

Graft eosinophilia in lung transplantation.

Graft eosinophilia was observed in lung biopsies from nine patients who received lung allografts. Five cases were associated with moderate to severe acute cellular rejection and responded well to steroid therapy. In this group the eosinophilia occurred early after transplantation and was associated with an elevated white blood cell count and occasional peripheral blood (one of five cases) and bronchoalveolar lavage (one of five cases) eosinophilia. A second group of four patients had graft eosinophilia due to infectious agents. In these cases patients frequently had underlying bronchiolitis obliterans (two of four cases) and developed tissue eosinophilia late after transplantation. Bronchoalveolar lavage cell profiles often demonstrated dramatic eosinophilia. Histologically, the biopsy specimens displayed an acute eosinophilic pneumonia, which was attributed to Aspergillus sp (two cases), coxsackie A2 virus (one case), and Pseudomonas maltophilia (one case). Two patients in this group died from infection. While eosinophils are a frequent cellular component of acute rejection reactions, they also may be the dominant cellular component in graft infection.     

Eosinophilic lung disease: immunological studies of blood and alveolar eosinophils.

Five patients with eosinophilic lung diseases and blood hypereosinophilia (PIE syndrome) were investigated clinically and by bronchoalveolar lavage (BAL). Comparative studies on blood and alveolar eosinophils were carried out after purification and selection of eosinophil subpopulations according to their density. A predominant 'hypodense' alveolar eosinophil population was found in BAL fluids of active chronic eosinophilic pneumonia (CEP). In addition, supernatants of alveolar macrophages obtained from CEP are able to enhance spontaneously the generation of eosinophil oxygen metabolites. Such eosinophil stimulation emphasizes a probable tissue cell cooperation. In addition, BAL permitted the study of membrane immunological markers on eosinophilic inflammatory cells endowed with migratory properties. An increase in eosinophils carrying surface IgE was demonstrated in alveolar cells from PIE Syndrome particularly with hypodense eosinophils from CEP patients. Although no specific stimulus is known at the present time, this work underlines the potential implication of IgE-mediated hypersensitivity processes in the pathogenesis of eosinophilic lung diseases.     

Morphology and density features of eosinophil leukocytes in eosinophilic pneumonia

Summary We compared the morphological characteristics and density properties of eosinophil leukocytes obtained from the blood and bronchoalveolar lavage fluid of a 29-year-old patient with chronic eosinophil pneumonia during exacerbation. The lavage eosinophils were significantly increased in size when compared with blood cells (surface area: 208 ± 12 m² versus 161 ± 13 m²). Moreover, eosinophils contained slightly more granules (23.4 versus 20.7 per cell surface area), but no difference was found when the number was corrected for cell size. Electron microscopy revealed a loss of granule contents in eosinophils from both blood and bronchoalveolar lavage. Finally, 61% of the lavage eosinophils were hypodense (with a density < 1.085 g/ml), whereas 96.3% of the blood cells were normodense. In conclusion, our data demonstrate that in chronic eosinophil pneumonia, eosinophils obtained from bronchoalveolar lavage and blood show differences in both their morphology and density, suggesting that eosinophils during migration into the lung may become activated.Abbreviations BAL bronchoalveolar lavage - FCS fetal calf serum - HBSS Hanks balanced salt solution - MBP major basic protein Supported by grants from the Deutsche Forschungsgemeinschaft (Kr 956/1-1), Bundesministerium für Forschung und Technologie/DLR (01KC8906/1), and Arbeitsgemeinschaft zur Förderung der Pneumologie an der Ruhrlandklinik     

Acute eosinophilic pneumonia associated with amitriptyline in a hemodialysis patient.

Drugs are well known causes of eosinophilic lung disease. In many patients, drug-induced eosinophilic lung disease presents with transient eosinophilic infiltrates that disappear after discontinuation of the drug. Some patients, however, experience a fulminant, acute eosinophilia-like disease. Recently, we experienced a case of amitriptyline-associated acute eosinophilic pneumonia with respiratory failure in a diabetic hemodialysis patient. Eight days after treatment with amitriptyline, sudden fever, chill, dry cough and dyspnea developed. Subsequently, multiple patch consolidations appeared on the chest radiographs. Bronchoalveolar lavage (BAL), established a diagnosis of acute eosinophilic pneumonia. After immediate discontinuation of amitriptyline, a rapid clinical and radiological improvement was observed. The present case indicates that the possibility of acute eosinophilic pneumonia should be fully considered in dialysis patients developing unexplained respiratory symptoms while on amitriptyline therapy.     

C1q content of serum and lung lavage fluid of rats exposed to toxic levels of oxygen

We used a sensitive hemolytic assay to measure the level of C1q, a subcomponent of the first complement protein in the classic pathway, in bronchoalveolar lavage fluid and serum of rats exposed to air and hyperoxia. The serum level was 125 +/- 5 micrograms/ml and the lavage level was 41 +/- 17 ng/ml in rats breathing air. In rats exposed to acute oxygen toxicity (95% O2 for 66 hr), the serum level was at 107 +/- 10 micrograms/ml, but the level in lavage fluid increased to 2457 +/- 400 ng/ml (p less than 0.05 compared to air). Administration of the proline analogue cis-4-hydroxy-L-proline to air- and O2-exposed rats reduced the serum C1q level by 28% and 34%, respectively (both p less than 0.05), presumably by interfering with metabolism of the collagen-like sequence of C1q. The level of C1q in bronchoalveolar lavage fluid is a sensitive marker of acute lung injury.     

Alveolar lymphocyte proliferation induced by Propionibacterium acnes in sarcoidosis patients

The proliferation of lymphocytes induced by Propionibacterium acnes (P. acnes) was measured by the in vitro incorporation of 3H-thymidine. The mean response rate of alveolar lymphocytes obtained by bronchoalveolar lavage was 2.23 +/- 0.89 in nine untreated sarcoidosis patients, 0.85 +/- 0.17 in five sarcoidosis patients given corticosteroids and 0.78 +/- 0.29 in 11 controls. The proliferation was significantly enhanced in the untreated patients compared to both the treated patients (p less than 0.01) and controls (p less than 0.001), but there was no significant difference in response rates between the treated patients and controls. The response rate of alveolar lymphocytes was significantly higher in four active patients (3.05 +/- 0.61) than in four inactive patients (1.77 +/- 0.44) (p less than 0.05) and in the controls (p less than 0.001). In sarcoidosis patients, the response rates showed a good correlation with activities of serum lysozyme (r = 0.695, p less than 0.01), and with percentages of lymphocytes in bronchoalveolar lavage fluid (r = 0.591, p less than 0.05). There was a low correlation between angiotensin-converting enzyme activities and the response rates (r = 0.508, p less than 0.1). Neither peripheral blood lymphocytes in sarcoidosis patients nor in controls showed any response to P. acnes, but alveolar lymphocytes of the untreated active sarcoidosis patients were sensitive to P. acnes. The lymphocytes activated by P. acnes may play a central role in the induction of alveolitis in sarcoidosis patients.     

Total serum IgE levels in eosinophilic lung diseases]

BACKGROUND: We previously reported elevated levels of total serum IgE in patients with asthma, regardless of their atopic status. We hypothesized that certain factors inherent to asthma may contribute to this non-specific elevation of total serum IgE. In the current study, to evaluate the role of eosinophils in the regulation of total serum IgE, we examined whether peripheral blood eosinophil count is associated with total serum IgE level in patients with eosinophilic lung diseases. METHODS: Ninety-nine healthy controls, 277 patients with asthma, 15 patients with acute eosinophilic pneumonia, 21 patients with chronic eosinophilic pneumonia were studied for total serum IgE levels and peripheral blood eosinophil counts. RESULTS: Patients with acute or chronic eosinophilic pneumonia had significantly increased total serum IgE levels compared with healthy controls regardless as atopic status (p<0.001). In non-atopic subjects with eosinophilic lung diseases, total serum IgE level was significantly correlated with peripheral blood eosinophil count (r=0.42, p<0.001, n=57). CONCLUSION: Our findings suggest that, in addition to antigen-specific IgE production, non-specific IgE production may contribute to elevated levels of total serum IgE in patients with asthma or eosinophilic pneumonia. An increased number of activated eosinophils may underlie an increased total serum IgE level in these conditions.     

Acute Eosinophilic Pneumonia Leading to Acute Respiratory Failure in a Current Systemic Corticosteroid User

A 69-year-old female patient visited the emergency room with fever (38.3℃) and dyspnea. She had been taking prednisolone (5 mg once per day) and methotrexate (2.5 mg once per week) for rheumatoid arthritis for 2 years. Chest computed tomography (CT) showed bilateral, multifocal ground glass opacity with interlobular septal thickening. Peripheral blood leukocyte count was 6,520/mm³ (neutrophils, 77.4%; eosinophils, 12.1%). During the night, mechanical ventilation was initiated due to the development of severe hypoxemia. Bronchoalveolar lavage fluid showed a high proportion of eosinophils (49%). Her symptoms improved dramatically after commencement of intravenous methylprednisolone therapy. This is the first report of idiopathic acute eosinophilic pneumonia developing in a current user of systemic corticosteroids.     

Granulocyte precursor cell studies in Schistosoma mansoni patients with eosinophilia

Eosinophilia is a common clinical presentation in patients with helminthic infections. A study was designed to determine the mechanism(s) for selective or preferential differentiation of precursor cells into mature eosinophils (eos). Thus, experiments were performed to delineate the frequency of colony forming units of eos (CFU-eos) in the peripheral blood of Egyptian patients with active Schistosoma mansoni infection with eosinophilia and normal healthy individuals. The number of CFU-eos among the nonadherent mononuclear cell population was assessed in a double layer soft agar culture with autologous unfractionated mononuclear cells serving as a source of colony stimulating factor(s). Following 14 days of incubation, discrete colonies were distinguished morphologically as eosinophilic, neutrophilic, or mixed. Results indicated a two-fold increase in the total number of colonies per 10(6) cultured nonadherent cells in patients with S. mansoni infection when compared to the number of colonies obtained with adult normal volunteers (57 +/- 10 vs. 24 +/- 4; P less than 0.025). However, the frequency of CFU-eos and CFU-neut was similar in patients and normal individuals (66 +/- 3 vs. 59 +/- 8 percent CFU-eos; 30 +/- 4 vs. 35 +/- 6 percent CFU-neut). These data suggest that: eosinophils may differentiate from progenitor cells at other anatomical sites; there may be an increase in the half life of mature eosinophils in patients; there is no strict correlation between the frequency of progenitor cells and the number of differentiating mature cells of this lineage at least as measured by this in vitro assay; and the in vitro assay may not quantitatively reflect the in vivo differentiating capacity of progenitor cells.     

Upper lobe relapse ofPneumocystis carinii Pneumonia during aerosolized pentamidine prophylaxis

Summary A patient with a history ofPneumocystis carinii pneumonia (PCP) inhaled aerosolized pentamidine (AP) for secondary prophylaxis of PCP. Nine months after the first PCP episode he presented with pulmonary upper-lobe infiltrations demonstrated by chest x-ray, and bronchoalveolar lavage confirmed the diagnosis of PCP. The clinical course and possible explanations for this unusual form of PCP are presented. The case emphasizes the importance of clinical controls for early diagnosis of relapse of PCP in patients inhaling aerosolized pentamidine. Monitoring of serum lactate dehydrogenase levels appeared to be important in the follow-up of the patient described.Abbreviations PCP Pneumocystis carinii pneumonia - AP aerosolized pentamidine - LDH lactate dehydrogenase - AIDS acquired immunodeficiency syndrome - HIV human immunodeficiency virus - BGA blood gas analysis - WBC white blood cell count - BAL bronchoalveolar lavage