Evaluation of tissue eosinophils in eosinophilic pneumonia]

Transbronchial biopsy specimens from ten patients with eosinophilic pneumonia were analysed to see whether the tissue contained activated eosinophils or secreted eosinophil cationic protein. The specimens showed many infiltrated tissue eosinophils in the intraalveolar spaces, and thickened alveolar septae and perivascular areas. Most of these eosinophils stained clearly with degranulation by immunohistochemical studies with monoclonal antibody EG2 (for the secreted form of eosinophil cationic protein), indicating that they were activated eosinophils. On the other hand, although pleural tissue obtained at bullectomy performed after pneumothorax showed eosinophilic infiltration, EG2-positive cells were few. Activated eosinophils may play an important role in the development of pulmonary lesions of eosinophilic pneumonia.     

Apoptotic response of eosinophils in chronic eosinophilic pneumonia.

To clarify the pathogenesis of chronic eosinophilic pneumonia (CEP), the apoptosis of eosinophils from bronchoalveolar lavage (BAL-Eos) was compared with that of eosinophils from peripheral blood (PB-Eos) in six cases of CEP. The survival rate of eosinophils and the percentage of apoptotic cells of both types of eosinophils were examined, and the effects of interleukin 5 (IL-5) were evaluated. The role of Fas expression in apoptosis of these eosinophils was also studied. The survival rate of BAL-Eos on the third day of culture was significantly higher than that of PB-Eos (p < 0.01). This was associated with a lower proportion of apoptotic cells in BAL-Eos than in PB-Eos; the percentages of apoptotic cells in PB-Eos and BAL-Eos after 24 h of incubation were 21.7 +/- 3.4% and 10.6 +/- 1.7% respectively. IL-5 suppressed apoptosis and increased the survival rate of both PB-Eos and BAL-Eos. It was found that the apoptotic character of BAL-Eos differed from that of PB-Eos in at least three ways. Firstly, the positive rate of Fas expression on PB-Eos was increased after 24 h of incubation, whereas that on BAL-Eos did not change. Secondly, the expression of Fas on PB-Eos was suppressed by IL-5 (18.5 +/- 4.2% - 8.3 +/- 3.2%, p < 0.05), whereas IL-5 failed to suppress Fas expression on BAL-Eos (3.3 +/- 1.6% - 3.6 +/- 1.0%). Lastly, binding of antibody to Fas antigen induced apoptosis of PB-Eos, but not of BAL-Eos. These data suggested that Fas seemed to be involved in the apoptosis of PB-Eos, whereas BAL-Eos were Fas-resistant in chronic eosinophilic pneumonia. In conclusion, apoptosis of eosinophils might be suppressed by proinflammatory cytokines such as IL-5 leading to their accumulation in the lung. Chronic stimulation of eosinophils in the alveolar space with IL-5 may play a crucial role chronic eosinophilic disorders.     

Cigarette smoke-induced acute eosinophilic pneumonia accompanied with neutrophilia in the blood

Smoking causes various changes in the lung. This report describes a case of cigarette smoke-induced acute eosinophilic pneumonia (CS-AEP) with neutrophilia in the blood. However, the precise mechanism is unknown, so we examined the effect of exposure to cigarette smoke extracts on the production of interleukin (IL)-4, IL-5, IL-8, IL-18, granulocyte macrophage-colony stimulating factor (GM-CSF), and vascular endothelial growth factor (VEGF) by human bronchial epithelial cells (HBECs) obtained from the patient. We found that IL-8 released from HBECs was involved in neutrophilia in the blood, and is a new factor in the development of AEP, especially in the early phase.     

GM-CSF-induced acute eosinophilic pneumonia

Summary. There is increasing evidence that haemopoietic growth factors are effective in reversal of neutropenia associated with large granular lymphocytes (LGLs) proliferation. A 19-year-old woman with CD3⁺/TCRγδ⁺, CD4⁻, CD8⁻ LGL proliferation and severe neutropenia repeatedly developed blood eosinophilia, fever and dyspnoea after administration of GM-CSF. Acute eosinophilic pneumonia with a lobar lung infiltrate pleural effusion, and marked bronchoalveolar lavage fluid eosinophilia was diagnosed. Treatment with corticosteroids and discontinuation of GM-CSF lead to rapid improvement. In addition, haematological analysis revealed that H*1 Technicon, a widely-used automated cell counter, may misinterpret eosinophils erroneously as neutrophils, therefore examination of blood smears to prevent eosinophil-medlated toxicity during GM-CSF treatment is recommended.     

Idiopathic acute eosinophilic pneumonia.

A previously healthy young man presented with acute respiratory distress, high fever and bilateral ground-glass appearance on chest radiograph. Bronchoalveolar lavage analysis demonstrated significant eosinophilia (72%) with no evidence of infection. The transbronchial lung biopsy showed that the walls of bronchioli and alveolar septa were markedly infiltrated with eosinophils. The patient rapidly improved with corticosteroid therapy. This case exemplifies the recently described idiopathic acute eosinophilic pneumonia. Similar cases published in the Japanese literature were reviewed and discussed.     

Ultrastructural observation of eosinophils in bronchoalveolar lavage fluid in eosinophilic pneumonia]

To investigate the morphological changes of local eosinophils in the lungs, we observed the ultrastructure of eosinophils in bronchoalveolar lavage fluid (BALF) from patients with eosinophilic pneumonia. We also measured the BALF concentration of eosinophil cationic protein (ECP) as an index of the activation of eosinophils. The eosinophils in BALF from patients with eosinophilic pneumonia showed various ultrastructural changes compared to eosinophils in BALF of the control patient. Changes included degranulation or disintegration of specific granules, cytoplasmic vacuolation, increased lipid droplets and the appearance of Charcot-Leiden crystals. These changes of BALF eosinophils were more prominent than those of peripheral blood eosinophils. ECP concentration (mean +/- SD) in BALF from patients with eosinophilic pneumonia was 12.2 +/- 7.78 micrograms/l which was significantly higher than the concentrations in patients with bronchial asthma not during an attack (1.36 +/- 2.08 micrograms/l) and in healthy control subjects (2.14 +/- 4.62 micrograms/l). These results suggest that local eosinophils in the lungs are activated and degranulated by various stimuli and undergo structural degeneration in eosinophilic pneumonia.     

Early-phase neutrophilia in cigarette smoke-induced acute eosinophilic pneumonia

Although cigarette smoking is a recognized cause of acute eosinophilic pneumonia (AEP), and an increase in eosinophils in the lung is a common occurrence in AEP, early-phase neutrophilia in AEP is not well understood. We describe three cases of cigarette smoke (menthol type)-induced AEP with neutrophilia in the lungs or blood. Increased in-vitro production of the neutrophil chemoattractant interleukin (IL)-8 by human bronchial epithelial cells (HBECs) was correlated with neutrophilia. We suggest that IL-8 released from HBECs is involved in neutrophilia in the lung in AEP, and is newly recognized as an important factor in the early phase of AEP development.     

Fatal idiopathic acute eosinophilic pneumonia with acute lung injury

A fatal case of idiopathic eosinophilic pneumonia with acute lung injury is described. The patient required treatment with mechanical ventilation and intravenous corticosteroids, however, she died on the third hospital day. At autopsy, both exudative and proliferative phases of diffuse alveolar damage were observed bilaterally. Marked eosinophilic infiltrate was noted in the alveolar wall and within the alveolar cavities with occasional abscess-like features. To our knowledge, this is the first report of fatal acute eosinophilic pneumonia, and provides important information for the management of this condition.     

Flavored cigar smoking induces acute eosinophilic pneumonia

Two cases of acute eosinophilic pneumonia (AEP) following smoking of flavored cigars were analyzed for characteristic features. None of our patients had a history of smoking flavored cigars/cigarettes in the past. One of them had never smoked, and the second patient was an ex-smoker who quit 17 years ago. Both patients presented with community-acquired pneumonia-like symptoms that did not respond to treatment with antibiotics. Their chest radiographs revealed bilateral diffuse infiltrates. The diagnosis of AEP was established based on the clinical picture, BAL that revealed an average eosinophil count > 45%, and immediate clinical improvement after introducing corticosteroids. All other possible causes were excluded during the initial workup.     

Desquamative interstitial pneumonia with a remarkable increase in the number of BAL eosinophils

A 57-year old man with desquamative interstitial pneumonia (DIP) showed a marked increase in eosinophils in the bronchoalveolar lavage (BAL) fluid. The patient was referred to our hospital for abnormal shadows on his chest X-ray with no symptoms in May 2007. Computed tomography (CT) showed patchy, peripheral predominate ground-glass opacity. The BAL fluid revealed an increase of the total number of cells, including markedly elevated levels of eosinophils (62.1%), in contrast with only a slight increase of peripheral blood eosinophils, or minimal eosinophils in the alveolar spaces and interstitium of the thoracoscopic lung biopsy specimen. Since the specimens showed findings compatible with a DIP pattern, we diagnosed the patient with DIP. Although it is a rare entity, we should therefore consider DIP in the differential diagnosis when we encounter patients with a marked increase in the number of BAL eosinophils.     

Activated eosinophils in familial eosinophilic gastroenteritis

Two siblings with eosinophilic gastroenteritis who presented with severe iron deficiency anemia and hypoalbuminemia associated with varying degrees of mucosal damage are described. Using a monoclonal antibody to the secreted form of eosinophil cationic protein, we demonstrated activated degranulating eosinophils in the gastrointestinal mucosa that correlated with the degree of histologic damage. This finding suggests that eosinophils may have a primary role in the tissue damage in this condition. Oral disodium cromoglycate (Nalcrom) failed to alter the clinical, radiologic, and histologic abnormalities. Prednisolone, however, was beneficial in 1 case but did not completely reverse the abnormalities.     

Clinicopathological differences between acute and chronic eosinophilic pneumonia

OBJECTIVE: Considerable confusion exists regarding the proper classification of idiopathic eosinophilic pneumonia (IEP). Furthermore, there are no reports describing the clinicopathological differences between the various forms of eosinophilic pneumonias. METHODOLOGY: The histological findings in acute eosinophilic pneumonia (AEP) and chronic eosinophilic pneumonia (CEP) were examined and the clinical and radiological features were contrasted with them. RESULTS: Radiologically, ground glass opacity and interlobular septal thickening were characteristic of the AEP cases, while air space consolidation was seen in all CEP cases. Histologically, interstitial oedema and fibrin deposition were prominent in the AEP cases. Type II cells were detached from the alveolar walls, although the basal lamina was predominantly intact. In CEP, in addition to cellular infiltration, there was prominent intraluminal fibrosis. Disruption of the basal lamina was observed and nests of intraluminal fibrosis were directly adjacent and connected to the alveolar walls. CONCLUSIONS: An essential histological difference between AEP and CEP is the severity of basal lamina damage and the amount of subsequent intraluminal fibrosis. In AEP particularly, these findings explain the radiographical findings, as well as the rapid and complete improvement noted in such cases.     

A case of sho-seiryu-to-induced pneumonia with a marked increase in peripheral eosinophils]

A 25-year-old woman presented with a high temperature, cough and dyspnea three days after taking sho-seiryu-to, a Chinese herbal preparation, for a cough and throat pain. A chest X-ray film and computed tomography (CT) scan revealed diffuse infiltrative shadows in both the middle and lower lung fields. Arterial blood gas analysis showed hypoxemia (PaO2 43Torr under room air). The white cell count was 40,800/mm3, with eosinophilic cells accounting for 56.5% of the cells. The patient was treated with methylprednisolone under a diagnosis of drug-induced pneumonia and the administration of sho-seiryu-to was discontinued. Immediately after the prednisolone administration, her chest X-ray film findings, clinical symptoms and laboratory data markedly improved. A lymphocyte stimulation test for sho-seiryu-to using peripheral lymphocytes was positive. In 29 cases of herbal medicine-induced pneumonia reported in Japanese medical literature over a 10-year period, sho-saiko-to has been the predominant cause of drug-induced pneumonia. This is the second case of sho-seiryu-to-induced pneumonia.     

Alterations in smoking habits are associated with acute eosinophilic pneumonia

BACKGROUND: Acute eosinophilic pneumonia (AEP) is characterized by a febrile illness, diffuse pulmonary infiltrates, and pulmonary eosinophilia. The etiology of AEP remains unknown, but several studies have proposed a relationship between cigarette smoking and AEP. However, most studies showing this possibility are single-case reports, and cigarette smoke has not been fully validated as a causative agent of AEP in a large series of patients. The present study was conducted to clarify the etiologic role of cigarette smoking in AEP, with special reference to alterations in smoking habits. METHODS: We took a detailed history of smoking habits before AEP onset in 33 patients with AEP, and performed a cigarette smoke provocation test. RESULTS: Of our AEP patients, all but one (97%) were current smokers. Interestingly, 21 of these were new-onset smokers, and 2 had restarted smoking after a 1- to 2-year cessation of smoking. The duration between starting smoking and AEP onset was within 1 month (0.67 +/- 0.53 months). Additionally, six of the remaining smokers had increased the quantity of cigarettes smoked daily, fourfold to fivefold, mostly within the month before AEP onset (0.81 +/- 0.58 months). Only three smokers had not changed their smoking habits before AEP onset. Cigarette smoke provocation tests revealed positive results in all nine patients tested. CONCLUSION: These data suggest that recent alterations in smoking habits, not only beginning to smoke, but also restarting to smoke and increasing daily smoking doses, are associated with the development of AEP.     

Increased vascular endothelial growth factor in acute eosinophilic pneumonia.

Acute eosinophilic pneumonia (AEP) is associated with the presence of diffuse pulmonary infiltrates on the chest radiograph and an increased number of eosinophils and an elevation of interleukin (IL)-5 levels in bronchoalveolar lavage (BAL) fluid. Vascular endothelial growth factor (VEGF) is a constitutively expressed protein encoded by messenger ribonucleic acid in human eosinophils and is released following stimulation with IL-5. However, the roles of IL-5 and VEGF in the pathogenesis or activity of this disease have not been clarified. The authors investigated the cells and the levels of these two factors in BAL fluid in five AEP patients and five normal controls before and after corticosteroid treatment. The absolute number of eosinophils-mL(-1), IL-5 and VEGF levels in patients before treatment were higher than in controls (53.8 versus 0.3 x 10(4) x mL(-1), 490.1 versus 5.2 pg x mL(-1) and 643.0 versus 133.9 pg x mL(-1), respectively). IL-5 and VEGF rapidly decreased to the control level in parallel with clinical improvement. The relationship between eosinophilia and IL-5 and VEGF levels was strongly significant. Elevated interleukin-5 in the lung may initiate the recruitment of eosinophils and enhance the release of mediators, such as vascular endothelial growth factor from eosinophils, which, in turn, increases the permeability of blood vessels.     

急性嗜酸粒细胞性肺炎2例并文献复习

目的:探讨急性嗜酸粒细胞性肺炎(AEP)的临床特点。方法:分析总结南京鼓楼医院集团宿迁医院确诊的2例急性嗜酸粒细胞性肺炎患者的临床诊治特点。分别以"急性嗜酸肺炎" "acute eosinophilic pneumonia"和"AEP"为检索词,检索2000-2021年的中国知网数据库及PubMed数据库并复习相关文献...     

Pranoprofen-induced lung injury manifesting as acute eosinophilic pneumonia]

A 48-year-old man was admitted to our hospital complaining of fever, dyspnea, and cough. He had been treated with pranoprofen and antibiotics by an outpatient clinic for the preceding 4 days. Chest X-ray films revealed Kerley B lines, perivascular cuffing, and hilar haze with pleural effusion in both lungs. Chest computed tomographic films showed non-segmental patchy infiltrates, and thickening of bronchovascular bundles and interlobular septa. Laboratory data showed eosinophilia in peripheral blood (28%) and severe hypoxemia (PaO2:60 torr). Bronchoalveolar lavage fluid disclosed an increased total cell count, eosinophils (39%), and CD 4/CD 8 ratio (2.1). Microscopic examination of transbronchial lung biopsy specimens showed infiltration of eosinophils and mononuclear cells into alveolar wall's and spaces. Acute eosinophilic pneumonia was suspected on the basis of Allen's diagnostic criteria (N Engl J Med: 1989). After discontinuation of pranoprofen, the patient's clinical symptoms, laboratory data, and chest X-ray findings improved rapidly without steroid therapy. A leukocyte migration test (LMT) for pranoprofen was positive and a challenge test for smoking was negative. An environmental provocation test in the patient's home gave negative results. A challenge test for pranoprofen was not performed due to the lack of informed consent. Based on these findings, our diagnosis was pranoprofen-induced lung injury manifesting as acute eosinophilic pneumonia.     

Clinicopathological differences between acute and chronic eosinophilic pneumonia]

Considerable confusion exists regarding the proper classification of idiopathic eosinophilic pneumonia (IEP). In addition, there are no reports that reveal clinicopathological differences between the various eosinophilic pneumonias. A problem persists in describing what the essential histological differences are between the different types of IEP. In this context, we examined the histological findings of acute eosinophilic pneumonia (AEP) and chronic eosinophilic pneumonia (CEP) and contrasted them with the clinical features and radiological findings. Radiologically, ground glass opacity and interlobular septal thickening were characteristic of the AEP cases studied, while air space consolidation was seen in all CEP cases. Histologically, interstitial edema and fibrin deposition were prominent in the AEP cases. Type II cells were detached from the alveolar walls, though the basal lamina was predominantly intact. In CEP, in addition to cellular infiltration, there was prominent intraluminal fibrosis. Disruption of the basal lamina was observed and nests of intraluminal fibrosis were directly adjacent and connected to the alveolar walls. From these findings, we conclude that the histological differences between AEP and CEP are the severity of basal lamina damage, the amount of subsequent intraluminal fibrosis, and the severity of interstitial edema. Especially in AEP, interstitial edema is an essential histological finding and this finding explains the acute onset, and the radiographic findings, as well as the rapid and complete improvement noted in such cases.