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.     

Chronic eosinophilic pneumonitis due to the inhalation of aerosolized face lotion: A case report

Rationale:Inhalation of toxic agents can induce eosinophilic pneumonia. However, only a few case reports demonstrate that exposure to materials can induce chronic eosinophilic pneumonia (CEP). Here, we describe a rare case of CEP with mild alveolar hemorrhage due to the inhalation of aerosols from face lotion. This is the first report of eosinophilic pneumonia caused by face lotion exposure.Patient concerns:A 39-year-old woman was admitted to our hospital with cough and dyspnea for 2 months, which coincided when she started to use a new aerosolized face lotion. Laboratory findings showed high blood eosinophil levels, and chest computed tomography (CT) scans revealed bilateral peripheral consolidation and ground-glass opacity mainly in the left upper lobe. She underwent flexible bronchoscopy. Eosinophils in bronchoalveolar lavage fluid (BALF) were slightly elevated, and the gross appearance of BALF was bloody. The histological examination of the transbronchial lung biopsy showed infiltration of eosinophils and macrophages in alveolar septa with edema and without vasculitis and granuloma formation; a small number of hemosiderin-laden macrophages were also observed. An inhalation challenge test involving the face lotion was performed. Six hours after the test, the blood test showed an increased white blood cell (WBC) count, and chest radiography showed slight exacerbation. Forced vital capacity decreased the following day.Diagnosis:According to histological analysis and positive result of an inhalation challenge test, she was diagnosed with CEP with mild alveolar hemorrhage due to inhalation of aerosols from the face lotion.Interventions and outcomes:She gradually improved without medication after stopping the use of face lotion.Lessons:To the best of our knowledge, this is the first report of CEP with mild alveolar hemorrhage due to the inhalation of face lotion. Various inhaled agents, such as face lotion, can induce CEP in rare cases.     

Eosinophilic pneumonia: A review of the previous literature,causes, diagnosis,and management

Eosinophilic pneumonia (EP) is a rare disorder, comprising several heterogeneous diseases. Two major types of EP are acute eosinophilic pneumonia (AEP) and chronic eosinophilic pneumonia (CEP), both of which are characterized by marked accumulation of eosinophils in lung tissues and/or BAL fluid. AEP and CEP share some similarities in terms of pathophysiology, radiological findings, and treatment response to corticosteroids. However, they distinctly differ in etiology, clinical manifestations, and the nature of disease course. Especially, although AEP and CEP respond well to corticosteroids, relapse frequently occurs in patients with CEP, but rarely in those with AEP. Although CEP occasionally persists and becomes corticosteroid dependent, most patients with AEP completely recover. This article reviews previous studies and discusses the etiology, clinical manifestations, and treatment of AEP and CEP.     

Bronchial involvement in chronic eosinophilic pneumonia: a case report

Chronic eosinophilic pneumonia (CEP) is an idiopathic chronic condition characterized by alveolar filling with mixed inflammatory infiltrate consisting largely of eosinophils. On CT, it is usually observed as consolidation, often peripheral and patchy in distribution, with upper lobe dominance. Airway involvement in CEP is very rare. We report on a case of bronchial involvement in CEP.     

Tracheobronchial lesions in eosinophilic pneumonia

BackgroundEosinophilic pneumonia (EP) is characterized by eosinophil infiltration in the lung parenchyma. However, tracheobronchial lesions associated with the disease have been poorly described. To clarify the frequency and characteristics of cases with tracheobronchial lesions in EP, we performed a retrospective review of EP patients.MethodsWe included 36 EP cases seen from January 2004 to December 2007 at the Kinki-Chuo Chest Medical Center. The incidence of tracheobronchial nodules and associated clinical features were analyzed.ResultsOf these 36 patients, 29 had chronic eosinophilic pneumonia (CEP); 1, acute EP; 3, drug-induced EP; 2, allergic bronchopulmonary aspergillosis; and 1, parasite-related EP. Only 2 of the 29 CEP cases had tracheobronchial lesions. For both of these cases, bronchoscopy revealed multiple whitish nodules on the tracheobronchial mucosa. The associated histopathological findings revealed squamous metaplasia and eosinophil infiltration in the subepithelial region. In both cases, the nodules disappeared after steroid therapy. The prevalence of tracheobronchial lesions was 6.9% in CEP patients and 5.6% in EP patients overall. EP patients were divided into 3 groups: CEP with nodules (n=2), CEP without nodules (n=27), and other EP (n=7). We found that the CEP with nodules group showed a relatively higher incidence of respiratory symptoms, higher white blood cell (WBC) count, and higher levels of peripheral and bronchoalveolar eosinophilia than the other groups.ConclusionsTracheobronchial nodules represent rare observations within the EP population, which are likely to reflect a severe disease condition.     

Acute eosinophilic pneumonia caused by composter vapor inhalation: A case report

A 65-year-old woman presented to a local hospital with a 4-day history of cough, fever, and dyspnea. She had started using a composter and had been exposed to the vapor for 18 days before her first visit. She was diagnosed with acute eosinophilic pneumonia (AEP) based on her symptoms, the presence of bilateral pulmonary opacities on computed tomography, and alveolar eosinophilia confirmed by bronchoalveolar lavage. Inhalation of the composter vapor was thought to be the cause of AEP. Aspergillus fumigatus was cultured from the composter soil and the bronchoalveolar lavage fluid. She fully recovered without systemic corticosteroid administration by avoiding the composter.     

Osteopontin levels are elevated in patients with eosinophilic pneumonia

Background and objective: Osteopontin is a key cytokine involved in pro‐inflammatory T helper type 1 (Th1)‐associated immune responses, which has recently been implicated in allergic diseases. We investigated the pathogenic role of osteopontin in eosinophilic pneumonia. Methods: The concentrations of osteopontin and Th1‐ or Th2‐associated cytokines were measured in BAL fluid (BALF) from 41 patients with eosinophilic pneumonia, including those with acute (AEP, n = 12), chronic (CEP, n = 16), or drug‐induced eosinophilic pneumonia (DEP, n = 13). The results were compared with those from patients with other interstitial lung diseases. Immunocytochemistry and double immunofluorescence labelling were performed to determine the cellular source of osteopontin. Results: Osteopontin was significantly elevated in BALF from patients with eosinophilic pneumonia as compared with BALF from patients with drug‐induced interstitial pneumonia, hypersensitivity pneumonitis, idiopathic interstitial pneumonia, or sarcoidosis, and also compared with BALF from healthy volunteers. Osteopontin concentrations elevated at the time of exacerbation decreased during clinical improvement, either spontaneously or as a result of corticosteroid therapy. Elevated concentrations of CXCL10, CCL17 and IL‐10 were also detected in BALF from patients with eosinophilic pneumonia. Osteopontin concentrations in BALF of AEP patients were correlated with IL‐5, as well as IL‐10, CCL11, CCL17 and CXCL10 concentrations. In AEP and DEP patients, serum osteopontin concentrations were also elevated. Double immunofluorescence labelling showed that in patients with eosinophilic pneumonia, osteopontin was expressed in lung eosinophils. Conclusions: Osteopontin is likely to contribute to the development of inflammation in patients with eosinophilic pneumonia.     

慢性嗜酸粒细胞肺炎1例并文献复习

目的 介绍1例慢性嗜酸粒细胞肺炎(CEP)并复习近7年的9篇国内文献报道共10例,以提高对这一少见病的认识.方法 对1例确诊为CEP患者的临床及随访资料进行分析,并结合文献讨论其临床特点、诊断及治疗.结果 CEP是一种病因不明的慢性肺嗜酸粒细胞性炎症.其特点为患者可有过敏性疾病史,多数患者有咯痰、发热、不同程度的呼吸困难,部分患者可以阴性,而在体检时发现.外周血嗜酸粒细胞及红细胞沉降率大部分明显增高,胸部X线片呈肺外周非肺段分布性进展性高密度浸润影,常有"肺水肿反向征",痰和(或)支气管肺泡灌洗液嗜酸粒细胞显著增高,抗感染治疗无效,而对口服糖皮质激素(OSCT)反应良好.OSCT治疗后阴影迅速吸收,总的预后良好.结论 对具有以上特征且抗生素治疗无效的肺炎患者,应疑诊CEP,及时行支气管肺泡灌洗嗜酸粒细胞计数或经皮肺活检可以明确诊断.     

Transbronchial biopsy is clinically useful in classifying patients with interstitial pneumonia associated with polymyositis and dermatomyositis

Background and objective: The histological type of intraluminal fibrosis is an important prognostic factor for interstitial pneumonia. We therefore examined whether transbronchial lung biopsy (TBLB) specimens are useful for predicting the clinical course and prognosis of patients with interstitial pneumonia associated with polymyositis and dermatomyositis (PM/DM), with particular attention to the different types of intraluminal fibrosis. Methods: Twenty‐five cases of interstitial pneumonia associated with PM/DM were classified according to the pattern of intraluminal fibrosis as assessed by TBLB, and the clinical course and response to treatment were compared. Interstitial fibrosis was evaluated by sequential thin‐section CT scans. Results: In 19 of 25 (76%) cases, there was sufficient intraluminal fibrosis to perform an evaluation. Intraluminal fibrosis was classified as bud (polyp) type or mural incorporation type (either alone or mixed with bud type). The bud type was seen in five cases and these improved following treatment with corticosteroids only. The mural incorporation type was seen in 14 cases. In 11 of these 14 cases, progressive long‐term fibrosis developed and four cases were fatal, in spite of corticosteroid and immunosuppressive therapy. The response to drugs (P < 0.01) and survival (P < 0.05) were significantly greater in patients with bud‐type than mural incorporation‐type intraluminal fibrosis. Conclusions: Classification of the pattern of intraluminal fibrosis as assessed by TBLB is useful for predicting the response to treatment, clinical course and prognosis of interstitial pneumonia associated with PM/DM.     

慢性嗜酸粒细胞肺炎的研究进展

慢性嗜酸粒细胞肺炎是一种病因不明的慢性肺嗜酸粒细胞性炎症,临床表现无特异性,其特点为周围性肺浸润影;外周血和(或)支气管肺泡灌洗液中嗜酸粒细胞数显著增高;抗感染治疗无效而对糖皮质激素的反应良好,但在减量或停用糖皮质激素时容易复发.     

Increased interleukin-5 levels in bronchoalveolar lavage fluid is a major factor for eosinophil accumulation in acute eosinophilic pneumonia.

BACKGROUND: Increased interleukin-5 (IL-5) levels have been reported in bronchoalveolar lavage fluid (BALF) from patients with acute eosinophilic pneumonia (AEP); however, it still remains to be determined whether IL-5 is responsible for the eosinophil accumulation in the lung. OBJECTIVE: We examined the effect of antibodies against cytokines on eosinophil chemotaxis induced by BALF from AEP patients to identify factors responsible for eosinophil accumulation. METHODS: We measured a series of specific cytokines, including IL-3, IL-4, IL-5, IL-6, IL-8, GM-CSF, RANTES, MCP-1, MIP-1alpha and eotaxin, in the BALF from 4 patients with AEP. BALF from 4 patients with chronic eosinophilic pneumonia (CEP) and 13 patients with non-eosinophilic interstitial lung diseases (ILD) were examined as controls. The eosinophil chemotactic activity in the BALF was examined using tissue culture insert furnished with a polycarbonate membrane. RESULTS: The total protein content in BALF from patients with AEP was extremely elevated. Even after standardization with protein concentration, IL-5 levels in AEP patients were significantly higher than those in CEP and ILD. IL-3 and chemokines were rather lower in the AEP group than in the CEP and ILD groups. In AEP BALF, anti-IL-5 neutralizing antibody significantly inhibited eosinophil chemotaxis. Antibodies against IL-3, GM-CSF, and IL-8 did not affect the eosinophil migration. CONCLUSION: These findings suggest that locally produced IL-5 plays an important role in eosinophil accumulation of AEP.     

High concentration of (1-->3)-beta-D-glucan in BAL fluid in patients with acute eosinophilic pneumonia

Our aim in the study was to investigate the pathogenesis of eosinophilic inflammation in patients with acute eosinophilic pneumonia (AEP), and to determine the levels of (1-->3)-beta-D-glucan, which is one of the major components of the cell wall of most fungi, in the BAL fluid (BALF) of those patients with AEP. Six patients with AEP and five patients with chronic eosinophilic pneumonia (CEP) that was in the acute stage and had been newly diagnosed, and nine healthy subjects from the Kurume University School of Medicine and the Social Institute Tagawa Hospital between 1995 and 2001 were entered into the study. In AEP patients, (1-->3)-beta-D-glucan was detected in BALF, and these findings were compared with BALF findings in patients with CEP as well as with those in healthy subjects. In the BALF of AEP patients, the mean concentration of (1-->3)-beta-D-glucan was significantly higher (p < 0.05) than that of CEP patients as well as healthy subjects. In patients with AEP, the mean concentration of (1-->3)-beta-D-glucan in BALF was significantly higher (p < 0.05) than that in the blood. In four of six patients with AEP, we measured serial changes in (1-->3)-beta-D-glucan levels, and the level of (1-->3)-beta-D-glucan in the BALF decreased with clinical improvement at follow-up. We concluded that inhaled (1-->3)-beta-D-glucan may be involved in the mechanisms of pulmonary inflammation in patients with AEP.     

Chronic eosinophilic pneumonia associated with Schizophyllum commune

We describe the first known Japanese patient with chronic eosinophilic pneumonia caused by Schizophyllum commune. The patient presented to Social Insurance Tagawa Hospital, Fukuoka, Japan with cough, wheezing, dyspnoea, and fever. Computed tomograms of the chest showed bilateral areas of consolidation with air bronchograms as well as interstitial infiltrates in the upper lobe, without ectasia of proximal bronchi. Fibreoptic bronchoscopy revealed no impacted mucus in the bronchi. BAL fluid from the right upper lobe yielded an increased total cell count with a high percentage of eosinophils. A transbronchial lung biopsy specimen showed a bronchoalveolar chronic inflammatory infiltrate composed of eosinophils, lymphocytes and plasma cells, associated with fibrosis of the alveolar walls. S. commune was identified in lavage fluid. Antibodies to this organism were present in the serum, confirming that S. commune was the cause of chronic eosinophilic pneumonia. Inhaled corticosteroids without accompanying oral corticosteroids or antifungal agents decreased the respiratory symptoms, and the infiltrates disappeared from the chest radiograph within a few days     

老年急性嗜酸粒细胞性肺炎1例及文献复习

目的：探讨急性嗜酸粒细胞性肺炎(acute eosinophilic pneumonia,AEP)患者的临床特点、诊治和预后,提高临床诊治水平。方法分析北京医院收治的1例老年男性 AEP 患者的临床、影像学和病理学特点,并结合文献复习加以总结。结果患者以咳嗽、咳痰、发热起病。胸部 CT 示双肺多发斑片影伴少量胸腔积液,抗感染治疗无效。经皮肺穿刺活检病理提示 AEP,给予糖皮质激素治疗后好转。结论 AEP 是一种少见病,易被误诊为细菌性肺炎,对糖皮质激素敏感,早期明确诊断,规范治疗,治愈后无复发,预后良好。     

A case of prolonged eosinophilic pneumonia with pulmonary emphysema and bronchial asthma diagnosed by open lung biopsy]

A 65-year-old man was admitted to our hospital complaining of productive cough, dyspnea and stridor. Chest X-ray disclosed overinflation with micronodular infiltrates. Blood examination showed mild eosinophilia and IgE elevation. Pulmonary function test disclosed severe airway obstruction and diffusion capacity impairment. Although clinical improvement was achieved after bronchodilator therapy, laboratory abnormalities continued. Open lung biopsy demonstrated mononuclear cellular and eosinophilic infiltration at alveolar lumen and vessel walls without prominent fibrosis, which was compatible for prolonged eosinophilic pneumonia. From above findings, this case was thought as a prolonged eosinophilic pneumonia combined with pulmonary emphysema and bronchial asthma.     

Traction bronchiectasis on high-resolution computed tomography may predict fatal acute eosinophilic pneumonia

Background

Most patients with acute eosinophilic pneumonia (AEP) show rapid improvement. However, some cases of AEP prove fatal. The aims of this study were to determine the clinical, radiographic, and pathologic characteristics of patients in whom AEP has a fatal outcome and to identify predictors of a poor prognosis.

Clinical Significance of Interleukin 33 (IL-33) in Patients with Eosinophilic Pneumonia

Background: Interleukin 33 (IL-33) works as a functional mediator in allergic disease by enhancing the activity of eosinophils and inducing expression of T helper 2 (Th2)-associated cytokines. However, the role of IL-33 in pulmonary eosinophilia has not been elucidated. We investigated the levels of IL-33 in eosinophilic pneumonia (EP) together with associated cytokines, and discussed the clinical significance of IL-33 in EP.Methods: Sera and bronchoalveolar lavage fluid (BALF) were obtained from 16 patients with EP, including acute eosinophilic pneumonia (AEP) and chronic eosinophilic pneumonia (CEP). Twelve patients with acute respiratory distress syndrome (ARDS) were also included for comparison. The concentration of IL-33 and Th2 cytokines (IL-4, IL-5, IL-13) were measured by enzyme-linked immunosorbent assay (ELISA).Results: The concentration of serum IL-33 was significantly higher in patients with AEP than in CEP. In CEP, only patients with atopic factors showed mild increase of serum IL-33. The concentration of BALF IL-33 was also significantly elevated in AEP, however, it remained quite low in CEP. Among Th2 cytokines, IL-5 was significantly increased in both serum and BALF in AEP, and the level of IL-5 was positively correlated with that of IL-33. ARDS showed no increase of serum and BALF IL-33.Conclusions: The remarkable increase of BALF IL-33 in AEP indicated the local production of IL-33 in lungs. IL-33 is considered to be a local key molecule for triggering pulmonary eosinophilia, together with IL-5. BALF IL-33 appears to be a useful marker for discriminating AEP from CEP and ARDS.     

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.     

Possible Role of IL-25 in Eosinophilic Lung Inflammation in Patients with Chronic Eosinophilic Pneumonia

Purpose

Interleukin (IL)-25 and IL-33 induce IL-5 production by various types of cells, such as type 2 helper T (Th2) cells and type 2 innate lymphoid cells. The number of Th2 cells and concentration of IL-5 in the bronchoalveolar lavage fluid (BALF) are increased in patients with eosinophilic pneumonia (EP). To examine the contribution of IL-25 and IL-33 to eosinophilic inflammation of the lung in humans, we evaluated IL-5, IL-25 and IL-33 levels in the BALF of patients with EP.

Methods

IL-5, IL-25, and IL-33 concentrations in the BALF were measured by enzyme-linked immunosorbent assay in patients with acute eosinophilic pneumonia (AEP), chronic eosinophilic pneumonia (CEP), idiopathic pulmonary fibrosis (IPF), and sarcoidosis.

Results

The absolute number of eosinophils, and IL-5 levels, but not IL-33 levels, in the BALF were significantly higher in patients with EP than in patients with IPF and sarcoidosis. IL-25 levels in the BALF were significantly higher in patients with CEP, but not in patients with AEP, than in patients with IPF and sarcoidosis. The absolute number of eosinophils was significantly correlated with the IL-5 concentration in the BALF of patients with EP. IL-5 concentrations were significantly correlated with IL-25 concentrations in the BALF of patients with CEP, but not in patients with AEP. IL-5 levels were not correlated with IL-33 levels in the BALF of patients with EP.

Conclusions

Our findings suggest that IL-25 plays an important role via IL-5 in eosinophilic lung inflammation in patients with CEP.

     

Chronic eosinophilic pneumonia associated with an initiation of rheumatoid arthritis

Although peripheral blood eosinophilia is observed in patients with active inflammatory rheumatoid arthritis (RA), RA is not a recognised cause of pulmonary eosinophilia. We describe a 55-year-old woman affected by chronic eosinophilic pneumonia (CEP) concomitantly with an initiation of RA. Both diseases responded rapidly and completely to high-dose corticosteroid therapy. In this patient, the initiation of RA and CEP was directly related, implying a common pathogenetic link between the two diseases.