Idiopathic chronic eosinophilic pneumonia. A clinical and follow-up study of 62 cases. The Groupe d'Etudes et de Recherche sur les Maladies "Orphelines" Pulmonaires (GERM"O"P).

Idiopathic chronic eosinophilic pneumonia (CEP) is a rare disorder of unknown cause with nonspecific respiratory and systemic symptoms but rather characteristic peripheral alveolar infiltrates on imaging, developing mainly in women and in atopic subjects. The disorder is highly responsive to oral corticosteroid therapy, but relapses are frequent on reducing or stopping treatment. The long-term course of the disease and data regarding outcome, particularly the need for prolonged oral corticosteroid therapy and the development of severe asthma, are somewhat contradictory. A multicentric retrospective study was conducted in an attempt to describe better the initial features and, above all, the later course of CEP in a large homogeneous series of 62 stringently selected patients of whom 46 were followed for more than 1 year. The prevalence of smokers was low (6.5%) and about half of our patients (51.6%) had a previous, and often prolonged, history of asthma. The clinical and roentgenographic features were in keeping with previous studies, but we found that computed tomography could disclose ground glass opacities not detected by X-ray, and that migratory infiltrates before treatment were more frequent (25.5%) than reported previously. The bronchoalveolar lavage cellular count always showed a striking eosinophilic pattern, thus allowing distinction between CEP and cryptogenic organizing pneumonia, both syndromes sharing many common clinical and imaging features. About two-thirds of the patients (68%) showed a ventilatory defect in pulmonary function tests, with about one-half of these presenting with an obstructive pattern, sometimes without previous asthma. Along with the submucosal eosinophilic infiltration noted in 2 patients without ventilatory defect, this is strong evidence to confirm that CEP is not only an alveolointerstitial but also an airway disease. The dramatic response to oral corticosteroid therapy was observed in all treated patients. Although only 1 patient initially treated for less than 6 months did not relapse, longer oral corticosteroid therapy in no way provided protection from further relapses. We thus propose to try to wean oral corticosteroid therapy after 6 months in patients without severe asthma, because recurrences remain responsive to oral steroids. However, prolonged oral corticosteroid therapy was necessary in the majority of patients, with 68.9% of those followed for more than 1 year still on oral corticosteroid therapy at the last follow-up, either because of relapse or because of severe asthma.

Interleukin-8 secretion in patients with allergic rhinitis after an allergen challenge: interleukin-8 is not the main chemotactic factor present in nasal lavages.

BACKGROUND: Interleukin-8 (IL-8) is a chemotactic cytokine for neutrophils and primed eosinophils. In allergic rhinitis, allergen exposure triggers leucocyte recruitment. OBJECTIVE: We evaluated in this study IL-8 secretion and the neutrophil chemotactic activity in nasal lavages collected after a nasal allergen challenge. Moreover, the participation of IL-8 in the neutrophil chemotactic activity was quantified. METHODS: Four healthy subjects and 19 patients with allergic rhinitis were exposed to a nasal allergen challenge. As a control, saline challenge was performed in four patients with allergic rhinitis. Concentration of IL-8 was measured by ELISA in nasal lavages collected before and after challenge. Neutrophil chemotactic assay was developed using a 48-well chemotaxis microassembly. RESULTS: After allergen challenge, the healthy subjects, the four patients receiving saline and one patient exposed to allergen did not respond; seven patients presented a single early reaction and 11 patients a dual response. For healthy subjects and the four patients exposed to saline, the level of IL-8 did not increase after challenge in comparison with that at baseline. After allergen challenge, two peaks of IL-8 release were observed for patients with allergic rhinitis during the early (30 min to 1 h 30 min) and the late periods (3 h 30 min to 9 h 30 min), however the difference was not significant for the early period. During the late period, a significant increase in IL-8 concentrations was detected for the patients developing a dual response, whereas the difference was not significant for those presenting only an early reaction. The neutrophil chemotactic activity of nasal lavages from patients with allergic rhinitis collected during the early and the late reactions (17 +/- 2.1 and 23.3 +/- 2.8 neutrophils per high power field (hpf), respectively) was significantly higher than the activity of lavage fluid collected at baseline (9.2 +/- 1.8 neutrophils per hpf). Nevertheless, the addition of a neutralizing anti-IL-8 antibody inhibited weakly the chemotactic activity of lavage fluid from rhinitic patients collected during the early or the late periods (18 and 11% of inhibition) (P = NS). CONCLUSION: These data show that allergen challenge increased significantly the secretion of IL-8 for the patients with allergic rhinitis. However, neutralization of IL-8 in nasal lavages by a specific antibody revealed that the role of this chemokine in granulocyte infiltrate was limited, suggesting that IL-8 acts in connection with other chemotactic factors in this recruitment.

Long-term follow-up of pulmonary function in chronic eosinophilic pneumonia. Groupe d'Etude en Pathologie Interstitielle de la Société de Pathologie Thoracique du Nord.

The prognosis of chronic eosinophilic pneumonia (CEP) is usually good under corticosteroid therapy (CST). The main complications are relapses when treatment is tapered or discontinued. The aim of this retrospective, multicentre study was to evaluate the long-term consequences of CEP on pulmonary function tests. Nineteen patients (mean +/- SEM age 51 +/- 16 yrs) with CEP were studied. Lung function tests were performed at the time of diagnosis and at follow-up, and included flow-volume curve. The results of the first pulmonary function test were normal in six patients, restrictive in nine, and obstructive in four. Relapses (recurrence of initial signs) occurred in nine patients. The last evaluation (mean +/- SEM follow-up of 49 +/- 44 months, range 12-142 months) showed a complete recovery in 8 of the 19 patients. One patient developed bilateral apical fibrosis. The remaining 10 patients, exhibited obstructive pulmonary function without relapse of CEP at this time. Bronchoalveolar lavage (BAL) eosinophilia at the time of the initial evaluation tended to be higher (p = 0.05) in these 10 patients than in those with normal pulmonary function findings at follow-up. This study demonstrates: firstly, that the development of an obstructive ventilatory defect is a common finding during the course of chronic eosinophilic pneumonia (CEP); secondly, that bronchial obstruction might appear despite the absence of clinical and radiological signs of relapse; and, thirdly, that a markedly increased bronchoalveolar lavage eosinophilia at the initial evaluation is associated with a higher risk of development of bronchial obstruction. These results suggest that pulmonary function tests should be included in the management of chronic eosinophilic pneumonia.

[Pulmonary artery hypertension caused by carcinomatous lymphangitis ]. / Lymphangite carcinomateuse à l'origine d'une hypertension artérielle pulmonaire.

A 58 year old man without significant past medical history developed a cough and effort dyspnoea of a few weeks. A computed tomographic scan showed bilateral interstitial disease with linear thickening of the septa and also a ground glass effect in the lung parenchyma. Echocardiography and right heart catheterisation confirmed the existence of pulmonary arterial hypertension (mean pulmonary artery pressure 45 mmHg) with a normal pulmonary artery wedge pressure (12 mmHg). There was a rapidly progressive worsening with an unfavourable outcome. A necropsy examination showed the development of bilateral pulmonary lymphangitis carcinomatosis secondary to an adenocarcinoma of the head of the pancreas. There was no metastatic emboli of the vessels but there was lymphatic infiltration and the physiopathological hypothesis suggested a compression of the pulmonary arterial vessels secondary to lymphatic obstruction.

Multiple calcified brain metastases revealing a lung carcinoma.

The case of a 50-year-old man with multiple calcified brain metastases revealing an undifferentiated lung carcinoma after a delay of two months, is reported. A slow and progressive clinical evolution was noted. Eight months after the brain lesion had been discovered, intramedullary and epidural spinal metastases appeared. However, the calcified brain metastases remained stable 11 months after the diagnosis. One month later the patient died after several episodes of generalized seizures.

Determinants of survival in pulmonary Langerhans' cell granulomatosis (histiocytosis X). Groupe d'Etude en Pathologie Interstitielle de la Société de Pathologie Thoracique du Nord.

The course of pulmonary Langerhans' cell granulomatosis (pulmonary LCG) is variable, difficult to predict and ranges from spontaneous remission to progressive respiratory insufficiency and death. To identify the determinants of survival, we performed a survival analysis on 45 patients with pulmonary LCG. The patients were aged 28 +/- 10 yrs (mean +/- SD) (range 12-62 yrs), 32 males and 13 females, almost exclusively current smokers (96%), and 78% presented symptoms at the time of diagnosis. Diagnosis was made by lung biopsy in 25 patients (56%) and by bronchoalveolar lavage (BAL) analysis in 20 patients (44%). The patients were followed for a median period of 6 yrs (range 1-29 yrs) after the diagnosis. During the period of observation, 33 (73%) patients survived (median follow-up period = 5.8 yrs; range, 1-29 yrs) and 12 (27%) died or underwent lung transplantation (median follow-up period = 8.4 yrs; range 1.4 - 16.1 yrs). The median survival was approximately 13 years. A univariate analysis demonstrated that diminished survival was significantly associated with: an older age at diagnosis (p = 0.0001); a lower forced expiratory volume in one second/forced vital capacity (FEV1/FVC) ratio at diagnosis (p = 0.005); a higher residual volume/total lung volume (RV/TLC) ratio at diagnosis (p = 0.02); and steroid therapy during follow-up (p = 0.03). Additional predictive information on mortality was: age > 26 yrs (sensitivity 83%, specificity 64%); FEV1/FVC ratio < 0.66 (sensitivity 75%, specificity 86%); and a RV/TLC ratio > 0.33 (sensitivity 75%, specificity 63%). In multivariate Cox analysis, the combination of factors which gave the best prognostic value was FEV1/FVC ratio and age (p < 0.01). The present findings suggest that adverse prognosis factors at diagnosis in pulmonary Langerhans' cell granulomatosis include older age, lower FEV1/FVC ratio and higher RV/TLC ratio, with additional predictive information on mortality if aged > 26 yrs, FEV1/FVC ratio < 0.66, and RV/TLC ratio > 0.33.

[Chronic eosinophilic pneumonia or Carrington's disease]. / La pneumonie chronique à éosinophiles ou maladie de Carrington.

Chronic eosinophilic pneumonia (CEP) was described by Carrington in 1969. It is twice as common in women as it is in men and is probably most common at middle age. Symptoms usually associated fever, weight loss, fatigue and dyspnoea. Extra-respiratory manifestations are rare but may involve many organs. Classical radiological findings are diffuse alveolar infiltrates, with a peripheral predominance which explains the classic description of a "negative of pulmonary edema". Peripheral blood eosinophilia is present in 90%. The inflammatory syndrome with an eosinophilic alveolitis is constant. Pulmonary function tests show a restrictive pattern with depressed DLCO and hypoxemia. In atypical cases, proof of diagnosis is supported by lung biopsies that show intra alveolar and interstitial accumulation of eosinophils in peripheral air spaces. Areas of bronchiolitis obliterans are also frequently seen. In some atypical forms of chronic eosinophilic pneumonia, other disorders have to be discussed, like bronchiolitis obliterans with an organizing pneumonia or cryptogenetic organizing pneumonia and even tuberculosis. After corticosteroid therapy, the resolution occurs very rapidly but relapses are frequent. Steroid-dependence is seen in 20 to 30% of patients.

[Eosinophilic lung disease caused by filariasis. Apropos of a case]. / Le poumon éosinophile filarien. A propos d'un cas.

A 23-year-old male Pondichery native consulted for vesperal dispnoea. The main abnormalities detected were blood and alveolar eosinophilia and bilateral micronodular lesions at radiography. The parasitic origin of these symptoms was suspected, then confirmed by serological tests for filaria. The outcome was favourable after antiparasitic therapy. The histopathological, clinical and evolutionary features of pulmonary eosinophilic filiariasis are described, with emphasis on the treatment and on follow-up laboratory tests.

Percutaneous transhepatic embolization of gastroesophageal varices: results in 400 patients.

During a 7-year period, bleeding esophageal varices were treated by means of percutaneous transhepatic embolization in 400 cirrhotic patients, including 258 patients with Child's class C cirrhosis (65%) and 142 patients with Child's class B cirrhosis (35%). Embolization was performed either with bucrylate or with absolute ethanol and stainless-steel coils. Variceal hemorrhage was controlled in 245 (83%) of the 297 patients in whom percutaneous transhepatic embolization was performed as an emergency treatment. The 10-day survival rate in the series was 76%, with 97 deaths occurring shortly after the procedure as a result of recurrent bleeding or liver failure. The actuarial rate of recurrent bleeding was 55% at 6 months (38% Child's class B, 70% Child's class C) and 81% at 2 years (71% Child's class B, 90% Child's class C). One-half the cases of recurrent bleeding were easily controlled by medical treatment; 56% of these patients were still alive at 6 months (79% Child's class B, 42% Child's class C), 48% were alive at 1 year, and 26% were alive at 5 years. Results indicated that the survival rate was significantly higher (p less than .01) in Child's class B patients than in Child's class C patients during the 5-year follow-up period. The overall technical failure and complication rates were 9% and 7%, respectively, but these rates declined progressively as we gained more experience with the procedure. In this large series, transhepatic embolization was a safe, easy-to-perform, and effective treatment for the control of variceal bleeding and was somewhat more efficacious than previously reported.