Hypereosinophilic obliterative bronchiolitis: a distinct, unrecognised syndrome

Abstract

Biopsy-proven cases of eosinophilic bronchiolitis have only been reported in isolation, and all come from Japan.We present six patients with hypereosinophilic obliterative bronchiolitis (HOB), defined by the following criteria: 1) blood eosinophil cell count .1 G?L -1 and/or bronchoalveolar lavage eosinophil count .25%; 2) persistent airflow obstruction despite high-dose inhaled bronchodilators and corticosteroids; and 3) eosinophilic bronchiolitis at lung biopsy (n51) and/or direct signs of bronchiolitis (centrilobular nodules and branching opacities) on computed tomography (n56). Chronic dyspnoea and cough which was often severe, without the characteristic features of asthma, were the main clinical manifestations. Atopy and asthma were present in the history of three and two patients, respectively. One patient met biological criteria of the lymphoid variant of idiopathic hypereosinophilic syndrome. Mean blood eosinophil cell count was 2.7 G?L -1 and mean eosinophil differential percentage at bronchoalveolar lavage was 63%. Mean initial forced expiratory volume in 1 s/forced vital capacity ratio was 50%, normalising with oral corticosteroid therapy in all patients. HOB manifestations recurred when oral prednisone was decreased to 10-20 mg?day -1, but higher doses controlled the disease. HOB is a characteristic entity deserving to be individualised among the eosinophilic respiratory disorders. Thorough analysis is needed to determine whether unrecognised and/or smouldering HOB may further be a cause of irreversible airflow obstruction in chronic eosinophilic respiratory diseases.

Eosinophilic bronchiolitis: is it a new syndrome?

“…The next step to exploit these new scenarios could be the collection of a significant number of patients with these clinical-radiological characteristics provided with pathological (and biological) data. In fact, CORDIER et al [1] reported histopathological information in only two patients. Interestingly, as the lesions are centrilobular, a bronchoscopic approach (transbronchial lung biopsy with common flexible forceps, jumbo forceps or even cryoprobes) could obviate the need of a surgical approach.…”

“…In this issue of the European Respiratory Journal, a new distinct syndrome, hypereosinophilic obliterative bronchiolitis, is described by CORDIER et al [1]. This syndrome is defined by: 1) a blood eosinophil cell count .1 G?L -1 and/or a bronchoalveolar lavage (BAL) eosinophil differential cell count .25%; 2) persistent airflow obstruction on lung function tests not modifiable after 4-6 weeks of inhaled corticosteroid therapy (2000 mg?day -1 of beclometasone or equivalent); and 3) a lung biopsy showing inflammatory bronchiolitis with prominent bronchiolar wall infiltration by eosinophils and/or characteristic direct high-resolution computed tomography (HRCT) features of bronchiolitis (poorly defined centrilobular nodules, branching opacities and tree-inbud pattern).…”

“…Interestingly, non-steroidal cytotoxic drugs improved the course of the disease. The description and data collected by CORDIER et al [1], therefore, add some other element of knowledge to this not yet welldefined ensemble: some patients had an autoimmune disorder (Churg-Strauss syndrome), others hypersensitivity behaviour (allergic bronchopulmonary mycosis), some had a disregulation of T-lymphocytes (probably including lymphocytes expressing and releasing interleukin-5), and some had elements indicating a drug reaction.…”

“…In the study by CORDIER et al [1], one patient had a limited form of Churg-Strauss syndrome. One patient showed an aberrant population of T-lymphocytes in the peripheral blood (CD3+ CD4+CD7-lymphocytes) with oligoclonal T-cell receptor gamma VG9J1J2 re-arrangement suggesting a relationship with the lymphocytic variant of hypereosinophilic syndrome [4].…”

“…Finally, from a pathological point of view, mucous eosinophilic plugs may fill both small bronchi and bronchioles, and marked goblet cell hyperplasia/metaplasia of bronchial/ bronchiolar epithelium, thickening of the basement membrane, bronchiolar smooth muscle hypertrophy, fibrosis of the bronchiolar wall with peribronchiolar lymphoid aggregates, and mixed inflammatory infiltrate with prominent eosinophils throughout airway walls are all detectable [3]. However, it is clear that the concept of ''severe and persistent asthma'' is still poorly understood and the article by CORDIER et al [1] may help to better define and appreciate the characteristics (clinical, radiographic, pathologic and biologic) of those patients that have symptoms, signs, imaging findings and even pathologic aspects as boundaries between severe asthma and some form of a not yet well-defined bronchiolitis.…”