Acute tropical pulmonary eosinophilia: characterization of the lower respiratory tract inflammation and its response to therapy

Although acute tropical pulmonary eosinophilia (TPE) is well recognized as a manifestation of filarial infection, the processes that mediate the abnormalities of the lung in TPE are unknown. To evaluate the hypothesis that the derangements of the lower respiratory tract in this disorder are mediated by inflammatory cells in the local milieu we utilized bronchoalveolar lavage to evaluate affected individuals before and after therapy. Inflaminatory cells recovered from the lower respiratory tract of individuals with acute, untreated TPE (a = 8) revealed a striking eosinophilic alveolitis, with marked elevations in both the proportion of eosinophils (TPE 54±5%; normal 2±5%; P < 0.001) and the concentration of eosinophils in the recovered epithelial lining fluid (ELF) (TPE 63±20 X 103/Al; normal 03±0.1 X 103/jl; P < 0.01). Importantly, when individuals (a = 5) with acute TPE were treated with diethylcarbamazine (DEC), there was a marked decrease of the lung eosinophils and concomitant increase in lung function. These observations are consistent with the concept that at least some of the abnormalities found in the lung in acute TPE are mediated by an eosinophil-dominated inflammatory process in the lower respiratory tract

Tropical Pulmonary Eosinophilia: Analysis of Antifilarial Antibody Localized to the Lung

Acute tropical pulmonary eosinophilia (TPE) is characterized by wheezing, pulmonary infiltrates, marked peripheral blood eosinophilia, and very high serum levels of filariaspecific antibodies. To evaluate the amount and character of the filaria-specific antibodies in the lungs in this disorder, bronchoalveolar lavage was carried out in individuals with acute TPE, in normal subjects, and in patients with elephantiasis or asthma. Striking elevations of total IgE were found in the lower respiratory tract epithelial lining fluid (ELF) of patients with TPE along with high levels of filarial-specific IgG, IgM, and IgE. When patients with acute TPE were treated with diethylcarbamazine and evaluated again 6-14 d iater, there was marked reduction in ELF parasite-specific IgG and IgE, which paralleled a rapid clinical response. Immunoblot comparison of the antigen recognition patterns of ELF and serum antibodies demonstrated a general similarity in parasite antigens recognized, but the lung IgE and IgG antibodies appeared to recognize only a certain subset of the parasite antigens recognized by serum antibodies. Thus. a profound antibody response to filarial infection is found in the lungs of patients with TPE, suggesting that these filaria-specific antibodies play an important role in the pathogenesis of this disorder

Localized Eosinophil Degranulation Mediates Disease in Tropical Pulmonary Eosinophilia

To explore the mechanisms underlying the eosinophil-mediated inflammation of tropical pulmonary eosinophilia (TPE), bronchoalveolar lavage (BAL) fluid, serum, and supernatants from pulmonary and blood leukocytes (WBC) from patients with acute TPE (n = 6) were compared with those obtained from healthy uninfected individuals (n = 4) and from patients with asthma (n = 4) or elephantiasis (n = 5). Although there were no significant differences in the levels of interleukin-4 (IL-4), IL-5, IL-13, eotaxin, granulocyte-macrophage colony-stimulating factor, RANTES, or eosinophil cationic protein, there was a marked increase in eosinophil-derived neurotoxin (EDN) both systemically and in the lungs of individuals with TPE compared to each of the control groups (P < 0.02). Moreover, there was a compartmentalization of this response, with EDN levels being higher in the BAL fluid than in the serum (P < 0.02). Supernatants from WBC from either whole blood or BAL cells were examined for chemokines, cytokines, eosinophil degranulation products, and arachidonic acid metabolites. Of the many mediators examined—particularly those associated with eosinophil trafficking—only EDN (in BAL fluid and WBC) and MIP-1α (in WBC) levels were higher for TPE patients than for the non-TPE control groups (P < 0.02). These data suggest it is the eosinophilic granular protein EDN, an RNase capable of damaging the lung epithelium, that plays the most important role in the pathogenesis of TPE