Oxidants play a key role in tropical pulmonary eosinophilia in causing both an acute disease and chronic interstitial pulmonary fibrosis. The eosinophil is central to this process, and, in contrast to acute eosinophilic pneumonia, the granules are empty and major basic protein has been extruded [29
]. This contributes to high oxidant stress in the terminal respiratory bronchioles and alveoli. TPE is an interstitial lung disease that results from a heightened immunologic response to the human filarial parasites, Wuchereria bancrofti
and Brugia malayi.
Individuals with acute TPE characteristically present with cough, dyspnea, nocturnal wheezing, and, occasionally, fever, anorexia, and weight loss. It occurs in both males and females in the younger age groups in India, Southeast Asia, and other tropical regions. Filariasis is spread by mosquitoes, but only a small portion of the population responds with the TPE syndrome. There are a marked peripheral blood eosinophilia (in contrast to acute eosinophilic pneumonia where our firefighter had a normal blood eosinophil count) and high serum concentrations of IgE and filarial specific antibodies. Although most individuals with acute TPE have a rapid clinical response to diethylcarbamazine or ivermectin, with reduced cough and dyspnea, some individuals progress to a chronic pulmonary fibrosis. It is thought that the pulmonary form of TPE results from degenerating microfilariae in the pulmonary structures, but few have been found in lung specimens, suggesting that most of the pathology seen and symptoms arise from the lung inflammation and oxidants.
In a clinical study of TPE in India conducted by a joint Indian Council of Medical Research and a NIH research team approved by Human Subjects Review utilizing bronchoalveolar lavage, eight individuals were bronchoscoped and a mean of 54% eosinophils recovered in BAL [29
]. Transmission EM showed marked loss of granule content and disappearance of dense central cores. Two of three individuals bronchoscoped one year later still had marked BAL eosinophilia, although reduced [29
One year later, 23 subjects who had been treated were reevaluated [30
]. They had a mean age of 26 years, and 15 still complained of cough and nocturnal wheezing. Only 3/20 had dyspnea, chest pain, or rales. They still had tenfold increased IgE and IgG antifilarial antibodies, but much less than when first studied [30
]. Their BAL had a mean of 6% eosinophils. There was a significant spontaneous increase in superoxide anion and hydrogen peroxide release by the BAL cells over 30 minutes following recovery in twenty chronic TPE subjects (6 smokers, 14 nonsmokers) compared to six normal nonsmokers a mean of 8 months following diethylcarbamazine therapy [30
]. In order to reduce the inflammation in the lower respiratory track, a short course of oral prednisone over one week was attempted. The dose was 50
mg followed by a daily 10
mg decline until they were off medication. Bronchoalveolar lavage was performed prior to the beginning of the trial and immediately thereafter. Twelve individuals completed the trial, and the BAL percent eosinophils declined or remained the same in all study subjects after a mean of seven days of oral prednisone (). Measurements of superoxide anion and hydrogen peroxide were done on fresh BAL cells recovered by bronchoscopy and superoxide anion declined in 10/12 study subjects (). In parallel, hydrogen peroxide declined in 9/11 study subjects. Several clinical series from India, Southeast Asia, Africa, the West Indies, and South America have described untreated TPE as a cause of chronic interstitial lung disease [31
]. In this regard, it is recognized that if acute TPE is allowed to persist for more than 6 months without treatment, restrictive lung impairment is common. Open lung biopsies of individuals with TPE untreated for >6 months reveal infiltration of the alveolar structures and bronchiolar walls, with macrophages and eosinophils together with granulomata laden with eosinophils and multinucleated giant cells and interstitial fibrosis. The role of oxidants in causing interstitial lung disease in chronic TPE is significant, and this inflammatory milieu can be modulated by anti-inflammatory treatment with prednisone or ivermectin [32
Suppression of lung eosinophils with prednisone in TPE patients following after diethylcarbamazine therapy. 7±1 days after prednisone therapy there was a reduction in the percent of eosinophils observed in 12 subjects.
Reduction in the spontaneous release of oxidants by lavage cells after prednisone therapy in TPE patients following diethylcarbamazine therapy. (a) Superoxide anion. (b) Hydrogen peroxide.