Persistent Lower Respiratory Tract Inflammation Associated with Interstitial Lung Disease in Patients with Tropical Pulmonary Eosinophilia following Conventional Treatment with Diethylcarbamazine

Abstract

Tropical pulmonary eosinophilia (TPE) presents as an acute syndrome with dyspnea, fluffy infiltrates, and rounded opacities on the chest radiograph, reduced lung function, marked eosinophilia in the blood and lower respiratory tract, and high titers of specific IgE and IgG antifilarial antibodies. The standard therapy for TPE is a 3-wk course of diethylcarbamazine (DEC) following which there is almost always a marked improvement in all parameters. However, clinical observations suggest that the disease can persist despite DEC therapy and lead to chronic dyspnea with restrictive lung impairment. To evaluate the concept that DEC therapy is not completely "curative" for TPE, but rather leaves most individuals with a mild, chronic form of TPE defined by persistent inflammation of the lower respiratory tract, we evaluated 23 individuals an average of 12 +/- 2 months following a standard 3-wk course of diethylcarbamazine for acute TPE. In the majority there were mild, persistent symptoms referrable to the lung, chest X-ray abnormalities, blood eosinophilia, and elevated serum IgE and filarial specific IgG. On the average, lung function was consistent with the presence of chronic, mild interstitial lung disease. When the inflammatory cells from the lower respiratory tract were examined, there was a persistent eosinophilic alveolitis (TPE/post-DEC 1769 +/- 376 eosinophils/microliters epithelial lining fluid; normal subjects 256 +/- 38, p less than 0.02). Evaluation of the lower respiratory tract inflammatory cells recovered from the TPE/post-DEC-treated individuals demonstrated spontaneous release of exaggerated amounts of O2-. and H2O2 compared to normal subjects (p less than 0.05, both comparisons).(ABSTRACT TRUNCATED AT 250 WORDS)

Localized Eosinophil Degranulation Mediates Disease in Tropical Pulmonary Eosinophilia

“…The impressively high levels of eosinophils found in the peripheral blood of TPE patients (Ͼ3,000/l) are surpassed in the lungs: levels have been determined to be 12-fold more concentrated in the epithelial lining fluid of the lungs than in the systemic circulation (26). Eosinophils are the predominant effector cell in the BAL fluid of patients with TPE, and unlike the rare eosinophils in the BAL fluid of normal lungs, the pulmonary eosinophils in TPE are degranulated and activated (26) and release abnormally high levels of toxic oxygen radicals even after antifilarial treatment (29). Filaria-specific IgE and IgG antibodies are found in both the serum and BAL fluid of TPE patients; however, the lung antibodies recognize a distinct subset of the filarial antigens recognized by the antibodies in the periphery (23), the most dominant being a parasite-derived ␥-glutamyl transpeptidase (16).…”

“…A mild form of interstitial lung disease persists in the majority of patients treated for TPE (29). For the untreated TPE patient, the outcome is more extreme: a progressive interstitial fibrosis.…”

Tropical Pulmonary Eosinophilia: Effect of Addition of Corticosteroids after Failure of Diethylcarbamazine Therapy

“…An incomplete response to DEC has been reported earlier in TPE [1,3,5,6] and may occur due to resistance to therapy, inadequate duration of therapy or a transition into a chronic inflammatory state. While resistance to DEC has not been documented, Vijayan et al [6] provided evidence of a chronic inflammatory state on bronchoalveolar lavage in patients with treatment failure with DEC. A mild eosinophilic inflammation of the lower respiratory tract was found with cells spontaneously releasing increased amounts of superoxide anion and hydrogen peroxide.…”

“…Wheezes and crackles may be found on examination although 20 per cent of patients may have no findings on examination [2]. Histopathologically, acute eosinophilic and histiocytic infiltration, eosinophilic bronchopneumonia and eosinophilic abscesses characterize the initial phases of the disease with generally well-marked fibrous tissue formation between six months to two years in more chronic cases [3]. Fibrosis is usually interstitial but also be peribronchial and perivascular in distribution.…”

Elevated Immunoglobulin E against RecombinantBrugia malayiγ-Glutamyl Transpeptidase in Patients with Bancroftian Filariasis: Association with Tropical Pulmonary Eosinophilia or Putative Immunity

“…Autoimmunity to the human enzyme might explain the presence of a persistent lower respiratory tract inflammation associated with interstitial lung disease even after extended antifilarial therapy of patients with TPE (47).…”