10-Year Follow-Up of Frequently Relapsed Chronic Eosinophilic Pneumonia Starting at 15 Years Old; Attempts to Treat with Inhaled Corticosteroid (A Case Report)

Background

A 15-year old female patient presented with a case of with eosinophilic pneumonia. Development of chronic eosinophilic pneumonia (Figure 1) in childhood is a rare phenomenon. We tried to analyze the immunological mechanism involved in the development of eosinophilic pneumonia. Eosinophilic pneumonia is recognized both as an eosinophil-associated disease as well as bronchial asthma. It is obvious that in eosinophilic pneumonia the site of eosinophilic infiltration is mainly the alveolus and the peripheral airway; the disability of pulmonary function is restrictive, as opposed to that of bronchial asthma, which has a relatively central side bronchus region and obstructive function. However, the antigen of eosinophilic pneumonia is still unknown, unlike bronchial asthma. Eosinophil- and T-lymphocyte-activated parameters such as ECP, CD4HLADR/CD4 (%), CD4CD25/CD4 (%), and IL-5 are the immunological factors usually discussednot only in the context of bronchial asthma [1] but also in eosinophilic pneumonia [2,3].

Case Report

Chronic eosinophilic pneumonia during childhood is very rare [4]. In December 1997, a 15-year-old girl with chronic refractory pneumonia was referred to Habikino Hospital for evaluation of respiratory distress, dry cough, high temperature, chest pain, pulmonary infiltration, and peripheral eosinophilia. In our hospital, she was diagnosed as having chronic eosinophilic pneumonia for the first time by eosinophilia both in bronchial alveolar lavage fluid (BALF) and in peripheral blood, and eosinophils mainly infiltrated the alveolus region, as shown by fiberscope biopsy. A report of laboratory investigations done on the patient is summarized in Table 1.

Clinical symptoms of eosinophilic pneumonia including increased body temperature, chest pain and dry cough were observed when the patient was admitted to the hospital. Laboratory investigations showed an increase in blood sedimentation rate (BSR). Serological testing (Table 1) results for sedimentation antibody of hypersensitivity pneumonia were all negative. Forced vital capacity (FVC) was found to be decreased and showed a restrictive pattern (%FVC; 39%) in spirometry.

Radiographic examinations (Figure 1) of recurrence showed a peripheral infiltration wandering shadow, which is characteristic of chronic eosinophilic pneumonia on plain chest radiograph and a computed tomography scan of the chest. The culture tests of BALF and sputum showed that they were negative. Trans-bronchial biopsy demonstrated intra-alveolar infiltration of eosinophils and interstitial infiltration of both eosinophils and lymphocytes. These features were consistent with the diagnosis of chronic eosinophilic pneumonia.

Figures 2 and 3 represent the parameters examined in activated T-cells and eosinophils.

Mononuclear cells from venous blood and BALF were double-stained using IgG monoclonal antibodies and analyzed by flow cytometry (FACScan, Becton-Dickinson, CA, USA). Concentrations of soluble interleukin 2 receptor in serum and BALF were measured by enzyme-linked immunoabsorbent assay (ELISA) using a commercially available kit (Cytoscreen, CA, USA). Concentrations of IL-5 in the serum and BALF were also measured by an ELISA current phase (Human IL-5 immunoassay, R and D Systems, MN, USA). Concentrations of ECP in serum and BALF were measured by Pharmacia CAP system ECP fluorescent immunoassay (FEIA, Pharmacia Diagnostics AB, Sweden). Changes in %FVC and forced expiratory volume/1 second (FEV1.0%) in the recurrence of the disease are shown in Table 2 and Figure 4.

Changed data of %FVC and FEV1.0% on recurrence are shown in Table 2 and Figure 4.

Percent FVC and FEV1.0% [4] was measured using a portable spirometer (Microspiro HI-601, NIHON-KPHDEN COPOLATION, Tokyo Japan). Data of %FVC changed slightly over time. The percent FVC measurement obtained using non-invasive methods like spirometry was taken as an indicator of her condition. On admission with eosinophilic pneumonia, her %FVC was extremely low (39%), and we thought that non-invasive spirometry testing could be used as a parameter for recurrence. There was an initial remission followed by a decrease in %FVC to values below 100%, indicating the disease recurrence. FEV1 also responded, so the patient might have had a slight tendency to bronchial asthma.

Table 3 shows 12 recurrences of eosinophilic pneumonia.

To control eosinophilic pneumonia, 5 different dosages of inhaled steroids were tried, chosen to avoid adverse effects due to long-term systemic administration of steroids. The controller (ICS) became a single use of steroid inhalation therapy, but several months later, the recurrence of eosinophilic pneumonia symptoms often appear. However systemic treatment using predonine can easily control the disease, and the laboratory data and clinical symptoms showed improvement.

Discussion

PULMONARY FUNCTION IN EOSINOPHILIC PNEUMONIA:

In this study, %FVC is recognized as a parameter for eosinophilic pneumonia. In fact, change in %FVC was observed along with clinical symptoms like a rise in temperature, chest pain, and respiratory distress, change in percentage of eosinophil in peripheral blood and altered BSR. Sveinsson et al. [7] previously reported that FEV1 and %FVC are decreased in eosinophilic pneumonia. In this study, it was observed that %FVC had a relationship with other clinical and laboratory parameters but not with FEV1%. As compared to other parameters, %FVC offers various advantages in prediction of chronic eosinophilia. The procedure to determine %FVC is non-invasive, quick, less expensive, and less laborious. This is the first study in which %FVC was used as a parameter for predicting eosinophilic pneumonia and in which the disease recurrences were managed using ICS treatments.

INHALED STEROID IN EOSINOPHILIC PNEUMONIA:

Our results show that activated T-cells and eosinophilic inflammation existed mainly in peripheral airways rather than in peripheral blood. We considered that inhaled steroid is useful [8] for treating peripheral airway inflammation in chronic eosinophilic pneumonia. But other group considered inhaled steroids not effective [8]. Chan et al. [9] reported a patient who underwent treatment with systemic corticosteroids followed by inhaled steroids and who remained in remission for 2 years. We tried 5 kinds of inhaled steroids during the active and the remission phases of eosinophilic pneumonia to avoid the adverse effects associated with systemic administration of steroids, but we could not achieve sufficient efficacy using inhaled steroids. A roentgen photograph (Figure 1) showed a borderless, cloudy, and wandering shadow-like appearance of the peripheral lung area. Pulmonary function of eosinophilic pneumonia showed a restrictive pattern. Single use of ICSs could not control the persistence of remission. Three reasons may have contributed to the lack of response. Firstly, the particle size of the inhaled steroid was large and hence could not reach the inflammation region and peripheral lung area, whereas Qval (Beclomethasone, pMDI) releases super-small aerosol (diameter 1.1 µm). The second reason could be the weak anti-inflammatory effect of inhaled steroids themselves. As seen in the roentgen image, the bronchus might be closed by the accumulation of inflammatory cells. Inhaled steroids with smaller particle size [10] and strong anti-inflammatory effects are needed for the treatment of eosinophilic pneumonia.

Conclusions

Our T-cell activation parameter data (HLADRCD4/CD4 percentages and CD25CD4/CD4 percentages) and eosinophil activation parameter data (IL-5) showed higher levels in BALF than in peripheral blood. The values were higher during the active phase than during the remission phase in the peripheral blood.

The principal inflammation region of eosinophilic pneumonia is considered to be in the peripheral bronchus and in the alveoli. Accordingly, inhaled steroids were considered effective to control eosinophilic pneumonia, but 5 kinds of ICS were not effective to maintain the remission of the disease. Determination of %FVC was useful to predict the recurrence of the disease.