Pulmonary Infiltration with Eosinophilia

8eL9CTeD RePORTS Pulmonary Infiltration with Eosinophilia • Recurrence in an Asthmatic Patient Treated with Beclomethasone Dipropionate David W. Hudgel, M.D., 00 and Sheldon L. Spector, M.D., F.C.C.P.t

We present the findings in a young woman diagnosed as having pulmonary infiltration with eosinophilia and asthma who was treated with beclomethasone dipropionate. Although the aerosol corticosteroid controlled bronchospasm, it did not prevent recurrent pulmonary infiltration with eosinophilia when the patient was not receiving oral therapy with corticosteroids. It is postulated that when administered in the usual dosage, an adequate amount of beclomethasone dipropionate does not reach the alveoli or interstitium to prevent or resolve the process of pulmonary infiltration with eosinophilla. This case suggests that patients with pulmonary infiltration and eosinopbilla who are treated with inhaled corticosteroids for asthma must be closely observed physiologically or roentgenographically for pulmonary infiltration. These patients may need to be protected from recurrent pulmonary infiltration by the concurrent oral use of corticosteroids.

A

ccording to Crofton et al, 1 pulmonary infiltration with eosinophilia of the blood occurs ( I ) transiently, (2) chronically, (3) in tropical pulmonary eosinophilia, ( 4) as a manifestation of periarteritis nodosa, and ( 5) with asthma. Pathologically, acute pulmonary infiltration with eosinophilia and asthma is characterized by a mononuclear-eosinophilic infiltrate in alveolar and interstitial locations. 2 In chronic disease a granulomatous infiltrate in the bronchiolar walls may cause bronchiolitis obliterans and may progress to fibrosis or bronchiectasis. a,• The acute process and occasionally the chronic process can be reversed with systemic administration of corticosteroids. 2 ·• Herein we present the findings in a patient with pulmonary infiltration with eosinophilia and asthma whose bronchospasm was readily controlled with administration of beclomethasone dipropionate, but whose pulmonary infiltration with eosinophilia recurred twice, once asymptomatically, while the patient was receiving aerosol therapy with this inhaled corticosteroid. °From the Department of Medicine, Section of Allergy and Clinical Immunology, National Jewish HoSPital and Research Center, and the Department of Medicine, School of Medicine, University of Colorado Medical Center, Denver. Supported in part by Allergic Disease Center grant AI10398. 00 Assistant Professor of Medicine. tHead, Section of Allergy and Clinical Immunology, and Assistant Professor of Medicine. Reprint requests: Dr. Hudgel, National Jewish Hospital, 3800 East Colfax, Denver 80206

CHEST, 72: 3, SEPTEMBER, 1977

CASE REroRT

A 25-year-old white woman developed perennial asthma after "pneumonia" at the age of ten years. By the age of 15 years, therapy with corticosteroids was required for control of her asthma. Between the ages of 16 and 21 years, the patient had numerous episodes of "allergic pneumonia" accompanied by eosinophilia, which were only partially resolved with systemic therapy with corticosteroids. Normal findings on biopsy of the gastrocnemius muscle made periarteritis nodosa unlikely. There was no evidence of parasitic diseases. An evaluation at National Jewish Hospital and Research Center, Denver, when the patient was asymptomatic and receiving therapy with prednisone ( 20 mg every other day) showed roentgenographic changes in the chest compatible with mild honeycombing in the upper pulmonary zones bilaterally (Fig 1). Other findings were as follows: no eosinophilia; changes in pulmonary function consistent with mild, partially reversible obstructive airway disease; normal diffusing capacity for carbon monoxide; normal quantitative levels of immunoglobulins; absence of serum precipitins to Aspergalus fumigatus and Micropolyaporia faeni. Over the next two years the patient had intermittent exacerbations of asthma without pulmonary infiltration and eosinophilia; these bouts were only partially controlled by therapy with methylprednisolone, troleandomycin,ll and aminophylline. During this period, no eosinophilia greater than 5 percent was recorded. Because of poor control of her asthma and side effects from administration of corticosteroids, the patient was placed on therapy with beclomethasone dipropionate ( 800 µ.g/day) in September 1974. During the subsequent year the patient was able to eliminate oral therapy with corticosteroids with continued control of the asthma; however, on two occasions, she developed multilobular pulmonary infiltrations ( Fig 2) with eosinophilia ( > 1,200 eosinophils per cubic millimeter).

FIGURE 1. Baseline chest x-ray film from asymptomatic patient, demonstrating increase in parenchymal markings in upper lobes and infiltrate in left upper lobe that was unchanged on repeated examinations.

PULMONARY INFILTRATION WITH EOSINOPHIUA 359

F'IcURE 2. Chest x-ray film of patient during acute episode of pulmonary infiltration with eosinophilia occurring when patient was receiving inhaled beclomethasone dipropionate and no oral therapy with corticosteroids. Film taken after five days of oral therapy with corticosteroids showed nearly total clearing of acute changes.

Bronchospasm did not worsen with either episode, and only one was accompanied by pyrexia. No bacterial or fungal pathogens or organisms causing tuberculosis were isolated from the sputum. The acute infiltrates were promptly resolved by short oral courses of corticosteroids, but the chronic changes persisted. DISCUSSION

Although this patient had never had a lung biopsy to document pulmonary infiltration with eosinophilia, the clinical picture and the response to oral therapy with corticosteroids was quite typical of the pulmonary infiltration with eosinophilia and asthma reported by Crofton et al. 1 The bronchospasm was well controlled by aerosol therapy with beclomethasone dipropionate, but this drug failed to prevent two episodes of pulmonary infiltration with eosinophilia when the patient was not receiving oral therapy with corticosteroids. In England, Paterson et al 6 reported three cases of pulmonary eosinophilia in asthmatic patients whose oral dosage of corticosteroids had been totally or nearly totally replaced by therapy with beclomethasone dipropionate. One of these patients had previous episodes of pulmonary infiltration with eosinophilia. Llke our patient, one of the episodes of pulmonary infiltration with eosinophilia occurred in a patient who was asymptomatic. Experiments performed in dogs have shown that approximately 10 percent of the inhaled dosage of beclo-

360 HUDGEL, SPECTOR

methasone dipropionate reaches beyond the major bronchi. In these animals, peripheral pulmonary tissue contains the least amount of the drug. Beclomethasone dipropionate is rapidly absorbed through the respiratory mucosa; pulmonary venous levels of the drug are ten times greater than pulmonary arterial levels soon after administration. The drug is rapidly cleared from the lung within 30 minutes (unpublished data, Schering Corp., Bloomfield, NJ). Beclomethasone dipropionate also has been shown to have potent antiin.flammatory properties. Its activity in the skin is about 500 times greater than that of dexamethasone, but beclomethasone dipropionate is less active as a systemic glucocorticosteroid after oral administration to man. 7 Many studies have shown this drug to be quite effective in the management of patients with chronic corticosteroid-dependent asthma. It is doubtful that the aerosol corticosteroid predisposed this patient to more frequent episodes of pulmonary infiltration with eosinophilia, since the episodes remained intermittent. When pulmonary infiltration with eosinophilia coexists with asthma, both processes often worsen simultaneously, but infiltrates may appear without aggravating the bronchospasm. 1 •3 Since fibrosis or bronchiectasis may result 1 in some patients with recurrent or persistent pulmonary infiltration with eosinophilia, close surveillance or treatment may be needed to prevent permanent pulmonary damage. Monitoring of the eosinophilic count is inadequate, since some patients with an active infiltrate do not always have eosinophilia. 3 The course of this patient's condition suggests that chest x-ray films or measurement of diffusing capacity or both should regularly be obtained in patients with pulmonary infiltration with eosinophilia and asthma who are not receiving oral therapy with corticosteroids. 2 If recurrent episodes indicate permanent bronchial or interstitial destruction, low oral doses of corticosteroids should be continued to prevent recurrence of pulmonary infiltration with eosinophilia in those patients treated with inhaled corticosteroids for concurrent asthma.

fu:FERENCFS 1 Crofton JW, Livingstone JL, Oswald NC, et al: Pulmonary eosinophilia. Thorax 7: 1-35, 1952 2 Rogers RM, Christiansen JR, Coalson JJ, et al: Eosinophilic pneumonia: Physiologic response to steroid therapy and observations on light and electron microscopic findings. Chest 68:665-671, 1975 3 Liebow AA, Carrington CB: The eosinophilic pneumonias. Medicine 48:251-285, 1969 4 Carrington CB, Addington WW, Goff AM, et al: Chronic eosinophilic pneumonia. N Engl J Med 280:787-798, 1969 5 Spector SL, Katz FH, Farr RS: Troleandomycin: Effectiveness in steroid-dependent asthma and bronchitis. J Allergy Clin lmmunol 54:367-379, 1974 6 Paterson IC, Cooke NJ, Murray K, et al: Pulmonary eosinophilia after substitution of aerosol for oral corticosteroid therapy. Br J Dis Chest 69:217-222, 1975 7 Martin LE, Tanner RJN, Clark TJH, et al: Absorption and metabolism of orally administered beclomethasone dipropionate. Clin Phannacol Ther 15:267-275, 1974

CHEST, 72: 3, SEPTEMBER, 1977