Asian Pacific Journal of Allergy and Immunology (1990) 8: 123·126

Allergic Bronchopulmonary Aspergillosis and Candida albicans Colonization of the Respiratory Tract in Corticosteroid· Dependent Asthma

S. Ramachandran, Ashok Shah, Kaushal Pant, Rajesh Bhagat, and O.P. Jaggl

"Corticosteroids are funda­ SUMMARY Fungal studies were conducted on 35 patients with corticosteroid· mental to the treatment of asthma", I dependent asthma (CSDA) and 20 asthmatics who had never received prednisolone. but prolonged use can alter pulmonary Candida albicans was repeatedly cultured from the sputa of 12 patients with CSDA. host defence mechanisms which Isolation was more frequent In those patients who were receiving more than 10 mg results in the airway providing a hos­ prednisolone for more than six months. Nearly half of these patients demonstrated pitable environment for the growth a positive Immediate cutaneous reaction and precipitating antibodies against C.albicans. of opportunistic fungi.:U This can Although no pathological significance, beside colonization, could be attributed to this finding, It was felt that It would be prudent to restrict the dally dose of prednl. also lead to systemic mycosis. 4,5 solone to less than 10 mg, when administered for more than six moths. Two patients Recent studies 6,7 have reported the with allergic bronchopulmonary aspergillosis (ABPA). were Identified, one from each occurance of allergic bronchopul­ group. The possibility of ABPA. however, remained open In two other patients with monary aspergillosis (ABPA) among CSDA. It is probable that some patients with CSDA may be suffering fro~ ABPA patients with corticosteroid - depen­ but characteristic features of the disease are masked by costlcosterold tnerapy, dent asthma (CSDA) and have also making It difficult to diagnose. highlighted the difficulty in diagnosis of ABPA in this group of asthmatics, as therapy with corticosteroids masks mum doses of 7.5 mg daily or 15 mg KOH directly on a slide and observed many of the characteristic features on alternate days. Clinical assessment microscopically for fungal elements. of the disease. This study on 35 pa­ of all patients was done along with All specimens were also streaked on tients of CSDA was prompted by routine investigations of blood and Sabouraud's dextrose agar (Emmon's the paucity of such information from urine, chest radiograph and spiro­ modification) containing chloram­ the subcontinent. metery. All studies were conducted phenicol (0.5 mg/mt) as well as chlo­ with patients maintained on doses ramphenicol and cycloheximide (0.5 of prednisolone required for control mg/ml). MATERIALS AND METHODS of their symptoms. Twenty asthmatics One set of these innoculated The study comprised 35 patients who had never received corticosteroids tubes was incubated at 25° C and the with CSDA attending the Clinical functioned as controls and underwent other was incubated at 37° C for 4 Research Centre of the vallabhai an identical work up as the study weeks. The identity of Candida albi­ Patel Chest Institute. Corticosteroid­ population. dependent asthma was defined as Mycological investigations in­ patients requiring prednisolone for cluded examination of sputum samples From the Department of Clinical Research, the control of their symptoms for a of patients from both, the study and Vallabhai Patel Chest Institute, University of Delhi, P.O. BOX 2101 Delhi·110007, India. I minimum period of 3 months or control groups. A loopfull of each more prior to presentation at mini- specimen was digested in 10 percent Correspondence: Dr. Ashok Shah 124 RAMACHANDRAN, ET AL.

cans was confirmed by Germ tube test pitating antibodies to A.jumigatus, and in I patient amongst the controls. and chlamydospore production. Iden­ A.flavus, A.niger and C.albicans were Bronchography demonstrated central tification of Aspergillus jumigatus, detected, by the gel double immuno­ bronchiectasis in one patient in the A. jlavus and A. niger was based on diffusion technique of Ouchterlony. 9 study group. their microscopic and macroscopic A total of 164 sputum samples, characteristics as seen on Sabouraud's RESULTS 104 from the study group and 60 from agar at 25° C and 37° C. There were 16 males and 19 the control group were studied for Skin tests were performed intra­ females in the study group with an pathogenic fungi. C.albicans was cutaneously on the forearm with anti­ age range of 11-16 years. The control isolated from 30 sputum samples from gens of Aspergillus jumigatus, A. group consisted of 12 females and 8 12 patients of the study group as niger, A.flavus and Candida albicans males. No significant occupational compared to a single patient from the il) dilutions of 1:500, obtained from history could be elicited in either control group. As many as 11 of Council of Scientific and Industrial group. Peripheral eosinophilia (> these 12 patients receiving predni­ Research-Centre of Biochemicals, 500/mm3) was observed in 17 patients solone had repeated heavy growth Delhi. All sites were examined after in the study group as compared to (arbitrarily taken as more than 10 20 minutes for immediate reaction 13 in the control group. Chest radio­ colonies per culture) of the fungus, and periodically over 4-8 hours for graphs showed transient pulmonary which was directly linked to the dose type-III reaction and graded. 8 Preci­ infiltrates in 3 patients with CSDA and duration of corticosteroid therapy

Table 1. Frequency of isolation of growth of Candida albicans in sputum of patients with corticosteroid-dependent asthma.

Duration of therapy

Dose of prednisolone Less than 6 months More than 6 months (mg per day) Positive Sputum Patient Positive Sputum Patient specimens number specimens number

Less than 10 a/a a/a 5/28 2/8 11-20 8/11 2/5 15/50 6/17 21-30 0/3 0/1 3/6 1/2 More than 30 0/3 0/1 3/3 1/1 Total 8/17 217 26/87 10/28

Table 2. Salient characteristics of patients with allergic bronchopulmonary aspergiliosts (ABPA) and probable ABPA.

Cutaneous hypersensitivity Sputum culture Serum Peripheral Chest Group Age/Sex against A. fumigatus Bronchogram for A. fumigatus precip itins eosinophilia X-ray Type-I Type-III

1, Study 45, F + + + + TPI CB 25, F* + + + TPI NO 37, M* + + + TPI NO 2. Control 26, M + + + + + TPI NO

Probable ABPA TPI Transient pulmonary infiltrates CB = Central bronchiectasis NO ~ Not done I FUNGAL STUDIES IN CORTICOSTEROID-DEPENDENT ASTHMA 125

II (Table I). Aspergillus species were However, apart from colonization, ACKNOWLEDGEMENTS t isolated from sputum of 11 patients no significance could be established, I We are thankful to Professor ~ in the study group and 4 in the control especially in view of the fact that H.S. Randhawa for helping with the group. many normal individuals have cutane­ mycological investigations. Of the 35 patients with CSDA, ous reactivity to Calbicans. 12 In­ ! 6 had cutaneous reactivity to candidin creased Calbicans colonization of i ! and 11 to aspergillin. One patient the respiratory tract must, neverthe­ References less, be viewed with concern, especially i exhibited both type I and III reaction I. Woolcock AJ. Use of corticosteroids in ! against A.jumigatus. Only 1 patient in light of the fact that corticosteroids treatment of patients with asthma. J I had an immediate cutaneous reaction alone or in combination with anti­ Allergy Clin Immunol 1989; 84 : 975-8. [ against Calbicans III the control biotics, supress neutrophilic responses 2. Chiu n, Wells I, Novey HS. Incidence group while 5 patients reacted posi­ to Candida which is crucial to the of fungal precipitins in patients treated I tively to aspergillin, one of whom defence against this organism. 13.14 with beclomethasone dipropionate t also demonstrated a type III reaction Furthermore, the possible role of aerosol. Ann Allergy 1981; 46: 137-9. t to A.jumigatus. Calbicans as an allergen in chronic 3. Kwong FK, Sue MA, Klaustermeyer WB. asthma must also be considered. 15 Serum precipitins against C Corticosteroid complications in respira­ Increased colonization assumes im­ tory disease. Ann Allergy 1987; 58 : 326-30. albicans, were demonstrated in 8 pa­ portance in context of the fact that tients with CSDA and in none of the 4. Anderson CJ, Craig S, Bardana EJ. Calbicans is not an airborne allergen, control group. Of the 12 patients in Allergic bronchopulmonary aspergillosis the only source of exposure being and bilateral fungal balls terminating in whom Calbicans was cultured in the saprophytic growth in the body. 16 disseminated aspergillosis. J Allergy Clin sputum, 7 had serum precipitins In view of our finding, it may there­ Immunol 1980; 65 : 140-4. against Calbicans. Serum precipi­ fore be prudent to restrict the dose 5. Dehan AL, Ketai L. Invasive aspergillosis. tins against A .jumigatus were detected of prednisolone to less than 10 mg Chest 1988; 94 : 1117-8. in 1 patient each from both groups. daily, when given for more than six 6. Clayton DE, Busse WW. Development On the basis of clinical and radio­ months. of allergic bronchopulmonary aspergil­ logical profile and supported by posi­ Two of our patients, one from losis during treatment of severe asthma tive mycological, immunological and each group, had ABPA. Two other with systemic corticosteroids. J Allergy serological data, a diagnosis of ABPA patients from the study group had Clin Immunol 1981; 67 : 243-6. was established in 2 patients, 1 from transient pulmonary infiltrates, peri­ 7. Basich JE, Graves TS, Baz MN, Scanlon each group (Table 11). Two other pheral eosinophilia and an immediate G, Hoffmann RG Patterson R, Fink IN. patients in the study group had tran­ cutaneous reaction to aspergillin. Allergic bronchopulmonary aspergillosis sient pulmonary infiltrates, with peri­ Serum precipitins to Aspergillus were in corticosteroid-dependent asthmatics. J Allergy C1in Immunol 1981; 68 : 98-102. pheral eosinophilia, A.jumigatus in not detected in these two patients nor sputum and a type I cutaneous hyper­ did they consent to bronchography. 8. Shivpuri DN, Agarwal MK. Studies on sensitivity against A.jumigatus. How­ A strong suspicion of ABPA, however, allergenic fungal spores of Delhi, India­ ever precipitating antibodies were remained. Corticosteroid-dependent metropolitan area-clinical aspects. J Allergy 1969; 44 : 204-13. not detected in their sera and they asthma stage IV of ABPA may be refused to undergo bronchography. clinically very similar to that of CSDA 9. Ouchterlony O. Handbook of immuno­ diffusion and immunoelectrophoresis. not associated with ABPA. 17 Infact, Ann Arbor. Ann Arbor Science Publishing DISCUSSION in a study of 42 patients of CSDA, Inc. 1968 :4-47. Oropharyngeal candidiasis has Basich et al 7isolated 12 patients sus­ 10. Cayton RM, Sontar CA, Stamford CF, been documented in asthmatics on pected of having ABPA. Our findings Turner GC, Nunn AS. Double blind corticosteroids, both on aerosols 10.11 appear to indicate the opinion ex­ trial comparing two dosage schedules of 3 7 as well as on oral drugs. Fungal colo­ pressed by Basich et al that corti­ beclomethasone diproprionate aerosol nization of the respiratory tract, as costeroid therapy may mask ABPA in the treatment of chronic asthma. in this study, was related to the dose making it a difficult disease to diag­ Lancet 1974; 2 : 303-7. and duration of therapy which re­ nose in asthmatics dependent on cor­ II. Sahay IN, Chatterjee SS, Stanbridge flects the increased susceptibility of ticosteroids. Since some patients TN. Inhaled corticosteroid aerosols and individuals receiving higher doses of with CSDA may actually be undiag­ candidiasis. Br J Dis Chest 1979; 73 : corticosteroids for a longer duration. nosed cases of ABPA, vigorous 164-8. More than half the patients in our attempts must therefore be made to 12. Rippon JW. Medical mycology: The study with repeated heavy growth of rule out ABPA in patients requiring pathogenic fungi and the pathogenic acti­ Calbicans in the sputum demons­ relatively high doses of corticosteroids nomycetes. Philadelphia. WB'Saunders, trated immediate cutaneous reactivity. to control their asthma. 1982 : 175-204. 126 RAMACHANDRAN, ET Al.

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