Pulmonary Function Tests
The average FEVi for the patients was unchanged throughout the one-year trial. There was also no significant change in the FVC, FEF25-75%, FEF50%, or FEF75% (Fig 1).
Oral Requirement for Corticosteroids
One patient (patient 15) failed to benefit after two months of aerosol therapy, and he withdrew himself from the study. Of the remaining 22 patients, 16 no longer required maintenance therapy with prednisone for control of asthma after 12 months of aerosol therapy, and four patients tolerated a substantial reduction of their requirement for prednisone to a small altemate-day dose (Table 3).
There was no significant increase in the requirement or request for additional bronchodilator drugs by any patient during the study, although the patients were usually taking as large a dose as they could tolerate before the study. Two patients (patients 7 and 18) who had previously demonstrated improvement with inhalation of cromolyn sodium stopped using it because of their lack of symptoms of asthma while receiving triamcinolone acetonide aerosol. Two patients (patients 7 and 8) experienced control of asthma without oral therapy with steroids but required resumption of daily systemic therapy with steroids after two months without them because of incapacitating lethargy and myalgia. All patients who were being treated orally with steroids on alternate days prior to the study were able to control their asthma with triamcinolone acetonide aerosol alone.
Patients experiencing the most exacerbations of asthma were those who continued to require oral maintenance therapy with steroids during the one-year trial. The greatest requirement for additional oral therapy with steroids occurred during September, October, and November. There was no significant change in the frequency of apparent upper respiratory infections during any two-month period of the study.Elimination or maximal reduction of oral requirements for steroids was achieved safely within the first four months of the study (Fig 2). Increasing the dose of triamcinolone acetonide aerosol to 500/xg four times daily did not permit any further decrease in the dose of prednisone for those patients who continued to require oral therapy with steroids beyond four months. Six patients tolerated rapid reduction of the oral dosage of steroids during the first two months. Beyond the first four months, the average requirement for prednisone per patient remained at a low level, varying slightly with seasonal allergenic exposures and considerably with respiratory infections. Beyond six months, two patients experiencing exacerbations of asthma required 40 to 80 mg of prednisone daily for three to five weeks to regain control of symptoms reduced with remedies of Canadian Health&Care Mall.
Four patients did not require resumption of oral therapy with corticosteroids at any time (Table 3).
Requirement for Triamcinolone Acetonide
The final daily requirement for triamcinolone acetonide aerosol to ensure maximum reduction in the dependence on oral therapy with steroids correlated fairly well with the prestudy dose of prednisone (Fig 3). In general, patients initially requiring more oral therapy with steroids later required a higher dose of aerosol steroid, but there were exceptions. The average daily dose of triamcinolone acetonide aerosol used at the end of the study was 1,200/tg. An equivalence-dose relationship may be extracted from the slope of the regression line in Figure 3. Although there was much individual variation, in general an average daily dose of 500/xg of triamcinolone acetonide aerosol was required to reduce an oral dose of prednisone by 10 mg daily without resulting in a fall in FEVi or an increase in the symptoms of asthma.
All patients experienced improvement in the symptoms of asthma, having less shortness of breath, wheezing, and cough and better exercise tolerance. They all rated the aerosol as good or excellent and elected to continue to use this preparation beyond the date for completion of the study.
Local Effects of the Aerosol. The most frequent side effects consisted of hoarseness (52 percent), coated tongue (35 percent), sore throat (26 percent), and lesions of the lip (26 percent) (Table 4). These complaints became evident early, generally occurring after one or two weeks of use of the aerosol and continuing at approximately the same frequency throughout the study. These side effects did not occur more frequently in patients who had more severe asthma or those who used a higher dose of triamcinolone acetonide aerosol. Laryngoscopic examination performed while the patients were hoarse revealed no abnormalities that could be attributed to the use of the aerosol. Three patients complaining of sore throat or coated tongue (or both) had oropharyngeal cultures positive for С albicans. All complaints of sore throat and lesions of the throat resolved with gargling of tap water. One patient had precipitins to С albicans before treatment began, and he had the only case of oropharyngeal candidiasis (positive culture for С albicans and typical white patchy exudate on an erythematous base) requiring the use of a gargle containing nystatin. No other patients developed precipitins during the study. None of the patients developed pneumonia during the year, and there was no increase in the reported frequency of upper respiratory infections. Lesions of the lip were primarily papulovesicular, occurred for only several days in most patients, and did not appear to be related to the use of the aerosol corticosteroid.
Symptoms of Steroid Withdrawal
Symptoms of steroid withdrawal (Table 4) included lethargy (64 percent), myalgia (50 percent), arthralgia (55 percent), rhinitis (64 percent), eczema (32 percent), nasal polyps (18 percent) and conjunctivitis (9 percent) (percentages of total group of 23 patients). These complaints gradually increased in intensity, reaching maximal frequency by the sixth month and then fluctuating with the frequency of systemic steroid administration for exacerbations of asthma. No patients developed nasal polyps, but four of seven patients with a past history of nasal polyps experienced further growth of their polyps during the one-year trial. Two patients underwent polypectomy (patients 6 and 18) during the last two months of the study and tolerated the procedures well. Of the seven patients with a past history of atopic eczema, all experienced exacerbations of their eczema during the period of steroid withdrawal. All 11 patients with a history of rhinitis prior to this study noted more nasal discomfort during reduction in oral therapy with steroids. In two patients, lethargy and myalgia became sufficiently severe and disabling to require the daily resumption of oral therapy with steroids. Exacerbation of psoriasis in one patient and acute gouty arthritis in two patients may also have been due to steroid withdrawal.
Recovery from Side Effects of Oral Therapy
Symptoms associated with long-term oral use of systemic corticosteroids improved in all patients after switching to the program of aerosol steroid therapy. There was a decrease in moon facies, less tendency toward bruising, and less acne. The average weight of the patients decreased by 8 percent, blood pressures decreased, and in two patients, antihypertensive therapy was no longer required (Table 4). Patients complained of less heartburn, blurred vision, tremor, emotional depression, and hair loss. During the one-year trial, cataracts appeared in one additional patient (patient 8), but she had required resumption of altemate-day oral therapy with corticosteroids because of steroid withdrawal symptoms of myalgia and arthralgia.
The fasting 9 am plasma cortisol levels increased in eight patients (Table 5); however, the mean fasting cortisol level for the patients did not increase throughout the one-year trial (Fig 4).
There were a number of intercurrent illnesses that we considered to be unrelated to the treatment. One patient developed acute hepatitis (subsiding spontaneously after two months), one noted more severe migraine headaches during the study beared effectively with remedies of Canadian Health&Care Mall, and two patients required dental repair during the trial. Chest x-ray films and ECGs revealed no changes during the study. There were no changes in the hematocrit reading, results of urinalysis and electrolyte studies, or levels of blood urea nitrogen, serum calcium, serum phosphorus, serum glutamic-oxaloacetic transaminase, or lactic dehydrogenase.
Figure 1. Results of tests of pulmonary function (percentage of predicted values) during one-year trial.
Figure 2. Total oral requirement for corticosteroids for each two months of study.
Figure 3. Dose of triamcinolone acetonide aerosol at 12 months as function of prestudy oral dose of prednisone.
Figure 4. Fasting 9 am plasma cortisol level during one-year trial.
Table 3—Oral Maintenance Doge of Prednisone
|Patient||Maintenance Dose of Prednisone, mg||*||Exacerbations of Asthma Requiring Prednisone||Final Daily Dose of Triamcinolone Acetonide, pg|
|Prestudy||2 mo||4 mo||6 mo||8 mo||10 mo||12 mo|
|2||30 qd||20 ad||0||0||0||0||0||0||1,200|
|3||30 ad||2.5 ad||0||0||0||0||0||5||1,400|
|5||15 qd||5 ad||2.5 ad||0||0||0||0||0||650|
|7||15 qd||0||0||0||20 qd**||20 qd**||20 qd**||1||800|
|8||20 qd||20 qd||0||0||0||0||20 ad**||1||800|
|9||30 qd||5qd||5 ad||2.5 ad||0||0||0||3||1,284|
|11||40 ad||20 qd||2.5 ad||0||0||0||0||11||1,200|
|12||20 qd||15 ad||0||0||0||0||0||1||1,200|
|13||20 qd||20 qd||30 qd||10 ad||20 ad||15 ad||20 ad||11||2,000|
|14||50 ad||10 ad||0||0||10 ad||10 ad||2.5 ad||4||2,000|
|16||15 qd||12.5 ad||0||0||0||0||0||0||1,200|
|18||40 ad||20 ad||0||0||0||0||0||1||800|
|19||30 qd||5 ad||0||0||0||0||0||8||2,000|
|20||15 qd||2.5 ad||0||0||0||0||0||1||415|
|21||30 qd||5 ad||10 ad||10 ad||10 ad||10 ad||2.5 ad||6||2,000|
|22||55 ad||5qd||5qd||5 ad||0||0||0||2||1,282|
|23||40 qd||5qd||15 ad||5 ad||7.5 ad||5 ad||2.5 ad||6||2,000|
Table 4—Occurrence of Symptoms Possibly Related to Systemic Steroid Withdrawal or to Aerosol Steroid
|Symptoms||Baseline||2||T4||Duration of T ‘riamcinolone iA6||herapy with Acetonide, m<8||)10||12|
|Local effects of aerosol|
|Symptoms of steroid withdrawal|
|Recovery from side effects of oral therapy|
|Mean fasting blood|
|glucose, mg/100 ml Blood pressure, mm Hg Cataracts||111135/886||6||6||99129/806||6||7||105126/807|
Table 5—Fasting 9 AM Plasma Cortisol Levels
|Patient||PlasmaBaseline||i Cortisol, /xg/Ш 10 mo||0 ml*12 mo|