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* From the University of Illinois at Chicago (Drs. Garey, Rubinstein, Gotfried, and Danziger; Mssrs. Varma and Khan), Chicago, IL; and The Good Samaritan Regional Medical Center (Dr. Gotfried), Phoenix, AZ.
Correspondence to: Israel Rubinstein, MD, FCCP, Section of Respiratory and Critical Care Medicine, Department of Medicine, University of Illinois at Chicago, 840 S. Wood St (M/C 787), Chicago, IL 60612-7323; e-mail: IRubinst{at}uic.edu
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Abstract |
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Key Words: anti-inflammatory • clarithromycin • macrolides • prednisone-dependent asthma
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Introduction |
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Case Report |
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Patient 1
A 63-year-old white man received a diagnosis of severe asthma in
1995 and had been prednisone-dependent since that time. He had received
a diagnosis of asthma as a child, and that condition had resolved as he
reached the age of 18 years. He had quit smoking approximately 20 years
before this study (14 pack-year history). Skin allergy tests were
positive for mold dust. Physical examination was significant for a
cushingoid appearance. Baseline FVC and FEV1 were
1.72 L and 1.12 L/s, respectively (44% and 36% predicted,
respectively). His current asthma treatment consisted of inhaled
triamcinolone, 1,600 µg daily; inhaled albuterol, 810 µg daily;
oral theophylline, 400 mg daily; and prednisone, 10 mg daily. His
symptoms were aggravated by attempts to taper his prednisone dose. In
August 1998, he was given clarithromycin, 500 mg bid. Five months
later, he discontinued prednisone entirely with no significant change
in spirometry. Due to unexplained ecchymoses while receiving
clarithromycin alone for 2 months, the drug was discontinued. The
patient experienced an acute exacerbation of asthma 1 month later and
was given oral prednisone and clarithromycin, 500 mg bid. Within 2
months, the patient discontinued prednisone. He has remained on
clarithromycin through 12 months of follow-up. No other changes were
made to his medications. Clarithromycin was well tolerated, and he has
remained asymptomatic.
Patient 2
A 65-year-old white woman received a diagnosis of severe asthma
in 1986. Her symptoms were frequently exacerbated by attempts to taper
her prednisone dose. Her medical history was significant for a 22-year
history of allergic rhinitis and infrequent symptoms of
gastroesophageal reflux. The patient had quit smoking at the age of 27
years (5 pack-year history). Baseline FVC and
FEV1 were 3.25 L and 2.26 L/s, respectively
(115% and 100% predicted, respectively). Current asthma treatment
regimen consisted of inhaled triamcinolone, 1,000 µg qd; inhaled
metaproterenol, 7.8 mg qd; inhaled cromolyn sodium, 6,400 µg qd; and
prednisone, 10 mg qd.
In February 1997, the patient was given clarithromycin, 500 mg bid. Within 3 months, she tapered her prednisone to 5 mg qd, with a concomitant increase in FVC and FEV1 to 3.54 L and 2.69 L/s, respectively (127% and 120% predicted, respectively). Three months later, she discontinued prednisone entirely. No changes in spirometry or adverse events were noted through 12 months of follow-up.
Patient 3
A 67-year-old white man had received a diagnosis of asthma in
1984 and had been dependent on prednisone for the past 1.5 years. He
experienced four to five acute exacerbations of asthma per year. His
medical history was significant for gastroesophageal reflux. He had no
smoking history. Baseline FVC and FEV1 were 4.12
L and 2.57 L/s, respectively (97% and 76% predicted, respectively).
He was treated with ipratropium, 144 µg qd; salmeterol, 84 µg qd;
flunisolide, 2,000 µg qd; beclomethasone, 168 µg qd; theophylline,
600 mg qd; and prednisone, 5 mg qd. He was given clarithromycin, 500 mg
bid, and within 3 months, FVC increased to 5.3 L (125% predicted) with
no change in FEV1. Plasma theophylline
concentrations were unchanged throughout the observation period. The
patient noted a significant improvement in quality of life, manifested
by increased energy levels and enthusiasm. Several attempts to taper
oral prednisone to 5 mg qd failed. Nonetheless, the patient did not
experience an acute exacerbation of asthma throughout the 12 months of
clarithromycin therapy. No adverse events were noted.
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Discussion |
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Previous studies from Japan have shown that relatively short-term (< 3 months) therapy with oral erythromycin and roxithromycin, two macrolide antibiotics, was associated with significant improvement in bronchial hyperreactivity in patients with asthma.6 7 8 However, the mechanisms underlying this response were not determined. Moreover, these patients were either children or adults. The results of our case studies support and extend these observations by showing that long-term treatment with clarithromycin may be beneficial in elderly patients with prednisone-dependent asthma. Whether the corticosteroid-sparing effects of this drug are related, in part, to downregulation of the inflammatory cascade in the airway of patients with asthma remains to be determined.4 9 10 11
Prolonged use of prednisone in patients with asthma, particularly elderly patients, is associated with devastating side effects, including osteoporosis.5 Hence, therapeutic measures to reduce or eliminate prednisone dependency in these patients are desirable. The results of this case report suggest that long-term administration of oral clarithromycin may be a useful approach to accomplish this goal. However, the mechanisms underlying the corticosteroid-sparing effect of clarithromycin were not elucidated in this study. Earlier studies had suggested possible interactions between macrolides and corticosteroids, causing increased concentrations of the steroid.12 This is unlikely in the cases reported here, as two patients were able to discontinue prednisone entirely for a sustained period while remaining in remission. Also, Fost et al13 recently demonstrated that clarithromycin did not affect the pharmacokinetics of prednisone. Clearly, additional prospective studies are indicated to investigate the role of long-term clarithromycin therapy in elderly patients with prednisone-dependent asthma.
In summary, long-term oral clarithromycin therapy may have a role in the treatment of elderly patients with prednisone-dependent asthma. Future research will be necessary to further elucidate their effects.
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Footnotes |
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Received for publication January 13, 2000. Accepted for publication April 13, 2000.
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This article has been cited by other articles:
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D. E. Stover and D. Mangino Macrolides: A Treatment Alternative for Bronchiolitis Obliterans Organizing Pneumonia? Chest, November 1, 2005; 128(5): 3611 - 3617. [Abstract] [Full Text] [PDF]
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M. H. Gotfried Macrolides for the Treatment of Chronic Sinusitis, Asthma, and COPD Chest, February 1, 2004; 125(2_suppl): 52S - 61S. [Abstract] [Full Text] [PDF]
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