Low-Dose Theophylline Not Effective at Reducing COPD ...

Oral theophylline has long been utilized as a bronchodilator to manage chronic obstructive pulmonary disease (COPD), but the need for high doses to see benefits has resulted in significant side effects and a shift towards better treatment options. Despite this, its low cost keeps it in use globally. A recent study aimed to determine if incorporating low-dose theophylline with inhaled corticosteroids could lower the frequency of COPD exacerbations, but the results were not encouraging.

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The study, published by JAMA, was a randomized clinical trial involving 1567 COPD patients, all of whom were using inhaled corticosteroids. Participants were divided into two groups: one receiving low-dose theophylline (200 mg once or twice daily) to achieve plasma concentrations of 1 to 5 mg/L (791 participants), and the other receiving a placebo (787 participants).

Participants had an average age of 68.4 years, with 54% being men. Each had a ratio of forced expiratory volume in the first second to forced vital capacity (FEV1/FVC) under 0.7 and had experienced at least two exacerbations in the past year, treated with antibiotics, oral corticosteroids, or both.

The addition of theophylline did not result in a significant reduction in the average number of exacerbations over one year compared to the placebo.

There were 3430 exacerbations in total: 1727 in the theophylline group (mean: 2.24 [95% CI, 2.10-2.38] exacerbations per year) versus 1703 in the placebo group (mean: 2.23 [95% CI, 2.09-2.37] exacerbations per year); unadjusted mean difference was 0.01 (95% CI, -0.19 to 0.21) and the adjusted incidence rate ratio was 0.99 (95% CI, 0.91-1.08).

Serious adverse events were noted in both groups, including cardiac events (2.4% in theophylline group, 3.4% in placebo group), gastrointestinal issues (2.7% versus 1.3%), nausea (10.9% versus 7.9%), and headaches (9.0% versus 7.9%).

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines do not recommend theophylline unless more effective bronchodilators are unavailable or too costly. However, GOLD does acknowledge the potential advantages of low-dose theophylline, though the clinical significance remains poorly understood with contradictory and limited evidence especially regarding exacerbations.

COPD could become the third-leading cause of death by 2020, a preventable condition frequently linked to smoking.

In an editorial accompanying the study, two physicians described the findings as "disappointing," noting that while theophylline is affordable, its anti-inflammatory properties are dose-dependent, often exceeding tolerable levels for patients. They mentioned the ongoing interest in theophylline for its potential, albeit unrealized, benefits in preventing exacerbations.

References

1. Devereux G, Cotton S, Fielding S, et al. Effect of theophylline as adjunct to inhaled corticosteroids on exacerbations in patients with COPD. JAMA. 2018;320(15):1548-1559. doi:10.1001/jama.2018.14432

2. Criner GJ, Celli BR. Failure of low-dose theophylline to prevent exacerbations in patients with COPD. JAMA. 2018;320(15):1541-1542. doi:10.1001/jama.2018.14295

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1. Why is Theophylline no longer used?

Theophylline is a weak bronchodilator and does not effectively reduce lung inflammation. Long-term usage can result in severe side effects, including toxicity in the central nervous system when plasma concentrations exceed 20 mg/L. Consequently, its use has significantly declined since the 1900s.

2. How long does it take for Theophylline to work?

Theophylline acts by relaxing the muscles in the airways and is a Beta2-agonist. It is available only in long-acting forms, making it unsuitable for immediate relief of sudden breathing problems. The effects typically begin within 1-2 days.

3. Can Theophylline be stopped immediately?

Suddenly halting theophylline usage might lead to the return of asthma symptoms and potentially fatal asthma attacks. The dosage should be gradually reduced under medical supervision to achieve a stable therapeutic level.

4. Is Theophylline a bronchodilator?

Yes, Theophylline is a bronchodilator that relaxes muscles in the bronchial tubes, increasing airflow and alleviating symptoms such as coughing, wheezing, and shortness of breath. It is used to control asthma and is administered orally.

5. When should you take Theophylline?

Theophylline is prescribed only for severe lung diseases like COPD or asthma and is typically paired with other medications to limit usage. Due to significant side effects, it must be taken exactly as prescribed under expert medical supervision.

6. Can alcohol be taken occasionally with Theophylline?

Alcohol and tobacco can lower plasma theophylline concentration levels and reduce its effectiveness. Caffeine-containing medications and foods should also be limited. Consult a doctor to avoid severe side effects.

7. Is Theophylline a steroid?

No, Theophylline is a xanthine drug and not a steroid. Unlike steroids, it is not a synthetic version of the body's hormones. It is primarily used to treat COPD and asthma but is not as effective as steroids in reducing inflammation.

8. Is Theophylline still prescribed?

Theophylline has been extensively used for lung diseases since 1922. Despite its narrow therapeutic window, resulting in the need for constant medical oversight, it remains prescribed due to its low cost.

9. When should you take Theophylline?

Theophylline is prescribed for severe lung conditions like COPD or asthma and is paired with other drugs to minimize use. It should only be taken under expert supervision due to severe side effects.

10. Is Theophylline still used for COPD?

Theophylline has been used as a bronchodilator for COPD since the 1900s. Although better drugs are available today, theophylline continues to be administered in low doses in combination with other drugs due to its affordability. The final decision rests with your doctor.

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