Three months of treatment with the common, generic antibiotic azithromycin safely reduced the number of coughs and cough severity, and improved the quality of life in adults with pulmonary sarcoidosis, a small, exploratory study concluded.
The findings support the further evaluation of azithromycin for these patients in a larger, controlled clinical trial.
The study, “Azithromycin for sarcoidosis cough: an open-label exploratory clinical trial,” was published in the European Respiratory Journal Open Research.
Chronic cough is a common symptom for people with sarcoidosis affecting the lungs. However, current treatments rely on suppressing the immune system, and in many cases these are ineffective and often come with adverse side effects. That is why there is a need for additional treatment options.
Azithromycin is a low-cost, readily available generic medicine used to treat certain bacterial infections of the lungs, ears, sinuses, skin, throat, and reproductive organs.
Studies have suggested that azithromycin reduces the activity of a protein in inflammatory cells called mTOR, whose activation is thought to help the formation of granulomas — small clumps of inflammatory cells that build up in organs, causing sarcoidosis.
Moreover, in clinical trials in people with chronic airways disease, regular treatment with azithromycin for up to one year reduced exacerbations (sudden worsening of symptoms) and was safe and well-tolerated.
Now, researchers based at Hull York Medical School in the U.K. conducted a small, open-label, exploratory clinical trial (NCT04020380, EudraCT 2019-000580-24) to evaluate the impact of azithromycin on chronic cough in people with pulmonary sarcoidosis. The trial was funded by the charitable organization SarcoidosisUK.
“Chronic cough is a distressing symptom for many people with pulmonary sarcoidosis, and for some, it can have a big impact on quality of life,” Simon Hart, PhD, study lead author, said in a press release. “An appealing strategy for investigating new treatments for sarcoidosis is to ‘re-purpose’ existing drugs that are safe for long-term use.”
The study included 21 people (nine men and 12 women) with a median age of 57 years diagnosed with pulmonary sarcoidosis and who had self-reported chronic cough attributed to sarcoidosis. All patients were Caucasian, which reflected the local population. Five participants were taking oral corticosteroids.
Clinical assessments were performed before azithromycin treatment (baseline) and at one and three months of therapy (oral 250 mg once daily). The primary endpoint (goal) was the number of coughs in 24 hours counted at home using an automated cough counter and software.
At baseline, overall, the median number of coughs in 24 hours was 228, ranging from 43 to 1,950. After one month of treatment, the median cough number was 122, ranging from 20 to 704, and after three months it was 81, ranging from 16 to 414.
After three months of azithromycin therapy, the relative number of coughs was reduced by a median of 49.6%. Whether a patient had received corticosteroids did not affect the overall findings.
As a secondary endpoint, a visual analog scale (VAS), running from 0 to 100, was used to assess cough severity and the urge to cough. The median VAS score for cough severity was 30.5 at baseline, which dropped to 24.0 after one month, and 19.0 at three months. The median VAS urge to cough score was 26.0 at baseline and after one month, but fell to 18.5 after three months of therapy.
Quality of life (QoL) assessments relating to cough and sarcoidosis also were evaluated using the Leicester cough questionnaire (LCQ). For 19 patients with complete data after three months, 11 (58%) had a clinically meaningful LCQ score improvement (1.3 points or more).
King’s sarcoidosis questionnaire (KSQ) scores for lung health (KSQ_lung), general health status (KSQ_GH), and combined lung and general health (KSQ_lung_GH), also showed meaningful improvements.
A total of 12 participants (63.2%) had an increase in KSQ_lung score of more than 4 points, 15 participants (79%) had an increase in KSQ_GH score greater than 8 points, and 13 (68.4%) had an increase in KSQ_lung_GH score of more than 5 points.
The absolute changes in the number of coughs (fewer coughs) correlated with LCQ and KSQ_GH changes (higher scores), but not with KSQ_lung or KSQ_lung_GH scores.
At baseline, the cough count was significantly higher (median 365 coughs) in patients with a VAS cough severity score greater than 40, compared with those scoring less than 40 (median 125 coughs). After three months of azithromycin treatment, the median decrease in the number of coughs was 78.8% less in participants with a baseline VAS severity score greater than 40 compared to 40.6% less in those with VAS below 40.
A total of 16 adverse side effects were reported by 10 patients, of which 11 were mild and five were moderate, with none leading to discontinuing treatment. No serious adverse side effects were reported.
The most common side effect was the common cold, occurring in six participants, with two reporting worsening cough intermittently. Two patients experienced transient stomach cramps and a slight reduction in appetite.
Because irregular heartbeat can be a serious side effect of azithromycin and related therapies, patients underwent an electrocardiogram (ECG) during the study. At baseline, one and three months, there were no significant changes to ECG.
Overall, “in our non-controlled, open-label trial in people with sarcoidosis who reported a chronic cough, 3 months of treatment with azithromycin led to improvements in a range of cough measurements, without significant side effects,” said Hart.
“The study did not have a placebo (dummy) arm so we cannot say how much of the effect was due to a placebo response, but we believe that the improvements were sufficiently large to merit further investigation of azithromycin as a treatment for sarcoidosis cough,” he added.
According to the team, these findings indicate that “azithromycin should be tested as a treatment for sarcoidosis cough in a randomized placebo-controlled trial,” the researchers wrote.
Henry Shelford, SarcoidosisUK chairman, said “This is a really exciting, potentially ground-breaking piece of research. Using this existing drug, that is relatively cheap and approved for use in the UK, offers the potential for a fast route to a new treatment.
“The fact of the reaction may also offer highly important insight into the disease mechanism, which itself might offer new treatment options. We thank everyone who has donated or supported the charity — without you this research wouldn’t have been possible,” he added.
We are sorry that this post was not useful for you!
Let us improve this post!
Tell us how we can improve this post?