A Losartan Dream for COPD

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Picture of Stephen Biehl
Stephen Biehl
Respiratory therapist specializing in lung health investigations. If not I’m the unit, find me in the PFT lab, bronch suite, rehab, or taking the stairs.

The Pre-brief

Working in a Pulmonary Function Lab plus providing in-patient care within the hospital, I see patients every day that have been diagnosed with chronic obstructive pulmonary disease (COPD). These patients frequently ask if they can be cured of COPD. I explain that unfortunately, COPD is not reversible, but explain that with medications and innovative minimally invasive treatments (if they qualify), they can hopefully see improvement in their breathing. I ask if they are smoking, or have ever smoked. I am quick to praise the ones that say they never smoked, as well as the ones who say they have quit. I encourage the ones who say that they are trying, as well as the ones who say that they are thinking of quitting. 

COPD continues to be a problem for many adults. It comes with increasing morbidity and mortality rates in Americans, as well as outside America, with over six million deaths reported worldwide each year. One form of COPD is chronic bronchitis, which is evident by airway inflammation and causes increased mucus secretion. A leading cause of COPD is cigarette smoking, for which there is no pharmacological agent to slow the progression of the disease. But studies have been looking for a drug that may be able to help.

Angiotensin Receptor Blockers (ARB)

Angiotensin Receptor Blockers (ARB) are a class of drugs used to treat hypertension in patients. A previous study by Mancini, et al, looked at patients with heart disease and COPD who were treated with statins, angiotensin-converting enzymes (ACE), ARB, or a combination of statins and ACE or ARB medications. New research is looking into patients who take one of these drugs, specifically Losartan, an ARB, due to its anti-inflammatory properties. 

These clinical trials have been looking at the use of Losartan in patients with COPD who have smoked. The trials are looking to see if Losartan helps to reduce the airway inflammation and mucus secretion caused by cigarette smoke. One such study looked to see if Losartan would decrease the mucous concentration by cutting down inflammation and removing mucus from the lungs. 

The Mancini trial found that patients benefited when using either statins, ACE, ARB, or a combination of statins and ACE or ARB. The use of the combination of drugs saw the greatest benefits in reducing COPD hospitalization and mortality. 

A study by Dr. Kim, et al, looked at the effects of Losartan on human bronchial epithelial cells. The results showed that Losartan decreased airway inflammation and mucus amounts to levels seen in normal mucociliary clearance patients in vitro. The study showed that whether the cells were from smokers with or without COPD, improvements in mucociliary function were seen with smoke exposure. This study confirmed findings that were previously seen in trials on mice, suggesting that Losartan could be effective with chronic airway disease caused by cigarette smoke in reducing inflammation and mucus secretions.

Another pilot study evaluated whether Losartan slows the progression of  emphysema. The study included 106 patients, 46 with emphysema and 60 with less severe COPD, who were current or former smokers with at least a 10 pack-year history. Patients with prior use of ACE or ARB were excluded. The Losartan group took 100 mg each day for one year and was assessed with a CT scan of the lung at the start, 6-month mark, and 12-month mark. In the group taking Losartan, there was a 0.72% regression of right-middle lobe emphysema compared to a 3.34% progression in the placebo group. There also reported a 0.32% reduction in emphysema overall in the Losartan group compared to the placebo group that showed a 2.18% progression, although this did not reach statistical significance. 

The Losartan Effects on Emphysema Progression (LEEP) Trial will look to definitively determine whether Losartan slows emphysema progression in patients with COPD through high resolution CT scan. Results of this study are forthcoming. 

With Losartan showing improvements in patients with COPD, there is a strong chance that its use will continue to grow. The ability to slow emphysema and chronic bronchitis, with the possibility of regression, will aid patients in being able to stay out of the emergency room and hospital, decreasing the overall costs of care. And while there will be limitations and exclusions for patients who qualify for treatments, being able to tell patients that there is hope is exciting.

The Debrief

  • Currently no pharmacological treatment to reverse COPD
  • Research has shown that using a combination of a statin and ARB or ACE could reduce hospitalizations and decrease morbidity.
  • Further research has shown patients who use Losartan have a regression of COPD in the right middle lobe
  • The potentiality of using Losartan to treat and reverse COPD caused by cigarette smoking will change how COPD treatment is approached.

References

  1. Kim, M. D., Baumlin, N., Dennis, J. S., Yoshida, M., Kis, A., Aguiar, C., Schmid, A., Mendes, E., & Salathe, M. (2021, January 1). Losartan reduces cigarette smoke-induced airway inflammation and mucus hypersecretion. European Respiratory Society. Retrieved March 1, 2022, from https://openres.ersjournals.com/content/7/1/00394-2020
  2. Mancini, G. B. J., Etminan, M., Zhang, B., Levesque, L. E., FitzGerald, J. M., & Brophy, J. M. (2006, May 2). Reduction of morbidity and mortality by statins, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers in patients with chronic obstructive pulmonary disease. Journal of the American College of Cardiology. Retrieved March 1, 2022, from https://www.sciencedirect.com/science/article/pii/S0735109706011077
  3. Publish date: October 30, 2015, & Mitchel L. Zoler, P. D. M. D. N. (2020, July 21). Chest: Losartan slows emphysema progression in pilot trial. CHEST Physician. Retrieved March 1, 2022, from https://www.mdedge.com/chestphysician/article/104017/pulmonology/chest-losartan-slows-emphysema-progression-pilot-trial
  4. Wise, R., Holbrook, J., Brown, R., Criner, G., Dransfield, M., Han, M. L., Krishnan, J., Looney, E., Neptune, E., Palombizio, V., & Rea, A. (2021, August 2). Losartan effects on emphysema progression randomized clinical trial: Rationale, design, recruitment, and retention. Chronic Obstructive Pulmonary Diseases:Journal of the COPD Foundation. Retrieved March 1, 2022, from https://journal.copdfoundation.org/jcopdf/id/1348/Losartan-Effects-on-Emphysema-Progression-Randomized-Clinical-Trial-Rationale-Design-Recruitment-and-Retention

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