Triple Drug Combinations, Stem Cell And Gene Therapies — Potential COPD Treatments In Future

Chronic obstructive pulmonary disease awareness month: Welcome back to “The Science Of Health”, ABP Live’s weekly science column. Last week, we explained how climate change and air pollution affect cardiovascular health, which communities are most vulnerable to the impacts of climate change, and what must be done to reduce the risk of heart diseases occurring as a result of climate change. This week, we discuss the latest advancements in the treatment of chronic obstructive pulmonary disease (COPD), and science advances that can serve as treatments in the future.

COPD is a group of diseases that results in airflow blockage due to damage to the airways or other parts of the lung, making it hard to breathe. COPD is primarily of two types: emphysema and chronic bronchitis. Emphysema involves damage to the lungs over time, while chronic bronchitis involves a long-term cough with mucus. 

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In emphysema, the air sacs in the lungs are affected. The elastic air sacs become filled with air when one breathes in, like small balloons, and deflate when one breathes out. The walls between many of the air sacs in the lungs become damaged when one suffers from emphysema. As a result, the air sacs lose shape and become floppy. 

Since the walls of the air sacs can also be damaged, there are fewer and larger air sacs instead of many tiny ones, making it harder for the lungs to move oxygen and carbon dioxide out of the body. 

In chronic bronchitis, there is inflammation and irritation of the bronchial tubes, which are airways carrying air to and from the air sacs in the lungs. When the bronchial tubes are irritated, mucus is produced. Due to the swelling of the tubes and mucus formation, the lungs find it hard to move oxygen in and carbon dioxide out of the body. 

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Current treatments for COPD

While there is no cure for COPD, it can be controlled, and one can take steps to ensure that the symptoms do not get worse. Since smoking is the main cause of COPD, people who smoke must quit this habit to slow lung damage. 

According to the US National Institutes of Health (NIH), medicines used to treat COPD are quick-relief drugs that help open the airways, anti-inflammatory drugs to reduce swelling in the airways, control drugs to reduce lung inflammation, and long-term antibiotics. 

When COPD is severe, one may need to receive steroids by mouth or intravenously, oxygen therapy, bronchodilators, and assistance from a machine to help breathing with the help of a mask or through an endotracheal tube. 

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Oxygen therapy may be required if one has a low level of oxygen in the blood.

Pulmonary rehabilitation is a medical programme aimed at making the lives of people with lung diseases better through exercise and education. This helps improve the physical function of patients, and reduces their symptoms. The patients are given exercise training, psychological counselling, and education. 

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Advanced treatments for COPD

Lung volume reduction surgery (LVRS) and bullectomy are some treatment options in which damaged, hyper-inflated, and non-functioning portions of the lungs are removed. This improves lung function because the remaining healthy portion of the lung can work better.

“Treatment options for some patients with severe COPD are lung volume reduction surgery (LVRS) and bullectomy which involves removing damaged, hyperinflated and non-functioning portions of the lung and improving lung function by allowing the remaining healthy lung parts to work better,” Dr Vikas Mittal, Associate Director, Pulmonology, Max Hospital, Shalimar Bagh. told ABP Live.

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Lung transplant

However, if one has advanced COPD, and their conditions keep worsening despite taking all precautions and undergoing all forms of treatment, they should opt for lung transplant.

“Lung transplant involves replacing the lungs affected by COPD with healthy lungs from an appropriate brain-dead donor. Lung transplantation requires meticulous patient selection and is a specialised procedure performed by a team of experts at select centres. It is a costly treatment option and needs long term immunosuppression treatment and follow ups,” said Dr Mittal.

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The reason why immunosuppression is needed is that the immune system may reject the newly replaced lungs.

Lung transplantation is an option people choose when they have end-stage COPD. 

“Lung transplantation offers renewed hope and extended life expectancy for eligible candidates,” Dr Ravi Shekhar Jha, Director & HOD, Pulmonology, Fortis Escorts Hospital, Faridabad, told ABP Live.

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Personalised therapies and targeted biologics

Targeted biologics, which are isolated from a variety of natural sources such as humans, animals, and microorganisms, and personalised therapies are some science advances that may potentially treat COPD in the future. Cutting-edge inhalers may be developed, and drug delivery systems may be enhanced, which improve patients’ prognosis. Respiratory support can be improved through non-invasive ventilation techniques, especially in severe cases.  

“Advanced pharmaceuticals, such as targeted biologics and personalised therapies, aim to mitigate symptoms and halt disease progression. Cutting-edge inhalers and drug delivery systems enhance efficacy and convenience for patients. Additionally, non-invasive ventilation techniques revolutionise respiratory support, particularly in severe cases. These collective advancements represent a transformative era in COPD care, underscoring a commitment to enhancing both longevity and quality of life for individuals affected by this chronic condition,” said Dr Jha.

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Triple drug combinations

Latest advancements in treatment of COPD include triple drug combinations that involve the use of long-acting beta antagonists (LABAs), long-acting muscarinic antagonists (LAMA), and inhaled steroids.

What are LABAs and LAMAs?

LABAs are used in combination with inhaled corticosteroids for the treatment of bronchoconstriction in patients with COPD, chronic bronchitis, and emphysema. Salmeterol, arformoterol, and formoterol are some LABAs approved by the US Food Drug and Administration (FDA). 

LAMAs improve lung function and reduce exacerbations when they are used with inhaled corticosteroids and LABAs, according to a study published in the Annals of Allergy, Asthma, and Immunology.

Tiotropium, umeclidinium, aclidinium, and glycopyrronium are some examples of LAMAs. 

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What are ultra long-acting bronchodilators?

Ultra long-acting bronchodilators are also some advanced treatments for COPD. These are used to provide control, and should only be used with inhaled steroids. They open the airways, and relieve the symptoms of respiratory conditions. 

According to the NIH, indacaterol, vilanterol, and olodaterol are the three ultra long-acting bronchodilators approved for the treatment of COPD. 

LABAs work for six to 12 hours, and ultra-long-acting bronchodilators work for 24 hours. 

These medications not only control COPD symptoms, but also decrease hospitalisation.

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“Latest advancements in the treatment of COPD include triple-drug combinations of long-acting beta antagonists (LABA), long-acting muscarinic antagonists (LAMA), and inhaled steroids.  Ultra-long-acting bronchodilators, such as indacaterol and vilanterol offer prolonged bronchodilation. They can be consumed once a day. These latest treatment options reduce worsening of COPD, decrease hospitalisation, and improve overall quality of life,” said Dr Mittal.

What are long-term macrolide antibiotics and PDE-4 inhibitors?

Long-term macrolide antibiotics can also be used to treat COPD and reduce the frequency of exacerbations in patients with bronchiectasis, a condition in which the bronchial tubes or airways become damaged, as a result of which they widen, and become loose and scarred. 

Phosphodiesterase-4 (PDE-4) inhibitors are used to block the breakdown of cyclic adenosine monophosphate, which is one of the essential agents involved in suppressing inflammatory responses. Therefore, in this way, PDE-4 inhibitors decrease airway inflammation, but have no direct bronchodilator activity. 

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The only PDE-4 inhibitor approved for the treatment of patients with severe COPD is roflumilast, according to the NIH.

“Other newer pharmacotherapy options are long term macrolides antibiotics and phosphodiesterase-4 (PDE-4) inhibitors, such as roflumilast,” said Dr Mittal.

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Combination inhalers

Combination inhalers are a latest advancement in which bronchodilators are used in combination with steroids to reduce airway inflammation. 

“Some combination inhalers combine the medication of short-acting bronchodilators with anticholinergic inhalers or long-acting bronchodilators with anticholinergic inhalers,” Dr Kuldeep Kumar Grover, Head of Critical care and Pulmonology, CK Birla Hospital, Gurugram, told ABP Live.

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Short-acting bronchodilators are used as short-term relief from sudden, unexpected attacks of breathlessness, and long-acting bronchodilators help control breathlessness in asthma and COPD, according to the National Health Service (NHS). 

Long-acting bronchodilators must always be taken with corticosteroids. 

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Salbutamol, levalbuterol, and pirbuterol are examples of short-acting bronchodilators.

Anticholinergic bronchodilators are drugs that block the action of acetylcholine, which is a chemical released by the nerves that can result in the tightening of the bronchial tubes. Therefore, anticholinergic function by blocking acetylcholine.

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Non-invasive ventilation and long-term oxygen therapy

Other advanced techniques to treat chronic respiratory failure in COPD patients include non-invasive ventilation, in which oxygen is delivered to the lungs with the help of positive pressure without the need for endotracheal intubation. At home, an oronasal mask can be used. As a result, the patient does not need to put much effort into breathing.

Patients who have had respiratory failure must undergo long-term oxygen therapy because it is the treatment proven to improve survival in COPD patients. Long-term oxygen therapy should be used for 15 to 16 hours a day, and if possible, 24 hours a day. It raises arterial oxygen levels to a desirable range. Oxygen cylinders and concentrators can be used to give long-term oxygen therapy. 

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“Non-invasive ventilation (NIV) at home has also improved the management of acute worsening and chronic respiratory failure in COPD patients. Domiciliary NIV means providing ventilatory support through an interface like oronasal mask at home. This reduces the work of breathing, thus improving respiratory failure and reducing mortality. Long-term oxygen therapy (LTOT) is the most important treatment for COPD patients who have developed respiratory failure and it aims to improve low blood oxygen levels, improve exercise tolerance, and quality of life and survival. LTOT can be given through stationary and portable oxygen concentrators, and oxygen cylinders,” said Dr Mittal.

Future potential treatments for COPD

Stem cell therapy and gene therapy are potential treatments for COPD. Stem cells collected from a donor or the body of the COPD patient can be used to repair and regenerate damaged lung tissues. This research is currently in the initial stages of clinical trials, and hence, medical practitioners will have to wait for the results of the ongoing trials to know the effectiveness and long-term safety of stem cell therapy in COPD treatment, according to Dr Mittal.

Researchers hope that once the stem cells are injected into the body of the patient, they will become specialised cells, and can help regenerate damaged lung tissue. 

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“Researchers believe stem cells could be used to create new alveolar cells. These are the cells that are responsible for the exchange of air and gases in the lungs. The FDA has approved stem cell therapy for COPD in human clinical trials, but it is not currently available as a treatment. If approved in the future, this type of treatment could be used to regenerate lung tissue and reverse lung damage,” said Dr Grover.

Gene therapy, which is in the preclinical stage, aims to correct genetic defects in COPD patients.

It is believed that gene therapy can be used to incorporate therapeutic genes into COPD patients to reverse the disease, according to Dr Mittal.

Therefore, triple drug combinations, non-invasive ventilation, lung volume reduction surgery, long-term oxygen therapy, and bullectomy are some advanced treatments for COPD, and stem cell therapy and gene therapy are potential treatments for COPD in the future.

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