Recent Drug Trials for the Treatment of Respiratory Diseases

Much confusion and frustration have marked the last few years surrounding the best available therapies for patients suffering from respiratory diseases. By all accounts, encouraging vaccination against COVID-19 and teaching good respiratory hygiene practices are the best ways to keep patients healthy.

However, there is still a need for effective treatments for patients once they’ve contracted COVID-19 (or any other respiratory condition, for that matter). This is especially true with regards to the Omicron variant of SARS-CoV-2, which can infect even fully vaccinated patients.

Currently, there are many treatments undergoing trials to treat COVID-19 and other pulmonary conditions, some of which are showing great promise.

The mechanisms of action of these therapeutics and medications are varied, and some of them are not yet well-understood. However, it’s still worth investigating these novel approaches geared toward addressing respiratory health conditions.

In this article, we will provide an overview of some of the antitussives undergoing clinical trials, and other treatments used in the field of pulmonary medicine.

Medications to Manage COVID-19

The NIH recently updated its recommendations on outpatient management of patients with COVID-19. The group’s guidance based on patient presentation is as follows:

High-Risk, Nonhospitalized Patients, Who Don’t Require Supplemental Oxygen

For this group, the NIH suggests the use of the following medications, listed below in descending order of preference:

Nirmatrelvir/ritonavir

An oral medication introduced by Pfizer, Paxlovid, has presented in clinical trials an efficacy of just under 90% for decreasing symptoms in high-risk patients with COVID-19.

Paxlovid works by binding with and blocking the action of an enzyme that is integral to the virus’s ability to replicate.

Sotrovimab

This intravenous medication has been cleared for emergency use authorization and is a promising treatment for patients suffering from COVID-19.

Sotrovimab is a monoclonal antibody designed to bind to the SARS-CoV-2 viral particles (spike protein), rendering them incapable of replicating in a currently unknown mechanism of action. The results of this medication thus far are promising, but this class of drugs needs further study to determine how well they work against respiratory diseases such as COVID-19.

Remdesivir

Although it has become a widely controversial drug, remdesivir appears as a suitable ancillary treatment for COVID-19. This drug terminates replication of the viral genome by competing with an essential component of the process. Furthermore, it has demonstrated efficacy through both in vivo and in vitro trials.

Some groups shied away from remdesivir due to mixed trial results and the political battle that has raged about the drug. Furthermore, a study in 2020 showed that the drug was ineffective, sending the world into a wide-ranging debate.

Now, nearly two years later, it appears that remdesivir is a good choice for use in some patients who are dealing with COVID-19. The evidence is mounting that this treatment is safe for patients, assuming that said patients are adequately screened and there is thoughtful consideration given to any contraindications.

Molnupiravir

Developed by Merck and cleared for emergency use authorization in some cases, molnupiravir introduces errors into the genetic sequence of the virus. The drug is taken orally and seems to work well in patients aged 19 and older. For younger patients, researchers are concerned that the drug may interfere with the normal development of bone tissue.

As is always the concern with any treatment, providers must weigh the potential harm the therapeutic may cause against the patient’s benefit and the relative risk against disease.

Glucocorticosteroids

Steroidal medication, such as dexamethasone, is contraindicated for the patient group of high-risk, non-hospitalized patients. Unless, of course, other factors necessitate the use of said drugs, or the patient’s symptoms are severe.

The recommendations on the use of dexamethasone have changed slightly throughout the pandemic. Some studies show significant benefits in the use of the medication, however, issues caused by the use of glucocorticosteroids for similar diseases in the past have made some physicians hesitant to prescribe the drug.

As time goes by, and our understanding of COVID-19 improves, we will be better able to understand how this novel virus differs from other infectious diseases we’ve encountered in the past. This will lead us toward better recognition of which therapies will be most effective and why this is the case.

Patients in Stable Condition, Released from Hospital, Not Requiring Oxygen Supplementation

Upon hospital discharge after COVID-19, the NIH does not recommend prescribing remdesivir. Furthermore, they advise against the prolonged use of steroidal medications such as dexamethasone.

Patients Given Supplemental Oxygen Upon Hospital Discharge

Currently, there isn’t a preponderance of evidence to recommend for or against the use of medications such as remdesivir and glucocorticosteroids for this group.

Patients with Increasingly Severe Symptoms, Who Must be Discharged from the Inpatient Setting

Due to overwhelmed hospitals, some patients have had to be discharged, even when their symptoms are worsening. This surge in hospital visits due to COVID-19 is made worse by the fact that many facilities are short-staffed as is.

Regardless of any of these factors, however, patients need to be seen when experiencing life-threatening symptoms. Therefore, patients who cannot receive care through traditional hospital emergency room visits in their area may receive home care or other methods of treatment as an alternative to an inpatient stay.

For this group, the NIH recommends the use of dexamethasone along with supplemental oxygen for up to 10 days. Moreover, Remdesivir may also be considered but should be used only on a case-by-case basis.

Antitussives Undergoing Clinical Trials

Various antitussive treatments have been developed or repurposed over the past few years in an effort to combat new respiratory issues as they arise.

Magnesium Infusion as an Antitussive

In one study, researchers investigated the use of magnesium infusions, as opposed to the traditional use of opioids, when inserting a double-lumen endotracheal tube into a patient’s respiratory pathway. During this procedure, patients will often cough, creating discomfort and risk of poor outcome for the patient and increased difficulty for the medical team.

Interestingly, the study found that with the use of magnesium infusions, coughs were reduced dramatically during this procedure. Furthermore, the magnesium infusions created no adverse reactions. Therefore, this finding may bear further investigation for the use of magnesium in antitussive medicine.

Montelukast for COVID-19

In a study from 2020, researchers found that montelukast, an asthma drug, may help reduce the severity of COVID-19 symptoms and help prevent the progression of the disease. The authors of the study point to the many unique properties of the medication and the low level of risk that it poses to patients across many different demographics, and with various comorbidities.

Furthermore, in 2021, the drug was used in hospitals to manage the symptoms of patients with COVID-19 and demonstrated positive outcomes.

But while the authors of both studies found value and potential in using montelukast to treat COVID-19, the drug is not without its share of drawbacks. For one, widespread use of the drug for COVID-19 may deprive asthma patients of this life-saving treatment. Secondly, further studies are certainly needed to determine the exact mechanism of action for the drug regarding COVID-19.

Capsicum for Idiopathic Coughing

In 2019, researchers began a study to determine whether oral chili extract could decrease symptoms in those with coughs of unknown origin. Specifically, they are testing whether capsicum supplementation can lead to a less sensitive cough reflex, thereby decreasing the frequency of coughs.

Hopefully, with the use of natural treatments such as the chili extract as mentioned above, we’ll have more tools with which to combat respiratory issues leading to coughing and other symptoms.

Dextromethorphan for Acute Cough in Pediatric Patients

In 2016, researchers initiated a study to determine whether the drug dextromethorphan would be effective for treating acute coughs in younger patients. The medication is widely used as an over-the-counter remedy for the treatment of cough-related disease, and researchers were interested in how it would affect newly-acquired cough symptoms in younger patients.

Unfortunately, this study was terminated due to low participation in 2019 and 2020.

Vibroacoustic Therapy for Respiratory Failure

Beyond medication-based treatments for respiratory symptoms, there are other options with which healthcare teams can address patients’ needs.

For example, in the respiratory therapy and physical therapy realm, vibroacoustic techniques have demonstrated effectiveness for patients over the years. A new study completed in July of 2020 sought to determine whether a device known as the Vibrolung was helpful for patients with respiratory failure caused by COVID-19.

In the age of COVID-19 and other respiratory diseases, it will likely take a combined effort from a team of medical professionals and device manufacturers to develop effective treatments. It’s possible that devices such as vibroacoustic pulmonary therapies and older treatments used in physical and respiratory therapy over the past few decades will become a part of the arsenal of tools available for the treatment of the new diseases we are now seeing.

Conclusion

The new developments in cough treatments and therapies have been remarkable. First off, we’ve developed numerous methods to prevent and treat COVID-19 as well as other conditions. Beyond that, researchers have continued to produce promising new medications to address health concerns related to many other respiratory conditions as well.

Hopefully, through continued investigation and rigorous study, we can produce medication-based antitussives that will make diseases like COVID-19 much less of a concern in the future. Beyond the use of medication, however, there are also compelling ongoing studies to determine the efficacy of devices and therapies for improving cough/respiratory symptoms in patients. Medical devices, manual therapy treatments, and cough exercises have been found to improve the outcome of patients after discharge from the hospital with COVID-19.

Concurrently, some companies have found ways to improve diagnostics and treatment recommendations for patients looking for a remote, mobile solution to respiratory symptoms such as cough. One group that is taking revolutionary strides toward improving the field of cough-related disease diagnosis and treatment is Hyfe. The team at Hyfe has developed a mobile app that helps patients track their cough symptoms through a smart device. To learn more about Hyfe’s innovative contribution to the field of respiratory medicine, check out their website here.