The Centre for Respiratory Research at McGill University and the Research Institute of the McGill University Health Centre
Category Archives: Lung Injury and Infection
Lung Injury and Infection Theme: The respiratory system is exposed to many environmental insults throughout life that can result in acute or chronic injury to the lungs. Both infectious and non-infectious agents can trigger inflammation, which is essential to combat infections but also requires exquisite regulation to avoid counterproductive lung damage. In addition to major respiratory pathogens such as tuberculosis (TB), dysregulated inflammation triggered by bacteria and viruses is a major contributing factor to numerous respiratory diseases (e.g., cystic fibrosis, chronic obstructive pulmonary disease). This theme investigates the key molecular signaling pathways underlying pulmonary inflammation under these conditions, with the goal of developing new targeted therapies and biomarkers predictive of disease responses. Our researchers are also leaders in the performance of large-scale diagnostic and treatment studies involving patients infected with TB.
Major scientific objectives for the lung injury and infection theme include:(1) Identify the key molecular effectors of innate and adaptive immunity required for an integrated response to respiratory pathogens such as influenza, TB, and cryptococcus neoformans. (2) Dissect host-pathogen interactions driving chronic infections versus acute infectious pulmonary exacerbations in chronic lung diseases (eg. Pseudomonas in cystic fibrosis). (3) Investigate the molecular underpinnings of beneficial versus pathological responses by different components of lung mucosal immunity. (4) Explore the mechanistic links between cellular metabolism and fibrogenic processes in the lung.
View posts, news, and publications related to this research theme below.
Congratulations Dr Nargis Khan (PDF) and Jeffrey Downey (PhD trainee), from the Dr. Maziar Divangahi laboratory, on their new study published today in Cell! The study shows that stem cells can be targeted for protective vaccination as well as be hijacked by a pathogen to increase TB virulence.
Dr. Maziar Divangahi’s latest study is in follow up to his previous work that showed that exposure of bone marrow stem cells to a live BCG vaccine (the only available vaccine for TB) reprograms these cells to generate protective innate immunity against TB. However, it was still not know what happened to these stem cells after they were exposed to the pathogen Mycobacterium tuberculosis (Mtb). In this study, the team demonstrates that soon after Mtb infection, the bacteria translocate from the lungs to the bone marrow and reprograms stem cells to impair innate immunity against TB.
“What’s new in this study is that we now know that Mtb hijacks the immune response at the very early phase of infection by accessing the bone marrow and manipulating stem cells. This leads to the generation of impaired innate immune cells, which are effectively incapacitated to fight the infection in the lung, thus allowing the bacteria to grow.”
Dr. Nargis Khan
Once the function of the stem cells has been corrupted by the Mtb pathogen, they lose their ability to fight off the infection in the lungs. In essence, alternative approaches that crack the protective code of stem cells in the bone marrow are urgently needed to eradicate TB.
Dr. Maziar Divangahi, Associate Director of RI-MUHC’s Meakins-Christie Laboratories, is an expert on tuberculosis and well known in the field of innate disease tolerance. In a recent interview with Markham Heid of Elemental.Medium.com, Dr. Divangahi confirms that tuberculosis is one of the world’s deadliest infectious diseases. Nevertheless, a great number of people who are infected with the bacteria do not exhibit any symptoms. They have developed an innate disease tolerance for the virus. Could we teach our bodies innate disease tolerance towards the SARS CoV-2 virus?
Dr. Divangahi explains how the body of some people reacts when the tuberculosis virus reaches their lower airways:
“Either the bacteria will be eliminated during the early phase of the infection, or the host will wall off (the virus) by forming granulomas.”
“We’ve developed very successful mechanisms that allow us to live with (this virus).”
“Rather than trying to eliminate the bug, we basically keep it in check.”
The elimination of the SARS CoV-2 virus would be ideal, however, the interview with Dr. Divangahi suggests that there may be acceptable alternatives.
Preliminary and not-yet-peer-reviewed studies suggest that flu vaccines may inhibit COVID-19 ‘s effect on the body. Dr. Maziar Divangahi, Associate Director of the RI-MUHC’s Meakins-Christie Laboratories, cautions against drawing the conclusion that flu vaccines prevent or diminish the effects of COVID-19 on the body. Much larger studies are required.
Numerous studies are taking place around the world to test the desired conclusion that flu vaccines do in fact inhibit COVID-19, but results that merely find correlations between behaviors and outcomes cannot establish cause and effect.
Dr. Nicole Ezer, of the RI-MUHC’s RESP Program, is looking for treatment options for COVID-19. Dr. Ezer is the lead researcher in the contain-covid.com study, an RI-MUHC trial that began in September 2020. The objective of the study is to find a medication that will keep COVID-19 patients at home longer, or ideally, eliminate the need for hospitalization completely.
Presently, Dr. Ezer is testing the efficiency ofciclesonide, an inhaled and nasal steroid drug currently used for asthma and nasal rhinitis, as one of the treatment options for COVID-19 in its early stages, or for patients with milder symptoms.
Dr. Ezer believes we will never be completely free of COVID-19, as vaccines are never 100% effective. Therefore it is important to have treatment options available, and to keep patients out of hospital whenever possible.
Dr. Ezer was interviewed about her research – the full story can be readhere:
A CBD Research Partnership Fund has been launched by the Association québécoise de l’industrie du cannabis (AQIC) and the McGill Research Centre for Cannabis. Dr. Carolyn Baglole, Director of the McGill Research Centre for Cannabis, believes this increased research funding will result in increased safety and effectiveness of medical CBD.
“We are pleased to partner with the AQIC in a project that provides much-needed financial support for CBD research, the results of which ultimately will give a better understanding of the safety and efficacy of CBD. A partnership between McGill and the private sector will allow us to combine resources, thereby raising the bar of scientific discovery, and the promise that medical cannabis holds.”
Dr. Carolyn Baglole
The launch of this CBD Research Partnership Fund marks the second anniversary of the legalization of the use of cannabis in Canada.
Dr. Carolyn Baglole of the Meakins-Christie Laboratories talks about the future of cannabis research in Canada, and how legalization has had a positive impact in this field. Funding opportunities have increased considerably and barriers to research, such as access to different cannabis products, have diminished. Stigmas surrounding medical cannabis continue to exist, but the future of cannabis research in Canada is evident.
We all know that 14 days of self-isolation is mandatory following exposure to the coronavirus, and this is a big problem when frontline health care workers come in close contact with infected patients. To avoid a shortage of essential medical staff, MI4 scientist Dr. Benjamin Smith is studying whether this isolation period could be shortened by as much as half. In this ongoing study, he is working with health care workers exposed to the coronavirus to find out. Each subject receives a COVID-19 test on days 7, 9, 10 and 14 after being exposed to determine how soon the virus can be detected. Preliminary results show that if the subject is going to develop COVID-19, the virus is usually detectable by day 7. Though further study is required to confirm this finding, it signals that, with the right testing strategy, isolation for health care workers may indeed be able to be reduced by half.
Dr. Smith is now expanding his study to confirm these preliminary results. The team is enrolling health care workers in the Lanaudière region and will now include family members and caregivers exposed to the coronavirus when caring for loved ones.
Dr. Nicole Ezer, of the RI-MUHC’s RESP Program, discusses COVID-19 treatment options with Claude Bernatchez of Radio-Canada’s Première Heure program.
Dr. Ezer explains how the virus causes uncontrolled inflammation in the body, which may result in serious respiratory issues. The steroid dexamethasone reduces inflammation and is currently given to hospitalized patients. Use of this steroid is favorable as it is not expensive and it has been used in the treatment of other other medical conditions for years. Thus, it is already known to physicians and specialists and has been is backed by numerous studies. Unfortunately, steroids used at such high doses as is needed to combat COVID-19 may cause other illnesses, such as diabetes; therefore, this treatment is only available to individuals who are hospitalized.
A second COVID-19 treatment option is antiviral medications, which slow the replication of the virus. Antivirals are being prescribed early in the COVID-19 diagnosis, with the intent of avoiding a future hospitalization of the patient.
Treatment with antibodies would boost the immune system and help the body to fight off the virus. Additional research could be done to determine the stage at which this type of treatment would have the greatest effect. At this point in time, the use of antibodies for treatment of COVID-19 has not been approved in Canada.
Dr. Ezer concludes by emphasizing the need for an effective and inexpensive treatment for COVID-19. A vaccine is needed, but vaccines are not always 100% effective. The virus will always be with us, and there will be many people worldwide who will catch it. We need to discover additional affordable COVID-19 treatment options.
Dr. Ezer’s interview on Radio-Canada can be heard here:
Dr. Jean Bourbeau contributed to an article in The Star on September 29, 2020. He highlights how our narrow focus on vaccines during the COVID-19 pandemic is a risk we cannot afford. Combating this virus requires an array of good treatments, based on good science (randomized, placebo-controlled clinical trials). This include antivirals, plasma trials, corticosteroids, repurposing of old drugs to address the virus, in addition to vaccines. Dr. Bourbeau is working on a Phase III clinical trial of a repurposed generic drug developed by Pulmonem, a Canadian biotech start-up, which could provide a quick, safe and cost-effective treatment for COVID-19.
Led by Dr. Nicole Ezer, a team of RI-MUHC researchers have initiated a clinical trial of ciclesonide to possibly prevent mild cases of COVID-19 from worsening.
Ciclesonide is an inhaled and nasal steroid drug currently used for asthma and nasal rhinitis. Laboratory studies have already shown that treatment with ciclesonide can decrease viral replication of SARS-Cov2, the virus responsible for the disease. This placebo-controlled randomized trial will confirm if the administration of inhaled and nasal ciclesonide can reduce the severity of respiratory symptoms among mild cases of COVID-19 and potentially avoid the need for hospitalization and oxygen.
Diagnosed with COVID? Contain COVID at the source. Protect your lungs! Register for a clinical trial of inhaled ciclesonide:
“We know the COVID-19 virus starts by multiplying in the nose and progresses downwards to the lower parts of the airways and lungs. We hope that targeting the site of viral replication with inhaled and nasal ciclesonide will reduce early viral replication and decrease severity of COVID-19 illness,”
– Nicole Ezer
Nicole Ezer, Respirologist, MD, MPH
James Martin, Respirologist, MD, Dsc
Todd Lee, Infectious Diseases, MD Msc
Emily Macdonald, Internal Medicine, MD, Msc
Susan Bartlett, Clinical Psychologist, Senior Scientist
Andrea Benedetti, Epidemiology and Biostatistics PHD