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.
Dr. Arnold Kristof was recently interviewed by La Presse and CTV News about a recent experience working in the Intensive Care Unit at the Royal Victoria Hospital. He shares how the pediatric and adult hospitals came together to save a pregnant woman diagnosed with a severe form of COVID-19, and to deliver her child.
25 Seconds to Save Bella is a piece about a woman in intensive care who experienced severe symptoms of COVID-19 while pregnant. She was having a lot of difficulty breathing. The baby was pressing on her diaphragm, adding to her breathing difficulties. With the adult and pediatric hospitals working together, Dr. Kristof and the team succeeded in saving the mom and successfully delivered her daughter as well. No other hospital has succeeded at what this team of dedicated medical professionals at the MUHC accomplished.
Teamwork and trust in the other members of the team are also essential elements for success.
During the pandemic, Dr. Kristof has continued his research program at the Meakins while working in the MUHC Intensive Care Unit.
Dr. Dao Nguyen and Dr. Sara Mahshid receive MI4 Seed Funding to develop an ultrasensitive colorimetric fluidic assay for rapid phenotypic antibiotic susceptibility testing. Antibiotic resistant bacteria are responsible for 700,000 deaths annually, a figure that is projected to rise to 10 million deaths per year by 2050 if no action is taken to halt this global threat. The overuse of antibiotics and the prescription of antibiotics to which bacteria are not susceptible, contribute to the rise of antibiotic resistance. This proposal will develop an ultrasensitive colorimetric fluidic assay for rapid phenotypic antibiotic susceptibility testing (AST). The project is anticipated to reduce the turnaround time of the AST to less than 1 hour compared to 3-4 days using conventional AST methods.
Over the past years the CIHR has provided substantial funding to Dr. Menzies and his research team at the TB Centre. Putting the funds to good use, Dr. Menzies has defined a treatment protocol for TB, which is now in use across North America. Now it is time to take that research further.
In response to a joint application made by CAB-V (Canada, Australia, Benin and Vietnam), an international network led by Dr. Menzies, the CIHR-III has awarded the McGill International TB Centre a further $17.2 million over the next ten years to continue its research and clinical trials on the treatment, diagnosis and prevention of TB. Further studies are being planned for the near future at sites and with co-investigators across Canada and around the world.
As a specialist in Interstitial Lung Disease (ILD) at the Meakins-Christie Laboratories, Ilan Azuelos, MD is an ardent promoter of improving outcomes for ILD patients. Treatment options for people with rare lung diseases, such as progressive fibrosing interstitial pulmonary fibrosis, may portend a life expectancy of between five and six and a half years after onset of symptoms. Dr. Azuelos knows that with research and education of the general public, this life expectancy can be improved.
“Ainsi, les personnes affligées de cette maladie seraient en mesure de passer plus de temps avec leur famille et de profiter au maximum de la vie.”
Ilan Azuelos, MD, MSc
Fortunately, programs have been initiated to address this area of medicine. MEDTEQ+, a pan-Canadian consortium for medical innovation, is bringing together industry leaders such as Boehringer Ingelheim Canada in partnership against PF-ILD. They aim to identify potential solutions to address the gaps in care for patients with IPD-PF, with the goal of accelerating access to treatments that delay the deterioration of lung function.
With the general public more aware of the symptoms of the onset of lung disease, patients could seek out treatment at an earlier stage. Increased funding for research would lead to a better understanding and the development of novel treatment options. Each would play an important role in a better, perhaps longer, life after diagnosis.
Read the following articles to learn more of the importance of improving education and treatment options for patients with ILD:
The Journal de Montreal reports the pursuits of our Quebec researchers and physicians in leading this trial. Ciclesonide has both anti-viral and anti-inflammatory properties. Of the few trials testing ciclesonide, the one led here at the MUHC is the only one that is studying the administration of the drug by nasal spray and inhaler. Inhalers and sprays have the advantage of acting directly in the nose, the airways, and the lungs, right were the SARS-CoV-2 virus is actually replicating. The goal of the trial is to determine whether ciclesonide reduces respiratory symptoms and in turn reduces hospitalizations.
Dr. Ezer is an Assistant Professor in the Department of Medicine at McGill University and a Junior Scientist with the RI-MUHC RESP Program.
The RI-MUHC is currently enrolling patients in RESOLUTION, a clinical trial of LAU-7b for the treatment of hospitalized COVID-19 patients. The drug acts on lung inflammation and showed potent antiviral effects in-vitro against SARS-CoV-2. Results from previous studies in adult CF patients showed an important reduction of key pro-inflammatory biomarkers at the onset of a pulmonary exacerbation episodes, suggestive of a protective effect of the drug on the lungs.
An original post from April 2020 described the start of the clinical trial:
Laurent Pharmaceuticals, a McGill spinoff, will run a Phase 2 clinical study with LAU-7b, a pro-resolving drug with potential antiviral properties against coronavirus.
Larry Lands is the Chief Medical Advisor for Laurent Pharmaceuticals. Laurent Pharmaceuticals Inc. is planning to test its lead drug LAU-7b in patients with COVID-19 disease. LAU-7b was recently identified as a potential anti-viral therapeutic option for COVID-19 during a drug-library screening effort.
The Research Institute of the MUHC is presently enrolling participants in the study, called RESOLUTION. LAU-7b is a novel oral form of a drug called fenretinide, which inhibits the inflammatory reaction of the body to the virus. This study could lead to improved treatments for hospitalized COVID-19 patients who are at higher risk of developing complications.
“Thanks to its inflammation-controlling properties, low-dose fenretinide triggers a natural mechanism – the body’s own resolution of the inflammation process – which keeps the inflammatory response under control without suppressing its protective immune role.”
It is World Antimicrobial Awareness Week and Dr. Dao Nguyen, a researcher at MI4 and clinician-scientist at the Meakins-Christie Laboratories and the RI-MUHC, dreams of applying her knowledge and skills to preventing a post-antibiotic world. We have all read about the increasing strength of bacteria and hear how our present-day antibiotics are becoming ineffective. In fact, it is estimated that 20-30% of currently existing bacteria are resistant to available drugs. The WHO estimates that by 2050 drug-resistant organisms will surpass cancer as the primary cause of death. This is the problem Dr. Nguyen would like to take on.
She would like to create an interdisciplinary Antimicrobial Resistance Centre where members of the scientific community can combine their knowledge and work towards preventing a post-antibiotic world. Thanks to the MUHC Foundation’s fundraising efforts, Dr. Nguyen’s dream of an Antimicrobial Resistance Centre will likely come to fruition – something we should each be thankful for. Dr. Nguyen explains:
“Let’s say you accidentally cut yourself. Right now, you can get treatment from a topical cream or take antibiotic pills to cure the infection in a few days,” says Dr. Nguyen. “With antibiotic-resistant bacteria, it wouldn’t be treated as easily and the infection could spread requiring an amputation.”
An amputation would be an extreme result from a simple cut on the finger, yet an all too possible outcome if research is not carried out and solutions are not found.
Dr. Mazer, Associate Scientific Director of the Taskforce, sums up the goal of their work as: to understand the prevalence of the virus in the community at large, and to learn about how the body responds to the virus. Completed studies in this area have revealed the following:
“We know that the prevalence of the antibodies in the population of healthy blood donors is between 0.7% and 1.0% of the population, as high as 2.9% in certain areas of Quebec and Ontario.”
Dr. Bruce Mazer
Although these numbers indicate a lack of herd immunity, he feels it is more important to understand how to treat individuals who are most at risk, to develop a vaccine, and to find answers to some of their yet-to-be-answered questions. Finding answers to questions such as why some people are more affected by this virus than others, why some people are more affected by previous viruses but not this one, and how long the antibodies created by vaccination will last in the body, would go a long way in decoding immunity to COVID-19.
Listen to Dr. Mazer’s interview by Julie Quenneville on:
Since the spring physicians have been discovering optimal treatments for COVID-19 symptoms. Dr. Nicole Ezer, a researcher with the RI-MUHC’s RESP Program, was interviewed on this subject on CJAD. Dr. Ezer explained:
Initially it was very challenging to know how to treat patients appropriately, in particular patients who presented in the emergency room and required lots of oxygen.
Dr. Nicole Ezer
Since the spring the medical community has learned a lot about this virus, thanks in part to the many publications that have come out.
The names of medications which have been found best to help hospitalized patients include the steroid dexamethasone and the antiviral remdesivir. These two medications have been very helpful in not only reducing the amount of time patients spend in hospital, but also the number of deaths caused by this virus. These were important discoveries for the medical community.
The focus remains on finding treatments to help patients with less severe symptoms. To this end, all residents of Quebec experiencing milder COVID-19 symptoms are encouraged to take part in an ongoing study at the MUHC called contain-covid19.com. No in-person visits are required. After acceptance into the trial participants will receive their medication by mail. All communications are done remotely. This is one way we can all be involved in the hunt for treatments for COVID-19.
Dr. Dao Nguyen is a researcher with the Meakins-Christie Labs and M[i]4(the McGill Interdisciplinary Initiative in Infection and Immunity). In this interview, which appears on the MUHC Foundation’s Health Matters Series, Dr. Nguyenexplains the value of the M[i]4 initiative. Not only does this initiative provide researchers with funding for their research, it also enables them to share ideas across numerous disciplines, thus increasing their chances of developing new ideas and finding solutions.
Dr. Nguyen believes that when the general public hears the word ‘infection’, their mind is likely to focus on COVID-19; however infection, antibiotics and immunity go far beyond this virus. Infection control is important for individuals in many circumstances, such as undergoing surgery, chemotherapy or even when someone cuts their hand. Over time, infections are getting stronger and new antibiotics are needed to treat them. Pharmaceutical companies were committed to the development of new treatments in the 60’s, 70’s and 80’s, but are now focusing their efforts in more profitable areas. This leaves a void which the M[i]4 initiative hopes to fill.
Although M[i]4 receives funding from various sources, donations also play an important role. A donation can help to move an idea from paper to the laboratory. Donations can help with the completion of a project or infrastructure. Dr. Nguyen highly values donations received, and appreciates this financial support for their valuable work.