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.

Systematic testing of groups at increased risk of SARS-CoV-2: an affordable and reasonable approach. Dr. Dick Menzies (centre) is a senior scientist in the Translational Research in Respiratory Diseases Program at the RI-MUHC. Jonathon Campbell, PhD, is a postdoctoral fellow at the RI-MUHC.

Systematic testing for SARS-CoV-2

In a new cost-analysis study, researchers recommend widespread SARS-CoV-2 testing of priority groups, including healthcare workers, school students and staff, and essential services employees. The study was led by Dr. Jonathon Campbell, postdoctoral Fellow and Dr. Dick Menzies, senior scientist in the Translational Research in Respiratory Diseases Program at the RI-MUHC.

“We believe that a strategy of actively testing large population groups who are at increased risk of acquiring SARS-CoV-2 is feasible and affordable in Canada. This testing approach should be an integral component of a broad strategy to allow all Canadians to return safely to work and school,”

The benefit of widespread testing would be detection and isolation of asymptomatic people infected with SARS-CoV-2. This could prevent community transmission, which otherwise could result in a second wave, and a second shutdown.

Read more:

About the publication

Active testing of groups at increased risk of acquiring SARS-CoV-2 in Canada: costs and human resource needs. Campbell JR, Uppal A, Oxlade O, Fregonese F, Bastos ML, Lan Z, Law S, Oh CE, Russell WA, Sulis G, Winters N, Yanes-Lane M, Brisson M, Laszlo S, Evans TG, Menzies D. CMAJ. 2020 Sep 9:cmaj.201128.

The Royal Society of Canada announced Dr. Maziar Divangahi as one of McGill's newest members to the College of New Scholars

Royal Society of Canada Class of 2020

Congratulations Dr. Maziar Divangahi! Dr. Maziar Divangahi is among the 50 new Members of the College, and among the ten McGill researchers honored by the Royal Society of Canada. The Royal Society of Canada (RSC) and its Members have elected this year’s new Fellows and named the incoming class of The College of New Scholars, Artists and Scientists. This year’s cohort includes some of McGill’s most accomplished researchers and scholars. For the Class of 2020, 87 new Fellows and 50 new members to The College of New Scholars, Artists and Scientists were announced.

“I am very proud to become a member of the RSC. This achievement reflects the amazing family, friends, colleagues, and McGill community that have supported me along the way,”

– Maziar Divangahi

New Members to the College are Canadians who, at an early stage in their career, have demonstrated a high level of achievement. Fifty-one Canadian universities and the National Research Council nominate members to the College, which is the first national system of multidisciplinary recognition for Canadian intellectual leadership. Each new cohort represents an emerging generation of scholarly, scientific and artistic leadership from coast-to-coast. Recognition by the RSC is the highest honour an individual can achieve in the Arts, Social Sciences and Sciences. The College provides the Royal Society of Canada with a multigenerational capacity to help Canada and the world address major challenges and seize new opportunities including those identified in emerging fields.

“The Royal Society of Canada is delighted to recognise this year’s exceptional cohort of inductees, as the contributions of these outstanding artists, scholars and scientists have significantly impacted their respective disciplines at both national and international levels.” 

RSC President Jeremy McNeil.

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About Dr. Maziar Divangahi:

Maziar Divangahi is an internationally renowned pulmonary immunologist who has made major contributions to our understanding of both innate and adaptive immunity to pulmonary infectious diseases. His pioneer work on innate immune memory has identified hematopoietic stem cells as potential target for the development of novel vaccine against pulmonary infections, such as tuberculosis (M. tuberculosis), influenza (H1N1), and coronaviruses (SARS-CoV2). He is currently holding the Strauss Chair in Respiratory Diseases (McGill University).

Dr. Irah King sheds some light about disease tolerance in light of the recent COVID-19 pandemic. - read about disease tolerance

COVID-19 and Disease Tolerance

There is much to be learned still as to why some people with COVID-19 are asymptomatic while others develop symptoms, sometimes severe. The prevailing theory is that their immune systems fight off the virus so efficiently that they never get sick. But some scientists are confident that the immune system’s aggressive response, the churning out of antibodies and other molecules to eliminate an infection, is only part of the story.

Our knowledge of how our immune system fights off a virus is constantly evolving and involves both disease tolerance and resistance. The phenomenon of disease tolerance, which is an inherent component of immunity, is defined as the ability of a host to limit the impact of pathogens. In other words, it is the mechanism that limits tissue damage independent of changes to pathogen burden. This is different from disease resistance, in which the host is able to prevent infection or reduce the number of pathogens. Disease tolerance is well-known in plants but has only been documented in animals within the last 15 years. Disease tolerance may at least partially explain why some infected people have mild symptoms or none at all.

Dr. Irah King sheds some light about disease tolerance in light of the recent COVID-19 pandemic. Read the full article here:

Why Do Some People Weather Coronavirus Infection Unscathed? Some scientists are confident that the immune system’s aggressive response to infection is only part of the story.

by Emily Laber-Warren

Drs. Irah King and Maziar Divangahi have also co-authored an editorial on the subject in Frontiers in Immunology:

Editorial: Evolving Mechanisms of Disease Tolerance. King IL, Divangahi M. Front Immunol. 2019 Dec 20;10:2974.

In this editorial, Divangahi and King discuss the history of disease tolerance. The concept of disease tolerance was first introduced following observations in plants in the late 19th century. It was only more than a century later that similar observations were seen in animals following infection. This then opened up a whole new field of immunology that started to tease out the cellular and molecular mechanisms of this concept.

A deeper understanding of disease tolerance could lead to “a new golden age of infectious disease research and discovery,”

Irah King and Maziar Divangahi

A series of reviews are featured in this issue that detail how this defense strategy is conserved from plants to humans against diverse forms of infection. Reviews by Meakins members are prominently featured, including:

Dr. Jean Bourbeau, member of the Translational Research in Respiratory Diseases Program and director of the Centre for Innovative Medicine at the Research Institute of the MUHC. Old drug, new therapy: RI-MUHC-sponsored phase III clinical trial ready to test repurposed dapsone to tone down lung inflammation caused by COVID-19

Drug Repurposing for COVID-19

Dr. Jean Bourbeau is leading a new Phase III clinical trial using dapson to target lung inflammation caused by COVID-19.

Dapsone is a decades-old safe and affordable oral antibacterial that has well-recognized anti-inflammatory and immuno-modulatory properties used against malaria, lupus, HIV and many other inflammatory infections. Repurposing drugs could be a quick, safe and cost-effective way to develop new COVID-19 therapies. Dapsone works on the adherence of immune cells called neutrophils to prevent the release of cytokines. Cytokines are proteins produced by white blood cells that help coordinate the body’s immune response.

“By administering the drug as soon as symptoms start, we hope to attenuate the lung inflammation that is the most frequent cause of worsening symptoms and complications requiring hospitalization.”

Dr. Jean Bourbeau

Read the full news release here: Old drug, new therapy: RI-MUHC-sponsored phase III clinical trial ready to test repurposed dapsone to tone down lung inflammation caused by COVID-19.

Dr. Jean Bourbeau in the News:

Dr. Jean Bourbeau is an Associate Member of the Meakins-Christie Laboratories, member of the RECRU, member of the Translational Research in Respiratory Diseases Program and director of the Centre for Innovative Medicine at the Research Institute of the MUHC.

Code Life Ventilator Challenge Peter Goldberg

COVID-19 Code Life Ventilator Challenge

Dr. Peter Goldberg is a COVID-19 Innovation Grant recipient for the Code Life Ventilator Challenge. The pandemic has exposed the critical shortage of ventilators in a number of health care settings. Ventilators are expensive — low-cost models range between $5,000-$10,000 — and are unavailable in many care settings. Dr. Peter Goldberg and his team launched the SubK Sprint to build a clinical-grade ventilator that can be produced cheaply and easily, anywhere in the world. 

Read more about the award: Code Life Ventilator Challenge – Made For All, McGill University.

About the Joule COVID-19 Innovation grant program: https://joulecma.ca/innovate/covid-grants.

Dr. Peter Goldberg is a member of the Meakins-Christie Laboratories, Associate Member of the RI-MUHC RESP program, leader of the SubK Sprint, and is the Director of the Department of Critical Care Medicine at the McGill University Health Centre.

Mortality in adults with multidrug-resistant tuberculosis and HIV by antiretroviral therapy and tuberculosis drug use: an individual patient data meta-analysis Menzies RI-MUHC RESP Program

Lifesaving HIV and tuberculosis medications

Dr. Dick Menzies and his research team played an important role in a recent study that found that implementing a combination of antiretroviral therapy (ART) for HIV and newer tuberculosis (TB) medications decreased the risk of death for adults with multidrug-resistant TB.

The findings, which were published in The Lancet, suggest that every effort should be made to quickly bring these life-saving medications to those in need.

Read the article here:

Mortality in adults with multidrug-resistant tuberculosis and HIV by antiretroviral therapy and tuberculosis drug use: an individual patient data meta-analysis.
Bisson GP, Bastos M, Campbell JR, Bang D, Brust JC, Isaakadis P, Lange C, Menzies D, Migliori GB, Pape JW, Palmero D, Baghei P, Tabarsi P, Viiklepp P, Vilbrun S, Walsh J, Marks SM. Lancet. 2020 Aug 8;396(10248):402-411.

For the full news release, read here: McGill Med e-News

Research suggests greater access to specific HIV and tuberculosis medications is needed worldwide.
A specific combination of HIV and TB treatments, difficult to obtain in certain parts of the world, decreased mortality risk for patients with HIV and multidrug-resistant TB

To complete their study, the research team examined the health records of over 10,000 patients with multidrug-resistant tuberculosis in many different countries. In the largest individual patient data meta-analysis study to assess mortality risk of people with both HIV and multidrug-resistant TB, scientists first compared the risk of death for HIV-positive people versus HIV-negative people, then examined how receiving ART and different types of TB drugs altered this risk. Because of the large sample size, associations of specific TB drugs with mortality were evaluated, focusing on the most effective drugs, categorized as “Group A” by the WHO. To accomplish this, data from over 100 different investigators managed at McGill by Dr. Dick Menzies was used. The database, originally compiled some 10 years ago and updated on a near annual basis, has previously been used to inform WHO guidelines and perform other timely analyses for multidrug-resistant TB.

For this latest study, the primary statistical analyses were carried out by McGill postdoctoral fellows Drs. Mayara Bastos and Jonathon Campbell. Ultimately, using data from 52 studies and 37 different countries, the investigators controlled for things like age, the wealth of the region in which the individuals lived, and severity of drug resistance. Researchers found that while patients with HIV infection were at higher risk of death, this risk was reduced substantially when Group A TB drugs and ART were used. As there are various types of Group A TB medications, the odds of survival varied based on which Group A medication or combination was employed. When looking at only those with HIV, the risk of death was reduced by over 80% with use of specific TB drugs, including bedaquiline.

This research lays a foundation to further investigate the success of specific ARTs in conjunction with TB medications. It also allows the medical community to study methods that might bring these treatments to those who have trouble affording them or accessing them where they live.

Source files from the University of Pennsylvania

Dr. Carolyn Baglole received a CIHR catalyst grant: Health Effects of Vaping for her grant entitled: Utility of a Preclinical Model to Study the Impact of Vaping Products on Cardiopulmonary Outcomes.

Impact of Vaping on Cardiopulmonary Outcomes

Dr. Carolyn Baglole, with Dr. Koren Kathleen Mann, received a CIHR Catalyst Grant: Health Effects of Vaping. The title of the grant is: “Utility of a Preclinical Model to Study the Impact of Vaping Products on Cardiopulmonary Outcomes.”.

The objective of the grant is to investigate the effects of vaping products on cardiopulmonary outcomes, alone and in conjunction with SARS-CoV-2 infection. They propose to develop a mouse model of vaping to understand the effects on the lung, as well as the heart, vessels, and immune system. They will further use a mouse model to test whether vaping can alter that infection of SARS-CoV-2, the virus responsible for COVID-19. This model could then be used to test new vaping products as they enter the market for toxicity and/or to test therapies to counter act the severe toxicities of vaping.

Congrats Carolyn and the rest of the team!

Read more about the project on the CIHR Funding Decision database and in the August 31, 2020 edition of Med e-News.

β-Glucan Induces Protective Trained Immunity against Mycobacterium tuberculosis Infection: A Key Role for IL-1

Using β-glucan to help fight TB Infection

Congratulations to Dr. Nargis Khan and Dr. Eva Kaufmann, postdoctoral fellows with Dr. Maziar Divangahi for their latest Cell Reports publication. Their work shows that β-glucan induces protective trained immunity in human monocytes infected with Mycobacterium tuberculosis, as well as in mice infected with Mycobacterium tuberculosis. Their work is paving the way for both prophylactic and therapeutic use of β-glucan in TB.

Some highlights from the article:

  • β-glucan induces protective trained immunity in human monocytes infected with Mtb
  • β-glucan induces protective trained immunity in mice infected with Mtb
  • β-glucan-mediated protection against Mtb is dependent on IL-1 signaling
  • β-glucan increases expansion of hematopoietic progenitors and myelopoiesis via IL-1

Read the entire publication here: β-Glucan Induces Protective Trained Immunity against Mycobacterium tuberculosis Infection: A Key Role for IL-1. Moorlag SJCFM, Khan N, Novakovic B, Kaufmann E, Jansen T, van Crevel R, Divangahi M, Netea MG. Cell Rep. 2020 May 19;31(7):107634. doi: 10.1016/j.celrep.2020.107634.

Opinion: All levels of government must take decisive, co-ordinated action now before it's too late opinion piece by salman qureshi and colleagues from the critical care network

Stepping up to COVID-19

Read the opinion piece co-written by Dr. Faiz Ahmad Khan in the Hill Times – published March 25, 2020 here:

With the arrival of COVID-19, Canada’s health-care system is being tested as never before. Canadian leaders must elicit the assistance of private industry to ensure its continued success, as health-care supplies and equipment are rapidly depleted. A substantial increase in testing for the virus together with significant financial investments in research, aimed at a deeper understanding of the virus and development of a vaccine, should also be top priorities. Solid financial support for all those impacted by the virus will ensure a rapid return to normal once the crisis has abated. Maintaining open communication and collaboration between leaders, the government, and with partners across the board is the key to our ultimate success.

Opinion piece by Salman Qureshi and colleagues from the Critical Care Infectious Disease Network in Canada: All levels of government must take decisive, co-ordinated action now before it's too late

COVID-19 Need for coordinated action

Dr. Salman Qureshi and colleagues from the Critical Care – Infectious Diseases Network in Canada speak to the critical actions needed as we experience this public health crisis.

Read the full new article in the National Post published on March 17, 2020 here:

Canadian leaders can reduce the damage caused by COVID-19 to Canadians and Canadian society by paying close attention to decisions taken in countries currently experiencing severe outbreaks. Strategies to mitigate the spread of the virus amongst the population, minimizing the strain of our healthcare system at any one time, coupled with a sharing of resources across boundaries as the demand for health-care fluctuates, will together play an important role on the ultimate long-term effect of this virus on our society.