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World Asthma Day Summary

On the day after World Asthma Day, May 3, 2022, we scanned the globe to find a statement that best sums up the current state of affairs regarding Asthma.

Kudos to tbe U.S National Institute of Environmental Health NIH Statement on World Asthma Day 2022: Toward Improved Asthma Care

Good enough of summary that we want to publish this in its entirety.

Asthma is a serious lung disease; causes chest tightness, wheezing, and coughing; can often be controlled with proper treatment.

Today (May 3, 2022) on World Asthma Day, the National Institutes of Health reaffirms its commitment to biomedical research aimed at preventing the onset of asthma, understanding its underlying causes, and improving the treatment of it. This chronic airway disease, which is characterized by periodic worsening of inflammation that can make it hard to breathe, affects more than 25 million people in the United States, including more than 5 million children. Left untreated, it can be life-threatening.

While scientists have made substantial progress in understanding asthma diagnosis, management, and treatment, therapies to permanently improve breathing for those who suffer from asthma remain elusive. Researchers around the globe are working steadily toward this goal while they seek to better understand and find new ways to manage the disease. They also are continuing research on the underlying causes of disparities in the incidence, care, and prevention of the disease. On the heels of recently updated management and treatment guidelines, researchers anticipate a brighter future for people living with asthma.

Three NIH institutes primarily support and conduct studies on asthma — the National Heart, Lung, and Blood Institute (NHLBI); the National Institute of Allergy and Infectious Diseases (NIAID); and the National Institute of Environmental Health Sciences (NIEHS). Other NIH Institutes and Centers also support and conduct asthma research. NIH scientists and grantees made important advances in understanding, treating, and managing asthma in 2021, which are briefly highlighted as follows:

Asthma and COVID-19

An NHLBI-funded study showed that during the pandemic, asthma attacks, also known as asthma exacerbations, significantly decreased in a large group of children and adolescents, compared to the year before the pandemic. The study also found that telehealth visits among these patients increased dramatically during this time. The study included nearly 4,000 participants aged 5-17 years with a prior diagnosis of asthma. Researchers believe a better understanding of the factors that contributed to these improved outcomes could lead to better asthma control in all children and adolescents, as researchers noted no racial or ethnic differences in health outcomes in this population.

A NIAID-funded study found that asthma does not increase the risk of becoming infected with SARS-CoV-2, the virus that causes COVID-19. This finding came from a six-month household survey of more than 4,000 children and adults conducted between May 2020 and February 2021.

Asthma Disparities

Researchers have known for decades that social determinants of health – conditions like housing, neighborhood, education, income, and healthcare access – can affect the quality of life and asthma-related health outcomes of people living with the disease. NIH scientists are now reporting new advances in understanding the relationship between social determinants of health and asthma.

Black and Hispanic children who live in low-income urban environments in the United States are at particularly high risk for asthma attacks. These children tend to be underrepresented in large trials of new biologic therapies for asthma.

In a recent NIAID-supported clinical trial, the monoclonal antibody mepolizumab decreased asthma attacks by 27% in Black and Hispanic children and adolescents who have a form of severe asthma, are prone to asthma attacks, and live in low-income urban neighborhoods.

In one study, NHLBI-funded investigators demonstrated the importance of housing interventions in improving the health of children with asthma. Poor quality housing is associated with a high level of asthma triggers – including mold, cockroach, mouse, and dust mite allergens – that can pose a health threat to children with asthma. The study showed the feasibility of using targeted interventions – including better pest management, improved ventilation, and moisture reduction – to achieve healthy housing. It showed that such interventions can result in reduced symptoms and hospitalizations due to asthma.

Environmental Exposures and Asthma

Researchers have known for years that asthma can be triggered by substances in the indoor and outdoor environment. New research shows that exposure to some asthma triggers might even occur before birth.

In an NIH-supported study that included grant support from NIEHS and the NHLBI, researchers reported that prenatal exposure to tiny air pollution particles significantly increased the risk for developing asthma in children. The study, which analyzed data from two different study cohorts, focused on a group of mothers and their children, mostly Black or Hispanic, in the Boston area who lived near major roadways with heavy traffic. It found that more than 18% of the children who were exposed to high levels of these so-called ultrafine particles in the womb developed asthma in their preschool years, compared to 7% of children overall in the United States.

An NIEHS clinical study will assess how environmental factors affect disease progression in non-smoking adults who have moderate or severe asthma. The study will focus on the microbiological and genetic factors associated with atopic asthma, also known as allergic asthma, which is triggered by pollen, dust mites, and other allergens. A better understanding of this data might lead to improved treatments for people with this type of asthma, researchers say.

Climate Change and Asthma

Studies have shown that climate change can increase air pollutants such as ground-level ozone, fine particulates, wildfire smoke, and dust, and that these pollutants can exacerbate asthma. Climate change can also affect the production, distribution, and severity of airborne allergens.

NIEHS, NHLBI, and other NIH institutes and centers are leading the NIH Climate Change and Health Initiative. This is a cross-cutting NIH effort to reduce health threats such as asthma that can develop or worsen because of climate change. The initiative will look at these threats across the lifespan and find ways to build health resilience in individuals, communities, and nations around the world. A strategic framework for the Initiative will help guide NIH investments in this area.

An NIEHS-funded study provides examples of how extreme weather events can affect asthma outcomes. For example, as heat waves and droughts become more frequent and prolonged, the risk of large wildfires will likely increase, resulting in poor air quality that makes it more difficult to control asthma. Other climate-change events can lead to longer and more intense pollen seasons, while mold and dampness in homes may cause asthma to develop or worsen preexisting cases.

About the National Institute of Allergy and Infectious Diseases (NIAID): NIAID conducts and supports research—at NIH, throughout the United States, and worldwide—to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website.

About the National Heart, Lung, and Blood Institute (NHLBI): NHLBI is the global leader in conducting and supporting research in heart, lung, and blood diseases and sleep disorders that advances scientific knowledge, improves public health, and saves lives. For more information, visit www.nhlbi.nih.gov. For additional information about NHLBI’s asthma resources, visit https://www.nhlbi.nih.gov/BreatheBetter.

About the National Institute of Environmental Health Sciences (NIEHS): NIEHS supports research to understand the effects of the environment on human health and is part of the National Institutes of Health. For more information on NIEHS or environmental health topics, visit

About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

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The World Asthma Foundation Announces Speakers for Microbiome First Summit

On this World Asthma Day, May 3, 2002, The Microbiome First – Pathway to Sustainable Healthcare Summit organization committee invites healthcare professionals, non-communicable disease community leaders, and stakeholders to participate in the inaugural Microbiome First Summit, a virtual event taking place online at MicrobiomeFirst.org this May, 17-19, 2022. FREE to participants.

For detailed information and to register, visit: https://microbiomefirst.org/

The event, Microbiome First – Pathway to Sustainable Healthcare Summit, kicks off the inaugural event underwritten and moderated by the
World Asthma Foundation (WAF), which is pleased to announce the
following speakers:

Event Keynote
RODNEY DIETERT, PHD
Cornell University Professor Emeritus
Ithaca, NY, USA
Author of The Human Superorganism.
Keynote: “Big Picture View of Our Tiny Microbes”

Researcher Sessions
MARIE-CLAIRE ARRIETA, PHD
Associate Professor, departments of Physiology, Pharmacology, and Pediatrics, University of Calgary
Calgary AB, CANADA
Session: “The early-life mycobiome in immune and metabolic development”

JAEYUN SUNG, PHD
Assistant Professor, Microbiome Program, Center for Individualized Medicine, Mayo Clinic.
Rochester, MN, USA
Session: “A predictive index for health status using species-level gut microbiome profiling”

KATRINE L. WHITESON, PHD
Assistant Professor, Molecular Biology and Biochemistry School of Biological Sciences
Associate Director, UCI Microbiome Initiative
Irvine, CA, USA
Session: “High-Fiber, Whole-Food Dietary Intervention Alters the Human Gut Microbiome but Not Fecal Short-Chain Fatty Acids”

LISA AZIZ-ZADEH, PHD
Cognitive neuroscientist; Expert in brain imaging, autism, body cognition
Associate Professor in the USC Chan Division of Occupational Science and Occupational Therapy
Los Angeles, CA, USA
Session: “Brain-Gut-Microbiome System: Pathways and Implications for Autism Spectrum Disorder”

MARTIN KRIEGEL, MD, PHD
Chief of Rheumatology and Clinical Immunology at University Hospital of Münster
GERMANY
Associate Professor Adjunct of Immunobiology at Yale School of Medicine.
Session: “Dietary Resistant Starch Effects on Gut Pathobiont Translocation and Systemic Autoimmunity”

ERICA & JUSTIN SONNENBURG, PHD
Senior research scientist and Associate Professor in the Department of Microbiology and Immunology at the Stanford University School of Medicine.
Palo Alto, CA, USA
Session: “Gut-microbiota-targeted diets modulate human immune status”

EMMA HAMILTON-WILLIAMS, PHD
Associate Professor
Principal Research Fellow
The University of Queensland Diamantina Institute
Faculty of Medicine
The University of Queensland
Translational Research Institute
Woolloongabba, QLD, AUSTRALIA
Session: “Metabolite-based Dietary Supplementation in Human Type 1 Diabetes is associated with Microbiota and Immune modulation”

ANDRES CUBILLOS-RUIZ, PHD
Scientist, Wyss Institute of Harvard University and Institute of Medical Engineering and Science at Massachusetts Institute of Technology
Cambridge, MA, USA
Session: “Protecting the Gut Microbiota from Antibiotics with Engineered Live Biotherapeutics”

EMERAN A MAYER, MD
Gastroenterologist, Neuroscientist, Distinguished Research Professor
Department of Medicine, UCLA David Geffen School of Medicine
Executive Director, G. Oppenheimer Center for Neurobiology of Stress and Resilience at UCLA
Founding Director, UCLA Brain Gut Microbiome Center.
Los Angeles, CA, USA
Session: “The Gut–Brain Axis and the Microbiome: Mechanisms and Clinical Implications”

BENOIT CHASSAING, PHD
Principal Investigator, Chassaing Lab
Associate professor, French National Institute of Health and Medical Research.
Paris, FRANCE
Session: “Ubiquitous food additive and microbiota and intestinal environment”

SEI WON LEE, MD, PHD
Associate Professor
College of Medicine, University of Ulsan
Department of Pulmonary and Critical Care, Asan Medical Center
Seoul, KOREA
Session: “The Therapeutic Application of Gut-Lung Axis in Chronic Respiratory Disease”

PATRICIA MACCHIAVERNI, PHD
Clinical and translational researcher
Research Fellow, The University of Western Australia
Perth, WA, AUSTRALIA
Honorary Research Associate, Telethon Kids Institute.
Session: “House Dust Mite Shedding in Human Milk: a Neglected Cause of Allergy Susceptibility?”

LIEKE VAN DEN ELSEN, PHD
Research Fellow, The University of Western Australia, Australia
Honorary Research Associate, Telethon Kids Institute.
Perth, WA, AUSTRALIA
Session: “Gut Microbiota by Breastfeeding: The Gateway to Allergy Prevention”

PAUL TURNER, PHD
Rachel Carson Professor of Ecology and Evolutionary Biology, Yale University
Microbiology faculty member, Yale School of Medicine.
New Haven, CT, USA
Session: “New Yale Center to Advance Phage Research, Understanding, Treatments, Training, Education”

ANDRES CUBILLOS- RUIZ, PHD
Scientist, Wyss Institute of Harvard University and Institute of Medical Engineering and Science of Massachusetts Institute of Technology MIT
Boston, MA, USA
Session: “Protecting the Gut Microbiota from Antibiotics with Engineered Live Biotherapeutics”

CLAUDIA S. MILLER, MD, MS
Emeritus Professor, Allergy/Immunology and Environmental Health University of Texas San Antonio, TX, USA
Session: “Toxicant-Induced Lost of Tolerance for Chemicals, Foods and Drugs: a Global Phenomenon”

Media Supporter Content
TONI HARTMAN
PRINCIPAL
Microbiome Courses
London, England UK
Session “Educating Parents About ‘Seeding And Feeding’ A Baby’s Microbiome”

Summit Details:

The goal of the Microbiome First – Sustainable Healthcare Summit is to
improve quality of life at reduced cost by addressing the microbiome
first, as recent research shows that all of these non-communicable diseases have a relationship to the microbiome.

For additional information visit https://microbiomefirst.org/ or on Twitter at @MicrobiomeFirst https://twitter.com/MicrobiomeFirst

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Bisphenol A or BPA in Pregnancy and Asthma Study

The Barcelona Institute for Global Health supported study concludes suggests that in utero BPA exposure may be associated with higher odds of asthma and wheeze among school-age girls.

Study Background

In utero, (before birth) exposure to bisphenols, widely used in consumer products, may alter lung development and increase the risk of respiratory morbidity in the offspring. However, evidence is scarce and mostly focused on bisphenol A (BPA) only.

Study Objectives

There is growing concern over the role of chemical pollutants on early life origins of respiratory diseases (Gascon et al., 2013, Vrijheid et al., 2016, Casas and Gascon, 2020, Abellan and Casas, 2021), specifically on bisphenols due to their large production worldwide (CHEMTrust, 2018) and its widespread exposure to human populations (Calafat et al., 2008, Haug et al., 2018). Bisphenol A (BPA) is the most commonly used bisphenol. It is present in polycarbonate plastics and epoxy resins, used in many consumer products, and diet is the main source of exposure (Liao and Kannan, 2013). In 2017, the European Chemical Agency considered BPA as a “substance of very high concern” (Calafat et al., 2008, Agency and Bisfenol, 2017). Consequently, BPA production is restricted in some countries, which has resulted in the emergence of substitutes such as bisphenol F (BPF) and bisphenol S (BPS), with suspected similar toxicity (Lehmler et al., 2018, Rochester and Bolden, 2015). Bisphenols can cross the placenta and are also found in breastmilk, which results in exposure to foetuses and newborns (Lee et al., 2018). To examine the associations of in utero exposure to BPA, bisphenol F (BPF), and bisphenol S (BPS) with asthma, wheeze, and lung function in school-age children, and whether these associations differ by sex.

Methods

We included 3,007 mother–child pairs from eight European birth cohorts. Bisphenol concentrations were determined in maternal urine samples collected during pregnancy (1999–2010). Between 7 and 11 years of age, current asthma and wheeze were assessed from questionnaires and lung function by spirometry. Wheezing patterns were constructed from questionnaires from early to mid-childhood. We performed adjusted random-effects meta-analysis on individual participant data.

In utero exposure to bisphenols, widely used in consumer products, may alter lung development and increase the risk of respiratory morbidity in the offspring. However, evidence is scarce and mostly focused on bisphenol A (BPA) only.

Study Objective

To examine the associations of in utero exposure to BPA, bisphenol F (BPF), and bisphenol S (BPS) with asthma, wheeze, and lung function in school-age children, and whether these associations differ by sex.

Results

Exposure to BPA was prevalent with 90% of maternal samples containing concentrations above detection limits. BPF and BPS were found in 27% and 49% of samples. In utero exposure to BPA was associated with higher odds of current asthma (OR = 1.13, 95% CI = 1.01, 1.27) and wheeze (OR = 1.14, 95% CI = 1.01, 1.30) (p-interaction sex = 0.01) among girls, but not with wheezing patterns nor lung function neither in overall nor among boys. We observed inconsistent associations of BPF and BPS with the respiratory outcomes assessed in overall and sex-stratified analyses.

Conclusion

This study suggests that in utero BPA exposure may be associated with higher odds of asthma and wheeze among school-age girl

According the U.S. National Institute of Health, Bisphenol A (BPA) is a chemical produced in large quantities for use primarily in the production of polycarbonate plastics. It is found in various products including shatterproof windows, eyewear, water bottles, and epoxy resins that coat some metal food cans, bottle tops, and water supply pipes.

How does BPA get into the body?

The primary source of exposure to BPA for most people is through the diet. While air, dust, and water are other possible sources of exposure, BPA in food and beverages accounts for the majority of daily human exposure.

Bisphenol A can leach into food from the protective internal epoxy resin coatings of canned foods and from consumer products such as polycarbonate tableware, food storage containers, water bottles, and baby bottles. The degree to which BPA leaches from polycarbonate bottles into liquid may depend more on the temperature of the liquid or bottle, than the age of the container. BPA can also be found in breast milk.

Why are people concerned about BPA?
One reason people may be concerned about BPA is because human exposure to BPA is widespread. The 2003-2004 National Health and Nutrition Examination Survey (NHANES III) conducted by the Centers for Disease Control and Prevention (CDC) found detectable levels of BPA in 93% of 2517 urine samples from people six years and older. The CDC NHANES data are considered representative of exposures in the United States. Another reason for concern, especially for parents, may be because some animal studies report effects in fetuses and newborns exposed to BPA.

If I am concerned, what can I do to prevent exposure to BPA?

Some animal studies suggest that infants and children may be the most vulnerable to the effects of BPA. Parents and caregivers can make the personal choice to reduce exposures of their infants and children to BPA:

  • Don’t microwave polycarbonate plastic food containers. Polycarbonate is strong and durable, but over time it may break down from over use at high temperatures.
    Plastic containers have recycle codes on the bottom. Some, but not all, plastics that are marked with recycle codes 3 or 7 may be made with BPA.
  • Reduce your use of canned foods.
    When possible, opt for glass, porcelain or stainless steel containers, particularly for hot food or liquids.
  • Use baby bottles that are BPA free.

There is growing concern over the role of chemical pollutants on early life origins of respiratory diseases (Gascon et al., 2013, Vrijheid et al., 2016, Casas and Gascon, 2020, Abellan and Casas, 2021), specifically on bisphenols due to their large production worldwide (CHEMTrust, 2018) and its widespread exposure to human populations (Calafat et al., 2008, Haug et al., 2018). Bisphenol A (BPA) is the most commonly used bisphenol. It is present in polycarbonate plastics and epoxy resins, used in many consumer products, and diet is the main source of exposure (Liao and Kannan, 2013). In 2017, the European Chemical Agency considered BPA as a “substance of very high concern” (Calafat et al., 2008, Agency and Bisfenol, 2017). Consequently, BPA production is restricted in some countries, which has resulted in the emergence of substitutes such as bisphenol F (BPF) and bisphenol S (BPS), with suspected similar toxicity (Lehmler et al., 2018, Rochester and Bolden, 2015). Bisphenols can cross the placenta and are also found in breastmilk, which results in exposure to foetuses and newborns (Lee et al., 2018).

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Asthma Rates and Mask – Good or Bad?

65% drop in serious asthma cases due to mask-wearing Israeli hospital reports

The Times of Israel reports that the Sheba Medical, an Israeli hospital reports 65% drop in serious asthma cases due to mask-wearing.

Here’s the 411 according to published reports:

• A study conducted by Sheba Medical Center found that the past year saw a 65 percent drop in serious asthma cases that required hospitalization.

• The drop was credited to widespread mask-wearing during the COVID-19 pandemic, which also helped decrease the spread of viruses such as the flu in the past year.

• By wearing masks, people are also less likely to suffer from seasonal allergies, as face coverings prevent pollen from flowers, trees, and grass coming into contact with the nose and mouth.

• The report follows Israel’s decision to drop the requirement to wear masks outdoors.

Israeli hospital reports 65% drop in serious asthma cases due to mask-wearing Jerusalemites wearing face masks walk in Jerusalem on February 04, 2021.

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Monoclonal Antibodies Anaphylaxis Risk For Severe Asthma Patients

Monoclonal antibodies

Most monoclonal antibodies increase the risk of anaphylaxis in severe asthma patients, according to a report published in Clinical and Translational Allergy. The study found 4 out of 5 common mAbs were associated with an increased risk of anaphylaxis. Each of the therapies had a different risk profile. One monoclonal antibody – dupilumab – exhibited a very low risk. The patients in this study were mainly young and middle-aged adults.

What You Need to Know

Monoclonal antibodies (mAbs) are a type of medication designed to work on one specific target, in contrast to conventional medications that often affect more than one site within the body. They differ from polyclonal treatments by binding specifically to a single place (an epitope) on their target protein. Monoclonal antibodies are found naturally, produced by cloned B cells called hybridomas.

For those with severe asthma, there are Clinical Safety Issues. Any severe asthmatic who experiences an anaphylactic reaction due to food or insect allergy must be made aware that the use of mAbs may cause an adverse reaction for them.

Severe asthma patients receiving monoclonal antibodies need close monitoring due to increased anaphylaxis risk, the new study found.

The report, published in Clinical and Translational Allergy, found 4 out of 5 common mAbs were associated with a heightened anaphylaxis risk, though the risk varied from therapy to therapy.

Key Takeaways

  • Monoclonal antibodies work with the immune system.
  • mAbs target cancer cells, viruses, bacteria, and other pathogens.
  • They may be beneficial in autoimmune diseases in place of other immunosuppressive agents.
  • mAbs generally prevent allergic reactions, but for some people, may cause a severe adverse reaction.
  • Regular doses of antihistamines and/or epinephrine may be used with the monoclonal antibodies.

Common monoclonal antibodies include:

– omalizumab (trade names Xolair and Omeclamox and used for allergies to asthma and insect bites)

– mepolizumab (trade name Nucala, a newer monoclonal antibody. It is used for Severe Persistent Asthma in those who have moderate to severe allergic asthma and do not respond well to conventional treatments.)

What Are Monoclonal Antibodies?

Monoclonal antibodies are secreted proteins that neutralize a pathogen or an undesirable substance. They derive from monocytes and can bind to target the protein which is responsible for activating B-cells during immune response. They function as a tool to modify the progression of disease by slowing down the symptoms of autoimmune reactions.

Monoclonal Antibodies (MAbs) function to eliminate pathogens or unwanted toxins. They may have diagnostic as well as treatment potentials in autoimmune disease-related disorders.

The World Asthma Foundation thanks the six expert researchers for their insight into how normally beneficial Monoclonal Antibodies may cause Anaphylactic reactions in severe asthmatics.

Li L, Wang Z, Cui L, Xu Y, Guan K, and Zhao B. “Anaphylactic risk related to omalizumab, benralizumab, reslizumab, mepolizumab, and dupilumab.” Published online June 3, 2021. doi:10.1002/clt2.12038

Monoclonal antibodies
Monoclonal antibodies, PR image.

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New Treatment for Asthma? Airway Collagen Affects Breathing

A new study finds that manipulating the stiffness of the collagen in the airway has an effect on breathing.

The airway consists of both a conducting region (larynx, trachea, bronchi, bronchioles) where air is humidified, warmed, and cleaned and a respiratory zone where gas exchange occurs. The airway is directly and continuously exposed to both macromechanical and micromechanical forces.

Macromechanics is the study of organ-level mechanical and material properties. Intrathoracic respiratory forces, perfusion, and cough represent some of the dynamic macromechanical forces exerted on the respiratory system. As the airway is composed of heterogeneous components (chondrocytes, epithelium, endothelium, muscle, extracellular matrix (ECM)), these constituents can be individually quantified using micromechanics.

Micromechanical properties drive the mechanotransduction in the airway, driving cell–cell and cell–matrix interactions [1].

Collagen is most abundant component in the airway extracellular matrix. It is also the primary component that determines mechanical properties of the airway. This discovery around the structure of airway cells could lead to a new treatment for asthma.

What You Need to Know

Abnormal airway collagen deposition is associated with the pathogenesis and progression of airway disease according to the researchers, Lumei Liu, Brooke Stephens, Maxwell Bergman, Anne May, and Tendy Chiang, in Columbus, Ohio.

Liu is with the Center of Regenerative Medicine, Abigail Wexner Research Institute, Nationwide Children’s Hospital in Columbus, OH.

Key Takeaways

  • collagen has a major role in airway mechanics
  • macro- and micro-scale approaches can quantify airway mechanics
  • collagen deposition affects pathologic changes in airway diseases.

The World Asthma Foundation would like to thank these experts for their research for their understanding how collagen affects healthy airway tissue mechanics is essential. The impact of abnormal collagen deposition and tissue stiffness has been an area of interest in pulmonary diseases such as cystic fibrosis, asthma, and chronic obstructive pulmonary disease. The researchers seek to provide biomechanical clues for targeted therapies and regenerative medicine to treat airway pathology and address airway defects.

airway collagen affects breathing. Image by OpenClipart-Vectors from Pixabay
Airway collagen affects breathing. Image by OpenClipart-Vectors from Pixabay

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Asthma and Bacteriophages – What We Know Now

What is a Bacteriophage

According to the U.S. National Institute of Health, Bacteriophages (or “phages”) are viruses that can kill or incapacitate specific kinds of bacteria while leaving other bacteria and human cells unharmed. By gathering naturally-occurring phages, or by modifying or engineering phages to display certain properties, researchers hope to create novel anti-bacterial therapeutics. Researchers connect Asthma and Bacteriophages.

Impact on Asthma

Staphylococcus aureus enterotoxins (intestinal toxins) have a demonstrated effect on airway disease including Asthma in early life according to multiple studies. These bacteria are in the gut and on the skin.

Because phages eliminate bacteria by infecting them, rather by generating compounds like antibiotics which kill bacteria, phages can be used to treat antibiotic-resistant infections. In addition, some evidence suggests that combination therapy containing both phages and antibiotics could prevent bacteria from becoming drug resistant.

Although scientists have been aware of phages and their ability to kill bacteria since 1917, the  first U.S.-based clinical trials of phage therapy have only recently begun. Individual U.S. patients have received phage therapy, but only under emergency investigational new drug protocols.  

World Asthma Foundation: Dr. Papadopoulos, what prompted your research into bacteriophages?

Asthma and Bacteriophages Video

Connecting Asthma and Bacteriophages

Dr. Nikolaos Papadopoulos: For many years, we have been working on the viral aspects of allergic diseases and particularly asthma based on the observation that most of the symptoms, especially the exacerbations of asthma, followed the common cold. There has been a link well-established, with lots of papers and lots of studying on the relationship of a particular virus, rhinoviruses with asthma exacerbations. Then there were more observations about associations, about bacterial infections, again in exacerbations.

Virus – Bacteria Interaction

We have discovered that the viral aspect also drives, to some extent, persistence of asthma, which means that viruses induce factors that trigger remodeling. Repeated infections might lead you to persistent asthma. Then we started looking at the interactions between viruses and bacteria. While we were looking at these specific micro-organisms, we realized that, as many other scientists did, we were actually focusing on our own little field without giving much attention to the wider perspective of the ecology of at least the local niche, the nose or the lungs where we have found in the last decade that you do have a growth of microbiome.

Lung Microbiome

In the past, we thought that in the lungs, there was no microbiome, but in fact, we know now that there is. Of course, there is increased interest generally in the microbiome and its disturbance, what we call dysbiosis in every condition. Then when we focus, we look at asthma. Wherever there is a focus on evaluating the microbiome in health and disease, there’s almost always this dysbiosis, this imbalance. We don’t know whether this is something that causes the disease or is a cause of the disease. However, it is very important to understand these characteristics.

Less Antibiotics

For us, it has been very important to place the different organisms and their interaction within a community and try to understand whether it’s possible, instead of trying to kill everything. That’s what we do with antibiotics. Instead of trying to eliminate our enemies, rather try to balance things and see whether we can have a community which is balanced and as considered resilient to external possible enemies. This is when and how we started looking into the meta-genome, and particularly the virion of the respiratory tract. That is how this all started.

World Asthma Foundation: What were the key findings?

Dr. Papadopoulos: Our observations so far, this is something I’ve been looking into more detail. As we expected, it is much more complicated rather than saying that one microorganism goes up and another one goes down. It’s much more about the ecology of the organisms rather than specific microorganisms.

Dynamics Between Microorganisms

I think this is a major understanding, a leap forward in that we shouldn’t think of microorganisms as individual forces that shape our internal microbiome health. It is the dynamic between microorganisms. It’s much more closer to health or disease because as you have one microorganism grow, then you have less resources for the other.

It is a balance, which is dynamic and happens all the time. This is where we got into bacteriophages in particular. This was something we did not expect. Also, it was not on the list of the viruses that we were focusing on because we’re focusing on the typical RNA viruses, the ones that harm, usually, like viral viruses of flu or RSV.

Bacteriophages As Main Player

Then we saw that the main player, one of the main players within the viral communities within the virion were the bacteriophages. In fact, and I think that’s our main finding, we’re the first to suggest is that there is a deficiency of bacteriophages in the upper respiratory tract, at least of children, this is where we have studied it.

Asthma and Bacteriophages 

We are now looking into different communities, different people, different geographies, et cetera, but the observation was repeated in another cohort. We don’t have many bacteriophages in an asthmatic airway. This is associated with looser network of microorganisms and less robust interaction network between the viruses and the bacteria.

Intervention With Phages

These key findings suggest that we might be able to intervene. This is a very good opportunity for intervention because we know that bacteriophages, mostly in most cases, they don’t harm.

They are in balance with the human host because they need to be there. It’s to both our benefits to control the bacterial populations for them not to overexpand. It’s a natural ally.

There is a possibility that we might be able to intervene using bacteriophages, but of course, this is not as straightforward as an antibiotic where you just give something, you kill whatever is susceptible and then it goes away.

We’re talking now about ecological balances. We need to understand exactly what type of bacteriophage you might need, what dose, at what time, et cetera. This is what we are actually doing now.

World Asthma Foundation: Thank you. What would you like asthmatics to know?

Dr. Papadopoulos: Well, we can look at the glass as half-full, as half-empty.

Glass Half Empty

The half-empty part is that for turning bacteriophage or different bacteriophages into therapy, we do need to do lots of things. Not only understand the mechanisms and select the bacteriophages, et cetera, but also, we have to overcome lots of regulatory hurdles because in our Western society, we can’t still use bacteriophages. They are living organisms. In order to standardize a living organism to provide it as medicine, it is really demanding.

Of course, there are all these questions and you’ve seen what happens now with the vaccines, even though most of them are not living organisms, still, it is very complex and we need to be very, very careful when we are exploring it.

Glass Half Full

On the other hand, what we are understanding of the half-full aspect is that by understanding the mechanisms and the dynamics of these microorganisms, we understand why healthy living, why being close to nature, why avoiding lots of pollutants makes us healthier in every aspect. This is also for people who have asthma.

Simple Advice

We know that some very simple and daily advice, like for example, being closer to nature, like eating healthy, for example, and avoiding things that generate pollution and things that generate inflammation is something that does improve their health.

I would suggest that asthmatics, as everybody else, should embrace the idea of a healthy environment and healthy people within this healthy environment.

Asthma and bacteriophages may soon be shown to be a very useful connection.

Bacteriophages research Dr. Nikolaos Papadopoulos reports.
Dr. Nikolaos Papadopoulos reports on bacteriophage research.
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World Asthma Day – May 5, 2021 – Spread the Word

World Asthma Foundation is supporting care of Asthma and asthmatics around the world. Please help those that suffer by spreading the word.

The WAF is doing it’s part by:

* Announcing the Defeating Asthma Project with the aim of shining a spotlight on getting to a cure

* Asthma education and advocacy for people with asthma who suffer

World Asthma Day May 5, 2021 Spread the Word

“We can move the needle by taking action now to make the difference for those that suffer from Asthma.” – Alan Gray, Director WAF Australia

We’ve hunkered down close to home here at the WAF. While doing so, we’re poring over volumes of available Asthma research data to share our understanding of the root causes of Asthma with emphasis on Severe Asthma.
Our ultimate goal is to understand the root cause of Severe Asthma (already considered a pandemic by many) while we aim for a cure. By banding together with other Asthmatics, including those that care about Asthmatics and clinicians that treat, we can defeat Asthma and we can do so now.

Why this Matters:

Asthma is not one disease but many and the causes underlying its development and manifestations are many including environmental issues

Asthma has reached pandemic levels around the globe

Asthma is a chronic lung disease that affects over 300 million worldwide

The projected rate will reach 400 million by 2025

Environmental exposures have been proven to play a significant role in the development of asthma and as triggers

Asthma is believed to be determined by a complicated set of one’s own genetics and environmental exposures including a multitude of toxic chemicals and the overuse of antibiotics

In the U.S., African Americans are almost three times more likely to die from asthma-related causes than the white population

Australia reported the highest rate of doctor diagnosed, clinical/treated asthma, and wheezing

Defining asthma remains an ongoing challenge and innovative methods are needed to identify, diagnose, and accurately classify asthma at an early stage to most effectively implement optimal management and reduce the health burden attributable to asthma

According to the U.S. Centers for Disease Control, The total annual cost of asthma in the United States, including medical care, absenteeism and mortality, was $81.9 Billion a year.

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Bacteriophages, Asthma, Airway Inflammation and Infection

To understand Bacteriophages and their role in airway inflammation, chronic infection and Asthma, World Asthma Foundation reached out to Dr. Bollyky, immunologist and infectious disease specialist at Stanford Medical Center for an introduction to these topics.

“Allergic disorders pose a growing challenge to medicine and our society. Therefore, novel approaches to prevention and therapy are needed. Recent progress in studies on bacterial viruses (phages) has provided new data indicating that they have significant immunomodulating activities. We show how those activities could be translated into beneficial effects in allergic disorders and present initial clinical data that support this hope.” – Society for Experimental Biology and Medicine

Introduction to Bacteriophages

World Asthma Foundation: Dr. Bollyky, can you introduce us to bacteriophages, their impact on chronic bacterial infections, airway inflammation and asthma?  

Video: Introducing Asthma and Bacteriophages – Airway Inflammation and Infection Interview with Dr. Bollyky, immunologist and infectious disease specialist at Stanford Medical Center

Dr. Bollyky: Yes, sure. First, just a little bit about the background of the lab and what we do. Then I’ll tell you about the bacteriophage we’re working on, and how we think it may relate to immune regulation, and airway inflammation in general.

We’re immunologists, as well as being infectious disease docs, and so my lab has worked now for a number of years trying to study immune regulation in the lung, and how populations of different regulatory cells sense allergens, and how they keep healthy folks from developing hypersensitivity to those allergens, and really where they go wrong in asthma. We’ve been doing that work about as long as I’ve been a professor at Stanford, which is about seven years. And a lot of that is funded by the NIH.

The other hat that I wear is as an infectious disease doc, and obviously anyone who has asthma will tell you that infections are among the triggers that seem to precipitate flares. 

There’s a lot of literature about asthma being related to flora, and to both episodic as well as long-term exposures to the microbial world. My lab studies a particular type of microorganism called the bacteriophage. These are viruses that are made by bacteria, and they are very abundant in your body as well as in your lungs, and really anywhere where bacteria tend to live. In the same way that you and I have viruses, your bacteria do too, and they produce these things in incredible amounts.

A fairly good rule of thumb is that you’re going to find somewhere in the neighborhood of 10 bacteriophages for every bacteria that you have at a site of chronic infection. The number is higher than that in sea water, but in most of the studies that have been done of the gut, or the oral tract, or the vagina, in spaces like this the numbers hold true. 

There’s less data in the lung, but I think you can be fairly confident that, again, anywhere where you’ve got long-term bacteria setting up shop, you have these phages. What we’ve been looking at recently is how your immune system sees these phages, and how they alter both the immune response to bacteria, but then sort of immune homeostasis in general.

One of the things that we found is that these phages tend to dampen responses to infection by bacteria, and they do that basically by being perceived as viruses, as you might expect, because that’s really what they are.

Phages and Asthma

World Asthma Foundation: How do  phages relate to asthma?

Dr. Bollyky: In two ways.

The first is, it may alter the microbiome of the lung and allow bacterial infections to persist, ironically longer than they might otherwise, because they keep immune clearance from happening. This may be counter-intuitive because most of us think of viruses as being bad for the host organisms, in this case bacteria, but both are probably true, meaning, bacteriophages are parasitized bacteria, but vis-a-vis the immune system they probably may also contribute to their persistence.

The other part about it, which is what we’ve been looking at recently, is how bacteriophages modulate the immune environment of the lung in general. There, it seems that, not unlike other viruses, that you see some interesting polarizing effects on immunity.

In all of this, there’s some very particular aspects of this that I think are relevant to the microbiome of the lung, and again, particularly to phages, but all of this highlights the complicated and, I think, fascinating immune and microbial environment of the lung in asthma, and how much we have to learn about that environment, and conversely, how many opportunities there would be to intervene in that system, if we only knew more.

Key Findings

World Asthma Foundation: What are the key findings?

Dr. Bollyky: A couple of things that folks who follow the literature will relate to. The first is there’s just been a lot more attention that’s being paid to the microbiology of the lung, and the idea – when I did my medical training, it’s getting close to 20 years now, what I learned at that time was that the lung was sterile, for example.

We know that that’s by far an oversimplification, and that there’s actually a lot of stuff going on there. Most of the past decade has been about characterizing the bacteria, and the fungi, and what have you, that are in the lung. Now, I think people are becoming alert, or attentive to the possibility, or to the fact that there are also endogenous viruses in these places, and that your lung has an ecology to it, where maybe not unlike, well, really any other ecology, the African Savanna, or your favorite fishing hole down the street.

There’s a lot of organisms that exist in competition, and in equilibrium at some points, and those are dynamic and living systems that we need to think about. That’s one trend, it’s just the attention to the microbiome and then the attention in particular to components of the microbiome.

I would put fungi in this, but also these bacteriophages that were relatively ignored until fairly recently, and then we’ve become kind of cognizant of what they do.

The other trend that I think is arising, that’s part and parcel of that in terms of asthma, is realizing that these different organisms, like fungi, like viruses and bacteria, exert opposing and, I think, important effects on the immune response, and that these things, the endogenous viruses you have, much like the endogenous bacteria, or the endogenous fungi can influence the ways that your immune system sees the rest of the world, and the ways in which it’s regulated.

Bacteriophages and Gut-Lung Interaction

World Asthma Foundation: We’ve been reporting on the Gut-Lung axis. Do you see that connection playing a role?

Dr. Bollyky: Yes, it’s a particularly interesting one too, because again, I think we tend to think of the lung in isolation, but the reality is that, both from above, in the form of your sinuses and secretions from there, but then also from below, meaning your gut.

Every time you sleep we know these secretions do go down. If you look at the microbiome of the lung, a lot of it tends to be oral flora, and a lot of it tends to be fairly transient, meaning, the studies that have been done would suggest that the bugs, the bacteria, and assuming it will probably be the case for the phages as well, but certainly the bacteria and the fungi that you have in your lung are fairly representative of the same organisms that you have in your sinus tract and in your gut. Your upper GI tract.

This ends up populating to a large extent your lungs. This big debate about whether your lungs are sterile or not really comes down to whether you think that these microbial interlopers are a part of a stable population or what their relationship is. As you are clearly aware, a lot of these same antibiotic resistance patterns, a lot of the same metabolites that your gut bacteria produces or that your sinus bacteria produce is going to end up in your lungs. Then, that’s going to influence the local immune response and ultimately asthma.

New Phage Research

World Asthma Foundation: Thank you Dr. Bollyky. What’s next?

Dr. Bollyky: We’re looking at phages and asthma models, and we’ve been studying a lot of infections, both human diseases like cystic fibrosis and in mouse models. Hopefully, I’ll be able to tell you more soon about phages and the allergens and regulatory T cell populations and that sort of stuff, and I’d love to come back.

World Asthma Foundation: We look forward to that. Thank you very much.

Dr. Bollyky: You got it.

See also Dr. Dietert’s interview about the Gut and Lung connection.

Find more information about Dr. Bollyky here.

Dr. Bollyky introduces bacteriophages, impact on chronic bacterial infections, airway inflammation and asthma
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Asthma and Bacteria: Nose to the Toes

Staphylococcus aureus enterotoxins (intestinal toxins) have a demonstrated effect on airway disease including Asthma in early life according to multiple studies. These bacteria are in the gut and on the skin.

To further the WAF misson to improve our understanding of what drives Severe Asthma, the World Asthma Foundation reached out to Rodney Dietert, PhD, for his thoughts on the topic of Asthma and Staphylococcus aureus.

Rodney Dietert, PhD is a Cornell University Professor Emeritus, Health Scientist Head of Translational Science + Education for SEED, and the Author of the Human Super-Organism How the Microbiome is Revolutionizing the Pursuit of a Healthy Life.

This is the third in the series of interviews on the topic of Asthma and Staphylococcus aureus with Rodney Dietert, Phd.

Today We Learn About

* Staphylococcus aureus beyond the nose including the skin and the gut

Video Interview

Bacteria – Staph A and Asthma

World Asthma Foundation: Dr. Dietert, can we talk about Staphylococcus aureus and Asthma beyond the nose? 

Rodney Dietert, PhD: There are skin and gut microbiome effects on the Staph A asthma connection as well. It’s not just the nose but the nose is a good starting point.

Staph A, diet consumption, the bacteria that are in place, particularly in the nose, but also to some extent in the gut and even the skin, can determine what’s going to happen later in the risk for conditions like asthma. I think the thing to realize is that that bacteria and early on, that’s when you’re still recruiting cells. Lung maturation is one of the late-maturing systems. The lung and brain are late compared to a lot of other physiological systems. You don’t really fully mature the lung until something like 18 or 20.

Those effects on recruiting and getting balance in your immune cells in the lung are really important. When you’ve got a bacterium there that is producing allergens, it is stimulating a population we didn’t use to know about, called T helper 9. These cells produce a cytokine called Interleukin-9. The important thing to know is that these cells interact exquisitely with mast cells. They actually have T helper 9 cells.

Immune cells have histamine receptors so they’re co-stimulating between these cells and mast cells. Imagine (the outcomes) when an infant is skewed toward producing that kind of immune cells in these tissues, like the lung, and them having that kind of interactions with mast cells.

See also Dr. Dietert’s interview about the Gut and Lung connection.

Staph A bacteria - Dr. Dietert.

For full story and video follow the link below

Asthma and Bacteria: Nose to the Toes