Category: Asthma and Children

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How the microbiome affects asthma: new insights from a Spanish study

The World Asthma Foundation (WAF). WAF is a nonprofit organization dedicated to improving the lives of people with asthma through education, research, and advocacy. In this blog post, I want to share with you some exciting findings from a recent study on the microbiome and asthma, published by Spanish researchers in the journal Nutrients.

The microbiome is the collection of microorganisms that live in and on our bodies, such as bacteria, fungi, viruses, and parasites. The microbiome plays an important role in our health and immunity, and can also influence our susceptibility and response to various diseases, including asthma.

Asthma is a chronic inflammatory disease of the airways that affects millions of people worldwide. Asthma can be triggered by different factors, such as allergens, infections, pollution, stress, and diet. Asthma can also have different phenotypes (characteristics), such as allergic or non-allergic, eosinophilic or non-eosinophilic, mild or severe.

What is the microbiome and how does it affect asthma?

The study by Valverde-Molina and García-Marcos reviews the current evidence and challenges on the relationship between the microbiome and asthma, specifically how microbial dysbiosis (an imbalance of the microbial communities in the body) can influence the origins, phenotypes, persistence, and severity of asthma.

How different factors can influence the microbiome and asthma

The study explores how different factors, such as diet, environment, genetics, and infections, can affect the microbiome and asthma, and how modulating the microbiome could be a potential strategy for preventing or treating asthma. The study also reviews the different methods and techniques used to study the microbiome and its interactions with the immune system and the respiratory system.

The gut-lung axis: a key connection between the microbiome and asthma

One of the key points of the study is the importance of the gut-lung axis in the origin and persistence of asthma. The gut-lung axis is the concept that describes how the gut and lung microbiomes communicate with each other through various pathways, such as metabolites, cytokines, antibodies, and immune cells. The gut-lung axis can modulate inflammation and allergic responses in both organs.

The study shows that the process of microbial colonization in the first three years of life is fundamental for health, with the first hundred days of life being critical. Different factors are associated with early microbial dysbiosis, such as caesarean delivery, artificial lactation and antibiotic therapy, among others.

How microbial dysbiosis can lead to different asthma phenotypes and severity

Longitudinal cohort studies on gut and airway microbiome in children have found an association between microbial dysbiosis and asthma at later ages of life. A low ?-diversity (the number of different species) and relative abundance of certain commensal gut bacterial genera in the first year of life are associated with the development of asthma. Gut microbial dysbiosis, with a lower abundance of Phylum Firmicutes (a group of bacteria that includes lactobacilli), could be related with increased risk of asthma.

Upper airway microbial dysbiosis, especially early colonization by Moraxella spp. (a type of bacteria that can cause respiratory infections), is associated with recurrent viral infections and the development of asthma. Moreover, the bacteria in the respiratory system produce metabolites (substances produced by metabolism) that may modify the inception of asthma and its progression.

The role of the lung microbiome in asthma development has yet to be fully elucidated. Nevertheless, the most consistent finding in studies on lung microbiome is
the increased bacterial load (the number of bacteria) and the predominance of proteobacteria (a group of bacteria that includes Haemophilus spp. and Moraxella catarrhalis), especially in severe asthma.

Candida albicans: a fungal culprit in asthma development and exacerbation

The study also mentions Candida albicans (a type of fungus that can cause infections) as one of the fungal genera that can affect the gut and lung microbiome and asthma. Candida albicans can trigger inflammation and autoimmune responses in the body. Candida albicans can also induce a Th17 response (a type of immune response) in the gut and lungs. Candida albicans can also increase lung bacterial load and exacerbate airway inflammation.

This study is very relevant to our own research and findings on Candida’s role in inflammation and autoimmune response: implications for severe asthma. We published an article on this topic on our website on October 13th 2021 which features findings from Mayo Clinic researchers who examined how intestinal fungal microbiota affects lung resident memory CD4+ T cells (a type of immune cell) in patients with asthma.

You can find our article here: https://worldasthmafoundation.org/candidas-role-in-inflammation-and-autoimmune-response-implications-for-severe-asthma.htm

How modulating the microbiome could be a promising strategy for asthma prevention and treatment

We think that these studies complement each other well and provide valuable insights into this important and emerging topic. We believe that understanding the microbiome and its impact on asthma is crucial for developing new and effective strategies for prevention, diagnosis, and treatment of this chronic disease.

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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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Minority Children Failed By Asthma Inhalers: Genomic Analysis Reveals Why

UCSF Highlights Need for More Precision Medicine Research in Underserved Populations

University of California San Francisco researchers report that the largest-ever whole-genome sequencing study of drug response in minority children has revealed new clues about why the front-line asthma drug albuterol does not work as well for African-American and Puerto Rican children as it does for European American or Mexican children.

Asthma is the most common chronic childhood disease in the world, according to World Health Organization estimates. Children with asthma experience difficulty breathing as a result of chronic inflammation of the airways. This inflammation can be alleviated by inhaling drugs called bronchodilators that make the muscles lining the airways relax, allowing them to reopen.

Albuterol is the most commonly prescribed bronchodilator in the world, and often the only medication available to minority children in lower income settings.

Minority Children Respond Least

However, albuterol and other inhaler drugs do not work equally well for all children. In the U.S., Puerto Rican and African-American children – who also have the highest prevalence of asthma nationwide – respond least well to these life-saving drugs.

This may contribute to the four- to fivefold higher rate of death from asthma among these groups, compared to European Americans and Mexicans. Read more of the complete report at UCSF website.

What Researchers Said

“Despite the much higher impact of asthma among African-American and Puerto Rican populations, over 95 percent of studies of lung disease have been performed on people of European descent,” Angel Mak, PhD said. Mak is the UCSF Asthma Collaboratory’s director of genetic research. He was one of the lead authors on the team’s newest study, published in an early online version on March 6, 2018 in the pulmonology journal, American Journal of Respiratory and Critical Care Medicine.

The lab conducted the first large-scale whole genome sequencing study of asthma drug response in African Americans and Latinos. The researchers’ aim was to discover the genetic factors contributing to reduced albuterol response more than was possible in previous association studies.

The test group were a diverse lineup of 1,441 children with asthma who had either very high or very low response to the drug. The genome sequencing was provided courtesy of Trans-Omics for Precision Medicine (TOPMed) Program of the National, Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health.

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Asthma Flare-ups in Children

Short-term increases in inhaled steroid doses do not prevent asthma flare-ups in children

NIH-funded findings challenge common practice of increasing doses at early signs of worsening symptoms.

Researchers have found that temporarily increasing the dosage of inhaled steroids when asthma symptoms begin to worsen does not effectively prevent severe flare-ups, and may be associated with slowing a child’s growth, challenging a common medical practice involving children with mild-to-moderate asthma.

The study, funded by the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health, will appear online on March 3 in the New England Journal of Medicine (NEJM) to coincide with its presentation at a meeting of the 2018 Joint Congress of the American Academy of Allergy, Asthma & Immunology (AAAAI) and the World Allergy Organization (WAO) in Orlando, Florida. It will appear in print on March 8th.

Asthma flare-ups in children are common and costly, and to prevent them, many health professionals recommend increasing the doses of inhaled steroids from low to high at early signs of symptoms, such as coughing, wheezing, and shortness of breath. Until now, researchers had not rigorously tested the safety and efficacy of this strategy in children with mild-to-moderate asthma.

“These findings suggest that a short-term increase to high-dose inhaled steroids should not be routinely included in asthma treatment plans for children with mild-moderate asthma who are regularly using low-dose inhaled corticosteroids,” said study leader Daniel Jackson, M.D., associate professor of pediatrics at the University of Wisconsin School of Medicine and Public Health, Madison, and an expert on childhood asthma. “Low-dose inhaled steroids remain the cornerstone of daily treatment in affected children.”

The research team studied 254 children 5 to 11 years of age with mild-to-moderate asthma for nearly a year. All the children were treated with low-dose inhaled corticosteroids (two puffs from an inhaler twice daily). At the earliest signs of asthma flare-up, which some children experienced multiple times throughout the year, the researchers continued giving low-dose inhaled steroids to half of the children and increased to high-dose inhaled steroids (five times the standard dose) in the other half, twice daily for seven days during each episode.

Though the children in the high-dose group had 14 percent more exposure to inhaled steroids than the low-dose group, they did not experience fewer severe flare-ups. The number of asthma symptoms, the length of time until the first severe flare-up, and the use of albuterol (a drug used as a rescue medication for asthma symptoms) were similar between the two groups.

Unexpectedly, the investigators found that the rate of growth of children in the short-term high-dose strategy group was about 0.23 centimeters per year less than the rate for children in the low-dose strategy group, even though the high-dose treatments were given only about two weeks per year on average. While the growth difference was small, the finding echoes previous studies showing that children who take inhaled corticosteroids for asthma may experience a small negative impact on their growth rate. More frequent or prolonged high-dose steroid use in children might increase this adverse effect, the researchers caution.

The study did not include children with asthma who do not take inhaled steroids regularly, nor did it include adults.

“This study allows caregivers to make informed decisions about how to treat their young patients with asthma,” said James Kiley, Ph.D., director of the NHLBI’s Division of Lung Diseases. “Trials like this can be used in the development of treatment guidelines for children with asthma.”

This work was supported by the following NHLBI grants: HL098102, HL098075, HL098090, HL098177, HL098098, HL098107, HL098112, HL098103, HL098115, HL098096. The NHLBI-funded study, Step Up Yellow Zone Inhaled Corticosteroids to Prevent Exacerbations (STICS) (NCT02066129), is part of the NHLBI AsthmaNet program, a nationwide clinical research network that explores new approaches in treating asthma from childhood to adulthood.

Part of the National Institutes of Health, the National Heart, Lung, and Blood Institute (NHLBI) plans, conducts, and supports research related to the causes, prevention, diagnosis, and treatment of heart, blood vessel, lung, and blood diseases; and sleep disorders. The Institute also administers national health education campaigns on women and heart disease, healthy weight for children, and other topics. NHLBI press releases and other materials are available online at https://www.nhlbi.nih.gov.

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.