The Impact of Ambient Environmental Exposures to Microbial Products on Asthma Outcomes from Birth to Childhood
Purpose of Review
Asthma is a chronic respiratory condition with increasing domestic and worldwide prevalence that burdens individuals and the healthcare system with high costs associated with long-term treatments and acute emergency room (ER) visits. It can be triggered by ambient microbes, including bacteria, viruses, and fungi. In this review, we examine the outcomes of asthma patients in relation to environmental exposures to ambient microbe products, focusing on whether exposure leads to asthma development from birth to childhood and if particular microbes are associated with worsened asthma exacerbations.
Bacterial endotoxin is more prominent in homes with pets and may cause cytokine cascades that lead to asthma exacerbation. However, some studies have demonstrated a protective effect with early exposure. Patients with positive Aspergillus skin testing are more prone to moderate-severe or severe-uncontrolled asthma. Fungal sensitization is also associated with earlier onset of asthma and demonstrates a dose-dependent relationship of symptom severity and duration. Among viruses, rhinovirus has the greatest association with decreased lung function, severe asthma, and asthma-related hospital admissions. Distribution of microbial products and associated asthma symptoms depends on the geographical climate. Genetic variations among individuals also mitigate the effects of microbial products on asthma development and symptom severity.
Microbial products of bacteria, fungi, and viruses are associated with the development of asthma, more severe asthma symptoms, and worse outcomes. However, some early exposure studies have also demonstrated a protective effect. Bacterial and fungal products are related to decreased lung function and earlier onset of asthma. Viral products are related to asthma-associated hospital admissions; and the climate and patient genetics can also temper or intensify the relationships between microbial products, asthma development, and asthma symptom severity. Further research should focus on the effects of early microbe exposure and its interaction with human immune systems and asthma-related outcomes.
KeywordsEarly microbial exposure Asthma outcomes Allergen sensitivity Bacteria Fungi Virus
Research reported in this publication is supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (Grant No: K24AI106822)
Compliance with Ethical Standards
All reported studies/experiments with human subjects performed by the authors have been previously published and compiled with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines).
Conflict of Interest
The authors declare no conflicts of interest relevant to this manuscript.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 1.CDC. Most Recent National Asthma Data. 2017. Available from: https://www.cdc.gov/asthma/most_recent_national_asthma_data.htm. Accessed 1 Sept 2019.
- 2.CDC. Asthma. 2019. Available from: https://www.cdc.gov/asthma/default.htm. Accessed 1 Sept 2019.
- 7.Longo DL. Harrison’s principles of internal medicine. 18th ed. New York: McGraw-Hill Companies; 2011.Google Scholar
- 8.• Tischer C, et al. Early exposure to bio-contaminants and asthma up to 10 years of age: results of the HITEA study. Eur Respir J. 2015;45(2):328–37 This study was able to examine 3 birth cohorts from 3 different cultures and examine the effect of endotoxin, (1,3)-β-d-glucan, and LPS on each cohort from different geographical regions for the development of asthma in children from birth to age 6 . It has been demonstrated that the climate and geographical region can affect asthma outcomes [14, 25]; and this was observed as high endotoxin levels were associated with asthma at age 6 for the PIAMA cohort (Dutch); an inverse relationship with the INMA cohort (Spanish), and no association with the LISAplus cohort (German). Also, other studies have shown that early constant animal exposure reduces the risk of asthma [13, 24, 72, 73] and this was observed with the INMA cohort, where many of the participants had a dog at home . As there is still controversy whether pets have a protective effect against asthma or the tendency to cause asthma development, this study gives additional clues about the environment that need to be considered. PubMedGoogle Scholar
- 11.• Lukkarinen M, et al. Rhinovirus-induced first wheezing episode predicts atopic but not nonatopic asthma at school age. J Allergy Clin Immunol. 2017;140(4):988–95 Previous studies have demonstrated that early infant exposure to human rhinovirus (HRV) is associated with triggering asthma attacks [15, 55–57]. However, little was known if exposure to HRV leads to the development of asthma later during childhood. This study demonstrated that early childhood exposure to rhinovirus significantly increased the risk for the development asthma, and found clinical markers that could be used to predict the development of atopic and non-atopic asthma in children . This study was different from previous studies, because it only included a birth cohort of healthy children and no high-risk infants. PubMedGoogle Scholar
- 24.•• O’Connor GT, et al. Early-life home environment and risk of asthma among inner-city children. J Allergy Clin Immunol. 2018;141(4):1468–75 Previous studies have demonstrated that exposure to animals has a protective effect against asthma development [8, 13, 24, 72, 73]. This study not only demonstrated this concept, following patients from birth to 7 years of age, but also found that the bacterial species Kocuria, Bifidobacterium, Alloiococcus, and Acinobacter are found in the home of children without asthma, but not in the homes of children with asthma . Furthermore, a previous study has demonstrated that the microbiome of infants’ nasopharynx is initially colonized with Alloiococcus when healthy and declines with acute respiratory infections and the development of asthma . Thus, this study shows key bacteria may have the potential to suppress or trigger the development of asthma from early childhood exposure. PubMedGoogle Scholar
- 27.den Hollander WJ, et al. Helicobacter pylori in children with asthmatic conditions at school age, and their mothers. Aliment Pharmacol Ther. 2016;43(8):933–43.Google Scholar
- 55.Segura N, Fraj J, Cubero JL, Sobrevía MT, Lezaun A, Ferrer L, et al. Mould and grass pollen allergy as risk factors for childhood asthma in Zaragoza, Spain. Allergol Immunopathol (Madr). 2016;44(5):455–60.Google Scholar
- 61.Saraya T, Kimura H, Kurai D, Ishii H, Takizawa H. The molecular epidemiology of respiratory viruses associated with asthma attacks: a single-center observational study in Japan. Medicine (Baltimore). 2017;96(42):e8204.Google Scholar
- 65.Itagaki T, Aoki Y, Matoba Y, Tanaka S, Ikeda T, Mizuta K, et al. Clinical characteristics of children infected with enterovirus D68 in an outpatient clinic and the association with bronchial asthma. Infect Dis (Lond). 2018;50(4):303–12.Google Scholar
- 82.Corren, J, et al. Dupilumab efficacy in patients with uncontrolled, moderate-to-severe allergic asthma. J Allergy Clin Immunol Pract. 2019. https://doi.org/10.1016/j.jaip.2019.08.050.