Category: Infections and Asthma

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Candida’s Role in Inflammation and Autoimmune Response: Implications for Severe Asthma

Welcome Message from the World Asthma Foundation

Hello to our dedicated community and newcomers alike.

At the World Asthma Foundation (WAF), we’re united by a singular, important mission: to Defeat Asthma. Our approach is rooted in fostering awareness, enhancing education, and promoting research that seeks to unravel the complexities of Asthma. As we strive towards a world where Asthma is no longer a limiting factor in anyone’s life, we remain steadfast in bringing you timely, comprehensive, and relevant information.

We’re excited to share our latest blog post with you. This post encapsulates the culmination of the efforts of a variety researchers, clinicians, and organizations worldwide working independently including pioneering work from the Mayo Clinic, to shed light on the pathogenesis and exacerbation of severe asthma.

Mayo Clinic Candida Study

We delve into the compelling evidence pointing towards the intricate interplay between Candida colonization, dysbiosis, inflammation, autoimmune responses, TNF-alpha dysregulation, and comorbidities.

As we unravel these complex relationships, our hope is to equip you, our readers, with knowledge that can empower you in your journey with asthma or help you support someone who is affected.

Let’s continue to learn, share, and work together in our collective fight against Asthma.

Thank you for being a part of our mission. We encourage you to share this information with your healthcare provider.

Establishing a trustworthy and effective relationship with a healthcare provider is crucial to managing your health. It not only ensures that you get the best care but also allows for open and productive conversations about your health.

Introduction

Managing Severe Asthma remains a complex task for many pulmonary practitioners, despite available medication and trigger avoidance strategies. Frequent attacks and poor symptom control often plague patients. Recent investigations, pieced together by the World Asthma Foundation over time have uncovered dozens of notable research groups that have illuminated the complex relationship between Candida colonization, dysbiosis, inflammation, autoimmune response, TNF-alpha dysregulation, and comorbidities in the pathogenesis and exacerbation of Severe Asthma. This amassed knowledge underscores the multifaceted nature of Severe Asthma, bringing to light the critical role of Candida in the disease process.

Recent studies reveal a potential link between Candida colonization, dysbiosis, inflammation, autoimmune response, TNF-alpha dysregulation, and comorbidities in the pathogenesis and exacerbation of Severe Asthma. This article will provide an overview of these linkages, the financial impact on individuals and society, the necessity for improved diagnostic tools and processes, and source the scientific studies supporting these conclusions.

Candida Colonization, Dysbiosis, and Fungal Sensitization

Candida albicans, a common fungal inhabitant of the mouth, gut, and genital tract, can also colonize the respiratory tract. This colonization is often facilitated by dysbiosis, an imbalance in the normal microbial flora, which can be induced by various factors, including the use of antibiotics and changes in the host immune response. Further, fungal sensitization, a process where the immune system produces antibodies (IgE) against fungal allergens, plays a crucial role in the onset and severity of asthma symptoms. Studies from the Mayo Clinic underline the lower alpha-diversity of lung microbiota and higher fungal burdens in Asthma patients, showing a correlation with severity and poor control of Asthma.

Case in Point

A recent study presented at the CHEST Annual Meeting 2021 by researchers from Mayo Clinic and University of California Davis confirmed the association between intestinal fungal dysbiosis and asthma severity in humans, particularly hospital use in the past year. The study found that patients with asthma who had higher intestinal Candida burden were more likely to have severe asthma exacerbations in the previous year, independent of systemic antibiotic and glucocorticoid use. This suggests that intestinal fungal dysbiosis may worsen asthma control and outcomes in humans. The study also showed that intestinal fungal dysbiosis can enhance the severity of allergic asthma in mice by increasing lung resident group 2 innate lymphoid cells (ILC2) populations, which are important mediators of the gut-lung axis effect. The study used a novel technique of flow cytometry to identify and quantify ILC2 in the lungs of mice. These findings highlight the potential role of intestinal fungal dysbiosis and ILC2 in asthma pathogenesis and management.

Role of Antibiotics and Gut-Lung Axis

Studies show that certain antibiotics prescribed for infections, such as Helicobacter pylori, can lead to gut microbiota dysbiosis, promoting Candida colonization. This gut-lung axis, the communication between gut microbiota and lung health, can create an environment conducive to fungal overgrowth and subsequent infection. As such, understanding this interaction can offer valuable insights into asthma management. Research from the Mayo Clinic suggests that antibiotic usage can significantly contribute to these interactions and, consequently, the pathogenesis of Severe Asthma.

Mechanisms of Candida Colonization

Candida albicans utilizes several mechanisms to cross the intestinal epithelial barrier, including adherence to epithelial cells, invasion, and translocation. Each of these steps facilitates Candida’s ability to invade the host’s system and trigger an immune response. Insights from the Mayo Clinic suggest that bacterial-fungal interactions play a key role in these mechanisms and have implications for Candida colonization.

Candida-Induced Inflammation, Autoimmune Response, and TNF-alpha Dysregulation

Once established, Candida colonization can incite inflammation by provoking the immune system to produce pro-inflammatory cytokines, such as TNF-alpha. While TNF-alpha aids in fighting off infections by initiating inflammation, its dysregulation can lead to chronic inflammation and autoimmune diseases, enhancing the severity of asthma. Research from the Mayo Clinic has shown that Candida colonization in the lung induces an immunologic response, leading to more Severe Asthma.

Autoimmune Response, Comorbidities, and Severe Asthma

Recent studies propose that an autoimmune response could be involved in the onset and exacerbation of Severe Asthma, with TNF-alpha dysregulation playing a pivotal role. Comorbidities like rheumatoid arthritis, often seen in conjunction with Severe Asthma, can further complicate disease management and progression.

Burden, Financial Impact, and Comorbidities

Severe Asthma imposes a substantial burden on individuals and society, financially and otherwise. Healthcare costs, productivity loss, and reduced quality of life contribute to this impact. Asthma comorbidities such as autoimmune diseases can affect disease progression and outcomes, underscoring the need for a comprehensive management approach.

The Necessity for Improved Diagnostic Tools

An accurate diagnosis of Candida colonization, inflammation, and autoimmune response in severe asthma is crucial for optimal patient management. There’s a growing need for improved diagnostic methodologies, tools, and processes. Advances in diagnostic techniques, such as bronchoscopy and bronchoalveolar lavage (BAL), can offer valuable insights into Candida colonization and the associated inflammatory and autoimmune processes. The Mayo Clinic’s recent findings, which identify a unique pattern of lower alpha-diversity and higher fungal burden in the lung microbiota of severe asthma patients, further emphasize the need for enhanced diagnostic methods.

Conclusion

Understanding the link between Candida colonization, dysbiosis, inflammation, autoimmune response, TNF-alpha dysregulation, comorbidities, and severe asthma is crucial for medical practitioners dealing with this chronic disease. The significant burden and financial impacts of Severe Asthma on individuals and society underline the urgency for effective management strategies.

Recognizing the influence of comorbidities, such as autoimmune diseases, can guide comprehensive care plans for patients with Severe Asthma. Moreover, enhanced diagnostic tools and processes will aid in early identification and more personalized treatment approaches, ultimately improving patient outcomes.

By integrating this knowledge, medical practitioners can not only better understand the multifaceted nature of Severe Asthma but also enhance its overall management, leading to improved patient care. With ongoing research, we can continue to unravel the complex relationships and mechanisms in asthma pathogenesis, providing new avenues for therapeutic interventions and improved patient outcomes.

Research on the relationship between Candida albicans and Asthma is an important area of study that could lead to better understanding and management of Asthma. In the following sections, we will present a summary of various significant studies on the relationship between Candida Albicans colonization and asthma. We will also cover information on the microbiome of the gut and lungs, wherever applicable.

Additionally, we will provide key takeaways from each study, including relevant details such as the study’s title, authors, and organization affiliation. Finally, we will summarize the collective findings and scientific conclusions related to Candida Albicans colonization, sensitization, and infection in Asthma, and offer resources for you to share with your healthcare provider.

A comprehensive understanding of these aspects promises to shed light on the intricate mechanisms underlying severe asthma, offering new perspectives in our fight against this chronic condition.

Further Study

Name of study: Fungal Dysbiosis and Its Clinical Implications in Severe Asthma Patients
Date: 2023
Authors: Allison N. Imamura, Hannah K. Drescher, Mai Sasaki, Daniel J. Peaslee, David S. Crockett, Alexander S. Adams, Marcia L. Wills, Stephen C. Meredith, and Andrew H. Limper
Organization: Mayo Clinic, Rochester, MN
Summary: This study discusses the fungal dysbiosis in severe asthma patients. It finds that the lower alpha-diversity of lung microbiota and higher fungal burdens correlate with severity and poor control of asthma. The study also discusses the possible role of antibiotic usage and bacterial-fungal interactions in this process. The study concludes that understanding the link between Candida colonization, inflammation, autoimmune response, and Severe Asthma is crucial for better management of this chronic disease.

Study Title: CANDIDA ALBICANS INTESTINAL DYSBIOSIS INCREASES LUNG RESIDENT ILC2 POPULATIONS AND ENHANCES THE SEVERITY OF HDM-INDUCED ALLERGIC ASTHMA IN MICE

•  Date: October 17-20, 202

Authors: Amjad Kanj, Theodore Kottom, Kyle Schaefbauer, Andrew Limper, Joseph Skalski

•  Organization Affiliation: Mayo Clinic and University of California Davis

Human Anti-fungal Th17 Immunity and Pathology Rely on Cross-Reactivity against Candida albicans. Cell 2019. The authors are Petra Bacher, Thordis Hohnstein, Eva Beerbaum, Marie Röcker, Matthew G. Blango, Svenja Kaufmann, Jobst Röhmel, Patience Eschenhagen, Claudia Grehn, Kathrin Seidel, Volker Rickerts, Laura Lozza, Ulrik Stervbo, Mikalai Nienen, Nina Babel, Julia Milleck, Mario Assenmacher, Oliver A. Cornely, Maren Ziegler, Hilmar Wisplinghoff, Guido Heine, Margitta Worm, Britta Siegmund, Jochen Maul, Petra Creutz, Christoph Tabeling, Christoph Ruwwe-Glösenkamp, Leif E. Sander, Christoph Knosalla, Sascha Brunke, Bernhard Hube, Olaf Kniemeyer, Axel A. Brakhage and Carsten Schwarz.
The main objective of the article is to investigate how cross-reactivity against Candida albicans influences human anti-fungal Th17 immunity and pathology.
• C. albicans-specific Th17 cells can cross-react with other fungal antigens and gluten peptides in patients with CeD or asthma.
• Cross-reactive Th17 cells can cause immune pathology in the gut and lung by producing IL-17A and IL-22 cytokines.
Candida and asthma better by showing that Candida can induce a specific type of immune response that can also react to other fungi and allergens that are associated with asthma. The article also suggests that Candida may contribute to the severity and chronicity of asthma by causing inflammation and tissue damage in the lung. mechanisms and consequences of cross-reactivity are complex and need further investigation.

Name of study: Candida auris: Epidemiology, biology, a:Authors:ntifungal resistance, and virulence
Date: 2020
Authors: Du, H., Bing, J., Hu, T., Ennis, C. L., Nobile, C. J., & Huang, G.
M

Name of study: Candida albicans pathogenicity and epithelial immunity
Date: 2014
Abstract Naglik, J. R., Richardson, J. P., & Moyes, D. L.
URL:

Name of study: Candida albicans interactions with the host: crossing the intestinal epithelial barrier
Date: 2019
Abstract: [Unavailable in given data]
Authors: Basmaciyan, L., Bon, F., Paradis, T., Lapaquette, P., & Dalle, F.
URL: https://doi.org/10.1080/21688370.2019.1612661

Name of study: ACG Clinical Guideline: Treatment of Helicobacter pylori Infection
Date: 2017
Abstract: Authors: Chey WD, Leontiadis GI, Howden CW, Moss SF.
URL: https://doi.org/10.1038/ajg.2016.563

Name of study: Asthma is inversely associated with Helicobacter pylori status in an urban population
Date: 2008
Abstract: [Unavailable in given data]
Authors: Reibman J, Marmor M, Filner J, et al.
URL: https://doi.org/10.1371/journal.pone.0004060

Name of resource: H pylori Probiotics: A Comprehensive Overview for Health Practitioners
Date: 2020
Abstract: Authors: Ruscio M.
URL: https://drruscio.com/h-pylori-probiotics/

Name of resource: Treatment regimens for Helicobacter pylori in adults
Date: 2022
Abstract:
Authors: Lamont JT.

Name of study: Effects of probiotics on the recurrence of bacterial vaginosis: a review
Date: 2014
Abstract:
Authors: Homayouni A, Bastani P, Ziyadi S, et al.

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Shedding Light on T2-Low Asthma: A Forgotten Frontier in Asthma Research

Introduction:

Welcome to the World Asthma Foundation blog, where we strive to inform and inspire our readers in support of our mission. Today, we turn our attention to a lesser-known aspect of asthma called T2-Low asthma. While much focus has been placed on T2-High asthma, which includes allergic and non-allergic inflammation, T2-Low asthma has remained in the shadows. This subtype encompasses various forms, such as paucigranulocytic asthma, Type 1 and Type-17 inflammation, and the neutrophilic form, which is particularly common in severe or refractory cases. By exploring the realm of T2-Low asthma, we hope to raise awareness, ignite discussion, and rally the asthma community towards much-needed research and innovation.

Subheading: Unraveling the Complexity of T2-Low Asthma

Understanding T2-Low Asthma:

T2-Low asthma comprises different subtypes, including paucigranulocytic asthma, Type 1 and Type-17 inflammation, and the prevalent neutrophilic form. While T2-Low asthma is generally associated with milder symptoms, it’s important to note that the neutrophilic form can result in severe or refractory cases. By recognizing the complexities of T2-Low asthma, we can gain a deeper understanding of the challenges it poses to patients and researchers alike.

The Need for Research:

Despite its impact on patients, T2-Low asthma has received limited attention in terms of biomarkers and effective treatments. The scarcity of research on T2-Low asthma hinders progress in developing targeted therapies and diagnostic tools. By emphasizing the need for increased research efforts, we can work towards improving the lives of individuals living with T2-Low asthma.

Subheading: Key Takeaways

Key Takeaways:

T2-Low asthma encompasses various subtypes, including paucigranulocytic asthma, Type 1 and Type-17 inflammation, and the neutrophilic form.
While T2-Low asthma is generally associated with milder symptoms, the neutrophilic form can result in severe or refractory cases.
Limited research has been conducted on T2-Low asthma, leading to a lack of biomarkers and effective treatments.
Raising awareness and supporting research on T2-Low asthma is crucial to unlocking innovative solutions and improving outcomes for patients.
The World Asthma Foundation is dedicated to addressing the gaps in T2-Low asthma research and advocating for the needs of affected individuals.
Conclusion:

As we conclude our exploration of T2-Low asthma, we invite you to take action and support the cause. T2-Low asthma remains an understudied and overlooked frontier in asthma research, leaving many patients without effective treatments or biomarkers. It is our collective responsibility to raise awareness, push for solutions, improve diagnostics, and ultimately strive for a cure. By joining hands with the World Asthma Foundation, we can make a significant impact on the lives of those affected by T2-Low asthma. Together, we can transform the future of asthma care and provide hope for a brighter tomorrow.

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Infectious Asthma: Understanding the Complex Interplay between Infections and Asthma

Greetings to Members and Subscribers of the World Asthma Foundation

As a chronic respiratory disease, asthma affects millions of individuals worldwide, causing inflammation and narrowing of the airways, leading to breathing difficulties, coughing, and wheezing. Asthma can have a significant impact on individuals and their families, as well as the broader society, due to the high cost of treatment and the potential for reduced quality of life. Recent research has explored the relationship between infections and asthma, with a focus on the role of infections in exacerbating asthma symptoms. The World Asthma Foundation aims to provide a comprehensive review of the latest research related to infections and asthma, and to explore potential strategies for managing and preventing infection-related asthma.

Introduction

While the exact causes of asthma are not fully understood, researchers have identified several factors that can contribute to the development and exacerbation of the disease, including infections. Infections can be caused by a range of pathogens, including respiratory viruses, bacterial infections, and fungi, among others. Although the relationship between infections and asthma has been widely studied, a fundamental question that remains to be addressed is whether infections may be responsible for creating the asthmatic predisposition in the first place. Understanding the relationship between infections and asthma is critical for the management and prevention of asthma.

Infectious Agents and Asthma

Recent studies have shown that various infectious agents may contribute to the development and exacerbation of asthma. Respiratory viral infections, particularly those caused by rhinovirus and respiratory syncytial virus, have been linked to the development of childhood asthma. In addition, certain bacterial infections, such as those caused by Streptococcus pneumoniae and Haemophilus influenzae, may also contribute to the development of asthma.

More recent research has also implicated Chlamydia pneumoniae, Staphylococcus aureus, and Candida albicans as potential infectious agents linked to the development and exacerbation of asthma.

Chlamydia pneumoniae has been associated with a specific type of asthma, known as Chlamydia pneumoniae-mediated asthma. Staphylococcus aureus has been linked to the development of severe asthma, particularly in patients with atopic dermatitis. Candida albicans has been linked to the development and exacerbation of asthma, particularly in patients with severe asthma or fungal sensitization.

Antibiotics and Asthma

In addition to preventive strategies, such as avoidance and good hygiene practices, antibiotics may also have a role in the management of severe asthma. Azithromycin, an antibiotic, has been shown to be effective in reducing asthma exacerbations. However, the exact mechanism of action is not established, so it is unknown whether azithromycin works vis its antibiotic effects or because of some non-infectious anti-inflamatory activity. While most asthma specialists believe that azithromycin works because it is an anti-inflammatory, recent research suggests that it may be due to its antimicrobial effects against chronic atypical respiratory infections such as Chlamydia pneumoniae and Mycoplasma pneumoniae. It is important to note that a growing amount of research reflects that antibiotic use can contribute to dysbiosis and the development of asthma, and appropriate antibiotic use is necessary to prevent this potential negative impact on the microbiome.

Antifungal Therapy and Asthma

Fungi, particularly Candida albicans and Aspergillus fumigatus, have been implicated in the development and exacerbation of asthma. Fungal sensitization has been associated with more severe asthma and poorer asthma control. Some studies have shown that antifungal therapy may be effective in reducing asthma symptoms and improving lung function in individuals with fungal sensitization. However, the evidence for antifungal therapy in asthma is limited and further research is needed to fully understand the potential benefits and risks of this treatment. Moreover, antifungal therapy raises issues about efficacy and resistance, as improper use of antifungal medications can contribute to the development of drug-resistant fungi. Therefore, accurate diagnosis and appropriate use of antifungal therapy are necessary to prevent the development of drug-resistant fungi and ensure the safe and effective management of asthma.

Microbiome and Asthma

Recent research has also explored the role of dysbiosis, or an imbalance in the microbiome, in the development and exacerbation of asthma. The microbiome may influence asthma through several potential mechanisms, including modulation of the immune system and production of metabolites. While microbiome-targeted therapies, such as probiotics and fecal microbiota transplantation, may have potential as treatments for asthma, it is important to note that overuse of antibiotics can contribute to dysbiosis and the development of asthma. Therefore, appropriate antibiotic use is essential to prevent antibiotic overuse and the potential negative impact on the microbiome. Furthermore, the exact mechanisms by which dysbiosis influences asthma are not fully understood and require further research.

Challenges and Barriers

While significant progress has been made in understanding the relationship between infections and asthma, challenges and barriers remain. The lack of well-established classification and terminology for different types of infectious asthma is one such challenge. Further research is needed to develop a more comprehensive understanding of the complex interplay between infections and asthma, including the identification of specific types of infections that are most likely to trigger asthma exacerbations and the potential role of infections in creating the asthmatic predisposition.

Key Takeaway

  • Infections, particularly respiratory infections, have been linked to the development and exacerbation of asthma. Future research is needed to fully understand the complex interplay between infections and asthma.
  • Dysbiosis, or an imbalance in the microbiome, may contribute to the development and exacerbation of asthma.
  • Overuse of antibiotics can contribute to dysbiosis and the development of asthma. Therefore, appropriate antibiotic use is essential to prevent antibiotic overuse and the potential negative impact on the microbiome.
  • Fungi, particularly Candida albicans and Aspergillus fumigatus, have also been implicated in the development and exacerbation of asthma.
  • Antifungal therapy may be effective in reducing asthma symptoms and improving lung function in individuals with fungal sensitization, but further research is needed to fully understand the potential benefits and risks of this treatment.
  • Improper use of antifungal medications can contribute to the development of drug-resistant fungi, so accurate diagnosis and appropriate use of antifungal therapy are necessary to prevent the development of drug-resistant fungi and ensure the safe and effective management of asthma.
  • The exact mechanisms by which infections, dysbiosis, and fungi influence asthma are not fully understood and require further research.
  • It is essential to accurately diagnose and manage asthma to reduce the risk of exacerbations and improve quality of life.
  • This includes identifying and managing potential triggers, such as infections and dysbiosis.
  • Collaboration between researchers, healthcare providers, and patients is necessary to advance our understanding of the complex interplay between infections, dysbiosis, fungi, and asthma and develop effective strategies for managing this challenging disease.

Call to Action: Improving Diagnostic Tools and Methodology for Asthma

While significant progress has been made in understanding the relationship between infections and asthma, there are still challenges and barriers to identifying and managing the infectious agents that contribute to asthma development and exacerbation. One of the biggest challenges is the lack of well-established diagnostic tools and methodology for identifying the specific types of infections that are most likely to trigger asthma exacerbations.

Therefore, the World Asthma Foundation must call for increased research into developing and validating new diagnostic tools and methodology for infectious asthma. This research should focus on identifying new biomarkers that can be used to distinguish between different types of infectious asthma, and on developing new diagnostic tests that are highly sensitive and specific for detecting these biomarkers.

In addition, the World Asthma Foundation should advocate for increased funding for research into infectious asthma, including research into the mechanisms by which infectious agents contribute to asthma development and exacerbation, and the potential role of dysbiosis and the microbiome in infectious asthma.

Improved diagnostic tools and methodology for infectious asthma will be critical for developing more effective strategies for managing and preventing this challenging disease. By supporting research in this area, the World Asthma Foundation can make a significant impact on improving the lives of individuals living with asthma.

Future reports will delve further into the challenges and opportunities related to developing improved diagnostic tools and methodology for infectious asthma, highlighting new research and potential strategies for addressing this critical need.

Let’s work together to improve our understanding of infectious asthma and develop better ways to manage and prevent it.

Conclusion

Asthma is a complex respiratory disease with various factors that can contribute to its development and exacerbation, including infections.

A comprehensive understanding of the complex interplay between infections and asthma is critical for the management and prevention of asthma.

Further research is needed to develop more effective strategies for managing and preventing infection-related asthma.

As the World Asthma Foundation, it is essential to continue supporting and encouraging research into the relationship between infections and asthma, to improve the lives of those living with asthma.

References

Darveaux JI, Lemanske RF Jr. Infection-mediated asthma: etiology, mechanisms and treatment options, with focus on
Chlamydia pneumoniae and macrolides. Respir Res. 2002;3:14. doi:10.1186/rr172

Infection-mediated asthma: etiology, mechanisms and treatment options, with focus on Chlamydia pneumoniae and macrolideviruses
Wilmore C. Webley & David L. Hahn https://respiratory-research.biomedcentral.com/articles/10.1186/s12931-017-0584-z

Jackson DJ, Johnston SL. The role of viruses in acute exacerbations of asthma. J Allergy Clin Immunol. 2010;125(6):1178-1187. doi:10.1016/j.jaci.2010.04.021

Huang YJ, Marsland BJ, Bunyavanich S, et al. The microbiome in allergic disease: Current understanding and future opportunities-2017 PRACTALL document of the American Academy of Allergy, Asthma & Immunology and the European Academy of Allergy and Clinical Immunology. J Allergy Clin Immunol. 2017;139(4):1099-1110. doi:10.1016/j.jaci.2017.02.007

Johnston SL. Azithromycin for acute asthma: the AMASE randomized clinical trial. JAMA. 2016;316(17):1711-1713. doi:10.1001/jama.2016.16302