Last reviewed: April 2026
Audience: Patients, carers, GPs, specialist nurses
This article explains how the immune system, environment, and emerging research all connect. If helpful, you can explore each topic in more detail using the links throughout this page.
Key Points
- Epigenetics controls how your genes behave without changing your DNA sequence.
- It helps explain why people with similar lung disease develop different forms of aspergillosis.
- Both the human immune system and the fungus itself use epigenetic mechanisms.
- These processes influence inflammation, immune response, and treatment effectiveness.
- Future treatments may combine antifungals, biologics, and epigenetic approaches.
- There are currently no epigenetic therapies for aspergillosis in routine NHS care.
Table of Contents
- What is epigenetics?
- How epigenetics works (simple explanation)
- Why this matters in aspergillosis
- Different diseases, different immune patterns
- Damp, mould, and environmental exposure
- Why treatment works differently
- Biologics vs epigenetics
- What research is trying to do
- Epigenetics in Aspergillus itself
- What this means for the future
- Common questions
- When to seek medical advice
- References
What is epigenetics?
If you are new to aspergillosis, you may find it helpful to first read our overview of what aspergillosis is.
Epigenetics refers to changes in how your genes are used by your body, without changing the underlying DNA sequence.
You can think of your DNA as a library of instructions. Epigenetics controls:
- Which instructions are read
- When they are used
- How strongly they are activated
This allows your body to adapt to its environment—but it can also contribute to disease.
How epigenetics works (simple explanation)
There are three main mechanisms:
- DNA methylation – switches genes off
- Histone modification – controls how tightly DNA is packaged (affecting access to genes)
- MicroRNAs – fine-tune gene activity
These processes are now recognised as key regulators of immune and fungal biology
(Nie et al., 2018).
Why this matters in aspergillosis
Patients often ask:
“Why did I develop this when others didn’t?”
Epigenetics helps explain why similar exposures to Aspergillus can result in:
- Allergic disease
- Chronic infection
- No disease
This reflects differences in immune system “programming”.
Importantly, this programming is influenced by:
- Past infections
- Lung damage (e.g. COPD, TB)
- Environmental exposure
- Medications
Is the body “testing” responses before they become permanent?
It can sometimes feel as though the body is “trying out” different ways of responding to infection or environmental exposure.
This idea comes close to how epigenetics works—but it is important to understand it carefully.
A useful way to think about it
Epigenetics allows the body to rapidly adjust how genes behave in response to the environment. This can happen over days, months, or years, and may influence how the immune system reacts to fungi such as Aspergillus.
In this sense, epigenetics can be thought of as allowing the body to explore different “settings” of immune response—for example:
- A stronger allergic response (as seen in ABPA)
- A weaker or less effective response (as seen in CPA)
- A balanced response with minimal symptoms
What epigenetics does not do
It is important to be clear that the body is not deliberately “testing” changes in a planned way, and epigenetic changes are not directly converted into permanent genetic mutations.
Instead:
- Epigenetic changes are fast and flexible
- Genetic changes (mutations) occur slowly and randomly
- Natural selection acts over long timescales to favour traits that improve survival
How the two processes connect
Although separate, epigenetics and evolution can interact over time.
If a particular way of responding to infection is consistently helpful, individuals whose genes naturally produce a similar response may be more likely to thrive over generations.
This means:
- Epigenetics shapes how the body responds in the short term
- Evolution shapes which responses persist in the long term
Why this matters in aspergillosis
This helps explain why:
- Different people respond very differently to the same fungal exposure
- Symptoms can change over time
- Modern environments (such as damp housing or long-term steroid use) may produce responses that our immune systems were not originally adapted for
Can epigenetic changes be inherited?
Most epigenetic changes happen within a single lifetime and are not passed on to children. However, there is growing evidence that some epigenetic changes may persist or be transmitted across generations under certain conditions.
This is sometimes called transgenerational epigenetic inheritance.
For example, research suggests that:
- Environmental exposures (such as diet, stress, or infection) may leave lasting epigenetic marks
- Some of these marks may influence how genes behave in the next generation
- This effect is usually partial and not always predictable
In humans, this area is still being studied, and the extent to which epigenetic changes are inherited remains uncertain.
What this means in practice
It is important not to overinterpret this idea:
- Epigenetic inheritance is not a replacement for genetic inheritance
- Most traits and diseases are still determined by DNA and environment
- There is currently no evidence that conditions like aspergillosis are directly passed on through epigenetic changes
However, this research does suggest that environment and health may have longer-term effects than previously thought, potentially influencing future generations in subtle ways.
In simple terms:
Epigenetics allows the body to adapt quickly. Evolution determines what lasts.
Different diseases, different immune patterns
See also:
Allergic pattern (ABPA)
- Strong Th2 immune response
- High IgE and eosinophils
- Exaggerated reaction to fungal spores
Epigenetic changes may increase expression of cytokines such as IL-4, IL-5, and IL-13, driving allergic inflammation.
Chronic infection pattern (CPA)
- Reduced ability to clear fungus
- Persistent infection in damaged lung areas
- Chronic inflammation and tissue damage
Epigenetic changes may “lock in” ineffective immune responses.
Damp, mould, and environmental exposure
Long-term exposure to damp and mould is highly relevant.
It may:
- Alter airway cell behaviour
- Increase sensitivity to fungal spores
- Promote ongoing inflammation
These effects may persist through epigenetic changes, even after exposure is reduced.
See:
Why treatment works differently
Epigenetics may explain why patients respond differently to treatment.
- Some respond well to steroids
- Others develop resistance or side effects
- Biologic response varies between individuals
A key mechanism involves reduced activity of enzymes such as histone deacetylase 2 (HDAC2), which is important for steroid response.
See also: Why antibiotics do not always work
Biologics vs epigenetics
Biologics
- Target specific immune signals (e.g. IgE, IL-5)
- Fast and precise
- Widely used in severe asthma and ABPA
Epigenetics
- Acts at a deeper level
- Influences multiple pathways
- May create longer-lasting effects
Epigenetics is unlikely to replace biologics—it is more likely to enhance and personalise them.
What research is trying to do
1. Restoring steroid sensitivity
Research is exploring how to restore HDAC2 activity and improve steroid effectiveness.
2. Trained immunity (immune memory)
Immune cells can be “trained” by past exposures. This may lead to:
- Better defence
- Or harmful chronic inflammation
Scientists are studying how to reset this balance.
3. MicroRNA biomarkers
MicroRNAs may help predict:
- Disease severity
- Risk of relapse
- Treatment response
4. Metabolic and immune reprogramming
Immune cell metabolism is closely linked to epigenetic regulation. Modifying this may improve immune function.
Epigenetics in Aspergillus itself
The fungus is not passive—Aspergillus fumigatus also uses epigenetic control.
This influences:
- Virulence (how aggressive it is)
- Biofilm formation
- Resistance to antifungal drugs
Recent research shows that epigenetic regulators directly affect fungal interaction with the host
(Liu et al., 2026).
Other studies show control of toxin production and colonisation
(Hao et al., 2023).
What this means for the future
The most realistic model is layered care:
- Antifungals
- Steroids
- Biologics
- Environmental control
- Future epigenetic approaches
Epigenetics may:
- Improve treatment response
- Reduce relapse
- Enable personalised care
These approaches are still in development.
Common Questions
Can I change my epigenetics?
Not directly. However, reducing damp exposure and maintaining general health may support better immune regulation.
Are these treatments available?
No. They are still in research.
Why do my symptoms fluctuate?
Immune regulation changes over time. Epigenetics may contribute alongside infection and exposure.
Is this the next generation of treatment?
It is better seen as an additional layer that may improve existing treatments.
When to seek medical advice
- Worsening breathlessness
- Increased cough
- Chest pain
- Weight loss
- Sudden symptom changes
This article is for education and does not replace clinical advice.
References
- Liu H et al. (2026)
- Nie X et al. (2018)
- Hao L et al. (2023)
- BTS Clinical Statement
- ISHAM Guidelines
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