Glowing healthy lungs held gently in a supportive hand, representing successful lung transplant and restored respiratory health.

Breathe Easier: How to Reverse Lung Damage and Improve Your Life After Transplant

Lena Voss in Health & Wellness December 2025 • 4 min read.

"New research reveals the key to fighting lung transplant rejection and reclaiming your respiratory health."

Lung transplants offer a lifeline for individuals battling severe respiratory diseases. However, the journey doesn't end with the surgery. Many recipients face a significant hurdle: bronchiolitis obliterans syndrome (BOS), a condition that causes the small airways in the lungs to become inflamed and blocked. This can lead to shortness of breath, wheezing, and a decline in lung function, impacting overall quality of life.

Unfortunately, standard immunosuppression therapies, including corticosteroids, often fail to prevent BOS. This is where groundbreaking research offers a beacon of hope. Scientists are delving deep into the cellular mechanisms behind BOS, uncovering potential targets for new and more effective treatments. Recent studies shed light on the role of specific immune cells and a critical enzyme called histone deacetylase 2 (HDAC2) in the development of BOS.

This article breaks down this complex research, revealing how decreased HDAC2 activity in certain immune cells contributes to steroid resistance and inflammation in the small airways after lung transplantation. More importantly, it explores promising therapeutic strategies that could potentially reverse this process, paving the way for improved lung function and long-term survival for transplant recipients.

The HDAC2 Connection: What's It All About?

Glowing healthy lungs held gently in a supportive hand, representing successful lung transplant and restored respiratory health.

To understand the breakthrough, let’s dive into the key player: HDAC2. Histone deacetylases, or HDACs, are enzymes that play a vital role in regulating gene expression. Think of them as molecular switches that can turn genes on or off. HDAC2, in particular, is crucial for the proper functioning of corticosteroids, which are powerful anti-inflammatory drugs commonly used to prevent transplant rejection. When HDAC2 activity is reduced, corticosteroids become less effective, leading to persistent inflammation.

Recent research has discovered a concerning trend in lung transplant recipients who develop BOS. These individuals often exhibit decreased HDAC2 activity in specific immune cells called lymphocytes, especially those residing in the small airways. This reduction in HDAC2 makes these lymphocytes resistant to the effects of steroids, allowing them to unleash pro-inflammatory molecules that damage the delicate lung tissue.

Steroid Resistance: Lower HDAC2 means standard anti-inflammatory drugs lose their punch.
Inflammation Surge: Unchecked lymphocytes cause ongoing damage in the lungs.
Small Airways Focus: The problem is most pronounced in the tiniest, most vulnerable parts of the lungs.

This connection between decreased HDAC2 and steroid resistance provides a crucial target for new therapies. If scientists can find ways to boost HDAC2 activity in these critical immune cells, they might be able to restore steroid sensitivity, quell inflammation, and ultimately prevent or reverse the progression of BOS.

A Breath of Fresh Air: Promising Therapies on the Horizon

The good news is that researchers are already exploring therapeutic strategies to increase HDAC2 activity and combat steroid resistance in lung transplant recipients. One promising approach involves the use of theophylline, a medication traditionally used to treat asthma and other respiratory conditions. Studies have shown that theophylline can act as an HDAC2 activator, boosting its activity and restoring steroid sensitivity. Combining theophylline with corticosteroids may create a synergistic effect, dampening inflammation and improving lung function.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1111/cei.13221, Alternate LINK

Title: Bos Is Associated With Decreased Hdac2 From Steroid Resistant Lymphocytes In The Small Airways

Subject: Immunology

Journal: Clinical and Experimental Immunology

Publisher: Oxford University Press (OUP)

Authors: G Hodge, S Hodge, A Yeo, P Nguyen, E Hopkins, H Liu, C L Holmes-Liew, M Holmes

Published: 2018-10-29

Everything You Need To Know

What is bronchiolitis obliterans syndrome (BOS) and why is it a concern for lung transplant recipients?

Bronchiolitis obliterans syndrome, or BOS, is a condition that affects lung transplant recipients, causing inflammation and blockage in the small airways of the lungs. This leads to symptoms like shortness of breath, wheezing, and a decline in lung function, significantly impacting the recipient's quality of life. BOS is concerning because it's a major cause of long-term morbidity and mortality after lung transplantation, and current immunosuppression therapies often prove ineffective in preventing or reversing its progression.

How does decreased HDAC2 activity contribute to steroid resistance in lung transplant recipients with BOS?

Decreased activity of histone deacetylase 2, known as HDAC2, impairs the effectiveness of corticosteroids, which are vital anti-inflammatory drugs used to prevent transplant rejection. When HDAC2 activity is reduced in immune cells like lymphocytes, particularly those in the small airways, the lymphocytes become resistant to steroids. This allows them to release pro-inflammatory molecules, leading to inflammation and damage to the delicate lung tissue. This resistance prevents the steroids from suppressing the immune response, contributing to the development and progression of BOS.

What role do lymphocytes play in the development of inflammation and damage in the lungs of transplant recipients?

Lymphocytes are a type of immune cell that can contribute to inflammation and damage in the lungs of transplant recipients, particularly when histone deacetylase 2, or HDAC2, activity is reduced. Lower HDAC2 activity makes these lymphocytes resistant to the effects of steroids, causing them to unleash pro-inflammatory molecules. These molecules damage delicate lung tissue. This unchecked inflammatory response contributes to the development of bronchiolitis obliterans syndrome, or BOS, leading to impaired lung function and other respiratory complications.

What potential therapeutic strategies are being explored to increase HDAC2 activity and combat steroid resistance in lung transplant recipients?

Researchers are exploring therapeutic strategies such as theophylline, traditionally used for asthma, to increase histone deacetylase 2, or HDAC2, activity and combat steroid resistance. Theophylline has demonstrated potential as an HDAC2 activator, boosting its activity and restoring steroid sensitivity. Combining theophylline with corticosteroids could create a synergistic effect, reducing inflammation and improving lung function. Restoring HDAC2 activity and steroid sensitivity offers a promising avenue for improving long-term outcomes for lung transplant recipients.

If theophylline can boost HDAC2 activity, what are the potential implications and benefits of combining it with corticosteroids for treating or preventing BOS after a lung transplant?

Combining theophylline, an HDAC2 activator, with corticosteroids may offer several potential benefits. By boosting HDAC2 activity, theophylline can restore sensitivity to corticosteroids in lymphocytes, allowing them to effectively suppress inflammation. This synergistic effect could lead to better control of inflammation in the small airways, potentially preventing or reversing the progression of bronchiolitis obliterans syndrome, or BOS. Improved lung function, reduced symptoms like shortness of breath and wheezing, and enhanced long-term survival are all potential outcomes. However, further research is needed to fully understand the optimal dosage, timing, and potential side effects of this combination therapy.