Many of our patients and their relatives ask if their likelihood of developing pulmonary fibrosis is written in their genetic code – is pulmonary fibrosis genetic?
Current research indicates that genes do play a role, particularly in cases where multiple family members are affected. This article explores the evidence linking pulmonary fibrosis to genetics, discusses known genetic links associated with the disease and explores what it means for patients with pulmonary fibrosis and their families.
Overview:
Pulmonary fibrosis is a lung condition that can be inherited, particularly in familial pulmonary fibrosis, which makes up about 20% of cases and appears to involve a genetic component.
Genetic variants, such as mutations (gene changes) in the MUC5B and TERT genes, have been identified as risk factors for pulmonary fibrosis. This helps us understand how the disease develops and may shed new light on how to treat it.
Genetic testing is recommended for people with pulmonary fibrosis in their family, especially when there is a history suggestive of telomerase gene dysfunction (which may include premature hair greying and abnormalities of liver or blood). This can help manage the disease and inform family members who might be at risk.
Understanding Pulmonary Fibrosis and its Types
Pulmonary fibrosis causes lung scarring, making it hard to breathe due to reduced oxygen uptake and lung function and this ultimately reduces the quality of life. Among interstitial lung diseases (ILD), idiopathic pulmonary fibrosis (IPF) stands out due to its unknown cause and for being notoriously hard to treat.
In addition to IPF, there are other forms of interstitial lung disease, like asbestosis and familial ILD, which can manifest long after exposure to certain environmental toxins, such as asbestos, silica or from an inherent genetic susceptibility. Common symptoms include a persistent cough and breathing difficulties.
For a more in-depth exploration of pulmonary fibrosis, click here.
The Genetic Connection in Pulmonary Fibrosis
Recent scientific efforts have started to unravel the genetic foundations of pulmonary fibrosis, indicating that the origins of the disease may be deeply embedded in our DNA. The discovery of genetic mutations, such as chromosome 11p15 (MUC5B and TOLLIP), has not only shed light on the mechanisms of the disease, but also offered a glimmer of hope. These pioneering discoveries help us understand how pulmonary fibrosis works and could lead to better treatments.
Familial Pulmonary Fibrosis: A Closer Look
When pulmonary fibrosis occurs among two or more first degree relatives, it is called ‘familial pulmonary fibrosis’, which accounts for approximately 20% of all cases. If a parent has pulmonary fibrosis, each child has a 50% chance of inheriting the gene that increases the risk.
Genetic testing is available on the NHS for anyone diagnosed with familial interstitial pneumonia. Such screening may help to understand how the disease might progress and to evaluate risk levels among family members.
Of note, alterations in telomere-associated genes, like TERT and TERC, are frequently found in affected families, but often a known gene is not identified. In these cases, the data is stored and can be re-examined when new genes are identified.
Known Genetic Variants Linked to Pulmonary Fibrosis
Specific genetic mutations (changes) have been found to contribute to pulmonary fibrosis. Mutations in telomerase are associated with accelerated shortening of telomeres, which may compromise the maintenance and regeneration of alveolar epithelial cells, predisposing to idiopathic pulmonary fibrosis following repeated injury. Shorter telomeres—which can be passed down through generations—worsen symptoms and lead to an earlier onset of pulmonary fibrosis in families. The presence of shortened telomeres not only indicates a more severe form of pulmonary fibrosis, but also highlights the importance of understanding how genetics influence the development of IPF within families.
In contrast, surfactant protein C mutations are known to raise the risk of familial pulmonary fibrosis by causing harmful effects, such as protein misfolding and stress on the cell’s endoplasmic reticulum.
Such uncommon variants, including those observed in genes like SFTPA1, reveal an underlying genetic susceptibility shared between sporadic cases of idiopathic pulmonary fibrosis (IPF) and familial interstitial pneumonia.
As well as these uncommon variants, there are more common variants, such as the MUC5B promoter polymorphism—a significant risk factor for pulmonary fibrosis that is found in 1 in 5 of the general population. Although people with this are about 15 times more likely to develop pulmonary fibrosis, the vast majority will not develop the condition.
Heredity and Idiopathic Pulmonary Fibrosis (IPF)
Our understanding of idiopathic pulmonary fibrosis has grown with the knowledge that there is a hereditary component. Known as familial idiopathic pulmonary fibrosis, or simply familial pulmonary fibrosis, this form is identified when two or more family members are diagnosed with it. Research indicates that up to 20% of those suffering from pulmonary fibrosis may have this inherited variant. There appears to be a genetic risk spectrum associated with both familial (inherited) or sporadic (random) idiopathic pulmonary fibrosis. Indeed, studies suggest that as many as 35% of individuals with IPF, even without known family members also affected, could have an innate susceptibility due in part to hereditary factors related to pulmonary fibrosis.
Rare Genetic Changes and their Impact
Rare genetic variants are crucial in triggering pulmonary fibrosis. In both familial pulmonary fibrosis and sporadic idiopathic pulmonary fibrosis, genes involved in surfactant metabolism and telomere maintenance are frequently implicated, indicating a shared genetic vulnerability. The identification of new mutations, such as those in the SFTPA1 gene, enhances our understanding of genetic factors contributing to this respiratory disease. Variants in the desmoplakin gene suggest they may play a key role in protecting the health and structure of cells lining the airways in the lungs.
These rare genetic variants typically lead to adult-onset pulmonary fibrosis, usually appearing after age 50, and can cause symptoms beyond respiratory issues by affecting other organs, like the liver, and showing early signs such as premature greying of the hair.
About 25% of people with familial pulmonary fibrosis carry these unique variants. Similarly, individuals with extremely short telomeres are often found among those with sporadic IPF.
Genetic Testing for Pulmonary Fibrosis
The introduction of genetic testing for pulmonary fibrosis has paved the way for precision medicine and is available in the UK on the NHS for those diagnosed with familial interstitial pneumonia or with a history suggestive of an underlying telomerase dysfunction syndrome. Although challenging, it is important for all patients diagnosed with idiopathic pulmonary fibrosis to have their family history comprehensively documented, irrespective of age. Not only does this help identify familial trends which could be indicative of the disease, but it also determines the need for a genetic evaluation.
Navigating Genetic Tests
Genetic counselling is essential as it helps patients understand the implications, whether medical, psychological or familial, that come with screening for a hereditary condition. When dealing with familial pulmonary fibrosis specifically, undergoing genetic testing may impact not only those individuals living with the condition, but also their relatives.
The Interaction Between Genetics and Environmental Factors
Pulmonary fibrosis, particularly the idiopathic variety, is caused by a complex mix of genetic risk factors and environmental influences. Both are crucial to how the disease presents itself and evolves over time. The likelihood of developing idiopathic pulmonary fibrosis is heightened by external factors, such as viral infections, exposure to tobacco smoke, air pollution and specific types of work-related exposures.
A person’s genetic predisposition establishes their risk for developing pulmonary fibrosis, but environmental triggers often worsen the condition by causing damage to lung epithelial cells, increasing oxidative stress and promoting inflammation in the respiratory system.
Personal lifestyle choices and socioeconomic health disparities further complicate the situation, as they can exacerbate conditions related to cellular aging. When combined with harmful environmental factors, these elements significantly contribute to an individual’s risk of developing idiopathic pulmonary fibrosis.
Treatment Options and Managing Genetic Risks
In the management of pulmonary fibrosis, especially idiopathic pulmonary fibrosis (IPF), treatment strategies often include anti-fibrotic medications, such as pirfenidone and nintedanib, due to their efficacy in significantly slowing down disease progression.
Patients afflicted by sporadic forms of IPF who also have shortened telomeres face heightened risks during a lung transplant, emphasising the role of genetic factors in forecasting treatment results. For these individuals, it might be beneficial to assess telomere lengths within peripheral blood mononuclear cells (PBMC) ahead of transplantation procedures. This testing can provide additional prognostic information that could influence the evaluation and decision-making process prior to a lung transplant.
Advances in Targeted Therapy
The range of treatments for pulmonary fibrosis is constantly developing, with emerging therapies aimed at stopping or even reversing the scarring process within idiopathic pulmonary fibrosis (IPF). Among those therapeutic agents currently undergoing clinical trials are:
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Inhibitors targeting integrins
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Inhibitors of autotaxin
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Therapies that focus on connective tissue growth factor
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Proteins produced through recombinant DNA technology
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Orally administered phosphodiesterase type 4B inhibitor, known as BI 1015550
These potential advancements in personalised medicine are crucial because they aim not only to slow down the development of the disease and lung function decline, but also to improve the patient’s quality of life.
Currently, there are no treatments for specific genetic mutations in pulmonary fibrosis, although it is hoped that one day this will be the case.
Living with Genetic Predisposition to Pulmonary Fibrosis
Living with a genetic predisposition to pulmonary fibrosis involves a lot of uncertainty and variation. The disease can show different patterns within families, such as varying ages of onset and severity of symptoms—a phenomenon known as ‘genetic anticipation.’ This means that later generations might experience more severe forms of the disease at a younger age. Understanding these genetic influences is essential because they help shape personalised management strategies and inform health decisions for those at risk.
Individuals with a genetic predisposition to pulmonary fibrosis face not only the physical challenges of the disease, but also significant emotional and psychological difficulties associated with having an inherited medical condition. Knowing about a genetic predisposition to pulmonary fibrosis helps patients and their families make informed decisions about treatment options, lifestyle changes and careful health monitoring. These steps are crucial for managing the disease effectively and maintaining the best possible quality of life.
Summary
We have learned that pulmonary fibrosis is a complex lung disease intrinsically linked to our genetic makeup and simultaneously shaped by environmental influences. While some forms of pulmonary fibrosis run in families, others can develop due to external factors.
New treatments and clinical trials offer hope for better management of pulmonary fibrosis, yet possessing a genetic predisposition to pulmonary fibrosis demands fortitude as well as strategic choices about care. If you have a genetic risk for pulmonary fibrosis, it is important to work closely with your healthcare team to make informed decisions about your care.
Frequently Asked Questions
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Does pulmonary fibrosis run in the family? – Yes, although not commonly seen as a hereditary condition, there are instances where pulmonary fibrosis is passed down through families.
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What is the age of onset for familial pulmonary fibrosis? – Familial pulmonary fibrosis usually appears between ages 50 to 70.
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Is there a genetic test for pulmonary fibrosis? – It is possible to carry out genetic testing for pulmonary fibrosis. This test can be performed using germline DNA taken from blood, saliva, cheek cells or a skin biopsy. Prior to proceeding with genetic testing for pulmonary fibrosis, engaging in genetic counselling is an essential step.
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What is the main cause of pulmonary fibrosis? – Several risk factors have been identified that may increase the chances of developing pulmonary fibrosis, although the exact cause often remains unknown. Risk elements include growing older, male gender, smoking tobacco products, genetic vulnerabilities to the condition, contact with hazardous substances, such as asbestos and silica dusts along with coal dust exposure. Particular drugs and viral infections can also increase the risk. If there is a known family history of idiopathic pulmonary fibrosis, this has been recognised as increasing the likelihood of being affected.
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What are the first signs of pulmonary fibrosis? – Early signs of pulmonary fibrosis include a persistent dry cough, shortness of breath, tiredness, unexplained weight loss and the widening or rounding of fingertips and toes (called clubbing). Should you notice any of these symptoms, it is important to consult your physician to obtain an accurate diagnosis.