What causes pulmonary fibrosis: understanding and managing this lung condition

What underlies pulmonary fibrosis?

Pulmonary fibrosis is a condition characterised by the thickening or scarring of lung tissue, specifically affecting the tissue surrounding the air sacs in the lungs, which is called the interstitial space. Hence, the disease that cause pulmonary fibrosis scars are collectively called the interstitial lung diseases (ILDs). This thickening of the interstitial space makes it harder for oxygen to move from the alveolar space into the bloodstream during inhalation. But what causes this damage? What are the triggers that initiate this transformation from healthy lung tissue to scarred, less flexible tissue?

The onset of pulmonary fibrosis, an interstitial lung disease, can be caused by various factors including, but not limited to:

• Exposure to environmental toxins like asbestos, coal dust or silica.
• Cumulative exposure to certain medications including amiodarone (a medication often used to treat fast or irregular heartbeat) or nitrofurantoin (a medication often used to treat and prevent lower urinary tract infections).
• Chronic hypersensitivity pneumonitis: for example, following exposure to fungal antigens, as in Farmer’s Lung.
• Autoimmune conditions: such as rheumatoid arthritis.
• Hereditary factors: as seen in familial forms of pulmonary fibrosis.

Despite this, the cause for many cases of pulmonary fibrosis is not identified and these are called idiopathic, of which the most severe form is called idiopathic pulmonary fibrosis (IPF).

Another significant complication of pulmonary fibrosis scars is pulmonary hypertension. This condition arises from the compression of the lungs’ arteries and capillaries by scar tissue, which increases resistance to blood flow and puts strain on the heart.

Environmental exposures

In the case of pulmonary fibrosis, the air we breathe may be an invisible enemy. Prolonged exposure to environmental toxins and pollutants can lead to lung damage, culminating in pulmonary fibrosis scars. The toxins involved are not rare, exotic substances but rather common elements in many industries, including metals, wood dust and chemicals.

These toxins and pollutants damage lung tissues through mechanisms involving oxidative stress and the production of free radicals, inducing injury to the lungs. The damage from these environmental exposures does not occur instantly, but builds up over time, resulting in a slow deterioration of lung function.

Medical treatments that affect lung tissue

Medications are designed to facilitate healing, but there are instances where they can inadvertently cause harm. Certain medications have been linked to lung damage and the development of pulmonary fibrosis. We call this drug-induced ILD. For instance, although short courses are not an issue, the long-term use of nitrofurantoin, a commonly prescribed antibiotic for urinary tract infections, or amiodarone, a drug commonly used to control the heart rhythm in atrial fibrillation, may lead to pulmonary fibrosis.

The mechanism behind this is thought to involve oxidative stress and the production of free radicals, leading to injury to the lung tissue. This underlines the significance of understanding the potential side effects of medications and the necessity for consistent monitoring for lung disease and consultation with healthcare providers.

Health conditions that can cause lung damage

Our bodies are a complex interconnected system where a condition affecting one part can have a ripple effect on another. Autoimmune disease such as rheumatoid arthritis and systemic sclerosis, which are types of connective tissue disease, have been linked to the development of interstitial lung disease. Although not all cases of autoimmune disease lead to lung scarring, a notable proportion of patients with connective tissue disease do develop interstitial lung diseases (CTD-ILD) and pulmonary fibrosis.

These autoimmune diseases contribute to lung damage through the activation of inflammatory signalling pathways, leading to scar tissue. This underlines the importance of consistent monitoring for lung disease in patients with these conditions.

Idiopathic pulmonary fibrosis: when the cause is unknown

Sometimes, despite our best efforts to understand a disease, it remains a mystery. Such is the case with idiopathic pulmonary fibrosis (IPF), a form of pulmonary fibrosis for which the cause remains unknown. Despite the unknowns, researchers have proposed several theories about potential risk factors and/or triggers for idiopathic pulmonary fibrosis, including:

• Viruses,
• Exposure to tobacco smoke,
• Genetic factors,
• Environmental factors.

Other potential risk factors being investigated are the relationship between gastro-oesophageal reflux disease (GORD), diabetes, changes in the lung microbiome and infection, and idiopathic pulmonary fibrosis.

The uncertainty surrounding its causes makes idiopathic pulmonary fibrosis particularly challenging to manage, highlighting the need for ongoing research.

Genetics and family history: their role in pulmonary fibrosis

While our environment and lifestyle choices play a significant role in our health, our genes also have a substantial impact. In the case of interstitial lung disease and pulmonary fibrosis, both a family history and specific genetic factors significantly increase the risk of developing the condition. So, what does this mean for you and your family?

Genetic tests can detect detrimental variants in genes that have been linked to pulmonary fibrosis. In some cases, these genes are rare and affect multiple family members – these tend to cause a premature ageing of the lung and susceptibility to lung scarring. In other cases, families may have common variants of genes that predispose to developing lung scarring. For example, a common form or the gene for mucin 5B (a protein found in sputum that gives it a stringy quality) occurs in 2 common forms. The less common form is found in around 1 in 5 of the population, but increases your risk of pulmonary fibrosis by over 10-fold. However, this still means that, even if you have the ‘MUC5B promoter polymorphism’ that predisposes you to the development of interstitial lung disease or idiopathic pulmonary fibrosis, your chances of developing lung disease and pulmonary fibrosis are very small, but the gene will increase your lifetime risk from less than 1 in 6000 to nearer 1 in 600. No-one knows why this happens, but we are actively trying to understand the mechanism by which increased amounts of MUC5B lead to lung scarring.

At the moment, we can test for some of the rarer and more common genes associated with pulmonary fibrosis. If you have a family history of pulmonary fibrosis, or if you and at least one of your first degree relatives both have pulmonary fibrosis, it is important to inform your healthcare provider who might suggest counselling to discuss the pros and cons of genetic testing.

The progression of pulmonary fibrosis and its impact on lungs

The prognosis from pulmonary fibrosis is very variable from one patient to another. In some, there is stability or even regression of the scarring whilst in others there may be a gradual but progressive change. Although there are no officially defined stages in types of pulmonary fibrosis, physicians may refer to the following, based on lung function and high resolution CT scan, to describe the progression of the disease:

• Mild fibrosis,
• Moderate fibrosis,
• Severe fibrosis,
• End-stage fibrosis.

With each stage, the disease leaves its mark on the lungs, reducing their flexibility and affecting their function.

As pulmonary fibrosis progresses, it leads to hard, stiff lung tissues that make it increasingly difficult to breathe. This condition may result in shortness of breath during routine tasks that were previously not tiring. As well as shortness of breath, patients may develop a dry, irritating cough.

One of the striking features of pulmonary fibrosis is that it can affect patients so differently, even very similar patients may have very different outcomes. The harsh reality is that pulmonary fibrosis may be a terminal illness in those patients most severely affected. However, this is not the same for all patients and every patient’s case will be different from another. This fact highlights the pressing need to understand how we can determine which patients are going to progress quickly and which patients will not. This will help us decide on the risks and benefits of the different treatments for each patient. At Breathing Matters, we are looking at new biomarkers (or clinical tests) that will determine the prognosis for individual patients, determine which treatment options are best for them, and also tell us whether patients are responding appropriately to specific treatments. This forms the basis of our mission to make personalised or precision medicine a reality in pulmonary fibrosis. Ultimately, we hope to find more effective treatments and eventually a cure.

Diagnosing pulmonary fibrosis: beyond the causes

The journey towards getting pulmonary fibrosis diagnosed begins with a discussion with your healthcare provider about your symptoms and medical history, along with a physical examination. The doctor may inquire about your work, smoking habits and potential exposures that could impact your lungs. This initial step is crucial in narrowing down the potential causes and guiding further diagnostic testing.

What are the first signs of pulmonary fibrosis?

The first signs of pulmonary fibrosis can include being short of breath, a persistent dry cough, fatigue and sometimes unexplained weight loss. If you experience any of these symptoms, it is important to speak to your doctor promptly to get an accurate diagnosis.

Getting an accurate diagnosis

An accurate diagnosis of pulmonary fibrosis is vital due to the highly variable treatment and prognosis for different types of the condition. To arrive at this diagnosis, your healthcare provider may suggest a range of tests, such as:

• Blood tests: looking for inflammation and markers of autoimmune disease,
• Imaging tests: such as chest x-ray and high resolution computed tomography (HRCT) scan,
• Pulmonary function tests: that tell us how well the lungs are working,
• Bronchoscopy: to look for ongoing inflammation in the alveoli or air sacs.

In some cases, when non-invasive tests are inconclusive, a lung biopsy may be necessary. This can be done relatively non-invasively at the same time as bronchoscopy or separately as keyhole surgery under general anaesthesia to remove a tissue sample for further examination.

Throughout the diagnostic process, it is crucial to maintain open communication with your healthcare provider, asking questions and discussing any concerns you may have. The more knowledge you have, the better armed you will be to cope with your pulmonary fibrosis diagnosis.

Treatment options for managing pulmonary fibrosis

After receiving a diagnosis of pulmonary fibrosis, the next step is to discuss treatment options with your healthcare provider. Although there is currently no cure for pulmonary fibrosis (apart from lung transplantation suitable for only a very small minority of patients), there are several treatments available that can help manage the symptoms and slow the progression of the disease.

The choice of treatment is influenced by various factors, including the specific cause of your pulmonary fibrosis.

Medications to reduce inflammation

Pulmonary fibrosis treated may involve medications, such as prednisolone and mycophenolate which are aimed at reducing inflammation and slowing scarring in the lungs.

Medications to slow scarring

Antifibrotic medications for pulmonary fibrosis aim to slow the progression of the disease. These antifibrotic medications, such as nintedanib and pirfenidone, inhibit the activation of receptors involved in the proliferation, migration and maturation of lung fibroblasts, reduce collagen fibril formation and slow the decline in lung function in individuals with progressive pulmonary fibrosis. Ongoing research is focused on the development of new drugs.

Beyond medications, other treatments for interstitial lung disease include:

• Oxygen therapy to relieve symptoms such as breathlessness and fatigue while improving oxygen levels in the lungs. Oxygen therapy, also known as supplemental oxygen, can potentially alleviate shortness of breath and facilitate increased physical activity for individuals with pulmonary fibrosis and is particularly important to take the strain off the heart in patients with pulmonary hypertension due to their lung disease.
• Management of other symptoms, such as cough and breathlessness.

• Physiotherapy to maximise effective use of breathing muscles, including the diaphragm.
• Pulmonary rehabilitation programs to improve lung function and overall quality of life. Pulmonary rehabilitation is another key component in managing pulmonary fibrosis. This comprehensive program incorporates exercise, education, and guidance aimed at assisting individuals in managing breathlessness. It can enhance exercise tolerance, teach patients breathing techniques to manage shortness of breath, improve exercise capacity, delay lung function decline and alleviate symptoms.
• Maintaining a healthy diet, sleep routine, exercise programme and healthy weight.
• Lung transplant: In certain severe cases, when other treatments have proven ineffective, a lung transplant might be considered. This surgical procedure involves replacing one or both affected lungs with healthy lungs from a donor. While a lung transplant can significantly improve the quality of life for some patients, it is not without its risks and is only suitable for a very small minority of patients. Potential complications can include rejection of the transplanted lung, infections and side effects stemming from the use of immunosuppressant medications to prevent rejection. Hence, the decision to proceed with a lung transplant should be made after an exhaustive discussion with your healthcare provider about the potential risks and benefits.

Considering all of these can help improve symptoms and overall lung health.

Preventing pulmonary fibrosis: is it possible?

While treating pulmonary fibrosis holds importance, wouldn’t prevention be a better approach? Certain lifestyle modifications, including regular exercise, avoiding pollutants and maintaining a healthy diet, may help to reduce the risk of developing pulmonary fibrosis.

In addition to these changes, quitting smoking plays a crucial role in managing the effects of living with pulmonary fibrosis and can also serve as a preventative measure. It not only improves respiratory symptoms, but also prevents excessive decline in lung function and in some cases of smoking-related interstitial lung disease, smoking cessation may even lead to spontaneous regression of the disease.

Living with pulmonary fibrosis: support and resources

Living with pulmonary fibrosis is undoubtedly challenging, but you don’t have to face it alone. Several support networks and resources are available to help you navigate this journey. Visit our Helpful Links page to access some of the societies that can provide customised support, resources and awareness campaigns for those impacted by pulmonary fibrosis, including Asthma and Lung UK, Pulmonary Fibrosis Trust and Action for Pulmonary Fibrosis. These resources can provide invaluable support and guidance in managing the disease and improving the quality of life for individuals living with pulmonary fibrosis and their caregivers.

Clinical trials and research: hope on the horizon

Although pulmonary fibrosis might appear as a daunting enemy, there is hope ahead. Clinical trials hold paramount importance in the battle against pulmonary fibrosis as they evaluate new drugs or reassess existing drugs in novel ways.

Breathing Matters is one of the UK’s main organisations committed to leading the charge in research efforts to find new treatments for pulmonary fibrosis.  Visit our research page to find out more about our research.  We encourage patients to talk to their clinical teams about taking part in a clinical trial.

By participating in these trials, patients can gain access to state-of-the-art treatments and contribute to the advancement of research in this field.

If you would like to support our vital research, you can visit our donation page.