Facing Idiopathic Pulmonary Fibrosis: A Guide To The Disease

Idiopathic Pulmonary Fibrosis (IPF), classified under ICD-10 code J84.112, is a lung disease that causes scarring in the lungs. The scarring gets worse over time and doesn’t heal. Doctors still don’t know what causes it, even with advances in medicine. Its complexity makes it hard to diagnose, treat, or predict how it will progress.

The Emergence of a Mysterious Illness

Idiopathic pulmonary fibrosis (IPF) has only recently been understood as a separate disease. 

Early on, its symptoms—such as a long-lasting dry cough and worsening shortness of breath—were often mistaken for other conditions like COPD, asthma, or tuberculosis. But as early as the 1900s, doctors performing autopsies noticed a pattern of scarring throughout the lungs and a distinct honeycomb-like texture. This unusual finding led to deeper investigation.

By the 1970s, experts agreed that IPF was different from other lung diseases that cause scarring, such as those linked to autoimmune conditions or long-term exposure to irritants like dust or chemicals. 

Studies identified a specific pattern of lung damage, now called usual interstitial pneumonia (UIP), as being unique to IPF. This pattern includes patchy scarring, clusters of active fibroblasts (cells that make scar tissue), and the characteristic honeycomb appearance in the lungs.

Why It’s Considered "Idiopathic"

The term "idiopathic" means the cause of IPF is still unknown. Unlike other lung-scarring conditions, such as asbestosis (caused by asbestos) or silicosis (caused by silica dust), IPF doesn’t have one clear trigger. 

However, scientists believe it happens due to a mix of factors, including genetics, exposure to certain environmental risks, and abnormal healing of tiny injuries in the lungs. Even now, researchers are still trying to figure out what starts this process.

IPF’s Hidden Destruction Within the Lungs

Idiopathic Pulmonary Fibrosis causes scarring to build up in the lungs. Healthy lung tissue is replaced with stiff scar tissue made of collagen. This scarring thickens the walls of the tiny air sacs (alveoli) and damages nearby blood vessels. These changes make it harder for oxygen to pass into the bloodstream. Over time, the lungs stiffen and stop expanding and contracting normally, making it harder to breathe.

The scarring often begins after repeated damage to the lining of the air sacs. This damage can happen from breathing in stomach acid, viral infections, or harmful particles in the air.

How Scarring Develops

The injury sets off a series of events:

• Damage to Air Sac Linings: Repeated injury kills the cells that line the air sacs. These cells release signals that trigger scarring.

• Fibroblasts Are Activated: Fibroblasts, which help repair damage, gather in the injured areas. They multiply and turn into myofibroblasts, which produce scar tissue.

• Scarring Builds Up: Collagen and other scar tissue accumulate, making the lungs stiffer. In severe cases, this creates a honeycomb-like structure visible in advanced disease.

What Happens at the Cellular Level

• Cells Change Roles: Some cells in the air sacs change into fibroblast-like cells, adding to the scar-producing cells. This process is driven by molecules like TGF-β and Wnt/β-catenin.

• Myofibroblasts Stay Active: Myofibroblasts usually disappear when healing is complete. In IPF, they stick around and keep producing scar tissue.

• Immune Cells Send Signals: Immune cells like macrophages release molecules such as TGF-β that encourage scarring. These signals worsen the problem, even though inflammation isn’t the main cause of IPF.

What Drives the Scarring

Several molecular pathways work together to cause and sustain scarring:

• TGF-β: This molecule is a key driver of scarring. It activates fibroblasts, keeps myofibroblasts alive, and increases scar tissue formation.

• Wnt/β-Catenin: This pathway increases fibroblast activity and worsens lung damage.

• Oxidative Stress: Damaged cells release harmful molecules called reactive oxygen species (ROS). These molecules increase lung damage and trigger more scarring.

• ER Stress: Lung cells can self-destruct if they can’t fold proteins properly. This creates even more damage.

• Low Oxygen Levels: Oxygen shortages in the lungs cause abnormal blood vessels to grow, which adds to the scarring.

How IPF Impacts Lung Function

As the lungs become more scarred, they lose their ability to function properly. Doctors monitor this decline using these tests:

• Forced Vital Capacity (FVC): This test measures how much air you can exhale in one breath. If this drops by 5–10% in a year, the disease is getting worse.

• Diffusing Capacity for Carbon Monoxide (DLCO): This test shows how well oxygen moves from the lungs into the blood. A lower DLCO means more damage to the air sacs and blood vessels.

• 6-Minute Walk Test (6MWT): This test measures how far you can walk in six minutes while tracking your oxygen levels. If your oxygen drops below 88%, it indicates advanced disease.

This steady loss of lung function proves the importance of diagnosing and monitoring IPF early.

How Do People Catch It?

Our genes can affect how likely we are to develop IPF. Though most cases don’t have a clear cause, certain genetic changes can make some people more prone to the disease.

• MUC5B Gene: The MUC5B gene helps make a protein that clears out dust and germs from the lungs. A specific variation in this gene (called rs35705950) can increase the risk of IPF. This change causes the gene to make too much of this protein, which can harm lung tissue and contribute to fibrosis.

• Telomerase Gene Mutations (TERT, TERC): Telomerase helps protect our chromosomes from damage. Mutations in the TERT and TERC genes cause telomeres (the protective caps at the ends of chromosomes) to shrink too quickly. This speeds up aging in lung cells, leading to fibrosis. These mutations are common in families with a history of IPF and cause the disease to develop earlier and progress more aggressively.

• Surfactant Protein Genes (SFTPC, SFTPA1, SFTPB): Surfactant proteins help keep the lungs' tiny air sacs working properly. Mutations in these genes make it harder for the lungs to stay healthy, leading to lung damage and fibrosis. These mutations are often seen in younger people with familial IPF.

• Other Genetic Factors: Researchers are still exploring other genetic factors that might increase the risk of IPF, including those related to the immune system and inflammation.

Environmental and Occupational Risks

Certain environmental and work-related exposures can also increase the risk of developing IPF.

• Cigarette Smoke: Smoking is a major risk factor for many lung diseases, including IPF. The toxins in cigarettes can cause damage to the lungs, leading to inflammation and scarring. Smokers with IPF often experience faster disease progression and worse outcomes.

• Workplace Exposures: People who work with harmful substances, like asbestos, silica dust, and wood dust, are at higher risk of IPF. Asbestos, for example, causes a similar lung disease called asbestosis, which shares many features with IPF. Silica dust, common in mining and construction, also triggers lung inflammation and fibrosis.

• Air Pollution and Viral Infections: Long-term exposure to pollution, including fine particles (PM2.5), nitrogen dioxide, and ozone, may increase the risk of lung fibrosis. Certain viruses, like Epstein-Barr virus (EBV) or herpesviruses, may also make IPF worse or trigger it in some people.

The Impact of IPF On Patients

IPF is a hard condition to deal with. Here’s a quick look at what it entails for any patient that has it. 

Worse Quality of Life

Living with IPF can be tough. Symptoms like breathlessness, tiredness, and a constant cough make everyday activities harder. Patients often feel anxious or depressed as they cope with the uncertainty of how the disease will progress.

Worse Treatment Costs

Treating IPF is expensive. Patients will need frequent hospital visits, medications, oxygen therapy, and sometimes lung transplants. This puts a financial strain on patients and the healthcare system.

How IPF Progresses: Acute Exacerbations 

Acute exacerbations are sudden worsening episodes of IPF that can seriously affect lung function and overall health

• Symptoms: During an acute exacerbation, people sometimes have a quick increase in shortness of breath, a cough, and low oxygen levels. These episodes can happen without warning, but are sometimes triggered by infections or other lung stress. Doctors can measure lung function with tests like forced vital capacity (FVC), which will usually show a decline during an acute episode.

• Imaging and Pathology: Radiology is a key tool for identifying changes in Idiopathic Pulmonary Fibrosis during these episodes. CT scans can reveal new areas of lung damage, such as ground-glass opacities or regions of denser scarring. These findings, combined with pathology results, often show patterns of acute injury and inflammation in the lungs.

• What Brings This Progression: We still don’t fully understand what causes them, but they might result from infection, aspiration, or the natural progression of fibrosis. While the exact causes aren’t fully understood, they are thought to involve infections, aspiration, or the progression of fibrosis itself.

How IPF Progression Is Predicted

IPF is hard to predict—some patients progress slowly, while others decline quickly. There are several ways doctors try to estimate disease progression:

• The GAP Index: This scoring system looks at Gender, Age, and lung function to predict how severe the disease might be. People with higher GAP scores tend to have worse survival outcomes.

• Clinical Markers: The rate of lung function decline, especially a decrease in FVC of more than 10% per year, is a bad sign. If a patient’s lung function stays stable, that’s a better outlook.

• Biomarkers: Proteins like KL-6 and SP-D are being studied as potential markers for disease progression. Higher levels of these proteins usually mean more inflammation and fibrosis in the lungs.

Treatments and New Possibilities

While there is no cure, some drugs can slow the disease by targeting the processes that cause fibrosis. These treatments aim to reduce lung damage and improve life quality. Below are key drugs used to treat IPF.

Anti-Fibrotic Drugs

These two drugs are FDA-approved and will slow down IPF. These medications target the processes in the body that cause fibrosis.

• Pirfenidone: Pirfenidone is a pill that slows down the fibrosis process by blocking several pathways that contribute to scarring, such as TGF-β signaling and oxidative stress. 

• Nintedanib: Nintedanib is another pill that works by blocking growth factors (like FGF and VEGF) that contribute to fibrosis. It can help prevent the scarring of lung tissue and even reduce the number of acute exacerbations.

Lung Transplantation

For patients with severe IPF, a lung transplant is the only option for long-term survival. But finding donor lungs is difficult, and after a transplant, there are risks like rejection and infection. Only people with very advanced disease are eligible for a transplant. 

Idiopathic Pulmonary Fibrosis survival rates are improving after transplants are improving, but many people pass away before they can receive one.

Idiopathic Pulmonary Fibrosis Life Expectancy

Most people with IPF live 3-5 years after diagnosis and before treatments, though some get worse faster than others. When the disease suddenly worsens and the patient enters the acute exacerbations phase, survival drops sharply - only 10% make it past 6 months. 

But there's help: drugs like Pirfenidone can cut decline or death by 79% and mortality by 86% through slowing the disease down. 

What’s Next: New Research and Hope

Treatment for IPF has already come a long way, and it’s still on track towards making significant milestones that will work out very well for patients.

Personalized Medicine and Biomarkers

Researchers are working on ways to personalize IPF treatment. By studying biomarkers like KL-6 or SP-D, doctors might be able to track disease progression more accurately and adjust treatment plans.

Additionally, understanding a patient’s genetic makeup could lead to more tailored treatments. For example, people with TERT mutations might benefit from gene therapy aimed at protecting their telomeres.

New Drugs and Stem Cell Research

Several new drugs are in clinical trials, including some that target specific pathways involved in IPF. For a start, drugs aimed at Wnt signaling have shown promise.

• Stem Cell Therapy: Scientists are researching how stem cells could help repair damaged lung tissue. Stem cells have the ability to reduce inflammation and fibrosis, and clinical trials are exploring whether they can improve lung function and stop fibrosis from worsening.

Gene Therapy and CRISPR/Cas9: New technologies like CRISPR/Cas9 are being tested to fix genetic mutations that cause IPF. For example, repairing mutations in the TERT gene could help protect lung cells from aging and reduce fibrosis. This approach is still experimental but could be a game-changer in the future for people with genetic forms of IPF.