About Idiopathic Pulmonary Fibrosis
Abbou Idiopathic Pulmonary Fibrosis (IPF)
Fibrosis leads to the gradual stiffening and thickening of lung tissue, reducing lung elasticity and making breathing difficult. In severe cases, patients may require a lung transplant.
Idiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive lung disease and the most common and severe form of idiopathic interstitial pneumonia, primarily affecting men aged 50 to 70 years and older. Fibrosis causes the lung tissue to gradually stiffen and thicken, leading to reduced lung elasticity and difficulty in breathing.
The cause of IPF is unknown, which is why it is termed “idiopathic.” The fibrosis leads to the formation of persistent scarring in the lungs, giving the lungs a sponge-like appearance, which has earned it the nickname “honeycomb lung.” This damage is irreversible and progressively worsens over time, although certain medications can slow the disease’s progression. In some severe cases, patients may require a lung transplant.
The median overall survival after diagnosis is approximately 2-3 years, with a 5-year survival rate of 20%, though this varies across different countries. In Japan, the median overall survival for IPF patients is 35 months, while the 5-year survival rate in Western countries ranges from 20% to 40%. Even lower than the 5-year cancer survival rate in Taiwan (which exceeds 60%). Research indicates that after 2000, the age-standardized mortality rate for IPF was 0.5 to 12 cases per 100,000 people annually, and as of 2010, there was no increasing trend in survival rates for IPF patients, although this may have improved since then. Patients who take anti-fibrotic medications have significantly better long-term survival rates than those who do not, highlighting the importance of developing anti-fibrotic drugs.
In the United States, between 2004 and 2017, the mortality rate decreased from 4.22 to 3.64 per 100,000 people annually, possibly due to a decline in smoking rates or changes in other environmental and genetic factors.
Symptoms of IPF
The symptoms of IPF typically develop gradually and worsen over time.
The main symptoms include:
- Persistent dry cough: A dry cough without phlegm is a typical symptom of IPF, often lasting for weeks or even months.
- Shortness of breath: Patients may experience difficulty breathing during physical activities or daily tasks.
- Fatigue: Due to reduced oxygen supply in the lungs, patients often feel unusually tired and weak.
- Changes in nails and fingertips: Some patients may develop clubbing of the fingers or thickening of the nails.
Chronic cough, dry cough, and shortness of breath also occur in many chronic respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD), making early diagnosis challenging. According to epidemiological data from Germany, 85.9% of patients present with shortness of breath, 74.7% have chronic cough, and 40% exhibit symptoms of fatigue. The primary symptoms include progressively worsening respiratory difficulty, accompanied by restrictive ventilatory dysfunction and impaired gas exchange, leading to hypoxemia and even respiratory failure. Since the disease is confined to the lungs, its pathological and imaging features closely resemble those of usual interstitial pneumonia (UIP).
High-risk groups should undergo regular pulmonary function tests. Additionally, they can monitor their condition by observing their daily walking pace or performing the “6-Minute Walk Test.” If they notice a slower walking speed or experience shortness of breath, they should seek medical attention promptly.
What is the 6-Minute Walk Test?
The 6-Minute Walk Test involves walking back and forth over a distance of approximately 30 meters at the fastest pace possible within six minutes, without running. If you feel tired or experience leg fatigue during the test, you may slow down or take a break. If you feel unwell, the test should be stopped immediately. Throughout the six minutes, the total distance walked, as well as heart rate, blood pressure, respiratory rate, and changes in oxygen saturation, will be recorded.
Shortness of breath
Chronic cough
Fatigue
Causes and Risk Factors of IPF
The exact cause of IPF is unknown, but several risk factors may be associated with the disease:
- Age: IPF is most common in adults over the age of 50.
- Gender: Men are at a higher risk of developing IPF than women.
- Smoking history: Smoking is a significant risk factor for IPF, and the risk persists even years after quitting.
- Environmental factors: Long-term exposure to certain industrial dust or harmful substances (such as asbestos or silica dust) may increase the risk.
- Family history: A family history of IPF may increase the likelihood of developing the disease.
Diagnosis of IPF
Diagnosing IPF typically requires a comprehensive assessment of multiple factors, including:
- Medical history and physical examination: Doctors will ask detailed questions about the patient’s symptoms, medical history, and family history, and perform a physical examination.
- Imaging tests: High-resolution computed tomography (HRCT) is the primary tool for diagnosing IPF, as it can reveal the characteristics of lung fibrosis.
- Pulmonary function tests: These tests assess lung function and oxygen exchange capacity.
- One-Stop Lung Health Screening: In October 2024, Taichung Veterans General Hospital launched the “Healthy Lung – Digital Dynamic Physiological Monitoring and Continuous Care Clinical Site,” integrating 7 related examinations. This provides the public with a one-stop smart medical screening station for lung diseases and comorbidities including cardiovascular, metabolic, and sarcopenia conditions while waiting for consultation (examinations that previously took an average of 10 days to complete can now be finished in less than 60 minutes) (Chinese News)
Current Treatments
Due to the limited effectiveness of existing medications and their minimal impact on improving patient survival and quality of life, many researchers are actively seeking more effective drugs and treatment methods.
Esbriet® (Pirfenidone)
- On October 15, 2014, Esbriet® (pirfenidone), a fibrosis inhibitor developed by Roche, was approved by the FDA for market release.
- Pirfenidone, with its pyridine chemical structure, is an oral fibrosis inhibitor that modulates various cytokines (e.g., INF-α, IL-1, IL-6) to promote the production of anti-inflammatory cytokine (IL-10) and inhibit the reduction of IFN-γ, thereby improving the balance between Th1 and Th2 cells. It also regulates fibrosis-related growth factors (TGF-β1, b-FGF, PDGF) to exert anti-inflammatory, anti-fibrotic, and antioxidant effects. Additionally, it inhibits fibroblast growth and collagen production. (Source: Package Insert)
- Common side effects of pirfenidone include photosensitivity reactions, rashes, loss of appetite, stomach discomfort, and nausea.
- Sandoz has announced the launch of its first generic pirfenidone in the US for treating idiopathic pulmonary fibrosis (IPF) in May 2022.
Ofev® (nintedanib)
On October 15, 2014, Ofev® (nintedanib), a multi-kinase inhibitor developed by Boehringer Ingelheim, was approved by the FDA for market release.
Ofev® is a multi-targeted kinase inhibitor that specifically inhibits the vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), and platelet-derived growth factor receptor (PDGFR). It received FDA designations such as Fast Track, Priority Review, Breakthrough Therapy, and Orphan Drug status.
The most common side effects in patients are mild to moderate diarrhea, nausea, and vomiting, which can be managed with symptomatic treatment or dosage adjustments.
- Lotus Pharmaceutical has received tentative approval from the US FDA for its Abbreviated New Drug Application (ANDA) for Nintedanib Capsules in January 2023, a generic version of Boehringer Ingelheim’s Ofev®.
- MNKD-201, developed by Mannkind, is an inhaled formulation of nintedanib. In a Phase 1 clinical trial, it was found to be safe and well-tolerated in healthy volunteers, without the typical adverse events commonly seen with oral nintedanib.
Drugs in Development
Nerandomilast
- Nerandomilast is an oral small-molecule drug developed by Boehringer Ingelheim. It is a phosphodiesterase 4B (PDE4B) inhibitor used for the treatment of idiopathic pulmonary fibrosis (IPF).
- In September 2024, Boehringer Ingelheim announced that a global, multicenter Phase III clinical trial named FIBRONEER™-IPF had achieved its primary efficacy endpoint, showing a significant difference in the change in forced vital capacity (FVC [mL]) at Week 52 compared to the placebo group.
- The company plans to submit a New Drug Application (NDA) for nerandomilast to the U.S. Food and Drug Administration (FDA) and other global health authorities for the treatment of IPF.
- In 2022, the FDA granted nerandomilast Breakthrough Therapy designation for IPF.
>>Source
ISM001-055
In September 2024, the results of the Phase IIa clinical trial were announced, showing positive outcomes. The 12-week study indicated that ISM001-055 demonstrated good safety and a dose-dependent response in improving lung function in IPF patients.
ISM001-055 is a chemical compound designed by Insilico Medicine through AI-based algorithms. Its mechanism of action involves targeting and inhibiting TNIK (Traf2/NCK-interacting kinase) to halt or reverse the fibrosis process, offering disease-modifying treatment for IPF patients.
>>news
AK3280
In August 2024, news revealed that the Phase II clinical trial conducted in China for AK3280 has completed patient enrollment.
AK3280 is a clinical-stage drug developed by Aikobio, designed for the treatment of idiopathic pulmonary fibrosis (IPF). This drug is an optimized version of the already marketed drug pirfenidone. It can modulate multiple pathways and biomarkers closely related to the fibrotic pathological process, including the expression of fibrosis-related genes and proteins induced by transforming growth factor (TGF-β) and lysophosphatidic acid (LPA). AK3280 reduces cell proliferation, inhibits the synthesis and accumulation of extracellular matrix, and thereby exerts its therapeutic effect on IPF.
>> news
EF-011
EF-011 is an investigational drug developed by Everfront Biotech for the treatment of idiopathic pulmonary fibrosis (IPF), currently in the preclinical research phase.
Our research has identified a specific binding site for SOX2 in the promoter of type I collagen. EF-011 can reduce the binding of SOX2 to the type I collagen promoter, thereby inhibiting the expression and accumulation of type I collagen. In a bleomycin-induced mouse model of pulmonary fibrosis, treatment with EF-011 significantly improved tissue pathology and respiratory function. Functional assessments, including respiratory rate, cumulative ventilation, maximum inspiratory volume, and maximum expiratory volume, showed that the therapeutic index of EF-011 is 20 times that of the small molecule pulmonary fibrosis drug pirfenidone.
More drug development information >> EF-011
Care and Precautions for IPF Patients
Oxygen Supplementation
Pulmonary fibrosis patients often experience difficulty breathing. When blood oxygen levels are low, oxygen therapy can help patients maintain mobility and comfort.
Pulmonary Rehabilitation Program
Pulmonary rehabilitation programs typically include exercise training, nutritional guidance, and psychological support, which can help improve patients’ quality of life.
Maintaining Quality of Life
The prognosis of IPF varies among individuals, but the disease usually worsens over 3 to 5 years. With appropriate treatment, many patients can still maintain a certain quality of life.
Regular Medical Visits and Follow-Up
Patients should closely collaborate with their healthcare team to develop a personalized treatment plan and undergo regular follow-ups to monitor disease progression.
