Rare lung diseases
Background
Healthy lungs are a pair of spongy, air-filled organs. Inhaled air travels into the lungs via the trachea and its tubular branches, the bronchi. These divide into smaller branches, the bronchioles, and eventually these bronchioles end in microscopic air sacs, the alveoli. Oxygen from the air is absorbed through the microscopically thin walls of the alveoli into the blood, and carbon dioxide travels from the blood into the alveoli, to be exhaled. The interstitium (the supporting framework of the lungs) is a thin layer of cells between the alveoli, which contains blood vessels and cells that support the alveoli.
Fibrotic lung disease
In patients with fibrotic lung disease, the lung tissue becomes thickened, stiff, and scarred. This results in less efficient absorption of oxygen, and breathing becomes increasingly difficult as the disease progresses, leading to dyspnoea. Severe, persistent dry cough is another particularly troubling symptom and correlates strongly with disease progression in conditions such as idiopathic pulmonary fibrosis (IPF). Other possible symptoms include fatigue, weight loss, aching muscles and joints, and widening and rounding of the fingertips.
Fibrotic lung disease.
Prognosis
Damage caused by fibrosis in the lung cannot be repaired, and patients have very limited therapeutic options. Quality of life is significantly impaired as the disease progresses and the prognosis is poor, with a life expectancy of 3-5 years after diagnosis in patients with IPF. The five-year survival rate for IPF is less than that for many cancers, including bladder, prostate, breast, thyroid, and colon cancer.
Increased pressure in the arteries of the lungs due to vascular compression by scar tissue and other pathological vascular changes can lead to pulmonary hypertension (PH) and subsequently to right heart failure. Pulmonary hypertension is a rare, often fatal, complication of lung diseases such as IPF.
The main immediate cause of death in patients with IPF is the disease itself (over 60% of patients), followed by coronary heart disease (around 15%). Women are less likely to die from the disease itself, and death from pneumonia is almost 10 times more common in men than in women. Another underlying cause of death is lung cancer, which is more likely to be the underlying cause of death in ex- and current smokers than in non-smokers.
Because of the debilitating symptoms and poor prognosis, patients face an uncertain future, and patients and their families or caregivers face daily challenges in terms of managing the disease and maintaining an acceptable quality of life.
At present, patients often have a tortuous path to a diagnosis of IPF, with little information about the disease when it is diagnosed, particularly if they are not treated at a specialist centre. Many patients do not immediately realize the gravity of their condition, and both patients and their families or caregivers can later be overwhelmed by the physical and psychological symptom burden, with relentlessly deteriorating quality of life and a continuous increase in distressing symptoms. For approximately 80% of patients, lung transplantation will not be possible because suitable donors are not available, and they currently have few other treatment options. The scientific literature supports the benefits of palliative care, but this is offered infrequently and usually late in the disease process.
Our sole focus at Vicore Pharma is to develop therapies for patients who are affected by fibrotic lung disease, a life-changing condition.
Fibrotic lung disease consists of several different disorders including:
- Idiopathic pulmonary fibrosis
- Systemic sclerosis (lung manifestations)
- Pulmonary sarcoidosis
Idiopathic pulmonary fibrosis
Idiopathic pulmonary fibrosis is the most common type of pulmonary fibrosis, and is a severe and devastating disease with no known cause. Debilitating symptoms of dyspnoea and severe, persistent dry cough typically appear between the ages of 50 and 70 years and, while the disease is more common in men, the number of cases in women is increasing.
The prevalence of pulmonary hypertension (PH) in people with IPF is difficult to ascertain, as estimates vary widely depending on the method used to identify PH. Right heart catheterization is the gold standard for the detection of PH.
Incidence and prevalence
The European Idiopathic Pulmonary Fibrosis and Related Disorders Foundation has estimated that between 80,000 and 111,000 people in the EU are currently living with IPF, with up to 35,000 new cases being diagnosed each year. In the USA, approximately 100,000 people are currently living with IPF according to the National Institutes of Health (NIH), with 30,000-40,000 new diagnoses per year. The NIH has estimated the overall prevalence worldwide to be 13-20/100,000 people.
Diagnosis and disease progression
Diagnosis is often delayed because the symptoms of IPF are similar to those of other lung diseases:
- Lung function testing, including spirometry, provides information on the amount of air that the lungs can hold and how forcefully air can be exhaled, which will indicate the severity of the disease
- A high-resolution CT scan can confirm the extent of lung scarring
Although IPF is progressive, the rate of scar tissue formation in the lungs varies among patients. The prognosis for patients diagnosed with IPF is usually poor, with patients surviving for only 3-5 years after diagnosis.
Treatment options
Currently, there is no cure for IPF, and treatment options are limited:
- Two medicines have been approved for use in IPF: pirfenidone and nintedanib. Both have been shown to slow the progression of the disease; however, associated side-effects have limited their use
- Although the antifibrotic drugs for IPF have a positive effect on disease progression, their effect on symptom control (e.g. cough) or quality of life is limited and not fully explored
- Supportive treatments include oxygen therapy, and immunization against pneumonia and influenza to avoid infections
Patients are advised to keep as active as possible and to follow a healthy diet with plenty of rest. Clearly, new treatments are urgently needed to reduce the significant burden of this disease.