Our work in respiratory diseases focuses on:
Asthma is a major public health problem affecting 52 million people around the world, including 2 million Australians and 15 million Americans. The disease is usually life-long and each year claims around 400 lives in Australia and 4,500 lives in the US. Recent studies have shown that the incidence of asthma in Australian children is increasing.
The disease has a major impact on the quality of life of asthmatics and their families, with many sufferers requiring daily medication and modifications in their lifestyle. In addition to the human price, asthma is a major component of the cost of the healthcare system. For example, the cost to the US healthcare system is in excess of US$15 billion per year.
The effective diagnosis, monitoring and management of asthma remain key challenges for doctors and asthmatics. The primary method currently used to diagnose asthma has remained unchanged for many years, with a diagnosis arrived at through a detailed history and physical examination of the patient.
Exercise challenge tests and methacholine inhalation tests are procedures used most frequently in clinical laboratories to evaluate airway responsiveness. While these tests can indicate the presence of asthma, they are not sensitive or specific enough for asthma, nor do they give a precise or objective measure of the seriousness of the patient’s condition. As a consequence, under-diagnosis and misdiagnosis of asthma continue to be serious medical issues that impact extensively on people’s health and quality of life.
There are a number of therapeutic options to treat the symptoms of asthma, including inhalers that expand the airways, and preventative measures such as anti-inflammatory medications.
The absence of an accurate test not only hinders the diagnosis of asthma, but also makes it difficult for doctors to monitor the severity of their patients’ asthma to ensure they receive the most appropriate dose of medication.
Many asthma sufferers have poor control of their disease, placing an over reliance on bronchodilators to control their asthma symptoms. At the other extreme, many people with asthma have few outward symptoms and can become less diligent with their asthma management.
Much of the deterioration in the quality of life of asthma sufferers could be prevented through correct early diagnosis of the disease, appropriate treatment, and effective ongoing monitoring. Pharmaxis is committed to meeting this medical need.
What product is Pharmaxis developing to target asthma?Cystic fibrosis (CF) is an inherited, life-limiting disease that affects the body’s exocrine glands, which produce mucus, saliva, sweat and tears. In CF, a genetic mutation disrupts the delicate balance of sodium, chloride and water within cells, causing the exocrine glands to secrete fluids that are poorly hydrated and therefore thicker and stickier than fluids in people without CF. This leads to chronic problems in various systems of the body, particularly the lungs and pancreas, and the digestive and reproductive systems.
In the lungs of a CF patient, the thick mucus and the thinning of the airway surface liquid make it nearly impossible for the cilia to clear bacteria from the airway. This severely impairs the natural airway-clearing processes and increases the potential for bacteria to be trapped, leading to respiratory infections that may require hospitalisation. Impairments in these vital lung defence mechanisms typically begin in early childhood and often result in chronic secondary infections, leading to progressive lung dysfunction and deterioration.
Although the life expectancy of CF sufferers has increased over the past few decades due to better management of the disease, the median life expectancy today for patients with cystic fibrosis is only 31 years of age.
There are 33,000 diagnosed CF patients in the US and 75,000 in the eight major pharmaceutical markets. In Australia, 2,500 people suffer from the disease, half of whom are children under five years of age.
Currently, there is no cure for CF. The goal for doctors treating CF sufferers is to hydrate, break down and move the excessive, sticky mucus secretions to improve lung function and reduce the number and severity of secondary lung infections. CF sufferers and their carers are generally able to manage the condition at home using a combination of exercise, daily physiotherapy, postural drainage, and chest percussion (to assist the sufferer to expel mucus from their lungs). Depending on the severity of the condition, caring for a person with CF can take several hours of at-home treatment every day.
Medications to treat CF are limited, and not beneficial in all patients. Nebulised medications, delivered by aerosol or a facemask, are used to make the mucus less thick and sticky and open up the airways. Antibiotics, either nebulised or by oral or intravenous administration may also be required to treat secondary infections.
What product is Pharmaxis developing to target cystic fibrosis?Bronchiectasis is a progressive lung disease, affecting 580,000 people worldwide. It is often mistaken for asthma or pneumonia and misdiagnosis is common.
In this disease the airway walls are chronically inflamed, with poor clearing of the increased mucus production. Chronic inflammation of the walls of the airway is common to all types of bronchiectasis. This is often a result of a vicious cycle of bacterial infection, in which damage to the lungs further predisposes the lung to more infections. The body repairs the damaged lung tissue by forming tough, fibrous material, which leads to changes that impair normal lung structure and function. Effects include:
These changes can ultimately lead to heart failure. Recurrent lung infections commonly reduce patients’ quality of life; progressive respiratory insufficiency is the most common cause of death.
Most cases of bronchiectasis develop during childhood, and can be a result of infections such as pneumonia or the inhalation of noxious substances.
The inside lining of our airways is covered by millions of fine hair-like structures called cilia, which are in turn covered by a thin layer of mucus, secreted by the lungs to defend against germs, dust particles and other foreign bodies.
In lung cells, salt moves through chloride channels in the cell membrane to the airway surface. Then, just as a dry sponge soaks up water, the chloride and sodium combination pulls water out of the cells to create a thin fluid layer that coats the airway surface and keeps the cilia moist so they can do their job of moving foreign particles along the airway and out of the lungs. The cilia move continuously and propel the overlying blanket of salt, water and mucus up to the throat, where secretions are swallowed or expelled as sputum (this normal and natural process is called mucociliary clearance).
This constant process, which is barely noticeable in healthy people, helps keep the airways clean, allows the passage of clean, warm air through the lungs, and removes any foreign bodies from the airways, preventing infection.
People with Bronchiectasis and cystic fibrosis are generally affected by a breakdown in the natural mechanism of cleansing, hydrating, and protecting the mucus lining their airways. They face the ongoing challenge of clearing excessive and thickened secretions from their congested lungs, usually by constant coughing.
A key therapeutic goal for clinicians treating these patients is to assist the natural process of keeping the mucus hydrated and clearing it from the lungs.
Maintaining a reasonable quality of life for bronchiectasis sufferers and their families is also a challenge; they have to deal with problems associated with breathing difficulties, respiratory infections, poor sleep, general discomfort, lifestyle limitations, and the gradual deterioration of lung function over the years.
Treatment today is aimed at controlling infections, secretions, airway obstructions and complications. There are no therapeutic products available to effectively clear excess mucus secretions and improve the quality of life of sufferers.
Current management of bronchiectasis often involves:
