Asthma is a serious condition in which the small airways of the affected person's lungs suddenly constrict when they are exposed to certain triggers, such as dust mites,pollen, exercise, or even dry air. During an asthma 'attack', the person's airway lining rapidly becomes inflamed and swollen, the muscles around the airways tighten, and excess mucus is produced as the body reacts to the trigger. This reaction causes reduced airflow into and out of the lungs, and the person has to gasp for breath.
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.
How is asthma currently managed?
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.
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 ofsodium, 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, a quarter of whom are children under five years of age.
How is cystic fibrosis currently managed?
Currently,there is no cure for CF. The goal for doctors treating CF sufferers is to hydrate, breakdown 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 face mask, 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.
Chronic Obstructive Pulmonary Disease, or COPD, encompasses a number of serious conditions affecting the lungs, including emphysema, chronic bronchitis and bronchiectasis and other chronic and acute pulmonary conditions.According to the World Health Organization, or WHO, 210 million people suffer from COPD and the disease was responsible for 3 million deaths in 2005. The WHO predicts that by 2030, it will be the third largest cause of mortality worldwide.
Since COPD is not diagnosed until it becomes clinically apparent, prevalence and mortality data greatly underestimate the socioeconomic burden of COPD.
According to Datamonitor, there are 16 million people diagnosed with COPD in the U.S., and more than 30 million people are affected with COPD in the seven major pharmaceutical markets. In 2005 there were more than 10million physician office visits and two million hospitalizations per year. The disease was estimated to cost the U.S. healthcare system U.S.$30 billion in 2000. According to a report by Datamonitor,worldwide sales in 2004 of the top seven respiratory therapeutics indicated for COPD were U.S.$4.8 billion.
How is COPD currently managed?
Management of COPD generally involves bronchodilators and steroids. However, only an estimated20%-25% of patients respond positively to steroids and itis currently not practical to determine in advance which patients will respond to steroids. We believe that only half of moderate and severe COPD patients achieve an adequate treatment outcome. Therefore, as with asthma, we believe there is room to improve both the diagnosis and management of COPD.
Bronchiectasisis a progressive lung disease, affecting 600,000 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:
Reduced lung capacity;
Poor gas-exchange;
Changes of the organisation of blood vessels; and
Overall increased blood flow through the lungs.
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.
How is bronchiectasis currently managed?
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:
Bronchodilators, to dilate the airways to help mucus clearance;
Steroids. However, only a minority of mild-moderate bronchiectatic patients respond positively to steroids;
Antibiotics to clear infections; and
Regular, daily postural drainage to remove bronchial secretions.
Patients with chronic bronchitis experience persistent airway inflammation and airflow obstruction, with symptoms including a chronic mucus-producing cough and shortness of breath. Due to the difficulties they have in clearing mucus from their lungs, sufferers are prone to periodic bacterial infections where their cough worsens, mucus production increases and breathing becomes more difficult.These episodes damage and scar the bronchial lining and contribute to continued chronic inflammation and immune-mediated cell damage as the body struggles to fight the infections. This cycle of infection and internal scarring may cause a progressive decline in lung function, reducing quality of life and ultimately causing death.
Many of the deaths associated with chronic bronchitis are included in the COPD figure that now accounts for over 100,000 deaths a year in the U.S. The disease is predominately caused by inhaling some form of lung irritant repeatedly for many years, usually cigarette smoke. Chronic bronchitis is slow to develop and is often not diagnosed until the sufferer is in their 40sor 50s.
How is chronic bronchitis currently managed?
Management of chronic bronchitis includes various general supportive measures such as giving up smoking, limiting exposure to dust and chemicals, avoiding sudden temperature changes, undertaking chest physiotherapy and deep-breathing exercises, and increasing fluid intake to keep the bronchial secretions thin.While there are a number of medications that dilate the airway and reduce airway inflammation, for chronic bronchitis sufferers, there are few therapeutic products available to effectively clear excess mucus secretions.This presents a major medical challenge, as ineffective mucus clearance is a major cause of infection and progression of the disease.
Treatments for chronic bronchitis include anti-cholinergic agents, steroids, antibiotics andoxygen. Anticholinergic agents, also known as antimuscarinics, are bronchodilators used for the relief of acute symptoms in both asthma and COPD, but tend to be more effective in COPD. Inhaled corticosteroids are less likely to cause systemic side effects than oral corticosteroids, and have been shown to be effective in asthmatics. However, the role of these agents in the management of COPD remains unclear. According to a recent scientific report (Chest, 2004,126, 1815) there are no indications that early treatment with inhaled corticosteroids modifies a rapid decline in lung function or respiratory symptoms and quality of life.
Pulmonary fibrosis is a serious disease that causes progressive scarring of the lung tissue. The scar formation is preceded by, and associated with,inflammation. Some common and some rare diseases can cause pulmonary fibrosis, but in the majority of cases the cause is never found.Pulmonary fibrosis can be a mild or severe disease; it can be so mild as to cause few symptoms, or it can be fatal. If the disease progresses, the lung tissues eventually thicken and become stiff. The work of breathing then becomes difficult, causing breathlessness. It can run a gradual course, remain unchanged or run a rapid course. It can also be fatal. Pulmonary fibrosis most often begins with repeated injury to the tissue within and between the tiny air sacs (alveoli) in your lungs. The damage eventually leads to scarring or fibrosis, which stiffens the lungs and makes breathing difficult. The most common symptoms are shortness of breath and a dry cough.
How is pulmonary fibrosis currently managed?
Current treatments for pulmonary fibrosis include medications and therapy to improve lung function and quality of life. A number of new therapies for pulmonary fibrosis are in clinical trials. In the meantime, a lung transplant may be an option for some people with pulmonary fibrosis.