Cystic fibrosis is the most common lethal genetic disease in Caucasians. One in every 25 Australians carry the cystic fibrosis gene, and about one in every 2,500 babies is born with cystic fibrosis. People with cystic fibrosis have a life expectancy of just 30 years. Although the disease affects many organ systems throughout the body, the effect on the lungs is the primary cause of death.

Cystic fibrosis is characterised by the accumulation of thick, tenacious and infected secretions in the lungs. These eventually lead to respiratory failure and an early death. Removing these secretions remains one of the cornerstones in caring for patients with cystic fibrosis.

The removal of these secretions can be measured by getting the patient to inhale a small amount of radioactive gas, which is deposited on the airway secretions. The patient is then placed under a special camera and the rate of removal of the secretions is monitored over a period of an hour. The Department of Respiratory Medicine undertakes these studies in collaboration with the Department of PET and Nuclear Medicine.

We have now developed a new method for assessing the deposition and clearance of the radioactive gas, which has been validated in a group of normal volunteers. This new method promises to further improve the sensitivity and utility of this measurement technique.

We have previously shown that a strong salt solution (hypertonic saline), when breathed in as a mist, significantly improved the clearance of secretions from the lung. We are now about to embark on a large-scale, national multi-centre trial to establish the effect of long-term use of this solution on lung function and the patient's quality of life.

We have also been investigating a dry powder preparation of mannitol, which can be inhaled as a therapy to enhance clearance of lung secretions. In this study, we found that mannitol was equally as effective as hypertonic saline in clearing the lung.

In addition to our success with patients with cystic fibrosis, we found that the beneficial effects of mannitol were most profound in those suffering from bronchiectasis, a chronic stretching of the bronchi with excessive secretions of mucus and chronic infection. In this group of patients, we demonstrated that clearance of the lung secretions could be normalised after a single dose of mannitol. This is a major breakthrough. We now know that clearance of lung secretions is impeded in bronchiectasis by excessive load, rather than any fundamental abnormality of the clearance mechanism. We now plan to carry out a two-week trial using mannitol daily in bronchiectasis patients with excess mucus production. The portable equipment, in the form of a dry powder inhaler, used to administer the mannitol should permit treatment to take place anywhere at anytime, improving the quality of life for many patients.

There appears to be more than one mechanism involved whereby mannitol enhances the clearance of mucus. Because it is an osmotic agent, mannitol causes water to move into the airways and this helps to hydrate the sticky mucus. Further, the mannitol appears to break the bonds within the mucus making it less viscous and thus easier to remove by cough and physiotherapy.

The Department of Respiratory Medicine has also completed a retrospective analysis of all the mucociliary studies conducted in the Department over the past 10 years. This represents the largest collection of mucociliary studies in cystic fibrosis patients ever conducted, and has given valuable insights into the nature of this disease.

The ability to perform everyday tasks with the arms is vital for living an independent life. Because of this, our research has continued to focus on arm exercise in patients with cystic fibrosis and in healthy people.

We have performed detailed studies of the way the lungs and breathing muscles behave during simple tasks such as holding and carrying loads at shoulder height. These tasks increase the work that the diaphragm is required to do for breathing. We found that in patients with more severe lung disease, overexpansion of the lungs causes the diaphragm to be low and flat, which makes its activity inefficient. Because it is less efficient, the diaphragm has to do more work to maintain adequate breathing during these arm tasks. This results in breathlessness which may stop the patient from completing the task.

These studies provide considerable new information on metabolic and respiratory responses, regulation of lung volume and respiratory muscle recruitment patterns during both supported and unsupported arm exercise in patients with cystic fibrosis and normal subjects. Further studies to commence in 2000 will examine the relationship between the strength of the arms and the amount of work the arms can do in a certain time (work capacity). In addition, the effects of arm training on arm work capacity will be studied in patients with cystic fibrosis and those with chronic airflow limitation.

Our past studies have shown that people with cystic fibrosis may breathe much more poorly when they are asleep than they do during the day. We are continuing our studies of the breathing of people with cystic fibrosis during sleep. Our current work is determining how common sleep-disordered breathing is among our cystic fibrosis patients. While doing this, we are also examining why this sleep-disordered breathing occurs and what treatments can be used to fix it.

We are offering diagnostic sleep studies to our cystic fibrosis patients who have an FEV1 of less than 65 per cent of normal levels. (The forced expiratory volume in one second (FEV1) test measures lung function.) Our preliminary results suggest that FEV1 % predicted and oxygen levels in the blood while awake and resting correlate the most strongly with a drop in oxygen levels in the blood during sleep in this group of patients. Lower FEV1 and lower day-time levels are associated with lower night-time levels.

In another project, we directly measured ventilation in cystic fibrosis patients who we had observed to have a drop in blood oxygen levels during sleep. We studied the effects of low flow oxygen and bi-level ventilatory support, with or without additional oxygen, and compared the results to breathing room air alone on measurements of: ventilation; sleep architecture; blood oxygen levels; arterial blood gas tensions; and transcutaneous carbon dioxide tension (TcCO2).

Our primary finding was that ventilation per minute is reduced in this patient group, especially in REM sleep, and that this decrease is associated with falls in blood oxygen levels and increases in TcCO2. This reduction in ventilation per minute was mainly due to a decrease in tidal volume. The reduction in ventilation per minute with REM sleep also occurred with the addition of low flow oxygen, although it did not occur with bi-level ventilatory support. Both low flow oxygen and bi-level ventilatory support improved night-time blood oxygen levels. With bi-level ventilatory support there was a significant reduction in the amplitude of the rise in TcCO2 seen with REM sleep compared with the magnitude of the rise in TcCO2 seen with no treatment or with low flow oxygen. We therefore conclude that bi-level ventilatory support is better able to maintain adequate night-time ventilation in this patient group.

We have also managed to use this non-invasive form of ventilatory support as a bridge to lung transplantation in some patients. As a result, we are conducting studies to try and improve our understanding of the appropriate timing of such therapy.

Our next project is to compare low flow oxygen and bi-level ventilatory support in a twelve month randomised controlled study in a group of patients with cystic fibrosis.

The Department of Respiratory Medicine is conducting a series of studies of the gas exchange characteristics of the lung in cystic fibrosis patients. While there is information available about the mechanical function of the lung in this disease, little is understood about the way oxygen is taken up and carbon dioxide expelled. These studies are concentrating on investigating the effects of two interventions that are designed to treat cystic fibrosis:

1. standard physiotherapy
2. longer term night-time ventilation with bi-level ventilatory support.

We found that the beneficial effect of the first intervention, standard physiotherapy, is not uniform in all patients. The majority of patients experienced an improvement in ventilation and perfusion matching (the way blood and gas mix and match in the lungs) following the physiotherapy. However, some patients experienced a dramatic deterioration in ventilation and perfusion matching, and felt worse following physiotherapy. It is not yet known why.

Our studies examining the second intervention, night-time ventilation, are in the very early stages. Our aim is to determine the influence of this increasingly important therapy on the primary cause of respiratory failure in cystic fibrosis; disturbed ventilation and perfusion matching.