Title: Effects of ambulatory oxygen on health status in patients with fibrotic lung disease
Funder: Department of Health and Social Care

Abstract: Background: There are many types of pulmonary fibrosis. The most common is idiopathic pulmonary fibrosis, a deadly progressive disease with a prognosis similar to that of lung cancer (1). Other fibrotic interstitial lung diseases (ILDs) are also characterised by progressive fibrosis, albeit at differing rates, and cause breathlessness on exertion and activity limitation. Although there is some evidence that ambulatory oxygen prevents desaturation on exercise under controlled conditions in patients with fibrotic ILD, no studies have been performed on the use of oxygen in normal, daily activities. Aims: 1) The primary aim of this study is to assess the impact of ambulatory oxygen on health status in patients with fibrotic ILD. 2) We will also explore the perceptions of individual patients on the advantages and drawbacks of ambulatory oxygen Plan of investigation: In 80 patients with fibrotic lung disease (including patients with idiopathic pulmonary fibrosis, other idiopathic interstitial pneumonias and fibrotic hypersensitivity pneumonitis), the impact of ambulatory oxygen on daily symptoms and activities will be evaluated by a four-week randomized crossover trial of cylinder oxygen for use during physical activity. The patients will be randomly assigned to a fortnight s use of oxygen delivered through a portable device and, subsequently or otherwise, to a similar period using no ambulatory oxygen. Before the start of the four week period, a placebo-controlled double-blind 6MWT (on oxygen and on air) will be performed, following standard procedures (7), to determine whether the effects of oxygen on 6MWT performance are predictive of quality of life benefits. A run in period of two weeks to ensure disease stability (as measured by clinical assessment and questionnaire data) will immediately precede the four week trial period. Patients will be asked to wear a physical activity monitor and to complete an activity diary for the four-week period. In addition, at the start of the study and at the end of each two-week period, patients will be asked to complete questionnaires on ILD-related health status, shortness of breath and psychological symptoms. At the same time points, serum samples will be taken for brain natriuretic peptide (BNP) measurement, as a marker of right ventricular dysfunction (8). The primary outcome will be change in self reported health status as assessed by a recently validated, easy to use, ILD-specific questionnaire, the K-BILD (9) developed from a collaboration between the RBH ILDU and King s Hospital, while secondary outcomes will include dyspnoea scores, global patient assessment, monitored and patient-recorded activity parameters, quality of life (QOL) scores, and serum BNP levels. In addition, semi-structured interviews at the end of the four-week period will be conducted to evaluate patients' and carers' experiences regarding the use of ambulatory oxygen and trial participation. Potential benefits to patients and NHS. The key determinant of quality of life in patients with ILD is breathlessness on exertion, associated with oxygen desaturation on exercise. However, ambulatory oxygen is not routinely used in ILD patients. The results of our retrospective studies (4; 10) suggest that ambulatory oxygen can lead to major improvements in breathlessness/mobility in fibrotic ILD. This in turn should increase the likelihood of patients continuing to lead an active life for longer, with increased independence, thus leading to reduced patient care expenses. There are no UK or international guidelines for use of ambulatory oxygen in ILDs. The results of our proposed study will form an essential precursor to guidelines for the use of ambulatory oxygen that are ILD-specific.

Lay abstract: Scarring of the lungs (lung fibrosis), represents a large unmet clinical need. In scarring lung diseases, the normally delicate architecture of the lungs is progressively replaced by scar tissue (fibrosis), such that the lungs are no longer able to function. The most common form is idiopathic pulmonary fibrosis (IPF), with approximately 5,000 new cases diagnosed every year in the UK (6), and an average survival of two-three years after diagnosis. Other patterns of lung scarring, although on average more responsive to treatment, also have a tendency to progress, and have similar symptoms. The diagnosis tends to be made when there is shortness of breath on exercise, initially only on more strenuous activities such as walking uphill, or climbing stairs, and, as the disease advances, on lighter activities, such as walking on the flat, or washing and getting dressed. Breathlessness triggerered by activity is associated with a drop in oxygen levels in the blood (called oxygen desaturation") from the normal level (more than 94%); supplemental oxygen can correct this desaturation. We aim to explore the benefits of oxygen use when performing activities ("ambulatory oxygen") on day to day breathlessness, quality of life and mobility. We plan to invite patients with falls in oxygen saturation to less than 88% on a six minute walk test, to participate in the study. The study will consist of comparisons of breathlessness, quality of life and mobility at the end of two weeks on ambulatory oxygen compared to no ambulatory oxygen supply for the same period in 80 patients with lung fibrosis. We also propose to explore in interviews patients' and carers' experiences of the use of a portable oxygen supply and trial participation in a subgroup of 20 patients and carers."

Research activity codes: 6.7 PHYSICAL
Health categories: RESPIRATORY