Queensland Cystic Fibrosis Research Program

Mycobacterium abscessus (MABS) are a group of non-tuberculous mycobacteria (NTM) found in water and soil habitats that exhibit high levels of intrinsic multi-drug resistance. They are recognised opportunistic human pathogens capable of causing chronic pulmonary infections, predominantly in individuals with underlying inflammatory lung diseases. MABS pulmonary disease (MABS-PD) can result in significant morbidity, increased healthcare utilisation, accelerated lung function decline, impaired quality of life, more challenging lung transplantation, and increased mortality. Furthermore, treatment regimens for MABS-PD are highly variable and not evidence-based and involve complex, expensive and often poorly tolerated drug combinations for prolonged periods (>12 months). Of particular concern is the increasing prevalence of pulmonary infections occurring worldwide in patients with bronchiectasis, and especially in the cystic fibrosis (CF) population.

Finding the Optimal Regimen for Mycobacterium abscessus Treatment (FORMaT) is a platform trial evaluating microbiological, functional, radiological and quality of life outcomes of currently used antibiotic therapies along with health care costs and cost effectiveness for treating MABS PD in all age groups in both Australia and Internationally.

The FORMaT trial aims to produce high quality evidence for the best treatment regimens to maximise health outcomes and minimise toxicity and treatment burden, as well as developing biomarkers (serology, gene expression signatures, and radiology) to guide decisions for starting treatment and measuring disease severity in patients with MABS PD. In so doing it will influence local as well as global practice.

Despite improvements in general health, early lung function and survival, premature loss of lung function, progressive lung disease, respiratory infection with an increasingly antibiotic resistant suite of bacteria and respiratory failure resulting in need for lung transplantation or death remains the major issue facing the CF community. Lung function decline begins in late childhood and continues unabated. Lack of knowledge about why and how this occurs presents a major challenge that needs to be overcome. Several factors are likely to be involved in this clinical problem, including: the lack of sensitivity of current clinical tools to detect the onset of lung disease; lack of methods for following lung disease activity, especially in early life; lack of ability to detect or prevent acute pulmonary exacerbations; and infections with antibiotic resistant organisms.

The ELO study aims to engage all patients attending the CF clinic at the QCH and adults with CF up to the age of 30 years attending TPCH. The study will use an Advanced Longitudinal Design method to develop disease trajectories from birth to 30 years of age to facilitate and understanding of why lung disease progresses. We will also develop a new understanding of early lung disease using novel lung function tests we have developed and biomarkers that indicate lung disease activity. Novel, non-invasive lung imaging techniques, using MRI, will be developed to give a better understanding of the relationship between early lung disease and loss of lung function.