Background Treatment of patients with Cystic Fibrosis homozygous for the Phe508del gene, with Lumacaftor / Ivacaftor (LUM/IVA) improves outcomes in patients with FEV1 > 40% predicted. We set out to observe the most sensitive clinical measure that would change with treatment in terms of exercise capacity or lung function in adults with severe lung disease as defined by an FEV1 < 40% predicted when clinically stable. Methods 10 adults homozygous for the Phe508del received LUM/IVA. We assessed; six minute walk test (6MWT), spirometry, gas transfer (DLCO), plethysmography, and nitrogen multiple breath washout (MBW) at baseline, 4, 12, 24 and 52 weeks. Comparison was made with 10 matched historical controls that had been observed over 12 months. Results There was a significant improvement in 6MWT by 4 weeks of treatment; with a mean increase of 78 m (SD 62.3) and this increased to 118.1 m (SD 80.9) (ANOVA p = 0.006) by 52 weeks. Significant improvements were also seen in the resting heart rate and the oxygen saturation (SaO2) after 6 min walking. A significant improvement was not seen in FEV1 though until 24 weeks, though this was maintained at 52 weeks (ANOVA, p = 0.0004). There were no significant differences seen in the MBW or DLCO. After 12 months treatment with LUM/IVA, in comparison to historical controls; the 6MWT increased by 118 m (SD 80.9), but fell in the controls − 61.3 m (SD 31.1). FEV1; LUM/IVA led to an increase of 0.398 L/min, compared to a fall in the controls − 0.18 (SD 0.2). Conclusion In adults homozygous for Phe508del with severe disease, treatment with LUM/IVA results in a clinically significant improvement in 6MWT that was evident at 4 weeks and maintained at 52 weeks. Improvement in exercise tolerance is an important outcome to consider in those with more severe airways disease. Trial registration This was an observational trial conducted on individuals who became eligible to receive LUM/IVA. All investigations were carried out as part of routine clinical care. The trial was registered in retrospect on the 13/5/2019 on the Australian New Zealand Clinical Trials registry; ACTRN12619000708156 .

Cystic fibrosis (CF) is Australia's most common life limiting genetic condition, characterised by declining health and quality of life (QoL) over time. Despite improvements in treatment, there remains no cure. Adolescents and young adults (AYAs) with CF experience broad impacts to psychosocial functioning and QoL, as well as major transitions in care, all at a time of significant developmental change. The importance of developmentally tailored approaches to youth health care and self-management for young people with CF are well understood. However, to date, models of youth specific self-management have been lacking and motivation for young people with CF has not been well explored. This qualitative study, based on a social constructionist epistemological framework, addresses this gap. A total of 21 AYAs aged 15-30 years were recruited through one paediatric and one adult Australian CF centre.Demographic, clinical and distress data were captured to describe health complexity. Semi-structured interviews were audio-recorded, transcribed and analysed using thematic analysis. Participants were representative of Australian AYAs with CF by demography and clinical status. Alarmingly, over a third reported clinically significant distress. Two themes emerged. The first Identified impacts to motivation and self-management resulting from the challenges of managing CF, life and care. These included time and competing priorities, changing health statis, mental health, social factors, unmet needs and health system complexity. The second identified factors that support motivation including: achievement, meaning and purpose; consequence avoidance; and accountability. These results illustrate the importance of AYA specific, theoretically founded, holistic self-management models which extend beyond current theoretical approaches that aim to understand behaviour change or address barriers, in isolation from motivation. Improved approaches to care based on these findings are essential to foster positive behavioural change, support self-management and foster the best health outcomes for young people living with CF.

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