The first ever digital European Cystic Fibrosis (CF) Conference took place 24–25th September 2020. Over 3,700 delegates registered from more than 70 countries. There was a notable increase in delegates from some countries, perhaps reflecting the greater ease of access the digital conference provides for healthcare teams who may not previously have had the ability to attend. For me, the underpinning theme of the eight symposia, which covered basic science to clinical care, was: ‘What will be the new normal for the CF community in light of the COVID-19 pandemic and in the era of the Highly Effective CFTR Modulator therapies (HEMT)?’
COVID-19 remains an ongoing global challenge but has been less common than feared amongst CF patients in Europe, with 180 CF COVID-PCR-positive cases across Europe to October 2020.1 Although COVID-19 is not a benign disease in CF, with a case fatality of 2.8% the outcomes for CF patients have been better than expected.1 There is ongoing work looking at potential hypotheses, such as the role of azithromycin, that might explain these reassuring outcomes.
Despite these better than expected outcomes, the effect of COVID-19 on the CF community as a whole has been profound. There has been reorganisation of care, disturbed follow up, and both transplants and clinical trials of novel therapeutics suspended. During the congress the effect of these changes were outlined, in particular the negative impacts of self-isolation on physical activity and psychological wellbeing, and the need for an awareness of the detection and provision of support for any post-traumatic stress response.
Although the world horizon seems bleak with the COVID-19 pandemic, global warming and economic downturn, there is suddenly a brighter horizon in the shape of HEMT therapies for people living with CF (pwCF) and their healthcare teams. Sometimes you need a storm to clear the air and allow the dust to settle. CF STORM (Simplifying Treatments Or Reducing Medication)2 will hopefully answer a key question that emerged during the James Lind Research Priority Setting partnership. The most burdensome aspect of CF care reported by pwCF and healthcare professionals are airways clearance techniques. Can pwCF established on elexacaftor-tezacaftor-ivacaftor stop nebulised mucoactive drugs (hypertonic saline or Pulmozyme®) without a significant fall in respiratory function at one year? This pragmatic trial aims to answer this question being posed increasingly frequently in CF clinics and chatrooms.
Talks outlined the effect of HEMT on the gastrointestinal system, illustrating improved gut inflammation and microbiome profile, the restoration of exocrine pancreatic function in some pwCF, but with a caution that there may be an increased risk of pancreatitis in others. We await with interest how HEMT may impact on cystic fibrosis related diabetes (CFRD).
Other presentations illustrated that with CFTR modulation there is a decrease in mucoid pseudomonas and rates of chronic pseudomonas, and posed the question: could ‘CF’ airways become ‘non CF’ bronchiectasis airways? Should we reinvigorate attempts to eradicate pseudomonas from airways in patients on HEMT? Clearly more studies will be needed, but with an awareness that spontaneously-expectorated sputum quantity and quality may decrease as more pwCF receive HEMT, and the role for induced sputum and pseudomonas antibody testing.
Aside from this effect on airways and sputum production, HEMT has the exciting potential to change other baseline characteristics in the CF population. We might expect lung function to be near normal, excellent nutritional status, a reduction in exacerbation frequency and improved quality of life. This ‘resetting’ of the baseline characteristics of the CF population as a whole will undoubtedly create a need to redesign future clinical trials in CF. Experts gave their thoughts on CF trials in a future of HEMT, including a focus on codesigning trials with pwCF. There will also undoubtedly be an emerging need for novel biomarkers and a call for longitudinal multicentre resources to enable large scale biomarker studies.
Currently, not all pwCF are eligible for HEMT. There was a strong sense at the conference of committing to finding solutions for all people with CF and finding a cure (#NoOneLeftBehind). Data from HIT-CF Europe,3 which has examined over 500 rectal biopsies from European pwCF with rare mutations, illustrates that centralised organoid generation and measurement is feasible and offers opportunities for treatment selection for pwCF with ultra rare mutations.
European CF Registry data was also presented, illustrating that the epidemiology of CF pathogens has shifted in the last ten years. Although pseudomonas and Staph aureus remain the highest prevalence there is an emergence of non-pseudomonas gram-negative pathogens, which present a unique challenge to care.
Another increasingly prevalent organism causing clinical debate is Mycobacterium abscessus (Mabs). ‘Should pwCF be offered eradication therapy following a first growth of Mabs?’ served as the premise for a pro/con debate. Pros citing evidence of a rapid decline with Mabs, establishment of a biofilm with time making eradication harder, prevalence rates increasing and the preclusion from lung transplantation in most centres. The cons countered that not all pwCF with a first isolate of Mabs develop disease, sample contamination and lab error occur, and the impact of therapies can be huge for pwCF with unnecessary inconvenience, cost, side-effects and potentially worsening nutritional status and mental wellbeing. We don’t know how this pro/con will play out in an era of HEMT, and further trials are awaited.
In summary, the ‘new normal’ for CF looks bright, but will bring novel challenges to reduce the burden of disease and develop self-monitoring, but with an awareness of the importance of mental health.
Dr Jamie Duckers, respiratory/cystic fibrosis consultant physician, Cardiff and Vale University Health Board