Subtheme 1.1: ‘Well, it doesn’t affect me anymore’ (Arthur, cwCF aged 12–15 years)

As this young man indicated when asked about the difference he experienced after ETI, he described how the symptoms he had experienced had disappeared. He felt that CF does not affect his health any longer. The majority of cwCF interviewed felt that their respiratory symptoms, such as cough and shortness of breath, had reduced and that their lung function had improved. For example, Anna (cwCF aged 12–15 years) said: ‘I would say that it has made my lungs feel better. It’s been less coughing overnight, which I appreciate … and less mucus which I appreciate’. Being more active and awake, having more energy, not being tired and sleeping well were all frequently described. Maggie (cwCF aged 16–18 years) spoke about her health after ETI:

I’d say a bit because it’s made me a lot better, more awake … I was really tired before and I’d have like nine hours of sleep and still be tired and just like I need another nap. Now it’s like I can wake up and just have a day and then sleep at the end instead of needing breaks during the day. Which is nice.

Subtheme 1.2: ‘Sense of release and more lightness’ (Helen, mother of a cwCF aged 12–15 years)

This subtheme focused on the psychological impact reported by children and their families. Many participants reported a positive change in their outlook towards their lives. Several children relayed how as long as they could remember they had experienced symptoms and that now they felt incredibly well comparatively. This healthy feeling meant for the first time they looked optimistically to the future. Rose (cwCF aged 16–18 years) talked about her feelings before and after ETI:

for such a very, very long time CF felt like a really untreatable thing, and everything you’re doing feels like you’re just trying to prolong something that- Like prolong a life that might not be as high a quality as a lot of people’s. But the Kaftrio has really been the first proper step towards an effective treatment, that actually does something more than necessarily prolonging … you feel more like other people and you feel more like you are healthy, even if you aren’t necessarily better properly.

Several parents also reported the positive impact of ETI on the quality of life of their child. Parenting an older cwCF can be challenging and arguments about taking of medication and doing ACTs frequent issues. Many parents have previously spent a huge amount of time caring for their children only to see them struggling as they got older due to increasing symptoms compounded by the stress of an ever-increasing treatment burden. After starting ETI their child was now much better than previously. A common emotion among parents was relief once they had confidence that ETI was working and was going to benefit their child. The following quote from Peter (father of a cwCF aged 12–15 years) illustrates the impact on their mental health of their child’s health improving with ETI:

even though [cwCF] was really well before and the health improvements that we’ve seen are probably minor compared to some of the improvements that other families have seen, it’s still an emotional safety net that has made us think, ‘Well, any issues that we probably were going to run into are going to be either milder or non-existent in the future’. It is a miracle drug.

Some cwCF expressed disappointment and frustration that they had not experienced as much benefit as some other people had. Several children had compared results with others who shared experiences on social media. For example, Ruby (cwCF aged 12–15 years) talked about her lung function and how she felt about not seeing the huge impact that she had been expecting

I don’t think there has been a huge impact. It’s probably in the 80s now, which is still good. It’s really good, but the difference, probably. I know some people who—well, I don’t say I know, I mean like on social media and stuff—that has gone from 30 to 90, like it has been incredible. Yes. I haven’t seen a huge impact from the lung function side … I think there are people who it has impacted their life and made a huge difference, and I think that’s amazing for them. For me, personally, yes, sports, for example, amazing. But apart from that, I haven’t really seen a huge impact. My doctors might say otherwise, but me personally, I think it has not really done that much.

The first theme, ‘Kaftrio changed my life’, highlights the physical and mental improvement reported by cwCF and their families and its influence on their day to day lives. The next theme that developed from the analysis related to treatment burden.

Subtheme 2.1: before ETI

Most children started ACTs from an early age and maintained that routine throughout their lives. This schedule places a constant demand on families. Children felt that their lives were limited by the treatment. Although they understood the importance of ACTs and nebulisers in their care, they were often seen as a tedious process. This regime was also a constant reminder that they have CF making them feel different. Talking about this issue Anna (cwCF aged 12–15 years) said: ‘it can be a bit annoying. You know, in your daily routine it takes time to just organise your life around that, I suppose. It can be time-consuming every now and then, but apart from that, it’s good for my health’.

Commenting on the burden on parents or carers, Olivia (mother of a cwCF aged 12–15 years) emphasised the struggle with motivating their children to do their daily treatment saying:

that responsibility of having to get everything done all the time. Just, yes, how did we feel? (Laughter) Well, Dad used to be stressed because it was just the constant- With the Aerobika or whatever, to saying, ‘Blow’, ‘Blow’, ‘Count’, ‘Concentrate’, or with nebulisers, ‘Are you holding that properly?’, ‘Are you sucking it up?’, ‘Are you doing this?’, and it is the constant nudging to make sure that it is done in the right way.

A small number reported they were resigned to their daily routine. They believed that acceptance was the best way to manage the treatment around their lives. As Martha (mother of a cwCF aged 12–15 years) put it: ‘We sort of didn’t make it a big deal. You’ve got it, there’s nothing we can do about it, so you’ve just got to manage the treatments. You’ve got to do them, but try and do them in a way that doesn’t monopolise all of your day’.

Subtheme 2.2: after ETI

Most participants felt treatment burden had diminished since starting ETI. Some cwCF stated that it was now easier to manage their treatment without it having an impact on their day. Going to school had become easier without needing to wake up early to complete physio. Children were also now able to engage in more social activities. Elisa (cwCF aged 16–18 years) stated that:

When I was doing it twice a day it was quite a lot, because I’d have to be waking up. The whole set would take me about an hour, so I would have to wake up an hour earlier before school. Then when I got home it meant that if I wanted to go stay over at somebody’s or was busy, it was quite difficult to fit it in. I’d have to know before the morning to pack everything to go to someone’s.

Sonny (cwCF aged 12–15 years) commented: ‘I remember when I first started school again after it, I found it ridiculous how fast you can get ready in the morning without it. It took maybe 10, 20 minutes, just to do everything without tons of the stuff in the way’.

Even the children whose treatment routine had not changed felt that it was easier to complete now because they have more energy. There was also evidence of less tension among family members about managing treatment and trying to get everything done. The time that was now freed up was regarded as a welcome bonus and allowed them to enjoy more quality family time as expressed by Helen (mother of a cwCF aged 12–15 years) who said:

I mean, it has completely changed, like, the social side of the family. Because there aren’t the little niggles and the tensions in the way that there used to be, to try and get everything done within the timeframe. We’re a lot more relaxed, now, about things. And it seems like so much more manageable.

In another example, Peter (father of a cwCF aged 12–15 years) described how the daily stress had been taken away from his family allowing them to enjoy more quality family time: ‘Any pressure that’s taken off them in that way I think would be a massive improvement …. I think that would probably pay off for the change in quality of life that it would bring’.

In this theme, cwCF and their families emphasised the impact of treatment burden and compared it before starting on ETI with how it feels now. The reduction in treatment load had improved quality of life for many. Following on from this the third theme was associated with thoughts and opinions around simplifying CF treatment post-ETI.

Subtheme 3.1: slow down

All HCPs interviewed explained that they start reducing other treatments gradually after seeing an improvement in children’s health. All HCPs recognised the importance of ACTs to maintain lung health. The lack of longer-term data has made decision-making difficult. Although HCPs understood how crucial reducing treatment burden is for the quality of life of many cwCF and their families. Suzi (a physiotherapist) commented that: ‘They [CFTR modulators] are new, we don’t know how long the effects are going to be, if they’re going to be sustained or not. That’s what makes me anxious, is that they are so new. I would love to think that we can reduce’. Another HCP Laura (a nurse specialist) said:

if it’s safe for us to do so and we can reduce that load and that burden on them then I am all for it. Because it is a very intense daily schedule that a lot of the kids have to go through, I wouldn’t want to do it myself and we’re asking them to do it every day, day in day our forever, essentially. Which if there is an option to reduce it down it’s going to make their quality of life so much better.

Like the HCPs, most parents expressed their hesitation to change their child’s routine and preferred to take things slowly. From their point of view, it was seen as safer to keep doing ACTs to keep children as healthy as possible. They believed that the routine of doing ACTs was helping children stay healthy and changing this idea was hard for some. Some had experienced what could happen if their child did not do ACTs in the past. As a result, some families found it easier to keep the routine going rather than disrupt it and risk needing to reintroduce it again. Some mentioned they needed a scientific answer and time to see the feasibility of simplifying physiotherapy yet maintaining their child’s health. This was summarised by Amy (mother of a cwCF aged 16–18 years) as follows:

I’m still very firmly of a mind that she must do it, she must do it to absolutely the best of her ability … for me, it’s easier just to carry on like that because for me I think it’s worse to have to start going up again with things. So, I would rather just do it absolutely maximally and then know you’ve done everything you can and then that’s just in the hands of whatever happens.

Martha (a mother of a cwCF aged 12–15 years) said:

I don’t want to be the person who stops doing the physio and then, six months later, research comes out saying you probably should have kept doing it. At the minute, I think we’re happy to just be patient, be grateful. The transformation is massive, so I kind of think I’ll never take that for granted.

Only a small number of cwCF themselves mentioned any uncertainty about reducing treatment being the right thing to do. Arthur (cwCF aged 12–15 years) comment illustrated this: ‘They offered me the chance, last time we were at clinic, to drop one physio completely. But I didn’t want to …. In case I stated coughing again’.

Subtheme 3.2: ‘Doing less would be better’ (Sonny, cwCF aged 12–15 years)

Contrary to the HCPs and carers’ views, most children themselves expressed enthusiasm about taking this step and thought that reducing ACTs would improve their lives. It was clear that the majority were keen to reduce their treatment as soon as possible. There was eagerness among some individuals who had reduced some ACTs to move on to the next level and do none. For example: ‘I’d rather try a break, because if you don’t try it you’re not going to know. Even if it does go wrong, you can just go back to it’ (Elizabeth, cwCF aged 12–15 years).

Subtheme 3.3: suggestions

Participants were asked to put forward suggestions about what should happen to ACTs and nebulised treatments following improvements with ETI. Several children and parents proposed that ACTs should become ‘as required’ rather than daily. This would mean they would feel more empowered and be able to contribute to the decision about when to introduce ACTs based on their judgement. Helen (mother of a cwCF aged 12–15 years) said: ‘I think, depending on how you feel, it should be the patient’s decision. It’s their health so they should be able to determine whether they need to or not with the guidance of the doctors’. (Pippa, a cwCF aged 16–18 years) A parent commented: ‘I feel like the next step would just be on an as-and-when basis, rather than a daily routine’.

Several HCPs advocated for a shift in treatment protocols where approaches are personalised and tailored to an individual’s needs. Although they were generally supportive of this change, they highlighted the need to have a structured process and to track progress and document any changes. This was summarised in this quote:

I think what we are doing is probably trying to reduce things, a little bit at a time, and monitoring the effects of that … I think trying to find a balance somewhere, because I don’t want to be very much, right, it’s fine, you're really well, we’ll just stop all your treatment. So, maybe at one clinic, you might say, ‘Instead of doing 10 cycles of your PEP mask, you could do 8’. And then the next clinic, if everything is okay, we might put that down a little bit more And I have to admit, I’m going slowly, slowly, rather than just. Right, that’s fine, stop everything’ (Sarah, a physiotherapist)

Another suggestion was to encourage children to do more exercise as ACTs were reduced. Several participants mentioned they believed that exercise could be an alternative option that helps maintain physical health and provides a ‘safety net’ when simplifying ACTs. As Mary (a physiotherapist) commented:

I also think that my advice about exercise is becoming more important, because I suspect that people’s- And this is the way I’ll sell it to them, is that their ticket out of doing routine airway clearance or day-to-day physio is probably to move more. So, ‘I would be happy to reduce your airway clearance to once a day, if you do some exercise’.

A patient perspective on this was:

I think it should still go on, I think you sort of need exercise still and everything like that, so I don’t see a need to stop at all, I think it does still help and stuff like that. Because although the Kaftrio helps I feel like you need something with it, so they work hand in hand, I think you still need them both. (Maggie, a cwCF aged 16–18 years)

In summary, after experiencing an improvement in their health the majority of cwCF were keen to reduce or even stop ACTs. Parents and HCPs are receptive to the idea of treatment simplification and willing to give suggestions but prefer a more cautious approach and would like to see more research performed in this area. The final theme focused on changes in attitudes and models of CF care post-ETI.

Subtheme 4.1: shift

A common view was that a shift was noticed after ETI was introduced. One of the changes that HCPs reported was a change in the attitudes of children and families towards ACTs, especially in those who experienced significant health benefits.

There was a sense of growing confidence in individuals to decide on their own treatment. Some participants questioned the need for ACTs. After starting ETI some children have felt much healthier and along with parents voiced that they may not need to do ACTs, especially those who had no secretions. As Joan (a physiotherapist) summarised: ‘I think some of the families and patients have almost voted with their feet a little bit, stopped things and then come and told us’. A parent commented that: ‘he’s not producing thick mucus with the drug. So, if he’s not producing thick mucus, and he can cough things up himself, or he doesn’t have a cough, then he doesn’t need physio …. Or if it maybe potentially- I don’t know’ (Helen, mother of a cwCF aged 14 years).

Another reported issue was a shift in the level of adherence with other treatment. Several HCPs felt adherence had deteriorated after the introduction of ETI because children and families felt they could miss some without any harm. However, some HCPs argued that simplifying treatment had helped patients then be more focused and committed to ACTs and to have the energy to do it. As Mary (a physiotherapist) put it about adherence issues: ‘think the challenges are still there and they’re still the same, but they have been exaggerated, if you like. So, adherence has got a lot worse, because actually they feel great, and they don’t understand why they would necessarily need to do this’. Laura (a nurse) commented that: ‘the simpler we can make their treatment, the better, because they’re more likely to do it’.

‘Good luck getting me to do it again’ (Sonny, a cwCF aged 12–15 years). This was how one of the children expressed his feeling about doing ACTs again after getting used to a simplified regime. This was a challenge that was also recognised by one of the physiotherapists when a patient experiences an exacerbation and is required to do ACTs and use nebulisers: ‘Because I think they’ve almost had a taste of the good life, whereby they’re doing less. I think it’s very hard to then build back up again’ (Mary, a physiotherapist).

Another shift HCPs described was a change in the workload. Historically, physiotherapists mainly concentrated on ACTs, while after ETI, they have turned their attention more towards promoting exercise and a healthy lifestyle. Other responses to this question talked about focusing on cwCF who do not have access to ETI and those who have not experienced a dramatic clinical benefit from it. These opinions are summarised by: ‘And maybe we have got the airway clearance there. But I think more emphasis on keeping them healthy, in terms of chest as well as exercise tolerance and lifestyle, will potentially go more towards the exercise side of things’ (Kate, a physiotherapist). Along with: ‘There’ll still be some that need it because you’ll always get the extremes with different kids that have difficulties. You’ve got the kids with the other genes that don’t necessarily get it’ (Suzi, a physiotherapist).

Subtheme 4.2: emerging crisis

Despite the positive impact of ETI, there are new challenges facing the CF multidisciplinary team. Weight management is a new challenge, in the past maintaining good nutritional status was a major focus of care. The normalisation of dietary advice for people who had required a high calorie intake previously is a dramatic new recommendation. This was summarised by Ruby (cwCF aged 12–15 years) as: ‘Before Kaftrio, yes, you could eat anything you want, because you wouldn’t put weight on. Now, there was a period of time where I was getting really upset, because all of a sudden, I had got a lot of weight on’. An HCP commented that:

I think one of the other challenges that we’re seeing now is not necessarily always physio-related, but I think will have a massive impact on physiotherapy, will be weight. A lot of these patients are now gaining weight a lot more rapidly than what they would have done, and they’re still in a lot of the habits from younger ages, where they’ve had a lot of calories, and they’ve fortified a lot of their foods, and now they’re actually gaining weight (Mary, a physiotherapist).

Some cwCF and their families questioned ‘what is next?’. Talking about this issue, a participant said she worried if the benefits from ETI would be sustained in the long-term and wondered if her health would deteriorate in the future. A small number of participants stated that observing the results of ETI raised the expectation of having a genuine cure for CF in the future: ‘I think now that I’ve got the drug and, obviously, we don’t know how long it’s going to last for, I guess, it could be 10 years, it could be 20 years before it’s starting to decline … It’s just like you're thinking about it’ (Pippa, cwCF aged 16–18 years). Peter (father of a cwCF aged 12–15 years) said: ‘I think Kaftrio is the closest thing that we’ve had so far. I know it sounds greedy, but having something that’s better than that would always be great’.

Overall, the interconnected themes demonstrate that ETI has had a significant impact on the health and lives of cwCF and their families. Treatment burden has and is being reduced and there is motivation to simplify treatment further. This is feeding in to changes in clinical practice and attitudes towards treatment.