Background: Recently, updated guidelines were published for the management of infants with CFSPID (cystic fibrosis screen positive, inconclusive diagnosis) 1 Barben et al. JCF. 2021; Google Scholar . Within our large tertiary paediatric centre in North West England, we do not have a separate CFSPID clinic, but manage CFSPID within CF clinic. We became aware that some older children, diagnosed prior to the label CFSPID existing, had been labelled and managed as though they had classical cystic fibrosis (CF).

Pancreatic insufficient children with cystic fibrosis (CF) are routinely supplemented with fat-soluble vitamins A, D, E, and K, and serum vitamin levels are checked in annual review assessments. Prior to 2018, the formulations involved preparations that provide Vitamin E, and K separately, but A and D together. This has proven to be challenging for parents and carers looking after young children with CF. Anew formulation (Paravit – CF), containing all the required vitamins in one easily deliverable format, became available, but uncertainty remained as to their efficacy in maintaining healthy vitamin levels. This study, temporally explored the efficacy of this approach, comparing data from before and after supplementation. Royal Manchester Children's Hospital (RMCH), a large tertiary CF centre in northwest England, cares for 330 children with CF, through direct input (200 children) and by shared care arrangements (130 children). For children under direct care at RMCH, an electronic registry (THRIVE) captures anonymised pre- and post-supplementation data, including vitamin levels and anthropometric parameters. This study temporally explored serum vitamin levels and growth parameters (weight, height, and BMI) before and after Paravit – CF supplementation. In this preliminary analysis, complete data was available on only 78 children. Vitamin A levels were slightly higher (p < 0.001), and vitamin E levels were slightly lower (p = 0.027), in the post-supplementation group. No significant change was observed in the vitamin D levels. Furthermore, anthropometric parameters remained stable. A new vitamin supplementation program using a single formulation did not result in a loss of efficacy in attaining desirable vitamin levels and in maintaining anthropometric parameters. Future research should explore parental satisfaction using patient-reported outcome measures.

CFTR modulators, improve lung function, body mass index, and reduce pulmonary exacerbations. There is some evidence from clinical trials1Rosenfeld et al.ARRIVAL.Lancet Resp Med. 2018 Jul; 6PubMed Google Scholar that CFTR modulators may restore some degree of pancreatic function, but this has not been thoroughly investigated in the "real world." A number of children from our centre's cohort, a large tertiary paediatric hospital in Northwest England, have reported a reduction in the symptoms of pancreatic insufficiency since commencing modulator therapy. We aim to investigate the effect of modulator therapy on pancreatic function by repeating faecal elastase (FE) sampling on children reporting improved symptoms. FE samples were repeated from children with clinical evidence of improved pancreatic function. Clinical symptoms were lack of malabsorption symptoms (loose and/or oily stools) when Creon doses were not given with food. Often with a change in bowel habit with greater tendency toward constipation (not resulting from change in dietary fibre and/or fluids). To date 8 children aged 2–14 yrs., with at least one delF508 mutation, have had a FE repeated. 3 patients had an improvement to over 200 ug/g with a FE at birth of <15 ug/g in all cases. 2 had an improvement to between 15–200 ug/g. 3 remained insufficient at <15 ug/g. Some patients on CFTR modulators demonstrate recovery to pancreatic sufficient levels, and others partial recovery. However, improvement of clinical symptoms of malabsorption does not always correlate with biochemical analysis, which can make advice/dosing of pancreatic replacement therapy challenging. Data collection is ongoing, with further data becoming available. Our data will have a direct impact on clinical practice and could change annual review screening for pancreatic sufficiency in all CF pancreatic insufficient patients.

Background: Pancreatic-insufficient children with cystic fibrosis (CF) are routinely supplemented with fat-soluble vitamins A, D, E, and K, according to national guidelines, and serum vitamin levels are checked in annual review assessments.Traditionally, the formulations have involved preparations that provide vitamins E and K separately and vitamins A and D together.This has proven to be challenging to parents and caregivers looking after young children with CF.A new formulation (Paravit-CF, Parapharm Development Ltd, Reading, UK) containing all the required vitamins in one easily deliverable format became available in the United Kingdom in 2018, but uncertainty remained as to its efficacy in maintaining healthy vitamin levels.This study explored the efficacy of this approach, comparing data from before and after.Methods: Royal Manchester Children's Hospital (RMCH), is a large tertiary CF center in northwest England that cares for 350 children with CF through direct input (200 children) and shared care arrangements (150 children).An electronic registry (THRIVE) captures anonymized pre-and postsupplementation data, including vitamin levels, anthropometric parameters, and patient-reported outcome measures, for children under direct care at RMCH.This study explores serum vitamin levels and growth parameters (weight, height, BMI) before and after Paravit-CF supplementation.Results: In this preliminary analysis, complete data were available for 45 children.No significant change was observed in vitamin A, D, and E levels before and after the Paravit-CF formulation was introduced0 and, anthropometric parameters remained stable.Conclusions: A new vitamin supplementation program using a single formulation did not result in a loss of efficacy in attaining desirable vitamin levels and in maintaining anthropometric parameters.Subsequent research should explore parental satisfaction using this approach using patient-reported outcome measures.

Introduction: Lung clearance index (LCI) is a measure of lung gas mixing, and a sensitive indicator of peripheral airway obstruction. In children born prematurely there have been previous reports of elevated LCI at birth and childhood. LCI in infants is highly challenging, requiring either 100% O2 to washout, or use of 4% SF6. Here we report on a novel method using a portable LCI device in non-sedated premature infants. Methods: LCI measurements were undertaken using 0.1% SF6 and washout on air. Premature infants no longer requiring oxygen were recruited just prior to discharge. Follow up measurements were planned 1 year later. Healthy controls were recruited opportunistically when attending non-thoracic MRI scan under sedation. Results: 13 premature babies (mean 30+6 weeks at birth, 37+6 corrected at measurement) were recruited and successful measurements were achieved on 9 (69%). LCI data are available for 36 healthy controls (mean 62weeks old, range 12-154 weeks). Mean LCI of the premature children (8.4, SD 1.6). was significantly higher than that of the healthy cohort (mean LCI 7.0, SD 0.6), p=<0.001. Median coefficient of variation of ex-premature LCI was 6.6%. Mean(SD) FRC was 68.95(47.96)ml (21 ml/kg (SD=3.19)). Only one child attended for a follow-up measurement (study interrupted by COVID pandemic); initial LCI of 7.3 at 38+6 (7 weeks of age) which increased to 8.0 at 61 corrected weeks of age. Conclusion: LCI is elevated in premature infants at time of discharge. This can be measured successfully using a portable device without high concentrations of SF6 or O2, and without sedation. The longitudinal change is still to be determined.

Introduction: Lung clearance index (LCI) is an important measure of lung function, especially in those with mild cystic fibrosis (CF). It is however challenging to deliver in infants, with current devices requiring 100% O2 washout or use of 4% SF6. We have previously described a novel portable method using 0.1% SF6 as the tracer gas. In this study we report longitudinal measurement of LCI using this method. Method: LCI measurements were undertaken using 0.1% SF6 and washout on air. All measurements were performed under light sedation, up to age 3.5 years. CF children, clinically stable at time of assessment, had LCI measured at initial visit, 2-4m later and 12-24m later. Healthy controls were measured once. The study took place in one US and two UK centres. Results: 32 CF infants had successful LCI at visit 1, six at visit 2 and five at visit 3 with data analysis still ongoing. Data are also available on 36 healthy infants. There was no difference in overall mean LCI in CF (mean 7.0, SD 0.7) vs controls (mean 7.0, SD 0.6), p=0.9. Median coefficient of variation of LCI repeats was 5.1%. Five of eight measurements in CF infants <52wks old and 15 of 35 measurements in infants >52wks of age showed LCI >7.0. Bland-Altman analysis of visits 1 vs 2 in six children showed a mean change of 0.25, and limits of agreement of -0.66 to 1.16 LCI units, similar to that described in older children. Conclusion: Infant LCI is feasible with light sedation and showed good short term repeatability. Although there was no overall difference in mean LCI, a large proportion of CF patients showed an elevated LCI in infancy.

Introduction and Background Non-cystic fibrosis bronchiectasis (NCFB) and primary ciliary dyskinesia (PCD) are increasingly recognised as important respiratory conditions in childhood with considerable morbidity and burden of care. Daily chest physiotherapy, repeated hospitalisations for intravenous antibiotics and frequent oral antibiotic courses remain the cornerstones of therapy. Aims This study aimed to explore the parental experience of, and satisfaction with, our tertiary paediatric service for children with NCFB and PCD. Methods Royal Manchester Children's Hospital (RMCH) offers tertiary services to children with complicated respiratory problems, from Greater Manchester and beyond. Parents/carers attending the tertiary NCFB/PCD Clinic at RMCH were invited to take part in a questionnaire-based survey (May - July 2019). This study specifically enquired about parental experience of outpatient and inpatient service provision, emergency care, and access to input from allied health professionals. Results Of the eligible 105 families (46 with PCD and 59 with NCFB), 30 families took part in this study (16 with PCD). Overall, parents responded overwhelmingly in favour of the quality of care received: 100% of respondents agreed that the team delivered high-quality care with a high level of satisfaction reported in all questions relating to outpatient clinics. 29/30 (97%) reported seeing a physiotherapist regularly but only 5/30 (17%) regularly saw a dietician and 1/30 (3%) a psychologist. 11/30 (37%) patients also had a general paediatrician involved in their care. Areas for improvement identified included planning for elective admissions (28% of parents felt they were given inadequate notice) and clear pathways for seeking emergency advice, with 18% of parents unsure who to contact in an emergency and 22% reporting difficulties contacting a team member. Information leaflets have subsequently been designed to address this. Conclusions As a service model, a specialist paediatric bronchiectasis clinic provides a high level of parent/carer satisfaction. There may be scope to incorporate additional dietetic and psychology input into such clinics. It is important to ensure good communication around all aspects of care including emergencies and inpatient admissions. Consideration must be given to the role of the local general paediatrician alongside the tertiary respiratory service.

Introduction Lung clearance index (LCI) is a sensitive measure of lung disease in infants, with potential applications in clinical practice and research. However, measuring LCI in infants is technically challenging and there is no simple method of assessing LCI outside of specialist research laboratories in this population. We have previously described an alternative method of measuring LCI, in which expired gas is collected and analysed to derive functional residual capacity (FRC) and LCI without directly measuring flow. This eliminates one of the major technical challenges, whilst also reducing the system’s dead space. This method is highly accurate in vitro, with a mean accuracy of FRC measurement to within 1%, down to FRC of 100ml.1 The method does not require large external gas tanks, and washout is performed breathing room air, making the system fully portable. Aim To assess the performance of this method in vivo. Method Healthy controls and infants with CF are currently being recruited to undergo LCI measurement using this method. Practical applicability of the system is determined by the number of successful tests and within-subject repeatability, defined as coefficient of variation (CV%) of same-visit repeats. Comparison will be made with LCI measurements obtained using a respiratory mass spectrometer, currently considered the gold standard for infant LCI measurement. Results To date, 10 healthy controls (mean age 53 weeks) and 2 infants with CF (mean age 55 weeks) have successfully undergone LCI measurement using this method. Mean LCI in controls was 6.62 (range 5.79–7.91). Mean within-subject CV% was 5.9%. Mean LCI in infants with CF was 7.63 (CV 5%). Conclusion Preliminary data suggest this is a feasible and reproducible method of performing LCI in infants. Results in both infants with CF and controls fall within ranges predicted by the respiratory mass spectrometer2 and within accuracy limits set by international guidelines. This could provide a more accessible alternative to current technologies, enabling this test to be offered in more centres. References Shawcross, et al. Ped Pulmonol 2016;51:491–497. Lum, et al. Eur Respir J 2013;41:1371–7.

Background In order for lung clearance index (LCI) to be a clinically useful measurement, a better understanding is required of short-term variability. LCI-SEARCH is a longitudinal study in children and adults with CF, with LCI measured at each clinical review using a portable closed-circuit wash-in system (www.lci-search.com). Here we report initial LCI repeatability from the adult cohort. Methods LCI measurements were performed in triplicate using a closed-circuit wash-in method (Horsley et al. ERJ open). The most recent paired LCI measurements were included providing they were within 6 months of each other, the patient was deemed clinically stable by a physician and the patient scored <2 on a 4 point respiratory symptom score. Repeatability was assessed by Bland-Altman analysis. Results Of 40 CF adults, paired data were available on 21 (7 subjects had completed only 1 assessment, 1 withdrawn, 11 clinically unstable). These 21 subjects (14 male) completed a median of 5 LCI measurements each (range 2–11), a median of 84 (range 42–189) days apart. Mean age was 28 yrs, mean FEV1 82% predicted, 11 pancreatic sufficient, 11 had never had pseudomonas infection. Mean (SD) LCI at visit 1 was 8.68 (2.96) vs 8.73 (2.81) at visit 2 (p = ns). Median coefficient of variation for LCI was 3.9% (visit 1) and 4.2% (visit 2). Mean change in LCI between visits was 0.05 (1% of baseline LCI). 95% limits of agreement (LOA) were −1.1 (−13.7)% to 1.0 (11.6)% of baseline LCI. In this very mild cohort, 7 patients had normal LCI (<7); exclusion of these did not substantially alter LOA (−13.9 to 13.1%). There was greater variability in FRC: mean bias −1.5% of baseline (LOA 30 to −33%). Conclusions Even in this very mild cohort of CF adults, patients are frequently unwell or more symptomatic at routine review. Within-visit repeatability was good, and similar to previous reports. When clinically stable, LCI variability over a period of up to 6months was approximately ± 10%. Addition of more adult as well as paediatric data to this assessment will widen the applicability of these confidence intervals.