Impact of elexacaftor/tezacaftor/ivacaftor on fat-soluble vitamin levels in children with cystic fibrosis.

BACKGROUND: Children with cystic fibrosis are at risk of fat-soluble vitamin deficiency. CFTR modulators positively effect nutritional status. This study aimed to assess changes in serum vitamins A, D & E after starting ETI therapy to ensure levels were not abnormally high. METHODS: Retrospective review of annual assessment data over 3½ years, before and after starting ETI in a specialist paediatric CF centre, including vitamin levels. RESULTS: 54 eligible patients were included, aged 5-15 yrs (median age 11.5). Median time to post measurements was 171 days. Median vitamin A was increased (1.38 to 1.63 µmol/L, p<0.001). Three patients (6%) had high vitamin A post-ETI, compared with none at baseline; and 2 (4%) had low levels compared to 4 (8%) at baseline. No changes in vitamins D&E. CONCLUSIONS: This study found increased vitamin A, sometimes to high levels. We recommend testing levels within 3 months of starting ETI.

Revisiting a diagnosis of cystic fibrosis - Uncertainties and considerations.

There is now increased knowledge and experience of newborn screening around the world. There is also a better understanding of CF gene analysis, informed by international databases. This has resulted in a small number of children and adults having their diagnosis of CF reversed. This article illustrates this issue with three cases. It considers how best to tell children and adults with their families, and the reactions that may be encountered. It also discusses practical issues of removing the diagnosis.

CFTR modulator therapies - Effect on life expectancy in people with cystic fibrosis.

CFTR modulators have dramatically changed the clinical course of CF in those fortunate enough to receive them. Inevitably, randomised controlled trials during the development of these drugs are too short to use mortality as an outcome. Evidence for their effect on life expectancy are best gained from real world registry studies specifically looking at mortality, but these are only available for ivacaftor to date. Therefore, indirect evidence must be obtained by looking at outcomes known to affect mortality and seeing the effect of these drugs on those outcomes.

Initiating home spirometry for children during the COVID-19 pandemic - A practical guide.

The COVID-19 pandemic has led to a rapid escalation in use of home monitoring and video consultations in children with a variety of chronic respiratory conditions. Our department set up a home spirometry service from scratch once it became evident that we needed to keep patients away from hospital clinics whenever possible. We faced a number of challenges but now have around 400 children using home spirometers. There are a number of portable spirometers available, some with online platforms. The technology, particularly the software/apps interface, has been improved by the companies in response to issues that have arisen. We believe the use of home monitoring is here to stay.

Environmental risks of Pseudomonas aeruginosa-What to advise patients and parents.

Pseudomonas aeruginosa (PsA) is commonly found in soil and water so is impossible to avoid completely. Parents/carers of children with cystic fibrosis (CF) are concerned about them acquiring PsA from the environment, and different families view risk differently. Our ethos is to enable children with CF to take part as much as possible in educational and fun home activities, in order to maintain their quality of life (and their family's), and not have them feel different from other children. This review presents advice for families as to what they must definitely avoid, what they must take precautions with but can allow, and what they must not avoid. It is mostly evidence-based, but where evidence is lacking it a consensus view from the Paediatric CF Unit at the Royal Brompton Hospital.

Communicating cystic fibrosis newborn screening results to parents.

The way results of cystic fibrosis (CF) newborn screening are communicated to parents is critical yet is done differently across the globe. We surveyed parents of 101 children in our tertiary London paediatric centre with a 48% response rate. Parental responses were as follows: 40/42 (95%) said the information could not have been given over the phone and 39/43 (91%) said they wanted both partners present; 27/42 (64%) said it was helpful having the health visitor also present; and 37/40 (92%) felt it was acceptable to wait until the next day for the sweat test. We have reduced the time from first contact to arriving in the home to 2-3 h.Conclusion: We believe that this survey backs up our approach of a home visit by a CF nurse specialist with the family's health visitor to break the news. This is challenging in the current COVID-19 pandemic. What is Known: • Breaking bad news can have a lasting impact on parents when not done the right way. • Giving results of cystic fibrosis (CF) newborn screening is done differently within the UK and around the world. What is New: • Our parental survey revealed that the majority (92%) believed this should be done face to face and not over the telephone. • There was a mixed response to whether the parents should be told the genotype (assuming the CF centre knew), and thus the CF diagnosis before the confirmatory sweat test was carried out.

European and United Kingdom COVID-19 pandemic experience: The same but different.

The global healthcare landscape has changed dramatically and rapidly in 2020. This has had an impact upon paediatricians and in particular respiratory paediatricians. The effects in Europe, with its mature healthcare system, have been far faster and greater than most authorities anticipated. Within six weeks of COVID-19 being declared a public health emergency by the World Health Organisation [WHO] in China, Europe had become the new epicentre of disease. A pandemic was finally declared by the WHO on March 11th 2020. Continued international travel combined with the slow response of some political leaders and a variable focus on economic rather than health consequences resulted in varying containment strategies in response to the threat of the initial wave of the pandemic. It is likely that this variation has contributed to widely differing outcomes across Europe. Common to all countries was the stark lack of preparations and initial poor co-ordination of responses between levels of government to this unforeseen but not unheralded global health crisis. In this article we highlight the impact of the first wave of the COVID-19 pandemic in Italy, Austria, Germany, and the United Kingdom.

Clinical papers of the year 2018 - Cystic fibrosis.

This paper reviews the most important clinical papers in cystic fibrosis published in 2018, having searched all the literature on Pubmed. Focus is on CFTR modulator therapy, randomised controlled trials, and infection/microbiology issues.

Diagnosis of cystic fibrosis in London and South East England before and after the introduction of newborn screening.

INTRODUCTION: Newborn screening (NBS) for cystic fibrosis (CF) was introduced to London and South East England in 2007. We wished to assess the details of missed cases, and to compare the age at diagnosis and other clinical parameters, prescreening and postscreening. METHODS: Retrospective and prospective case notes and database review of all newly diagnosed CF patients in our 7 CF centres, for 18 months before and 4 years after NBS started. RESULTS: 347 patients were diagnosed with CF. 126 patients were not screened (born before or abroad), and had a median age at diagnosis of 2.4 years, excluding those with meconium ileus (MI). Their median time to diagnosis from initial symptoms was 1 year, and in 10% it was >6 years. After NBS started, 170 were diagnosed by NBS (48% were already symptomatic); 7 moved into the region after NBS elsewhere; 34 presented with MI (6 were negative on NBS); and 10 screened children were missed (false negative cases). Median age of diagnosis was 3 weeks. Prevalence was 1 in 3991 live births. By 2 years of age (with data on 104 patients), 49 children (47%) had their first isolation of Pseudomonas aeruginosa, while 37 (36%) had their first growth of Staphylococcus aureus from respiratory cultures. CONCLUSIONS: NBS has significantly reduced the age of diagnosis, although many were symptomatic even at 3 weeks of age. A small number of patients with CF can still be missed by the screening programme, and the diagnosis should be considered even with a negative screen result.

Fitness to fly testing in term and ex-preterm babies without bronchopulmonary dysplasia.

BACKGROUND: During air flight, cabin pressurisation produces an effective fraction of inspired oxygen (FiO(2)) of 0.15. This can cause hypoxia in predisposed individuals, including infants with bronchopulmonary dysplasia (BPD), but the effect on ex-preterm babies without BPD was uncertain. The consequences of feeding a baby during the hypoxia challenge were also unknown. METHODS: Ex-preterm (without BPD) and term infants had fitness to fly tests (including a period of feeding) at 3 or 6 months corrected gestational age (CGA) in a body plethysmograph with an FiO(2) of 0.15 for 20 min. A 'failed' test was defined as oxygen saturation (SpO(2)) <90% for at least 2 min. RESULTS: 41 term and 30 ex-preterm babies (mean gestational age 39.8 and 33.1 weeks, respectively) exhibited a significant median drop in SpO(2) (median -6%, p<0.0001); there was no difference between term versus ex-preterm babies, or 3 versus 6 months. Two term (5%) and two ex-preterm (7%) babies failed the challenge. The SpO(2) dropped further during feeding (median -4% in term and -2% in ex-preterm, p<0.0001), with transient desaturation (up to 30 s) <90% seen in 8/36 (22%) term and 9/28 (32%) ex-preterm infants; the ex-preterm babies desaturated more quickly (median 1 vs 3 min, p=0.002). CONCLUSIONS: Ex-preterm babies without BPD and who are at least 3 months CGA do not appear to be a particularly at-risk group for air travel, and routine preflight testing is not indicated. Feeding babies in an FiO(2) of 0.15 leads to a further fall in SpO(2), which is significant but transient.

Increased incidence of bronchopulmonary fistulas complicating pediatric pneumonia.

BACKGROUND: The frequency of complicated pneumococcal disease, including necrotizing pneumonia, has increased over the last decade. During 2008-2009, we noted an increase in the number of children whose empyema was complicated by the development of a bronchopleural fistula and air leak. We studied these children to see if there was an associated cause. METHODS: This was a retrospective case note and database review of children admitted to our tertiary unit with a parapneumonic effusion or empyema from 2002 to 2007, compared with 2008 to 2009. For the latter period, we also compared the outcomes of those with a bronchopleural fistula to those without. RESULTS: During the 8-year period, 310 children were admitted. In the first 6 years, the frequency of air leaks was 1% (2/258) rising to 33% (16/49) in the last 2 years (P<0.0001). Three children were excluded as their fistulas were possibly iatrogenic. This was associated with a significant increase in median hospital stay (7 vs. 10 days, P<0.0001) and surgical intervention rate (2% vs. 14%, P=0.001). In the latter 2 years, S. pneumoniae serotype 3 was identified in 10/16 (91%) of those with a bronchopleural fistula compared to 1/33 (3%) of those without. CONCLUSIONS: The frequency of bronchopleural fistulas increased markedly in the 2 years 2008-2009. Although these cases were associated with pneumococcal serotype 3 infection, which was not covered by the heptavalent pneumococcal vaccine Prevenar® in use at that time, we do not know whether the increased incidence of fistulas was due to a change in serotype 3 prevalence.

Use of home oxygen for children in England and Wales.

BACKGROUND: With the introduction of a standardised ordering system in February 2006, the opportunity arose to collect data on children requiring home oxygen in England and Wales. The authors' aim was to determine the incidence and patterns of home oxygen prescribing. METHODS: A paediatric home oxygen clinical network and the Children's Home Oxygen Record Database were established. During a 3-year period (February 2006 to January 2009), prescribers were requested to submit copies of the Home Oxygen Order Forms. In addition, anonymised point prevalence data on all patients currently receiving home oxygen in June 2007 were obtained from the four provider companies. RESULTS: Children's Home Oxygen Record Database--Forms were analysed for 888 children <16 years (58% boys) with a median age of 4.1 months; 656 (74%) were <1 year. 541 (68%) had a diagnosis of chronic neonatal lung disease; 53 (7%), neurodisability; and 49 (6%), cardiac disease. Order forms were often incomplete, and prescribing practice was variable. Provider's cross-sectional survey--There were 3338 children <16 years, representing 4% of all patients on home oxygen. Median age was 3.1 years with a peak at 6 months. The prevalence for paediatric home oxygen use in England and Wales was 0.33 per 1000, with a peak of 1.08 per 1000 for those <1 year. Marked regional variation was noted. CONCLUSIONS: This is the first national dataset available for children prescribed home oxygen in England and Wales. The study emphasises the need for a coordinated approach to home oxygen prescribing and justifies the recent publication of evidence-based guidelines.

Growth in children with cystic fibrosis-related diabetes.

Cystic fibrosis-related diabetes (CFRD) is associated with a shortened life expectancy and greater deterioration in lung function than in CF patients with normal glucose metabolism. There are few published data on how CFRD affects growth in childhood. We carried out a retrospective case controlled study of growth and lung function in 34 children with CFRD attending three specialist centers in London. We found that for the 2 years leading to CFRD diagnosis (at a mean age of 13.1 years), the mean height velocity was significantly less compared to controls: 4.9 (standard deviation-SD 1.6) cm/year vs. 6.0 (SD 1.9) cm/year (P = 0.005). For the 2 years following diagnosis, height velocity remained significantly lower (3.4 (SD 2.2) cm/year vs. 4.4 (SD 2.2) cm/year, P = 0.02). Mean FEV(1) was reduced prior to diagnosis and at diagnosis, but was similar to controls 2 years after diagnosis. This study highlights the compromise in height velocity and lung function that occurs prior to diagnosis of CFRD in children with CF, and a reduction in height velocity should be considered an indicator of impaired glucose metabolism. It would be useful to know whether early treatment with insulin can help promote catch up growth.