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This retrospective study calculated the cumulative radiation dose for children with ... from chest and abdominal radiographs was estimated from typical dose area product (D.A.P.) measurements in our department for 6 age groups (0-2, 2-3, 3-5, ...
Cumulative Radiation Exposure in Children with Cystic Fibrosis R OReilly, S Ryan, V Donoghue, C Saidlear, E Twomey, DM Slattery Children’s University Hospital, Temple St, Dublin 1 Abstract This retrospective study calculated the cumulative radiation dose for children with cystic fibrosis (CF) attending a tertiary CF centre. Information on 77 children with a mean age of 9.5 years, a follow up time of 658 person years and 1757 studies including 1485 chest radiographs, 215 abdominal radiographs and 57 computed tomography (CT) scans, of which 51 were thoracic CT scans, were analysed. The average cumulative radiation dose was 6.2 (0.04-25) mSv per CF patient. Cumulative radiation dose increased with increasing age and number of CT scans and was greater in children who presented with meconium ileus. No correlation was identified between cumulative radiation dose and either lung function or patient microbiology cultures. Radiation carries a risk of malignancy and children are particularly susceptible. Every effort must be made to avoid unnecessary radiation exposure in these patients whose life expectancy is increasing. Introduction Cystic fibrosis (CF) is the most common autosomal recessive disease in Western Europe with a 1 prevalence of 1 in 1,461 births in the Irish population . It is a multisystem disorder affecting primarily the respiratory and gastrointestinal tracts, caused by mutations in the cystic fibrosis transmembrane conductance regulator protein (CFTR) gene. Aggressive clinical management including proactive treatment of respiratory infections, nutritional supplementation, chest physiotherapy and newer medication regimens have significantly improved life expectancy. The predicted median survival for babies born2 in the United Kingdom in the 21st century is now more than 50 years . Death is primarily due to respiratory failure. Imaging studies that use ionising radiation are a useful and necessary tool for evaluating and monitoring disease progression and response to treatment in CF. CT scans in particular are associated with high radiation dose. Children are ten times more sensitive to radiation 3 induced cancer than adults with girls twice as radiosensitive as boys . Children have a longer lifetime over which to develop cancer and developing organs such as4 the thyroid, bone marrow, breast, brain and skin are especially vulnerable . As life expectancy of children with CF increases so do concerns regarding repeated radiation exposure and cancer risk. Increasing concern has been expressed in the literature about the referring doctor’s 5 inadequate knowledge of radiation doses incurred during radiological procedures . A recent study of doctors in Northern Ireland demonstrated that only 20% of those surveyed knew the 6 effective radiation dose of a chest radiograph . The aim of this retrospective study was threefold: firstly to determine the cumulative radiation dose associated with imaging in a paediatric population with CF; secondly to identify risk factors that may contribute to this cumulative radiation dose, in particular age, gender, presentation with meconium ileus, lung function, patient microbiology cultures and type of radiological studies performed; and thirdly to propose ways of reducing the cumulative radiation dose. Methods Medical and radiological records of children attending our CF centre were reviewed. Children who attend more than one institution for shared CF care were excluded. Information regarding age, initial clinical presentation, lung function tests, microbiological cultures was gathered for all patients. Lung function tests were performed on all CF patients 5 years. Reproducible data was collected. The forced expiratory volume in 1 second (FEV1) at the nearest well outpatient clinic within 3 months of data collection was recorded. The number and type of radiological studies performed on each patient was recorded. The effective radiation dose from chest and abdominal radiographs was estimated from typical dose area product (D.A.P.) measurements in our department for 6 age groups (0-2, 2-3, 3-5, 5-10, 10-15, 15-20 years) using a dosimetry calculator (Childdose patient dosimetry calculator) 8 and National Radiological Protection Board (UK) data files . Images from CT scans were reviewed and where sufficient data on exposure factors and technique were available to do so, an effective dose was calculated using the ImPACT patient dosimetry calculator studies where adequate details were not available, data from the literature was used to 10,11 estimate effective CT radiation dose . Dose estimation for contrast studies was derived 12 from the literature . An estimate of radiation dose was assigned to each study and a lifetime cumulative effective dose was calculated for each patient. JMP statistical package (Cary NC), Wilcoxon/ Kruskal Wallis, Chi squared and ANOVA tests were used in statistical analysis.

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Results Data was collected for 77 children, 27 girls and 50 boys, with a mean age of 9.5 (1-19.25) years and a follow up time of 658 person years. The average follow up time was 8.5 years. The 77 patients had an average of 19.3 chest radiographs each. Thirty one children had an average of 4.7 abdominal radiographs each; 26 children had an average of 1.1 barium meals each; 11 patients had an average of 2.1 enemas each and 29 patients had 1.7 C.T. scans each. The average cumulative radiation dose was 6.2 (0.04-25) mSv per C.F. patient. There was no significant difference in cumulative radiation dose between boys and girls (p=0.47). The cumulative radiation dose in each age group is shown in Table 1. Cumulative radiation dose increased with patient age (r =0.36, p=0.0014) (see Figure 1). Figure 1: Cumulative radiation dose versus age Fifteen percent (n=12), presented with meconium ileus in the newborn period. Cumulative radiation dose was greater in these patients (9mSv) compared with those who did not present with meconium ileus (n=65), (5.5mSv), (p=0.03, independent of age). Nine of these twelve neonates presenting with meconium ileus had 21 neonatal contrast enemas in total, (average 2.3 per patient), compared with only 2 contrast enemas in total in children without meconium ileus. When the radiation dose of these enemas was subtracted, there was no significant difference in cumulative radiation dose between children with and children without meconium ileus (p=0.46).

There was no significant correlation between lung function as measured by FEV1 and cumulative radiation dose. No association was identified between microbiology cultures (particularly Staphloccocus aureus and Pseudomonas aeruginosa) and cumulative radiation dose. Twenty nine patients had a total of 51 CT scans of the thorax with a maximum number of 4 scans per patient. Most of these studies were done as high resolution studies with 1mm slices at 1cm intervals. Radiation dose increased with number of CT studies per patient independent of the number of other x-ray or contrast examinations done (p=0.0004).

Discussion This retrospective study provides an estimate of the average cumulative radiation dose of the paediatric CF population currently attending our centre. To our knowledge this is the first study examining cumulative radiation exposure in the Irish CF population, either paediatric or adult, and provides valuable baseline information against which effects of changes in practice may be measured. As expected, we documented that cumulative radiation dose increases with age, up to 15 years. Interestingly those aged 15-20 years had a lower mean cumulative radiation dose than those aged 10-15 years. This may be explained by the fact that the care of all cystic fibrosis patients was transferred at our institution to a respiratory paediatrician 7 years ago and that practices between the former and current paediatrician are slightly different. Traditionally studies have reported that females with cystic fibrosis have poorer lung function and a worse prognosis than males. Based on this, one might expect to have identified an increased cumulative radiation dose in females. We identified no gender difference in our study. Interestingly, the previously pronounced gender gap in CF (male survival longer than female) was also not documented in the recent 13 Canadian CF Foundation patient Data Registry Report . At our institution children presenting with meconium ileus (n=12; 15%) had a higher radiation dose than those who did not present this way. This risk is independent of age. Data analysis reveals that the greater radiation dose in these children is due to the use of contrast enemas in the newborn period in 9 of these patients for the non-operative management of meconium ileus which was successful in 7 of the 9 (77%). A recent study of the non-operative management of meconium ileus in our city, revealed that our institution demonstrated a success rate of 79% compared with 49% in pooled data from 9 published 14 studies . We attribute this success rate to our willingness to perform multiple attempts at

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reduction in each patient (1.9 attempts per patient in that study, 2.3 in the current study versus 1.1 per patient in published data). In our paediatric CF population who were old enough to perform reproducible lung function testing (n= 62), no correlation was found between lung function and cumulative radiation dose. Traditionally disease progression in CF has been monitored by a combination of clinical assessment, chest radiographs and pulmonary function tests. Increase in Brasfield scores of chest radiographs in CF over time has correlated significantly with the decline in 15 FEV1 . The lack of correlation between lung function and cumulative radiation dose in our study may be explained by the fact that the majority of our children had normal lung function (n=44, 71%). An adult CF population with more advanced lung disease and more severe reduction in lung function tests may demonstrate an increased cumulative radiation dose. FEV1 is employed internationally as a marker for severity of respiratory involvement in CF and a predictor of death, though its limitations are well documented. Performance of lung function tests although routine in older children and adults with cystic fibrosis, is technically much more difficult in infants and preschool children. Lung function tests are an indirect measure of lung structure and are insensitive to localised or early damage in pulmonary function may be preceded by structural change detected on CT scan younger patient, in the absence of lung function tests, CT thorax, where clinically indicated, may be very useful in identifying disease progression.

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Analysis of patient microbiology cultures (n=77) in particular Staph aureus (n=44) and Pseudomonas aeruginosa (n=29) did not reveal any correlation with cumulative radiation dose. Four patients grew commensals only on cough swab culture and sensitivity. Chronic infection with P. aeruginosa which causes a more rapid decline in lung function than Staph aureus, is an important predictor of survival and is the most important cause of morbidity expect that people with CF who are chronically infected with P. aeruginosa as opposed to Staph aureus would have more reduced lung function and an associated higher cumulative radiation dose. Our study did not demonstrate a correlation between microbiology cultures and cumulative radiation dose. This may be explained by our relatively small number of patients infected with P. aeruginosa and their overall associated good lung function. We documented that cumulative radiation dose increases with the number of CTs performed. Previously a UK study demonstrated that while the number of CT scans represented only 4% of radiological procedures in the 19 UK, CT contributed to 40% of the population radiation dose from medical exposures . CT is also the largest contributor to cumulative radiation dose in our study. The radiation dose per CT in CF children can vary widely depending on the technique used. While one study estimated the mean radiation dose per CT to be 6.5mSv (range 1.5-29.3) others estimate it to be much less than 1mSv for limited CT scans in CF children of radiation doses from CT in adults demonstrated that that mean doses per scan were in 21 general 50% lower in 2003 than 1991 . This suggests that cumulative radiation doses for children born more recently will be significantly lower than those born 1 decade ago, assuming there is not a large increase in the number of CTs performed. Some techniques that can be used to reduce the radiation dose in thoracic CT in children and the effect of these on radiation dose are summarised in Table 2.

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Controversy exists regarding cancer risk of diagnostic imaging studies. While De Jong estimated the radiation induced cancer mortality 20 from annual CT to be approximately 2% at age 40 years and 13% at age 65 years , others estimate a smaller cancer risk of 0.02-0.5% in 25 CF patients with annual CT thorax, assuming median survival to 36 years . These estimated risks are likely flawed because they are calculated from effects of radiation exposure on survivors of the Japanese atomic bombs. An observational study would require follow up of hundreds of thousands of people for their entire lifetime to have sufficient power to detect cancer risk. No data exists regarding the radiation risk with relatively small doses associated with medical imaging. Although ionising radiation dose per CT study has reduced significantly over the past 20 years, this may be partially counterbalanced by both the 21 increased use of CT in CF and the increased median survival of this population . Cumulative radiation exposure in our paediatric CF population compares favourably with that in other institutions worldwide where routine CT thorax is performed. Cumulative radiation dose increases with age, number of CT scans, and at our institution, a history of meconium ileus. In our group, no association was identified between cumulative radiation dose and either microbiology cultures or lung function as measured by FEV1. We recommend that physicians and radiologists work together discussing each individual case, aiming for a scan that maximises disease identification while minimising radiation exposure, as is done in our institution. Newer scanners, breast shields, reduction of tube kilovoltage and current all reduce radiation dose in a susceptible population based on young age and life long radiation exposure. Correspondence: R O’ Reilly c/o Dr Dubhfeasa Slattery, Children’s University Hospital, Temple St, Dublin 1 Email: [email protected] References 1. Devaney J, Glennon M, Rutledge M . Cystic Fibrosis mutation frequencies in an Irish population. Clin Genet 2003; 63:121-125 2. Dodge JA, Lewis PA, Stanton M, Wilsher J. Cystic fibrosis mortality and survival in the U.K.:1947-2003. Eur Respir J 2007;29:522-526 3. Brenner DJ. Estimating cancer risks from pediatric CT: going to the qualitative to the quantitive. Pediatr Radiol 2002;32:228-3 4. Kleinerman R. Cancer risks following diagnostic and therapeutic radiation exposure in children. Pediatr Radiol 2006;36:121-125 5. Lee CI, Haims AH, Monico EP. Diagnostic CT Scans: Assessment of patient, physician and radiologist awareness of radiation dose and possible risks. Radiology 2004; 231:393-398 6. Soye JA, Paterson A. A survey of awareness of radiation dose among health professionals in Northern Ireland. Br J Radiol, 2008; 81(969):725-9 7. Le Heron JC. CHILDOSE Ministry of Health, National Radiation Laboratory, Christchurch, New Zealand, 1998. 8. Hart D. National Radiological Protection Board (UK) data files reference. Coefficients for Estimating Effective Dose from Paediatric X-Ray Examinations, NRPB-R279 ~National Radiological Protection Board, Oxon, 1996. 9. ImPACT Dose calculator (version 0.99x, 2006) (http://www.impactscan.org/ctdosimetry.htm). 10. Brody AS. Radiation risk to Children from Computed Tomography. Pediatrics 2007;120:677-6828 11. Donadieu J. Estimation of the radiation dose from thoracic CT scans in a CF population Chest 2007;132:1233-1238 12. Hiorns MP, Saini A, Marsden PJ. A review of current local dosearea product levels for paediatric fluoroscopy in a tertiary referral centre compared with national standards. Why are they so different? BJR 2006; 79:326330 13. Canadian Cystic Fibrosis Foundation. Report of the canadian Patient Data Registry 2002. Toronto, Ontario, 2002. 14. Khan NA, Rea DJ, Hayes R, Puri P, Donoghue V, Ryan S. Non-operative Management of Uncomplicated Meconium Ileus With Gastrograffin Enema: Factors That Contribute to Success. Presented at Eur Soc Ped Radiology Annual Meeting, 2005. 15. Cleveland RH. Cystic fibrosis: a system for assessing and predicting progression. AJR Am J Roentgen 1998; 170:1067-72 16. De Jong PA. Progressive damage on high resolution computerised tomography despite stable lung function in cystic fibrosis. De Jong. Eur Respr J 2004;23:93-97 17. Tiddens HAWM. Detecting early structural damage in cystic fibrosis. Pediatr Pulmonology 2002;34:228-231 18. Lyczak JB, Cannon CL, Peir GM. Lung infections associated with cystic fibrosis. Clin Microbiol Rev 2002;15:194-222. 19. hrimpton PC, Edyvean S. CT Scanner Dosimetry. Br J Radiol1998;71:1-3 20. De Jong PA, Mayo JR. Estimation of cancer mortality with repeditive computed tomography scanning. AMJCCM 2006;173:199-203 21. Shrimpton PC, Hillier MC, Lewis MA. National Survey of doses from CT in the UK:2003. Br J Radiol. 2006, 79(748):968-80 22. Mc Cullough CH, Bruesewitz RT, kofler JM. CT dose reduction and dose management tools: Overview of available options. Radiographics 2006; 26:503-512. 23. Fricke BL, Donnelly LF, Frush DP et al. In-plane bismuth breast shields for pediatric CT: effects on radiation dose and image quality using experimental and clinical data. Am J Roentgenol 2003; 180:407-11 24. Garcia-Peˆ–a P, Lucaya J. HRCT in children: technique and indications. Eur Radiol 2004; 14 Suppl 4:L13-30 25. Berrington de Gonzˆ¡lez A, Kwang PK, Samet SM. Barrington de Gonzales. Radiation induced cancer risk from annual computed tomography for patients with Cystic fibrosis. Am J Respir Crit Care Med 2007; 176:970-973

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