Paediatric Respiratory Reviews 15 (2014) 1–2
Contents lists available at ScienceDirect
Paediatric Respiratory Reviews
Editorial
Cystic Fibrosis: Passion, perception and education
Cystic fibrosis [CF] remains one of the most challenging, lifelimiting conditions that we manage as respiratory paediatricians. Pleasing gains have been made over the 75 years since Dorothy Anderson’s description of ‘‘Cystic fibrosis of the pancreas’’ in 1938 [1]. The average survival has improved from several years to currently 38 years during this time, and is expected to move towards the age of 50 years with children born today with CF[2]. The improvement in survival is clearly multifactorial and complex, reflecting advances in antibiotic therapy, nutritional strategies, airway clearance techniques, newborn screening, lung imaging, genetics, the understanding of cystic fibrosis transmembrane receptor [CFTR] structure and function and medications that can augment CFTR function [3–5]. As such, the progress that has been made reflects favourably upon the scientific rigour and its application in the clinical setting. Testament to the integration of basic science and clinical endeavours has been the evolution of large European and North American CF Foundations with annual conferences that showcase the best of contemporary research. Both have their distinct flavours to an onlooker from the antipodes, the European more clinically orientated and the North American more aligned to basic science. The North American meeting has a pervasive sense of enthusiasm, a touch of ‘‘razzle dazzle’’, perhaps akin to an American electoral convention without the balloons and banners. In contrast, the European meeting is a little more demure in its mood, belying their muted fashion flamboyance with coloured suit jackets! Nonetheless, there is a unifying determination to improve the care of people living with CF that pervades these meetings. There is understandably a degree of overlap in the content of the meetings, which in the last year have focussed on the role of CFTR correctors and potentiators [6]. Notwithstanding the expense of the drug, the dramatic successes of Ivacaftor [KalydecoTM] in children [7] with the G551D mutation were passionately embraced whilst cautionary encouragement was proposed for Lumacaftor/VX 809, VX 661, and PTC124. There is evidence in Fischer rat thyroid cells that Ivacaftor may potentiate the function of multiple CFTR channels with gating mutations [8]. Nonetheless, for the majority of CF patients, homozygous or heterozygous with the class II mutation delta F 508 [p.Phe508del], the most important short-term research consideration is the role of medication combinations [eg ivacaftor with lumacaftor] to increase trafficking of CFTR to the apical membrane and simultaneously increase CFTR activity which thus far has lead to more modest improvements in FEV1 in the region of 5% -10% [9]. Consequently, there are no ‘‘magic bullets’’ for the overwhelming majority [95%] of people living with CF at this point in time. Much promise, but early days as yet!
1526-0542/$ – see front matter ß 2014 Published by Elsevier Ltd. http://dx.doi.org/10.1016/j.prrv.2013.11.010
So when the cheering dies down, what are we left with to discuss with CF families in the outpatient setting? Gene therapy is still on the wish list and from the patients’ perspective has progressed little in twenty years. We are left with basic practice principles. That is doing the basics better. Part of this requires the clinician to understand the nuances of CF, be amenable to new ideas but not purely because they are new. A considered view of new therapies, prompted by valid scientific rationale and clinical pragmatism, will enable the enquiring mind to escape the myths, mistakes and dogma of CF care, as espoused by Rubin in this issue of Paediatric Respiratory Reviews [10]. Therefore, when things are not going well with our patients, we can challenge ourselves to rethink treatment options or, more importantly, to openly discuss treatment adherence. What we prescribe and what our patients take could at times best represented by minimally overlapping shapes in a Venn diagram! The approach to a medical consultation has evolved like much in medicine over time, but the fundamentals remain the same- it is how we as clinicians optimally engage with our patients that remain unchanged. Optimising the consultation process was reviewed in detail by Brand et al. in a recent minisymposium on consultation skills entitled: ‘‘Using communication skills to improve adherence in children with chronic disease: The adherence equation’’ [11]. A sound clinician is optimistic but grounded in the reality of the situation before them in the consulting room. For CF, family dynamics are arguably as important as genotype. The ability to relate meaningfully to a family will involve an understanding of their health expectations, social supports and financial resources. The availability of educational resources has blossomed in recent years. There are two major online resources which offer excellent information on disease causing CFTR mutations for families which are from the Hospital for Sick Children in Toronto [www.genet.sickkids.on.ca/cftr/Home.html] and from the Johns Hopkins Hospital in Baltimore CFTR2 database [www. cftr2.org]. Additionally, the CF Foundation has educational pamphlets and fact sheets as resources for families [www.cff.org] whilst the European Cystic Fibrosis Society has resources for health care professionals though its website [www.ecfs.eu]. National CF societies will have additional resources available on line which will cater for the nuances of local treatment preferences which may pertain to the availability of drugs and therapeutic devices. Further, topical review articles on a diverse range of issues in CF are regularly published in Paediatric Respiratory Reviews and these have recently included articles on physiotherapy [12], CT scanning in staging lung disease [13], end stage lung disease [14], liver disease [15], carrier screening [16], vitamin D as an anti-microbial
2
Editorial / Paediatric Respiratory Reviews 15 (2014) 1–2
and anti-inflammatory therapy [17] and a summary of the Cochrane Review on growth hormone therapy in CF [18]. The provision of current educational resources for the families and carers of children with CF that we care for must also be a priority for clinicians. This has not been done well in the past with people relying on adapted older heavy tomes which are less appealing to the modern parent in the age of on-line resources at the click of a mouse or the tap of a finger on the mobile phone! Recently, we have published a guide for parents, families, general practitioners, early childhood clinic nurses, childcare workers, preschool teachers and school teachers of young children with CF entitled ‘‘The Cystic Fibrosis Passport’’ [Clareville Press, 2013] which is available in paperback [booktopia.com;] and as an ebook which can be downloaded onto ipads, kindles and mobile phones [i-tunes.apple.com;amazon.com]. As clinicians we are naturally always striving to do our best for our patients but similarly, as educators, we have to continue to engage our families through optimising our consultation strategies, sharing and explaining the context of promising new therapies in CF, remaining wary of dogma and embracing new educational strategies for the families of children that we care for.
[7] Davies JC, Wainwright CE, Canny GJ, Chilvers MA, Howenstine MS, Munck A, et al. Efficacy and safety of ivacaftor in patients aged 6 to 11 years with cystic fibrosis with a G551D mutation. Am J Respir Crit Care Med 2013;187:1219–25. [8] Yu H, Burton B, Huang C-J, et al. Ivacaftor potentiation of multiple CFTR channels with gating mutations. J Cyst Fibrosis 2012;11:237–45. [9] Galietta LJ. Managing the underlying cause of cystic fibrosis: a future role for potentiators and correctors. Paediatr Drugs 2013;15:393–402. [10] Rubin B. Cystic Fibrosis: Myths, mistakes and dogma. Paediatr Respir Rev 2014; 15:113–6. [11] Brand PLP, Klok T, Kaptein AA. Using communication skills to improve adherence in children with chronic disease: The adherence equation. Paediatr Respir Rev 2013;14:219–23. [12] Rand S, Hill L, Prasad SA. Physiotherapy in cystic fibrosis: optimising techniques to improve outcomes. Paediatr Respir Rev 2013;14:263–9. [13] Tiddens HAWM, Stick SS, Davis S. Multi-modality monitoring of cystic fibrosis lung disease: The role of chest computed tomography. Paediatr Respir Rev 2014;15:92–7. [14] Ringholz F, Devins M, McNally P. Managing end stage lung disease in children. Paediatr Respir Rev 2014;15:75–81. [15] Leeuwen L, Fitzgerald DA, Gaskin KG. Liver disease in cystic fibrosis. Paediatr Respir Rev 2014;15:69–74. [16] Massie J, Delatycki MB. Cystic fibrosis carrier screening. Paediatr Respir Rev 2013;14:270–5. [17] Herscovitch K, Dauletbaev N, Lands LC. Vitamin D as an anti-microbial and anti-inflammatory therapy for cystic fibrosis. Paediatr Respir Rev 2014. http:// dx.doi.org/10.1016/j.prrv.2013.11.002. in press. [18] Thaker V, Carter B. Recombinant growth hormone therapy for cystic fibrosis in children and young adults. Paediatr Respir Rev 2014;14:232–3.
References [1] Andersen DH. Cystic fibrosis of the pancreas and its relation to celiac disease. A clinical and pathologic study. Am J Dis Child 1938;56:344–99. [2] Edwards J, Clarke A, Greenop D. Adults with cystic fibrosis - responding to a new ageing population. Chronic Illn 2013;9:312–9. [3] Dijk FN, McKay K, Barzi F, Gaskin KJ, Fitzgerald DA. Improved survival in cystic fibrosis patients diagnosed by newborn screening compared to a historical cohort from the same centre. Arch Dis Child 2011;96:1118–23. [4] Bhatt JM. Treatment of pulmonary exacerbations in cystic fibrosis. Eur Respir Rev 2013;22:205–16. [5] Yen EH, Quinton H, Borowitz D. Better nutritional status in early childhood is associated with improved clinical outcomes and survival in patients with cystic fibrosis. J Pediatr 2013;162. 530–535.e1. [6] Van Goor F, Hadida S, Grootenhuis PD, Burton B, Stack JH, Straley KS, Decker CJ, Miller M, McCartney J, Olson ER, Wine JJ, Frizzell RA, Ashlock M, Negulescu PA. Correction of the F508del-CFTR protein processing defect in vitro by the investigational drug VX-809. Proc Natl Acad Sci U S A 2011 Nov 15;108(46):18843–8.
Dominic A. Fitzgerald* Department of Respiratory Medicine, The Children’s Hospital at Westmead, Sydney, Locked Bag 4001, Westmead, 2145, Sydney, NSW, Australia *Discipline of Paediatrics and Child Health, Sydney Medical School, University of Sydney, Australia. Tel.: +61 2 9845 3397; fax: +61 2 9845 3396 E-mail address: Dominic.fi[email protected]
Contents lists available at ScienceDirect
Paediatric Respiratory Reviews
Editorial
Cystic Fibrosis: Passion, perception and education
Cystic fibrosis [CF] remains one of the most challenging, lifelimiting conditions that we manage as respiratory paediatricians. Pleasing gains have been made over the 75 years since Dorothy Anderson’s description of ‘‘Cystic fibrosis of the pancreas’’ in 1938 [1]. The average survival has improved from several years to currently 38 years during this time, and is expected to move towards the age of 50 years with children born today with CF[2]. The improvement in survival is clearly multifactorial and complex, reflecting advances in antibiotic therapy, nutritional strategies, airway clearance techniques, newborn screening, lung imaging, genetics, the understanding of cystic fibrosis transmembrane receptor [CFTR] structure and function and medications that can augment CFTR function [3–5]. As such, the progress that has been made reflects favourably upon the scientific rigour and its application in the clinical setting. Testament to the integration of basic science and clinical endeavours has been the evolution of large European and North American CF Foundations with annual conferences that showcase the best of contemporary research. Both have their distinct flavours to an onlooker from the antipodes, the European more clinically orientated and the North American more aligned to basic science. The North American meeting has a pervasive sense of enthusiasm, a touch of ‘‘razzle dazzle’’, perhaps akin to an American electoral convention without the balloons and banners. In contrast, the European meeting is a little more demure in its mood, belying their muted fashion flamboyance with coloured suit jackets! Nonetheless, there is a unifying determination to improve the care of people living with CF that pervades these meetings. There is understandably a degree of overlap in the content of the meetings, which in the last year have focussed on the role of CFTR correctors and potentiators [6]. Notwithstanding the expense of the drug, the dramatic successes of Ivacaftor [KalydecoTM] in children [7] with the G551D mutation were passionately embraced whilst cautionary encouragement was proposed for Lumacaftor/VX 809, VX 661, and PTC124. There is evidence in Fischer rat thyroid cells that Ivacaftor may potentiate the function of multiple CFTR channels with gating mutations [8]. Nonetheless, for the majority of CF patients, homozygous or heterozygous with the class II mutation delta F 508 [p.Phe508del], the most important short-term research consideration is the role of medication combinations [eg ivacaftor with lumacaftor] to increase trafficking of CFTR to the apical membrane and simultaneously increase CFTR activity which thus far has lead to more modest improvements in FEV1 in the region of 5% -10% [9]. Consequently, there are no ‘‘magic bullets’’ for the overwhelming majority [95%] of people living with CF at this point in time. Much promise, but early days as yet!
1526-0542/$ – see front matter ß 2014 Published by Elsevier Ltd. http://dx.doi.org/10.1016/j.prrv.2013.11.010
So when the cheering dies down, what are we left with to discuss with CF families in the outpatient setting? Gene therapy is still on the wish list and from the patients’ perspective has progressed little in twenty years. We are left with basic practice principles. That is doing the basics better. Part of this requires the clinician to understand the nuances of CF, be amenable to new ideas but not purely because they are new. A considered view of new therapies, prompted by valid scientific rationale and clinical pragmatism, will enable the enquiring mind to escape the myths, mistakes and dogma of CF care, as espoused by Rubin in this issue of Paediatric Respiratory Reviews [10]. Therefore, when things are not going well with our patients, we can challenge ourselves to rethink treatment options or, more importantly, to openly discuss treatment adherence. What we prescribe and what our patients take could at times best represented by minimally overlapping shapes in a Venn diagram! The approach to a medical consultation has evolved like much in medicine over time, but the fundamentals remain the same- it is how we as clinicians optimally engage with our patients that remain unchanged. Optimising the consultation process was reviewed in detail by Brand et al. in a recent minisymposium on consultation skills entitled: ‘‘Using communication skills to improve adherence in children with chronic disease: The adherence equation’’ [11]. A sound clinician is optimistic but grounded in the reality of the situation before them in the consulting room. For CF, family dynamics are arguably as important as genotype. The ability to relate meaningfully to a family will involve an understanding of their health expectations, social supports and financial resources. The availability of educational resources has blossomed in recent years. There are two major online resources which offer excellent information on disease causing CFTR mutations for families which are from the Hospital for Sick Children in Toronto [www.genet.sickkids.on.ca/cftr/Home.html] and from the Johns Hopkins Hospital in Baltimore CFTR2 database [www. cftr2.org]. Additionally, the CF Foundation has educational pamphlets and fact sheets as resources for families [www.cff.org] whilst the European Cystic Fibrosis Society has resources for health care professionals though its website [www.ecfs.eu]. National CF societies will have additional resources available on line which will cater for the nuances of local treatment preferences which may pertain to the availability of drugs and therapeutic devices. Further, topical review articles on a diverse range of issues in CF are regularly published in Paediatric Respiratory Reviews and these have recently included articles on physiotherapy [12], CT scanning in staging lung disease [13], end stage lung disease [14], liver disease [15], carrier screening [16], vitamin D as an anti-microbial
2
Editorial / Paediatric Respiratory Reviews 15 (2014) 1–2
and anti-inflammatory therapy [17] and a summary of the Cochrane Review on growth hormone therapy in CF [18]. The provision of current educational resources for the families and carers of children with CF that we care for must also be a priority for clinicians. This has not been done well in the past with people relying on adapted older heavy tomes which are less appealing to the modern parent in the age of on-line resources at the click of a mouse or the tap of a finger on the mobile phone! Recently, we have published a guide for parents, families, general practitioners, early childhood clinic nurses, childcare workers, preschool teachers and school teachers of young children with CF entitled ‘‘The Cystic Fibrosis Passport’’ [Clareville Press, 2013] which is available in paperback [booktopia.com;] and as an ebook which can be downloaded onto ipads, kindles and mobile phones [i-tunes.apple.com;amazon.com]. As clinicians we are naturally always striving to do our best for our patients but similarly, as educators, we have to continue to engage our families through optimising our consultation strategies, sharing and explaining the context of promising new therapies in CF, remaining wary of dogma and embracing new educational strategies for the families of children that we care for.
[7] Davies JC, Wainwright CE, Canny GJ, Chilvers MA, Howenstine MS, Munck A, et al. Efficacy and safety of ivacaftor in patients aged 6 to 11 years with cystic fibrosis with a G551D mutation. Am J Respir Crit Care Med 2013;187:1219–25. [8] Yu H, Burton B, Huang C-J, et al. Ivacaftor potentiation of multiple CFTR channels with gating mutations. J Cyst Fibrosis 2012;11:237–45. [9] Galietta LJ. Managing the underlying cause of cystic fibrosis: a future role for potentiators and correctors. Paediatr Drugs 2013;15:393–402. [10] Rubin B. Cystic Fibrosis: Myths, mistakes and dogma. Paediatr Respir Rev 2014; 15:113–6. [11] Brand PLP, Klok T, Kaptein AA. Using communication skills to improve adherence in children with chronic disease: The adherence equation. Paediatr Respir Rev 2013;14:219–23. [12] Rand S, Hill L, Prasad SA. Physiotherapy in cystic fibrosis: optimising techniques to improve outcomes. Paediatr Respir Rev 2013;14:263–9. [13] Tiddens HAWM, Stick SS, Davis S. Multi-modality monitoring of cystic fibrosis lung disease: The role of chest computed tomography. Paediatr Respir Rev 2014;15:92–7. [14] Ringholz F, Devins M, McNally P. Managing end stage lung disease in children. Paediatr Respir Rev 2014;15:75–81. [15] Leeuwen L, Fitzgerald DA, Gaskin KG. Liver disease in cystic fibrosis. Paediatr Respir Rev 2014;15:69–74. [16] Massie J, Delatycki MB. Cystic fibrosis carrier screening. Paediatr Respir Rev 2013;14:270–5. [17] Herscovitch K, Dauletbaev N, Lands LC. Vitamin D as an anti-microbial and anti-inflammatory therapy for cystic fibrosis. Paediatr Respir Rev 2014. http:// dx.doi.org/10.1016/j.prrv.2013.11.002. in press. [18] Thaker V, Carter B. Recombinant growth hormone therapy for cystic fibrosis in children and young adults. Paediatr Respir Rev 2014;14:232–3.
References [1] Andersen DH. Cystic fibrosis of the pancreas and its relation to celiac disease. A clinical and pathologic study. Am J Dis Child 1938;56:344–99. [2] Edwards J, Clarke A, Greenop D. Adults with cystic fibrosis - responding to a new ageing population. Chronic Illn 2013;9:312–9. [3] Dijk FN, McKay K, Barzi F, Gaskin KJ, Fitzgerald DA. Improved survival in cystic fibrosis patients diagnosed by newborn screening compared to a historical cohort from the same centre. Arch Dis Child 2011;96:1118–23. [4] Bhatt JM. Treatment of pulmonary exacerbations in cystic fibrosis. Eur Respir Rev 2013;22:205–16. [5] Yen EH, Quinton H, Borowitz D. Better nutritional status in early childhood is associated with improved clinical outcomes and survival in patients with cystic fibrosis. J Pediatr 2013;162. 530–535.e1. [6] Van Goor F, Hadida S, Grootenhuis PD, Burton B, Stack JH, Straley KS, Decker CJ, Miller M, McCartney J, Olson ER, Wine JJ, Frizzell RA, Ashlock M, Negulescu PA. Correction of the F508del-CFTR protein processing defect in vitro by the investigational drug VX-809. Proc Natl Acad Sci U S A 2011 Nov 15;108(46):18843–8.
Dominic A. Fitzgerald* Department of Respiratory Medicine, The Children’s Hospital at Westmead, Sydney, Locked Bag 4001, Westmead, 2145, Sydney, NSW, Australia *Discipline of Paediatrics and Child Health, Sydney Medical School, University of Sydney, Australia. Tel.: +61 2 9845 3397; fax: +61 2 9845 3396 E-mail address: Dominic.fi[email protected]
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