Treating Cystic Fibrosis in Resource Poor Environment

Transcription

1 Treating Cystic Fibrosis in Resource Poor Environment SK Kabra, M Kabra, R Lodha, S Shastri Department of Pediatrics All India Institute of Medical Sciences New Delhi India Corresponding author: S K Kabra, skkabra@rediffmail.com Abstract Cystic fibrosis (CF) is now recognized as a pan-ethnic disease. Problems in management in resource poor setting includes: lack of awareness among clinicians, non-availability of sweat testing facility, non-availability of medications and shortage of trained health care personnel for management and poor networking among centers providing services for CF patients. We are trying to create awareness among pediatricians by using a case scenario based interactive module on CF. Sweat test can be performed by an inexpensive indigenous method. In case of non-availability of sweat test facility an algorithm based on supportive laboratory tests can be used in the management of children suspected to have CF. For shortage of trained manpower, collaboration with CF units in developed countries may be used for transfer of knowledge and skills. To begin with, a nurse can be trained as multipurpose worker to perform duties of nurse, dietician and physiotherapist. Locally available inexpensive medications, diet and antibiotics may be used with little financial inputs. A regular follow up of children with cystic fibrosis and education of their parents may be a low cost intervention. Formation of cystic fibrosis welfare associations can provide help in different aspects of care and support. Key words: Cystic fibrosis, resource poor setting, developing countries, sweat testing Cystic fibrosis (CF) is the commonest inherited life limiting disease in Caucasian population. Over last six decades, significant improvement has occurred in understanding of CF. Now with improved understanding and management of CF, the survival has improved to median of more than three decades from a potentially lethal condition earlier. The improvement in survival and quality of life has occurred with a network of centers that are committed to high-quality, evidence-based care. The basic pillars of care include nutritional repletion, antibiotics, aggressive treatment of airway obstruction by physiotherapy, suppression of inflammation and regular follow up (1). Cystic fibrosis is a complex disease requiring a holistic approach to treatment (2). Center care by a team of trained and experienced health professionals is essential for optimal patient management and outcome (3). Such care involves frequent clinical evaluations and monitoring for complications, by physicians and other healthcare workers specifically trained in the management of CF and early treatment interventions. Standards of care define the optimal service provision necessary to deliver the best outcomes possible for patients. Several guidelines have been written to assist CF 1

2 caregivers in the evaluation and monitoring of patients, detection of complications and prevention of clinical deterioration (4 8). Intensive treatments, both prophylactic and as a response to acute events, decrease morbidity and increase survival and quality of life. Over last two decades, several reports have been published from different part of world with CF. These reports suggest that CF is not restricted to Caucasian population; it is a pan ethic disease. Though with information technology, all details of care of children with CF are available all over world; it may not possible to start a CF service based on the recommendations of various consensus statements because of several problems. The problems include: lack of awareness among clinicians, non availability of sweat testing facility, poor/non-availability of drugs, shortage of trained health care personnel for management and poor networking among centers providing services for CF patients. CF is now recognized as one of the emerging illnesses in the Indian subcontinent (9). We will now discuss the problems faced in management of CF in India. Problems in early diagnosis of cystic fibrosis Lack of awareness among clinicians Because of strong belief that CF is a disease of whites that does not affect non Caucasians, diagnostic facilities for CF have not been developed in countries in Indian sub continent. As most pediatricians may not have seen even a single case of CF during their training, they are not aware about the clinical features of CF. To overcome this problem in India a group of pediatricians specializing in respiratory diseases have developed a module to create awareness among general pediatricians by a case scenario based interactive discussion. The module will be used to create awareness among pediatricians by arranging workshops for three hours at different cities in India. Other method for creating awareness among pediatricians is to have lectures on CF in the pediatric conferences. Non availability of sweat test and mutation analysis Diagnostic facilities in form of sweat testing and mutation analysis may not be available in most of the resource poor setting. These facilities are not well-developed as CF is not considered as a problem and secondly, the cost of equipment and ongoing cost for each test may be very high and commercially non-viable for commercial laboratories. To overcome this problem we developed and validated a sweat chloride estimation method based on Gibson and Cooke method (10). In this method, sweat is collected by pilocarpine iantophoresis and sweat chloride is estimated by doing titration. The method is inexpensive and can be started in any medical care setup with help of trained person. The total cost of equipment is approximately US$ 10and each test cost s approximately US$0.5. To popularize this method we obtained a small grant of US$ 2500 from pharmaceutical company (Solvay). One technician was trained in the method by our team; he has then trained various pediatricians and technicians in different parts of the country. Pediatricians who were interested in starting sweat testing at their center are provided training and support (equipment and chemicals) in the beginning; they were encouraged to sustain thereafter from local resources. We could encourage five more centers to start sweat testing facilities over last 12 months. 2

3 The basic defect in CF is a mutation in the gene for chloride conductance channel that is cystic fibrosis transmembrane conductance regulator (CFTR). The CF gene, identified in 1989, is located on the long arm of chromosome number 7 at position q31.2. (11, 12). Nearly 1,550 mutations in the gene have been recognized (13). These mutations result in an abnormality of camp regulated chloride conductance by epithelial cells on mucosal surface. The failure of chloride conductance by epithelial cells leads to dehydration of secretions that are too viscid and difficult to clear (14). The prevalence of genetic mutations varies from one population to other. The commonest mutation is p. F508del, which constitutes about 70% of the total cases (15). There are few reports on genotype of CF in Indian subcontinent and suggest that genotypes are very heterogeneous (16) In view of the non-availability of sweat test facility at most centers in India and genetic mutation profile being heterogeneous and unlikely to become a widely available diagnostic test, we propose an algorithm for management of patients when sweat chloride estimation is not available (17). The algorithm includes: doing arterial blood gas, serum sodium, chloride, and potassium; stool examination for fat globules, and sputum/respiratory secretion culture for pseudomonas for documentation of hypochloremia, hyponatremia, hypokalemia, metabolic alkalosis, numerous fat globules on stool microscopy, and pseudomonas species in respiratory secretions. If more than two abnormalities are present, patient may be followed up as suspected CF and treated with enzymes, fat soluble vitamin, and physiotherapy. Diagnosis of CF may be confirmed in such patients after doing sweat testing or mutation testing (Fig. 1). Problems in management The problems faced in the management of CF in India include: lack of trained manpower, non-availability of drugs and poor understanding of specific problems. In addition, inadequate experience in the management of chronic conditions in children and social factors also add to the complex problems. Shortage of trained personnel Most pediatricians may not be aware about the clinical features of CF as they may not have seen, diagnosed and managed cases during their training. Similarly other personnel involved essential for the of CF patents such as dieticians, physiotherapist and nurses may not know the problems in the management of CF patients. There are not many reports from India or developing countries addressing the specific issue of problems in the management. We tried to solve the problem of lack of training by collaborating with CF services in Southampton (UK). There were exchange visits of CF team from Southampton (UK) CF clinic to Delhi and CF team from newly established CF services (All India Institute of Medical Sciences, New Delhi) to Southampton. Discussions took place between the members of two teams and a decision was taken to use locally available resources to start CF services in Delhi. One nurse was trained to perform duties of multipurpose CF worker including that of a nurse. The duties of nurse included sweat collection, education of parents about physiotherapy, recording dietary intake in addition to measure anthropometry, and helping in explaining prescriptions. The nurse also helped 3

4 in providing home intravenous antibiotic treatment whenever indicated. This module helped us in providing CF services with minimal input (18). The entire process of training and sustaining CF services for seven years was established in US $ granted by International Cystic Fibrosis (mucoviscidosis) Association (now called Cystic Fibrosis Worldwide). Now this center is providing training to health care professionals from other centers in India. They visit this center for few weeks and learn sweat testing and care of CF patients. The trainees either get financial support from their respective government or themselves meet the expenses. Management of children with CF has changed significantly. To provide good care to children with CF in India and other resource limited setting it may be advisable to develop partnership with CF units of western countries. A twinning program between Southampton (UK) and Moscow CF units provided a successful model for collaboration between two countries (19). Efforts are also made to support the pediatricians to take care of acute problems in children with cystic fibrosis who come from other cities/ states; so that the family does not have to travel long distances for seeking treatment for acute problems. Non availability of Medications for management of CF/ devices to assist airway clearance Medications used for management of CF patients may not be available in many parts of the country. Specifically, enzyme preparation that can be used in infants and young children were not available till 4 5 years ago. Inhaled antibiotics and mucolytics (Alfa dornase) are not available freely. Even if medications are available in market, they are beyond affordability of most of the parents. It is difficult to apply the model of care of CF patients being followed up in developed countries. If patients were finding it difficult to get hospitalized for intravenous antibiotics, they were encouraged to get IV antibiotics by local pediatricians and to come to nurse every alternate day for maintaining IV lines. To overcome the problems of non-availability of enzymes or inadequate doses of enzymes, parents were encouraged to give more food to children and give more food cooked in coconut oil (rich in medium chain triglycerides) and to supplement food with sweets prepared from coconut. To overcome problems of non-availability of DNAse, hypertonic saline and aggressive physiotherapy was used. Efforts also need to be made to decrease the prices of some of the essential medications such as enzyme preparations; duty exemptions by the government may be required for this. Similarly, the local pharmaceutical industry needs to be encouraged to make the medications available. Recently, tobramycin for nebulization has been produced and marketed by an Indian company. Similar efforts are required to make devices that assist airway clearance available. Or else, indigenous substitutes for the commercial devices like PEP mask, etc may be developed. Inadequate experience in the management of chronic conditions in children. There is a widely prevailing perception that chronic disorders do not occur in children. In many resource poor countries, the experience of health care providers, including the pediatricians is limited in providing care for chronic diseases. The capacity to handle CF, which necessitates a new paradigm of life-long therapy, introduces 4

5 complexities both at the health system and health care provider level. The same perception is also carried by the parents/ care givers; this may interfere with the adherence to management protocols. In addition, the concern about the adverse effects of medications ( too strong ) that are given long term to the child are likely to interfere with successful therapy. Often, the diagnosis of CF is not disclosed to the child; this again may interfere with the adherence. We have tried to address this issue by education of the care givers and parents. Parent education programs are organized regularly, where experts explain the disease pathophysiology in local language and also the rationale for various components of the management. The parents are encouraged to express their doubts and efforts are made to resolve these. At the clinic level, parents are encouraged to make regular follow up visits and this is reinforced by giving appointments for regular check ups, usually at 4-6 weeks interval. At these visits, the nurse interviews the parents/ child about the symptoms, records the medications and anthropometry. The child is then examined by a pediatrician and appropriate management is prescribed. Microbiologic samples are also collected. This helps in early identification of colonization with pseudomonas. Lack of social and financial support for families of children with cystic fibrosis As CF is a chronic illness and requires resources for appropriate management, there is need for having some support for the families. In many countries, the state takes care of some of these needs. Similar mechanisms should be considered in countries like India. Formation of the Cystic Fibrosis Welfare Association may be able to raise some of these issues and garner support for financially weak families to ensure adequate management of these children. Impact of CF services at All India Institute of Medical Sciences, New Delhi There are not many studies from India or other resource poor setting that report the outcome of CF patients. Initial reports of management of CF patient in India and their follow up are encouraging. In a report of 180 patients diagnosed over 7 years, 25 patients had died, 30 were lost to follow up, and remaining were in follow up. The oldest surviving patient was 34 years. 15% of the patients were above 15 years of age (18). Factors that were associated with decreased survival were: age of onset <2 months, severe malnutrition at the time of diagnosis, colonization with Pseudomonas at the time of diagnosis, and frequency of acute lower respiratory tract infections (ALRTI) >4 episodes/year (20). With early diagnosis, regular follow up and treatment; all of these factors except age of onset before 2 months of age can be modified. Conclusion It can be concluded that cystic fibrosis is now recognized as pan-ethnic disease. Apart from creating awareness about CF in doctors it is also necessary to develop diagnostic facilities and service centers for holistic management of CF patients. There is need to develop a feasible model for management of these patients based on locally available resources. 5

6 References 1. Davis PB. Cystic fibrosis since Am J Respir Crit Care Med 2006;173: Walters S. Doctor patient relationship in cystic fibrosis a patient s perspective. Holist Med 1990; 6: Mahadeva R, Webb K, Westerbeek RC, et al. Clinical outcome in relation to care in centres specializing in cystic fibrosis: cross sectional study. BMJ 1998; 316: Cystic Fibrosis Trust Clinical Standards and Accreditation Group. Standards for the clinical care of children and adults with cystic fibrosis in the UK. London 7 Cystic Fibrosis Trust; Schidlow DV, Taussig LM, Knowles MR. Cystic Fibrosis Foundation consensus conference report on pulmonary complications of cystic fibrosis. Pediatr Pulmonol 1993; 15: Doring G, Conway SP, Heijerman HG, et al. Antibiotic therapy against Pseudomonas aeruginosa in cystic fibrosis: a European consensus. Eur Respir J 2000;16: Consensus conference. Management of patients with cystic fibrosis. Observation, nutrition, gastroenterology and metabolism. Arch Pediatr 2003; 10 (Suppl. 3):382s 97s. 8. Kerem E, Conway S, Elborn S, Heijerman H. For the Consensus Committee Standards of care for patients with cystic fibrosis: a European consensus. J Cystic Fibrosis 2005; 4: Kabra SK, Kabra M. Cystic Fibrosis in India. NMJI 2003; 16: Kabra SK, Kabra M, Gera S, et al. An indigenously developed method for sweat collection and estimation of chloride for diagnosis of cystic fibrosis. Indian Pediatr 2002; 39: Kerem B, Rommens JM, Buchanan JA, et al. Identification of the cystic fibrosis gene: genetic analysis. Science. 1989; 245: Riordan JR, Rommens JM, Kerem B et al. Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science. 1989; 245: Erratum in: Science 1989; 245: Cystic Fibrosis Mutation Database. accessed on December 17, Frizzel RA. Functions of cystic fibrosis transmembrane conductance regulatory protein. Am J Respir Crit Care Med 1995; S54 S Wilmott RW. Making the diagnosis of cystic fibrosis. J Pediatr 1998; 132: Shastri SS, Kabra M, Kabra SK, Pandey RM, Menon PS. Characterisation of mutations and genotype-phenotype correlation in cystic fibrosis: Experience from India. J Cyst Fibros Aug 21 [Epub ahead of print] 17. Kabra S K, Kabra M, Lodha R, Shastri S. Cystic fibrosis in India. Pediatric Pulmonol 2007; 42: Kabra SK, Kabra M, Shastri S, Lodha R. Diagnosing and managing cystic fibrosis in the developing world. Paediatr Respir Rev. 2006;7 Suppl 1:S

7 19. Kapranov N, Ginter E, Kashirskaja N, Hill CM, Ilangovan P, Rolles CJ. Cystic fibrosis in Russia: background and a model for future collaboration with the West. J R Soc Med. 1996; 89 Suppl 27: Kabra SK, Kabra M, Ghosh M, Khanna A, Pandey RM. Cystic fibrosis in Indian children: Clinical profile of 62 children. Pediatr Pulmonol 1999;19:337 (Abstract). Fig 1. Suggested algorithm for diagnosis and management of cystic fibrosis in resource limited setting Children with failure to thrive, recurrent/persistent chest infection, frequent bulky stools Suspect CF Sweat test facility available Sweat test facility not available Get sweat chloride estimation High (60 meq/l) Borderline (40-60 meq/l) <40 meq/l Do arterial blood gas, serum sodium, chloride and potassium, stool for fat globules and sputum/ respiratory secretion culture for pseudomonas Repeat Treat as CF, if repeat test result is also > 60 meq/ L Repeat Persistently borderline Try to get mutation analysis Not CF Look for: hypochloremia, hyponatremia, hypokalemia, metabolic alkalosis, numerous fat globules on stool microscopy, pseudomonas species in respiratory secretions If > 2 abnormalities are present Follow up as suspected CF, start empirical enzyme replacement, vitamin supplements and chest physiotherapy and vitamin supplement if more than one abnormality present, Give diagnosis of confirmed CF only after getting sweat test or mutation analysis from centers where this facility is available 7