|Year : 2020 | Volume
| Issue : 1 | Page : 8-12
Cystic fibrosis in asia
Shakil Ahmed1, Gary Cheok2, Anne E N Goh3, Aye Han4, SJ Hong5, Wahyuni Indawati6, A R M Lutful Kabir7, SK Kabra8, Harutai Kamalaporn9, Hyung Young Kim10, Shen Kunling11, Sorasak Lochindarat12, Mohammad Ashkan Moslehi13, Anna Marie Nathan14, Daniel Ng15, Nguyen Ng The Phung16, V Singh17, Masato Takase18, Rina Triasih19, Zen-Kong Dai20
1 Department of Pediatrics, Shaheed Suhrawardy Medical College, Dhaka, Bangladesh, India
2 Yee Wui Medical Centre, Macau SAR, China
3 Department of Paediatrics, KK Women's and Children's Hospital, Singapore
4 Department of Paediatrics, University of Medicine, Yangon, Myanmar
5 Department of Pediatrics, Childhood Asthma Atopy Center, Humidifier disinfectant Health Center, Asan Medical Center, University of Ulsan College of Medicine Seoul, Republic of Korea
6 Respirology Division, Child Health Department, Jakarta, Indonesia
7 Department of Pediatrics, Ad-din Women's Medical College, Dhaka, Bangladesh, India
8 Department of Pediatrics, All India Institute of Medical Sciences, New Delhi 110029, India
9 Department of Pediatrics, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
10 Department of Pediatrics, Pusan National University Yangsan Hospital, Pusan, Republic of Korea
11 Department of Respiratory, Beijing Children's Hospital, Capital Medical University, Beijing, China
12 Department of Pediatric Intensive Care and Respiratory Medicine, Queen Sirikit National Institute of Child Health Bangkok, Thailand
13 Pediatric Interventional Pulmonology Division, Department of Pediatric, Shiraz University of Medical Sciences, Shiraz, Iran
14 Department of Pediatrics, University Malaya, Kuala Lumpur, Malaysia
15 Department of Pediatrics, Hong Kong Sanatorium and Hospital, Hong Kong SAR, China
16 Department of Pediatrics, University of Medicine and Pharmacy at Ho Chi Minh City, Vietnam
17 Kalawati Saran Children Hospital, Lady Hardinge Medical College, New Delhi 110029, India
18 Department of Pediatrics, Nippon Medical School Tama-Nagayama Hospital, Tokyo, Japan
19 Department of Pediatrics, Dr. Sardjito Hospital, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia
20 Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Taiwan
|Date of Submission||13-Jul-2020|
|Date of Decision||28-Jul-2020|
|Date of Acceptance||24-Aug-2020|
|Date of Web Publication||08-Dec-2020|
S K Kabra
Department of Pediatrics, All India Institute of Medical Sciences, New Delhi - 110 029
Source of Support: None, Conflict of Interest: None
Background: Cystic fibrosis (CF) is the most common inherited life-limiting illness in the Caucasian population. It is considered to be rare in Asia, but recent reports suggest that CF does occur in Asia. Methods: We carried out a questionnaire-based survey to determine the prevalence of CF across Asian countries and the diagnostic and therapeutic capabilities available in member countries. A questionnaire was sent to member countries of the Asian Pediatric Pulmonology Society. The questionnaire included the total number of children diagnosed with CF seen in the country and the available resources. available resources for diagnosis and management. Results: Fifteen countries responded to the questionnaire. Three countries/regions (Myanmar, Vietnam, and Macau) have not recorded any case of CF. The remaining 12 countries have recorded a variable number of cases which have also been reported in the literature. Sweat chloride testing facilities were available in all the countries except Taiwan that reported cases of CF. Some countries such as India and Bangladesh have developed their own indigenous method for sweat testing. Some countries have facilities for mutation testing. Basic medications such as pancreatic enzyme supplementation and antibiotics were available in all the countries where children with CF have been diagnosed. Inhaled antibiotics and dornase alfa were available only in a few countries. Some other countries reported using the injectable preparation of gentamicin and amikacin for inhalation therapy. Testing for genetic mutation wherever available showed a low frequency of the Delta F 508 mutation which is the most common mutation found in the Caucasian population. Only two countries (India and Japan) have formal CF associations for the affected community. Two countries Japan and China maintain a CF registry, whereas India already started the process of developing it. Conclusion: CF is increasingly being diagnosed over the past two decades in Asian countries. There is a need to create awareness among pediatricians and to develop regional or country-specific protocols and tools for the diagnosis and treatment of children with CF.
Keywords: Child, cystic fibrosis, dornase alfa, pancreatic enzyme, sweat test, tobramycin
|How to cite this article:|
Ahmed S, Cheok G, N Goh AE, Han A, Hong S J, Indawati W, Lutful Kabir A R, Kabra S K, Kamalaporn H, Kim HY, Kunling S, Lochindarat S, Moslehi MA, Nathan AM, Ng D, The Phung NN, Singh V, Takase M, Triasih R, Dai ZK. Cystic fibrosis in asia. Pediatr Respirol Crit Care Med 2020;4:8-12
|How to cite this URL:|
Ahmed S, Cheok G, N Goh AE, Han A, Hong S J, Indawati W, Lutful Kabir A R, Kabra S K, Kamalaporn H, Kim HY, Kunling S, Lochindarat S, Moslehi MA, Nathan AM, Ng D, The Phung NN, Singh V, Takase M, Triasih R, Dai ZK. Cystic fibrosis in asia. Pediatr Respirol Crit Care Med [serial online] 2020 [cited 2021 Apr 13];4:8-12. Available from: https://www.prccm.org/text.asp?2020/4/1/8/302705
| Introduction|| |
Cystic fibrosis (CF) is the most common inherited life-limiting illness in the Caucasian population. Till a few years ago, it was considered extremely rare in the non-Caucasian community. With the publication of multiple reports over the last two decades from Asia and other parts of the world, it is clear that CF does occur in Asia.[1-8] The diagnosis is delayed due to multiple causes including the strong belief that CF does not occur in non-Caucasian populations and the nonavailability of diagnostic tests predominantly the analysis of sweat chloride. Now with the availability of genetic tests mainly new generation sequencing, many centers have confirmed cases of CF from this continent.
The management of CF has evolved over the past 6–7 decades with the improvement of survival to the fourth decade of life from a 6-month survival about six decades ago. The important contributing factors for improved survival include better understanding of the pathophysiology of illness, early diagnosis, and treatment by a multidisciplinary team. With better awareness and well-developed networking, CF is diagnosed before 6 months of age at most centers in the America and Europe.
It is important to assess the magnitude of the problem of CF in Asian countries to improve care and survival. Keeping this in mind, a study was conducted to have a broad understanding of the burden of CF and management capacities within Asia.
| Methods|| |
An estimation of the prevalence of CF was carried out by sending a questionnaire to members of the Asian Pediatric Pulmonology Society (APPS). The APPS has representation from 19 Asian countries. Excluded were countries that have a robust CF program and awareness such as Israel and Russia, Central Asian Republics, Turkey, and Arab countries in the Middle East. The questionnaire included the total number of children diagnosed with CF seen in the country and the available resources [Table 1]. To improve the response rate, reminders were sent through E-mail on three occasions with the help of the APPS secretariat.
The results of the questionnaire were compiled and a simple descriptive analysis for each variable was carried out.
| Results|| |
E-mails were sent to all APPS member countries through their representatives (list provided by APPS office) in June 2018. Of the 19 countries contacted, a total of 15 questionnaires were available from 15 countries. A summary of the results is found in [Table 2]. Three countries (Myanmar, Vietnam, and Macau) have not recorded any case of CF and did not have facilities to perform sweat chloride analysis. The remaining 12 countries have recorded a variable number of cases which had also been reported in published literature.[1-8] Sweat chloride testing facilities were available in all the countries except Taiwan that reported cases of CF. However, in some countries such as India and Bangladesh, a locally developed machine was being used for sweat collection and testing. The method developed in India was validated and is being used in a few centers across the country.
Pancreatic enzyme supplementation is available in all the countries where children with CF have been diagnosed. Dornase alfa is available in some countries (Japan, Hong Kong, Singapore, Bangladesh, Taiwan, and Malaysia), whereas India has reported some patchy availability in the gray market, through nonofficial channels. Inhaled antibiotics are available in Japan, Hong Kong, China, India, Bangladesh, Taiwan, and Malaysia. However, inhaled tobramycin is not available in all countries, resulting in the continued use of injectable preparations of gentamicin and amikacin through the inhalational routes in these countries (Malaysia).
Gene mutation analyses were performed either locally or the samples were sent to facilities in other countries. It was obvious that all countries that recorded mutations had very low prevalence of the delta F508 mutation, which is the most common mutation reported among Caucasians. The reported CF mutations were very variable across countries. Only two countries (India and Japan) have formal CF associations.
A CF registry is present in Japan and China and under development in India.
| Discussion|| |
The results of our survey support that CF does occur in the Asian population. The precise magnitude of the problem is not known from this survey as this was only based on the report of cases that were acknowledged by the responders who are members of APPS but do not necessarily have access to information in more remote areas of their countries, and many countries in the region lack the facilities to diagnose CF. The genetic mutations found in Asia are very different from the Caucasian population. The ability to manage and treat these children with CF is almost nonexistent in many countries such as the availability of pancreatic enzyme supplementation and inhaled antibiotics.
Asia, being a very large continent, has significant variability in its ethnic, historical, cultural, and socioeconomic background. All these may affect the epidemiology of diseases like CF. The management of the disease is further affected as many Asian countries have health-care systems which are not so advanced and they are largely focused on managing the other common illnesses and malnutrition. Hence, the availability of diagnostics and medications may largely depend on the type of insurance available for indigent populations.
Information on CF in countries from Asia is limited to case series or case reports. Some reports estimating the prevalence of CF in Asian countries are based on CF found in the immigrant population in the United Kingdom, the United States of America, and Canada.
Information in the literature suggests that in West and Central Asia, which were not included in our present analysis, CF is well documented and is a significant problem. The incidence of CF in the Middle East varies according to the ethnic background and the degree of consanguinity. The expected rates of CF in these Middle Eastern countries range from 1 in 2560 to 1 in 15,876. The incidence of CF is reported to be around 1 in 2500 live births in Jordan, in 5000 in Bahrain, while in Russia, it is about 1: 5263, and the UAE has the lowest at 1:15,876.[13-17] It is possible that the higher prevalence in some of these countries may be determined by the relative prevalence of Caucasian ancestries.
For the South Asian population, estimates from the immigrant population in the United Kingdom, United States, and Canada suggest a prevalence of CF in people from Asia as 1: 10,000, 1:40,000, and 1: 9000, respectively.[18-20] Majority of people included in these studies are migrant populations from the Indian subcontinent (India, Bangladesh, and Pakistan). A single study to estimate CF in India was based on the identification of the Delta F508 mutation in cord blood, and it suggested an incidence of 1 in 40,000–1 in 100,000 live births. Information on CF from East Asia is limited to case series., In Japan, it is as low as 1 in 350,000 live births.
Results of our survey as well as information available in the literature suggest that CF is poorly recognized and reported in Asian countries, whereas in West and Central Asia, it is well recognized. It is getting recognized across South Asia only in the past two decades.
Recognition of CF in East Asia has started more recently. It is evident that in South and East Asia, the increased diagnosis of CF was based on the development of low-cost sweat chloride estimation and by genetic testing. In other countries in Asia, the diagnosis of CF is missed mainly due to the lack of awareness among pediatricians and the nonavailability of diagnostic sweat testing facilities.
There is a wide heterogeneity in Asian countries in the availability of resources. Except for a few countries, most of the Asian countries have limited resources including the availability of diagnostic tests and trained manpower (respirologists, physiotherapists, respiratory nurses, dieticians, etc.,). The available guidelines for standard management and care of CF patients are largely developed keeping in mind the facilities in advanced health infrastructure in the US and Europe. These cannot be effectively adopted in low- and middle-income countries. Therefore, there is a need to develop cost-effective and country-specific or region-specific protocols for the diagnosis and management of children with CF.
There are a number of limitations of this study including the relatively small numbers of countries involved and the limited response rate (prominent in absence is the Philippines). Also the uncertainty as to the extent that the information captured by the few specialists reporting the data, actually captures the wider population of large and hugely dispersed populations (e.g., the very small numbers in Indonesia). However, this should be viewed as an exploratory effort, and as such the lead taken by APPS to get a broad-based survey about the disease in this continent is the first step in the right direction. The respective participants need to develop a curriculum in medical schools and engage governmental agencies in allocating resources to develop regional bona fide sweat testing centers, and for those, who develop their own test, to ascertain rigorous controls compared to standard sweat testing. They should also take lead for developing a program to increase the awareness among pediatricians, as well as to develop region-specific management protocols by promoting interaction between its members.
We would like to thank Dr. Sudipta Roy, Assistant Professor of Pediatrics, AWMC, Dhaka, and Dr. Rahat Bin Habib, Consultant Pediatrics, Dhaka, for helping in data collection.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Kabra SK, Kabra M, Lodha R, Shastri S. Cystic fibrosis in India. Pediatr Pulmonol 2007;42:1087-94.
Xu J, Yin Y, Zhang L, Zhang J, Yuan S, Zhang H. Four case reports of Chinese cystic fibrosis patients and literature review. Pediatr Pulmonol 2017;52:1020-8.
Li N, He B, Wang GF, Tang XY. A case report of cystic fibrosis and review of 16 cases of cystic fibrosis in Chinese patients. Zhonghua Jie He He Hu Xi Za Zhi 2003;26:559-62.
Suwanjutha S, Huang NN, Wattanasirichaigoon D, Sura T, Harris A, Macek M Jr., Case report of a Thai male cystic fibrosis patient with the 1898+1G-->T splicing mutation in the CFTR gene: A review of East Asian cases. Mutations in brief no. 196. Online. Hum Mutat ->T splicing mutation in the CFTR gene: A review of East Asian cases. Mutations in brief no. 196. Online. Hum Mutat 1998;12:361.
Nathan AM, Thong MK, Bruyne D, Hany AF. First study on the prevalence of the delF 508 mutation in children diagnosed with cystic fibrosis in UMMC, Malaysia. J Paediatr Child Health 2011;47:572-5.
Nathan AM, Muthusamy A, Thavagnanam S, Hashim A, Bruyne JD. Chronic suppurative lung disease in a developing country: Impact on child and parent. Pediatr Pulmonol 2014;49:435-40.
Norzila M, Norrashidah A, Rusanida A, Chan P, Azizi B. Cystic fibrosis in Malaysian children. Med J Malaysia 2005;60:54-61.
Teeratakulpisarn J, Kosuwon P, Srinakarin J, Panthongviriyakul C, Sutra S. Cystic fibrosis in three northeast Thai infants is CF really a rare disease in the Thai population? J Med Assoc Thai 2006;89:1756-61.
Bell SC, Mall MA, Gutierrez H, Macek M, Madge S, Davies JC, et al
. The future of cystic fibrosis care: A global perspective. Lancet Respir Med 2020;8:65-124.
MacKenzie T, Gifford AH, Sabadosa KA, Quinton HB, Knapp EA, Goss CH, et al
. Longevity of patients with cystic fibrosis in 2000 to 2010 and beyond: Survival analysis of the Cystic Fibrosis Foundation patient registry. Ann Intern Med 2014;161:233-41.
Kabra SK, Kabra M, Gera S, Lodha R, Sreedevi KN, Chacko S, et al
. An indigenously developed method for sweat collection and estimation of chloride for diagnosis of cystic fibrosis. Indian Pediatr 2002;39:1039-43.
The Molecular Genetic Epidemiology of Cystic Fibrosis Report of a Joint Meeting of WHO/ECFTN/ICF (M) A/ECFS Genoa, Italy, 19 June; 2002.
Nazer HM. Early diagnosis of cystic fibrosis in Jordanian children. J Trop Pediatr 1992;38:113-5.
Kakish KS. Cystic fibrosis in Jordan: Clinical and genetic aspects. Bahrain Med Bull 2001;23:157-9.
Al-Mahroos F. Cystic fibrosis in Bahrain incidence, phenotype, and outcome. J Trop Pediatr 1998;44:35-9.
Al-Gazali L, Ali BR. Mutations of a country: A mutation review of single gene disorders in the United Arab Emirates (UAE). Hum Mutat 2010;31:505-20.
Barbitoff YA, Skitchenko RK, Poleshchuk OI, Shikov AE, Serebryakova EA, Nasykhova YA, et al
. Whole-exome sequencing provides insights into monogenic disease prevalence in Northwest Russia. Mol Genet Genomic Med 2019;7:e964.
Goodchild MC, Insley J, Rushton DI, Gaze H. Cystic fibrosis in 3 Pakistani children. Arch Dis Child 1974;49:739-41.
Powers CA, Potter EM, Wessel HU, Lloyd-Still JD. Cystic fibrosis in Asian Indians. Arch Pediatr Adolesc Med 1996;150:554-5.
Mei-Zahav M, Durie P, Zielenski J, Solomon M, Tullis E, Tsui LC, et al
. The prevalence and clinical characteristics of cystic fibrosis in South Asian Canadian immigrants. Arch Dis Child 2005;90:675-9.
Shastri SS, Kabra M, Kabra SK, Pandey RM, Menon PS. Characterization of mutations and genotype-phenotype correlation in cystic fibrosis: Experience from India. J Cyst Fibros 2008;7:110-5.
Zilfalil BA, Sarina S, Liza-Sharmini AT, Oldfield NJ, Stenhouse SA. Detection of F508del mutation in cystic fibrosis transmembrane conductance regulator gene mutation among Malays. Singapore Med J 2006;47:129-33.
Norzila MZ, Azizi BH. Cystic fibrosis in Malay children – A report of three cases. Singapore Med J 1996;37:273-4.
Yamashiro Y, Shimizu T, Oguchi S, Shioya T, Nagata S, Ohtsuka Y. The estimated incidence of cystic fibrosis in Japan. J Pediatr Gastroenterol Nutr 1997;24:544-7.
Smyth AR, Bell SC, Bojcin S, Bryon M, Duff A, Flume P, et al
. European cystic fibrosis society standards of care: Best practice guidelines. J Cyst Fibros 2014;13 Suppl 1:S23-42.
Kabra SK, Kabra M, Shastri S, Lodha R. Diagnosing and managing cystic fibrosis in the developing world. Paediatr Respir Rev 2006;7 Suppl 1:S147-50.
[Table 1], [Table 2]