|Year : 2019 | Volume
| Issue : 2 | Page : 116-121
|Asthma and obesity in the Middle East region: An overview
Samer Hammoudeh1, Wessam Gadelhak1, Ibrahim A Janahi2
1 Medical Research Center, Research Affairs, Hamad Medical Corporation, Doha, Qatar
2 Medical Research Center, Research Affairs; Pediatric Pulmonology, Hamad Medical Corporation, Doha, Qatar
|Date of Submission||18-Apr-2018|
|Date of Acceptance||07-Aug-2018|
|Date of Web Publication||5-Apr-2019|
Dr. Ibrahim A Janahi
Hamad Medical Corporation, P. O. Box: 3050, Doha
| Abstract|| |
This paper aims to cover the current status of asthma and obesity in the Middle East, as well as to introduce the various studies tying the two diseases; further expanding on the proposed mechanisms. Finally, the paper covers recent literature related to sphingolipids and its role in asthma, followed by recommendations and future directions. In preparation of this paper, we searched PubMed and Google Scholar, with no restrictions, using the following terms; asthma, obesity, Middle East, sphingolipids. We also used the reference list of retrieved articles to further expand on the pool of articles that were used for this review.
Keywords: Asthma, obesity, Qatar, sphingolipids, Middle East
|How to cite this article:|
Hammoudeh S, Gadelhak W, Janahi IA. Asthma and obesity in the Middle East region: An overview. Ann Thorac Med 2019;14:116-21
Globally, asthma presents as a major public health concern,, with a varying prevalence rate among children. The International Study of Asthma and Allergies in Childhood in 2013 reported a global prevalence rate of 14.1% among children ages 13–14 years, and 11.7% among children ages 6–7 years. Global prevalence rates of rhinoconjunctivitis and eczema, among children ages 13–14 years, were 14.6% and 7.3%, respectively. Among those 6–7 years of age, the prevalence rates were 8.5% and 7.9% for rhinoconjunctivitis and eczema, respectively.
As for the Middle East region, in 2017, a systematic review in a sample which included more than a quarter million children across the region, reported that the Middle East has lower asthma rates than developed countries, as a total asthma rate of 7.57% was reported among 13–14 year old children, and 7.43% among 6–7 year old children. The review also showed that the prevalence of asthma was higher among males. Baghdad, Iraq had the highest prevalence rate (22.3%), while Isfahan, Iran had the lowest (0.7%). According to Waness et al. in a review of respiratory disorders in the Middle East, the region continues to suffer respiratory-related illnesses due to a wide array of factors and obstacles. Pulmonologists, pediatricians, and family physicians, as well as other specialists, continue to face challenges in the region due to several distinctive environmental and cultural factors. As for asthma in specific, Behbehani et al. indicates that much can be done when it comes to controlling asthma in the region.
Locally in Qatar, in 2006, Janahi et al. (n = 3283) reported a prevalence rate of 19.8% for asthma, 30.5% for allergic rhinitis, 22.5% for eczema, and 11.9% for chest infections, among school children ages 6–12 years. Similar rates were reported in an earlier study in 2005 as well. In the Gulf region, in 2017, a study from Saudi Arabia reported an asthma prevalence rate of 24% among children in Makkah, with more males being affected than females, in a sample of children below 5 years of age. In 2000, a study in Kuwait showed that males predominance was also reported in a sample of 13–14 year old children, with an asthma prevalence of 16.8%. In 2008, a prevalence rate of 15.6% was reported among 13–14-year-old children in another study from Kuwait as well. In Oman, a study in 2003 reported a prevalence rate of 20.7% for asthma, 10.5% for allergic rhinitis, and 14.4% for eczema, among school children ages 13–14 years. Among 6–7-year-old children, the rates were as follows: asthma 10.5%, allergic rhinitis 7.4%, and eczema 7.5%. In the United Arab Emirates (UAE) in 2013, asthma prevalence rate was reported at 13% among 12–16 year old children. Body mass index (BMI) was non significantly higher among asthmatics compared to nonasthmatics.
Asthma is one of those diseases that modern research has failed to ascertain a causation factor or element that can be targeted for management and control purposes., Genetics and environmental elements have been cited as contributing factors in the development of asthma.,,,,,, In the Gulf region, a study by Bener et al. (n = 1432) reported exposure to outdoor air pollutants as a contributing factor to the development of asthma among school children. Another local study conducted on a sample size of 3204 children showed that family history of asthma outweighed other factors such as environmental factors in contributing to childhood asthma. Similar findings were reported in another study in the UAE with a sample size of 406 children, ages 6–18 years. Another UAE study reported family history and UAE nationality as predictors of asthma among adolescents and adults. In Iraq, a study on 644 children, ages 6–12 years, reported family history, prematurity, crowding, low birth weight, and low parental education as risk factors for asthma.
| Asthma and Obesity|| |
Obesity is another major public health concern that has gone rampant across the globe, whether among adults or children.,,,, In Qatar, Rizk et al. reported a metabolic syndrome prevalence rate of 3.0%, and an obesity/overweight rate of 31.3% among children ages 6–12 years. Mandeya and Al-Oballi Kridli list social norms, dietary practices, sedentary lifestyle, and lack of physical activity, as risk factors for obesity and overweight among children in Qatar. The authors attribute these risk factors to the higher financial status among the population which has led many more to utilize a modern western lifestyle. The rates of overweight and obesity they found when comparing the various studies in Qatar was comparable to other Gulf countries.
A study from UAE reported a prevalence rate of 44% for metabolic syndrome, and a mean BMI of 35.3 ± 6.1, among 260 young obese participants. An earlier study from the UAE as well, conducted on a sample size of 4381 children, ages 5–17 years, reported a prevalence rate of 21.5% for being overweight and a 13.7% for being obese. A more recent UAE study reported an overweight and obesity rates of 14.7% and 18.9%, respectively, among 1541 children, ages 6–19 years. Nahhas et al. reported asthma to be associated with obesity in both genders, but stronger among females, in a sample of Saudi children ages 6–8 years.
While the link between the two diseases, asthma and obesity remain to be debatable and subject to future scrutiny,,,, A plethora of studies have attempted to shed the light on the aforementioned. Among adults, a meta-analysis reported a dose-response relationship between asthma incidence and weight in both genders. In a similar fashion, children with a BMI equivalent to the 85th percentile or greater were found to be at risk of developing asthma among 10 years old from both genders, and 2–3-year-old boys. Another study reported a positive correlation between obese children and asthma among 2–5 and 9–13 years old. A meta-analysis which covered six studies reported that an increased risk of developing asthma among obese children when compared to nonobese children. In addition, a significant dose response was observed for BMI and asthma incidence.
Michelson et al. showed that asthma severity was associated with a higher BMI, as well as higher levels of the inflammation marker C-reactive protein. An earlier Brazilian study reported a positive association between asthma symptoms/severity and obesity, among children ages 13–14 years. On the contrary, Ross et al. reported no difference between obese and nonobese asthmatic children, in regards to asthma severity, airway obstruction, and inflammation. In a similar fashion, a negative association was found between BMI and asthma severity in another study. Others investigated the relationship between weight and asthma in regards to indoor pollutant exposure and showed that obese or overweight children had more symptoms when exposed to fine particles compared to normal weight children. A systematic review by Ali and Ulrik showed that asthma and obesity have similar or overlapping risk and causation elements such as genetic factors, physical activity, and nutrition.
| Pathophysiology|| |
Not much is known in regards to the mechanisms behind obesity and asthma. Ali and Ulrik listed epigenetic, hormonal, environmental, genetic, mechanical, and immunological factors as possible mechanism routes tying the two diseases.
Lang reported that obesity is usually associated with factors that play a role in the development of asthma. Such include obesity comorbidities, airway narrowing, and inflammation., The latter induces an amplified response in the lungs due to the production of adipokines by fatty tissue. Others reported that obese asthmatics have more comorbidities and lower lung functions when compared to normal weight asthmatics. While von Mutius showed that BMI affects asthma either by mechanical or inflammatory means and not by allergic airway inflammation. A significant association was found between obesity and asthma among children and adolescents in the NHANES study, where non atopic asthma had a stronger association when compared to atopic asthma.
Two phenotypes have been reported as related to asthma and obesity: early onset and late onset., Early onset is characterized by the following features: onset begins in an earlier age, increased atopy or allergens, airway epithelium production of cytokines including Th2 and weight loss reduces exacerbations. The late onset type is characterized by the following features: mechanical restriction of tidal volume, increase in metabolic inflammation markers, decrease in eosinophilia and Th2, weight loss improves airway closure, corticosteroids decrease exacerbations, severity increases with weight gain, and weight loss reduces exacerbations. Baffi et al. grouped the implications of excess adipose tissue among obese asthmatic patients into mechanical/physiological and immune/metabolic implications. The mechanical involves lung function and changes in airway, while the immune/metabolic implications involve immune and metabolic functions. In the first type of asthma, obesity alters the allergic component, while in the second obesity alters the lungs itself.
Numerous studies commented on the management/treatment options of obese asthmatic patients which revolve around avoiding triggers, treating comorbidities, and pharmacotherapy.,,,, These studies agree that obese asthmatics are less responsive to therapy than others.,,, Others have reported on the management approaches of the obesity aspect for obese asthma patients which are mainly lifestyle oriented and include weight loss strategies, physical activity on regular basis, dietary approaches, and reduction of sedentary lifestyle patterns.,, Furthermore, several studies have shown the effectiveness of behavior modification attempts in inducing weight loss among obese non asthmatic children., A randomized clinical trial conducted on 8–17 years old obese asthmatic children showed improvements in static lung function and asthma control after a 10 week diet-induced weight loss regimen. Others have reported on the positive role that physical activity plays in reducing both asthma severity and incidence., However, the overall picture in regards to the role of physical activity on pediatric asthma remains subject to further scrutiny.,,, In all, Rastogi et al. suggested that the most influential factor that aids in reducing obesity-related asthma morbidity comes through focusing on the obesity aspect of the illness, both onset and progression.
Based on the preceding, it becomes of dire need that novel therapeutic/management options be discovered and sustained by future research. One of the possible promising routes is managing a better understanding of the role of sphingolipids.,,
| Role of Sphingolipids|| |
Sphingolipids are an integral part of cell membranes with various functions, including molecule signaling,,, regulation of cell growth and death, migration, and role in inflammation., Sphingolipids have been reported to play a role in the pathogenesis of asthma by inducing airway remodeling, smooth muscle contractility, and changes in inflammatory cell functioning., The mechanism that these lipids influence inflammation can occur through different routes.
Furthermore, the orosomucoid-like (ORMDL) proteins have been reported to play a role in the sphingolipid pathway involving the synthesis and homeostasis of sphingolipids.,,, They are responsible for regulating the enzyme serine palmitoyl CoA transferase (SPT) which initiates the production of sphingolipids., In addition, they play a role in controlling the amount of ceramide inside cells., Research by Worgall et al. showed that decrease in SPT induces airway hyperreactivity without inflammation, a decrease in lung sphingolipids, and alteration of magnesium lung homeostasis. Russo et al. reported that the synthesis of sphingolipids becomes interrupted in adipose tissue as a result of the influx of fatty acid. Worgall reported that ORMDL3 is tied to asthma by its inhibition of the synthesis of sphingolipids.
ORMDL3 is of particular interest as several studies have associated genetic variances of ORMDL3 with asthma.,,,,,, More specifically, the genetic variant in the 17q21 haploblock, which modifies the expression of ORMDL3, has been shown to be linked to increased risk of developing asthma.,,,, Others confirmed the role of locus 17q21 but in relation to genes other than the ORMDL3. Moreover, 17q12-21 polymorphisms have been linked to asthma in numerous studies.,,,, Within the 17q21 region, several studies reported single-nucleotide polymorphism (SNP) rs2872507, which modulates the ORMDL3 gene expression, to be significantly correlated with asthma.,, Others reported the same, but in relation to SNP rs8067378, and rs7216389.,
While the above has been studied in relation to asthma, not much has been done in relation to obesity-induced asthma. That being said, further work would need to focus on studying ORMDL3, sphingolipids, in relation to obesity-induced asthma in specific. Future directions revolve around the following themes: (a) the degradation of ORMDL, as well as the mechanisms involving the expression of ORMDL on asthma, (b) identifying a direct link between ORMDL3 to SPT activity (c) tailored therapeutic and prevention strategies based on one's genotype and environmental exposure.
| Conclusion|| |
In all, the emerging evidence of the involvement of sphingolipids in both, the initiation and maintenance of inflammation, may open the door to new therapeutic approaches involving novel agents.,,, The same applies to the role of decreased de novo synthesis of sphingolipids described by Worgall et al. As the number of asthma/obesity cases continues to rise, so does the dire need for more efforts directed toward creating new approaches of management. The literature cited here involving sphingolipids seems to be promising. On the population level, intensifying health education efforts in regards to nutrition and physical activity seem to be crucial to curb the pandemic phenomenon of obesity.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Bousquet J, Bousquet PJ, Godard P, Daures JP. The public health implications of asthma. Bull World Health Organ 2005;83:548-54.
Pawankar R. Allergic diseases and asthma: A global public health concern and a call to action. World Allergy Organ J 2014;7:12.
Lai CK, Beasley R, Crane J, Foliaki S, Shah J, Weiland S, et al.
Global variation in the prevalence and severity of asthma symptoms: Phase three of the international study of asthma and allergies in childhood (ISAAC). Thorax 2009;64:476-83.
Mallol J, Crane J, von Mutius E, Odhiambo J, Keil U, Stewart A, et al.
The international study of asthma and allergies in childhood (ISAAC) phase three: A global synthesis. Allergol Immunopathol (Madr) 2013;41:73-85.
Mirzaei M, Karimi M, Beheshti S, Mohammadi M. Prevalence of asthma among Middle Eastern children: A systematic review. Med J Islam Repub Iran 2017;31:9.
Waness A, El-Sameed YA, Mahboub B, Noshi M, Al-Jahdali H, Vats M, et al.
Respiratory disorders in the Middle East: A review. Respirology 2011;16:755-66.
Behbehani N, Al-Jahdali H, Alqaseer A, Estephan A, Gjurovic A, Haouichat H, et al
. Asthma Control in the Middle East and North Africa: The ESMAA Study. A59. Epidemiology of Airways and Chronic Lung Diseases. American Thoracic Society International Conference Abstracts: American Thoracic Society; 2017. p. A2023.
Janahi IA, Bener A, Bush A. Prevalence of asthma among qatari schoolchildren: International study of asthma and allergies in childhood, qatar. Pediatr Pulmonol 2006;41:80-6.
Bener A, Janahi IA, Sabbah A. Genetics and environmental risk factors associated with asthma in schoolchildren. Eur Ann Allergy Clin Immunol 2005;37:163-8.
Harthi SA, Wagdani AA, Sabbagh A, Al-Ghamdi A, Abu-Duruk I. Prevalence of asthma among Saudi children in Makkah Saudi Arabia. Int J Adv Res 2017;5:1209-14.
Behbehani NA, Abal A, Syabbalo NC, Abd Azeem A, Shareef E, Al-Momen J, et al.
Prevalence of asthma, allergic rhinitis, and eczema in 13- to 14-year-old children in Kuwait: An ISAAC study. International study of asthma and allergies in childhood. Ann Allergy Asthma Immunol 2000;85:58-63.
Owayed A, Behbehani N, Al-Momen J. Changing prevalence of asthma and allergic diseases among Kuwaiti children. An ISAAC study (Phase III). Med Princ Pract 2008;17:284-9.
Al-Riyami BM, Al-Rawas OA, Al-Riyami AA, Jasim LG, Mohammed AJ. A relatively high prevalence and severity of asthma, allergic rhinitis and atopic eczema in schoolchildren in the sultanate of Oman. Respirology 2003;8:69-76.
Al-Hammadi S, Al-Zaabi O. Asthma diagnosis and treatment – 1027. Body mass index of asthmatic children in United Arab Emirates. World Allergy Organ J 2013;6 Suppl 1:P26.
Anderson GP. Endotyping asthma: New insights into key pathogenic mechanisms in a complex, heterogeneous disease. Lancet 2008;372:1107-19.
Moffatt MF, Gut IG, Demenais F, Strachan DP, Bouzigon E, Heath S, et al.
Alarge-scale, consortium-based genomewide association study of asthma. N
Engl J Med 2010;363:1211-21.
Bener A, Abdulrazzaq YM, Al-Mutawwa J, Debuse P. Genetic and environmental factors associated with asthma. Hum Biol 1996;68:405-14.
Ono JG, Worgall TS, Worgall S. Airway reactivity and sphingolipids-implications for childhood asthma. Mol Cell Pediatr 2015;2:13.
Lu KD, Breysse PN, Diette GB, Curtin-Brosnan J, Aloe C, Williams DL, et al.
Being overweight increases susceptibility to indoor pollutants among urban children with asthma. J Allergy Clin Immunol 2013;131:1017-23, 1023.e1-3.
Duffy DL, Martin NG, Battistutta D, Hopper JL, Mathews JD. Genetics of asthma and hay fever in Australian twins. Am Rev Respir Dis 1990;142:1351-8.
Lang JE. Obesity, nutrition, and asthma in children. Pediatr Allergy Immunol Pulmonol 2012;25:64-75.
Levy BD. Sphingolipids and susceptibility to asthma. N
Engl J Med 2013;369:976-8.
Bener A, Ehlayel M, Sabbah A. The pattern and genetics of pediatric extrinsic asthma risk factors in polluted environment. Eur Ann Allergy Clin Immunol 2007;39:58-63.
Moussa MA, Skaik MB, Yaghy OY, Salwanes SB, Bin-Othman SA. Factors associated with asthma in school children. Eur J Epidemiol 1996;12:583-8.
Alsowaidi S, Abdulle A, Bernsen R. Prevalence and risk factors of asthma among adolescents and their parents in al-Ain (United Arab emirates). Respiration 2010;79:105-11.
Al-Kubaisy W, Ali SH, Al-Thamiri D. Risk factors for asthma among primary school children in Baghdad, Iraq. Saudi Med J 2005;26:460-6.
He L, Ren X, Chen Y, Jin Y, Pan R, Wei N, et al.
Prevalence of overweight and obesity among primary school children aged 5 to 14 years in Wannan area, China. Nutr Hosp 2014;30:776-81.
Al Junaibi A, Abdulle A, Sabri S, Hag-Ali M, Nagelkerke N. The prevalence and potential determinants of obesity among school children and adolescents in Abu Dhabi, United Arab emirates. Int J Obes (Lond) 2013;37:68-74.
Saeidlou SN, Rezaiegoyjeloo F, Ayremlou P, Babaie F. Trend of overweight and obesity, based on population study among school children in North West of Iran: Implications for when to intervene. Maedica (Buchar) 2015;10:214-20.
Ahrens W, Pigeot I, Pohlabeln H, De Henauw S, Lissner L, Molnár D, et al.
Prevalence of overweight and obesity in European children below the age of 10. Int J Obes (Lond) 2014;38 Suppl 2:S99-107.
Ogden CL, Carroll MD, Lawman HG, Fryar CD, Kruszon-Moran D, Kit BK, et al.
Trends in obesity prevalence among children and adolescents in the United States, 1988-1994 through 2013-2014. JAMA 2016;315:2292-9.
Rizk N, Amin M, Yousef M. A pilot study on metabolic syndrome and its associated features among qatari schoolchildren. Int J Gen Med 2011;4:521-5.
Eapen V, Mabrouk A, Yousef S. Metabolic syndrome among the young obese in the United Arab emirates. J Trop Pediatr 2010;56:325-8.
Malik M, Bakir A. Prevalence of overweight and obesity among children in the United Arab emirates. Obes Rev 2007;8:15-20.
Nahhas M, Bhopal R, Anandan C, Elton R, Sheikh A. Investigating the association between obesity and asthma in 6- to 8-year-old saudi children: A matched case-control study. NPJ Prim Care Respir Med 2014;24:14004.
Shore SA. Obesity and asthma: Possible mechanisms. J Allergy Clin Immunol 2008;121:1087-93.
Schachter LM, Peat JK, Salome CM. Asthma and atopy in overweight children. Thorax 2003;58:1031-5.
Baruwa P, Sarmah KR. Obesity and asthma. Lung India 2013;30:38-46.
] [Full text]
Umetsu DT. Mechanisms by which obesity impacts upon asthma. Thorax 2017;72:174-7.
Beuther DA, Sutherland ER. Overweight, obesity, and incident asthma: A meta-analysis of prospective epidemiologic studies. Am J Respir Crit Care Med 2007;175:661-6.
Rodríguez MA, Winkleby MA, Ahn D, Sundquist J, Kraemer HC. Identification of population subgroups of children and adolescents with high asthma prevalence: Findings from the third national health and nutrition examination survey. Arch Pediatr Adolesc Med 2002;156:269-75.
Mannino DM, Mott J, Ferdinands JM, Camargo CA, Friedman M, Greves HM, et al.
Boys with high body masses have an increased risk of developing asthma: Findings from the National Longitudinal Survey of Youth (NLSY). Int J Obes (Lond) 2006;30:6-13.
Guibas GV, Manios Y, Xepapadaki P, Moschonis G, Douladiris N, Mavrogianni C, et al.
The obesity-asthma link in different ages and the role of body mass index in its investigation: Findings from the genesis and healthy growth studies. Allergy 2013;68:1298-305.
Chen YC, Dong GH, Lin KC, Lee YL. Gender difference of childhood overweight and obesity in predicting the risk of incident asthma: A systematic review and meta-analysis. Obes Rev 2013;14:222-31.
Michelson PH, Williams LW, Benjamin DK, Barnato AE. Obesity, inflammation, and asthma severity in childhood: Data from the National Health and Nutrition Examination Survey 2001-2004. Ann Allergy Asthma Immunol 2009;103:381-5.
Cassol VE, Rizzato TM, Teche SP, Basso DF, Centenaro DF, Maldonado M, et al.
Obesity and its relationship with asthma prevalence and severity in adolescents from Southern Brazil. J Asthma 2006;43:57-60.
Ross KR, Hart MA, Storfer-Isser A, Kibler AM, Johnson NL, Rosen CL, et al.
Obesity and obesity related co-morbidities in a referral population of children with asthma. Pediatr Pulmonol 2009;44:877-84.
Tantisira KG, Litonjua AA, Weiss ST, Fuhlbrigge AL; Childhood Asthma Management Program Research Group. Association of body mass with pulmonary function in the childhood asthma management program (CAMP). Thorax 2003;58:1036-41.
Ali Z, Ulrik CS. Obesity and asthma: A coincidence or a causal relationship? A systematic review. Respir Med 2013;107:1287-300.
Lang JE, Williams ES, Mizgerd JP, Shore SA. Effect of obesity on pulmonary inflammation induced by acute ozone exposure: Role of interleukin-6. Am J Physiol Lung Cell Mol Physiol 2008;294:L1013-20.
Pakhale S, Doucette S, Vandemheen K, Boulet LP, McIvor RA, Fitzgerald JM, et al.
Acomparison of obese and nonobese people with asthma: Exploring an asthma-obesity interaction. Chest 2010;137:1316-23.
von Mutius E, Schwartz J, Neas LM, Dockery D, Weiss ST. Relation of body mass index to asthma and atopy in children: The National Health and Nutrition Examination Study III. Thorax 2001;56:835-8.
Visness CM, London SJ, Daniels JL, Kaufman JS, Yeatts KB, Siega-Riz AM, et al.
Association of childhood obesity with atopic and nonatopic asthma: Results from the National Health and Nutrition Examination Survey 1999-2006. J Asthma 2010;47:822-9.
Mohanan S, Tapp H, McWilliams A, Dulin M. Obesity and asthma: Pathophysiology and implications for diagnosis and management in primary care. Exp Biol Med (Maywood) 2014;239:1531-40.
Bates JHT, Poynter ME, Frodella CM, Peters U, Dixon AE, Suratt BT, et al.
Pathophysiology to phenotype in the asthma of obesity. Ann Am Thorac Soc 2017;14:S395-8.
Baffi CW, Winnica DE, Holguin F. Asthma and obesity: Mechanisms and clinical implications. Asthma Res Pract 2015;1:1.
Lang JE. Obesity and asthma in children: Current and future therapeutic options. Paediatr Drugs 2014;16:179-88.
Vijayakanthi N, Greally JM, Rastogi D. Pediatric obesity-related asthma: The role of metabolic dysregulation. Pediatrics 2016;137. pii: e20150812.
Forno E, Lescher R, Strunk R, Weiss S, Fuhlbrigge A, Celedón JC, et al.
Decreased response to inhaled steroids in overweight and obese asthmatic children. J Allergy Clin Immunol 2011;127:741-9.
Jensen ME, Gibson PG, Collins CE, Hilton JM, Wood LG. Diet-induced weight loss in obese children with asthma: A randomized controlled trial. Clin Exp Allergy 2013;43:775-84.
Mitka M. Programs to reduce childhood obesity seem to work, say cochrane reviewers. JAMA 2012;307:444-5.
Kelishadi R, Azizi-Soleiman F. Controlling childhood obesity: A systematic review on strategies and challenges. J Res Med Sci 2014;19:993-1008.
Lucas SR, Platts-Mills TA. Physical activity and exercise in asthma: Relevance to etiology and treatment. J Allergy Clin Immunol 2005;115:928-34.
Carson KV, Chandratilleke MG, Picot J, Brinn MP, Esterman AJ, Smith BJ, et al.
Physical training for asthma. Cochrane Database Syst Rev;(9):CD001116.
Moreira A, Delgado L, Haahtela T, Fonseca J, Moreira P, Lopes C, et al.
Physical training does not increase allergic inflammation in asthmatic children. Eur Respir J 2008;32:1570-5.
Pakhale S, Luks V, Burkett A, Turner L. Effect of physical training on airway inflammation in bronchial asthma: A systematic review. BMC Pulm Med 2013;13:38.
Rastogi D, Canfield SM, Andrade A, Isasi CR, Hall CB, Rubinstein A, et al.
Obesity-associated asthma in children: A distinct entity. Chest 2012;141:895-905.
Nixon GF. Sphingolipids in inflammation: Pathological implications and potential therapeutic targets. Br J Pharmacol 2009;158:982-93.
Maceyka M, Spiegel S. Sphingolipid metabolites in inflammatory disease. Nature 2014;510:58-67.
Russo SB, Ross JS, Cowart LA. Sphingolipids in obesity, type 2 diabetes, and metabolic disease. Handb Exp Pharmacol 2013;216:373-401.
Lingwood D, Simons K. Lipid rafts as a membrane-organizing principle. Science 2010;327:46-50.
Breslow DK, Weissman JS. Membranes in balance: Mechanisms of sphingolipid homeostasis. Mol Cell 2010;40:267-79.
Hannun YA, Obeid LM. Principles of bioactive lipid signalling: Lessons from sphingolipids. Nat Rev Mol Cell Biol 2008;9:139-50.
Paulenda T, Draber P. The role of ORMDL proteins, guardians of cellular sphingolipids, in asthma. Allergy 2016;71:918-30.
Ghidoni R, Caretti A, Signorelli P. Role of sphingolipids in the pathobiology of lung inflammation. Mediators Inflamm 2015;2015:487508.
Gulbins E, Petrache I. Sphingolipids in Disease (Handbook of Experimental Pharmacology). Austria: Springer-Verlag Wien; 2013. VIII, p. 478.
Chalfant CE, Spiegel S. Sphingosine 1-phosphate and ceramide 1-phosphate: Expanding roles in cell signaling. J Cell Sci 2005;118:4605-12.
Siow DL, Wattenberg BW. Mammalian ORMDL proteins mediate the feedback response in ceramide biosynthesis. J Biol Chem 2012;287:40198-204.
Worgall TS, Veerappan A, Sung B, Kim BI, Weiner E, Bholah R, et al.
Impaired sphingolipid synthesis in the respiratory tract induces airway hyperreactivity. Sci Transl Med 2013;5:186ra67.
Worgall TS. Sphingolipids, ORMDL3 and asthma: What is the evidence? Curr Opin Clin Nutr Metab Care 2017;20:99-103.
Moffatt MF, Kabesch M, Liang L, Dixon AL, Strachan D, Heath S, et al.
Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma. Nature 2007;448:470-3.
Galanter J, Choudhry S, Eng C, Nazario S, Rodríguez-Santana JR, Casal J, et al.
ORMDL3 gene is associated with asthma in three ethnically diverse populations. Am J Respir Crit Care Med 2008;177:1194-200.
Breslow DK, Collins SR, Bodenmiller B, Aebersold R, Simons K, Shevchenko A, et al.
Orm family proteins mediate sphingolipid homeostasis. Nature 2010;463:1048-53.
Siow D, Sunkara M, Dunn TM, Morris AJ, Wattenberg B. ORMDL/serine palmitoyltransferase stoichiometry determines effects of ORMDL3 expression on sphingolipid biosynthesis. J Lipid Res 2015;56:898-908.
Toncheva AA, Potaczek DP, Schedel M, Gersting SW, Michel S, Krajnov N, et al.
Childhood asthma is associated with mutations and gene expression differences of ORMDL genes that can interact. Allergy 2015;70:1288-99.
Yang FF, Huang Y, Li QB, Dai JH, Fu Z. Single nucleotide polymorphisms in the ORM1-like 3 gene associated with childhood asthma in a Chinese population. Genet Mol Res 2012;11:4646-53.
Yu X, Yu C, Ren Z, Deng Y, Song J, Zhang H, et al.
Genetic variants of 17q21 are associated with childhood-onset asthma and related phenotypes in a Northeastern Han Chinese population: A case-control study. Tissue Antigens 2014;83:330-6.
Schmiedel BJ, Seumois G, Samaniego-Castruita D, Cayford J, Schulten V, Chavez L, et al.
17q21 asthma-risk variants switch CTCF binding and regulate IL-2 production by T cells. Nat Commun 2016;7:13426.
Leung TF, Sy HY, Ng MC, Chan IH, Wong GW, Tang NL, et al.
Asthma and atopy are associated with chromosome 17q21 markers in Chinese children. Allergy 2009;64:621-8.
Blekic M, Kljaic Bukvic B, Aberle N, Marinho S, Hankinson J, Custovic A, et al
. 17q12-21 and asthma: Interactions with early-life environmental exposures. Ann Allergy Asthma Immunol 2013;110:347-5300.
Ono JG, Worgall TS, Worgall S 17q21 locus and ORMDL3: An increased risk for childhood asthma. Pediatr Res 2014;75:165-70.
Flory JH, Sleiman PM, Christie JD, Annaiah K, Bradfield J, Kim CE, et al
. 17q12-21 variants interact with smoke exposure as a risk factor for pediatric asthma but are equally associated with early-onset versus late-onset asthma in north americans of european ancestry. J Allergy Clin Immunol 2009;124:605-7.
Bouzigon E, Corda E, Aschard H, Dizier MH, Boland A, Bousquet J, et al.
Effect of 17q21 variants and smoking exposure in early-onset asthma. N
Engl J Med 2008;359:1985-94.
van der Valk RJ, Duijts L, Kerkhof M, Willemsen SP, Hofman A, Moll HA, et al.
Interaction of a 17q12 variant with both fetal and infant smoke exposure in the development of childhood asthma-like symptoms. Allergy 2012;67:767-74.
Sleiman PM, Flory J, Imielinski M, Bradfield JP, Annaiah K, Willis-Owen SA, et al.
Variants of DENND1B associated with asthma in children. N
Engl J Med 2010;362:36-44.
Berce V, Kozmus CE, Potočnik U. Association among ORMDL3 gene expression, 17q21 polymorphism and response to treatment with inhaled corticosteroids in children with asthma. Pharmacogenomics J 2013;13:523-9.
Zhai WH, Song CY, Huang ZG, Sha H. Correlation between the genetic polymorphism of ORMDL3 gene and asthma risk: A meta-analysis. Genet Mol Res 2015;14:7101-12.
Vercelli D. Discovering susceptibility genes for asthma and allergy. Nat Rev Immunol 2008;8:169-82.
Wills-Karp M, Ewart SL. Time to draw breath: Asthma-susceptibility genes are identified. Nat Rev Genet 2004;5:376-87.
Bikman BT. A role for sphingolipids in the pathophysiology of obesity-induced inflammation. Cell Mol Life Sci 2012;69:2135-46.
| Article Access Statistics|
| Viewed||1911 |
| Printed||94 |
| Emailed||0 |
| PDF Downloaded||286 |
| Comments ||[Add] |