Immunological characteristics and management considerations in obese patients with asthma

References

• Ng M, Fleming T, Robinson M, et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 2014;384(9945):766-81
   PubMed Web of Science ®Google Scholar
• Beuther DA, Sutherland ER. Overweight, obesity, and incident asthma: a meta-analysis of prospective epidemiologic studies. Am J Respir Crit Care Med 2007;175(7):661-6
   PubMed Web of Science ®Google Scholar
• Schatz M, Hsu JW, Zeiger RS, et al. Phenotypes determined by cluster analysis in severe or difficult-to-treat asthma. J Allergy Clin Immunol 2014;133(6):1549-56
   PubMed Web of Science ®Google Scholar
• Dixon A. The treatment of asthma in obesity. Expert Rev Respir Med 2012;6(3):331-40
   PubMed Web of Science ®Google Scholar
• Shore SA. Obesity and asthma: lessons from animal models. J Appl Physiol 2007;102(2):516-28
   Google Scholar
• Speakman J, Hambly C, Mitchell S, Krol E. The contribution of animal models to the study of obesity. Lab Anim 2008;42(4):413-32
   Google Scholar
• Leiria LO, Martins MA, Saad MJ. Obesity and asthma: beyond T2 inflammation. Metabolism 2015;64(2):172-81
   Google Scholar
• Zhang Y, Proenca R, Maffei M, et al. Positional cloning of the mouse obese gene and its human homologue. Nature 1994;372(6505):425-32
   PubMed Web of Science ®Google Scholar
• Considine RV, Caro JF. Leptin and the regulation of body weight. Int J Biochem Cell Biol 1997;29(11):1255-72
   Google Scholar
• Okamoto Y, Kihara S, Funahashi T, et al. Adiponectin: a key adipocytokine in metabolic syndrome. Clin Sci (Lond) 2006;110(3):267-78
   PubMed Web of Science ®Google Scholar
• Despres JP, Lemieux I. Abdominal obesity and metabolic syndrome. Nature 2006;444(7121):881-7
   PubMed Web of Science ®Google Scholar
• Campfield LA, Smith FJ, Guisez Y, et al. Recombinant mouse OB protein: evidence for a peripheral signal linking adiposity and central neural networks. Science 1995;269(5223):546-9
   PubMed Web of Science ®Google Scholar
• Tartaglia LA, Dembski M, Weng X, et al. Identification and expression cloning of a leptin receptor, OB-R. Cell 1995;83(7):1263-71
   PubMed Web of Science ®Google Scholar
• Ingalls AM, Dickie MM, Snell GD. Obese, a new mutation in the house mouse. J Hered 1950;41(12):317-18
   PubMed Web of Science ®Google Scholar
• Hummel KP, Dickie MM, Coleman DL. Diabetes, a new mutation in the mouse. Science 1966;153(3740):1127-8
   PubMed Web of Science ®Google Scholar
• Lu FL, Johnston RA, Flynt L, et al. Increased pulmonary responses to acute ozone exposure in obese db/db mice. Am J Physiol Lung Cell Mol Physiol 2006;290(5):L856-65
   Google Scholar
• Rivera-Sanchez YM, Johnston RA, Schwartzman IN, et al. Differential effects of ozone on airway and tissue mechanics in obese mice. J Appl Physiol (1985) 2004;96(6):2200-6
   Google Scholar
• 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(5):L1013-20
   Google Scholar
• Johnston RA, Zhu M, Rivera-Sanchez YM, et al. Allergic airway responses in obese mice. Am J Respir Crit Care Med 2007;176(7):650-8
   PubMed Web of Science ®Google Scholar
• Wolf AM, Wolf D, Rumpold H, et al. Adiponectin induces the anti-inflammatory cytokines IL-10 and IL-1RA in human leukocytes. Biochem Biophys Res Commun 2004;323(2):630-5
   PubMed Web of Science ®Google Scholar
• Medoff BD, Okamoto Y, Leyton P, et al. Adiponectin deficiency increases allergic airway inflammation and pulmonary vascular remodeling. Am J Respir Cell Mol Biol 2009;41(4):397-406
   PubMed Web of Science ®Google Scholar
• Kasahara DI, Kim HY, Mathews JA, et al. Pivotal role of IL-6 in the hyperinflammatory responses to subacute ozone in adiponectin-deficient mice. Am J Physiol Lung Cell Mol Physiol 2014;306(6):L508-20
   Google Scholar
• Shore SA, Terry RD, Flynt L, et al. Adiponectin attenuates allergen-induced airway inflammation and hyperresponsiveness in mice. J Allergy Clin Immunol 2006;118(2):389-95
   PubMed Web of Science ®Google Scholar
• Coleman DL, Eicher EM. Fat (fat) and tubby (tub): two autosomal recessive mutations causing obesity syndromes in the mouse. J Hered 1990;81(6):424-7
   Google Scholar
• Johnston RA, Theman TA, Shore SA. Augmented responses to ozone in obese carboxypeptidase E-deficient mice. Am J Physiol Regul Integr Comp Physiol 2006;290(1):R126-33
   PubMed Web of Science ®Google Scholar
• Dahm PH, Richards JB, Karmouty-Quintana H, et al. Effect of antigen sensitization and challenge on oscillatory mechanics of the lung and pulmonary inflammation in obese carboxypeptidase E-deficient mice. Am J Physiol Regul Integr Comp Physiol 2014;307(6):R621-33
   Google Scholar
• Yang ZH, Miyahara H, Takeo J, Katayama M. Diet high in fat and sucrose induces rapid onset of obesity-related metabolic syndrome partly through rapid response of genes involved in lipogenesis, insulin signalling and inflammation in mice. Diabetol Metab Syndr 2012;4(1):32
   PubMedGoogle Scholar
• Ge XN, Greenberg Y, Hosseinkhani MR, et al. High-fat diet promotes lung fibrosis and attenuates airway eosinophilia after exposure to cockroach allergen in mice. Exp Lung Res 2013;39(9):365-78
   PubMed Web of Science ®Google Scholar
• Calixto MC, Lintomen L, Schenka A, et al. Obesity enhances eosinophilic inflammation in a murine model of allergic asthma. Br J Pharmacol 2010;159(3):617-25
   PubMed Web of Science ®Google Scholar
• Mathews JA, Wurmbrand AP, Ribeiro L, et al. Induction of IL-17A precedes development of airway hyperresponsiveness during diet-induced obesity and correlates with complement factor D. Front Immunol 2014;5:440
   PubMed Web of Science ®Google Scholar
• Wilson RH, Whitehead GS, Nakano H, et al. Allergic sensitization through the airway primes Th17-dependent neutrophilia and airway hyperresponsiveness. Am J Respir Crit Care Med 2009;180(8):720-30
   PubMed Web of Science ®Google Scholar
• Williams AS, Chen L, Kasahara DI, et al. Obesity and airway responsiveness: role of TNFR2. Pulm Pharmacol Ther 2013;26(4):444-54
   Google Scholar
• Kim HY, Lee HJ, Chang YJ, et al. Interleukin-17-producing innate lymphoid cells and the NLRP3 inflammasome facilitate obesity-associated airway hyperreactivity. Nat Med 2014;20(1):54-61
   PubMed Web of Science ®Google Scholar
• Ather JL, Foley KL, Suratt BT, et al. Airway epithelial NF-kappaB activation promotes the ability to overcome inhalational antigen tolerance. Clin Exp Allergy 2015. [Epub ahead of print]
   Google Scholar
• Martin RA, Ather JL, Lundblad LK, et al. Interleukin-1 receptor and caspase-1 are required for the Th17 response in nitrogen dioxide-promoted allergic airway disease. Am J Respir Cell Mol Biol 2013;48(5):655-64
   PubMed Web of Science ®Google Scholar
• Coppack SW. Pro-inflammatory cytokines and adipose tissue. Proc Nutr Soc 2001;60(3):349-56
   PubMed Web of Science ®Google Scholar
• Shore SA. Obesity and asthma: possible mechanisms. J Allergy Clin Immunol 2008;121(5):1087-93; quiz 1094-1085
   PubMed Web of Science ®Google Scholar
• Priceman SJ, Kujawski M, Shen S, et al. Regulation of adipose tissue T cell subsets by Stat3 is crucial for diet-induced obesity and insulin resistance. Proc Natl Acad Sci USA 2013;110(32):13079-84
   PubMed Web of Science ®Google Scholar
• Cipolletta D. Adipose tissue-resident regulatory T cells: phenotypic specialization, functions and therapeutic potential. Immunology 2014;142(4):517-25
   Google Scholar
• Zhu M, Williams AS, Chen L, et al. Role of TNFR1 in the innate airway hyperresponsiveness of obese mice. J Appl Physiol (1985) 2012;113(9):1476-85
   Google Scholar
• Nie Z, Jacoby DB, Fryer AD. Hyperinsulinemia potentiates airway responsiveness to parasympathetic nerve stimulation in obese rats. Am J Respir Cell Mol Biol 2014;51(2):251-61
   Google Scholar
• Arteaga-Solis E, Zee T, Emala CW, et al. Inhibition of leptin regulation of parasympathetic signaling as a cause of extreme body weight-associated asthma. Cell Metab 2013;17(1):35-48
   Google Scholar
• Ramalho R, Almeida J, Beltrao M, et al. Substance P antagonist improves both obesity and asthma in a mouse model. Allergy 2013;68(1):48-54
   Google Scholar
• Ramalho R, Almeida J, Beltrao M, et al. Neurogenic inflammation in allergen-challenged obese mice: a missing link in the obesity-asthma association? Exp Lung Res 2012;38(6):316-24
   PubMed Web of Science ®Google Scholar
• Ramalho R, Almeida J, Fernandes R, et al. Neurokinin-1 receptor, a new modulator of lymphangiogenesis in obese-asthma phenotype. Life Sci 2013;93(4):169-77
   PubMed Web of Science ®Google Scholar
• Ober C, Chupp GL. The chitinase and chitinase-like proteins: a review of genetic and functional studies in asthma and immune-mediated diseases. Curr Opin Allergy Clin Immunol 2009;9(5):401-8
   Google Scholar
• Lee CG, Elias JA. Role of breast regression protein-39/YKL-40 in asthma and allergic responses. Allergy Asthma Immunol Res 2010;2(1):20-7
   Google Scholar
• Ahangari F, Sood A, Ma B, et al. Chitinase 3-like-1 regulates both visceral fat accumulation and asthma-like Th2 inflammation. Am J Respir Crit Care Med 2015;191(7):746-57
   PubMed Web of Science ®Google Scholar
• Allan KM, Prabhu N, Craig LC, et al. Maternal vitamin D and E intakes during pregnancy are associated with asthma in children. Eur Respir J 2015;45(4):1027-36
   PubMed Web of Science ®Google Scholar
• Cook-Mills JM, Avila PC. Vitamin E and D regulation of allergic asthma immunopathogenesis. Int Immunopharmacol 2014;23(1):364-72
   Google Scholar
• Weiss ST, Litonjua AA. The in utero effects of maternal vitamin D deficiency: how it results in asthma and other chronic diseases. Am J Respir Crit Care Med 2011;183(10):1286-7
   PubMedGoogle Scholar
• Weiss ST. Bacterial components plus vitamin D: the ultimate solution to the asthma (autoimmune disease) epidemic? J Allergy Clin Immunol 2011;127(5):1128-30
   PubMed Web of Science ®Google Scholar
• Chen F, Marquez H, Kim YK, et al. Prenatal retinoid deficiency leads to airway hyperresponsiveness in adult mice. J Clin Invest 2014;124(2):801-11
   Google Scholar
• Paul G, Brehm JM, Alcorn JF, et al. Vitamin D and asthma. Am J Respir Crit Care Med 2012;185(2):124-32
   PubMed Web of Science ®Google Scholar
• Ly NP, Litonjua A, Gold DR, Celedon JC. Gut microbiota, probiotics, and vitamin D: interrelated exposures influencing allergy, asthma, and obesity? J Allergy Clin Immunol 2011;127(5):1087-94; quiz 1095-1086
   PubMedGoogle Scholar
• Bonet ML, Ribot J, Felipe F, Palou A. Vitamin A and the regulation of fat reserves. Cell Mol Life Sci 2003;60(7):1311-21
   Google Scholar
• Backhed F, Ding H, Wang T, et al. The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci USA 2004;101(44):15718-23
   PubMed Web of Science ®Google Scholar
• Ley RE, Backhed F, Turnbaugh P, et al. Obesity alters gut microbial ecology. Proc Natl Acad Sci USA 2005;102(31):11070-5
   PubMed Web of Science ®Google Scholar
• Turnbaugh PJ, Ley RE, Mahowald MA, et al. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 2006;444(7122):1027-31
   PubMed Web of Science ®Google Scholar
• Trompette A, Gollwitzer ES, Yadava K, et al. Gut microbiota metabolism of dietary fiber influences allergic airway disease and hematopoiesis. Nat Med 2014;20(2):159-66
   PubMed Web of Science ®Google Scholar
• Holguin F, Bleecker ER, Busse WW, et al. Obesity and asthma: an association modified by age of asthma onset. J Allergy Clin Immunol 2011;127(6):1486-1493.e1482
   PubMed Web of Science ®Google Scholar
• Sutherland ER, Goleva E, King TS, et al. Cluster analysis of obesity and asthma phenotypes. PLoS One 2012;7(5):e36631
   PubMed Web of Science ®Google Scholar
• Juniper EF, O’byrne PM, Guyatt GH, et al. Development and validation of a questionnaire to measure asthma control. Eur Respir J 1999;14(4):902-7
   PubMed Web of Science ®Google Scholar
• Dixon AE, Pratley RE, Forgione PM, et al. Effects of obesity and bariatric surgery on airway hyperresponsiveness, asthma control, and inflammation. J Allergy Clin Immunol 2011;128(3):508-15; e501-502
   PubMed Web of Science ®Google Scholar
• Mclaughlin T, Liu LF, Lamendola C, et al. T-cell profile in adipose tissue is associated with insulin resistance and systemic inflammation in humans. Arterioscler Thromb Vasc Biol 2014;34(12):2637-43
   PubMed Web of Science ®Google Scholar
• Rastogi D, Fraser S, Oh J, et al. Inflammation, metabolic dysregulation, and pulmonary function among obese urban adolescents with asthma. Am J Respir Crit Care Med 2015;191(2):149-60
   PubMed Web of Science ®Google Scholar
• Fracchia KM, Walsh CM. Metabolic mysteries of the inflammatory response: T cell polarization and plasticity. Int Rev Immunol 2015;34(1):3-18
   Web of Science ®Google Scholar
• De Vries A, Hazlewood L, Fitch PM, et al. High-fat feeding redirects cytokine responses and decreases allergic airway eosinophilia. Clin Exp Allergy 2009;39(5):731-9
   Google Scholar
• Sandig H, Mcdonald J, Gilmour J, et al. Human Th2 cells selectively express the orexigenic peptide, pro-melanin-concentrating hormone. Proc Natl Acad Sci USA 2007;104(30):12440-4
   Google Scholar
• Todd DC, Armstrong S, D’silva L, et al. Effect of obesity on airway inflammation: a cross-sectional analysis of body mass index and sputum cell counts. Clin Exp Allergy 2007;37(7):1049-54
   PubMed Web of Science ®Google Scholar
• Sutherland TJ, Cowan JO, Young S, et al. The association between obesity and asthma: interactions between systemic and airway inflammation. Am J Respir Crit Care Med 2008;178(5):469-75
   PubMed Web of Science ®Google Scholar
• Van Veen IH, Ten Brinke A, Sterk PJ, et al. Airway inflammation in obese and nonobese patients with difficult-to-treat asthma. Allergy 2008;63(5):570-4
   PubMed Web of Science ®Google Scholar
• Lessard A, Turcotte H, Cormier Y, Boulet LP. Obesity and asthma: a specific phenotype? Chest 2008;134(2):317-23
   PubMed Web of Science ®Google Scholar
• Desai D, Newby C, Symon FA, et al. Elevated sputum interleukin-5 and submucosal eosinophilia in obese individuals with severe asthma. Am J Respir Crit Care Med 2013;188(6):657-63
   PubMed Web of Science ®Google Scholar
• Kato H, Ueki S, Kamada R, et al. Leptin has a priming effect on eotaxin-induced human eosinophil chemotaxis. Int Arch Allergy Immunol 2011;155(4):335-44
   PubMed Web of Science ®Google Scholar
• Grotta MB, Squebola-Cola DM, Toro AA, et al. Obesity increases eosinophil activity in asthmatic children and adolescents. BMC Pulm Med 2013;13:39
   Web of Science ®Google Scholar
• Telenga ED, Tideman SW, Kerstjens HA, et al. Obesity in asthma: more neutrophilic inflammation as a possible explanation for a reduced treatment response. Allergy 2012;67(8):1060-8
   PubMed Web of Science ®Google Scholar
• Scott HA, Gibson PG, Garg ML, et al. Dietary restriction and exercise improve airway inflammation and clinical outcomes in overweight and obese asthma: a randomized trial. Clin Exp Allergy 2013;43(1):36-49
   PubMed Web of Science ®Google Scholar
• Wood LG, Garg ML, Gibson PG. A high-fat challenge increases airway inflammation and impairs bronchodilator recovery in asthma. J Allergy Clin Immunol 2011;127(5):1133-40
   PubMed Web of Science ®Google Scholar
• Lumeng CN, Bodzin JL, Saltiel AR. Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest 2007;117(1):175-84
   PubMed Web of Science ®Google Scholar
• Mccubbrey AL, Curtis JL. Efferocytosis and lung disease. Chest 2013;143(6):1750-7
   PubMed Web of Science ®Google Scholar
• Fernandez-Boyanapalli R, Goleva E, Kolakowski C, et al. Obesity impairs apoptotic cell clearance in asthma. J Allergy Clin Immunol 2013;131(4):1041-7; 1047.e1041-1043
   Google Scholar
• Jensen ME, Gibson PG, Collins CE, Wood LG. Airway and systemic inflammation in obese children with asthma. Eur Respir J 2013;42(4):1012-19
   PubMed Web of Science ®Google Scholar
• Lugogo NL, Hollingsworth JW, Howell DL, et al. Alveolar macrophages from overweight/obese subjects with asthma demonstrate a proinflammatory phenotype. Am J Respir Crit Care Med 2012;186(5):404-11
   PubMed Web of Science ®Google Scholar
• Mancuso P, Myers MGJr, Goel D, et al. Ablation of leptin receptor-mediated ERK activation impairs host defense against Gram-negative pneumonia. J Immunol 2012;189(2):867-75
   Google Scholar
• Sideleva O, Suratt BT, Black KE, et al. Obesity and asthma: an inflammatory disease of adipose tissue not the airway. Am J Respir Crit Care Med 2012;186(7):598-605
   PubMed Web of Science ®Google Scholar
• Sutherland ER, Goleva E, Strand M, et al. Body mass and glucocorticoid response in asthma. Am J Respir Crit Care Med 2008;178(7):682-7
   PubMed Web of Science ®Google Scholar
• Periyalil HA, Wood LG, Scott HA, et al. Macrophage activation, age and sex effects of immunometabolism in obese asthma. Eur Respir J 2015;45(2):388-95
   PubMed Web of Science ®Google Scholar
• Moore WC, Meyers DA, Wenzel SE, et al. Identification of asthma phenotypes using cluster analysis in the Severe Asthma Research Program. Am J Respir Crit Care Med 2010;181(4):315-23
   PubMed Web of Science ®Google Scholar
• Komakula S, Khatri S, Mermis J, et al. Body mass index is associated with reduced exhaled nitric oxide and higher exhaled 8-isoprostanes in asthmatics. Respir Res 2007;8:32
   PubMed Web of Science ®Google Scholar
• Holguin F, Comhair SA, Hazen SL, et al. An association between L-arginine/asymmetric dimethyl arginine balance, obesity, and the age of asthma onset phenotype. Am J Respir Crit Care Med 2013;187(2):153-9
   PubMed Web of Science ®Google Scholar
• Kacmarek RM, Ripple R, Cockrill BA, et al. Inhaled nitric oxide. A bronchodilator in mild asthmatics with methacholine-induced bronchospasm. Am J Respir Crit Care Med 1996;153(1):128-35
   Google Scholar
• Peters-Golden M, Swern A, Bird SS, et al. Influence of body mass index on the response to asthma controller agents. Eur Respir J 2006;27(3):495-503
   PubMed Web of Science ®Google Scholar
• Boulet LP, Franssen E. Influence of obesity on response to fluticasone with or without salmeterol in moderate asthma. Respir Med 2007;101(11):2240-7
   PubMed Web of Science ®Google Scholar
• Parikh SJ, Edelman M, Uwaifo GI, et al. The relationship between obesity and serum 1,25-dihydroxy vitamin D concentrations in healthy adults. J Clin Endocrinol Metab 2004;89(3):1196-9
   PubMed Web of Science ®Google Scholar
• Chambers ES, Suwannasaen D, Mann EH, et al. 1alpha,25-dihydroxyvitamin D3 in combination with transforming growth factor-beta increases the frequency of Foxp3(+) regulatory T cells through preferential expansion and usage of interleukin-2. Immunology 2014;143(1):52-60
   Google Scholar
• Aljada A, Mohanty P, Ghanim H, et al. Increase in intranuclear nuclear factor kappaB and decrease in inhibitor kappaB in mononuclear cells after a mixed meal: evidence for a proinflammatory effect. Am J Clin Nutr 2004;79(4):682-90
   PubMed Web of Science ®Google Scholar
• Deopurkar R, Ghanim H, Friedman J, et al. Differential effects of cream, glucose, and orange juice on inflammation, endotoxin, and the expression of Toll-like receptor-4 and suppressor of cytokine signaling-3. Diabetes Care 2010;33(5):991-7
   PubMed Web of Science ®Google Scholar
• Patel C, Ghanim H, Ravishankar S, et al. Prolonged reactive oxygen species generation and nuclear factor-kappaB activation after a high-fat, high-carbohydrate meal in the obese. J Clin Endocrinol Metab 2007;92(11):4476-9
   PubMed Web of Science ®Google Scholar
• Al-Alwan A, Bates JH, Chapman DG, et al. The nonallergic asthma of obesity. A matter of distal lung compliance. Am J Respir Crit Care Med 2014;189(12):1494-502
   PubMed Web of Science ®Google Scholar
• Bates JH, Dixon AE. Potential role of the airway wall in the asthma of obesity. J Appl Physiol 2015;118(1):36-41
   Google Scholar
• Kapadia SG, Wei C, Bartlett SJ, et al. Obesity and symptoms of depression contribute independently to the poor asthma control of obesity. Respir Med 2014;108(8):1100-7
   PubMed Web of Science ®Google Scholar
• Dixon AE, Clerisme-Beaty EM, Sugar EA, et al. Effects of obstructive sleep apnea and gastroesophageal reflux disease on asthma control in obesity. J Asthma 2011;48(7):707-13
   Web of Science ®Google Scholar
• Chen Y, Dales R, Jiang Y. The association between obesity and asthma is stronger in nonallergic than allergic adults. Chest 2006;130(3):890-5
   Google Scholar
• Boulet LP, Turcotte H, Martin J, Poirier P. Effect of bariatric surgery on airway response and lung function in obese subjects with asthma. Respir Med 2012;106(5):651-60
   PubMed Web of Science ®Google Scholar
• Ma J, Strub P, Xiao L, et al. Behavioral weight loss and physical activity intervention in obese adults with asthma. A randomized trial. Ann Am Thorac Soc 2015;12(1):1-11
   PubMed Web of Science ®Google Scholar
• Castro M, King TS, Kunselman SJ, et al. Effect of vitamin D3 on asthma treatment failures in adults with symptomatic asthma and lower vitamin D levels: the VIDA randomized clinical trial. JAMA 2014;311(20):2083-91
   PubMed Web of Science ®Google Scholar
• Lu KD, Breysse PN, Diette GB, et al. Being overweight increases susceptibility to indoor pollutants among urban children with asthma. J Allergy Clin Immunol 2013;131(4):1017-23; 1023.e1011-1013
   PubMed Web of Science ®Google Scholar
• Dong GH, Qian Z, Liu MM, et al. Obesity enhanced respiratory health effects of ambient air pollution in Chinese children: the Seven Northeastern Cities study. Int J Obes 2013;37(1):94-100
   PubMed Web of Science ®Google Scholar