The effect of diet composition on serum leptin levels To the Editor: I read with interest the report by Nehus et al in which the authors aimed to investigate the relative associations of renal function, obesity, and inflammation with serum leptin levels in children with chronic kidney disease.1 Increased leptin production was found to be associated with female sex, older age; adiposity and renal function were not associated with serum leptin level. However, some issues should be discussed. As indicated in previous studies, serum leptin levels can easily be affected by diet composition and supplements, particularly omega-3 fatty acid.2,3 Kratz et al proposed that serum leptin levels were affected by the high amount of alpha-linolenic acid.2 Omega-3 was observed to decrease circulating levels of leptin in non-obese subjects; however, omega-3-associated increases in leptin levels have been observed in obese subjects.3 Moreover, in a study evaluating the effects of fasting on serum leptin levels in lean children, short-term fasting (6 hours) was shown to cause a decline in leptin levels, and this decline was claimed to be caused by the suppression of insulin secretion.4 However, information about the nutritional/dietary intake of nutrients, which possibly affects serum leptin levels, is missing in the study. On the other hand, there are studies providing conflicting results about the serum leptin levels and nutritional status.5-7 Therefore, it would be important to assess nutritional status of patients in the original study. Nevertheless, the nutritional status of participants has not been evaluated and/or there is no effective laboratory indicator identifying malnutrition provided in the current study. In conclusion, assessing the usage of drugs/dietary supplements likely to affect serum leptin levels and nutritional status of the participants would improve credibility of the study.
Erdim Sertoglu, MD Department of Medical Biochemistry Anittepe Dispensary Ankara Mevki Military Hospital Ankara, Turkey http://dx.doi.org/10.1016/j.jpeds.2015.01.028
References 1. Nehus E, Furth S, Warady B, Mitsnefes M. Correlates of leptin in children with chronic kidney disease. J Pediatr 2014;165:825-9. 2. Kratz M, von Eckardstein A, Fobker M, Buyken A, Posny N, Schulte H, et al. The impact of dietary fat composition on serum leptin concentrations in healthy nonobese men and women. J Clin Endocrinol Metab 2002;87:5008-14. 3. Gray B, Steyn F, Davies PS, Vitetta L. Omega-3 fatty acids: a review of the effects on adiponectin and leptin and potential implications for obesity management. Eur J Clin Nutr 2013;67:1234-42. 1324
4. Levitt Katz LE, Abraham M, Johansen L, Jawad AF. Leptin levels decline steadily during prolonged fasting in lean children. J Pediatr 2006;149:798802. 5. Czaja-Bulsa G, Garanty-Bogacka B, Gebala A, Syrenicz M, Krupa B. Serum leptin concentrations in children with mild and moderate malnutrition. Ann Acad Med Stetin 2010;56:22-7. 6. Besbas N, Ozaltin F, Cos¸kun T, Ozalp S, Saatc¸i U, Bakkaloglu A, et al. Relationship of leptin and insulin-like growth factor I to nutritional status in hemodialyzed children. Pediatr Nephrol 2003;18:1255-9. 7. Peng DZ, Liu XW, Huang L, Zhu XF, Zheng YQ, Wang LX. Relationship between leptin and chronic inflammatory state in uremic patients. Eur Rev Med Pharmacol Sci 2014;18:2882-5.
Reply To the Editor: Sertoglu raises the question of the potential effects of nutrition and diet on serum leptin levels, specifically mentioning omega-3 fatty acids. We acknowledge that diets rich in omega-3 fatty acids have been associated with changes in leptin levels. We did not have specific information on the diet of study participants. As this study was observational and did not impose any strict adherence to a particular diet, we do not suspect that this would have had a large effect on serum leptin levels. Regarding nutritional status, data associating inflammation-associated cachexia with leptin is largely limited to animal models of nephrectomized mice. Our study involved subjects with mild to moderate chronic kidney disease, who typically do not display uremic cachexia. The median body mass index (BMI) percentile of our cohort was 59, and only 4% had a BMI less than the fifth percentile. Therefore, it was not the ideal set of patients to investigate the role of leptin in uremia-associated cachexia. Furthermore, as the authors mentioned, clinical studies investigating the association of leptin with malnutrition have not been conclusive. Nevertheless, we do acknowledge the limitations raised by the reviewers. However, we feel that our main findings are still credible and would not be altered had we included diet composition or measures of nutritional status (other than BMI) in our analysis.
Edward Nehus, MD Mark Mitsnefes, MD Division of Nephrology and Hypertension Cincinnati Children’s Hospital Medical Center Cincinnati, Ohio http://dx.doi.org/10.1016/j.jpeds.2015.02.051
Treatment of asthma based on symptoms To the Editor: We read with interest the report by Schifano et al1 but we disagree with authors’ conclusions. The mismatch between
Vol. 166, No. 5 May 2015 asthma symptom and spirometry in childhood has been documented.2 There is little evidence that addition of biomarkers and spirometry to validate symptom score improves asthma control.3 From Schifano et al we can infer that a substantial number of children with mild asthma should be treated with inhaled steroids based on a spirometry-determined severity. Conversely, we believe that this is a deleterious consequence of the customary use of spirometry. The majority of children have mild asthma, with a good long-term prognosis.4 In mild asthma, spirometric abnormalities are infrequent, with a risk of serious asthma exacerbations identical to that of children with normal spirometry.5 Strunk et al demonstrated that the clinical improvement in the control of asthma achieved during 4-6 years of continuous treatment with budesonide does not persist after treatment is discontinued; conversely, a significant height reduction persists.6 Therefore, we should be careful when prescribing treatments based only on spirometric criteria in patients who are clinically well. In our experience, the limitation of treatment to clinically-determined persistent asthma led to an important reduction of inhaled corticosteroid prescription without any increase in reliever drug use.7 Finally, we should not forget that therapy directed by spirometry removes any meaning to self-management, which is essentially based on a careful evaluation of symptom scores.
Cristina Bibalo, MD Giorgio Longo, MD University of Trieste Alessandro Ventura, MD University of Trieste Institute for Maternal and Child Health IRCCS Burlo Garofolo Trieste, Italy
7. Berti I, Longo G, Visintin S. Treatment of mild asthma. N Engl J Med 2005;353:424-7. author reply 424-7.
Reply To the Editor: We appreciate the comments by Bibalo et al regarding the use of spirometry in children with asthma. Our sample population is not representative of the general population but is representative of a low-income, publicly-insured, underserved, minority population, a group with high asthma morbidity. For this population, spirometry abnormalities were common and are consistent with poorer outcomes. What is not known, however, is whether these abnormalities are reversible with therapy. Use of inhaled corticosteroids, however, has clearly been shown to increase the number of symptom-free days in children with persistent disease. Thus, we concur with the current National Asthma Education and Prevention Program Expert Panel Report 3 (NAEPP-EPR-3) recommendation that the risk of a small decrease in height (approximately 0.9 cm in total) is balanced by the benefits of inhaled corticosteroids for children with persistent asthma, and that spirometry plays an important part in asthma management in children. Michelle M. Cloutier, MD Jessica P. Hollenbach, PhD Department of Pediatrics University of Connecticut Health Center Children’s Center for Community Research Connecticut Children’s Medical Center Hartford, Connecticut http://dx.doi.org/10.1016/j.jpeds.2015.01.035
Spirometry remains an unfulfilled right for children with asthma
http://dx.doi.org/10.1016/j.jpeds.2015.01.029
References 1. Schifano ED, Hollenbach JP, Cloutier MM. Mismatch between asthma symptoms and spirometry: implications for managing asthma in children. J Pediatr 2014;165:997-1002. 2. Bacharier LB, Strunk RC, Mauger D, White D, Lemanske RF Jr, Sorkness CA. Classifying asthma severity in children mismatch between symptoms, medication use, and lung function. Am J Respir Crit Care Med 2004;170:426-32. 3. Turner S, Paton J, Higgins B, Douglas G. British guidelines on the management of asthma: what’s new for 2011? Thorax 2011;66:1104-5. 4. Tai A, Tran H, Roberts M, Clarke N, Gibson AM, Vidmar S, et al. Outcomes of childhood asthma to the age of 50 years. J Allergy Clin Immunol 2014;133:1572-8.e3. 5. Fuhlbrigge AL, Weiss ST, Kuntz KM, Paltiel AD, CAMP Research Group. Forced expiratory volume in 1 second percentage improves the classification of severity among children with asthma. Pediatrics 2006;118:e347-55. 6. Strunk RC, Sternberg AL, Szefler SJ, Zeiger RS, Bender B, Tonascia J, Childhood Asthma Management Program (CAMP) Research Group. Long-term budesonide or nedocromil treatment, once discontinued, does not alter the course of mild to moderate asthma in children and adolescents. J Pediatr 2009;154:682-7.
To the Editor: Spirometry testing continues to be underused even though, when appropriately used, its effectiveness is widely documented, and expert panel reports stress its utilization as part of asthma care. Schifano et al readdress the importance of spirometry and its implications in managing asthma in children.1 There are 2 main findings and implications from their work. The first relates to the role of pediatricians in diagnosing and monitoring childhood asthma appropriately, and the second has to do with the essential value of spirometry in defining asthma severity. Although the measurement of lung function should lead to more rational treatment and should, therefore, be of practical value, we have previously found that only 30% of Italian children with asthma are referred by their pediatrician/general practitioner to specialists for spirometry.2 This increases to 35% in severe cases of asthma (defined as frequent users of asthma medications). Furthermore, it has been reported that females have a lower level of asthma control in adulthood,3 yet females, independently of disease severity, are referred for spirometry less than males, with a 1325
Erdim Sertoglu, MD Department of Medical Biochemistry Anittepe Dispensary Ankara Mevki Military Hospital Ankara, Turkey http://dx.doi.org/10.1016/j.jpeds.2015.01.028
References 1. Nehus E, Furth S, Warady B, Mitsnefes M. Correlates of leptin in children with chronic kidney disease. J Pediatr 2014;165:825-9. 2. Kratz M, von Eckardstein A, Fobker M, Buyken A, Posny N, Schulte H, et al. The impact of dietary fat composition on serum leptin concentrations in healthy nonobese men and women. J Clin Endocrinol Metab 2002;87:5008-14. 3. Gray B, Steyn F, Davies PS, Vitetta L. Omega-3 fatty acids: a review of the effects on adiponectin and leptin and potential implications for obesity management. Eur J Clin Nutr 2013;67:1234-42. 1324
4. Levitt Katz LE, Abraham M, Johansen L, Jawad AF. Leptin levels decline steadily during prolonged fasting in lean children. J Pediatr 2006;149:798802. 5. Czaja-Bulsa G, Garanty-Bogacka B, Gebala A, Syrenicz M, Krupa B. Serum leptin concentrations in children with mild and moderate malnutrition. Ann Acad Med Stetin 2010;56:22-7. 6. Besbas N, Ozaltin F, Cos¸kun T, Ozalp S, Saatc¸i U, Bakkaloglu A, et al. Relationship of leptin and insulin-like growth factor I to nutritional status in hemodialyzed children. Pediatr Nephrol 2003;18:1255-9. 7. Peng DZ, Liu XW, Huang L, Zhu XF, Zheng YQ, Wang LX. Relationship between leptin and chronic inflammatory state in uremic patients. Eur Rev Med Pharmacol Sci 2014;18:2882-5.
Reply To the Editor: Sertoglu raises the question of the potential effects of nutrition and diet on serum leptin levels, specifically mentioning omega-3 fatty acids. We acknowledge that diets rich in omega-3 fatty acids have been associated with changes in leptin levels. We did not have specific information on the diet of study participants. As this study was observational and did not impose any strict adherence to a particular diet, we do not suspect that this would have had a large effect on serum leptin levels. Regarding nutritional status, data associating inflammation-associated cachexia with leptin is largely limited to animal models of nephrectomized mice. Our study involved subjects with mild to moderate chronic kidney disease, who typically do not display uremic cachexia. The median body mass index (BMI) percentile of our cohort was 59, and only 4% had a BMI less than the fifth percentile. Therefore, it was not the ideal set of patients to investigate the role of leptin in uremia-associated cachexia. Furthermore, as the authors mentioned, clinical studies investigating the association of leptin with malnutrition have not been conclusive. Nevertheless, we do acknowledge the limitations raised by the reviewers. However, we feel that our main findings are still credible and would not be altered had we included diet composition or measures of nutritional status (other than BMI) in our analysis.
Edward Nehus, MD Mark Mitsnefes, MD Division of Nephrology and Hypertension Cincinnati Children’s Hospital Medical Center Cincinnati, Ohio http://dx.doi.org/10.1016/j.jpeds.2015.02.051
Treatment of asthma based on symptoms To the Editor: We read with interest the report by Schifano et al1 but we disagree with authors’ conclusions. The mismatch between
Vol. 166, No. 5 May 2015 asthma symptom and spirometry in childhood has been documented.2 There is little evidence that addition of biomarkers and spirometry to validate symptom score improves asthma control.3 From Schifano et al we can infer that a substantial number of children with mild asthma should be treated with inhaled steroids based on a spirometry-determined severity. Conversely, we believe that this is a deleterious consequence of the customary use of spirometry. The majority of children have mild asthma, with a good long-term prognosis.4 In mild asthma, spirometric abnormalities are infrequent, with a risk of serious asthma exacerbations identical to that of children with normal spirometry.5 Strunk et al demonstrated that the clinical improvement in the control of asthma achieved during 4-6 years of continuous treatment with budesonide does not persist after treatment is discontinued; conversely, a significant height reduction persists.6 Therefore, we should be careful when prescribing treatments based only on spirometric criteria in patients who are clinically well. In our experience, the limitation of treatment to clinically-determined persistent asthma led to an important reduction of inhaled corticosteroid prescription without any increase in reliever drug use.7 Finally, we should not forget that therapy directed by spirometry removes any meaning to self-management, which is essentially based on a careful evaluation of symptom scores.
Cristina Bibalo, MD Giorgio Longo, MD University of Trieste Alessandro Ventura, MD University of Trieste Institute for Maternal and Child Health IRCCS Burlo Garofolo Trieste, Italy
7. Berti I, Longo G, Visintin S. Treatment of mild asthma. N Engl J Med 2005;353:424-7. author reply 424-7.
Reply To the Editor: We appreciate the comments by Bibalo et al regarding the use of spirometry in children with asthma. Our sample population is not representative of the general population but is representative of a low-income, publicly-insured, underserved, minority population, a group with high asthma morbidity. For this population, spirometry abnormalities were common and are consistent with poorer outcomes. What is not known, however, is whether these abnormalities are reversible with therapy. Use of inhaled corticosteroids, however, has clearly been shown to increase the number of symptom-free days in children with persistent disease. Thus, we concur with the current National Asthma Education and Prevention Program Expert Panel Report 3 (NAEPP-EPR-3) recommendation that the risk of a small decrease in height (approximately 0.9 cm in total) is balanced by the benefits of inhaled corticosteroids for children with persistent asthma, and that spirometry plays an important part in asthma management in children. Michelle M. Cloutier, MD Jessica P. Hollenbach, PhD Department of Pediatrics University of Connecticut Health Center Children’s Center for Community Research Connecticut Children’s Medical Center Hartford, Connecticut http://dx.doi.org/10.1016/j.jpeds.2015.01.035
Spirometry remains an unfulfilled right for children with asthma
http://dx.doi.org/10.1016/j.jpeds.2015.01.029
References 1. Schifano ED, Hollenbach JP, Cloutier MM. Mismatch between asthma symptoms and spirometry: implications for managing asthma in children. J Pediatr 2014;165:997-1002. 2. Bacharier LB, Strunk RC, Mauger D, White D, Lemanske RF Jr, Sorkness CA. Classifying asthma severity in children mismatch between symptoms, medication use, and lung function. Am J Respir Crit Care Med 2004;170:426-32. 3. Turner S, Paton J, Higgins B, Douglas G. British guidelines on the management of asthma: what’s new for 2011? Thorax 2011;66:1104-5. 4. Tai A, Tran H, Roberts M, Clarke N, Gibson AM, Vidmar S, et al. Outcomes of childhood asthma to the age of 50 years. J Allergy Clin Immunol 2014;133:1572-8.e3. 5. Fuhlbrigge AL, Weiss ST, Kuntz KM, Paltiel AD, CAMP Research Group. Forced expiratory volume in 1 second percentage improves the classification of severity among children with asthma. Pediatrics 2006;118:e347-55. 6. Strunk RC, Sternberg AL, Szefler SJ, Zeiger RS, Bender B, Tonascia J, Childhood Asthma Management Program (CAMP) Research Group. Long-term budesonide or nedocromil treatment, once discontinued, does not alter the course of mild to moderate asthma in children and adolescents. J Pediatr 2009;154:682-7.
To the Editor: Spirometry testing continues to be underused even though, when appropriately used, its effectiveness is widely documented, and expert panel reports stress its utilization as part of asthma care. Schifano et al readdress the importance of spirometry and its implications in managing asthma in children.1 There are 2 main findings and implications from their work. The first relates to the role of pediatricians in diagnosing and monitoring childhood asthma appropriately, and the second has to do with the essential value of spirometry in defining asthma severity. Although the measurement of lung function should lead to more rational treatment and should, therefore, be of practical value, we have previously found that only 30% of Italian children with asthma are referred by their pediatrician/general practitioner to specialists for spirometry.2 This increases to 35% in severe cases of asthma (defined as frequent users of asthma medications). Furthermore, it has been reported that females have a lower level of asthma control in adulthood,3 yet females, independently of disease severity, are referred for spirometry less than males, with a 1325
