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July-September 2010


Asian Journal of

Paediatric Practice Contents

An IJCP Group Publication Dr Sanjiv Chopra Prof. of Medicine & Faculty Dean Harvard Medical School Group Consultant Editor

EdItorial

Dr Deepak Chopra Chief Editorial Advisor

Dr KK Aggarwal CMD, Publisher and Group Editor-in-Chief Dr Veena Aggarwal Joint MD and Group Executive Editor Anand Gopal Bhatnagar Editorial Anchor AJPP Speciality Board Chief Editor Dr (Mrs.) Swati Y Bhave Editorial Board International (Group) Dr Adenike Grange (Lagos Nigeria) Dr Alberto Bissot (Panama) Dr Anagha (New Zealand) Dr Andreas Constantopoulos (Greece) Dr Dilip Patel (USA) Dr Donald E Greydanus (USA) Dr Ellis D Avner (USA) Dr Giorgio Tamburlini (Italy) Dr Helen Pratt (USA) Dr James Tumwne (Kampala, Uganda) Dr Jesson Unni (Kerala) Prof. Jose Boix Ochoa (Barcelona) Dr Manuel Katz (Israel) Dr Manuel Moya (Spain) Dr MC Rahimy (West Africa) Dr Murat Yurdakok (Turkey) Dr Najwa Khuri-Bulos (Jordan) Dr Sergio Augusto Cabral (Brazil) Dr Shiv Aggarwal (Florida) Dr VB Sanghi (Michigan) Dr Yoshikatsu Eto (Japan) Dr Zulfiquar Bhutta (Pakistan) Dr Zulfi Bhutta (Pakistan) Anand S Vasudev (New Delhi)

Editorial

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Swati Y Bhave

From the desk of group editor-in-chief Smokers in the House, a Risk Factor for Hospitalization of Children with Flu

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KK Aggarwal

drug therapy Montelukast with Levocetirizine for Asthma and Allergic Rhinitis

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Aru Handa

practice guidelines Asthma Management in Pediatric Age Group

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IJCP Editorial Board Dr Alka Kriplani Asian Journal of Obs & Gynae Practice Dr VP Sood Asian Journal of Ear, Nose and Throat Dr Praveen Chandra Asian Journal of Clinical Cardiology Dr Swati Y Bhave Asian Journal of Paediatric Practice Dr Vijay Viswanathan The Asian Journal of Diabetology Dr M Paul Anand, Dr SK Parashar Cardiology Dr CR Anand Moses, Dr Sidhartha Das, Dr A Ramchandran, Dr Smith A Sethi Diabetology Dr Ajay Kumar Gastroenterology Dr Koushik Lahiri Dermatology Dr Georgi Abraham Nephrology Dr Sidharth Kumar Das Rheumatology Dr V Nagarajan Neurology Dr Thankam Verma, Dr Kamala Selvaraj Obs and Gyne

Advisory Bodies Heart Care Foundation of India Non-Resident Indians Chamber of Commerce & Industry World Fellowship of Religions

for the clinician The Coughing Child: Ensuring a Good Night’s Sleep

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KK Aggarwal, VP Sood

clinical algorithm Approach to Cough

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clinical question Acute Otitis Media in Children

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Asian Journal of

Paediatric Practice Contents

Published, Printed and Edited by Dr KK Aggarwal, on behalf of IJCP Publications Pvt. Ltd. and Published at Daryacha, 39, Hauz Khas Village, New Delhi - 110 016. E-mail: editorial@ijcp.com Printed at SR Offset, Chennai

clinical algorithm Nontoxic Infant or Young Child with Fever

Š Copyright 2010 IJCP Publications Pvt. Ltd All rights reserved. The copyright for all the editorial material contained in this journal, in the form of layout, content including images and design, is held by IJCP Publications Pvt. Ltd. No part of this publication may be published in any form whatsoever without the prior written permission of the publisher. Cover Photograph by Jeevan Vamsi

Editorial policies The purpose of IJCP Academy of CME is to serve the medical profession and provide print continuing medical education as a part of their social commitment. The information and opinions presented in IJCP group publications reflect the views of the authors, not those of the journal, unless so stated. Advertising is accepted only if judged to be in harmony with the purpose of the journal; however, IJCP group reserves the right to reject any advertising at its sole discretion. Neither acceptance nor rejection constitutes an endorsement by IJCP group of a particular policy, product or procedure. We believe that readers need to be aware of any affiliation or financial relationship (employment, consultancies, stock ownership, honoraria, etc.) between an author and any organization or entity that has a direct financial interest in the subject matter or materials the author is writing about. We inform the reader of any pertinent relationships disclosed. A disclosure statement, where appropriate, is published at the end of the relevant article.

Note Asian Journal of Paediatric Practice, does not guarantee, directly or indirectly, the quality or efficacy of any product or service described in the advertisements or other material which is commercial in nature in this issue.

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clinical study Relation Between Anemia and Blood Levels of Lead, Copper, Zinc and Iron among Children 21 Amal A Hegazy, Manal M Zaher, Manal A Abd el-hafez, Amal A Morsy, Raya A Saleh

Television Viewing and Sleep are Associated with Overweight among Urban and Semi-urban South Indian Children

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Rebecca Kuriyan, Swarnarekha Bhat, Tinku Thomas, Mario Vaz, Anura V Kurpad

photo quiz Infant with Vesicular Rash

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Journal Scan From the Journals...

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Editorial

Dr Swati Y Bhave Chief Editor (AJPP)

Dear Readers, Welcome to another new issue of Asian Journal of Paediatric Practice. Nearly 80% of asthmatics have some form of allergic rhinitis or hay fever. Asthma and hay fever often exist together. The incidence of allergic rhinitis and asthma is increasing to epidemic proportions, both in the developed and the developing world with consequent reduced quality-of-life, lower productivity and increasing medical costs in children. The article ‘Montelukast with Levocetirizine for Asthma and Allergic Rhinitis’ discusses the links between allergic rhinitis and asthma and sheds light on the new concept of the management of United Airway Disease. The focus on latest asthma guidelines in the article ‘Asthma Management in Pediatric Age Group’ should be of special interest to all pediatricians to update themselves on management of asthma in children. Cough is one of the most common symptoms that children present with. It is important to diagnose the cause of cough as most often cough is only a symptom. It is important to treat the underlying cause. ‘The Coughing child: Ensuring a Good Night’s Sleep’ elucidates on the approach to treating cough in children. We also have an interesting article that addresses the role of some trace elements and heavy metals in causing anemia among children. Another article, which is most pertinent today, with the rising incidence of childhood obesity in India, deals with potential risk factors for obesity in urban children should be worth reading for pediatricians. Clinical Algorithms on Cough and Fever describe a step-wise approach to managing patients who present with these complaints. Clinical Questions on ‘Acute Otitis Media in Children’ focus on effective antimicrobial management of these children. We also have our regular features of Photo Quiz and Journal Scan. Happy Reading...

Dr Swati Y Bhave Executive Director AACCI, Association of Adolescent and Child Care in India Senior Visiting Consultant, Indraprastha Apollo Hospitals, New Delhi IPA Coordinator of Development (International Pediatric Association) VIMHANS, New Delhi Address for correspondence IJCP Group of Publications 39, Daryacha, Hauz Khas Village New Delhi - 110 016

Asian Journal of Paediatric Practice, Vol. 14, No. 1




From the desk of group Editor-in-chief

Smokers in the House, a Risk Factor for Hospitalization of Children with Flu Dr KK Aggarwal Padma Shri and Dr BC Roy National Awardee Sr Physician and Cardiologist, Moolchand Medcity President, Heart Care Foundation of India Group Editor-in-Chief, IJCP Group Editor-in-Chief, eMedinewS Chairman Ethical Committee, Delhi Medical Council Director, IMA AKN Sinha Institute (08-09) Hony. Finance Secretary, IMA (07-08) Chairman, IMA AMS (06-07) President, Delhi Medical Association (05-06) emedinews@gmail.com

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large retrospective case-control study reported at the annual meeting of the Infectious Diseases Society of America (IDSA) says that having smokers in the house increases the possibility of a young child with flu needing inpatient care.

Data from more than 1,300 laboratory-confirmed cases of children with influenza, collected by 10 sites in the CDC’s Emerging Infections Program in 2005-2008 were analyzed to identify risk factors for hospitalization associated with laboratory-confirmed influenza. Analysis showed that if more than half of household members were smokers it doubled the chances a child would have a serious case of flu. According to Nila Dharan, MD, of the division of infectious diseases at the NYU School of Medicine in New York City, a family member who had been vaccinated against flu was protective, even if the child was not fully protected by immunizations. The study included 290 children ages six to 59 months (median age 20 months) with serious cases of flu; 1,089 age- and zip code-matched children with the flu who did not need inpatient care during the three influenza seasons acted as controls. The salient observations were as below. Age of the mother: if ≤26 years, the odds were doubled. The odds ratio (OR) was 2.1, with a 95% confidence interval (CI) from 1.3 to 3.4. The risk was increased if the child’s vaccinations were not up-to-date. The OR was 1.7, with a 95% CI from 1.1 to 2.7. If more than half of household members smoked, the child’s risk of needing inpatient care was doubled. The OR was 2.3, with a 95% CI from 1.0 to 5.3. The risk was similar to having any pulmonary condition, including asthma. If the child was not fully vaccinated for the flu, having any household member immunized was protective. The OR was 0.5, with a 95% CI from 0.3 to 0.8. Underlying medical conditions also had an important role; presence of a hematologic or oncologic condition increased the risk by a factor of 12. According to Dr Dharan, other researchers have examined a possible association between exposure to smoking and a child’s risk of needing inpatient care for flu, but this is the largest study to date. n



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Asian Journal of Paediatric Practice, Vol. 14, No. 1


drug therapy

Montelukast with Levocetirizine for Asthma and Allergic Rhinitis Aru Handa

Abstract Allergic rhinitis (AR) occurs commonly with asthma and also could be an independent risk factor for the development of asthma. Persistent AR and asthma impair the quality-of-life of patients. Patients who have asthma and AR tend to have more severe disease with higher treatment costs and they require almost life-long therapy. The search for treatments to improve the symptoms of patients afflicted with AR and asthma has targeted the cysteinyl leukotrienes by antileukotriene agents. In persistent AR patients, the combination of montelukast with levocetirizine is more effective than monotherapy. The role of montelukast as a combined therapy with levocetirizine for both AR and asthmatic patients is an emerging hope for such patients. Key words: Levocetirizine, montelukast, asthma, allergic rhinitis

Epidemiological Features of Asthma and Allergic Rhinitis Allergic rhinitis (AR), an inflammation of nasal mucosa of allergic origin, is one of the most common chronic disorders in practice, with prevalence ranging from 3% to 19% in various countries.1 AR is a heterogeneous disorder that includes seasonal AR (SAR) symptoms (‘hay fever’) and the more difficult diagnostic category, perennial AR (PAR). Asthma is one of the most prevalent chronic illnesses in the United States, affecting 9 million children (12.7%); also there is an increase in morbidity and mortality related to pediatric asthma.2,3 SAR is also becoming more common, affecting 20-40 million people yearly, with an estimated 40% being children.4 It has been estimated that between 60-78% of people with asthma also suffer from AR.4 AR occurs commonly with asthma and could be an independent risk factor for the development of asthma.2 An emerging theory is that asthma and AR are two conditions along the same continuum of inflammatory processes involving a common airway instead of two distinct diseases of the upper and lower airway.4 In fact, researchers have labeled the two conditions the ‘united airway disease’5 and ‘asthmarhinitis disorder’.6 Rhinitis and asthma are often

Senior Consultant Dept. of ENT Moolchand Medcity, New Delhi

Asian Journal of Paediatric Practice, Vol. 14, No. 1

associated and are two disorders which interact at various levels. Rhinitis typically precedes the development of asthma and can contribute to unsatisfactory asthma control. The presence and type of asthma is influenced by sensitization, and the duration and severity of AR. Both asthma and SAR are associated with significant costs and morbidity. Together, these two illnesses have had a great impact on healthcare economics. In the US, approximately $3 billion yearly is spent on asthma-related costs including direct costs, such as medical costs and indirect costs related to caregiver missed work days.7 The costs associated with SAR are similar.1 It is estimated that approximately $2.7 billion in direct and indirect costs are associated with SAR.1,4 Concept of United Airways Disease: Rhinitis and Asthma Link A new concept of united airways disease has recently come up.7 The all types of relationships between the upper and lower airways have been confirmed now, which are now an increasing evidence for the frequent coexistence of these two diseases i.e. AR and asthma. The role of upper airways infections in increasing the asthma attacks is now established.7 Rhinitis has been identified as an independent risk factor for asthma development. The nose-bronchi link has shed the light on the fact that allergy is not a disease of the nose itself, but a disorder of the whole upper and lower respiratory tract with a wide-range of clinical features, all these observations have led to a new term ‘united airways diseases’.7 


drug therapy There is a major involvement of airway epithelial cells in the pathogenesis of both asthma and AR. Impact of Allergic Rhinitis on Asthma

AR and its impact on asthma in collaboration with the World Health Organization (WHO) initiative reclassified AR, like asthma, by duration and severity. The levocetirizine in Persistent Rhinitis Trial is the first large, long-term clinical trial studying patients with persistent rhinitis as defined by AR and its impact on asthma.8 The levocetirizine in Persistent Rhinitis trial was a 6month double-blind, placebo-controlled, multicenter, multi-national trial in 551 patients. Adults with persistent rhinitis sensitized to both grass pollen and house dust mite were randomized to receive levocetirizine 5 mg/day or placebo. A total of 421 patients completed the full study. In this study, levocetirizine significantly improved both the rhinoconjunctivitis quality-of-life questionnaire overall score and the total five symptoms score from week 1-6 months (all p < 0.001). Medical Outcomes Survey Short Form 36 (SF-36) summary scores were also improved in the levocetirizine group compared with the placebo group. Treatment cessation because of lack of effect, comorbidities and overall costs of disease, and comorbidities per working patient per month (160.27 vs 108.18) were lower in the levocetirizine group. Levocetirizine was shown to improve quality-of-life and symptoms and to decrease the overall costs of the disease over the 6-month treatment period. Integrated Disease Management of Allergic Rhinitis and Asthma The common comorbidities and shared pathophysiologies of asthma and AR have led to the concept of ‘one airway, one disease’ and the need for a common therapeutic approach. To achieve optimal treatment for patients, it is the recommendation of the AR and its impact on asthma workshop group in collaboration with the WHO that patients with persistent AR should be evaluated for asthma, and that patients with asthma should be evaluated for rhinitis.9 A strategy combining the treatment of both upper and lower airway disease in terms of efficacy and safety appears 

to be optimal.9 In many ways, leukotriene receptor antagonists represent a rational approach to such ‘one airway’ disease management. Leukotriene receptor antagonists are an established treatment option for asthma, with evidence to support their use in mild, persistent disease, pediatric asthma, exercise-induced bronchoconstriction. Evidences are accumulating in AR to suggest that both alone and in combination with an antihistamine leukotriene receptor antagonists like montelukast can alleviate the signs and symptoms of AR. Montelukast

Montelukast is a cysteinyl leukotriene (CysLT) receptor antagonist, an orally active compound that binds with high affinity and selectivity to the cysteinyl leukotriene type 1 (CysLT1), receptor. It is a selective and orally active leukotriene receptor antagonist that inhibits the CysLT1 receptor without any agonist activity. The CysLT (LTC4, LTD4, LTE4) are potent inflammatory eicosanoids released from various cells including mast cells and eosinophils. These important pro-asthmatic mediators bind to CysLT receptors. The CysLT1 receptor is found in the human airway (including airway smooth muscle cells and airway macrophages) and on other pro-inflammatory cells (including eosinophils and certain myeloid stem cells). Mechanism of Action of Montelukast in Allergic Rhinitis and Asthma

CysLTs are endogenous mediators of inflammation and play an important role in allergic airway disease by stimulating bronchoconstriction, mucus production, mucosal edema and inflammation, airway infiltration by eosinophils and dendritic cell maturation that prepares for future allergic response. Montelukast inhibits all these actions by blocking type 1 CysLT receptors found on immunocytes, smooth muscle and endothelium in the respiratory mucosa. CysLTs have been correlated with the pathophysiology of asthma and AR. In AR, CysLTs are released from the nasal mucosa after allergen exposure during both early- and late-phase reactions and are associated with symptoms of AR. Intranasal challenge with CysLTs has been shown to increase nasal airway resistance and symptoms of nasal obstruction. Asian Journal of Paediatric Practice, Vol. 14, No. 1


drug therapy Clinical Effects of Montelukast in Allergic Rhinitis and Asthma

Levocetirizine in Persistent Allergic Rhinitis and Asthma

Montelukast was initially developed as a treatment for asthma, now it has more recently found use in the treatment of AR.

Levocetirizine has been shown to be effective in AR. A study evaluated clinical efficacy, antiinflammatory actions of levocetirizine and its effects on quality-of-life with a specific instrument in the asthma-rhinitis comorbidity.11 Fifty adult patients with persistent rhinitis with/without asthma were enrolled. After a 1-week run-in for baseline evaluation, they were randomized to levocetirizine or placebo for eight weeks. Cromolyn and salbutamol were permitted on demand. Rhinoconjunctivitis and asthma symptoms were evaluated by diary cards. Quality-of-life was assessed by the specific rhinasthma questionnaire and the generic SF-36 at different time-points. Nasal scrapings and lavages were also performed for inflammatory cell count and mediator assessment. Symptoms began to decrease in the active group at the second week of treatment when the difference with the placebo group became significant and so remained until the end of the trial. Starting from two weeks of therapy, there was a significant decrease versus baseline in all the four components of the rhinasthma questionnaire only in the active group. The intergroup comparison became significant (p < 0.05) at four weeks.

Systematic reviews10 have evaluated montelukast in the treatment of SAR and PAR, with and without concomitant asthma. In this primary consideration was given to large, randomized, placebo-controlled, double-blind clinical trials in which AR endpoints were assessed and the use of concurrent treatments for AR was excluded. Eight such studies were found in the literature. The primary endpoint in these was daytime nasal symptom severity represented by a composite score derived from individual self-ratings of nasal congestion, rhinorrhea, nasal pruritus and sneezing. Secondary endpoints have included these individual nasal symptom scores, additional scores for eye, ear and throat symptoms, the impact of rhinitis on quality of sleep, global evaluations of outcome by patients and physicians, and measures of the severity of concomitant asthma. A general outcome was that patients treated with montelukast had significantly greater improvements in their symptoms of SAR and PAR than did patients who were given a placebo. In patients with AR with co-morbid asthma, montelukast treatment has significantly resulted in improvements in both their symptoms, as compared to placebo. Montelukast is well-tolerated and has a favorable safety profile; adverse events have occurred at similar frequencies in patients taking either montelukast or placebo. Montelukast provides an effective and well-tolerated oral treatment for allergic airway inflammation in patients with SAR or PAR without asthma, and in patients in whom AR is co-morbid with asthma. Levocetirizine

It is the R-enantiomer of cetirizine, and potent and selective antagonist of peripheral H1-receptors. Binding studies reveal that levocetirizine has high affinity for human H1-receptors (Ki = 3.2 nmol/l). Levocetirizine has an affinity 2-fold higher than that of cetirizine (Ki = 6.3 nmol/l). Levocetirizine dissociates from H1â&#x20AC;&#x2018;receptors with a half-life of 115 Âą 38 minutes. After single administration, levocetirizine shows receptor occupancy of 90% at four hours and 57% at 24 hours. Asian Journal of Paediatric Practice, Vol. 14, No. 1

The SF-36 detected only sporadic differences between groups. Eosinophils and neutrophils in nasal scraping were significantly decreased in the levocetirizine group versus baseline at all times. Nasal mediators were under the detection limits and no analysis could be performed. In the active group, only two patients used rescue medications compared with 13 patients in the placebo group. They were of opinion that levocetirizine is clinically effective and capable of improving the rhinitis-asthma-related quality-of-life. Rationale of Use of Montelukast and Levocetirizine Combination AR and asthma are common disorders affecting large percentages of the population of Western countries including India. There are multiple treatment options available for AR and asthma and stepwise approaches to therapy have been recommended. Montelukast is a CysLT receptor antagonist that has been found to be effective both in the treatment of AR and asthma. Montelukast has a dual effect on both the nasal as well as bronchial epithelium, 


drug therapy so it can be a very good treatment modality for a patient suffering from both bronchial asthma and AR. The dose-dependent beneficial effect of levocetirizine in asthmatic patients with AR is also an added advantage. Combining montelukast with levocetirizine benefits the patients to a great extent. Treatment with concomitant administration of an antileukotriene (montelukast) and an antihistamine (levocetirizine), provides significantly better symptom relief compared with the modest improvement of AR and asthma symptoms with each of the treatments alone. Role of Montelukast and Levocetirizine Combination in Patients of Allergic Rhinitis and Asthma The use of montelukast in combination with antihistamines such as loratadine or cetirizine has generally resulted in greater efficacy than when these agents were used alone, and in some studies has produced results comparable with intranasally applied corticosteroids. The review of the literature4 establishes montelukast as a viable alternative for the treatment of SAR. In a randomized, double-blind, placebo-controlled crossover study12 done to investigate the effects of six weeks of treatment of persistent AR with desloratadine, levocetirizine or montelukast alone or in combination. Patients were assigned to two arms: 20 received montelukast, 10 mg/day, desloratadine, 5 mg/day, or both or placebo and 20 received montelukast, levocetirizine or both, 5 mg/day, or placebo. The treatment periods were separated by 2-week washout periods. Symptom scoring, skin prick tests, spirometry, rhinometry and nasal lavage were performed the day before and the last days of the treatment periods. Eosinophil cationic protein levels were evaluated by means of nasal lavage. The mean ± SD total baseline nasal symptom score was 7.7 ± 0.49 before treatment, 3.74 ± 0.54 after desloratadine use, 3.6 ± 0.48 after montelukast use and 3.04 ± 0.4 after montelukastdesloratadine use. The mean ± SD baseline nasal symptom score was 7.95 ± 0.68 before treatment, 3.02 ± 0.64 after levocetirizine use, 3.44 ± 0.55 after montelukast use and 2.14 ± 0.39 after montelukastlevocetirizine use. The greatest improvement in nasal symptoms occurred after combination treatment. Decreases in the level of eosinophil cationic protein were greater after the combined use of montelukast 10

and antihistamine than after each agent given alone. Combining montelukast with levocetirizine gives additional benefits in comparison to each agent alone and it can be considered for patients whose qualityof-life is impaired by persistent AR and asthma. A study on this area assessed the extent to which treating persistent AR with montelukast, desloratadine and levocetirizine alone or in combination improved quality-of-life.13 It was a 32-week randomized, doubleblind, placebo-controlled, crossover study in two arms: 20 patients received montelukast 10 mg/day and/or desloratadine 5 mg/day or placebo; 20 patients received montelukast 10 mg/day and/or levocetirizine 5 mg/day or placebo. The treatment periods were separated by 2-week washout periods. Quality-of-life was assessed on the day before starting treatment and on the last day of each treatment period using the rhinoconjunctivitis quality-of-life questionnaire. Sleep problems were also assessed. In the desloratadine plus montelukast arm, the mean (SEM) quality-of-life score before treatment was 3.1 (0.41). After placebo, this score was 2.16 (0.43), after desloratadine it was 1.79 (0.38), after montelukast it was 1.48 (0.37) and after montelukast plus desloratadine it was 1.59 (0.37). In the montelukast plus levocetirizine arm, the mean quality-of-life score before treatment was 2.58 (0.49). After placebo it was 1.78 (0.46); after levocetirizine it was 1.38 (0.42); after montelukast it was 1.36 (0.37) and after montelukast plus levocetirizine it was 1.26 (0.39). Placebo, montelukast, desloratadine and levocetirizine significantly improved quality-of-life. Conclusion AR is a very common entity in patients with asthma, with prevalence upto 100%, in those with allergic asthma. The temporal relation of AR and asthma diagnosis is variable; the diagnosis of AR often precedes that of asthma. Rhinitis is an independent risk factor for the subsequent development of asthma in both atopic and nonatopic individuals. There are conflicting results regarding the benefits for asthma symptoms of treating co-morbid AR with intranasal corticosteroids. Montelukast reduces the symptoms of AR, and is comparable with antihistamines and oral decongestants; Cont’d on page 19... Asian Journal of Paediatric Practice, Vol. 14, No. 1


practice guidelines

Asthma Management in Pediatric Age Group

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sthma is commonly seen in children. It is a leading cause of hospital admissions and school absences. Children with asthma may be able to breathe normally most of the time. When they encounter a ‘trigger’, an asthma attack (exacerbation) can occur. Asthma is a major cause of chronic morbidity and mortality throughout the world in pediatric age group. Evidences are accumulating on its increasing prevalence considerably in last 20 years, especially in children. Asthma guidelines are being developed since last 17 years for three major purposes: a) To increase the awareness of asthma among health professionals, b) to improve asthma management, c) to evaluate published reports on asthma and d) to promote international collaboration in asthma research. Currently there are five major guidelines focus on the management of asthma in young children.1 The salient features of these guidelines are discussed herein. Among these guidelines, the Global Initiative for Asthma (GINA) guidelines are the most recent. l Canadian Pediatric Asthma Consensus Guidelines in 2003 l The Expert Pannel Report 3 (EPR-3) of the National Asthma Education and Prevention Programme (NAEPP) in 2007 l The PRACTALL Consensus Report of the European Academy of Asthma and Allergy in 2008 l The European Respiratory Society (ERS) Task Force Pediatric Guideline, published in the European Respiratory Journal in 2008 l GINA published new evidence-based guidelines for the diagnosis and management of asthma in children five years and younger in 2009. Canadian Pediatric Asthma Consensus Guidelines These guidelines2 emphasize that optimal management of asthma requires adequate evaluation of the patient and his or her environment. Asthma control should be assessed only using specific criteria. The guidelines say that “Asthma severity is more difficult to assess and may only be defined after asthma control is achieved. Asthma control should be assessed at each visit. If Asian Journal of Paediatric Practice, Vol. 14, No. 1

control is inadequate, the reasons should be identified and maintenance therapy should be modified. Any new treatment should be considered a therapeutic trial and its effectiveness should be re-evaluated after 4-6 weeks”. These guidelines also emphasize that, if good control has been sustained, consideration should be given to gradually reducing maintenance therapy, with regular reassessments to ensure that adequate control remains. Asthma education is an essential component of asthma care. These guidelines recommend that, poor asthma control is not usually due to a lack of efficacy of the medication, but is more often related to suboptimal use of medication or aggravating factors, comorbidities, poor inhaler technique, poor environmental control or a lack of continuity of care. The guidelines say that suboptimal use of asthma medication may be the result of inappropriate physician recommendation, poor adherence or both, perhaps as a result of undue fear of adverse effects of therapy. EPR-3 Guidelines of National Asthma Education and Prevention Programme The EPR-3 guidelines3 on asthma were developed by an expert panel commissioned by the NAEPP Coordinating Committee (CC), coordinated by the National Heart, Lung and Blood Institute (NHLBI) of the National Institutes of Health. The literature review and updated recommendations for managing asthma long-term and for managing exacerbations were structured using the 1997 EPR-2 guidelines and the 2002 update on select topics as a framework. The final guidelines revolve around four essential components of asthma care: Assessment and monitoring, patient education, control of factors contributing to asthma severity, and pharmacologic treatment. In the guidelines, EPR-3’s six key messages for successful management of asthma are: l Clinicians should base treatment on each patient’s individual needs and asthma control level. l EPR-3 promotes use of multiple measures of functional impairment and risk for exacerbation. 11


practice guidelines l

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Patients whose symptoms seem to be well-controlled too can be at risk for severe exacerbation. Asthma is a dynamic disease, and the degree of control can change, sometimes rapidly, over time. Patients who have a written asthma action plan are able to better manage better than patients without plans. New treatment options are recommended. Patients can learn valuable self-management skills by expanding educational opportunities through multiple portals of care to include the clinician and clinical staff, school nurses, pharmacists, asthma educators and community-based interventions.

PRACTALL Consensus Report The PRACTALL (PRACTicing ALLergology program on childhood asthma) initiative4 is recommended by European Academy of Allergology and Clinical Immunology (EAACI) and the American Academy of Allergy, Asthma and Immunology (AAAAI), which nominated expert teams to formulate consensus for clinical practice in Europe and North America. It is the first extensive diagnosis and treatment guideline developed by pediatric respiratory specialists for treating children. The report focuses on the natural history and pathophysiology of childhood asthma and recommendations for diagnosis, management and monitoring. Additionally, specific recommendations for use of inhalers as well as management of the following are also included like: a) Children 0-2 years, b) children 3-5 years, c) acute asthma episodes, d) exercise-induced asthma and e) difficult asthma. The highlights of the PRACTALL consensus report are as below: l Complete focus on children l Breakdown into four age groups: 0-2, 3-5, 6-12 and adolescence l A discussion of asthma phenotypes in childhood and the heterogeneity of childhood asthma l Emphasis on allergy testing of children with suspected asthma l Definition of asthma control for children l Sample questions for asthma monitoring l Exhaled nitric oxide proposed as useful adjunct to routine clinical assessment in asthma management 12

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l

A greater role, as compared with GINA, for leukotriene receptor antagonists (LTRAs), which are listed as an alternative to inhaled corticosteroids (ICS) as first-line treatment for persistent asthma, particularly if the child has concomitant rhinitis Research recommendations

The European Respiratory Society Task Force Pediatric Guideline The ERS Task Force published5 a document in 2008, using an ‘evidence-based approach’ in order to improve guidelines for the management in children with wheezy illnesses aged five years or less. These guidelines stress that there is poor agreement on the definitions of different phenotypes for pre-school wheezing disorders that patients may move from one phenotype to another. The Task Force recommended that wheeze in young children, five years or less in age, should be classified as ‘episodic’ (viral) or ‘multiple trigger’ wheeze, which are not mutually exclusive. In children five years or less with multiple trigger wheezes, treatment should begin with a trial of an ICS, upto beclomethasone dipropionate, 400 µg equivalent or fluticasone, 200 µg/day for a period of about three months. The ICS should be withdrawn, if there is a good clinical response to treatment to confirm the need for its ongoing use and to check for spontaneous remission. Such an approach avoids use of ICS for longer duration as long-term use may affect the hypophyseal-pituitary-adrenal axis (HPA). ICS does not lessen the risk of persistent wheeze at the age of six years in children with episodic viral wheeze. In such children, symptoms recur when glucocorticoids are stopped. Global Initiative for Asthma Guidelines for Children The Global Initiative for Asthma (GINA) was developed to create and increase awareness of asthma among health professionals, public health authorities, general public as well as to improve prevention and management through a concerted worldwide effort.6 It has reported on asthma management based on the best available scientific evidence and it encourages dissemination and implementation of the recommendations and promotes Asian Journal of Paediatric Practice, Vol. 14, No. 1


practice guidelines international collaboration on asthma research. In 2009, GINA published a new strategy for asthma management and prevention for children five years in particular. These guidelines focus on five areas: l Risk factors associated with development of asthma l Diagnosis of asthma l Management of asthma l Treatment of asthma including education, control, pharmacotherapy and management of acute exacerbations and chronic asthma. Definition of Asthma

The GINA guidelines define asthma as a â&#x20AC;&#x153;chronic inflammatory disorder of airways in which cells and its elements play role in airways hyperresponsiveness leading to recurrent episodes of wheezing, breathlessness, chest tightness and cough in night or morningâ&#x20AC;?.

without viral infections and wheeze symptoms that persist in children above three years point to a diagnosis of asthma in children. Evidence-based Categories in GINA Guidelines GINA guidelines include four evidence-based categories. l Category A is derived from a rich body of data and from randomized controlled trials. l Category B from a limited body of controlled trial data, posthoc analysis or meta-analysis of randomized controlled trial. l Category C for nonrandomized or observational studies. l Category D for panel consensus judgment. Evidence A

Risk Factors of Asthma

l

The risk factors identified in guidelines are: a) Host factors and b) environmental factors. The important host factors identified are: Genetic factors, obesity and sex. The important environmental factors implicated in asthma are: Allergens, infections, occupational sensitizers, tobacco smoke, pollution and diet.

l

Diagnosis of Asthma

l

As per these guidelines, the clinical diagnosis of asthma can be made when patient presents with symptoms of recurrent episodes of wheezing, breathlessness, chest tightness and cough. These guidelines stress on lung function measurement by spirometry or peak expiratory flow (PEF) for severity and confirmation of diagnosis of asthma. To aid the clinical management of asthma, levels of control have been defined in these guidelines: Asthma Control

As per the guidelines asthma is considered in control if there are: a) No day/night-time symptoms or night awakenings, b) patient can exercise, c) does not require reliever treatment for two weeks, d) normal lung function and e) no exacerbations.

l

Evidence B

For children under five years, asthma management plans based on the level of respiratory symptoms are just as effective as approach based on self-monitoring of lung function. Evidence C

The Asthma Predictive Index (API) as per the Tuscan Respiratory study shows that a child with a positive API has a 4-10 fold greater chance of developing asthma between ages 6 and 13 while 95% of children with a negative API remained free of asthma. Evidence D l

Diagnosis of Asthma in Children

The GINA guidelines state that: Frequent episodes of wheeze, activity-induced cough, nocturnal cough Asian Journal of Paediatric Practice, Vol. 14, No. 1

The initial treatment can be a dose of rapidly-acting inhaled b2 agonist every 4-6 hours as needed for a day or more until symptoms disappear in under five years. Antileukotrienes improve asthma outcomes in young children. Cromolyn sodium is not recommended for children under five years. Inhaled glucocorticosteroids are effective in the management of asthma in young children.

l

Regular controlled treatment may be indicated in a child with less frequent but with more severe episodes of viral-induced wheeze. Long-acting bronchodilators are not recommended for children under five years. 13


practice guidelines l

A therapeutic trial with short-acting bronchodilators and inhaled glucocorticosteroids for at least 8-12 weeks may provide some guidance for the presence of asthma.

GINA: Pharmacotherapy for Children Under Five Years Inhalation Therapy

This therapy is the cornerstone of asthma management as all children can be effectively treated with use of this route. A metered dose inhaler is better than Nebulizer for children. Controlling Medications

The GINA report focuses on use of following medications in children: Systemic and inhaled glucocorticosteroids, leukotriene modifiers, long-acting inhaled b2 agonists, theophyllines, cromones, long-acting oral b2 agonists. Inhaled Glucocorticosteroids

These medications are cornerstone of asthma treatment in children. There is a significant improvement in clinical symptoms when these drugs like budesonide are used in low doses 100-200 mg in children both below and above five years without any significant side effects. Systemic Glucocorticosteroids

Their prolonged use should be avoided because of their side effects. They can be used only for treating acute severe exacerbations in children. Leukotriene Modifiers

They provide clinical benefit for children above five years at any level of asthma severity but their effect is lower than that of ICS. They provide partial protection against exercise-induced bronchoconstriction. In five years children under, they reduce viral-induced asthma exacerbations with a history of intermittent asthma. Long-acting Inhaled β2 agonists

They must be used only as an add-on therapy when results from ICS are not good in children above five years. The results are better than under five years children. Theophyllines

In children above 5 years, these medication show good results not only as monotherapy but also a combination 14

therapy with inhalational or oral glucocorticosteroids. These results are seen even in children below five years. Cromones

Sodium cromoglycate and nedocromil sodium have a limited role in long-term treatment of asthma in children. Long-acting oral β2 agonists (Salbutamol and Terbutaline)

These medications reduce nocturnal symptoms of asthma but their use is not recommended due to the associated side effects. Rapid-acting inhaled β2 agonists

They are considered to be the most effective bronchodilators for treating acute asthma in children. They cause more rapid bronchodilation in lower doses by oral or IV route, along with good control of exerciseinduced bronchoconstriction. References 1. Potter PC. Current guidelines for the management of asthma in young children. Allergy Asthma Immunol Res 2010;2(1):1-13. 2. Becker A, Lemiere C, Berube D, Boulet LP, Ducharme FM, Fitzgerald M, et al; Asthma Guidelines Working Group of the Canadian Network For Asthma Care* and the Canadian Thoracic Society; Canadian Pediatric Asthma Consensus Guidelines, 2003. CMAJ 2005;173 (6 Suppl): S1-S56. 3. National Heart, Lung, and Blood Institute National Asthma Education and Prevention Program Expert Panel Report 3 (EPR-3): Guidelines for the diagnosis and management of asthma - Summary Report. NHLBI 2007. 4. Bacharier LB, Boner A, Carlsen KH, Eigenmann PA, Frischer T, Gotz M, et al; European Pediatric Asthma Group. Diagnosis and treatment of asthma in childhood: a PRACTALL consensus report. Allergy 2008;63(1):5-34. 5. Brand PL, Baraldi E, Bisgaard H, Boner AL, CastroRodriguez JA, Custovic A, et al. Definition, assessment and treatment of wheezing disorders in preschool children: an evidence-based approach. Eur Respir J 2008;32(4):1096-110. 6. Global Initiative for Asthma: Global strategy for the diagnosis and management of asthma in children 5 years and younger [Internet]. 2009. Available from: www. ginasthma.org Asian Journal of Paediatric Practice, Vol. 14, No. 1


for the clinician

The Coughing Child: Ensuring a Good Night’s Sleep KK Aggarwal*, VP Sood

Abstract The usual reasons for giving a cough suppressant to a child is if the cough is dry and causing discomfort/pain, if it is severe enough to seriously disturb sleep or may have an underlying allergic component. Key words: Dry cough, cough suppressant

C

ough is the fifth most common symptom for which patients seek care, resulting in approximately 30 million visits to the doctor’s clinic per year.1 Cough is a physiological reflex occurring when sensitive receptors located in upper airways and the larynx are activated. The cough reflex is a protective mechanism that helps in clearing the respiratory tract, however, often the reflex can be a source of intense misery for the afflicted child forcing the concerned parents to seek medical aid.

Some viruses and bacteria can attack the larynx and/ or the glottis. A common example is croup, which occurs when a virus attacks the larynx and windpipe. Typically, a child with croup has a ‘barking’ cough that sounds like a seal, with noise (‘stridor’) on inhaling. Croup usually can be treated with steam or with cool, moist air; rarely do we need medicines to reduce the swelling in the larynx.

Diagnosing the cause of a cough is important since cough is often only a symptom and it should not necessarily be the only target for treatment.

Pneumonia may also cause coughing, but this is rarer and there are other symptoms as well. Another reason for coughing is irritation in the small airways or bronchiolitis, or in the large airways (bronchitis). Both bacteria and viruses can cause this kind of irritation. One particular virus that appears every winter is respiratory syncytiaI virus (RSV), which can also cause pneumonia as well as bronchiolitis.

The most common cause of cough in children is reactive airways. Because cough receptors also reside in the pharynx, paranasal sinuses, stomach and external auditory canal, the source of a persistent cough may need to be sought beyond the lungs. Specific lower respiratory stimuli include excessive secretions, aspirated foreign material, inhaled dust particles or noxious gases and an inflammatory response to infectious agents or allergic processes.

Cough may persist long after an upper respiratory tract infection so, there may be no obvious underlying cause. Reassurance and explanation to the parents to this effect is often sufficient and backing this up with an information leaflet to take home may be useful. The usual reasons for giving a cough suppressant to a child is if the cough is dry and causing discomfort/ pain, if it is severe enough to seriously disturb sleep or may have an underlying allergic component.

Many lung disorders whether acute or chronic may have an underlying allergic etiology, commonest being bronchial asthma and the other being allergic rhinitis or ‘hay fever’.2

Treatment of Cough

Causes of Cough

*Sr Physician and Cardiologist Moolchand Medcity New Delhi

Asian Journal of Paediatric Practice, Vol. 14, No. 1

A simple rule of the thumb in treatment of cough is: l Dry cough: Identify underlying cause and initiate specific therapy + suppress the cough. l Productive cough: Specific therapy for underlying cause and suppress the cough only if it is exhausting the patient. 15


for the clinician Cough Suppressants or Antitussives

Cough, being a reflex, has peripheral and central centers. Peripheral arm of the reflex is primarily mediated through the vagus nerve.3 Central component of the cough reflex involves several centers and/or mechanisms, which are distinct from ones involved in regulation of respiration. Most commonly used centrally-acting antitussives belong to opioid group of drugs, such as codeine and hydrocodone.4 However, apart from constipation, they also carry a great liability on part of the treating clinician due to the risk of abuse and dependance. Dextromethorphan

Dextromethorphan is an oral, nonprescription drug used as an three antitussive. The D-isomer has a selective antitussive action (raises threshold of cough center) while the I-isomer is analgesic. It is as two effective as codeine, does not depress mucociliary function of the airway mucosa and is practically devoid of constipating and addicting actions. Mechanism of action: Dextromethorphan exerts its antitussive action by increasing the threshold for coughing.5 Various sites in brain binding dextromethorphan have been identified,6 but they are not bound by codeine and other opioid antitussives. Thus, the ability of naloxone to inhibit antitussive action of codeine and not of dextromethorphan suggest that cough suppression can be achieved through variety of mechanisms. Dextromethorphan does not act through opioid receptors and is as potent as codeine with few gastrointestinal and other side effects as compared to the latter.7

Diphenhydramine blocks the action of histamine resulting in increased capillary permeability and formation of edema/wheal (triple response). Its mild atropine-like action may also decrease secretion in cholinergically innervated glands and decrease ongoing secretions e.g. in respiratory tree. Cough and the common cold are closely related and it is common knowledge that antihistaminedecongestant-antitussive therapy is an effective treatment. Conclusion These effective formulations are often the weapon a pediatrician uses in his fight against a child’s dry cough. Many a mother finds solace in this combination and has a peaceful night’s sleep with her toddler. References 1. Braman SS, Corrao WM. Chronic cough. Diagnosis and treatment. Prim Care I985;12(2):217-25. 2. Jarvis D, Burney P. ABC of allergics. The epidemiology of allergic disease. BMJ 1998;316:607-10. 3. In: Harrison’s Principles of Internal Medicine. 14th edition. 4. Eddy NB. Codeine and its alternative for pain and cough relief. Ann Intern Med 1969;71(6):1209-12.

Clinical efficacy: A study done by Lee et al,8 evaluated the role of dextromethorphan in cough associated with acute upper respiratory tract infection. The data of this double-blind, stratified, randomized and parallel group design study provides support for the clinically significant antitussive activity of dextromethorphan in patients with cough associated with acute upper respiratory tract infections.

5. In: Goodman and Gilman’s Textbook of Pharmacology.

Combination Therapies

8. Lee PCL, Jawad MS, Eccles R. Antitussive efficacy of dextromethorphan in cough associated with acute upper respiratory tract infection. J Pharm Pharmacol 2000;52(9):1137-42.

However, as mentioned earlier, there may be an allergic component to a cough which also needs to be tackled in 16

order to achieve greater control over the nonproductive cough. Combination therapy is a practical and prudent approach to prescribe treatment in combinations as this improves compliance as well as targets the various components of cough, which may disturb the child. In this regard, diphenhydramine an antihistaminic, has been found to be a useful adjunct.

6. Craviso GL, Musacchio IM. High-affinity dextromethorphan binding sites in guinea pig brain II. Competition experiments. Mol Pharmacol 1983;23(3):629-40. 7. Matthys H, Bleicher B, Bleicher V. Dextromethorphan and codeine: objective assessment of antitussive activity in patients with chronic cough. J Int Med Res 1983;11(2):92-100.

Asian Journal of Paediatric Practice, Vol. 14, No. 1


clinical algorithm

Approach to Cough

Cough

If accompanied by wheeze or stridor

?Paroxysmal cough or high suspicion of foreign body

Yes

? Referral to appropriate team for bronchoscopy

No

Dry wheezy cough Fever Nasal discharge Fine inspiratory crackles and/or high-pitched expiratory wheeze No

Pneumonia

Mild/moderate distress

Yes

Chest X-ray

Combination of cough+ breathing difficulty and one or more of: Fever High respiratory rate Grunting Chest indrawing

Yes

Bronchiolitis

Trial of bronchodilator Stop if no clinical improvment Monitor O2 saturation No steroids No routine blood tests/X-ray

Yes

Severe distress

? Severe distress No

X-ray child under 2 months/if no response to antibiotics/recurrent pneumonia No routine blood tests Oral antibiotics if clinically suspected Home with follow up instructions

Chest X-ray Oral/IV antibiotics according to local protocol FBC and blood culture if requires IV antibiotics No routine blood tests if on oral rx ADMIT

Asian Journal of Paediatric Practice, Vol. 14, No. 1

No

Discuss with senior clinician Consider trial of nebulized adrenaline Admit for close observation e.g. HDU/PICU

Admit if: Signs of serious illness Complicating factors Increased risk of serious disease

Re-assess child

17


clinical question

Acute Otitis Media in Children

What is the Best Way to Manage Uncomplicated Acute Otitis Media (AOM) in Otherwise Healthy Children? Evidence Summary

The American Academy of Pediatrics and the American Academy of Family Physicians recently released an evidence-based practice guideline to help physicians provide the most up-to-date care for children with AOM.1 The subcommittee that developed the guideline included primary care physicians, pediatricians, and experts in the fields of infectious disease, epidemiology, and otolaryngology. The subcommittee reviewed the best available evidence before making its recommendations. All recommendations have been substantiated by research evidence and have been assigned a rating for the strength of the evidence. The guideline applies to otherwise healthy children between two months and 12 years of age with uncomplicated AOM. A specific definition of AOM is provided: “a diagnosis of acute otitis media requires a history of acute onset of signs and symptoms, the presence of middle-ear effusion, and signs and symptoms of middle ear inflammation.”1 Children suspected of having AOM who do not meet all three criteria are described as having an uncertain diagnosis of AOM. It also is important to distinguish AOM from otitis media with effusion, because only patients with AOM have the potential to benefit from antibiotics. The guideline1 strongly recommends assessment of the child’s pain. Too often, an antibiotic is prescribed, but no recommendation for analgesia is provided. Use of acetaminophen or ibuprofen is recommended, although topical and naturopathic agents also have evidence of efficacy. The choice of analgesic should be based on an evaluation of risks and benefits, with consideration of the preference of the parent/caregiver and patient. The decision to prescribe an antibiotic depends on the child’s age, the certainty of the diagnosis, and the Source: Adapted from Am Fam Physician 2004;69(12):2896-8.

18

severity of the symptoms. Severe AOM is characterized by severe otalgia and/or a temperature of at least 39°C (102.2°F). Observation without antibiotic therapy is an option in some children, provided that follow-up in 48 to 72 hours can be assured and analgesia is provided. Observation should be considered in children six months to two years of age with an uncertain diagnosis and nonsevere symptoms, children older than two years with a certain diagnosis but nonsevere symptoms, and children older than two years with an uncertain diagnosis. The guideline1 cites studies demonstrating that the majority of children improve within three days of presentation, even without antibiotics,2,3 and that the risk of complications is no higher when antibiotic therapy is delayed.4 If antibiotics are necessary for initial management, the recommended agents are amoxicillin (40 to 45 mg per kg orally twice daily) for children with nonsevere illness and amoxicillinclavulanate (45 mg per kg/3.2 mg per kg orally twice daily) for children with severe symptoms or children in whom additional coverage for beta-lactamase-positive Haemophilus influenzae and Moraxella catarrhalis is desired. The accompanying patient encounter form for children two months to 12 years of age who present with earache includes an assessment of pain, the definition of AOM, clinical decision support for the use of an antibiotic, guidance on selection of the most appropriate antibiotic, and a reminder to recommend analgesia. Applying the Evidence

A two-year-old boy presents with one day of tugging at his right ear, a runny nose, and a temperature of 37.9°C (100.2°F). His appetite and fluid intake are good. Although the child is a bit irritable, he is not lethargic or toxic-appearing. On examination, the tympanic membrane is dull but not erythematous; the membrane has limited mobility. What is the diagnosis, and how should the patient be managed? Asian Journal of Paediatric Practice, Vol. 14, No. 1


clinical question Answer: This patient has an uncertain diagnosis of AOM. Although there is evidence of effusion and an acute onset of symptoms, there is no evidence of inflammation. Furthermore, the illness is not severe (i.e., low-grade fever, nonspecific tugging at the right ear). It would be reasonable to provide analgesia in the form of acetaminophen and to have the parents observe the child carefully for 48 to 72 hours. If the child does not improve or shows signs of worsening, he should be reevaluated. If an antibiotic is required but symptoms are not severe, amoxicillin in a dosage of 45 mg per kg per day orally twice daily is the best choice if the patient is not allergic to penicillin.

References 1. Subcommittee on Management of Acute Otitis Media. Diagnosis and management of acute otitis media. Pediatrics. 2004;113:1451-65. 2. Rosenfeld RM, Kay D. Natural history of untreated otitis media. In: Rosenfeld RM, Bluestone CD, eds. Evidence-based otitis media. 2d ed. Hamilton, Ontario: Decker; 2003:180-98. 3. Little P, Gould C, Williamson I, Moore M, Warner G, Dunleavey J. Pragmatic randomised controlled trial of two prescribing strategies for childhood acute otitis media. BMJ. 2001;322:336-42. 4. Van Buchem FL, Peeters MF, vant Hof MA. Acute otitis media: a new treatment strategy. Br Med J Clin Res. 1985;290:1033-7.

n

n

n

...Cont’d from page 10 it is also effective in both SAR and PAR, and improves lung functioning in asthma. Effectiveness increases with greater levels of allergen exposure, and efficacy is also increased when asthma symptoms are more severe. As a result, montelukast is a suggested treatment for both conditions. So, antileukotriene agents such as the leukotriene receptor antagonists (montelukast) offer benefits for treating both AR and asthma and this effect can be amplified if it is combined with antihistamines like levocetirizine. References 1. Skoner DP. Allergic rhinitis: definition, epidemiology, pathophysiology, detection, and diagnosis. J Allergy Clin Immunol 2001;108(1 Suppl):S2-8. 2. Shah A, Pawankar R. Allergic rhinitis and co-morbid asthma: perspective from India - ARIA Asia-Pacific Workshop Report. Asian Pac J Allergy Immunol 2009;27: 71-7. 3. CDC 2003. Asthma in US. Available at: http://www. cdc.gov/nchs/fastats/asthma.htm. 4. Gonyeau MJ, Partisano AM. A clinical review of montelukast in the treatment of seasonal allergic rhinitis. Formulary 2003;38(6):368-78. 5. Passalacqua G, Ciprandi G, Canonica GW. The nose-lung interaction in allergic rhinitis and asthma: united airways disease. Curr Opin Allergy Clin Immunol 2001;1(1):7‑13. 6. Passalacqua G, Ciprandi G, Pasquali M, Guerra L, Asian Journal of Paediatric Practice, Vol. 14, No. 1

Canonica GW. An update on the asthma-rhinitis link. Curr Opin Allergy Clin Immunol 2004;4(3):177-83. 7. Compalcti E, Ridolo E, Passalacqua G, Braido F, Villa E, Canonica GW. The link between allergic rhinitis and asthma: the united airways disease. Expert Rev Clin Immunol 2010;6(3):413-23. 8. Bachert C, Bousquet J, Canonica GW, Durham SR, Klimek L, Mullol J, et al. Levocetirizine improves qualityof-life and reduces costs in long-term management of persistent allergic rhinitis. J Allergy Clin Immunol 2004;114(4):838-44. 9. WHO Report ARIA. Available at: www.cks.nhs.uk/ allergic_rhinitis/evidence/references 10. Nayak A, Langdon RB. Montelukast in the treatment of allergic rhinitis: an evidence-based review. Drugs 2007;67(6):887-901. 11. Pasquali M, Baiardini I, Rogkakou A, Riccio AM, Gamalero C, Desculzi D, et al. Levocetirizine in persistent allergic rhinitis and asthma: effects on symptoms, quality-of-life and inflammatory parameters. Clin Exp Allergy 2006;36(9):1161-7. 12. Ciebiada M, Górska-Ciebiada M, DuBuske LM, Górski P. Montelukast with desloratadine or levocetirizine for the treatment of persistent allergic rhinitis. Ann Allergy Asthma Immunol 2006;97(5):664-71. 13. Ciebiada M, Ciebiada MG, Kmiecik T, DuBuske LM, Gorski P. Quality-of-life in patients with persistent allergic rhinitis treated with montelukast alone or in combination with levocetirizine or desloratadine. J Investig Allergol Clin Immunol 2008;18(5):343-9.

19


clinical algorithm

Nontoxic Infant or Young Child with Fever

Previously healthy, nontoxic infant or child (3 months - 3 years) with fever without source

Temperature ≥39°C (102.2°F)

20

l

Urine culture in all infants and children <2 years of age who are prescribed empiric antibiotics

l

Chest radiograph for clinical findings; consider radiograph if infant or child is asymptomatic and has a WBC count >20,000/mm3 (20 × 109/l)

l

Stool culture: No new recommendations

l

Blood culture: Consider selection of temperature and WBC count thresholds based on risk

l

Empiric antibiotic therapy; consider selection of temperature and white blood cell count threasholds based on risk

l

Follow-up: Clinical course remains the most sensitive indicator for serious illness

Temperature <39°C (102.2°F)

l

Careful physical examination to identify potential focal infection (e.g., pneumonia, abscess, cellulitis, sinusitis, otitis media, osteomyelitis, impetigo, lymphadenitis, impetigo, lymphadenitis, scarlet fever, streptococcal pharyngitis)

l

No tests or antibiotics if infant or young child looks well and no possible bacterial source is identified

l

Antipyretic such as paracetamol, as needed

l

Follow-up: Re-evaluation if fever persists >48 hours or condition deteriorates

Asian Journal of Paediatric Practice, Vol. 14, No. 1


clinical study

Relation Between Anemia and Blood Levels of Lead, Copper, Zinc and Iron among Children Amal A Hegazy, Manal M Zaher, Manal A Abd el-hafez, Amal A Morsy, Raya A Saleh

Abstract Background: Anemia is a health problem among infants and children. It is often associated with a decrease in some trace elements (iron, zinc, copper) and an increase in heavy metals as lead. This study was done to determine the association of blood lead level >10 μg/dl, with the increased risk to anemia, also, to investigate the relationship between anemia and changes in blood iron, zinc and copper levels, and measure lead level in drinking water. The study is a cross-sectional performed on 60 children. Venous blood samples were taken from the studied population for estimating hematological parameters as well as iron and ferritin levels. The concentrations of zinc, copper, and lead were measured. The studied population was divided into anemic and non-anemic (control) groups. The anemic group was further classified into mild, moderate and severe anemia. The study subjects were also categorized into low and high blood lead level groups. Findings: Approximately 63.33% of children had blood lead levels ≥10 μg/dl. At the blood lead level range of 10-20 μg/dl, a significant association was found for mild and severe anemia. The blood level of iron and ferritin was found to be significantly lower in high blood lead level and anemic groups than those of the low blood lead level and control groups. Lead level in drinking water was higher than the permissible limit. Conclusion: Lead level ≥10 μg/dl was significantly associated with anemia, decreased iron absorption and hematological parameters affection. High blood lead levels were associated with low serum iron and ferritin. Lead level in drinking water was found to be higher than the permissible limits. Key words: Trace elements, heavy metals, anemia, hypochromic microcytic anemia

D

eficiency of certain trace elements generally causes hypochromic microcytic anemia. Iron deficiency not only causes hypochromic microcytic anemia, but also increases the absorption of other elements such as lead (Pb) and cadmium (Cd). Therefore, in patients with hypochromic microcytic anemia, the serum levels of these elements may increase causing deterioration of anemia. Generally, heavy exposure to (Pb and Cd) causes hypochromic microcytic anemia.1 Iron absorption occurs predominantly in the duodenum and jejunum. A number of dietary factors influence iron absorption, ascorbate and citrate increase iron uptake. Lead is a particularly pernicious element to iron metabolism, as it is taken up by the iron absorption machinery, and secondarily blocks iron through competitive inhibition. Furthermore, it interferes with a number of important iron dependent metabolic steps such as heme biosynthesis.2 Lead poisoning has been a significant public health problem for centuries. In children, it is defined as a blood lead level equal to or greater than 10 μg/dl,3 it is also associated with adverse behavioral Citation: Hegazy et al., Relation between anemia and blood levels of lead, copper, zinc and iron among children. BMC Research Notes 2010, 3:133.

Asian Journal of Paediatric Practice, Vol. 14, No. 1

and developmental outcomes. However, a level <10 μg/dl is considered unsafe.4 Human exposure to lead occurs primarily through diet, air, drinking water and ingestion of paint chips where absorption increases mainly in persons suffering from iron and calcium deficiency.5 Environmental lead exposure occurs from automobile exhaust in areas of the world where leaded gasoline is still used. At home, exposure among children may occur either due to ingestion of old leaded chips or pigments and glazes used in pottery.6 For centuries, lead plumbing has helped in the contamination of drinking water and contributed to elevated blood lead concentrations in children.7 The mobilization of heavy metals in the environment, due to industrial activities, is a serious concern due to their toxicity in humans and other forms of life.8 These toxic metals (mercury, lead and cadmium) are called ‘‘the big three’’ due to their major impact on the environment. Where they tend to persist, circulating and eventually accumulate throughout the food chain.9 21


clinical study Copper as an essential trace element exists in the diet, it is needed to absorb and utilize iron.10 Zinc is absorbed in the small intestine; absorption is inhibited by the presence of phytates and fiber in the diet, as well as dietary iron and calcium.11 Anemia in children leads to increased morbidity and mortality.12 Adverse health effects of anemia in children include impaired psychomotor development and renal tubular function, poor cognitive performance and mental retardation.13,14 Therefore, this study was done to determine the association of blood lead level >10 μg/dl, with the increased risk to anemia compared to levels less than 10 μg/dl, also, to investigate the relationship between anemia and changes in blood iron (Fe), zinc (Zn) and copper (Cu) levels, and measure lead level in drinking water. Methods Study Population

This research was carried out on a total of 60 children from the pediatric clinic in Al-Zhraa Univerisity hospital and a special pediatric clinic in a rural area. They were selected by a systematic random sample. Exclusion criteria of cases were children having chronic hemolytic anemia or those suffering from chronic illness associated with anemia. The control group was selected from those attending the out patients clinic for evaluating physical fitness for different sports. Mothers of children were informed about the aim of the study and their consent was obtained. Data related to age, gender, residence, source of drinking water, degree of father and mother’s education and their occupation, also, socioeconomic status data was collected from the mothers. According to the WHO definition of anemia based on hemoglobin level less than 11 g/dl, the studied population was divided into anemic and control groups.15 The anemic group was further classified into categories of mild (Hb level 10-10.9 g/dl), moderate (Hb level 8-9.9 g/dl) and severe (Hb level <8 g/dl) anemia. Also, according to serum blood level, the studied population was classified into two groups, <10 μg/dl and ≥10 μg/dl. Laboratory Investigations

A venous blood sample was taken from each child and divided into three tubes. The first tube (containing 22

EDTA) used for estimation of hematological parameters using Celttac autoanalyzer, these parameters included the red blood cell count (RBC), hemoglobin (Hb), hematocrit (Hct), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and red cell distribution width (RDW). The second tube (containing heparin) for estimation of lead, copper and zinc by the atomic absorption spectrophotometer.16 (Perkin Elmer HGA 460-Germany). The blood lead level (BLL) was determined by the graphite furnace atomic absorption spectrophotometer, where as Cu and Zn concentrations were measured with the flame atomic absorption spectrophotometer. The third tube, Hitachi 911 autoanalyzer was used for serum iron estimation using Roche reagent kits whereas Elecsys 1010 - Japan was used for estimating serum ferritin. Environmental Assessment

Drinking water Samples were taken from tap and hand pump water for detection of lead level using the atomic absorption spectrophotometer (Graphite Furnace, Perkin Elmer HGA-600, USA). Lead level in piped water was found to be 2.9 μg/dl and 3.6 μg/dl in the urban and rural areas, respectively. Hand pump, water collected from two separate hand pumps in the rural area, revealed lead levels to be 3.1 μg/dl and 2.3 μg/dl. Statistical Analysis

Data was analyzed by SPSS (Statistical Package for Social Sciences) version 12. Chi-square test was performed to compare individual characteristics and the t-test was performed to compare the hematological parameters between anemic and control groups. Results were expressed as the mean ± standard deviation (SD). Significant values of P at <0.05 and <0.001 were considered. A correlation was performed for the levels of lead, Fe, Cu and Zn in blood versus the different hematological parameters. Results This study was done on 60 children with ages ranging from 2 to 14 years with a mean value of 6.27 ± 3.40 years. According to the blood lead level, ranging between 7 to 20 μg/dl, approximately 63.33% (n = 38) of children had a blood lead ≥10 μg/dl (high blood lead level group {HBLL}) and 36.67% (n = 22) Asian Journal of Paediatric Practice, Vol. 14, No. 1


clinical study had a blood lead level <10 μg/dl (low blood lead level group {LBLL}), The socioeconomic characteristics were studied among the high and low blood lead level (Table 1). Although, higher BLL was among children >6 years old and those consuming tap water, yet no statistical difference was detected between those having high blood levels. Also, blood lead level was higher in males than females and those of low social standard. In addition,

it was higher in children of illiterate mothers and fathers, unemployed mothers and employed fathers. A significantly greater proportion of children with lead levels ≥10 μg/dl (63.2%) had anemia compared to those with lead levels <10 μg/dl (27.3%) (Table 2). The presence of different categories

of anemia among the high (≥10 μg/dl) and low (>10 μg/dl) blood lead level groups was demonstrated in Table 3. The difference in distribution was significant for the mild and severe form of anemia (HBLL 28.9%; LBLL 4.5%) and (HBLL 21.1%; LBLL 4.5%), respectively. Comparison between mean values of different hematological parameters and serum ferritin in anemic and control groups were studied (Table 4). Regarding the hematological parameters, nearly all values were significantly lower among the anemic than the control group except for the RDW, which showed a highly significant elevation among the anemic group. As for the RBC count, no statistically significant difference was detected between the groups.

Table 1. Distribution of Individual Characteristics in Relation to Blood Lead Levels Characters of studied group

Blood lead level Low <10 μg/dl (n = 22) No (%)

High ≥10 μg/dl (n = 38) No (%)

Test of significance

Age l School children (≥6 years old) l Pre-school children (<6 years old)

9 (40.9) 13 (59.1)

20 (52.6) 18 (47.4)

×2 = 0.76 p = 0.4

Gender l Male l Female

9 (40.9) 13 (59.1)

23 (60.5) 15 (39.5)

×2 = 2.15 p = 0.1

Residency l Urban l Rural

12 (54.5) 10 (45.5)

20 (52.6) 18 (47.4)

×2 = 0.21 p = 1.0

Mother education l Education l Illiterate

3 (13.6) 19 (86.4)

4 (10.5) 34 (89.5)

×2 = 0.15 p = 0.9

Father eduction l Education l Illiterate

3 (13.6) 19 (86.4)

4 (10.5) 34 (89.5)

×2 = 0.34 p = 0.8

Mother work l Employed l Unemployed

3 (13.6) 19 (86.4)

4 (10.5) 34 (89.5)

×2 = 0.13 p = 0.7

Father work l Employed l Unemployed

16 (72.7) 6 (27.3)

28 (73.7) 10 (26.3)

×2 = 0.07 p = 0.9

12 (54.5) 10 (45.5)

20 (52.6) 18 (47.4)

×2 = 0.02 p = 1.0

3 (13.6) 19 (86.4)

4 (10.5) 34 (89.5)

×2 = 0.13 p = 0.7

Sources of drinking water l l

Tap water Hand pump water

Socioeconomic level l l

Middle Low

×2 = Chi-square test

Asian Journal of Paediatric Practice, Vol. 14, No. 1

23


clinical study Table 2. Prevalence of Anemia in Relation to Blood Lead Levels Low blood lead level <10 μg/dl (n = 22) No (%)

High blood lead level ≥10 μg/dl (n = 38) No (%)

Test of significance

No anemia

16 (72.7)

14 (36.8)

x2 = 7.17 p = 0.00

Anemia

6 (27.3)

24 (63.2)**

**p = 0.00

Table 3. Distribution of Hemoglobin Level in Relation to Blood Lead Levels Categories of anemia according to hemoglobin level

Low blood lead level <10 μg/dl (n = 22) No (%)

High blood lead level ≥10 μg/dl (n = 38) No (%)

Test of significance

16 (72.7)

14 (36.8)

x2 = 10.5 p = 0.01

Mild anemia (Hb level 10-10.9 g/dl)

1 (4.5)

11 (28.9)*

Moderate anemia (Hb level 8-9.9 g/dl)

4 (18.3)

5 (13.2)

Severe anemia: (Hb level < 8 g/dl)

1 (4.5)

8 (21.1)*

No anemia (Hb level ≥11 g/dl)

*p ≤ 0.05

Table 4. Comparison Between Mean Values of Different Hematological Parameters and Serum Level of Ferritin in Anemic and Control Groups Anemic group (n = 30) mean ± SD

Non-anemic control (n = 30) mean ± SD

Test of significance

RBC (×106 mm3)

4.05 ± 0.51

4.24 ± 0.28

t = –1.7 p = 0.08

Hb (g/dl)

8.97 ± 0.88

12.13 ± 0.46**

t = –17.2 p = 0.00

Hct

28.59 ± 2.26

36.56 ± 2.01**

t = –14.5 p = 0.00

MCV(μ )

70.02 ± 14.80

81.48 ± 6.70**

t = –3.8 p = 0.00

MCH

21.74 ± 3.21

27.08 ± 1.23**

t = –8.5 p = 0.00

MCHC

31.38 ± 1.98

33.54 ± 1.91**

t = –4.2 p = 0.00

RDW

17.27 ± 2.66

13.24 ± 0.60**

t = 8.0 p = 0.00

Ferritin (ng/ml)

40.21 ± 23.46

82.28 ± 9.76**

t = –9.0 p = 0.00

3

**p = 0.00 t = t-test

Comparing the results of Cu, Fe and Zn levels between the anemic and control groups revealed a significant decrease in the level of Fe among the anemic than the control group (p < 0.001). Whereas no statistically significant difference was seen between both groups for Cu and Zn levels (Fig. 1). As for the BLL between anemic and control groups, a significantly high BLL was found among anemic in comparison to control group (p < 0.001; Fig. 2). Table 5 reveals the correlation between the different hematological parameters and the blood levels of lead, Cu and Zn. According to lead a significant negative correlation is seen between it and Hb, Hct, MCV, MCH, Fe, and ferritin (r = –0.461, r = –0.484, r = –0.267, r = –0.381, r = –0.470 and r = –0.552, respectively) (p < 0.001). Whereas a significant positive correlation 24

existed between it and RDW (r = 0.458; p = 0.001). In addition, Cu showed a positive significant correlation with RBC (r = 0.264; p < 0.05) and a negative significant correlation with ferritin (r = –0.257; p < 0.05). Moreover Zn levels revealed a positive significant correlation in relation to Hb, Hct, MCH and ferritin (r = 0.324, r = 0.305, r = 0.308 and r = 0.314) and a negative significant correlation with RDW (r = –0.266) (p < 0.05). Assessment of mean values of iron (Fe) and ferritin among the low and high blood lead level groups revealed (Table 6) significantly lower blood iron and ferritin levels in the high BLL group than those of the low BLL group (48.86 ± 19.05 and 51.32 ± 24.52, 60.80 ± 21.27 and 78.39 ± 24.70, respectively). Asian Journal of Paediatric Practice, Vol. 14, No. 1


clinical study Copper Zinc

Iron

Lead

90

14

80

12

70

10

60 40

µg/dl

µg/dl

50 *

30

6 4

20

2

10 0

8

Anemic group

Control group

Figure 1. Comparison between mean values of copper, zinc and iron levels in anemic and control groups.

0

Anemic group

Control group

Figure 2. Comparison between mean values of blood lead levels in anemic and control groups.

*Significant

Table 5. Correlation of Different Hematological Parameters, Serum Iron and Ferritin Levels in Relation to Blood Lead, Copper and Zinc Hematological parameters

Blood lead level r-value (p-value)

Copper r-value (p-value)

Zinc r value (p-value)

0.118 (0.37)

0.264* (0.04)

0.015 (0.90)

Hb (g/dl)

–0.461** (0.00)

–0.159 (0.22)

0.324* (0.01)

Hct

–0.484** (0.00)

–0.209 (0.11)

0.305* (0.01)

MCV(μ )

–0.267* (0.03)

–0.177 (0.17)

0.248 (0.05)

MCH

–0.381** (0.00)

–0.156 (0.23)

0.308* (0.01)

MCHC

–0.155 (0.23)

–0.020 (0.87)

0.120 (0.36)

RDW

0.458** (0.00)

0.238 (0.06)

–0.266* (0.04)

Ferritin (ng/ml)

–0.552** (0.00)

–0.257* (0.04)

0.314* (0.01)

Fe (μg/dl)

–0.470** (0.00)

–0.136 (0.30)

0.186 (0.15)

RBC (×106 mm3)

3

*p ≤ 0.05 ** p = 0.00 r = Correlation coefficient

Table 6. Mean Values of Serum Iron (Fe) and Ferritin in Relation to Blood Lead Levels Low blood lead level <10 μg/dl (n = 22) mean ± SD

High blood lead level ≥10 μg/dl (n = 38) mean ± SD

Test of significance

Fe (μg/dl)

60.80 ± 21.27

48.86 ± 19.05*

Ferritin (ng/ml)

78.39 ± 24.70

51.32 ± 24.52**

t = 2.24 p = 0.02 t = 4.10 p = 0.00

*p ≤ 0.05 **p = 0.00

Discussion More than half of the study children (63.33%) had BLL ≥10 μg/dl, similar to a study done by Jain et al.6 who also reported a significant association of moderate and severe anemia with 10-19.9 μg/dl blood lead levels. while the present study reported a significant association Asian Journal of Paediatric Practice, Vol. 14, No. 1

of mild and severe anemia with 10-20 μg/dl blood lead levels, the difference in results may be due to a small sample size in the present study. However the current study is similar to the estimation obtained for children in India.17,18 The cutoff value of l0 μg/dl defined by the Center for Disease Control and Prevention as a limit for an elevated blood lead level primarily is based 25


clinical study on neurological toxicity.19 Recently, no level less than 10 μg/dl is considered safe.4 Schwartz et al20 reported that children living near primary lead smelters in the US of Idaho, had blood lead levels near 25 μg/dl and were associated with anemia in a dose-related manner. In addition, Drossos et al21 reported that children with BLL >30 μg/dl had a linear decline in hemoglobin level. Whereas on the contrary, Froom et al22 suggested that hemoglobin level did not correlate well with BLL and suggested that anemia is not related to lead at low BLL. However, other studies reported a variable association.23-27 Lead causes anemia by impairing heme synthesis and increasing the rate of red blood cell destruction.28 On the other hand, it is also possible that iron deficiency, which is a proven cause of anemia, leads to increase in the absorption of lead in the body, resulting in high BLL.29,30 Although a causal pathway cannot be determined, yet the study findings clearly demonstrate an association between varying severity of anemia and elevated BLL.

In accordance, although the present study revealed the Cu level to be higher in the anemic more than control group yet, this increase was not statistically significant. However, Cu has a role in the absorption of iron. The oxidation of ferrous iron into ferric state is carried by ceruloplasmin. This depletion of Cu could impair iron absorption.33 In the present study, the serum level of Pb in the anemic group was significantly higher than in the control. A possible explanation is that Fe deficiency increases absorption of Pb from the intestines. Similarly a study carried out in Canada, revealed high BLL in babies with Fe deficiency.25 Other studies revealed significant associations between Fe deficiency and high blood lead level.30,34

In the current study high BLL among school children (>6 years old) may be due to usage of crayon in school and high BLL in male children than female children may explain by more hobbies in males.

The current results showed that Hb, Hct, MCV, MCH and ferritin values of children with anemia decreased and RDW level increased in comparison to control group.

Fe, Cu and Zn are essential elements for the maintenance of life and health. Pb which is a heavy metal, can be harmful to human health. Therefore, the blood level of these elements in children was determined. Because of the presence of high BLL in drinking water, as reported by the WHO, this study was carried out to reveal the relationship between high blood lead levels, trace elements as well as hematological parameters in children.

Also, blood lead levels were higher in anemic children. This could be due to that decreasing iron level increases lead absorption that in turn affects heme synthesis, thus negatively affecting hematological parameters.28 Moreover high BLLs were found to be associated with lower iron and ferritin levels than lower lead levels. This may be that iron absorption occurs predominantly in the duodenum and jejunum. Also, a number of dietary factors influence iron absorption, where ascorbate and citrate increase its uptake. Lead in particular is a pernicious element to iron metabolism. As it is taken up by the iron absorption machinery instead of iron, and through competitive inhibition. Further more, it interferes with a number of important iron dependent metabolic steps such as heme biosynthesis.2

In the present study, the level of iron in the anemic group was found to be significantly lower than the control as was expected, similarly Jain et al6 represented measure finding. As Fe has an essential role in many biological processes and as deficiency is a World health problem, especially for infants and rapidly growing adolescents. Therefore, it is important to maintain iron concentration within its narrow normal range.31 In the present study serum Zn level of the anemic group is insignificantly lower than the control group. There is an antagonism between Zn and Fe absorption 26

from the gastrointestinal tract, as an increase iron concentration in the intestinal lumen may antagonize the uptake of Zn.32 A study done by Sebahat et al1 found a decrease in serum Zn level and an increase in serum Cu level in the anemic group compared to the control group.

In investigated water samples were considered suitable for drinking according to the EMH35 as the lead level was lower than the permissible limit (5 μg/dl), although the WHO36 considered higher than the permissible limit to be 1 μg/dl. In Dakahlya-Egypt, lead level in drinking water was higher than the permissible limit Asian Journal of Paediatric Practice, Vol. 14, No. 1


clinical study according to the WHO. In Egypt, the control of lead is not efficient, so that the level of lead in drinking water in some sporadic areas is still high level.37 In 20032004, tap water in Washington, DC, exceeded the Environmental Protection Agency (EPA) regulations. This was because of a change in water disinfection procedures, which increased the water ability to leach lead from connector pipes between water mains and interior plumbing in old houses.38 In developing countries such as India, control of lead pollution is much slower and more sporadic. Some studies estimated that more than half of children in India have blood lead levels >10 μg/dl.18 The present work revealed an association between blood lead level and low serum iron and ferritin levels. This is similar to several studies reporting higher proportions of children with elevated blood lead levels among those with low iron and ferritin levels.39-41 These results suggest that inadequate iron status may amplify the effect of lead contamination in the environment by increasing absorption and possibly retention of lead in the body.39 On the contrary Hershko et al42 reported a lack of correlation between iron and blood lead in older children. Conclusion In the present study, lead levels ≥10 μg/dl in children were associated with an increased risk of mild and severe anemia, decreasing iron absorption and negatively affecting the hematological parameters. High BLLs were associated with low blood level of iron and ferritin. Lead level in drinking water was high according to the WHO, and this may be one of the leading causes for elevating BLL in children. Lead pollution might be controlled and steps should be taken to reduce the prevalence of childhood anemia. Competing Interests The authors declare that they have no competing interests. Acknowledgements We would like to thank Prof. Dr. Gamal H. El-Samra, Prof. of occupational Health and Industrial Medicine, (Cairo University) for his help and cooperation. We thank Prof. Dr. Mona Z. El-Baz, Prof. of community medicine (Alazhar Univerisity) for her help and guidance. Asian Journal of Paediatric Practice, Vol. 14, No. 1

References 1. Sebahat T, Aziz P, Murat I, Gunfer T, Gulten E, Mevlut B, Yasin KT, Osman G: Interaction between anemia and blood levels of iron, zinc, copper, cadmium and lead in children. Indian J Pediatr 2007, 74:827-30. 2. Goyer RA: Lead toxicity: current concerns. Environ Health Perspect 1993, 100:177-87. 3. Ellis MR, Kane KY: Lightening the lead load in children. Am Fam Physician 2000, 62:545-54.559-60. 4. CDC: Preventing lead poisoning in young children: a statement by the Center for Disease Control and Prevention. Atlanta, GA 2005 [http://www.cdc.gov/ nceh/lead/publications/prevleadpoisoning.pdf ]. 5. Abdel-Maaboud RM, El-Attar MM, Mohamad NA, Ahmed SA, Medhat A: Lead toxicity in some rural communities in Assiut Governorate. Ass Un Bull Environ Res 2005, 8:57-66. 6. Jain NB, Laden F, Culler U, Shankar A, Kazani S, Garshick E: Relation between blood lead levels and childhood anemia in India. Am J Epidemiol 2005, 161:968-73. 7. Lanphear BP, Matte TD, Rogers J: The contribution of lead contaminated house dust and residential soil to children’s blood lead levels. A pooled analysis of 12 epidemiologic studies. Environ Res 1998, 79:51-68. 8. Igwe JC, Abia AA: Equilibrium sorption isotherm studies of Cd (II), Pb (II) and Zn (II) ions detoxification from waste water using unmodified and EDTA-modified maize husk. Electronic J Biotechnology 2007, 10:536-48. 9. Volesky B, Holan ZR: Biosorption of heavy metals. Biotechnology Progress 1995, 11:235-50. 10. Jones AA, Disilveslro RA, Coleman M, Wanger TL: Copper supplementation of adult man: effect on blood copper enzyme activities and indicators of cardiovascular disease risk. Metabolism 1997, 46:1380-3. 11. Lonnerdal B: Dietary factors influencing zinc absorption. J Nutr 2000, 30:1378s. 12. Kapur D, Agarwal KN, Agarwal DK: Nutritional anemia and its control. Indian J Pediatr 2002, 69:607-16. 13. Lozoff B, Wolf AW, Jimenez E: Iron-deficiency anemia and infant development: effect of extended oral iron therapy. J Pediatr 1996, 129:382-9. 14. Ozcay F, Derbent M, Aldemir D: Effect of iron deficiency anemia on renal tubular function in childhood. Pediatr Nephrol 2003, 18:254-6. 15. World Health Organization. United Nations Children’s Fund: Iron deficiency anemia, assessment, prevention and control: a guide for programme managers. Geneva, Switzerland: WHO; 2001.

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clinical study 16. Fernandez FJ, Kahn L: Graphite Atomic Absorption Spectrophotometry for metals. Atomic Absorption, New sletter 1971, 10:65. 17. Kaul B: Lead exposure and iron deficiency among Jammu and New Delhi children. Indian J Pediatr 1999, 66:27â&#x20AC;&#x2018;35. 18. Patel AB, Williams SV, Frumkin H: Blood lead in children and its determinants in Nagpur, India. Int J Occup Environ Health 2001, 7:119-26. 19. Franko EM, Palome JM, Brown MJ, Kennedy CM, Moore LV: Blood lead levels in young children-United States and selected states, 1996-1999. Morb Mortal Wkly Rep 2000, 49:1133-7.

analysis of children followed in an urban primary care clinc. J Pediatr 2003, 142:9-14. 31. Andrews NC: Disorders of iron metabolism. New Engl J Med 1999, 341:1986-95. 32. Ece A, Uyanik BS, Iscan A, Ertan P, Yigitoglu MR: Increased serum copper and decreased serum zinc level in children with iron deficiency anemia. Biol Trace Elem Res 1997, 59:31-9. 33. Newhouse IJ, Clement DB, Lai C: Effects of iron supplementation and discontinuation on serum copper, zinc, calcium and magnesium levels in women. Med Sci Sports Exerc 1993, 25:562-71.

20. Schwaetz J, Landrigan PJ, Baker EL: Lead induced anemia: dose response relation and evidence for a threshold. Am J Public Health 1990, 80:165-8.

34. Kaufmann RB, Clouse TL, Olson DR, Matte TD: Elevated blood lead levels and lead screening among US children aged one to five years:1988-1994. Pediatrics 2000, 106:E79.

21. Drossos CG, Mavroids KT, Papadopoulov-Dafotis Z: Environmental lead pollution in Greece. Am Ind Hyg Assoc J 1982, 43:796-8.

35. Egyptian Ministry of Health (EMH): Standards for drinking water. 1995. Internal Report

22. Froom P, Kristal-Bonch E, Benbassat J: Lead exposure in battery-factors workers is not associated with anemia. J Occup Environ Med 1999, 41:120-3. 23. Bashir R, Khan DA, Saleem M: Blood lead levels and anemia in lead exposed workers. J Pak Med Assoc 1995, 45:64-6. 24. Carvalho FM, Barreto ML, Silvany-Neto AM: Multiple causes of anemia amongst children living near a lead smelter in Brazil. Sci Total Environ 1984, 35:71-84. 25. Cohen AR, Trotzky MS, Pincus D: Reassessment of the microcytic anemia of lead poisoning. Pediatr 1981, 67:904-6. 26. Osterode W, Barnas U, Geissler K: Dose dependent reduction of erythroid progenitor cells and inappropriate erythropoietin response in exposure to lead: new aspects of anemia induced by lead. Occup Environ Med 1999, 56:106-9. 27. Willows ND, Gray-Donald K: Blood lead concentration and iron deficiency in Canadian aboriginal infants. Sci Total Environ 2002, 289:255-60. 28. Goyer RA, Rhyne BC: Pathological effects of lead. Int Rev Exp Pathol 1973, 12:1-77. 29. Bradman A, Eskenazi B, Sutton P, Goldman LR: Iron deficiency associated with higher blood lead level in children living in contaminated environments. Environ Health Perspect 2001, 109:1079-84. 30. Wright RO, Tsaih SW, Schwartz J: Association between iron deficiency and blood lead level in a longitudinal

36. World Health Organization (WHO): Guideline for drinking water quality health criteria and other supporting information. Geneva 1997, 2:254-66. 37. Ghanem AA, EI-Azab SM, Mandour RA, EI-Hamady MS: Relationship between lead levels in drinking water and mother breast milk-Dakahlya-Egypt. The Internal J of Toxi 2008, 5:1559-3916. 38. American Academy of Pediatrics: Lead exposure in children: prevention, detection and management. Pediatrics 2005, 116:1036-46. 39. Bradman A, Eskenazi B, Sutton P, Athanasoulis M, Goldman LR: Iron deficiency associated with higher blood lead in children living in contaminated environments - Childrenâ&#x20AC;&#x2122;s Health Articles. Environ Health Perspect 2001, 109:1079-84. 40. Yip R, Dallman PR: Developmental changes in erythrocyte protoporphyrin: the roles of iron deficiency and lead toxicity. J Pediatr 1984, 104:710-30. 41. Yip R: Multiple interactions between childhood iron deficiency and lead poisoning: evidence that childhood lead poisoning is an adverse consequence of iron deficiency. In: Recent Knowledge on Iron and Folate Deficiencies in the World Edited by: Hercberg S, Galan P, Dupin H. Paris: Colloque INSERM; 1990: 523-32. 42. Hershko C, Konijn AM, Moreb J, Link G, Grauer F, Weissenberg E: Iron depletion and blood lead levels in a population with endemic lead poisoning. Isr J Med Sci 1984, 20:1039-43.

n

28

n

n

Asian Journal of Paediatric Practice, Vol. 14, No. 1


clinical study

Television Viewing and Sleep are Associated with Overweight among Urban and Semi-urban South Indian Children Rebecca Kuriyan, Swarnarekha Bhat, Tinku Thomas, Mario Vaz, Anura V Kurpad

Abstract Background: Childhood obesity is an emerging problem in urban Indian children and increases in childhood overweight and obesity may be major contributors to the adult obesity epidemic. Thus, identifying potential risk factors for childhood obesity and formulating early interventions is crucial in the management of the obesity epidemic. The present study was aimed at evaluating dietary and physical activity patterns as determinants of overweight in a sample of children. Methods: Five hundred and ninety eight children aged 6-16 years, visiting St. Johnâ&#x20AC;&#x2122;s Medical College Hospital, Bangalore City, India for minor complaints or routine checkups were recruited into the study. These children were studied for their physical activity patterns, sleep duration, sedentary habits and eating behaviours as potential determinants of overweight. Results: Decreased duration of sleep and increased television viewing were significantly associated with overweight. Among the eating behaviours, increased consumption of fried foods was significantly associated with overweight. Conclusion: Our data suggests that duration of sleep, television viewing and consumption of fried foods may be significant factors that contribute to overweight. Further longitudinal studies are needed to confirm these findings. Key words: Risk factors, childhood obesity, physical activity patterns

Findings Childhood obesity is emerging as a major health problem in India, especially in children from urban higher socioeconomic areas; for example, about 30% of children were overweight in an affluent Delhi school.1 The adverse health effects of obesity in children justify the need to look for potential risk factors and provide suitable interventions. Factors contributing to childhood obesity, such as parental obesity, eating behaviors, TV viewing and lack of physical activity have been studied in Western settings.2,3 Recent studies suggest that sleep duration is an important behavioural antecedent of obesity.4,5 Indian studies are presently lacking with regard to the determinants of overweight/ obesity among children. The aim of the present study was to evaluate dietary and physical activity patterns as determinants of overweight in a sample of children from different socioeconomic backgrounds, visiting a hospital for routine health checks or for minor complaints. This was a cross-sectional, questionnaire based study on 598 otherwise healthy children (male and female) aged 6-16 years, recruited from children visiting St. Johnâ&#x20AC;&#x2122;s Citation: Kuriyan et al. Television viewing and sleep are associated with overweight among urban and semi-urban South Indian children. BMC, Nutrition Journal 2007, 6:25.

Asian Journal of Paediatric Practice, Vol. 14, No. 1

Medical College Hospital, Bangalore, for vaccinations or minor complaints. None of the children had a history of recent weight loss. The study was approved by the institutional ethical review committee and parental informed consent was obtained. Information was collected by a trained nutritionist from parents and, in older children, from themselves. Information included the date of birth, address, parentâ&#x20AC;&#x2122;s occupation/income, habitual frequency and duration of different activities in school, games, travel, tuition, sedentary habits at home, household work, hobbies, exercise and sleep. The level of occupation, education and income of the parents were combined to arrive at an indicator for the socioeconomic status of the child. The habitual frequency (per week) of consumption of chocolates, ice-creams, bakery foods, soft drinks, fried foods and non-vegetarian food, as well as the frequency of eating out, was obtained. Anthropometric measurements included body weight (nearest 0.1 kg) and height (0.1 cm), from which body mass index (BMI) (kg/m2) was calculated. In addition, waist and hip circumferences were measured according to a standardized protocol.6 The children were classified as overweight or normal weight, based on their BMI.7 Their habitual activities 29


clinical study were grouped into 3 broad domains, consisting of sedentary activities (all sedentary activities at school and home), rigorous activities (physical training at school, games and exercise at and after school) and sleep. The duration of TV viewing was considered separately as an independent variable. Separate logistic regression analyses were performed to identify the significant associations of overweight with each of the habitual activity categories or eating behavior, while adjusting for age, gender, home location (urban or periurban) and socioeconomic status. Finally, associations between different significant predictors of overweight/ obesity were also explored using cross tabulation and logistic regression with all three significant predictors (duration of sleep, duration of TV viewing and frequency of eating fried food) in the same model which examined the independent effect of all the three predictors and the interaction effect between them. Urban children constituted 73% of the whole group, while the remaining children were from semi-urban areas (small towns). Fifty four percent (n = 324) of the children were male. The range of body weight was

from 14 to 68 kg and the body mass index (BMI) ranged from 9.8 to 29.8 kg/m.2 Their ages ranged from 6 to 16 years, and the children came from lower to middle socioeconomic status households. Based on their BMI,7 6.4% (n = 38) of the children were overweight. The duration of sleep and TV viewing were significantly associated with overweight. Children who slept less than 8.5 hours/day had significantly higher odds (6.7, p = 0.013) of being overweight when compared to children who slept more than 9.5 hours/day, after adjustments for age, gender, location of stay and socioeconomic status (Table 1). The adjusted odds of being overweight for children who viewed television for greater than or equal to 1.5 hours/day was 19.6 (p = 0.001), when compared to children who viewed television for less than or equal to 45 minutes/day (Table 1). Among eating behaviors, the consumption of fried food items, more than 6 times/week, was associated with significantly higher odds of being overweight (3.1, p = 0.014) when compared to fried

Table 1. Relationship Between Habitual Activities/Eating Behaviors and Overweight (OW) Activity/Eating behavior Sleep (hours/day)

Sedentary activities (hours/day) 2

Rigorous activities (hours/day) 3

TV viewing (hours/day)

Fried foods (frequency/week)

Tertiles

n (%)

Median (IQR)

OR1

95% CI

p

OR4

95% CI

≤8.5

203 (33.9)

8 (7.5-8.5)

6.7

1.5, 30.2

0.013

6.8

1.4, 32.1

8.51-9.5

257 (43)

9 (9-9.5)

3.6

0.8, 16.3

0.09

3.7

0.8, 17.4

>9.5

138 (23.1)

10 (10-10.5)

1

-

-

1

-

≤7.4

200 (33.4)

6.7 (6.2-7.1)

1

-

-

7.41-8.9

199 (33.3)

8.1 (7.8-8.5)

0.6

0.3, 1.5

0.27

-

-

>8.91

199 (33.3)

10.2 (9.5-11.2)

0.9

0.4,2.2

0.91

≤1.61

195 (32.6)

1 (0.6-1.4)

1.7

0.8, 3.8

0.20

1.62-2.61

203 (33.9)

2.0 (1.8-2.3)

0.8

0.3, 2.0

0.65

-

-

>2.61

200 (33.4)

3.4 (3-4.1)

1

-

-

≤0.75

217 (36.3)

0.7 (0.5-0.75)

1

-

-

1

-

0.76-1.5

266 (44.5)

1 (1-1.5)

3.1

0.8, 11.3

0.09

3.1

0.8, 11.4

>1.5

115 (19.2)

2 (2-3)

19.6

5.5, 69.4

<0.001

19.8

5.4, 71.9

≤2.5

199 (33.3)

1 (0.3-2.0)

1

-

-

1

-

2.5-6

199 (33.3)

3.7 (3.0-4.7)

0.5

0.2, 1.6

0.27

0.4

0.1, 1.1

>6

200 (33.4)

10.8 (8.0-16.5)

3.1

1.3, 7.6

0.014

1.6

0.7, 3.9

IQR = Interquartile range, OR = Odds ratio, 95% CI = 95% Confidence Interval, p = Level of significance. ORs were adjusted for age, gender, living location and socioeconomic status. Includes all sedentary activities at school and home. 3 Includes physical training at school, games at and after school and exercise. 4 OR were adjusted for age, gender, living location and socioeconomic status and the other significant predictors of overweight in the data. 1 2

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Asian Journal of Paediatric Practice, Vol. 14, No. 1


clinical study food consumption less than 2.5 times/week. None of the other eating behaviours were found to be significantly associated with being overweight. Short sleep duration has been shown to be a risk factor for obesity in children,4,5 through the modulation of hormones such as leptin and ghrelin, the reduced levels of which can increase hunger and appetite and influence weight gain.8,9 In this study, the duration of sleep was based on self reportage and this might represent an overestimate in absolute terms as sleep was reported as ‘going to bed’ and ‘rising’ rather than as actual sleep. However, it is unlikely that errors in self reportage would have contributed to a systematic error in between those who reported sleeping less or more. Children with television sets in their rooms, spent less time in bed on weekdays and reported higher overall levels of being tired.10-12 It is likely that behaviours could cluster within individuals, and that increased television viewing could be associated with lower sleep duration. It was observed that the distribution of TV viewing in its tertiles was 34%, 45% and 21% in children who slept less than 8.5 hours (lowest tertile of sleep). Hence, there was no significant clustering observed in the present study. It has also been recommended that the children’s total media time (TV, video and video games) to be limited to no more than 1 to 2 hours of quality programming per day,13 however, it seems that even within this recommendation, there may be potential for a graded response towards weight gain with increasing duration of television viewing. None of the children in the present study played video games regularly. With regard to diet, there is evidence of a demographic, epidemiological and nutrition transition in India particularly in the urban areas characterized by a shift in dietary patterns toward a higher fat and sugar content linked to an ongoing epidemic of chronic disease and obesity.14 The results of the present study demonstrate that the increased consumption of fried and high fat foods were significantly associated with overweight. Similar results were seen in a previous study on children aged 9-14 years, where the higher consumption of fried foods from outside home was associated with greater total energy intakes, poorer diet quality and excessive weight gain.15 In the present study again, there was no clustering effect observed between Asian Journal of Paediatric Practice, Vol. 14, No. 1

the high fat or junk food consumption and potentially unhealthy behaviours such as television viewing. The percentage distribution of TV viewing in its tertiles was 33%, 45% and 23% in the highest tertile of fried food consumption. The findings of the present study suggest that behavioral modifications to increase sleep time, limit television viewing, as well as the limiting of consumption of fried foods may be useful for health promotion programs to prevent weight gain in childhood. Reducing television viewing to a minimum (1 to 1.5 hours/day) is desirable, as is encouraging children to sleep for at least 9 hours a day. Another simple message might be to reduce the frequency of eating fried and high fat foods to a minimum (2-3 times per week). Further longitudinal and dose response studies are however needed to confirm the potential link between these variables. Acknowledgements Parental informed consent was obtained for publication.

References 1. Kapil U, Singh P, Pathak P, Dwivedi SN, Bhasin S: Prevalence of obesity amongst affluent adolescent school children in Delhi. Indian Pediatr 2002, 39:449-452. 2. Burke V, Beilin LJ, Simmer K, Oddy WH, Blake KV, Doherty D, Kendall GE, Newnham JP, Landau LI, Stanley FJ: Predictors of body mass index and associations with cardiovascular risk factors in Australian children: a prospective cohort study. Int J Obes 2005, 29:15-23. 3. Jago R, Baranowski T, Baranowski JC, Thompson D, Greaves KA: BMI from 3-6 year of age is predicted by TV viewing and physical activity, not diet. Int J Obes 2005, 29:557-564. 4. Agras WS, Hammer LD, McNicholas F, Kraemer HC: Risk factors for childhood overweight: a prospective study from birth to 9.5 years. J Pediatr 2004, 145:20-25. 5. Sekine M, Yamagami T, Handa K, Saito T, Nanri S, Kawaminami K, Tokui N, Yoshida K, Kagamimori S: Child Care Health Dev 2002, 28:163-70. 6. Harrison GG, Buskirk ER, Carter JEL, Johnston FE, Lohman TG, Pollock ML, Roche AF, Wilmore J: Skinfold Thicknesses and Measurement Technique. In Anthropometric Standardization Reference Manual Edited by: Lohman TG, Roche AF, Martorell R. Human Kinetics Books, Illinois; 1988:55-71. 7. Cole TJ, Bellizzi NC, Flegal KM, Dietz WH: Establishing a standard definition for child overweight and obesity worldwide: international survey. BMJ 2000, 320:1240‑1246.

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clinical study 8. Spiegel K, Tasali E, Penev P, Van Cauter E: Brief communication: Sleep curtailment in healthy young men is associated with decreased leptin levels, elevated ghrelin levels, and increased hunger and appetite. Ann Intern Med 2004, 141:846-850. 9. Taheri S, Lin L, Austin D, Young T, Mignot E: Short sleep duration is associated with reduced leptin, elevated ghrelin, and increased body mass index. PLoS Med 2004, 1:e62. Epub Dec 7. 10. Davison KK, Marshall SJ, Birch LL: Cross-sectional and longitudinal associations between TV viewing and girlsâ&#x20AC;&#x2122; body mass index, overweight status, and percentage of body fat. J Pediatr 2006, 149:32-37. 11. Dennison BA, Erb TA, Jenkins PL: Television viewing and television in bedroom associated with overweight

risk among low-income preschool children. Pediatrics 2002, 109:1028-1035. 12. Van den Bulck J: Television viewing, computer game playing, and Internet use and self-reported time to bed and time out of bed in secondary-school children. Sleep 2004, 27(1):101-104. 13. American Academy of Pediatrics: Committee on Public Education. Pediatrics 2001, 107:423-426. 14. Shetty PS: Nutrition transition in India. Public Health Nutr 2002, 5(1A):175-182. 15. Taveras EM, Berkey CS, Rifas-Shiman SL, Ludwig DS, Rockett HR, Field AE, Colditz GA, Gillman MW: Association of consumption of fried food away from home with body mass index and diet quality in older children and adolescents. Pediatrics 2005, 116(4): e518â&#x20AC;&#x2018;524.

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Asian Journal of Paediatric Practice, Vol. 14, No. 1


photo quiz

Infant with Vesicular Rash

A

seven-month-old girl presented with a rash on her face that had worsened over the previous two days. The patient had a history of eczema and was given hydrocortisone and emollients in the emergency department one week earlier. The rash improved, but then rapidly worsened. On physical examination, she was non-toxic but had a body temperature of 102.1°F (38.9°C). She was very fussy and scratched at her arms and body. Physical examination also revealed multiple small, elevated vesicles and papules on her face (Figure 1). Many of the vesicles were ruptured or umbilicated, and some coalesced to form crusted plaques. A cluster of vesicles and bullae were noted on her right hand (Figure 2), and scattered ruptured vesicles were noted on her chest and back.

Figure 1.

Question Based on the patient’s history and physical examination, which one of the following is the most likely diagnosis? A. Contact dermatitis. B. Eczema herpeticum. C. Eczema vaccinatum. D. Impetigo. E. Varicella. Discussion The answer is B: eczema herpeticum. Eczema herpeticum is characterized by erythematous, ruptured, and crusting vesicles. The rash typically begins on the head or neck as dome-shaped vesicles that subsequently umbilicate, rupture, and often coalesce. The rash usually occurs on areas affected by atopic dermatitis, although it may also affect previously healthy skin.1 Eczema herpeticum is pruritic and may be accompanied by fever, malaise, lymphadenopathy, vomiting, and diarrhea. It is most common in children

Source: Adapted from Am Fam Physician 2010;81(9):1143-4.

Asian Journal of Paediatric Practice, Vol. 14, No. 1

Figure 2.

two to three years of age,2 although it may occur at any age. Eczema herpeticum is caused by primary herpes simplex virus 1 infection in patients with a disrupted skin barrier from underlying atopic dermatitis.2 The Cont’d on page 37... 33


journal scan

From the Journals...

Is Acetaminophen as Effective as an Antihistamine-decongestantacetaminophen Combination in Relieving Symptoms of Acute Nasopharyngitis in Children? A Randomized, Controlled Trial Objectives: To determine the efficiency of drugs, which include antihistaminic-decongestant-acetaminophen agents versus only acetaminophen in symptomatic treatment of acute nasopharyngitis in children. Methods: This clinical, randomized, controlled, single blind drug efficacy comparison research was conducted in 148 patients with acute nasopharyngitis between ages 2 and 12 years. After randomization, Group-1 consisted of cases (n = 86), which used OTC drugs [acetaminophen + diphenhydramine + pseudoephedrin] and Group-2 consisted of cases (n = 62), which used only acetaminophen. After receiving nasal swab for showing the viral etiology, symptoms were scored clinically on admission and then on 10 days follow-up period, and re-evaluated on the third and fifth days of the drug therapy with the same scoring scale. Any complications were noted during the 1-month follow-up period after taking the drugs. Results: The virus isolation rate in Group-1 was 27.9% and in Group-2 was 22.6%. At the first day of study, before medication, clinic scores of the groups did not show a significant difference (Group-1 1.7 vs Group-2 2.0). Clinic scores in both groups on the third (Group-1 4.0 vs Group-2 4.1) and fifth days of therapy (Group-1 1.7 vs Group-2 2.0) were not different either. Also, the complication rate was not different during the 1-month follow-up period (Group-1 2.3% vs Group2 8.0%, p: 0.12). The family response for the drug satisfaction in both groups was similar and positive. Conclusion: For relieving symptoms of acute nasopharyngitis in children, acetaminophen without any combination is as effective as OTC drugs containing acetaminophen, decongestant and antihistaminics. Unuvar E, Yildiz I, Kilic A, et al. Int J Pediatr Otorhinolaryngol 2007;71(8):1277-85.

Asian Journal of Paediatric Practice, Vol. 14, No. 1

Low Zinc in Drinking Water is Associated with the Risk of Type 1 Diabetes in Children Aim: To explore if drinking water may influence the development of type 1 diabetes in children, either via enterovirus spread via drinking water or quality of drinking water related to acidity or concentration of certain minerals. Methods: One hundred and forty-two families with a child with diabetes and who lived either in seven municipalities with a high annual diabetes incidence during 1977-2001 and in six municipalities with the lowest incidence during those 25 years were asked to participate. Three hundred and seventy-three families in these communities were used as controls. The families filled a 200 ml plastic bottle with their tap drinking water and returned it by mail. The water samples were analyzed for pH, zinc, iron, nitrate, nitrite, nitrate-nitrogen and nitrite-nitrogen and occurrence of enterovirus RNA. Results: Enterovirus RNA was not found in the tap water samples. The concentration of zinc, nitrate and nitrate-nitrogen was lower in the municipalities with high incidence of type 1 diabetes. The water samples from families with a child with diabetes had lower concentration of zinc than water samples from control families. Conclusion: Low zinc in drinking water is associated with the risk of developing type 1 diabetes during childhood. Enterovirus does not seem to be spread via drinking water in a country with modern water works. Ulf S, Sami O, Heikki H, et al. Pediatr Diabetes 2010 Sep.7): [Epub ahead of print]

Randomized Trial of the Effect of Zinc Supplementation on the Mental Health of School-age Children in Guatemala Background: Rates of mental illness in children are increasing throughout the world. Observational studies of depression, anxiety and attention-deficit hyperactivity disorder suggest that zinc is an alternative treatment. Objective: We examined the effect of zinc supplementation on the mental health of school-age 35


journal scan children in Guatemala. Design: From January to October 2006, we conducted a six months randomized, doubleblind controlled trial comparing zinc supplementation (10 mg ZnO/day for 5 day/week) with a placebo (10 mg glucose) in 674 Guatemalan children in grades 1-4. Outcome measures included internalizing (i.e., depression and anxiety) and externalizing (i.e., hyperactivity and conduct disorder) problem behaviours, positive behaviours (i.e., socialization and leadership) and serum zinc concentrations. Results: Zinc and placebo groups did not differ significantly in any behavioral measures at baseline or at followup. At baseline, 21.4% of children had serum zinc concentrations <65 μg/dl. At follow-up, both groups improved significantly, and zinc concentrations were higher in the zinc group. Increases in serum zinc concentrations were inversely associated with decreases in depressive symptoms (estimate: -0.01 points/μg Zn/dl; p = 0.01), anxiety (estimate: –0.012 points/μg Zn/dl; p = 0.02), internalizing symptoms (estimate: -0.021 points/μg Zn/dl; p = 0.02) and social skills (estimate: -0.019 points/μg Zn/dl; p = 0.01) in adjusted models that were controlled for child age, sex, socioeconomic status, household and treatment group. Conclusions: Six months of zinc supplementation did not induce differences in mental health outcomes between zinc and placebo groups. However, increases in serum zinc concentrations were associated with decreases in internalizing symptoms (i.e., depression and anxiety) in a community-based sample of children at risk of zinc deficiency. Digirolamo AM, Ramirez-Zea M, Wang M, et al. Am J Clin Nutr 2010;92(5):1241-50.

Infant Anemia is Associated with Infection, Low Birth Weight and Iron Deficiency in Rural Bangladesh Aim: Iron deficiency, growth, infection and other micronutrient deficiencies. Methods: Using data from MINIMat, a randomized maternal food and micronutrient  supplementation trial, we assessed the associations between anemia (Hemoglobin <105 g/l) in 580 infants at six months and deficiencies of iron,

36

vitamin A, vitamin B12, zinc and folate, infection and anthropometric indices. Variables associated with anemia in bivariate analyses were evaluated in logistic regression models, adjusting for potential confounders. Results: Anemia was  found in 46% of the infants and among these 28% had iron deficiency (plasma ferritin <9 μg/l). Elevated C-reactive protein (>10 mg/l) (OR = 2.7, 95% CI: 1.6, 4.7), low birth weight (OR = 2.3, 95% CI: 1.5, 3.5) and iron deficiency (OR = 2.2, 95% CI: 1.4, 3.6) were independently associated with increased risk for anemia. We also observed a seasonal variation in anemia not mediated through the other factors studied. Conclusion: In a cohort in rural Bangladesh, anemia at  age six months was common and associated with infection, low birth weight and iron deficiency. Eneroth H, Persson LA, El Arifeen S, et al. Acta Paediatr 2010 Sep.24. [Epub ahead of print]

Montelukast as Monotherapy in Children with Mild Persistent Asthma The cysteinyl leukotrienes cause bronchoconstriction, increased mucus production and airway inflammation, three major features of asthma. Several randomized controlled trials have shown the efficacy of leukotriene receptor antagonists for improving asthma outcomes. The drug is favored for treating childhood asthma, where poor compliance with inhalation therapy is a therapeutic challenge. To assess the effectiveness of Montelukast in asthmatic children under real-life conditions, a prospective, single-arm, multicenter, open-label observational study was performed on asthmatic children 2- to 14-years-old with a history of physician-diagnosed mild persistent asthma. Montelukast was given once daily for 12 consecutive weeks. By the end a significant improvement of the daytime asthma symptom score, night-time asthma score, peak expiratory flow rate (PEFR) and mean score of the investigators’ global evaluation was noted (p < 0.05). These results suggest that montelukast is an effective monotherapy controller in children with mild persistent asthma. Wu WF, Wu JR, Dai ZK, et al. Asian Pac J Allergy Immunol 2009;27(4):173-80.

Asian Journal of Paediatric Practice, Vol. 14, No. 1


photo quiz ...Contâ&#x20AC;&#x2122;d from page 33 diagnosis is clinical and is based on history of atopic dermatitis and rapid development of the characteristic rash. This can be confirmed using polymerase chain reaction testing, direct fluorescent antibody staining, or viral culture.3 Eczema herpeticum is often accompanied by a staphylococcal infection,1 although this is not the primary etiology. Eczema herpeticum is a dermatologic emergency. To prevent further dissemination, acyclovir therapy should be initiated when eczema herpeticum is suspected, and not delayed for laboratory confirmation.3 Additional treatment may include cool compresses; an emollient, such as petroleum jelly; antihistamines to decrease pruritus; and treatment of any bacterial superinfection.3 The condition has a mortality rate of up to 10 percent, even with treatment.2 Topical steroids should be avoided to prevent further insult to the skinâ&#x20AC;&#x2122;s immune response.

Summary Table Condition

Characteristics

Contact dermatitis

Occurs in all age groups; distribution is related to exposure; primarily appears as erythema, but vesicles or bullae may occur; pruritic; widespread crusting is uncommon

Eczema herpeticum

Most common in children two to three years of age; begins on head or neck; dome-shaped vesicles that umbilicate, rupture, and often coalesce; caused by herpes simplex virus 1 infection

1

The distribution of the contact dermatitis rash is related to the exposure. Erythema is the most common presentation, although vesicles or bullae may occur. Contact dermatitis is pruritic and may lead to visible excoriations. Widespread crusting is uncommon.1 Eczema vaccinatum is a rare cutaneous reaction to smallpox immunization (vaccinia virus). The condition is marked by development of umbilicated vesicles and papules, usually in a uniform stage of development. It occurs in persons with predisposing factors, such as a history of atopic dermatitis, after receiving the smallpox vaccine or after a close contact receives the vaccine.4 Impetigo is common in children and can occur anywhere on the body. The condition sometimes begins as a small vesicle or pustule, but rarely demonstrates widespread vesiculation. The crusting is typically honey-colored, rather than red or brown, and erythema usually is not present.1

Eczema vaccinatum Occurs on areas affected by atopic dermatitis after exposure to smallpox vaccine; umbilicated papules and vesicles usually in a uniform stage of development Impetigo

Common in children; can occur anywhere on the body; may begin as a vesicle or pustule, but is rarely widespread; honey-colored crusting

Varicella

Begins on trunk then spreads to face and extremities; vesicle on a pink papule; multiple stages present simultaneously

Varicella typically begins on the trunk and spreads to the face and extremities. The classic lesion is a pink or red papule that develops into an overlying vesicle. The vesicle then ruptures and crusts. Multiple stages may appear simultaneously.1 References 1. Habif TP. Clinical Dermatology. 5th ed. St. Louis, Mo.: Mosby; 2010:135,335,473-474. 2. Buccolo LS. Severe rash after dermatitis. J Fam Pract. 2004;53(8):613-615. 3. Stricker T, Lips U, Sennhauser FH. Visual diagnosis. An 8-month-old infant who has an erupting rash. Pediatr Rev. 2007;28(6):231-234. 4. Moses AE, Cohen-Poradosu R. Images in clinical medicine. Eczema vaccinatumâ&#x20AC;&#x201D;a timely reminder. N Engl J Med. 2002;346(17):1287. n

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AJPP july-Sect2010