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1.  Ready-to-use therapeutic food with elevated n-3 polyunsaturated fatty acid content, with or without fish oil, to treat severe acute malnutrition: a randomized controlled trial 
BMC Medicine  2015;13:93.
Ready-to-use therapeutic foods (RUTF) are lipid-based pastes widely used in the treatment of acute malnutrition. Current specifications for RUTF permit a high n-6 polyunsaturated fatty acid (PUFA) content and low n-3 PUFA, with no stipulated requirements for preformed long-chain n-3 PUFA. The objective of this study was to develop an RUTF with elevated short-chain n-3 PUFA and measure its impact, with and without fish oil supplementation, on children’s PUFA status during treatment of severe acute malnutrition.
This randomized controlled trial in children with severe acute malnutrition in rural Kenya included 60 children aged 6 to 50 months who were randomized to receive i) RUTF with standard composition; ii) RUTF with elevated short chain n-3 PUFA; or iii) RUTF with elevated short chain n-3 PUFA plus fish oil capsules. Participants were followed-up for 3 months. The primary outcome was erythrocyte PUFA composition.
Erythrocyte docosahexaenoic acid (DHA) content declined from baseline in the two arms not receiving fish oil. Erythrocyte long-chain n-3 PUFA content following treatment was significantly higher for participants in the arm receiving fish oil than for those in the arms receiving RUTF with elevated short chain n-3 PUFA or standard RUTF alone: 3 months after enrolment, DHA content was 6.3% (interquartile range 6.0–7.3), 4.5% (3.9–4.9), and 3.9% (2.4–5.7) of total erythrocyte fatty acids (P <0.001), respectively, while eicosapentaenoic acid (EPA) content was 2.0% (1.5–2.6), 0.7% (0.6–0.8), and 0.4% (0.3–0.5) (P <0.001). RUTF with elevated short chain n-3 PUFA and fish oil capsules were acceptable to participants and carers, and there were no significant differences in safety outcomes.
PUFA requirements of children with SAM are not met by current formulations of RUTF, or by an RUTF with elevated short-chain n-3 PUFA without additional preformed long-chain n-3 PUFA. Clinical and growth implications of revised formulations need to be addressed in large clinical trials.
Trial registration NCT01593969. Registered 4 May 2012.
Electronic supplementary material
The online version of this article (doi:10.1186/s12916-015-0315-6) contains supplementary material, which is available to authorized users.
PMCID: PMC4407555  PMID: 25902844
Fatty acid; Fish oils; Growth; Omega-3; Ready-to-use therapeutic food; Severe acute malnutrition
2.  Wheezing symptoms and parental asthma are associated with a doctor diagnosis of asthma in children with sickle cell anemia 
The Journal of pediatrics  2013;164(4):821-826.e1.
To identify factors associated with asthma associated with increased sickle cell anemia (SCA).
Study design
Children with SCA (n=187; mean age 9.6 years, 48% male) were classified as having “asthma” based on parent report of doctor diagnosis plus prescription of asthma medication (n=53) or “no asthma” based on the absence of these features (n=134). Pain and acute chest syndrome (ACS) events were collected prospectively.
Multiple variable logistic regression model identified three factors associated with asthma: parent with asthma (p=0.006), wheezing causing shortness of breath (p=0.001), and wheezing after exercise (p < 0.001). When two or more features were present, model sensitivity was 100%. When none of the features were present, model sensitivity was 0%. When only one feature was present, model sensitivity was also 0% and presence of 2 or more positive allergy skin tests, airway obstruction on spirometry, and bronchodilator responsiveness did not improve clinical utility. ACS incident rates were significantly higher in individuals with asthma than those without asthma (IRR 2.21, CI 1.31-3.76); pain rates were not (IRR 1.28, CI 0.78-2.10).
For children with SCA, having a parent with asthma and specific wheezing symptoms are the best features to distinguish those with and without parent report of a doctor diagnosis of asthma and identify those at higher risk for ACS events. The value of treatment for asthma in prevention of SCA morbidity needs to be studied.
PMCID: PMC3962704  PMID: 24388323
Parental history of asthma; Wheezing symptoms; Allergy to aeroallergens
3.  Mesalazine in the initial management of severely acutely malnourished children with environmental enteric dysfunction: a pilot randomized controlled trial 
BMC Medicine  2014;12:133.
Environmental enteric dysfunction (EED) is an acquired syndrome of impaired gastrointestinal mucosal barrier function that is thought to play a key role in the pathogenesis of stunting in early life. It has been conceptualized as an adaptive response to excess environmental pathogen exposure. However, it is clinically similar to other inflammatory enteropathies, which result from both host and environmental triggers, and for which immunomodulation is a cornerstone of therapy.
In this pilot double-blind randomized placebo-controlled trial, 44 children with severe acute malnutrition and evidence of EED were assigned to treatment with mesalazine or placebo for 28 days during nutritional rehabilitation. Primary outcomes were safety and acceptability of the intervention.
Treatment with mesalazine was safe: there was no excess of adverse events, evidence of deterioration in intestinal barrier integrity or impact on nutritional recovery. There were modest reductions in several inflammatory markers with mesalazine compared to placebo. Depression of the growth hormone – insulin-like growth factor-1 axis was evident at enrollment and associated with inflammatory activation. Increases in the former and decreases in the latter correlated with linear growth.
Intestinal inflammation in EED is non-essential for mucosal homeostasis and is at least partly maladaptive. Further trials of gut-specific immunomodulatory therapies targeting host inflammatory activation in order to optimize the growth benefits of nutritional rehabilitation and to address stunting are warranted. Funded by The Wellcome Trust.
Trial registration
Registered at NCT01841099.
Electronic supplementary material
The online version of this article (doi:10.1186/s12916-014-0133-2) contains supplementary material, which is available to authorized users.
PMCID: PMC4243388  PMID: 25189855
Barrier function; Inflammatory bowel disorders; Malnutrition; Mucosal immunity; Tropical gastroenterology
4.  Nocturnal temperature controlled laminar airflow for treating atopic asthma: a randomised controlled trial 
Thorax  2011;67(3):215-221.
To determine whether environmental control using nocturnal temperature controlled laminar airflow (TLA) treatment could improve the quality of life of patients with persistent atopic asthma.
Randomised, double-blind, placebo-controlled, parallel-group trial.
Nineteen European asthma clinics.
312 patients aged 7–70 with inadequately controlled persistent atopic asthma.
Main outcome measure
Proportion of patients with an increase of ≥0.5 points in asthma quality of life score after 1 year of treatment.
TLA devices were successfully installed in the bedrooms of 282 (90%) patients included in the primary efficacy analysis. There was a difference in treatment response rate between active (143 of 189, 76%) and placebo (56 of 92, 61%) groups, difference 14.8% (95% CI 3.1 to 26.5, p=0.02).3 In patients aged ≥12, on whom the study was powered, the difference in response rate was similar-active 106 of 143 (74%), placebo 42 of 70 (60%), difference 14.1% (0.6 to 27.7, p=0.059). There was a difference between groups in fractional exhaled nitric oxide change of −7.1 ppb (−13.6 to −0.7, p=0.03). Active treatment was associated with less increase in cat-specific IgE than placebo. There was no difference in adverse event rates between treatment groups.
Inhalant exposure reduction with TLA improves quality of life, airway inflammation and systemic allergy in patients with persistent atopic asthma. TLA may be a treatment option for patients with inadequately controlled persistent atopic asthma.
Trial registration number
Clinical Trials NCT00986323.
PMCID: PMC3282042  PMID: 22131290
Asthma; exposure control; temperature controlled laminar air flow; protexo; quality of life; allergic lung disease; paediatric physician; paediatric asthma; asthma pharmacology; aspergillus lung disease; copd mechanisms; eosinophil biology
6.  Enuresis Associated with Sleep Disordered Breathing in Children with Sickle Cell Anemia 
The Journal of urology  2012;188(4 0):1572-1576.
Enuresis and sleep disordered breathing are common among children with sickle cell anemia. We evaluated whether enuresis is associated with sleep disordered breathing in children with sickle cell anemia.
Materials and Methods
Baseline data were used from a multicenter prospective cohort study of 221 unselected children with sickle cell anemia. A questionnaire was used to evaluate, by parental report during the previous month, the presence of enuresis and its severity. Overnight polysomnography was used to determine the presence of sleep disordered breathing by the number of obstructive apneas and/or hypopneas per hour of sleep. Logistic and ordinal regression models were used to evaluate the association of sleep disordered breathing and enuresis.
The mean age of participants was 10.1 years (median 10.0, range 4 to 19). Enuresis occurred in 38.9% of participants and was significantly associated with an obstructive apnea-hypopnea index of 2 or more per hour after adjusting for age and gender (OR 2.19; 95% CI 1.09, 4.40; p = 0.03). Enuresis severity was associated with obstructive apneas and hypopneas with 3% or more desaturation 2 or more times per hour with and without habitual snoring (OR 3.23; 95% CI 1.53, 6.81; p = 0.001 and OR 2.07; 95% CI 1.09, 3.92; p = 0.03, respectively).
In this unselected group of children with sickle cell anemia, sleep disordered breathing was associated with enuresis. Results of this study support that children with sickle cell anemia who present with enuresis should be evaluated by a pulmonologist for sleep disordered breathing.
PMCID: PMC3722896  PMID: 22910247
enuresis; sleep; anemia; sickle cell
7.  Prenatal Vitamin D Supplementation and Child Respiratory Health: A Randomised Controlled Trial 
PLoS ONE  2013;8(6):e66627.
Observational studies suggest high prenatal vitamin D intake may be associated with reduced childhood wheezing. We examined the effect of prenatal vitamin D on childhood wheezing in an interventional study.
We randomised 180 pregnant women at 27 weeks gestation to either no vitamin D, 800 IU ergocalciferol daily until delivery or single oral bolus of 200,000 IU cholecalciferol, in an ethnically stratified, randomised controlled trial. Supplementation improved but did not optimise vitamin D status. Researchers blind to allocation assessed offspring at 3 years. Primary outcome was any history of wheeze assessed by validated questionnaire. Secondary outcomes included atopy, respiratory infection, impulse oscillometry and exhaled nitric oxide. Primary analyses used logistic and linear regression.
We evaluated 158 of 180 (88%) offspring at age 3 years for the primary outcome. Atopy was assessed by skin test for 95 children (53%), serum IgE for 86 (48%), exhaled nitric oxide for 62 (34%) and impulse oscillometry of acceptable quality for 51 (28%). We found no difference between supplemented and control groups in risk of wheeze [no vitamin D: 14/50 (28%); any vitamin D: 26/108 (24%) (risk ratio 0.86; 95% confidence interval 0.49, 1.50; P = 0.69)]. There was no significant difference in atopy, eczema risk, lung function or exhaled nitric oxide between supplemented groups and controls.
Prenatal vitamin D supplementation in late pregnancy that had a modest effect on cord blood vitamin D level, was not associated with decreased wheezing in offspring at age three years.
Trial Registration ISRCTN68645785
PMCID: PMC3691177  PMID: 23826104
8.  Perinatal nutrition and immunity to infection 
Epidemiological data provide strong evidence for a relationship between undernutrition and life-threatening infection in infants and children. However, the mechanisms that underlie this relationship are poorly understood. Through foetal life, infancy and childhood, the immune system undergoes a process of functional maturation. The adequacy of this process is dependent on environmental factors, and there is accumulating evidence of the impact of pre- and post-natal nutrition in this regard. This review outlines the impact of nutrition during foetal and infant development on the capacity to mount immune responses to infection. It provides an overview of the epidemiologic evidence for such a role and discusses the possible mechanisms involved.
PMCID: PMC2949400  PMID: 20337968
malnutrition; foetal nutrition disorders; neonatal immunity, maternally acquired; immunity; mucosal; immune disorders
9.  Recommendations for Competency in Allergy Training for Undergraduates Qualifying as Medical Practitioners: A Position Paper of the World Allergy Organization 
The Council acknowledges specific comments from: The American Academy of Allergy, Asthma and Immunology (AAAAI) (Amal H Assa'ad); The American College of Allergy, Asthma and Immunology (ACAAI) (Mark Dykewicz, D. Betty Lew, Bryan L. Martin); The Argentine Association of Allergy and Immunology (Ledit RF Ardusso); The Argentine Society of Allergy and Immunopathology (Estrella Asayag); The Australasian Society of Clinical Immunology and Allergy (ASCIA) (Jill Smith); The British Society for Allergy and Clinical Immunology (Stephen Durham); The Brazilian Society of Allergy and Immunopathology (Nelson Rosario); The Bulgarian Society of Allergology (Vasil Dimitrov); The Canadian Society of Allergy and Clinical Immunology (CSACI) (Richard Warrington); The Chilean Society of Allergy and Immunology (Jessica Salinas); The Chinese Society of Allergology (Zhang Hongyu, Yin Jia); The Czech Society of Allergology and Clinical Immunology (Jiri Litzman); The Danish Society of Allergology (Lone Winther, Peter Plaschke); The Egyptian Society of Allergy and Clinical Immunology (Kamal Maurice Hanna); The Egyptian Society of Pediatric Allergy and Immunology (Yehia El-Gamal); The German Society for Allergy and Clinical Immunology (Thilo Jakob, Claus Bachert, Bernhard Przybilla); The Hungarian Society of Allergology and Clinical Immunology (Kristof Nekam); The Icelandic Society of Allergy and Clinical Immunology (Björn R. Lúðvíksson); The Italian Association of Territorial and Hospital Allergists (Riccardo Asero); The Italian Society of Allergy and Clinical Immunology (Luigi Fontana); The Japanese Society of Allergology (Sankei Nishima); The Korean Academy of Asthma Allergy and Clinical Immunology (Joon Sung Lee, Hae-Sim Park); The Latvian Association of Allergists (Ieva Cirule); The Lebanese Society of Allergy & Immunology (Fares Zaitoun); The Mongolian Society of Allergology (S. Munkhbayarlakh); The Allergy and Clinical Immunology Society (Singapore) (Chng Hiok Hee); The Allergy Society of South Africa (Sharon Kling); The Spanish Society of Allergy and Clinical Immunology (Tomás Chivato); The Swiss Society for Allergology and Immunology (SSAI-SGAI) (Beat A. Imhof, Andreas Bircher); The Allergy and Immunology Society of Thailand (Pakit Vichyanond); The Turkish National Society of Allergy and Clinical Immunology (Omer Kalayci); and The Venezuelan Society of Allergy, Asthma and Immunology (Luis F Sarmiento).
PMCID: PMC3651006  PMID: 23283109
Undergraduate Medical Education; Training and Competencies in Allergy
12.  Resolution of peanut allergy: case-control study 
BMJ : British Medical Journal  1998;316(7140):1271-1275.
Objectives: To determine whether there are any differences between children who remain mildly or moderately allergic to peanut and children with similar histories but a negative reaction on challenge with peanut.
Design: Case-controls matched for age and sex.
Setting: Children’s day wards in two teaching hospitals.
Intervention: Open food challenge with peanut.
Subjects: 15 children with resolved peanut allergy (resolvers) and 15 with persistent allergy (persisters).
Main outcome measure: Reaction on challenge with peanut, serum total and peanut specific IgE concentrations.
Results: The groups had a similar median age at first reaction to peanut (11 months, range 5-38) and similar symptoms. Allergy to other foods was less common in resolvers (2/15) than persisters (9/15) (P=0.02). On skin prick testing with peanut all 13 resolvers tested but only 3/14 persisters had a weal of <6 mm (P<0.0001). Total and peanut specific IgE concentrations did not differ much between the groups.
Conclusion: Appropriately trained clinicians must be prepared to challenge preschool children with peanut as some will be tolerant despite a history of reactions to peanut and a positive skin prick test with peanut. Preschool children whose apparent peanut allergy is refuted by food challenge show allergy to other foods less often than those in whom peanut allergy persists. The size of weal on skin prick testing to peanut predicts reactivity but not severity on peanut challenge.
Key messages Peanut allergy rarely resolves in older children and adults Skin prick testing with peanut has a high negative predictive value, but some people with positive skin tests do not react to peanut challenge Some preschool children with a convincing history of reaction to peanut may become tolerant of peanut. Such children have fewer other manifestations of atopy than children whose peanut allergy persists Paediatricians must be prepared to undertake peanut challenges or refer children to units that will undertake such challenges
PMCID: PMC28527  PMID: 9554896

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