Effects of Zinc Combined with Probiotics on Antibiotic-associated Diarrhea Secondary to Childhood Pneumonia

By Rong Xiang, MS, Qing Tang, PhD, Xiu-Qi Chen, MS, Mu-Yan Li, MS, Mei-Xiong Yang, MS, Xiang Yun, MS, Li Huang, MS, Qing-Wen Shan

Journal of Tropical Pediatrics. October 2019


The aim of this study was to evaluate the impact of zinc combined with probiotics (Bifico) on antibiotic-associated diarrhea (AAD) secondary to pneumonia. A total of 50 patients with AAD secondary to pneumonia were randomly divided into a probiotics group (Bifico) and a combined group (zinc combined with Bifico) and 25 pneumonia patients without AAD as the control group. Serum levels of zinc, diamine oxidase (DAO) activity, D-lactate and intestinal flora [Bifidobacterium, Escherichia coli and Bifidobacterium/E. coli (B/E) ratio] were detected before and after intervention. The results showed that zinc combined with Bifico had significantly higher overall efficiency than Bifico alone for treatment of AAD secondary to pneumonia. Notably, the combined treatment increased the population of Bifidobacterium, while the number of E. coli was reduced, the B/E value was improved and DAO activity and D-lactate levels were markedly reduced. Patients with AAD secondary to pneumonia benefit from zinc supplementation of probiotic treatment.

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Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure

By Alpha A. Fowler III, Jonathon D. Truwit, R. Duncan Hite, Peter E. Morris, Christine DeWilde, Anna Priday, Bernard Fisher, Leroy R. Thacker II, Ramesh Natarajan, Donald F. Brophy, Robin Sculthorpe, Rahul Nanchal, Aamer Syed, Jamie Sturgill, Greg S. Martin, Jonathan Sevransky, Markos Kashiouris, Stella Hamman, Katherine F. Egan, Andrei Hastings, Wendy Spencer, Shawnda Tench, Omar Mehkri, James Bindas, Abhijit Duggal, Jeanette Graf, Stephanie Zellner, Lynda Yanny, Catherine McPolin, Tonya Hollrith, David Kramer, Charles Ojielo, Tessa Damm, Evan Cassity, Aleksandra Wieliczko, Matthew Halquist. Published in JAMA. October 1, 2019.


Experimental data suggest that intravenous vitamin C may attenuate inflammation and vascular injury associated with sepsis and acute respiratory distress syndrome (ARDS). To determine the effect of intravenous vitamin C infusion on organ failure scores and biological markers of inflammation and vascular injury in patients with sepsis and ARDS. The CITRIS-ALI trial was a randomized, double-blind, placebo-controlled, multicenter trial conducted in 7 medical intensive care units in the United States, enrolling patients (N = 167) with sepsis and ARDS present for less than 24 hours. The study was conducted from September 2014 to November 2017, and final follow-up was January 2018. Patients were randomly assigned to receive intravenous infusion of vitamin C (50 mg/kg in dextrose 5% in water, n = 84) or placebo (dextrose 5% in water only, n = 83) every 6 hours for 96 hours. The primary outcomes were change in organ failure as assessed by a modified Sequential Organ Failure Assessment score (range, 0-20, with higher scores indicating more dysfunction) from baseline to 96 hours, and plasma biomarkers of inflammation (C-reactive protein levels) and vascular injury (thrombomodulin levels) measured at 0, 48, 96, and 168 hours. Among 167 randomized patients (mean [SD] age, 54.8 years [16.7]; 90 men [54%]), 103 (62%) completed the study to day 60. There were no significant differences between the vitamin C and placebo groups in the primary end points of change in mean modified Sequential Organ Failure Assessment score from baseline to 96 hours (from 9.8 to 6.8 in the vitamin C group [3 points] and from 10.3 to 6.8 in the placebo group [3.5 points]; difference, −0.10; 95% CI, −1.23 to 1.03; P = .86) or in C-reactive protein levels (54.1 vs 46.1 μg/mL; difference, 7.94 μg/mL; 95% CI, −8.2 to 24.11; P = .33) and thrombomodulin levels (14.5 vs 13.8 ng/mL; difference, 0.69 ng/mL; 95% CI, −2.8 to 4.2; P = .70) at 168 hours. In this preliminary study of patients with sepsis and ARDS, a 96-hour infusion of vitamin C compared with placebo did not significantly improve organ dysfunction scores or alter markers of inflammation and vascular injury. Further research is needed to evaluate the potential role of vitamin C for other outcomes in sepsis and ARDS.

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Effect of Vitamin D Supplementation in the Prevention of Recurrent Pneumonia in Under-Five Children.

By Neha SinghEmail authorDnyanesh KambleEmail authorN. S. Mahantshetti

The Indian Journal of Pediatrics. July 25, 2019


To assess the effect of vitamin D supplementation in the prevention of recurrent pneumonia in under-five children.

The present one year 8 months longitudinal, community-based randomized controlled study included a total of 100 under-five children with pneumonia. Children were divided into two groups: intervention group (Group I: standard treatment with vitamin D 300,000 IU; n = 50) and control group (Group C: standard treatment only; n = 50). As nine samples were hemolyzed, groups I and C comprised of 46 and 45 children, respectively. The children were followed up for 1 y and signs of upper respiratory tract infections (URTI), lower respiratory tract infections (LRTI), vitamin D deficiency, and vitamin D toxicity were recorded.

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Misrecognition and Critical Consciousness — An 18-Month-Old Boy with Pneumonia and Chronic Malnutrition

By Héctor Carrasco, M.D., M.P.H., Luke Messac, M.D., Ph.D., and Seth M. Holmes, M.D., Ph.D.

The New England Journal of Medicine June 20, 2019


An 18-month-old boy in La Soledad, Mexico, presents with pneumonia, to which he was predisposed by malnutrition. When nutrition education and food-production efforts fail, a physician and a community collaborative work to elucidate the deeper roots of the problem.

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Effect of High-Dose Vitamin D Supplementation on Upper Respiratory Tract Infection Symptom Severity in Healthy Children

By Katrina Hueniken, Mary Aglipay, Catherine S. Birken, Patricia C. Parkin, Mark B. Loeb, Kevin E.Thorpe, David W.H. Dai, Andreas Laupacis, Muhammad Mamdani, Tony Mazzulli, Jonathon L. Maguire on behalf of the TARGet Kids! Collaboration

The Pediatric Infectious Disease Journal, June 2019


Observational studies support the role of vitamin D in reducing viral upper respiratory tract infection (URTI) symptom severity in adults and children. This study assessed whether wintertime high-dose vitamin D supplementation (2000 IU/day) reduces URTI symptom severity compared with standard-dose (400 IU/day) supplementation in preschool children. Secondary objectives were to assess effects of high-dose supplementation on outpatient physician visits, emergency department (ED) visits and antibiotic prescriptions for URTI.

This was a secondary analysis of a multisite randomized clinical trial involving 703 healthy 1- to 5-year-old children in Toronto, Canada. High-dose or standard-dose oral vitamin D was randomly assigned for 1 winter season. For each URTI, parents completed symptom checklists based on the Canadian Acute Respiratory and Flu Scale. Symptom severity, frequency of outpatient visits, ED visits and antibiotic prescriptions for URTI between groups were analyzed using negative binomial regression.

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Day clinic versus hospital care of pneumonia and severe malnutrition in children under five: a randomized trial

By Hasan Ashraf  Nur H. Alam  Marufa Sultana  Selina A. Jahan  Nurshad Begum  Sharmin Farzana  Mohammod J. Chisti  Mohiuddin Kamal, et al.


Tropical Medicine & International Health, May 2, 2019


Randomized clinical trial where children aged 2 months to 5 years with pneumonia and severe malnutrition were randomly allocated to DC or inpatient hospital care. We used block randomization of variable length from 8-20 and produced computer-generated random numbers that were assigned to one of the two interventions. Successful management was defined as resolution of clinical signs of pneumonia and being discharged from the model of care (DC or hospital) without need for referral to a hospital (DC), or referral to another hospital. All the children in both DC and hospital received intramuscular ceftriaxone, daily nutrition support and micronutrients

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A meta-analysis of randomized controlled trials: Efficacy of selenium treatment for sepsis

by S Li, T Tang, P Guo, Q Zou, X Ao, L Hu, and L Tan

Published in Medicine, March 2019. doi: 10.1097/MD.0000000000014733


Researchers aimed to better understand the clinical outcomes of selenium therapy in patients with sepsis syndrome by conducting a meta-analysis of randomized controlled trials (RCT).


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High burden of co-morbidity and mortality among severely malnourished children admitted to outpatient therapeutic programme facilities in the conflict setting of Borno, Nigeria: a retrospective review

by Chamla D, Oladeji O, Maduanusi I, Mele S, Mshelia H, and Safi N

Published in Public Health Nutrition, 19 February 2019. doi: 10.1017/S1368980018003968



The study objective was to present evidence on the burden and outcomes of co-morbidities among severely malnourished (SAM) children admitted to outpatient therapeutic programme (OTP) facilities in the conflict setting of Borno, Nigeria.

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Growth trajectories of breastfed HIV-exposed uninfected and HIV-unexposed children under conditions of universal maternal antiretroviral therapy: a prospective study

by Stanzi M le Roux, MBChB; Prof Elaine J Abrams, MD; Kirsten A Donald, PhD; Kirsty Brittain, MPH; Tamsin K Phillips, MPH; Kelly K Nguyen, MPH; et al.

Published in The Lancet Child & Adolescent Health, 14 February 2019. DOI: https://doi.org/10.1016/S2352-4642(19)30007-0



Over 1 million HIV-exposed uninfected (HEU) children are born in sub-Saharan Africa annually. Little data exist on the risk of impaired growth in this population under current policies of universal maternal antiretroviral therapy (ART) with breastfeeding. Researchers aimed to study the growth of breastfed HEU children born to women who initiated ART during pregnancy and compare their growth with that of breastfed HIV-unexposed (HU) children drawn from the same community.  A prospective cohort of HIV-uninfected and HIV-infected pregnant women, who were initiating ART, were enrolled at their first antenatal care visit in a primary care centre in Gugulethu, Cape Town, South Africa. HIV infected women were participants of the Maternal Child Health Antiretroviral Therapy (MCH-ART) study, and HIV-uninfected pregnant women were participants in the HIV-Unexposed-Uninfected (HU2) study. All women were followed up during pregnancy, through delivery, to the early postnatal visit, which was scheduled for the first week after birth. At this visit, eligible breastfeeding mother–child pairs were recruited for continuation of postnatal follow-up until approximately age 12 months. Child anthropometry was measured at around 6 weeks, and every 3 months from month 3 to month 12. Weight-for-age (WAZ), length-for-age (LAZ), weight-for-length (WLZ), head circumference-for-age, and body-mass index-for-age Z scores were compared between HEU and HU children longitudinally using mixed effects linear regression. At 12 months, proportions of HEU and HU children with moderate or severe malnutrition were compared cross-sectionally using logistic regression. MCH-ART is registered with ClinicalTrials.gov, number NCT01933477.  Between June, 2013, and April, 2016, 884 breastfeeding mothers and their newborn babies (HEU, n=471; HU, n=413) were enrolled into postnatal follow-up. Excluding 12 children who tested HIV positive during follow-up, 461 HEU and 411 HU children attended 4511 study visits in total, with a median of 6 visits (IQR 5–6) per child. Birth characteristics were similar (overall, 94 [11%] of 872 preterm [<37 weeks] and 90 [10%] small-for-gestational age [birthweight <10th percentile]). Median duration of breastfeeding was shorter among HEU than HU children (3·9 months [IQR 1·4–12·0] vs 9·0 months [IQR 3·0–12·0]). Although WAZ scores increased over time in both groups, HEU children had consistently lower mean WAZ scores than HU children (overall β −0·34, 95% CI −0·47 to −0·21). LAZ scores decreased in both groups after 9 months. At 12 months, HEU children had lower mean LAZ scores than HU children (β −0·43, −0·61 to −0·25), with a higher proportion of children stunted (LAZ score <–2: 35 [10%] of 342 HEU vs 14 [4%] of 342 HU children; odds ratio [OR] 2·67, 95% CI 1·41 to 5·06). Simultaneously, overweight (WLZ score >2) was common in both groups of children at 12 months (54 [16%] of 342 HEU vs 60 [18%] of 340 HU children; OR 0·87, 95% CI 0·58 to 1·31).  Compared with HU children, HEU children have small deficits in early growth trajectories under policies of universal maternal ART and breastfeeding. Large proportions of both HEU and HU children were overweight by 12 months, indicating substantial risks for early onset obesity among South African children. Although the longer-term metabolic effects of ART exposure in the context of childhood obesity warrants further investigation, addressing childhood obesity should be an urgent public health priority in this setting.  This study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Elizabeth Glaser Pediatric AIDS Foundation, South African Medical Research Council, and the Fogarty Foundation.    Article access can be found here.    
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Validation of the Subjective Global Nutrition Assessment (SGNA) and Screening Tool for the Assessment of Malnutrition in Paediatrics (STAMP) to Identify Malnutrition in Hospitalized Malaysian Children

by Shu Hwa Ong, Winnie Siew Swee Chee, L Mageswary Lapchmanan, Shan Ni Ong, Zhi Chin Lua, and Jowynna Xia-Ni Yeo

Published in Journal of Tropical Pediatrics, 01 February 2019. https://doi.org/10.1093/tropej/fmy009


Early detection of malnutrition in hospitalized children helps reduce length of hospital stay and morbidity. A validated nutrition tool is essential to correctly identify children at risk of malnutrition or who are already malnourished. This study compared the use of the Subjective Global Nutrition Assessment (SGNA, nutrition assessment tool) and Screening Tool for the Assessment of Malnutrition in Paediatrics (STAMP, nutrition screening tool) with objective nutritional parameters to identify malnutrition in hospitalized children.


A cross-sectional study was carried out in two general paediatric wards in a public hospital. SGNA and STAMP were performed on 82 children (52 boys and 30 girls) of age 1–7 years. The scores from both methods were compared against Academy of Nutrition and Dietetics/American Society of Parental and Enteral Nutrition Consensus Statement for identification of paediatric malnutrition. The objective measurements include anthropometry (weight, height and mid-arm circumference), dietary intake and biochemical markers (C-reactive protein, total lymphocytes and serum albumin). Kappa agreement between methods, sensitivity, specificity and cross-classification were computed.

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Undernutrition and Tuberculosis: Public Health Implications

by Pranay Sinha, Juliana Davis, Lauren Saag, Christine Wanke, Padmini Salgame, Jackson Mesick, C Robert Horsburgh, Jr, and Natasha S Hochberg

Published in The Journal of Infectious Diseases, 22 November 2018.


Almost 800 million people are chronically undernourished worldwide, of whom 98% are in low- and middle-income countries where tuberculosis is endemic. In many tuberculosis-endemic countries, undernutrition is a driver of tuberculosis incidence and associated with a high population attributable fraction of tuberculosis and poor treatment outcomes. Data suggest that undernutrition impairs innate and adaptive immune responses needed to control Mycobacterium tuberculosis infection and may affect responses to live vaccines, such as BCG. Given its impact on tuberculosis, addressing undernutrition will be a vital component of the World Health Organization End TB strategy. This narrative review describes the effect of undernutrition on the immune response, vaccine response, and tuberculosis incidence, severity, and treatment outcomes.


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Pneumonia in HIV-exposed and Infected Children and Association With Malnutrition

by Iroh Tam, Pui-Ying, MD; Wiens, Matthew O., PhD; Kabakyenga, Jerome, PhD; Kiwanuka, Julius, MBChB; Kumbakumba, Elias, MB ChB; Moschovis, Peter P., MD

Published in the Pediatric Infectious Disease Journal, October 2018



"We evaluated the association between HIV exposed-uninfected (HEU) status, malnutrition and risk of death in Ugandan children hospitalized with pneumonia. Both HIV exposure and infection were associated with lower anthropometric indices on univariate analysis, and mid-upper arm circumference was significantly associated with overall mortality (odds ratio (OR), 0.96) in a multivariable model. HIV infection (OR 5.0) but not HEU status was associated with overall mortality. Malnutrition may contribute to poor pneumonia outcomes among HIV-infected and HEU children requiring hospitalization."

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Reduction in child mortality in Ethiopia: analysis of data from demographic and health surveys

by Doherty T, Rohde S, Besada D, Kerber K, Manda S, Loveday M, Nsibande D, Daviaud E, Kinney M, Zembe W, Leon N, Rudan I, Degefie T, Sanders D. 


Using the Lives Saved Tool in combination with coverage of child survival interventions and nutritional status of children in Ethiopia between 2000 and 2011, researchers estimated  the impact of changes in coverage of child survival interventions on under-5 lives saved. These estimates were generated using 3 Ethiopia Demographic and Health Surveys (between 2000 and 2011):


"The mortality rate in children younger than 5 years decreased rapidly from 218 child deaths per 1000 live births in the period 1987-1991 to 88 child deaths per 1000 live births in the period 2007-2011. The prevalence of moderate or severe stunting in children aged 6-35 months also declined significantly. Improvements in the coverage of interventions relevant to child survival in rural areas of Ethiopia between 2000 and 2011 were found for tetanus toxoid, DPT3 and measles vaccination, oral rehydration solution (ORS) and care-seeking for suspected pneumonia. The LiST analysis estimates that there were 60 700 child deaths averted in 2011, primarily attributable to decreases in wasting rates (18%), stunting rates (13%) and water, sanitation and hygiene (WASH) interventions (13%)." 

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Relationship between growth and illness, enteropathogens and dietary intakes in the first 2 years of life: findings from the MAL-ED birth cohort study

Published in BMJ Global Health


While factors like diet and illness affect the risk of growth faltering, the role that enteropathogens play is less clear. As part of the Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) study, researchers aimed to quantify the effects of enteropathogen infection, diarrhoea and diet on child growth.


Using a linear piecewise spline model researchers "quantified associations of each factor with growth velocity in seven of eight MAL-ED sites; cumulative effects on attained size at 24 months were estimated for mean, low (10th percentile) and high (90th percentile) exposure levels. Additionally, the six most prevalent enteropathogens were evaluated for their effects on growth."

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Changes in susceptibility to life-threatening infections after treatment for complicated severe malnutrition in Kenya

by authors Ngari MM, Mwalekwa L, Timbwa M, Hamid F, Ali R, Iversen PO, Fegan GW, Berkley JA


To treat severe acute malnutrition (SAM) and prevent short-term mortality, better understanding how quickly and how much the risk of serious illness changes during rehabilitation could inform improving intervention design and scope. Researchers aimed to investigate changes in the risk of life-threatening events (LTEs) in relation to anthropometric recovery from SAM. 


Through a secondary analysis of a clinical trial, researchers found that "anthropometric response was associated with a rapid and substantial reduction in risk of LTEs. However, reduction in susceptibility lagged behind anthropometric improvement. Disease events, together with anthropometric assessment, may provide a clearer picture of the effectiveness of interventions." Furthermore, researchers call for "robust protocols for detecting and treating poor anthropometric recovery and addressing broader vulnerabilities that complicated SAM indicates" to help save lives. 

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Zinc as an adjunct therapy in the management of severe pneumonia among Gambian children: randomized controlled trial

Published in the Journal of Global Health, June 2018


The use of zinc as an adjunct therapy for cases of severe pneumonia has not been well-established. To assess the benefit(s) of adjunct zinc therapy, researchers used a randomized, double-blind placebo-controlled trial to determine if study children were zinc deficient:


"The study was a randomized, parallel group, double-blind, placebo-controlled trial with an allocation ratio of 1:1 conducted in children with severe pneumonia to evaluate the efficacy of daily zinc as an adjunct treatment in preventing 'treatment failure' (presence of any sign of severe pneumonia) on day-5 and day-10 and in reducing the time to resolution of signs of severe pneumonia ... Percentage of treatment failure were similar in placebo and zinc arms both on day 5 and day 10. The time to resolution for all respiratory symptoms of severity was not significantly different between placebo and zinc arms and in the six months follow-up sub-group, there was no significant difference in height gain, height-for-age and weight-for-height Z-scores, mid upper arm circumference, plasma zinc concentrations, and anergy at six months post-enrolment."

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The impact of malnutrition on childhood infections

Almost 50% all childhood deaths worldwide occur in children with malnutrition. This review by authors Judd Walson and James Berkley explains the mechanisms by which malnutrition and (serious) infections interact with each other and with the environments of children, leading to greater serious adverse health outcomes. "It has become clear that whilst malnutrition results in increased incidence, severity and case fatality of common infections, risks continue beyond acute episodes resulting in significant postdischarge mortality. A well established concept of a ‘vicious-cycle’ between nutrition and infection has now evolving to encompass dysbiosis and pathogen colonization as precursors to infection; enteric dysfunction constituting malabsorption, dysregulation of nutrients and metabolism, inflammation and bacterial translocation. All of these interact with a child's diet and environment. Published trials aiming to break this cycle using antimicrobial prophylaxis or water, sanitation and hygiene interventions have not demonstrated public health benefit so far."While further trials are underway, key gaps in knowledge remain. These critical gaps can be filled via the applications of new tools and innovations to re-examine old questions relating to competency of the immune system both during and after infection events and changes in nutritional status. New tools may also help to better characterize overt and subclinical infection, intestinal permeability to bacteria and the role of antimicrobial resistance using specific biomarkers.Read the article here. 

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Innovative antibiotic gets recognition from Johnson & Johnson’s “GenH Challenge”

Child wasting (severe, recent episodes of malnutrition) is one of the leading risks of death from pneumonia. Sangwei Lu, a scientist from the University of California Berkeley, has developed "NutMox," a mix of the recommended child-friendly antibiotic amoxicillin with a ready-to-eat therapeutic food allowing malnourished children being treated for pneumonia to also be treated for underlying malnutrition. The subsequent partnership with Michael Chansler from PATH has accelerated its development to market. This collaboration has been recognized as one of six winners of Johnson & Johnson's "Gen H" Challenge grant. We congratulate Sangwei Lu and Michael Chansler, both committed members of the Pneumonia Innovations Network, and wish them success in the next stages of development. Read more here.

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Efficacy of Oral Zinc Supplementation in Radiologically Confirmed Pneumonia: Secondary Analysis of a Randomized Controlled Trial

Researchers evaluated the effect of zinc as an adjuvant therapy in radiologically confirmed pneumonia in children 2–24 months of age. Time to recovery was compared between zinc and control groups in 212 children:"Time to recovery was similar in both groups. The absolute risk reduction for treatment failure was 5.2% with zinc supplementation. There was no significant beneficial effect of zinc on the duration of recovery or risk of treatment failure in children with radiologically confirmed pneumonia."

The full article can be found here. 

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Relationship Between Body Mass Index and Outcomes Among Hospitalized Patients With Community-Acquired Pneumonia

The effect of body mass index (BMI) on community-acquired pneumonia (CAP) severity is unclear. Researchers investigated the relationship between BMI and CAP outcomes in hospitalized CAP patients from the Centers for Disease Control and Prevention Etiology of Pneumonia in the Community (EPIC) study. Age, demographics, underlying conditions and smoking status (for adults only) were adjusted for. 


"Compared with normal-weight children, odds of ICU admission were higher in children who were overweight and odds of mechanical ventilation were higher in children with obesity. When stratified by asthma (presence/absence), these findings remained significant only in children with asthma. Compared with normal-weight adults, odds of LOS >3 days were higher in adults who were underweight and odds of mechanical ventilation were lowest in adults who were overweight."


Researchers concluded that overweight or obese or obese children, particularly those with asthma, had higher odds of ICU admission or mechanical ventilation. In contrast, underweight adults had longer LOS. These results underscore the complex relationship between BMI and CAP outcomes.

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