Factors associated with stunting in under-five children with environmental enteropathy in slum areas of Jimma town, Ethiopia.

Introduction: Stunting is a major public health issue with a significant influence on the health and development of children in low-income countries, where it affects up to 32% of children. Nutritional intake is impacted by alterations in intestinal permeability and underlying chronic inflammation, which hinder children's normal linear growth. Environmental enteropathy is a poorly understood condition with chronic intestinal inflammation. The purpose of this study was to identify the magnitude of stunting, change in growth, and factors associated with stunting and change in height for the age Z-score of children with an elevated lactulose-to-mannitol ratio. Methods: An observational follow-up study was conducted to follow children with an elevated lactulose-to-mannitol ratio for changes in their linear growth. A lactulose-mannitol test was performed to identify children with elevated lactulose-to-mannitol ratios, indicative of environmental enteropathy. After a 1-year follow-up, anthropometry was repeated to assess their linear growth. A multivariable logistic regression analysis was performed to identify the independent predictors for stunting in children with elevated lactulose-to-mannitol ratios. All tests were two-sided, and a p-value of <0.05 was considered significant. Results: The prevalence of stunting in children with an elevated L:M at baseline and end line was found to be 72.4% (95% CI: 60.3, 84.5) and 78.4% (95% CI: 66.7, 90.2), respectively. In a multivariate analysis, a low dietary diversity score (<4 food groups), presence of flies and insects in the toilet area, poor handwashing practices during a critical time, and MUAC z < -2 were significantly associated with stunting. Flies and insects in the toilet area and unsafe disposal of feces were significantly associated with changes in HAZ in children with elevated lactulose-to-mannitol ratios, an indicator of environmental enteropathy. Conclusion: Most of the children with an elevated lactulose-to-mannitol ratio in the study population were stunted, and no significant change in their linear growth was observed after 1-year follow-up. Therefore, further investigation and urgent intervention are needed to prevent environmental enteropathy and stunting among under-five children in this community who are exposed to very poor sanitary conditions and other risk factors for malnutrition.

Intestinal permeability assessment using lactulose and mannitol in celiac disease.

Alterations in intestinal permeability can lead to increased uptake of luminal antigens, which has been linked to several intestinal diseases, such as inflammatory bowel diseases, celiac disease, and irritable bowel syndrome, but also to extra-intestinal diseases. Promising therapies that target intestinal permeability could be developed, for instance tight junction modulators. Consequently, permeability assays are increasingly being used as treatment endpoints in clinical studies. Therefore, reliable, reproducible, and feasible methods for measuring intestinal permeability in the clinical setting are necessary. Currently, a variety of in vivo, ex vivo, and in vitro tests are available, some of which are only applicable to basic research. Despite the various options available to measure gut permeability, their use in clinical setting is still limited because of their heterogeneity. Here, we describe a clinical method to measure intestinal permeability using two non-metabolizable sugars.

Environmental Enteropathy and Anaemia Status Among Under-Five Children, in Slum Areas of Jimma Town, Ethiopia.

Background: The most important anemia next to iron deficiency is anemia of inflammation. Micronutrient deficits, such as those in zinc and iron, can be caused by intestinal permeability and gut inflammation brought on by environmental enteric dysfunction. This study was aimed to evaluate the prevalence and association of anemia with Environmental Enteropathy. Methods: Data on water sanitation and hygiene indicators and sociodemographic characteristics were collected using structured questionnaire. The lactulose to mannitol ratio (L:M) was calculated from the concentration of both sugars in the urine. Level of Hemoglobin was detected by using Hemocue-301 digital photometer. Blood and urine sample was collected from three hundred children aged 12-59 months to determine the status of Anaemia and Environmental Enteropathy respectively. Results: Data were analyzed by using Descriptive statistics, cross-tabulation, and logistic regression model to indicate prevalence and association of anemia with environmental Enteropathy in children less than five years old. The prevalence of anemia in children with environmental enteropathy was 63.8% (95% CI: 57.6, 71.7), and there was a significant association (p = 0.0001, AOR 3.502, 95% CI: 1.929-6.371) between anemia and environmental enteropathy. In a multivariate analysis, children aged 1-3 years with caretakers who had no or only primary education and with monthly income of less than 3000 ETB were more likely to develop anemia. Conclusion: The result of this study indicated that two-thirds of children less than five with environmental enteropathy had developed anemia, and there is a significant association between environmental enteropathy and anemia. Even though there are other causes of anemia, based on the findings of this study, more research is needed to identify factors associated with environmental enteropathy to mitigate anemia due to intestinal permeability or malabsorption and its impact in children under the age of five.

Evaluation of the Diagnostic Accuracy of Non-Specific Bronchial Provocation Tests in the Diagnosis of Asthma: A Randomized Cross-Over Study

Introduction: The role of bronchial provocation tests in the diagnosis of asthma remains to be fully explored. We aimed to evaluate methacholine and mannitol challenge testing, and explore the factors associated with this broncoprovocation response.Methods: Observational, cross-over, randomized trial evaluating adult cases with suspected asthma, naïve to treatment, with normal pre-bronchodilator spirometry, and negative bronchodilator test. Patients were randomized to start with methacholine or mannitol. The diagnosis of bronchial asthma was confirmed if there was a good functional and clinical response to one month with twice daily formoterol/budesonide 9/320. The diagnostic profile and the concordance were calculated. Factors associated with a positive provocation test were entered into a multivariate binomial logistic regression analysis, and classification trees were created for both tests.Results: The study included 108 cases (50.0% diagnosed with asthma and 51.9% cases starting with methacholine). The percentage of cases positive to methacholine and mannitol were 30.6% and 25.0% respectively. Kappa values were 0.40 (p<0.001). The diagnostic profile for methacholine was sensitivity 59.3% and specificity 98.1%, while for mannitol it was sensitivity 48.1% and specificity 98.1%. Variables associated with a positive methacholine response included sex, atopy, FEV1, FEV1/FVC and FENO, whereas they were FEV1/FVC and FENO for mannitol. A FENO value>26ppb, FEV1≤103.3% and female sex correctly classified 78.7% of methacholine responders. FENO value>26ppb was enough to correctly classify 81.5% of mannitol responders.Conclusions: Our study confirms the diagnostic profile of methacholine and mannitol challenge tests and describes the variable associated to their positivity with new proposed cutoff values. (AU)

Evaluation of the Diagnostic Accuracy of Non-Specific Bronchial Provocation Tests in the Diagnosis of Asthma: A Randomized Cross-Over Study.

INTRODUCTION: The role of bronchial provocation tests in the diagnosis of asthma remains to be fully explored. We aimed to evaluate methacholine and mannitol challenge testing, and explore the factors associated with this broncoprovocation response. METHODS: Observational, cross-over, randomized trial evaluating adult cases with suspected asthma, naïve to treatment, with normal pre-bronchodilator spirometry, and negative bronchodilator test. Patients were randomized to start with methacholine or mannitol. The diagnosis of bronchial asthma was confirmed if there was a good functional and clinical response to one month with twice daily formoterol/budesonide 9/320. The diagnostic profile and the concordance were calculated. Factors associated with a positive provocation test were entered into a multivariate binomial logistic regression analysis, and classification trees were created for both tests. RESULTS: The study included 108 cases (50.0% diagnosed with asthma and 51.9% cases starting with methacholine). The percentage of cases positive to methacholine and mannitol were 30.6% and 25.0% respectively. Kappa values were 0.40 (p<0.001). The diagnostic profile for methacholine was sensitivity 59.3% and specificity 98.1%, while for mannitol it was sensitivity 48.1% and specificity 98.1%. Variables associated with a positive methacholine response included sex, atopy, FEV1, FEV1/FVC and FENO, whereas they were FEV1/FVC and FENO for mannitol. A FENO value>26ppb, FEV1≤103.3% and female sex correctly classified 78.7% of methacholine responders. FENO value>26ppb was enough to correctly classify 81.5% of mannitol responders. CONCLUSIONS: Our study confirms the diagnostic profile of methacholine and mannitol challenge tests and describes the variable associated to their positivity with new proposed cutoff values.

Putative Biomarkers of Environmental Enteric Disease Fail to Correlate in a Cross-Sectional Study in Two Study Sites in Sub-Saharan Africa.

Environmental enteric dysfunction (EED) is an elusive, inflammatory syndrome of the small intestine thought to be associated with enterocyte loss and gut leakiness and lead to stunted child growth. To date, the gold standard for diagnosis is small intestine biopsy followed by histology. Several putative biomarkers for EED have been proposed and are widely used in the field. Here, we assessed in a cross-sectional study of children aged 2-5 years for a large set of biomarkers including markers of protein exudation (duodenal and fecal alpha-1-antitrypsin (AAT)), inflammation (duodenal and fecal calprotectin, duodenal, fecal and blood immunoglobulins, blood cytokines, C-reactive protein (CRP)), gut permeability (endocab, lactulose-mannitol ratio), enterocyte mass (citrulline) and general nutritional status (branched-chain amino acids (BCAA), insulin-like growth factor) in a group of 804 children in two Sub-Saharan countries. We correlated these markers with each other and with anemia in stunted and non-stunted children. AAT and calprotectin, CRP and citrulline and citrulline and BCAA correlated with each other. Furthermore, BCAA, citrulline, ferritin, fecal calprotectin and CRP levels were correlated with hemoglobin levels. Our results show that while several of the biomarkers are associated with anemia, there is little correlation between the different biomarkers. Better biomarkers and a better definition of EED are thus urgently needed.

Alterations of the Intestinal Permeability are Reflected by Changes in the Urine Metabolome of Young Autistic Children: Preliminary Results.

Several metabolomics-based studies have provided evidence that autistic subjects might share metabolic abnormalities with gut microbiota dysbiosis and alterations in gut mucosal permeability. Our aims were to explore the most relevant metabolic perturbations in a group of autistic children, compared with their healthy siblings, and to investigate whether the increased intestinal permeability may be mirrored by specific metabolic perturbations. We enrolled 13 autistic children and 14 unaffected siblings aged 2-12 years; the evaluation of the intestinal permeability was estimated by the lactulose:mannitol test. The urine metabolome was investigated by proton nuclear magnetic resonance (1H-NMR) spectroscopy. The lactulose:mannitol test unveiled two autistic children with altered intestinal permeability. Nine metabolites significantly discriminated the urine metabolome of autistic children from that of their unaffected siblings; however, in the autistic children with increased permeability, four additional metabolites-namely, fucose, phenylacetylglycine, nicotinurate, and 1-methyl-nicotinamide, strongly discriminated their urine metabolome from that of the remaining autistic children. Our preliminary data suggest the presence of a specific urine metabolic profile associated with the increase in intestinal permeability.

A case for improved assessment of gut permeability: a meta-analysis quantifying the lactulose:mannitol ratio in coeliac and Crohn's disease.

BACKGROUND: A widely used method in assessing small bowel permeability is the lactulose:mannitol test, where the lactulose:mannitol ratio (LMR) is measured. However, there is discrepancy in how the test is conducted and in the values of LMR obtained across studies. This meta-analysis aims to determine LMR in healthy subjects, coeliac and Crohn's disease. METHODS: A literature search was performed using PRISMA guidance to identify studies assessing LMR in coeliac or Crohn's disease. 19 studies included in the meta-analysis measured gut permeability in coeliac disease, 17 studies in Crohn's disease. Outcomes of interest were LMR values and comparisons of standard mean difference (SMD) and weighted mean difference (WMD) in healthy controls, inactive Crohn's, active Crohn's, treated coeliac and untreated coeliac. Pooled estimates of differences in LMR were calculated using the random effects model. RESULTS: Pooled LMR in healthy controls was 0.014 (95% CI: 0.006-0.022) while pooled LMRs in untreated and treated coeliac were 0.133 (95% CI: 0.089-0.178) and 0.037 (95% CI: 0.019-0.055). In active and inactive Crohn's disease, pooled LMRs were 0.093 (95% CI: 0.031-0.156) and 0.028 (95% CI: 0.015-0.041). Significant differences were observed in LMR between: (1) healthy controls and treated coeliacs (SMD = 0.409 95% CI 0.034 to 0.783, p = 0.032), (2) healthy controls and untreated coeliacs (SMD = 1.362 95% CI: 0.740 to 1.984, p < 0.001), (3) treated coeliacs and untreated coeliacs (SMD = 0.722 95% CI: 0.286 to 1.157, p = 0.001), (4) healthy controls and inactive Crohn's (SMD = 1.265 95% CI: 0.845 to 1.686, p < 0.001), (5) healthy controls and active Crohn's (SMD = 2.868 95% CI: 2.112 to 3.623, p < 0.001), and (6) active Crohn's and inactive Crohn's (SMD = 1.429 (95% CI: 0.580 to 2.278, p = 0.001). High heterogeneity was observed, which was attributed to variability in protocols used across different studies. CONCLUSION: The use of gut permeability measurements in screening and monitoring of coeliac and Crohn's disease is promising. LMR is useful in performing this function with significant limitations. More robust alternative tests with higher degrees of clinical evidence are needed if measurements of gut permeability are to find widespread clinical use.

Gut permeability and its clinical relevance in schizophrenia.

AIM: We aimed to examine the gut permeability in patients with schizophrenia and its relevance to schizophrenia symptoms, medication, cognitive functions, and blood immune markers. METHODS: We selected 22 patients with schizophrenia (mean age: 37.9 ± 10.5 years) comprising 9 men and 13 women. Furthermore, we included 86 healthy controls (mean age: 43.5 ± 11.0 years) comprising 41 men and 45 women. All participants were biologically unrelated and of Japanese descent. We used the Positive and Negative Syndrome Scale (PANSS) and Brief Assessment of Cognition in Schizophrenia (BACS) to measure the severity of schizophrenia symptoms and cognitive functions, respectively. The lactulose-mannitol loading test was used to measure the permeability of the small intestine. Furthermore, we used the lactulose to mannitol ratio (LMR) as an index of gut permeability. We measured the C-reactive protein and natural killer (NK) cell activity in the blood as highly sensitive immune markers. RESULTS: The patients had a significantly higher rate of "leaky gut" (defined as LMR ≥ 0.1) compared to the control group (22.7% vs. 5.8%, odds ratio: 4.8 [95% confidence interval, 1.2-18.3], Fisher's exact test, P = 0.03). There was no significant correlation between the LMR and PANSS scores or in the daily antipsychotic dose. In addition, the LMR was negatively correlated with the total Z-score of the BACS and NK cell activity in the patients. CONCLUSIONS: Our results suggest a higher rate of abnormally increased gut permeability in patients with schizophrenia than in controls. Moreover, gut permeability may be related to the cognitive and cellular immunity function of patients with schizophrenia.

Higher doses of ascorbic acid may have the potential to promote nutrient delivery via intestinal paracellular absorption.

The significance of plasma ascorbic acid (AA) is underscored by its enzymatic and antioxidant properties as well as involvement in many aspects of health including the synthesis of biomolecules during acute illness, trauma and chronic health conditions. Dietary intake supports maintenance of optimal levels with supplementation at higher doses more likely pursued. Transient increased intestinal paracellular permeability following high dose AA may be utilised to enhance delivery of other micronutrients across the intestinal lumen. The potential mechanism following dietary intake however needs further study but may provide an avenue to increase small intestinal nutrient co transport and absorption, including in acute and chronic illness.

Biomarkers of environmental enteric dysfunction are differently associated with recovery and growth among children with moderate acute malnutrition in Sierra Leone.

BACKGROUND: Environmental enteric dysfunction (EED) may influence growth during and recovery from moderate acute malnutrition (MAM), however, biomarkers to assess these relations have yet to be identified. OBJECTIVES: The objectives of this study were to: 1) develop a score for EED based on host fecal mRNA transcripts, 2) compare biomarkers of EED with each other, and 3) examine associations between the EED biomarkers and recovery from MAM and growth outcomes. METHODS: In a cohort of 520 Sierra Leonean MAM children, biomarkers of EED included the lactulose: mannitol (L: M) test, 15 host fecal mRNA transcripts, and host fecal proteins [α-1-antitrypsin (AAT), myeloperoxidase (MPO), neopterin (NEO)]. Anthropometry data were also collected and z scores were computed for length-for-age (LAZ) and weight-for-length (WLZ). Recovery from MAM was defined as midupper arm circumference ≥12.5 cm. Factor analysis was used to identify EED scores using the mRNA transcripts, and mixed effects regression was conducted to test for associations. RESULTS: The 15 host fecal mRNA transcripts were clustered into 3 scores: gut inflammation (GI) score, gut structure (GS) score, and gut defense (GD) score. We found agreement between certain inflammation markers (GI score and MPO), and permeability markers (GS score and AAT; AAT and the L: M excretion ratio). Antimicrobial gut defense (GD score) was inversely associated with percent lactulose excreted, a measure of intestinal permeability. LAZ (ß: -0.08; 95% CI: -0.14, -0.02) and WLZ (ß: -0.03; 95% CI: -0.06, -0.01) were negatively associated with GI score. A high GD score (ß: 0.36; 95% CI: 0.08, 0.64) and low AAT (ß: -1.35; 95% CI: -2.35, -0.36) were associated with recovery from MAM. CONCLUSIONS: Scores derived from host fecal mRNA transcript variably correlated with the L: M test and host fecal proteins. Markers of intestinal inflammation, permeability, and defense were associated with growth outcomes and recovery from MAM.

Airway hyperresponsiveness to mannitol improves in both type 2 high and type 2 low asthma after specialist management.

OBJECTIVES: Type 2 low (T2-low) asthma is reported to respond less to anti-inflammatory treatment compared with Type 2 high (T2-high) asthma. Airway hyperresponsiveness (AHR) to mannitol, a marker of airway mast cell activation, may be indicative of response to treatment in patients with T2-low disease. We investigated whether AHR to mannitol improves in patients with T2-low asthma after specialist management. METHODS: Patients with asthma or suspected asthma, referred to our specialist outpatient clinic, were enrolled consecutively and assessed with FeNO, asthma control, blood eosinophils, mannitol and methacholine tests and induced sputum. T2-low asthma was defined in patients with FeNO < 25ppb and sputum eosinophils < 3% and blood eosinophils < 300µl-1 at inclusion. Patients with asthma and AHR to mannitol (PD15 ≤ 635 mg) were followed and reassessed after 12 months of specialist management. RESULTS: Thirty-two patients (Females: 56%, age: 22 years (15-59)) were followed. Fourteen (44%) with T2-high and 18 (56%) with T2-low asthma. Baseline AHR to mannitol was comparable: Gmean PD15: 150 mg (95% CI 61-368) and 214 mg (95% CI 106-432) for T2-high and T2-low asthma respectively (P = 0.51). Both groups improved equally: Gmean PD15: 488 mg (95% CI 311-767) and 507 mg (95% CI 345-746); corresponding to a doubling-dose of: 3.00 (95% CI 1.58-5.74, P = 0.003) and 2.28 (95% CI 1.47-3.53, P = 0.001) respectively. There were no concomitant improvements in AHR to methacholine. CONCLUSION: Patients with asthma and AHR to mannitol improve similarly in responsiveness to mannitol after 12 months of specialist management regardless of Type 2 inflammatory biomarker levels. Mechanisms driving AHR in T2-low asthma need to be further elucidated.

Alanyl-glutamine protects the intestinal barrier function in trained rats against the impact of acute exhaustive exercise

Strenuous exercise triggers deleterious effects on the intestinal epithelium, but their mechanisms are still uncertain. Here, we investigated whether a prolonged training and an additional exhaustive training protocol alter intestinal permeability and the putative effect of alanyl-glutamine (AG) pretreatment in this condition. Rats were allocated into 5 different groups: 1) sedentary; 2 and 3) trained (50 min per day, 5 days per week for 12 weeks) with or without 6 weeks oral (1.5 g/kg) AG supplementation; 4 and 5) trained and subjected to an additional exhaustive test protocol with or without oral AG supplementation. Venous blood samples were collected to determine gasometrical indices at the end of the 12-week protocol or after exhaustive test. Lactate and glucose levels were determined before, during, and after the exhaustive test. Ileum tissue collected after all experimental procedures was used for gene expression analysis of Zonula occludens 1 (ZO-1), occludin, claudin-2, and oligopeptide transporter 1 (PepT-1). Intestinal permeability was assessed by urinary lactulose/mannitol test collected after the 12-week protocol or the exhaustive test. The exhaustive test decreased pH and base excess and increased pCO2. Training sessions delayed exhaustion time and reduced the changes in blood glucose and lactate levels. Trained rats exhibited upregulation of PEPT-1, ZO-1, and occludin mRNA, which were partially protected by AG. Exhaustive exercise induced intestinal paracellular leakage associated with the upregulation of claudin-2, a phenomenon protected by AG treatment. Thus, AG partially prevented intestinal training adaptations but also blocked paracellular leakage during exhaustive exercise involving claudin-2 and occludin gene expression.

Monobutyrin Reduces Liver Cholesterol and Improves Intestinal Barrier Function in Rats Fed High-Fat Diets.

Butyric acid has been shown to reduce high-fat diet-related metabolic disturbances and to improve intestinal barrier function due to its potent anti-inflammatory capacity. This study investigates whether a butyric acid ester, monobutyrin (MB) affects lipid profiles and gut barrier function in a dose-response manner in rats fed butter- or lard-based high-fat diets. Four-week-old male Wistar rats were fed butter-based diets containing 0, 0.25, 0.75 and 1.5 MB g/100 g (dry weight basis) or 0.5 glycerol g/100 g, and diets with lard (La) containing 0 and 0.5 MB g/100 g or a low-fat control diet for 3⁻4 weeks. Lipid profiles in blood and liver tissue, intestinal permeability and cecal short-chain fatty acids were examined. The results showed a dose-dependent decrease in liver total cholesterol for 1.5 MB (p < 0.05) and liver triglycerides for 0.75 MB (p < 0.05) and 1.5 MB (p = 0.08) groups compared to the high-fat control group. Furthermore, a lower excretion of mannitol in urine in the 1.5 MB group indicated improved intestinal barrier function. When MB was supplemented in the lard-based diet, serum total cholesterol levels decreased, and total amount of liver high-density lipoprotein-cholesterol increased. Thus, MB dietary supplementation can be effective in counteracting lipid metabolism disturbances and impaired gut barrier function induced by high-fat diets.

EB 2017 Article: Interpretation of the lactulose:mannitol test in rural Malawian children at risk for perturbations in intestinal permeability.

The dual sugar absorption test, specifically the lactulose:mannitol test, is used to assess gut health. Lactulose absorption is said to represent gut damage and mannitol absorption is used as a measure of normal small bowel function and serves as normalizing factor for lactulose. A underappreciated limitation of this common understanding of the lactulose:mannitol test is that mannitol is not absorbed to any substantial extent by a transcellular process. Additionally, this interpretation of lactulose:mannitol is not consistent with current understanding of paracellular pathways, where three pathway types exist: pore, leak, and unrestricted. Pore and leak pathways are regulated biological constructions of the small bowel barrier, and unrestricted pathways represent micropathological damage. We analyzed 2334 lactulose:mannitol measurements rigorously collected from 622 young rural Malawian children at high risk for poor gut health in light of the pathway model. An alternative method of normalizing for gut length utilizing autopsy data is described. In our population, absorbed lactulose and mannitol are strongly correlated, r = 0.68 P <0.0001, suggesting lactulose and mannitol are traversing the gut barrier via the same pathways. Considering measurements where pore pathways predominate, mannitol flux is about 14 times that of lactulose. As more leak pathways are present, this differential flux mannitol:lactulose falls to 8:1 and when increased numbers of unrestricted pathways are present, the differential flux of mannitol:lactulose is 6:1. There was no substantial correlation between the lactulose:mannitol and linear growth. Given that mannitol will always pass through a given pathway at a rate at least equal to that of lactulose, and lactulose absorption is a composite measure of flux through both physiologic and pathologic pathways, we question the utility of the lactulose:mannitol test. We suggest using lactulose alone is as informative as lactulose:mannitol in a sugar absorption testing in subclinical gut inflammation. Impact statement Our work integrates the standard interpretation of the lactulose:mannitol test (L:M), with mechanistic insight of intestinal permeability. There are three paracellular pathways in the gut epithelium; pore, leak, and unrestricted. Using thousands of L:M measurements from rural Malawian children at risk for increased intestinal permeability, we predict the differential flux of L and M through the pathways. Our findings challenge the traditional notions that little L is absorbed through a normal epithelial barrier and that M is a normalizing factor for L. Our observations are consistent with pore pathways allowing only M to pass. And that substantial amounts of L and M pass through leak pathways which are normal, regulated, cell-junctional adaptations. So M is a composite measure of all pathways, and L is not a measure solely of pathologic gut damage. Using L alone as a probe will yield more information about gut health than L:M.

High bacterial load of indoor air in hospital wards: the case of University of Gondar teaching hospital, Northwest Ethiopia.

BACKGROUND: The air inhaled by people is abundantly populated with microorganisms which also are called bioaerosols. Bioaerosols is a colloidal suspension, formed by liquid droplets and particles of solid matter in the air, whose components contain or have attached to them viruses, fungal spores and conidia, bacterial endospores, plant pollen and fragments of plant tissues. They account for 5-34 % of indoor air pollution. METHODS: A cross-sectional study was conducted to assess the bacteriological concentration and to identify specific species of bacteria in the indoor air of Gondar University teaching hospital. Air samples were taken from 14 randomly selected wards. Bacterial measurements were made by passive air sampling technique i.e., the settle plate method. In each ward five Petri dishes were exposed for 30 and 60 min in the morning and afternoon. Bacteria were collected on nutrient agar and blood agar media. Both quantitative and qualitative analyses were conducted. The quantitative analysis was mainly conducted to determine bacterial load or number of bacteria in the indoor air. Bacterial load was enumerated as colony forming units. Qualitative analysis was conducted to identify specific species of bacteria. For this study we have selected Staphylococcus aureus and Streptococcus which had high public health concern. Mannitol test was used to isolate Staphylococcus aureus, whereas Bacitracin test was conducted to isolate Streptococcus pyogene. RESULT: The result of this study indicated that the highest bacterial load which was 1468 CFU/m(3) has been recorded at 2:00 PM in Ward C at 60 min exposure time and the lowest bacterial concentration (i.e., 480 CFU/m(3)) was recorded at 8:00 AM in physiotherapy ward. Based on the result bacterial concentration of indoor air of Gondar University teaching hospital was found between 480 and 1468 CFU/m(3). The result of one way ANOVA showed that the highest mean bacterial concentration (1271.00 CFU/m(3)) was found in Medical ward and the least (583.25 CFU/m(3)) concentration was found in ward D and the grand total average concentration was 878.43 CFU/m(3). Favorable conditions for growth and multiplication of bacteria like temperature (26.5-29.5 °C), humidity (64.5-85 %), presence of unhygienic attached toilets, poor waste management system and poor ventilation system were observed during the survey. Staphylococcus aureus was identified in 10 wards and Streptococcus pyogenes was isolated in 8 hospital wards. CONCLUSIONS: Compared with different indoor air biological standards, higher concentration of indoor air bacterial load was found in Gondar University teaching hospital. The higher bacterial load may be due to temperature, humidity, presence of unhygienic attached toilets, poor waste management system and poor ventilation system. Therefore, attention must be given to control those environmental factors which favor the growth and multiplication of microbes in indoor environment. In addition, also the ventilation condition, cleanliness of toilets, sweeping methods and waste disposal system of the compound should be improved.

Exercise-induced bronchospasm diagnosis in children. Utility of combined lung function tests.

BACKGROUND: The diagnosis of exercise-induced asthma or bronchospasm (EIB) is a complex dare in daily clinical practice. The consensus is that if bronchial hyper-responsiveness (BHR) is demonstrated in a patient with symptoms consistent with EIB, then that patient can be diagnosed with exercise-induced bronchospasm. The aim of this study was to determine which BHR test is the most efficient to diagnose EIB. METHODS: Children under 16, without previous asthma diagnosis, or with stable asthma, complaining of asthma-like symptoms triggered by exercise were included. Bronchodilator, methacholine, mannitol, and exercise tests were performed on all patients, following established protocols. The performance of single and combined tests was determined. RESULTS: Of 46 patients (median age: 12 yr, ranged 8-16 y.o.) were recruited, 30 (70%) previously diagnosed of asthma. BHR was detected in 93.47% of the children. The exercise challenge test detected BHR in 11 of 46 (23.90%) patients, bronchodilator test in 10 of 46 (21.70%), mannitol in 36 of 45 (80%) and methacholine in 41 of 45 (91.11%). The total number of patients with BHR was detected using a combination of the methacholine and mannitol tests. A combination of the methacholine test performed first, followed by the mannitol test, was able to diagnose BHR in 100% of children with lower number of tests (n = 45) than if the order was reversed (n = 50). CONCLUSIONS: Methacholine and mannitol tests detect BHR in most children with suspected EIB. Bronchodilator and exercise tests show a low positivity rate. A combination of the methacholine test, followed by the mannitol test, gives the highest return to identify BHR in children for the diagnosis of EIB.

Assessment of environmental enteropathy in the MAL-ED cohort study: theoretical and analytic framework.

Individuals in the developing world live in conditions of intense exposure to enteric pathogens due to suboptimal water and sanitation. These environmental conditions lead to alterations in intestinal structure, function, and local and systemic immune activation that are collectively referred to as environmental enteropathy (EE). This condition, although poorly defined, is likely to be exacerbated by undernutrition as well as being responsible for permanent growth deficits acquired in early childhood, vaccine failure, and loss of human potential. This article addresses the underlying theoretical and analytical frameworks informing the methodology proposed by the Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) cohort study to define and quantify the burden of disease caused by EE within a multisite cohort. Additionally, we will discuss efforts to improve, standardize, and harmonize laboratory practices within the MAL-ED Network. These efforts will address current limitations in the understanding of EE and its burden on children in the developing world.