Acquired Phagocyte Dysfunction

Craddock, Philip R.; Yawata, Yoshihito; Vansanten, L.; Gilberstadt, S; Silvis, Stephen E.; Jacob, Harry S.

doi:10.1056/nejm197406202902504

Cited by 271 publications

(18 citation statements)

References 19 publications

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“…It is also plausible that hypophosphatemia by itself may contribute to thymus atrophy. Hypophosphatemia has been found to cause leukocyte dysfunction [31], and phosphorus is a type II nutrient, essential for growth and maintenance of lean body mass [32]. Thymus atrophy occurs in animals deficient in other type II nutrients, like zinc [33] and magnesium [34], and a recent study found thymus size in low-birth-weight infants to be associated with zinc levels in cord-blood [35].…”

Section: Discussionmentioning

confidence: 99%

Correlates of thymus size and changes during treatment of children with severe acute malnutrition: a cohort study

et al. 2017

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BackgroundThe impairment of immune functions associated with malnutrition may be one reason for the high mortality in children with severe acute malnutrition (SAM), and thymus atrophy has been proposed as a marker of this immunodeficiency. The aim of this study was to identify nutritional and clinical correlates of thymus size in children with SAM, and predictors of change in thymus size with nutritional rehabilitation.MethodsIn an observational study among children aged 6–59 months admitted with SAM in Uganda, we measured thymus area by ultrasound on hospital admission to treatment with F75 and F100, on hospital discharge and after 8 weeks of nutritional rehabilitation with ready-to-use therapeutic food, as well as in well-nourished healthy children. We investigated anthropometric, clinical, biochemical and treatment-related correlates of area and growth of the thymus.ResultsEighty-five children with SAM with a median age of 16.5 months were included. On admission 27% of the children had a thymus undetectable by ultrasound. Median thymus area was 1.3 cm2 in malnourished children, and 3.5 cm2 in healthy children (p < 0.001). Most anthropometric z-scores, hemoglobin and plasma phosphate correlated positively with thymus area. Thymus area correlated negatively with caretaker-reported severity of illness, plasma α-1 acid glycoprotein, and C-reactive protein >5 mg/L. At follow-up after 8 weeks, median thymus area had increased to 2.5 cm2 (p < 0.001). Increase in thymus area during treatment was associated with simultaneous increase in mid-upper-arm circumference, with 0.29 cm2 higher increase in thymus area per cm larger increment in MUAC (p = 0.03). Children whose F-75 had partially been replaced by rice porridge during their hospital admission had less increase in thymus area after 8 weeks.ConclusionMalnutrition and inflammation are associated with thymus atrophy, and thymus area seems positively associated with plasma phosphate. Substituting therapeutic formula with unfortified rice porridge with the aim of alleviating diarrhea may impair regain of thymus size with nutritional rehabilitation. This calls for research into possible effects of phosphate status on thymus size and other immunological markers.Trial registrationThe study is based on data from the FeedSAM study, ISRCTN55092738.

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Section: Discussionmentioning

confidence: 99%

Correlates of thymus size and changes during treatment of children with severe acute malnutrition: a cohort study

et al. 2017

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“…[ 29 – 32 ] Its harmful effects can be exemplified by decreased myocardial contraction, increased development of arrhythmia, impaired response to vasopressors, and decreased granulocyte phagocytic activity. [ 33 – 37 ] The reason for the discrepancy in findings concerning phosphate levels and mortality among studies is unclear. Interestingly, most of the adverse effects caused by hypophosphatemia result from very severe phosphate deficiency.…”

Section: Discussionmentioning

confidence: 99%

Electrolyte and mineral disturbances in septic acute kidney injury patients undergoing continuous renal replacement therapy

et al. 2016

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“…Therefore, depleted phosphorus stores, reflected by hypophosphatemia, might lead to insufficient and reduced ATP production which subsequently impairs several vital systemic functions including the immune system and the ability of the lungs to clear edema [ 24 ]. Craddock et al have shown that severe hypophosphatemia causes acquired phagocyte dysfunction reflected by defected chemotaxis, phagocytosis and bactericidal activity [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

“…Hypophosphatemia is known to play an essential role in impaired chemotaxis, phagocytosis, and bactericidal activity of macrophages [ 21 ]. Hypophosphtemia can lead to ATP depletion, a shift from oxidative phosphrylation toward glycolysis, and subsequently, organ dysfunction .and, especially, muscle weakness.…”

Section: Introductionmentioning

confidence: 99%

Serum inorganic phosphorus levels predict 30-day mortality in patients with community acquired pneumonia

et al. 2015

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BackgroundCommunity acquired pneumonia is a major cause of morbidity and mortality. The association between serum phosphorus levels on admission and the outcome of patients with community acquired pneumonia has not been widely examined. We aimed to investigate the prognostic value of serum phosphorus levels on admission on the 30- day mortality.MethodsThe cohort included patients of 18 years old or older who were diagnosed with community acquired pneumonia between 2006 and 2012. Patients were retrospectively analyzed to identify risk factors for a primary endpoint of 30-day mortality. Binary logistic regression analysis was used for the calculation of the odds ratios (OR) and p values in bivariate and multivariate analysis to identify association between patients’ characteristic and 30-day mortality.ResultsThe cohort included 3894 patients. In multivariate regression analysis, variables associated with increased risk of 30-day mortality included: age >80 years, increased CURB-65 score, RDW >15, hypernatremia >150 mmol/l, hypoalbuminemia <2 gr/dl and abnormal levels of phosphorus. Levels of <1.5 mg/dl and >4.5 mg/dl were significantly associated with excess 30-day mortality, 38 % (OR 2.9, CI 1.8-4.9, P = 0.001) and 39 % (OR 3.4, CI 2.7-4.2, P = 0.001), respectively. Phosphorus levels within the upper normal limits (4-4.5 mg/dl) were associated with higher mortality rates compared to levels between 1.5-3.5 mg/dl, the reference group, 24 % (OR 1.9, CI 1.5-2.4, P = 0.001).ConclusionsAbnormal phosphorus levels on admission are associated with increased mortality rates among patients hospitalized with Community acquired pneumonia.

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Acquired Phagocyte Dysfunction

Cited by 271 publications

References 19 publications

Correlates of thymus size and changes during treatment of children with severe acute malnutrition: a cohort study

Correlates of thymus size and changes during treatment of children with severe acute malnutrition: a cohort study

Electrolyte and mineral disturbances in septic acute kidney injury patients undergoing continuous renal replacement therapy

Serum inorganic phosphorus levels predict 30-day mortality in patients with community acquired pneumonia

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