Serum 25-hydroxyvitamin D fluctuations in military personnel during 6-month summer operational deployments in Afghanistan.

Soldier operational performance is determined by their fitness, nutritional status, quality of rest/recovery, and remaining injury/illness free. Understanding large fluctuations in nutritional status during operations is critical to safeguarding health and well-being. There are limited data world-wide describing the effect of extreme climate change on nutrient profiles. This study investigated the effect of hot-dry deployments on vitamin D status (assessed from 25-hydroxyvitamin D (25(OH)D) concentration) of young, male, military volunteers. Two data sets are presented (pilot study, n 37; main study, n 98), examining serum 25(OH)D concentrations before and during 6-month summer operational deployments to Afghanistan (March to October/November). Body mass, percentage of body fat, dietary intake and serum 25(OH)D concentrations were measured. In addition, parathyroid hormone (PTH), adjusted Ca and albumin concentrations were measured in the main study to better understand 25(OH)D fluctuations. Body mass and fat mass (FM) losses were greater for early (pre- to mid-) deployment compared with late (mid- to post-) deployment (P<0·05). Dietary intake was well-maintained despite high rates of energy expenditure. A pronounced increase in 25(OH)D was observed between pre- (March) and mid-deployment (June) (pilot study: 51 (sd 20) v. 212 (sd 85) nmol/l, P<0·05; main study: 55 (sd 22) v. 167 (sd 71) nmol/l, P<0·05) and remained elevated post-deployment (October/November). In contrast, PTH was highest pre-deployment, decreasing thereafter (main study: 4·45 (sd 2·20) v. 3·79 (sd 1·50) pmol/l, P<0·05). The typical seasonal cycling of vitamin D appeared exaggerated in this active male population undertaking an arduous summer deployment. Further research is warranted, where such large seasonal vitamin D fluctuations may be detrimental to bone health in the longer-term.

Detailed characterization of a long-term rodent model of critical illness and recovery.

OBJECTIVE: To characterize a long-term model of recovery from critical illness, with particular emphasis on cardiorespiratory, metabolic, and muscle function. DESIGN: Randomized controlled animal study. SETTING: University research laboratory. SUBJECTS: Male Wistar rats. INTERVENTIONS: Intraperitoneal injection of the fungal cell wall constituent, zymosan or n-saline. MEASUREMENTS AND MAIN RESULTS: Following intervention, rats were followed for up to 2 weeks. Animals with zymosan peritonitis reached a clinical and biochemical nadir on day 2. Initial reductions were seen in body weight, total body protein and fat, and muscle mass. Leg muscle fiber diameter remained subnormal at 14 days with evidence of persisting myonecrosis, even though gene expression of regulators of muscle mass (e.g., MAFbx, MURF1, and myostatin) had peaked on days 2-4 but normalized by day 7. Treadmill exercise capacity, forelimb grip strength, and in vivo maximum tetanic force were also reduced. Food intake was minimal until day 4 but increased thereafter. This did not relate to appetite hormone levels with early (6 hr) rises in plasma insulin and leptin followed by persisting subnormal levels; ghrelin levels did not change. Serum interleukin-6 level peaked at 6 hours but had normalized by day 2, whereas interleukin-10 remained persistently elevated and high-density lipoprotein cholesterol persistently depressed. There was an early myocardial depression and rise in core temperature, yet reduced oxygen consumption and respiratory exchange ratio with a loss of diurnal rhythmicity that showed a gradual but incomplete recovery by day 7. CONCLUSIONS: This detailed physiological, metabolic, hormonal, functional, and histological muscle characterization of a model of critical illness and recovery reproduces many of the findings reported in human critical illness. It can be used to assess putative therapies that may attenuate loss, or enhance recovery, of muscle mass and function.

Energy expenditure, nutritional status, body composition and physical fitness of Royal Marines during a 6-month operational deployment in Afghanistan.

Understanding the nutritional demands on serving military personnel is critical to inform training schedules and dietary provision. Troops deployed to Afghanistan face austere living and working environments. Observations from the military and those reported in the British and US media indicated possible physical degradation of personnel deployed to Afghanistan. Therefore, the present study aimed to investigate the changes in body composition and nutritional status of military personnel deployed to Afghanistan and how these were related to physical fitness. In a cohort of British Royal Marines (n 249) deployed to Afghanistan for 6 months, body size and body composition were estimated from body mass, height, girth and skinfold measurements. Energy intake (EI) was estimated from food diaries and energy expenditure measured using the doubly labelled water method in a representative subgroup. Strength and aerobic fitness were assessed. The mean body mass of volunteers decreased over the first half of the deployment ( - 4·6 (sd 3·7) %), predominately reflecting fat loss. Body mass partially recovered (mean +2·2 (sd 2·9) %) between the mid- and post-deployment periods (P< 0·05). Daily EI (mean 10 590 (sd 3339) kJ) was significantly lower than the estimated daily energy expenditure (mean 15 167 (sd 1883) kJ) measured in a subgroup of volunteers. However, despite the body mass loss, aerobic fitness and strength were well maintained. Nutritional provision for British military personnel in Afghanistan appeared sufficient to maintain physical capability and micronutrient status, but providing appropriate nutrition in harsh operational environments must remain a priority.

Long-term tolerance after allergen immunotherapy is accompanied by selective persistence of blocking antibodies.

BACKGROUND: Grass pollen immunotherapy for allergic rhinitis is a disease-modifying treatment that results in long-term clinical tolerance lasting years after treatment discontinuation. Active treatment is associated with generation of inhibitory grass pollen-specific IgG antibodies capable of blocking allergen-IgE interactions. OBJECTIVES: We sought to investigate the involvement of IgG-associated inhibitory antibodies with long-term clinical tolerance after discontinuation of grass pollen immunotherapy. METHODS: We conducted a 4-year study in which patients who had moderate-to-severe allergic rhinitis underwent a randomized, double-blind, placebo-controlled discontinuation of subcutaneous grass pollen immunotherapy. All subjects received grass pollen immunotherapy injections for 2 years (n = 13), followed by a further 2 years of either active (n = 7) or placebo (n = 6) injections. Clinical outcomes included seasonal symptoms and use of rescue medication. Serum specimens were collected at baseline and after 2 and 4 years for quantification of allergen-specific IgG antibodies. Sera were also tested for IgG-dependent inhibitory bioactivity against IgE-allergen binding in cellular assays by using flow cytometry and confocal microscopy to detect binding of IgE-grass pollen allergen complexes to B cells. RESULTS: Clinical improvement was maintained after 2 years of discontinuation. Although immunotherapy-induced grass pollen-specific IgG1 and IgG4 levels decreased to near-preimmunotherapy levels during discontinuation, inhibitory bioactivity of allergen-specific IgG antibodies was maintained unchanged. CONCLUSION: Grass pollen immunotherapy induces a subpopulation of allergen-specific IgG antibodies with potent inhibitory activity against IgE that persists after treatment discontinuation and that could account for long-term clinical tolerance.

Impact of ghrelin on body composition and muscle function in a long-term rodent model of critical illness.

BACKGROUND: Patients with multiple injuries or sepsis requiring intensive care treatment invariably develop a catabolic state with resultant loss of lean body mass, for which there are currently no effective treatments. Recovery can take months and mortality is high. We hypothesise that treatment with the orexigenic and anti-inflammatory gastric hormone, ghrelin may attenuate the loss of body mass following critical illness and improve recovery. METHODS: Male Wistar rats received an intraperitoneal injection of the fungal cell wall derivative zymosan to induce a prolonged peritonitis and consequent critical illness. Commencing at 48h after zymosan, animals were randomised to receive a continuous infusion of ghrelin or vehicle control using a pre-implanted subcutaneous osmotic mini-pump, and continued for 10 days. RESULTS: Zymosan peritonitis induced significant weight loss and reduced food intake with a nadir at Day 2 and gradual recovery thereafter. Supra-physiologic plasma ghrelin levels were achieved in the treated animals. Ghrelin-treated rats ate more food and gained more body mass than controls. Ghrelin increased adiposity and promoted carbohydrate over fat metabolism, but did not alter total body protein, muscle strength nor muscle morphology. Muscle mass and strength remained significantly reduced in all zymosan-treated animals, even at ten days post-insult. CONCLUSIONS: Continuous infusion of ghrelin increased body mass and food intake, but did not increase muscle mass nor improve muscle function, in a long-term critical illness recovery model. Further studies with pulsatile ghrelin delivery or additional anabolic stimuli may further clarify the utility of ghrelin in survivors of critical illness.

Changes in gut hormones and leptin in military personnel during operational deployment in Afghanistan.

OBJECTIVE: Understanding the mechanisms that drive weight loss in a lean population may elucidate systems that regulate normal energy homeostasis. This prospective study of British military volunteers investigated the effects of a 6-month deployment to Afghanistan on energy balance and circulating concentrations of specific appetite-regulating hormones. METHODS: Measurements were obtained twice in the UK (during the Pre-deployment period) and once in Afghanistan, at Mid-deployment. Body mass, body composition, food intake, and appetite-regulatory hormones (leptin, active and total ghrelin, PYY, PP, GLP-1) were measured. RESULTS: Repeated measures analysis of 105 volunteers showed body mass decreased by 4.9% ± 3.7% (P < 0.0001) during the first half of the deployment. Leptin concentrations were significantly correlated with percentage body fat at each time point. The reduction in percentage body fat between Pre-deployment and Mid-deployment was 8.6%, with a corresponding 48% decrease in mean circulating leptin. Pre-deployment leptin and total and active ghrelin levels correlated with subsequent change in body mass; however. no changes were observed in the anorectic gut hormones GLP-1, PP, or PYY. CONCLUSIONS: These data suggest that changes in appetite-regulating hormones in front line military personnel occur in response to, but do not drive, reductions in body mass.

Increases in allergen-specific IgE in BAL after segmental allergen challenge in atopic asthmatics.

IgE is important in both early and late allergic responses. Increases in the numbers of RNA transcripts coding for IgE have been observed in the bronchial mucosa of asthmatics and in the nasal mucosa of hay fever patients both during natural allergen exposure and after nasal allergen challenge, suggesting that IgE may be synthesized locally in the mucosa. In this study we have examined bronchoalveolar lavage (BAL) taken before and 24 h after bronchoscopic segmental allergen challenge from 18 atopic asthmatic patients, looking for evidence of increases in IgE protein. Allergen-specific IgG and total and allergen-specific IgE were measured in BAL using a fluoroenzyme immunoassay. There was a significant increase in allergen-specific IgE (Ku/L) in the BAL after allergen challenge [before [median (interquartile range)] 0 (0, 0); after 0.35 (0, 1.87): p = 0.009] which was not observed for allergen-specific IgG (p = 1.0) or for IgE specific to an allergen to which the subject was sensitized but was not used for provocation (p = 1.0). Correction for corresponding increases in total IgE, albumin, and urea in BAL did not affect the observed changes in allergen-specific IgE. These data indicate that allergen provocation results in a selective local accumulation of isotype-specific and allergen-specific IgE antibody within the bronchi, independent of alterations in circulating IgE.

Grass pollen immunotherapy for hayfever is associated with increases in local nasal but not peripheral Th1:Th2 cytokine ratios.

Grass pollen immunotherapy is the only treatment for hayfever that is both effective and confers long-term benefit. Immunotherapy may act by altering the local nasal mucosal T helper type 2 (Th2) to type 1 (Th1) cytokine balance either by down-regulation and/or immune deviation of T-lymphocyte responses. There is controversy as to whether these changes are detectable in peripheral blood. We therefore examined both local nasal and peripheral T-cell responses to allergen exposure in the same subjects before and after immunotherapy. In a double-blind trial of grass pollen immunotherapy, nasal biopsies were obtained at baseline and during the peak pollen season following 2 years of immunotherapy. Placebo-treated patients showed a seasonal increase in CD3(+) T cells (P = 0.02) and in interleukin-5 (IL-5) mRNA(+) cells (P = 0.03) and no change in interferon-gamma (IFN-gamma ) mRNA(+) cells (P = 0.2) in the nasal mucosa. In contrast, in the immunotherapy-treated group, there were no changes in the number of CD3(+) T cells (P = 0.3) and IL-5 mRNA+ cells (P = 0.2) but a significant increase in the number of IFN-gamma mRNA(+) cells (P = 0.03). Furthermore, clinical improvement in the immunotherapy-treated group was accompanied by a seasonal increase in the ratio of IFN-gamma to IL-5 mRNA(+) cells in the nasal mucosa (P = 0.03). In contrast, there were no significant changes in peripheral T-cell proliferative responses or cytokine production for IFN-gamma or IL-5 in response to grass pollen either within or between the two treatment groups. We conclude that successful grass pollen immunotherapy was associated with an increase in the ratio of IFN-gamma to IL-5 mRNA(+) cells in the nasal mucosa, whereas these changes were not reflected by alterations in peripheral blood T-cell proliferative responses or cytokine production before/after treatment.