Sputum proteomic signature of gastro-oesophageal reflux in patients with severe asthma.

Gastro-oesophageal reflux disease (GORD) has long been associated with poor asthma control without an established cause-effect relationship. 610 asthmatics (421 severe/88 mild-moderate) and 101 healthy controls were assessed clinically and a subset of 154 severe asthmatics underwent proteomic analysis of induced sputum using untargeted mass spectrometry, LC-IMS-MSE. Univariate and multiple logistic regression analyses (MLR) were conducted to identify proteins associated with GORD in this cohort. When compared to mild/moderate asthmatics and healthy individuals, respectively, GORD was three- and ten-fold more prevalent in severe asthmatics and was associated with increased asthma symptoms and oral corticosteroid use, poorer quality of life, depression/anxiety, obesity and symptoms of sino-nasal disease. Comparison of sputum proteomes in severe asthmatics with and without active GORD showed five differentially abundant proteins with described roles in anti-microbial defences, systemic inflammation and epithelial integrity. Three of these were associated with active GORD by multiple linear regression analysis: Ig lambda variable 1-47 (p = 0·017) and plasma protease C1 inhibitor (p = 0·043), both in lower concentrations, and lipocalin-1 (p = 0·034) in higher concentrations in active GORD. This study provides evidence which suggests that reflux can cause subtle perturbation of proteins detectable in the airways lining fluid and that severe asthmatics with GORD may represent a distinct phenotype of asthma.

Effect of priming/booster immunisation protocols on immune response to canine parvovirus peptide induced by vaccination with a chimaeric plant virus construct.

Expression of a 17-mer peptide sequence from canine parvovirus expressed on cowpea mosaic virus (CPMV) to form chimaeric virus particles (CVPs) creates vaccine antigens that elicit strong anti-peptide immune responses in mice. Systemic (subcutaneous, s.c.) immunisation and boosting with such CVP constructs produces IgG(2a) serum antibody responses, while mucosal (intranasal, i.n.) immunisation and boosting elicits intestinal IgA responses. Combinations of systemic and mucosal routes for priming and boosting immunisations were used to examine their influence on the level, type and location of immune response generated to one of these constructs (CVP-1). In all cases, s.c. administration, whether for immunisation or boosting, generated a Th1-biased response, reflected in a predominantly IgG(2a) serum antibody isotype and secretion of IFN-gamma from in vitro-stimulated lymphocytes. Serum antibody responses were greatest in animals primed and boosted subcutaneously, and least in mucosally vaccinated mice. The i.n. exposure also led to IFN-gamma release from in vitro-stimulated cells, but serum IgG(2a) was significantly elevated only in mice primed intranasally and boosted subcutaneously. Peptide- and wild-type CPMV-specific IgA responses in gut lavage fluid were greatest in animals exposed mucosally and least in those primed and boosted subcutaneously or primed subcutaneously and boosted orally. Lymphocytes from immunised mice proliferated in response to in vitro stimulation with CPMV but not with peptide. The predominant secretion of IFN-gamma from all immunising/boosting combinations indicates that the route of vaccination and challenge does not alter the Th1 bias of the response to CVP constructs. However, optimal serum and intestinal antibody responses were achieved by combining s.c. and i.n. administration.

Energy metabolism and hormonal profile in children with edematous protein-calorie malnutrition.

Modifications in energy metabolism and endocrine homeostasis (plasma insulin and growth hormone values, glucose and free fatty acid levels, serum thyroxine and TSH, free thyroxine index, and urinary catecholamines) were investigated in eight children with edematous protein-calorie malnutrition. Caloric expenditure was low at admission and correlated linearly with increased caloric intake throughout the study. The hormonal changes at admission were characterized by a negligible insulin response to intravenous arginine or glucose and by markedly elevated growth hormone levels which were neither increased by arginine nor suppressed by intravenous glucose. Serum thyroxine values were low, but free thyroxine index and serum TSH levels were within normal limits. At admission to the study, 24-hour urinary excretion of dopamine and norepinephrine was relatively reduced in relation to the excretion of epinephrine. All these modifications were corrected at time of the recovery study. It is suggested that in edematous protein-calorie malnutrition, insulin acts as the primary regulator of peripheral fuel release and that the high, nonsuppressible growth hormone levels may form part of an important homeostatic mechanism to provide substrates for brain metabolism via lipolysis.

Relationship between muscle potassium and body potassium in infants with malnutrition

Specimens of muscle were obtained with a biopsy needle from 23 Jamaican children who were recovering from malnutrition. The samples were analysed for water, fat, nitrogen, and potassium, total body potassium was also measured. Muscle water is increased, but potassium concentration declines in malnutrition. A significant relationship exists between the depletions of muscle potassium and of total body potassium in malnourished infants. Analysis of muscle biopsy samples may lead to a better understanding of the response of tissue to protein depletion at the cellular level (Summary)