Objectives: In all patients with cystic fibrosis (CF), gastrointestinal (GI) tract CF transmembrane conductance regulator dysfunction occurs early in life. The identical pathophysiological triad of obstruction, infection, and inflammation causes disease of the airways and in the intestinal tract (CF enteropathy). Mucus accumulation within GI tract is a niche for abnormal microbial colonization, leading to dysbiosis. Fecal calprotectin (FC) is a neutrophil cytosolic protein released during apoptosis and necrosis and reflects inflammatory status. Systemic antibiotic treatment for pulmonary exacerbations has been shown to improve systemic inflammatory markers and serum and sputum calprotectin. Antibiotic treatment aimed at pulmonary complaints may improve GI tract inflammatory status. We hypothesized that high levels of FC present during pulmonary exacerbation are due, in part, to multiorgan dysbiosis and thus should diminish with systemic antibiotic treatment. Methods: This prospective pilot study enrolled 14 patients with CF, with no current GI symptoms. FC levels and lung function were measured at the beginning and end of systemic antibiotic treatment. Results: Compared to preantibiotic treatment baseline values, end of treatment FC levels declined significantly after antibiotic treatment, P = 0.004 and similarly, there was significant improvement in forced expiratory volume in 1 second, P = 0.002. Conclusions: High levels of FC during respiratory exacerbation may reflect a systemic exacerbation rather than solely pulmonary. Antibiotic treatment lowered the FC levels possibly by its impact on the intestinal microbiome.
BackgroundRedox-active iron, a catalyst in the production of hydroxyl radicals via the Fenton reaction, is one of the key participants in ROS-induced tissue injury and general inflammation. According to our recent findings, an excess of tissue iron is involved in several airway-related pathologies such as nasal polyposis and asthma.ObjectiveTo examine the anti-inflammatory properties of a newly developed specific iron–chelating complex, Zn/Ga−DFO, in a mouse model of asthma.Materials and methodsAsthma was induced in BALBc mice by ovalbumin, using aluminum hydroxide as an adjuvant. Mice were divided into four groups: (i) control, (ii) asthmatic and sham-treated, (iii) asthmatic treated with Zn/Ga−DFO [intra-peritoneally (i/p) and intra-nasally (i/n)], and (iv) asthmatic treated with Zn/Ga−DFO, i/n only. Lung histology and cytology were examined. Biochemical analysis of pulmonary levels of ferritin and iron-saturated ferritin was conducted.ResultsThe amount of neutrophils and eosinophils in bronchoalveolar lavage fluid, goblet cell hyperplasia, mucus secretion, and peri-bronchial edema, showed markedly better values in both asthmatic-treated groups compared to the asthmatic non-treated group. The non-treated asthmatic group showed elevated ferritin levels, while in the two treated groups it returned to baseline levels. Interestingly, i/n-treatment demonstrated a more profound effect alone than in a combination with i/p injections.ConclusionIn this mouse model of allergic asthma, Zn/Ga−DFO attenuated allergic airway inflammation. The beneficial effects of treatment were in accord with iron overload abatement in asthmatic lungs by Zn/Ga−DFO. The findings in both cellular and tissue levels supported the existence of a significant anti-inflammatory effect of Zn/Ga−DFO.
There is growing evidence that nutrition is part of the environmental factors affecting the incidence of various diseases. The effect starts in the prenatal life and affects fetal growth and continues in early life and throughout childhood. The effect has been shown on various disease states such as allergic diseases, hyperlipidemia and cardiovascular diseases, obesity, type II diabetes and metabolic syndrome, and immunologic diseases such as celiac disease and type 1 diabetes mellitus. It seems that the recommendations of exclusive breastfeeding until the age of 4 months and subsequently exposure to various solid foods has beneficial effect in terms of allergic, immunologic, and cardiovascular diseases prevention. Will these recommendations change the natural course of these diseases is unknown yet, but there is accumulating evidence that indeed this is the case. In this review, we review the evidence of early nutritional intervention and future disease prevention.
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