Periostin in exhaled breath condensate and in serum of asthmatic patients : relationship to upper and lower airway disease

PURPOSE: Periostin is considered a biomarker for eosinophilic airway inflammation and have been associated with NSAID-Exacerbated Respiratory Disease (NERD) and chronic rhinosinusitis (CRS). In this study, we aimed to evaluate periostin in exhaled breath condensate (EBC) and in serum of patients with various asthma phenotypes. METHODS: The study included 40 asthmatic patients (22 with NERD) and 17 healthy controls. All the procedures (questionnaire, spirometry, FeNO, nasal swabs, EBC collecting, and blood sampling) were performed on the same day. Periostin concentrations were measured using an ELISA kit. RESULTS: Periostin was detected in EBC from 37 of 40 asthmatics and in 16 from 17 of controls. The concentration of periostin in EBC did not differ between the study groups and was not associated with NERD or asthma severity. However, the EBC periostin was significantly higher in asthmatics with CRS as compared to those without (3.1 vs 2 ng/mL, P=0.046). Patients with positive bacterial culture from nasal swabs had higher EBC periostin concentrations than those without (3.2 vs 2.1 ng/mL; P=0.046). The mean serum periostin level was higher in asthmatics with a 1-year history of exacerbation than in those without (3.2 vs 2.3 ng/mL, P=0.045). Asthmatics with skin manifestation of NSAIDs hypersensitivity had higher serum periostin levels as compared to those without (3.5 vs 2.3 ng/mL; P=0.03). CONCLUSIONS: EBC periostin levels seem to reflect intensity of upper airway disease in asthmatics, while serum levels of periostin are associated with asthma activity (exacerbations or FeNO) or NERD subphenotypes

Apoptotic cell clearance in chronic inflammation of lateral neck cysts

The mechanism driving accumulation of large numbers of apoptotic and necrotic neutrophils in inflamed lateral neck cysts (LNC), in the absence of infection, remains obscure. The cellular content of cysts obtained from 17 patients was co-cultured with human macrophages. Phagocytosis levels of cyst-derived neutrophils were determined and compared to the uptake of spontaneously apoptotic neutrophils. Simultaneously, the expression of cytokines in macrophages exposed to cyst contents was measured. In comparison to spontaneously apoptotic neutrophils, the phagocytosis of LNC-derived neutrophils by macrophages was inefficient. An inverse correlation between neutrophil content in LNC and their uptake was observed. Macrophages co-cultured with cyst contents responded with variable expression of IL-6, TNF-α and IL-10. The hindered clearance of apoptotic neutrophils in LNC may lead to secondary necrosis of these cells and stimulation of the inflammatory reaction. Together with local production of anti-inflammatory cytokines, this may fuel chronic inflammation in the cysts

Stem cell factor and its soluble receptor (c-kit) in serum of asthmatic patients- correlation with disease severity

<p>Abstract</p> <p>Background</p> <p>SCF (stem cell factor) is a pleiotropic cytokine exerting its role at different stages of bone marrow development and affecting eosinophil activation, mast cells and basophil chemotaxis and survival. The aim of the study was to assess concentration of SCF and its soluble receptor c-kit (sc-kit) in peripheral blood of patients with asthma referring it to asthma severity and phenotype.</p> <p>Methods</p> <p>The study involved 107 patients with bronchial asthma, well characterized with respect to severity and 21 healthy controls. Concentration of SCF and sc-kit in the patients serum were measured by ELISA method.</p> <p>Results</p> <p>Mean serum SCF level in the group of asthmatics (n = 88) was significantly higher as compared to healthy controls (1010 pg/ml ± 37 vs 799 ± 33; p < 0,001). The level of SCF was higher in patients with severe asthma as compared to patients with non-severe asthma (1054 +/- 41 pg/ml vs 819 +/- 50; p < 0,01) and correlated with dose of inhaled glucocorticosteroids taken by the patients to achieve asthma control (R = 0,28; p < 0,01). The mean sc-kit serum level did not differ between asthmatic patients and healthy controls, however the level of sc-kit in non-severe asthmatics was significantly higher as compared to patients with severe asthma and healthy controls. In asthmatic patients (n = 63) the level of sc-kit correlated positively with FEV1% predicted value (R = 0,45; p < 0,001) and MEF25% predicted value (R = 0,33; p < 0,01). The level of sc-kit inversely correlated with the dose of inhaled glucocorticosteroids taken by the patients (R = -0,26; p < 0,01).</p> <p>Conclusion</p> <p>Serum levels of SCF and its soluble receptor c-kit seem to be reflect asthma severity suggesting a role for these molecules in asthmatic inflammation.</p

Obstructive Sleep Apnea: From Intermittent Hypoxia to Cardiovascular Complications via Blood Platelets

Obstructive sleep apnea is a chronic condition characterized by recurrent episodes of apneas or hypopneas during sleep leading to intermittent hypoxemia and arousals. The prevalence of the sleep disordered breathing is estimated that almost 50% of men and 24% of women suffer from moderate to severe form of the disorder. Snoring, collapse of upper airways and intermittent hypoxia are main causes of smoldering systemic inflammation in patients suffering from obstructive sleep apnea. The systematic inflammation is considered one of the key mechanisms leading to significant cardiovascular complications. Blood platelets, formerly not even recognized as cells, are currently gaining attention as crucial players in the immune continuum. Platelet surface is endowed with receptors characteristic for cells classically belonging to the immune system, which enables them to recognize pathogens, immune complexes, and interact in a homo- and heterotypic aggregates. Platelets participate in the process of transcellular production of bioactive lipids by delivering both specific enzymes and substrate molecules. Despite their lack of nucleus, platelets synthetize proteins in a stimuli-dependent manner. Atherosclerosis and consequent cardiovascular complications result from disruption in homeostasis of both of the platelet roles: blood coagulation and inflammatory processes modulation. Platelet parameters, routinely evaluated as a part of complete blood count test, were proposed as markers of cardiovascular comorbidity in patients with obstructive sleep apnea. Platelets were found to be excessively activated in this group of patients, especially in obese subjects. Persistent activation results in enhanced spontaneous aggregability and change in cytokine production. Platelet-lymphocyte ratio was suggested as an independent marker for cardiovascular disease in obstructive sleep apnea syndrome and continuous positive air pressure therapy was found to have an impact on platelet parameters and phenotype. In this literature review we summarize the current knowledge on the subject of platelets involvement in obstructive sleep apnea syndrome and consider the possible pathways in which they contribute to cardiovascular comorbidity

Wpływ lipoksyny A4 na uwalnianie cytokin przez komórki jednojądrowe pacjentów chorych na łuszczycowe zapalenie stawów

Background: Up to 40% of patients with psoriasis suffer from psoriatic arthritis (PsA), an underrecognized inflammatory arthropathy of incompletely understood pathogenesis. PsA affects axial joints, surrounding ligaments, tendons and entheses. One hypothesis links repeated microinjuries with disorders of inflammation resolution mechanisms that lead to chronic inflammation, which spreads to surrounding tissues. An example of the mediators which lead to resolution of inflammation in physiological conditions are derivatives of arachidonic acid – lipoxins. Objectives: The aim of the study was to compare if the influence of lipoxin A4 on the synthesis of pro-inflammatory cytokines by peripheral blood mononuclear cells (PBMCs) isolated from peripheral blood of patients with PsA and healthy individuals. Methods: 10 patients with PsA and 5 matching healthy controls were enrolled in the study. PBMSc were isolated by gradient-density centrifugation technique and incubated with lipopolysaccharide with or without the addition of lipoxin A4 for 24 hours. The levels of IL-1β, IFN-α, IFN-γ, TNFα, MCP-1, IL-6, IL-8, IL-10, IL-17, IL-12, IL-18, IL-23 and IL-33 in cell culture supernatants were quantified by cytometric bead array system. Results: Incubation of PBMCs with LPS, increased production of all cytokines assessed either in patients with psoriatic arthritis or in healthy controls. In PBMCs from healthy controls incubation of cells with lipoxine A4 decrease production of proinflammatory cytokines. However, in patients with psoriatic arthritis addition of lipoxine A4 did not inhibited LPS – induced proinflammatory cytokines release. Conclusions: The anti-inflammatory effect of lipoxin A4 is reversed in PsA PBMCs, supporting the hypothesis of defective resolution of inflammation in the pathogenesis of PsA.Wprowadzenie: Patogeneza łuszczycowego zapalenie stawów (ŁZS), które występuje u ok. 40% pacjentów chorych na łuszczycę, jest nie do końca poznana i wyjaśniona. ŁZS obejmuje stawy osiowe (kręgosłup i stawy krzyżowo-biodrowe), stawy obwodowe, więzadła, ścięgna i przyczepy ścięgniste. Jedna z hipotez mówi, że powtarzające się mikrourazy oraz upośledzenie mechanizmów rezolucji procesu zapalnego, prowadzi do przewlekłego zapalenia, które obejmuje otaczające tkanki. Do mediatorów, prowadzących do ustąpienia stanu zapalnego w warunkach fizjologicznych należą lipoksyny pochodzące z kwasu arachidonowego. Cel pracy: Celem pracy było porównanie wpływu lipoksyny A4 na syntezę cytokin prozapalnych przez komórki jednojądrowe krwi obwodowej (PBMC) izolowane z krwi obwodowej pacjentów chorych na ŁZS i osób zdrowych. Metody: Do badania włączono 10 pacjentów chorych na łuszczycowe zapalenie stawów oraz 5 osób zdrowych. Komórki jednojądrowe krwi obwodowej izolowano techniką wirowania w gradiencie gęstości, a następnie inkubowano z lipopolisacharydem Escherichia coli O111:B4 z dodatkiem lub bez lipoksyny A4 przez 24 godziny. Poziomy IL-1β, IFN-α, IFN-γ, TNFα, MCP-1, IL-6, IL-8, IL-10, IL-17, IL-12, IL-18, IL-23 i IL -33 w supernatantach hodowli komórkowej oznaczono metodą cytometrii przepływowej. Wyniki: Inkubacja PBMC z LPS zwiększała produkcję wszystkich cytokin zarówno u pacjentów z łuszczycowym zapaleniem stawów i osób zdrowych. W PBMC osób zdrowych inkubacja komórek z lipoksyną A4 zmniejszała wytwarzanie cytokin prozapalnych. Jednak u pacjentów z łuszczycowym zapaleniem stawów dodanie lipoksyny A4 nie hamowało indukowanego przez LPS uwalniania cytokin prozapalnych. Wnioski: Przeciwzapalne działanie lipoksyny A4 jest odwrócone w PBMC u chorych na ŁZS, co potwierdza hipotezę o zaburzeniach rezolucji zapalenia w patogenezie ŁZS