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Background: The course of asthma may differ between elderly asthmatics (EA) and non-elderly asthmatics (nEA), which may be partially associated with an age-dependent aberrant immune response. The aim of the study was to determine the influence of serum miRNA expression on asthma characteristics and systemic inflammation markers in EA and nEA., Methods: Control and severity of asthma, pulmonary function and FeNO were assessed in 28 EA and 31 nEA patients. The control group included 59 elderly and non-elderly healthy individuals. The expression of selected miRNAs in serum was measured with rt-PCR, and proinflammatory cytokine activity was assayed by ELISA or flow cytometry., Results: No difference in serum miRNA expression was observed between the asthmatics and healthy controls. EA demonstrated lower expression of miRNA-106a and miRNA-126a than nEA (p = 0.003 and p = 0.02) and EC had lower expression of miRNA-146a, -126a, -106a and 19b than nEC (p = 0.001, p = 0.003, p = 0.005 and p < 0.001 respectively). Only nEA demonstrated a relationship between the expression of selected miRNAs and the level of asthma control (assessed with ACT) and with airway inflammation, measured by FeNO level. All patients with asthma demonstrated elevated TNFα, IL-6 and sTNF RI levels compared to controls (p = 0.026, p = 0.03 and p < 0.001 respectively). EA demonstrated a higher TNFα level than EC (p < 0.001), and EA had a higher level of sTNF RI than nEA (p < 0.001). A significant correlation was observed between serum levels of proinflammatory cytokines and selected miRNAs., Conclusion: Serum miRNA expression was found to correlate with clinical characteristics of asthma and systemic inflammation in an age-dependent fashion, suggesting that miRNA may differentially contribute to asthma pathogenesis in elderly and non-elderly patients.

Introduction: Innate lymphoid cells (ILCs) represent a diverse family of cells of the innate immune system, which play an important role in regulation of tissue homeostasis, immunity and inflammation. Emerging evidence has highlighted the importance of ILCs in both protective immunity to respiratory infections and their pathological roles in the lungs. Therefore, the aim of this review is to summarize the current knowledge, interpret and integrate it into broader perspective, enabling greater insight into the role of ILCs in respiratory diseases. Areas covered: In this review we highlighted the role of ILCs in the lungs, citing the most recent studies in this area. PubMed searches (2004- July 2017) were conducted using the term 'innate lymphoid cells respiratory viral infections' in combination with other relevant terms including various respiratory viruses. Expert commentary: Since studies of ILCs have opened new areas of investigation, understanding the role of ILCs in respiratory infections may help to clarify the mechanisms underlying viral-induced exacerbations of lung diseases, providing the basis for novel therapeutic strategies. Potential therapeutic targets have already been identified. So far, the most promising strategy is cytokine-targeting, although further clinical trials are needed to verify its effectiveness.

Peroxisome proliferator-activated receptors-gamma (PPAR-gamma) are members of the nuclear receptor superfamily containing transcription factors regulating gene expression. PPAR-gamma have attracted attention so far as key factors in adipogenesis, lipid metabolism, insulin sensitivity, and apoptosis. Recently, growing evidence points to their implication in the regulation of the immune response, particularly in inflammation control. Not only are PPAR-gamma found in various structures of the immune system, but many inflammatory mediators, such as arachidonic acid and its metabolites, also act as potent and specific ligands of them. Inflammation is the basis of the pathogeneses of such chronic diseases as bronchial asthma, atherosclerosis, rheumatoid arthritis, and chronic inflammatory bowel diseases. The causative relationship between PPAR-gamma activity and the pathogeneses of these inflammatory disorders has been found in specific animal models. Moreover, PPAR-gamma agonists have been shown to act as potent anti-inflammatory agents. Thus, PPAR-gamma can serve as potential therapeutic targets in the treatment of inflammation. The aim of this paper is to present the characteristics of PPAR-gamma regarding their gene and protein structures, ligand selectivity, mechanisms of action, and target genes. The review highlights the roles that PPAR-gamma play in inflammation and immune responses. Particular emphasis is focused on their roles in asthma, atheroclerosis, rheumatoid arthritis and chronic inflammatory bowel diseases.

The effect of rhinovirus on airway epithelium is very well described. However, its influence on the vascular endothelium is unknown. The current study assesses the effect of rhinovirus HRV16 on the antiviral and inflammatory response in the human vascular endothelial cells (ECs). HRV16 increased IFN‐β, RANTES, and IP‐10 mRNA expression and protein release. HRV16 copy number in ECs reached maximal value 10 h after incubation. Increase in virus copies was accompanied by the enhancement of Toll‐ and RIG‐I‐like receptors: TLR3, RIG‐I, and MDA5. Additionally, HRV16 increased OAS‐1 and PKR mRNA expression, enzymes responsible for virus degradation and inhibition of replication. ICAM‐1 blockade decreased HRV16 copy number in ECs and inhibited IFN‐β, RANTES, IP‐10, OAS1, PKR, TLR3, RIG‐I, and MDA5 mRNA expression increase upon subsequent induction with HRV16. The vascular endothelium may be infected by human rhinovirus and generate antiviral and inflammatory innate response. Results of the study indicate the possible involvement of the vascular endothelium in the immunopathology of rhinoviral airway infections. [ABSTRACT FROM AUTHOR]

The outbreak of the SARS‐CoV‐2‐induced coronavirus disease 2019 (COVID‐19) pandemic re‐shaped doctor‐patient interaction and challenged capacities of healthcare systems. It created many issues around the optimal and safest way to treat complex patients with severe allergic disease. A significant number of the patients are on treatment with biologicals, and clinicians face the challenge to provide optimal care during the pandemic. Uncertainty of the potential risks for these patients is related to the fact that the exact sequence of immunological events during SARS‐CoV‐2 is not known. Severe COVID‐19 patients may experience a "cytokine storm" and associated organ damage characterized by an exaggerated release of pro‐inflammatory type 1 and type 3 cytokines. These inflammatory responses are potentially counteracted by anti‐inflammatory cytokines and type 2 responses. This expert‐based EAACI statement aims to provide guidance on the application of biologicals targeting type 2 inflammation in patients with allergic disease. Currently, there is very little evidence for an enhanced risk of patients with allergic diseases to develop severe COVID‐19. Studies focusing on severe allergic phenotypes are lacking. At present, noninfected patients on biologicals for the treatment of asthma, atopic dermatitis, chronic rhinosinusitis with nasal polyps, or chronic spontaneous urticaria should continue their biologicals targeting type 2 inflammation via self‐application. In case of an active SARS‐CoV‐2 infection, biological treatment needs to be stopped until clinical recovery and SARS‐CoV‐2 negativity is established and treatment with biologicals should be re‐initiated. Maintenance of add‐on therapy and a constant assessment of disease control, apart from acute management, are demanded. [ABSTRACT FROM AUTHOR]

Introduction: Periostin is a matricellular protein expressed by many tissues. Its release may be enhanced, among others, through mechanical stimulation of muscles and bones as well as by cytokines of allergic inflammation. Objectives: Our aim was to assess periostin levels in serum and exhaled breath condensate (EBC) of professional athletes, asthmatics and healthy controls. We also sought to determine whether acute treadmill exercise influences serum and EBC periostin. Methods: Study groups included 9 competitive swimmers, 10 mild-to-moderate asthmatics and 7 healthy controls. Athletes were assessed twice (in- and off-training period) while asthmatics and controls in one time-point. Data on demographics, allergy symptoms and exercise load were acquired through Allergy Questionnaire for Athletes (AQUA) and International Physical Activity Questionnaire (IPAQ). Serum and EBC were collected before and after treadmill exercise challenge. Results: Baseline serum periostin in swimmers during training period was significantly higher (5- to 7-fold) than in asthmatics (P = .01) and controls (P < .05). In EBC, lowest periostin levels were seen in athletes in-training as compared with offtraining period (P < .01) and with asthmatics (P < .03). Acute bout of exercise did not induce significant changes neither in serum nor in EBC periostin in any group. Conclusion: Increased serum, but not EBC, periostin levels in competitive athletes are probably because of permanently increased exercise load leading to stimulation, injury and regeneration of musculoskeletal tissues. Periostin may be considered marker of long-term exercise overload after confirmation in larger groups. [ABSTRACT FROM AUTHOR]

Background: Nasal polyposis is a multifactorial disease characterized by a chronic eosinophilic inflammation of the sinus mucosa, often associated with asthma and aspirin sensitivity. We have recently shown that the presence of IgE antibodies to Staphylococcus aureus enterotoxins (SAEs) was related to the severity of eosinophilic inflammation in nasal polyp tissue. In this study, we therefore aimed to determine, whether aspirin sensitivity was related to an immune response to SAEs, and how both criteria would be related to eosinophilic inflammation. Methods: 40 subjects with nasal polyposis (NP) were classified as aspirin-sensitive (n = 13, ASNP) or aspirin-tolerant (n = 27, ATNP) based on a bronchial aspirin challenge test. Homogenates prepared from nasal polyp tissue and inferior nasal turbinates from healthy subjects (n = 12) were analyzed for concentrations of IL-5 by enzyme immunoassay and for ECP, total and IgE to a mix of SAEs (A, C, TSST-1) using the ImmunoCAP system. Results: Concentrations of IL-5, ECP, total IgE, and IgE to an SAE mix were significantly increased in ASNP compared with ATNP patients and controls. In addition, a subgroup analysis showed an increase in eosinophilic markers in ATNP-SAE(+) compared to ATNP-SAE(–). This relationship, however, was not found in ATNP-SAE(+) and ATNP-SAE(–) subjects, indicating that SAE immune response is overlapped or not relevant in this condition. Conclusions: Aspirin sensitivity was associated with increased concentrations of eosinophil-related mediators, as well as IgE antibodies to SAEs in nasal polyp tissue. However, a direct impact of S. aureus could not be established. It seems that aspirin sensitivity and immune reactions to SAEs are independently related to eosinophilic inflammation. Copyright © 2004 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Fractional exhaled nitric oxide (FeNO) is a non-invasive marker for eosinophilic airway inflammation and has been used for monitoring asthma. Here, we assess the characteristics of FeNO from preschool to school age, in parallel with asthma activity. A total of 167 asthmatic children and 66 healthy, age-matched controls were included in the 2-year prospective PreDicta study evaluating wheeze/asthma persistence in preschool-aged children. Information on asthma/rhinitis activity, infections and atopy was recorded at baseline. Follow-up visits were performed at 6-month intervals, as well as upon exacerbation/cold and 4–6 weeks later in the asthmatic group. We obtained 539 FeNO measurements from asthmatics and 42 from controls. At baseline, FeNO values did not differ between the two groups (median: 3.0 ppb vs. 2.0 ppb, respectively). FeNO values at 6, 12, 18 and 24 months (4.0, CI: 0.0–8.6; 6.0, CI: 2.8–12.0; 8.0, CI: 4.0–14.0; 8.5, CI: 4.4–14.5 ppb, respectively) increased with age (correlation p ≤ 0.001) and atopy (p = 0.03). FeNO was non-significantly increased from baseline to the symptomatic visit, while it decreased after convalescence (p = 0.007). Markers of disease activity, such as wheezing episodes and days with asthma were associated with increased FeNO values during the study (p < 0.05 for all). Age, atopy and disease activity were found to be important FeNO determinants in preschool children. Longitudinal and individualized FeNO assessment may be valuable in monitoring asthmatic children with recurrent wheezing or mild asthma. [ABSTRACT FROM AUTHOR]

Background: Impaired regeneration of airway epithelium may lead to persistence of inflammation and remodelling. Regeneration of injured epithelium is a complex phenomenon and the role of toll-like receptors (TLRs) in the stimulation of respiratory virus products in this process has not been established. Objective: This study was undertaken to test the hypothesis that the wound repair process in airway epithelium is modulated by microbial products via toll-like receptors. Methods: Injured and not-injured bronchial epithelial cells (ECs) (BEAS-2B line) were incubated with the TLR agonists poly(I:C), lipopolisacharide (LPS), allergen Der p1, and supernatants from virus-infected epithelial cells, either alone or in combination with TLR inhibitors. Regeneration and immune response in injured and not-injured cells were studied. Results: Addition of either poly(I:C) or LPS to ECs induced a marked inhibition of wound repair. Supernatants from RV1b-infected cells also decreased regeneration. Preincubation of injured and not-injured ECs with TLR inhibitors decreased LPS and poly(I:C)-induced repair inhibition. TGF-β and RANTES mRNA expression was higher in injured ECs and IFN-α, IFN-β, IL-8, and VEGF mRNA expression was lower in damaged epithelium as compared to not-injured. Stimulation with poly(I:C) increased IFN-α and IFN-β mRNA expression in injured cells, and LPS stimulation decreased interferons mRNA expression both in not-injured and injured ECs. Conclusion: Regeneration of the airway epithelium is modulated by microbial products via toll-like receptors. [ABSTRACT FROM AUTHOR]

ILC2s are a very important element of the innate immunity. Physiologically, the take part in the defense of the host against helmint infections. In pathological conditions, they become a link in the series of immune events of allergic inflammatory response. ILC2s activated by tissue-derived alarmins, such as IL-33, IL-25 and TSLP, release IL-4 and IL-5 affecting immune effectory cells, thus enhancing T2-dependent immune responses. [ABSTRACT FROM AUTHOR]

Background Current phenotyping of chronic rhinosinusitis (CRS) into chronic rhinosinusitis with nasal polyps (CRSwNP) and chronic rhinosinusitis without nasal polyps (CRSsNP) might not adequately reflect the pathophysiologic diversity within patients with CRS. Objective We sought to identify inflammatory endotypes of CRS. Therefore we aimed to cluster patients with CRS based solely on immune markers in a phenotype-free approach. Secondarily, we aimed to match clusters to phenotypes. Methods In this multicenter case-control study patients with CRS and control subjects underwent surgery, and tissue was analyzed for IL-5, IFN-γ, IL-17A, TNF-α, IL-22, IL-1β, IL-6, IL-8, eosinophilic cationic protein, myeloperoxidase, TGF-β1, IgE, Staphylococcus aureus enterotoxin–specific IgE, and albumin. We used partition-based clustering. Results Clustering of 173 cases resulted in 10 clusters, of which 4 clusters with low or undetectable IL-5, eosinophilic cationic protein, IgE, and albumin concentrations, and 6 clusters with high concentrations of those markers. The group of IL-5–negative clusters, 3 clusters clinically resembled a predominant chronic rhinosinusitis without nasal polyps (CRSsNP) phenotype without increased asthma prevalence, and 1 cluster had a T H 17 profile and had mixed CRSsNP/CRSwNP. The IL-5–positive clusters were divided into a group with moderate IL-5 concentrations, a mixed CRSsNP/CRSwNP and increased asthma phenotype, and a group with high IL-5 levels, an almost exclusive nasal polyp phenotype with strongly increased asthma prevalence. In the latter group, 2 clusters demonstrated the highest concentrations of IgE and asthma prevalence, with all samples expressing Staphylococcus aureus enterotoxin–specific IgE. Conclusion Distinct CRS clusters with diverse inflammatory mechanisms largely correlated with phenotypes and further differentiated them and provided a more accurate description of the inflammatory mechanisms involved than phenotype information only. [ABSTRACT FROM AUTHOR]

Bacteriophages show anti-inflammatory properties by affecting the immune system by lowering the level of cytokines and other pro-inflammatory mediators. The epithelium of the respiratory tract is an important mechanical defensive barrier of immunity. It also plays a key role in controlling many of the functions of the airways. It is a source of cytokines and mediators involved in the inflammatory process. In this study, a divergent, time- and concentration-dependent effect on the synthesis of 15-HETE as well as the regenerative properties of the respiratory epithelium was demonstrated. The results obtained in the study may allow for a better understanding of the influence of bacteriophages present in the human body on immunological processes. [ABSTRACT FROM AUTHOR]

Introduction. High mobility group box-1 (HMGB-1) was originally described as a DNA binding protein involved in maintenance of proper nucleosome structure and regulation of gene transcription. Aim of the study. Recent studies have demonstrated also cytokine-like role for extracellular HMGB-1, further considered as a late mediator of systemic blood inflammation. We aimed to compare HMGB-1 release by peripheral blood mononuclear cells (PBMCs) from both atopic and non-atopic patients, followed by stimulation with phytohemagglutin in (PHA). Material and methods. PBMCs isolated from the 12 allergic patients (30±10 yrs; 5 men and 7 women) and 11 healthy donors (31±10 yrs, 2 men and 9 women) were cultured for 48 hours in complete medium (IMDM) with or without PHA (25μg/mL.). Cell apoptosis and necrosis were determined by flow cytometry with the use of anti-Annexin V-FITC monoclonal antibodies and propidium iodine. HMGB-1 concentrations in supernatants were assessed by ELISA method. Results. In both groups, there was a significant increase of PHA-induced HMGB-1 release, compared to spontaneous release (mean±SD (min-max): 19.7±5.7 (13.6-32.1) ng/mL vs. 12.6±2.8 (8.3-18.1) ng/mL, p=0.0013 and 33.2±16.6 (11.5-68.7) ng/mL vs. 15.2±6.0 (9.2-30.5) ng/mL, p=0.0051) for atopic and healthy respectively. The increase was smaller in atopic patients (by 62±50 (0-120) % vs. 111±45 (25-164) % in healthy individuals, p=0.012). PHA induced on necrosis. There were no marked correlations between HMGB-1 levels and apoptosis or necrosis. Conclusion. These data show that HMGB-1 may be released extracellular by PHA and suggest the difference in HMGB-1 release by PBMCs between atopic and non-atopic patients. [ABSTRACT FROM AUTHOR]