Sofie Claeys

Differentiation of chronic sinus diseases by measurement of inflammatory mediators

Background:  Chronic rhinosinusitis (CRS) clinically is a heterogeneous group of sinus diseases, which may cover different disease entities, or may represent a disease continuum. Studying inflammatory cells and mediators in clearly defined disease subgroups may lead to a better differentiation of chronic sinus diseases.

Comment on “Potent Phagocytic Activity with Impaired Antigen Presentation Identifying Lipopolysaccharide-Tolerant Human Monocytes: Demonstration in Isolated Monocytes from Cystic Fibrosis Patients”

Monocyte exposure to LPS induces a transient state in which these cells are refractory to further endotoxin stimulation. This phenomenon, termed endotoxin tolerance (ET), is characterized by a decreased production of cytokines in response to the proinflammatory stimulus. We have established a robust model of ET and have determined the time frame and features of LPS unresponsiveness in cultured human monocytes. A large number of genes transcribed in tolerant monocytes were classified as either “tolerizable” or “nontolerizable” depending on their expression levels during the ET phase. Tolerant monocytes exhibit rapid IL-1R-associated kinase-M (IRAK-M) overexpression, high levels of triggering receptor expressed on myeloid cells-1 (TREM-1) and CD64, and a marked down-regulation of MHC molecules and NF-κB2. These cells combine potent phagocytic activity with impaired capability for Ag presentation. We also show that circulating monocytes isolated from cystic fibrosis patients share all the determinants that characterize cells locked in an ET state. These findings identify a new mechanism that contributes to impaired inflammation in cystic fibrosis patients despite a high frequency of infections. Our results indicate that a tolerant phenotype interferes with timing, efficiency, and outcome of the innate immune responses against bacterial infections.

Human beta-defensins and toll-like receptors in the upper airway.

Background:  Measurement of innate markers in nasal mucosa, tonsils and adenoids might lead to new views about the role of innate immunity in the upper airway. In this study, the expression of human β‐defensins (HBD) 2 and 3 and toll‐like receptors (TLR) 2 and 4 in various upper airway diseases was investigated.

Alternatively activated macrophages and impaired phagocytosis of S-aureus in chronic rhinosinusitis

To cite this article: Krysko O, Holtappels G, Zhang N, Kubica M, Deswarte K, Derycke L, Claeys S, Hammad H, Brusselle GG, Vandenabeele P, Krysko DV, Bachert C. Alternatively activated macrophages and impaired phagocytosis of S. aureus in chronic rhinosinusitis. Allergy 2011; 66: 396–403.

Important research questions in allergy and related diseases: 3-chronic rhinosinusitis and nasal polyposis - a GALEN study.

Chronic rhinosinusitis is one of the most common health care challenges, with significant direct medical costs and severe impact on lower airway disease and general health outcomes. The diagnosis of chronic rhinosinusitis (CRS) currently is based on clinical signs, nasal endoscopy and CT scanning, and therapeutic recommendations are focussing on 2 classes of drugs, corticosteroids and antibiotics. A better understanding of the pathogenesis and the factors amplifying mucosal inflammation therefore seems to be crucial for the development of new diagnostic and therapeutic tools. In an effort to extend knowledge in this area, the WP 2.7.2 of the GA2LEN network of excellence currently collects data and samples of 1000 CRS patients and 250 control subjects. The main objective of this project is to characterize patients with upper airway disease on the basis of clinical parameters, infectious agents, inflammatory mechanisms and remodeling processes. This collaborative research will result in better knowledge on patient phenotypes, pathomechanisms, and subtypes in chronic rhinosinusitis. This review summarizes the state of the art on chronic rhinosinusitis and nasal polyposis in different aspects of the disease. It defines potential gaps in the current research, and points to future research perspectives and targets.

Nasal polyps in patients with and without cystic fibrosis: a differentiation by innate markers and inflammatory mediators

Background The dysfunction of the mucosal interface of the upper respiratory tract in cystic fibrosis (CF) patients is clinically visible by the development of nasal polyps (NP) at a young age. Innate defence markers and inflammatory mediators in NP from patients with CF were compared with non‐cystic fibrosis nasal polyps (non‐CF‐NP) to determine a possible different immunological background in macroscopically similar tissue.

Rhinosinusitis and Asthma: A Link for Asthma Severity

The term rhinosinusitis describes an inflammation of the mucosal lining of the nose and sinuses; however, recent evidence points to the need to differentiate patients with chronic rhinosinusitis without nasal polyps from those with nasal polyps. Asthma comorbidity is especially common in nasal polyp disease and may be associated with aspirin-exacerbated respiratory disease. Of interest, asthma comorbidity is uncommon in some parts of the world but common in others. A further analysis of the inflammatory patterns also revealed that nasal polyps do not represent one single entity; interleukin (IL)-5–positive nasal polyps can be differentiated from IL-5–negative forms by different inflammatory patterns (predominance of eosinophils vs neutrophils). Staphylococcus aureus superantigens frequently colonize IL-5–positive nasal polyps and may amplify the eosinophilic inflammation, induce a polyclonal local IgE formation, and increase the risk of asthma comorbidity. Recent findings in severe asthma patients confirm the role of superantigens in lower airway disease.

The Innate Immune System and Its Role in Allergic Disorders

Background: There has been an increasing prevalence of allergic diseases in the Western world over the last decades. The hygiene hypothesis has been proposed as a possible explanation for this epidemical trend in allergy. A key role in this theory is assigned to the reduced microbial stimulation of the Toll-like receptors (TLRs) in early life, which could lead to a weaker Th1 response and a stronger Th2 response to allergens. The individual immunological response is determined by the interplay between the dose and timing of exposure to endotoxins, other environmental factors and genetic predisposition. In the development and progression of allergic disorders, the innate immune system plays an important role. Objective: In this review, we discuss the paradoxical effects that may appear when the innate immune components are triggered. We review the influence of changes in the gene sequence and TLR expression in relation to the overall pattern of commensals and pathogens. We explored the possibility of alternative stimulations of the immune system by CpG oligodeoxynucleotides and probiotics as therapeutic devices against this endemic disease in Western society. Methods: Selection of papers was based on the importance of their contribution to the understanding of innate immunity and its implications. Results and Conclusion: The innate immune system plays an important role in both the protection against and the enhancement of allergic disorders, but the mechanisms are still unclear. Nevertheless, gene polymorphisms and triggers of the innate immune system provide therapeutic targets for protection against and treatment of allergic disorders.

The Treatment of Muscle Tension Dysphonia: A Comparison of Two Treatment Techniques by Means of an Objective Multiparameter Approach

The purpose of the present study is to measure the effectiveness of two treatment techniques--vocalization with abdominal breath support and manual circumlaryngeal therapy (MCT)--in patients with muscle tension dysphonia (MTD). The vocal quality before and after the two treatment techniques was measured by means of the dysphonia severity index (DSI), which is designed to establish an objective and quantitative correlate of the perceived vocal quality. The DSI is based on the weighted combination of the following set of voice measurements: maximum phonation time (MPT), highest frequency, lowest intensity, and jitter. The repeated-measures analysis of variance (ANOVA) revealed a significant difference between the objective overall vocal quality before and after MCT. No significant differences were measured between the objective overall vocal quality before and after vocalization with abdominal breath support. This study showed evidence that MCT is an effective treatment technique for patients with elevated laryngeal position, increased laryngeal muscle tension, and MTD. The precise way in which MCT has an effect on vocal quality has not been addressed in this experiment, but merits study. Further research into this topic could focus on electromyography (EMG) recordings in relation to vocal improvements with larger sample of subjects.

Macrophage mannose receptor in chronic sinus disease

Background:  The role of infectious agents in the onset and maintenance of chronic sinus disease is still not fully understood. Macrophage mannose receptor (MMR), an innate pattern recognizing receptor, capable of phagocytosis of invaders and signal transduction for proinflammatory mechanisms, might be of importance in immune interactions in chronic sinus disease.