Sanna Toppila-Salmi

Caveolar transport through nasal epithelium of birch pollen allergen Bet v 1 in allergic patients.

BACKGROUND Previous work in type I pollen allergies has focused on aberrant immunoresponses. OBJECTIVE Our systems-level analyses explore the role of epithelium in early pathogenesis of type I allergic reactions. METHODS We began top-down analyses of differences in human nasal epithelial cells and biopsy specimens obtained from patients with birch allergy and healthy control subjects in the resting state and after intranasal in vivo birch pollen challenges. Immunohistochemistry, immunotransmission electron microscopy, mass spectrometry, transcriptomics, and integration of data to a pathway were conducted. RESULTS Bet v 1 allergen bound to epithelium immediately after in vivo birch pollen challenge during winter only in allergic individuals. It also travelled through epithelium with caveolae to mast cells. Sixteen unique proteins were found to bind to the Bet v 1 column only in lysates from allergic epithelial cells; 6 of these were caveolar and 6 were cytoskeletal proteins. The nasal epithelial transcriptome analysis from allergic and healthy subjects differed during the winter season, and these subjects also responded differentially to birch pollen challenge. Within this pollen-induced response, the gene ontology categories of cytoskeleton and actin cytoskeleton were decreased in allergic patients, whereas the actin-binding category was enriched in healthy subjects. Integration of microscopic, mass spectrometric, and transcriptomic data to a common protein-protein binding network showed how these were connected to each other. CONCLUSION We propose a hypothesis of caveolae-dependent uptake and transport of birch pollen allergen in the epithelium of allergic patients only. Application of discovery-driven methodologies can provide new hypotheses worth further analysis of complex multifactorial diseases, such as type I allergy.

The multi-faceted role of allergen exposure to the local airway mucosa.

Airway epithelial cells are the first to encounter aeroallergens and therefore have recently become an interesting target of many studies investigating their involvement in the modulation of allergic inflammatory responses. Disruption of a passive structural barrier composed of epithelial cells by intrinsic proteolytic activity of allergens may facilitate allergen penetration into local tissues and additionally affect chronic and ongoing inflammatory processes in respiratory tissues. Furthermore, the ability of rhinoviruses to disrupt and interfere with epithelial tight junctions may alter the barrier integrity and enable a passive passage of inhaled allergens through the airway epithelium. On the other hand, epithelial cells are no longer considered to act only as a physical barrier toward inhaled allergens, but also to actively contribute to airway inflammation by detecting and responding to environmental factors. Epithelial cells can produce mediators, which may affect the recruitment and activation of more specialized immune cells to the local tissue and also create a microenvironment in which these activated immune cells may function and propagate the inflammatory processes. This review presents the dual role of epithelium acting as a passive and active barrier when encountering an inhaled allergen and how this double role contributes to the start of local immune responses.

Allergy as an epithelial barrier disease.

The objective of this review is to focus on putative modified epithelial functions related to allergy. The dysregulation of the epithelial barrier might result in the allergen uptake, which could be the primary defect in the pathogenesis of allergic reaction. We review the literature of the role of respiratory epithelium as an active barrier, how allergens are transported through it and how it senses the hostile environmental allergens and other dangerous stimuli.

Time-series nasal epithelial transcriptomics during natural pollen exposure in healthy subjects and allergic patients.

To cite this article: Mattila P, Renkonen J, Toppila‐Salmi S, Parviainen V, Joenväärä S, Alff‐Tuomala S, Nicorici D, Renkonen R. Time‐series nasal epithelial transcriptomics during natural pollen exposure in healthy subjects and allergic patients. Allergy 2010; 65: 175–183.

Endothelial L-selectin ligand expression in nasal polyps

Background:  L‐selectins on leukocytes and their counter‐receptors on endothelial cells have been shown to be involved in leukocyte recruitment in chronic rhinosinusitis without nasal polyps (NP).

Molecular Mechanisms of Nasal Epithelium in Rhinitis and Rhinosinusitis

Allergic rhinitis, nonallergic rhinitis, and chronic rhinosinusitis are multifactorial upper airway diseases with high prevalence. Several genetic and environmental factors are proposed to predispose to the pathogenesis of the inflammatory upper airway diseases. Still, the molecular mechanisms leading toward the onset and progression of upper airway diseases are largely unknown. The upper airway epithelium has an important role in sensing the environment and regulating the inhaled air. As such, it links environmental insults to the host immunity. Human sinonasal epithelium serves as an excellent target for observing induced early-phase events, in vivo, and with a systems biological perspective. Actually, increasing number of investigations have provided evidence that altered homeostasis in the sinonasal epithelium might be important in the chronic upper airway inflammation.

Sensitization pattern affects the asthma risk in Finnish adult population

There is a large global variation in the sensitization pattern and its association with allergic diseases. In temperate and tropical urban environments, mite monosensitization can be the predominant cause of allergic airway diseases, whereas in other environments, polysensitization is more typical. Sensitization to mite allergens associates with asthma. However, it is suggested that mite sensitization might play a minor role in Northern Europe. The aim of the study was to analyze how sensitization pattern affects the asthma risk in Finnish adults, with a special focus on mites.

Endoscopic sinus surgery might reduce exacerbations and symptoms more than balloon sinuplasty.

Background Endoscopic sinus surgery (ESS) is considered after medical therapy failure of chronic rhinosinusitis (CRS). The balloon sinuplasty dilates the natural ostium without moving mucosa or bone. It still lacks evidence from randomized controlled trials. The aim of this retrospective controlled study was to compare the symptom outcomes after maxillary sinus surgery with either the ESS or the balloon sinuplasty technique. No previous or additional sinonasal operations were accepted. Methods Two hundred eight patients with CRS without nasal polyps underwent either balloon sinuplasty or ESS. The patients who met with the inclusion criteria (n = 45 in ESS group and n = 40 in balloon group) replied to a questionnaire of history factors, exacerbations, and a visual analog scale (VAS) scoring of the change in symptoms, on average 28 ± 6 (mean ± SD) months postoperatively. Results The groups were identical in the response rate (64%), patient characteristics, and the improvement in all of the asked symptoms. Patients with CRS-related comorbidity and/or present occupational exposure had a statistically significantly better symptom reduction after ESS than after balloon sinusotomy. Moreover, the balloon sinusotomy group reported a statistically significant higher number of maxillary sinus punctures and antibiotic courses during the last 12 months. Conclusion ESS might be superior to balloon sinuplasty, especially in patients with risk factors. There is a need to perform more controlled studies on the treatment choices of CRS.

Predictors of post-operative response to treatment: a double blind placebo controlled study in chronic rhinosinusitis patients

BACKGROUND In the majority of CRS patients suffering from primary or recurrent CRS, topical glucocorticoids are highly effective. A subset of CRS patients, however, does not respond to (topical) glucocorticoids and requires surgical intervention. Although surgery is highly effective in those individuals, recurrence of disease is observed in some. In this study we describe our search for one or more predictors predicting the response to surgery in combination with peri-operative oral glucocorticoids in CRS patients. METHODS Thirty-five inferior turbinate specimens were randomly selected from a larger group of CRS patients requiring FESS for persistent disease that either responded favorably or demonstrated recurrent disease. Tissue biopsies were taken at the time of surgery and compared for inflammatory markers, endothelial cell markers, and various leukocyte subsets using immunohistochemistry. RESULTS Compared to non-responders, the baseline level of lamina propria activated eosinophils is significantly increased in CRS patients responding to surgery in combination with peri-operative oral glucocorticoids treated or not treated post-operatively with topical glucocorticoids. No significant differences were observed for all other studied parameters. Post-operative treatment with FPANS 100 μg q.i.d. was significantly associated with response to treatment. A trend towards association was observed for increased numbers of eosinophils at baseline. CONCLUSION Our data suggest that CRS patients with higher levels of eosinophils are less likely to suffer from post-operative recurrent sinonasal disease when treated post-operatively with FPANS 100 μg q.i.d.

Computed tomography findings after endoscopic sinus surgery with preserving or enlarging maxillary sinus ostium surgery

Endoscopic sinus surgery (ESS) is the main surgical approach in the treatment of chronic rhinosinusitis (CRS) after failure of medical treatment. ESS is based on the theory that obstruction of the maxillary sinus ostium is mainly behind the pathogenesis of CRS. Controversy remains concerning the enlargement of the natural maxillary sinus ostium. The aim of this study was to compare computed tomography (CT) findings after preservation or enlargement of the maxillary sinus ostium. Thirty patients with non-polypous CRS underwent randomized endoscopic sinus surgery with uncinectomy on one side and additional middle meatal antrostomy on the other side. Lund-Mackay (LM) scores and the ostium diameters were analysed from CT scans taken preoperatively and nine months postoperatively, and were used for comparison of the two operative techniques. In addition, the correlation between CT findings and subjective outcomes was studied. Comparison of the preoperative and postoperative CT scans revealed that significant reduction of LM score was achieved on both sides, regardless of the type of procedure performed. The postoperative area of the ostium remained significantly larger on the antrostomy side compared to the uncinectomy side. A large maxillary sinus ostium size seems to associate with lower postoperative LM score, but does not seem to provide superior symptom relief.