Wouter Huvenne

Prevalence of allergic sensitization versus allergic rhinitis symptoms in an unselected population

Background: Allergic rhinitis (AR) is the most common allergic disorder and its prevalence has significantly increased worldwide, nowadays affecting up to 40% of the population in young adults. The objective of the present survey was to evaluate the prevalence of allergic sensitization and the prevalence of clinically diagnosed AR in a sample of the Belgian population, and to estimate the effect of age and gender. Methods: We performed a cross-sectional population-based study at an annual public fair in Ghent. Participants underwent a skin prick test (SPT) to 3 aeroallergens: a mix of trees (hazel, alder, and birch), grass pollen, and house dust mite (HDM). The clinical relevance of sensitization was assessed by relating relevant symptoms of AR to the corresponding SPT. Results: A total of 2,320 participants (1,475 females, median age 44.7 years, range 3–86) were included in this study. The standardized prevalence rates of sensitization were 13.2% for tree mix, 25.9% for grass pollen, and 25.9% for HDM. Sensitization to at least one of the allergens was present in 40.3% of the subjects. Symptomatic sensitization related to trees was reported in 9.7% of cases, grass-related AR was 17.6%, and HDM-related AR was 17.1%. The overall prevalence of AR was 30.9%. Conclusion: In this study we demonstrated a 40.3% prevalence of a positive SPT to one or more common aeroallergens. A clinical diagnosis of AR was present in 30.9% of cases, peaking in the third and fourth decades of life. It is to be expected that in the next decades, when this generation grows older, the general AR prevalence will further increase.

Th2-associated immunity to bacteria in teenagers and susceptibility to asthma

Bacterial colonisation of the airways is associated with increased risk of childhood asthma. Immunoglobulin (Ig)E against bacterial antigens has been reported in some asthmatics, suggesting a role for bacterial-specific type-2 immunity in disease pathogenesis. We aimed to investigate relationships between bacterial-specific IgE amongst teenagers and asthma susceptibility. We measured titres of IgE against Haemophilus influenzae, Streptococcus pneumoniae and Staphylococcus aureus in 1,380 teenagers, and related these to asthma symptomatology and immunophenotypes. IgE titres against S. aureus-derived enterotoxins were highest amongst atopics and were associated with asthma risk. Surprisingly, IgE titres against H. influenzae and S. pneumoniae surface antigens were higher, not stratified by atopy and independently associated with decreased asthma risk. The positive association between type-2 immunity to S. aureus and asthma phenotypes probably reflects IgE-mediated effector cell activation via enterotoxin super antigens which are secreted in soluble form. The contrasting benign nature of type-2 immunity to H. influenzae and S. pneumoniae antigens may reflect their lower availability in soluble forms that can crosslink IgE receptors. We theorise that instead they may be processed by antigen presenting cells and presented to type-2 memory cells leading to mucosal secretion of interleukin (IL)-4/IL-13, a mechanism widely recognised in other tissues to attenuate T-helper-1 associated bacterial-induced inflammation.

Staphylococcus aureus enterotoxin B facilitates allergic sensitization in experimental asthma

Background Staphylococcus aureus Enterotoxin B (SEB) has immunomodulatory effects in allergic airway disease. The potential contribution of SEB to the sensitization process to allergens remains obscure.

Role of staphylococcal superantigens in airway disease

Staphylococcus aureus is a common human pathogen, which is regularly part of the normal microflora found in the nose and skin. It represents a significant threat to human health, not in the least because of its capability to produce exotoxins, which have superantigenic properties. These exotoxins, in particular the staphylococcal enterotoxins (SEs), are known to be involved in the modulation and aggravation of airway inflammation. Indeed, recent studies show an important impact of SEs on the natural course of allergic rhinitis, nasal polyposis, asthma and COPD. This review outlines the current knowledge on the influence of SEs on airway inflammation. We highlight, in particular, the recent evidence on their role in asthma.

Staphylococcus aureus enterotoxin B augments granulocyte migration and survival via airway epithelial cell activation

To cite this article: Huvenne W, Callebaut I, Reekmans K, Hens G, Bobic S, Jorissen M, Bullens DMA, Ceuppens JL, Bachert C, Hellings PW. Staphylococcus aureus enterotoxin B augments granulocyte migration and survival via airway epithelial cell activation. Allergy 2010; 65: 1013–1020.

Different regulation of cigarette smoke induced inflammation in upper versus lower airways

BackgroundCigarette smoke (CS) is known to initiate a cascade of mediator release and accumulation of immune and inflammatory cells in the lower airways. We investigated and compared the effects of CS on upper and lower airways, in a mouse model of subacute and chronic CS exposure.MethodsC57BL/6 mice were whole-body exposed to mainstream CS or air, for 2, 4 and 24 weeks. Bronchoalveolar lavage fluid (BAL) was obtained and tissue cryosections from nasal turbinates were stained for neutrophils and T cells. Furthermore, we evaluated GCP-2, KC, MCP-1, MIP-3α, RORc, IL-17, FoxP3, and TGF-β1 in nasal turbinates and lungs by RT-PCR.ResultsIn both upper and lower airways, subacute CS-exposure induced the expression of GCP-2, MCP-1, MIP-3α and resulted in a neutrophilic influx. However, after chronic CS-exposure, there was a significant downregulation of inflammation in the upper airways, while on the contrary, lower airway inflammation remained present. Whereas nasal FoxP3 mRNA levels already increased after 2 weeks, lung FoxP3 mRNA increased only after 4 weeks, suggesting that mechanisms to suppress inflammation occur earlier and are more efficient in nose than in lungs.ConclusionsAltogether, these data demonstrate that CS induced inflammation may be differently regulated in the upper versus lower airways in mice. Furthermore, these data may help to identify new therapeutic targets in this disease model.

Exacerbation of cigarette smoke-induced pulmonary inflammation by Staphylococcus aureus enterotoxin B in mice

BackgroundCigarette smoke (CS) is a major risk factor for the development of COPD. CS exposure is associated with an increased risk of bacterial colonization and respiratory tract infection, because of suppressed antibacterial activities of the immune system and delayed clearance of microbial agents from the lungs. Colonization with Staphylococcus aureus results in release of virulent enterotoxins, with superantigen activity which causes T cell activation.ObjectiveTo study the effect of Staphylococcus aureus enterotoxin B (SEB) on CS-induced inflammation, in a mouse model of COPD.MethodsC57/Bl6 mice were exposed to CS or air for 4 weeks (5 cigarettes/exposure, 4x/day, 5 days/week). Endonasal SEB (10 μg/ml) or saline was concomitantly applied starting from week 3, on alternate days. 24 h after the last CS and SEB exposure, mice were sacrificed and bronchoalveolar lavage (BAL) fluid and lung tissue were collected.ResultsCombined exposure to CS and SEB resulted in a raised number of lymphocytes and neutrophils in BAL, as well as increased numbers of CD8+ T lymphocytes and granulocytes in lung tissue, compared to sole CS or SEB exposure. Moreover, concomitant CS/SEB exposure induced both IL-13 mRNA expression in lungs and goblet cell hyperplasia in the airway wall. In addition, combined CS/SEB exposure stimulated the formation of dense, organized aggregates of B- and T- lymphocytes in lungs, as well as significant higher CXCL-13 (protein, mRNA) and CCL19 (mRNA) levels in lungs.ConclusionsCombined CS and SEB exposure aggravates CS-induced inflammation in mice, suggesting that Staphylococcus aureus could influence the pathogenesis of COPD.

Pilot study using doxycycline-releasing stents to ameliorate postoperative healing quality after sinus surgery

Poor postoperative healing after sinus surgery is associated with high concentrations of matrix metalloproteinase‐9 (MMP‐9). The frontal recess is especially vulnerable to restenosis, and frontal sinus stents have been used to overcome this problem. However, the long‐term success rate is still controversial and may be poor. In this perspective, we developed doxycycline (DC)‐releasing stents, delivering the MMP‐9 synthesis‐suppressing agent locally to the frontal recess area. We evaluated postoperative MMP‐9 levels, bacterial colonization, healing quality, and symptom scores in patients suffering from chronic rhinosinusitis with (CRSwNP) and without nasal polyposis (CRSsNP) (n=10) who underwent functional endoscopic sinus surgery during which the DC‐releasing and placebo stents were placed. We found that MMP‐9 concentrations were significantly lower at the side of the DC‐releasing stent (3,414±582 ng/mL) compared with the contralateral placebo stent (9,172±2,564 ng/mL) (p<0.05) at month 3 postsurgery. DC stents adequately suppressed bacterial growth compared with placebo stents. Furthermore, the visual analog scale (VAS) for the frontal region was significantly better (mean value 75.1 vs. 52.8, p<0.001) compared with its placebo counterpart. We conclude that compared with placebo stents, DC‐releasing stents significantly lowered MMP‐9 concentrations and bacterial colonization locally, and improved postoperative healing quality after functional endoscopic sinus surgery, as demonstrated by visual analog scale and ostial closure.

High-dose reirradiation with intensity-modulated radiotherapy for recurrent head-and-neck cancer: Disease control, survival and toxicity

PURPOSE To evaluate disease control, survival and severe late toxicity after high-dose fractionated reirradiation using intensity-modulated radiotherapy (IMRT) for recurrent head-and-neck cancer. MATERIALS AND METHODS Sixty consecutive patients were reirradiated with IMRT between 1997 and 2011. The median prescribed dose was 70 Gy in 35 daily fractions until 2004 and 69.12 Gy in 32 daily fractions thereafter. The median cumulative dose was 132 Gy. Sixty-seven percent of patients had non-metastatic stage IV disease. Surgery prior to reirradiation and concomitant systemic therapy was performed in 13 (22%) and 20 (33%) patients, respectively. RESULTS Median follow-up in living patients was 18.5 months. Actuarial 1-, 2- and 5-year locoregional control was 64%, 48% and 32%, respectively. Median overall (OS) and disease-free survival was 9.6 and 6.7 months, respectively. Actuarial 1-, 2- and 5-year OS was 44%, 32% and 22%, respectively. Seventeen (27%) and 2 (3%) patients had grade 3 and 4 acute toxicity, respectively. Cumulative incidence of late grade≥3 toxicity was 23%, 27% and 66% at 1, 2 and 5 years, respectively. In 4 patients, death was attributed to toxicity: fatal bleeding (n=2), aspiration pneumonia (n=1) and skin necrosis (n=1). CONCLUSIONS High-dose fractionated reirradiation with IMRT offers 5-year disease control and OS in recurrent head-and-neck cancer for 1/3 and 1/4 patients, respectively. Severe late toxicity after 1-2 and 5 years occurs in 1/4 and 2/3 patients, respectively.

A chest physician's guide to mechanisms of sinonasal disease

The upper and lower airways are closely linked from an anatomical, histological and immunological point of view, with inflammation in one part of the airways influencing the other part. Despite the concept of global airway disease, the upper airways tend to be overlooked by respiratory physicians. We provide a clinical overview of the most important and recent insights in rhinitis and rhinosinusitis in relation to lower airway disease. We focus on the various exogenous and endogenous factors that play a role in the development and aggravation of chronic upper airway inflammation. In addition to the classical inhaled allergens or microorganisms with well-defined pathophysiological mechanisms in upper airway disease, environmental substances such as cigarette smoke, diesel exhaust particles and occupational agents affecting lower airway homeostasis have recently gained attention in upper airway research. We are only at the beginning of understanding the complex interplay between exogenous and endogenous factors like genetic, immunological and hormonal influences on chronic upper airway inflammation. From a clinical perspective, the involvement of upper and lower airway disease in one patient can only be fully appreciated by doctors capable of understanding the interplay between upper and lower airway inflammation.