K. Verbruggen

Occupational Noise, Smoking, and a High Body Mass Index are Risk Factors for Age-related Hearing Impairment and Moderate Alcohol Consumption is Protective: A European Population-based Multicenter Study

A multicenter study was set up to elucidate the environmental and medical risk factors contributing to age-related hearing impairment (ARHI). Nine subsamples, collected by nine audiological centers across Europe, added up to a total of 4,083 subjects between 53 and 67 years. Audiometric data (pure-tone average [PTA]) were collected and the participants filled out a questionnaire on environmental risk factors and medical history. People with a history of disease that could affect hearing were excluded. PTAs were adjusted for age and sex and tested for association with exposure to risk factors. Noise exposure was associated with a significant loss of hearing at high sound frequencies (>1 kHz). Smoking significantly increased high-frequency hearing loss, and the effect was dose-dependent. The effect of smoking remained significant when accounting for cardiovascular disease events. Taller people had better hearing on average with a more pronounced effect at low sound frequencies (<2 kHz). A high body mass index (BMI) correlated with hearing loss across the frequency range tested. Moderate alcohol consumption was inversely correlated with hearing loss. Significant associations were found in the high as well as in the low frequencies. The results suggest that a healthy lifestyle can protect against age-related hearing impairment.

Contribution of the N-acetyltransferase 2 polymorphism NAT2*6A to age-related hearing impairment

Background: Age-related hearing impairment (ARHI) is the most common sensory impairment in older people, affecting 50% of those aged 80 years. The proportion of older people is increasing in the general population, and as a consequence, the number of people affected with ARHI is growing. ARHI is a complex disorder, with both environmental and genetic factors contributing to the disease. The first studies to elucidate these genetic factors were recently performed, resulting in the identification of the first two susceptibility genes for ARHI, NAT2 and KCNQ4. Methods: In the present study, the association between ARHI and polymorphisms in genes that contribute to the defence against reactive oxygen species, including GSTT1, GSTM1 and NAT2, was tested. Samples originated from seven different countries and were combined into two test population samples, the general European population and the Finnish population. Two distinct phenotypes for ARHI were studied, Zlow and Zhigh, representing hearing in the low and high frequencies, respectively. Statistical analysis was performed for single polymorphisms (GSTM1, GSTT1, NAT2*5A, NAT2*6A, and NAT2*7A), haplotypes, and gene–environment and gene–gene interactions. Results: We found an association between ARHI and GSTT1 and GSTM1 in the Finnish population sample, and with NAT2*6A in the general European population sample. The latter finding replicates previously published data. Conclusion: As replication is considered the ultimate proof of true associations in the study of complex disorders, this study provides further support for the involvement of NAT2*6A in ARHI.

A case-control study of the relation between plasma selenium and asthma in European populations : a GAL2EN project

Background:  There is evidence that selenium levels are relatively low in Europe and may be falling. Low levels of selenium or low activity of some of the enzymes dependent on selenium have been associated with asthma.

Anti-IgE for the Treatment of Allergic Rhinitis - and Eventually Nasal Polyps?

In allergic rhinitis, cross-linking of IgE molecules upon allergen contact induces degranulation of mast cells and basophils within the mucosal tissue and results in the release of typical mediators, which consecutively induce the well-known symptoms. Omalizumab counteracts these interactions by reducing serum levels of free IgE. Therapy targeted at IgE also interferes with its binding to the low-affinity receptors inhibiting the amplification of the Th2-type response. Treatment of allergic rhinitis with anti-IgE has been shown to be safe and to reduce specific symptoms. Furthermore, the combination of omalizumab with specific immunotherapy may not only increase efficacy but also safety in selected patients. Therefore, we reviewed previously published studies on omalizumab therapy in allergic rhinitis, either as monotherapy or in combination with immunotherapy. In patients with nasal polyps, a local multiclonal IgE response has recently been described, initiated by Staphylococcus aureus-derived enterotoxins, which at least modifies the inflammatory reaction within the tissue. Evidence accumulates that these enterotoxins act as superantigens resulting in a multiclonal T- and B-cell activation with massive IgE formation within the airways. Because of the multiclonality, a range of allergens could possibly maintain a constant degranulation of mast cells present in the polyp tissue, which may contribute to disease severity. We here discuss a proof-of-concept treatment trial with omalizumab in nasal polyposis, which – in case of a positive therapeutic response – would also pave the way for anti-IgE treatment approaches for severe non-atopic lower airway disease.

Familial aggregation of pure tone hearing thresholds in an aging European population.

Objective To investigate the familial correlations and intraclass correlation of age-related hearing impairment (ARHI) in specific frequencies. In addition, heritability estimates were calculated. Study Design Multicenter survey in 8 European centers. Subjects One hundred ninety-eight families consisting of 952 family members, screened by otologic examination and structured interviews. Subjects with general conditions, known to affect hearing thresholds or known otologic cause were excluded from the study. Results We detected familial correlation coefficients of 0.36, 0.37, 0.36, and 0.30 for 0.25, 0.5, 1, and 2 kHz, respectively, and correlation coefficients of 0.20 and 0.18 for 4 and 8 kHz, respectively. Variance components analyses showed that the proportion of the total variance attributable to family differences was between 0.32 and 0.40 for 0.25, 0.5, 1, and 2 kHz and below 0.20 for 4 and 8 kHz. When testing for homogeneity between sib pair types, we observed a larger familial correlation between female than male subjects. Heritability estimates ranged between 0.79 and 0.36 across the frequencies. Discussion Our results indicate that there is a substantial shared familial effect in ARHI. We found that familial aggregation of ARHI is markedly higher in the low frequencies and that there is a trend toward higher familial aggregation in female compared with male subjects.

Anti-IgE zur Behandlung der Rhinitis allergica -und der Polyposis nasi?

In allergic rhinitis, cross linking of IgE molecules upon allergen contact induces degranulation of mast cells and basophils within the mucosal tissue, and results in the release of typical mediators, which consecutively induce the well-known symptoms. Omalizumab counteracts these interactions by a reduction in serum levels of free IgE. Therapy targeted against IgE also interferes with its binding to the high- as well as the low-affinity receptors, inhibiting the amplification of the Th2-type response. Treatment of allergic rhinitis with anti-IgE has been shown to be safe and to reduce specific symptoms. Furthermore, the combination ofomalizumab with specific immunotherapy (SIT) may offer not only an increase in efficacy, but also in safety in appropriate patients. The currently available studies with omalizumab in allergic rhinitis, as monotherapy or in combination with immunotherapy, are summarized. In nasal polyp disease, a local polyclonal IgE response has recently been described, initiated by Staphylococcus aureus-derived enterotoxins, which at least modifies the inflammatory reaction within the tissue. Evidence accumulates that these enterotoxins act as superantigens resulting in a polyclonal T- and B cell activation with massive IgE formation within the airways. Because of the polyclonality, a range of allergens could possibly maintain a constant degranulation of mast cells present in polyp tissue, which may contribute to the disease severity. We here discuss a proof-of-concept treatment trial with omalizumab in nasal polyposis, which in case of a positive therapeutic response, also would open the door for anti-IgE treatment approaches for severe nonatopic lower airway disease.