Interaction between filaggrin null mutations and tobacco smoking in relation to asthma.

BACKGROUND: The mechanisms underlying the association between filaggrin (FLG) deficiency and asthma are not known. It has been hypothesized that FLG deficiency leads to enhanced percutaneous exposure to environmental substances that might trigger immune responses. We hypothesized that interactions between FLG deficiency and environmental exposures play a role in asthma development. OBJECTIVE: We sought to investigate possible interactions between FLG null mutations and tobacco smoking in relation to asthma. METHODS: A total of 3471 adults from a general population sample participated in a health examination. Lung function and serum specific IgE levels to inhalant allergens were measured, and information on asthma and smoking was obtained by means of questionnaire. Participants were genotyped for the 2 most common FLG null mutations in white subjects: R501X and 2282del4. Another Danish population was used for replication. RESULTS: The FLG null mutation genotype was significantly associated with a higher prevalence of asthma and decreased FEV(1)/forced vital capacity ratio. In logistic regression analyses with asthma as the outcome, a significant interaction was found between FLG null mutations and smoking status (P = .02). This interaction was confirmed, although it was not statistically significant, in another Danish population study. Interactions between FLG genotype and cumulated smoking exposure were found in relation to asthma (P = .03) and decreased FEV(1)/forced vital capacity ratio (P = .03). A 3-way interaction was found among FLG genotype, smoking, and asthma, suggesting that the FLG-smoking interaction mainly played a role in nonatopic subjects. CONCLUSION: FLG null mutations modified the effects of smoking on the risk of asthma. This finding might have implications for risk stratification of the population.

Phenotypes of individuals affected by airborne chemicals in the general population.

OBJECTIVE: To characterise the chemical exposures and symptoms affecting individuals with subsequent adjustments of social life or occupational conditions, and further characterise these severely affected individuals. METHODS: All individuals (n = 1,134) who reported symptoms from airborne chemical exposures in a population-based questionnaire study of 6,000 individuals were included and dichotomised according to severity. Logistic regression models were used to characterise the group of severely affected individuals. RESULTS: Severely affected individuals reported more symptoms and exposures related to symptoms than less severely affected individuals, and the number of symptoms was more predictive for severity than the number of exposures. Most predictive for the severity of reported symptoms were CNS-symptoms other than headache (OR = 3.2, P < 0.001) and exposure to freshly printed papers or magazines (OR = 2.0, P = 0.001). CONCLUSION: CNS-symptoms except from headache were a main characteristic of individuals severely affected by common chemical exposures in a general population-based sample.

Chemical intolerance among hairdressers in Denmark.

OBJECTIVES: To investigate the prevalence and the severity of fragrance-related symptoms among hairdressers in Denmark compared with the Danish general population. Further, to characterize former hairdressers who are severely chemically intolerant to fragranced products in relation to sex, age and health- and work-related reasons for leaving the hairdressing profession. METHODS: The study population consisted of all hairdressers who graduated from the public vocational schools in Denmark during 1985 and 2007 (n = 7840) and a random sample of individuals from the Danish general population (n = 6000). Both populations received a postal questionnaire on symptoms from inhalation of fragranced products and the resultant behavioural consequences. All former hairdressers also answered additional questions on health- and work-related reasons for leaving the profession. RESULTS: No differences were found in the prevalence (OR = 1.0, CI = 0.89-1.14) or the severity (OR = 1.1, CI = 0.80-1.51) of symptoms from inhalation of fragranced products in hairdressers compared with the general population. Among hairdressers, however, experience of fragrance-related symptoms (OR = 1.2, CI = 1.01-1.31) and adjustments of social (OR = 1.8, CI = 1.12-2.80) and occupational conditions (OR = 2.8, CI = 1.84-4.25) were reported significantly more often by former hairdressers than current hairdressers. CONCLUSIONS: The prevalence and the severity of fragrance-related symptoms were similar in hairdressers and the general population. Former hairdressers were more affected by fragranced products than current hairdressers were. Although fragrance-related symptoms did not seem to be more frequent among hairdressers, the hairdressing profession might pose a problem for those who are chemically intolerant.

Evaluation of the quick environmental exposure and sensitivity inventory in a Danish population.

OBJECTIVES: To evaluate a Danish translation of the Quick Environmental Exposure and Sensitivity Inventory (QEESI). METHODS: The study included two groups: one comprised a random sample of 2000 individuals drawn from the Danish Civil Registration System; the other comprised 315 patients with chemical intolerance. RESULTS: The evaluation suggested good reliability for the four QEESI scales in terms of internal consistency and coefficients between test and retest scores. The discriminatory validity was the largest for the Chemical (inhalant) Intolerance and Life Impact Scales. Using combined cut-off scores for these two scales provided a sensitivity of 92.1 and a specificity of 91.8 and yielded a prevalence of 8.2% in the population group. CONCLUSIONS: The Danish translation of the QEESI showed overall good reliability and validity. We recommend the use of the combined Chemical (inhalant) Intolerance and Life Impact Scales in future studies.

Non-allergic cutaneous reactions in airborne chemical sensitivity--a population based study.

Multiple chemical sensitivity (MCS) is characterised by adverse effects due to exposure to low levels of chemical substances. The aetiology is unknown, but chemical related respiratory symptoms have been found associated with positive patch test. The purpose of this study was to investigate the relationship between cutaneous reactions from patch testing and self-reported severity of chemical sensitivity to common airborne chemicals. A total of 3460 individuals participating in a general health examination, Health 2006, were patch tested with allergens from the European standard series and screened for chemical sensitivity with a standardised questionnaire dividing the participants into four severity groups of chemical sensitivity. Both allergic and non-allergic cutaneous reactions--defined as irritative, follicular, or doubtful allergic reactions--were analysed in relationship with severity of chemical sensitivity. Associations were controlled for the possible confounding effects of sex, age, asthma, eczema, atopic dermatitis, psychological and social factors, and smoking habits. In unadjusted analyses we found associations between allergic and non-allergic cutaneous reactions on patch testing and the two most severe groups of self-reported sensitivity to airborne chemicals. When adjusting for confounding, associations were weakened, and only non-allergic cutaneous reactions were significantly associated with individuals most severely affected by inhalation of airborne chemicals (odds ratio = 2.5, p = 0.006). Our results suggest that individuals with self-reported chemical sensitivity show increased non-allergic cutaneous reactions based on day 2 readings of patch tests.

Genetic susceptibility factors for multiple chemical sensitivity revisited.

Multiple chemical sensitivity (MCS) is characterised by adverse effects due to exposure to low levels of chemical substances. Various genes, especially genes of importance to the metabolism of xenobiotic compounds, have been associated with MCS, but findings are inconsistent. The purpose of this study was to investigate genetic susceptibility factors for MCS and self-reported chemical sensitivity in a population sample. Ninety six MCS patients and 1,207 controls from a general population divided into four severity groups of chemical sensitivity were genotyped for variants in the genes encoding cytochrome P450 2D6, arylamine N-acetyltransferase 2, paraoxonase 1, methylene tetrahydrofolate reductase, and the cholecystokinin 2 receptor. No hypotheses were consistently confirmed. An apparent association between number of active cytochrome P450 2D6 alleles and MCS status was not statistically significant (OR=1.2, p=0.28). Fast arylamine N-acetyltransferase 2 metaboliser status was associated with severity of chemical sensitivity only in the most severely affected group in the population sample (OR=3.1, p=0.04). The cholecystokinin 2 receptor allele with 21 CT repeats was associated with MCS when compared in post hoc analyses with all individuals from the population sample (p=0.02). Genetic variants in paraoxonase 1 and methylene tetrahydrofolate reductase were not associated with MSC or with self-reported chemical sensitivity in the population sample. Our results suggest that variants in the genes examined are of less importance to MCS than previously reported or that gene-environment interactions or significant degrees of genetic heterogeneity in MCS underlie inconsistent findings in the literature.

Prevalence of self-reported symptoms and consequences related to inhalation of airborne chemicals in a Danish general population.

OBJECTIVE: To estimate the prevalence and consequences of self-reported symptoms related to inhalation of airborne chemicals in a Danish general population. METHODS: A random sample of 18-69-year-old individuals (n = 6,000) was drawn from the Danish Civil Registration System. A questionnaire on self-reported symptoms related to inhalation of 11 categories of airborne chemicals was mailed to the population. Respondents who reported symptoms received an additional questionnaire to verify the reported symptoms and to characterise factors related to the initial onset of symptoms. RESULTS: The response rate to the primary questionnaire was 71%. A total of 1,134 individuals (27%, 95% CI 25-28) reported symptoms related to inhalation of airborne chemicals, 141 individuals (3.3%, 95% CI 2.8-3.9) reported adjustments of social life or occupational conditions due to symptoms, whereas 20 individuals (0.5%, 95% CI 0.3-0.7) had made adjustments of both social life and occupational conditions. Women reported more exposures as annoying than men and had more symptoms related to inhalation of airborne chemicals (P < 0.001). However, sex had no effect on the reporting of adjustments of social life or occupational conditions (P = 0.54). CONCLUSION: Symptoms related to inhalation of airborne chemicals were common in this general population, and a minority reported that these symptoms affected social life or occupational conditions. Women as compared to men reported more symptoms but not adjustments of social life or occupational conditions.