Respiratory health and endotoxin: associations and modification byCD14/-260 genotype

Abstract

Exposure to endotoxin has been associated with increased respiratory symptoms and decrements in lung function in occupational settings but little is known about the health effects of domestic exposure in adults. Here, we describe the association of respiratory disease, immunoglobulin (Ig)E sensitisation, bronchial reactivity and lung function with mattress endotoxin levels in adults, and determine whether these associations are modified by polymorphisms in CD14.Endotoxin levels in mattress dust from a population-based sample of 972 adults were measured. Associations were examined using generalised linear mixed models, adjusting for individual and household confounders. Effect modification of these associations by CD14/-260 (rs2569190) was assessed.Mattress endotoxin levels varied from 0.1 to 402.6 EU?mg -1. Although there was no overall association of lung function with endotoxin exposure, there was evidence that the association of forced expiratory volume in 1 s and forced vital capacity with endotoxin was modified by CD14/-260 genotype (p-value for interaction 0.005 and 0.013, respectively). There was no evidence that symptoms, IgE sensitisation or bronchial reactivity were associated with mattress endotoxin levels.In this large epidemiological study of adults, there was no evidence that mattress endotoxin level was associated with respiratory symptoms or IgE sensitisation but the association of lung function with endotoxin levels may be modified by CD14 genotype.

Predictors of microbial agents in dust and respiratory health in the Ecrhs

“…In other epidemiological studies, endotoxin, a component of the bacterial cell wall of mostly gram-negative bacteria [ 33 ] has been widely used as a proxy for bacterial exposure in settled dust. In a previous ECRHS investigation among the same study participants, there was no evidence of an association between exposure to endotoxin levels in mattress dust and the asthma score, however, an association with lung function might be modified by CD14 genotype [ 19 ]. A nationwide study of more than 2500 adult subjects in the U.S. (the National Survey of Allergens in Housing (NSLAH)), reported that increased exposure to endotoxin from bedding was most strongly associated with wheezing ever, wheezing in the past month and within the past year in adjusted analysis.…”

“…The (1,3)-ß-D-glucan inhibition EIA makes use of affinity-purified polyclonal rabbit antibodies, and with the algae-derived glucan laminarin as the coated antigen and the calibration standard, as described previously [ 25 ]. For the current investigation, only the results of the (1,3)-ß-D-glucan measurements will be considered in relation to health, as results on endotoxin have been published previously [ 19 ]. However, endotoxin will be included, investigating the correlation between different microbial parameters.…”

“…We also considered the results of lung function measurements in which each participant had been given up to nine attempts to provide two technically satisfactory forced expiratory manoeuvres. The highest recorded FEV 1 and FVC, which fulfilled the American Thoracic Society criterion for reproducibility, were used as the outcomes [ 6 , 19 ]. In addition, blood samples had been analysed for specific IgE.…”

Association of CD14 C159T polymorphism with atopic asthma susceptibility in children from Southeastern China: a case-control study

“…Thus, an increasing number of studies have examined the relationship between CD14 gene variations and disease susceptibility. It has been reported that the -159 C/T variant in the CD14 gene plays an important role in regulating CD14 expression and is associated with the susceptibility to various diseases, including allergies (Sengler et al, 2003;Bakolis et al, 2012;Wang et al, 2012). Previous studies focused on the association between atopic asthma and CD14 gene variations (Kedda et al, 2005;Nishimura et al, 2006;Zhao et al, 2011), but the results are contradictory.…”

Subgroup differences in the associations between dog exposure during the first year of life and early life allergic outcomes

“…The study of CD14 as a modifier of the effects of endotoxin on allergy‐related outcomes is an excellent example for why interaction should be studied . Interactions between the level of endotoxin and CD14 polymorphisms have been reported to relate to total IgE levels , lung function , eczema and sensitization . The current work extends this successful approach to the investigation of non‐genetic factors, and the results suggest that it is an approach that needs continued application in allergic disease research.…”