Toward the Proteome of the Human Peripheral Blood Eosinophil

Eosinophils (EOSs) are granular leukocytes that have significant roles in many inflammatory and immunoregulatory responses, especially asthma and allergic diseases. We have undertaken a fairly comprehensive proteomic analysis of purified peripheral blood EOSs from normal human donors primarily employing 2‐DE with protein spot identification by MALDI‐MS. Protein subfractionation methods employed included IEF (Zoom^® Fractionator) and subcellular fractionation using differential protein solubilization. We have identified 3141 proteins, which had Mascot expectation scores of 10^?3 or less. Of these 426 were unique and non‐redundant of which 231 were novel proteins not previously reported to occur in EOSs. Ingenuity Pathway Analysis showed that some 70% of the non‐redundant proteins could be subdivided into categories that are clearly related to currently known EOS biological activities. Cytoskeletal and associated proteins predominated among the proteins identified. Extensive protein posttranslational modifications were evident, many of which have not been previously reported that reflected the dynamic character of the EOS. This data set of eosinophilic proteins will prove valuable in comparative studies of disease versus normal states and for studies of gender differences and polymorphic variation among individuals.     

Indoor mold levels and current asthma among school‐aged children in Saskatchewan,Canada

Current knowledge regarding the association between indoor mold exposures and asthma is still limited. The objective of this case–control study was to investigate the relationship between objectively measured indoor mold levels and current asthma among school‐aged children. Parents completed a questionnaire survey of health history and home environmental conditions. Asthma cases had a history of doctor‐diagnosed asthma or current wheeze without a cold in the past 12 months. Controls were age‐ and sex‐matched to cases. Vacuumed dust samples were collected from the child's indoor play area and mattress. Samples were assessed for mold levels and quantified in colony‐forming units (CFU). Sensitization to mold allergens was also determined by skin testing. Being a case was associated with family history of asthma, pet ownership, and mold allergy. Mold levels (CFU/m²) in the dust samples of children's mattress and play area floors were moderately correlated (r = 0.56; P < 0.05). High mold levels (≥30 000 CFU/m²) in dust samples from play [adjusted odds ratio (aOR) = 2.6; 95% CI: 1.03–6.43] and mattress (aOR) = 3.0; 95% CI: 1.11–8.00) areas were significantly associated with current asthma. In this study high levels of mold are a risk factor for asthma in children.     

Phosphorus flame retardants in indoor dust and their relation to asthma and allergies of inhabitants

Organophosphate esters are used as additives in flame retardants and plasticizers, and they are ubiquitous in the indoor environment. Phosphorus flame retardants (PFRs) are present in residential dust, but few epidemiological studies have assessed their impact on human health. We measured the levels of 11 PFRs in indoor floor dust and multi‐surface dust in 182 single‐family dwellings in Japan. We evaluated their correlations with asthma and allergies of the inhabitants. Tris(2‐butoxyethyl) phosphate was detected in all samples (median value: 580 μg/g in floor dust, 111 μg/g in multi‐surface dust). Tris(2‐chloro‐iso‐propyl) phosphate (TCIPP) was detected at 8.69 μg/g in floor dust and 25.8 μg/g in multi‐surface dust. After adjustment for potential confounders, significant associations were found between the prevalence of atopic dermatitis and the presence of TCIPP and tris(1,3‐dichloro‐2‐propyl) phosphate in floor dust [per log₁₀‐unit, odds ratio (OR): 2.43 and 1.84, respectively]. Tributyl phosphate was significantly associated with the prevalence of asthma (OR: 2.85 in floor dust, 5.34 in multi‐surface dust) and allergic rhinitis (OR: 2.55 in multi‐surface dust). PFR levels in Japan were high compared with values reported previously for Europe, Asia‐Pacific, and the USA. Higher levels of PFRs in house dust were related to the inhabitants' health status.     

Exposure to organophosphate and polybrominated diphenyl ether flame retardants via indoor dust and childhood asthma

Although the ubiquitous detection of polybrominated diphenyl ether (PBDE) and organophosphate flame retardants (PFRs) in indoor dust has raised health concerns, only very few epidemiological studies have assessed their impact on human health. Inhalation of dust is one of the exposure routes of FRs, especially in children and can be hazardous for the respiratory health. Moreover, PFRs are structurally similar to organophosphate pesticides, which have been associated with allergic asthma. Thus, we investigated whether the concentrations of PFRs and PBDEs in indoor dust are associated with the development of childhood asthma. We selected 110 children who developed asthma at 4 or at 8 years old and 110 matched controls from a large prospective birth cohort (BAMSE – Barn, Allergy, Milieu Stockholm Epidemiology). We analyzed the concentrations of 7 PFRs and 21 PBDEs in dust collected around 2 months after birth from the mother's mattress. The abundance rank in dust was as follows: TBOEP?TPHP>mmp‐TMPP>EHDPHP~TDCIPP>TCEP~TCIPP~BDE‐209?BDE‐99>BDE‐47>BDE‐153>BDE‐183>BDE‐100. There was no positive association between the FRs in mattress dust and the development of childhood asthma. In contrast, dust collected from mattresses of the mothers of children who would develop asthma contained significant lower levels of TPHP and mmp‐TMPP. This study provides data on a wide range of PFRs and PBDEs in dust samples and development of asthma in children.     

Next‐generation DNA sequencing reveals that low fungal diversity in house dust is associated with childhood asthma development

Dampness and visible mold in homes are associated with asthma development, but causal mechanisms remain unclear. The goal of this research was to explore associations among measured dampness, fungal exposure, and childhood asthma development without the bias of culture‐based microbial analysis. In the low‐income, Latino CHAMACOS birth cohort, house dust was collected at age 12 months, and asthma status was determined at age 7 years. The current analysis included 13 asthma cases and 28 controls. Next‐generation DNA sequencing methods quantified fungal taxa and diversity. Lower fungal diversity (number of fungal operational taxonomic units) was significantly associated with increased risk of asthma development: unadjusted odds ratio (OR) 4.80 (95% confidence interval (CI) 1.04–22.1). Control for potential confounders strengthened this relationship. Decreased diversity within the genus Cryptococcus was significantly associated with increased asthma risk (OR 21.0, 95% CI 2.16–204). No fungal taxon (species, genus, class) was significantly positively associated with asthma development, and one was significantly negatively associated. Elevated moisture was associated with increased fungal diversity, and moisture/mold indicators were associated with four fungal taxa. Next‐generation DNA sequencing provided comprehensive estimates of fungal identity and diversity, demonstrating significant associations between low fungal diversity and childhood asthma development in this community.     

Impact of asthma,exposure period,and filters on human responses during exposures to ozone and its initiated chemistry products

The impact of asthma, exposure period, and filter condition downstream of the mixing box of air‐conditioning system on building occupants' perceptual response, work performance, and salivary α‐amylase secretion during exposures to ozone and its initiated chemistry products is studied. The experiments were conducted in a field environmental chamber (FEC) (240 m³) simulating an office environment. Experiments were conducted during periods when the air‐handling system operated with new or used pleated panel filters at constant recirculation (7/h) and ventilation (1/h) rates. Average ozone and secondary organic aerosols (ozone‐initiated chemistry products) measured during non‐asthmatic and asthmatic subjects' 3‐h exposures in the FEC were in the ranges approximately 20–37 ppb and approximately 1.6–3 μg/m³, respectively. Asthmatic subjects' perceived odor intensity and sensory (eye, nose, and throat) irritation ratings were generally lower than those of non‐asthmatic subjects, possibly explaining why asthmatic subjects accept perceived air quality more than non‐asthmatic subjects. However, asthmatic subjects' perceived physiological‐like symptom ratings (flu, chest tightness, and headache) and concentrations of secreted salivary α‐amylase were generally higher than those of non‐asthmatic subjects. Asthmatic subjects had significantly lower accuracy than non‐asthmatic subjects in a task that required higher concentration although they had higher work speed. Filter condition did not make any significant difference for subjects' responses.     

Asthma and COPD proteomics: Current approaches and future directions

Although asthma and chronic obstructive pulmonary disease COPD represent the two most common chronic respiratory diseases worldwide, the mechanisms underlying their pathobiology need to be further elucidated. Presently, differentiation of asthma and COPD are largely based on clinical and lung function parameters. However, the complexity of these multifactorial diseases may lead to misclassification and to inappropriate management strategies. Recently, tremendous progress in MS has extended the sensitivity, accuracy, and speed of analysis, enabling the identification of thousands of proteins per experiment. Beyond identification, MS has also greatly implemented quantitation issues allowing to assess qualitative–quantitative differences in protein profiles of different samples, in particular diseased versus normal. Herein, we provide a summary of recent proteomics-based investigations in the field of asthma/COPD, highlighting major issues related to sampling and processing procedures for proteomic analyses of specific airway and parenchymal specimens (induced sputum, exhaled breath condensate, epithelial lining fluid, bronchoalveolar and nasal lavage fluid), as well as blood-derived specimen (plasma and serum). Within such a context, together with current difficulties and limitations mainly due to lack of general standardization in preanalytical sampling procedure, our discussion will focus on the challenges and possible benefits of proteomic studies in phenotypic stratification of asthma and COPD.     

Estimates of Improved Productivity and Health from Better Indoor Environments

Abstract The existing literature contains strong evidence that characteristics of buildings and indoor environments significantly influence rates of respiratory disease, allergy and asthma symptoms, sick building symptoms, and worker performance. Theoretical considerations, and limited empirical data, suggest that existing technologies and procedures can improve indoor environments in a manner that significantly increases health and productivity. At present, we can develop only crude estimates of the magnitude of productivity gains that may be obtained by providing better indoor environments; however, the projected gains are very large. For the U.S., we estimate potential annual savings and productivity gains of $6 billion to $19 billion from reduced respiratory disease; $1 billion to $4 billion from reduced allergies and asthma, $10 billion to $20 billion from reduced sick building syndrome symptoms, and $12 billion to $125 billion from direct improvements in worker performance that are unrelated to health. Sample calculations indicate that the potential financial benefits of improving indoor environments exceed costs by a factor of 18 to 47. The policy implications of the findings are discussed and include a recommendation for additional research.