Publications

OBJECTIVE

To assess the contribution of workplace exposures to chronic obstructive pulmonary disease (COPD) risk in a community with a heavy burden of past industrial employment.

METHODS

A random population sample of Sheffield, U.K. residents aged over 55 years (n=4000), enriched with a hospital-based supplemental sample (n=209), was approached for study. A comprehensive self-completed questionnaire elicited physician-made diagnoses, current symptoms, and past workplace exposures. The latter were defined in three ways: self-reported exposure to vapours, gases, dusts and fumes (VGDF); response to a specific exposure checklist; and through a job exposure matrix (JEM) assigning exposure risk likelihood based on job history independent of respondent-reported exposure. A subset of the study group underwent lung function testing. Population attributable risk fractions (PAR%), adjusted for age, sex and smoking, were calculated for association between workplace exposure and COPD.

RESULTS

2001 (50%) questionnaires were returned from the general population sample and 60 (29%) by the hospital supplement. Among 1754 with complete occupational data, any past occupational exposure to VGDF carried an adjusted excess risk for report of a physician's diagnosis of COPD, emphysema, or chronic bronchitis (ORs 3.9; 95% CI 2.7 to 5.8), with a corresponding PAR% value of 58.7% (95% CI 45.6% to 68.7%). The PAR% estimate based on JEM exposure was 31%. From within the subgroup of 571 that underwent lung function testing, VGDF exposure was associated with a PAR% of 20.0% (95% CI -7.2 to 40.3%) for Global initiative for chronic obstructive lung disease (GOLD) 1 (or greater) level of COPD.

CONCLUSION

This heavy industrial community-based population study has confirmed significant associations between reported COPD and both generic VGDF and JEM-defined exposures. This study supports the predominantly international evidence-based notion that workplace conditions are important when considering the current and future respiratory health of the workforce.

UNLABELLED

We introduce GO-Elite, a flexible and powerful pathway analysis tool for a wide array of species, identifiers (IDs), pathways, ontologies and gene sets. In addition to the Gene Ontology (GO), GO-Elite allows the user to perform over-representation analysis on any structured ontology annotations, pathway database or biological IDs (e.g. gene, protein or metabolite). GO-Elite exploits the structured nature of biological ontologies to report a minimal set of non-overlapping terms. The results can be visualized on WikiPathways or as networks. Built-in support is provided for over 60 species and 50 ID systems, covering gene, disease and phenotype ontologies, multiple pathway databases, biomarkers, and transcription factor and microRNA targets. GO-Elite is available as a web interface, GenMAPP-CS plugin and as a cross-platform application.

AVAILABILITY

http://www.genmapp.org/go_elite

A majority of the novel orally administered, molecularly targeted anticancer therapies are weak bases that exhibit pH-dependent solubility, and suppression of gastric acidity with acid-reducing agents could impair their absorption. In addition, a majority of cancer patients frequently take acid-reducing agents to alleviate symptoms of gastroesophageal reflux disease, thereby raising the potential for a common but underappreciated drug-drug interaction (DDI) that could decrease the exposure of anticancer medication and result in subsequent failure of therapy. This article is a review of the available clinical literature describing the extent of the interaction between 15 orally administered, small-molecule targeted anticancer therapies and acid-reducing agents. The currently available clinical data suggest that the magnitude of this DDI is largest for compounds whose in vitro solubility varies over the pH range 1-4. This range represents the normal physiological gastric acidity (pH ~1) and gastric acidity while on an acid-reducing agent (pH ~4).