The object of this study was to assess the relationship between occupational dust exposure and chronic obstructive pulmonary disease (COPD). Studies were identified using MEDLINE (January 1966 to July 1991), SCISEARCH, manual review of reference lists, and personal contact with more than 30 international experts. Studies of COPD, lung function, emphysema, chronic bronchitis, or mortality in workers exposed to nonorganic dust were retrieved. Studies were included if dust exposure was measured quantitatively, and a quantitative relationship between dust exposure and one of the outcomes of interest was calculated while controlling at least for smoking and age. Methodological rigor was assessed, and data regarding the study populations, prognostic factors, and outcomes were extracted independently by two reviewers. Thirteen reports derived from four cohorts of workers met our inclusion criteria. Three of the cohorts were of coal miners and one was of gold miners. All of the studies found a statistically significant association between loss of lung function and cumulative respirable dust exposure. It was estimated that 80 (95% CI, 34 to 137) of 1,000 nonsmoking coal miners with a cumulative respirable dust exposure of 122.5 gh/m3 (considered equivalent to 35 years of work with a mean respirable dust level of 2 mg/m3) could be expected to develop a clinically important (> 20%) loss of FEV1 attributable to dust. Among 1,000 smoking miners the comparable estimate was 66 (95% CI, 49 to 84). The risk of a clinically important loss of lung function attributable to dust among nonsmoking gold miners was estimated to be three times as large as for coal miners at less than one fifth of the cumulative respirable dust exposure (21.3 gh/m3), the maximal exposure observed among the cohort of gold miners. We conclude that occupational dust is an important cause of COPD, and the risk appears to be greater for gold miners than for coal miners. One possible explanation of the greater risk among gold miners is the higher silica content in gold mine dust.

No abstract

Coronary artery disease (CAD) has a significant genetic contribution that is incompletely characterized. To complement genome-wide association (GWA) studies, we conducted a large and systematic candidate gene study of CAD susceptibility, including analysis of many uncommon and functional variants. We examined 49,094 genetic variants in ∼2,100 genes of cardiovascular relevance, using a customised gene array in 15,596 CAD cases and 34,992 controls (11,202 cases and 30,733 controls of European descent; 4,394 cases and 4,259 controls of South Asian origin). We attempted to replicate putative novel associations in an additional 17,121 CAD cases and 40,473 controls. Potential mechanisms through which the novel variants could affect CAD risk were explored through association tests with vascular risk factors and gene expression. We confirmed associations of several previously known CAD susceptibility loci (eg, 9p21.3:p<10−33; LPA:p<10−19; 1p13.3:p<10−17) as well as three recently discovered loci (COL4A1/COL4A2, ZC3HC1, CYP17A1:p<5×10−7). However, we found essentially null results for most previously suggested CAD candidate genes. In our replication study of 24 promising common variants, we identified novel associations of variants in or near LIPA, IL5, TRIB1, and ABCG5/ABCG8, with per-allele odds ratios for CAD risk with each of the novel variants ranging from 1.06–1.09. Associations with variants at LIPA, TRIB1, and ABCG5/ABCG8 were supported by gene expression data or effects on lipid levels. Apart from the previously reported variants in LPA, none of the other ∼4,500 low frequency and functional variants showed a strong effect. Associations in South Asians did not differ appreciably from those in Europeans, except for 9p21.3 (per-allele odds ratio: 1.14 versus 1.27 respectively; P for heterogeneity = 0.003). This large-scale gene-centric analysis has identified several novel genes for CAD that relate to diverse biochemical and cellular functions and clarified the literature with regard to many previously suggested genes.

No abstract

The postnatal growth of the pre-acinar or conducting airways of the lung was examined by measuring the dimensions of selected axial pathways in lungs at different stages of development. The material included both formalin-fixed specimens and bronchograms. A method of comparing the relative sizes of each part of the pathways was developed which allowed for differences between the number of branches or generations measured in each specimen. The results indicate that the pre-acinar airways of the infant may be regarded as a miniature version of those in the adult and that this relationship persists during postnatal growth. Each individual branch grows in a symmetrical fashion both in length and in diameter and bears a constant relation to the whole. The physiological function of the conducting airways during growth was investigated using published data on the breathing pattern of infants. Particular attention was given to the conditions of airflow, to the warming and humidification of inhaled air, and to the filtration of airborne dust.