Lung function parameters in omalizumab responder patients: An interesting tool?

BACKGROUND: Omalizumab, an anti-IgE antibody, is used to treat patients with severe allergic asthma. The evolution of lung function parameters over time and the difference between omalizumab responder and nonresponder patients remain inconclusive. The objective of this real-life study was to compare the changes in forced expiratory volume in 1 second (FEV1) of omalizumab responders and nonresponders at 6 months. METHODS: A multicenter analysis was performed in 10 secondary and tertiary institutions. Lung function parameters (forced vital capacity (FVC), pre- and postbronchodilator FEV1, residual volume (RV), and total lung capacity (TLC) were determined at baseline and at 6 months. Omalizumab response was assessed at the 6-month visit. In the omalizumab responder patients, lung function parameters were also obtained at 12, 18, and 24 months. RESULTS: Mean prebronchodilator FEV1 showed improvement in responders at 6 months, while a decrease was observed in nonresponders (+0.2±0.4 L and -0.1±0.4 L, respectively, P<.01). After an improvement at 6 months, pre- and postbronchodilator FEV1 remained stable at 12, 18, and 24 months. The FEV1/FVC remained unchanged over time, but the proportion of patients with an FEV1/FVC ratio <0.7 decreased at 6, 12, 18, and 24 months (55.2%, 54.0%, 54.0%, and 44.8%, respectively, P<.05). Mean RV values decreased at 6 months but increased at 12 months and 24 months (P<.05). Residual volume/total lung capacity (RV/TLC) ratio decreased at 6 months and remained unchanged at 24 months. CONCLUSION: After omalizumab initiation, FEV1 improved at 6 months in responder patients and then remained stable for 2 years. RV and RV/TLC improved at 6 months.

Effects of n-3 polyunsaturated dietary supplementation on the reproductive capacity of male turkeys.

To measure the effects of dietary n-3 polyunsaturated fatty acid (PUFA) supplementation on the reproductive capacity of adult male turkeys in industrial flocks, the males of 22 commercial farms were fed either a standard diet or a fish oil diet enriched in n-3 PUFAs. The fatty acid composition of the spermatozoa and reproductive performance were measured throughout the reproductive period. The fish oil diet very effectively increased the percentage of n-3 fatty acids (FA) (22:5n-3 and 22:6n-3) in spermatozoa and correspondingly decreased the percentage of n-6 PUFAs (20:4-6 and 22:4n-6): the n-3/n-6 ratio in spermatozoa fatty acids were 0.04-0.07 with the standard diet and 0.32-0.4 with the fish oil diet. These changes did not affect the spermatozoa content of n-9 PUFAs, particularly of 22:3n-9 which is abundant in turkey spermatozoa (9-12% of the total fatty acids). The supplementation was effective in the middle as at the end of the reproductive period. The reproductive capacity of males was modified by the diet and the positive effect of the n-3 supplemented diet increased with age (increase in hatching rates of nearly 2 points at 48-58 weeks for males fed fish oil diet). These results indicate that an increase in the dietary ratio of n-3/n-6 PUFAs is valuable to sustain the reproductive capacity of male turkeys especially when they are getting older.

[Development of a job-exposure matrix in the heavy-metal industry in France]. / Elaboration d'une matrice emplois-expositions dans l'industrie productrice de métaux durs en France.

A job exposure matrix (JEM) was developed by a committee of experts using the DELPHI method, in the French hard metal industry, in order to assess occupational exposures to cobalt along with tungsten carbide resulting from the industrial process. This JEM is part of a nested case-control study, carried out within the historical cohort of workers ever employed in these factories, aimed at assessing lung cancer risk. The committee included 8 experts: hygienists, chemical engineers, occupational physicians and epidemiologists. The JEM was developed in four stages: (i) visit of factories, (ii) definition of lines (job-periods) and columns (exposures) of the JEM, (iii) definition of coding procedures, (iv) coding the cells of the JEM. This last stage used a method derived from the DELPHI method. Throughout the study period 1945-1994. 320 job-periods and 21 agents were defined. A quantitative assignment (level 0 to level 9) along with a frequency code (1 to 3) was attempted for 4 agents, whereas only a qualitative assignment (non exposed/exposed, i.e. 0/l) was done for the other agents. An additional probability code (1 to 3) was assigned to all agents. This procedure led to 46 columns and 14,720 cells in the JEM. When applying the DELPHI method, the consensus of the committee was obtained for 85% of all cells after the first individual assignment of experts, 88% after the second individual assignment and 100% after the third assignment by the experts all together. In order to validate the JEM, these expert assignments will be brought together with the results of exposure measurements that were performed in some workplaces of these factories. The JEM will also be linked with the data base of the case-control study for the exposure assessment of cases and controls.

Lung cancer mortality in a site producing hard metals.

OBJECTIVES: To study the mortality from lung cancer from exposures to hard metal dust at an industrial site producing hard metals--pseudoalloys of cobalt and tungsten carbide--and other metallurgical products many of which contain cobalt. METHODS: A historical cohort was set up of all subjects who had worked for at least 3 months on the site since its opening date in the late 1940s. A full job history could be obtained for 95% of the subjects. The cohort was followed up from January 1968 to December 1992. The exposure was assessed by an industry specific job exposure matrix (JEM) characterising exposure to hard metal dust from 1 to 9 and other possibly carcinogenic exposures as present or absent. Smoking information was obtained by interview of former workers. Standard lifetable methods and Poisson regression were used for the statistical analysis of the data. RESULTS: Mortality from all causes was close to the expected (standardised mortality ratio (SMR) 1.02, 399 deaths) whereas mortality from lung cancer was significantly increased among men (SMR 1.70; 46 deaths, 95% confidence interval (95% CI) 1.24 to 2.26). By workshop, lung cancer mortality was significantly higher than expected in hard metal production before sintering (SMR 2.42; nine deaths; 95%CI 1.10 to 4.59) and among maintenance workers (SMR 2.56; 11 deaths; 95%CI 1.28 to 4.59), whereas after sintering the SMR was lower (SMR 1.28; five deaths; 95%CI 0.41 to 2.98). The SMR for all exposures to hard metal dust at a level >1 in the JEM was in significant excess (SMR 2.02; 26 deaths; 95%CI 1.32 to 2.96). The risks increased with exposure scores, duration of exposure, and cumulative dose reaching significance for duration of exposure to hard metal dust before sintering, after adjustment for smoking and known or suspected carcinogens. CONCLUSION: Excess mortality from lung cancer was found among hard metal production workers which cannot be attributed to smoking alone. This excess occurred mostly in subjects exposed to unsintered hard metal dust.

[Cobalt and sintered metal carbides. Value of the determination of cobalt as a tracer of exposure to hard metals]. / Cobalt et carbures métalliques frittés. Intérêt du dosage de cobalt comme traceur de l'exposition aux métaux durs.

Cobalt urinary excretion should be a good way to know the level of exposition of subjects submitted to hard metals. The study is done on 28 workers of 3 different workrooms. Sunday 24 hours diuresis is retained. For 5 workers, the urinary cobalt measurements are done from samples made at the beginning and the end of work during 5 days. Atmospheric dust measurements are realized in different points of the 3 workrooms (individual and general samples). For measures atomic absorption spectrometry is used. The results show a good correlation between cobalt exposure and urinary concentrations. Friday evening urinary cobalt is a good expression of week exposure. The results obtained well correlate with those of others authors. Cobalt urinary measures are proposed for supervision of workers exposed to hard metals.

Respiratory function in flour-mill workers.

The frequency of bronchial symptoms and the alteration of respiratory function parameters were studied in a group of 63 workers of an industrial flour-mill, and in a control group matched according to age, social class, and tobacco intake. In the exposed group the answers to a questionnaire indicated a greater incidence of cough (p less than 0.01) and chronic expectoration (p less than 0.01) as well as clinical airway hyperreactivity (p less than 0.01). No differences were noted for either asthma or allergy. The respiratory function parameters did not differ between the two groups studied. These results suggest that workers exposed to the vegetable dust found in fluor-mills are subject to develop chronic bronchial irritation.

T cell receptor gamma variable gene locus polymorphism in patients with rheumatoid arthritis.

OBJECTIVE: We sought new susceptibility markers for rheumatoid arthritis (RA) among the T cell receptor gamma (TCR gamma) genes. METHODS: We analyzed restriction fragment length polymorphisms (RFLP) of the first variable subgroup of TCR gamma genes in a group of French control subjects and a group of French RA patients. RESULTS: No significant difference in Eco RI RFLP was found between the 2 study populations: Allele frequencies were virtually identical. There was no polymorphism using Hind III. CONCLUSION: These results exclude TCRV gamma I polymorphism as a disease susceptibility marker in RA.

Lung cancer risk in hard-metal workers.

An industry-wide mortality study on the association between lung cancer and occupational exposure to cobalt and tungsten carbide was carried out in the French hard-metal industry. This case-control study was nested in the historical cohort of workers ever employed in this industry's 10 facilities, most of which are located in eastern France. Workers were followed up from 1968 to 1991. Occupational exposure was assessed using a job-exposure matrix that provided semiquantitative scores for 320 job periods. These scores were significantly correlated with the levels of cobalt measured in 744 historical air samples. In this cohort, which comprised 5,777 males and 1,682 females, the death rate from lung cancer was significant (63 deaths, standardized mortality ratio=1.30, 95% confidence interval (CI) 1.00-1.66) when compared with national death rates. Sixty-one cases and 180 controls were included in the study. When the exposures during the last 10 years were ignored, a twofold lung cancer risk was observed among workers simultaneously exposed to cobalt and tungsten carbide (odds ratio (OR)=1.93, 95% CI 1.03-3.62) adjusted for other cobalt exposure (OR=2.21, 95% CI 0.99-4.90). The odds ratios increased with cumulative exposure (first quartile, OR=1.00; second quartile, OR=2.64; third quartile, OR=2.59; fourth quartile, OR=4.13) and, to a lesser degree, with duration of exposure (one decade, OR=1.00; two decades, OR=1.61; three decades, OR=2.77; four decades, OR=2.03). Adjustments for smoking and for exposures to known or suspected carcinogens did not change the results, yet the odds ratio for smoking (3.38) was lower than expected, suggesting the possibility of some misclassification. Occupational risk was highest among smokers. This study supports the hypothesis that workers who manufacture hard metals have an increased mortality from lung cancer due to simultaneous exposure to cobalt and tungsten carbide.