The impact of airway-irritating exposure and wet work on subjects with allergy or other sensitivity : epidemiology and mechanisms

The prevalence of asthma and allergies is increasing, which means that the proportion of workers on the labour market with allergy or other sensitivity also increases. It is as of yet not known to what extent these persons with an elevated sensitivity in the airways or the skin are affected by exposure to irritating substances at work.

The main aims of this thesis were to investigate how subjects with allergy or other sensitivity are exposed at work places compared to healthy subjects and consequences of an airway diagnosis early in life.

A job-exposure matrix (JEM) for Swedish conditions, for estimation of airway irritating exposure and wet work was developed in Study I. The JEM was applied on two large population cohorts, the Conscription cohort and the People Health Survey. In both cohorts, subjects with asthma had exposed jobs to nearly the same extent as healthy subjects, while subjects with allergic rhinitis rarely had jobs assessed as exposed. Wet work was more associated to symptoms caused by occupational exposure (hand eczema) than to symptoms appearing in childhood (atopic eczema).

In Study II the consequences of an airway diagnosis for health was studied in the Conscription cohort, which revealed that asthmatic subjects had an increased risk for morbidity and mortality compared to healthy subjects and subjects with allergic rhinitis.

In Study III-V the exposure to inhaled particles was studied, especially the lung deposition and permeability of ultrafine combustion particles. In collaboration with a German research group we modified a method for the production of ultrafine radiolabelled combustion particles. Asthmatics, smokers and healthy subjects inhaled the particles. The modified method yielded particles with a stable radioactive label and a stable particle size, making it a suitable method for the study of inhaled particles. We found that the translocation from the lungs to the circulation was negligible for both 100 nm and 35 nm particles. The dose to the lung was however higher in subjects with asthma and in smokers, compared to in healthy subjects.

In conclusion, an increasing proportion of the workers today is sensitive and reacts with symptoms already at low levels of airway-irritating exposure. To be able to give appropriate information and develop prevention, we have to know where efforts are needed. With a JEM for airway-irritating agents it is possible to find associations between sensitive groups and exposure, something that we have poor knowledge of today. This thesis has revealed some sensitive groups that do not voluntarily avoid health detrimental exposures, groups that are known to have poor health, high unemployment and absence due to sickness. We found little evidence for the hypothesis that the vulnerability of susceptible individuals should be a consequence of a higher direct dose of particles to target organs. It is, however, possible that a higher particle dose to the lung contribute to systemic effects. More research is needed to establish if a minimal fraction of translocated particles is sufficient to cause harmful effects.

List of scientific papers

I. Wiebert P, Svartengren M, Lindberg M, Hemmingsson T, Lundberg I, Nise G (2007). "Development of a Job-exposure matrix for airway-irritating agents and wet work and its application on two Swedish cohorts." (Manuscript)

II. Wiebert P, Svartengren M, Lindberg M, Hemmingsson T, Lundberg I, Nise G (2007). "Mortality, morbidity and occupational exposure to airway irritating agents among men with a respiratory diagnosis in adolescence." Occup Environ Med Aug 6: Epub ahead of print
https://pubmed.ncbi.nlm.nih.gov/17681997

III. Möller W, Felten K, Seitz J, Sommerer K, Takenaka S, Wiebert P, Philipson K, Svartengren M, Kreyling WG (2006). "A generator for the production of radiolabelled ultrafine carbonaceous particles for deposition and clearance studies in the respiratory tract." J Aerosol Sci

IV. Wiebert P, Sanchez-Crespo A, Seitz J, Falk R, Philipson K, Kreyling WG, Möller W, Sommerer K, Larsson S, Svartengren M (2006). "Negligible clearance of ultrafine particles retained in healthy and affected human lungs." Eur Respir J 28(2): 286-90. Epub 2006 Apr 26
https://pubmed.ncbi.nlm.nih.gov/16641121

V. Wiebert P, Sanchez-Crespo A, Falk R, Philipson K, Lundin A, Larsson S, Möller W, Kreyling WG, Svartengren M (2006). "No significant translocation of inhaled 35-nm carbon particles to the circulation in humans." Inhal Toxicol 18(10): 741-7
https://pubmed.ncbi.nlm.nih.gov/16774863