Exposure to occupational agents like gases/fumes, mineral dust or biological dust, and possible adverse health effects.

Abstract

Many workers are daily exposed to occupational agents like gases/fumes, mineral dust or biological dust, which could induce adverse health effects. Epigenetic mechanisms, such as DNA methylation, have been suggested to play a role. We therefore aimed to identify differentially methylated regions (DMRs) upon occupational exposures in never-smokers and investigated if these DMRs associated with gene expression levels. To determine the effects of occupational exposures independent of smoking, 903 never-smokers of the LifeLines cohort study were included. We performed three genome-wide methylation analyses (Illumina 450 K), one per occupational exposure being gases/fumes, mineral dust and biological dust, using robust linear regression adjusted for appropriate confounders. DMRs were identified using comb-p in Python. Results were validated in the Rotterdam Study (233 never-smokers) and methylation-expression associations were assessed using Biobank-based Integrative Omics Study data (n = 2802). Of the total 21 significant DMRs, 14 DMRs were associated with gases/fumes and 7 with mineral dust. Three of these DMRs were associated with both exposures (RPLP1 and LINC02169 (2×)) and 11 DMRs were located within transcript start sites of gene expression regulating genes. We replicated two DMRs with gases/fumes (VTRNA2-1 and GNAS) and one with mineral dust (CCDC144NL). In addition, nine gases/fumes DMRs and six mineral dust DMRs significantly associated with gene expression levels. Our data suggest that occupational exposures may induce differential methylation of gene expression regulating genes and thereby may induce adverse health effects. Given the millions of workers that are exposed daily to occupational exposures, further studies on this epigenetic mechanism and health outcomes are warranted. Hum Mol Genet. 2019 Aug 1; 28(15): 2477–2485. Apr 2. doi: 10.1093/hmg/ddz067 Occupational exposure to gases/fumes and mineral dust affect DNA methylation levels of genes regulating expression Diana A van der Plaat,1,2Judith M Vonk,1,2Natalie Terzikhan,3,1Kim de Jong,1,2Maaike de Vries,1,2Sacha La Bastide-van Gemert,1Cleo C van Diemen,5Lies Lahousse,3,1,4Guy G Brusselle,3,1,4Ivana Nedeljkovic,4Najaf Amin,1 BIOS Consortium , Hans Kromhout,6Roel C H Vermeulen,7Dirkje S Postma,7,2Cornelia M van Duijn,1 and H Marike Boezen1,2

I wish to tell you about my friend Paula, and what we learnt about her and her birth history and her first two years of life before she and her family moved to better physical conditions in Montreal Canada.  I hope that this will help to inform your research.

My friend Paula has an unusual [or maybe not so unusual] history of occupational exposure as a baby.  Her parents were poor, her father was a furrier and had a workshop in their home,  The apartment was heated by a coke oven. Ventilation in the apartment was poor.  There were a lot of fumes, allergens, irritants even poisons in the air.

Paula was conceived in this apartment.  She got stuck in the birth canal due to her mothers crooked pelvic bones, most likely from  childhood Rickets.  Paula was born not breathing, swallowed meconium, was suctioned, was resuscitated and even transfused.  Then she was fine.         That was in 1955 Paris France.


The family moved to Montreal Canada when she was 2 and a half, and their living and working conditions were much improved.


Paula only found out that she had a ventilatory defect/injury in a basic first aid class. Her breathing rate is 3 breaths per minute at rest, with active exhaling. Her tidal volume is .5 L.  Her lungs are normal. Her minute ventilation is 1.5 L instead of the “assumed” 6-8 L. 

No one can explain it.  Her HCO3 and O2 are normal [pulse oximetry-not the best measure, in this case, perhaps.]  No one has measured her PCO2 because she is fine.

Maybe exchanging less air than normal when breathing, [as Paula does] is advantageous when one has experienced early exposure to poisonous fumes, allergens and irritants, as Paula and her family have ? Her breathing rate does increase with exercise, but sluggishly.


But it seems that genes are turned on or off in response to the first transition at birth  to air and fuel. Paula is pulling off an exceptional feat when breathing at such as slow rate.


We think this is interesting, especially since in the early 20th century, Dr Emile Kraepelin found thousands of patients in the asylums with the same respiratory defect as Paula.
PCO2 is a cerebral vasodilator and can be a reversible [if you do not die] delirant, intoxicant, depressant, euphoriant and asphyxiant.


Yet no doctor measures respiratory rate any more and no one examines the state of the unprotected peripheral system involved in the control of breathing.  Instead everyone assumes it to be normal. Even Paula feels normal. She is not.  She has a defect which interferes with her ability to maintain her levels of PCO2. It is important for Paula’s doctors to know this, especially in times of physical illness.

Science requires careful measurement not assumption.  

Respiratory rate at rest is a complex motor act known to the brain stem and the autonomic nervous system, if not our own minds.


Paula and I are not scientists. We are not doctors. And this is an unexplained scientific mystery that we have stumbled upon.


Please read what Paula and I have been discovering for the past 20 years, since her discovery of her [hidden] respiratory defect. Please read our other blog post commentaries as we explore the topics of hypercapnia, birth injury, exposure to poisons and asphyiants in the air, the function of the ventilatory system, control of breathing and mind and loss of mind.

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