Developments in laboratory diagnostics for Isocyanate Asthma

Purpose of review

Isocyanates, reactive chemicals used to generate polyurethane, are a leading cause of occupational asthma worldwide. Workplace exposure is the best-recognized risk factor for disease development, but is challenging to monitor. Clinical diagnosis and differentiation of isocyanates as the cause of asthma can be difficult. The gold-standard test, specific inhalation challenge, is technically and economically demanding, and is thus only available in a few specialized centers in the world. With the increasing use of isocyanates, efficient laboratory tests for isocyanate asthma and exposure are urgently needed.

Recent findings

The review focuses on literature published in 2005 and 2006. Over 150 articles, identified by searching PubMed using keywords ‘diphenylmethane’, ‘toluene’ or ‘hexamethylene diisocyanate’, were screened for relevance to isocyanate asthma diagnostics. New advances in understanding isocyanate asthma pathogenesis are described, which help improve conventional radioallergosorbent and enzyme-linked immunosorbent assay approaches for measuring isocyanate-specific IgE and IgG. Newer immunoassays, based on cellular responses and discovery science readouts are also in development.

Summary

Contemporary laboratory tests that measure isocyanate-specific human IgE and IgG are of utility in diagnosing a subset of workers with isocyanate asthma, and may serve as a biomarker of exposure in a larger proportion of occupationally exposed workers.

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Introduction

Diisocyanates (toluene diisocyanate, TDI; hexamethylene diisocyanate, HDI; and diphenylmethane diisocyanate, MDI) or functionally similar polymeric isocyanates are the obligate cross-linking agent for the commercial production of polyurethane, a polymer upon which modern society has become dependent. Millions of tons of isocyanate are produced and consumed annually throughout the world in a wide variety of end-use work environments [1,2–5,6•,7•]. Workplace exposure remains the best-recognized risk factor for isocyanate asthma, but is complicated to quantitate, involving mixtures of isomers and ‘prepolymers’ diluted in solvents, in aerosol and vapor phases. In certain occupational settings, exposure can cause isocyanate asthma and long-lasting bronchial hyperreactivity [1,8,9,10•,11•]. Early recognition of isocyanate asthma and prompt removal from isocyanate exposure improves the long-term prognosis for sensitive individuals [9]. There thus exists the need for practical screening/diagnostic tests for isocyanate asthma as well as tests that can monitor personal exposure.

The clinical presentation of isocyanate asthma is strikingly similar to common environmental asthma, prompting the hypothesis that the disease has an immunological basis, although subtle differences have been noted [9,10•,12•]. Animal models support this hypothesis, and are beginning to dissect the potential role of individual genes with transgenic strains [13••,14••,15,16••,17,18]. Allergists and immunologists have overcome substantial challenges working with reactive isocyanates to develop serology assays for isocyanate-specific antibodies [19–21]. Such assays have provided evidence to support allergic asthma to isocyanate in a small percentage of workers, but cannot detect isocyanate-specific IgE in the majority of sensitive individuals. These results have left great uncertainty in the field. Does isocyanate asthma involve mechanisms of pathogenesis (e.g. non-IgE) distinct from those in common atopic asthma or are specific IgE antibodies present, but our detection assay for them is flawed? Are we using the wrong antigenic form of isocyanate in our serology tests, or testing workers at the wrong time (after removal from exposure)? Does isocyanate asthma, as presently defined, possibly represent a spectrum of diseases, which only in some cases is associated with an antibody response [3,9,10•]?

The present review summarizes the rationale and use of clinical laboratory tests for immune responses that reflect isocyanate exposure and asthma, with emphasis on data generated within the past year. The potential utility of ‘isocyanate-specific’ serum IgE and IgG as biomarkers and the isocyanate antigen recognized by these immunoglobulins are described [22••,23]. Clinical usage and limits of contemporary assays for isocyanate asthma and exposure are discussed along with promising future assays [20,24,25••].

Read more on the US National Center for Biotechnology Information

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3131002/

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The Irish Army Air Corps has dismissed a number of previously fit personnel as suffering from asthma. It has never carried out a health study of personnel exposed long term and without protection to Isocyanates and has never carried out adequate risk specific health surveillance. Neither has the Air Corps ever carried out risk specific health surveillance for personnel who suffered long term exposure to jet fuel & jet exhaust gasses. 

Bizarrely serving and former Air Corps personnel have been “reassured” by Air Corps medical personnel that their asthma does not have a workplace related cause despite no evidence of any testing for them to form a conclusion either way.

Considering what is now known about the extremely poor chemical health & safety environment in the Irish Air Corps any doctor, dismissing without appropriate testing, any possibility of a workplace casual link is surely opening himself or herself up to accusations of professional misconduct.

Irish Air Corps Chemical List Update – Mastinox 6856k

We have just added some links to information on the constituent chemicals for Mastinox 6856k from PubChem the Open Chemistry Database. Please have a look at green links on our chemical info page here. We will add more on a regular basis.

Mastinox 6856k is a corrosion inhibitor and contains the following

  • Strontium Chromate
  • Barium Chromate
  • Xylene
  • Toluene
  • Ethylbenzene
  • N-Octane
  • Naptha
  • Heptane
  • Methylcyclohexane

Biological monitoring for Isocyanates

Organic diisocyanates are a significant occupational health problem.

They are respiratory and skin sensitizers and a major cause of occupational asthma in the UK. The most common are hexamethylene diisocyanate (HDI), toluene diisocyanate (TDI), isopherone diisocyanate (IPDI) and methylene-diphenyl diisocyanate (MDI) in decreasing order of volatility. HDI and IPDI are used for varnishes, coatings and two-pack spray paints used in motor vehicle repair. TDI and MDI are used for flexible and rigid polyurethane foams, floor coverings and adhesives. This wide range of uses means that there are thousands of workers potentially exposed to isocyanates.

In the UK, a management control system is required for workers exposed to isocyanates and for this to be successful workers should not become sensitized. Apart from occupational asthma, airway irritation and asthma-like symptoms such as cough, wheezing and dyspnoea are commonly reported. Other respiratory effects are hypersensitivity pneumonitis, rhinitis and accelerated rate of decline in lung function. Diisocyanates can also cause both irritant and allergic contact dermatitis as well as skin and conjunctival irritation.

Health surveillance that detects occupational asthma is recording failure – there needs to be intervention earlier in the exposure-to-disease paradigm. Although there is evidence that detecting respiratory symptoms early and removing workers from exposure improves prognosis, the goal should be to control exposure to prevent any symptoms.

Please read more on the Society of Occupational Medicine website from September 2007.


This is a long article but a very informative read and is especially relevant for those on post 1995 contracts who were dismissed from the Irish Army Air Corps due to occupational asthma.

Skin Cancer in Irish Air Corps personnel – Basal Cell Carcinoma

Photo of BCC on the leg of a former Air Corps employee who worked daily with Ardrox 666. This person also has cancerous growths on his arm & scalp.

Basal Cell Carcinoma’s are abnormal, uncontrolled growths or lesions that arise in the skin’s basal cells, which line the deepest layer of the epidermis (the outermost layer of the skin). BCCs often look like open sores, red patches, pink growths, shiny bumps, or scars and are usually caused by a combination of cumulative and intense, occasional sun exposure.

Both long-term sun exposure over your lifetime and occasional extended, intense exposure (typically leading to sunburn) combine to cause damage that can lead to BCC. Almost all BCCs occur on parts of the body excessively exposed to the sun — especially the face, ears, neck, scalp, shoulders, and back.

On rare occasions, however, tumors develop on unexposed areas. In a few cases, contact with arsenic, exposure to radiation, open sores that resist healing, chronic inflammatory skin conditions, and complications of burns, scars, infections, vaccinations, or even tattoos are contributing factors.

It is not possible to pinpoint a precise, single cause for a specific tumor, especially one found on a sun-protected area of the body or in an extremely young individual.

Skin cancer (non-melanoma)
Causes grouped by strength of evidence
Strong  Good  Limited 
arsenic aromatic amines acrylamide
benzo(a)pyrene arsenical pesticides vinyl chloride
coal tars benz(a)anthracene
ionizing radiation creosotes
mineral oils dibenz(a,h)anthracene
shale oils dimethyl benzanthracene
UV radiation ethylene oxide
methylcholanthrene
oryzalin
PAHs
pesticides

We are aware of a number of current & former Air Corps technicians who have developed Basal Cell Carcinoma. It is interesting to note that there is good evidence to link creosotes with Basal Cell Carcinoma. Creosotes are a component chemical of Ardrox 666.

However, Basal Cell Carcinoma is a very common cancer and so the occurrence may not be unusual.

Key point as with almost all of the illnesses suffered by Air Corps Chemical Abuse Survivors is of course vigilance. Don’t delay going to your doctor.

No plan to probe missing Irish Army Air Corps Health & Safety reports

The Government says the Defence Forces have no intention of investigating how health and safety reports at the centre of an alleged ‘cover up’ within the Air Corps have gone missing.

The State is facing at least six lawsuits from former Air Corps technicians who suffer chronic illnesses that they say were caused by their working environment at Casement Aerodrome.

All six have seen a toxico-pathologist who has given his medical opinion that their illnesses — including cancer, depression, anxiety, sleep disturbance, and memory loss — were caused by their exposure to harmful chemicals.

Last week the Irish Examiner revealed that health and safety reports arising from inspections of Casement Aerodrome in the 1990s — a period during which the six worked for the Air Corps —cannot be found by military authorities.

Sinn Féin defence spokesperson, Aengus Ó Snodaigh, has told the Dáil that he has seen the reports in question, and that they are critical of health and safety management at Casement Aerodrome at the time.

Mr Ó Snodaigh has questioned whether the disappearance of the documents is part of a cover-up to disguise the fact that the Defence Forces did not follow up on the inspections recommendations.

However, despite confirming that the inspections in question took place, and that the reports arising from these probes cannot be located, Junior Defence Minister Paul Kehoe has said there are no plans to look into how or why the documents went missing.

Read more on the Irish Examiner website.

State has plenty of questions left to answer over Air Corps

Health and safety issues in the Air Corps have not gone away. Why is an investigation not underway, Joe Leogue wants to know

Revelations that the Air Corps has doubts over its own health and safety management raises further questions about the State’s treatment of former members who now suffer a litany of illnesses that they claim came as a result of their exposure to toxic chemicals.

Today’s Irish Examiner reveals that an internal Air Corps report from 2014 cast doubt over whether adequate protection was given to technicians who would have worked with cancer-causing solvents on a daily basis. It also states that staff could have ingested the airborne chemical because their tea room was in an adjacent room, and that their clothes could have been contaminated due to their lockers being in the room where the chemical was used.

The Air Corps could not find any records stating its staff had received any training on the dangers of the chemicals they were tasked with using.

The details of this report come a week after this newspaper revealed that the Government “cannot locate” documents that opposition TDs say show that health and safety concerns were raised more than 20 years ago.

The 2014 report’s admissions make the State’s refusal to investigate potential links between the workers’ illnesses and their exposure more inexplicable.

It also calls into question the State’s decision to drag claims made by former staff through the courts.

Read more on the Irish Examiner website.

Report queried Air Corps safety efforts

A 2014 internal Air Corps report into staff exposure to a cancer-causing cleaning agent over a 27-year period has cast doubt on whether the force did all in its power to protect workers’ health.

The document states it is possible staff may have ingested the chemical and suffered other exposures because there was no record that protective measures were in place to mitigate the impact of the toxic solvent.

The time under review in the report — 1980 to 2007 — coincides with the period during which a number of Air Corps staff who are suing the State would have worked at Casement Aerodrome, Baldonnel.

It is understood the document was prepared for the State Claims Agency, who is defending the case in the High Court.

The report, seen by the Irish Examiner, investigates the working environment in a since-demolished engine workshop building and was published over two-and-a-half years before the Health and Safety Authority raised a number of concerns about conditions in Baldonnel.

In its summary on precautions taken with the Triklone N solvent, the report issued by the Air Corps’ Formation Safety Office asks “can the Defence Forces be found not to have done everything reasonably practicable?”.

Triklone N contains trichloroethylene, a known carcinogen, and is a vapour degreaser that was used to clean engine parts. The report stated that:

  • No records show that personal protective equipment (PPE) was made available to staff.
  • No records exist suggesting that any training on the dangers of using Triklone N took place.
  • Work areas were not segregated and doors to adjoining areas were left open.
  • Workers’ tea room and meeting area were located in an adjoining area, raising the risk of food being contaminated.
  • Workers clothes could have been contaminated as personnel lockers were located in the immediate area where the chemical was used.

Read more on the Irish Examiner website.

Dáil Éireann Written Answers 17/05/17 – Department of Defence – Protected Disclosures

Aengus Ó Snodaigh (Dublin South Central, Sinn Fein)

To ask the Taoiseach and Minister for Defence if he has received and read a recent protected disclosure on serious breaches of health and safety procedures at Casement Aerodrome, including claims that personnel have died prematurely as a result of handling hazardous chemicals without adequate protection from retired Air Corps personnel who worked on the base; and his plans to deal with these latest revelations. [23196/17]

Paul Kehoe (Wexford, Fine Gael)

There are a number of elements to the correspondence to which the Deputy refers. I am arranging for the elements of the correspondence which relate to previous protected disclosures concerning health and safety issues in the Air Corps to be sent to the independent third party I appointed last year to review those allegations. Legal advice has recently been received in respect of the correspondence referred to by the Deputy and is being considered.

Once a final review is to hand, I will determine any further steps required and ensure that all recommendations will be acted upon to ensure the safety of the men and women of the Air Corps.

Call for healthcare screening for Defence Forces members

Fianna Fáil has called on the Government to establish healthcare screening for members of the Defence Forces, as well as a health package for those who have suffered illnesses as a result of their exposures while working for the State.

The demand comes as it was confirmed Junior Defence Minister Paul Kehoe has written to Sinn Féin to confirm that military authorities cannot find inspection reports from the 1990s that raised concerns about the working environment at the Air Corps headquarters at Casement Aerodrome.

The confirmation came following attempts by this newspaper to have the documents released under the Freedom of Information Act.

The State is defending itself in a number of legal actions brought against it by Air Corps staff who say they are suffering illnesses as a result of their exposure to chemicals while working at Casement Aerodrome.

Fianna Fáil defence spokeswoman Lisa Chambers was critical of the Government’s approach to the matter.

“It is quite astonishing that the Department of Defence cannot locate these reports given I and others have seen copies of same,” Ms Chambers said.

“Simply saying they cannot be located is not good enough, there needs to be some explanation provided as to how these reports could have conveniently disappeared, given they point to serious health and safety issues at Casement Aerodrome dating back to the early 90s.

Read more on the Irish Examiner website.

Air Corps controversy: Minister says reports on toxicity at Baldonnel “can’t be found”

At least six people are taking action against the State for alleged exposure to chemicals whilst in the Air Corps.

Reports detailing the levels of toxicity in the air at Baldonnel Airfield have disappeared, The Journal.ie can reveal.

A letter seen by this publication, which was sent to a TD, says two reports into the measurement of potentially dangerous levels of carbon monoxide and other airborne toxins cannot be located by the Defence Forces.

The letter from Paul Kehoe, Minister of State with responsibility for Defence, reads:

“I have now been advised by the military that there was a report on measuring CO (Carbon Monoxide) fumes from aircraft compiled by Forbairt [which later became Enterprise Ireland] in 1995 and a further report on monitoring air contaminants in workshops in 1997 which was also compiled by Forbairt.

“In addition, an internal report was compiled by the Air Corps in 2014 in relation to a litigation case and in 2017, an occupational air survey was carried out by an independent environmental services company.

“Unfortunately, following an extensive search and their having consulted with Enterprise Ireland (which superseded Forbairt), I am advised by the military authorities that it has not been possible to locate the earlier Forbairt reports.”

Read more on The Journal website here.