Persistence of Toluene Diisocyanate-Induced Asthma Despite Negligible Workplace Exposures: DISCUSSION
Five of the six workers with TDI-induced asthma were moved to areas with negligible TDI exposures. Worker 3 developed asthma while working in an area thought to have negligible or no exposure. The need for less or additional asthma therapy in these six workers was not predictable. Although bronchial responsiveness persisted in these six subjects, there was no clear trend toward increasing or decreasing responsiveness during this study. The lung function changes of these asthmatic subjects showed changes similar to the bronchial responsiveness measurements. The TDI exposures for the asthmatic group were minimal and significantly less than exposures in the rest of the workplace, implying that these workers were segregated from the main work force. Mean TWA for the asthmatic group was less than 5 percent of the Occupational Safety and Health Administration permissible exposure limit of 20 ppb, yet chest symptoms and bronchial hyperresponsiveness persisted.
The natural history of TDI-induced asthma is not clearly defined. Two case reports have shown resolution of airway hyperresponsiveness to TDI by specific inhalation challenge tests. Butcher et al reported a worker with TDI-induced asthma who lost bronchial hyperresponsiveness to methacholine 11 months after leaving the workplace and TDI reactivity within two years after ceasing TDI exposure. Banks and Rando reported a worker who had recovered from the symptoms of TDI-induced asthma after five years and was specific challenge-test-negative after 11 years.
Numerous investigators have studied workers to assess the outcome of occupationally induced asthma. The results have not been uniform. A study by Hudson et al showed a reasonably good outcome for TDI- induced asthma. This group reported 63 workers with occupational asthma caused by numerous agents for at least six months after ceasing exposure. Resolution of symptoms appeared to depend on the causative agent. In general, those with snow crab- and TDI- induced asthma did better (only two of ten with isocyanate-induced asthma had persistent symptoms), while those with Western red cedar-induced asthma did poorly. A later study done by this group specifically addressed the outcome of snow crab-induced asthma approximately five years post-diagnosis. At follow- up, 10 of 31 workers sensitized to snow crab required asthma medication (primarily beta agonist inhalers); only two of 31 had an FEV1 less than 80 percent predicted; yet bronchial hyperresponsiveness persisted, but declined, in the majority of participants. Since outcome of occupational asthma may be related to the agent causing asthma or the mechanism by which it occurs, it may be difficult to extrapolate the work of Chan-Yeung et al showing the relatively poor outcome of asthma due to Western red cedar and that of Burge regarding the poor respiratory fate of asthma induced by colophony to the outcome associated with isocyanate-induced asthma.
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Yet, most studies reflect the poor outcome of isocyanate-induced asthma. Paggiaro et al studied 27 workers with TDI-induced asthma approximately two years after diagnosis. Although symptoms of dyspnea and wheeze were less frequent in the 12 that had left the industry, only four were without respiratory symptoms. In just one of 15 who remained in the workplace did resolution of respiratory complaints occur. More than half who remained developed chronic cough with phlegm. No data stating whether those who remained in the workplace were moved to jobs associated with lesser TDI exposures was provided.
Moller et al reported seven workers with TDI- induced asthma. In six, asthma persisted for as long as 12 years (mean, 4.5 years) despite leaving the workplace. Lozewicz et al suggested many with isocyanate-induced asthma persist with respiratory complaints. Forty-one of 50 workers away from isocya- nate exposure for at least four years continued with respiratory complaints and 22 required respiratory medication at least once weekly. In these workers, the frequency of complaints was similar among workers who had left the workplace and in those who had relocated in their original workplace to jobs without recognized direct isocyanate exposures.
Only one study measuring TDI sensitivity both at diagnosis and follow-up has been reported. Mapp et al reported repeat testing of 35 workers with TDI- induced asthma at a mean follow-up of ten months.
Eight of 30 who had left the workplace lost TDI reactivity at follow-up testing. Five who remained in the same jobs had persistent asthma. Those who recovered from TDI sensitization were younger, had a shorter duration of exposure and symptoms prior to diagnosis and were more likely to have either an immediate or dual asthmatic response. At follow-up, those who recovered had significantly less bronchial responsiveness to methacholine and a significant increase in FEVp. eriacta 100 mg
We recognize the outcome of isocyanate-induced asthma to be variable. It is possible that respiratory symptoms of these six subjects would have persisted despite ceasing exposure. Although we could not have predicted asthma outcome had these workers left the workplace and ceased isocyanate exposure entirely, occupational asthma persisted despite negligible TDI exposures. It appears that the best chance for altering the outcome of isocyanate-induced asthma is avoidance of further workplace exposure to this sensitizing agent.