My Personal Story - by John Lea: Richardson/Burge Paper
Occupational asthma due to indirect exposure to lauryl dimethylbenzyl ammonium chloride, used in a floor cleaner.
Occupational Lung Disease Unit
East Birmingham Hospital
Bordesley Green East
Birmingham B9 5ST, UK
We describe the case of a pharmacist who developed severe occupational asthma threatening his continued employment, confirmed with serial measurement of peak expiratory flow at home and work. The cause was found to be the cleaning agent used in his office when it was unoccupied. Bronchial challenge testing identified lauryl dimethylbenzyl ammonium chloride, a constituent of the floor cleaner, as the specific agent to which he was sensitised. Substitution of the floor cleaner lead to a substantial improvement in his asthma, confirmed with repeated serial peak flow measurements.
A number of cleaning agents and biocides have been described as causes of occupational asthma, including chlorhexidine,(l-3) , glutaraldehyde (4,5), formaldehyde (6-9), isothiozolinones (10) and chloramine T (11-14). All cases described so far have been in those using these chemicals. It is possible that the protein denaturing properties of these chemicals is the method by which sensitisation occurs, creating neo-antigens from human proteins; their chemical dissimilarity would favour such a mechanism.
Methods and Results.
An administrative hospital pharmacist had his first attack of asthma at the age of 22 following a spill of chloroxylenol on the floor. The attack was associated with cyanosis, it lasted a few hours. He noticed that symptoms would return on contact with trichlorophenol. His asthma remitted until one year after moving to a new pharmacy, containing a clean-room manufacturing area. It became progressively worse over the next six years requiring several periods off work. It became more severe as the working week progressed, and improved at weekends and holidays. Thursdays were often his worst day, despite working similar hours on Fridays. It would start noticeably on the second working day after about three hours at work, associated with running eyes end aching in the limbs with a sensation of fever, although the temperature was normal when he measures it. Symptoms would often wake him from sleep. He had been a county standard long distance runner in his teens. Spirometry and gas transfer measurements were all above predicted in the clinic. Skin prick tests to common environmental allergens were negative, total IgE was less than 25ku/l and total IgA reduced at 0.7G/1. Histamine reactivity on a day away from work was increased at 0.9umol (normal >8) by the Yan method. Two hourly recording of peak expiratory flow at home and work showed clear occupational asthma (Fig1).
We searched for a cause in his pharmacy. His work was largely in his office, with some visits to the wards. The building was air-conditioned, but the humidifier was not used There was no handling of bulk ispaghula or enzyme preparations. The floor of the whole pharmacy was cleaned with a biocidal cleaner, usually on Wednesdays. Substitution of this cleaner with a general detergent, initially unknown to him, resulted in substantial improvement in his asthma. He was admitted for bronchial provocation testing, staying in an individual room with the floor cleaned with plain water only. The biocidal floor cleaner contained two biocides, one of which was lauryl dimethyl benzyl ammonium chloride, as well as two colourants, a perfume and two non-ionic surfactants. Histamine reactivity was 6.5umol on admission. On separate days challenges were carried out by putting one ml of a 1:400 dilution in water of each ingredient onto a gauze in front of him for one minute. There was no reaction following exposure to the detergent cleaner. Exposure to the commercial biocidal cleaner caused a small immediate reaction, followed by chills, wheeze and breathlessness maximal 9 hours post challenge (Fig 2). This was reproduced the next day with exposure to lauryl dimethylbenzyl ammonium chloride. There was no immediate reaction, but a significant late asthmatic reaction starting at 7 hours, with a fall in FEV1 from 4.1 to 2.31 litres. On the final day all the other constituents including the second biocide were mixed. There was no reaction following this challenge. Subsequent return to work, with use only of the detergent cleaner in the pharmacy, lead to substantial resolution of symptoms (Fig1), Five months later Histamine reactivity was >8umol, but one year later was 4umol, associated with the reemergence of minor symptoms which appeared work related.
Benzylkonium chloride is the name given to a group of biocides with the general formula alkyl dimethyl benzyl ammonium chloride, the present biocide contains the lauryl derivative. There has been one previous report of occupational asthma from benzylkonium chloride in a laundry worker (15) with a dual reaction following challenge, blocked by sodium cromoglycate. The same material has been implicated in the transient wheeze seen following atrovent nebulisation from multidose vials (16,17). The exposure in our patient was indirect, as he never handled the substance himself, suggesting that his exposure was very low. This, together with the near normal histamine reactivity prior to challenge, the very small exposure given, and the pronounced late asthmatic reaction seen, suggests that the mechanism was of hypersensitivity rather than irritancy in our patient, although the reactions in asthmatics following nebulisation are usually more characteristic of an irritant mechanism.
Click for a larger version of Fig 1 left section
Click for a larger version of Fig 1 right section
Plot of daily maximum (top line), mean (middle line) and minimum (bottom line) peak expiratory flow carried, out approximately two hourly from waking to sleeping. Days at work have a shaded background, days away from work a clear background. The [left] section shows the record when the floor cleaner contained lauryl dimethylbenzyl ammonium chloride. There is progressive deterioration in the first, third and fifth workweeks, with irregular deterioration in the fourth and sixth workweeks. There is definite improvement in four weekends and equivocal improvement in one; peak flow varies from 420-680 i/min, The [right] section shows a similar record when his floor was cleaned with detergent. There is a single day at work with deterioration, peak flow varies from 570-660.
Click for a larger version of Fig 2 left section
Click for a larger version of Fig 2 right section
Bronchial provocation testing showing in the [left] section stable FEV1 following exposure to the detergent cleaner and a predominately late reaction to the cleaner containing biocides. The [right] section shows a specific late asthmatic reaction to the lauryl dimethyl benzyl ammonium chloride, maximal 10 hours post challenge, with no reaction after exposure to another constituent of the cleaner.
Abstract of Richardson/Burge Paper
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