In this study, we have described the largest group of hairdressers published to date referring to a clinical unit for suspected occupational asthma. We found that one half of these exposed workers had OA, which was caused by persulfate salts in most cases.
It is interesting to note that nearly half of the patients studied, although reporting symptoms at the work place, did not receive a diagnosis of asthma or OA. We hypothesize that their respiratory symptoms could be irritative and transitory, being related to the particular environment in hairdresser salons, where many irritating factors are often present (temperature, vapors, solvents, perfumes, and dust).
OA was associated with occupational rhinitis in 54.2% of cases, and in 52.4% of cases of persulfate asthma. These data confirm the association between asthma and rhinitis[35,36] also in this occupational sector. In our cases of persulfate asthma, rhinitic symptoms preceded bronchial symptoms in a percentage of cases lower than that reported by Munoz et al. This percentage, however, recalls previous findings of our group in a wide group of patients with OA due to low-molecular-weight (LMW) agents in Italy (32.7%). In three of the present cases, one due to persulfate, an isolated rhinitis without asthma was found; since rhinitis is considered an early marker of asthma, it could be interesting to follow up these patients to evaluate the possible development of asthma. A percentage of 38.1 of persulfate asthma cases was associated with occupational dermatitis, confirming the high frequency of contact dermatitis in hairdressers.
No difference was found between the patients with persulfate asthma and patients without concerning atopy and smoking habits. Similarly to previous studies, only half of patients with persulfate asthma were atopics, confirming that atopy is not an important risk factor in OA due to LMW agents.
In agreement with a previous study, our patients had been working as hairdressers for a long time before being referred to us for clinical investigation. The duration of exposure was not different between patients with or without persulfate asthma. Hairdressers are exposed to several risk factors, but we have no data on the levels of work exposure of our patients, particularly regarding the exposure to bleaching materials. Therefore, we cannot assume that similar duration of exposure means similar total dose of exposure.
Sensitization to LMW agents usually requires a shorter interval of time than sensitization to high- molecular-weight agents. In our patients with persulfate asthma, the latent period between the beginning of exposure and the onset of symptoms was longer than that reported in previous studies.[2,7,15,19] This could be due to the fact that hairdressers, particularly at the beginning of their employment, carry out a variety of tasks and might not be continuously exposed to the same agent, thus requiring a longer time for sensitization.
The time elapsed between the onset of symptoms and diagnosis was relatively short. The patients were seen in an early phase of the disease, and this finding may probably explain the absence of impairment in respiratory function.
In patients with persulfate asthma, the clinical history was highly suggestive, and the stop/resume test result was positive in all patients with a specific association with the job of bleaching in most patients, confirming that history is a key point in the diagnostic workup of OA. Nevertheless, the finding of a positive stop/resume test result also in 13 patients of the group who had a negative response to the SIC underlines that clinical history should be confirmed by objective means. However, it is remarkable that negative stop/resume test results have been found only in the SIC-negative subgroup; this finding strongly suggest a role of this test in predicting a negative outcome of the SIC.
The skin-prick test result with ammonium persulfate performed in a subgroup of patients with persulfate asthma, as confirmed by a positive SIC finding, was negative in all patients. Positive SPT results to persulfate salts have been reported in a variable proportion of the cases that have been published to date,[2,7,8,15,16,19] and also in exposed patients without symptoms. The method we used for SPTs is the same described by Wrbitzky et al in 1995, and similar to that reported by other authors;[15,19] thus, our negative results may not be accounted by a methodologic difference. Our findings cannot confirm the presence of an IgE mechanism in persulfate asthma, as suggested by previous authors.[16,19]
Sputum analysis is a noninvasive tool for measuring airway inflammation in asthma[42,43] and in OA.[22,44] In the present study, 70% of patients with persulfate asthma who underwent this test had an eosinophilic inflammation. Neutrophils remained in the normal range, as defined by Spanevello et al in both groups of patients (SIC positive and SIC negative), although a lower percentage of sputum neutrophils were found in SIC-positive patients) To our knowledge, there is only another report in the literature on airway inflammation in five cases of occupational asthma due to persulfate salts, in which only one patient had an eosinophilic inflammation; however, three of the remaining four patients had undergone a corticosteroid treatment, possibly reducing airway inflammation. Whether exposure to LMW agents results in a prevalent eosinophilic or neutrophilic airway inflammation is still a question of debate. Anees et al reported that among the OA patients sensitized to LMW agents enrolled in their study, only 36.8% had sputum eosinophilia, and that sputum eosinophils did not relate to the causative agents, duration of exposure, or lack of treatment. Lemiereetal found that sputum eosinophils were higher at baseline in patients with OA due to LMW agents compared to high-molecular-weight agents, suggesting that eosinophilic airway inflammation could be associated in these patients to the more frequent late asthmatic reaction. Otherwise, some authors reported a prevalent neutrophilic inflammation in patients with occupational asthma due to LMW agents both at baseline and after SIC.[49,50]
In previous studies, the challenge with persulfate salts has been carried out with different methods. In the article by Pepys et al and in more recent studies,[2,9,10,13] the occupational method was used, attempting to reproduce in the laboratory the conditions at the workplace. Macchioni et al exposed the patients to bleaching dust containing potassium and ammonium persulfate through a mask. Munoz et al[19,51] performed the test on consecutive days with increasing quantity of potassium persulfate mixed with lactose. The estimated concentration of this substance in the air was from 1 to 6 mg/μL. Other authors administered a solution of 1:50 weight/ volume potassium persulfate extract through a nebulizer. In our study, we described a new method of exposure to ammonium persulfate, which consists of nebulizing a solution of ammonium persulfate in an inhalation chamber. The method was designed and standardized in order to overcome two major pitfalls in currently used methods, eg, lack of reproducibility, related to tipping substances from one shelf to the other by the patients themselves (occupational methods), and costly and prolonged investigations, related to progressively increasing exposure over several consecutive days.
Considering that the threshold limit value (TLV)/ short time exposure limit for ammonium persulfate is not known, and that no data are available in the literature on the levels of exposure at the workplace, we took as a reference the TLV/time-weighted average (TWA). This is the value below which no health effect should be suffered by a normal worker exposed for 8 working h, 5 d/wk, over his/her lifetime. In order not to exceed the maximal total daily dose (calculated by TLV-TWA for 8 h), we considered that for an exposure of 30 min the maximal allowable concentration should be lower than 16 times the TLV-TWA (1.6 mg/μL). For safety reasons and in order to reduce as much as possible triggering of asthma through an irritative mechanism, we further reduced the concentration in the inhalation chamber to approximately 1 mg/μL. This method of exposure is simple and technically more reproducible than those employed up to now. It has proved effective in distinguishing responders and nonresponders with the cutoff of FEV1 fall of 20% (Fig 1). It has also proved devoid of any irritative effects in all patients (responders and nonresponders, with or without bronchial hyperreactivity). Finally, it has proved safe, being all bronchial responses, including the most severe, progressive in their onset and promptly reversed after inhaled bronchodilator.
Similarly to most previous studies,[2,7,10,11,15,18,19] a late response was the most frequently observed, which was isolated in 14 of 21 cases and associated with an early component (dual response) in 3 other cases. These findings are in agreement with the clinical histories of our patients, who reported a late onset of symptoms, most frequently 1 h after the beginning of the working day. The degree of bronchial response to persulfate inhalation was moderate (maximal FEV1 fall of 29%), and in no case were medications needed to reverse the bronchoconstriction, showing the safety of the inhalation method we used. The finding that the time onset of the late component both in late and in dual responses negatively correlated with the overall duration of exposure suggests that patients with a longer duration of exposure have a higher degree of underlying airway inflammation.
Regarding the mechanisms involved in persulfate asthma, our findings of a positive response to the SIC in only a proportion of exposed workers, the presence of a latent period between first exposure and the onset of symptoms, the relatively low prevalence of atopy, and the high frequency of association of asthma with other diseases such as dermatitis and rhinitis suggest the involvement of an immunologic mechanism. However, the finding of negative responses to the SPT with ammonium persulfate and of an isolated late response in most cases tends to exclude an IgE-mediated mechanism. An underlying IgE mechanism in persulfate asthma has been suggested by other authors,[16,19] and previous findings by our group of an anaphylactoid reaction to patch testing with ammonium persulfate also supported the hypothesis of the involvement of an IgE-mediated mechanism. Nevertheless, specific IgE has not been found in the serum of patients with respiratory diseases to persulfate salts, nor any other specific serum Ig. Other non IgE mechanisms have been suggested. Blainey et al found a significant increase in neutrophil chemotactic activity after challenge with bleach powder, suggesting the involvement of mast cells. In the Italian study by Pisati et al, the bronchial response to the SIC with bleaching powder was inhibited by previous administration of disodium cromoglycate, also suggesting the involvement of mast cells in the bronchial response. The mechanism by which mast cells activation may occur in persulfate asthma is not understood. A study on animal mast cell preparation has shown that persulfate salts can release histamine directly, but this finding cannot explain why only some individuals are affected. Yawalkar et al suggested a role of T cells both in cutaneous and in respiratory and rhinoconjunctival reactions to persulfate salts. Nevertheless, at present, the mechanism of asthma due to persulfate salts still remains unknown and requires further studies.
In conclusion, in the present study we have described the characteristics of the largest group of hairdressers with work-related respiratory symptoms published to date, finding that half of them had OA and rhinitis due to persulfate salts. The lack of difference in the duration of exposure to bleaching agents before the onset of symptoms in the two groups of patients (sensitized vs nonsensitized) suggests that sensitization to persulfate salts may be more related to an individual hypersusceptibility than to environmental factors, although evaluation of more accurate markers of exposure, ie, air concentrations, in the workplace are needed to confirm this hypothesis.
Although some observations suggest an underlying immunologic mechanism, we cannot confirm the involvement of an IgE-mediated mechanism for persulfate salt-induced asthma. Therefore, we confirm that the SIC is the "gold standard" for the diagnosis of persulfate asthma.
BSA = bovine serum albumin; LMW = low molecular weight; OA = occupational asthma; 20 = provocative dose of methacholine causing a 20% fall in FEV1;SIC = specific inhalation challenge; SPT = skin- prick test; TLV = threshold limit value; TWA = time-weighted average
Gianna Moscato, MD, Servizio di Allergologia e Immunologia Clinica, Fondazione Salvatore Maugeri, IRCCS, Localita` Cravino, 27100 Pavia, Italy; E-mail: gmoscato@ fsm.it .
CHEST. 2005;128(5):3590-3598. © 2005 American College of Chest Physicians
Cite this: Occupational Asthma and Occupational Rhinitis in Hairdressers - Medscape - Nov 01, 2005.