Occupational Medicine 2015;65:165–168Advance Access publication 20 December 2014 doi:10.1093/occmed/kqu183

© The Author 2014. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Cough-variant asthma: a diagnostic dilemma in the occupational setting

A. Lipińska-Ojrzanowska, M. Wiszniewska and J. Walusiak-Skorupa

Department of Occupational Diseases and Clinical Toxicology, Nofer Institute of Occupational Medicine, 91-348 Lodz, Poland.

Correspondence to: A. Lipińska-Ojrzanowska, Department of Occupational Diseases and Clinical Toxicology, Nofer Institute of Occupational Medicine, 8 Teresy St, 91-348 Lodz, Poland. Tel: +48 (42) 631 4769; fax: +48 (42) 631 4764; e-mail: lipinska@imp.lodz.pl

Background Cough-variant asthma (Corrao’s syndrome) is defined as the presence of chronic non-productive cough in patients with bronchial hyperresponsiveness (BHR) and response to bronchodilator ther-apy. This variant of asthma may present a diagnostic problem in occupational medicine.

Aims To describe additional evaluation of cough-variant asthma in a cyanoacrylate-exposed worker in whom standard diagnostic testing was negative.

Methods A female beautician was evaluated for suspected occupational allergic rhinitis and asthma. A specific inhalation challenge test (SICT) was performed with cyanoacrylate glues used for applying artifi-cial eyelashes and nails. Spirometry and peak expiratory flow (PEF) measurements were recorded hourly for 24 h; methacholine challenge testing was performed and nasal lavage (NL) samples were analysed for eosinophilia.

Results After SICT, the patient developed sneezing, nasal airflow obstruction and cough. Declines in forced expiratory volume in 1 s and PEF were not observed. Eosinophil proportions in NL fluid increased markedly at 4 and 24 h after SICT. A significant increase in BHR also occurred 24 h after SICT.

Conclusions Clinical symptoms, post-challenge BHR and increased NL eosinophil counts confirmed a positive response to SICT and validated the diagnosis of cough-variant occupational asthma. SICT may be useful in cases where history and clinical data suggest cough-variant asthma and spirometric indices are negative.

Key words Beautician; Corrao’s syndrome; cough-variant asthma; inhalation challenge test; occupational asthma; sensitization to cyanoacrylates.

Introduction

In 1979, Corrao et al. [1] described six patients suffering from chronic cough without wheezing who had baseline normal lung function but evidence of bronchial hyper-responsiveness (BHR). Cases with cough, BHR and a good clinical response to bronchodilator therapy were recognized as a cough variant of asthma, also known as Corrao’s syndrome. Since then, the natural history of this asthma variant has been more completely described [2]. Traditional pulmonary function testing in the workplace, including serial peak expiratory flow (PEF) and forced expiratory volume in 1 s (FEV1) monitoring, are consid-ered standard diagnostic tools for occupational asthma (OA) [3]. However, false-negative results may occur in cough-variant OA.

A number of reports describing occupational sensiti-zation to cyanoacrylates [4–6], in conjunction with their

increasingly common use in beauty salons, underscores the importance of attention to the health hazards of these materials and recognition of associated disorders. In this report, we describe a case of cough-variant asthma in a female beautician reporting work-related respiratory symptoms linked to cyanoacrylates in glues used for application of artificial eyelashes and nails.

Case report

A 27-year-old non-smoking woman who had been work-ing for 3 years as a self-employed beautician developed sneezing, nasal congestion and a persistent dry cough. Review of material safety data sheets identified the follow-ing materials in glues used for cosmetic procedures: ethyl 2-cyanoacrylate, alkoxy-2-cyanoacrylate, poly methyl methacrylate, carbon black and 1,2-dihydroxybenzene. The patient completed a detailed questionnaire on

Case report

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medical history and relationship between symptoms and work exposure and a physical examination, a chest radio-graph and skin prick testing (SPTs) to common aller-gens with commercial available extracts (Allergopharma, Germany and Stallergenes, France) were performed. Spirometric testing and methacholine inhalation chal-lenge tests were performed using MasterScope PC spirometer equipment (Jaeger, uSA). The patient under-went a single-blind, placebo-controlled and specific inhalation challenge test (SICT) with cyanoacrylates. The control challenge involved nebulizing 2 ml of 0.9% saline. Two days later, the patient applied cyanoacrylate glues to a glass surface for 120 min in a 6 m3 chamber.

Nasal lavage (NL) samples were collected before the SICTs as well as 4 and 24 h afterwards. During the 24 h post-challenge period, hourly spirometry, PEF and peak nasal inspiratory flow (PNIF) measurements were monitored with 8 h allotted for a night’s rest. BHR was assessed in 24th hour after the specific challenge.

Ethical approval for the study was granted by the Bioethical Committee at the Nofer Institute of Occupational Medicine in Lodz (decision number 20/2011) and informed consent was obtained from the patient prior to the procedures.

Questionnaire data indicated a strong positive associa-tion between the patient’s sneezing and cough and her

Figure 1. Hourly PEF (litre) and FEV1 (litre) recording (upper panel) and peak nasal inspiratory flow (PNIF; l/min) (lower panel) before (0*) and after specific inhalation challenge test (SICT; with placebo and cyanoacrylate glues). *Measurement performed 15 min before SICT.

Table 1. Cytological analysis of NL samples collected before SICT and 4 and 24 h after SICT with placebo and with cyanoacrylate glues

Time point % of cells in NL

Epithelial cells Neutrophils Eosinophils Basophils Lymphocytes Monocytes

Before SICT 2 94 3 0 0 14 h after SICT with placebo 12 83 2 0 3 124 h after SICT with placebo 8 86 1 0 5 04 h after SICT with cyanoacrylates 33 10 57 0 0 024 h after SICT with cyanoacrylates 9 13 76 1 1 0

A. LIPIńSkA-OJRzANOwSkA et al.: COuGH-VARIANT ASTHMA IN A BEAuTICIAN 167

presence in the work environment. She was symptom-free on weekends and holidays. A  physical examina-tion and chest X-ray did not reveal any abnormalities. SPTs to common allergens were negative. The baseline spiro metry values were within normal predicted limits. Baseline inhalant methacholine challenge test showed borderline non-specific BHR (with marked provocative methacholine concentration PC20 = 8 mg/ml).

Placebo inhalation challenge testing produced no clin-ical or cytological changes. Spirometric measurements, PEF and PNIF values (Figure 1) and eosinophil counts in NL samples showed no significant changes (Table 1). Methacholine-induced BHR after the placebo-inhalant test did not increase (PC20 = 9.2 mg/ml).

One hour after the SICT with cyanoacrylate glues, the patient reported sneezing and nasal obstruction. Two hours later, a non-productive cough was noted. A dual-phase nasal reaction with a 35% fall in PNIF 4 h after challenge and a 60% drop at 10 h was observed (Figure 1, lower panel). Neither FEV1 nor PEF fell >15% during the 24 h post-challenge (Figure 1, upper panel). An air-ways allergic reaction was demonstrated by the signifi-cant increase of eosinophilic cell counts in NL samples at 4 and 24 h after the SICT (Table 1). BHR significantly increased with a PC20 = 0.9 mg/ml. we concluded that the combination of nasal symptoms and dry cough with increased BHR after exposure to cyanoacrylates estab-lished a diagnosis of occupational allergic rhinitis and cough-variant asthma.

Discussion

The increase in cyanoacrylate use in cosmetic procedures has increased hazards to workers’ health in the beauty industry. A  3-fold increased risk of OA development among beauticians who work with cyanoacrylates has been reported [6]. OA as well as eosinophilic inflamma-tion and marked reduction in pulmonary function have been observed after exposure to cyanoacrylate [4–6]. To our knowledge, the current report is the first of cough-variant OA arising from cyanoacrylate exposure.

The principal limitation of our study was lack of analysis of airborne vapour distribution in the subject’s breathing zone while working. Moreover, although we were not able to obtain a sample of sputum from the patient for analysis, based on the involvement of both the upper and lower respiratory tracts [7], we can indirectly conclude on the basis of the NL sample analysis that the same inflammatory process is occurring in both.

Although the patient’s dry cough was related to the work environment, the presence of an occupational air-ways allergy was not irrefutable. Questionnaire data are considered as sensitive but not highly specific tools for detecting OA [8]. PEF shows reproducibility and sen-sitivity similar to well standardized FEV1, but is more dependent on subject effort [9]. Pulmonary function

tests performed at the workplace may not be a sufficient diagnostic tool in occupational Corrao’s syndrome [3] because they may result in false-negative findings. A sig-nificant increase in post-SICT BHR provides evidence of positive clinical asthmatic response when changes in FEV1 are indeterminate [10].

In conclusion, inhalation challenge testing performed under controlled conditions is the most useful diagnostic test in the assessment of potential occupational cough-variant asthma. SICT may be advisable in cases where history and other clinical data indicate a likely relationship between cough and other respiratory symptoms and work exposures, when pulmonary function tests are negative.

Funding

Polish National Centre of Science (DEC-2011/03/N/Nz7/06284).

Conflicts of interest

None declared.

References

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5. Quirce S, Baeza ML, Tornero P, Blasco A, Barranco R, Sastre J. Occupational asthma caused by exposure to cyanoacrylate. allergy 2001;56:446–449.

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7. Bourdin A, Gras D, Vachier I, Chanez P. upper airway x 1: allergic rhinitis and asthma: united disease through epithe-lial cells. thorax 2009;64:999–1004.

Key points

• widespread use of cyanoacrylates in cosmetic procedures has resulted in increased work-place health hazards among beauty industry workers.

• Specific inhalation challenge testing may be the only reliable method of diagnosing occu-pational cough-variant asthma.

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8. Becklake M, Malo J, Chen-Yeung M. Epidemiological approaches in occupational asthma. In: Bernstein I, Chen-Yeung M, Malo J, Bernstein D, eds. asthma in the Workplace. New York: Marcel Dekker, 1999; 27–65.

9. weytjens k, Malo JL, Cartier A, Ghezzo H, Delwiche JP, Vandenplas O. Comparison of peak expiratory flows and

FEV1 in assessing immediate asthmatic reactions due to occupational agents. allergy 1999;54:621–625.

10. Vandenplas O, Suojalehto H, Aasen TB et al.; ERS Task Force on Specific Inhalation Challenges with Occupational Agents. Specific inhalation challenge in the diagnosis of occupational asthma: consensus statement. eur Respir J 2014;43:1573–1587.