Sputum Inflammatory Patterns are Associated with Distinct Clinical Characteristics in Subjects with Occupational Asthma Independently from the Causal Agent.

BACKGROUND AND OBJECTIVES: Clinical heterogeneity in sensitizer-induced occupational asthma (OA) and its relationship to airway inflammatory profiles remain poorly elucidated. To further characterize the interactions between induced sputum inflammatory patterns, asthma-related outcomes and the high- or low-molecular-weight category of causal agents in a large cohort of subjects with OA. METHODS: This multicenter, retrospective, cross-sectional study was conducted among 296 subjects with OA ascertained by a positive specific inhalation challenge who completed induced sputum assessment before and 24 hours after challenge exposure. RESULTS: Multivariate logistic regression analysis revealed that sputum eosinophilia ≥3% was significantly associated with a high dose of inhaled corticosteroid (odds ratio [95% confidence interval], 1.31 [1.11-1.55] for each 250-µg increment in daily dose), short-acting b2-agonist use less than once a day (3.54 [1.82-7.00]), and the level of baseline nonspecific bronchial hyperresponsiveness (mild: 2.48 [1.21-5.08]); moderate/severe: 3.40 [1.44-8.29]). Sputum neutrophilia ≥76% was associated with age (1.06 [1.01-1.11]), male gender (3.34 [1.29-9.99]), absence of corticosteroid use (5.47 [2.09-15.16]), short-acting b2-agonist use once or more a day (4.09 [1.71-10.01]), ≥2 severe exacerbations during the last 12 months at work (4.22 [1.14-14.99]), and isolated early reactions during the SIC (4.45 [1.85-11.59]). CONCLUSIONS: The findings indicate that sputum inflammatory patterns in subjects with OA are associated with distinct phenotypic characteristics and further highlight the differential effects of neutrophils and eosinophils on asthma-related outcomes. These associations between inflammatory patterns and clinical characteristics share broad similarities with what has been reported in nonoccupational asthma and are not related to the type of causal agent.

Occupational exposure to cytostatic fumes during hyperthermic intraperitoneal chemotherapy.

Hyperthermic intraperitoneal chemotherapy (HIPEC)-heated, intra-abdominal chemotherapy-has become the treatment of choice for treating peritoneal metastases from ovarian, stomach or colorectal cancers. HIPEC has several advantages and disadvantages. The major benefit is minimal systemic toxicity for the patient, but there is a risk of occupational exposure for operating room staff. We have not found any reports of workers with chronic aplastic anaemia as a result of exposure to cytostatic fumes during HIPEC. The aim of this case report is to raise the awareness of potential negative health effects of inhalation exposure to cytostatic drugs. We present a rare case of a 43-year-old woman, suffering from aplastic anaemia as a long-term consequence of exposure to cytostatics. During the HIPEC procedure, surgical revision of the peritoneal cavity was undertaken which resulted in release of cytostatic fumes. Despite awareness of the health effects of occupational exposure to cytostatic drugs and well-developed procedures for safely handling them, unexpected exposure may occur causing serious medical conditions. These may develop in sensitive subjects although accidental high-level exposure may lead to unexpected long-term consequences in all workers. Medical staff need to be informed of the risks of HIPEC and safety guidelines to reduce the risk of exposure.

Predicting occupational allergy in culinary and hairdressing apprentices.

BACKGROUND: Apprentices are usually exposed to the same workplace agents as qualified professionals. There is therefore a risk of the development of occupational allergy in apprentices exposed to high (HMW-A) and low molecular inhalant allergens (LMW-A). AIMS: To evaluate and compare the occurrence of work-related allergy-like symptoms in apprentices exposed to HMW-A and LMW-A in a culinary and hairdressing school during the first and second year of vocational training. METHODS: We asked culinary and hairdressing apprentices in their first and second year of vocational training to complete a questionnaire about work-related allergy-like symptoms. In first-year apprentices, we undertook spirometry, skin prick tests for occupational allergens and blood tests for allergen-specific Immunoglobulin E (IgE) antibodies. RESULTS: Hypersensitivity to occupational allergens was more frequent in first-year apprentices exposed to HMW-A compared to LMW-A (P < 0.05). Apprentices exposed to LMW-A reported increasing occurrence of skin disorders and upper respiratory tract symptoms between the first and second years of training. First-year apprentices exposed to HMW-A more frequently reported rhino-conjunctivitis and dyspnoea (approximately P < 0.001 and P < 0.05) and those exposed to LMW-A more often reported skin symptoms (P < 0.05). CONCLUSIONS: Periodic skin and respiratory health surveillance for apprentices exposed to LMW-A or HMW-A might help with early identification and management of occupational allergy.

Subclinical chronic left ventricular systolic dysfunction resulting from phosphine poisoning.

We present a case of a 32-year-old male crew member of a cargo ship, accidentally exposed to phosphine, a fumigating substance. He and other crew members developed increasing fatigue and digestive disorders 24 h later; two died from acute pulmonary oedema. The patient was admitted to hospital, where bilateral pneumonia, acute nephritis, hepatopathy, electrolyte imbalance and leucopenia were diagnosed. He was discharged from hospital 3 weeks later. He was examined 4 months later for possible chronic consequences of acute phosphine poisoning, which included echocardiography showing normal heart size and cardiac function. However, on advanced quantitative analysis, using two-dimensional speckle tracking echocardiography, depressed global longitudinal strain was found. Our report extends previously published findings of phosphine-induced left ventricular (LV) dysfunction by demonstrating that subclinical myocardial dysfunction resulting from acute phosphine exposure may persist several months after the exposure in an otherwise asymptomatic patient, and potentially may not be entirely reversible. The persistence of subclinical abnormalities of LV longitudinal function can be diagnosed using the advanced quantitative echocardiographic analysis we describe.

How to diagnose mould allergy? Comparison of skin prick tests with specific IgE results.

BACKGROUND: Diagnosis of mould allergy is complicated due to the heterogeneity of the test material and the decrease in the number of commercial mould skin test solutions that are currently available. OBJECTIVES: The aim of this study was to compare skin prick tests (SPT) from different manufacturers to one another and concurrently with sIgE tests for Aspergillus fumigatus (Asp f), Cladosporium herbarum (Cla h), Penicillium chrysogenum (Pen ch), Alternaria alternata (Alt a) and Aspergillus versicolor (Asp v) to ascertain a feasible diagnostic procedure for mould sensitization. METHODS: In this multi-centre study, 168 patients with mould exposure and/or mould-induced respiratory symptoms were included. Mould SPT solutions were analysed biochemically and tested in duplicate on patients' arms. Specific IgE (sIgE) concentrations to corresponding mould species and mould mix (mx1) were measured by ImmunoCAP. SPTs in accordance with one another and with sIgE were further considered. The test efficiency was calculated using receiver-operating characteristic (ROC) analysis. RESULTS: Mould sensitization was more frequently detected by the SPT (90 of 168) than by the sIgE tests (56 of 168). Concordances of double SPT positives were only sufficient (≥ 80%) for environmental allergens, two Asp f and three Alt a SPT solutions, whereas all other mould solutions revealed concordances < 80%. The antigen content of SPT solutions was positively associated with concordant SPT double values as well as with sIgE. Taking sIgE as the 'positive standard', all mould SPT solutions revealed test efficiencies > 80%, but varied up to 20% in sensitivity and positive predictive value with the exception of Alt a. CONCLUSIONS: SPT solutions are sensitive and essential diagnostic tools for the detection of mould sensitization. Our recommendation for diagnosis would be to test at least Alt a, Asp f and Pen ch using SPT and additional sIgE test to mx1.

Occupational hypersensitivity pneumonitis: an EAACI position paper.

The aim of this document was to provide a critical review of the current knowledge on hypersensitivity pneumonitis caused by the occupational environment and to propose practical guidance for the diagnosis and management of this condition. Occupational hypersensitivity pneumonitis (OHP) is an immunologic lung disease resulting from lymphocytic and frequently granulomatous inflammation of the peripheral airways, alveoli, and surrounding interstitial tissue which develops as the result of a non-IgE-mediated allergic reaction to a variety of organic materials or low molecular weight agents that are present in the workplace. The offending agents can be classified into six broad categories that include bacteria, fungi, animal proteins, plant proteins, low molecular weight chemicals, and metals. The diagnosis of OHP requires a multidisciplinary approach and relies on a combination of diagnostic tests to ascertain the work relatedness of the disease. Both the clinical and the occupational history are keys to the diagnosis and often will lead to the initial suspicion. Diagnostic criteria adapted to OHP are proposed. The cornerstone of treatment is early removal from exposure to the eliciting antigen, although the disease may show an adverse outcome even after avoidance of exposure to the causal agent.

Sensitization to xylanolytic enzymes: an underestimated health hazard among bakers.

BACKGROUND: The most important occupational allergens in baking include flour and enzymes, especially α-amylase. Although xylanolytic enzymes have previously been described as sensitizers, they may be overlooked during assessment of bakery workers with work-related symptoms. AIMS: To report a case of a baker who suffered from work-related respiratory, ocular and skin symptoms as a consequence of sensitization to xylanolytic enzymes. METHODS: Physical examination, chest X-ray, routine laboratory tests, skin prick tests (SPTs) with common and occupational allergens (wheat, pearl, rye, corn and oat flours, α-amylase, bakery adjuvants) and spirometric measurements, as well as assessments by a laryngologist, dermatologist and ophthalmologist were performed. Specific IgE (sIgE) to occupational agents were evaluated for flours, α-amylase, xylanase, cellulose and glucoamylase. Specific inhalation challenges (SICs) with flours and bakery adjuvants were carried out. RESULTS: Hypersensitivity to Aspergillus moulds, flours and α-amylase was confirmed in SPTs; however, SIC with those agents gave a negative result. Further investigation revealed the presence of sIgE to xylanolytic enzymes. During SIC with bakery adjuvants, allergic skin, ocular and respiratory symptoms occurred and were confirmed by objective assessment. CONCLUSIONS: In the assessment of work-related allergic symptoms in bakers, sensitization to xylanolytic enzymes should be considered. Completion of diagnostic procedures having excluded asthma and rhino-conjunctivitis related to flour hypersensitivity might result in a false-negative assessment.

Anaphylactic reaction in a hairdresser due to sensitization to persulphates.

Severe occupational systemic reactions to persulphates have rarely been described and if so mainly after skin contact with bleaching products. We report the first case of a hairdresser with an allergy to persulphates obtained during professional work, who developed anaphylaxis caused by persulphates present in dental cement during dental treatment. This case documents that sensitization to occupational allergens can induce severe systemic reactions outside the workplace. Additionally, it also recommends the need for greater awareness of medical professionals, including dentists, of the possibility of anaphylaxis in patients with occupational allergy.

Occupational anaphylaxis--an EAACI task force consensus statement.

Anaphylaxis is a systemic allergic reaction, potentially life-threatening that can be due to nonoccupational or, less commonly, to occupational triggers. Occupational anaphylaxis (OcAn) could be defined as anaphylaxis arising out of triggers and conditions attributable to a particular work environment. Hymenoptera stings and natural rubber latex are the commonest triggers of OcAn. Other triggers include food, medications, insect/mammal/snake bites, and chemicals. The underlying mechanisms of anaphylactic reactions due to occupational exposure are usually IgE-mediated and less frequently non-IgE-mediated allergy or nonallergic. Some aspects of work-related allergen exposure, such as route and frequency of exposure, type of allergens, and cofactors may explain the variability of symptoms in contrast to the nonoccupational setting. When assessing OcAn, both confirmation of the diagnosis of anaphylactic reaction and identification of the trigger are required. Prevention of further episodes is important and is based on removal from further exposure. Workers with a history of OcAn should immediately be provided with a written emergency management plan and an adrenaline auto-injector and educated to its use. Immunotherapy is recommended only for OcAn due to Hymenoptera stings.

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

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 therapy. 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 artificial eyelashes and nails. Spirometry and peak expiratory flow (PEF) measurements were recorded hourly for 24h; 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 24h after SICT. A significant increase in BHR also occurred 24h 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.

EAACI Position Paper on assessment of cough in the workplace.

Cough is a nonspecific and relatively common symptom that can present difficulties in diagnosis and management, particularly when it is reported to be associated with the workplace. The present consensus document, prepared by a taskforce of the Interest Group on Occupational Allergy of the European Academy of Allergy and Clinical Immunology by means of a nonsystematic review of the current literature, is intended to provide a definition and classification of work-related chronic cough (WRCC) to assist the daily practice of physicians facing with this symptom. The review demonstrates that several upper and lower airway work-related diseases may present with chronic cough; hence, the possible link with the workplace should always be considered. Due to the broad spectrum of underlying diseases, a multidisciplinary approach is necessary to achieve a definite diagnosis. Nevertheless, more epidemiological studies are necessary to estimate the real prevalence and risk factors for WRCC, the role of exposure to environmental and occupational sensitizers and irritants in its pathogenesis and the interaction with both upper and lower airways. Finally, the best management option should be evaluated in order to achieve the best outcome without adverse social and financial consequences for the worker.

Monitoring of occupational and environmental aeroallergens-- EAACI Position Paper. Concerted action of the EAACI IG Occupational Allergy and Aerobiology & Air Pollution.

Exposure to high molecular weight sensitizers of biological origin is an important risk factor for the development of asthma and rhinitis. Most of the causal allergens have been defined based on their reactivity with IgE antibodies, and in many cases, the molecular structure and function of the allergens have been established. Significant information on allergen levels that cause sensitization and allergic symptoms for several major environmental and occupational allergens has been reported. Monitoring of high molecular weight allergens and allergen carrier particles is an important part of the management of allergic respiratory diseases and requires standardized allergen assessment methods for occupational and environmental (indoor and outdoor) allergen exposure. The aim of this EAACI task force was to review the essential points for monitoring environmental and occupational allergen exposure including sampling strategies and methods, processing of dust samples, allergen analysis, and quantification. The paper includes a summary of different methods for sampling and allergen quantification, as well as their pros and cons for various exposure settings. Recommendations are being made for different exposure scenarios.

EAACI position paper: irritant-induced asthma.

The term irritant-induced (occupational) asthma (IIA) has been used to denote various clinical forms of asthma related to irritant exposure at work. The causal relationship between irritant exposure(s) and the development of asthma can be substantiated by the temporal association between the onset of asthma symptoms and a single or multiple high-level exposure(s) to irritants, whereas this relationship can only be inferred from epidemiological data for workers chronically exposed to moderate levels of irritants. Accordingly, the following clinical phenotypes should be distinguished within the wide spectrum of irritant-related asthma: (i) definite IIA, that is acute-onset IIA characterized by the rapid onset of asthma within a few hours after a single exposure to very high levels of irritant substances; (ii) probable IIA, that is asthma that develops in workers with multiple symptomatic high-level exposures to irritants; and (iii) possible IIA, that is asthma occurring with a delayed-onset after chronic exposure to moderate levels of irritants. This document prepared by a panel of experts summarizes our current knowledge on the diagnostic approach, epidemiology, pathophysiology, and management of the various phenotypes of IIA.

EAACI position paper: skin prick testing in the diagnosis of occupational type I allergies.

Skin prick testing (SPT) in combination with the clinical history of the patient is one important step in the diagnosis of IgE-mediated occupational allergies. However, skin test performance is related to the quality of allergen extracts. The present consensus document was prepared by an EAACI Task Force consisting of an expert panel of allergologists and occupational physicians from Germany, Italy, Spain, France, Austria, and Poland. All members of the panel were also involved in the data collection within the European multicentre study STADOCA (Standard diagnosis for occupational allergy). The aim of this Task Force was the assessment of the quality of commercially available SPT solutions for selected occupational allergens under standardized procedure conditions in different European centres and institutes of Occupational Medicine. The data evaluation shows a wide variability among SPT solutions and also indicates that the sensitivity of several SPT solutions is low. Therefore, improvement and standardization of SPT solutions for occupational allergens is highly recommended. Clinical practitioners should also not presume that their SPT solutions are fully reliable. The main objective of the document is to issue consensus suggestions for the use of SPT with occupational allergens based on the European multicentre study STADOCA, on existing scientific evidence and the expertise of a panel of allergologists.

Asthma and exposure to cleaning products - a European Academy of Allergy and Clinical Immunology task force consensus statement.

Professional and domestic cleaning is associated with work-related asthma (WRA). This position paper reviews the literature linking exposure to cleaning products and the risk of asthma and focuses on prevention. Increased risk of asthma has been shown in many epidemiological and surveillance studies, and several case reports describe the relationship between exposure to one or more cleaning agents and WRA. Cleaning sprays, bleach, ammonia, disinfectants, mixing products, and specific job tasks have been identified as specific causes and/or triggers of asthma. Because research conclusions and policy suggestions have remained unheeded by manufactures, vendors, and commercial cleaning companies, it is time for a multifaceted intervention. Possible preventive measures encompass the following: substitution of cleaning sprays, bleach, and ammonia; minimizing the use of disinfectants; avoidance of mixing products; use of respiratory protective devices; and worker education. Moreover, we suggest the education of unions, consumer, and public interest groups to encourage safer products. In addition, information activities for the general population with the purpose of improving the knowledge of professional and domestic cleaners regarding risks and available preventive measures and to promote strict collaboration between scientific communities and safety and health agencies are urgently needed.

Evaluation of commercial skin prick test solutions for selected occupational allergens.

BACKGROUND: Skin prick testing (SPT) is an important step in the diagnosis of IgE-mediated occupational allergic diseases. The outcome of SPT is related to the quality of allergen extracts. Thus, the aim of the study was to assess different commercially available SPT solutions for selected occupational allergens. METHODS: SPT was performed in 116 bakers, 47 farmers and 33 subjects exposed to natural rubber latex (NRL), all with work-related allergic symptoms. The SPT solutions from different manufacturers (n = 3-5) for wheat flour, rye flour, soy, cow hair/dander, storage mites (Tyrophagus putrescentiae, Lepidoglyphus destructor, Acarus siro) and NRL were analysed with respect to their protein and antigen contents. SPT was carried out in 16 allergy centres in six European countries using standardized procedures. Specific IgE values were used as the gold standard to calculate the sensitivity and specificity of SPT solutions. The optimal cut-point for each SPT solution was determined by Youden Index. RESULTS: Protein and antigen contents and patterns of the SPT solutions varied remarkably depending on the manufacturer. While SPT solutions for wheat flour and soy reached overall low sensitivities, sensitivities of other tested SPT solutions depended on the manufacturer. As a rule, solutions with higher protein and antigen content showed higher sensitivities and test efficiencies. CONCLUSIONS: There is a wide variability of SPT solutions for occupational allergens, and the sensitivity of several solutions is low. Thus, improvement and standardization of SPT solutions for occupational allergens is essential.

Chlorhexidine--still an underestimated allergic hazard for health care professionals.

Chlorhexidine is a low molecular weight occupational sensitizer that can cause different delayed and immediate-type allergic reactions including anaphylaxis. It is widely used as an antiseptic and disinfectant and not only in the occupational environment as it is present in toothpaste, mouthwash, nose and eye drops and ointments. We present three cases of occupationally exposed workers with airway allergy to chlorhexidine. The role of chlorhexidine as an occupational allergen was confirmed by placebo-controlled specific inhalative challenge tests monitored by spirometry and analysis of induced sputum (influx of eosinophils after provocation has been observed). One of these patients presented with a systemic reaction with ordinary environment exposure. These findings are a reminder to clinicians of chlorhexidine's ability to cause various hypersensitivity reactions and the potential risk of this widely used antiseptic.

Occupational allergy to squid (Loligo vulgaris).

Occupational allergy from exposure to squid has been rarely described, mainly as contact dermatitis or urticaria. Our report presents the first case of occupational asthma, rhinitis, conjunctivitis and contact urticaria to squid in a 33-year-old seafood production worker, with documented increased eosinophilia in the nasal and tear fluids after specific inhalation challenge test (SICT) with squid. IgE-mediated sensitization to squid was confirmed by positive skin prick test and opened skin test with squid extract. SICT demonstrated a direct and significant link between the exposure to squid and the allergic response from the respiratory system and conjunctiva.

EAACI consensus statement for investigation of work-related asthma in non-specialized centres.

Work-related asthma (WRA) is a relevant problem in several countries, is cause of disability and socioeconomic consequences for both the patient and the society and is probably still underdiagnosed. A correct diagnosis is extremely important to reduce or limit the consequences of the disease. This consensus document was prepared by a EAACI Task Force consisting of an expert panel of allergologists, pneumologists and occupational physicians from different European countries. This document is not intended to address in detail the full diagnostic work-up of WRA, nor to be a formal evidence-based guideline. It is written to provide an operative protocol to allergologists and physicians dealing with asthma useful for identifying the subjects suspected of having WRA to address them to in-depth investigations in a specialized centre. No evidence-based system could be used because of the low grade of evidence of published studies in this area, and instead, 'key messages' or 'suggestions' are provided based on consensus of the expert panel members.

Occupational asthma due to spruce wood.

Workers exposed to a variety of wood dusts are known to experience work-related respiratory symptoms, including occupational asthma. There are, however, few reports of occupational asthma due to spruce wood. We present the case of a 31-year-old sawmill owner with severe asthma caused by exposure to spruce wood dust, who developed asthmatic symptoms after 2 years of working. Investigations included clinical examination, routine laboratory tests, spirometry, chest X-ray, total serum immunoglobulin E (IgE) and specific serum IgEs against various woods and other occupational allergens. Additionally, we monitored the peak expiratory flow rate (PEFR) and symptom score both at work and when off work. Specific serum IgE for spruce wood was detected (7.8 IU/ml). The results of PEFR and workplace symptom-score monitoring, coupled with an elevated eosinophil count in induced sputum, supported the diagnosis of occupational asthma. To our knowledge, this is the first well-documented case of occupational asthma induced by spruce wood dust. A type I immunological mechanism seems to be responsible.