Gender and occupational allergy: Report from the task force of the EAACI Environmental and Occupational Allergy Interest Group.

Women's work has traditionally been considered less hazardous to health in comparison with men's work. The increased women's participation in the workforce has led to an increased attention to women's working conditions. Women and men are unequally represented in individual professions or sectors (horizontal segregation), with women also under-represented in leadership positions (vertical segregation). The selection of specific occupations can result in differences between types and levels of occupational exposures among women and men and can affect prevalence of occupational allergy. Gender distribution of work-related asthma appears to vary across countries without clear global difference. Occupational rhinitis tends to be higher in women, although is not clear if this is related to a sex/gender effect or to differences in work exposure. Women are more likely to have occupational contact dermatitis, mainly due to wet work. No clear effects of gender on rates of hypersensitivity pneumonitis have been shown. Besides variation in exposures, physical and physiological characteristics, different behaviours and health consciousness have an impact on the occupational health hazards of women and men. Occupational allergy health promotion strategies need to consider approaches for women and men adjusted by gender, and legislative actions similarly could be implemented in a more gender-sensitive way.

Food processing and occupational respiratory allergy- An EAACI position paper.

Occupational exposure to foods is responsible for up to 25% of cases of occupational asthma and rhinitis. Animal and vegetable high-molecular-weight proteins present in aerosolized foods during food processing, additives, preservatives, antioxidants, and food contaminants are the main inhalant allergen sources. Most agents typically cause IgE-mediated allergic reactions, causing a distinct form of food allergy (Class 3 food allergy). The allergenicity of a food protein, allergen exposure levels, and atopy are important risk factors. Diagnosis relies on a thorough medical and occupational history, functional assessment, assessment of sensitization, including component-resolved diagnostics where appropriate, and in selected cases specific inhalation tests. Exposure assessment, including allergen determination, is a cornerstone for establishing preventive measures. Management includes allergen exposure avoidance or reduction (second best option), pharmacological treatment, assessment of impairment, and worker's compensation. Further studies are needed to identify and characterize major food allergens and define occupational exposure limits, evaluate the relative contribution of respiratory versus cutaneous sensitization to food antigens, evaluate the role of raw versus cooked food in influencing risk, and define the absolute or relative contraindication of patients with ingestion-related food allergy, pollinosis, or oral allergy syndrome continuing to work with exposure to aerosolized food allergens.

Are high- and low-molecular-weight sensitizing agents associated with different clinical phenotypes of occupational asthma?

BACKGROUND: High-molecular-weight (HMW) proteins and low-molecular-weight (LMW) chemicals can cause occupational asthma (OA) although few studies have thoroughly compared the clinical, physiological, and inflammatory patterns associated with these different types of agents. The aim of this study was to determine whether OA induced by HMW and LMW agents shows distinct phenotypic profiles. METHODS: Clinical and functional characteristics, and markers of airway inflammation were analyzed in an international, multicenter, retrospective cohort of subjects with OA ascertained by a positive inhalation challenge response to HMW (n = 544) and LMW (n = 635) agents. RESULTS: Multivariate logistic regression analysis showed significant associations between OA caused by HMW agents and work-related rhinitis (OR [95% CI]: 4.79 [3.28-7.12]), conjunctivitis (2.13 [1.52-2.98]), atopy (1.49 [1.09-2.05]), and early asthmatic reactions (2.86 [1.98-4.16]). By contrast, OA due to LMW agents was associated with chest tightness at work (2.22 [1.59-3.03]), daily sputum (1.69 [1.19-2.38]), and late asthmatic reactions (1.52 [1.09-2.08]). Furthermore, OA caused by HMW agents showed a higher risk of airflow limitation (1.76 [1.07-2.91]), whereas OA due to LMW agents exhibited a higher risk of severe exacerbations (1.32 [1.01-1.69]). There were no differences between the two types of agents in the baseline sputum inflammatory profiles, but OA caused by HMW agents showed higher baseline blood eosinophilia and a greater postchallenge increase in fractional nitric oxide. CONCLUSION: This large cohort study describes distinct phenotypic profiles in OA caused by HMW and LMW agents. There is a need to further explore differences in underlying pathophysiological pathways and outcome after environmental interventions.

Specific inhalation challenge in the diagnosis of occupational asthma: consensus statement.

This consensus statement provides practical recommendations for specific inhalation challenge (SIC) in the diagnosis of occupational asthma. They are derived from a systematic literature search, a census of active European centres, a Delphi conference and expert consensus. This article details each step of a SIC, including safety requirements, techniques for delivering agents, and methods for assessing and interpreting bronchial responses. The limitations of the procedure are also discussed. Testing should only be carried out in hospitals where physicians and healthcare professionals have appropriate expertise. Tests should always include a control challenge, a gradual increase of exposure to the suspected agent, and close monitoring of the patient during the challenge and for at least 6 h afterwards. In expert centres, excessive reactions provoked by SIC are rare. A positive response is defined by a fall in forced expiratory volume in 1 s ≥ 15% from baseline. Equivocal reactions can sometimes be clarified by finding changes in nonspecific bronchial responsiveness, sputum eosinophils or exhaled nitric oxide. The sensitivity and specificity of SIC are high but not easily quantified, as the method is usually used as the reference standard for the diagnosis of occupational asthma.

Asthma and rhinitis in cleaning workers: a systematic review of epidemiological studies.

OBJECTIVE: This article presents a systematic review of epidemiological studies linking cleaning work and risk of asthma and rhinitis. METHODS: Published reports were identified from PubMed covering the years from 1976 through June 30, 2012. In total, we identified 24 papers for inclusion in the review. The quality of studies was evaluated using the Strengthening of the Reporting of Observational Studies in Epidemiology (STROBE) statement checklist of 22 items for cross-sectional, cohort and case-control studies. RESULTS: Increased risk of asthma or rhinitis has been shown in 79% of included epidemiological studies. In four studies the increased risk of asthma in cleaning workers was confirmed by objective tests, such as bronchial hyper-reactivity or airflow obstruction. Level of exposure to cleaning products, cleaning sprays, bleach, ammonia, mixing products and specific job tasks has been identified as specific causes of asthma and rhinitis. CONCLUSIONS: Possible preventive measures encompass the substitution of cleaning sprays, bleach and ammonia, avoidance of mixing products, the use of respiratory protective devices, worker education and medical surveillance.

Oxidative activity of ammonium persulfate salt on mast cells and basophils: implication in hairdressers' asthma.

BACKGROUND: Persulfate salts are components of bleaching powders widely used by hairdressers during hair-bleaching procedures. Hairdressers are at high risk for occupational asthma and rhinitis, and ammonium persulfate is the main etiologic agent. OBJECTIVE: To explore the effects of ammonium persulfate on human albumin, mast cells, and basophils in order to evaluate a possible effect of ammonium persulfate oxidizing activity in the mechanism of ammonium persulfate-induced occupational asthma. METHODS: High-performance liquid chromatography/mass spectrometry was performed on ammonium persulfate-incubated human albumin. The activation of LAD2 human mast cell and KU812 human basophil cell lines incubated with ammonium persulfate was evaluated. CD63 expression on persulfate-in-vitro-incubated blood basophils from nonexposed healthy controls (n = 31) and hairdressers with work-related respiratory symptoms (n = 29) was assessed by flow cytometry. RESULTS: No persulfate-albumin conjugate was found. An oxidative process on tryptophan and methionine was detected. Ammonium persulfate induced reactive oxygen species (ROS) generation and the degranulation of LAD2 and KU812 cells. Human basophils from healthy controls, incubated in vitro with ammonium persulfate, showed increased CD63 expression and ROS production. In hairdressers with ammonium persulfate-caused occupational asthma (positive persulfate challenge), basophil-CD63 expression was higher than in those with a negative challenge and in healthy controls. CONCLUSIONS: Ammonium persulfate incubated with human albumin did not generate any adduct but oxidized some amino acids. This oxidizing activity induced human mast cell and basophil activation which might be crucial in the mechanism of persulfate-induced occupational asthma and rhinitis.

Focus on work-related asthma.

Work-related asthma, encompassing both occupational asthma and work-exacerbated asthma, accounts for 10%-25% of adult asthma in Europe and occupational asthma is currently one of the most common forms of occupational lung disease in many industrialized countries. It is cause of direct and indirect costs for the worker, the employer and the society and it is probably still underdiagnosed. Hence, the possibility of work-related asthma should be considered in all adult patients in whom asthma started or worsened during their working life. The investigation of WRA includes assessing the presence of asthma, and demonstrating its work-relatedness, that requires training and expertise. Due to the frequent association of occupational asthma and rhinitis, the expertise. Due to the frequent association of occupational asthma and rhinitis, the presence of both upper and lower airway symptoms should be investigated. Furthermore, since is work-related asthma is a preventable disease all efforts should be made for effective prevention strategies.

Occupational nonasthmatic eosinophilic bronchitis: current concepts.

BACKGROUND: Nonasthmatic eosinophilic bronchitis (NAEB) is an important cause of chronic cough, since it is present in 10-15% of patients referred for specialist investigation. The syndrome is considered a variant of occupational asthma when it develops as a consequence of occupational exposure, hence it should be considered in the spectrum of work-related airway diseases. OBJECTIVES AND METHODS: The aim of this paper was to update and expand the previous reviews on the clinical and pathophysiological features of NAEB and analyze available data on the occupational causes of the disease. Literature on the topic between the years 1990 and 2010 was reviewed with a Med Line search. RESULTS: The disease is probably underdiagnosed and an occupational origin was demonstrated only in isolated cases, probably due to the rarity of the disease and the lack of systematic evaluation of bronchial inflammation. CONCLUSIONS: In view of the current knowledge on this condition and the development of techniques to evaluate bronchial inflammation, occupational NAEB cannot be neglected any more and has been rightly included in the spectrum of occupational respiratory disorders.

The use of fractional exhaled nitric oxide in investigation of work-related cough in a hairdresser.

BACKGROUND: Occupational and environmental factors may be a cause of nonasthmatic eosinophilic bronchitis (NAEB). The diagnosis of occupational NAEB requires evidence of sputum eosinophilia. Nevertheless, a minority of patients are not able to produce suitable sputum specimens. METHODS: This case report describes a 25-year-old woman, working as a hairdresser since the age of 20 years and handling ammonium persulfate, who came under our observation for work-related rhinitis and cough. RESULTS: A specific inhalation challenge with ammonium persulfate elicited dry cough, without any significant change in forced expiratory volume in 1 s (FEV(1) ). Sputum induction was unsuccessful both pre- and after specific inhalation challenge. Fractional exhaled nitric oxide (FeNO) values significantly increased after specific inhalation challenge, suggesting a diagnosis of occupational NAEB due to ammonium persulfate. CONCLUSIONS: From this observation we suggest that FeNO measurement should be added to the investigation of work-related cough during specific inhalation challenge, and may be considered as an alternative to induced sputum to evaluate bronchial inflammation when sputum collection is unavailable or unsuccessful.

[Fractional exhaled nitric oxide measurement during specific inhalation challenge tests]. / La misurazione dell'ossido nitrico nel test di provocazione bronchiale specifico.

The aim of the work is to evaluate the usefulness of the evaluation of the fractional exhaled nitric oxide (FeNO) in patients with suspected occupational asthma (OA) during the specific inhalation challenge (SIC). We evaluated 5 subjects with OA confirmed by SIC and 7 subjects with negative SIC result. In subjects with confirmed OA, but not in SIC negative subjects, a significant increase in FeNO values has been reported. In conclusion, FeNO measurement may be considered a useful tollfor the evaluation of bronchial inflammation during the SIC.

Nasal blown secretion evaluation in specific occupational nasal challenges.

PURPOSE: To investigate the usefulness of nasal blown secretion evaluation during specific nasal provocation test (sNPT) in diagnosing occupational rhinitis (OR). METHODS: To validate the method, nasal blown secretions from 103 healthy subjects and 30 allergic rhinitis patients were analyzed. Furthermore, we analyzed nasal blown secretions, collected before and after sNPT, of 29 subjects with work-related rhinitis symptoms (WRRS) who underwent the diagnostic pathway for OR. Rhinoscopy and nasal symptom score were used to define a positive sNPT. RESULTS: A total of 89.6% WRRS subjects provided suitable nasal secretions. Eosinophils significantly increased after positive sNPTs compared to negative ones (P = 0.006). Four percent and/or 1 x 10(4) eosinophils/ml was the cut-off for a significant post-sNPT eosinophil increase. A total of 4/13 (33%) WRRS subjects with negative sNPT, assessed by rhinoscopy and nasal symptom score, presented a significant post-sNPT nasal eosinophil increase, and were identified as possible OR. CONCLUSION: Eosinophil evaluation in nasal blown secretions is an important tool in monitoring the response to occupational specific nasal challenges.

Phenotyping Occupational Asthma Caused by Acrylates in a Multicenter Cohort Study.

BACKGROUND: While acrylates are well-known skin sensitizers, they are not classified as respiratory sensitizers although several cases of acrylate-induced occupational asthma (OA) have been reported. OBJECTIVE: To evaluate the characteristics of acrylate-induced OA in a large series of cases and compare those with OA induced by other low-molecular-weight (LMW) agents. METHODS: Jobs and exposures, clinical and functional characteristics, and markers of airway inflammation were analyzed in an international, multicenter, retrospective cohort of subjects with OA ascertained by a positive inhalation challenge to acrylates (n = 55) or other LMW agents (n = 418) including isocyanates (n = 125). RESULTS: Acrylate-containing glues were the most prevalent products, and industrial manufacturing, dental work, and beauty care were typical occupations causing OA. Work-related rhinitis was more common in acrylate-than in isocyanate-induced asthma (P < .001). The increase in postchallenge fractional exhaled nitric oxide was significantly greater in acrylate-induced OA (26.0; 8.2 to 38.0 parts per billion [ppb]) than in OA induced by other LMW agents (3.0; -1.0 to 10.0 ppb; P < .001) or isocyanates (5.0; 2.0 to 16.0 ppb; P = .010). Multivariable models confirmed that OA induced by acrylates was significantly and independently associated with a postchallenge increase in fractional exhaled nitric oxide (≥17.5 ppb). CONCLUSIONS: Acrylate-induced OA shows specific characteristics, concomitant work-related rhinitis, and exposure-related increases in fractional exhaled nitric oxide, suggesting that acrylates may induce asthma through different immunologic mechanisms compared with mechanisms through which other LMW agents may induce asthma. Our findings reinforce the need for a reevaluation of the hazard classification of acrylates, and further investigation of the pathophysiological mechanisms underlying their respiratory sensitizing potential.

EAACI position paper on occupational rhinitis.

The present document is the result of a consensus reached by a panel of experts from European and non-European countries on Occupational Rhinitis (OR), a disease of emerging relevance which has received little attention in comparison to occupational asthma. The document covers the main items of OR including epidemiology, diagnosis, management, socio-economic impact, preventive strategies and medicolegal issues. An operational definition and classification of OR tailored on that of occupational asthma, as well as a diagnostic algorithm based on steps allowing for different levels of diagnostic evidence are proposed. The needs for future research are pointed out. Key messages are issued for each item.

Severe Occupational Asthma: Insights From a Multicenter European Cohort.

BACKGROUND: Although sensitizer-induced occupational asthma (OA) accounts for an appreciable fraction of adult asthma, the severity of OA has received little attention. OBJECTIVE: The aim of this study was to characterize the burden and determinants of severe OA in a large multicenter cohort of subjects with OA. METHODS: This retrospective study included 997 subjects with OA ascertained by a positive specific inhalation challenge completed in 20 tertiary centers in 11 European countries during the period 2006 to 2015. Severe asthma was defined by a high level of treatment and any 1 of the following criteria: (1) daily need for a reliever medication, (2) 2 or more severe exacerbations in the previous year, or (3) airflow obstruction. RESULTS: Overall, 162 (16.2%; 95% CI, 14.0%-18.7%) subjects were classified as having severe OA. Multivariable logistic regression analysis revealed that severe OA was associated with persistent (vs reduced) exposure to the causal agent at work (odds ratio [OR], 2.78; 95% CI, 1.50-5.60); a longer duration of the disease (OR, 1.04; 95% CI, 1.00-1.07); a low level of education (OR, 2.69; 95% CI, 1.73-4.18); childhood asthma (OR, 2.92; 95% CI, 1.13-7.36); and sputum production (OR, 2.86; 95% CI, 1.87-4.38). In subjects removed from exposure, severe OA was associated only with sputum production (OR, 3.68; 95% CI, 1.87-7.40); a low education level (OR, 3.41; 95% CI, 1.72-6.80); and obesity (OR, 1.98; 95% CI, 0.97-3.97). CONCLUSIONS: This study indicates that a substantial proportion of subjects with OA experience severe asthma and identifies potentially modifiable risk factors for severe OA that should be targeted to reduce the adverse impacts of the disease.

Comparison between exhaled and bronchoalveolar lavage levels of hydrogen peroxide in patients with diffuse interstitial lung diseases.

The aim of the present study was to compare hydrogen peroxide (H2O2) levels resulting from oxidative stress in exhaled breath condensate (EBC) and bronchoalveolar lavage (BAL) supernatants of subjects with different diffuse interstitial lung diseases (DILDs). Twenty-one patients who underwent BAL procedure for various DILDs were studied. EBC, which was collected the day before bronchoscopy, was obtained by cooling exhaled breath; BAL was processed for differential cellular count and supernatant was stored. H2O2 in both fluids was measured using a commercial fluorimetric kit with a limit of detection of 0.01 microM. No difference in H2O2 levels in EBC and in BAL was observed [median (range), 0.07 microM (0.01-0.6) and 0.08 microM (0.01-0.8), respectively]. No correlation was observed between BAL and EBC levels. H2O2 in BAL did not correlate with differential cellular count, whereas H2O2 EBC did correlate positively with the percentage of epithelial cells (r = 0.5, p = 0.007) and negatively with the number of macrophages (r = -0.4, p = 0.03). No correlation was observed between H2O2 levels either in EBC or BAL and lung function data. The data show that in DILDs H2O2 can be detected in both EBC and supernatants of BAL and that their relative concentrations are similar but not correlated with each other. The positive correlation between H2O2 levels in EBC and percentage of epithelial cells leads to the speculation that airway epithelia may play a relevant contribution in H2O2 production in the airway lumen.

[Consensus Document. Update on latex exposure and use of gloves in Italian health care settings]. / Documento di Consenso. Aggiornamenti in tema di esposizione a latice e impiego di guanti in ambito sanitario.

This consensus document was prepared by an Italian working group including occupational health professionals involved for many years in the management of glove- and latex-related problems in health care settings. The aim of this document was to address the most significant technical, epidemiological, clinical, environmental and prevention problems related to the use of gloves and latex. The group's recommendations are based on scientific evidence and practical experience but they cannot be considered as final. These topics need to be periodically revised. The following points should be taken into account: glove quality seems to have improved considerably but the information on glove features provided by the manufacturers is often still inaccurate or incomplete; the regulations in force provide that the manufacturers perform tests to supply evidence for the quality of the products but they do not indicate which analytical method should be used and they do not require that the results be reported in the technical data sheets. Thus the manufacturers have only to declare that their products are "in accordance with the rules"; therefore, purchasers should require the manufacturing companies to supply detailed information and verify their reliability. Moreover, the rules should be adapted to higher quality standards; occupational physicians must be involved for the correct choice and purchase of protective gloves; the use of gloves (in particular latex gloves) and latex devices in health care settings should be based on specific criteria: procedures must be available stating which kind of gloves are suitable for specific tasks. When exposure to latex cannot be avoided it is necessary to choose products that have good biocompatibility (e.g., powder free-gloves with low allergen content); once and for all latex powdered gloves should no longer be commercially available! labels for latex devices (including gloves) should report the extractable latex allergen content. Limit values for extractable latex allergens should be established; the use of synthetic rubber gloves should be encouraged since some materials (e.g., neoprene and nitrile rubber) appear to have physical properties and protective efficacy similar to latex, plus good biocompatibility; more studies should be promoted to verify the protective efficacy of new synthetic materials; health care workers should be informed about the advisability and usefulness of using materials other than latex; health care services should not cause additional risks but rather highlight the advantages for workers and patients if the use of latex gloves and devices is minimized.

Clusterization of patients with idiopathic pulmonary fibrosis with chemokine receptors: a possible role in the diagnostic work-up of idiopathic pulmonary fibrosis?

Background and objective: Idiopathic pulmonary fibrosis (IPF) is a chronic and irreversible interstitial lung disease whose diagnosis often requires surgical lung biopsies (SLB) in cases without consistent radiological findings. We previously published that the expression of the chemokine receptors CXCR3 and CCR4 on T cells is significantly different in bronchoalveolar lavage (BAL) of IPF patients from other interstitial lung diseases. The aim of the study was to evaluate cut-off values of CXCR3 and CCR4 receptors expressed on bronchoalveolar lavage (BAL) and peripheral blood (PB) T cells useful for a differential diagnosis. Methods: Ninety-three patients were enrolled: 35 IPF, 36 interstitial lung diseases (nIPF) and 22 sarcoidosis. CXCR3 and CCR4 were evaluated on BAL and PB T lymphocytes with flow cytometry. Results: Among PB and BAL variables considered, the values of the ratio of BAL and PB CXCR3 on CD4 cells were clustered in the most informative way to obtain a classification rule for the diagnosis of patients without steroid therapy (n = 66/93). Patients with a CXCR3 ratio BAL/PB on CD4 T cells lower or equal than 1.43 were assigned to the IPF group with sensitivity = 0.87 and specificity = 0.90. All the other variables considered showed lower sensitivity and specificity in discriminating IPF patients. Conclusions: The evaluation of chemokine receptors on BAL and PB T lymphocytes could aid to discriminate IPF in subjects without steroid therapy, particularly in those patients with a high-resolution computed tomography (HRCT) non typical for Usual Interstitial Pneumonia (UIP). (Sarcoidosis Vasc Diffuse Lung Dis 2018; 35: 35-43).

International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis.

BACKGROUND: Critical examination of the quality and validity of available allergic rhinitis (AR) literature is necessary to improve understanding and to appropriately translate this knowledge to clinical care of the AR patient. To evaluate the existing AR literature, international multidisciplinary experts with an interest in AR have produced the International Consensus statement on Allergy and Rhinology: Allergic Rhinitis (ICAR:AR). METHODS: Using previously described methodology, specific topics were developed relating to AR. Each topic was assigned a literature review, evidence-based review (EBR), or evidence-based review with recommendations (EBRR) format as dictated by available evidence and purpose within the ICAR:AR document. Following iterative reviews of each topic, the ICAR:AR document was synthesized and reviewed by all authors for consensus. RESULTS: The ICAR:AR document addresses over 100 individual topics related to AR, including diagnosis, pathophysiology, epidemiology, disease burden, risk factors for the development of AR, allergy testing modalities, treatment, and other conditions/comorbidities associated with AR. CONCLUSION: This critical review of the AR literature has identified several strengths; providers can be confident that treatment decisions are supported by rigorous studies. However, there are also substantial gaps in the AR literature. These knowledge gaps should be viewed as opportunities for improvement, as often the things that we teach and the medicine that we practice are not based on the best quality evidence. This document aims to highlight the strengths and weaknesses of the AR literature to identify areas for future AR research and improved understanding.

Uteroglobin-related protein 1 and clara cell protein in induced sputum of patients with asthma and rhinitis.

RATIONALE: Uteroglobin-related protein 1 (UGRP1) and Clara cell protein (CC16), members of the secretoglobin family, increasingly appear to play a role in airway inflammatory response. OBJECTIVE: To explore levels of UGRP1 and CC16 in induced sputum of patients with asthma and rhinitis. METHODS: Induced-sputum samples of patients with asthma or rhinitis (n = 32 each; atopic asthma, n = 24; atopic rhinitis, n = 20) and from 19 nonsmoking nonatopic control subjects were analyzed for cytology and levels of UGRP1, CC16, and albumin. MEASUREMENTS AND MAIN RESULTS: Sputum UGRP1 increased in both asthma and rhinitis, most strikingly so in asthma, in which changes were most significant in atopic individuals. By contrast, sputum CC16 did not change significantly in either condition, although it was positively correlated with UGRP1 in patients and control subjects. Changes in sputum UGRP1 in atopic asthma were not linked to permeability changes reflected by increased albumin levels but correlated positively with sputum macrophages and negatively with eosinophils. The observed differences in UGRP1 and CC16 may be linked to different cell populations being responsible for their secretion; UGRP1 is mainly secreted in larger conducting airways, whereas CC16 is mainly secreted by the nasal and peripheral airways epithelium. CONCLUSIONS: The increase in UGRP1 but not of CC16 in asthma and rhinitis suggests that UGRP1 may play a role in these inflammatory diseases.