Diagnostic Accuracy of Specific IgE Against Wheat and Rye in Flour-Induced Occupational Asthma.

BACKGROUND: Assessment of IgE-mediated sensitization to flour allergens is widely used to investigate flour-induced occupational asthma. The diagnostic efficiency of detecting specific IgE antibodies (sIgE) against wheat and rye flour, however, has not been thoroughly compared to other diagnostic procedures. OBJECTIVE: We sought to evaluate the diagnostic accuracy of sIgE against wheat and rye compared to specific inhalation challenge (SIC) with flour as the reference standard. METHODS: This retrospective multicenter study included 264 subjects who completed a SIC with flour in eight tertiary centers, of whom 205 subjects showed a positive SIC result. RESULTS: Compared with SIC, sIgE levels ≥0.35 kUA/L against wheat and rye provided similar sensitivities (84%-85%, respectively), specificities (71%-78%), positive predictive values (91%-93%), and negative predictive value (56%-61%). Increasing the threshold sIgE value to 5.10 kUA/L for wheat and to 6.20 kUA/L for rye provided a specificity ≥95% and further enhanced the positive predictive value to 98%. Among subjects with a positive SIC, those who failed to demonstrate sIgE against wheat and rye (n=26) had significantly lower total serum IgE level and blood and sputum eosinophil counts, and a lesser increase in post-challenge fractional exhaled nitric oxide as compared to the subjects with detectable sIgE. CONCLUSION: High levels of sIgE against wheat and/or rye flour strongly support a diagnosis of flour-induced occupational asthma without the need for performing a SIC. The absence of detectable sIgE against wheat and rye in subjects with a positive SIC seems to be associated with lower levels of TH2 biomarkers.

Comment on 'Limitations in evaluating COVID-19 protective face masks using open circuit spirometry systems: respiratory measurement mask introduces bias in breathing pressure and perceived respiratory effort'.

We comment on the paper by Seibt and coworkers (Seibtet al2023) which investigates whether wearing an additional respiratory measurement mask during open-circuit spirometry assessments (respirometry mask) shows any effect on breathing pressure and perceived respiratory effort when wearing protective face masks commonly worn during the COVID-19 pandemic.

ATS/ ERS spirometry quality criteria in real life. Results of two occupational field studies.

Spirometry is a widely used test and the American Thoracic Society and the European Respiratory Society (ATS/ERS) provide standardised recommendations. However, detailed information on test quality is often incomplete in publications. In light of the 2005 ATS/ERS recommendations, we investigated the acceptability and repeatability criteria of spirometry performed under occupational field conditions in 242 practicing welders (WELDOX study, median age 41.5 years, all male) and 312 first-year veterinary students (AllergoVet study, median age 20.0 years, 84.3% female). At least three acceptable or usable measurements could be identified for 233 welders and 305 students. The repeatability for welders was 96.1% for the forced expiratory volume in the first second (FEV1) and 97.0% for forced vital capacity (FVC). The corresponding results for students were 95.7% and 95.4%, respectively. The overall repeatability of test sessions at the 150-mL level was 90.5% (219/242) for welders and 90.1% (281/312) for students. Spirometry can be performed with reliable quality in an occupational field setting.

Influence of face masks on the subjective impairment at different physical workloads.

To quantify the subjective and cognitive impairment caused by wearing face masks at work, 20 men and 20 women (median age 47 years, range 19-65) were tested under different ergometer workloads while wearing surgical mask, community mask, FFP2 respirator or no mask in a randomized and partially double-blinded design. Masks were worn also at the workplace for four hours. Subjective impairment was recorded by questionnaires. Cognitive performance was tested before and after the workplace examination. Subjective feeling of heat, humidity, and difficult breathing increased with rising physical exertion and wearing time for all three mask types, most notably for FFP2. Even when blinded, participants with FFP2 reported difficult breathing already at rest. During physical exertion, individuals with low tolerance to discomfort reported significantly stronger impairment (OR 1.14, 95% CI 1.02-1.27). Regarding light work, older subjects (OR 0.95, 95% CI 0.92-0.98) and women (OR 0.84, 95% CI 0.72-0.99) showed significantly lower and atopic subjects stronger impairment (OR 1.16, 95% CI 1.06-1.27). No significant influence of mask wearing was detected on cognitive performance. Wearing a mask had no effect on cognitive performance, but led to discomfort which increased with physical exertion and wearing time. Individuals who tolerate discomfort poorly felt more impaired by wearing a mask during physical exertion.

Effects of wearing different face masks on cardiopulmonary performance at rest and exercise in a partially double-blinded randomized cross-over study.

The use of face masks became mandatory during SARS-CoV-2 pandemic. Wearing masks may lead to complaints about laboured breathing and stress. The influence of different masks on cardiopulmonary performance was investigated in a partially double-blinded randomized cross-over design. Forty subjects (19-65 years) underwent body plethysmography, ergometry, cardiopulmonary exercise test and a 4-h wearing period without a mask, with a surgical mask (SM), a community mask (CM), and an FFP2 respirator (FFP2). Cardiopulmonary, physical, capnometric, and blood gas related parameters were recorded. Breathing resistance and work of breathing were significantly increased while wearing a mask. During exercise the increase in minute ventilation tended to be lower and breathing time was significantly longer with mask than without mask. Wearing a mask caused significant minimal decreases in blood oxygen pressure, oxygen saturation, an initial increase in blood and inspiratory carbon dioxide pressure, and a higher perceived physical exertion and temperature and humidity behind the mask under very heavy exercise. All effects were stronger when wearing an FFP2. Wearing face masks at rest and under exercise, changed breathing patterns in the sense of physiological compensation without representing a health risk. Wearing a mask for 4-h during light work had no effect on blood gases.

No inflammatory effects after acute inhalation of barium sulfate particles in human volunteers.

BACKGROUND: Most threshold limit values are based on animal experiments. Often, the question remains whether these data reflect the situation in humans. As part of a series of investigations in our exposure lab, this study investigates whether the results on the inflammatory effects of particles that have been demonstrated in animal models can be confirmed in acute inhalation studies in humans. Such studies have not been conducted so far for barium sulfate particles (BaSO4), a substance with very low solubility and without known substance-specific toxicity. Previous inhalation studies with zinc oxide (ZnO), which has a substance-specific toxicity, have shown local and systemic inflammatory respones. The design of these human ZnO inhalation studies was adopted for BaSO4 to compare the effects of particles with known inflammatory activity and supposedly inert particles. For further comparison, in vitro investigations on inflammatory processes were carried out. METHODS: Sixteen healthy volunteers were exposed to filtered air and BaSO4 particles (4.0 mg/m3) for two hours including one hour of ergometric cycling at moderate workload. Effect parameters were clinical signs, body temperature, and inflammatory markers in blood and induced sputum. In addition, particle-induced in vitro-chemotaxis of BaSO4 was investigated with regard to mode of action and differences between in vivo and in vitro effects. RESULTS: No local or systemic clinical signs were observed after acute BaSO4 inhalation and, in contrast to our previous human exposure studies with ZnO, no elevated values of biomarkers of inflammation were measured after the challenge. The in vitro chemotaxis induced by BaSO4 particles was minimal and 15-fold lower compared to ZnO. CONCLUSION: The results of this study indicate that BaSO4 as a representative of granular biopersistent particles without specific toxicity does not induce inflammatory effects in humans after acute inhalation. Moreover, the in vitro data fit in with these in vivo results. Despite the careful and complex investigations, limitations must be admitted because the number of local effect parameters were limited and chronic toxicity could not be studied.

Occupational Asthma Caused by Quaternary Ammonium Compounds: A Multicenter Cohort Study.

BACKGROUND: Quaternary ammonium compounds (QACs) are used extensively for cleaning and disinfection and have been documented in scattered reports as a cause of occupational asthma (OA) through bronchoprovocation tests (BPTs). OBJECTIVE: To examine the clinical, functional, and inflammatory profile of QAC-induced OA compared with OA caused by other low-molecular weight (LMW) agents. METHODS: The study was conducted in a retrospective multicenter cohort of 871 subjects with OA ascertained by a positive BPT. Subjects with QAC-induced OA (n = 22) were identified based on a positive BPT to QACs after exclusion of those challenged with cleaning products or disinfectants that contained other potential respiratory sensitizers. They were compared with 289 subjects with OA caused by other LMW agents. RESULTS: Most subjects with QAC-induced OA were working in the health care sector (n = 14). A twofold or greater increase in the postchallenge level of nonspecific bronchial hyperresponsiveness was recorded in eight of 11 subjects with QAC-induced OA (72.7%) and in 49.7% of those with OA caused by other LMW agents. Although sputum assessment was available in only eight subjects with QAC-induced OA, they showed a significantly greater median (interquartile) increase in sputum eosinophils (18.1% [range, 12.1% to 21.1%]) compared with those with OA caused by other LMW agents (2.0% [range, 0% to 5.2%]; P < .001). CONCLUSIONS: This study indicates that QAC-induced OA is associated with a highly eosinophilic pattern of airway response and provides further evidence supporting the sensitizing potential of QACs. The findings highlight the heterogeneous nature of the pathobiologic pathways involved in OA caused by LMW agents.

Characterization of Occupational Eosinophilic Bronchitis in a Multicenter Cohort of Subjects with Work-Related Asthma Symptoms.

BACKGROUND: Occupational eosinophilic bronchitis (OEB) has been described only as anecdotal case reports. OBJECTIVE: We investigated the clinical and inflammatory characteristics of subjects with OEB identified in a cohort of subjects who completed a specific inhalation challenge (SIC) with occupational agents. METHODS: In this retrospective multicenter study, OEB was defined by (1) a fall in FEV1 less than 15% during the SIC and the absence of nonspecific bronchial hyperresponsiveness both before and after the SIC and (2) a postchallenge increase of 3% or more in sputum eosinophils. The subjects who fulfilled these criteria were compared with 226 subjects with a negative SIC and 30 subjects with a positive SIC who failed to show baseline nonspecific bronchial hyperresponsiveness. RESULTS: An isolated increase in postchallenge sputum eosinophils was documented in 33 of 259 subjects (13%) with a negative SIC. These subjects reported significantly more often an isolated cough at work compared with the negative and positive SIC controls. When compared with positive SIC controls, the subjects with OEB experienced less frequently work-related wheezing and reported a shorter duration of symptoms at work. The sensitivity of the post-SIC increase in fractional exhaled nitric oxide in identifying OEB among subjects with a negative SIC was low, ranging from 43% to 24% using cutoff values of 8 ppb to 17.5 ppb, whereas the specificity was high (90%-97%). CONCLUSIONS: This study highlights the relevance of induced sputum analysis in the investigation of work-related asthma symptoms to identify isolated increases in sputum eosinophils that are consistent with a diagnosis of OEB.

Health effects after inhalation of micro- and nano-sized zinc oxide particles in human volunteers.

Inhalation of ZnO particles can cause inflammation of the airways and metal fume fever. It is unclear if different sizes of the particles alter these effects. However, various studies report higher biological activity of other nano-sized particles compared to microparticles. No effects at all were observed after inhalation of micro- and nano-sized zinc oxide (ZnO) particle concentrations of 0.5 mg/m3. Studies with different particle sizes of ZnO at higher exposures are not available. Accordingly, we hypothesized that inhalation of nano-sized ZnO particles induces stronger health effects than the inhalation of the same airborne mass concentration of micro-sized ZnO particles. 16 healthy volunteers (eight men, eight women) were exposed to filtered air and ZnO particles (2.0 mg/m3) for 2 h (one session with nano- and one with micro-sized ZnO) including 1 h of cycling at moderate workload. Effect parameters were symptoms, body temperature, inflammatory markers in blood and in induced sputum. Induced sputum was obtained at baseline examination, 22 h after exposure and at the end of the final test. The effects were assessed before, immediately after, about 22 h after, as well as two and three days after each exposure. Neutrophils, monocytes and acute-phase proteins in blood increased 22 h after micro- and nano-sized ZnO exposure. Effects were generally stronger with micro-sized ZnO particles. Parameters in induced sputum showed partial increases on the next day, but the effect strengths were not clearly attributable to particle sizes. The hypothesis that nano-sized ZnO particles induce stronger health effects than micro-sized ZnO particles was not supported by our data. The stronger systemic inflammatory responses after inhalation of micro-sized ZnO particles can be explained by the higher deposition efficiency of micro-sized ZnO particles in the respiratory tract and a substance-specific mode of action, most likely caused by the formation of zinc ions.

Occupational health hazards of street cleaners - a literature review considering prevention practices at the workplace.

Street cleaning is an integral part of the solid waste management system. There are different ways to achieve clean streets depending on the availability of equipment, the type and magnitude of dirt, the surface conditions encountered or traffic conditions. In general, hand sweeping by an individual worker or a group, hose flushing, or machine sweeping or flushing are applied. In order to obtain information about the occurrence and relevance of occupational health hazards of street cleaners, the current international literature, as well as corresponding German regulations, were reviewed and evaluated. Street cleaning includes a variety of health hazards for employees. These can be subdivided into effects of occupational tasks and effects of working conditions such as weather or road traffic. The hazards result from physical, chemical and biological exposures, but may also be due to physiological and psychological burden or inadequate safety aspects. The most commonly reported work-related complaints are musculoskeletal and respiratory disorders, cuts, slips, and road traffic accidents. In developing countries, street cleaners seem to be still heavily exposed to dust and, in most cases, no suitable protective measures are available. Especially in industrialized countries there exist a number of standards and recommendations for waste workers that aim to reduce their occupational health impacts. Int J Occup Med Environ Health. 2020;33(6):701-32.

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.

Heart rate variability and cardiac repolarization after exposure to zinc oxide nanoparticles in healthy adults.

BACKGROUND: Exposure to airborne zinc oxide (ZnO) particles occurs in many industrial processes, especially in galvanizing and welding. Systemic inflammation after experimental inhalation of ZnO particles has been demonstrated previously, but little is known about the impact on the cardiovascular system, particularly on the autonomic cardiac system and the risk of arrhythmias. In this study we investigated the short-term effects of ZnO nanoparticles on heart rate variability (HRV) and repolarization in healthy adults in a concentration-dependent manner at rest and during exercise in a controlled experimental set-up. METHODS: Sixteen healthy subjects were exposed to filtered air and ZnO particles (0.5, 1.0 and 2.0 mg/m3) for 4 h, including 2 h of cycling at low workloads. Parameters were assessed before, during, immediately after, and about 24 h after each exposure. For each subject, a total number of 46 10-min-sections from electrocardiographic records were analyzed. Various parameters of HRV and QT interval were measured. RESULTS: Overall, no statistically significant effects of controlled ZnO inhalation on HRV parameters and QT interval were observed. Additionally, a concentration-response was absent. CONCLUSION: Inhalation of ZnO nanoparticles up to 2.0 mg/m3 for 4 h does not affect HRV and cardiac repolarization in healthy adults at the chosen time points. This study supports the view that cardiac endpoints are insensitive for the assessment of adverse effects after short-term inhalation of ZnO nanoparticles.

Serial fractional exhaled nitric oxide measurements off and at work in the diagnosis of occupational asthma.

BACKGROUND: Fractional exhaled nitric oxide (FeNO) before and after specific inhalation challenge has been postulated as an additional tool in the diagnosis of occupational asthma (OA), but little is known about serial FeNO measurements at home and at work. The aim of the present study was to assess the contribution of serial measurements of FeNO off and at work toward the diagnosis of OA. METHODS: Forty-one subjects with suspected (n = 35) or diagnosed (n = 6) OA performed FeNO measurements once daily during a 2-week holiday and a subsequent 2-week work period. A work-related increase in FeNO by 20 ppb (parts per billion) or more was considered positive. Subjects with negative or doubtful specific inhalation challenge but a FeNO increase of 20 ppb or more were evaluated individually by an overall expert rating taking into account all available information. RESULTS: Seven of 35 subjects (20%) with suspected and three of six subjects (50%) with diagnosed OA showed a work-related FeNO increase of 20 ppb or more. Six of the seven with suspected OA were reclassified as having an OA diagnosis by the overall expert rating which also considered these FeNO changes. CONCLUSIONS: Serial FeNO measurements off and at work provide complementary information in the diagnosis in about one-fifth of cases with suspected OA, especially if specific inhalation challenges are negative or cannot be performed.

Non-invasive tools beyond lung function before and after specific inhalation challenges for diagnosing occupational asthma.

PURPOSE: Increases of fractional exhaled nitric oxide (FeNO), sputum eosinophils, and methacholine responsiveness have been described after specific inhalation challenges (SIC) with occupational allergens, but limited information is available about their comparative performance. It was the aim of the study to assess the diagnostic accuracy of these non-invasive tests before and after SIC for the diagnosis of occupational asthma (OA). METHODS: A total of 122 subjects with work-related shortness of breath were included. The 'gold standard' was defined as airway obstruction (pulmonary responders) and/or an increase of FeNO of at least 13 ppb after SIC. The results were compared with those obtained using the pulmonary responder status alone as 'gold standard'. RESULTS: If the pulmonary responder status and/or an increase of FeNO was used as 'gold standard' for SIC, 28 out of 39 positives (72%), but also 20 out of 83 negatives (24%) showed an increase of sputum eosinophils and/or bronchial hyperresponsiveness after SIC. If the pulmonary responder status alone was used as 'gold standard', an increase of FeNO with a sensitivity of 0.57 and a specificity of 0.82 showed a higher accuracy than increases of sputum eosinophils (0.52/0.75) or bronchial hyperresponsiveness (0.43/0.87). Individual case analyses suggest that a few cases of OA may be detected by increases of sputum eosinophils or bronchial hyperresponsiveness alone, but probably false-positive tests dominate. CONCLUSION: It is recommended to use both lung function and increase of FeNO as primary effect parameters of SIC. Changes of sputum eosinophils and bronchial hyperresponsiveness after SIC have a low additional diagnostic value, but may be useful in individual cases.

Airway inflammation after inhalation of nano-sized zinc oxide particles in human volunteers.

BACKGROUND: Workers in the zinc production and processing of galvanized sheet steel are exposed to a complex mixture of particles and gases, including zinc oxide (ZnO) that can affect human health. We aimed to study the effects of short-term controlled exposure to nano-sized ZnO on airway inflammatory markers in healthy volunteers. METHODS: Sixteen subjects (8 females, 8 men; age 19-42, non-smokers) were exposed to filtered air and ZnO nanoparticles (0.5, 1.0 and 2.0 mg/m3) for 4 h, including 2 h of cycling with a low workload. Induced sputum samples were collected during a medical baseline and a final examination and also about 24 h after each exposure. A number of inflammatory cellular and soluble markers were analyzed. RESULTS: Frequency and intensity of symptoms of airway irritation (throat irritation and cough) were increased in some subjects 24 h after ZnO exposures when compared to filtered air. The group comparison between filtered air and ZnO exposures showed statistically significant increases of neutrophils and interleukin-8 (IL-8), interleukin-6 (IL-6), matrix metalloproteinase (MMP-9) and tissue inhibitors of metalloproteinases (TIMP-1) in sputum starting at the lowest ZnO concentration of 0.5 mg/m3. However, a concentration-response relationship was absent. Effects were reversible. Strong correlations were found between neutrophil numbers and concentrations of total protein, IL-8, MMP-9, and TIMP-1. CONCLUSIONS: Controlled exposures of healthy subjects to ZnO nanoparticles induce reversible airway inflammation which was observed at a concentration of 0.5 mg/m3 and higher. The lack of a concentration-response relationship warrants further studies.

An increase of fractional exhaled nitric oxide after specific inhalation challenge is highly predictive of occupational asthma.

PURPOSE: An increase of fractional exhaled nitric oxide (FeNO) has been described after specific inhalation challenges (SICs) with occupational allergens, but the clinical role of FeNO measurements before and after SIC is unknown. It was the aim of this study to assess the diagnostic accuracy of FeNO measurements before and after SIC in subjects with suspected occupational asthma (OA). METHODS: One hundred forty-eight patients with suspected OA were examined by SIC with various occupational allergens. Subjects were assigned to pulmonary responders, nonresponders or doubtful by standard lung function criteria. FeNO was measured before SIC (baseline) and 24 h afterwards. Subjects with negative or doubtful SIC but increase of FeNO were evaluated individually by an overall expert rating. Effect modifiers of FeNO increases were assessed by regression analyses. RESULTS: Thirty-one patients (21%) were classified as pulmonary responders, 105 (71%) as nonresponders and 12 (8%) as doubtful. With the pulmonary responder status as gold standard an increase of FeNO ≥ 13 ppb showed a specificity of 0.9 and a sensitivity of 0.5. Seventeen subjects with negative or doubtful responder status showed such an increase of FeNO, among them 13 subjects with definitive or probable OA after expert rating. Regression analyses revealed no significant modifiers for the FeNO increase. CONCLUSION: An increase of FeNO after SIC is highly predictive of OA and should be regarded as an additional criterion for the interpretation of SIC with occupational agents.