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Hypersensitivity pneumonitis (HP) is a rare, mostly occupational allergic disease of the lungs. There are many inhalable antigens that can cause HP. Most are organic dusts, rarely chemicals. A clinical case of HP is presented in a cable production worker with exposure to plasticizers who was initially diagnosed with idiopathic pulmonary fibrosis. The presence of specific IgG antibodies (sIgG) to phthalic anhydride in the patient's serum, together with reduced carbon monoxide diffusion capacity, hypoxemia at rest and on exertion, and the findings on computed tomography and histology, seemed to confirm the diagnosis of chronic HP due to phthalates, particularly as exposure to phthalate compounds at work was reported by the Technical Inspection Service. A review of the literature revealed that there is evidence of plasticizer alveolitis. While in four previous case reports phthalic anhydride was suspected as the cause of occupational HP because of work-related symptoms, we were able to detect sIgG to phthalic anhydride for the first time. This case illustrates that phthalates, which have rarely been described as triggers of HP, should be considered in cases of suspected occupational HP., Competing Interests: All authors declare no conflict of interest. The authors VvK, CE, TB, and RM are employees of IPA. They are independent from the DGUV in access to the collected data, responsibility for data analysis and interpretation, and the right to publish. Table 1.Characteristics, symptoms, and test results of the patient with suspected occupational hypersensitivity pneumonitis at the time of examination in our outpatient clinic. CaseSex, age (years)Male, 59Smoking statusFormer (30 years ago)Suspected allergenPhthalate compoundsWork-related symptomsCough, fatigue, dyspneaDuration of symptoms (years)5Lung function test   RV %pred. [%] (z-score*)77 (–1.3)   TLC %pred. [%] (z-score)66 (–3.4)   RV%TLC [%] (z-score)108 (0.6)   FEV1%pred. [%] (z-score)58 (–2.7)   FVC %pred. [%] (z-score)59 (–2.9)   FEV1/FVC [%] (z-score)100 (0.0)Diffusing capacity   DLCO %pred. [%]57   KCO %pred. [%]89Blood gases (ergometry) – at rest:   pO2 (mmHg) (%pred. [%])66 (81)   pCO2 (mmHg) (%pred. [%])37 (94)– on exercise (50 W):   pO2 (mmHg)57   pCO2 (mmHg)42Total IgE (kU/L)6.1Specific IgE (sIgE) to (kU/L)   Phthalic anhydride (k79)0.00   Maleic anhydride (Rk210)0.00FEV1 = forced expiratory volume in 1 second; FVC = forced vital capacity; KCO = carbon monoxide coefficient; pO2 = partial pressure of oxygen in the blood; pCO2 = partial pressure of carbon dioxide in the blood; RV = residual volume; TLC = total lung capacity; DLCO = transfer factor of the lung for carbon monoxide. *A z-score greater than −1.645 is considered normal [18]. Figure 1.Computed tomography scan showing a florid inflammatory alveolar process with ubiquitous ground glass-like infiltrates in both lungs, cystic transformation, fibrotic changes, and septal thickening in the lower-lung zone with left-sided predominance and dilatation of the bronchi of both lower lobes. Table 2.Results of specific IgG antibody testing and evaluation of test results according to [19].AntigenmgA/LRating95% quantile of 121 referencesAspergillus fumigatus22.93n.e. (52.3% quantile)97.22Aureobasidium pullulans22.84high (98.8% quantile)12.28Penicillium chrysogenum18.29n.e. (52.6% quantile)71.55Mould mixture17.44n.e. (81.7% quantile)26.80Saccharopolyspora rectivirgula10.95high (98.8% quantile)5.17Thermoactinomyces vulgaris15.95n.e. (88.1% quantile)21.46Chicken feathers35.71higher than max. control12.62Goose feathers26.73higher than max. control11.54Phthalic anhydride5.89high (97.7% quantile)3.70Human serum albumin (HSA)2.93n.e. (95.4% quantile)2.74Antigens for which the patient had sIgG values above the 97.5% quantile of the reference group are shown in bold. n.e. = not elevated. Figure 2.Histological specimens showing giant cells with cholesterol deposits (yellow arrow), multiple giant cells with inflammatory cells (blue arrows); lymphocytic intra-alveolar and interstitial inflammation with fibrosis (asterisk)., (© Dustri-Verlag Dr. K. Feistle.)

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 (sIgEs) against wheat and rye flour, however, has not been thoroughly compared with other diagnostic procedures., Objective: We sought to evaluate the diagnostic accuracy of sIgE against wheat and rye compared with specific inhalation challenge (SIC) with flour as the reference standard., Methods: This retrospective multicenter study included 264 subjects who completed an SIC with flour in eight tertiary centers, of whom 205 subjects showed a positive SIC result., Results: Compared with SIC, sIgE levels of 0.35 kU A /L or greater against wheat and rye provided similar sensitivities (84% to 85%, respectively), specificities (71% to 78%), positive predictive values (91% to 93%), and negative predictive values (56% to 61%). Increasing the threshold sIgE value to 5.10 kU A /L for wheat and to 6.20 kU A /L for rye provided a specificity of 95% or greater 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 postchallenge FeNO compared with subjects with a 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 to perform an SIC. The absence of detectable sIgE against wheat and rye in subjects with a positive SIC seems to be associated with lower levels of T H 2 biomarkers., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Background: Clinical heterogeneity in sensitizer-induced occupational asthma (OA) and its relationship to airway inflammatory profiles remain poorly elucidated. Objectives: To further characterize 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 patients with OA., Methods: We conducted a multicenter, retrospective, cross-sectional study of 296 patients with OA confirmed 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 (OR [95%CI], 1.31 [1.11 1.55] for each 250-μg increment in daily dose), short-acting ß2-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 sex (3.34 [1.29-9.99]), absence of corticosteroid use (5.47 [2.09-15.16]), use of short-acting ß2-agonists once or more a day (4.09 [1.71-10.01]), ≥2 severe exacerbations during the previous 12 months at work (4.22 [1.14-14.99]), and isolated early reactions during the specific inhalation challenge (4.45 [1.85-11.59])., Conclusions: The findings indicate that sputum inflammatory patterns in patients 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 findings reported in nonoccupational asthma and are not related to the type of causal agent.

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 (FEV 1 ) 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., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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., (© 2023. The Author(s).)

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., (© 2023. The Author(s).)

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 (BaSO 4 ), 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 BaSO 4 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 BaSO 4 particles (4.0 mg/m 3 ) 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 BaSO 4 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 BaSO 4 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 BaSO 4 particles was minimal and 15-fold lower compared to ZnO., Conclusion: The results of this study indicate that BaSO 4 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., (© 2022. The Author(s).)

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., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Competing Interests: The authors have no conflicts of interest.

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 FEV 1 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., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

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/m 3 . 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/m 3 ) 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.