Contact with laboratory animals and veterinary medicine are fields with a heightened risk of sensitization, allergy, and occupational respiratory and skin disease [1] [2] . Studies have reported that the prevalence of respiratory symptoms ranges from 40% to 60% among veterinarians [3] [4] . Most occupational lung diseases are caused by repeated, long-term exposure, with occupational asthma and chronic obstructive pulmonary disease (COPD) being the most commonly diagnosed respiratory diseases [5] [6] . Close contact with various animals and pets can lead to sensitization and allergic diseases of the upper (rhinitis) and lower respiratory tract (allergic asthma) in exposed workers [4] [7] . Occupational asthma is the leading occupational lung disease in both developing and industrialized nations, accounting for approximately 15% of all asthma cases and an annual incidence rate of up to 18 per 100,000 [8] . Based on inflammatory mechanisms, it can be categorized into allergic and non-allergic asthma [9] . Besides allergic (and infectious) risks, bacteria and fungi can cause inflammatory reactions through the inhalation of endotoxins or ß-glucans [10] , leading to non-allergic reactions like non-allergic rhinitis, organic dust toxic syndrome (ODTS), non-allergic asthma, bronchitis, and COPD [11] [12] .

In addition, personal characteristics such as atopy status can influence the extent of sensitization to animals, respiratory symptoms, and the impairment of lung function [13] [14] . It was found that both sensitization and exposure to laboratory animal allergens contributed independently to lung function decline in subjects who had been working with laboratory animals. Nevertheless, data for the group of veterinarians and assistant staff in veterinary practices are scarce.

Previous reports based on data from this study described determinants of exposure, work-related respiratory symptoms, and physician-confirmed diseases [4] [15] . Here, we assessed spirometry and body plethysmography in veterinarians and assistants. We investigated risk factors for lung function impairment in subjects without physician-diagnosed lung diseases and related lung function to occupational exposures and personal characteristics like atopic status and specific sensitization against cats and/or dogs.

When working with animals, humans are exposed to various particulate, biological, or chemical agents [1] . These exposures can lead to specific (e.g. TH2-type) or non-specific inflammatory responses in the airways or lung parenchyma. Among the 122 individuals in our study, 13 had physician-confirmed asthma, of which 9 were atopic and 4 were non-atopic concerning sx1 level. The prevalence of 11% for physician-confirmed asthma was in the range previously reported [21] [22] . Most of the asthmatics were properly treated, and only one participant had a manifest obstructive ventilation disorder. A discussion of the prevalence of

asthma and symptoms associated with existing atopy or specific sensitization to furry animals can be found in our recent publication [4] .

In our current analyses, we investigated the lung function of 109 subjects without known respiratory disease. In addition to obstructive changes, restrictive impairments were considered. Correct differentiation can be difficult if the ATS criteria for lung function tests are not met. Often the fulfillment of the acceptability and repeatability criteria is not specified [17] . In this study, we could rely on quality-assured measurements. A test result was considered indicative of disease if it fell outside the normal range. Both the ATS and ERS recommended using the 5th centile (minus 1.64 z-score) to define the lower limit of normal (LLN) for lung function parameters. Unlike percent predicted values, z-scores are free from bias due to age, height, sex, or ethnic group [18] .

Typically, the diagnosis of airway obstruction is predicated on the observation of a diminished ratio of FEV₁ to FVC (Tiffeneau-Index). The degree of severity is gauged by the decrease in FEV₁, while FVC tends to remain constant. Both parameters can be assessed by spirometry. In addition, we measured the MMEF, which is sensitive to peripheral expiratory flow obstruction, and an available methodology to assess small airway function. MMEF might serve as an early indicator of obstructive pulmonary disease [23] .

A restrictive disorder can be suspected from spirometry when VC is reduced and the Tiffeneau-Index either is normal or elevated. It is proven, however, only by a decrease in TLC [19] . TLC assessment is the gold standard for the diagnosis of restrictive impairment, which is defined as TLC being below the 5th percentile of reference. In our study, the determination of TLC was based on body plethysmography in combination with quality-assured spirometry according to ATS recommendations [16] . Reference values and LLN for TLC were recently published [20] .

Our subjects showed an expected TLC z-score of −0.04 and a normal distribution. Nevertheless, there were values indicating a restrictive ventilatory dysfunction concerning LLN in five subjects. Referring to the LLN of TLC corresponding to the 5th percentile, the observed prevalence of 4.6% (5 of 109) was exactly within the expected range of the GLI reference distribution [20] .

In our study, the median z-scores of the Tiffeneau index and MMEF, parameters used to identify obstructive ventilatory limitation, showed a shift to the left and were significantly lower compared to the corresponding GLI data [18] [23] . Ten workers (8.2%) had a formal obstructive ventilatory disorder with a Tiffeneau z-score below the LLN. This is therefore more than the GLI reference distribution suggests [18] . The prevalence was slightly higher in non-atopic subjects (9.1% vs. 6.3% in atopic subjects). Such a prevalence in individuals who are neither atopic nor asthmatic suggests that non-allergic mechanisms should be carefully considered when investigating lung function and occupational diseases [24] . Specifically, veterinary staff are constantly exposed to animal dander during work. This dander not only contains high molecular weight allergens but also irritative components of microbial origin such as endotoxins and β-glucan. For example, pet ownership is strongly associated with high indoor endotoxin levels [25] . Additionally, veterinary staff is exposed to irritative substances like cleaning agents and disinfectants [3] [26] .

Overall, subjects with respiratory symptoms had a significantly lower Tiffeneau-index z-score than symptom-free subjects, accompanied by a similar trend in MMEF z-scores. There was no association between the severity of symptoms and obstructive impairment. In addition, four symptom-free subjects had obstructive lung disease (Tiffeneau z-score < −1.64), which corresponds to a prevalence of 44.4% for obstructive individuals. This is consistent with the results in patients diagnosed with COPD. While symptoms such as chronic cough (45%), sputum production (38%), and dyspnoea on exertion (52.5%) were frequently observed, 32% reported no symptoms [27] .

In subjects without asthma, no significant differences were found in the overall reduced FEV₁ and MMEF values between subjects with and without atopy. This suggests that atopy per se was not the main factor in reducing these lung function values in workers without asthma.

An important result, however, was the effect of specific sensitization. Almost half of the atopic subjects were specifically sensitized to cat and/or dog allergens. These atopic subjects with sensitization to furry animals showed reduced lung function parameters indicative of obstructive impairment. Significant differences in MMEF were found between atopics with such specific sensitization and other atopics, suggesting that sensitization to furry animals may contribute to obstructive impairment in atopic individuals. No significant associations were found between occupation, type of practice, or duration of work and lung function parameters indicating obstructive impairment. However, exposure to animals does not only occur in an occupational context but also the personal environment [15] [21] . Eighty-two percent of the employees in our study had cats and dogs as pets. Animal allergens are also frequently found in schools and on public transport [28] [29] .

Effects on respiratory health have been investigated in longitudinal studies for laboratory animal workers, but data for the veterinarians and staff group is scarce. In a 5-year follow-up study of 319 laboratory workers, an excessive decrease in FEV₁ and FVC was found in sensitized workers (FEV₁/FVC data were not provided) [30] . The decline was greatest in subjects exposed to the animals to which they were sensitized. In a study on 70 newly employed subjects a progressive lung function impairment was seen within two years from the start of exposure to laboratory animals [14] . Time-related impairment was observed in the whole study population irrespective of allergic sensitization, suggesting that exposure to animal facilities could be harmful. In a Swedish 5-year follow-up study of 88 animal-exposed laboratory technicians, no significant decrease in lung function was found [31] . The authors considered a concomitant decrease in smoking habits during the follow-up, a better working environment, and the use of anti-allergic medication as possible confounding factors.

Cigarette smoking is widely recognized as an important risk factor for diseases such as chronic bronchitis and COPD [32] . Moreover, smoking could amplify the adverse effects of occupational exposure on lung function [33] . Our results are in line with these findings and confirm the assumption of possible interactions between specific sensitization and smoking on lung function [34] . Thus, our findings underscore the importance of considering both immunological and lifestyle factors in the assessment and management of lung function. Even though smoking could explain part of the respiratory impairment, it should be emphasized that our results suggest that veterinary staff and veterinarians are potentially at risk due to their occupational exposure.

Although our study provides quality-assured findings on the lung function of workers in veterinary practices, there are potential limitations that should be taken into account. This cross-sectional study recruited a total of 122 participants, including female assistants and a small number of veterinarians. Factors for non-participation could be a lack of interest in the study or concerns about disclosing animal-related symptoms to their employer. Subjects with respiratory health problems might be more willing to participate. On the other hand, people with health problems may leave work earlier, making it difficult to establish a link between health problems and exposure in the workplace (healthy worker effect) [35] . Thus, larger and longitudinal studies may provide more robust and generalizable results.

In our study, almost half of the atopic subjects were specifically sensitized to cat and/or dog allergens. Sensitization to other allergens was not analyzed. The study did not account for exposure to secondhand smoke, or irritants, which could significantly impact lung function.

The results of our study suggest that occupational exposure to furry animals and the development of sensitization against animal allergens may have a significant impact on lung function in employees. Identifying and addressing the actual workplace exposure and the early detection of workers at risk can lead to the prompt initiation of preventive measures such as workplace adjustment, regular check-ups, and guidance for quitting smoking. Objective lung function assessments possess the capability to detect alterations even when overt clinical manifestations are not present. Therefore, lung function tests (spirometry) should be used as a screening tool and preventive measure, both at an early stage and on an ongoing basis.

The authors thank the employees of the veterinary practices for their support and participation in this study.

We thank Anne Lotz and Christoph Nöllenheidt for data management.

This study (IPA-148-AllergoMed) was financially supported by Institution for Statutory Accident Insurance and Prevention in the Health and Welfare Services (BGW) and the German Social Accident Insurance (DGUV).