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

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Abstract

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.

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Acknowledgements

We thank the patients for their participation and all involved technical assistants of the Institute for Prevention and Occupational Medicine (IPA) for their excellent assistance. Authors’ contributions were as follows. Study design: R. Merget and J. Engel; data collection: J. Engel, R. Merget, O. Hagemeyer, and M. Raulf; data analysis: J. Engel, and V. Gering; writing: J. Engel, R. Merget, and V. van Kampen; data interpretation: J. Engel, R. Merget, M. Raulf, and V. van Kampen; critical review: V. Gering, O. Hagemeyer, T. Brüning, and M. Raulf.

Funding

This research was performed in the Institute for Prevention and Occupational Medicine of the German Social Accident Insurance. For this study, we received no further specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bürkle-de-la-Camp-Platz 1, 44789, Bochum, Germany

    Julia Engel, Vera van Kampen, Vitali Gering, Olaf Hagemeyer, Thomas Brüning, Monika Raulf & Rolf Merget

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  1. Julia Engel
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  2. Vera van Kampen
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  3. Vitali Gering
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  4. Olaf Hagemeyer
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  5. Thomas Brüning
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  6. Monika Raulf
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  7. Rolf Merget
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Correspondence to Rolf Merget.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all participants for being included in the study.

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Appendix

Appendix

Association between SIC results and type of agent

Type of agent

Positivesa (n = 39)

Negatives (n = 83)

Total (n = 122)

HMW

Enzymes n = 1

Animal dander=2

Molds n = 1

Wash nut n = 1

Flour n = 3

Plants n = 1

Molds n = 1

Flour n = 1

Pectin n = 1

Feathers n = 1

Milk protein n = 2

Straw, grain n = 1

Heated cotton mat n = 1

Gammarus n = 1

Latex n = 1

 

Total n = 9

Total n = 10

Total n = 19

LMW

Platinum salts n = 7

Persulfate salts n = 2

Cobalt powder n = 1

Hairdressing products n = 5

Platinum salts n = 3

Disinfectants n = 5

Acrylates n = 2

Primer coating n = 1

Teflon n = 1

Adhesive n = 1

Sodium sulphite n = 1

Persulfate salts n = 2

 

Total n = 10

Total n = 21

Total n = 31

Isocyanates

MDI n = 18

NDI n = 1

IPDI n = 1

MDI n = 26

HDI n = 21

IPDI n = 2

TDI n = 3

 

Total n = 20

Total n = 52

Total n = 72

  1. Animal dander cow and mouse, HMW high-molecular weight allergens, LMW low-molecular weight allergens excluding isocyanates, MMA methyl methacrylate, MDI diphenylmethane-4,4’-diisocyanate, NDI naphthylene-1,5-diisocyanate, HDI 1,6-hexamethylene diisocyanate, IPDI isophorone diisocyanate, TDI toluene diisocyanate
  2. aSIC Pulmonary responders and/or increase of FeNO ≥ 13ppb

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Engel, J., van Kampen, V., Gering, V. et al. Non-invasive tools beyond lung function before and after specific inhalation challenges for diagnosing occupational asthma. Int Arch Occup Environ Health 92, 1067–1076 (2019). https://doi.org/10.1007/s00420-019-01439-y

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