Old and New Causes of Occupational Asthma

Work-related asthma (WRA) is a condition of asthma symptoms that has a connection with a workplace. Based on the different types of exposure at the workplace and onset of asthma symptoms, WRA is broadly divided into two categories: occupational asthma (OA) and work-exacerbated asthma (WEA). OA and WEA can be further categorized based on various clinical and immunological definitions, and their clinical course and etiology are different. In this chapter, we discuss the clinical features, diagnostic approaches, and prevention and management of the WRA.

Exposures at work can give rise to different phenotypes of “work-related asthma.” The focus of this review is on the diagnosis and management of sensitizer-induced occupational asthma (OA) caused by either a high- or low-molecular-weight agent encountered in the workplace. The diagnosis of OA remains a challenge for the clinician because there is no simple test with a sufficiently high level of accuracy. Instead, the diagnostic process combines different procedures in a stepwise manner. These procedures include a detailed clinical history, immunologic testing, measurement of lung function parameters and airway inflammatory markers, as well as various methods that relate changes in these functional and inflammatory indices to workplace exposure. Their diagnostic performances, alone and in combination, are critically reviewed and summarized into evidence-based key messages. A working diagnostic algorithm is proposed that can be adapted to the suspected agent, purpose of diagnosis, and available resources. Current information on the management options of OA is summarized to provide pragmatic guidance to clinicians who have to advise their patients with OA.

Spray cleaning and disinfection products have been associated with adverse respiratory effects in professional cleaners and among residents doing domestic cleaning. This review combines information about use of spray products from epidemiological and clinical studies, in vivo and in vitro toxicological studies of cleaning chemicals, as well as human and field exposure studies. The most frequent chemicals in spray cleaning and disinfection products were compiled, based on registrations in the Danish Product Registry. The chemicals were divided into acids, bases, disinfectants, fragrances, organic solvents, propellants, and tensides. In addition, an assessment of selected cleaning and disinfectant chemicals in spray products was carried out. Chemicals of concern regarding respiratory effects (e.g. asthma) are corrosive chemicals such as strong acids and bases (including ammonia and hypochlorite) and quaternary ammonium compounds (QACs). However, the evidence for respiratory effects after inhalation of QACs is ambiguous. Common fragrances are generally not considered to be of concern following inhalation. Solvents including glycols and glycol ethers as well as propellants are generally weak airway irritants and not expected to induce sensitization in the airways. Mixing of certain cleaning products can produce corrosive airborne chemicals. We discuss different hypotheses for the mechanisms behind the development of respiratory effects of inhalation of chemicals in cleaning agents. An integrative assessment is needed to understand how these chemicals can cause the various respiratory effects.

We are now in the epoch of “molecular allergology” and numerous clinically relevant allergenic molecules are available improving the performance of in vitro allergen tests and allergen detection methods. This review is focusing on characterized occupational allergens and their implementation into the in vitro diagnosis for occupational allergy and in allergen detection methods.

More than 400 occupational agents are identified and documented as being ‘respiratory sensitizers’, but currently only a limited number of them are characterized on the molecular level and available for routine diagnosis as native or recombinant allergens. One exception, however, is natural rubber latex (NRL) from Hevea brasiliensis still remaining an important occupational allergen source. Characterization of 15 NRL allergens led to the development of assays for the determination of allergen content of NRL materials and the implementation of component-resolved diagnosis (CRD) for specific IgE antibody measurement. Microarray or singleplex using recombinant or native allergens are reliable tools for NRL allergy diagnosis. In addition, NRL allergy is an excellent model for improving extract-based specific IgE measurement by amplification of NRL extract preparation with stable recombinant major allergen rHev b 5. Despite the many efforts to characterize the occupationally relevant wheat allergens for baker’s asthma, the most frequently occurring forms of occupational asthma, the results are highly diverse. Wheat sensitization profiles of bakers showed great interindividual variability and no wheat allergen could be classified as the major allergen. For diagnosis of baker’s asthma, a whole wheat extract is still the best option for specific IgE determination. But single wheat allergens might help to discriminate between wheat-induced food allergy, grass pollen allergy and baker’s asthma. For workplace-related allergens like coffee, wood, soybean, seafood and moulds allergens are characterized and few of them are available, but their relevance for occupational sensitization routes should be verified in the further studies.

Each year, approximately 300 million people worldwide are diagnosed with asthma, and more than 250,000 deaths annually are attributed to asthma. However, the sources and mechanisms behind the development of asthma are diverse. High-molecular-weight proteins, including detergent enzymes and common allergens, contribute to an immunoglobulin E (IgE)-mediated atopic asthma response. Low-molecular-weight chemicals typically are haptens that form hapten–protein complexes resulting in IgE-mediated or IgE-independent immune-mediated asthma. Hapten–protein exposures typically occur at the workplace and can include acid anhydrides, isocyanates, as well as others. Irritant-induced asthma typically results from a single, accidental exposure to a highly concentrated irritant in the workplace that induces pulmonary damage by releasing proinflammatory mediators that lead to asthma. Additionally, ingestion of certain medications including aspirin, β-blockers, or angiotensin-converting enzyme inhibitors can cause drug-induced asthma by enzymatic reactions leading to the production of proinflammatory mediators and modulation of smooth muscle function. Overall, the diversity of asthma makes this prevalent lung disease difficult to diagnose and manage. This article compares and contrasts phenotypes, mechanisms, and possible treatments for these differing types of drug- and chemical-induced asthma that are currently understudied.

Chemicals and proteins can cause hypersensitivity reactions in the respiratory tract via multiple mechanisms. Hypersensitivity responses require a latency period and develop in two stages: An induction or sensitization phase, during which the immune system learns to recognize the allergen, and an elicitation or effector phase with appearance of symptoms. Often, the hypersensitivity reaction to a given allergen involves a combination of both humoral (Types I–III) and cell-mediated (Type IV) components leading to disease. This article focuses on hypersensitivity reactions in the respiratory tract that are most often encountered by toxicologists including allergic rhinitis, allergic asthma, anaphylaxis, and hypersensitivity pneumonitis. In addition, chronic beryllium disease will be presented as an example of a Th1-mediated hypersensitivity reaction. Current knowledge of mechanisms will be presented as well as animal models used in research in hypersensitivity reactions in the respiratory tract.