Comparison of high- and low-molecular-weight sensitizing agents causing occupational asthma: an evidence-based insight

ABSTRACT

Introduction

The many substances used at the workplace that can cause sensitizer-induced occupational asthma are conventionally categorized into high-molecular-weight (HMW) agents and low-molecular-weight (LMW) agents, implying implicitly that these two categories of agents are associated with distinct phenotypic profiles and pathophysiological mechanisms.

Areas covered

The authors conducted an evidence-based review of available data in order to identify the similarities and differences between HMW and LMW sensitizing agents.

Expert opinion

Compared with LMW agents, HMW agents are associated with a few distinct clinical features (i.e. concomitant work-related rhinitis, incidence of immediate asthmatic reactions and increase in fractional exhaled nitric oxide upon exposure) and risk factors (i.e. atopy and smoking). However, some LMW agents may exhibit ‘HMW-like’ phenotypic characteristics, indicating that LMW agents are a heterogeneous group of agents and that pooling them into a single group may be misleading. Regardless of the presence of detectable specific IgE antibodies, both HMW and LMW agents are associated with a mixed Th1/Th2 immune response and a predominantly eosinophilic pattern of airway inflammation. Large-scale multicenter studies are needed that use objective diagnostic criteria and assessment of airway inflammatory biomarkers to identify the pathobiological pathways involved in OA caused by the various non-protein agents.

KEYWORDS:

• Occupational asthma
• high molecular weight agents
• low molecular weight agents
• sputum cells
• phenotype

Article highlights

• This review provides strong evidence that high-molecular-weight (HMW) agents causing occupational asthma are associated with a few distinct phenotypic characteristics compared with low-molecular-weight (LMW) agents. However, LMW agents may exhibit some of these ‘HMW-like features,’ indicating that LMW compounds represent a heterogeneous group.

• Evidence is convincing that atopy, baseline nonspecific bronchial hyperresponsiveness, and smoking are significant risk factors for the inception of IgE-mediated sensitization and occupational asthma caused by HMW agents, but atopy and smoking are also associated with an increased risk of IgE-mediated sensitization to some LMW agents (i.e. platinum salts and acid anhydrides).

• Regardless of the presence of detectable specific IgE antibodies, both HMW and LMW agents are associated with a mixed Th1/Th2 immune response and a predominantly eosinophilic pattern of airway inflammation upon exposure to the causal agent.

• The conventional classification of the sensitizing agents causing occupational asthma into HMW and LMW agents is arbitrary and the threshold molecular weight differentiating these two groups of agents has never been substantiated; labeling these two categories of agents as ‘protein agents’ vs. ‘non-protein agents’ seems more meaningful in terms of the chemical nature of the sensitizing agents.

Declaration of interest

O Vandenplas and V Doyen declare grant support from Astrazeneca, Chiesi, and GSK. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was funded in part by the Fondation Mont-Godinne.