Geneviève Evrard

Incidence of Severe Asthmatic Reactions After Challenge Exposure to Occupational Agents

BACKGROUND Specific inhalation challenges (SICs) with occupational agents are used to establish the diagnosis and etiology of occupational asthma. The aim of this study was to assess the frequency and determinants of severe asthmatic reactions induced by various occupational agents during SICs performed using realistic methods of exposure. METHODS The SIC records of 335 consecutive subjects with a positive SIC (ie, ≥ 20% fall in FEV1) due to various occupational agents were reviewed. Asthmatic reactions were graded as moderate when requiring repeated administration of an inhaled short-acting β₂-agonist (SABA) and severe when requiring repeated SABA and systemic corticosteroids. RESULTS Overall, 68 of the 335 subjects (20%) required an inhaled SABA during the SICs. The multivariate logistic regression analysis showed that the need for an inhaled SABA increased when the SIC involved a low-molecular-weight agent (LMW) (OR, 2.47; 95% CI, 1.43-4.28) and marginally so when the subjects required regular treatment with an inhaled corticosteroid (OR, 1.62; 95% CI, 0.93-2.80). The severity of asthmatic reactions was graded as moderate in 12% and severe in 3% of the subjects. Of the 10 severe reactions, five developed after exposures ≤ 5 min. Multivariate logistic regression analysis showed that challenging subjects with a LMW agent was the only significant determinant for the development of moderate/severe reactions (OR, 3.05; 95% CI, 1.62-5.73). CONCLUSIONS Challenges with LMW agents are associated with a higher risk of an asthmatic reaction requiring pharmacologic treatment. This study may provide useful guidelines for further improving the safety of SICs.

Asthma related to cleaning agents: a clinical insight

Objective To determine the agents causing asthmatic reactions during specific inhalation challenges (SICs) in workers with cleaning-related asthma symptoms and to assess the pattern of bronchial responses in order to identify the mechanisms involved in cleaning-related asthma. Design A retrospective case series analysis. Setting The study included all participants who completed an SIC procedure with the cleaning/disinfection products suspected of causing work-related asthma over the period 1992–2011 in a tertiary centre, which is the single specialised centre of the French-speaking part of Belgium where all participants with work-related asthma are referred to for SIC. Results The review identified 44 participants who completed an SIC with cleaning/disinfection agents. Challenge exposure to the suspected cleaning agents elicited a ≥20% fall in forced expiratory volume in 1 s (FEV1) in 17 (39%) participants. The cleaning products that induced a positive SIC contained quaternary ammonium compounds (n=10), glutaraldehyde (n=3), both of these agents (n=1) and ethanolamines (n=2). Positive SICs were associated with a significant decrease in the median (IQR) value of the provocative concentration of histamine causing a 20% fall in FEV1 (PC20) from 1.4 (0.2–4.2) mg/mL at baseline to 0.5 (0.4–3.0) mg/mL after the challenge and a significant increase in sputum eosinophils from 1.8 (0.8–7.2)% at baseline to 10.0 (4.1–15.9)% 7 h after the challenge exposure while these parameters did not significantly change in participants with a negative SIC. Overall, 11 of 17 participants with positive SICs showed greater than threefold decrease in postchallenge histamine PC20 value, a >2% increase in sputum eosinophils, or both of these outcomes. Conclusions These data indicate that a substantial proportion of workers who experience asthma symptoms related to cleaning materials show a pattern of bronchial reaction consistent with sensitiser-induced occupational asthma. The results also suggest that quaternary ammonium compounds are the principal cause of sensitiser-induced occupational asthma among cleaners.

Persistence of asthma following allergen avoidance is associated with proTh2 myeloid dendritic cell activation.

Background The natural history of asthma includes in some patients periods of disease remission, but the underlying mechanisms are unknown. Objectives We explored whether type 1 myeloid dendritic cell (mDC) dysfunction could be involved in the persistence of asthma, studying the controlled setting of occupational asthma after allergen avoidance. Methods We recruited 32 patients with occupational asthma to flour or latex ascertained by specific inhalation challenge and who were no longer exposed to the causal allergen. Leukapheresis was performed in each patient to isolate and characterise blood type 1 mDCs, and their functionality was studied in coculture with allogeneic CD4+ T cells from controls. Results At follow-up, 11/32 patients (34%) were characterised by the absence of symptoms and non-specific bronchial hyper-responsiveness to histamine and were considered to be cured. When compared with cured patients, mDCs from patients with persistent disease increased the production of interleukin (IL) 5 and IL-13 by CD4+ T cells, and upregulated programmed death ligand 2 (PD-L2) upon allergen pulsing. In addition, IL-5 and IL-13 responses could be reversed by exogenous IL-12, as well as by PD-L2 blockade. Conclusions This study indicates that pro-Th2 features of mDCs correlate with disease activity in asthma after cessation of exposure to the causal allergen. The findings also highlight that the Th2 programming by dendritic cells is flexible and partly mediated by PD-L2.

Assessment of eosinophilic airway inflammation as a contribution to the diagnosis of occupational asthma.

Ascertaining the presence of asthma through the assessment of nonspecific bronchial hyperresponsiveness (NSBH) is a key step in the diagnosis of occupational asthma (OA). We aimed at investigating whether indices of airway inflammation including fractional exhaled nitric oxide (FeNO) and sputum eosinophils would be useful adjuncts to the measurement of NSBH in diagnosing OA defined as a positive specific inhalation challenge (SIC).

Defects in Plasmacytoid Dendritic Cell Expression of Inducible Costimulator Ligand and IFN-α Are Associated in Asthma with Disease Persistence.

Plasmacytoid dendritic cells (pDCs) represent a subset of DCs specialized in antiviral defense. Originating from a different lineage than myeloid DCs and displaying a plasma cell–like morphology, they are able to secrete large amounts of type 1 IFN when activated by viruses through toll-like receptor 7 (TLR7) and TLR9 (1). In addition to their antiviral function, pDCs play a role in peripheral tolerance to allergens; in a seminal study, de Heer and colleagues showed that allergen-pulsed pDCs were able to restore tolerance in experimental ovalbumin-induced asthma (2). In addition, it was shown that pDCs from patients with asthma display impaired IFN-a secretion on TLR9 ligation by A-CpG (3). pDC-mediated tolerance is notably related to their expression of the ligand to inducible costimulatory molecule (ICOS-L), as the ICOS/ICOS-L costimulatory pathway has been linked to the priming of IL-10– producing regulatory T cells (4) and to tumor-induced tolerance (5). Mechanisms underlying the persistence of allergic asthma remain poorly understood. This could be related to a multitude of factors that may contribute to disease persistence, among which are persistent allergen exposure and host-related factors. IgE-mediated occupational asthma (OA) offers a unique opportunity to address this question, as one third of patients completely recover (from both symptoms and nonspecific bronchial hyper-responsiveness) after complete cessation of exposure to the causal allergen (6). Given their tolerogenic role, we sought to explore pDCs for their expression of ICOS-L and IFN-a production in 29 patients with OA diagnosis to flour (n = 14) or latex (n = 15), according to a specific inhalation challenge (performed between 2001 and 2011). All patients had been removed from their workplace and were no longer exposed to the causal allergen. Study subjects were defined

Occupational asthma caused by an epoxy amine hardener

We describe a 43-year-old epoxy floor layer who developed work-related asthma while exposed to an epoxy hardener based on isophorone diamine (IPDA). Challenge exposures to the curing of the epoxy resin system and subsequently to the polyfunctional amine hardener containing IPDA both elicited delayed asthmatic reactions. This report further indicates that exposure to epoxy hardeners containing polyfunctional amines should be considered as a potential cause of occupational asthma. Appropriate work hygiene measures should be implemented to minimize airborne exposure to these volatile compounds.