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.

Occupational asthma phenotypes identified by increased fractional exhaled nitric oxide after exposure to causal agents.

BACKGROUND: The added value of fractional exhaled nitric oxide (Feno) remains controversial in the investigation of occupational asthma (OA). OBJECTIVE: We sought to assess whether or not the increase of Feno levels following positive specific inhalation challenge (SIC) was restricted to phenotypes of subjects sharing common clinical characteristics by using a statistical cluster analysis. METHODS: Subjects were investigated for possible OA in a tertiary center using SICs from 2006 to 2012. Feno levels and sputum eosinophil counts were assessed at baseline and 24 hours after SIC. We performed a 2-step cluster analysis of the subgroup of subjects with OA. A multivariate logistic regression was performed in order to identify the variables associated with an increase in Feno in subjects with OA. RESULTS: One hundred and seventy-eight subjects underwent SIC; 98 had a positive test. The cluster analysis performed in the OA subgroup identified 3 clusters. Despite a positive SIC, there was no increase in the Feno levels after exposure to occupational agents in Cluster 3, in which subjects were only exposed to low-molecular-weight (LMW) agents. The molecular weight of the agent (high molecular weight vs LMW) was the only factor associated with an increase in Feno (OR: 4.2 [1.1-16.8]) in subjects with a positive SIC. CONCLUSION: An increase in Feno after exposure to agents causing OA seems to occur more consistently in subjects with OA caused by high molecular weight than in those with OA due to LMW.

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.

Inhalation challenges with occupational agents: threshold duration of exposure.

OBJECTIVES: The aim of this study was to characterize the threshold duration of exposure needed to elicit an asthmatic reaction during specific inhalation challenges (SIC) with various occupational agents and to determine the duration of exposure that should be completed before the test can be considered negative. METHODS: This retrospective study analysed the cumulative duration of challenge exposure that was required to elicit a ≥20% fall in forced expiratory volume in one second in 335 consecutive subjects with a positive SIC. RESULTS: The threshold duration of challenge exposure required to induce an asthmatic reaction was ≤60 min in 179 (53%) subjects, between 61 and 120 min in 74 (22%) subjects, and longer than 120 min in 82 (25%) subjects. The multivariate linear regression analysis showed that a longer duration of exposure was associated with exposure to low-molecular-weight agents (p < 0.001), a higher level of baseline non-specific bronchial hyperresponsiveness to histamine (p = 0.015), increasing age (p = 0.011), and a shorter duration of asthma symptoms at work (p = 0.060). CONCLUSIONS: This study demonstrates that the sensitivity of SICs for diagnosing OA is highly dependent upon the duration of the challenge exposure. These data may provide useful guidance for improving the reliability of SICs performed with realistic methods of exposure.

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 ß2-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.

Time trends in occupational asthma in Belgium.

OBJECTIVES: There is little information on the changes in the pattern of occupational asthma (OA) over time. The objective of this study was to evaluate the time trends in the incidence and causes of immunological OA in Belgium using workers' compensation data. METHODS: Cases of OA were identified through a retrospective review of all claims submitted by salaried workers to the Belgian Workers' Compensation Board from 1993 to 2002. The likelihood of OA was categorized as definite, probable, or possible based upon the results of from diagnostic procedures. Time trends were evaluated using Spearman's rank correlation for crude numbers of cases and through the negative binomial regression for incidence rates of OA per industry. RESULTS: From a total of 1852 claims, 971 were categorized as having definite, probable, or possible OA. There was a downward trend in the annual number of cases due to the main causes of OA (i.e. flour, isocyanates, woods, and enzymes) and an apparent increase in cases of latex-induced OA. The estimated average annual incidence of OA was 29.4 (95% CI: 27.6-31.3) new cases per million salaried workers during the 1993-2002 period. There was a significant decline in the overall incidence rate of OA throughout the study period from 35.5 new cases per million salaried workers in 1993 to 25.8 in 2002. CONCLUSIONS: These compensation-based data indicate that there has been a global downward trend in the incidence of OA during the nineties, although the factors that determined this reduced incidence should be further investigated.

Investigation of occupational asthma: sputum cell counts or exhaled nitric oxide?

BACKGROUND: The measure of sputum eosinophil counts is a useful tool in the investigation of occupational asthma (OA), but processing sputum is time consuming. Measuring the fractional concentration of exhaled nitric oxide (FENO) may be an alternative in clinical practice. The aim of this study was to assess the respective changes of sputum eosinophil counts and FENO following exposure to occupational agents in the routine practice of two tertiary centers in North America and Europe. METHODS: Workers undergoing specific inhalation challenges (SICs) for possible OA in tertiary clinics in both Canada and Belgium were enrolled. Sputum cell counts and FENO were collected at the end of the control day and at 7 and 24 h after exposure to the offending agent. RESULTS: Forty-one subjects had a negative SIC; 26 subjects had OA proven by a positive SIC. In subjects with positive SIC, there was a significant increase in sputum eosinophils at 7 h (9.0 [9.9]%) and 24 h (11.9 [14.9]%) after exposure compared with the baseline (2.8 [4.2]%), whereas there was a significant increase in FENO only 24 h after exposure (26.0 [30.5] ppb) compared with the baseline (16.6 [18.5] ppb). A 2.2% change in sputum eosinophil counts achieved a much higher sensitivity and positive predictive value than a 10-ppb change in FENO with similar specificity and negative predictive value for predicting a 20% decrease in FEV(1) during SICs. CONCLUSIONS: Sputum eosinophil counts constitute a more reliable tool than FENO to discriminate positive and negative SICs.

Rhinitis in subjects with work-exacerbated asthma.

OBJECTIVES: This study aimed at characterizing the nature, severity, and timing of nasal and ocular symptoms in subjects with work-exacerbated asthma (WEA). METHODS: Among the 363 subjects referred to a tertiary-care hospital for the investigation of work-related asthma symptoms, 105 subjects who demonstrated non-specific bronchial hyperresponsiveness to histamine, but a negative response to a specific inhalation challenge with the suspected occupational agent(s) were considered as having WEA. Their characteristics were compared with those of 172 subjects with occupational asthma (OA), ascertained by a positive response to a specific inhalation challenge. RESULTS: A high proportion of subjects with WEA (83%) and OA (90%) reported at least one nasal symptom at work. Sneezing/itching and rhinorrhea were more frequent in subjects with OA (78% and 70%, respectively) than in those with WEA (61%, p = 0.004 and 57%, p = 0.038, respectively), while post-nasal discharge was more common in WEA (30%) than in OA (18%, p = 0.019). Nasal symptoms were less severe in WEA (median [25th-75th percentiles] global severity score: 4 [2-6]) as compared to OA (5 [4-7], p < 0.001). Nasal symptoms preceded less frequently those of asthma in subjects with WEA (17%) than in subjects with OA (43%, p = 0.001). CONCLUSIONS: Nasal symptoms are highly prevalent in subjects with WEA, although their clinical pattern differs from that found in OA. Further investigations of the health and socio-economic impacts of upper airways symptoms in WEA are required to improve the understanding and management of this common condition.

Rhinitis and its impact on work.

PURPOSE OF REVIEW: Health-related work disability has been increasingly recognized as an important component of the economic and societal burden of a disease. The purpose of this review is to summarize recently published data pertaining to the impact of rhinitis on work disability. RECENT FINDINGS: Recent studies have investigated the impact of rhinitis on both the amount of time missed from work (absenteeism) and the level of work effectiveness while on the job (presenteeism). These studies have shown that rhinitis has a rather modest effect on absenteeism, with estimated productivity losses of approximately 1-4% resulting from missed work time. By contrast, rhinitis is associated with substantial impairment in at-work performance. Estimates of lost productivity attributable to reduced on-the-job effectiveness ranged from 11 to 40%. The impact of rhinitis on work productivity is affected by symptom severity, and allergen exposure, and it can be reduced by second-generation antihistamines. SUMMARY: The impact of rhinitis on work productivity should be further characterized and taken into account for establishing cost-effective management strategies.