Validation of an Exposure System to Particles for the Diagnosis of Occupational Asthma

doi:10.1378/chest.102.2.402

Chest

Volume 102, Issue 2, August 1992, Pages 402-407

https://doi.org/10.1378/chest.102.2.402 Get rights and content

Study Objective: We previously described a closed-circuit system for exposure to particles in humans. This system has three components: a particle generator, an exposure chamber connected to an orofacial mask, and monitors. We describe results of challenges in 56 subjects who underwent challenges with the apparatus using occupational sensitizers in particles.

Subjects: Fifty-six consecutive subjects referred for the investigation of occupational asthma to occupational sensitizers in particles were included. The agents were the following: flour and grains (n = 19), cedar (n = 10), psyllium (n = 9), guar gum (n = 9), drugs (n = 3), persulfate (n = 2), and miscellaneous (n = 4).

Intervention: The duration of exposure was progressive and varied from one breath to a maximum of 180 min depending on the reaction. When no significant fall in FEV₁ occurred after exposure with the aerosolization device, the standard approach of tipping particles from one tray to another was used.

Results: Twenty-nine subjects (52 percent) had a significant (≥20 percent) fall in FEV₁ after exposure. This includes 18 subjects with isolated immediate reactions, four with dual asthmatic reactions, and two with atypical reactions. In 20/24 instances (83 percent), the percentage of fall in FEV₁ did not exceed 30 percent, thus showing that dose-response curves can generally be obtained in a safe way. In all instances except one (26/27 cases), subsequent exposures using the traditional method did not result in significant falls in FEV₁.

Conclusion: This new procedure results in safe tests in terms of the percentage of changes in FEV₁ during the immediate reactions and very rare false-negative challenges.

Section snippets

Apparatus

As previously described and shown in Figure 1, the apparatus consists of three parts: a particles generator, an aerosol delivery system connected to an orofacial mask, and monitors—a photometer and a cascade impactor.⁹ The dry powder (dessication made beforehand) is placed into a small plastic box (dimension = 10 × 10 × 6 cm) that undergoes constant vibration. The vibrator feeds the powder into an endless screw that collects it at the bottom of the reservoir and brings it to a rotating plate.

RESULTS

Eighteen subjects experienced an isolated immediate reaction; five, an isolated late reaction; four, a dual reaction; and two, an atypical bronchospastic reaction (squared-wave pattern, ie, no significant recovery after the immediate reaction until 8 h after ending exposure).¹⁵ In 27 subjects, no significant reaction was documented. Twenty-seven (93 percent) of 29 subjects with positive inhalation challenges had significant bronchial responsiveness as compared with 19 (73 percent) of 27

DISCUSSION

It is reported that Charles Blackley was the first author who performed specific inhalation challenges using pollens.¹⁶ Specific inhalation challenges were used in the 20th century using common allergens by various authors.17, 18, 19, 20 Herxheimer²¹ described late bronchial reactions after exposure to common allergens. In the 1970s, Pepys and Hutchcroft¹ introduced this procedure using occupational sensitizers by asking subjects to reproduce their working environment in small, well-ventilated

ACKNOWLEDGMENTS

The authors want to thank the Institut de recherche en santé et sécurité du travail for their financial support and Katherine Tallman for reviewing the manuscript.

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Cited by (33)

Bronchial Challenge Testing
2014, Middleton's Allergy: Principles and Practice: Eighth Edition
Inhalation challenges with occupational agents: Threshold duration of exposure
2013, Respiratory Medicine
Citation Excerpt :
However, standardized and validated extracts of occupational agents are lacking for most occupational agents.28 Closed-circuit devices that make it possible to deliver known and stable concentrations of occupational agents in various forms have been developed,23,29,30 but these apparatuses are expensive and require a pre-calibration process for each tested agent.31 Even with such sophisticated devices, measuring the levels of airborne particles during the SIC does not accurately reflect the actual dose of allergens inhaled by the subjects.
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.
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.
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).
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.
Clinical Assessment of Occupational Asthma and its Differential Diagnosis
2011, Immunology and Allergy Clinics of North America
Citation Excerpt :
With powders, like flour or red cedar, patients may be exposed to a fine dust that mimics work exposure by pouring the dust from one tray to another. Using a dust generator allows proper monitoring, regulation of exposure, generation of dose-response curves, and reduces the risks of severe bronchospasm or irritant reactions.43 The agent may be diluted initially with an inert agent, such as lactose, to avoid severe reactions.
Provocation studies in the diagnosis of occupational asthma
2003, Immunology and Allergy Clinics of North America
Changes in sputum cell counts after exposure to occupational agents: What do they mean?
2001, Journal of Allergy and Clinical Immunology
Background: Exposure to occupational agents can induce eosinophilic inflammation in subjects with occupational asthma (OA). It might also induce nonspecific changes in airway inflammation in subjects without OA. Objectives: We sought to investigate the changes in airway inflammation induced by exposure to occupational agents in subjects with and without OA and to determine which changes in sputum eosinophil numbers and bronchial responsiveness to methacholine should be regarded as clinically significant for predicting a 20% fall in FEV₁. Methods: We performed specific inhalation challenges (SICs) in 3 groups of subjects: subjects reporting a history consistent with OA with a positive SIC response (n = 17); subjects reporting a history consistent with OA with a negative SIC response (n = 14); and asthmatic subjects without any history of OA (n = 10). Induced sputum and methacholine challenges were performed at the end of the control day and again at the end of the last day of exposure; the last day of exposure was always performed in the laboratory. Results: There was an increase in median sputum eosinophil and neutrophil numbers in subjects with positive SIC responses. Cell counts remained unchanged after exposure in asthmatic subjects without OA. A combination of a greater than 0.26 10⁶/mL increase in sputum eosinophil numbers and a decrease in the concentration of methacholine inducing a 20% fall in FEV₁ of at least 1.8-fold compared with baseline values predicted a 20% fall in FEV₁ in 96% (95% CI, 70%-99%) of patients. Conclusion: Exposure to occupational agents per se does not induce airway inflammation. Changes in both sputum eosinophil counts and methacholine responsiveness are satisfactory predictors of a significant bronchial responsiveness to occupational agents. (J Allergy Clin Immunol 2001;107:1063-8.)
Characterization of airway inflammation after repeated exposures to occupational agents
2000, Journal of Allergy and Clinical Immunology
Background: Little is known about the comparative kinetics of eosinophil recruitment after exposure to low- and high-molecular-weight sensitizers in subjects with occupational asthma (OA). Objectives: The aims of the study were to investigate the kinetics of changes in inflammatory mediators associated with eosinophil infiltration (IL-5 and eotaxin) and to examine the nature of the airway inflammation induced in response to different types of occupational agents. Methods: We investigated 15 subjects with OA caused by high- and low-molecular-weight agents. The subjects were exposed to increasing doses of the relevant occupational agent over 3 to 4 days until a 20% fall in FEV₁ occurred. Methacholine challenge and sputum induction were performed at the end of each day of exposure. Sputum samples were assessed for differential cell counts, including eosinophils, IL-5, and eotaxin messenger RNA. Results: There was an increase in sputum eosinophils, eotaxin, and IL-5 on the day preceding the occurrence of asthmatic reaction, although there was no change in functional parameters (FEV₁ and PC₂₀). Increase in sputum eosinophils was more prominent in subjects exposed to low-molecular-weight agents than to high-molecular-weight agents. Conclusion: Changes in eosinophils, IL-5, and eotaxin precede functional changes after exposure to occupational agents in subjects with OA. Eosinophil inflammation is a feature of exposure to both high- and low-molecular-weight agents. Induced sputum may be a useful tool in the early diagnosis of OA. (J Allergy Clin Immunol 2000;106:1163-70.)

View all citing articles on Scopus

: Manuscript received July 31; revision accepted November 12.

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Chest

Clinical InvestigationsValidation of an Exposure System to Particles for the Diagnosis of Occupational Asthma

Section snippets

Apparatus

RESULTS

DISCUSSION

ACKNOWLEDGMENTS

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

Rev Franç Mal Resp

J Allergy Clin Immunol

Chest

Bronchial provocation tests in etiologic diagnosis and analysis of asthma

Am Rev Respir Dis

Is the clinical history a satisfactory means of diagnosing occupational asthma?

Am Rev Respir Dis

Occupational asthma and IgE sensitization in a pharmaceutical company processing psyllium

Am Rev Respir Dis

Peak flow rate records in the diagnosis of occupational asthma due to isocyanates

Thorax

Peak flow rate records in the diagnosis of occupational asthma due to colophony

Thorax

New methodology for specific inhalation challenges with occupational agents in powder form

Eur Respir J

Standardization of spirometry—1987 update

Am Rev Respir Dis

Bronchial reactivity to inhaled histamine: a method and clinical survey

Clin Allergy

Changes in the normal maximal expiratory flow-volume curve with growth and aging

Am Rev Respir Dis

Clinical Investigations
Validation of an Exposure System to Particles for the Diagnosis of Occupational Asthma