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The Use of Induced Sputum as an Additional Diagnostic Indicator of an Asthmatic Reaction to Red Cedar after Specific Inhalation Challenge Testing
RS2003/04-022
Final Report Date: March 2008
| Principal Investigator: | Raja Abboud (UBC) |
| Co-Investigator: | Moira Yeung (UBC) |
For more information about this project, please contact Dr. Raja Abboud.
Issue
Red cedar asthma is the most common occupational asthma in B.C. Diagnosing it usually requires a procedure called inhalation challenge testing, in which subjects inhale plicatic acid (the chemical in red cedar wood causing the asthma). The diagnosis is confirmed if there is an immediate or delayed asthmatic reaction. However, this method is time consuming and can involve side effects. This project assessed a potential alternative method for diagnosing red cedar asthma based on changes in biomarkers in induced sputum (the mucus or phlegm induced and coughed up by inhalation of hypertonic saline).
Key findings
- Sputum samples for participants who had an asthmatic reaction after inhalation challenge testing showed an increase in eosinophils, eosinophil cationic protein (ECP), and eotaxin. However, there were no significant increases in the leukotrienes LTB4 and LTC4.
- The results suggest that differences in biomarkers in induced sputum (while subjects were working compared to when they were off work for 2 weeks) may be used to confirm the diagnosis of red cedar asthma and reduce the requirement for red cedar inhalation challenge testing.
Objectives
- To evaluate biomarkers of asthma activation in induced sputum before and after inhalation challenge testing with plicatic acid
- To determine which biomarkers would be useful in confirming occupational asthma, when applied to workers both during work exposure and off work
Methods
During the study period, 42 subjects were evaluated for suspected red cedar asthma by red cedar inhalation challenge testing. Out of these, 22 subjects consented to take part in the research study by having induced sputum on the control day and again on the red cedar extract challenge day, resulting in a participation rate of 52%.
Because induced sputum samples for three of the participants were not obtained on the plicatic acid challenge day, there were a total of 19 participants who had sputum induction both before and after cedar challenge. A further sample was frozen during transportation, resulting in a total of 18 pairs of before and after samples.
The sputum samples were analyzed to assess whether biomarkers had changed between the control day and challenge day, for individuals who had an asthmatic reaction to red cedar extract compared with those who did not.
Results
Of the 18 participants, ten developed bronchoconstriction (narrowing of the airways in the lungs) after exposure to plicatic acid, confirming the diagnosis of red cedar asthma, while eight did not, excluding the diagnosis.
In those who experienced a reaction, median values in induced sputum after plicatic acid inhalation compared to the control day increased as follows: sputum eosinophils from 6.5% to 25.0% (p<0.01), a trend for an increase in eosinophil cationic protein (ECP) from 260 to 456 ng/ml, and increased eotaxin from 58 to 133 pg/ml (p<0.01). However, there were no significant increases in the leukotrienes LTB4 and LTC4.
No significant changes in biomarkers were detected in the samples of those who did not react to inhalation challenge testing for red cedar.
Conclusions
The markers of eosinophil activation, ECP and eotaxin, in induced sputum are better indicators of a positive reaction to specific inhalation challenge in red cedar asthma than leukotrienes.
The results suggest that sputum induction while subjects are working and after being off work for 2 weeks, to evaluate changes in eosinophil counts and percentages, as well as eotaxin, may confirm the diagnosis of red cedar asthma and reduce the requirement for red cedar inhalation challenge testing.
Future directions
A study (trial) comparing the assessment of induced sputum biomarkers with cedar inhalation challenge testing may be required to further explore the potential application of this method.
Publications and Presentations
Presentation at the UBC Wednesday (VGH-St Paul’s) Respiratory Medicine Seminars. March 2008.
Poster presentation at the “Lung Health Research and Policy Day” Meeting. Vancouver, March 27, 2008.
Oral Presentation at the European Respiratory Society International Lung Conference in Berlin in October 2008. Abstract available on line: ERS Berlin 2008
Tuesday Oct 7, 2008, 10:45-12:45 Oral presentation Session 340, Asthma and inhalational Injuries at work; Abstract 3196
http://www.ersnet.org/learning_resources_player/abstract_print_08/main_frameset.htm