Simone Chaboillez

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.

Frequency of work-related respiratory symptoms in workers without asthma.

BACKGROUND Clinicians are faced with subjects complaining of work-related respiratory symptoms (WRS) without any evidence of asthma. We sought to assess the prevalence of subjects with WRS without asthma in a cohort of workers referred for possible work-related asthma (WRA) as well as compare the characteristics and the work environment of subjects with WRS to subjects with WRA. METHODS A prospective observational study of workers referred for possible WRA over a 1-year period. Detailed medical and occupational questionnaires were administered. Pulmonary function tests as well as specific-inhalation challenges were performed. RESULTS One hundred twenty workers were investigated. Fifty-one had WRA while 69 had WRS. The type and the severity of the respiratory symptoms were similar in both groups, except for wheezing which was more frequently reported in subjects with WRA (32 (62.7%)) than in subjects with WRS (16 (23.2%)) (P < 0.01). Both the workers with WRS and WRA were mainly employed in the manufacturing sector (64.7% (WRA) and 71% (WRS)). At the time of the first assessment 64.7% of subjects with WRA and 56.5% with WRS had left their workplace because of their bothersome respiratory symptoms. CONCLUSIONS Subjects with WRS without asthma represent a large proportion of the subjects assessed in clinics specialized in the field of WRA. Like subjects with WRA, the population with WRS is likely to represent a significant medical burden. The similarity of the symptoms between the WRA and the WRS groups emphasizes the need to perform a thorough and objective investigation to diagnose WRA.

Cost-Effectiveness of Various Diagnostic Approaches for Occupational Asthma

BACKGROUND Diagnosis of occupational asthma (OA) by specific inhalation challenge (SIC) can be costly and is not always available. The use of sputum testing to avoid this in some patients may be a more cost-effective alternative. OBJECTIVES To compare the cost-effectiveness of SIC with serial measurements of sputum cell counts (sputum testing) and peak expiratory flow (PEF) monitoring. METHODS Clinical data and testing costs for OA in 49 patients were collected during a previously published trial, modelled and compared using TreeAge Pro. Clinical outcome was the percentage of accurately diagnosed patients, using SIC as the gold standard. The PEF approach used the most accurate assessment of five experts who were blinded to SIC results. Differences in the proportion of eosinophils during periods on and off work were used for the sputum testing approach and in PEF/sputum for the combined approach. Unit costs were estimated from charges in Canadian hospitals. Data were analyzed by one-way and two-way analyses, and by probabilistic sensitivity analysis using a Monte Carlo simulation technique. RESULTS The PEF approach had an estimated accuracy of 52% and cost

Airway Inflammatory Responses Following Exposure to Occupational Agents

365 per patient tested. Compared with PEF monitoring, sputum testing was more accurate and cost an estimated

A Kit to Facilitate and Standardize the Processing of Sputum for Measurements of Airway Inflammation

255 for each additional OA patient correctly diagnosed. SIC costs per additional correct diagnosis were

Effects of a Short Course of Inhaled Corticosteroids in Noneosinophilic Asthmatic Subjects

11,032 compared with sputum testing and

Protocol: Influence of Budesonide and Budesonide/Formoterol on Asthma Control in Smoking Asthmatic Adults

6,458 compared with PEF monitoring. The combined PEF/sputum testing approach was not cost-effective in the base case analysis, but cannot be excluded according to probabilistic sensitivity analyses. CONCLUSIONS Although SIC remains the reference test to diagnose OA, when this test is not available, sputum testing is a cost-effective alternative to PEF for diagnosis of OA.

Noneosinophilic responders with occupational asthma: A phenotype associated with a poor asthma prognosis

BACKGROUND Airway inflammatory responses to specific inhalation challenges (SICs) with low-molecular-weight (LMW) and high-molecular-weight (HMW) agents have not been studied thoroughly. We assessed the changes in airway inflammatory cells following SIC in sensitized workers, and looked at the influence of various factors on the pattern of inflammatory responses to SIC. METHODS Induced sputum analysis was performed in workers sensitized to LMW (n = 41) or HMW agents (n = 41) after a control day and after a positive SIC. Cell counts were compared with lung function and various clinical parameters. RESULTS In the LMW group, eosinophils were increased following late asthmatic responses (median [interquartile range], 0.02 [0.04] × 10(6) cells/g vs 0.30 [0.80] × 10(6) cells/g and 1.0% [3.5] vs 8.9% [8.0], P < .05), as were neutrophil numbers (0.8 [1.3] × 10(6) cells/g vs 2.3 [5.4] × 10(6) cells/g, P = .04). In the HMW group, eosinophil percentages increased both after early (1.0% [2.2] vs 5.5% [14.5], P = .003) and dual asthmatic responses (4.5% [3.7] vs 15.0% [13.7], P = .02). In the LMW group, the increases in neutrophils were higher in current smokers than in ex-smokers or nonsmokers. The length of exposure to the agent, tobacco use, and baseline percentage of eosinophils were independent predictors of the change in eosinophils, whereas age and baseline neutrophil percentage were predictors of the change in neutrophils. CONCLUSIONS This study confirms that eosinophils and neutrophils are increased after SIC, whatever the causal agent. The type of agent is not predictive of the inflammatory response to SIC. Smoking is associated with a more neutrophilic response after SIC with an LMW agent.

Chlorine Inhalation Challenge in Humans: Development of a New Closed-Circuit Methodology

BACKGROUND The use of inflammometry has been shown to be effective for managing asthma. However, sputum processing can be time consuming. Furthermore, methods of sputum processing can vary among facilities. To help with standardization and to simplify the procedure for laboratory staff, a novel, commercially available processing device (Accufilter, Cellometrics Inc, Canada) has been developed. OBJECTIVE To assess the validity of the Accufilter device and kit for recovery of treated specimens, and for quantitative sputum inflammatory cell counts by comparing intrasample measurements with those using the same procedure without the Accufilter device and kit. METHODS The present study was a wet laboratory comparison of induced sputum cell counts obtained from sputum processed with versus without the device and kit. Comparisons of each sputum specimen were performed by the same technologist in random order. RESULTS A total of 39 samples were processed using both the standard method and the Accufilter device. The intraclass correlation coefficients were high for the weight of the filtrate, and for eosinophil and neutrophil differential counts. CONCLUSION A good degree of agreement of results was apparent when the two methods were compared. The differences noted between both methods were minimal and did not modify clinical interpretation. The use of the Accufilter device and kit can be used in place of the standard method for sputum quantitative analysis, especially in centres with large sample loads.

An Effective Strategy for Diagnosing Occupational Asthma Use of Induced Sputum

BACKGROUND Noneosinophilic asthma has been regarded as a distinct phenotype characterized by a poor response to inhaled corticosteroids (ICS). OBJECTIVE To determine whether noneosinophilic, steroid-naive asthmatic subjects show an improvement in asthma control, asthma symptoms and spirometry after four weeks of treatment with ICS, and whether they further benefit from the addition of a long-acting beta-2 agonists to ICS. METHODS A randomized, double-blind, placebo-controlled, multicentre study comparing the efficacy of placebo versus inhaled fluticasone propionate 250 mcg twice daily for four weeks in mildly uncontrolled, steroid-naive asthmatic subjects with a sputum eosinophil count of 2% or less. This was followed by an open-label, four-week treatment period with fluticasone propionate 250 mcg⁄salmeterol 50 mcg, twice daily for all subjects. RESULTS After four weeks of double-blind treatment, there was a statistically significant and clinically relevant improvement in the mean (± SD) Asthma Control Questionnaire score in the ICS-treated group (n = 6) (decrease of 1.0 ± 0.5) compared with the placebo group (n = 6) (decrease of 0.09 ± 0.4) (P = 0.008). Forced expiratory volume in 1 s declined in the placebo group (-0.2 ± 0.2 L) and did not change in the ICS group (0.04 ± 0.1 L) after four weeks of treatment (P = 0.02). The open-label treatment with fluticasone propionate 250 mcg⁄salmeterol 50 mcg did not produce additional improvements in those who were previously treated for four weeks with inhaled fluticasone alone. CONCLUSION A clinically important and statistically significant response to ICS was observed in mildly uncontrolled noneosinophilic asthmatic subjects.