Several studies on the prognosis of occupational asthma have shown that a significant proportion of patients continue to experience asthmatic symptoms and nonspecific bronchial hyperresponsiveness after cessation of work. The determinants of this unfavourable prognosis of asthma are: long duration of exposure before the onset of asthma; long duration of symptoms before diagnosis; baseline airway obstruction; dual response after specific challenge test; and the persistence of markers of airway inflammation in bronchoalveolar lavage fluid and bronchial biopsy. The relevance of immunological markers in the outcome of occupational asthma has not yet been assessed.Further occupational exposure in sensitized subjects leads to persistence and sometimes to progressive deterioration of asthma, irrespective of the reduction of exposure to the specific sensitizer, and only the use of particular protective devices effectively prevents the progression of the disease. A long-term follow-up study of toluene diisocyanate (TDI)-induced asthma showed that the improvement in bronchial hyperresponsiveness to methacholine occurred in a small percentage of subjects and only a long time after work cessation. Bronchial sensitivity to TDI may disappear, but nonspecific bronchial hyperresponsiveness often persists unchanged, suggesting a permanent deregulation of airway tone. Steroid treatment significantly reduces nonspecific bronchial hyperresponsiveness only when started immediately after diagnosis.

To determine whether inhaled budesonide given after allergen inhalation challenge inhibits the late asthmatic response (LAR) and/or the associated increase of airway responsiveness to methacholine, we performed a double-blind randomized cross-over study in 12 adult asthmatics (eight male, four female; mean age, 20.3 yr; range, 18 to 29 yr) sensitized to Dermatophagoides pteronyssinus (DP) previously shown to develop early and late asthmatic response to allergen challenge with DP. On different days each subject was randomized to receive budesonide 800 micrograms by Turbuhaler or placebo, given three times; (1) after allergen inhalation, after the onset of LAR, when FEV1 had fallen by > or = 15%; (2) 2 h later; (3) 4 h later. Airway responsiveness to methacholine was measured before allergen challenge at 8 to 10 h from allergen inhalation and 24 h after the allergen inhalation. Inhaled budesonide significantly reduced the LAR induced by allergen (maximal % fall in FEV1, delta FEV1%: -23 +/- 6% with budesonide versus -38 +/- 9% with placebo; p < 0.001) and inhibited the associated increase of airway responsiveness (geometric mean of PD20FEV1 methacholine: 0.047 mg after budesonide versus 0.033 mg after placebo at 8 to 10 h, p < 0.05; 0.119 mg after budesonide versus 0.062 mg after placebo at 24 h, p < 0.01). These results suggest that inhaled budesonide may not only prevent but also reduce the late asthmatic response induced by allergen and that it might also be considered in the treatment of exacerbation of asthma.

To evaluate the sensitivity of peak expiratory flow (PEF), obtained by portable peak flow meter, in detecting mild changes in airway caliber as assessed by forced expiratory volume in 1 sec (FEV1), we studied 184 subjects who underwent different bronchial challenge tests for suspected bronchial asthma. We measured FEV1 and PEF during bronchoconstriction induced by different stimuli: allergen, methacholine, toluene diisocyanate vapors, exercise, or distilled water inhalation; a total of 186 tests were examined. Before and at different times after challenge, FEV1 was measured, and immediately after, PEF was obtained by Mini-Wright or Assess Peak Flow Meter; each time FEV1 and PEF were taken as the best of three satisfactory tracings. The median FEV1 change from baseline value of all steps in the different challenge tests was 7.5% (range: 0-66%). The correlation coefficients between FEV1 and PEF percent changes in different challenge tests were low (Spearman's p: 0.27-0.69), with high scattering of the data. The concordance between classes of percent changes in FEV1 and PEF was also low (Cohen's weighted kappa: 0.28-0.42). In subjects with a FEV1 fall > 15% after challenge, the median PEF change after bronchoconstriction was lower than the corresponding FEV1 change [17% (0-52) vs. 27% (17-66)]. When different cutoff limits of PEF percent change were considered, the sensitivity of PEF to detect a significant change in FEV1 (15 or 20% change) during bronchoconstriction was low; specificity was in general higher than sensitivity. We conclude that PEF and FEV1 changes are poorly related during mild bronchoconstriction induced by different stimuli. The low sensitivity of PEF to detect mild changes in airway caliber may represent a limit in the use of PEF in the day-to-day monitoring of asthma.

Background-The long acting 2 agonist salmeterol is very eVective in preventing asthmatic responses to specific stimuli, and this eVect could theoretically be due to some anti-inflammatory property in addition to bronchodilator property. Methods-The protective eVect of a single dose of salmeterol (50 µg) on allergen induced early and late responses and on the associated airway inflammation was investigated in a double blind, placebo controlled, crossover study in 11 atopic asthmatic subjects. Eosinophil percentages and concentrations of eosinophil cationic protein (ECP) in peripheral blood and in hypertonic saline induced sputum were measured 24 hours after allergen inhalation. Results-Salmeterol eVectively inhibited both early and late asthmatic responses in comparison with placebo. Salmeterol also inhibited the increase in the percentage of eosinophils in the sputum 24 hours after allergen inhalation (median (range) baseline 6% (1-36), after placebo 31% (5-75), after salmeterol 12% (1-63)). However, the increase in both sputum and serum ECP concentrations 24 hours after allergen challenge was not aVected by pretreatment with salmeterol. Conclusions-A single dose of salmeterol inhibits the allergen induced airway responses and the increase in sputum eosinophils after allergen challenge. (Thorax 1999;54:622-624) Keywords: agonist; salmeterol; asthma; allergen bronchial challenge; eosinophils It is known that long acting 2 agonists are eVective in controlling asthma symptoms and improving lung function.1 Additionally, long acting 2 agonists have shown some in vitro anti-inflammatory properties but it is controversial whether they have similar eVects in vivo. There is indirect evidence that long acting 2 agonists inhibit the late asthmatic reaction (LAR) following inhaled allergen challenge and the associated increase in bronchial hyperresponsiveness.2 Moreover, pretreatment with salmeterol before allergen challenge induced a significant decrease in the concentration of eosinophil cationic protein (ECP) but not of the diVerential cell count in bronchoalveolar lavage (BAL) fluid obtained 24 hours after allergen inhalation.3 By analysis of sputum induced by inhalation of hypertonic saline, some investigators reported no eVect of a single dose of salmeterol on the increase in eosinophil percentages induced by allergen inhalation in sensitised asthmatics. 4 In this study we examined whether a single dose of salmeterol is able to reduce the increase in the number of sputum eosinophils induced by allergen challenge in sensitised asthmatic subjects. MethodsEleven mild asthmatic subjects (eight men) of mean age 20 years (range 16-27) with positive skin prick tests to Dermatophagoides pteronyssinus were selected. All subjects showed normal baseline forced expiratory volume in one second (FEV 1 ) (mean 93% predicted (range 83-121)), non-specific bronchial hyperresponsiveness to methacholine (geometric mean 0.134 mg (range 0.037-0.59)), and an early asthmatic response (EAR) followed by an LAR to specific bronchial ...

Background: Although general practitioners (GPs) are frequently the first healthcare professionals whom asthma patients refer to for their symptoms, few studies have explored the extent of adherence to guidelines for asthma management based on data provided directly by GPs.