L Bancalari

Prognosis of occupational asthma

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 non-specific 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.

Comparison between hypertonic and isotonic saline-induced sputum in the evaluation of airway inflammation in subjects with moderate asthma

Background Hypertonic saline‐indueed sputum has recently been used for the evaluation of airway inflammation in asthma.

Comparison Between Peak Expiratory Flow and Forced Expiratory Volume in One Second (FEV1) During Bronchoconstriction Induced by Different Stimuli

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 (Spearmans 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 (Cohens 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.

Effect of short-term NO2 exposure on induced sputum in normal, asthmatic and COPD subjects

The aim of this study was to assess the effects of short-term exposure to low levels of nitrogen dioxide (NO2) on airway inflammation. We studied seven normal, eight mild asthmatic and seven chronic obstructive pulmonary disease (COPD) subjects. All subjects were exposed to air or to 0.3 parts per million (ppm) NO2 for 1 h, with moderate intermittent exercise, on different days and in random order. Before and 2 h after exposure, symptom score and results of pulmonary function tests (PFTs) were assessed. All subjects performed nasal lavage and hypertonic saline (HS) inhalation to collect sputum 2 h after both exposures. Asthmatic subjects had a higher percentage of eosinophils than normal and COPD subjects in HS-induced sputum after air (asthmatics: median 13 (range 0.4-37)%; normals: 0 (range 0-2)%; COPD 1.8 (range 0.1-19)%), whilst COPD patients showed a higher percentage of neutrophils than the two others groups. No significant differences in PFT values or percentages of inflammatory cells were observed in nasal lavage and in HS-induced sputum in normal, asthmatic and COPD subjects after NO2 exposure compared to air exposure, except for a mild decrease in forced expiratory volume in one second (FEV1) 2 h after NO2 exposure in COPD patients. Symptom score showed a mild increase after NO2 exposure both in normal subjects and in COPD patients. We conclude that short-term exposure to 0.3 ppm nitrogen dioxide does not induce an early detectable acute inflammation in proximal airways of normal subjects or of patients with asthma or chronic obstructive pulmonary disease.

Blood markers of early and late airway responses to allergen in asthmatic subjects. Relationship with functional findings.

We evaluated the relationship between blood markers of mast‐cell (plasma histamine and serum level of heat‐stable neutrophil chemotactic activity [NCA]) and eosinophil (serum eosinophil cationic protein [ECP]) activation during early airway response (EAR) and late airway response (LAR) to allergen inhalation in 24 asthmatic subjects. After EAR, 14 subjects showed significant LAR (FEV1 fall: 25%), while 10 subjects showed equivocal LAR (FEV1 fall: 15–20%). A significant increase from baseline value was observed in plasma histamine and in serum NCA during both EAR and LAR, while serum ECP significantly increased only during LAR. The sensitivity of different markers to detect significant FEV1 fall during EAR and LAR was low, except for NCA. Changes in blood mediators were similar in both groups with significant and equivocal LAR. There was a significant relationship between the increase in NCA during EAR and the severity of LAR. Stepwise regression between changes in different blood markers showed a significant relationship between histamine increase during EAR and ECP increase during LAR. Thus, serum NCA is a more sensitive marker of EAR and LAR than plasma histamine and serum ECP, and its increase during EAR seems predictive of the severity of the subsequent LAR.

Early increase in urinary leukotriene E4 (LTE4) is dependent on allergen dose inhaled during bronchial challenge in asthmatic subjects

Background: Urinary leukotriene E4 (LTE4) excretion is a good marker of the rate of total body production of sulfidopeptide leukotrienes released during allergen challenge.

Beclomethasone dipropionate blunts allergen-induced early increase in urinary LTE4

Eur J Clin Invest 2010; 40 (6): 566–569

Duration of preventive effect of inhaled salbutamol on early airway response to allergen in asthmatic subjects

Salbutamol is known to effectively prevent early asthmatic response (EAR) after specific bronchial provocation test (sBPT) in asthmatic subjects, but the time-course of this protection is not known. In this study the effects of 200 micrograms salbutamol inhaled 2 h before sBPT were compared with 200 micrograms salbutamol inhaled 10 min before sBPT in eight asthmatic subjects sensitized to Phleum pratensis (PP) or Dermatophagoides pteronyssinus (DP). All subjects showed an EAR (% decrease in FEV1 from baseline value: 30.4 +/- 11%) in a preliminary sBPT performed with cumulated doses of extracts of PP or DP titrated in biological units (BU). Each subject performed, on two different days, in a random, double-blind, cross-over study, two puffs of placebo 2 h before sBPT and two puffs of salbutamol 10 min before sBPT (treatment A) or two puffs of salbutamol 2 h before sBPT and two puffs of placebo 10 min before sBPT (treatment B). Baseline FEV1 were similar in both tests. In treatment B, 10 min, 1 h and 2 h after salbutamol inhalation, FEV1 increased significantly with respect to placebo inhalation in treatment A. Ten minutes after salbutamol inhalation in treatment A, FEV1 became similar to that obtained 2 h after salbutamol inhalation and 10 min after placebo in treatment B. Allergen inhalation induced an EAR in only one out of eight subjects after treatment A, and five of the eight subjects after treatment B.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of systemic glucocorticosteroids on peripheral neutrophil functions in asthmatic subjects: an ex vivo study

In 21 asthmatic subjects, several functions of isolated peripheral neutrophils (chemokinesis and chemotaxis toward 10% E. coli; superoxide anion generation after PMA; leukotriene B4 (LTB4) release from whole blood and isolated neutrophtls, before and after different stimuli) were evaluated during an acute exacerbation of asthma, and after 14 – 54 days of treatment with systemic glucocorticosteroids (GCS). During acute exacerbation, superoxide anion generation was higher in asthmatics than in eleven normal subjects (39.2 ± 14.1 vs. 25.2 ± 7.3 nmol, p < 0.05); there was a significant correlation between FEV1 (% of predicted) and neutrophil chemotaxis (r = −0.52, p = 0.04). After treatment, there was no significant change in all neutrophil functions, except for a decrease in neutrophil chemotaxis in subjects who showed an FEV1 increase > 20% after GCS treatment (from 131 ± 18 to 117 ± 21 μm, p = 0.005). Chemokinesis sicantly decreased in all subjects, and the changes significantly correlated with an arbitrary score of the total administered dose of GCS (r = 0.57, p < 0.05). These data suggest that neutrophil activation plays a minor role in asthma, and that treatment with GCS is not able to modify most functions of peripheral neutrophils in asthmatic subjects; chemotaxis seems to be related only to the severity of the asthma and it could reflect the improvement of the disease.