Predictors of early- and late-phase reactions to bronchial allergen challenge

The influence of inhaled steroids and predictive factors on the response to bronchial allergen challenge (BCA) was evaluated in. 80 asthmatics allergic to Dermatophagoides pteronyssinus (Der p). All underwent BCA with Der p and measurement of early (EAR) and late asthmatic reaction (LAR). The cumulative dose of allergen producing 20% fall in FEV₁, in the EAR (PD₂₀) was calculated. Bronchial histamine provocation, conjunctival provocation test (CPT), and skin prick test with Der p extract were performed. Specific IgE to Der p in serum (RAST), blood eosinophil (EOS) count, serum eosinophil cationic protein, and eosinophil protein X were measured. Thirty patients (38%) were treated with inhaled steroids. All patients had at least a 20% fall in FEV₁ in EAR. Some 42% of nonsteroid- and 33% of steroid-treated patients had LAR with fall in peak flow of at least 20%. For patients not treated with steroid, 35% of variation in PD₂₀ was explained by RAST and histamine reactivity, and 53% of variation of observed PD₂₀ could be predicted. The baseline FEV₁, EOS, and EAR explained 28% of variation in LAR, and 28% of variation in observed LAR could be predicted. For patients treated with steroids, 38% of variation in PD₂₀ was explained by EOS and histamine reactivity, and only 18% of variation of observed PD₂₀ could be predicted. For patients treated with steroids, it was impossible to predict LAR. We conclude that to achieve a quantitative estimation of allergen-specific EAR and LAR, BCA cannot be replaced by the tests used in this study. Treatment with inhaled steroids modifies the response to BCA, making quantitative prediction of EAR less accurate and prediction of the magnitude of LAR impossible.     

Measurement of serum levels of eosinophil cationic protein to monitor patients with seasonal respiratory allergy induced by Parietaria pollen (treated and untreated with specific immunotherapy)

This trial studied the behavior of a marker of eosinophilicc inflammation, eosinophil cationic protein (ECP), in the peripheral blood of two groups of subjects with seasonal allergic respiratory symptoms (rhinitis and mild bronchial asthma) induced by pollen allergens of Parietaria judaica (P.j.) (One group treated and another untreated with specific immunotherapy [SIT], to determine what contribution these serial measurements might provide, in comparison with various other tools now available for pollinosis monitoring. In a previously randomized order, we selected 25 patients with monitoring. In a previously randomized order, we selected 25 patients with monosensitization to P.j. pollen allergens: among them, 12 had started SIT with a P.j. extract in autumn 1993. As a control group, 13 patients were untreated. All patients were studied with various tests at four different times: time I - November 1993; time II - February 1994; time III - end of May 1994; and lime IV - September 1994. Blood samples for determination of serum HOP were collected at each time. Methacholine challenge tests were performed at times I and III. A pollen count was also carried out. A statostocally significant difference ( P < 0.05) was observed in mean ECP levels at times I and II in SIT treated and untreated patients The interaction between groups and time was not significant. No statistically significant difference was found between PD₂₀ FEV₁ values at times I and III in either group. After I year of treatment, we did not find any effect of SIT on bronchial hyperresponsiveness or on ECP Serum values.     

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.     

Recovery of FEV1 after histamine challenge in asthmatic children

Factors that influence the time necessary for complete recovery of FEV₁ after inhaling histamine were analysed in forty-five children with asthma. These included the initial bronchial obstruction (baseline FEV₁), the provocation dose of histamine producing a 20% fall in FEV₁ (PD₂₀) and the fall in FEV₁ after the histamine challenge. In addition it was also investigated whether a second challenge carried out after complete recovery of FEV₁ would produce a reproducible PD₂₀-histamine value. The time for complete recovery varied widely from 15 to more than 75 min. The time needed for complete recovery of FEV₁ after the histamine challenge seems to be mainly determined by the PD₂₀ value. The other factors such as initial bronchial obstruction and the fall in FEV₁ after the challenge showed no significant relationship with the recovery time. A second challenge with histamine resulted in a highly reproducible PD₂₀ value. The clinical implication of this study is that other tests can only be performed when FEV₁ has returned to 95% of baseline.     

Comparative study of the effects of nedocromil sodium (4 mg) and sodium cromoglycate (10 mg) on adenosine-induced bronchoconstriction in asthmatic subjects

The effect of nedocromil sodium (4 mg; 7.8 × 10⁻⁶ m ) on adenosine-induced bronchoconstriction was compared with that of a higher dose of sodium cromoglycate (10 mg; 24.1 × 10⁻⁶ m ). Eleven allergic asthmatic patients (mean age 26.28 ± 12.21 years) were studied. Adenosine (0.03–4.00 mg) was administered as nebulized aerosol. The dose of adenosine producing a 20% change in FEV₁(PD₂₀) was calculated from the individual semi-logarithmic dose-response curves. Patients were studied on 4 separate days. On the first day the adenosine challenge was performed; on subsequent days patients were pretreated (20 min before challenge) with either placebo or test drug (nedocromil sodium 2 × 2 mg or sodium cromoglycate 2 × 5 mg) administered by pressurized aerosol in a randomized, double-blind manner. Statistical analysis was performed by two-way analysis of variance. Neither sodium cromoglycate nor nedocromil sodium showed a significant bronchodilator effect. In patients treated with placebo, inhalation of adenosine produced a dose-related bronchoconstriction with a geometric mean PD₂₀ of 0.42 mg. After drug administration the mean PD₂₀ values were 1.29 mg with sodium cromoglycate and 2.30 mg with nedocromil sodium. Both drugs produced a significant increase in mean PD₂₀ value in comparison with placebo and baseline ( P < 0.01). These results demonstrate that nedocromil sodium (4 mg) is significantly more potent than a larger dose of sodium cromoglycate (10 mg) in inhibiting adenosine-induced bronchoconstriction ( P < 0.05).     

Effect of nedocromil on bronchospasm induced by inhalation of substance P in asthmatic subjects

Several studies have demonstrated that neuropeptides are present in peptidergic fibres of bronchial tissue. The aim of the present study was to evaluate in vivo the effect of nedocromil sodium (2 × 2 mg) on bronchospasm induced by inhalation of substance P. Six moderate asthmatic patients, mean age 25.17 years, were studied. Airway response was measured as FEV₁ and the dose of substance P (using a dose range of 23–736 nmol) producing a 20% decrease in FEV₁ (PD₂₀) was calculated from the individual semilogarithmic dose-response curves. Patients were studied on 3 separate days in a randomized, double-blind manner. On the first day a baseline PD₂₀ value was determined. On subsequent days substance P challenge was performed after pretreatment (20 min before challenge) with either placebo or nedocromil sodium. Student's paired t -test and Wilcoxon's test were used for statistical analysis. The results of this study demonstrated that inhalation of substance P causes a dose-dependent bronchoconstriction and that the bronchoconstriction induced by substance P can be prevented by pre-treatment with nedocromil sodium.     

Allergen specific immunotherapy attenuates early and late phase reactions in lower airways of birch pollen asthmatic patients: a double blind placebo-controlled study

BACKGROUND: Few placebo-controlled studies have examined the effect of allergen specific immunotherapy (SIT) on early and late phase asthmatic reactions. In this placebo-controlled study we have investigated the effect of 1 year of SIT with standardized birch pollen extract on early and late phase asthmatic reactions in adult asthmatic patients. METHODS: Nineteen patients with a history of birch-pollen-induced seasonal symptoms from upper and lower airways, positive skin prick test and in vitro specific immunoglobulin E to birch pollen extract were included. Allergen and methacholine bronchial challenges were performed and blood samples obtained for analyses of total eosinophil count and eosinophil cationic protein (ECP) in serum, before and after 1 year of immunotherapy treatment. RESULTS: All patients developed early and 16 of 19 both early and late phase asthmatic reactions. A significant increase in allergen dose was required to evoke early asthmatic reaction in the immunotherapy group (P < 0.01) after 1 year of treatment. The difference between the groups was significant (P < 0.01). Also the size of late asthmatic reaction was significantly reduced in the SIT group compared with placebo treated patients (P < 0.01). Twenty-four hours after allergen challenge methacholine sensitivity, number of total eosinophils and ECP increased significantly in the placebo (P < 0.02, P < 0.05 and P < 0.05 respectively), but not in the SIT group. CONCLUSION: Allergen SIT with standardized birch pollen extract decreased early and late asthmatic responses following bronchial challenge in pollen allergic patients, thus confirming anti-inflammatory effect of the treatment.     

Inhaled lysine acetylsalicylate (L-ASA) attenuates histamine-induced bronchoconstriction in asthma

When administered by inhalation, histamine provokes dose-related bronchoconstriction in asthmatic subjects mainly by a direct activation of histamine H1-receptors on airway smooth muscle. However, little is known of the change in airway responsiveness to histamine after cyclooxygenase blockade. The aim of the study was to investigate the effect of the potent cyclooxygenase inhibitor, lysine acetylsalicylate (L-ASA), administered by inhalation on histamine-induced bronchoconstriction in a group of 16 asthmatic subjects. The subjects studied attended the laboratory on four separate occasions to receive nebulized L-ASA (solution of 90 mg/ml) or matched placebo (glycine solution of 30 mg/ml) 15 min before bronchoprovocation tests with histamine and methacholine in a randomized, double-blind order. Changes in airway caliber were followed as forced expiratory volume in 1 s (FEV₁), and agonist responsiveness was expressed as the provocative concentration causing a 20% fall in FEV₁ from baseline (PC₂₀). Administration of both L-ASA and glycine solution caused a small but significant acute fall in FEV₁ from baseline, which returned to normal within 15 min. When compared to placebo, inhaled L-ASA reduced the airway responsiveness to histamine in 13 of the 16 subjects studied, the geometric mean (range) values for PC₂₀ histamine increasing significantly ( P < 0.001) from 1.72 (0.13–5.49) mg/ml to 3.31 (0.36–12.00) mg/ml after placebo and L-ASA, respectively. No significant change in airway responsiveness to methacholine was recorded after L-ASA. Acute administration of L-ASA by inhalation protects the asthmatic airways against histamine-induced bronchoconstriction, thus suggesting that endogenous prostaglandins may play a contributory role in the airways response to histamine in human asthma.     

Prevention of fog-induced bronchospasm by nedocromil sodium

A single dose double-blind crossover study was performed to compare the efficacy of nedocromil sodium (4 mg) and placebo administered from pressurized aerosols against bronchoconstriction induced by the inhalation of ultrasonically nebulized distilled water (fog) in twelve asthmatic subjects. Neither active nor placebo pre-treatment produced any significant change in baseline FEV₁ and SRaw. Nedocromil sodium significantly attenuated fog-induced falls in FEV₁ ( P < 0.001) and increased specific airways resistance (SRaw, P < 0.01). The results provide further evidence of the potential therapeutic usefulness of nedocromil sodium in the management of chronic obstructive airways disease.     

Eosinophil activity markers in peripheral blood have high predictive value for bronchial hyperreactivity in patients with suspected mild asthma

The present study aimed to evaluate the predictive value of eosinophils and markers of their activity for bronchial hyperreactivity (BHR) in a population of patients with recently developed clinical symptoms of asthma. The activation of eosinophils was estimated by measuring eosinophil cationic protein (ECP) in serum. In addition, flow cytometry was used to measure the expression of the EG2-epitope on intracellular ECP in eosinophils from peripheral blood. Twenty-eight consecutive patients with clinical history of asthma were studied. Of the 28 patients, 18 had a positive bronchial challenge test measured as PD₂₀≤ 1600 μg histamine. A significantly higher concentration of eosinophils and a trend to higher ECP in the peripheral blood was found in the hyperreactive group than in the nonreactive group. However, the intracellular expression of ECP did not correlate with the PD₂₀ value, and no significant difference between the groups was found. With one eosinophil activity marker, either serum ECP or EG2, BHR could be predicted in 70% of the patients. If we combined any two of the activity markers (serum ECP, EG2, or the percentage of eosinophils), the predictive value increased to 100%. We conclude that the blood eosinophil concentration, as well as, to some extent, serum ECP, has a high specificity for BHR in patients with recently developed clinical symptoms of asthma. Despite normal bronchial reactivity, some patients had signs of activated eosinophils, i.e., high serum ECP and increased EG2 expression. Thus, these markers may reflect early stages in the development of BHR. Our results also indicate that a combined evaluation of percentage of eosinophils and of eosinophil activity markers is of clinical value to predict BHR.     

Bronchial hyperresponsiveness in two populations of Australian schoolchildren. I. Relation to respiratory symptoms and diagnosed asthma

In order to explore the relationship between bronchial hyperresponsiveness (BHR) to inhaled histamine, respiratory symptoms and diagnosed asthma in children, we undertook a cross-sectional study of 2363 Australian schoolchildren aged 8–11 years. The methods used included a self-administered questionnaire to parents, which was shown to have a high degree of repeatability, and a histamine inhalation test to measure bronchial responsiveness (BR). The study showed that 17.9% of children had BHR, defined as a 20% fall in FEV₁ at a provoking dose of histamine (PD₂₀ FEV₁) of less than 7.8 μmol. The distribution of PD₂₀ FEV₁ appeared to be continuous. Most children with PD₂₀ FEV₁ values < 1.0μmol had symptoms of asthma. However, 6.7% of children had BHR without symptoms or a previous diagnosis of asthma and 5.6% had had a diagnosis of asthma but had no BHR. Although there was a good association between BHR and respiratory symptoms, questionnaire data of wheeze and diagnosed asthma do not reflect accurately the level of BHR in the community. We conclude that cross-sectional studies of BR to identify children with BHR probably do not reflect the prevalence of asthma in populations of children. However, the strong association between BHR and symptoms, particularly in children with severe and moderate BHR, suggests that measurements of BR in populations are useful for defining a group of children whose airways behave differently from those of the majority. Prospective studies are needed to define the level of BHR that is associated with important sequelae.     

Comparison of the effects of salmeterol and salbutamol on clinical activity and eosinophil cationic protein serum levels during the pollen season in atopic asthmatics

Background In atopic asthma there is strong evidence of eosinophils playing an active role in pathogencsis. Some investigations demonstrated that eosinophil cationic protein (ECP) serum levels increased in atopic patients with asthma during pollen season. Objective The aim of the study was to evaluate the effects of short-term (1 week) β2-agonist treatment on lung function and eosinophil activity in asthmatic patients. Methods We used an open, randomized, cross-over design to compare the effects of salbutamol (200μg q.i.d.) and salmeterol (50μg b.i.d.) on peak expiratory flow rate (PEFR), blood eosinophil count and serum levels of ECP as a measure of eosinophil activity in 20 mild atopic asthmatics. Results Morning and evening PEFR values were both significantly higher during salmeterol treatment than during the salbutamol period. Conversely, both morning and evening daily asthma symptom scores were significantly lower during salmeterol treatment compared with those recorded during the salbutamol period. The mean basal eosinophil blood count on salmeterol treatment (601 ± 189mm³) was not higher than the mean count on salbutamol treatment (612 ± 204 mm³). After both treatments the mean eosinophil blood counts were unchanged (619 ± 189mm³ and 576 ±212 mm³, respectively). No significant differences in blood eosinophil counts were observed between or within treatments at any time. No significant difference was observed in baseline mean ECP serum concentration (43.8 ± 263 μg L on salmeterol treatment and 41.7 ± 29.8 μg L on salbutamol treatment, respectively). After salmeterol treatment the mean ECP serum concentration had fallen significantly to 20.9± 18.6μg/L (P < 0.01), whereas after salbutamol treatment it was unchanged (42.0 ± 25.1 μg /L). Salmeterol treatment produced a decrease in ECP serum levels without any changes in blood eosinophil count. Conclusion This study demonstrates that salmeterol affords a significant improvement in asthma control during the pollen season, measured by both subjective and objective parameters, compared with salbutamol. This greater efficacy may be related to inhibition of eosinophil degranulation during the pollen season.     

Role of symptoms and lung function in determining asthma control in smokers with asthma

Background:  Cigarette smoking in asthma increases the severity and accelerates the decline in lung function. The relative role of symptoms and lung function in determining asthma control in smokers with asthma is not known.
Aim of the study:  The aim of this study was to compare asthma control in smokers vs never-smokers with asthma, using the validated Juniper asthma control questionnaire (ACQ), and assess if any difference was because of a particular symptom or the forced expiratory volume in one second (FEV₁) value.
Methods:  This was a cross-sectional study of 134 asthmatics (74 never-smokers and 60 smokers) with ≥15% reversibility in FEV₁ after salbutamol. All subjects completed the ACQ, recording FEV₁ and asthma symptoms (night awakening, morning symptoms, dyspnoea, wheeze, activity limitation and use of reliever inhaler).
Results:  Compared with the never-smokers, smokers with asthma had significantly worse median (IQR) total asthma control score [1.6 (1.1–2.3) vs 2.8 (1.7–3.4); ( P  < 0.0001)] and in each of the six individual symptom question scores ( P  < 0.001), but no difference in FEV₁ levels ( P  = 0.908).
Conclusion:  Asthma control is significantly worse in asthmatics who smoke compared with never-smokers, with all symptoms related to asthma control uniformly worse in smokers, independent of FEV₁.     

Clinical efficacy of budesonide Turbuhaler® compared with that of beclomethasone dipropionate pMDI with volumatic spacer

A total of 102 patients had their asthma treatment with beclomethasone dipropionate (BDP) optimized in order to achieve the best possible control of symptoms. Thereafter, the BDP doses were gradually reduced over a 2-year period (1988–90) to the lowest possible without deterioration of their asthmatic condition. In the beginning of 1990, treatment was changed in 76 patients (group A) to the nearest possible dose of budesonide delivered via Turbuhaler® Twenty-six randomly selected patients (25% of the study population; group B) continued treatment with BDP. In both groups, dose reductions were tried during 1990–2 every third month as long as the patients remained symptom-free and without significant decreases in FEV₁ or PEF. In group A, the maintenance dose could be reduced from 1003.9 ± 325.4 μg BDP (mean ± SD) to 602.9 ± 454.4 μg budesonide Turbuhaler ( P <0.001). In group B, no significant dose reduction was possible; the mean dose was ± SD 1067.3 ± 36.6 μg in 1990, and 1019.2 ± 324.7 μg in 1992. The results indicate that, in efficacy, 0.6 mg budesonide Turbuhaler corresponds to approximately 1.0 mg BDP with volumatic spacer. This difference is probably due to an improved pulmonary delivery of budesonide with Turbuhaler.     

Sensitivity and maximal response to methacholine in perennial and seasonal allergic rhinitis

Background Airway hyperresponsiveness to pharmacological agonists is a common feature in subjects with allergic rhinitis.
Objective The aim of this study was to investigate differences in threshold value and shape of the concentration-response curves to methacholine between subjects with perennial allergic rhinitis and subjects with seasonal rhinitis.
Methods We studied a sample of 72 non-asthmatic patients with allergic rhinitis. They were subdivided into two groups: subjects with only seasonal symptoms and skin sensitization to grass and/or Parietaria pollen allergens (seasonal group, n = 38), and subjects with perennial symptoms and skin sensitization to house dust mite, alone or with other allergens (perennial group, n = 34). They were challenged with methacholine (up to 200mg/mL), and concentration-response curves were characterized by the threshold value (PC₂₀= provocative concentration of methacholine required to produce a 20% fall in FEV₁) and maximal response plateau, if possible. The measurements in the seasonal group were done within the pollen season.
Results The geometric mean methacholine PC₂₀ for subjects of the perennial group was 6.9mg/mL, compared with 23.4mg/mL in subjects of the seasonal group ( P 0.01). A plateau response was detected in 16 subjects of the perennial group and in 28 subjects of the seasonal group (p 0.05). Moreover, the level of plateau was higher in subjects of the perennial group when compared with subjects of the seasonal group (23.8 ±2.0% vs 19.2 ±1.6%, P 0.05).
Conclusion In subjects with allergic rhinitis, sensitization to perennial allergens is associated not only with lower methacholine threshold values, but also with lower prevalence and higher level of plateau than sensitization to pollen allergens.     

Adherence rate to inhaled corticosteroids and their impact on asthma control

Background:  Poor asthma control is associated to high morbidity. The objective of this study was to assess the association between adherence rates to beclomethasone dipropionate (BDP) and the degree of asthma control.
Methods:  A cohort concurrent study was carried out for 12 months with 122 asthmatic patients, aged 3–12 years, randomly selected in a pediatric pulmonology outpatient clinic, who received BDP free of charge. Adherence rates were verified by pharmacy records. Clinical control was assessed through a scoring system comprised four variables (nocturnal and morning symptoms, limitation of physical activities and exacerbations). Total score was 16 points. Patients whose score was below or equal to two were considered controlled (group 1), and patients whose score was above or equal to three were considered uncontrolled (group 2). For patients able to perform spirometry, we considered as controlled the patients with forced expiratory volume in 1 s (FEV₁) equal to or above 80% of the predicted value, and as uncontrolled the patients with FEV₁ below 80%.
Results:  Fewer than half (40.3% maximum) of the 122 patients maintained asthma control. Median adherence rate of groups 1 and 2 were 85.5% and 33.8%, ( P  < 0.001) in the 4th month, 90.0% and 48.0% ( P  < 0.001) in the 8th month and 84.4% and 47.0% in the 12th month ( P  < 0.001), respectively.
Conclusion:  In all periods, there were statistically significant differences in adherence rates for maintaining or not maintaining the asthma control. Optimal asthma control entailed adherence rate higher than 80%. Strategies for reducing asthma morbidity should include a regular monitoring of adherence to inhaled steroids.     

Bronchial responsiveness to methacholine and adenosine 5'-monophosphate in young children with asthma: their relationship with blood eosinophils and serum eosinophil cationic protein

BACKGROUND: Bronchial hyperresponsiveness is a characteristic feature of asthma, and is usually measured by bronchial challenges using direct or indirect stimuli. Blood eosinophil numbers and serum levels of eosinophil cationic protein (ECP) are considered as indirect measures of airway inflammation in asthma. The aim of this study was to investigate whether bronchial responsiveness to adenosine 5'-monophosphate (AMP) is more closely associated with blood eosinophil markers, compared with that to methacholine, in young children with asthma. METHODS: Methacholine and AMP bronchial challenges were performed in 4- to 6-year-old children with asthma (n = 77) and in healthy controls (n = 32), using a modified auscultation method. The end-point was defined as the appearance of wheezing and/or oxygen desaturation. The peripheral blood eosinophil counts and serum ECP concentrations were determined in each subject. RESULTS: A positive response to methacholine (end-point concentration < or =8mg/ml) and to AMP (end-point concentration < or =200 mg/ml) was observed in 74 (96.1%) and 66 asthmatic children (85.7%), respectively. A majority of controls was unresponsive to both challenges. In the asthma group, there was no significant correlation between methacholine end-point concentration and the eosinophil counts (r = -0.111, P = 0.337) or serum ECP levels (r = -0.126, P = 0.274). In contrast, AMP end-point concentration correlated significantly with the eosinophil counts (r = -0.372, P = 0.001) and with serum ECP levels (r = -0.371, P = 0.001). CONCLUSIONS: Our results suggest that bronchial responsiveness to AMP is more closely related to airway inflammation, compared with that to methacholine, and support the potential usefulness of AMP challenges in detecting inflammatory changes in young children with asthma.     

The first 20 minutes after a single dose of inhaled salmeterol in asthmatic children

Very little is known as yet about the effect of salmeterol in pediatric asthma, so a trial was performed on children with mild asthma to compare salmeterol with salbutamol in terms of how quickly they took effect. The double-blind study involved 11 children (mean age 13.4 years) randomly assigned to inhale salmeterol 50 μg, salbutamol 200 μg, or a placebo three times on alternate days. Peak expiratory flow (PEF), heart rate, and blood pressure were measured before and 5, 10, 15, and 20 min after administering the medication. With salbutamol, PEF was higher at 5 and 10 min, subsequently dropping off at 15 and 20 min; with salmeterol, PEF was better at 10 and 20 min. Forced expiratory volume at 1 s (FEV₁) measurements taken at the baseline and after 10 and 20 min revealed an important and consistent rise in values after salmeterol, whereas salbutamol was more effective after 10 min than after 20 min. No significant changes were recorded in heart rate or blood pressure after salbutamol; after salmeterol, there was a significant increase in heart rate after 5 min, but not at subsequent measurements. In conclusion, salmeterol begins to take effect already within 10 min of a single administration in asthmatic children, although the onset of its effect is slower than with salbutamol.     

Twenty-four-hour time course of eosinophil granule proteins ECP and EPX during bronchial allergen challenges in serum of asthmatic children

To study in vivo monitoring variables for bronchial allergen challenges, we investigated the time course of the eosinophil granule proteins, eosinophil cationic protein (ECP) and eosinophil protein × (EPX) after allergen provocation in serum. Thirty-two asthmatic children sensitive to house-dust mites and six healthy young adult controls were challenged by bronchial allergen provocations with Dermatophagoides pteronyssinus and D. farinae. Blood samples were taken at regular intervals up to 24 h. Base-line concentrations of ECP ( P <0.004), EPX ( P <0.002), and eosinophils ( P <0.001) were found to be increased in asthmatic children, as compared with healthy controls. ECP and EPX concentrations showed a uniform pattern with two characteristic features: 1) a rapid increase for both mediators up to 30 min after provocation over base-line values ( P <0.0001 and P <0.001), followed by a rapid decrease nearly to base-line values in the next 30 min; and 2) a steady increase for ECP and EPX up to 10 h ( P <0.02 and P <0.01), and even higher levels at 24 h, after challenge ( P <0.002 and P <0.003). We conclude that although eosinophils are activated in asthmatic children after bronchial allergen challenge, ECP and EPX concentrations are not suitable monitoring variables. Base-line eosinophils seem to predict the occurrence of a late-phase asthmatic reaction after allergen provocation.     

Influence of total IgE and seasonal increase of eosinophil cationic protein on bronchial hyperreactivity in asthmatic grass-sensitized farmers

BACKGROUND: This study correlates biomarkers of atopy (serum total and specific IgE) and inflammation (serum eosinophil cationic protein) with bronchial hyperreactivity assessed after the complete end of pollination, in a group of farmers suffering from grass-allergic asthma. METHODS: A total of 28 asthmatic farmers, with allergy to grass pollen, reporting persistent asthma symptoms after grass pollination, were enrolled. An accurate allergologic screening excluded other sensitizations. Analysis of total and grass-specific IgE and eosinophil cationic protein was carried out before (March) and during (May) the following spring. After the complete end of pollination, bronchial hyperreactivity was assessed. RESULTS: Symptoms (cough, wheezing) persisted during the autumn for a mean period of 41 days (range 13-69). Total IgE was moderately high and grass-specific IgE ranged from 9.25 to 41.12 kU/l without significant differences before and during spring. On the contrary, serum ECP levels significantly increased during the pollination period. PD20 methacholine evaluated after the end of grass pollination was negatively significantly correlated with levels of total IgE (r=-0.73; P<0.01) and the increase (from March to May) of serum ECP (r=-0.75; P<0.01). However, PD20 methacholine did not correlate with grass-specific IgE and serum ECP absolute values of both March and May. A positive correlation was found between number of postseasonal days with symptoms and both spring increase of serum ECP (r=0.75; P=0.04) and levels of total IgE (r=0.76; P<0.01). The number of postseasonal days with symptoms inversely correlated with postseason PD20 methacholine (r=-0.76; P<0.01). CONCLUSIONS: The study demonstrates that in grass-sensitized farmers with asthmatic symptoms persisting for several weeks after grass pollination has ceased, the degree of airways hyperreactivity and the duration of postseasonal symptoms are directly related to the spring increase of ECP levels, as well as to the level of total IgE in serum. This allows us to identify two candidate biomarkers for the risk of developing prolonged asthma symptoms, and for the effective monitoring of anti-inflammatory treatment and allergen-specific immunotherapy.