Histamine bronchoconstriction reduces airway responsiveness in asthmatic subjects

Tachyphylaxis occurs to repeated challenges with inhaled histamine but not with inhaled acetylcholine in asthmatic subjects. This study was undertaken to determine whether prior histamine bronchoconstriction reduces airway responsiveness to inhaled acetylcholine in mild asthmatic subjects demonstrating histamine tachyphylaxis. All subjects developed histamine tachyphylaxis with repeated histamine challenge. The mean histamine PC20 increased from 3.74 to 5.92 mg/ml (p less than 0.005) when the histamine challenges were separated by 1 h. Prior acetylcholine bronchoconstriction did not reduce airway responsiveness to subsequent inhalation of either acetylcholine or histamine in these subjects. However, histamine inhalation did reduce airway responsiveness to acetylcholine in all subjects. The mean acetylcholine PC20 following acetylcholine inhalation was 3.37 mg/ml (%SD 2.17) and this increased to 7.76 mg/ml (%SD 1.80) after histamine inhalation (p less than 0.0005). Thus, this study demonstrates that prior histamine, but not acetylcholine, bronchoconstriction can partially protect against bronchoconstriction caused by both histamine and acetylcholine. Therefore, reduced airway responsiveness caused by histamine bronchoconstriction is specific for histamine and is not due to bronchoconstriction per se. However, the reduced airway responsiveness following histamine bronchoconstriction, is nonspecific.     

Methacholine airway responsiveness decreases during exercise in asthmatic subjects

In many asthmatic subjects, bronchoconstriction develops 2 to 5 min after exercise, reaches a maximum at approximately 10 min, and declines over the next 60 min. However, bronchodilation is typically observed during and immediately after exercise. We measured the bronchoconstrictor responses to increasing concentrations of inhaled methacholine at rest and during two levels of exercise in seven asthmatic subjects to determine the protection against bronchoconstriction afforded by exercise. On the first day, an incremental Stage 1 exercise test was performed to determine the work capacity (Wcap) of each subject. On the second, third, and fourth days, methacholine was inhaled at rest or during steady-state exercise at one-third or two-thirds of Wcap. The bronchoconstrictor response to methacholine was significantly reduced during exercise (p less than 0.0001). The concentration of methacholine required to produce a 20% reduction in FEV1 (PC20) increased from 2.80 mg/ml (%SEM, 1.62) at rest to 7.29 mg/ml (%SEM, 1.43) during exercise at one-third Wcap, and to 31.03 mg/ml (%SEM, 1.74) during exercise at two-thirds Wcap (p less than 0.001). This study has demonstrated that there is greater than tenfold protection against bronchoconstriction by methacholine during exercise, and the magnitude of the protection depends on the intensity of exercise performed. The mechanism of this protection is not known, but may have clinical utility.     

Increased airway responsiveness to acetaldehyde in asthmatic subjects with alcohol-induced bronchoconstriction.

Bronchial responsiveness to acetaldehyde, a main factor in alcohol-induced bronchoconstriction, and methacholine were compared between 10 subjects with alcohol-induced bronchoconstriction and 16 asthmatic subjects without alcohol sensitivity. In the alcohol-sensitive group, the geometric mean (geometric SEM (GSEM)) of the provocative concentration of methacholine (PC20,meth) and acetaldehyde (PC20,acet) causing a 20% fall in forced expiratory volume in one second were 0.947 mg x mL(-1) (GSEM 0.139) and 21.0 mg x mL(-1) (GSEM 0.112), respectively, which were not significantly different from those in the nonalcohol-sensitive group, which were 0.634 mg x mL(-1) (GSEM 0.115) and 31.7 mg x mL(-1) (GSEM 0.077), respectively. The ratio of airway responsiveness to acetaldehyde relative to methacholine (log PC20,acet/PC20,meth) was 1.345+/-0.093 (mean+/-SEM) in the alcohol-sensitive group, which was significantly different from the value of 1.699+/-0.059 in the nonalcohol-sensitive group (p=0.0025). A significant correlation was observed between PC20,meth and PC20,acet in both the alcohol-sensitive group (r=-0.742, p=0.0115) and nonsensitive group (r=0.882, p<0.0001). In conclusion, the airways of asthmatic subjects with alcohol-induced bronchoconstriction have a selective hyperresponsiveness to acetaldehyde.     

Bronchoalveolar lavage does not alter airway responsiveness in asthmatic subjects

Bronchoalveolar lavage (BAL) during fiberoptic bronchoscopy is being used increasingly for the investigation of asthma. Airway responsiveness to methacholine is a sensitive indicator of the presence and severity of asthma. Therefore, we studied the effect of BAL on methacholine airway responsiveness in stable asthmatics. Geometric mean methacholine PC20 was 1.34 mg/ml before and 1.80 mg/ml after BAL (p = 0.26) in asthmatics. Immediate symptoms of airway narrowing after BAL occurred only in the 3 asthmatics with moderate to severe hyperresponsiveness. These symptoms were rapidly relieved by inhaled bronchodilator. There was no relationship between the occurrence of symptoms and the amount of topical lidocaine used for local anaesthesia or the volume of lavage fluid returned. The absence of an effect of BAL on airway responsiveness supports the safety of this procedure in the controlled asthmatic patient with near normal FEV1, irrespective of the level of baseline airway responsiveness.     

A comparison of airway responsiveness in smokers with chronic bronchitis and in asthmatic subjects

Fifty-two of 95 smokers with a forced expiratory volume in one second (FEV1) above 70% predicted and with chronic bronchitis were found to have increased bronchial responsiveness, expressed as PC20FEV1, upon challenge with inhaled histamine. The degree of responsiveness was significantly below that found in matched asthmatics, but substantially higher than that reported in normals. The degree of responsiveness was significantly correlated to prechallenge ventilatory capacity, age and tobacco consumption but not to sex. PC40MEF50 showed the same distribution as PC20FEV1, but did not add further information. The slope of the dose response curve expressing the maximum expiratory flow at 50% of vital capacity expired (MEF50) did not correlate with any of the parameters measured. The slope of the FEV1 dose-response curves showed significant correlation with tobacco consumption. The degree of bronchial responsiveness as an indication for future disability needs to be investigated.     

The effect of insecticide aerosols on lung function, airway responsiveness and symptoms in asthmatic subjects.

The object of this study was to compare the effect of standard and "low irritant" insecticide aerosols on lung function, airway hyperresponsiveness (AHR) and symptoms in asthmatic subjects. A double blind randomized, crossover study was conducted in 25 asthmatic subjects who reported sensitivity to insecticide aerosols. All subjects were exposed for 30 min, on separate occasions, to two standard insecticide formulations (A and B), one low irritant formulation (C) and a negative control aerosol. Spirometric function and chest, nose and eye symptoms were recorded during, and for 90 min after, the exposure. AHR to methacholine was measured 90 min after the exposure. Compared to the negative control, the maximum fall in forced expiratory volume in one second (FEV1) was slightly greater after standard insecticides (mean differences from control +/-95% confidence interval: aerosol A, 3.3+/-3.6%, p=0.08; aerosol B, 5.1+/-4.7%, p=0.04), AHR was significantly more severe (mean difference from control: aerosol A, 0.35+/-0.29 doubling doses, p=0.028; aerosol B, 0.52+/-0.43 doubling doses, p=0.028), and symptoms were more severe. The low irritant test aerosol (C) did not differ significantly from the negative control with respect to FEV1, AHR or symptoms. It is concluded that some insecticide aerosols trigger symptoms and falls in lung function in some people with asthma. Furthermore, these aerosols may also increase airway hyperresponsiveness, although the mechanism of this effect has not been determined. The low irritant formulation did not appear to have the same effects.     

Acute exposure to sawdust does not alter airway calibre and responsiveness to histamine in asthmatic subjects

We investigated the effects of particles of sawdust delivered through a special device at known concentrations (close to the threshold limit value-short term exposure limit (TLV-STEL) of 10 mg.m-3) on FEV1 and PC20 in 12 asthmatic subjects free of clinical sensitization to this product. Subjects were studied over two days (day 1: exposure to sawdust; day 2: sham exposure) in random order with a maximum interval of 1 week. On each day, after the assessment of spirometry and PC20, subjects underwent exposure to sawdust or sham exposure. Sawdust was inhaled for a total of 30 min at average concentrations varying from 8.0 to 19.3 mg.m-3 (mean = 11.5 mg.m-3). Twenty-five to 39.7% (mean = 34.6%) of inhaled particles had a diameter less than 10 mu (diameter allowing deposition in the trachea and lower respiratory tract). At the end of each period of exposure, FEV1 was assessed. After recovery, the second PC20 was obtained. Serial measurements of FEV1 were carried out every hour for up to 6 h after the end of exposure. At that time, PC20 was reassessed. Only one subject showed an acute bronchoconstriction immediately after exposure to sawdust (maximum fall of 14% in FEV1) with complete recovery 10 min later. Overall, inhalation of sawdust did not modify PC20 by comparing the mean result of the first test with the second and the third assessments. Also, the mean changes in PC20 at each interval after exposure to sawdust were not significantly different from the variations in PC20 on the sham day.(ABSTRACT TRUNCATED AT 250 WORDS)     

Diesel exhaust exposure enhances the expression of IL-13 in the bronchial epithelium of healthy subjects

Epidemiological studies have demonstrated adverse health effects of environmental pollution. Diesel exhaust (DE) is an important contributor to ambient particulate matter pollution. DE exposure has been shown to induce a pronounced inflammatory response in the airways, with an enhanced epithelial expression of IL-8, and Gro-alpha in healthy subjects. The present investigation was aimed to further characterise the epithelial response to DE in vivo, with particular reference to possible TH2 response, in non-atopic healthy subjects. To determine this response, 15 healthy, non-atopic non-smoking subjects with normal lung function were exposed to DE (PM10 300 microg/m3) and filtered air during 1 h on two separate randomised occasions. Bronchoscopy sampling of bronchial mucosal biopsies was performed 6 h after exposure. Immunohistochemical staining were performed using mAb for IL-10, IL-13 and IL-18 expression. DE exposure induced a significant increase in the expression of IL-13 in the bronchial epithelium cells, 2.1 (1.35-4.88) Md (Q1-Q3) vs. air 0.94 (0.53-1.23); P = 0.009. No significant changes were seen in IL-10 and IL-18 expression. This finding suggests an TH2-inflammatory response in the airways of non-atopic healthy individuals.     

Hyperosmolarity-induced increases in airway responsiveness and late asthmatic responses

Airway responsiveness to inhaled methacholine was assessed before and after bronchial challenge with ultrasonically nebulized hyperosmolar saline (UNHS), and these changes were correlated with the development of late asthmatic responses (LAR). Sixteen subjects with mild to moderate asthma had two consecutive methacholine challenges before and one after a cumulative-dose challenge with UNHS. Twelve of these subjects also had a single-dose hyperosmolar challenge to document the occurrence of LAR and determine if UNHS had a significant cumulative-dose effect. If a LAR was observed, a control day without challenge completed the study. Responsiveness to methacholine was similar on the 2 baseline methacholine challenges with a provocative concentration producing a 20% fall in forced expiratory volume in one second (PC20) (mean +/- SEM) of 1.11 +/- 0.94 and 1.16 +/- 0.94 mg.ml.1 (r: 0.98). However, it was significantly increased after the inhalation of UNHS with a PC20 (mean +/- SEM) of 0.57 +/- 1.00 mg.ml.1 (p less than 0.001). Two subjects developed a late fall in forced expiratory volume in one second (FEV1) of 19 and 46% after hyperosmolar challenge. In this last subject, the LAR, not reproduced on the control day, was associated with a marked post-UNHS change in PC20, going from a baseline of 4.4 to 0.7 mg.ml.1 after UNHS. The % fall in FEV1 following the dose-response hyperosmolar challenge and the single-dose hyperosmolar challenge were not different, with mean values +/- SEM of 34.9 +/- 2.2 and 35.8 +/- 4.1, respectively, (p greater than 0.5). In conclusion, airway responsiveness to methacholine may increase following hyperosmolar saline inhalation, often unrelated to LAR.     

Effect of salmeterol on seasonal changes in airway responsiveness and exhaled nitric oxide in pollen-sensitive asthmatic subjects

OBJECTIVE: Using a model of natural allergen exposure, we examined the effect of regular treatment with salmeterol on allergen-induced changes in airway responsiveness and exhaled nitric oxide (ENO). DESIGN: Double-blind, randomized, parallel-group study. SETTING: Specialist allergy unit in a university hospital. PATIENTS: Asthmatic patients sensitized to pollen allergens were randomly allocated to monotherapy with salmeterol (n = 14) or placebo (n = 13). INTERVENTIONS: Salmeterol, 25 micro g, and placebo inhalers, two puffs bid, for 6 weeks. MEASUREMENTS: Spirometry, the level of a provocative concentration of a substance (methacholine) causing a 20% fall in FEV(1) (PC(20)), the PC(20) level for adenosine 5'-monophosphate (AMP), and ENO were measured before the pollen season and were repeated at the height of the pollen season after 6 weeks of treatment with salmeterol or placebo. RESULTS: The decrease in FEV(1) during the pollen season was significantly larger in the placebo group than in the salmeterol group, the mean difference in the change between the groups being 0.20 L (95% confidence interval, 0.03 to 0.35; p = 0.047). Changes in PC(20) for methacholine, PC(20) for AMP, and ENO levels were not significantly different between treatment groups. However, a mean (+/- SEM) decrease in the PC(20) for methacholine of -1.0 +/- 0.4 doubling concentrations was observed within the placebo group (p = 0.03), whereas no significant changes were observed within the salmeterol group. A significant decrease in PC(20) for AMP (doubling concentrations) was observed within the placebo group (-2.1 +/- 0.6; p = 0.003) and the salmeterol group (-1.5 +/- 0.4; p = 0.003). ENO concentrations increased significantly among the placebo and the salmeterol groups during natural pollen exposure. CONCLUSION: These observations indicate that natural allergen exposure and the regular use of salmeterol are not associated with a greater increase in ENO and airway responsiveness than allergen exposure alone.     

Cough receptor sensitivity and bronchial responsiveness in normal and asthmatic subjects.

We examined whether airway cough receptor sensitivity correlates to nonspecific bronchial responsiveness. We measured cough threshold, the lowest concentration of inhaled tartaric acid eliciting five or more coughs, and the provocative concentration of methacholine producing a 20% fall in forced expiratory volume in one second (PC20FEV1) in 38 normal and 11 asthmatic subjects. All subjects were nonsmokers. The geometric mean value of PC20FEV1 was 25.7 mg.ml-1 (GSEM1.29) and 0.63 mg.ml-1 (GSEM1.29) and the geometric mean value of the cough threshold was 115 mg.ml-1 (GSEM1.20) and 95.5 mg.ml-1 (GSEM1.35) in normal and asthmatic subjects, respectively. The PC20FEV1 was significantly (p less than 0.01) lower in asthmatics than in normals but the cough threshold did not differ between them. No significant correlation was observed between the cough threshold and the PC20FEV1 in normal subjects or in asthmatics. These results indicate that cough sensitivity does not directly correlate to bronchial responsiveness in normal and asthmatic subjects.     

Effects of inhaled lidocaine on airway function in asthmatic subjects.

We measured the effect of inhaled lidocaine on pulmonary function in 8 asthmatic subjects. Plethysmographic specific airways conductance (SGaw) and the 1-sec forced expired volume (FEV1) were measured before and after the inhalation of 2cm3 of lidocaine (4%). Responses were also measured after patients were pretreated with either aerosolized isoproterenol, aerosolized atropine, or intramuscular atropine. In response to lidocaine alone, we observed a 23.4 +/- (SE) 4.8% fall in FEV1 and a 64.1 +/-(SE)3.8% fall in SGaw (p is less than 0.001). These effects were reversed with aerosolized atropine or isoproterenol. After pretreatment with aerosolized atropine or isoproterenol, the bronchoconstrictor effect of lidocaine were either prevented or markedly reduced. The protective effects of intramuscular atropine varied in different subjects, but in general, aerosolized bronchodilators afforded better protection against the bronchoconstrictor effect of lidocaine. Although lidocaine is theoretically capable of blocking neurogenic reflexes in the lung, our studies indicate that this topical anesthetic agent produces untoward reflex-mediated bronchoconstriction in patients with asthma and hyperirritable airways.     

Influence of short-term passive smoking on symptoms, lung mechanics and airway responsiveness in asthmatic subjects and healthy controls.

We studied the acute effect of passive smoking on symptoms, lung mechanics and airway responsiveness. Twenty four patients with mild to moderate bronchial asthma (11 male and 13 female; mean(SD) age 34(15) yrs; forced expiratory volume in one second (FEV1) 91(17) % pred) were investigated. Sixteen of them had a history of passive smoke-induced respiratory symptoms. For comparison we studied 16 controls (7 male and 9 female; mean(SD) age 31(9) yrs; FEV1 106(13) % pred). On two different days, the subjects were exposed in an exposure chamber for one hour to either ambient air (Sham) or environmental tobacco smoke (ETS). During exposure to ETS, the mean concentrations of particles and CO were 3,095 micrograms.m-3 and 20.3 ppm, respectively. Before and immediately after exposure, symptoms and lung mechanics were assessed, followed by an inhalation challenge to determine the provocative concentrations of methacholine necessary to increase specific airway resistance (sRaw) by 100%, (PC100sRaw), and to decrease FEV1 by 20% (PC20FEV1). In the asthmatic subjects, during Sham exposure, mean (SEM) decrease of sRaw and FEV1 was 0.23(0.22) cmH2O.s and 0.04(0.03) l, respectively, (NS). During ETS, mean(SEM) decrease of sRaw and FEV1 was 0.55(0.46) cmH2O.s and 0.13(0.06) l, respectively. The significance of this decrease, however, disappeared when taking into account the individual variability of FEV1. Geometric mean(SEM) PC100sRaw and PC20FEV1 were 0.35(1.32) and 0.23(1.34) mg.ml-1 after Sham, and 0.34(1.37) and 0.28(1.36) mg.ml-1 after ETS, respectively, with no difference between the two study days. In the controls, the two exposure conditions did not exert any significant effects on sRaw, FEV1 and airway responsiveness.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prednisone inhibits late asthmatic reactions and the associated increase in airway responsiveness induced by toluene-diisocyanate in sensitized subjects

To determine whether late asthmatic reactions and the associated increase in airway responsiveness induced by toluene diisocyanate (TDI) are linked to airway inflammation, we investigated whether they are inhibited by prednisone. Ten "sensitized" subjects were studied in 2 sets of experiments. In the first set, each subject was given no treatment and was studied before and for 8 h after exposure to TDI. In the second set, 2 to 4 wk later, each subject was studied before treatment and then during treatment with prednisone (50 mg once a day for 3 days, orally), both before and after exposure to TDI. To assess late asthmatic reactions to TDI, we measured FEV1 immediately before and after exposure, then hourly for 8 h. To assess changes in airway responsiveness, we measured the provocation dose (mg) of methacholine causing a 20% decrease in FEV1 (PD20FEV1) before and 8 h after exposure to TDI. When the subjects received no prednisone treatment, TDI caused late asthmatic reactions and increased airway responsiveness. By contrast, when the subjects received prednisone, TDI caused no late asthmatic reaction or increased airway responsiveness. Prednisone did not change baseline airway caliber or airway responsiveness. These results suggest that late asthmatic reactions and the associated increase in airway responsiveness induced by TDI in "sensitized" subjects may depend on the development of a steroid-responsive acute inflammatory reaction within the airways.     

Short-term exposure to 0.3 ppm nitrogen dioxide does not potentiate airway responsiveness to sulfur dioxide in asthmatic subjects

Whether short-term exposure to low levels of nitrogen dioxide (NO2) enhances airway responsiveness in asthmatic subjects is controversial. Because it is well established that asthma is associated with increased airway responsiveness to another common air pollutant, sulfur dioxide (SO2), we examined whether short-term exposure of asthmatic subjects to 0.3 ppm NO2 potentiates airway responsiveness to inhaled SO2. We exposed nine subjects with clinically stable asthma to 0.3 ppm NO2 or filtered air in an environmental room for 30 min on 2 separate days at least 1 wk apart in a double-blind, randomized fashion. A questionnaire about common symptoms related to inhaled irritants was completed before and immediately after each exposure. Each subject exercised (60 to 80 W) on a cycloergometer during the first 20 min of each exposure. We measured specific airway resistance (SRaw) and FEV1/FVC before, 5 min after, and 1 h after completion of the air or NO2 exposure. The single-breath nitrogen test (SBN2) was also performed before and 1 h after completion of the air or NO2 exposures and closing volume was determined; subsequently, SO2 dose-response curves (0.25 to 4.0 ppm) were performed via a mouthpiece. Each dose of SO2 was inhaled at a minute ventilation of 20 L/min for 4 min and was doubled until SRaw increased by at least 8 U above baseline. The dose of SO2 required to provoke an increase in SRaw of 8 U above baseline was determined by linear interpolation from the dose-response curve (PD8Uso2).(ABSTRACT TRUNCATED AT 250 WORDS)     

Nedocromil sodium inhibits responsiveness to inhaled mannitol in asthmatic subjects

Nedocromil sodium inhibits the response to exercise-induced asthma (EIA). Mannitol given as a powder by inhalation is an osmotic stimulus that identifies EIA. We studied the acute effect of nedocromil on airway responsiveness to mannitol in 24 asthmatic subjects. After a control day, nedocromil (8 mg) or its placebo was administered randomized, double blind, 10 min before a challenge with progressively increasing doses of mannitol. Nedocromil inhibited the response to mannitol and there was a significant increase in the dose of mannitol required to cause a 15% reduction in FEV(1) (PD(15)) after nedocromil 409 (316,503) mg compared with placebo 156 (106,229) mg (p < 0.001). In the presence of nedocromil 12 subjects no longer recorded a 15% decrease in FEV(1) in response to mannitol. The remaining 12 required a significantly greater dose of mannitol to achieve a 15% decrease in FEV(1) after nedocromil. Following nedocromil, a plateau in responsiveness to mannitol was observed in 14 subjects. Nedocromil significantly inhibits the responsiveness to inhaled mannitol in asthmatic subjects.     

Endogenous sensory neuropeptide release enhances nonspecific airway responsiveness in guinea pigs.

To test whether endogenous sensory neuropeptide release results in airway hyperresponsiveness to exogenous bronchoconstrictor stimuli, male Camm-Hartley guinea pigs were exposed either to capsaicin aerosol for 10 min (CAP-AER) or to saline aerosol (SAL-AER) as a control condition. The following day, animals were anesthetized, tracheostomized, and beta-adrenergically blocked with propranolol, and their bronchoconstrictor responses to intravenously administered acetylcholine (ACh), neurokinin A (NKA), or capsaicin were measured. The bronchoconstriction induced by isocapnic dry gas hyperpnea also was assessed. Compared with the SAL-AER control group, the CAP-AER-treated animals exhibited augmented bronchoconstrictor responses to ACh and NKA. In contrast, the SAL-AER and CAP-AER groups had equivalent bronchoconstrictor responses to dry gas hyperpnea and to intravenously administered capsaicin. CAP-AER treatment caused neutrophilic airway inflammation, as reflected in increased numbers of neutrophils in bronchoalveolar lavage fluid obtained from CAP-AER-treated animals. Ablation of airway c-fiber neuron function (by chronic pretreatment with capsaicin prior to capsaicin aerosol inhalation) eliminated the ACh hyperresponsiveness observed in the CAP-AER-treated animals, demonstrating that sensory nerve products play a key role in the development of this nonspecific hyperresponsiveness. Our results demonstrate that sensory nerve stimulation with capsaicin aerosol leads to nonspecific bronchoconstrictor hyperresponsiveness and cellular airway inflammation, and thus disclose another potentially important role of sensory nerves in regulating airway function.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ozone enhances the airway inflammation initiated by diesel exhaust

Exposure to air pollution is associated with adverse health effects, with particulate matter (PM) and ozone (O(3)) both indicated to be of considerable importance. Diesel engine exhaust (DE) and O(3) generate substantial inflammatory effects in the airways. However, as yet it has not been determined whether a subsequent O(3) exposure would add to the diesel-induced airway inflammatory effects. Healthy subjects underwent two separate exposure series: A 1-h DE exposure at a PM-concentration of 300 microg/m(3), followed after 5h by a 2-h exposure to filtered air and 0.2 ppm O(3), respectively. Induced sputum was collected 18 h after the second exposure. A significant increase in the percentage of neutrophils (PMN) and concentration of myeloperoxidase (MPO) was seen in sputum post DE+O(3) vs. DE+air (p<0.05 and <0.05, respectively). Significant associations were observed between the responses in MPO concentration and total PMN cells (p=0.001), and also between MPO and matrix metalloproteinase-9 (MMP-9) (p<0.001). The significant increase of PMN and MPO after the DE+O(3) exposures, compared to DE+air, denotes an O(3)-induced magnification of the DE-induced inflammation. Furthermore, the correlation between responses in MPO and number of PMNs and MMP-9 illustrate that the PMNs are activated, resulting in a more potent inflammatory response. The present study indicates that O(3) exposure adds significantly to the inflammatory response that is established by diesel exhaust. This interaction between exposure to particulate pollution and O(3) in sequence should be taken into consideration when health effects of air pollution are considered.     

Exhaled nitric oxide, serum ECP and airway responsiveness in mild asthmatic children.

The purpose of the present study was to assess the possible relationships between exhaled nitric oxide (ENO), a circulating marker of eosinophil activation, serum eosinophil cationic protein (SECP), level of airway responsiveness to methacholine and lung function in asthmatic children, as well as to compare these markers between children with and without inhaled steroid therapy. In a cross-sectional study ENO, SECP and bronchial hyperresponsiveness to methacholine were evaluated in a group of 57 asthmatic children (21 without and 36 with regulator inhaled steroid therapy; aged 6-13 yrs). ENO was significantly lower in steroid treated children (p<0.01). No significant differences between steroid treated and untreated children were observed for the provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (FEV1; PC20), SECP and FEV1. In the whole study population significant increase correlations were observed between PC20 and SECP (r=-0.329, p=0.013) and between ENO and FEV1% of predicted (r=-0.348, p<0.01). In the group not receiving inhaled steroids the inverse relationship between PC20 and SECP was more evident (r=-0.581, p<0.001). In the steroid-treated group a significant inverse relationship was observed between ENO and FEV1 (r=-0.426, p=0.0011). The level of exhaled nitric oxide and the relationships between lung function, bronchial reactivity and markers of inflammation are different between steroid-treated and untreated asthmatic children. This has implications for the monitoring of asthma in childhood.