Background. Oxidative stress plays a role in the pathogenesis of many chronic inflammatory lung diseases. Exhaled breath condensate (EBC) collection is a noninvasive method to investigate pulmonary ...oxidative stress biomarkers such as malondialdehyde (MDA). Subjects and Methods. We measured MDA levels in EBC in a large number of patients (N=194) with respiratory diseases: asthma (N=64), bronchiectasis (BE, N=19), chronic obstructive pulmonary disease (COPD, N=73), idiopathic pulmonary fibrosis (IPF, N=38). Fourteen healthy nonsmoking subjects were included as controls. Results. Excluding IPF subjects, MDA levels were significantly higher in all disease groups than in control group. MDA was significantly higher in COPD than asthmatic and BE subjects. Among asthmatics, corticosteroids-treated subjects had lower MDA levels than untreated subjects. COPD subjects showed an inverse correlation between MDA concentrations and FEV1% (rho: −0.24, P<.05). Conclusions. EBC-MDA is increased in subjects with chronic airway disorders, particularly in COPD, and it is related to FEV1 reduction.
Few data are reported on the effects of a reduction of exposure to specific sensitizers in occupational asthma (OA). The objective of this study was to evaluate the clinical outcome of subjects with ...OA, comparing the effect of a reduction with that of the persistence or cessation of occupational exposure to the specific sensitizer.
Forty-one subjects with OA due to different sensitizers were diagnosed via a specific inhalation challenge. After a follow-up interval of 3.5 years, subjects were reexamined by clinical assessment, bronchial hyperresponsiveness (BH) and induced sputum.
At follow-up, subjects who had reduced occupational exposure (n = 22) showed a significant improvement in BH and a nonsignificant improvement in sputum eosinophilia (from 5.3 to 1.1%, n.s.), while subjects still exposed (n = 10) showed a significant decrease in FEV(1). Subjects who ceased work (n = 9) showed a trend of improvement in BH and sputum eosinophilia. Logistic analysis showed that the major determinant of improvement in BH at follow-up was the severity of BH at diagnosis, with a minimal contribution from the duration of exposure and treatment with inhaled corticosteroids during follow-up; reduction of work exposure did not enter into any model.
The reduction of occupational exposure could not be considered to be as effective as work cessation, which remained the best treatment for OA. However, it was not associated with a deterioration of FEV(1) as observed in subjects with persistent exposure.
Long-term follow-up of diisocyanate-induced occupational asthma has been occasionally reported.
We studied the outcome of toluene diisocyanate (TDI)-induced asthma in 46 patients at diagnosis and ...after a follow-up of 11 ± 3.6 years. Symptoms, anti-asthma therapy, forced expiratory volume in 1 s (FEV1) and bronchial hyperresponsiveness to methacholine were assessed.
A significant improvement in FEV1 (% predicted) and PD20FEV1 methacholine was observed at follow-up in comparison with diagnosis. Anti-asthma treatment was performed by 42% of patients at diagnosis and by 70% at follow-up. At the time of follow-up, 32 subjects had been removed from exposure for 6.0 ± 6.9 years, whereas 14 subjects continued to work with reduced exposure to TDI. There was a significant reduction in the prevalence of attacks of shortness of breath and dyspnoea at follow-up, but only in unexposed patients. PD20FEV1 was significantly improved only in patients with a lower FEV1 at diagnosis and in those who have ceased work. Logistic regression analysis, using different models with some independent variables, showed that there were no significant determinants of improvement in FEV1 at follow-up, while a shorter duration of symptoms before diagnosis was a significant predictor of improvement in PD20FEV1 at follow-up.
Asthma-like symptoms, bronchial hyperresponsiveness and airway obstruction improved, but did not normalize, after a long-term follow-up with cessation or reduction in TDI exposure, mainly in subjects with an early diagnosis of occupational asthma and in patients with a lower baseline FEV1 no longer exposed to TDI.
In order to identify predictors of recurrence of asthma symptoms after withdrawal of therapy in mild persistent asthmatics, asymptomatic on low-dose inhaled corticosteroids (ICS), we studied 87 ...asthmatic patients regularly treated with ICS for at least 6 months. At the enrollment visit (T1), 71 on ICS were asymptomatic over the past 3 months and discontinued asthma treatment. Symptoms and PEF were then monitored for up to 3 months or until symptoms recurred (T2). At T1 and T2, all subjects underwent methacholine challenge and sputum induction.
Thirtynine out of 71 patients experienced symptom recurrence. At T1, clinical and functional data and sputum eosinophilia between patients with or without recurrence of symptoms were similar. Age >40
yr, and disease duration >5
yr were significantly associated with recurrence of asthma symptoms, while the presence of allergic rhinitis, low baseline FEV
1 and untreated time span >60 months showed a trend to be associated with symptoms recurrence. At T2, symptoms, pulmonary function, bronchial hyperresponsiveness and sputum eosinophilia deteriorated in patients with symptom recurrence but not in patients without symptom recurrence.
In conclusion, age and asthma duration were the best predictors of symptom recurrence in mild persistent asthmatics who withdrew pharmacological therapy, as recommended in the step-down of international guidelines.
The aim of this study was to assess whether hyperosmolarity affects granulocyte mediator levels in induced sputum of asthmatic subjects. A total of 32 mild-to-moderate asthmatics, who inhaled either ...hypertonic (HS; 4.5% NaCl) or isotonic (IS; 0.9% NaCl) solutions for 15 min, were studied. Selected sputum was used for analysis. Eosinophil cationic protein (ECP), eosinophil protein X (EPX), myeloperoxidase (MPO) and free neutrophil elastase (NE) were measured in sputum supernatant. Sample weight, total and differential cell counts, as well as viability and squamous cell percentage were no different after the two tests. No significant differences in ECP, EPX, MPO or NE levels were observed between HS- and IS-induced sputum. Repeatability of the two tests was good for macrophages, neutrophils, eosinophils, ECP, EPX and NE, but not for lymphocytes and MPO. In conclusion, hyperosmolarity does not affect sputum cell counts and the levels of most granulocyte degranulation markers examined in this study, confirming that both hypertonic and isotonic solutions can be reliably used to induce sputum in asthmatics.
The prognostic role of low sputum eosinophils in steroid-naïve, symptomatic asthmatic patients is controversial.
To verify whether low sputum eosinophils predict poor response to treatment with ...inhaled corticosteroids.
Sixty-seven symptomatic asthmatic patients with moderate asthma were examined before and after 2 weeks and 4 weeks of treatment with beclomethasone dipropionate, 500 μg bid. None received corticosteroids in the 3 months preceding the study. At each visit, all patients underwent spirometry, methacholine challenge, and sputum induction. The patients recorded symptom scores and peak expiratory flow (PEF) throughout the study.
Seventeen patients had low sputum eosinophils despite being symptomatic. Patients with high (> 3%) sputum eosinophils at baseline showed significant improvement in symptoms, pulmonary function, and bronchial hyperresponsiveness after treatment, whereas patients with low sputum eosinophils showed no significant improvement in most clinical and functional outcomes. Among the baseline indexes examined, sputum eosinophils had the highest negative predictive value but low positive predictive value for the response to treatment. Multiple stepwise regression showed that only baseline FEV1 and sputum eosinophil percentages significantly correlated with changes in FEV1 after treatment.
We suggest that, among the indexes examined, low sputum eosinophils are the best predictor for poor corticosteroid effects in asthma.
Inhaled corticosteroids and long-acting beta2-agonists effectively control asthma symptoms and improve airway function. The effects of beclomethasone were compared with those of salmeterol on markers ...of eosinophilic inflammation in induced sputum in steroid-naive asthmatic subjects with moderate asthma. Fifteen moderate asthmatics were treated with either beclomethasone dipropionate (500 microg b.i.d.) or salmeterol (50 microg b.i.d.) for 4 weeks, according to a randomised, double-blind, parallel-group study design. All patients underwent spirometry, methacholine test, sputum induction, and blood sampling before and after 2 and 4 weeks of treatment. They also recorded daily symptoms and peak expiratory flow (PEF). Sputum eosinophils, eosinophil cationic protein (ECP) and eosinophil protein X (EPX), and blood eosinophils, as well as the forced expiratory volume in one second (FEV1) and morning PEF, significantly improved after beclomethasone but not after salmeterol. PEF variability, the symptom score and rescue beta2-agonist use significantly improved after both treatments, although the improvement in the symptom score tended to be greater after beclomethasone. After 2 and 4 weeks of beclomethasone treatment, both serum ECP and EPX decreased. With salmeterol, only serum EPX decreased, after 4 weeks. Bronchial hyperresponsiveness to methacholine did not change after either treatment. The authors conclude that beclomethasone, but not salmeterol, substantially improves airway inflammation in asthma. Beclomethasone also had an overall greater clinical effect, although the improvement in symptoms and peak expiratory flow variability was similar after both treatments.
In the aim to evaluate the relationship between sputum eosinophil percentages and eosinophil cationic protein (ECP) concentrations, as markers of airway inflammation, and different levels of asthma ...severity, we examined 223 patients consecutively observed in our asthma clinic. Diagnosis of asthma was made according to internationally accepted criteria. Asthma severity was evaluated according to frequency of symptoms, FEV
1, peak expiratory flow variability and level of asthma treatment needed to control asthma. Spontaneous or induced sputum was collected. Adequate sputum samples were obtained in 68 untreated subjects and in 117 subjects regularly treated with ICS. A control group of 14 normal subjects was also examined.
In untreated subjects, mild intermittent asthmatics showed a lower sputum eosinophil percentage in comparison with other groups of asthma severity, while no difference in ECP levels was detected. In treated subjects, severe asthmatics showed higher levels of sputum eosinophils and ECP in comparison with other groups of asthma severity. Mild persistent and moderate persistent patients did not differ for sputum eosinophils or ECP in both untreated and treated subjects. Controls were significantly different from all groups of untreated and treated asthmatics.
In conclusion, the assessment of asthma severity according to clinical and functional findings only partially corresponds to the severity of eosinophilic airway inflammation as assessed by induced sputum analysis.
BACKGROUND The long acting β2 agonist salmeterol is very effective in preventing asthmatic responses to specific stimuli, and this effect could theoretically be due to some anti-inflammatory property ...in addition to bronchodilator property. METHODS The protective effect 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 effectively 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 affected 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.
Summary
Background
Hypertonic saline (HS) has been shown to modulate in vitro cell functions according to the state of cell activation; however, few studies have evaluated the effect of HS in vivo. ...Chronic airway inflammation, a major feature of chronic obstructive pulmonary disease (COPD), is associated with an activation of inflammatory and resident cells, which in turn makes them more prompt to respond to further stimuli.
Objective
To evaluate whether HS might modulate, also in vivo, the release of preformed mediators and intracellular chemokines from airway cells of COPD patients.
Methods
Sputum was induced by inhalation of either HS (4.5% w/v) or isotonic saline (IS 0.9% w/v) solution and processed by plug selection. We measured eosinophil cationic protein (ECP), neutrophil elastase (NE), IL‐8 and monocyte chemoattractant protein‐1 (MCP‐1) in sputum samples obtained by either HS or IS inhalation in 24 COPD patients.
Results
No significant difference in mediators measured in sputum samples obtained by the two different inductions was observed; also, there was no significant difference in sputum sample volumes, cell viability, total and differential cell counts. Repeatability between the two tests was high for ECP, NE, macrophages, neutrophils and eosinophils, and satisfactory for IL‐8 and MCP‐1.
Conclusions
Hyperosmolarity does not affect the levels of the inflammatory mediators and chemokines examined or the cell counts measured in induced sputum obtained from COPD patients. This study does not support the hypothesis that HS can stimulate chemokine and mediator release from airway cells of COPD patients. Therefore, HS and IS can be interchangeably used to measure inflammatory mediators in the sputum supernatant of COPD patients.
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