Ml Bartoli

Malondialdehyde in Exhaled Breath Condensate as a Marker of Oxidative Stress in Different Pulmonary Diseases

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.

Comparison of anti-inflammatory and clinical effects of beclomethasone dipropionate and salmeterol in moderate asthma

Inhaled corticosteroids and long-acting β2‐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-naïve asthmatic subjects with moderate asthma. Fifteen moderate asthmatics were treated with either beclomethasone dipropionate (500 µg b.i.d) or salmeterol (50 µg 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 β2‐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.

LEUKOCYTE COUNTS IN HYPERTONIC SALINE-INDUCED SPUTUM IN SUBJECTS WITH OCCUPATIONAL ASTHMA

We measured markers of eosinophilic inflammation in the blood and in the sputum induced by hypertonic saline (HS) inhalation of 24 subjects with occupational asthma who were still exposed to high molecular weight compounds (HMWCs, n = 8) or to low molecular weight compounds (LMWCs, n = 16); all subjects were symptomatic and showed bronchial hyperresponsiveness to methacholine at the time of study. Sputum cell counts were also measured in 14 normal subjects and in 24 subjects with non-occupational asthma with asthma severity similar to that of occupational asthmatics. Both occupational and non-occupational asthmatic subjects showed higher neutrophil percentages in HS-induced sputum than normal subjects, asthmatics with LMWC-induced asthma showing the highest values. Eosinophil percentages in HS-induced sputum were higher in non-occupational asthmatics and in asthmatics with HMWC-induced asthma than in normal subjects and in subjects with occupational asthma due to LMWCs. No difference in bronchial responsiveness, peak expiratory flow variability and serum eosinophil cationic protein (ECP) levels were observed among the different asthma groups. Although sputum eosinophil percentages significantly correlated with blood eosinophil percentages, sputum allowed the detection of a higher number of subjects with eosinophilic inflammation than blood. Serum ECP levels were normal in most asthmatic subjects. A significant correlation between sputum eosinophil percentages and bronchial hyperresponsiveness to HS was observed. Despite a similar degree of functional abnormalities, subjects with asthma due to LMWCs and still exposed to the occupational sensitizer showed a lower degree of eosinophilic inflammation and a higher degree of neutrophilic inflammation in the airways than subjects with occupational asthma due to HMWCs or non-occupational asthmatics. Furthermore, sputum eosinophil counts detect, better than blood indices, the degree of airway inflammation in both occupational and non-occupational asthma.

Granulocyte markers in hypertonic and isotonic saline-induced sputum of asthmatic subjects

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.

Are sputum eosinophil cationic protein and eosinophils differently associated with clinical and functional findings of asthma

Sputum eosinophil counts and eosinophil cationic protein (ECP) levels are usually increased in asthmatic patients. The correlation between sputum eosinophils or ECP and clinical findings of asthma has been previously investigated but many of these studies have been performed on small samples of asthmatic patients, considering only few clinical indices and often including patients on oral or inhaled corticosteroids, which might be confounding when interpreting the relationship between disease activity and airway inflammation.

Can hypertonic saline inhalation influence preformed chemokine and mediator release in induced sputum of chronic obstructive pulmonary disease patients? Comparison with isotonic saline

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.

May the Reduction of Exposure to Specific Sensitizers Be an Alternative to Work Cessation in Occupational Asthma? Results from a Follow-Up Study

Background: 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. Subjects and Methods: 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. Results: 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 FEV1. 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. Conclusion: 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 FEV1 as observed in subjects with persistent exposure.

Quality evaluation of samples obtained by spontaneous or induced sputum: comparison between two methods of processing and relationship with clinical and functional findings

The aim of the study was to assess, on a large group of spontaneous or induced sputum samples, the difference in quality between slides processed by two different methods, and the relationship between quality assessment and some clinical and functional characteristics of the examined subjects. We examined 631 sputum samples obtained from 337 subjects with proven (n = 291) or suspected bronchial asthma. Of these, 467 samples were processed using the whole-sample method (Group I), while 164 samples were processed using the plug method (Group II). Salivary contamination, cell distribution on the slide, and cell borders were evaluated, and samples were classified as inadequate, adequate, or good. Inadequate samples were equally represented in both groups, while good samples were represented more in Group II. No significant difference in most clinical and functional findings was observed between the different quality categories of both groups. A higher proportion of inadequate samples was observed in Group I samples spontaneously collected. Mild intermittent asthmatics produced a better quality of slides in comparison with other groups of asthma severity. In conclusion, sputum quality partially depends on the different methods of sputum collection and/or processing, although the percentage of inadequate samples is similar for the two methods of processing. Sputum quality is only marginally affected by clinical and functional characteristics of asthma, or by asthma severity.