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E Pizzichini

Publications and source records attributed to E Pizzichini.

At least 19 recordsLinked to original sources
PubMed2006

Stable COPD: predicting benefit from high-dose inhaled corticosteroid treatment.

The role of inhaled corticosteroids in the management of chronic obstructive pulmonary disease (COPD) remains controversial. The purpose of this study was to evaluate whether sputum eosinophilia (defined as eosinophils > or = 3%) predicts clinical benefit from inhaled corticosteroid treatment in patients with smoking-related clinically stable moderate-to-severe COPD. Forty consecutive patients with effort dyspnoea (mean age 67 yrs; 52 pack-yr smoking history; post-bronchodilator forced expiratory volume in one second (FEV1) <60% predicted, consistent with moderate-to-severe smoking-related chronic airflow limitation) were enrolled. Subjects were treated with inhaled placebo followed by inhaled budesonide (Pulmicort Turbuhaler 1,600 microg.day(-1)), each given for 4 weeks. While the treatment was single-blind (subject level), sputum cell counts before and after treatment interventions were double-blind, thus removing bias. Outcome variables included spirometry, quality-of-life assessment and 6-min walk test. Sputum eosinophilia was present in 38% of subjects. In these, budesonide treatment normalised the eosinophil counts and, in comparison to placebo treatment, resulted in clinically significant improvement in the dyspnoea domain of the disease-specific chronic respiratory questionnaire (0.8 versus 0.3) and a small but statistically significant improvement in post-bronchodilator spirometry (FEV1 100 mL versus 0 mL; p<0.05). In conclusion, sputum eosinophilia predicts short-term clinical benefit from high-dose inhaled corticosteroid treatment in patients with stable moderate-to-severe chronic obstructive pulmonary disease.

Administration, Inhalation↗
PubMed2006

Determining asthma treatment by monitoring sputum cell counts: effect on exacerbations.

One important goal of asthma treatment is to reduce exacerbations. The current authors investigated if the use of sputum cell counts to guide treatment would achieve this goal. A total of 117 adults with asthma were entered into a multicentre, randomised, parallel group-effectiveness study for two treatment strategies over a 2-yr period. In one strategy (the clinical strategy: CS) treatment was based on symptoms and spirometry. In the other (the sputum strategy: SS) sputum cell counts were used to guide corticosteroid therapy to keep eosinophils 250 microg, and was due to fewer eosinophilic exacerbations. The cumulative dose of corticosteroid during the trial was similar in both groups. Monitoring sputum cell counts was found to benefit patients with moderate-to-severe asthma by reducing the number of eosinophilic exacerbations and by reducing the severity of both eosinophilic and noneosinophilic exacerbations without increasing the total corticosteroid dose. It had no influence on the frequency of noneosinophilic exacerbations, which were the most common exacerbations.

Adult↗
PubMed2005

Steroid naive eosinophilic asthma: anti-inflammatory effects of fluticasone and montelukast.

BACKGROUND: Inhaled corticosteroids and leukotriene receptor antagonists reduce airway eosinophilia and have been used as first line anti-inflammatory therapy for mild persistent asthma. METHODS: A multicentre, randomised, placebo controlled, parallel group study was performed to compare the anti-inflammatory effects of fluticasone propionate and montelukast as measured by sputum eosinophils in 50 adults with symptomatic steroid naive asthma and sputum eosinophilia of > or =3.5%. RESULTS: Eighteen patients received low dose fluticasone (250 mug/day), 19 received montelukast (10 mg/day), and 13 were given placebo for 8 weeks. Fluticasone treatment resulted in a greater reduction in sputum eosinophils (geometric mean (SD) 11.9 (2.3)% to 1.7 (5.1)%) than montelukast (10.7 (2.3)% to 6.9 (3.8)%; p = 0.04) or placebo (15.4 (2.4)% to 7.8 (4.2)%; p = 0.002), and improvement in FEV(1) (mean (SD) 2.6 (0.9) l to 3.0 (0.9) l) than montelukast (2.8 (0.7) l to 2.8 (0.9) l; p = 0.02) or placebo (2.4 (0.8) l to 2.4 (0.9) l; p = 0.01). Treatment with fluticasone suppressed sputum eosinophilia within a week while montelukast only attenuated it. The effect of montelukast was maximal at 1 week and was maintained over 4 weeks. The effect of fluticasone was maintained over 8 weeks while that of montelukast was not. CONCLUSIONS: Montelukast is not as effective as low dose fluticasone in reducing or maintaining an anti-inflammatory effect in steroid naive eosinophilic asthma.

Acetates↗
PubMed2005

Failure of montelukast to reduce sputum eosinophilia in high-dose corticosteroid-dependent asthma.

Sputum eosinophilia is a sensitive predictor of benefit from corticosteroid treatment. Montelukast is a cysteinyl leukotriene antagonist, which also reduces sputum and blood eosinophils. The present study examined the possibility that montelukast has an added eosinophil-lowering effect in subjects with asthma who are corticosteroid responsive but relatively corticosteroid resistant. A total of 14 clinically stable adults with asthma requiring minimum treatment with a high-dose inhaled steroid or prednisone, with baseline sputum eosinophilia (> or =5%), were randomised to receive 4 weeks of 10 mg montelukast or placebo daily in a double-blind crossover trial. The primary outcome was the effect of treatment on the percentage of sputum eosinophils. Secondary outcomes were changes in the blood eosinophil count, symptoms, forced expiratory volume in one second, peak expiratory flow and the need for salbutamol. The median (interquartile range, i.e. 75th-25th centile) for sputum eosinophils at baseline was 15.7% (22). The effect of adding montelukast was not significantly different from that of placebo, sputum eosinophils being 9.3% (18.9) after montelukast and 11.3% (22.8) after placebo. No difference was detected on secondary outcomes. No crossover interactions were observed. In conclusion, the addition of montelukast to existing high-dose corticosteroid therapy in subjects with asthma with elevated sputum eosinophils does not provide additional attenuation of airway eosinophilia.

Acetates↗
PubMed2004

Monitoring response to treatment in asthma management: food for thought.

Asthma is a chronic inflammatory disorder of the airways that is characterized by episodic symptoms. In this regard, asthma management has classically involved periodic re-assessment by the health-care provider, during which therapy is altered mainly based on clinical and physiological parameters, such as assessment of symptoms, spirometry and peak expiratory flow monitoring. In this context, various markers of airway inflammation (e.g. eosinophils in the induced sputum, nitric oxide in the exhaled air) have been proposed to assess the severity of asthma and to adjust the therapy accordingly. The evaluation of airway hyper-responsiveness with different stimuli has also been suggested as a new tool to monitor asthma. However, the lack of definite relationships between airway inflammation and asthmatic symptoms strongly limit the use of markers of asthma severity in the clinical setting. Therefore, the need of new tools to assess the severity of asthma is raised. The ideal measurement employed to establish the proper asthmatic therapy should be safe, non-invasive, easy to perform, reproducible and accurate, and have the capability to monitor the changes induced by the therapeutic interventions. A careful review of the available techniques, and the evaluation of their sensitivity and specificity in the clinical setting is warranted.

Asthma↗
PubMed2000

Clinical judgement of airway inflammation versus sputum cell counts in patients with asthma.

The inflammatory component of asthma is usually assessed indirectly by symptoms and spirometry, these may be inaccurate. It can now be assessed directly and reliably by the examination of sputum cell counts. There is no information on how clinical assessment of the presence and type of airway inflammation compares with actual measurements. In this single-centre observational study, sputum was collected from 76 consecutive adults with asthma attending a tertiary chest clinic after their physicians had recorded the expected cell counts in sputum. The authors examined the extent of agreement between clinical judgement of sputum cell counts and actual counts in asthmatic patients (Cohen's Kappa) and the possible predictors of agreement (multiple logistic regression). Sixty-seven of the 76 sputum samples were suitable for analysis. Agreement between expected and actual cell counts occurred in 30/67 patients. The overall agreement for the different cell types was poor (estimated K=0.14, 95% confidence interval (CI)=0.02, 0.26). The experience of the physician in using sputum cell counts in clinical practice, steroid requirement at the time of assessment, and control of asthma as assessed by the physician or by the patient could not predict the chances of agreement or disagreement. Unaware of the sputum results, the physicians often changed treatment in a way that seemed inappropriate for the cell counts present. There is poor agreement between clinical judgement of the presence and type of airway inflammation in asthmatic patients and sputum cell counts. The impact of sputum examination on the outcomes of anti-inflammatory treatment now needs investigation.

Adult↗
PubMed1999

Montelukast reduces airway eosinophilic inflammation in asthma: a randomized, controlled trial.

Leukotrienes are pro-inflammatory mediators which may contribute to tissue, sputum, and blood eosinophilia seen in allergic and inflammatory diseases, including asthma. Montelukast is a cysteinyl leukotriene1 (CysLT1) receptor antagonist which improves asthma control; the aim of this study was to investigate its effect on induced sputum eosinophils. Montelukast 10 mg (n=19) or placebo (n=21) were administered orally once in the evening for 4 weeks to 40 chronic adult asthmatic patients, aged 19-64 yrs, in a double-blind, randomized, parallel group study. Patients were included if, at prestudy, they had >5% sputum eosinophils, symptomatic asthma with a forced expiratory volume in one second > or =65% of the predicted value and were being treated only with "as needed" inhaled beta2-agonists. In addition to sputum eosinophils, blood eosinophils and clinical endpoints were also assessed. Four weeks of montelukast treatment decreased sputum eosinophils from 7.5% to 3.9% (3.6% decrease, 95% confidence interval (CI) -16.6-0.4). In contrast, placebo treatment was associated with an increase in sputum eosinophils from 14.5% to 17.9% (3.4% increase, 95% CI -3.5-9.8). The least squares mean difference between groups (-11.3%, 95% CI -21.1-(-1.4)) was significant (p=0.026). Compared with placebo, montelukast significantly reduced blood eosinophils (p=0.009), asthma symptoms (p=0.001) and beta2-agonist use (p<0.001) while significantly increasing morning peak expiratory flow (p=0.001). Montelukast was generally well tolerated in this study, with a safety profile similar to the placebo. These results demonstrate that montelukast decreases airway eosinophilic inflammation in addition to improving clinical parameters. Its efficacy in the treatment of chronic asthma may be due, in part, to the effect on airway inflammation.

Acetates↗
PubMed1999

Prednisone-dependent asthma: inflammatory indices in induced sputum.

The kinetics of changes in inflammatory indices in induced sputum from eight prednisone dependent asthmatics whose minimum clinical maintenance and exacerbation doses were known were investigated. The study began on the last day of a course of 30 mg prednisone daily for one week. Thereafter, the daily prednisone was reduced in a structured way to below the maintenance dose. This treatment was continued until a clinical exacerbation occurred. Prednisone 30 mg daily was then given again for one week. The mean duration of prednisone reduction was 7.4 weeks and the median dose was 7.5 mg x day(-1). Increases in sputum eosinophils preceded increases in blood eosinophils by 4 weeks and worsening of symptoms and forced expiratory volume in one second by 6 weeks. The clinical exacerbation was also accompanied by sputum neutrophilia and increases in sputum eosinophil cationic protein (ECP), fibrinogen and interleukin (IL)-5. Treatment with prednisone suppressed median sputum eosinophilia (from 16.3 to 0%, p<0.001), decreased sputum ECP (from 7,480 to 700 microg x L(-1), p = 0.01), but did not improve neutrophil numbers, fibrinogen or IL-5. The results show that the reduction of prednisone treatment in prednisone-dependent asthmatics evokes a severe airway eosinophilic inflammatory response. Clinical and blood indices deteriorate later than those in sputum suggesting that sputum examination may be useful to identify the minimum regular dose of prednisone required in these patients.

Adult↗
PubMed1998

Potential masking effects of salmeterol on airway inflammation in asthma.

We hypothesized that regular use of long-acting beta-agonists could delay recognition of ("mask") increasing airway inflammation. We studied steroid-sparing and "masking" effects of salmeterol versus placebo in 13 asthmatic individuals requiring >= 1,500 microgram inhaled corticosteroid daily. Corticosteroid doses were reduced weekly until criteria were met for an exacerbation or the corticosteroid was fully withdrawn. Subjects were restabilized on their original dose of inhaled corticosteroid for 4 wk before crossover to the alternative treatment. Subjects maintained symptom and peak expiratory flow (PEF) diaries, and underwent weekly spirometric, methacholine challenge, sputum eosinophil, and serum eosinophil cationic protein (ECP) measurements. Mean corticosteroid dose was reduced by 87% during salmeterol treatment, versus 69% with placebo (p = 0.04). Sputum eosinophils increased before exacerbation despite stable symptoms, FEV1, and PEF. In the week before clinical exacerbation, sputum eosinophil counts were higher in the salmeterol-treatment arm (19.9 +/- 29.8% [mean +/- SD], versus placebo 9.3 +/- 17.6%; p = 0.006). Five subjects showed > 10% sputum eosinophilia before exacerbation during salmeterol treatment, as compared with two receiving placebo. In this model, salmeterol controlled symptoms and lung function until inflammation became significantly more advanced. We conclude that the bronchodilating and symptom-relieving effects of salmeterol can mask increasing inflammation and delay awareness of worsening asthma.

Administration, Inhalation↗
PubMed1998

Asthma and natural colds. Inflammatory indices in induced sputum: a feasibility study.

We examined the feasibility of using induced sputum to evaluate the airway inflammatory response to natural acute respiratory virus infections. We recruited eight asthmatics and nine healthy subjects on Day 4 of a cold. Viral infection was confirmed in six of the asthmatics (influenza A or B) and six of the healthy subjects (influenza A, rhinovirus, adenovirus, respiratory syncytial virus, and coronavirus). In the subjects with confirmed virus infection, five of the asthmatics had an objective exacerbation of asthma during the cold. Their sputum on Day 4 showed a high median total cell count of 19.7 x 10(6) cells/ml with a modest neutrophilia (58. 5%) and high levels of interleukin-8 (IL-8) (16,000 pg/ml), eosinophilic cationic protein (ECP) (1,880 microgram/L) and very high levels of fibrinogen (250 mg/L). In contrast, the proportion (1.3%) and absolute number of eosinophils was low. IL-2 levels were within the normal range, whereas IL-5 and interferon gamma were under the limit of detection of the assays. In the healthy subjects with a confirmed virus infection the sputum findings were qualitatively similar but significantly less prominent. Sputum IL-8 on Day 4 was strongly correlated with neutrophils (rs = 0.8, p < 0.001). This correlation was also significant when each group was analyzed separately. On Day 21 there was a fall in the absolute number of neutrophils and in ECP and fibrinogen levels in both groups. Similar results were found in the two asthmatic and three healthy subjects with a cold of comparable severity but in whom viral infection was not confirmed. We conclude that induced sputum examination can be used to study the effects of natural colds and influenza on the airways of the lungs. The results also suggest that natural colds, on Day 4, cause neutrophilic lower airway inflammation that is greater in asthmatics than in healthy subjects. The greater inflammatory response in asthmatics may be due to the changes associated with trivial eosinophilia or to the different viruses involved.

Acute Disease↗
PubMed1998

Sputum eosinophilia predicts benefit from prednisone in smokers with chronic obstructive bronchitis.

A reliable predictor of benefit from corticosteroid treatment in patients with chronic airflow limitation is needed. In a single-blind, sequential crossover trial of placebo and prednisone (30 mg/day) treatment, with each given for 2 wk, we investigated whether an increased proportion of sputum eosinophils (>= 3%) predicts a beneficial effect of prednisone in smokers with severe obstructive bronchitis. Patients were seen before and after each treatment. Clinical measurements were made blind to the laboratory findings and vice-versa. Eighteen of 20 patients completed the study. Eight had sputum eosinophilia and similar clinical and physiologic characteristics to those of 10 patients without a finding of sputum eosinophilia. Only in patients with sputum eosinophilia did prednisone, as compared with placebo, produce a statistically significant and clinically important mean effect on effort dyspnea of 0.8 (95% confidence interval [CI]: 0.3 to 1.2), p = 0.008, and in quality of life of 1.96 (95% CI: 0.5 to 3.3), p = 0.01, associated with a small improvement in FEV1 of 0.11 L (95% CI: - 0.04 to 0.23 L), p = 0.05. In these patients, prednisone also produced a significant decline in the median sputum eosinophil percentage, from 9.7% to 0.5% (p = 0.002), eosinophil cationic protein (ECP), from 6, 000 microgram/L to 1,140 microgram/L (p < 0.001), and fibrinogen, from 25. 3 mg/L to 5.4 mg/L (p < 0.001). These findings indicate that in smokers with severe airflow limitation, sputum eosinophilia predicts a beneficial effect of prednisone treatment. Improvement in FEV1, after prednisone treatment in this population, is small, and may not be appreciated in clinical practice.

Adult↗
PubMed1998

Induced sputum, bronchoalveolar lavage and blood from mild asthmatics: inflammatory cells, lymphocyte subsets and soluble markers compared.

Airway inflammation in asthma can be measured directly by invasive bronchoalveolar lavage (BAL), directly and relatively noninvasively by induced sputum and indirectly from peripheral blood. We compared cellular and fluid phase indices of inflammation in induced sputum, BAL and blood from 11 adults with mild stable asthma. On one day, induced sputum selected from saliva was collected and on the next, blood and BAL. Median results of sputum compared with BAL showed a higher number of nonsquamous cells (53 versus 0.8 x 10(6) cells x mL(-1), p=0.003), more neutrophils (34.3 versus 1.0%, p<0.001), CD4+ and CD19+ T-cells (76.5 versus 54.7%, p=0.01 and 5.2 versus 1.1%, p=0.03, respectively), fewer macrophages (603 versus 95.0%, p=0.002) and markedly higher levels of eosinophil cationic protein (ECP) (264 versus 2.0 microg x L(-1), p<0.001), tryptase (17.6 versus 2.2 UI x L(-1), p<0.001) and fibrinogen (1,400 versus 150 microg x L(-1), p=0.001). Sputum and BAL neutrophils and CD4+ T-cells were strongly correlated. Sputum and BAL differed from blood by having higher proportions of T-cells (94.9 and 98.9% versus 87.7%, p=0.002) and lower proportions of CD19+ T-lymphocytes (p=0.04 and 0.006). Sputum also differed from blood by having higher proportions of CD4+ T-cells (76.5 versus 51.4%, p=0.001), lower proportions of CD8+ cells (24.0 versus 403%, p=0.04) and a higher CD4+/CD8+ ratio (3.3 versus 1.4, p=0.01). We conclude that in mild asthmatics, sputum, bronchoalveolar lavage and blood measure different compartments of inflammation. Induced selected sputum has the advantage over bronchoalveolar lavage of higher density of cell recovery and stronger signal for fluid-phase markers.

Adult↗
PubMed1998

Serial sputum cell counts in the management of chronic airflow limitation.

This case study illustrates the usefulness of serial induced sputum cell counts from cytospins to investigate the nature of airway inflammation in a patient presumed to have prednisone-dependent asthma for 30 yrs. She had bronchiectasis and chronic airflow limitation. Exacerbations of breathlessness were associated with an increase in chronic airflow limitation with little or no sputum. Induced sputum showed elevated total cell and neutrophil counts at each exacerbation with no increase in the proportion of eosinophils. Pathogenic bacteria were cultured at each flare-up. The dose of prednisone was reduced progressively and each exacerbation was treated with an appropriate antibiotic without increasing the dose of prednisone, as was the case previously. The infections were associated with bronchiectasis of the right upper lobe which was removed. Examination of the specimen confirmed neutrophilic infiltration and did not show the usual airway structural changes of asthma. These results provide further evidence of the value of sputum cell counts in practice, in this case to prevent overtreatment with prednisone in a patient with recurrent deteriorations in airflow which were due to recurrent infections.

Asthma↗
PubMed1997

Measuring airway inflammation in asthma: eosinophils and eosinophilic cationic protein in induced sputum compared with peripheral blood.

BACKGROUND: Airway eosinophilic inflammation is a characteristic feature of asthma. This can be assessed directly by measurement of eosinophils and eosinophilic cationic protein (ECP) in sputum or indirectly by measurement of the same markers in blood. We investigated the performance of these markers of airway eosinophilic inflammation in a population of patients with asthma compared with control subjects and the extent to which the markers differed. METHODS: In a cross-sectional study, subject characteristics were documented on day 1 and induced sputum and blood samples were obtained on day 2. Nineteen patients with asthma and 20 control subjects (10 healthy subjects and 10 smokers with nonobstructive bronchitis) were consecutively enrolled in the study. Sputum (selected from saliva) and blood samples were processed by persons blind to the clinical details. Results are presented as median values (minimum-maximum); differences were measured by Mann-Whitney U test. The accuracy of the tests (sensitivity and specificity) was measured by plotting the data in receiver-operating characteristic (ROC) curves and comparing the areas under the curve for each marker. RESULTS: Patients with asthma in comparison with control subjects had a higher proportion of sputum eosinophils (5.2% [0.2% to 93%] vs 0.3% [0% to 1.7%], p < 0.001), higher numbers of blood eosinophils (350.0 x 10(6)/L [144.0 to 1520.0 x 10(6)/L] vs 155.0 x 10(6)/L [34.0 to 426.0 x 10(6)/L], p = 0.003), and higher levels of ECP in sputum (1040.0 micrograms/L [76.8 to 32,000.0 micrograms/L] vs 455.3 micrograms/L [54.4 to 1280.0 micrograms/L], p = 0.001) but not in serum (25.0 micrograms/L [5.6 to 52.4 micrograms/L] vs 16.5 micrograms/L [3.3 to 36.0 micrograms/L], p = 0.08). Markers of airway inflammation in induced sputum and blood samples were correlated with clinical and physiologic variables. The area under the ROC curve showed that eosinophils in sputum (0.90) are significantly more accurate markers than blood eosinophils (0.72) and serum ECP (0.67) (p = 0.02). Although the area under the ROC curve for sputum ECP was greater than those for blood eosinophils and serum ECP, the differences could have occurred by chance (p > or = 0.1). CONCLUSION: We conclude that the proportion of eosinophils in sputum is a more accurate marker of asthmatic airway inflammation than the proportions of blood eosinophils or serum ECP.

Adult↗