Antonella - Di Franco

Azienda Ospedaliero-Universitaria Pisana · Dipartimento cardio toraco vascolare

Sputum eosinophilia in Chronic Obstructive Pulmonary Disease (COPD) patients seems to be associated with a better response to inhaled corticosteroids (ICS). To verify if this feature could identify a specific subpopulation of COPD patients, we retrospectively compared functional and inflammatory parameters of 110 COPD patients according to the pres...

Background and aims Severe asthma may require the prescription of one of the biologic drugs currently available, using surrogate markers of airway inflammation (serum IgE levels and allergic sensitization for anti-IgE, or blood eosinophils for anti-IL5/IL5R). Our objective: to assess upper and lower airway inflammation in severe asthmatics divided...

Background According to ATS/ERS document on severe asthma (SA), the management of these patients requires the identification and proper treatment of comorbidities, which can influence the control of asthma. Methods The aim of this study was to assess the independent effect of different comorbidities on clinical, functional and biologic features of...

Abbiamo caratterizzato un gruppo di pazienti asmatici gravi in presenza o assenza di ostruzione non reversibile, correlandovi specifici marcatori di infiammazione e rimodellamento. Sull’espettorato indotto dei pazienti, in terapia di mantenimento con ICS/LABA ad alta dose, sono state effettuate conta cellulare e quantificazione di periostina, TGF-β...

We analysed blood and sputum eosinophilia and fractional exhaled nitric oxide (FeNO) levels in severe asthmatic patients with frequent exacerbations, correlating different biomarkers levels with different exacerbation rates (≥1 vs ≥3 in the last 12 months). Submitted to the ERS Annual International Congress 2018, Paris, France.

Background: The upper airway disease is a common comorbidity in patients with CSA and EGPA but in literature are not described differences that can orient for a specific diagnosis Aim: To evaluate the differences in ENT diagnosis and airway inflammation in patients with EGPA and CSA and the relationship between asthma or nasal disease in affecting...

In difficult-to-treat asthmatics, uncontrolled despite a high level of therapy and followed for 3 years with a mean number of sputum samples/patient = 10, sputum eosinophilia (≥3%) was observed in 87% of all sputum samples. Persistent sputum eosinophilia is a characteristic of severe uncontrolled asthma. © 2015 S. Karger AG, Basel.

To evaluate the potential determinants of forced expiratory volume in 1 s (FEV1) decline in workers with occupational asthma (OA) still exposed to the causative agent. We hypothesised that sputum eosinophilia might be a predictor of poor asthma outcome after diagnosis. In a specialistic clinical centre of the University Hospital of Pisa, we studied...

Sputum eosinophil counts and 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 patien...

Background: Long-term follow-up of diisocyanate-induced occupational asthma has been occasionally reported. Methods: 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 hyperresp...

Background and objective: Symptomatic, steroid-naïve asthmatic patients may have low sputum eosinophil numbers. The aim of the study was to determine whether low sputum eosinophil numbers persisted over time, during treatment with salmeterol monotherapy. Methods: Forty steroid-naïve, symptomatic asthmatic patients, with sputum eosinophils <3%, w...

Asthma Control Test (ACT) is a simple tool for assessing the level of asthma control in clinical practice, and it has been validated in comparison with a general clinical assessment of asthma control, including forced expiratory volume in the first second (FEV(1)). To evaluate the relationship between ACT score and clinical and functional findings...

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 subjec...

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). We measured MDA levels in EBC in a large number of patients (N = 194) with respiratory diseases: asthma (...

Occupational asthma (OA) is a heterogeneous disease, and the characteristics of the sensitizer responsible for OA may induce different clinical, functional, and biological manifestations. We examined the characteristics of 74 patients with OA induced by low molecular weight compounds (LMWC) or by high molecular weight compounds (HMWC) and diagnosed...

Severe asthma occurs in a heterogeneous group of patients in whom symptoms and airway inflammation persist despite maximal antiasthma treatment. To verify whether a short-term course of oral steroids would modify sputum inflammatory cytokine and sputum eosinophil concentrations and whether this effect is related to the presence of sputum eosinophil...

The inhibitory effect of corticosteroids (CS) on the secretions of cysteinyl-leukotrienes (Cys-LTs) in asthma is controversial. The aim of this study was to evaluate the effect of CS on allergen-induced increase in urinary leukotriene E4 (uLTE4) during early (EAR) and late (LAR) asthmatic responses in mild untreated asthmatics. Nine subjects with m...

The discrepancy between functional and inflammatory airway response to ozone has been reported in normal subjects, but few data are available for stable asthmatics regularly treated with inhaled corticosteroids. Twenty-three well controlled, regularly treated, mild-to-moderate asthmatic patients underwent two sequential randomised exposures to eith...

The concept of asthma control represents nowaday the main criterium for the management of asthma and for the adaptation of the level of asthma treatment. The evaluation of the control requires a composite measurement of all main clinical findings of asthma which should be all satisfied; this represents the real situation of asthma better than the e...

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease characterized by a combination of 3 different disorders, namely chronic asthma, chronic bronchitis and pulmonary emphysema, sometimes simultaneously present in the same subject. The aim of our study was to compare sputum inflammatory markers in patients with different phenotype...

Late asthmatic response (LAR) to allergen challenge is a validated method for studying the pathogenesis of and new treatments for asthma in the laboratory. To evaluate the relationship between the magnitude of allergen-induced LAR and clinical and biological determinants, including sputum and blood eosinophil percentages and eosinophil cationic pro...

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...

To find some simple clinical factors which can predict the quality of the sputum samples obtained in a large group of asthmatic subjects. We compared the presence of sputum productive cough in the days preceding the test, easiness in expectoration during the test, and sputum macroscopic aspect (presence of visible plugs) with the quality of slides...

The effect of corticosteroids on the ozone (O3)-induced airway inflammation is still debated. The aim of the study was to confirm the effect of a short-term treatment with oral glucocorticosteroids on O3-induced airway inflammation, detected by induced sputum analysis, and on functional response in glucocorticosteroid-naive subjects. A randomized,...

In order to assess whether the administration of salmeterol/fluticasone propionate combination (50/250 mcg by Diskus) for 1 week induces tolerance to the bronchoprotective effect of salmeterol on allergen challenge, a single-blind, cross-over study was carried out. We studied nine subjects (eight men and one woman; mean age+/-SD: 31.3+/-11.0 yr) wi...

Severe asthma represents a heterogeneous group of patients whose characteristics of airway inflammation are poorly known. To evaluate the sputum cytokine profiles of different phenotypes of severe asthma. Severe asthmatic patients (n = 45) were divided into 3 groups: frequent exacerbations, persistent bronchoconstriction, and both features. Two oth...

The aim of this study was to evaluate whether fluticasone propionate (FP) is effective as well as prednisone (P) in reducing sputum eosinophilia and in improving airway obstruction due to asthma exacerbations not requiring hospitalization. We measured, in a parallel-group, double-blind double-dummy, randomized study, sputum and blood inflammatory c...

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 di...

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 wit...

The efficacy of nebulized corticosteroids in the prevention of exacerbation of chronic obstructive pulmonary disease (COPD) has been poorly studied. To evaluate the efficacy and tolerability of nebulized flunisolide (1 mg) + salbutamol/ipratropium bromide (1,875/375 microg) b.i.d. in comparison with placebo + salbutamol/ipratropium bromide. This wa...

In summary, papers like that of Cirillo et al [14] underline the need to study rhinitic subjects accurately and frequently, in order to check for early asthma symptoms and functional abnormalities. Considering that early diagnosis and early treatment in asthma has been associated with a favourable course of the disease [25], this attention to asthm...

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 p...

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 crite...

Salmeterol is an effective long-acting beta(2)-agonist bronchodilator, able to inhibit, as a single dose, asthmatic responses induced by several stimuli including allergen, and the subsequent increase in sputum eosinophilia. Aim of the present study was to investigate whether these effects of salmeterol persisted after 1 week of continuous treatmen...

Twenty-seven subjects with moderate asthma at the time of diagnosis, well controlled under regular fluticasone propionate (FP) (250 microg b.i.d.) for 6 months at least, were randomized to receive in double-blind fashion: FP 125 microg b.i.d. (Group 1) or FP 50 microg b.i.d. (Group 2) or placebo (Group 3) for 3 months or until symptom recurrence. D...

Acute airway inflammation is considered to characterize asthma exacerbations, but its specific cellular pattern has not yet been completely evaluated. To evaluate the prevalence of sputum eosinophilia during acute asthma exacerbations of moderate severity, compared with a stable phase of the disease, and to assess the concordance between changes in...

In a single blind study, the short-term efficacy of the addition of leukotriene receptor antagonists (LTRA: montelukast 10 mg o.d. in 15 subjects, zafirlukast 20 mg b.i.d. in 11 subjects) to the current therapy was evaluated in severe asthmatics, unstable under regular treatment with high dose inhaled corticosteroids, bronchodilators and, in seven...

The aim of this study was to assess the distribution of the occurrence of tolerance to the protective effect of salmeterol on allergen challenge in a large sample of asthmatic subjects. We investigated 53 subjects (45 male and eight female), mean age 24+/-8.2 years, with mild intermittent asthma, in stable phase of the disease, never previously tre...

To evaluate the reproducibility of induced sputum analysis, and to estimate the sample size required to obtained reliable results, sputum was induced by hypertonic saline inhalation in 29 asthmatic subjects on two different days. The whole sample method was used for analysis, and inflammatory cells were counted on cytospin slides. Reproducibility,...

We investigated whether exposure to ozone (O(3)) 24 hours after an allergen challenge test would increase airway eosinophilia induced by allergen in subjects with mild asthma with late airway response. Twelve subjects with mild atopic asthma participated in a randomized, single-blind study. Subjects underwent allergen challenge 24 hours before a 2...

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 subjec...

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...

Ambient ozone concentration is related to asthma exacerbation, but few findings are available regarding the effects of pharmacologic asthma treatment on this relationship. The purpose of this study was to investigate whether inhaled corticosteroids inhibit ozone-induced airway neutrophilic inflammation, as detected in induced sputum, and reduce fun...

To assess whether the withdrawal of salmeterol treatment for 3 days (72 h) can restore its bronchoprotective ability on specific bronchial provocative test (sBPT) with allergen, which was completely lost after 1 week of regular treatment with salmeterol. Single-blind design. We investigated 10 nonsmoking subjects (8 men and 2 women; mean +/- SD age...

In asthmatic subjects cough can be related to the degree of airway inflammation. The aim of this study was to evaluate the effect of treatment with high dose inhaled beclomethasone dipropionate (BDP) on cough threshold in asthmatic subjects. Cough threshold to inhaled capsaicin (one breath of 10(-8)-10(-4)M solution) and to citric acid (one breath...

To assess whether sputum eosinophilia predicts the recurrence of asthma symptoms after withdrawal of therapy in moderate stable asthmatics on low-dose inhaled corticosteroids. Randomized, double-blind, placebo-controlled study involving 30 subjects with stable asthma, asymptomatic, with low PEF variability measured over two run-in weeks, on treatme...

It is known that exposure to seasonal allergen in sensitized asthmatics increases non-specific bronchial responsiveness, but it is controversial if exposure to seasonal allergen influences the presence and the severity of the late asthmatic response (LAR) to allergen. Fifteen asthmatic subjects sensitized to grass pollen performed a specific bronch...

The specific bronchial provocative test (sBPT) coupled with allergen is used to investigate asthma. Very few studies have examined the reproducibility of responses to allergen challenge. The aim of this study was to measure the reproducibility of PD20FEV1 allergen and late asthmatic response (LAR) in 53 asthmatics and to relate the reproducibility...

To determine the protective effect of salbutamol, 100 microg, inhaled by different devices (pressurized metered-dose inhaler [pMDI; Ventolin; GlaxoWellcome; Greenford, UK], pMDI + spacer [Volumatic; GlaxoWellcome], or breath-activated pMDI [Autohaler; 3M Pharmaceuticals; St. Paul, MN]) on bronchoconstriction induced by methacholine. Randomized, dou...

In order to compare the efficacy of different asthma treatment in subjects with mild-to-moderate asthma, three groups of 11 patients were treated with nedocromil sodium (NS), beclomethasone dipropionate (BDP) and beclomethasone dipropionate plus salmeterol (BDP + S) in an open, randomized study. Symptom score, peak expiratory flow (PEF) maximal amp...

The long acting beta2 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. The protective effect of a single dose of salmeterol (50 microg) on allergen induced early and late responses and on t...

Sputum induction by inhalation of hypertonic saline (HS) is usually preceded by beta2-agonist pretreatment, to prevent severe bronchoconstriction. To evaluate whether salbutamol pretreatment may influence cell counts and concentrations of soluble mediators in induced sputum. We studied 22 patients who randomly underwent HS sputum induction after pr...

One week of regular treatment with salmeterol can induce tolerance to the protective effect of a beta2-agonist on early airway response to allergen (EAR). The objective was to assess whether inhaled corticosteroids revert tolerance to salmeterol. The study had a randomized, double-blind, placebo-controlled design. Twelve subjects with mild allergic...

The aim of this study was to evaluate whether ozone exposure induces a similar airway inflammatory response in subjects with different degrees of asthma severity. Two groups of asthmatic subjects were studied: seven with intermittent mild asthma not requiring regular treatment (group A); and seven with persistent mild asthma requiring regular treat...

The usefulness and safety of the analysis of blood inflammatory markers in asthma are widely recognized. Recently, the analysis of induced sputum has been proposed as a safe, non-invasive tool in the study of airway inflammation in asthma. Our aim was to test whether sputum analysis is more useful than blood analysis in the evaluation of airway inf...

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 hyperrespon...

In order to evaluate the relationship between allergen-induced heat-stable neutrophil chemotactic activity (HS-NCA) release during early asthmatic reaction (EAR) and the presence of a late asthmatic reaction (LAR), serum HS-NCA was measured at three serum dilutions (1:5, 1:40, 1:200) during EAR induced by allergen in 26 atopic asthmatics, 13 with i...

To evaluate the sensitivity of peak expiratory flow (PEF), obtained by portable peak flow meter, in detecting mild changes in airway caliber as assessed by forced expiratory volume in 1 sec (FEV1), we studied 184 subjects who underwent different bronchial challenge tests for suspected bronchial asthma. We measured FEV1 and PEF during bronchoconstri...

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...

Hypertonic saline-induced sputum has recently been used for the evaluation of airway inflammation in asthma. To assess the effect of hypertonicity on airway inflammation. We compared the inflammatory cell composition of hypertonic saline-induced sputum with that of isotonic saline-induced sputum in 21 asthmatic subjects and, at baseline and 30 min...

Long-term treatment with inhaled beta 2-agonists may be associated with a deterioration in asthma control, potentially due to tolerance. Regular use of short-acting beta 2-agonists has been shown to induce tolerance to allergen or adenosine 5'-monophosphate challenge. The aim of the study was to detect the efficacy of a single dose and a short-term...

The aim of this study was to assess the effects of short-term exposure to low levels of nitrogen dioxide (NO2) on airway inflammation. We studied seven normal, eight mild asthmatic and seven chronic obstructive pulmonary disease (COPD) subjects. All subjects were exposed to air or to 0.3 parts per million (ppm) NO2 for 1 h, with moderate intermitte...

The aim of this study was to compare the clinical efficacy of salmeterol versus theophylline in the treatment of moderate-to-severe asthma. One hundred and eighty nine asthmatic patients (forced expiratory volume in one second (FEV1) or peak expiratory flow (PEF) >50% of predicted) were randomized to receive either salmeterol dry powder, 50 microg...

The aim of this study was to assess the effects of short-term exposure to low levels of nitrogen dioxide (NO2) on airway inflammation. We studied seven normal, eight mild asthmatic and seven chronic obstructive pulmonary disease (COPD) subjects. All subjects were exposed to air or to 0.3 parts per million (ppm) NO2 for 1 h, with moderate intermitte...

Comparison of inhaled salmeterol and individually dose-titrated slow-release theophylline in patients with reversible airway obstruction. P.L. Paggiaro, D. Giannini, A. Di Franco, R. Testi on behalf of a European Study Group. ©ERS Journals Ltd 1996. ABSTRACT: The aim of this study was to compare the clinical efficacy of salme- terol versus theophyl...

The role of peak expiratory flow (PEF) monitoring in the diagnosis of occupational asthma has recently been assessed by several studies, which agree that this procedure should always be used to confirm the relationship between symptoms and occupational exposure. Some specific issues should be satisfied: a minimum number of four PEF measurements in...

In order to assess whether treatment with oral slow-release theophylline prevents early (EAR) and/or late (LAR) airway responses to allergen, we treated six asthmatic subjects with either placebo or oral theophylline (350 mg b.i.d.) for one week before specific bronchial provocation test (sBPT) with allergen, in a double-blind, cross-over, placebo-...

To determine whether inhaled budesonide given after allergen inhalation challenge inhibits the late asthmatic response (LAR) and/or the associated increase of airway responsiveness to methacholine, we performed a double-blind randomized cross-over study in 12 adult asthmatics (eight male, four female; mean age, 20.3 yr; range, 18 to 29 yr) sensitiz...

Several studies on the prognosis of occupational asthma have shown that a significant proportion of patients continue to experience asthmatic symptoms and nonspecific bronchial hyperresponsiveness after cessation of work. The determinants of this unfavourable prognosis of asthma are: long duration of exposure before the onset of asthma; long durati...

In order to investigate if bronchial asthma is associated with enhanced markers of activation in peripheral neutrophils, the migratory capacity of neutrophils in venous blood was measured by means of the Boyden chamber technique in 29 subjects with bronchial asthma of differing severity. Random migration (random motility), but not locomotion toward...

Long-term change in nonspecific and specific bronchial hyperresponsiveness was studied in 16 subjects with asthma induced by toluene diisocyanate (TDI). A significant positive correlation between months of follow-up and provocative dose inducing a 20 percent fall in FEV1 (PD20FEV1) methacholine was observed in 5 of 16 subjects. In 4 of these 5 subj...

Salbutamol is known to effectively prevent early asthmatic response (EAR) after specific bronchial provocation test (sBPT) in asthmatic subjects, but the time-course of this protection is not known. In this study the effects of 200 micrograms salbutamol inhaled 2 h before sBPT were compared with 200 micrograms salbutamol inhaled 10 min before sBPT...

The measurement of peak expiratory flow rate (PEFR) has been extensively used to monitor asthma, mainly in relation to pharmacological treatment and/or triggering factors, but a final statement on the usefulness of PEFR monitoring is still lacking. Since 1988, several studies from different groups in Italy have focused on: 1) technical evaluation o...

The aim of this study was to assess the effects of short-term exposure to low levels of nitrogen dioxide (NO2) on airway inflammation. We studied seven normal, eight mild asthmatic and seven chronic obstructive pul- monary disease (COPD) subjects. All subjects were exposed to air or to 0.3 parts per million (ppm) NO2 for 1 h, with moderate intermit...