Maria Pia Foschino - Academia.edu (original) (raw)

Papers by Maria Pia Foschino

Allergy, Apr 21, 2011

Asthma is a chronic respiratory disease characterized by variable airflow limitation, airway hype... more Asthma is a chronic respiratory disease characterized by variable airflow limitation, airway hyperresponsiveness and airway inflammation, accompanied with episodic symptoms of shortness of breath, cough, wheezing and chest tightness (1). There is evidence that respiratory infections are a contributor to the pathogenesis of asthma (2) and that they play a role in the inception, exacerbations and chronicity of airways inflammation in asthma. First, infant human rhinovirus (HRV) infections appear to be the strongest predictor of subsequent childhood wheezing at age 3 (3, 4). Second, respiratory viruses are closely associated with exacerbations of pre-existing asthma (5-7). And third, it has been postulated that latent or persistent infection can contribute to the chronicity of airway inflammation (8, 9), potentially driven by epithelial-derived pro-inflammatory cytokines and chemokines (10, 11). A recent cross-sectional study has demonstrated elevated presence of rhinovirus in endobronchial biopsies from patients with stable asthma as compared to control subjects (12). This indicates that rhinovirus can be present in lower airway tissue in asthma, but it

Medical Oncology, Sep 1, 2015

Recently the exhaled breath temperature (EBT) was seen to increase in non-small cell lung cancer ... more Recently the exhaled breath temperature (EBT) was seen to increase in non-small cell lung cancer and was subsequently proposed as a possible non-invasive tool for its diagnosis. The need for further studies that confirm the previous findings and support the potential scope of this method underlies the main aim of this study that seeks to explore the pathogenic mechanisms determining the EBT in lung cancer. We enrolled 44 consecutive patients with a radiological suspicion of lung cancer and ten healthy nonsmoker volunteers, after which their EBT was measured. On the same day, the subjects underwent breath condensate collection for the measurement of leukotriene (LTB)-4 and of the vascular endothelial growth factor (VEGF), the former being a marker of airways inflammation and the latter of neoangiogenesis. We confirmed the presence of a higher EBT in lung cancer patients compared to the controls. The multiple linear regression model showed that the exhaled VEGF was the only predictor of elevations of EBT. In conclusion, it can be stated that for the first time in this study, we have shown that EBT is higher in subjects with lung cancer and that the airways angiogenesis drives the increase in EBT in lung cancer. Moreover, the study suggests the potential for the use of EBT in monitoring the lung cancer progression, although the implementation of more in-depth studies to verify this result is recommended. Keywords Lung cancer Á Non-invasive methods Á Angiogenesis Á Airways inflammation Á Exhaled breath condensate Á Exhaled breath temperature

Multidisciplinary Respiratory Medicine, Feb 4, 2022

Background: Dupilumab is a humanized monoclonal antibody targeting the IL4/IL13 signaling pathway... more Background: Dupilumab is a humanized monoclonal antibody targeting the IL4/IL13 signaling pathway, already used for atopic dermatitis and chronic rhinitis with nasal polyps, recently approved for severe type-2 asthma. Its efficacy has been demonstrated in randomized control trials. The aim of our study is to evaluate possible early clinical improvement and type 2 biomarkers modifications in severe asthmatic patients treated with dupilumab in a real-life setting. Methods: We included 12 patients with severe, uncontrolled asthma and dupilumab was chosen if there was at least one evidence of blood eosinophils> 150 cells/ml and/or FeNO>25 ppb during last year. Recent blood eosinophil count report, assessment through ACT, FeNO test and spirometry were performed at baseline and after 3 months of treatment. We calculated also the number of patients achieving a minimal, yet clinically relevant difference in FEV 1 and ACT. Results: After three months of treatment with dupilumab, ACT had a significant improvement (mean ACT pre 13.25±4.65 vs mean ACT post 19.17±4.45; p<0.01), so as FEV 1 % (mean FEV 1 % pre 62.58±15.73 vs mean FEV 1 % post 71.00±13.11; p<0.01). FeNO had a significant reduction (median FeNO 32 pre, IQR 19-48.5 vs median FeNO19 post, IQR 16.5-26), differently from eosinophils blood count (median eosinophils pre 280, IQR 193.8-647.3 vs median eosinophils post 349.5, IQR 103-836.8; p=0.52). Four patients (33%) had a positive MCID for FEV 1 , and eight patients (67%) had a positive MCID for ACT. Conclusions: In RCTs performed during clinical development program dupilumab showed an early efficacy in increasing FEV 1 , reducing FeNO and improving asthma control. Our study demonstrates early improvement in asthmatic symptoms, lung function and FeNO in severe type-2 asthma patients after only 3 months of dupilumab biologic therapy. The introduction of FeNO levels evaluation in the selection criteria for dupilumab, further helps the identification of eligible patients among type-2 severe asthma patients and allows a complete outpatient assessment. Further real-life studies with a longer follow up time will be useful to confirm dupilumab efficacy and to promote its use in clinical practice.

BMC Pulmonary Medicine, Feb 12, 2016

Background: Mitochondria contain their own DNA (MtDNA) that is very sensitive to oxidative stress... more Background: Mitochondria contain their own DNA (MtDNA) that is very sensitive to oxidative stress and as a consequence could be damaged in quantity. Oxidative stress is largely recognized to play a key role in the pathogenesis of asthma and COPD and might have a role in the new intermediate phenotype ACOS (asthma-COPD overlap syndrome). The aim of this study was to investigate MtDNA alterations, as an expression of mitochondrial dysfunction, in ACOS and to verify whether they might help in the identification of this new phenotype and in its differentiation from asthma and COPD. Methods: Ten (10) ACOS according to Spanish guidelines, 13 ACOS according to GINA guidelines, 13 COPD, 14 asthmatic patients and ten normal subjects were enrolled. They further underwent a blood, induced sputum and exhaled nitric oxide collection. Content of MtDNA and nuclear DNA (nDNA) were measured in the blood cells of patients by Real Time PCR. Results: ACOS patients showed an increase of MtDNA/nDNA ratio. Dividing ACOS according to guidelines, those from the Spanish showed a higher value of MtDNA/nDNA compared to those from GINA/GOLD (92.69 ± 7.31 vs 80.68 ± 4.16). Spanish ACOS presented MtDNA/nDNA ratio closer to COPD than asthma. MtDNA was higher in asthmatic, COPD, GINA and Spanish ACOS patients compared to healthy subjects (73.30 ± 4.47-137.0 ± 19.45-80.68 ± 4.16-92.69 ± 7.31 vs 65.97 ± 20.56). Conclusion: We found an increase of MtDNA/nDNA ratio in ACOS subjects that led us to conclude that there is presence of mitochondrial dysfunction in this disease, that makes it closer to COPD than to asthma. Although the MtDNA/nDNA ratio results are a useful marker for differential diagnosis from asthma, COPD and ACOS, further studies are needed to confirm the potentiality of MtDNA/nDNA ratio and to a better characterization of ACOS.

Journal of Clinical Medicine

Background: Mepolizumab and benralizumab are monoclonal antibodies directed against anti-IL-5 and... more Background: Mepolizumab and benralizumab are monoclonal antibodies directed against anti-IL-5 and anti-IL5R, respectively, and their use reduces the exacerbation rate and maintains oral corticosteroid requirements in severe eosinophilic asthma. Previous studies have tested the therapeutic switch between two biologics with excellent results, further demonstrating the heterogeneity of asthmatic disease and the complexity of the therapeutic choice. It remains unclear if such patients may improve following a switch from mepolizumab to benralizumab. Aims: Within a multicentre real-life setting, we decided to evaluate the potential effectiveness of a therapeutic switch to benralizumab in patients with severe eosinophilic asthma initially treated with mepolizumab, who experienced sub-optimal responses. The secondary aim was to identify the clinical factors associated with a better response to benralizumab. Methods: We retrospectively assessed patients with severe eosinophilic asthma treate...

Frontiers in Immunology

BackgroundThe efficacy of dupilumab as biological treatment of severe asthma and chronic rhinosin... more BackgroundThe efficacy of dupilumab as biological treatment of severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) depends on its ability to inhibit the pathophysiologic mechanisms involved in type 2 inflammation.ObjectiveTo assess in a large sample of subjects with severe asthma, the therapeutic impact of dupilumab in real-life, with regard to positive or negative skin prick test (SPT) and CRSwNP presence or absence.MethodsClinical, functional, and laboratory parameters were measured at baseline and 24 weeks after the first dupilumab administration. Moreover, a comparative evaluation was carried out in relation to the presence or absence of SPT positivity and CRSwNP.ResultsAmong the 127 recruited patients with severe asthma, 90 had positive SPT, while 78 reported CRSwNP. Compared with the 6 months preceding the first dupilumab injection, asthma exacerbations decreased from 4.0 (2.0-5.0) to 0.0 (0.0-0.0) (p < 0.0001), as well as the daily prednisone intake fell fr...

Clocks & Sleep

Background and Aim: Sleep-disordered breathing (SDB) is an extremely common disorder with a high ... more Background and Aim: Sleep-disordered breathing (SDB) is an extremely common disorder with a high impact on morbidity and mortality. The purpose of this study was to compare overlap syndrome (OS) and obesity hypoventilation syndrome (OHS) and to highlight and understand the differences between them. Material and Methods: The study was conducted retrospectively on 132 subjects selected by consecutive sampling from those attending our unit for suspected SDB. After clinical evaluation as well as functional and sleep investigations, the population was divided according to diagnosis in OS and OHS; then, the clinical parameters of two groups were compared with different statistical analysis. Results: The subjects with OHS were younger and reported higher rated daytime sleepiness (p = 0.005). In addition, they presented more nocturnal respiratory events (apnea-hypopnea index (AHI) 63.61 ± 22.79 events·h−1 vs. AHIOS 42.21 ± 22.91 events·h−1, p < 0.0001) at the sleep investigation as worse...

Life

Idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), asthma and sle... more Idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), asthma and sleep disorders are chronic respiratory diseases that affect the airways, compromising lung function over time. These diseases affect hundreds of millions of people around the world and their frequency seems to be increasing every year. Extracellular vesicles (EVs) are small-sized vesicles released by every cell in the body. They are present in most body fluids and contain various biomolecules including proteins, lipids, mRNA and non-coding RNA (micro-RNA). The EVs can release their cargo, specifically micro-RNAs (miRNAs), to both neighboring and/or distal cells, playing a fundamental role in cell–cell communication. Recent studies have shown their possible role in the pathogenesis of various chronic respiratory diseases. The expression of miRNAs and, in particular, of miRNAs contained within the extracellular vesicles seems to be a good starting point in order to identify new potential bio...

The Lancet Respiratory Medicine

R., ... van den Berge, M. (2023). Predictors and associations of the persistent airflow limitatio... more R., ... van den Berge, M. (2023). Predictors and associations of the persistent airflow limitation phenotype in asthma: a post-hoc analysis of the ATLANTIS study. The Lancet.

Scientific Reports, 2021

Severe asthma is burdened by frequent exacerbations and use of oral corticosteroids (OCS), which ... more Severe asthma is burdened by frequent exacerbations and use of oral corticosteroids (OCS), which worsen patients’ health and increase healthcare spending. The aim of this study was to assess the clinical and economic impact of switching from omalizumab (OMA) to mepolizumab (MEP) in patients eligible for both biologics, but not optimally controlled by omalizumab. We retrospectively enrolled uncontrolled severe asthmatic patients who switched from OMA to MEP during the last two years. Information included blood eosinophil count, asthma control test (ACT), spirometry, serum IgE, fractional exhaled nitric oxide (FeNO), OCS intake, drugs, exacerbations/hospitalizations, visits and diagnostic exams. Within the perspective of Italian National Health System, a pre- and post-MEP 12-month standardized total cost per patient was calculated. 33 patients were enrolled: five males, mean age 57 years, disease onset 24 years. At OMA discontinuation, 88% were OCS-dependent with annual mean rate of 4...

Respirology Case Reports, 2020

Obstructive sleep apnoea (OSA) syndrome, the most frequent sleep‐disordered breathing, is a comor... more Obstructive sleep apnoea (OSA) syndrome, the most frequent sleep‐disordered breathing, is a comorbidity of asthma, whose prevalence covers about 49.5% of asthmatic adult patients. A 61‐year‐old female patient, affected by severe allergic asthma and obesity, started treatment with omalizumab and underwent polysomnography showing a severe OSA pattern (apnoea/hypopnoea index (AHI): 72.7). After six months, she showed functional improvement and good asthma symptoms control and underwent a new polygraphy for the persistence of the night symptoms which showed an ameliorated, despite still severe, OSA pattern (AHI: 31.9). The patient obtained complete polygraphic normalization after adequate positive airway pressure (PAP) titration. While bronchodilator efficacy in chronic obstructive pulmonary disease (COPD)/OSA overlap syndrome has been proven in raising nocturnal oxygen saturation, there is no such evidence about biological therapy in patients affected by severe asthma and OSA. This is ...

Journal of Clinical Medicine, 2019

Background: Bronchiectasis exacerbations are often treated with prolonged antibiotic use, even th... more Background: Bronchiectasis exacerbations are often treated with prolonged antibiotic use, even though there is limited evidence for this approach. We therefore aimed to investigate the baseline clinical and microbiological findings associated with long courses of antibiotic treatment in exacerbated bronchiectasis patients. Methods: This was a bi-centric prospective observational study of bronchiectasis exacerbated adults. We compared groups receiving short (≤14 days) and long (15–21 days) courses of antibiotic treatment. Results: We enrolled 191 patients (mean age 72 (63, 79) years; 108 (56.5%) females), of whom 132 (69%) and 59 (31%) received short and long courses of antibiotics, respectively. Multivariable logistic regression of the baseline variables showed that long-term oxygen therapy (LTOT), moderate–severe exacerbations, and microbiological isolation of Pseudomonas aeruginosa were associated with long courses of antibiotic therapy. When we excluded patients with a diagnosis ...

Oncotarget, 2018

Introduction: MicroRNAs (miRNAs) are small non coding RNAs which play a role in several cellular ... more Introduction: MicroRNAs (miRNAs) are small non coding RNAs which play a role in several cellular processes. MiRNA expression is influenced by oxidative stress, inflammatory cascade and hypoxia. Effects of different types of hypoxia (intermittent and chronic) have been poorly investigated. The aim of this study was to evaluate how intermittent and chronic hypoxia influence the expression of a pool of miRNAs. Results: Subjects with HI presented higher levels of miR-21, miR-23b, miR-145 and miR-210 compared to the other groups, while higher levels of miR-26 was observed in the HC group. Subjects with HCHI had lower levels of all selected miRNAs. A strong correlation was found between miR-23b and miR-210 and both correlated with PaO2, age and FEV1. MiR-145 is correlated with miR-21 but no correlations were found with other parameters. The level of miR-26a seems to be correlated only with BMI. Materials and Methods: We used RT-PCR to detect the miRNAs expression in three different models of hypoxemia: intermittent (HI), chronic (HC) and both of them (HCHI). Expression of miRNAs was analyzed using ANOVA and post hoc analysis, moreover, Spearman correlation and Cluster analysis were applied to study the relationship between miRNAs and main clinical parameters. Conclusions: Intermittent hypoxia induces the expression of some miRNAs more than chronic hypoxia. These miRNAs may play an important role in the development of different diseases usually associated with OSA such as cardiovascular disease. In addition, mechanisms involved in cancer progression may be induced in the presence of chronic and more often intermittent hypoxia.

The Journal of Allergy and Clinical Immunology: In Practice, 2018

Background: Severe Asthma Network in Italy (SANI) is a registry of patients recruited by accredit... more Background: Severe Asthma Network in Italy (SANI) is a registry of patients recruited by accredited centers on severe asthma. Objective: to analyze epidemiological, clinical, inflammatory, functional and treatment characteristics of severe asthmatics from the SANI registry Methods: All consecutive patients with severe asthma were included into the registry, without exclusion criteria in order to have real-life data on demographics, asthma control, treatments (including biologics), inflammatory biomarkers and comorbidities. Results: 437 patients (mean age: 54.1 years, 57.2% females, 70.7% atopics, 94.5% in GINA severity step 5) were enrolled into the study. Mean annual exacerbation rate was 3.75. Mean blood eosinophil level was 536.7 cells/mcl and average serum total IgE was 470.3 kU/l. About 64% of patients were on regular oral corticosteroid treatment, 57% with omalizumab and 11.2% with mepolizumab. Most common comorbidities were rhinitis, nasal polyposis and bronchiectasis. Patients with nasal polyposis had higher age of disease onset, higher blood eosinophil count and lower frequency of atopy and atopic eczema. Bronchiectasis was associated with more frequent severe exacerbations, higher blood eosinophils and total IgE. Stratifying patients,, those with late-onset asthma were less frequently atopic (with less frequent allergic rhinitis and food allergy), and more frequently with nasal polyposis and higher serum total IgE levels. Conclusions: This study revealed a high frequency of relevant comorbidities and that a substantial proportion of patients have a late-onset asthma; all these features define specific different disease phenotypes. Severe asthma complexity and comorbidities require multidisciplinary approaches, led by specifically trained Pulmonologists and Allergists.

International Journal of Immunopathology and Pharmacology, 2007

Chronic obstructive pulmonary diseases (COPD) is a pulmonary disease characterized by systemic ab... more Chronic obstructive pulmonary diseases (COPD) is a pulmonary disease characterized by systemic abnormalities. The aim of this study is to investigate inflammation and systemic effects in mild COPD. Twenty-seven mild stable smoking related COPD patients and 15 age-matched healthy subjects were enrolled in the study. IL-6, TNF-α and IL-4 in plasma, sputum and exhaled breath condensate were measured. We also measured exhaled nitric oxide (NO) and pH in sputum and in breath condensate. Moreover, fat-free mass, body mass index (BMI), respiratory muscle strength, plasma oxidative stress and C-reactive protein (CRP) were measured. Higher concentrations were found of CRP, of diacron reactive oxygen metabolites (DROMs) and of IL-6, TNF-α and IL-4 either in plasma or in supernatant of induced sputum or in exhaled breath condensate of COPD subjects compared to healthy controls. Furthermore, higher concentrations were observed of exhaled NO and lower exhaled pH in breath condensate of COPD when...

Respiratory Medicine, 2016

Background Asthma in the elderly seems to be more severe compared to asthma in younger patients, ... more Background Asthma in the elderly seems to be more severe compared to asthma in younger patients, with a possible reduced responsiveness to treatment. The aim of this study was to evaluate long-term effects of Omalizumab in elderly asthmatics in a real-life setting. Methods: 105 consecutive severe asthmatics (step 4-5 according to GINA criteria; mean FEV 1 :66±15.7%) on treatment with Omalizumab for at least 1 year (mean 35.1±21.7 months) were included into the study and divided into 3 groups according to the age at the onset of Omalizumab treatment: 18-39, 40-64 and ≥65 years. Results: Older subjects differed from the other groups for number of comorbidities, prevalence of overweight/obese subjects and for later asthma onset. A significant and similar reduction of controller therapy and use of SABA on demand was observed in the three groups during omalizumab therapy. FEV 1 increased significantly and similarly in all the groups. Asthma Control Test (ACT) improved significantly (p < 0.001) in the three groups , increasing from 15 [12-18] to 24 [22-25] in the younger, from 14 [10-16] to 21 [20-23] in the 40-64 years group and from 15 [12-16] to 20 [18-22] in the elderly, the improvement being lesser than in the other groups (p = 0.039). The decrease in asthma exacerbation was significant in all the groups, but the percentage of patients free of exacerbations was higher in the younger (76.9%) compared to middle aged patients (49.2%) and elderly(29%) (p=0.049). Conclusion: Omalizumab improved all asthma outcomes independently of age, but the magnitude of the effects observed in the elderly were significantly lesser than in the other age groups.

Allergy and Asthma Proceedings, 2016

Background: The presence of virus and bacteria in the airways of subjects with asthma is common a... more Background: The presence of virus and bacteria in the airways of subjects with asthma is common and seems to be associated with a deterioration due to the disease. The microbiologic study of airways in asthma is foreseen by guidelines with induced sputum that is often ineffective and contraindicated in severe asthma. Aim: To analyze the fungal microbiome in the exhaled breath condensate (EBC) of subjects with asthma by evaluating a possible correlation with anthropometric and asthma severity data. Methods: We enrolled 47 consecutive subjects with asthma (28 with atopic asthma and 19 with nonatopic asthma) and 20 controls. Enrolled subjects underwent EBC and sputum collection. Fungal microbiome was assessed by culture on EBC and sputum samples by using Czapek yeast extract agar. Results: A fungal colonization in the EBC of 70% of enrolled subjects with asthma was detected (none detected in the controls). An overlap of fungal microbiome in EBC and sputum was observed (100% of overlap). Fungal colonization was higher in subjects without atopic, obesity, and severe and uncontrolled asthma. Conclusion: When considering the high morbidity and mortality of patients with severe asthma in whom we found an important fungal airways colonization, we support the use of the analysis of exhaled fungal microbiome in these subjects.

International Journal of Chronic Obstructive Pulmonary Disease, 2016

Background: Microparticles (MPs) are small membrane vesicles of 0.1-1 µm which are released by ce... more Background: Microparticles (MPs) are small membrane vesicles of 0.1-1 µm which are released by cells following chemical, physical, and apoptotic stimuli. MPs represent more than a miniature version of the cell. Their composition and function depend not only on cellular origin, but also on stimuli. Chronic obstructive pulmonary disease (COPD) is a lung disease characterized by nearly irreversible lung destruction which results in airway limitation. Purpose: We investigated the presence and source of MPs in sputum of COPD patients to evaluate if changes in MP number and origin may reflect the pathophysiological conditions of disease and may serve as potential biomarkers for diagnostic and prognostic use. Methods: Induced sputum samples were collected from 18 male subjects and liquefied with Sputasol. MPs obtained were immunolabeled for leukocyte (CD11a), granulocyte (CD66b), monocyte-macrophage (CD11b), platelets and megakaryocytic cells (CD41), endothelial cells (CD31), and red blood cells (CD235ab) and analyzed by cytofluorimetry. Results: There was a negative correlation between CD31-MPs and forced expiratory volume in 1 second (R=−53, P,0.05) and CD66b-MP level was correlated with worse performance index of COPD such as the Body mass index airflow Obstruction, Dyspnea, and Exercise capacity (BODE); they were negatively correlated with 6-minute walking test: 0.65 and −0.64, respectively (P,0.05). CD235ab-MPs showed a negative correlation with body mass index (R=−0.86, P,0.05), while there was a positive correlation with dyspnea index (R=0.91, P,0.05). Conclusion: The main finding of this study was that MPs were detected in the sputum of patients affected by COPD. The phenotype of some of them was related to the main COPD parameters. These results suggest that MPs could be implicated in the pathogenesis of COPD.

Monaldi Archives for Chest Disease, 2016

Background. An altered balance of oxidants/anti-oxidants is one of the pathological mechanisms of... more Background. An altered balance of oxidants/anti-oxidants is one of the pathological mechanisms of many agedependent disorders. We aimed to investigate the age-related airways oxidative stress, using non invasive, safe and repeatable techniques; to evaluate the correspondence between systemic and local oxidative stress in healthy subjects of different age ranges; to analyse the correlation between systemic and local oxidative stress with lung function and with cognitive impairment. Methods. Thirty consecutive healthy high school graduated subjects (8 M, 22 F), divided in three ranges of age (60 years) were enrolled. All subjects underwent oxygen free radicals and exhaled nitric oxide measurement (by the diacron reactive oxygen metabolites test and by a rapid-response chemiluminescence nitric oxide analyzer), lung function tests, and cognitive impairment scales (Mini Mental State Examination and Geriatric Depression Scale). Results. A significant increase of oxygen free radicals, exha...

Respiratory Research, 2015

Background: Obstructive Sleep Apnea (OSAS) is a disease associated with the increase of cardiovas... more Background: Obstructive Sleep Apnea (OSAS) is a disease associated with the increase of cardiovascular risk and it is characterized by repeated episodes of Intermittent Hypoxia (IH) which inducing oxidative stress and systemic inflammation. Mitochondria are cell organelles involved in the respiratory that have their own DNA (MtDNA). The aim of this study was to investigate if the increase of oxidative stress in OSAS patients can induce also MtDNA alterations.