Giovanni Rossi - Academia.edu (original) (raw)

Papers by Giovanni Rossi

Archives of Disease in Childhood, Oct 1, 1995

Frontiers in Immunology, May 19, 2021

Rationale. Non-typeable Haemophilus influenzae (NTHi), the leading cause of localized upper respi... more Rationale. Non-typeable Haemophilus influenzae (NTHi), the leading cause of localized upper respiratory tract infection in children, can be the causative agents of lower respiratory tract disorders and chronic lung disorder exacerbations. Infection of bronchial epithelial cells by NTHi is characterized by a sustained neutrophilic inflammation that is thought to play a key pathogenetic role in lung parenchyma damage. Methods. To characterize the mechanisms involved in BEC activation in response to NTHi, a human cell line (BEAS-2B) was stimulated with NTHi lysates. The production of TNF-α, and the expression of TLR2, the microbial ligand that recognizes NTHi molecular patterns, and of ICAM-1, an adhesion molecule required for neutrophil adhesion, were evaluated. The respective role of TNF-α and ICAM-1 in neutrophil adhesion to BEAS-2B cells was then evaluated by inhibition of their activity by specific monoclonal antibodies (mAbs). Results. A time-and dose-dependent induction of TNF-α synthesis and release by BEAS-2B cells was detected after 24-hour exposure to NTHi lysates (0.4 to 1.6 mg/ml). TNF-α, but also directly NTHi lysates, significantly amplified ICAM-1 and TLR2 expression and synthesis by BEAS-2B cells. Stimulation of BEAS-2B cells with NTHi lysates or with TNF-α induced a dose-dependent increase neutrophil adhesion, stronger after NTHi lysates exposure, associated with MPO production. Finally, the NTHi lysates-induced neutrophil adhesion to BEAS-2B cells was significantly inhibited by anti-TNF-α and anti-ICAM-1 mAbs. Conclusion. Exposure to NTHi lysates induced functional and structural changes in BEAS-2B cells leading to neutrophil recruitment, adhesion, and activation. The observation that all these BEAS-2B cell changes were also induced by TNF-α can at least partially explain the sustained inflammation seen in NTHi infections. HIGHLIGHTS BOX Non-typeable Haemophilus in�luenzae (NTHi) airway infection is characterized by a sustained neutrophilic in�lammation leading to parenchymal lung damage. Bronchial epithelial cells exposed to NTHi lysate promoted a powerful neutrophil recruitment and activation with a positive feedback loop.

The European respiratory journal, Mar 1, 2005

CASE HISTORY A 24-yr-old Caucasian female was evaluated in May, 2003 at the San Martino hospital,... more CASE HISTORY A 24-yr-old Caucasian female was evaluated in May, 2003 at the San Martino hospital, Genoa, Italy, for the presence of ''sudden onset'' chest pain and nonproductive cough. Past medical history was only characterised by the presence of frequent headaches. The patient had been playing competitive tennis from the age of 6-20 yrs and, after retirement from competitions, had been smoking cigarettes (0.5 pack?day-1) for the last 4 yrs. The patient was nulliparous and reported the use of oral contraceptive in the last 3 yrs. Any suggestion of respiratory symptoms, including cough, shortness of breath or physical limitations during exercise were denied.

European Respiratory Journal

To evaluate the effects of thymomodulin (TMD), a thymic biological response modifier derived from... more To evaluate the effects of thymomodulin (TMD), a thymic biological response modifier derived from calf thymus, on the release of various cytokines involved in the lung immune reactions, human alveolar macrophages (AM) and peripheral blood lymphocytes (PBL) were cultured either alone or in co-cultures. In co-cultures of AM with PBL, TMD did not induce any change in gamma-interferon (gamma-IFN) and interleukin-1 (IL-1) secretion, while it was able to increase the level, of tumour necrosis factor (TNF) (TMD 100 micrograms.m-1, p < 0.05 vs control cultures), and of granulocyte macrophage colony-stimulating factor (GM-CSF) (TMD 1, 10 and 100 micrograms.ml-1 p < 0.05, < 0.05 and < 0.01, respectively, vs control cultures). In cultures of AM alone, TMD did not induce changes in the levels of any of the tested cytokines, whilst in supernatants from PBL lymphocyte cultures, TMD at 1, 10 and 100 micrograms.ml-1 increased the amounts of GM-CSF (p < 0.01 each comparison vs control...

British Journal of Pharmacology, 1995

The mechanisms underlying bradykinin (BK)‐mediated contractions in strips of guinea‐pig gallbladd... more The mechanisms underlying bradykinin (BK)‐mediated contractions in strips of guinea‐pig gallbladder (GPG) were examined by use of selective bradykinin (BK) receptor agonists and antagonists. Addition of BK and related kinins (0.1 pM‐10μm) after 2 h of equilibration of the preparation caused graded contractions characterized by two distinct phases: high affinity (0.1 pM‐1 nM) and low affinity (3 nM‐10 μm). The rank order of potency for the first phase (mean EC50, PM) was: BK (1.36) = Hyp3‐BK (1.44) = Lys‐BK (1.54)>Tyr8‐BK (2.72)> Met‐Lys‐BK (4.30). The rank order of potency for the second phase (mean EC50, nM, at concentration producing 50% of the contraction caused by 80 mM KC1) was: Hyp3‐BK (8.95)> Met‐Lys‐BK (12.78)>Tyr8‐BK (33.75)> Lys‐BK (60.92)> BK (77.35). The contractile responses (g of tension) to 3 μm of BK (the highest concentration tested) were: Hyp3‐BK, 1.76 ±0.09; BK, 1.65 ±0.12; Lys‐BK, 1.45 ±0.13; Tyr8‐BK, 1.36 ±0.15 and Met‐Lys‐BK, 1.36 ±0.15. The s...

Frontiers in Pediatrics

Respiratory tract infections (RTI) are mainly viral in origin and among the leading cause of chil... more Respiratory tract infections (RTI) are mainly viral in origin and among the leading cause of childhood morbidity globally. Associated wheezing illness and asthma are still a clear unmet medical need. Despite the continuous progress in understanding the processes involved in their pathogenesis, preventive measures and treatments failed to demonstrate any significant disease-modifying effect. However, in the last decades it was understood that early-life exposure to microbes, may reduce the risk of infectious and allergic disorders, increasing the immune response efficacy. These results suggested that treatment with bacterial lysates (BLs) acting on gut microbiota, could promote a heterologous immunomodulation useful in the prevention of recurrent RTIs and of wheezing inception and persistence. This hypothesis has been supported by clinical and experimental studies showing the reduction of RTI frequency and severity in childhood after oral BL prophylaxis and elucidating the involved m...

Thorax, 1984

Different lymphocyte subpopulations have been evaluated in bronchoalveolar fluid and blood obtain... more Different lymphocyte subpopulations have been evaluated in bronchoalveolar fluid and blood obtained from six patients with active and six with inactive pulmonary sarcoidosis and from six normal subjects by means of two recently described monoclonal antibodies, 5/9 and MLR4. The percentages of OKT4 positive (helper) and OKT8 positive (suppressor) T cells were also determined. Patients with active sarcoidosis had significantly higher proportions of 5/9 positive T cells in the bronchoalveolar fluid than patients with inactive disease (p < 0.01) or normal subjects (p < 0.001). In contrast, the proportions of 5/9 positive blood T cells were similar in the three groups studied. Patients with active sarcoidosis had also a greater proportion proportion of MLR4 positive T lymphocytes in bronchoalveolar fluid than patients with inactive disease or normal subjects (p < 0*01 for each comparison), but similar proportions of MLR4 positive blood T cells were found in each group. The ratio of 5/9 positive to MLR4 positive T cells was higher in the bronchoalveolar fluid (but not in the blood) in patients with either active or inactive sarcoidosis than in normal subjects. These observations suggest that the MLR4 negative fraction rather than the MLR4 positive fraction of the 5/9 positive T cells is preferentially expanded in the lungs of patients with pulmonary sarcoidosis and may indicate a secondary role for the MLR4 positive T cells in producing lung injury in this disorder. Comparisons of the OKT4 positive and 5/9 positive T cells showed that in patients with active disease most of the lung T lymphocytes expressed both the OKT4 and the 5/9 surface antigens, so the 5/9 monoclonal antibody may be considered a good marker of activity in this disorder. Pulmonary sarcoidosis may be characterised by the preferential expansion of helper T cell subsets at sites of disease activity. Sarcoidosis is a generalised disorder of unknown aetiology characterised by non-caseating granulomas in the affected organs'-5 and by polyclonal hypergammaglobulinaemia.6'3 Recent studies on pulmonary sarcoidosis have shown that in patients with active disease (high intensity alveolitis) both granuloma formation and immunoglobulin production appear to be modulated by activated T lymphocytes.'2-5 Patients with high intensity

Frontiers in Cellular and Infection Microbiology

To describe microbiota profiles considering potential influencing factors in pre-school children ... more To describe microbiota profiles considering potential influencing factors in pre-school children with recurrent respiratory tract infections (rRTIs) and to evaluate microbiota changes associated with oral bacterial lysate OM-85 treatment, we analyzed gut and nasopharynx (NP) microbiota composition in patients included in the OM-85-pediatric rRTIs (OMPeR) clinical trial (https://www.clinicaltrialsregister.eu/ctr-search/trial/2016-002705-19/IT). Relative percentage abundance was used to describe microbiota profiles in all the available biological specimens, grouped by age, atopy, and rRTIs both at inclusion (T0) and at the end of the study, after treatment with OM-85 or placebo (T1). At T0, Firmicutes and Bacteriodetes were the predominant genera in gut and Proteobacteria, Firmicutes, and Actinobacteria were the predominant genera in NP samples. Gut microbiota relative composition differed with age (<2 vs. ≥2 years) for Firmicutes, Proteobacteria, Actinobacteria (phyla) and Bifidob...

The immunopathology of respiratory syncytial virus (RSV) infection, the most common cause of lowe... more The immunopathology of respiratory syncytial virus (RSV) infection, the most common cause of lower respiratory tract infections (LRTI) in the pediatric population, with severe disease being the exception. The variability of the clinical presentation is incompletely explained by host, viral and environmental factors but, in infants and young children, disease severity is certainly linked to the physiological immune immaturity. There is evidence that the maturation of the host immune response is, at least in part, promoted by the composition of the nasopharyngeal microbiome that, modulating excessive inflammation, can counteract the predisposition to develop viral respiratory infections and lower the risk of disease severity. However, interaction between the nasopharyngeal microbiota and respiratory viruses can be bidirectional. Microbial dysbiosis can drive disease pathogenesis but may also represents a reflection of the disease-induced alterations of the local milieu. Moreover, viru...

International Journal of Immunopathology and Pharmacology, 2013

Asthma is a chronic airway inflammatory disease associated with airway hyperresponsiveness which ... more Asthma is a chronic airway inflammatory disease associated with airway hyperresponsiveness which affects subjects with genetic predisposition. An association has been reported between some polymorphisms in various cytokine genes and asthma. Most of them are single nucleotide polymorphisms (SNPs). These polymorphisms are detected in the protein coding sequence or in the promoter region thus influencing cytokine production. We investigated the involvement of SNP mapping in 5 cytokine genes in mild to severe asthmatics of Italian Caucasians. The frequency of alleles and genotypes, relatively to 10 allelic specificities of the cytokine genes, was defined in 57 asthmatics and in 124 control subjects by a Polymerase Chain Reaction-Sequence Specific Primer method. TNF-α -308A and TNF-α -238A allele frequencies were higher in asthmatics than in controls (p<0.001). Significant differences in the frequency of IL-4 -590T allele and of IL-4Rα + 1902A allele were also detected in asthmatics i...

Italian Journal of Pediatrics, 2014

Acute bronchiolitis is the leading cause of lower respiratory tract infection and hospitalization... more Acute bronchiolitis is the leading cause of lower respiratory tract infection and hospitalization in children less than 1 year of age worldwide. It is usually a mild disease, but some children may develop severe symptoms, requiring hospital admission and ventilatory support in the ICU. Infants with pre-existing risk factors (prematurity, bronchopulmonary dysplasia, congenital heart diseases and immunodeficiency) may be predisposed to a severe form of the disease. Clinical diagnosis of bronchiolitis is manly based on medical history and physical examination (rhinorrhea, cough, crackles, wheezing and signs of respiratory distress). Etiological diagnosis, with antigen or genome detection to identify viruses involved, may have a role in reducing hospital transmission of the infection. Criteria for hospitalization include low oxygen saturation (<90-92%), moderate-to-severe respiratory distress, dehydration and presence of apnea. Children with pre-existing risk factors should be carefully assessed. To date, there is no specific treatment for viral bronchiolitis, and the mainstay of therapy is supportive care. This consists of nasal suctioning and nebulized 3% hypertonic saline, assisted feeding and hydration, humidified O 2 delivery. The possible role of any pharmacological approach is still debated, and till now there is no evidence to support the use of bronchodilators, corticosteroids, chest physiotherapy, antibiotics or antivirals. Nebulized adrenaline may be sometimes useful in the emergency room. Nebulized adrenaline can be useful in the hospital setting for treatment as needed. Lacking a specific etiological treatment, prophylaxis and prevention, especially in children at high risk of severe infection, have a fundamental role. Environmental preventive measures minimize viral transmission in hospital, in the outpatient setting and at home. Pharmacological prophylaxis with palivizumab for RSV bronchiolitis is indicated in specific categories of children at risk during the epidemic period. Viral bronchiolitis, especially in the case of severe form, may correlate with an increased incidence of recurrent wheezing in pre-schooled children and with asthma at school age. The aim of this document is to provide a multidisciplinary update on the current recommendations for the management and prevention of bronchiolitis, in order to share useful indications, identify gaps in knowledge and drive future research.

Mediators of Inflammation, 1994

To test the hypothesis that mononuclear cell products could increase the expression of HLA-DR and... more To test the hypothesis that mononuclear cell products could increase the expression of HLA-DR and ICAM-1 molecules in bronchial epithelial cells (BECs), subconfluent cultures of human BECs, obtained from surgically resected bronchi, were incubated with PHA-activated blood mononuclear cell conditioned media (BCM-CM) or recombinant IFN-γ. The presence of HLA-DR and ICAM-1 molecules on BECs was then evaluated by specific antibody staining and flow-cytometry analysis. The addition to BEC cultures of different concentrations of PHA-stimulated BMC-CM, or of IFN-γ induced a dosedependent increase of HIA-DR and ICAM-1 expression, while no effect was observed with unstimulated BMC-CM. The ability of nedocromil sodium and, as control, of dexamethasone, to prevent the upregulation of HLA-DR and ICAM-1 expression on BECs was then tested. Increasing concentrations (10−7to 10−4M) of nedocromil significandy inhibited HLA-DR and ICAM-1 expression by BECs in a dose-dependent fashion. A similarly dos...

Canadian Respiratory Journal, 2021

Oral bacterial lysates (OBLs) can reduce the frequency and severity of recurrent respiratory trac... more Oral bacterial lysates (OBLs) can reduce the frequency and severity of recurrent respiratory tract infections in children from viral and bacterial origins. OBL-induced early innate immune reaction was already shown, but the specific features of different OBLs have never been studied and compared. A study was conducted to assess in vitro the protective effects on rhinovirus- (RV-) infected human bronchial epithelial cells (BECs) of two slightly different OBLs: OM-85 and Pulmonarom. Furthermore, since immune cells represent the key arm for antiviral defence, the capacity of these OBLs to induce selected cytokine production in mouse bone marrow-derived DCs (BMDCs) was also evaluated. Although different OBLs may share some mechanisms to protect host cells from virus infection, some product-specific antimicrobial activities were observed on RV-infected human BECs and mouse BMDCs. These results are consistent with a product-specific response possibly triggered by different pathogen-associ...

Paediatric Respiratory Reviews, 2011

A34. AIRWAY INFLAMMATION, 2009

Infection, 2020

Novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) became pandemic by the end of ... more Novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) became pandemic by the end of March 2020. In contrast to the 2002–2003 SARS-CoV outbreak, which had a higher pathogenicity and lead to higher mortality rates, SARSCoV-2 infection appears to be much more contagious. Moreover, many SARS-CoV-2 infected patients are reported to develop low-titer neutralizing antibody and usually suffer prolonged illness, suggesting a more effective SARS-CoV-2 immune surveillance evasion than SARS-CoV. This paper summarizes the current state of art about the differences and similarities between the pathogenesis of the two coronaviruses, focusing on receptor binding domain, host cell entry and protease activation. Such differences may provide insight into possible intervention strategies to fight the pandemic.

Pediatric Pulmonology, 2019

Infection and Immunity, 1991

To detect possible differences in phenotype and fine specificity for mycobacterial antigens betwe... more To detect possible differences in phenotype and fine specificity for mycobacterial antigens between CD4-positive T cells from peripheral blood (PB) and from inflammatory sites, we identified four patients presenting with a mycobacterial pleural exudate (PE) rich in PPD-specific lymphocytes and with a negative skin test to tuberculin purified protein derivative (PPD) and a negative proliferative response of PB lymphocytes to PPD at the same time. Several weeks after chemotherapy, these patients converted to PPD responsiveness in the periphery, and PPD-specific clones could be generated from PB at this stage. The phenotypic comparison of PE lymphocytes and concomitant PB lymphocytes obtained before treatment showed an increase of CD8 cells and a high frequency of HLA-DR-positive activated T cells in PE. The frequency of tetanus toxoid-specific and Candida albicans-specific proliferating T cells was lower than that of PPD-specific cells in PE but not in PB. PPD-specific clones were der...

Italian Journal of Pediatrics, 2019

Background The only pharmacologic prophylaxis against respiratory syncytial virus (RSV) infection... more Background The only pharmacologic prophylaxis against respiratory syncytial virus (RSV) infection in preterm infants is the humanized monoclonal antibody palivizumab. After the 2014 modification of the American Academy of Pediatrics (AAP) recommendations, the Italian Medicines Agency (AIFA) limited the financial coverage for palivizumab prescriptions to otherwise healthy preterm infants with < 29 weeks of gestational age (wGA) aged < 12 months at the beginning of the 2016–2017 RSV season. However, due to the effect on disease severity and hospitalizations following this limitation, shown by several Italian clinical studies, in November 2017 AIFA reinstated the financial coverage for these infants. In this systematic review, we critically summarize the data that show the importance of palivizumab prophylaxis. Methods Data from six Italian pediatric institutes and the Italian Network of Pediatric Intensive Care Units (TIPNet) were retrieved from the literature and considered. Th...