The role of neutrophil elastase (NE) is poorly understood in bronchiectasis because of the lack of preclinical data and so most of the assumptions made about NE inhibitor potential benefit is based ...on data from CF. In this context, NE seems to be a predictor of long-term clinical outcomes and a possible target of treatment. In order to better evaluate the role of NE in bronchiectasis, a systematic search of scientific evidence was performed.Two investigators independently performed the search on PubMed and included studies published up to May 15, 2017 according to predefined criteria. A final pool of 31 studies was included in the systematic review, with a total of 2679 patients. For each paper data of interest were extracted and reported in table.In this review sputum NE has proved useful as an inflammatory marker both in stable state bronchiectasis and during exacerbations and local or systemic antibiotic treatment. NE has also been associated with risk of exacerbation, time to next exacerbation and all-cause mortality. This study reviews also the role of NE as a specific target of treatment in bronchiectasis. Inhibition of NE is at a very early stage and future interventional studies should evaluate safety and efficacy for new molecules and formulations.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We conducted a prospective, observational study at the Adult CF Center, Ospedale Policlinico, Milano, Italy, from March 2017 to September 2019 to assess the prevalence and serotypes of
Streptococcus ...pneumoniae
(SP) in adults with CF naive to pneumococcal vaccination. Spontaneous sputum samples from 129 patients were analyzed for SP DNA and serotyped. SP was found in 24 subjects (19%) and the most common serotypes were 19F (16%), 4 (6%), and 9VA (3%). Higher FEV1 and non-pseudomonas infection significantly associate with SP on sputum. These results define a subgroup of patients that might deserve implementation of microbiological techniques directed to pneumococcal detection.
Identifying single nucleotide polymorphisms (SNPs) in the genes involved in sepsis may help to clarify the pathophysiology of neonatal sepsis. The aim of this study was to evaluate the relationships ...between sepsis in pre-term neonates and genes potentially involved in the response to invasion by infectious agents. The study involved 101 pre-term neonates born between June 2008 and May 2012 with a diagnosis of microbiologically confirmed sepsis, 98 pre-term neonates with clinical sepsis and 100 randomly selected, otherwise healthy pre-term neonates born during the study period. During the study, 47 SNPs in 18 candidate genes were genotyped on Guthrie cards using an ABI PRISM 7900 HT Fast real-time and MAssARRAY for nucleic acids instruments. Genotypes CT and TT of rs1143643 (the IL1β gene) and genotype GG of rs2664349GG (the MMP-16 gene) were associated with a significantly increased overall risk of developing sepsis (p = 0.03, p = 0.05 and p = 0.03), whereas genotypes AG of rs4358188 (the BPI gene) and CT of rs1799946 (the DEFβ1 gene) were associated with a significantly reduced risk of developing sepsis (p = 0.05 for both). Among the patients with bacteriologically confirmed sepsis, only genotype GG of rs2664349 (the MMP-16 gene) showed a significant association with an increased risk (p = 0.02). Genotypes GG of rs2569190 (the CD14 gene) and AT of rs4073 (the IL8 gene) were associated with a significantly increased risk of developing severe sepsis (p = 0.05 and p = 0.01). Genotype AG of rs1800629 (the LTA gene) and genotypes CC and CT of rs1341023 (the BPI gene) were associated with a significantly increased risk of developing Gram-negative sepsis (p = 0.04, p = 0.04 and p = 0.03). These results show that genetic variability seems to play a role in sepsis in pre-term neonates by influencing susceptibility to and the severity of the disease, as well as the risk of having disease due to specific pathogens.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Bronchiectasis is characterized by neutrophilic inflammation and frequent exacerbations often associated with infections. Lipid mediators play critical roles in the inflammatory response, and the ...balance between anti-inflammatory and pro-inflammatory mediators could drive to chronic inflammation. The aim of this study was to evaluate the metabolites of docosahexaenoic acid and arachidonic acid in sputum of adults with bronchiectasis defining their associations with clinical data, bacterial load and neutrophil elastase.
An observational, cross-sectional study was conducted at the bronchiectasis program of the Policlinico Hospital in Milan, Italy, where patients were enrolled. Active neutrophil elastase was measured by enzyme-linked immunosorbent assay, pro-resolving and pro-inflammatory fatty acid-derived mediators were evaluated by mass spectrometry and respiratory pathogens were assessed by real-time PCR. Analysis were performed on sputum collected during stable state and clinical data were also collected.
Levels of pro-inflammatory mediators derived from arachidonic acid metabolism showed association with neutrophil elastase, were proportional to Pseudomonas aeruginosa identifications and were linked with radiological gravity index, while the concentrations of pro-resolution mediators derived from docosahexaenoic acid were associated with a better health status, highlighted by the inverse correlation with radiological gravity index, bacterial infections and sputum volume production.
Pro-inflammatory mediators derived from FA metabolisms are associated with severity of bronchiectasis while DHA-derived metabolites are inversely associated with severity of the disease, which may be used for personized treatment of bronchiectasis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Different steps and conditions for DNA extraction for microbiota analysis in sputum have been reported in the literature. We aimed at testing both dithiothreitol (DTT) and enzymatic treatments of ...sputum samples and identifying the most suitable DNA extraction technique for the microbiota analysis of sputum. Sputum treatments with and without DTT were compared in terms of their median levels and the coefficient of variation between replicates of both DNA extraction yield and real-time PCR for the 16S rRNA gene. Treatments with and without lysozyme and lysostaphin were compared in terms of their median levels of real-time PCR for
. Two enzyme-based and three beads-based techniques for DNA extraction were compared in terms of their DNA extraction yield, real-time PCR for the 16S rRNA gene and microbiota analysis. DTT treatment decreased the coefficient of variation between replicates of both DNA extraction yield and real-time PCR. Lysostaphin (either 0.18 or 0.36 mg/mL) and lysozyme treatments increased
detection. One enzyme-based kit offered the highest DNA yield and 16S rRNA gene real-time PCR with no significant differences in terms of alpha-diversity indexes. A condition using both DTT and lysostaphin/lysozyme treatments along with an enzymatic kit seems to be preferred for the microbiota analysis of sputum samples.
Group A Streptococcus (GAS) causes multiple clinical manifestations, including invasive (iGAS) or even life-threatening (severe-iGAS) infections. After the drop in cases during COVID-19 pandemic, in ...2022 a sharp increase of GAS was reported globally.
GAS strains collected in 09/2022-03/2023 in two university hospitals in Milan, Italy were retrospectively analyzed. Clinical/epidemiological data were combined with whole-genome sequencing to: (i) define resistome/virulome, (ii) identify putative transmission chains, (iii) explore associations between
types and clinical severity.
Twenty-eight isolates were available, 19/28 (67.9%) from adults and 9/28 (32.1%) from pediatric population. The criteria for iGAS were met by 19/28 cases (67.9%), of which 11/19 (39.3%) met the further criteria for severe-iGAS. Pediatric cases were mainly non-invasive infections (8/9, 88.9%), adult cases were iGAS and severe-iGAS in 18/19 (94.7%) and 10/19 (52.6%), respectively. Thirteen
-types were detected, the most prevalent being
1 and
12 (6/28 strains each, 21.4%). Single nucleotide polymorphism (SNP) analysis of
1.0 and
12.0 strains revealed pairwise SNP distance always >10, inconsistent with unique transmission chains.
12.0-type, found to almost exclusively carry virulence factors
H and
I, was mainly detected in children and in no-iGAS infections (55.6 vs. 5.3%,
= 0.007 and 66.7 vs. 0.0%,
< 0.001, respectively), while
1.0-type was mainly detected in severe-iGAS (0.0 vs. 45.5%,
= 0.045).
This study showed that multiple
-types contributed to a 2022/2023 GAS infection increase in two hospitals in Milan, with no evidence of direct transmission chains. Specific
-types could be associated with disease severity or invasiveness. Overall, these results support the integration of classical epidemiological studies with genomic investigation to appropriately manage severe infections and improve surveillance.
The existence of common inflammatory biomarkers linking obesity and asthma in children has been hypothesized. Nevertheless, laboratory and clinical characteristics of children with obesity and asthma ...are still poorly defined. The primary aim of the present study is to investigate the lung function and the cytokine profile, in children with obesity and asthma. In this prospective, cross-sectional pilot study, pulmonary function tests, biochemical parameters, and serum cytokines levels were compared in three groups of 28 children each, matched for age and sex. Obese children showed normal forced spirometry values except an increased distal airway resistance in subjects with obesity and no asthma. Both groups including obese children showed higher leptin and IL-10 levels and lower adiponectin and TNF-alpha levels compared to children with no obesity and asthma. IL-33 and TGF-beta1 levels were higher in children with obesity and asthma vs. children with normal weight and asthma. Finally, IL-6 was undetectable in approximately 70% of obese children with no asthma, in 57% obese asthmatic children and in 100% of children with normal-weight and asthma. Children with obesity and asthma show the most striking cytokine profile, suggesting a pro-inflammatory role of fat mass in asthma development.
Wheezing during early life is a very common disorder, but the reasons underlying the different wheezing phenotypes are still unclear. The aims of this study were to analyse the potential correlations ...between the risk of developing recurrent wheezing and the presence of specific polymorphisms of some genes regulating immune system function, and to study the relative importance of the associations of different viruses and genetic polymorphisms in causing recurrent episodes.
The study involved 119 otherwise healthy infants admitted to hospital for a first episode of wheezing (74 of whom subsequently experienced recurrent episodes) and 119 age- and sex-matched subjects without any history of respiratory problem randomly selected from those attending our outpatient clinic during the study period. All of the study subjects were followed up for two years, and 47 single nucleotide polymorphisms (SNPs) in 33 candidate genes were genotyped on whole blood using an ABI PRISM 7900 HT Fast Real-time instrument.
IL8-rs4073AT, VEGFA-rs833058CT, MBL2-rs1800450CT and IKBKB-rs3747811AT were associated with a significantly increased risk of developing wheezing (p = 0.02, p = 0.03, p = 0.05 and p = 0.0018), whereas CTLA4-rs3087243AG and NFKBIB-rs3136641TT were associated with a significantly reduced risk (p = 0.05 and p = 0.04). IL8-rs4073AT, VEGFA-rs2146323AA and NFKBIA-rs2233419AG were associated with a significantly increased risk of developing recurrent wheezing (p = 0.04, p = 0.04 and p = 0.03), whereas TLR3-rs3775291TC was associated with a significantly reduced risk (p = 0.03). Interestingly, the study of gene-environment interactions showed that rhinovirus was significantly associated with recurrent wheezing in the presence of IL4Ra-rs1801275GG and G (odds ratio OR 6.03, 95% confidence interval CI: 1.21-30.10, p = 0.03) and MAP3K1-rs702689AA (OR 4.09, 95% CI: 1.14-14.61, p = 0.03).
This study shows a clear relationship between the risk of wheezing and polymorphisms of some genes involved in the immune response. Although further studies are needed to confirm the results, these findings may be useful for the early identification of children at the highest risk of developing recurrent episodes and possibly subsequent asthma.
Recently, two vaccines against meningococcal serogroup B (MenB) have been developed. They are prepared according to the reverse vaccinology approach and contain 4 (4CMenB) and 2 (MenB-FHbp) ...cross-reactive surface proteins. In Italy 4CMenB vaccine has been included in the official vaccination schedule only recently and recommended only for infants and toddlers, whereas MenB-FHbp is not licensed. In order to collect information about the present carriage of Neisseria meningitidis serogroup B (MenB) in Italian adolescents and to evaluate the potential protection offered by the presently available MenB vaccines, 2,560 otherwise healthy, high school students aged 14-21 years (907 males, 35.4%, median age 16.2 years) were enrolled in Milan, Italy. A swab to collect posterior pharynx secretions was collected from each subject and meningococcal identification, serogrouping, multilocus sequence typing analysis, sequence alignments and phylogenetic analysis were performed. A total of 135 (5.3%) adolescents were meningococcal carriers. Strains belonging to serogroup B were the most common (n = 58; 2.3%), followed by MenY (n = 32; 1.2%), MenC (n = 7; 0.3%), MenW (n = 6; 0.3%) and MenX (n = 5; 0.2%). The remaining bacteria were not capsulated. The identified MenB strains belonged to eleven clonal complexes (CCs): ST-162 CC (n = 12; 20.7%), ST-865 CC (n = 12; 20.7%), ST-41/44/Lin.3 CC (n = 11; 19.0%), ST-35 CC (n = 6; 10.3%), ST-32/ET-5 CC (n = 4; 6.9%), ST-269 CC (n = 3; 5.2%), ST-213 CC (n = 2; 3.4%), ST-198 CC (n = 1; 1.7%), ST-461 CC (n = 1; 1.7%), ST-549 CC (n = 1; 1.7%), and ST-750 CC (n = 1; 1.7%). This study showed that MenB was the most commonly carried meningococcal serogroup found in adolescents living in Milan, Italy. The MenB vaccines presently licensed could have theoretically induced the production of antibodies effective against the greatest part of the identified MenB strains (100% in the case of 4CMenB and 95% in case of MenB-FHbp) Monitoring carriage remains essential to evaluate MenB circulation, but further studies are necessary to evaluate the effect on carriage and the final efficacy of both new MenB vaccines.
Despite following a gluten-free diet, which is currently the only effective therapy for celiac disease, about 5% of patients can develop serious complications, which in the case of refractory type 2 ...could evolve towards intestinal lymphoma. In this study, we have identified a set of 15 microRNAs in serum discriminating between the two types of refractory disease. Upregulated miR-770-5p, miR-181b-2-3p, miR-1193, and miR-1226-3p could be useful for the better stratification of patients and the monitoring of disease development, while miR-490-3p was found to be dysregulated in patients with refractory type 1. Finally, by using bioinformatic tools applied to the analysis of the targets of dysregulated microRNAs, we have completed a more precise assessment of their functions. These mainly include the pathway of response to Transforming Growth Factor β cell–cell signaling by Wnt; epigenetic regulation, especially novel networks associated with transcriptional and post-transcriptional alterations; and the well-known inflammatory profiles.
PDF
