We report the use of a new multiplex Real-Time PCR platform to simultaneously identify 24 pathogens and 3 antimicrobial-resistance genes directly from respiratory samples of COVID-19 patients. Results were compared to culture-based diagnosis.Secondary infections were detected in 60% of COVID-19 patients by molecular analysis and 73% by microbiological assays, with no significant differences in accuracy, indicating Gram-negative bacteria as the predominant species. Among fungal superinfections, Aspergillus spp. were detected by both methods in more than 7% of COVID-19 patients. Oxacillin-resistant S. aureus and carbapenem-resistant K. pneumoniae were highlighted by both methods.Secondary microbial infections in SARS-CoV-2 patients are associated with poor outcomes and an increased risk of death. Since PCR-based tests significantly reduce the turnaround time to 4 hours and 30 minutes (compared to 48 hours for microbial culture), we strongly support the routine use of molecular techniques, in conjunction with microbiological analysis, to identify co/secondary infections.

Patients with chronic obstructive pulmonary disease (COPD) often suffer from other conditions, such as cardiovascular disease, that further increase the risk of adverse outcomes in this group. Serum homocysteine concentrations are positively associated with cardiovascular risk and have also been reported to be increased in COPD. This meta-analysis investigated the association between homocysteine concentrations and COPD. A systematic search of publications in the electronic databases PubMed, Web of Science, Scopus, and Google Scholar, from inception to September 2021, was conducted using the following terms: “Homocysteine” or “Hcy” and “Chronic Obstructive Pulmonary Disease” or “COPD”. Weighted mean differences (WMDs) were calculated to evaluate differences in homocysteine concentrations between COPD patients and non-COPD subjects. Risk of bias and certainty of evidence were assessed using the Joanna Briggs Institute Critical Appraisal Checklist and GRADE, respectively. Nine studies in 432 COPD patients (mean age 65 years, 65

Chronic obstructive pulmonary disease (COPD) is a progressive disease that is characterized by a state of persistent inflammation and oxidative stress. The presence of oxidative stress in COPD is the result of an imbalance between pro-oxidant and antioxidant mechanisms. The aim of this review was to investigate a possible association between glutathione peroxidase (GPx), a key component of antioxidant defense mechanisms, and COPD. A systematic search for relevant studies was conducted in the electronic databases PubMed, Web of Science, Scopus, and Google Scholar, from inception to June 2021. Standardized mean differences (SMDs) were used to express the differences in GPx concentrations between COPD patients and non-COPD subjects. Twenty-four studies were identified. In 15 studies assessing whole blood/erythrocytes (GPx isoform 1), the pooled results showed that GPx concentrations were significantly lower in patients with COPD (SMD = −1.91, 95% CI −2.55 to −1.28, p < 0.001; moderate certainty of evidence). By contrast, in 10 studies assessing serum/plasma (GPx isoform 3), the pooled results showed that GPx concentrations were not significantly different between the two groups (very low certainty of evidence). The concentration of GPx-1, but not GPx-3, is significantly lower in COPD patients, suggesting an impairment of antioxidant defense mechanisms in this group.

Background: Chronic Obstructive Pulmonary Disease (COPD) is a progressive disease characterized by a not fully reversible airflow limitation associated with an abnormal inflammatory response. Exacerbations of COPD are of major importance in the acceleration of disease progression, in healthcare costs, and negatively affect the patient's quality of life. Exacerbations are characterized by a further increase in the airway inflammation likely driven by oxidative stress. In order to deepen the knowledge about this topic, several studies have focused on oxidative stress biomarkers levels. This review summarizes the literature findings about oxidative stress biomarkers in exacerbated COPD patients compared to ones in the stable state. Methods: a systematic search in electronic databases Pubmed, Web of Science, Scopus and Google Scholar from inception to January 2021, was conducted using the terms: "oxidative stress", "chronic obstructive pulmonary disease" or "COPD", "exacerbation". Results: 23 studies were selected for the systematic review. They showed the presence of an imbalance between oxidant and antioxidant molecules in favor of the former in exacerbation of COPD. Conclusions: future studies using standardized methods in better characterized population are needed. However, this review suggests that targeting oxidative stress could be useful in monitoring the disease progression in COPD patients and especially in those more susceptible to exacerbations.

Oxidative stress induced by nocturnal intermittent hypoxia plays a significant pathophysiological role in obstructive sleep apnea (OSA). Malondialdehyde (MDA), one of the most commonly investigated markers of lipid peroxidation, might assist with the monitoring of oxidative balance in OSA. We conducted a systematic review and meta-analysis to evaluate the differences in circulating MDA concentrations between patients with OSA and non-OSA controls. A systematic search was conducted in the electronic databases Pubmed, Web of Science, Scopus and Google Scholar from inception to December 2020 by using the following terms: "malondialdehyde" or "MDA"; and "Obstructive Sleep Apnea Syndrome", "OSAS" or "OSA". We identified 26 studies in 1223 OSA patients and 716 controls. The pooled MDA concentrations were significantly higher in patients with OSA (standardized mean difference (SMD) 1.43 μmol/L, 95% confidence interval (CI) 1.03 to 1.83 μmol/L, p < 0.001). There was extreme heterogeneity between the studies (I2 = 92.3%, p < 0.001). In meta-regression analysis, the SMD was significantly associated with age, the assay type used and publication year. In our meta-analysis, MDA concentrations were significantly higher in OSA patients than in controls. This finding suggests that MDA, which is a marker of lipid peroxidation, is involved in the pathogenesis of OSA and provides insights for future studies investigating its potential clinical use.

BACKGROUND:Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease that may have a negative impact on both patients' quality of life and survival. Patients with COPD frequently suffer from heart failure (HF), likely owing to several shared risk factors.AIM:To evaluate the differences in treatment of COPD with and without HF comorbidity according to COPD severity in the general practitioner setting.METHODS:We conducted an observational, retrospective study using data obtained from the Italian Health Search Database, which collects information generated by the routine activity of general practitioners. The study sample included 225 patients with COPD, alone or combined with HF.FINDINGS:It has been found that the prevalence of some comorbidities such as diabetes and HF significantly increases with the severity of COPD. Regarding pharmacological treatment, a reduction in the prescription of individually administered long-acting β 2-agonists (LABAs) and long-acting anticholinergics (LAMAs) has been observed with increasing severity of the disease. Moreover, an increase in the prescription of both the combination of the two bronchodilators (LABA + LAMA) and their association with inhaled corticosteroids has been observed with increasing severity of COPD. The prescription of β-blockers in patients with COPD suffering from HF comorbidity decreases from 100% in stage I to less than 50% in the other stages of COPD. This study shows that general practitioners do not follow the guidelines recommendations for the management of patients with COPD in the different stages of the disease, with and without HF comorbidity, as well as in the management of HF. Further efforts must be made to ensure adequate treatment for these patients.

It is amply reported that patients with chronic obstructive pulmonary disease (COPD) have increased risk of cardiovascular disease (CVD). Recent evidence suggests that COPD patients have elevated concentrations of plasma homocysteine (Hcy), a transsulfuration pathway analyte that is commonly regarded as a CVD risk factor.

Introduction. Chronic obstructive pulmonary disease (COPD) is a progressive disease characterized by airflow limitation that is not fully reversible after inhaled bronchodilator use associated with an abnormal inflammatory condition. The biggest risk factor for COPD is cigarette smoking. The exposure to noxious chemicals contained within tobacco smoke is known to cause airway epithelial injury through oxidative stress, which in turn has the ability to elicit an inflammatory response. In fact, the disruption of the delicate balance between oxidant and antioxidant defenses leads to an oxidative burden that has long been held responsible to play a pivotal role in the pathogenesis of COPD. There are currently several biomarkers of oxidative stress in COPD that have been evaluated in a variety of biological samples. The aim of this review is to identify the best studied molecules by summarizing the key literature findings, thus shedding some light on the subject. Methods. We searched for relevant case-control studies examining oxidative stress biomarkers in stable COPD, taking into account the analytical method of detection as an influence factor. Results. Many oxidative stress biomarkers have been evaluated in several biological matrices, mostly in the blood. Some of them consistently differ between the cases and controls even when allowing different analytical methods of detection. Conclusions. The present review provides an overview of the oxidative stress biomarkers that have been evaluated in patients with COPD, bringing focus on those molecules whose reliability has been confirmed by the use of different analytical methods.

Small airways were historically considered to be almost irrelevant in the development and control of pulmonary chronic diseases but, as a matter of fact, in the past few years we have learned that they are not so “silent”. Asthma is still a worldwide health issue due to the great share of patients being far from optimal management. Several studies have shown that the deeper lung inflammation plays a critical role in asthma pathogenesis, mostly in these not well-controlled subjects. Therefore, assessing the degree of small airways inflammation and impairment appears to be a pivotal step in the asthmatic patient’s management. It is now possible to evaluate them through direct and indirect measurements, even if some obstacles still affect their clinical application. The success of any treatment obviously depends on several factors but reaching the deeper lung has become a priority and, for inhaled drugs, this is strictly connected to the molecule’s size. The aim of the present review is to summarize the recent evidence concerning the small airway involvement in asthma, its physiopathological characteristics and how it can be evaluated in order to undertake a personalized pharmacological treatment and achieve a better disease control.

Background: The forced expiratory volume at first second (FEV1) during spirometry reflects the severity of chronic obstructive pulmonary disease (COPD) and is known to be an important prognostic factor. It is uncertain whether the response to short-acting bronchodilators may predict long-term outcomes such as hospitalizations and mortality.Methods: We retrospectively studied a total of 1203 consecutive COPD patients without significant comorbidities during a mean (+/- SD) of 69 +/- 39 months of follow-up. At baseline the subjects were classified as those with positive or negative bronchodilator test (BDT) and also in quartiles of absolute bronchodilator response to 400 jig of salbutamol. Hospital visits and mortality were the end points.Results: A positive bronchodilator test was observed in 332 (27.6%) of the patients. There were 73 (21.9%) deaths in patients with a positive BDT versus 253 (28.7%) in those with a negative BDT (p = 0.04). In adjusted Cox regression analysis a positive BDT was significantly associated with a prolonged time to first hospitalization. After stratifying the population by quartiles of response to BDT, a dose response relationship was observed with the best outcomes in the quartile with highest level of airflow reversibility, even after controlling for age, sex, BMI, smoking status and baseline postbronchodilator FEV1.Conclusions: In a large population of well characterized COPD patients without significant co-morbidities, those demonstrating higher levels of reversibility at baseline presented better long-term outcomes even after controlling for other known prognostic factors. (C) 2014 Elsevier Ltd. All rights reserved.

1897 Objectives We further investigated (111)In-pentetreotide SPECT/CT role in GEP tumor diagnosis also evaluating whether the method may have an incremental value than conventional imaging procedures (CIP) such as US, CT and MRI. Methods We studied 135 GEP tumor patients, 91 with functioning and 44 non functioning forms, 89 at initial diagnosis and staging and 46 in follow-up. At histology, 88 GEP were classified as grade 1, 30 as grade 2, 10 as neuroendocrine carcinoma, 4 as mixed adenoneuroendocrine carcinoma and 3 as unknown neuroendocrine origin metastases. All patients underwent at least 2 CIP procedures before (111)In-pentetreotide SPECT/CT performed at 4h and 24h over abdomen or other suspect regions using a hybrid double head system including a low-dose x-ray tube (Infinia, GE Medical System). Results Neoplastic lesions were found in 96/135 patients; SPECT/CT was true positive in 81/96 (84.4%) cases, while CIP in 70/96 (72.9%). Both SPECT/CT and CIP were concordantly true positive in 54/96 cases, only SPECT/CT in 27/96 and only CIP in 15/96. SPECT/CT and CIP comparison for per-patient sensitivity (84.4 vs 71.9%), specificity (100 vs 100%) and accuracy (88.9 vs 80.0%) was not statistically significant. In the 96 positive patients 342 lesions were ascertained (91 hepatic, 137 abdominal extra-hepatic, 114 extra-abdominal) and SPECT/CT detected 289/342 and CIP 228/342 with per-lesion sensitivity of 84.5 vs 66.7% (p Conclusions (111)In-pentetreotide SPECT/CT proved a reliable diagnostic tool in our GEP tumor patients giving useful information for more correct therapeutic strategy. SPECT/CT resulted more sensitive than CIP although the highest performance seems to be achieved with their combined use.

With the aim of providing better clinical characterisation of patients with α1-antitrypsin deficiency (AATD), we analysed the data of adult patients with severe AATD enrolled in the Spanish and Italian national registries. We assessed 745 subjects, 416 of whom were enrolled in the Spanish registry and 329 in the Italian registry. 57.2% were male and 64.9% were smokers or former smokers with a mean±sd age of 49.9±13.8 years. Most (81.2%) were index cases, mainly having the PI*ZZ genotype (73.4%), and the mean±sd diagnostic delay was 9.0±12.1 years. Patients with chronic bronchitis were younger, had better preserved lung function and lower tobacco consumption. Overlap patients (chronic obstructive pulmonary disease with asthma) were mainly females, more frequently never-smokers and received respiratory medications more often. 48% of emphysema, 27.5% of chronic bronchitis and 44.8% of overlap subjects were receiving augmentation therapy. Compared with PI*ZZ patients (n=547), the PI*SZ (n=124) subjects were older at diagnosis and had more preserved lung function, despite a higher mean smoking consumption. Early diagnosis of AATD is still an unmet need. Augmentation therapy is administered to similar proportions of patients with different clinical phenotypes. PI*ZZ patients in both registries had more severe respiratory disease than those with PI*SZ, despite lower smoking levels.

Alpha-1 antitrypsin deficiency (AATD) is a rare genetic condition associated with pulmonary disease, for which national and international registries play a crucial role. Methods: With the aim of providing a clinically better characterisation of AADT patients, we conducted an observational cross sectional study on adult patients affected by severe AATD enrolled in the Spanish and Italian national registries. Results: We assessed 745 subjects, 416 enrolled in the Spanish and 329 in the Italian Registries with a mean age of 49.9 years (SD=13.8). The 57.2% of subjects were male and the 64.9% smokers or former smokers. The majority were index cases (81.2%), mostly with PI*ZZ genotype (73.4%), the mean diagnostic delay was 9 years (SD=12.1). Compared with PI*ZZ (n=547), PI*SZ (n=124) subjects had an older age at diagnosis and better preserved lung function despite a higher mean smoking consumption. Characteristics of PI*ZZ patients with chronic obstructive pulmonary disease (COPD)(n=412) were compared according to GOLD severity stages. Mean age was similar in GOLD I, III and IV, but subjects in GOLD II were older. In GOLD I women and non-index cases were prevailing. The rate of never smokers significantly decreased when severity of COPD increased. Augmentation therapy was administered to 19% of GOLD I, 48% of GOLD II, 59% of GOLD III and 51% of GOLD IV patients. Conclusions: Early diagnosis of AATD is still an unmet need. PI*ZZ patients in both registries had more severe respiratory disease than PI*SZ, despite less smoking consumption. Augmentation therapy is provided to similar proportions of patients with all degrees of severity of airflow obstruction from GOLD II to IV.

Despite the current availability of diagnostic procedures, the diagnosis of solitary pulmonary nodules still remains challenging. The aim of this clinical study is to evaluate the lung magnetic resonance imaging (MRI) with focused conventional sequences and diffusion weighted imaging. Methods: we assessed 55 subjects with pulmonary lesions under blinded conditions using a MRI scanner. The exam was carried out with diffusion-weighted sequences (B500 and B1000 DWIBS) and ADC map with a qualitative and quantitative study. Results: Out of 5 mm nodules (n=23) studied with DWIBS, 16 did not show abnormalities and were unchanged in 1 year follow-up and 3 were not identified compared with CT. DWIBS was positive in 2 cases, false-positive in 1 case and false-negative in 1 case. In 32 lesions >10 mm, histologically confirmed, DWIBS helped the biopsy planning, the definition of neoplastic tissue within atelectatic lung parenchyma, the differentiation of parietal pleura from pleural effusion and the characterization of mediastinal lymph nodes. Conclusion: The study on large size lesions and nodules showed a considerable statistical significance (p

The definition of chronic obstructive pulmonary dis-ease (COPD) as a preventable and treatable conditioncharacterized by a not completely reversible chronicairflow obstruction [1] is so broad and imprecise thatmany different types of patients with distinct clinicalcharacteristics, prognosis and response to treatmentsmay fit in. These different types are now described as“clinical phenotypes” and the interest in their defin-ition and characterisation is growing [2]. Among thesephenotypes, the so-called overlap of syndromes withairflow obstruction is usually poorly considered [3].In a first step of phenotyping, a COPD patient canpotentially be classified as a predominant parenchymaldestructive or predominant airflow limitation phenotypeby using a few clinical, radiological and functional findings[4]. However, when a patient presents characteristics andsymptoms of two or more respiratory diseases at the sametime, this is described as an overlap syndrome. In particu-lar, the asthma-COPD overlap phenotype has beendescribed as symptoms of increased variability of airflowin association with an incompletely reversible airflowobstruction [5]. From a clinical point of view it usuallycorresponds to individuals diagnosed with asthma beforethe age of 40 who, at an older age, fulfil the criteria forCOPD [6]. Recent estimations of its prevalence report thatabout 13-20% of subjects with COPD have the overlapphenotype [6,7], with an increasing trend in the elderlypopulation (up to 50% in those aged over 70 years) [7].Since they have been systematically excluded from bothCOPD and asthma pharmacological clinical trials as notbeing “pure” subjects, it is clear that we cannot really knowthe response to pharmacological treatment of a significantnumber of patients with COPD.Increased reversibility is one of the key differentialaspects of individuals with the overlap asthma-COPDphenotype. Reversibility in COPD is not only possiblebut it is also not so infrequent: indeed, significant re-versibility in COPD is observed frequently in everydayclinical practice and in a series of patients included in thenewly designed clinical trials [8]. Over one half to almosttwo-thirds of the patients with moderate-to-very-severeCOPD participating in the large clinical trial UPLIFT metthe most commonly used criteria for acute bronchodilatorresponsiveness [9]. In a recent study of COPD patientswithout a prior history of asthma, 44% of the subjectsshowed a positive bronchodilator test with an inverse cor-relation between bronchodilator reversibility and theGOLD severity stages [10].Reversibility, however, has not been considered to be areliable parameter to diagnose or classify patients; thereason being that a patient may be reversible or irrevers-ible in different determinations at different time points[11]. This is a consequence of dichotomising a continu-ous variable as positive or negative. In fact, this approachcould be valid for epidemiologic studies but should neverbe used to guide clinical decisions in an individualpatient. Reversibility in clinical practice must be consid-ered as a continuous variable, and therapeutic decisionsshould be made according to the magnitude of thechange. One example will help to explain this concept: apatient with a reversibility of 11.8% in forced expiratoryvolume in the 1

Spirometric reference values for over 80 year-old populations have not been calculated yet. The present study is aimed at estimating the LLN equations for Caucasians. In an ongoing clinical study, 214 subjects aged 80-88 performed valid lung function tests (according to the acceptability and reproducibility criteria of the American Thoracic Society) in 2001/2011 at the University Hospital of Sassari in Sardinia (Italy). During the clinical examination, these subjects: (i) did not report a diagnosis of respiratory diseases, symptoms of dyspnoea at rest/productive cough/bronchospasm, drug use for respiratory problems, and comorbidities (associated with impaired lung function) during lifetime; (ii) reported to be non smokers or to have quit smoking for ≥20 years. Past smokers with >15 pack-years were excluded. Among the 120 males and 94 females, the mean height was 162 and 151 cm, and the percentage of past smokers was 59.2 and 4.3%, respectively. The sex-age specific mean (standard deviation) of FEV1, FVC, and FEV1/FVC ratio is reported in the following table: On average, the FEV1/FVC ratio did not significantly decrease according to age among males (p=0.42), whereas it slightly increased among females (p=0.054). These preliminary results suggest that the reference equations obtained from younger populations cannot be used for the long-term survivors. Appropriate LLN equations will be computed when a greater sample size is reached.