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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. [ABSTRACT FROM AUTHOR]

Desmoplastic small round cell tumor of the pleura is a rare malignancy, with only a few cases reported in the scientific literature. The aim of the present review is to discuss the demographic, pathological, clinical, and therapeutic features of this rare tumor. English-language articles published since 1989, when the first case of desmoplastic small round cell tumor of the pleura was described, were retrieved, and fifteen cases included in fourteen articles were revised. The mean age of the patients was 25.5 years, out of them 60% were males. Chest pain, pleural effusion, and dyspnea were the most common clinical manifestations, while chest roentgenogram and computed tomography were the imaging techniques most commonly used. Surgical biopsy was employed in 80% of the cases for diagnosis. A multidisciplinary approach consisting in a combination of surgery with chemotherapy and radiation therapy was adopted in most cases. Only two patients (13.3%) were alive at 3 years from diagnosis, reflecting the aggressiveness of the disease, and the poor outcomes of the treatments currently available. Desmoplastic small round cell tumors of the pleura are extremely aggressive and challenging to diagnose, because of their rarity and unspecific demographic, clinical, and radiological features. An in-depth knowledge of such features is necessary for the optimal management of patients with this rare malignancy. [ABSTRACT FROM AUTHOR]

A better capacity to identify patients with idiopathic pulmonary fibrosis (IPF) at risk of acute exacerbation (AEIPF) might improve outcomes and reduce healthcare costs. We critically appraised the available evidence of the differences in clinical, respiratory, and biochemical parameters between AEIPF and IPF patients with stable disease (SIPF) by conducting a systematic review and meta-analysis. PubMed, Web of Science and Scopus were reviewed up until August 1, 2022, for studies reporting differences in clinical, respiratory, and biochemical parameters (including investigational biomarkers) between AEIPF and SIPF patients. The Joanna Briggs Institute Critical Appraisal Checklist was used to assess the risk of bias. Twenty-nine cross-sectional studies published between 2010 and 2022 were identified (all with a low risk of bias). Of the 32 meta-analysed parameters, significant differences were observed between groups, assessed through standard mean differences or relative ratios, with age, forced vital capacity, vital capacity, carbon monoxide diffusion capacity, total lung capacity, oxygen partial pressure, alveolar-arterial oxygen gradient, P/F ratio, 6 min walk test distance, C-reactive protein, lactate dehydrogenase, white blood cell count, albumin, Krebs von den Lungen 6, surfactant protein D, high mobility group box 1 protein, and interleukin-1β, 6, and 8. We identified significant differences between AEIPF and SIPF patients in age and specific parameters of respiratory function, inflammation, and epithelial lung damage. Prospective studies are warranted to determine the capacity of these parameters to predict AEIPF more accurately (PROSPERO registration number: CRD42022356640). [ABSTRACT FROM AUTHOR]

It has been reported that during and/or after acute trigeminal nerve stimulation (TNS) a state of sedation, decreased attention and vigilance, with a tendency to fall asleep, occurs. Whether these effects are due to a hypnotic action of TNS is yet to be demonstrated. This pilot study investigates whether acute TNS affects the latency of sleep using the Multiple Sleep Latency Test (MSLT) in healthy subjects. MSLT was performed in 14 healthy subjects after 20 min of real- and a sham-TNS, delivered in two different sessions. Mean latency of sleep across the five naps accorded and the latency of sleep for each nap was determined. All subjects reported a state of relaxation or drowsiness after the real-TNS session. Repeated-measures ANOVA showed no significant differences in sleep latency between the real and sham conditions. The sedative effects of acute TNS do not seem associated to a hypnotic effect. [ABSTRACT FROM AUTHOR]

Tuberculosis remains the major cause of morbidity and mortality by a single infectious agent, particularly in developing countries. In recent years, we have witnessed the emergence of uncommon radiographic patterns of chest tuberculosis. Lymphadenitis is the most common extrapulmonary tuberculosis (TB) manifestation which, in developed countries, occurs more frequently in childhood, but also among adult immigrants from endemic countries and in HIV-infected people. Isolated and asymptomatic mediastinal lymphadenitis is uncommon in immunocompetent adults. We report a case of a young adult man from Senegal affected by sovraclavear and mediastinal TB lymphadenitis, which contains some uncommon elements: no compromised immunity, especially no HIV-infection, no lung lesions, no symptoms of infection or of mediastinum involvement, and rapid response to therapy in terms of mass size reduction. Examination of extra-thoracic lymph nodes and the patient's characteristics guided our diagnostic process to suspect TB. Surgical biopsy and subsequent histopathological and microbiological examinations of lymph material, first by Lowestein-Jensen and BACTEC cultures that remain the gold standard of diagnosis, confirmed the diagnosis. Chest X-ray was inconclusive; however, CT played an important role in the diagnostic course and in the management of the patient, particularly in determining disease activity, offering mediastinum and parenchymal details, as well as in identifying typical features of tuberculous lymph nodes and also of active/non active disease. Six months of antimycobacterial regimen is the recommended treatment in TB lymphadenitis of HIV-negative adults. [ABSTRACT FROM AUTHOR]

The identification of novel prognostic biomarkers might enhance individualized management strategies in patients with idiopathic pulmonary fibrosis (IPF). Although several patient characteristics are currently used to predict outcomes, the prognostic significance of the body mass index (BMI), a surrogate measure of excess fat mass, has not been specifically investigated until recently. We systematically searched PubMed, Web of Science, and Scopus, from inception to July 2022, for studies investigating associations between the BMI and clinical endpoints in IPF. The Joanna Briggs Institute Critical Appraisal Checklist was used to assess the risk of bias. The PRISMA 2020 statement on the reporting of systematic reviews was followed. Thirty-six studies were identified (9958 IPF patients, low risk of bias in 20), of which 26 were published over the last five years. Significant associations between lower BMI values and adverse outcomes were reported in 10 out of 21 studies on mortality, four out of six studies on disease progression or hospitalization, and two out of three studies on nintedanib tolerability. In contrast, 10 out of 11 studies did not report any significant association between the BMI and disease exacerbation. Our systematic review suggests that the BMI might be useful to predict mortality, disease progression, hospitalization, and treatment-related toxicity in IPF (PROSPERO registration number: CRD42022353363). [ABSTRACT FROM AUTHOR]

Human serum paraoxonase-1 (PON-1) is a critical antioxidant defence system against lipid oxidation. Decreased PON-1 activity has been associated with systemic oxidative stress in several disease states. We conducted a systematic review and meta-analysis of plasma/serum concentrations of PON-1 in asthma, a chronic inflammatory airway disease. The electronic databases PubMed, Web of Science, Scopus and Google Scholar were searched from inception to February 2022. In total, 8 studies in 355 asthmatic patients and 289 healthy controls were included in the meta-analysis. Serum PON-1 concentrations were significantly lower in asthmatic patients (SMD = −1.58, 95% CI −2.53 to −0.63; p = 0.001). The pooled SMD values were not substantially altered in sensitivity analysis. There was no publication bias. There were non-significant differences in PON-1 concentrations in patients with severe vs. mild-to-moderate asthma (SMD = − 0.39, 95% CI − 1.00 to 0.22, p = 0.21). Our meta-analysis has shown that serum PON-1 concentrations are significantly lower in patients with asthma, suggesting the presence of an impaired antioxidant defense in this group. [ABSTRACT FROM AUTHOR]

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% males) and 311 controls (mean age 65 years, 56% males) were identified. Pooled results showed that serum homocysteine concentrations were significantly higher in patients with COPD (WMD = 2.91 µmol/L, 95% CI 2.00–3.82 µmol/L; p < 0.001; high certainty of evidence). No publication bias was observed. Our results support the hypothesis that increased homocysteine concentrations are significantly associated with COPD and may account, at least in part, for the increased cardiovascular risk in these patients. [ABSTRACT FROM AUTHOR]

Background: The identification of circulating markers of oxidative stress and systemic inflammation might enhance risk stratification in obstructive sleep apnea (OSA). We investigated the association between specific haematological parameters, as easily measurable markers of oxidative stress and inflammation, and the degree of hypoxia during polysomnography using the apnea hypopnea index (AHI), oxygen desaturation index (ODI), and oxygen saturation (SpO2), in OSA patients. Methods: Associations between polysomnographic parameters and demographic, clinical, and laboratory characteristics were assessed in a consecutive series of patients with OSA attending the Respiratory Disease Unit of the University Hospital of Sassari, north Sardinia (Italy), between 2015 and 2019. Results: In 259 OSA patients (195 males and 64 females), the body mass index (BMI) was significantly and positively associated with the AHI and ODI, and negatively associated with the mean SpO2. No haematological parameter was independently associated with the AHI or ODI. By contrast, albumin, neutrophil, and monocyte counts, and the systemic inflammatory response index (SIRI) were independently associated with a lower SpO2. Conclusions: Our results suggest that albumin and specific haematological parameters are promising markers of reduced oxygen saturation in OSA. [ABSTRACT FROM AUTHOR]

Although polysomnography is the gold standard method to diagnose obstructive sleep apnea syndrome (OSAS), there is an ongoing quest for simpler and relatively inexpensive biomarkers of disease presence and severity. To address this issue, we conducted a systematic review of the potential diagnostic role of the red blood cell distribution width (RDW), a routine hematological parameter of red blood cell volume variability, in OSAS. A total of 1478 articles were initially identified in the databases PubMed, Web of Science, Scopus, Embase, and Google Scholar, from their inception to February 2023, and 20 were selected for final analysis. The RDW was significantly higher in OSAS than in non-OSAS subjects (SMD = 0.44, 95% CI 0.20 to 0.67, p < 0.001; low certainty of evidence). In univariate meta-regression, the mean oxygen saturation (SpO2) was significantly associated with the effect size. No significant between-group differences were observed in subgroup analyses. Notably, in OSAS subjects, the RDW SMD progressively increased with disease severity. In conclusion, these results suggest that the RDW is a promising biomarker of OSAS (PROSPERO registration number: CRD42023398047). [ABSTRACT FROM AUTHOR]

Derived inflammatory indexes from routine hematological parameters might be useful for predicting early-response vs. late/non-response to dupilumab, the first biological agent approved for moderate-to-severe atopic dermatitis (AD). We tested this hypothesis by retrospectively investigating the association between pre-specified baseline inflammatory indexes and dupilumab response (≥50% reduction in the Eczema Area and Severity Index, EASI 50) at 4 and 16 weeks in a consecutive series of 66 AD patients (38 males and 28 females). Forty-six patients (69.7%) were early-responders at 4 weeks, whereas the remaining twenty (30.3%) were late/non-responders at 16 weeks. In logistic regression, the platelet-to-lymphocyte ratio (PLR) was independently associated with early-response (OR = 1.0159, 95% CI 1.0005 to 1.0315, p = 0.0426). The predictive performance of PLR and other derived indexes towards early-response was further improved by their combination with serum IgE concentrations, with a maximum AUC value for the combined systemic immune inflammation index (SII)-IgE of 0.797 (95% CI = 0.677 to 0.884, p < 0.0001). Derived inflammatory indexes, particularly SII-IgE, might be useful to identify early-responders to dupilumab and develop alternative treatment protocols for late/non-responders. [ABSTRACT FROM AUTHOR]

Background: In epidemiological studies, continuous measures of asthma severity should be used to catch the heterogeneity of phenotypes. This study aimed at developing and validating continuous measures of asthma severity in adult patients with ever asthma from the general population, to be used in epidemiological studies. Methods: Respiratory symptoms, anti-asthmatic treatment and lung function were measured on 520 patients with ever asthma aged 20–64 years from the general Italian population (GEIRD study; 2007/2010). The variables that represent the same dimension of asthma severity were identified through an exploratory factor analysis and were summarized through a multiple factor analysis. Results: Only respiratory symptoms and anti-asthmatic treatment were summarized in a continuous score (STS). STS ranges from 0 (no symptoms/treatment) to 10 (maximum symptom frequency and treatment intensity). STS was positively correlated with the Global Initiative for Asthma classification of asthma severity computed on the 137 cases with a doctor's diagnosis (Spearman’s coefficient = 0.61, p-value<0.0001) (concurrent validity). Furthermore, using a cohort of 1,097 European asthmatics (ECRHS II study; 1999/2002), increasing STS levels at baseline (1991/1993) were positively associated with long-term outcomes (hospitalization and lost workdays for breathing problems, asthma attack frequency and use of asthma controllers) (predictive validity). Finally, the STS scores computed from the GEIRD and ECRHS II data were comparable (Lin’s coefficient = 0.95, p-value<0.0001) (replication analysis). Conclusions: STS is a valid and replicable measure of asthma severity in adults, which could be used in association studies. [ABSTRACT FROM AUTHOR]

The neutrophil-to-lymphocyte ratio (NLR) predicts adverse outcomes in stable chronic obstructive pulmonary disease (COPD); however, its prognostic role in acute exacerbations (AECOPD) is less clear. We conducted a systematic review and meta-analysis of the association between the NLR on admission and adverse outcomes (mortality, need for mechanical ventilation, transfer to the intensive care unit, length of stay, pulmonary hypertension, or their combination) in AECOPD by searching PubMed, Web of Science, and Scopus from inception to April 2022. Risk of bias and certainty of evidence were assessed using the Joanna Briggs Institute Critical Appraisal Checklist and the Grades of Recommendation, Assessment, Development, and Evaluation, respectively. In 15 studies (n = 10,038 patients), the NLR was significantly associated with the risk of adverse outcomes (odds ratio = 1.054, 95% CI 1.016 to 1.093, p = 0.005; low certainty of evidence; standard mean difference = 0.82, 95% CI 0.57 to 1.06, p < 0.001; high certainty of evidence). Pooled sensitivity, specificity, and area under the curve were 0.71 (95% CI 0.64 to 0.77), 0.73 (95% CI 0.65 to 0.80), and 0.78 (95% CI 0.74 to 0.81), respectively. In our study, the NLR on admission was significantly associated with adverse outcomes in AECOPD patients, suggesting the potential utility of this biomarker for early risk stratification and management in this group. [ABSTRACT FROM AUTHOR]

Background: Chronic obstructive pulmonary disease (COPD) is a complex, progressive respiratory condition characterized by heterogeneous clinical presentations (phenotypes). The aim of this study was to assess the prevalence of the main COPD phenotypes and match each phenotype to the most fitting clinical and lung function profile. Methods: The CLIMA (Clinical Phenotypes in Actual Clinical Practice) study was an observational, cross-sectional investigation involving twenty-four sites evenly distributed throughout Italy. Patients were tentatively grouped based on their history and claimed prevailing symptoms at recruitment: chronic cough (CB, suggesting chronic bronchitis); dyspnoea (possible emphysema components, E); recurrent wheezing (presuming asthma components, A). Variables collected were: anagraphics; smoking habit; history of asthma; claim of >1 exacerbations in the previous year; blood eosinophil count; total blood IgE and alpha1 anti-trypsin (α1-AT) levels; complete lung function, and the chest X-ray report. mMRC, CAT, BCS, EQ5d-5L were also used. The association between variables and phenotypes were checked by Chi-square test and multinomial logistic regression. Results: The CB phenotype was prevalent (48.3%), followed by the E and the A phenotypes (38.8% and 12.8%, respectively). When dyspnea was the prevailing symptom, the probability of belonging to the COPD-E phenotype was 3.40 times higher. Recurrent wheezing was mostly related to the COPD-A phenotype. Lung function proved more preserved in the COPD-CB phenotype. Smoke; n. exacerbations/year; VR, and BODE index were positively correlated with the COPD-E phenotype, while SpO2, FEV1/FVC, FEV1/VC, and FEV1 reversibility were negatively correlated. Lower DLco values were highly probative for the COPD-E phenotype (p<0.001). Conversely, smoke, wheezing, plasma eosinophils, FEV1 reversibility, and DLco were positively correlated with the COPD-A phenotype. The probability of belonging to the COPD-A phenotype raised by 2.71 times for any increase of one unit in % plasma eosinophils (p<0.001). Also multiparametrical scores contributed to discriminate the three phenotypes. Conclusion: the recognition of the main phenotypes of COPD can be effectively pursued by means of a few clinical and instrumental parameters, easy to obtain also in current daily practice. The phenotypical approach is crucial in the management of COPD as it allows to individualize the therapeutic strategy and to obtain more effective clinical outcomes [ABSTRACT FROM AUTHOR]

Background: Haemoptysis is a challenging symptom that can be associated with potentially life-threatening medical conditions. Follow-up is key in these patients to promptly detect new or misdiagnosed pathologic findings. Few prospective studies have evaluated long-term prognostic outcomes in patients with haemoptysis. Furthermore, the role played by antiplatelet and anticoagulant drugs on mortality and recurrence rates is unclear. The aim of this study was to assess mortality after 18 months of follow-up. Furthermore, the incidence of recurrence and the risk factors for recurrence and death were evaluated (including the role played by anticoagulant and antiplatelet drugs).Methods: Observational, prospective, multicentre, Italian study.Results: 451/606 (74.4%) recruited patients with haemoptysis completed the 18 months follow-up. 22/604 (3.6%) diagnoses changed from baseline to the end of the follow-up. 83/604 (13.7%) patients died. In 52/83 (62.7%) patients, death was the outcome of the disease which caused haemoptysis at baseline. Only the diagnosis of lung neoplasm was associated with death (OR (95%CI): 38.2 (4.2-347.5); p-value: 0.0001). 166 recurrences were recorded in 103/604 (17%) patients. The diagnosis of bronchiectasis was significantly associated with the occurrence of a recurrence (OR (95% CI): 2.6 (1.5-4.3)); p-value < 0.0001). Anticoagulant, antiaggregant, and anticoagulant plus antiaggregant drugs were not associated with an increased risk of death and recurrence.Conclusions: Our study showed a low mortality rate in patients with haemoptysis followed-up for 18 months. Pulmonary malignancy was the main aetiology and the main predictor of death, whereas bronchiectasis was the most frequent diagnosis associated with recurrence. Antiplatelet and/or anticoagulant therapy did not change the risk of death or recurrence. Follow-up is recommended in patients initially diagnosed with lower airways infections and idiopathic bleeding.Trial Registration: NCT02045394. [ABSTRACT FROM AUTHOR]

Introduction: The early identification of factors that predict the length of hospital stay (HS) in patients affected by coronavirus desease (COVID-19) might assist therapeutic decisions and patient flow management. Methodology: We collected, at the time of admission, routine clinical, laboratory, and imaging parameters of hypoxia, lung damage, inflammation, and organ dysfunction in a consecutive series of 50 COVID-19 patients admitted to the Respiratory Disease and Infectious Disease Units of the University Hospital of Sassari (North-Sardinia, Italy) and alive on discharge. Results: Prolonged HS (PHS, >21 days) patients had significantly lower PaO2/FiO2 ratio and lymphocytes, and significantly higher Chest CT severity score, C-reactive protein (CRP) and lactic dehydrogenase (LDH) when compared to non-PHS patients. In univariate logistic regression, Chest CT severity score (OR = 1.1891, p = 0.007), intensity of care (OR = 2.1350, p = 0.022), PaO2/FiO2 ratio (OR = 0.9802, p = 0.007), CRP (OR = 1.0952, p = 0.042) and platelet to lymphocyte ratio (OR = 1.0039, p = 0.036) were significantly associated with PHS. However, in multivariate logistic regression, only the PaO2/FiO2 ratio remained significantly correlated with PHS (OR = 0.9164; 95% CI 0.8479-0.9904, p = 0.0275). In ROC curve analysis, using a threshold of 248, the PaO2/FiO2 ratio predicted PHS with sensitivity and specificity of 60% and 91%, respectively (AUC = 0.780, 95% CI 0.637-0.886 p = 0.002). Conclusions: The PaO2/FiO2 ratio on admission is independently associated with PHS in COVID-19 patients. Larger prospective studies are needed to confirm this finding. [ABSTRACT FROM AUTHOR]

Increased concentrations of serum aspartate transaminase (AST) and alanine transaminase (ALT) are common in COVID‐19 patients. However, their capacity to predict mortality, particularly the AST/ALT ratio, commonly referred to as the De Ritis ratio, is unknown. We investigated the association between the De Ritis ratio on admission and in‐hospital mortality in 105 consecutive patients with coronavirus disease of 2019 (COVID‐19) admitted to three COVID‐19 referral centres in Sardinia, Italy. The De Ritis ratio was significantly lower in survivors than nonsurvivors (median: 1.25; IQR: 0.91‐1.64 vs 1.67; IQR: 1.38‐1.97, P =.002) whilst there were no significant between‐group differences in ALT and AST concentrations. In ROC curve analysis, the AUC value of the De Ritis ratio was 0.701 (95% CI 0.603‐0.787, P =.0006) with sensitivity and specificity of 74% and 70%, respectively. Kaplan‐Meier survival curves showed a significant association between the De Ritis ratio and mortality (logrank test P =.014). By contrast, no associations were observed between the ALT and AST concentrations and mortality (logrank test P =.83 and P =.62, respectively). In multivariate Cox regression analysis, the HR in patients with De Ritis ratios ≥1.63 (upper tertile of this parameter) remained significant after adjusting for age, gender, smoking status, cardiovascular disease, intensity of care, diabetes, respiratory diseases, malignancies and kidney disease (HR: 2.46, 95% CI 1.05‐5.73, P =.037). Therefore, the De Ritis ratio on admission was significantly associated with in‐hospital mortality in COVID‐19 patients. Larger studies are required to confirm the capacity of this parameter to independently predict mortality in this group. [ABSTRACT FROM AUTHOR]

Purpose: Inflammation and immunity play a pivotal but yet unclear role in idiopathic pulmonary fibrosis (IPF), a chronic disorder characterized by progressive damage of lung parenchyma and severe loss of lung function despite optimal treatment. However, the pathophysiological and predictive role of combined blood cell count indexes of inflammation in IPF is uncertain. Methods: Seventy-three patients with IPF and 62 healthy subjects matched for age, gender and smoking status were included in this cross-sectional study. Results: We found significant differences in neutrophil to lymphocyte ratio (NLR), derived neutrophil to lymphocyte ratio (dNLR), monocyte to lymphocyte ratio (MLR), platelet to lymphocyte ratio (PLR), systemic inflammation response index (SIRI) and aggregate index of systemic inflammation (AISI) between IPF patients and healthy controls. In logistic regression, all combined blood inflammation indexes, barring PLR, were independently associated with the presence of IPF after adjusting for age, gender, body mass index and smoking status. Furthermore, significant associations between FVC% and NLR, LMR, SIRI and AISI, and between DLCO% and NLR, dNLR, LMR, SIRI and AISI, were observed. Conclusions: In conclusion, our data indicate significant alterations of combined blood cell count indexes of inflammation in IPF. [ABSTRACT FROM AUTHOR]

Objective: To analyse the associations between chronic respiratory diseases and intakes of total flavonoids and their major subclasses (flavanones, anthocyanins, flavan-3-ols, flavonols, flavones, polymers and proanthocyanidins).Design: Multi-case-control study.Setting: The analysis was conducted in the frame of the Genes Environment Interaction in Respiratory Diseases (GEIRD) study. The European Prospective Investigation into Cancer and Nutrition FFQ was used to ascertain dietary intake. Multinomial regression models adjusting for age, sex, centre, BMI, smoking habit, alcohol intake, education, total energy intake, vitamin C intake and total fruit intake were used to examine the associations between dietary exposures and the relative risk ratio (RRR) of being a case.Participants: Individuals (n 990) hierarchically defined as follows: cases with asthma (current, n 159; past, n 78), chronic bronchitis (n 47), rhinitis (allergic rhinitis, n 167; non-allergic rhinitis, n 142) and controls (n 97).Results: An increase of 1 sd in flavanones was associated with a reduced risk of non-allergic rhinitis (adjusted RRR = 0·68, 95 % CI 0·47, 0·97); a similar result was found comparing the highest v. lowest quartile of flavanones intake (adjusted RRR = 0·24, 95 % CI 0·10, 0·59).Conclusions: Flavonoids contained in fruits and vegetables, especially flavanones, might reduce the risk of non-allergic rhinitis. No associations were found between other flavonoids and the considered outcomes. [ABSTRACT FROM AUTHOR]

Background: 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. Design: We comprehensively investigated the plasma concentrations of transsulfuration pathway analytes, and their relationship with markers of oxidative stress and inflammation, to identify which low molecular thiols might play a pathophysiological role both in CVD and in COPD. Hcy, cysteine (Cys), glutathione (GSH), cysteinylglycine (CysGly), glutamylcysteine (GluCys), taurine (Tau), oxidative stress markers (TBARS and protein‐SH, PSH) and the inflammation marker kynurenine/tryptophan (Kyn/Trp) ratio were measured in 54 COPD patients and 54 control subjects. Results: We found increased concentrations of total Hcy (P <.01) and total CysGly (P <.05) in COPD patients when compared to controls. Total Hcy and CysGly were also significantly associated with abnormal lung function parameters and COPD severity. In COPD patients, total Hcy was significantly associated with the Kyn/Trp ratio (P =.0017) whereas total CysGly was significantly associated with both PSH (P =.0298) and the Kyn/Trp ratio (P = <.0001). Conclusion: Both total Hcy and CysGly concentrations were significantly associated with the presence and severity of COPD and with markers of oxidative stress (total CysGly) and inflammation (total Hcy and CysGly). This suggests that specific low molecular mass thiols might play a role in the inflammatory and oxidative stress pathways involved in both CVD and COPD. [ABSTRACT FROM AUTHOR]

Introduction: Coronavirus disease 19 (COVID-19) is the greatest pandemic in modern history. Laboratory test alterations have been described in COVID-19 patients, but differences with other pneumonias have been poorly investigated to date, especially in Caucasian populations. The aim of this study was to investigate differences and prognostic potential of routine blood tests in a series of Italian patients with COVID-19 and non-COVID-19 interstitial pneumonia. Methodology: Clinical data and routine laboratory tests of a consecutive series of 30 COVID-19 patients and 30 age and sex matched patients with non COVID-19 interstitial pneumonia have been retrospectively collected. Differences in laboratory tests between patients with COVID- 19 and non COVID-19 pneumonias have been investigated, as well as differences between COVID-19 survivors and non survivors. Results: COVID-19 patients had lower white blood cells, monocytes, neutrophils, and higher platelet counts. In addition, COVID-19 patients showed higher mean platelet volume, lower C reactive protein concentrations, and higher De Ritis ratio. Combined blood cell indexes of systemic inflammation were significantly lower in COVID-19 patients. In further analysis of the COVID-19 group, the neutrophil count, neutrophil to lymphocyte ratio (NLR), derived NLR, systemic inflammation response index and De Ritis ratio, were significantly higher in non survivors than in survivors, while the number of platelets was significantly lower in non survivors. Conclusions: Our study showed several alterations in blood cell populations and indexes in patients with COVID-19 pneumonia in comparison with patients with non COVID-19 pneumonia. Some of these indexes showed promising prognostic abilities. Further studies are necessary to confirm these results. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) is a heterogeneous entity with different clinical phenotypes, such as asthma-COPD overlap (ACO). The aim of this retrospective study was to compare routine blood biomarkers in patients with ACO and the remaning COPD phenotypes. Data were collected from stable COPD patients visited in during 2018, including C-reactive protein (CRP), fibrinogen, neutrophyl/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR).A total of 77 patients with COPD were included, 24 (31%) fulfilled the diagnosis of ACO. Clinically, patients with ACO presented more dyspnoea and wheezing. Regarding laboratory parameters, both groups had low levels of lymphocytes, especially the non-ACO group (24.2% vs. 29.3%; p = 0.031), patients with ACO had significantly higher eosinophil counts (4.7% vs. 1.9%; p < 0.001) but a lower percentage of neutrophils (56.8% vs. 64.7%; p = 0.003), NLR and PLR (2.5 vs. 3.8; p = 0.013 and 115 vs. 160; p = 0.063, respectively). In conclusion, besides the expected eosinophilic inflammation in patients with ACO, both groups had low levels of lymphocytes, especially the non-ACO group. The low levels of lymphocytes, in particular in non-ACO patients, should be confirmed in larger studies. [ABSTRACT FROM AUTHOR]

Background and objectives: Cardiovascular and respiratory diseases can frequently coexist. Understanding their link may improve disease management. We aimed at assessing the associations of chronic bronchitis (CB), asthma and rhinitis with cardiovascular diseases and risk factors in the general population. Methods: We used data collected in the Gene Environment Interactions in Respiratory Diseases study, an Italian multicentre, multicase-control study. Among 2463 participants (age 21–86, female 50%) who underwent standardized interviews, skin prick and lung function tests, we identified 254 cases of CB without airflow obstruction, 418 cases of asthma without CB, 959 cases of rhinitis alone, and 832 controls. The associations of respiratory diseases with reported cardiovascular risk factors (lifestyles, hypertension, dyslipidaemia), heart disorders (myocardial infarction, coronary thrombosis, angina, aorta or heart surgery) and intermittent claudication were estimated through relative risk ratios (RRR) by multinomial logistic regression models. Results: Compared to controls, CB cases were more likely to be heavy smokers, alcohol consumers, physically inactive, and to suffer from hypertension or dyslipidaemia; rhinitis cases were less obese but more likely to have hypertension. Asthma was significantly associated with current smoking. After adjusting for cardiovascular risk factors, heart disorders were associated with CB (RRR[95%CI]: 1.58[1.12–2.22]) and rhinitis (1.35[0.98–1.85]) and intermittent claudication was associated with CB (3.43[2.52–4.67]), asthma (1.51[1.04–2.21]) and rhinitis (2.03[1.34–3.07]). Conclusions: CB, asthma and rhinitis were associated with cardiovascular risk factors and diseases. In particular, CB shared with cardiovascular diseases almost all risk factors and was strongly associated with a higher risk of heart disorders and intermittent claudication. [ABSTRACT FROM AUTHOR]

Summary: Background: Fat intake has been associated with respiratory diseases, with conflicting results. Objective: We studied the association between asthma and rhinitis with dietary fats, and their food sources in an Italian population. Methods: Clinical and nutritional information was collected for 871 subjects (aged 20‐84) from the population‐based multi‐case‐control study Genes Environment Interaction in Respiratory Diseases (GEIRD): 145 with current asthma (CA), 77 with past asthma (PA), 305 with rhinitis and 344 controls. Food intake was collected using the EPIC (European Investigation into Cancer and Nutrition) Food Frequency Questionnaire. The associations between fats and respiratory diseases were estimated by multinomial models. Fats and their dietary sources were analysed both as continuous variables and as quartiles. Results: Monounsaturated fatty acids and oleic acid were associated with a reduced risk of CA in both continuous (RRR = 0.68, 95%CI: 0.48; 0.96; RRR = 0.69; 95%CI: 0.49; 0.97, per 10 g, respectively) and per‐quartile analyses (p for trend = 0.028 and 0.024, respectively). Olive oil was associated with a decreased risk of CA (RRR = 0.80; 95%CI: 0.65; 0.98 per 10 g). An increased risk of rhinitis was associated with moderate total fat and SFA intake. Conclusions: High dietary intakes of oleic acid and of olive oil are associated with a lower risk of asthma but not of rhinitis. [ABSTRACT FROM AUTHOR]

In this study we aimed at identifying main demographic, laboratory and environmental factors influencing the level of urinary biomarkers (DNA-derived 8-oxodG and lipid membrane-derived 8-isoprostane), and deriving their adjusted 95% reference intervals (RI) in a sample of healthy people from the general population. Data from 281 healthy subjects from the Gene Environment Interactions in Respiratory Diseases survey were used in this study. Generalized additive models for location, scale and shape (GAMLSS) were used to find determinants of the biomarkers among gender, age, season and distance from collection (DFC), and to predict their RI. The RI of the biomarkers stratified by season and adjusted for DFC showed a slight statistically significant decrease in the biomarkers at the increasing DFC in two seasons, except the 8-oxodG during the warm season: median levels at the min and max values of DFC were (ng/mgcreat) 7.0–1.1 in the cold and 3.9–3.9 in the warm seasons for 8-oxodG, 0.7–0.2 in the cold and 1.3–0.6 in the warm seasons for 8-isoprostane. Both the biomarkers should be evaluated in association with the DFC and season in large epidemiological studies. The (semi)parametric GAMLSS method is a useful and flexible technique, which makes it possible to estimate adjusted RI. [ABSTRACT FROM AUTHOR]

Experimental evidence suggests that oxidative stress (OS) may increase the activity of arginine methylating enzymes that produce the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA). In addition, it is well documented that OS can significantly decrease the synthesis and/or activity of ADMA degrading enzymes, thus causing ADMA accumulation in biological fluids. Recent reports have focused on circulating methylated arginine concentrations in chronic obstructive pulmonary disease, a disease characterized by a significant increase in OS. This review discusses the results of these studies and the opportunities for further research in this area. [ABSTRACT FROM AUTHOR]

Background: Tobacco consumption is the largest avoidable health risk. Understanding changes of smoking over time and across populations is crucial to implementing health policies. We evaluated trends in smoking initiation between 1970 and 2009 in random samples of European populations. Methods: We pooled data from six multicentre studies involved in the Ageing Lungs in European Cohorts consortium, including overall 119,104 subjects from 17 countries (range of median ages across studies: 33–52 years). We estimated retrospectively trends in the rates of smoking initiation (uptake of regular smoking) by age group, and tested birth cohort effects using Age-Period-Cohort (APC) modelling. We stratified all analyses by sex and region (North, East, South, West Europe). Results: Smoking initiation during late adolescence (16–20 years) declined for both sexes and in all regions (except for South Europe, where decline levelled off after 1990). By the late 2000s, rates of initiation during late adolescence were still high (40–80 per 1000/year) in East, South, and West Europe compared to North Europe (20 per 1000/year). Smoking initiation rates during early adolescence (11–15 years) showed a marked increase after 1990 in all regions (except for North European males) but especially in West Europe, where they reached 40 per 1000/year around 2005. APC models supported birth cohort effects in the youngest cohorts. Conclusion: Smoking initiation is still unacceptably high among European adolescents, and increasing rates among those aged 15 or less deserve attention. Reducing initiation in adolescents is fundamental, since youngsters are particularly vulnerable to nicotine addiction and tobacco adverse effects. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: The main white blood cell populations, neutrophils and lymphocytes, are involved in the pathophysiology of chronic obstructive pulmonary disease (COPD). We conducted a systematic review and meta‐analysis of studies investigating the relationship between the neutrophil to lymphocyte ratio (NLR, a marker of subclinical inflammation), presence of COPD, and its exacerbations. Methods: A comprehensive literature search was conducted in Pubmed, Web of Science and Scopus databases; two investigators independently reviewed suitable studies. Results: Nine studies, from 247 initially identified, were included in the meta‐analysis. Seven studies, in 775 COPD patients with stable disease and 496 healthy controls, showed a significant increase in NLR values in stable COPD (standardised mean difference, SMD, 0.773, 95% CI 0.410‐1.136; P < 0.001). Furthermore, in six studies in 527 COPD patients with acute exacerbation and 620 COPD patients with stable disease, NLR values were significantly higher in patients with exacerbations (random effects SMD 0.850, 95% CI 0.549‐1.151; P < 0.001). Conclusions: Our meta‐analysis showed that NLR values are significantly higher in stable COPD patients when compared to healthy individuals, although the magnitude of the difference is reduced after trim and fill adjustment, and in patients with COPD exacerbations when compared to patients with stable disease. Further studies, in larger cohorts, are needed to confirm whether the NLR is a useful tool in discriminating between COPD patients with stable disease, those with acute exacerbations, and subjects without the disease. [ABSTRACT FROM AUTHOR]

air pollution is a complex mixture; novel multipollutant approaches could help understanding the health effects of multiple concomitant exposures to air pollutants. to assess the relationship of long-term air pollution exposure with the prevalence of respiratory/allergic symptoms and diseases in an Italian multicenter study using single and multipollutant approaches. 14420 adults living in 6 Italian cities (Ancona, Pavia, Pisa, Sassari, Turin, Verona) were investigated in 2005–2011 within 11 different study cohorts. Questionnaire information about risk factors and health outcomes was collected. Machine learning derived mean annual concentrations of PM 10 , PM 2.5 , NO 2 and mean summer concentrations of O 3 (μg/m3) at residential level (1-km resolution) were used for the period 2013–2015. The associations between the four pollutants and respiratory/allergic symptoms/diseases were assessed using two approaches: a) logistic regression models (single-pollutant models), b) principal component logistic regression models (multipollutant models). All the models were adjusted for age, sex, education level, smoking habits, season of interview, climatic index and included a random intercept for cohorts. the three-year average (± standard deviation) pollutants concentrations at residential level were: 20.3 ± 6.8 μg/m3 for PM 2.5 , 29.2 ± 7.0 μg/m3 for PM 10 , 28.0 ± 11.2 μg/m3 for NO 2 , and 70.9 ± 4.3 μg/m3 for summer O 3. Through the multipollutant models the following associations emerged: PM 10 and PM 2.5 were related to 14–25% increased odds of rhinitis, 23–34% of asthma and 30–33% of night awakening; NO 2 was related to 6–9% increased odds of rhinitis, 7–8% of asthma and 12% of night awakening; O 3 was associated with 37% increased odds of asthma attacks. Overall, the Odds Ratios estimated through the multipollutant models were attenuated when compared to those of the single-pollutant models. this study enabled to obtain new information about the health effects of air pollution on respiratory/allergic outcomes in adults, applying innovative methods for exposure assessment and multipollutant analyses. • Air pollution is related to increased global prevalence of allergic disease. • New evidence on health effects in adults has been added. • The multipollutant approach has given a thorough information on health effects. • New evidence has been brought about NO 2 and summer O 3 health effects. • PM 2.5 and PM 10 have been confirmed as main drivers of health effects. [ABSTRACT FROM AUTHOR]

Clinical and radiological manifestations of tuberculosis (TB) are heterogeneous, and differential diagnosis can include both benign and malignant diseases (e.g., sarcoidosis, metastatic diseases, and lymphoma). Diagnostic dilemmas can delay appropriate therapy, favoring Mycobacterium tuberculosis transmission. We report on a case of TB in an immunocompetent, Somalian 22-year-old boy admitted in the respiratory unit of an Italian university hospital. His symptoms and clinical signs were thoracic pain, weight loss, latero-cervical, mediastinal, and abdominal lymphadenopathy. Smear microscopy and PCR were negative for Mycobacterium tuberculosis . The unclear histological pattern, the unusual clinical presentation, the CT scan signs, the BAL lymphocytes suggested the suspicion a lymphoma. Culture conversion proved Mycobacterium tuberculosis infection. This case report highlights the risk of misdiagnosis in patients with generalized lympho-adenopathy and pulmonary infiltrates, particularly in Africans young patients. [ABSTRACT FROM AUTHOR]

An exploratory study of trace elements in ALS and their relationships with clinical severity was detected. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that causes irreversible damage in humans, with the consequent loss of function of motoneurons (MNs), with a prognosis up to 5 years after diagnosis. Except to genetic rare cases it is not known the etiology of the disorder. Aim of our research is to investigate the possible role of heavy metals in the severity of the disease. In this study, by the use of plasma mass (ICP-MS), we have analyzed the content of essential and heavy metals such: Pb, Cd, Al, Hg, Mn, Fe, Cu, Zn, Se, Mg, and Ca, in blood, urine and hair of ALS patients and controls; moreover we divided the patients in two groups for disease severity and analyzed the difference among the groups, in order to study a possible involvement of metals in the severity of the damage. Our results suggest a protective role of Selenium, involved in protective antioxidant mechanisms, and a risk factor in the case of presence of Lead in blood. The levels of the other metals are not easy to interpret, because these may be due to life style and for essential metals a consequence of the disease condition, not a cause. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Deciduoid mesothelioma is a rare variant of malignant epithelioid mesothelioma. It often involves the peritoneum, but also thoracic cases have been reported. The aim of the present review is to describe the demographic, clinical, radiological, and pathological features of such a rare variant of thoracic mesothelioma, and the state of the art regarding the therapeutic approaches currently available. Data source: English‐language articles published from 1985 to June 2016, and related to thoracic deciduoid mesothelioma cases were retrieved using the Pubmed database. Study selection: The search terms were “mesothelioma,” “thoracic mesothelioma,” “epithelial mesothelioma,” “pleural mesothelioma,” and “deciduoid mesothelioma.” Results: Forty‐four cases included in 16 articles, published in the period under investigation, were analyzed in detail. Conclusions: The mean age of the patients was 63 years, and the male to female ratio 1.7:1. Approximately 58% had exposure to asbestos, and 73% had a smoking history; familiarity was rarely reported. The most common anatomical site of origin was the right pleura, and the most frequent clinical manifestations were chest pain, dyspnea, cough, and weight loss. Thoracic X‐ray and computed tomography were the imaging techniques most employed for diagnosis and surgical planning. The pathological diagnosis was obtained by examination of surgical or biopsy specimens in most cases. The best treatment strategy of deciduoid mesothelioma is a matter of debate; nevertheless a multidisciplinary approach is currently the best option for the choice of the adequate therapeutic scheme. [ABSTRACT FROM AUTHOR]

Background Alterations in global DNA methylation have been associated with oxidative stress (OS). Since chronic obstructive pulmonary disease (COPD) is characterized by increased oxidative stress we aimed to evaluate the levels of global DNA methylation in this patient group. Methods We assessed methylcytosine (mCyt) levels in DNA from blood collected in 43 COPD patients (29 with mild and 14 with moderate disease) and 43 age- and sex-matched healthy controls. Results DNA methylation was significantly lower in COPD patients vs. controls (4.20 ± 0.18% mCyt vs. 4.29 ± 0.18% mCyt, p = 0.02). Furthermore, DNA methylation in COPD patients with moderate disease was significantly lower than that in patients with mild disease (4.14 ± 0.15% mCyt vs. 4.23 ± 0.19% mCyt, p < 0.05). Univariate logistic regression analysis showed that lower DNA methylation levels were associated with presence of COPD (crude OR = 0.06, 95% CI 0.00 to 0.67, p = 0.023). This relationship remained significant after adjusting for several confounders (OR 0.03, 95% CI 0.00 to 0.67; p = 0.028). Receiver operating characteristics (ROC) curve analysis demonstrated the area under the curve of mCyt was 0.646, with 46.6% sensitivity and 79.1% specificity for presence of COPD. Conclusions There were no significant correlations between methylation and OS indices. The presence and severity of COPD is associated with progressively lower DNA methylation in blood. However, this epigenetic alteration seems independent of oxidative stress. [ABSTRACT FROM AUTHOR]

Sardinian (Italy) island population has a uniquely high incidence of amyotrophic lateral sclerosis (ALS). Essential trace element levels in blood, hair, and urine of ALS Sardinian patients were investigated in search of valid biomarkers to recognize and predict ALS. Six elements (Ca, Cu, Fe, Mg, Se, and Zn) were measured in 34 patients compared to 30 age- and sex-matched healthy controls by a validated method. Levels of Ca and Cu in blood and of Se and Zn in hair were significantly higher in ALS than in controls, while urinary excretion of Mg and Se was significantly decreased. The selected cut-off concentrations for these biomarkers may distinguish patients with or without ALS with sufficient sensitivity and specificity. Many positive (as Se-Cu and Se-Zn) and negative associations (as Ca-Mg and Ca-Zn) between elements suggested that multiple metals involved in multiple mechanisms have a role in the ALS degeneration. [ABSTRACT FROM AUTHOR]

Background Pollen exposure has acute adverse effects on sensitized individuals. Information on the prevalence of respiratory diseases in areas with different pollen concentrations is scanty. Aim We performed an ecologic analysis to assess whether the prevalence of allergic rhinitis and asthma in young adults varied across areas with different pollen concentrations in Italy. Methods A questionnaire on respiratory diseases was delivered to random samples of 20–44 year-old subjects from six centers in 2005–2010. Data on the daily air concentrations of 7 major allergologic pollens ( Poaceae , Urticaceae , Oleaceae , Cupressaceae , Coryloideae , Betula and Ambrosia ) were collected for 2007–2008. Center-specific pollen exposure indicators were calculated, including the average number of days per year with pollens above the low or high concentration thresholds defined by the Italian Association of Aerobiology. Associations between pollen exposure and disease prevalence, adjusted for potential confounders, were estimated using logistic regression models with center as a random-intercept. Results Overall, 8834 subjects (56.8%) filled in the questionnaire. Allergic rhinitis was significantly less frequent in the centers with longer periods with high concentrations of at least one (OR per 10 days = 0.989, 95%CI: 0.979–0.999) or at least two pollens (OR = 0.974, 95%CI: 0.951–0.998); associations with the number of days with at least one (OR = 0.988, 95%CI: 0.972–1.004) or at least two (OR = 0.985, 95%CI: 0.970–1.001) pollens above the low thresholds were borderline significant. Asthma prevalence was not associated with pollen concentrations. Conclusions Our study does not support that the prevalence of allergic rhinitis and asthma is greater in centers with higher pollen concentrations. It is not clear whether the observed ecologic associations hold at the individual level. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) is a progressive condition characterized by airflow limitation associated with an abnormal inflammatory response of the lungs to noxious particles and gases, caused primarily by cigarette smoking. Increased oxidative burden plays an important role in the pathogenesis of COPD. There is a delicate balance between the toxicity of oxidants and the protective function of the intracellular and extracellular antioxidant defense systems, which is critically important for the maintenance of normal pulmonary functions. Several biomarkers of oxidative stress are available and have been evaluated in COPD. In this review, we summarize the main literature findings about circulating oxidative stress biomarkers, grouped according to their method of detection, measured in COPD subjects. [ABSTRACT FROM AUTHOR]

Background: The existence of a cause-effect relation between active smoking and new-onset asthma in adults, although supported by several studies, has not been proven yet. Aims: We aimed to prospectively study asthma incidence as a function of smoking habits in the Italian adult population. Methods: A population-based cohort of 5,241 non-asthmatics was enrolled in Verona and Sassari in 1998- 2000. The cohort was contacted again in 2007-2009 within the Gene-Environment Interactions in Respiratory Diseases study, and 3,187 subjects (60.8%) answered a screening questionnaire on smoking habits and respiratory disorders. The relation between smoking habits and self-reported newonset asthma, defined as asthma attacks/use of medicines for asthma, was investigated by a multivariable logistic model. Results: During follow-up, 145 new cases of asthma were observed, yielding a cumulative incidence of 4.6% (95% CI 3.9-5.4); cumulative incidence of asthma did not significantly differ among never-smokers (76/1,666 = 4.6%), ex-smokers (30/554 = 5.4%) and current smokers (39/883 = 4.4%) (p = 0.641). In a multivariable analysis, the most important risk factor for asthma onset was allergic rhinitis (OR = 4.00, 95% CI 3.68-4.35). Compared to never-smokers, the risk of asthma onset was slightly increased in ex-smokers (OR = 1.28, 1.09-1.49) but not in current smokers (OR 1.01, 0.66- 1.53). Current smoking became a significant predictor only when both new-onset wheezing and new-onset asthma were considered as the outcome (OR = 2.03, 1.35-3.05). Conclusions: In this prospective study, current smoking was not a risk factor for new-onset asthma, unless new-onset wheezing was also considered. The increase in asthma incidence among ex-smokers was likely due to reverse causation. [ABSTRACT FROM AUTHOR]

Background: Elevated plasma concentrations of the endogenous nitric oxide synthase (NOS) inhibitor asymmetric dimethylarginine (ADMA) have been observed in respiratory conditions such as asthma and cystic fibrosis. Since oxidative stress has been shown to increase the activity of arginine methylating enzymes, hence increased ADMA synthesis, and to reduce ADMA degrading enzymes, hence increased ADMA concentrations, we assessed methylated arginines concentrations in chronic obstructive pulmonary disease (COPD), a disease characterized by increased oxidative stress. Methods: Plasma arginine, ADMA and symmetric dimethylarginine (SDMA), oxidative stress markers (thiobarbituric acid reactive substances, TBARS, and plasma proteins SH, PSH) and antioxidants (taurine and paraoxonase 1, PON1, activity) were measured in 43 COPD patients with mild (n = 29) or moderate (n = 14) disease and 43 age- and sex-matched controls. Results: TBARS significantly increased with COPD presence and severity (median 2.93 vs 3.18 vs 3.64 μmol/L, respectively in controls, mild and moderate group, p<0.0001 by ANOVA) whereas PSH decreased (6.69±1.15 vs 6.04±0.85 vs 5.33±0.96 μmol/gr prot, p<0.0001 by ANOVA). Increased ADMA/arginine ratio, primarily due to reduced arginine concentrations, was also observed with COPD presence and severity (median 0.0067 vs 0.0075 vs 0.0100, p<0.0001 by ANOVA). In multiple logistic regression analysis, only TBARS (OR 0.44, 95% CI 0.25–0.77; p = 0.0045) and ADMA/Arginine ratio (OR 1.72, 95% CI 2.27–13.05; p = 0.02) were independently associated with COPD severity. Conclusion: COPD presence and severity are associated with increased oxidative stress and alterations in arginine metabolism. The reduced arginine concentrations in COPD may offer a new target for therapeutic interventions increasing arginine availability. [ABSTRACT FROM AUTHOR]

Background: Tracheobronchopathia Osteochondroplastica (TBPO) is an uncommon and benign condition characterized by osseous or metaplastic cartilaginous 1-3 mm nodules in the submucosa of the tracheobronchial tree. Posterior membranous wall of trachea is typically spared. Ecchondrosis and exostosis nodules can cause chronic inflammation and mucosal metaplasia, stiffness and airway obstruction. The prevalence of this disease, often asymptomatic or associated with nonspecific symptoms, is underestimated, and the mean age at diagnosis is 50 years. Case presentation: We report a case of a 49 year old male, non-smoker. He was a smith, homeless, born in Romania and reported a diagnosis of asthma since childhood. He was admitted to our Respiratory Unit presenting low-grade fever with profuse sweating, cough, purulent sputum, and ground-glass opacity with irregularity in main bronchi detected by High-Resolution Computed Tomography (HRCT) scan. Fibrobronchoscopy revealed the presence of mucosal irregularities up to the segmental bronchi entrance. Histological examination showed nodules of osseouscartilaginous nature, consistent with TBPO. Microbiological tests of Bronchoalveolar Lavage fluid also revealed an infection by Pseudomonas Aeruginosa. Conclusion: TBPO is a rare disease characterized by wheezing, cough, hemoptysis, and recurrent pulmonary infections, with typical onset during adulthood. In the case reported, the symptoms began in childhood, although they had been misinterpreted as asthma. Even if childhood-onset is not reported in literature, it is likely that small changes occur in the first few years of life and become more evident in adulthood. The involvement of segmental and sub-segmental bronchi, usually spared in TBPO, could explain the presence of wheezing and non-productive cough reported by our patient since childhood. [ABSTRACT FROM AUTHOR]

Background: It has been suggested that there is some overlap between allergic rhinitis (AR), sinusitis and polyposis, but this has not been fully documented. The present study aimed to evaluate the prevalence of these co-existing diseases and their impact on bronchial asthma in the general population of Italy. Methods: Within the frame of the multicentre Gene Environment Interactions in Respiratory Diseases (GEIRD) study, a postal screening questionnaire including questions about self-reported symptoms of asthma, AR, AR with sinusitis without nasal polyps (AR + SsNP) and AR with sinusitis with nasal polyps (AR + SwNP) was administered. Random samples of subjects aged between 20 and 44 years (n = 5,162) answered the postal questionnaire in 4 Italian centres (Pavia, Sassari, Turin, Verona). In AR subjects, the association among AR only, AR + SsNP, AR + SwNP and bronchial asthma was estimated by the relative risk ratio (RRR) using multinomial regression models. Results: The prevalence of AR in the sample was 25.4% (95% CI 24.2-26.6). A self-reported diagnosis of AR + SsNP and AR + SwNP was reported by 5.7% (95% CI 5.0-6.3) and by 1.2% (95% CI 0.9-1.5) of the subjects, respectively. Current asthma was reported by 17.5% of the AR subjects. In the adjusted multivariate analysis, the risk of having current asthma (RRR = 2.31, 95% CI 1.29-4.15), of having at least 1 asthma attack per year (RRR = 2.30, 95% CI 1.19-4.46) and of having had an emergency department admission for respiratory diseases (RRR = 5.61, 95% CI 1.81-23.92) was higher for subjects with AR + SwNP than subjects with AR only. Conclusions: The diagnosis of AR in the epidemiological setting includes heterogeneous upper airway diseases that affect the clinical features of AR and its interactions with asthma. © 2016 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease ( COPD) and asthma are both characterized by heterogeneous chronic airway inflammation and obstruction as well as oxidative stress ( OS). However, it is unknown whether OS occurs in early disease and how to best assess its presence. Plasma OS markers ( TBARS, PSH, taurine, GSH, ergothioneine and paraoxonase 1 activity) and lung function tests were measured in patients with mild stable asthma ( n = 24) and mild stable COPD ( n = 29) and in age- and sex-matched controls. Forced expiratory volume in 1 s ( FEV1) was associated with age both in patients and control groups. By contrast, FEV1 was positively correlated with PSH only in COPD (ρ = 0·49, P = 0·007). In multiple logistic regression analysis, lower PSH was the only OS marker independently associated with increased odds of both asthma ( OR = 0·32, 95% CI 0·13-0·78, P = 0·01) and COPD ( OR = 0·50, 95% CI 0·26-0·95, P = 0·03). These findings suggest that proteins -SH are a sensitive OS marker in early COPD and asthma. [ABSTRACT FROM AUTHOR]

The association between exposure to toxic metals and amyotrophic lateral sclerosis (ALS) was explored in a population-based case–control study in the Sardinia island (Italy), a region characterized by elevated rates of ALS cases. In 34 patients with ALS (mean age, 62 ± 10 years) and 30 controls (mean age, 65 ± 11 years), Al, Cd, Hg, Mn and Pb were determined in blood, hair and urine by sector field inductively coupled mass spectrometry. Results indicated that, in blood, concentrations of Al (p = 0.045) and Pb were higher (p = 0.026) in ALS patients than in control subjects. In hair, a depletion of Al (p = 0.006) and Mn (p = 0.032) concentrations in ALS subjects respect to controls was found. In urine, no significant differences between cases and controls were observed. Thus, some metals seemed to be associated with ALS degeneration, but a definitive conclusion is still far considering the multiple risk factors (genetic mutations, environmental toxicants and stressors) involved in the disease. Finally, the interpretation that deregulated metal concentrations can be a consequence of the degenerative process, rather than a cause, is also valid. [ABSTRACT FROM AUTHOR]

Background: Few population-based studies have assessed the prevalence and the risk factors of non-allergic rhinitis (NAR) in comparison to allergic rhinitis (AR). Moreover, epidemiologic data on rhinitis in the elderly subjects and in southern Europe are scarce. Objective: This study aimed at estimating the prevalence and at comparing the risk factor distribution of AR and NAR in a general population sample aged 20-84 years in Italy. Methods: A questionnaire on respiratory symptoms and risk factors was administered to random samples of the Italian population aged 20-44 (n = 10,494) 45-64 (n = 2167) and 65-84 (n = 1030) in the frame of the Gene Environment Interactions in Respiratory Diseases (GEIRD) study. Current AR and NAR were defined according to the selfreported presence of nasal allergies or of nasal symptoms without a cold or the flu. Results: NAR showed a significant descending pattern in females from 12.0 % (95 % CI 11.1, 13.1) in the 20-44 year age class, to 7.5 % (5.4, 10.3) in the 65-84 year age class (p = 0.0009), and a roughly stable pattern in males, from 10.2 % (9.3, 11.2) to 11.1 % (8.4, 13.9) (p = 0.5261). AR decreased from 26.6 % (25.7, 27.6) in 20-44 years age class to 15.6 % (13.3, 18.0) in the 65-84 years age class (p < 0.0001), without gender difference. Subjects living near industrial plants and ex- and current smokers had a higher risk of NAR. Current smokers had a lower risk and subjects living in a Mediterranean climate a higher risk of AR. Conclusion: AR and NAR are fairly distinct conditions, as they have a different age, gender and risk factor distribution. [ABSTRACT FROM AUTHOR]

Background: It is well known that asthma prevalence has been increasing all over the world in the last decades. However, few data are available on temporal trends of incidence and remission of asthma. Objective: To evaluate the rates of asthma incidence and remission in Italy from 1940 to 2010. Methods: The subjects were randomly sampled from the general Italian population between 1991 and 2010 in the three population-based multicentre studies: ECRHS, ISAYA, and GEIRD. Individual information on the history of asthma (age at onset, age at the last attack, use of drugs for asthma control, co-presence of hay-fever) was collected on 35,495 subjects aged 20–84 and born between 1925–1989. Temporal changes in rates of asthma incidence and remission in relation to age, birth cohort and calendar period (APC) were modelled using Poisson regression and APC models. Results: The average yearly rate of asthma incidence was 2.6/1000 (3,297 new cases among 1,263,885 person-years). The incidence rates have been linearly increasing, with a percentage increase of +3.9% (95%CI: 3.1–4.5), from 1940 up to the year 1995, when the rates begun to level off. The stabilization of asthma incidence was mainly due to a decrease in the rates of atopic asthma after 1995, while non-atopic asthma has continued to increase. The overall rate of remission was 43.2/1000person-years, and it did not vary significantly across generations, but was associated with atopy, age at asthma onset and duration of the disease. Conclusions: After 50 years of a continuous upward trend, the rates of asthma incidence underwent a substantial stabilization in the late 90s. Despite remarkable improvements in the treatment of asthma, the rate of remission did not change significantly in the last seventy years. Some caveats are required in interpreting our results, given that our estimates are based on self-reported events that could be affected by the recall bias. [ABSTRACT FROM AUTHOR]

Background: This study aimed to evaluate inducible protein-10 (IP-10) as a biomarker besides interferon-gamma (IFN-?) to improve the identification of active tuberculosis (TB) and latent tubercular infection (LTBI) in a country with a low incidence of TB. Methods: Whole blood from Mycobacterium tuberculosis-infected subjects was stimulated with region-of-difference-1 (RD1)-specific peptides and with heparin-binding hemagglutinin (HBHA) to determine the release of IP-10 and IFN-?. Results: No statistically significant difference was observed between positive rates of IP-10 and IFN-? after RD1-specific peptide stimulation in the TB and LTBI groups; a different response was detected in QuantiFERON TB-gold test-negative (QFT-) subjects. A significantly different proportion of positive responses was observed between IP-10 and IFN-? following HBHA stimulation in the TB group and in the QFT- group but not in the LTBI group. Conclusions: The IP-10 test seemed to identify false-negative QFT results in some subjects with a positive IFN-?/IP-10/HBHA pattern. [ABSTRACT FROM AUTHOR]

Alpha-1-antitrypsin deficiency (AATD) is an inherited disorder responsible for early onset emphysema associated with a significant impairment of health-related quality of life (HRQoL). Our aim was to assess the usefulness of different instruments to evaluate the HRQoL in patients with AATD compared to non-AATD COPD. Observational, cross-sectional study in which all patients filled out a series of questionnaires: the COPD severity score (COPDSS), the EuroQoL 5-Dimensions (EQ-5D), the Living with COPD (LCOPD) and the COPD Assessment Test (CAT). A total of 96 patients were included, 35 with AATD (mean age 56.5 yrs, 57.1% male and mean FEV1(%) 48.7% and 61 non-AATD COPD (70.3 yrs, 80.3% men and FEV1(%) 47%. The questionnaire scores were similar, with a tendency towards worse scores in AATD for the EQ-5D (VAS) (64.8 (20.2) vs. 71.6 (17.1); p = 0.08). The correlations between the different scores and FEV1(%) were significant in both groups for COPDSS and LCOPD, but not for CAT and EQ-5D. In general, the correlations of scores with FEV1(%) were stronger for AATD compared with non-AATD COPD patients: COPDSS r = −0.570, p < 0.01 for AATD and r = −0.260, p < 0.05 for COPD; LCOPD r = −0.502, p < 0.001 for AATD and r = −0.304, p < 0.05 for non-AATD COPD. Patients with AATD have a similar degree of HRQoL impairment as older subjects with non-AATD COPD and showed a stronger correlation between HRQoL measurements and lung function impairment compared with non-AATD COPD. This may be related to the characteristics of the disease in these patients who are usually younger, with less co-morbidity and lower smoking consumption. [ABSTRACT FROM AUTHOR]

Mediastinal lymphadenopathy is a condition in which one or more mediastinal lymph nodes are enlarged for malignant or benign causes, generally more than 10 mm. For a long time, the only way to approach the mediastinum was surgery, while in last decades endoscopic techniques gained their role in neoplastic diseases. At the present time, EBUS is the technique of choice for studying the mediastinum in the suspicion of cancer, while there are not strong indications in guidelines for the study of benign mediastinal lymphadenopathy. We reviewed the literature, looking for evidence of the role of EBUS in the diagnostics of non-neoplastic mediastinal lymphadenopathy, with special regard for granulomatous disease, both infectious and non-infectious. EBUS is a reliable alternative to surgery in non-neoplastic mediastinal lymphadenopathy, even if more evidence is needed for granulomatous diseases other than tuberculosis and sarcoidosis. [ABSTRACT FROM AUTHOR]

Background: Only few longitudinal studies on the course of asthma among adults have been carried out. Objective: The aim of the present prospective study, carried out between 2000 and 2009 in Italy, is to assess asthma remission and control in adults with asthma, as well as their determinants. Methods: All the subjects with current asthma (21–47 years) identified in 2000 in the Italian Study on Asthma in Young Adults in 6 Italian centres were followed up. Asthma remission was assessed at follow-up in 2008–2009 (n = 214), asthma control at baseline and follow-up. Asthma remission and control were related to potential determinants by a binomial logistic and a multinomial logistic model. Separate models for remission were used for men and women. Results: The estimate of the proportion of subjects who were in remission was 29.7% (95%CI: 14.4%;44.9%). Men who were not under control at baseline had a very low probability of being in remission at follow-up (OR = 0.06; 95%CI:0.01;0.33) when compared to women (OR = 0.40; 95%CI:0.17;0.94). The estimates of the proportion of subjects who were under control, partial control or who were not under control in our sample were 26.3% (95%CI: 21.2;31.3%), 51.6% (95%CI: 44.6;58.7%) and 22.1% (95%CI: 16.6;27.6%), respectively. Female gender, increasing age, the presence of chronic cough and phlegm and partial or absent asthma control at baseline increased the risk of uncontrolled asthma at follow-up. Conclusion: Asthma remission was achieved in nearly 1/3 of the subjects with active asthma in the Italian adult population, whereas the proportion of the subjects with controlled asthma among the remaining subjects was still low. [ABSTRACT FROM AUTHOR]