Comparison among populations with severe and intermediate alpha1-antitrypsin deficiency and chronic obstructive pulmonary disease.

BACKGROUND: Severe alpha1-antitrypsin (AAT) deficiency (AATD) is associated with a high risk of airflow obstruction and emphysema. The risk of lung disease in those with intermediate AAT deficiency is unclear. Our aims were to compare pulmonary function, time of onset of symptoms, and indicators of quality of life among patients with severe AATD (PI*ZZ), patients with intermediate AATD (PI*MZ) from the Italian Registry of AATD with a chronic obstructive pulmonary disease (COPD) cohort of patients without AATD (PI*MM). METHODS: We considered a total of 613 patients: 330 with the PI*ZZ genotype, 183 with the PI*MZ genotype and 100 with the PI*MM genotype. Radiological exams, pulmonary function test, and measurement of quality of life have been performed on all cohorts of patients. RESULTS: The three populations differ significantly in terms of age at COPD/AATD diagnosis (P=0.00001), respiratory function (FEV1, FVC, DLCO P<0.001), quality of life (P=0.0001) and smoking history (P<0.0001). PI*ZZ genotype had 24.9 times a higher likelihood of developing airflow obstruction. The MZ genotype is not associated with a significant early risk of airflow obstruction. CONCLUSIONS: The comparison of populations with PI*ZZ, MZ and MM genotypes allows to delineate the role of alpha1-antitrypsin deficiency on respiratory function and on the impact on quality of life, in relation to other risk factors. These results highlight the crucial role of primary and secondary prevention on smoking habits in PI*MZ subjects and the importance of an early diagnosis.

Inhaled corticosteroids and risk of osteoporosis in late-middle-aged subjects: a multicenter European cohort study.

BACKGROUND: Inhaled corticosteroids have been widely used for the regular treatment of asthma and chronic obstructive pulmonary diseases (COPD) over the past few decades. To date, studies investigating the effects of inhaled corticosteroids (ICS) on bone in populations including asthma and COPD patients, show conflicting results. The skeletal effects of ICS remain poorly understood. We assessed the association between ICS exposure and self-reported osteoporosis diagnosis in a European cohort study. METHODS: The analysis was carried out by using clinical and questionnaire data available for subjects participating in the ECRHS III (European Community Respiratory Health Survey) with age >55 years. RESULTS: Among the 3004 enrolled subjects, 245 were ICS users with an exposure ≥12 months. Osteoporosis was reported by 16 subjects in the ICS group (6.5%) and by 167 in the not exposed group (6.1%). The adjusted risk of osteoporosis in ICS users (≥12 months) was not greater in exposed subjects when compared with the unexposed ones (OR=1.02, 95CI%: 0.51, 2.03). The same result was observed even when considering in the analysis a longer exposure to the ICS use (≥36.5 months, the median ICS exposure for all subjects). History of COPD, use of oral corticosteroids, Body Mass Index, smoking and physical activity did not show any evidence of an association with osteoporosis. CONCLUSIONS: Our study did not show any significant association between long- term ICS use and self-reported diagnosis of osteoporosis in subjects aged >55 years. To explore the real effect of ICS on bone status, further studies are needed, especially in the long-term ICS exposure.

Comparison between Suspected and Confirmed COVID-19 Respiratory Patients: What Is beyond the PCR Test.

COVID-19 modified the healthcare system. Nasal-pharyngeal swab (NPS), with real-time reverse transcriptase-polymerase (PCR), is the gold standard for the diagnosis; however, there are difficulties related to the procedure that may postpone it. The study aims to evaluate whether other elements than the PCR-NPS are reliable and confirm the diagnosis of COVID-19. This is a cross-sectional study on data from the Lung Unit of Pavia (confirmed) and at the Emergency Unit of Palermo (suspected). COVID-19 was confirmed by positive NPS, suspected tested negative. We compared clinical, laboratory and radiological variables and performed Logistic regression to estimate which variables increased the risk of COVID-19. The derived ROC-AUCcurve, assessed the accuracy of the model to distinguish between COVID-19 suspected and confirmed. We selected 50 confirmed and 103 suspected cases. High Reactive C-Protein (OR: 1.02; CI95%: 0.11-1.02), suggestive CT-images (OR: 11.43; CI95%: 3.01-43.3), dyspnea (OR: 10.48; CI95%: 2.08-52.7) and respiratory failure (OR: 5.84; CI95%: 1.73-19.75) increased the risk of COVID-19, whereas pleural effusion decreased the risk (OR: 0.15; CI95%: 0.04-0.63). ROC confirmed the discriminative role of these variables between suspected and confirmed COVID-19 (AUC 0.91). Clinical, laboratory and imaging features predict the diagnosis of COVID-19, independently from the NPS result.

Depression is associated with poor control of symptoms in asthma and rhinitis: A population-based study.

BACKGROUND: Although many studies have highlighted the link between asthma/rhinitis and depression, it is still unclear which characteristics of these diseases are associated with the risk of depression. We aimed to explore the relationship between depression and asthma or rhinitis in a representative sample of the Italian general population. METHODS: The data were collected in GEIRD, an Italian multicenter, population-based, multicase-control study. 2227 participants (age 21-86 years, female 50%) underwent standardized interviews, skin prick and lung function tests, and were divided into cases of current asthma (n = 528), rhinitis without asthma (n = 972), and controls (n = 727). Two specific questions from the Patient Health Questionnaire (PHQ-2) were asked to identify symptoms of depressed mood and anhedonia, which were used as a proxy of major depression disorder. RESULTS: The prevalence of depression was 16.7%, 11.9%, and 5.1% in subjects with asthma, rhinitis and controls, respectively. Both in asthma and rhinitis, subjects with depression had worse respiratory-health related quality of life and more frequent disease-related symptoms than their non-depressed counterparts. In asthma, depression was associated with poorer disease control. In rhinitis, depression was significantly associated with a disease-related limitations in daily activities and greater risk of symptom exacerbations and prescriptions of medicines for breathing. Cases of rhinitis with depression were less likely to be atopic. CONCLUSIONS: Our results suggest that rhinitis exacerbations, particularly in non-atopic subjects, and low asthma control are strongly related to the presence of depressed mood in adults from the general population.

Persistent exercise limitation after successful pulmonary endoarterectomy: frequency and determinants.

BACKGROUND: After successful pulmonary endoarterectomy (PEA), patients may still suffer from exercise limitation, despite normal pulmonary vascular resistance. We sought to assess the proportion of these patients after the extension of PEA to frail patients, and the determinants of exercise limitation. METHODS: Out of 553 patients treated with PEA from 2008 to 2016 at our institution, a cohort of 261 patients was followed up at 12 months. They underwent clinical, haemodynamic, echocardiographic, respiratory function tests and treadmill exercise testing. A reduced exercise capacity was defined as Bruce test distance < 400 m. RESULTS: Eighty patients did not had exercise testing because of inability to walk on treadmill and/or ECG abnormalities Exercise limitation 12 months after PEA was present in 74/181 patients (41, 95%CI 34 to 48%). The presence of COPD was more than double in patients with exercise limitation than in the others. Patients with persistent exercise limitation had significantly higher mPAP, PVR, HR and significantly lower RVEF, PCa, CI, VC, TLC, FEV1, FEV1/VC, DLCO, HbSaO2 than patients without. The multivariable model shows that PCa at rest and TAPSE are important predictors of exercise capacity. Age, COPD, respiratory function parameters and unilateral surgery were also retained. CONCLUSIONS: After successful PEA, most of the patients recovered good exercise tolerance. However, about 40% continues to suffer from limitation to a moderate intensity exercise. Besides parameters of right ventricular function, useful information are provided by respiratory function parameters and COPD diagnosis. This could be useful to better address the appropriate therapeutic approach.

Renal fibrogenesis and platinum compounds in a rat model: a novel Pt (II) complex vs. cisplatin.

BACKGROUND/AIM: A new platinum compound, (Pt(O,O'-acac)(γ-acac)(DMS)) (PtAcacDMS), has been shown to possess higher cytotoxic activity than cisplatin on several cancer and chemoresistant cell lines. The aim of the present study was to compare the nephrotoxic effects - particularly renal fibrogenesis- of PtAcacDMS and cisplatin in rats after the subcutaneous administration of a single dose (5 mg/Kg b.w., s.c.) of either compound to ten-day-old rats. MATERIALS AND METHODS: Control and treated rats were killed 1 day (PD11), 7 days (PD17), 21 days (PD31) and 40 days (PD50) after the injection. Kidneys were processed for light and electron microscopy, and platinum determination. Antibodies against E-cadherin (E-cad), vimentin (VIM) and α-smooth muscle actin (αSMA) were used to identify epithelial and mesenchymal cells. RESULTS AND CONCLUSION: Cisplatin produced progressive cortical fibrotic lesions displaying a variable number of VIM-positive tubules and interstitial αSMA-positive cells around. By contrast, PtAcacDMS induced a minimal number of histopathological changes, which declined in the adult samples, while the renal platinum content was generally higher after PtAcacDMS than after cisplatin. The present experimental model was proven suitable to investigate the occurrence of epithelial-mesenchymal transition (EMT) in renal fibrogenesis induced by the platinum-based compounds.

The course of asthma in young adults: a population-based nine-year follow-up on asthma remission and control.

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.

Evaluation of the anti-proliferative activity of three new pyrazole compounds in sensitive and resistant tumor cell lines.

BACKGROUND: In previous papers we demonstrated that the activity of short heteroretinoids as anti-proliferative and pro-apoptotic compounds was deeply linked to their heterocyclic moiety and that ionone-derived 1,5-pyrazoles had the highest anti-proliferative activity in our preliminary experiments. We then demonstrated the high and pharmacologically significant anti-proliferative and apoptotic activities of the pyrazole compounds 2-(1-(4-chlorophenyl)-1H-pyrazol-5-yl)-5-methoxyphenol (EN12-4), 5-methoxy-2-(1-(pyridin-2-yl)-1H-pyrazol-5-yl)phenol (EN12-2A) and 2-(5-(4-methoxyphenyl)-1H-pyrazol-1-yl)pyridine (EN7-2) establishing, especially for EN12-2A, a possible mechanism of action involving the cell microtubular system. METHODS: Here, the anti-proliferative activity of these pyrazole compounds was analyzed in vitro by the MTT assay in six drug-resistant cell lines, five of which were selected after exposure to increasing concentrations of cisplatin (L1210/DDP), doxorubicin (A2780/DX3), 5-fluorouracil (HCT-8/5FU), taxol (A549/T24) and etoposide (MCF-7/VP), and one was obtained by transfection of the ABCG2 membrane transporter (HEK-293/R2). RESULTS: Our data show that these compounds have a similar anti-proliferative activity in nearly all resistant and sensitive cell lines, demonstrating their ability to overcome the most common mechanisms of drug resistance with two exceptions regarding the MCF-7/VP cell line over-expressing the ABCC1 (MRP1) transporter, and the MDR1 over-expressing A2780/DX3 cells, with a calculated RI = 3.2 for EN12-2A, relative to their sensitive cellular counterpart. On the other hand, the taxol-resistant A549/T24 cell line showed a significantly increased sensitivity to our compounds. CONCLUSIONS: Our data suggest that our pyrazole compounds are able to overcome in vitro the most common drug-resistance mechanisms demonstrating a significant anti-proliferative activity and confirming a mechanism of action involving the depolymerization of microtubules.

The rapid FEV(1) decline in chronic obstructive pulmonary disease is associated with predominant emphysema: a longitudinal study.

BACKGROUND: Early identification of patients with COPD and prone to more rapid decline in lung function is of particular interest from both a prognostic and therapeutic point of view. The aim of this study was to identify the clinical, functional and imaging characteristics associated with the rapid FEV(1) decline in COPD. METHODS: Between 2001 and 2005, 131 outpatients with moderate COPD in stable condition under maximum inhaled therapy underwent clinical interview, pulmonary function tests and HRCT imaging of the chest and were followed for at least 3 years. RESULTS: Twenty-six percent of patients had emphysema detected visually using HRCT. The FEV(1) decline was 42 ± 66 mL/y in the total sample, 88 ± 76 mL/y among rapid decliners and 6 ± 54 mL/y among the other patients. In the univariable analysis, the decline of FEV(1) was positively associated with pack-years (p < 0.05), emphysema at HRCT (p < 0.001), RV (p < 0.05), FRC (p < 0.05), FEV(1) (p < 0.01) at baseline and with number of hospitalizations per year (p < 0.05) during the follow-up. Using multivariable analysis, the presence of emphysema proved to be an independent prognostic factor of rapid decline (p = 0.001). When emphysema was replaced by RV, the model still remained significant. CONCLUSIONS: The rapid decline in lung function may be identified by the presence of emphysema at HRCT or increased RV in patients with a long smoking history.