Publications by authors named "Paolo Solidoro"

88 Publications

Management of patients with severe acute respiratory failure due to SARSCoV-2 pneumonia with non-invasive ventilatory support outside Intensive Care Unit.

Minerva Med 2021 Jan 19. Epub 2021 Jan 19.

Cardiovascular and Thoracic Department, Respiratory Diseases Unit U, AOU Città della Salute e della Scienza, Turin, Italy.

Background: COVID-19 has high mortality rate mainly stemming from acute respiratory distress leading to respiratory failure (ARF ). Aim of the study is evaluating the management of severe ARF due to COVID-19 pneumonia using non-invasive ventilatory support (NIVS), studing safety and effectiveness of non-invasive ventilatory support (NIVS).

Methods: This is a retrospective, multicenter study. Primary outcomes were NIVS failure with intubation rate and hospital mortality . Secondary outcomes were: hospital stay and factors related to NIVS failure and mortality. These outcomes were compared with patients intubated and admitted to ICU.

Results: 162 patients were hospitalized because of severe respiratory failure ( PaO2/FiO2 ratio < 250 ). 138 patients were admitted to Respiratory Intermediate Care Unit (RICU) for a NIVS trial. One hundred patients were treated successfully with NIVS (74.5%); 38 failed NIVS trial (27.5%). In-hospital mortality was 23.18% in RICU group and 30.55% in ICU group. Patients with NIVS failure were older, had a lower number of lymphocytes, a higher IL-6 , lower PaO2, PaCO2, PaO2/FiO2 ratio, higher respiratory rate (RR) and heart rate at admission and lower PaO2 and PaO2/FiO2 ratio and higher RR after 1-6 hours . Multivariate analysis identified higher age, C-reactive protein as well as RR after 1-6 hours and PaO2/FiO2 ratio after 1-6 hours as an independent predictor mortality.

Conclusions: NIVS is a safe and effective strategy in the treatment of severe ARF due to COVID 19 related pneumonia, that reduces mortality and length of hospital stay in the carefully selected patient.
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http://dx.doi.org/10.23736/S0026-4806.21.07134-2DOI Listing
January 2021

Fever and dyspnoea in a tracheostomised patient.

Breathe (Sheff) 2020 Dec;16(4):200115

Dept of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy.

https://bit.ly/3hZHBA0.
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http://dx.doi.org/10.1183/20734735.0115-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792835PMC
December 2020

COVID-19 Diagnosis in Case of Two Negative Nasopharyngeal Swabs: Association between Chest CT and Bronchoalveolar Lavage Results.

Radiology 2021 03 5;298(3):E152-E155. Epub 2021 Jan 5.

From the Medical Department, Respiratory Diseases Unit (F.P., P.E.B.), Department of Diagnosis and Treatment Services, Radiodiagnostics (A.C., Z.F., A.P.), Emergency Medicine Department (F.G.), and Medical Department, Internal Medicine Unit (M.B., P.P.S.), Azienda Ospedaliero Universitaria Maggiore della Carità di Novara, C.so Mazzini 18, 28100 Novara, Italy; Translational Medicine Department, University of Piemonte Orientale Amedeo Avogadro, Novara, Italy (F.P., F.G., C.A., M.B.); and Medical Sciences Department, University of Torino, Turin, Italy (P.S.).

See also the editorial by Little in this issue.
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http://dx.doi.org/10.1148/radiol.2020203776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903987PMC
March 2021

Cellular and humoral cytomegalovirus immunity changes in one-year combined prophylaxis after lung transplantation: suggestions from and for clinical practice.

Ther Adv Respir Dis 2020 Jan-Dec;14:1753466620981851

Division of Respiratory Medicine, Cardiovascular and Thoracic Department, AOU Città della Salute e della Scienza di Torino, Torino, Italy.

Background: Immune responses, both cellular and humoral, against cytomegalovirus (CMV) are used to predict CMV manifestations in solid organ recipients. The aim of this study is to evaluate CMV enzyme-linked immunospot (ELISPOT) assay and serology during CMV infections, their concordance and variations after lung transplantation (LTx).

Methods: We retrospectively analysed in one year the follow-up data of 43 patients receiving combined CMV prophylaxis with antiviral agents and CMV-specific immunoglobulin G (IgG). CMV infections were investigated by using molecular analyses on both 167 bronchoalveolar lavage and biopsy specimens and 1134 blood samples. Cellular CMV immunity was assessed with specific ELISPOT whereas the humoral one was assessed by quantifying specific immunoglobulins.

Results: At the first month after LTx the majority of patients were ELISPOT responders (52.3%) and 30.9% were non-responders. ELISPOT responders had a lower incidence of CMV viremia ( = 0.047), whereas neither effects on CMV pulmonary asymptomatic infection nor on acute rejection were observed. Responders had a higher CMV IgG titre ( < 0.0001) in particular at the first month after LTx ( = 0.0001). Concordance among CMV ELISPOT assay and IgG levels was moderate (Cohen's K 0.524), with an agreement of 89.8%. All ELISPOT responders maintained their status and almost all non-responders became responders during follow-up (92.3%); the percentage of IgG seropositive subjects increased from 74.4% at the first month of follow-up to 97.4% after 1 year.

Conclusions: Despite a moderate concordance with serology, ELISPOT response predicted a lower incidence of CMV viremia in LTx patients; no effects were reported on pulmonary clinical manifestations nor on acute rejection. The ELISPOT response as well as serology changed during the follow-up, not only after first CMV contact.
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http://dx.doi.org/10.1177/1753466620981851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780175PMC
December 2020

Severe asthma and COVID-19: lessons from the first wave.

J Asthma 2020 Dec 16:1-7. Epub 2020 Dec 16.

Medical Sciences Department, University of Turin, Torino, Italy.

Objective: Severe asthma is considered a risk factor for SARS-Coronavirus 2 (SARS-CoV-2) infection but scientific evidences are lacking.

Methods: we performed a literature search and review based on PubMed database national, international recommendations as well as papers on severe asthmatic patients and their management during SARS-CoV-2 pandemic.

Results: the majority of international recommendations, expert panels and editorials provide indications about management of severe asthmatic patients. No published studies evaluated the effects of biologic agents on severe asthmatic patients during SARS-CoV-2 pandemic.

Conclusions: the relationship between SARS-CoV-2 and asthma is variable worldwide and severe asthmatic patients were seldom reported in published cohorts. International recommendations suggest maintaining asthma under control to limit exacerbations occurrence, by using all available treatment. The minimum steroid dosage effective to control symptoms should be maintained to avoid exacerbations; biologic agents administration should be regularly scheduled encouraging patient support programmes.
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http://dx.doi.org/10.1080/02770903.2020.1861622DOI Listing
December 2020

At the peak of COVID-19 age and disease severity but not comorbidities are predictors of mortality: COVID-19 burden in Bergamo, Italy.

Panminerva Med 2021 Mar 27;63(1):51-61. Epub 2020 Nov 27.

Unit of Gastroenterology 1, Hepatology and Transplantation, ASST Papa Giovanni XXIII, Bergamo, Italy.

Background: Findings from February 2020, indicate that the clinical spectrum of COVID-19 can be heterogeneous, probably due to the infectious dose and viral load of SARS-CoV-2 within the first weeks of the outbreak. The aim of this study was to investigate predictors of overall 28-day mortality at the peak of the Italian outbreak.

Methods: Retrospective observational study of all COVID-19 patients admitted to the main hospital of Bergamo, from February 23 to March 14, 2020.

Results: Five hundred and eight patients were hospitalized, predominantly male (72.4%), mean age of 66±15 years; 49.2% were older than 70 years. Most of patients presented with severe respiratory failure (median value [IQR] of PaO2/FiO2: 233 [149-281]). Mortality rate at 28 days resulted of 33.7% (N.=171). Thirty-nine percent of patients were treated with continuous positive airway pressure (CPAP), 9.5% with noninvasive ventilation (NIV) and 13.6% with endotracheal intubation. 9.5% were admitted to Semi-Intensive Respiratory Care Unit, and 18.9% to Intensive Care Unit. Risk factors independently associated with 28-day mortality were advanced age (≥78 years: odds ratio [OR], 95% confidence interval [CI]: 38.91 [10.67-141.93], P<0.001; 70-77 years: 17.30 [5.40-55.38], P<0.001; 60-69 years: 3.20 [1.00-10.20], P=0.049), PaO2/FiO2<200 at presentation (3.50 [1.70-7.20], P=0.001), need for CPAP/NIV in the first 24 hours (8.38 [3.63-19.35], P<0.001), and blood urea value at admission (1.01 [1.00-1.02], P=0.015).

Conclusions: At the peak of the outbreak, with a probable high infectious dose and viral load, older age, the severity of respiratory failure and renal impairment at presentation, but not comorbidities, are predictors of 28-day mortality in COVID-19.
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http://dx.doi.org/10.23736/S0031-0808.20.04063-XDOI Listing
March 2021

SARS-CoV-2 Detection on Bronchoalveolar Lavage: An Italian Multicenter experience.

Respiration 2020 19;99(11):970-978. Epub 2020 Oct 19.

Cardiovascular and Thoracic Department, Respiratory Diseases Unit U, "AOU Città della Salute e della Scienza", Torino, Italy.

Background: Bronchoscopy with bronchoalveolar lavage (BAL) during the SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) pandemic should be reserved to a limited number of clinical indications. The yield of BAL for the diagnosis of suspected or confirmed pulmonary SARS-CoV-2 infection is still unknown.

Objectives: We aimed to evaluate the diagnostic ratio of BAL in detecting SARS-CoV-2 pulmonary infection in patients undergoing bronchoscopy for different indications as well as describe the clinical, radiological, and endoscopic characteristics of patients with SARS-CoV-2 on BAL.

Method: We conducted a multicenter retrospective study including all patients who underwent bronchoscopy for the detection of SARS-CoV-2 on BAL. Clinical, computed tomography (CT), endoscopic, and microbiologic data were gathered from March 16th to May 27th, 2020.

Results: 131 patients were included. Bronchoscopy was performed for suspected SARS-CoV-2 infection (65.5%), alternative diagnosis (12.9%), suspected superinfections (19.8%), and lung atelectasis (1.5%). SARS-CoV-2 was isolated on BAL 43 times (32.8%) and the highest isolation rate was in patients with suspected SARS-CoV-2 infection (74.4%); 76% of positive patients had a double-negative nasopharyngeal swab. Peripheral, posterior and multilobar CT opacities were more frequent in SARS-CoV-2 patients, and the number of CT findings was higher in positive patients, particularly those with suspected SARS-CoV-2 infection. We recorded a progressive reduction of SARS-CoV-2 isolation during the observation period.

Conclusions: In our centers, the rate of detection of SARS-CoV-2 on BAL in patients with suspected infection was 37.2%. The agreement of BAL with nasopharyngeal swabs was high; CT alterations could predict the pretest probability of SARS-CoV-2 infection, but suspicion of viral infection should be always considered.
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http://dx.doi.org/10.1159/000511964DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649696PMC
January 2021

Serum biomarkers in idiopathic pulmonary fibrosis.

Panminerva Med 2020 Aug 5. Epub 2020 Aug 5.

Medical Sciences Department, University of Torino, Torino, Italy.

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http://dx.doi.org/10.23736/S0031-0808.20.04049-5DOI Listing
August 2020

The Hidden Burden of Severe Asthma: From Patient Perspective to New Opportunities for Clinicians.

J Clin Med 2020 Jul 27;9(8). Epub 2020 Jul 27.

Quebec Heart and Lung Institute, Laval University, Quebec City, QC G1V 0A6, Canada.

Severe asthma is an important topic in respiratory diseases, due to its high impact on morbidity and mortality as well as on health-care resources. The many challenges that still exist in the management of the most difficult-to-treat forms of the disease, and the acknowledgement of the existence of unexplored areas in the pathophysiological mechanisms and the therapeutic targets represent an opportunity to gather experts in the field with the immediate goals to summarize current understanding about the natural history of severe asthma and to identify gaps in knowledge and research opportunities, with the aim to contribute to improved medical care and health outcomes. This article is a consensus document from the "International Course on Severe Asthma" that took place in Palermo, Italy, on May 10-11, 2019. Emerging topics in severe asthma were addressed and discussed among experts, with special focus on patient's needs and research opportunities, with the aim to highlight the unanswered questions in the diagnostic process and therapeutic approach.
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http://dx.doi.org/10.3390/jcm9082397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463666PMC
July 2020

Severe asthma at COVID-19 time: what is new on biologic therapies.

Minerva Med 2021 02 19;112(1):114-117. Epub 2020 Jun 19.

Unit U of Pneumology, Department of Cardiovascular and Thoracic Medicine, Città della Salute e della Scienza, University of Turin, Turin, Italy.

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http://dx.doi.org/10.23736/S0026-4806.20.06727-0DOI Listing
February 2021

Determinants of self-reported adherence to inhaler therapy in patients with chronic obstructive pulmonary disease.

Multidiscip Respir Med 2020 Jan 5;15(1):654. Epub 2020 May 5.

S.C. Pneumologia U, Respiratory Clinic Città della Salute e della Scienza, Turin, Italy.

Background: Adherence to therapy is crucial for COPD patients, since non-adherence leads to worse quality of life, increased health-care expenditure and poor clinical outcome. The aim of this study was to identify the main determinants of suboptimal adherence to therapy in a cohort of COPD patients.

Methods: General information (age, BMI, smoking, comorbidities, education, life style), lung function, exacerbations, symptoms and COPD treatment were collected. Adherence to therapy was assessed by self-reported 4-item Morisky Medication Adherence Scale (MMAS-4), and was related to anthropometric, socio/economic and health status data, obtained by questionnaires (COPD Assessment Test, CAT; Treatment Satisfaction Questionnaire, HRQoL; Katz Index of Independence of Daily Living Activities, Lawton Instrumental Activities of Daily Living Scale).

Results: 136 COPD patients were studied (age 72±8 yrs; 73.5% men; BMI 28.5±7.4 kg/m; FEV 53.5±19.0 % predicted). Nearly half of the patients (46.3%) had suboptimal adherence to therapy (score >0) and, as compared to those with optimal adherence, had higher prevalence of women and coronary artery disease, heavier smoking history and worse CCQ overall score. The results of multivariate analysis showed that the determinants of suboptimal adherence were female sex (OR 4.339, 95%CI 1.509-12.474, =0.006), amount of pack/years smoked (OR 1.947, 95%CI 1.141-3.323, =0.015), higher CCQ overall score (OR 3.318, 95%CI 1.050-9.892, =0.049) and higher education (OR 2.758, 95%CI 1.083-7.022, =0.033). Adherence was better in patients assuming triple inhaler therapy.

Conclusions: Suboptimal adherence is frequent among COPD patients, particularly in women, heavy smokers and subjects with high educational level. Interventions to improve adherence should be especially addressed to patients with these characteristics.
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http://dx.doi.org/10.4081/mrm.2020.654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7205009PMC
January 2020

Lung function in relation to six-minute walk test in pulmonary hypertension.

Eur Clin Respir J 2020 7;7(1):1745492. Epub 2020 Apr 7.

Department of Medical Sciences: Clinical Physiology, Uppsala University, Uppsala, Sweden.

: Pulmonary hypertension (PH) is a progressive disorder of the pulmonary circulation, associated with diverse medical conditions. Exercise limitation is the most prominent symptom in PH. Exercise capacity, commonly assessed through a six-minute walk test (6MWT), correlates with both functional status and survival in PH. Few studies have analysed the relation between respiratory function and exercise limitation. Therefore, we investigated the relationship between resting pulmonary function, exercise capacity, and exertional desaturation, assessed through the 6MWT, in unselected PH patients. : Fifty consecutive patients with PH diagnosis, referred for pulmonary function testing (lung volume, spirometry, and diffusing capacity for carbon monoxide (DLCO)) and 6MWT, were recruited at Molinette University Hospital, Turin. : The majority of the patients (54%) had PH due to left heart disease. Airway obstruction (FEV/VC-ratio < 0.7) was found in 46% of the patients and they performed significantly worse in the 6MWT than unobstructed patients (307 m vs. 377 m). Patients with PH due to left heart disease also performed significantly poorer 6MWT when airway obstruction was present (305 m vs. 389 m). Twenty-two patients (44%) presented exertional desaturation upon 6MWT. Lower DLCO divided by the alveolar volume (DLCO/VA), FEV/VC-ratios and resting PaO-values were significantly correlated with exertional desaturation after adjustments for age, sex, BMI, and smoking habits. DLCO/VA was the main determinant of exertional desaturation in a stepwise regression model. : Spirometric parameters of airway obstruction were related to walk distance and exercise-induced desaturation in PH patients. This suggests a place for spirometry in clinical monitoring of PH patients.
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http://dx.doi.org/10.1080/20018525.2020.1745492DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7178896PMC
April 2020

Gender differences in community-acquired pneumonia.

Minerva Med 2020 Apr 12;111(2):153-165. Epub 2020 Mar 12.

Unit of Pneumology U, Cardiovascular and Thoracic Department, Molinette Hospital, Città della Salute e della Scienza, University of Turin, Turin, Italy.

Introduction: Community-acquired pneumonia (CAP) is the most common type of lower respiratory tract infection and a major cause of morbidity and mortality in adults worldwide. Sex and gender play an active role in the incidence and outcomes of major infectious diseases, including CAP.

Evidence Acquisition: We searched the following electronic databases from January 2001 to December 2018: MEDLINE, EMBASE, CINHAIL, CENTRAL (Cochrane Central register of Controlled Trials), DARE (Database of Abstracts of Reviews of Effectiveness), Cochrane Database of Systematic Reviews and ACP Journal Club database.

Evidence Synthesis: Several studies have reported higher male susceptibility to pulmonary infections and higher risk of death due to sepsis. Biological differences (e.g. hormonal cycles and cellular immune-mediated responses) together with cultural, behavioral and socio-economic differences are important determinants of the course and outcome of CAP. However, gender-related bias in the provision of care and use of hospital resources has been reported among women, resulting in delayed hospital admission and consequently necessary care.

Conclusions: CAP is more severe in males than in females, leading to higher mortality in males, especially in older age. To identify gender differences in CAP can guide patient's prognostication and management.
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http://dx.doi.org/10.23736/S0026-4806.20.06448-4DOI Listing
April 2020

Impact of imipenem concentration in lung perfusate and tissue biopsy during clinical ex-vivo lung perfusion of high-risk lung donors.

Minerva Anestesiol 2020 Jun 27;86(6):617-626. Epub 2020 Jan 27.

Department of Medical and Surgical Sciences, Anesthesia, and Intensive Care Medicine, Sant'Orsola Polyclinic Hospital, Alma Mater Studiorum University of Bologna, Bologna, Italy.

Background: Normothermic ex-vivo lung perfusion (EVLP) limits organ donor shortage by potentially using high-risk donor lungs. Microbial burden reduction has been demonstrated after EVLP using antibiotic prophylaxis with imipenem. However, no data have been published on the clinical consequences of the potential residual bacterial burden.

Methods: Imipenem concentration was measured every hour (T0 to T6) in the lung perfusate and at the end of EVLP (Tf) in biopsies. The antimicrobial activity of perfusate at T1 and Tf against E. coli and K. pneumoniae was evaluated. Lungs were distinguished: no bacterial species in recipients and donors (donor-/recipient-); bacterial species isolated from donors and not from recipients (donor+/recipient-); same bacterial species in both recipients and donors (donor+/recipient+). Interleukin 6 (IL-6) and IL-8 concentrations in lung perfusate, clinical pulmonary infection score (CPIS) and primary graft dysfunction (PGD) were evaluated.

Results: Imipenem concentration in perfusate decreased over time. T1 and Tf perfusates exhibited bactericidal activity against E. coli and K. pneumoniae. Overall, T1 perfusates yielded higher bactericidal titers (BTs) than Tf. The donor+/recipient+ group (26% of cases) had higher IL-6 and IL-8 in perfusate and higher CPIS.

Conclusions: Recipients with the same bacterial species isolated in their donors had higher risk of pulmonary inflammation and early post-transplant pneumonia. Improvements in antimicrobial strategies during EVLP are warranted to minimize the consequences of donor associated respiratory infection.
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http://dx.doi.org/10.23736/S0375-9393.20.13840-9DOI Listing
June 2020

Vanishing Middle Bronchus in Bilateral Lung Transplant After Ex Vivo Lung Perfusion.

Exp Clin Transplant 2020 02 24;18(1):133-135. Epub 2019 Dec 24.

From the Cardiothoracic and Vascular Department, Division of Respiratory Medicine, "Città della Salute e della Scienza" Hospital and University of Torino, Turin, Italy.

Lung transplant has become the mainstay of therapy for most end-stage lung diseases. Airway complications are one of the most important problems during the first year after lung transplant. In this context, the most severe form of bronchial stenosis reported in the literature is vanishing bronchus syndrome, which is the obliteration with atresia of the ostium of a lobar bronchus, usually related to ischemia and infection. Ex vivo lung perfusion is a novel strategy forlung allograft preservation that keeps the organs at physiologic protective conditions. Nevertheless, many ex vivo systems work with lungs in supine position, and upperregions (middle lobe and lingula) can have lower perfusion supply, increasing the risk of a relative ischemia. We report a case of vanishing middle bronchus after ex vivo reconditioning bilateral lung transplant in a 45-year-old man with nonspecific interstitial pneumonia, whose posttransplant course was complicated by Aspergillusfumigatus infection.
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http://dx.doi.org/10.6002/ect.2019.0073DOI Listing
February 2020

Tailored combined cytomegalovirus management in lung transplantation: a retrospective analysis.

Ther Adv Respir Dis 2019 Jan-Dec;13:1753466619878555

Public Health and Pediatrics Department, Division of Virology, University of Turin, Città della Salute e della Scienza di Torino, Torino, Italy.

Background: There is no univocal prophylactic regimen to prevent cytomegalovirus (CMV) infection/disease in lung transplantation (LT) recipients. The aim of this study is to evaluate short-term clinical outcomes of a tailored combined CMV management approach.

Methods: After 1-year follow up, 43 LT patients receiving combined CMV prophylaxis with antiviral agents and CMV-specific IgG were evaluated in a retrospective observational study. Systemic and lung viral infections were investigated by molecular methods on a total of 1134 whole blood and 167 bronchoalveolar lavage (BAL) and biopsy specimens. CMV immunity was assessed by ELISPOT assay. Clinical and therapeutic data were also evaluated.

Results: We found 2/167 cases of CMV pneumonia (1.2%), both in the donor-positive/recipient-positive (D/R) population, and 51/167 cases of CMV pulmonary infection (BAL positivity 30.5%). However, only 32/167 patients (19.1%) were treated due to their weak immunological response at CMV ELISPOT assay. Viremia ⩾100,000 copies/mL occurred in 33/1134 specimens (2.9%). Regarding CMV-serological matching (D/R), the D/R population had more CMV viremia episodes ( < 0.05) and fewer viremia-free days ( < 0.001).

Conclusions: Compared to previous findings, our study shows a lower incidence of CMV pneumonia and viremia despite the presence of a substantial CMV load. In addition, our findings further confirm the D/R group to be a high-risk population for CMV viremia. Overall, a good immunological response seems to protect patients from CMV viremia and pneumonia but not from CMV alveolar replication.
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http://dx.doi.org/10.1177/1753466619878555DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6769221PMC
March 2020

Clinical and Functional Characteristics of COPD Patients Across GOLD Classifications: Results of a Multicenter Observational Study.

COPD 2019 08 9;16(3-4):215-226. Epub 2019 Sep 9.

Cardiovascular and Thoracic Department, SC Pneumologia U, Città Della Salute e Della Scienza (Molinette) University Hospital , Turin , Italy.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease. The severity grading systems proposed by the Global initiative for Chronic Obstructive Lung Disease (GOLD) have changed over time. The aim of the study was to evaluate if the different GOLD classifications can capture the complexity of the disease by investigating the distribution of lung function and clinical parameters across the GOLD classification systems. This was an observational, retrospective, multicentre study. COPD patients were stratified according to the GOLD severity grading proposed in the 2007, and to the ABCD assessment tool present in the 2011, and 2017 versions of the initiative. Data from body plethysmography, DLCO, comorbidities, exacerbation history, pharmacological therapy and eosinophil counts were collected. A total of 1360 patients (73.4% males) were included in the analysis. Overall, 37% of the patients were severe-very severe according to GOLD 2007. Compared with GOLD 2011, applying the GOLD 2017 criteria, the proportion of the at risk categories (C and D) was reduced by ∼23%. Impairment in inspiratory capacity, DLCO and the prevalence of emphysema paralleled the GOLD 2007 classification only. The proportion of patients with ≥ 200 eosinophils/µL was higher in GOLD 2007 stages 3-4 compared with stages 1-2 ( = 0.008). Eosinophil levels were similar across risk classes in GOLD 2011 and 2017. Overall, 41.8% and 52.4% of the patients in the low risk groups according to GOLD 2011 and 2017 were exposed to inhaled corticosteroids. The GOLD 2011 and 2017 classifications, despite exploring symptoms and exacerbations, might miss other relevant patients' clinical characteristics such as lung function and phenotypes, which have a significant impact on outcomes and disease severity.
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http://dx.doi.org/10.1080/15412555.2019.1659760DOI Listing
August 2019

Comparing a fixed combination of budesonide/formoterol with other inhaled corticosteroid plus long-acting beta-agonist combinations in patients with chronic obstructive pulmonary disease: a review.

Expert Rev Respir Med 2019 11 13;13(11):1087-1094. Epub 2019 Sep 13.

Allergy & Respiratory Diseases, DIMI Department of Internal Medicine, University of Genoa , Genoa , Italy.

: Inhaled corticosteroid (ICS) plus long-acting β-agonist (LABA) combinations are commonly used in the treatment of patients with chronic obstructive pulmonary disease (COPD). At least four fixed-dose ICS/LABA combinations are available, including budesonide/formoterol, beclomethasone/formoterol, fluticasone/vilanterol and fluticasone/salmeterol, but there is little guidance for clinicians on which of these combinations to prescribe. : The aim of this in-depth review was to identify studies that compared budesonide/formoterol with the other ICS/LABA combinations and assess the data on exacerbations, safety, and patient quality of life. PubMed and Ovid databases were searched, and 14 studies were identified. Our findings highlight the lack of prospective, randomized, controlled trials comparing LABA/ICS combinations in the treatment of COPD as only two such studies were identified. However, current evidence suggests that the effects of budesonide/formoterol on reducing exacerbations and improving quality of life may be similar to, or more marked than, those of other LABA/ICS combinations in COPD and, compared with the other LABA/ICS combinations, budesonide/formoterol may be associated with a lower incidence of serious pneumonia events and oral candidiasis. : To better guide clinicians in selecting between the available ICS/LABA, robust meta-analyses and well-designed head-to-head clinical trials are urgently needed.
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http://dx.doi.org/10.1080/17476348.2019.1665514DOI Listing
November 2019

Non-invasive ventilation in palliative care: a systematic review.

Minerva Med 2019 Dec 30;110(6):555-563. Epub 2019 Jul 30.

Unit of Intensive Care, Morales Meseguer Hospital, Murcia, Spain.

Introduction: An ageing population and steady increase in the rates of neoplasms and chronic degenerative diseases poses a challenge for societies and their healthcare systems. Because of the recent and continued advances in therapies, such as the development and widespread use of non-invasive ventilation (NIV), survival rates have increased for these pathologies. For patients with end-stage chronic respiratory diseases, the use of NIV following the onset of acute or severe chronic respiratory failure is a valid option when intubation has been excluded.

Evidence Acquisition: The following electronic databases were searched from their inception to January 2000 to December 2017: MEDLINE, EMBASE, CINHAIL, CENTRAL (Cochrane Central register of Controlled Trials), DARE (Database of Abstracts of Reviews of Effectiveness), the Cochrane Database of Systematic Reviews, ACP Journal Club database.

Evidence Synthesis: The available evidence strongly supports the use of NIV in patients presenting with an exacerbation of chronic obstructive pulmonary disease, as well end-stage neuromuscular disease. Few studies support the use of NIV in end-stage interstitial lung disease and in morbid obesity patients. In patients with cancer has been recommend offering NIV as palliative care to improve dyspnea.

Conclusions: The decision regarding the treatment should be made by the patient, ideally before reaching the terminal stage and after having a frank dialogue with healthcare professionals and family members.
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http://dx.doi.org/10.23736/S0026-4806.19.06273-6DOI Listing
December 2019

A Position Paper on IgM-Enriched Intravenous Immunoglobulin Adjunctive Therapy in Severe Acute Bacterial Infections: The TO-PIRO SCORE Proposal.

New Microbiol 2019 Jul 3;42(3):176-180. Epub 2019 Jun 3.

Anesthesia and Intensive Care Unit, University Hospital of Modena, Modena, Italy.

IgM-enriched immunoglobulins (e-IgM) may be useful in patients with severe acute bacterial infections. The evidence for the administration of e-IgM is not extensive and a definitive consensus has never been reached on its best use in patients with acute infections as well as in critically ill patients. However, the official indication in several countries, including Italy, is quite wide and mainly refers to supportive treatment of patients with acute severe bacterial infections. A multidisciplinary meeting of Italian Experts in Infectious Diseases, Anesthesia and Critical Care, Pneumology, Microbiology and Oncohaematology aimed to produce a statement on the best practical methodological score that could improve the use of e-IgM in patients with different infections, variable severity of disease and etiology. The Expert Panel reviewed the literature and the available guidelines, discussed the experience and eventually proposed to adapt the PIRO score to the practical methodological needs of a simple tool that could guide the administration of e-IgM.
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July 2019

Predictors of reversible airway obstruction with omalizumab in severe asthma: a real-life study.

Ther Adv Respir Dis 2019 Jan-Dec;13:1753466619841274

Department of Medical Sciences, University of Turin, Corso Dogliotti 14 10126 Turin, Italy.

Background: Omalizumab may modulate airway remodeling in severe asthma. Using forced expiratory volume in 1 second (FEV) as a surrogate of airway remodeling, we aimed to investigate if an omalizumab add-on in severe allergic asthma may lead to a persistent reversal of airway obstruction and to evaluate the potential biomarkers of airway obstruction reversibility.

Methods: Data were collected before (T0) and after omalizumab add-on for 1 year (T1, 32 patients), 2 years (T2, 26 patients) and 4 years (T4, 13 patients). All patients had baseline FEV below 80 % predicted (60.5 ± 12.5 %). After omalizumab, 18 patients showed FEV normalization (reversible airway obstruction; RAO+) already at T1 (88.7 ± 14.9 %, p < 0.0001) that persisted up to T4 (83.2 ± 7.9, p < 0.01), while 14 patients (RAO-) had FEV persistently decreased, from T1 (65.2 ± 8.4%, p < 0.05) up to T4 (61.4 ± 6.2%, not significant). Both groups had significant improvement of symptoms and exacerbations after omalizumab at T1, which persisted up to T4. The comparison between pretreatment characteristics of the two groups showed that RAO+ patients, had higher values of circulating eosinophils, exhaled nitric oxide (FNO), prevalence of rhinitis and nasal polyps, need of oral corticosteroids, shorter asthma duration, higher FEV and response to albuterol test. The optimal cut-off points predicting FEV normalization after omalizumab add-on were 30.5 ppb for FNO and 305 cells/µl for eosinophils.

Conclusions: This study suggests that omalizumab add-on contributes to the persistent reversal of airway obstruction in a consistent number of patients with severe allergic asthma, and this beneficial effect is predicted by elevated pretreatment FNO and circulating eosinophils.
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http://dx.doi.org/10.1177/1753466619841274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6475845PMC
November 2019

Extracorporeal membrane oxygenation after lung transplantation: risk factors and outcomes analysis.

Ann Cardiothorac Surg 2019 Jan;8(1):54-61

Cardiac Surgery Division, Surgical Sciences Department, Città della Salute e della Scienza, University of Torino, Turin, Italy.

Background: Lung transplantation is the treatment of choice for end-stage pulmonary disease in selected patients. However, severe primary graft dysfunction is a significant complication of transplant and requires the implantation of an extracorporeal support. The aim of the study is to evaluate the impact of extracorporeal membrane oxygenation (ECMO) after transplant in our center.

Methods: From January 2008 till June 2018, 195 consecutive unselected patients receiving a lung transplant were considered. Mean age was 49±15 years. Main indications for transplant were idiopathic pulmonary fibrosis in 72 patients, chronic obstructive pulmonary disease in 60 patients, and cystic fibrosis in 40 patients. Prior to transplant, 18 patients were on mechanical ventilation and 14 were on ECMO.

Results: Twenty-five patients required venous-venous ECMO after transplant. Vascular disease as cause of transplant [relative risk (RR) 7.8, 95% CI: 1.5-41, P=0.02], donor age (RR 1.6, 95% CI: 1.03-2.3, P=0.03) and need for cardiopulmonary by-pass during transplant (RR 3.1, 95% CI: 1.02-9, P=0.04) were associated with ECMO implantation. Patients requiring post-transplant ECMO received more transfusions (P<0.01), had a longer mechanical ventilation (P<0.01) and ICU stay (P<0.01) and had a higher hospital mortality (P<0.01). Post-transplant ECMO significantly influenced one- and five-year survival [hazard ratio (HR) 5.5, 95% CI: 3-10, P<0.001 and HR 3.5, 95% CI: 2-6, P<0.001, respectively]. However, conditional survival after t months is similar for patients with or without post-transplant ECMO.

Conclusions: In our experience, although ECMO is a reliable and effective strategy to support pulmonary function, severe graft dysfunction after lung transplantation still has a significant impact on early and late results.
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http://dx.doi.org/10.21037/acs.2018.12.10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6379200PMC
January 2019

A Comment on Helicobacter pylori and Lung Transplant Outcome: Is Serology the Ideal Diagnostic Approach?

Lung 2019 06 11;197(3):391-392. Epub 2019 Feb 11.

Division of Pulmonology, Cardiothoracic and Vascular Department, AOU Città della Salute e della Scienza di Torino, C.so Bramante 88/90, 10128, Turin, Italy.

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http://dx.doi.org/10.1007/s00408-019-00199-3DOI Listing
June 2019

Non-invasive ventilation in acute respiratory failure of patients with obesity hypoventilation syndrome.

Minerva Med 2018 Dec;109(6 Suppl 1):1-5

Unit of Respiratory Diseases and Allergies, Department of Internal Medicine (DiMI), San Martino University Hospital, Genoa, Italy.

Introduction: Non-invasive ventilation (NIV) has been used successfully for the management of acute respiratory failure (ARF) more often in the last two decades compared to prior decades. There are particular groups of patients that are more likely to benefit from NIV. One of these groups is patients with obesity hypoventilation syndrome (OHS). The aim of this review is to evalue the effectiveness of NIV in acute ARF.

Evidence Acquisition: MEDLINE, EMBASE, CINHAIL, Cochrane Central Register of Controlled Trials, DARE, the Cochrane Database of Systematic Reviews, and the ACP Journal Club database were searched from January 2001 to December 2017.

Evidence Synthesis: More than 30% of them have been diagnosed when hospitalized for ARF. NIV rarely failed in reversing ARF. OHS patients who exhibited early NIV failure had a high severity score and a low HCO3 level at admission; more than half of hypercapnic patients with decompensated OHS exhibited a delayed but successful response to NIV.

Conclusions: Patients with decompensation of OHS have a better prognosis and response to NIV than other hypercapnic patients. They required more aggressive NIV settings, a longer time to reduce paCO2 levels, and showed more frequently a delayed but successful response to NIV.
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http://dx.doi.org/10.23736/S0026-4806.18.05921-9DOI Listing
December 2018

The importance of a diagnostic pathway in the diagnosis of haemoptysis.

Adv Respir Med 2018 Dec 30. Epub 2018 Dec 30.

Cardiothoracic and Vascular Department, Respiratory Diseases Unit, University of Turin, Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino, Italy, Cso Bramante 88, 10126 Turin, Italy.

The role of interventional pulmonology in both the diagnostic and therapeutic aspects of haemopthysis is far to be completely defined. Even if we have to differentiate massive from mild and moderate bleeding it seems to be reasonable to asses that a bronchoscopy (fiberoptic or rigid) can be safely proposed in skilled centers with a wide range of immediate therapeutical interventional options, whether pneumological, either radiological or surgical.
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http://dx.doi.org/10.5603/ARM.a2018.0053DOI Listing
December 2018

The European Society of Thoracic Surgeons (ESTS) lung neuroendocrine tumors (NETs) database.

J Thorac Dis 2018 Oct;10(Suppl 29):S3528-S3532

Department of Surgical Sciences, Unit of Thoracic Surgery, University of Torino, Torino, Italy.

Histological characteristics and clinical behaviour define lung neuroendocrine tumors (NETs), which are classified into four groups: typical (TC) and atypical carcinoids (AC), large-cell neuroendocrine carcinomas (LCNCs) and small-cell lung cancers (SCLCs). Historically, outcome and treatment of these rare neoplasms have been based on small, usually mono-institutional clinical series. Furthermore, their rarity makes quite impossible to design randomised clinical trial to compare different treatments especially in unusual clinical presentations. In 2012, the European Society of Thoracic Surgeons (ESTS) launched a new working-group, specifically dedicated to lung NETs, with the aim to develop modern knowledge on biology and behaviour of these tumors, and to disseminate it within the scientific community. A dedicated retrospective database was at first developed and sent to all the ESTS centres interested to this project. More than 2,000 operated NETs cases have been rapidly collected, and they represented the clinical substrate of several published scientific studies. The retrospective data collection intrinsic limitations in term of patients' selection and treatment, along with the problem of possible missing data, were the reasons why the ESTS NETs working-group decided in 2015 to design and promote a new prospective database, employing the official ESTS platform. The aim of this review paper is to report the ESTS Lung NETs working-group history and to explain the architecture and use of the lung NETs databases.
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http://dx.doi.org/10.21037/jtd.2018.04.104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6230831PMC
October 2018

Competences in bronchoscopy for Intensive Care Unit, anesthesiology, thoracic surgery and lung transplantation.

Panminerva Med 2019 Sep 31;61(3):367-385. Epub 2018 Oct 31.

Department of Anesthesiology, Resuscitation and Intensive Care, University of Chieti-Pescara, Pescara, Italy.

Over the last decades, the use of flexible bronchoscopy has greatly increased in intensive care, anesthesia and thoracic surgery for diagnostic purpose, management of critical patients and to facilitate airway management for tracheal intubation, one lung ventilation and lung transplant management. The huge availability of endoscopic instruments and devices for airway management has amplified indications and possibilities for bronchoscopic procedures performed by intensive care physicians, anesthesiologist, endoscopists, and surgeons too. These practices need adequate technical skills that can be acquired only through defined learning pathways. This manuscript summarizes the indications and the competencies needed to perform bronchoscopic procedures in intensive care, anesthesia and thoracic surgery settings.
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http://dx.doi.org/10.23736/S0031-0808.18.03565-6DOI Listing
September 2019

Chronic obstructive lung disease "expert system": validation of a predictive tool for assisting diagnosis.

Int J Chron Obstruct Pulmon Dis 2018 28;13:1747-1753. Epub 2018 May 28.

Unit of Pulmonology, Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino, Torino, Italy.

Purpose: The purposes of this study were development and validation of an expert system (ES) aimed at supporting the diagnosis of chronic obstructive lung disease (COLD).

Methods: A questionnaire and a WebFlex code were developed and validated in silico. An expert panel pilot validation on 60 cases and a clinical validation on 241 cases were performed.

Results: The developed questionnaire and code validated in silico resulted in a suitable tool to support the medical diagnosis. The clinical validation of the ES was performed in an academic setting that included six different reference centers for respiratory diseases. The results of the ES expressed as a score associated with the risk of suffering from COLD were matched and compared with the final clinical diagnoses. A set of 60 patients were evaluated by a pilot expert panel validation with the aim of calculating the sample size for the clinical validation study. The concordance analysis between these preliminary ES scores and diagnoses performed by the experts indicated that the accuracy was 94.7% when both experts and the system confirmed the COLD diagnosis and 86.3% when COLD was excluded. Based on these results, the sample size of the validation set was established in 240 patients. The clinical validation, performed on 241 patients, resulted in ES accuracy of 97.5%, with confirmed COLD diagnosis in 53.6% of the cases and excluded COLD diagnosis in 32% of the cases. In 11.2% of cases, a diagnosis of COLD was made by the experts, although the imaging results showed a potential concomitant disorder.

Conclusion: The ES presented here (COLD) is a safe and robust supporting tool for COLD diagnosis in primary care settings.
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http://dx.doi.org/10.2147/COPD.S165533DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5978461PMC
January 2019

Alpha1-antitrypsin deficiency: what's new after European Respiratory Society Statement.

Panminerva Med 2018 Sep 24;60(3):101-108. Epub 2018 Apr 24.

Division of Pulmonology, Cardiothoracic and Vascular Department, AOU Città della Salute e della Scienza, Turin, Italy.

Alpha-1 antitrypsin deficiency (AATD) is a clinically under-recognized inherited disorder affecting the lungs and the liver. The most common manifestations are pulmonary emphysema, bronchiectasis and liver disease. The recent publication of the European Respiratory Society statement on diagnosis and treatment of pulmonary diseases has replaced the 2003 American Thoracic Society and European Respiratory Society one. New outcome parameters have been introduced and validated by observational and randomized clinical trials, and new information about efficacy and safety of augmentation therapy have been published. In this narrative review we have commented the crucial points of the new European Respiratory Society statement on AATD, including a review of the literature on liver involvement and treatments.
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http://dx.doi.org/10.23736/S0031-0808.18.03450-XDOI Listing
September 2018

Safety of nintedanib before lung transplant: an Italian case series.

Respirol Case Rep 2018 05 13;6(4):e00312. Epub 2018 Mar 13.

Department of Cardiac, Thoracic, and Vascular Sciences University of Padova PadovaItaly.

Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal disease that can only be cured by lung transplantation. Pharmacological agents play a role in preserving lung function and prolonging survival until a suitable donor organ becomes available. However, data on the effects of newer antifibrotic therapies on lung transplantation outcomes in IPF patients are lacking. The nine patients included in this case series were treated with nintedanib 150 mg twice daily for 3-30 (mean 13 ± 9) months before lung transplant surgery. Lung function was relatively preserved during nintedanib therapy, and no acute IPF exacerbations occurred. Transplant surgery was generally uneventful; eight of the nine patients are still alive. There were no extraordinary bleeding complications or issues with postoperative thoracic wound healing or dehiscence. Only one patient experienced bronchial anastomotic stenosis a few months later. In conclusion, nintedanib preserved lung function up to transplantation, was well tolerated, and had no detrimental effects on the short-term outcome of lung transplant.
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http://dx.doi.org/10.1002/rcr2.312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5849579PMC
May 2018