Publications by authors named "Stefano Centanni"

99 Publications

The impact of COVID-19 on total mortality in Italy up to November 2020.

Panminerva Med 2021 Jan 25. Epub 2021 Jan 25.

Respiratory Unit, Department of Health Sciences, ASST Santi Paolo e Carlo, Università degli Studi di Milano, Milan, Italy.

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http://dx.doi.org/10.23736/S0031-0808.21.04301-9DOI Listing
January 2021

Vitamin D in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients with non-invasive ventilation support.

Panminerva Med 2021 Jan 25. Epub 2021 Jan 25.

Respiratory Unit, ASST Santi Paolo e Carlo, San Paolo Hospital, Department of Health Sciences, Università degli Studi di Milano, Milan, Italy -

Background: Vitamin D (VitD) deficiency has been reported to be associated with respiratory tract infection. In this work we evaluated the concentration of VitD in COVID-19 patients experiencing acute respiratory infections of different levels of severity excluding those who underwent invasive respiratory support.

Methods: The levels of serum VitD and C-reactive protein (CRP) were analyzed in 118 consecutive hospitalized COVID-19 patients (74M, 44F), confirmed with rRT-PCR. Of these patients with ventilation support 52 (44.1%) received oxygen via nasal cannula, oxygen mask or an oxygen mask with a reservoir, 48 (40.7%) were on a continuous positive airway pressure device (CPAP) and 18 (15,3%) on non-invasive mechanical ventilation (NIMV).

Results: The median values (range) of VitD and of CRP were 15.1 ng/mL (1.3-73.3) and 14.2 mg/L (5.0-151.2), respectively. A negative correlation from VitD levels and those of CRP (correlation coefficient - 0.259: P=0.005) was observed. VitD levels in O2 support patients were significantly higher than in both CPAP and NIMV patients. No statistical differences were found for CRP levels (P=0.834) among the three type of oxygen support. Fewer patients with O2 support had VitD <30 ng/mL and <20 ng/mL than CPAP and NIMV patients. There were no relationships between VitD and the three classes of IgM (P=0.419) and of IgG (P=0.862) SARS-CoV-2 antibodies values. The behavior was the same for CRP.

Conclusions: Our study shows that a significant proportion of COVID-19 patients have a VitD deficiency and that this condition is more frequent in CPAP and in NIMV patients.
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http://dx.doi.org/10.23736/S0031-0808.21.04277-4DOI Listing
January 2021

The Many Faces of Covid-19 at a Glance: A University Hospital Multidisciplinary Account From Milan, Italy.

Front Public Health 2020;8:575029. Epub 2021 Jan 8.

Respiratory Medicine, Department of Health Sciences, San Paolo University Hospital, Azienda Socio Sanitaria Territoriale Santi Paolo e Carlo, University of Milan Medical School, Milan, Italy.

In March 2020, northern Italy became the second country worldwide most affected by Covid-19 and the death toll overtook that in China. Hospital staff soon realized that Covid-19 was far more severe than expected from the few data available at that time. The Covid-19 pandemic forced hospitals to adjust to rapidly changing circumstances. We report our experience in a general teaching hospital in Milan, the capital of Lombardy, the most affected area in Italy. First, we briefly describe Lombardy's regional Covid-19-related health organizational changes as well as general hospital reorganization. We also provide a multidisciplinary report of the main clinical, radiological and pathological Covid-19 findings we observed in our patients.
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http://dx.doi.org/10.3389/fpubh.2020.575029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820812PMC
February 2021

Why two doses of the BNT162b2 mRNA Covid-19 vaccine? A different strategy to speed up the vaccination process: single-dose of the BNT162b2 mRNA Covid-19 and other vaccines.

Panminerva Med 2021 Jan 22. Epub 2021 Jan 22.

Management Engineering Tourbillon Tech srl, Padova, Italy -

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http://dx.doi.org/10.23736/S0031-0808.21.04286-5DOI Listing
January 2021

Measuring vital capacity in amyotrophic lateral sclerosis: Effects of interfaces and reproducibility.

Respir Med 2021 Jan 3;176:106277. Epub 2020 Dec 3.

Division of Pulmonary and Critical Care Medicine, Hines Veterans Affairs Hospital and Loyola University of Chicago Stritch School of Medicine, Hines, IL, 60141, USA. Electronic address:

Background: Deterioration of vital capacity (VC) in amyotrophic lateral sclerosis (ALS) signifies disease progression and indicates need for non-invasive ventilation. Weak facial muscles consequent to ALS, with resulting poor mouth seal, may interfere with the accuracy of VC measurements.

Objectives: To determine whether different interfaces affect VC measurements in ALS patients and whether the interface yielding the largest VC produces an even higher VC when re-measured after one week (learning effect). To explore the relationship between optimal interface VC and sniff nasal pressure (SNIP), a measurement of global inspiratory muscle strength.

Methods: Thirty-five patients (17 bulbar and 18 spinal ALS) were studied. Three interfaces (rigid-cylindrical, flanged, oronasal mask) were tested. One week after the first visit, VC was recorded using the optimal interface. SNIP recordings were also obtained.

Results: In the bulbar ALS group, median (interquartile range) VC with the flanged mouthpiece was 8.4% (3.9-15.5) larger than with the cylindrical mouthpiece (p < 0.001). VC values with oronasal mask were intermediate to VC with the other two interfaces. In spinal ALS, flanged mouthpiece VC was 4.6% (2.3-7.5) larger than with oronasal mask (p < 0.0006). The latter was 4.5% (0.6-5.2) smaller than with the cylindrical mouthpiece (p = 0.002). In both groups, VC during the second visit was greater than during the first visit (p < 0.025). SNIPs were logarithmically related to VC values recorded with the flanged mouthpiece.

Conclusion: A flanged mouthpiece yields the largest values of VC in patients with bulbar and spinal ALS.
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http://dx.doi.org/10.1016/j.rmed.2020.106277DOI Listing
January 2021

Decreased serum level of sphingosine-1-phosphate: a novel predictor of clinical severity in COVID-19.

EMBO Mol Med 2021 01 9;13(1):e13424. Epub 2020 Dec 9.

Department of Medical Biotechnology and Translational Medicine, LITA-Segrate, Università degli Studi di Milano, Milan, Italy.

The severity of coronavirus disease 2019 (COVID-19) is a crucial problem in patient treatment and outcome. The aim of this study is to evaluate circulating level of sphingosine-1-phosphate (S1P) along with severity markers, in COVID-19 patients. One hundred eleven COVID-19 patients and forty-seven healthy subjects were included. The severity of COVID-19 was found significantly associated with anemia, lymphocytopenia, and significant increase of neutrophil-to-lymphocyte ratio, ferritin, fibrinogen, aminotransferases, lactate dehydrogenase (LDH), C-reactive protein (CRP), and D-dimer. Serum S1P level was inversely associated with COVID-19 severity, being significantly correlated with CRP, LDH, ferritin, and D-dimer. The decrease in S1P was strongly associated with the number of erythrocytes, the major source of plasma S1P, and both apolipoprotein M and albumin, the major transporters of blood S1P. Not last, S1P was found to be a relevant predictor of admission to an intensive care unit, and patient's outcome. Circulating S1P emerged as negative biomarker of severity/mortality of COVID-19 patients. Restoring abnormal S1P levels to a normal range may have the potential to be a therapeutic target in patients with COVID-19.
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http://dx.doi.org/10.15252/emmm.202013424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744841PMC
January 2021

Forecasting the burden of COVID-19 hospitalized patients during the SARS-CoV-2 second wave in Lombardy, Italy.

Panminerva Med 2021 03 13;63(1):86-87. Epub 2020 Nov 13.

Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.

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http://dx.doi.org/10.23736/S0031-0808.20.04212-3DOI Listing
March 2021

Prolonged Low-Dose Methylprednisolone in Patients With Severe COVID-19 Pneumonia.

Open Forum Infect Dis 2020 Oct 12;7(10):ofaa421. Epub 2020 Sep 12.

Department of Pulmonology, University Hospital of Cattinara, Trieste, Italy.

Background: In hospitalized patients with coronavirus disease 2019 (COVID-19) pneumonia, progression to acute respiratory failure requiring invasive mechanical ventilation (MV) is associated with significant morbidity and mortality. Severe dysregulated systemic inflammation is the putative mechanism. We hypothesize that early prolonged methylprednisolone (MP) treatment could accelerate disease resolution, decreasing the need for intensive care unit (ICU) admission and mortality.

Methods: We conducted a multicenter observational study to explore the association between exposure to prolonged, low-dose MP treatment and need for ICU referral, intubation, or death within 28 days (composite primary end point) in patients with severe COVID-19 pneumonia admitted to Italian respiratory high-dependency units. Secondary outcomes were invasive MV-free days and changes in C-reactive protein (CRP) levels.

Results: Findings are reported as MP (n = 83) vs control (n = 90). The composite primary end point was met by 19 vs 40 (adjusted hazard ratio [aHR], 0.41; 95% CI, 0.24-0.72). Transfer to ICU and invasive MV were necessary in 15 vs 27 ( = .07) and 14 vs 26 ( = .10), respectively. By day 28, the MP group had fewer deaths (6 vs 21; aHR, 0.29; 95% CI, 0.12-0.73) and more days off invasive MV (24.0 ± 9.0 vs 17.5 ± 12.8;  = .001). Study treatment was associated with rapid improvement in PaO:FiO and CRP levels. The complication rate was similar for the 2 groups ( = .84).

Conclusion: In patients with severe COVID-19 pneumonia, early administration of prolonged MP treatment was associated with a significantly lower hazard of death (71%) and decreased ventilator dependence. Treatment was safe and did not impact viral clearance. A large randomized controlled trial (RECOVERY trial) has been performed that validates these findings. ClinicalTrials.gov NCT04323592.
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http://dx.doi.org/10.1093/ofid/ofaa421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7543560PMC
October 2020

Respiratory dysfunction in Parkinson's disease: a narrative review.

ERJ Open Res 2020 Oct 5;6(4). Epub 2020 Oct 5.

"Aldo Ravelli" Center for Neurotechnology and Experimental Brain Therapeutics, Dept of Health Sciences, University of Milan, Milan, Italy.

The presence of respiratory symptoms in Parkinson's disease (PD) has been known since the first description of the disease, even though the prevalence and incidence of these disturbances are not well defined. Several causes have been reported, comprising obstructive and restrictive pulmonary disease and changes in the central ventilatory control, and different pathogenetic mechanisms have been postulated accordingly. In our review, we encompass the current knowledge about respiratory abnormalities in PD, as well as the impact of anti-Parkinsonian drugs as either risk or protective factors. A description of putative pathogenetic mechanisms is also provided, and possible treatments are discussed, focusing on the importance of recognising and treating respiratory symptoms as a key manifestation of the disease itself. A brief description of respiratory dysfunctions in atypical Parkinsonism, especially α-synucleinopathies, is also provided.
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http://dx.doi.org/10.1183/23120541.00165-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7533305PMC
October 2020

Oral CorticoSteroid sparing with biologics in severe asthma: A remark of the ().

World Allergy Organ J 2020 Oct 20;13(10):100464. Epub 2020 Sep 20.

Personalized Medicine, Asthma & Allergy, Humanitas Clinical and Research Center, IRCCS, Rozzano, MI, Italy.

According to the data derived from several national and international registries, including SANI (Severe Asthma Network Italy), and considering the strong impact that frequent or regular use of oral corticosteroid has on quality of life (QoL) of severe asthmatics, as well as on the costs for managing corticosteroid-related diseases, oral corticosteroid sparing up to withdrawal should be considered a primary outcome in the management of severe asthma. New biologics have clearly demonstrated that this effect is possible, with concomitant reduction in the rate of exacerbations and in symptom control. Then, there is no reason for using so frequently oral corticosteroid before having explored all alternatives currently available for a large part of severe asthmatics.
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http://dx.doi.org/10.1016/j.waojou.2020.100464DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509464PMC
October 2020

Inpatient Care during the COVID-19 Pandemic: A Survey of Italian Physicians.

Respiration 2020 5;99(8):667-677. Epub 2020 Aug 5.

Dipartimento di Scienze della Salute, Università degli Studi di Milano, Milan, Italy,

Background: Coronavirus disease 2019 (COVID-19) is a potentially fatal disease that is of great global public health concern.

Objective: We explored the clinical management of inpatients with COVID-19 in Italy.

Methods: A self-administered survey was sent by email to Italian physicians caring for adult patients with COVID-19. A panel of experts was selected according to their clinical curricula and their responses were analyzed.

Results: A total of 1,215 physicians completed the survey questionnaire (17.4% response rate). Of these, 188 (15.5%) were COVID-19 experts. Chest computed tomography was the most used method to detect and monitor COVID-19 pneumonia. Most of the experts managed acute respiratory failure with CPAP (56.4%), high flow nasal cannula (18.6%), and non-invasive mechanical ventilation (8%), while an intensivist referral for early intubation was requested in 17% of the cases. Hydroxychloroquine was prescribed as an antiviral in 90% of cases, both as monotherapy (11.7%), and combined with protease inhibitors (43.6%) or azithromycin (36.2%). The experts unanimously prescribed low-molecular-weight heparin to patients with severe COVID-19 pneumonia, and half of them (51.6%) used a dose higher than standard. The respiratory burden in patients who survived the acute phase was estimated as relevant in 28.2% of the cases, modest in 39.4%, and negligible in 9%.

Conclusions: In our survey some major topics, such as the role of non-invasive respiratory support and drug treatments, show disagreement between experts, likely reflecting the absence of high-quality evidence studies. Considering the significant respiratory sequelae reported following COVID-19, proper respiratory and physical therapy programs should be promptly made available.
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http://dx.doi.org/10.1159/000509007DOI Listing
October 2020

SARS-CoV-2 specific serological pattern in healthcare workers of an Italian COVID-19 forefront hospital.

BMC Pulm Med 2020 Jul 29;20(1):203. Epub 2020 Jul 29.

Respiratory Unit, ASST Santi Paolo e Carlo, San Paolo Hospital, Department of Health Sciences, Università degli Studi di Milano, Milan, Italy.

Background: COVID-19 is an infectious disease caused by a novel coronavirus (SARS-CoV-2). The immunopathogenesis of the infection is currently unknown. Healthcare workers (HCWs) are at highest risk of infection and disease. Aim of the study was to assess the sero-prevalence of SARS-CoV-2 in an Italian cohort of HCWs exposed to COVID-19 patients.

Methods: A point-of-care lateral flow immunoassay (BioMedomics IgM-IgG Combined Antibody Rapid Test) was adopted to assess the prevalence of IgG and IgM against SARS-CoV-2. It was ethically approved ("Milano Area 1" Ethical Committee prot. n. 2020/ST/057).

Results: A total of 202 individuals (median age 45 years; 34.7% males) were retrospectively recruited in an Italian hospital (Milan, Italy). The percentage (95% CI) of recruited individuals with IgM and IgG were 14.4% (9.6-19.2%) and 7.4% (3.8-11.0%), respectively. IgM were more frequently found in males (24.3%), and in individuals aged 20-29 (25.9%) and 60-69 (30.4%) years. No relationship was found between exposure to COVID-19 patients and IgM and IgG positivity.

Conclusions: The present study did show a low prevalence of SARS-CoV-2 IgM in Italian HCWs. New studies are needed to assess the prevalence of SARS-CoV-2 antibodies in HCWs exposed to COVID-19 patients, as well the role of neutralizing antibodies.
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http://dx.doi.org/10.1186/s12890-020-01237-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388425PMC
July 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

COVID-19 mortality rates in the European Union, Switzerland, and the UK: effect of timeliness, lockdown rigidity, and population density.

Minerva Med 2020 Aug 2;111(4):308-314. Epub 2020 Jun 2.

Service of Pneumology, Hospital Universitario de la Princesa, Madrid, Spain -

Background: To date, the European experience with COVID-19 mortality has been different to that observed in China and Asia. We aimed to forecast mortality trends in the 27 countries of the European Union (EU), plus Switzerland and the UK, where lockdown dates and confinement interventions have been heterogeneous, and to explore its determinants.

Methods: We have adapted our predictive model of COVID-19-related mortality, which rested on the observed mortality within the first weeks of the outbreak and the date of the respective lockdown in each country. It was applied in a training set of three countries (Italy, Germany and Spain), and then applied to the EU plus the UK and Switzerland. In addition, we explored the effects of timeliness and rigidity of the lockdown (on a five-step scale) and population density in our forecasts. We report r2, and percent variation of expected versus observed deaths, all following TRIPOD guidance.

Results: We identified a homogeneous distribution of deaths, and found a median of 24 days after lockdown adoption to reach the maximum daily deaths. Strikingly, cumulative deaths up to April 25th, 2020 observed in Europe separated countries in three waves, according to the time lockdown measures were adopted following the onset of the outbreak: after a week, within a week, or even prior to the outbreak (r2=0.876). In contrast, no correlation neither with lockdown rigidity nor population density were observed.

Conclusions: The European experience confirms that early, effective interventions of lockdown are fundamental to minimizing the COVID-19 death toll.
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http://dx.doi.org/10.23736/S0026-4806.20.06702-6DOI Listing
August 2020

Natural history of incidental sporadic and tuberous sclerosis complex associated lymphangioleiomyomatosis.

Respir Med 2020 07 28;168:105993. Epub 2020 Apr 28.

Divisao de Pneumologia, Instituto Do Coracao (InCor), Hospital Das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil. Electronic address:

Lymphangioleiomyiomatosis (LAM) is a rare disease affecting women in childbearing age. A sporadic form (S-LAM) affecting previously healthy women, and a form associated with Tuberous Sclerosis Complex (TSC-LAM) are described. Some data suggested that TSC-LAM could be a milder disease compared to S-LAM. To investigate whether the different disease behavior is real or due to overdiagnosis of screened TSC women, we compared the natural history of S-LAM and TSC-LAM in patients with incidental diagnosis. Clinical, and functional data from 52 patients (23 with S-LAM and 29 with TSC-LAM) were analysed. At diagnosis functional impairment was mild without differences between groups [FEV1 % pred was 97% (88-105) and 94% (82-106) in TSC-LAM and S-LAM, respectively, p = 0.125]. Patients with S-LAM had less renal angiomyolipoma, and lower VEGF-D serum levels than TSC-LAM. There was no difference in the baseline extent of pulmonary cysts on CT scan and no difference in yearly rate of functional decline between TSC-LAM, and S-LAM patients [e.g. yearly rate of decline of FEV1 % pred was -0.51 (-1.59-2.24) and -0.90 (-1.92--0.42) in TSC-LAM and S-LAM, respectively, p = 0.265]. In conclusion, the natural history of TSC-LAM and S-LAM, when a potential selection bias due to screening in the latter group is balanced, is similar. Our study suggests that the prevalence of S-LAM can be significantly underestimated due to a tendency to diagnosis more frequently patients with more severe impairment, without identifying several ones with asymptomatic disease.
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http://dx.doi.org/10.1016/j.rmed.2020.105993DOI Listing
July 2020

First ultrastructural autoptic findings of SARS -Cov-2 in olfactory pathways and brainstem.

Minerva Anestesiol 2020 06 13;86(6):678-679. Epub 2020 May 13.

Department of Health Sciences, University of Milan, Milan, Italy.

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http://dx.doi.org/10.23736/S0375-9393.20.14772-2DOI Listing
June 2020

Advanced forecasting of SARS-CoV-2-related deaths in Italy, Germany, Spain, and New York State.

Allergy 2020 07 11;75(7):1813-1815. Epub 2020 May 11.

Departments of Pneumology, Intensive Care Medicine, Center for Internal Medicine, Universitätsmedizin Rostock, Rostock, Germany.

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http://dx.doi.org/10.1111/all.14327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7264667PMC
July 2020

The role of phenotype on ventilation and exercise capacity in patients affected by COPD: a retrospective study.

Multidiscip Respir Med 2020 01 3;15(1):476. Epub 2020 Feb 3.

Department of Health Sciences, University of Milan, Respiratory Unit, ASST Papa Giovanni XXIII Hospital, Bergamo.

Background: The idea of phenotype in chronic obstructive pulmonary disease (COPD) has evolved in the last decades, and the importance of peculiar treatment strategies has now been acknowledged. Although dyspnea and exercise limitation are hallmarks of COPD, this aspect has never been fully explored in literature in terms of disease phenotype. The aim of the present study was to explore the relevance of clinical COPD phenotypes on exercise ventilation and maximal capacity.

Methods: In this observational cohort retrospective study we analyzed the data of 50 COPD patients who underwent cardiopulmonary exercise test, categorized as emphysematous (n=29), and non-emphysematous (n=21) according to a previously validated model.

Results: We found a significant difference in terms of VE/VCO slope (median values 32.4 28.0, =0.015) and VE/VCO ratio at nadir (median values 37 . 33, =0.004), which resulted higher in emphysematous patients, who also presented lower PCO values (median values 32.6 35.6, =0.008). In a subgroup of 31 tests which met the maximality criteria, emphysematous patients presented a significantly lower work rate at peak (median value 51 72% predicted, =0.016), and showed a lower peak oxygen consumption, although at the limit of significance (median values of 63 85 % predicted, =0.051).

Conclusions: This study extends our knowledge about the characterization of the COPD phenotypical expression of disease, showing that patients affected by emphysema are more prone to ventilatory inefficiency during exercise, and that this is likely to be an important cause of their overall reduced exercise capacity.
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http://dx.doi.org/10.4081/mrm.2020.476DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7037504PMC
January 2020

New perspectives on difficult-to-treat tuberculosis based on old therapeutic approaches.

Int J Infect Dis 2020 Mar 27;92S:S91-S99. Epub 2020 Feb 27.

Clinical Epidemiology and Medical Statistics Unit, Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari, Italy. Electronic address:

Tuberculosis (TB) is an important clinical and public health issue worldwide. Despite improved treatment success rates following the introduction of antibiotics in daily clinical practice, the expected decline in incidence has been hampered by HIV epidemics and multi- and extensively drug-resistant TB. During the pre-antibiotic era, TB therapies were mainly based on improving hygiene conditions, strengthening the immune system, and targeting the rest of the affected lungs with invasive techniques. Detailed knowledge of old non-pharmacological therapies might support physicians and researchers in the identification of new solutions for difficult-to-treat patients. We performed a narrative literature review on the main old therapeutic options prescribed for patients with TB. The main recommendations and contraindications of sanatorium therapies (i.e., bed rest, fresh air, sunlight) and pulmonary collapse techniques are reviewed, evaluating their physiological basis and their impact on patient outcomes. We report studies describing new interventional pulmonary and surgical techniques and assess new perspectives based on old medical and surgical treatments, whose potential implementation could help complicated patients.
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http://dx.doi.org/10.1016/j.ijid.2020.02.039DOI Listing
March 2020

Clinical Use and Barriers of Thoracic Ultrasound: A Survey of Italian Pulmonologists.

Respiration 2020;99(2):171-176. Epub 2020 Jan 10.

Casa Cura Policlinico, Department of Neurorehabilitation Sciences, Milan, Italy.

Introduction: Thoracic ultrasound is accurate in the diagnosis of a wide range of respiratory diseases. Yet the extent of its use is unknown. Through a national survey, we aimed to explore the clinical use of thoracic ultrasound and the barriers to the diffusion of the technique in Italy.

Methods: Accademia di Ecografia Toracica (AdET) developed a self-administered survey which was sent by email to Italian pulmonologists via national scientific societies and networks.

Results: Of the 2010 physicians invited, 514 completed the survey (26% response rate). According to 99% of responders, thoracic ultrasound had a relevant clinical role. Seventy-nine percent of the responders used thoracic ultrasound at least once a month. The main settings were: 53% pulmonology ward, 15% outpatient clinic, 15% interventional pulmonology room, 10% internal medicine ward, 4% respiratory intensive care units, and 9% other. Thoracic ultrasound was primarily used: (1) with both diagnostic and interventional aims (72%), (2) as diagnostic imaging (17%), and (3) as guidance for interventional procedures (11%). The main clinical applications were: (1) diagnosis and management of pleural effusion, (2) pneumothorax, (3) pneumonia, (4) cardiac failure, and (5) acute dyspnea. Twenty-one percent of the responders do not use thoracic ultrasound. The main reported bar-riers were: (1) availability of an ultrasound system (52%), (2) lack of protected time and training (22%), and (3) use of the technique by other specialists (15%).

Conclusion: Thoracic ultrasound is widely used by Italian pulmonologists and considered a clinically relevant tool. The availability of dedicated ultrasound systems seems to be a major limit of the use of the technique.
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http://dx.doi.org/10.1159/000504632DOI Listing
January 2020

Chest pain and a left parasternal soft tissue swelling in an immunocompetent refugee with disseminated tuberculosis.

Int J Infect Dis 2020 Jan 4;90:116-118. Epub 2019 Nov 4.

Clinical Epidemiology and Medical Statistics Unit, Department of Medical, Surgical and Experimental Medicine, University of Sassari, Sassari, Italy. Electronic address:

An immunocompetent migrant with chest pain was admitted to an Italian hospital. Computed tomography showed a left pectoral abscess and osteomyelitis of the sternum. The infection had spread into the anterior mediastinum near to the pericardium and the heart, where an atrial mass was confirmed by echocardiography. Disseminated tuberculosis was diagnosed.
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http://dx.doi.org/10.1016/j.ijid.2019.10.033DOI Listing
January 2020

Impact of ICS/LABA and LABA/LAMA FDCs on functional and clinical outcomes in COPD: A network meta-analysis.

Pulm Pharmacol Ther 2019 12 19;59:101855. Epub 2019 Oct 19.

Department of Experimental Medicine and Surgery, University of Rome "Tor Vergata", Rome, Italy.

Background: Inhaled corticosteroid (ICS)/long-acting β agonist (LABA) fixed-dose combinations (FDCs) and LABA/long-acting muscarinic antagonist (LAMA) FDCs are extensively used to treat chronic obstructive pulmonary disease (COPD). The aim of the present network meta-analysis was to assess the comparative efficacy of all the currently available dual therapies in patients with moderate-to-severe COPD.

Methods: A network meta-analysis (≥3 nodes, Bayesian method) was performed by searching for randomized clinical trials (RCTs) that compared the impact of different LABA/LAMA FDCs vs. ICS/LABA FDCs on both primary and secondary endpoints. The primary endpoints were: the change from baseline in trough forced expiratory volume in 1 s (FEV) and the risk of exacerbation of COPD (AECOPD). The secondary endpoints were: peak FEV, St' George's Respiratory Questionnaire (SGRQ), Transition Dyspnea Index (TDI), and rescue medication use.

Results: Data of 17,734 COPD patients were extracted from 16 RCTs. The length of treatment ranged from 6 weeks to 52 weeks. All LABA/LAMA FDCs, except aclidinium/formoterol, produced a statistically significant improvement compared to ICS/LABAs in trough FEV. The surface under the cumulative ranking curve (SUCRA) analysis indicated that umeclidinium/vilanterol, glycopyrronium/indacaterol and glycopyrrolate/formoterol fumarate were the most effective FDCs in improving trough FEV. Across the FDCs analyzed for the risk of AECOPD, glycopyrronium/indacaterol significantly reduced the exacerbation risk compared to fluticasone propionate/salmeterol and resulted the most effective combination in the SUCRA analysis. Similar trend were also observed for the peak FEV. No significant differences were detected across the investigated FDCs regarding SGRQ, TDI, and use of rescue medication.

Conclusions: The results of this meta-analysis show that LABA/LAMA combinations are consistently more effective than ICS/LABA FDCs for most of the evaluated outcomes. However, differences have also been observed between FDCs belonging to the same class. Across the investigated LABA/LAMA FDCs, glycopyrronium/indacaterol revealed a consistent and robust efficacy profile.
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http://dx.doi.org/10.1016/j.pupt.2019.101855DOI Listing
December 2019

The unmet need for pertussis prevention in patients with chronic obstructive pulmonary disease in the Italian context.

Hum Vaccin Immunother 2020 6;16(2):340-348. Epub 2019 Sep 6.

Respiratory Unit, Department of Health of Sciences, ASST Santi Paolo e Carlo, University of Milan, Milan, Italy.

Despite high rates of vaccination, pertussis resurgence has been reported worldwide in recent years, including in Italy, especially in older adults.Chronic obstructive pulmonary disease (COPD) is a respiratory disease associated with progressive inflammation of the respiratory tract. Regional population studies have shown the prevalence of COPD in Italy to be approximately 15% with an age-dependent increase in proportion of COPD cases.Emerging data shows that individuals with COPD are at high risk of contracting pertussis. Furthermore, those who develop pertussis could experience exacerbation of their pre-existent COPD and further susceptibility to other infections.Immunization programs in Italy currently recommend a decennial reduced-antigen-content diphtheria-tetanus-acellular pertussis booster vaccine dose for adults. Active measures to encourage booster vaccination, especially for high-risk adults such as those with COPD, could positively impact pertussis morbidity and the associated healthcare burden.
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http://dx.doi.org/10.1080/21645515.2019.1652517DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7062424PMC
September 2019

Bronchoscopy to assess patients with hemoptysis: which is the optimal timing?

BMC Pulm Med 2019 Feb 11;19(1):36. Epub 2019 Feb 11.

Clinical Epidemiology and Medical Statistics Unit, Department of Medical, Surgical, Experimental Sciences, University of Sassari, Sassari, Italy.

Background: Bronchoscopy plays a key role to diagnose the etiology, to localize the site, and to identify the sources of the bleeding in patients with hemoptysis, but the ideal timing of an endoscopic examination is still unclear.

Methods: We performed a secondary analysis of an observational and multicenter study, aimed at evaluating the epidemiology of hemoptysis in Italy and the diagnostic yield of the most frequently prescribed examinations. The aim of the study was to evaluate whether an early bronchoscopy (i.e., performed during active bleeding/≤48 h after hemoptysis stopped) helps localize bleeding (i.e., site, lobe, lung) and increase diagnostic yield in comparison with a delayed examination.

Results: Four hundred eighty-six consecutive adult patients (69.2% males; median [IQR] age: 67 [53-76] years) with hemoptysis requiring an etiological diagnosis and undergoing bronchoscopy were recruited. Bleeding focus could be located more frequently in case of moderate-severe bleedings than in cases of mild hemoptysis (site: 70/154, 45.4%, VS. 73/330, 22.1%; p-value < 0.0001; lobe: 95/155, 61.3%, VS. 95/331, 28.7%; p-value < 0.0001; lung: 101/155, 65.1%, VS. 111/331, 33.5%; p-value < 0.0001). Early bronchoscopy showed a higher detection rate of bleeding source in comparison with delayed examination (site: 76/214, 35.5%, VS. 67/272, 24.6%; p-value = 0.01; lobe: 98/214, 45.8%, VS. 92/272, 33.8%; p-value = 0.007; lung: 110/214, 51.4%, VS. 102/272, 37.5%; p-value = 0.002). Early bronchoscopy did not provide any advantages in terms of increased diagnostic yield, in the total cohort (113/214, 52.8%, VS. 123/272, 45.2%; p-value = 0.10) and in the severity subtypes (mild: 56/128, 43.8%, VS. 88/203, 43.4%; p-value = 0.94; moderate-severe: 57/86, 66.2%, VS. 35/69, 50.7%; p-value = 0.051).

Conclusions: Early bronchoscopy helps detect bleeding sources, particularly in cases of moderate-severe hemoptysis, without increasing diagnostic accuracy.

Trial Registration: ClinicalTrials.gov (identifier: NCT02045394 ).
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http://dx.doi.org/10.1186/s12890-019-0795-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6371580PMC
February 2019

Enlightening chronic obstructive pulmonary disease through patients' and caregivers' narratives.

Int J Chron Obstruct Pulmon Dis 2018;13:3095-3105. Epub 2018 Oct 5.

Health Care Area, Fondazione ISTUD, Milan, Italy,

Purpose: The primary aim of this research was to raise awareness for COPD through real narratives of patients, caregivers, and pulmonologists. The second objective includes providing clinicians new means of caring for and treating patients with COPD.

Methods: Using narrative medicine, testimonies from patients, their caregivers, and clinicians were collected through an online questionnaire enriched by a narrative plot. Narrations were analyzed throughout descriptive statistics and an elaboration of recurring words and expressions.

Results: Throughout the project, 350 narratives were collected from 235 patients, 55 caregivers, and 60 physicians. Though a generally neutral reaction had been observed upon diagnosis, COPD had been found to have a high impact on the patients' and caregivers' lives. Metaphors utilized by patients and caregivers were suggestive of fear and panic unlike those utilized by clinicians who usually had a more technical approach. Smoking was a significant concern for not only patients and caregivers but also clinicians.

Conclusion: Physicians are therefore challenged to find new ways of communicating COPD to raise awareness on this pathology and encourage corrective habits. An important social objective should be the implementation of a health system that is able to optimize patients' and caregivers' lives.
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http://dx.doi.org/10.2147/COPD.S172214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6178274PMC
March 2019

Haemoptysis and fever in a young refugee from Somalia.

Int J Infect Dis 2018 Dec 10;77:57-60. Epub 2018 Oct 10.

Clinical Epidemiology and Medical Statistics Unit, Department of Medical, Surgical and Experimental Medicine, University of Sassari, Via Padre Manzella, 4, Sassari, Italy. Electronic address:

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http://dx.doi.org/10.1016/j.ijid.2018.10.002DOI Listing
December 2018

Interventional pulmonology techniques in elderly patients with comorbidities.

Eur J Intern Med 2019 01 29;59:14-20. Epub 2018 Sep 29.

Department of Biomedical and Clinical Sciences (DIBIC), University of Milan, Milan, Italy; Division of Respiratory Diseases, "Luigi Sacco" University Hospital; ASST Fatebenefratelli-Sacco, Milan, Italy.

Respiratory diseases are common cause of disability in the elderly and are often concomitant with other non-respiratory medical conditions. Interventional pulmonology includes advanced diagnostic and therapeutic techniques, successfully employed for benign and malignant pulmonary diseases with a good safety profile. A few studies are available on the efficacy and the safety of these procedures (both bronchoscopic and pleural techniques) in the elderly. Paucity of data in these patients may support reluctant clinicians. We carried out a non-systematic review aimed at describing the scientific literature on interventional pulmonology techniques in elderly patients with comorbidities. We summarized indications, performance characteristics, and safety profile of bronchoscopic techniques in the elderly, comparing outcomes between older and younger patients. We explored the role of age on anesthesia and sedation protocols during endoscopic procedures and assessed the influence of comorbidities on bronchoscopic outcomes. This review underlines that older age is not a barrier for implementing interventional pulmonology for diagnostic and therapeutic purposes.
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http://dx.doi.org/10.1016/j.ejim.2018.09.015DOI Listing
January 2019

Bronchoscopy in Patients With Hemoptysis and Negative Imaging Tests.

Chest 2018 06;153(6):1510-1511

Clinical Epidemiology and Medical Statistics Unit, Department of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy.

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http://dx.doi.org/10.1016/j.chest.2017.12.028DOI Listing
June 2018