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Article ; Online: Cardiovascular Complications in Community-Acquired Pneumonia

Antonio Desai / Stefano Aliberti / Francesco Amati / Anna Stainer / Antonio Voza

Microorganisms, Vol 10, Iss 2177, p

2022 Volume 2177

Abstract: Community-acquired pneumonia (CAP) is accountable for high mortality in both pediatric and adult populations worldwide, about one-third of hospitalized patients pass away within a year of being discharged from the facility. The high mortality and ... ...

Abstract	Community-acquired pneumonia (CAP) is accountable for high mortality in both pediatric and adult populations worldwide, about one-third of hospitalized patients pass away within a year of being discharged from the facility. The high mortality and morbidity rates are closely related to cardiovascular complications that are consequent or concomitant to the acute episode of pneumonia. An updated perspective on the major pathophysiological mechanisms, prevalence, risk factors, outcomes, and relevant treatments of cardiovascular events in CAP patients is provided in the current study. It is possible to evaluate the pathophysiology of cardiac disease in this population based on plaque-related events, such as acute myocardial infarction, or events unrelated to plaque, such as arrhythmias and heart failure. With an absolute rate of cardiovascular problems ranging broadly from 10% to 30%, CAP raises the risk of both plaque-related and plaque-unrelated events. Both in- and out-patients may experience these issues at admission, throughout hospitalization, or even up to a year following discharge. At long-term follow-up, cardiac events account for more than 30% of deaths in CAP patients, making them a significant cause of mortality. If patients at risk for cardiac events are stratified, diagnostic tools, monitoring, and preventive measures may be applied to these patients. A prospective evaluation of cardioprotective treatments is urgently required from a research point of view.
Keywords	acute myocardial infarction ; arrhythmia ; cardiovascular complications ; community-acquired pneumonia ; heart failure ; stroke ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2022-11-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Identify Drug-Resistant Pathogens in Patients with Community-Acquired Pneumonia

Francesco Amati / Francesco Bindo / Anna Stainer / Andrea Gramegna / Marco Mantero / Mattia Nigro / Linda Bussini / Michele Bartoletti / Francesco Blasi / Stefano Aliberti

Advances in Respiratory Medicine, Vol 91, Iss 18, Pp 224-

2023 Volume 238

Abstract: A substantial increase in broad-spectrum antibiotics as empirical therapy in patients with community-acquired pneumonia (CAP) has occurred over the last 15 years. One of the driving factors leading to that has been some evidence showing an increased ... ...

Abstract	A substantial increase in broad-spectrum antibiotics as empirical therapy in patients with community-acquired pneumonia (CAP) has occurred over the last 15 years. One of the driving factors leading to that has been some evidence showing an increased incidence of drug-resistant pathogens (DRP) in patients from a community with pneumonia, including methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa . Research has been published attempting to identify DRP in CAP through the implementation of probabilistic approaches in clinical practice. However, recent epidemiological data showed that the incidence of DRP in CAP varies significantly according to local ecology, healthcare systems and countries where the studies were performed. Several studies also questioned whether broad-spectrum antibiotic coverage might improve outcomes in CAP, as it is widely documented that broad-spectrum antibiotics overuse is associated with increased costs, length of hospital stay, drug adverse events and resistance. The aim of this review is to analyze the different approaches used to identify DRP in CAP patients as well as the outcomes and adverse events in patients undergoing broad-spectrum antibiotics.
Keywords	community-acquired pneumonia ; drug-resistant pathogens ; broad-spectrum antibiotics ; Diseases of the respiratory system ; RC705-779 ; Medicine (General) ; R5-920
Subject code	610
Language	English
Publishing date	2023-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Unmet needs and perspectives in rheumatoid arthritis-associated interstitial lung disease

Anna Stainer / Antonio Tonutti / Maria De Santis / Francesco Amati / Angela Ceribelli / Gabriele Bongiovanni / Chiara Torrisi / Antonio Iacopino / Giuseppe Mangiameli / Stefano Aliberti / Carlo Selmi

Frontiers in Medicine, Vol

A critical review

2023 Volume 10

Abstract: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by synovitis as the most common clinical manifestation, and interstitial lung disease (RA-ILD) represents one of the most common and potentially severe extra-articular ... ...

Abstract	Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by synovitis as the most common clinical manifestation, and interstitial lung disease (RA-ILD) represents one of the most common and potentially severe extra-articular features. Our current understanding of the mechanisms and predictors of RA-ILD is limited despite the demonstration that an early identification of progressive fibrosing forms is crucial to provide timely treatment with antifibrotic therapies. While high resolution computed tomography is the gold standard technique for the diagnosis and follow-up of RA-ILD, it has been hypothesized that serum biomarkers (including novel and rare autoantibodies), new imaging techniques such as ultrasound of the lung, or the application of innovative radiologic algorithms may help towards predicting and detecting early forms of diseases. Further, while new treatments are becoming available for idiopathic and connective tissue disease-associated forms of lung fibrosis, the treatment of RA-ILD remains anecdotal and largely unexplored. We are convinced that a better understanding of the mechanisms connecting RA with ILD in a subgroup of patients as well as the creation of adequate diagnostic pathways will be mandatory steps for a more effective management of this clinically challenging entity.
Keywords	progressive pulmonary fibrosis ; biomarkers ; immunology ; precision medicine ; rheumatoid arthritis ; interstitial lung disease ; Medicine (General) ; R5-920
Subject code	610
Language	English
Publishing date	2023-03-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Walking the path of treatable traits in interstitial lung diseases

Francesco Amati / Paolo Spagnolo / Christopher J. Ryerson / Justin M. Oldham / Andrea Gramegna / Anna Stainer / Marco Mantero / Nicola Sverzellati / Donato Lacedonia / Luca Richeldi / Francesco Blasi / Stefano Aliberti

Respiratory Research, Vol 24, Iss 1, Pp 1-

2023 Volume 15

Abstract: Abstract Interstitial lung diseases (ILDs) are complex and heterogeneous diseases. The use of traditional diagnostic classification in ILD can lead to suboptimal management, which is worsened by not considering the molecular pathways, biological ... ...

Abstract	Abstract Interstitial lung diseases (ILDs) are complex and heterogeneous diseases. The use of traditional diagnostic classification in ILD can lead to suboptimal management, which is worsened by not considering the molecular pathways, biological complexity, and disease phenotypes. The identification of specific “treatable traits” in ILDs, which are clinically relevant and modifiable disease characteristics, may improve patient’s outcomes. Treatable traits in ILDs may be classified into four different domains (pulmonary, aetiological, comorbidities, and lifestyle), which will facilitate identification of related assessment tools, treatment options, and expected benefits. A multidisciplinary care team model is a potential way to implement a “treatable traits” strategy into clinical practice with the aim of improving patients’ outcomes. Multidisciplinary models of care, international registries, and the use of artificial intelligence may facilitate the implementation of the “treatable traits” approach into clinical practice. Prospective studies are needed to test potential therapies for a variety of treatable traits to further advance care of patients with ILD.
Keywords	Treatable traits ; Biomarkers ; Endotype ; Phenotype ; Interstitial lung diseases ; Personalized medicine ; Diseases of the respiratory system ; RC705-779
Subject code	610
Language	English
Publishing date	2023-10-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Heterogeneity of weight gain after initiation of Elexacaftor/Tezacaftor/Ivacaftor in people with cystic fibrosis

Andrea Gramegna / Fabio Majo / Gianfranco Alicandro / Gloria Leonardi / Luca Cristiani / Francesco Amati / Martina Contarini / Stefano Aliberti / Alessandro Giovanni Fiocchi / Francesco Blasi

Respiratory Research, Vol 24, Iss 1, Pp 1-

2023 Volume 7

Abstract: Abstract Background The introduction of the novel therapy, Elexacaftor/Tezacaftor/Ivacaftor (ETI) has been effective in improving weight gain in both clinical trials and real-world studies. However, the magnitude of this effect appears to be ... ...

Abstract	Abstract Background The introduction of the novel therapy, Elexacaftor/Tezacaftor/Ivacaftor (ETI) has been effective in improving weight gain in both clinical trials and real-world studies. However, the magnitude of this effect appears to be heterogeneous across patient subgroups. This study aims to identify potential determinants of heterogeneity in weight gain following 6-month ETI therapy. Methods We conducted a multicenter, prospective cohort study enrolling 92 adults with CF at two major CF centers in Italy with follow-up visit at one month and six months from ETI initiation. The treatment’s effect on weight changes was evaluated using mixed effect regression models that included subject-specific random intercepts and fixed effects for potential predictors of treatment response, time and a predictor-by-time interaction term. Results The mean weight gain at six months from the start of treatment was 4.6 kg (95% CI: 2.3–6.9) for the 10 patients with underweight, 3.2 kg (95% CI: 2.3-4.0) for the 72 patients with normal weight, and 0.7 kg (95% CI: -1.6-3.0) for the 10 patients with overweight. After six months of ETI treatment, 8 (80%) of the patients with underweight transitioned to the normal weight category, while 11 (15.3%) of the normal-weight patients became overweight. The major determinants of heterogeneity in weight gain were the baseline BMI and the presence of at least one CFTR residual function mutation, explaining 13% and 8% of the variability, respectively. Conclusions Our results indicate that ETI is highly effective in improving weight gain in underweight subjects with CF. However, our data also suggests the need for close monitoring of excess weight gain to prevent potential cardiometabolic complications.
Keywords	Weight gain ; Response to treatment ; Personalized medicine ; CFTR modulators ; Elexacaftor ; Overweight ; Diseases of the respiratory system ; RC705-779
Subject code	616
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Treatable traits and challenges in the clinical management of non-tuberculous mycobacteria lung disease in people with cystic fibrosis

Andrea Gramegna / Sofia Misuraca / Andrea Lombardi / Chiara Premuda / Ivan Barone / Margherita Ori / Francesco Amati / Mariangela Retucci / Erica Nazzari / Gianfranco Alicandro / Maurizio Ferrarese / Luigi Codecasa / Alessandra Bandera / Stefano Aliberti / Valeria Daccò / Francesco Blasi

Respiratory Research, Vol 24, Iss 1, Pp 1-

2023 Volume 11

Abstract: Abstract Introduction Over the last ten years an increasing prevalence and incidence of non-tuberculous mycobacteria (NTM) has been reported among patients with cystic fibrosis (CF) Viviani (J Cyst Fibros, 15(5):619–623, 2016). NTM pulmonary disease has ... ...

Abstract	Abstract Introduction Over the last ten years an increasing prevalence and incidence of non-tuberculous mycobacteria (NTM) has been reported among patients with cystic fibrosis (CF) Viviani (J Cyst Fibros, 15(5):619–623, 2016). NTM pulmonary disease has been associated with negative clinical outcomes and often requires pharmacological treatment. Although specific guidelines help clinicians in the process of diagnosis and clinical management, the focus on the multidimensional assessment of concomitant problems is still scarce. Main body This review aims to identify the treatable traits of NTM pulmonary disease in people with CF and discuss the importance of a multidisciplinary approach in order to detect and manage all the clinical and behavioral aspects of the disease. The multidisciplinary complexity of NTM pulmonary disease in CF requires careful management of respiratory and extra-respiratory, including control of comorbidities, drug interactions and behavioral factors as adherence to therapies. Conclusions The treatable trait strategy can help to optimize clinical management through systematic assessment of all the aspects of the disease, providing a holistic treatment for such a multi-systemic and complex condition.
Keywords	Cystic fibrosis ; NTM pulmonary disease ; Personalized medicine ; Treatable traits ; Diseases of the respiratory system ; RC705-779
Subject code	610
Language	English
Publishing date	2023-12-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Comparison of different sets of immunological tests to identify treatable immunodeficiencies in adult bronchiectasis patients

Stefano Aliberti / Francesco Amati / Andrea Gramegna / Barbara Vigone / Martina Oriano / Giovanni Sotgiu / Marco Mantero / Edoardo Simonetta / Laura Saderi / Anna Stainer / Serena Tammaro / Paola Marchisio / Eva Polverino / James D. Chalmers / Francesco Blasi

ERJ Open Research, Vol 8, Iss

2022 Volume 1

Abstract: Background The reported prevalence of immunodeficiencies in bronchiectasis patients is variable depending on the frequency and extent of immunological tests performed. European Respiratory Society guidelines recommend a minimum bundle of tests. ... ...

Abstract	Background The reported prevalence of immunodeficiencies in bronchiectasis patients is variable depending on the frequency and extent of immunological tests performed. European Respiratory Society guidelines recommend a minimum bundle of tests. Broadening the spectrum of immunological tests could increase the number of patients diagnosed with an immunodeficiency and those who could receive specific therapy. The primary objective of the present study was to assess the performance of different sets of immunological tests in diagnosing any, primary, secondary or treatable immunodeficiencies in adults with bronchiectasis. Methods An observational, cross-sectional study was conducted at the Bronchiectasis Program of the Policlinico University Hospital in Milan, Italy, from September 2016 to June 2019. Adult outpatients with a clinical and radiological diagnosis of bronchiectasis underwent the same immunological screening during the first visit when clinically stable consisting of: complete blood count; immunoglobulin (Ig) subclass tests for IgA, IgG, IgM and IgG; total IgE; lymphocyte subsets; and HIV antibodies. The primary endpoint was the prevalence of patients with any immunodeficiencies using five different sets of immunological tests. Results A total of 401 bronchiectasis patients underwent the immunological screening. A significantly different prevalence of bronchiectasis patients diagnosed with any, primary or secondary immunodeficiencies was found across different bundles. 44.6% of bronchiectasis patients had a diagnosis of immunodeficiency when IgG subclasses and lymphocyte subsets were added to the minimum bundle suggested by the guidelines. Conclusion A four-fold increase in the diagnosis of immunodeficiencies can be found in adults with bronchiectasis when IgG subclasses and lymphocyte subsets are added to the bundle of tests recommended by guidelines.
Keywords	Medicine ; R
Subject code	610
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	European Respiratory Society
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Lung Microbiome in Idiopathic Pulmonary Fibrosis and Other Interstitial Lung Diseases

Francesco Amati / Anna Stainer / Marco Mantero / Andrea Gramegna / Edoardo Simonetta / Giulia Suigo / Antonio Voza / Anoop M. Nambiar / Umberto Cariboni / Justin Oldham / Philip L. Molyneaux / Paolo Spagnolo / Francesco Blasi / Stefano Aliberti

International Journal of Molecular Sciences, Vol 23, Iss 977, p

2022 Volume 977

Abstract: Interstitial lung diseases represent a heterogeneous and wide group of diseases in which factors leading to disease initiation and progression are not fully understood. Recent evidence suggests that the lung microbiome might influence the pathogenesis ... ...

Abstract	Interstitial lung diseases represent a heterogeneous and wide group of diseases in which factors leading to disease initiation and progression are not fully understood. Recent evidence suggests that the lung microbiome might influence the pathogenesis and progression of interstitial lung diseases. In recent years, the utilization of culture-independent methodologies has allowed the identification of complex and dynamic communities of microbes, in patients with interstitial lung diseases. However, the potential mechanisms by which these changes may drive disease pathogenesis and progression are largely unknown. The aim of this review is to discuss the role of the altered lung microbiome in several interstitial lung diseases. Untangling the host–microbiome interaction in the lung and airway of interstitial lung disease patients is a research priority. Thus, lung dysbiosis is a potentially treatable trait across several interstitial lung diseases, and its proper characterization and treatment might be crucial to change the natural history of these diseases and improve outcomes.
Keywords	microbiome ; interstitial lung diseases ; treatable traits ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Nontuberculous mycobacteria infection and pulmonary disease in bronchiectasis

Kseniia Suska / Francesco Amati / Giovanni Sotgiu / Andrea Gramegna / Marco Mantero / Margherita Ori / Maurizio Ferrarese / Luigi Ruffo Codecasa / Anna Stainer / Francesco Blasi / Stefano Aliberti

ERJ Open Research, Vol 8, Iss

2022 Volume 4

Abstract: Background Although interest in nontuberculous mycobacteria (NTM) infection has increased in the last decades, published data vary according to different geographical areas, diagnostic facilities and quality of study design. This study aims at assessing ... ...

Abstract	Background Although interest in nontuberculous mycobacteria (NTM) infection has increased in the last decades, published data vary according to different geographical areas, diagnostic facilities and quality of study design. This study aims at assessing both prevalence and incidence of NTM infection and NTM pulmonary disease (NTM-PD) among adults with bronchiectasis, to describe patients’ characteristics, therapeutic options and clinical outcomes. Methods Bronchiectasis adults who had been tested for NTM were enrolled at the Bronchiectasis Program of the Policlinico Hospital in Milan, Italy, from 2016 to 2018. Results Among the 373 patients enrolled, 26.1% had at least one respiratory sample positive for NTM and 12.6% reached a diagnosis of NTM-PD. Incidence rates for NTM infection and NTM-PD were 13 (95% CI 10–16) and 4 (95% CI 2–6) per 100 person-years, respectively. The most prevalent NTM species causing NTM-PD were M. intracellulare (38.3%), M. avium (34.0%), M. abscessus (8.5%) and M. kansasii (8.5%). Once treatment for NTM-PD was initiated, a favourable outcome was documented in 52.2% of the patients, while a negative outcome was recorded in 32.6%, including recurrence (17.4%), treatment failure (10.9%), re-infection (2.2%) and relapse (2.2%). Treatment halted was experienced in 11 (23.9%) patients. Conclusions NTM infection is frequent in bronchiectasis patients and the presence of NTM-PD is relevant. The low success rate of NTM-PD treatment in bronchiectasis patients requires a call to action to identify new treatment modalities and new drugs to improve patients’ outcomes.
Keywords	Medicine ; R
Subject code	610
Language	English
Publishing date	2022-12-01T00:00:00Z
Publisher	European Respiratory Society
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Protease–Antiprotease Imbalance in Bronchiectasis

Martina Oriano / Francesco Amati / Andrea Gramegna / Anthony De Soyza / Marco Mantero / Oriol Sibila / Sanjay H. Chotirmall / Antonio Voza / Paola Marchisio / Francesco Blasi / Stefano Aliberti

International Journal of Molecular Sciences, Vol 22, Iss 5996, p

2021 Volume 5996

Abstract: Airway inflammation plays a central role in bronchiectasis. Protease–antiprotease balance is crucial in bronchiectasis pathophysiology and increased presence of unopposed proteases activity may contribute to bronchiectasis onset and progression. ... ...

Abstract	Airway inflammation plays a central role in bronchiectasis. Protease–antiprotease balance is crucial in bronchiectasis pathophysiology and increased presence of unopposed proteases activity may contribute to bronchiectasis onset and progression. Proteases’ over-reactivity and antiprotease deficiency may have a role in increasing inflammation in bronchiectasis airways and may lead to extracellular matrix degradation and tissue damage. Imbalances in serine proteases and matrix-metallo proteinases (MMPs) have been associated to bronchiectasis. Active neutrophil elastase has been associated with disease severity and poor long-term outcomes in this disease. Moreover, high levels of MMPs have been associated with radiological and disease severity. Finally, severe deficiency of α1-antitrypsin (AAT), as PiSZ and PiZZ (proteinase inhibitor SZ and ZZ) phenotype, have been associated with bronchiectasis development. Several treatments are under study to reduce protease activity in lungs. Molecules to inhibit neutrophil elastase activity have been developed in both oral or inhaled form, along with compounds inhibiting dipeptydil-peptidase 1, enzyme responsible for the activation of serine proteases. Finally, supplementation with AAT is in use for patients with severe deficiency. The identification of different targets of therapy within the protease–antiprotease balance contributes to a precision medicine approach in bronchiectasis and eventually interrupts and disrupts the vicious vortex which characterizes the disease.
Keywords	bronchiectasis ; proteases ; neutrophilic inflammation ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2021-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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