Phenotypes and Serum Biomarkers in Sarcoidosis.

Sarcoidosis is a multisystem disease, which is diagnosed on a compatible clinical presentation, non-necrotizing granulomatous inflammation in one or more tissue samples, and exclusion of alternative causes of granulomatous disease. Considering its heterogeneity, numerous aspects of the disease remain to be elucidated. In this context, the identification and integration of biomarkers may hold significance in clinical practice, aiding in appropriate selection of patients for targeted clinical trials. This work aims to discuss and analyze how validated biomarkers are currently integrated in disease category definitions. Future studies are mandatory to unravel the diverse contributions of genetics, socioeconomic status, environmental exposures, and other sociodemographic variables to disease severity and phenotypic presentation. Furthermore, the implementation of transcriptomics, multidisciplinary approaches, and consideration of patients' perspectives, reporting innovative insights, could be pivotal for a better understanding of disease pathogenesis and the optimization of clinical assistance.

Exacerbation Burden in COPD and Occurrence of Mortality in a Cohort of Italian Patients: Results of the Gulp Study.

Objective: To describe the burden of moderate to severe exacerbations and all-cause mortality; the secondary objectives were to analyze treatment patterns and changes over follow-up. Design: Observational, multicenter, retrospective, cohort study with a three year follow-up period. Setting: Ten Italian academic secondary- and tertiary-care centers. Participants: Patients with a confirmed diagnosis of COPD referring to the outpatient clinics of the participating centers were retrospectively recruited. Primary and Secondary Outcome Measures: Annualized frequency of moderate and severe exacerbations stratified by exacerbation history prior to study enrollment. Patients were classified according to airflow obstruction, GOLD risk categories, and divided in 4 groups: A = no exacerbations; B = 1 moderate exacerbation; C = 1 severe exacerbation; D = ≥2 moderate and/or severe exacerbations. Overall all-cause mortality stratified by age, COPD category, and COPD therapy. A logistic regression model assessed the association of clinical characteristics with mortality. Results: 1111 patients were included (73% males), of which 41.5% had a history of exacerbations. As expected, the proportion of patients experiencing ≥1 exacerbation during follow-up increased according to pre-defined study risk categories (B: 79%, C: 84%, D: 97.4%). Overall, by the end of follow-up, 45.5% of patients without a history of exacerbation experienced an exacerbation (31% of which severe), and 13% died. Deceased patients were significantly older, more obstructed and hyperinflated, and more frequently active smokers compared with survivors. Severe exacerbations were more frequent in patients that died (23.5%, vs 10.2%; p-value: 0.002). Chronic heart failure and ischemic heart disease were the only comorbidities associated with a higher odds ratio (OR) for death (OR: 2.2, p-value: 0.001; and OR: 1.9, p-value: 0.007). Treatment patterns were similar in patients that died and survivors. Conclusion: Patients with a low exacerbation risk are exposed to a significant future risk of moderate/severe exacerbations. Real life data confirm the strong association between mortality and cardiovascular comorbidities in COPD.

Spirometric patterns in young and middle-aged adults: a 20-year European study.

BACKGROUND: Understanding the natural history of abnormal spirometric patterns at different stages of life is critical to identify and optimise preventive strategies. We aimed to describe characteristics and risk factors of restrictive and obstructive spirometric patterns occurring before 40 years (young onset) and between 40 and 61 years (mid-adult onset). METHODS: We used data from the population-based cohort of the European Community Respiratory Health Survey (ECRHS). Prebronchodilator forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) were assessed longitudinally at baseline (ECRHS1, 1993-1994) and again 20 years later (ECRHS3, 2010-2013). Spirometry patterns were defined as: restrictive if FEV1/FVC≥LLN and FVC<10th percentile, obstructive if FEV1/FVC

Inhaled recombinant GM-CSF reduces the need for whole lung lavage and improves gas exchange in autoimmune pulmonary alveolar proteinosis patients.

RATIONALE: Whole lung lavage (WLL) is a widely accepted palliative treatment for autoimmune pulmonary alveolar proteinosis (aPAP) but does not correct myeloid cell dysfunction or reverse the pathological accumulation of surfactant. In contrast, inhaled recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) is a promising pharmacological approach that restores alveolar macrophage functions including surfactant clearance. Here, we evaluate WLL followed by inhaled rGM-CSF (sargramostim) as therapy of aPAP. METHODS: 18 patients with moderate-to-severe aPAP were enrolled, received baseline WLL, were randomised into either the rGM-CSF group (receiving inhaled sargramostim) or control group (no scheduled therapy) and followed for 30 months after the baseline WLL. Outcome measures included additional unscheduled "rescue" WLL for disease progression, assessment of arterial blood gases, pulmonary function, computed tomography, health status, biomarkers and adverse events. Patients requiring rescue WLL were considered to have failed their assigned intervention group. RESULTS: The primary end-point of time to first rescue WLL was longer in rGM-CSF-treated patients than controls (30 versus 18 months, n=9 per group, p=0.0078). Seven control patients (78%) and only one rGM-CSF-treated patient (11%) required rescue WLL, demonstrating a 7-fold increase in relative risk (p=0.015). Compared to controls, rGM-CSF-treated patients also had greater improvement in peripheral arterial oxygen tension, alveolar-arterial oxygen tension difference, diffusing capacity of the lungs for carbon monoxide and aPAP biomarkers. One patient from each group withdrew for personal reasons. No serious adverse events were reported. CONCLUSIONS: This long-term, prospective, randomised trial demonstrated inhaled sargramostim following WLL reduced the requirement for WLL, improved lung function and was safe in aPAP patients. WLL plus inhaled sargramostim may be useful as combined therapy for aPAP.

Early life exposures contributing to accelerated lung function decline in adulthood - a follow-up study of 11,000 adults from the general population.

Background: We aimed to assess whether exposure to risk factors in early life from conception to puberty continue to contribute to lung function decline later in life by using a pooled cohort comprising approx. 11,000 adults followed for more than 20 years and with up to three lung function measurements. Methods: Participants (20-68 years) in the ECRHS and NFBC1966 cohort studies followed in the periods 1991-2013 and 1997-2013, respectively, were included. Mean annual decline in maximum forced expired volume in 1 s (FEV1) and forced vital capacity (FVC) were main outcomes. Associations between early life risk factors and change in lung function were estimated using mixed effects linear models adjusted for sex, age, FEV1, FVC and height at baseline, accounting for personal smoking. Findings: Decline in lung function was accelerated in participants with mothers that smoked during pregnancy (FEV1 2.3 ml/year; 95% CI: 0.7, 3.8) (FVC 2.2 ml/year; 0.2, 4.2), with asthmatic mothers (FEV1 2.6 ml/year; 0.9, 4.4) (FEV1/FVC 0.04 per year; 0.04, 0.7) and asthmatic fathers (FVC 2.7 ml/year; 0.5, 5.0), and in women with early menarche (FVC 2.4 ml/year; 0.4, 4.4). Personal smoking of 10 pack-years contributed to a decline of 2.1 ml/year for FEV1 (1.8, 2.4) and 1.7 ml/year for FVC (1.3, 2.1). Severe respiratory infections in early childhood were associated with accelerated decline among ever-smokers. No effect-modification by personal smoking, asthma symptoms, sex or cohort was found. Interpretation: Mothers' smoking during pregnancy, parental asthma and early menarche may contribute to a decline of FEV1 and FVC later in life comparable to smoking 10 pack-years. Funding: European Union's Horizon 2020; Research Council of Norway; Academy of Finland; University Hospital Oulu; European Regional Development Fund; Spanish Ministry of Science and Innovation; Generalitat de Catalunya.

Severe Asthma Network Italy Definition of Clinical Remission in Severe Asthma: A Delphi Consensus.

Severe asthma affects about 10% of the population with asthma and is characterized by low lung function and a high count of blood leukocytes, mainly eosinophils. Various definitions are used in clinical practice and in the literature to identify asthma remission: clinical remission, inflammatory remission, and complete remission. This work highlights a consensus for asthma remission using a Delphi method. In the context of the Severe Asthma Network Italy, which accounts for 57 severe asthma centers and more than 2,200 patients, a board of six experts drafted a list of candidate statements in a questionnaire, which has been revised to minimize redundancies and ensure clear and consistent wording for the first round (R1) of the analysis. Thirty-two statements were included in the R1 questionnaire and then submitted to a panel of 80 experts, which used a 5-point Likert scale to measure agreement regarding each statement. Then, an interim analysis of R1 data was performed, and items were discussed and considered to produce a consistent questionnaire for round 2 (R2) of the analysis. Then, the board set the R2 questionnaire, which included only important topics. Panelists were asked to vote on the statements in the R2 questionnaire afterward. During R2, the criteria of complete clinical remission (the absence of the need for oral corticosteroids, symptoms, exacerbations or attacks, and pulmonary function stability) and those of partial clinical remission (the absence of the need for oral corticosteroids, and two of three criteria: the absence of symptoms, exacerbations or attacks, and pulmonary stability) were confirmed. This Severe Asthma Network Italy Delphi analysis defined a valuable and independent tool that is easy to use, to test the efficacy of different treatments in patients with severe asthma enrolled into the SANI registry.

Smart Sensors and Microtechnologies in the Precision Medicine Approach against Lung Cancer.

BACKGROUND AND RATIONALE: The therapeutic interventions against lung cancer are currently based on a fully personalized approach to the disease with considerable improvement of patients' outcome. Alongside continuous scientific progresses and research investments, massive technologic efforts, innovative challenges, and consolidated achievements together with research investments are at the bases of the engineering and manufacturing revolution that allows a significant gain in clinical setting. AIM AND METHODS: The scope of this review is thus to focus, rather than on the biologic traits, on the analysis of the precision sensors and novel generation materials, as semiconductors, which are below the clinical development of personalized diagnosis and treatment. In this perspective, a careful revision and analysis of the state of the art of the literature and experimental knowledge is presented. RESULTS: Novel materials are being used in the development of personalized diagnosis and treatment for lung cancer. Among them, semiconductors are used to analyze volatile cancer compounds and allow early disease diagnosis. Moreover, they can be used to generate MEMS which have found an application in advanced imaging techniques as well as in drug delivery devices. CONCLUSIONS: Overall, these issues represent critical issues only partially known and generally underestimated by the clinical community. These novel micro-technology-based biosensing devices, based on the use of molecules at atomic concentrations, are crucial for clinical innovation since they have allowed the recent significant advances in cancer biology deciphering as well as in disease detection and therapy. There is an urgent need to create a stronger dialogue between technologists, basic researchers, and clinicians to address all scientific and manufacturing efforts towards a real improvement in patients' outcome. Here, great attention is focused on their application against lung cancer, from their exploitations in translational research to their application in diagnosis and treatment development, to ensure early diagnosis and better clinical outcomes.

Practical dietary advices for subjects with alpha-1 antitrypsin deficiency.

Congenital alpha-1 antitrypsin deficiency (AATD) is a rare inherited disorder caused by the mutation of the SERPINA1 gene on chromosome 14. At pulmonary level, AAT deficiency leads to an increased risk of chronic obstructive pulmonary disease (COPD) and emphysema, starting from the third-fourth decade of life. At hepatic level, some variants of the allelic, in particular PI*Z, cause a conformational change of the AAT molecule, which polymerizes within the hepatocytes. Excessive hepatic accumulation of these abnormal molecules can lead to liver disease in both adults and children, with clinical presentation ranging from cholestatic jaundice in the newborn to abnormal blood indices of liver function in children and adults, up to fatty liver, cirrhosis and hepatocarcinoma. Nutritional interventions in AATD aim to provide the necessary calories, stop protein catabolism, prevent and treat malnutrition as in the case of common COPD, and even take into account any liver disease that is a distinctive trait, compared to common COPD. Actually, there is a lack of formal research regarding the effects of specific nutritional recommendations in patients with AATD, proper eating habits may help to preserve lung and liver function. For practical dietary advice in patients with AATD and COPD, recently a food pyramid proposal has been published. It has been observed that there is a marked overlap between AATD liver disease and obesity-related liver disease, suggesting shared molecular basis and, therefore, similar nutritional strategies. In this narrative review dietary advice for all possible stages of liver disease have been reported.

Exploring the Role of Immune System and Inflammatory Cytokines in SARS-CoV-2 Induced Lung Disease: A Narrative Review.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative pathogen of coronavirus disease 19 (COVID-19). COVID-19 can manifest with a heterogenous spectrum of disease severity, from mild upper airways infection to severe interstitial pneumonia and devastating acute respiratory distress syndrome (ARDS). SARS-CoV-2 infection may induce an over activation of the immune system and the release of high concentrations of pro-inflammatory cytokines, leading to a "cytokine storm", a recognized pathogenetic mechanism in the genesis of SARS-CoV-2-induced lung disease. This overproduction of inflammatory cytokines has been recognized as a poor prognostic factor, since it can lead to disease progression, organ failure, ARDS and death. Moreover, the immune system shows dysregulated activity, particularly through activated macrophages and T-helper cells and in the co-occurrent exhaustion of lymphocytes. We carried out a non-systematic literature review aimed at providing an overview of the current knowledge on the pathologic mechanisms played by the immune system and the inflammation in the genesis of SARS-CoV-2-induced lung disease. An overview on potential treatments for this harmful condition and for contrasting the "cytokine storm" has also been presented. Finally, a look at the experimented experimental vaccines against SARS-CoV-2 has been included.

Incidence of Tracheal Stenosis in ICU Hospitalized COVID-19 Patients: Results from a Prospective, Observational, Multicenter Study.

Background: Tracheal stenosis represents a fearsome complication that substantially impairs quality of life. The recent SARS-CoV-2 pandemic increased the number of patients requiring invasive ventilation through prolonged intubation or tracheostomy, increasing the risk of tracheal stenosis. Study design and methods: In this prospective, observational, multicenter study performed in Lombardy (Italy), we have exanimated 281 patients who underwent prolonged intubation (more than 7 days) or tracheostomy for severe COVID-19. Patients underwent CT scan and spirometry 2 months after hospital discharge and a subsequent clinical follow-up after an additional 6 months (overall 8 months of follow-up duration) to detect any tracheal lumen reduction above 1%. The last follow-up evaluation was completed on 31 August 2022. Results: In the study period, 24 patients (8.5%, CI 5.6-12.4) developed tracheal stenosis in a median time of 112 days and within a period of 200 days from intubation. Compared to patients without tracheal stenosis, tracheostomy was performed more frequently in patients that developed stenosis (75% vs 54%, p = 0.034). Tracheostomy and alcohol consumption (1 unit of alcohol per day) increased risk of developing tracheal stenosis of 2.6-fold (p = 0.047; IC 0.99-6.8) and 5.4-fold (p = 0.002; CI 1.9-16), respectively. Conclusions: In a large cohort of patients, the incidence of tracheal stenosis increased during pandemic, probably related to the increased use of prolonged intubation. Patients with histories of prolonged intubation should be monitored for at least 200 days from invasive ventilation in order to detect tracheal stenosis at early stage. Alcohol use and tracheostomy are risk factors for developing tracheal stenosis.

Genetic and Serum Screening for Alpha-1-Antitrypsin Deficiency in Adult Patients with Cystic Fibrosis: A Single-Center Experience.

Cystic fibrosis (CF) and alpha-1 antitrypsin (AAT) deficiency are two of the commonest genetic diseases affecting the Caucasian population. Neutrophil-mediated inflammation due to protease-antiprotease imbalance leads to progressive pulmonary involvement in both diseases. The aim of this study was to investigate the prevalence of AAT deficiency in CF adults. A prospective study enrolling CF adults was conducted at the Adult CF Center based in Milan from January 2018 to March 2019. Patients were tested for AAT serum protein quantification and expanded genotyping characterization of SERPINA1 during clinical stability. Genotyping characterization of SERPIN1 was compared to a control population of 2848 Caucasian individuals with the same geographical origin and similar demographic characteristics. Among 173 patients included in the study, the prevalence of AAT deficiency was 0. Genotype analysis was piMM in 166 (94.9%) patients and piMS in 9 patients (5.1%), respectively. No differences in terms of genotype characterization were found between the CF population and the control population. These data show that AAT deficiency is not common among adults with CF.

Idiopathic pulmonary fibrosis and lung cancer: targeting the complexity of the pharmacological interconnection.

INTRODUCTION: Many data already suggested that cancer and IPF are underlined by a number of common pathogenic biologic pathways. However, fewer data regards the interconnections, in terms of synergy or increased toxicities, of drugs used in cancer and IPF. Particularly, how the specific therapy influences the concurrent condition and prognostic factors of response in patients with both lung cancer and IPF are far to be clarified. Similarly, identification of features of IPF patients with higher risk of developing pulmonary adverse events when treated with chemotherapy, immune checkpoint inhibitors, TKIs, or radiotherapy is of primary importance in clinical practice. AREAS COVERED: We will discuss the scientific rationale, based on the extensive analysis of literature data, by consulting several databases for combining anticancer and antifibrotic treatments and for the design of novel therapeutic strategies. The role of immunotherapy in cancer aroused in IPF context will be discussed with specific interested, based on the continuously increasing role of immune checkpoint inhibition against lung tumors. EXPERT OPINION: This work will help to improve knowledge, based on a multidisciplinary perspective, on IPF and cancer patients, which identify an unmet clinical need. A better management during each phase of disease progression will require the design innovative trials and the development of new drugs and molecules both in the oncologic and respiratory medicine pipeline.

Electrophysiological evidence of subclinical trigeminal dysfunction in patients with COVID-19 and smell impairment: A pilot study.

Background: Smell and taste disturbances are among the most frequent neurological symptoms in patients with COVID-19. A concomitant impairment of the trigeminal nerve has been suggested in subjects with olfactory dysfunction, although it has not been confirmed with objective measurement techniques. In this study, we explored the trigeminal function and its correlations with clinical features in COVID-19 patients with impaired smell perception using electrophysiological testing. Methods: We enrolled 16 consecutive patients with mild COVID-19 and smell impairment and 14 healthy controls (HCs). Olfactory and gustatory symptoms were assessed with self-reported questionnaires. Electrophysiological evaluation of the masseter inhibitory reflex (MIR) and blink reflex (BR) was carried out to test the trigeminal function and its connections within the brainstem. Results: Masseter inhibitory reflex (MIR) analysis revealed higher latency of ipsilateral and contralateral early silent period in patients when compared with HCs. No significant differences between groups were detected as regards the duration of the early and late silent period. However, several patients showed a prolonged duration of the early silent period. BR evaluation disclosed only an increased amplitude of early components in patients. Conclusions: Patients with COVID-19 and smell impairment show a subclinical trigeminal nerve impairment. Trigeminal alterations mainly involve the oligosynaptic pathway, as a result of either direct viral damage or secondary neuroinflammation of the peripheral trigeminal fibers, whereas the polysynaptic ponto-medullary circuits seem to be spared. The prolonged duration of the early silent period and the increased amplitude of early BR response might reflect a compensatory upregulation of the trigeminal function as a consequence of the olfactory dysfunction.

Improving the Laboratory Diagnosis of M-like Variants Related to Alpha1-Antitrypsin Deficiency.

Alpha1-antitrypsin (AAT) is a serine protease inhibitor that is encoded by the highly polymorphic SERPINA1 gene. Mutations in this gene can lead to AAT deficiency (AATD), which is associated with an increased risk of lung and/or liver disease. On the basis of electrophoretic migration, AAT variants are named with capital letters; M (medium) signifies the normal protein. Among pathological variants, the M-like ones represent a heterogeneous group of rare allelic variants that exhibit the same electrophoretic pattern as the M wild-type protein, which makes them difficult to detect with routine methods. In order to avoid their misdiagnosis, the present study defines and validates effective methods for the detection of two pathogenic M-like variants, Mwurzburg and Mwhitstable. Comparison of protein phenotypes using isoelectric focusing of samples that presented the Mwurzburg variant, as revealed by exons 5 sequencing, identified a particular electrophoretic pattern amenable to the Mwurzburg protein. The specific phenotyping pattern was retrospectively validated, thus enabling the detection of 16 patients with Mwurzburg variant among the subjects already tested but not sequenced according to our diagnostic algorithm. The Mwhitstable allele was detected by intron 4 sequencing of SERPINA1 gene. Mwurzburg and Mwhitstable are often misdiagnosed and the introduction of diagnostic improvements can help the clinical management, especially in patients with established lung disease without any other reported risk factors.

Pragmatic Expectancy on Microbiota and Non-Small Cell Lung Cancer: A Narrative Review.

It is well known that lung cancer relies on a number of genes aberrantly expressed because of somatic lesions. Indeed, the lungs, based on their anatomical features, are organs at a high risk of development of extremely heterogeneous tumors due to the exposure to several environmental toxic agents. In this context, the microbiome identifies the whole assemblage of microorganisms present in the lungs, as well as in distant organs, together with their structural elements and metabolites, which actively interact with normal and transformed cells. A relevant amount of data suggest that the microbiota plays a role not only in cancer disease predisposition and risk but also in its initiation and progression, with an impact on patients' prognosis. Here, we discuss the mechanistic insights of the complex interaction between lung cancer and microbiota as a relevant component of the microenvironment, mainly focusing on novel diagnostic and therapeutic objectives.

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

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

The oncogenic landscape of the idiopathic pulmonary fibrosis: a narrative review.

Background and Objective: Translational research is a source of continuous innovation in medicine, more particularly for clinical research on new treatment modalities in idiopathic pulmonary fibrosis (IPF) patients. However, the heterogeneity of the disease is well recognized, and different pathological and molecular settings have been identified. The molecular mechanisms by which IPF proceeds in time and space remains poorly understood. Although some IPF features are reminiscent of cancer, the dynamics of malignant divergent clonal selective pressure and heterogeneity clearly differ from those occurring in IPF. This is reflected in the absence of patient proper selection and stratification to biological agents (pirfenidone, nintedanib) which limit therapeutic efficacy. Consequently, increased costs are related to the clinical management of advanced IPF patients. Steady collaboration and fluid communication between pneumo-oncologists, radiologists and molecular biologists is a clear priority for the correct interpretation of tests and the definition of effective personalized strategies against this orphan disease. The present work aims at providing the most relevant hints shared by cancer and IPF. Methods: A systematic literature review was performed to identify all relevant data. The examined databases were Scopus, Web of Science, Cochrane, Google Scholar, and PubMed. The last search was run on January 5, 2022. We have primarily conducted separated research for lung cancer, IPF, genetics, epigenetics, surgery in IPF and cancer. Key Content and Findings: The data here presented mainly focus on gene mutations, epigenetics and novel therapeutic approaches. Moreover, epidemiology, prognostic variables and in new treatment strategies adopted in patients with IPF and lung cancer are discussed as well. Conclusions: Overall, the findings of this narrative review will be of help in defining the key molecular features that could applied in IPF setting with promising rationale to improve therapy and to better manage those cases carrying IPF and cancer concomitantly.

A mini-whole lung lavage to treat autoimmune pulmonary alveolar proteinosis (PAP).

BACKGROUND: PAP is an ultra-rare respiratory syndrome characterized by the accumulation of surfactant within the alveoli. Whole lung lavage (WLL) is the current standard of care of PAP, however it is not a standardized procedure and the total amount of fluid used to wash each lung is still debated. Considering ICU hospitalization associated risks, a "mini-WLL" with anticipated manual clapping and reduced total infusion volume and has been proposed in our center. The aim of the study is to retrospectively analyze the efficacy of mini-WLL compared to standard WLL at the Pavia center. METHODS: 13 autoimmune PAP patients eligible for WLL were included: 7 patients were admitted to mini-WLL (9 L total infusion volume for each lung) and 6 patients underwent standard WLL (14 L of infusion volume). Functional data (VC%, FVC%, TLC%, DLCO%) and alveolar-arterial gradient values (A-aO2) were collected at the baseline and 1, 3, 6, 12, 18 months after the procedure. RESULTS: A statistically significant improvement of VC% (p = 0.013, 95%CI 3.49-30.19), FVC% (p = 0.016, 95%CI 3.37-32.09), TLC% (p = 0.001, 95%CI 7.38-30.34) was observed in the mini-WLL group in comparison with the standard WLL group, while no significant difference in DLCO% and A-aO2 mean values were reported. CONCLUSION: Mini-WLL has demonstrated higher efficacy in ameliorating lung volumes, suggesting that a lower infusion volume is sufficient to remove the surfactant accumulation and possibly allows a reduced mechanical insult of the bronchi walls and the alveoli. However, no statistically significant differences were found in terms of DLCO% and Aa-O2.

Mortality due to COVID-19 during the pandemic: A comparison of first, secondo and third SMAtteo COvid19 REgistry (SMACORE).

COVID-19 tide had shattered on European countries with three distinct and tough waves, from March and April, 2020; October and November, 2020 and March and April, 2021 respectively. We observed a 50% reduction in the hazard of death during both wave II and III compared with wave I (HR 0.54, 95%CI 0.39-0.74 and HR 0.57, 95%CI 0.41-0.80, respectively). Sex and age were independent predictors of death. We compare in-hospital mortality of COVID-19 patients admitted at our Referral Hospital of Northern Italy during the different waves, discuss the reasons of the observed differences and suggest approaches to the challenges ahead.

Mild/Moderate Asthma Network in Italy (MANI): a long-term observational study.

OBJECTIVE: The prevalence of asthma in Italy is estimated to be around 4%; it affects approximately 2,000,000 citizens, and up to 80-90% of patients have mild-to-moderate asthma. Despite the clinical relevance of mild-to-moderate asthma, longitudinal observational data are very limited, including data on disease progression (worsening vs. improvement), the response to treatment, and prognosis. Studies are needed to develop long-term, observational, real-life research in large cohorts. The primary outcomes of this study will be based on prospective observation and the epidemiological evolution of mild and moderate asthma. Secondary outcomes will include patient-reported outcomes, treatments over time, disease-related functional and inflammatory patterns, and environmental and life-style influences. METHODS: This study, called the Mild/Moderate Asthma Network of Italy (MANI), is a research initiative launched by the Italian Respiratory Society and the Italian Society of Allergology, Asthma and Clinical Immunology. MANI is a cluster-based, real world, cross-sectional, prospective, observational cohort study that includes 20,000 patients with mild-to-moderate asthma. (ClinicalTrials.gov Identifier: NCT04796844). RESULTS AND CONCLUSION: Despite advances in asthma care, several research gaps remain to be addressed through clinical research. This study will add important new knowledge about long-term disease history, the transferability of clinical research results to daily practice, the efficacy of currently recommended strategies, and their impact on the burden and evolution of the disease. ABBREVIATIONS: MANI:Mild/Moderate Asthma Network of ItalySANI:Severe Asthma Network ItalyGINA:Global Initiative for AsthmaSABA:short acting ß2-agonistsICS:inhaled corticosteroidsCRF:Case Report Form.