Implementation of the Care Bundle for the Management of Chronic Obstructive Pulmonary Disease with/without Heart Failure.

Chronic obstructive pulmonary disease (COPD) is often part of a more complex cardiopulmonary disease, especially in older patients. The differential diagnosis of the acute exacerbation of COPD and/or heart failure (HF) in emergency settings is challenging due to their frequent coexistence and symptom overlap. Both conditions have a detrimental impact on each other's prognosis, leading to increased mortality rates. The timely diagnosis and treatment of COPD and coexisting factors like left ventricular overload or HF in inpatient and outpatient care can improve prognosis, quality of life, and long-term outcomes, helping to avoid exacerbations and hospitalization, which increase future exacerbation risk. This work aims to address existing gaps, providing management recommendations for COPD with/without HF, particularly when both conditions coexist. During virtual meetings, a panel of experts (the authors) discussed and reached a consensus on the differential and paired diagnosis of COPD and HF, providing suggestions for risk stratification, accurate diagnosis, and appropriate therapy for inpatients and outpatients. They emphasize that when COPD and HF are concomitant, both conditions should receive adequate treatment and that recommended HF treatments are not contraindicated in COPD and have favorable effects. Accurate diagnosis and therapy is crucial for effective treatment, reducing hospital readmissions and associated costs. The management considerations discussed in this study can potentially be extended to address other cardiopulmonary challenges frequently encountered by COPD patients.

The impact of elexacaftor/tezacaftor/ivacaftor therapy on the pulmonary management of adults with cystic fibrosis: An expert-based Delphi consensus.

BACKGROUND: The advent of elexacaftor/tezacaftor/ivacaftor (ETI) resulted in unprecedented clinical benefits for eligible adults with CF. As a result, the question of whether chronic treatments can be safely stopped or adapted to this new situation has become a matter of great interest. Our objective was to derive a consensus among Italian experts on the impact of ETI on the current clinical management of CF lung disease. METHODS: From December 2021 to April 2022 a panel of Italian experts endorsed by the national CF scientific society derived and graded a set of statements on the pulmonary management of adults with cystic fibrosis through a modified Delphi methodology. RESULTS: The panel produced 13 statements exploring possible modifications in the fields of inhaled antibiotics and mucoactives; airway clearance and physical activity; chronic macrolides and bronchodilators; and lung transplant referral. The areas that the experts considered most urgent to explore were the impact of ETI on the role of inhaled antibiotics and lung transplant. CONCLUSIONS: The list of priorities that emerged from this study could be useful to guide and inform clinical research on the most urgent area of impact of ETI on CF lung disease and its clinical management.

Effectiveness and Safety of Remdesivir in Treating Hospitalised Patients with COVID-19: A Propensity Score Analysis of Real-Life Data from a Monocentric Observational Study in Times of Health Emergency.

BACKGROUND AND OBJECTIVES: Remdesivir is an antiviral agent, which was shown to be safe and effective in treating early COVID-19, but its favourable impact in hospitalised patients with non-critical disease is still under investigation. The present study aimed to assess the effectiveness and safety of remdesivir as a treatment for hospitalised patients with COVID-19 by a propensity score analysis of observational data. METHODS: In this monocentric retrospective cohort study, the effectiveness and safety of a 5-day course of remdesivir (200 mg intravenously at Day 1, then 100 mg from Days 2-5) in association with the standard of care were assessed in comparison with the standard of care only. The primary endpoint was the proportion of recovery on Day 14. RESULTS: Of 3662 eligible inpatients who tested positive for the severe acute respiratory syndrome coronavirus 2 genome by nasopharyngeal swab at admission, 861 (24%) non-critical patients were included in a propensity score analysis and 281 (33%) were exposed to remdesivir. In total, 242/281 (86.1%) and 435/580 (75.0%) patients recovered in exposed and non-exposed, respectively, with a relative improvement of 11.1% (95% CI + 5.8 to 16.5%; unadjusted odds ratio: 2.07, 95% CI 1.40-3.05, p = 0.0001; after adjustment by propensity score weighting, odds ratio: 1.92, 95% CI 1.30-2.83, p = 0.001). In treated patients, 1 (0.03%) anaphylactic reaction and 1 (0.03%) acute reaction during drug injection were reported, and 24 (8.5%) patients stopped the treatment due to adverse reactions. No significant differences were found with respect to the secondary efficacy endpoints (in-hospital all-cause death, need for intensive care treatments, clinical improvement score at Day 28) and safety endpoints (any and serious adverse reactions). CONCLUSION: A 5-day course of remdesivir in association with the standard of care effectively promoted recovery from COVID-19 among non-critical in-hospital patients and had an acceptable safety profile.

Trends in all-cause mortality of hospitalized patients due to SARS-CoV-2 infection from a monocentric cohort in Milan (Lombardy, Italy).

Background: Robust data on case fatality rate (CFR) among inpatients with COVID-19 are still lacking, and the role of patient characteristics in in-hospital deaths remains under-investigated. This study quantified the overall CFR and described its trend in a cohort of hospitalized patients with SARS-CoV-2 in Italy. Admission to ICU, death, or discharge were the secondary outcomes. Methods: This retrospective study is based on administrative health data and electronic case records of inpatients consecutively admitted to Niguarda Hospital between 21 February and 8 November 2020. Results: An overall CFR of 18% was observed. CFR was significantly reduced during the second wave of contagion (1 June to 30 September, 16%) compared with the first wave (21 February to 31 May, 21% p = 0.015). Such reduction was mainly observed among male inpatients between 40 and 80 years with limited comorbidities. Admission to ICU was associated with a high risk of mortality in both waves. The incidence of severe disease and the need for ICU admission were lower in the second wave. Conclusion: CFR in SARS-CoV-2 inpatients was demonstrated to decrease over time. This reduction may partly reflect the changes in hospital strategy and clinical practice. The reasons for this improvement should be further investigated to plan an exit strategy in case of future outbreaks. Key messages: What is already known on this topic Before the advent of anti-COVID-19 vaccines, a multi-wave pattern of contagion was observed, and this trend conditioned the inpatient case fatality rate (CFR), which varied over time accordingly to the waves of contagion.Only preliminary results on the in-hospital mortality trend are available, along with a partial analysis of its determinants. Consequently, robust data on CFR among inpatients with SARS-CoV-2 infection are still lacking, and the role of patient characteristics in in-hospital deaths remains under-investigated. What this study adds This study shows that the in-hospital mortality in patients with SARS-CoV-2 infection decreases over time.Such reduction was mainly observed among male inpatients between 40 and 80 years with limited comorbidities. Admission to ICU was invariably associated with a high risk of mortality during the whole study period (21 February to 8 November 2020), but the incidence of severe disease and the need for ICU admission were lower in the second wave of contagions (1 October to 8 November 2020). This reduction may partly reflect the impact of changes in hospital strategy and clinical practice. The reasons for this improvement should be further investigated to inform the response to future outbreaks and to plan exit strategy by prioritizing high-risk populations. Supplementary Information: The online version contains supplementary material available at 10.1007/s10389-021-01675-y.

Sex differences in electrolyte imbalances caused by SARS-CoV-2: A cross-sectional study.

BACKGROUND: Since SARS-CoV-2 spread, evidence regarding sex differences in progression and prognosis of COVID-19 have emerged. Besides this, studies on patients' clinical characteristics have described electrolyte imbalances as one of the recurrent features of COVID-19. METHODS: We performed a cross-sectional study on all patients admitted to the emergency department (ED) from 1 March to 31 May 2020 who had undergone a blood gas analysis and a nasopharyngeal swab test for SARS-CoV-2 by rtPCR. We defined positive patients as cases (n = 710) and negatives as controls (n = 619), for a total number of patients of 1.329. The study was approved by the local ethics committee Area 3 Milan. Data were automatically extracted from the hospital laboratory SQL-based repository in anonymised form. We considered as outcomes potassium (K+ ), sodium (Na+ ), chlorine (Cl- ) and calcium (Ca++ ) as continuous and as categorical variables, in their relation with age, sex and SARS-CoV-2 infection status. RESULTS: We observed a higher prevalence of hypokalaemia among patients positive for SARS-CoV-2 (13.7% vs 6% of negative subjects). Positive patients had a higher probability to be admitted to the ED with hypokalaemia (OR 2.75, 95% CI 1.8-4.1, P < .0001) and women were twice as likely to be affected than men (OR 2.43, 95% CI 1.67-3.54, P < .001). Odds ratios for positive patients to manifest with an alteration in serum Na+ was (OR 1.6, 95% CI 1.17-2.35, P < .001) and serum chlorine (OR 1.6, 95% CI 1.03-2.69, P < .001). Notably, OR for positive patients to be hypocalcaemic was 7.2 (95% CI 4.8-10.6, P < .0001) with a low probability for women to be hypocalcaemic (OR 0.63, 95% CI 0.4-0.8, P = .005). CONCLUSIONS: SARS-CoV-2 infection is associated with a higher prevalence of hypokalaemia, hypocalcaemia, hypochloraemia and sodium alterations. Hypokalaemia is more frequent among women and hypocalcaemia among men.

Neurological manifestations in patients hospitalized with COVID-19: A retrospective analysis from a large cohort in Northern Italy.

SARS-CoV2 infection is a systemic disease that may involve multiple organs, including the central nervous system (CNS). Aims of our study are to describe prevalence and clinical features of neurological manifestations, mortality and hospital discharge in subjects hospitalized with COVID-19. All individuals admitted for to our hospital COVID-19 were retrospectively included. Patients were classified according to the symptoms at hospital entry in (1) isolated respiratory, (2) combined respiratory and neurologic, (3) isolated neurologic and (4) stroke manifestations. Descriptive statistics and nonparametric tests to compare the groups were calculated. Kaplan Meier probability curves and multivariable Cox regression models for survival and hospital discharge were applied. The analysis included 901 patients: 42.6% showed a severe or critical disease with an overall mortality of 21.2%. At least one neurological symptom or disease was observed in 30.2% of subjects ranging from dysgeusia/anosmia (9.1%) to postinfective diseases (0.8%). Patients with respiratory symptoms experienced a more severe disease and a higher in-hospital mortality compared to those who showed only neurologic symptoms. Kaplan Meier estimates displayed a statistically significant different survival among groups (p = 0.003): subjects with stroke had the worst. After adjusting for risk factors such as age, sex and comorbidity, individuals with isolated neurologic manifestations exhibited a better survival (aHR 0.398, 95% CI [0.206, 0.769], p = 0.006). Neurologic manifestations in COVID-19 are common but heterogeneous and mortality in subjects with isolated neurologic manifestations seems lower than in those with respiratory symptoms.

Safety and efficacy of anti-il6-receptor tocilizumab use in severe and critical patients affected by coronavirus disease 2019: A comparative analysis.

BACKGROUND: As the novel SARS-CoV-2 pandemic occurred, no specific treatment was yet available. Inflammatory response secondary to viral infection might be the driver of severe diseases. We report the safety and efficacy (in terms of overall survival and hospital discharge) of the anti-IL6 tocilizumab (TCZ) in subjects with COVID-19. METHODS: This retrospective, single-center analysis included all the patients consecutively admitted to our Hospital with severe or critical COVID-19 who started TCZ treatment from March 13th to April 03rd, 2020. A 1:2 matching to patients not treated with TCZ was performed according to age, sex, severity of disease, P/F, Charlson Comorbidity Index and length of time between symptoms onset and hospital admittance. Descriptive statistics and non-parametric tests to compare the groups were applied. Kaplan Meier probability curves and Cox regression models for survival, hospital discharge and orotracheal intubation were used. RESULTS: Seventy-four patients treated with TCZ were matched with 148 matched controls. They were mainly males (81.5%), Caucasian (82.0%) and with a median age of 59 years. The majority (69.8%) showed critical stage COVID-19 disease. TCZ use was associated with a better overall survival (HR 0.499 [95% CI 0.262-0.952], p = 0.035) compared to controls but with a longer hospital stay (HR 1.658 [95% CI 1.088-2.524], p = 0.019) mainly due to biochemical, respiratory and infectious adverse events. DISCUSSION: TCZ use resulted potentially effective on COVID-19 in terms of overall survival. Caution is warranted given the potential occurrence of adverse events. FINANCIAL SUPPORT: Some of the tocilizumab doses used in the subjects included in this analysis were provided by the "Multicenter study on the efficacy and tolerability of tocilizumab in the treatment of patients with COVID-19 pneumonia" (EudraCT Number: 2020-001110-38) supported by the Italian National Agency for Drugs (AIFA). No specific funding support was planned for study design, data collection and analysis and manuscript writing of this paper.

Bronchoalveolar Lavage-microRNAs Are Potential Novel Biomarkers of Outcome After Lung Transplantation.

Primary graft dysfunction, infections, and acute rejection (AR) worsen lung transplantation (LTx) outcome and patient survival. Despite significant efforts, reliable biomarkers of acute lung allograft dysfunction are lacking. To address this issue, we profiled the bronchoalveolar lavage (BAL) miRNome in LTx patients. METHODS: BAL-microRNAs (miRNAs) from 16 patients were collected 7 days (T0), 15 days (T1), and 3 months (T2) after bilateral LTx and profiled on low-density array. Unsupervised and supervised analyses were used to identify miRNAs associated with clinical features, pneumonia, or AR. Prognostic markers were identified using the Cox model. Targeted signaling pathways were predicted in silico. A second series of 11 patients were used to validate AR-associated miRNAs. RESULTS: Variation in BAL-miRNAs was associated with acute lung allograft dysfunction. Increased levels of miR-23b-3p at T2 were detected in patients with pneumonia, whereas let-7f-5p, miR-146b-3p, miR-22-5p, miR-29c-5p, miR-362-5p, and miR-452-5p were upregulated at T2 in patients with AR. miR-148b-5p and miR-744-3p distinguished LTx patients with AR in both cohorts. Low miR-148b-5p and high miR-744-3p expression levels were significantly associated with a shorter time to AR either within the first year after LTx or during follow-up. Combination of the 2 miRNAs identified LTx patients with higher AR risk independently of clinical variables. CONCLUSIONS: Our data provide new insights into the roles of BAL-miRNAs in regulating the pulmonary environment after transplantation and suggest that these miRNAs could serve as biomarkers of early- or mid-stage events. If validated, these findings could pave the way to a personalized clinical approach in LTx patients.

The impaired diaphragmatic function after bilateral lung transplantation: A multifactorial longitudinal study.

BACKGROUND: Lung transplantation is a complex but effective treatment of end-stage pulmonary disease. Among the post-operative complications, phrenic nerve injury, and consequent diaphragmatic dysfunction are known to occur but are hitherto poorly described. We aimed to investigate the effect of lung transplantation on diaphragmatic function with a multimodal approach. METHODS: A total of 30 patients were studied at 4 time points: pre-operatively, at discharge after surgery, and after approximately 6 and subsequently 12 months post surgery. The diaphragmatic function was studied in terms of geometry (assessed by the radius of the diaphragmatic curvature delineated on chest X-ray), weakness (considering changes in forced vital capacity when the patient shifted from upright to supine position), force (maximal pressure during sniff), mobility (excursion of the dome of the diaphragm delineated by ultrasound), contractility (thickening fraction assessed by ultrasound), electrical activity (latency and area of compound muscle action potential during electrical stimulation of phrenic nerve), and kinematics (relative contribution of the abdominal compartment to tidal volume). RESULTS: Despite good clinical recovery (indicated by spirometry and 6 minutes walking test), a reduction of the diaphragmatic function was detected at discharge; it persisted 6 months later to recover fully 1 year after transplantation. Diaphragmatic dysfunction was demonstrated in terms of force, weakness, electrical activity, and kinematics. Our data suggest that the dysfunction was caused by phrenic nerve neurapraxia or moderate axonotmesis, potentially as a consequence of the surgical procedure (i.e., the use of ice and pericardium manipulation). CONCLUSIONS: The occurrence of diaphragmatic dysfunction in patients with a good clinical recovery indicates that the evaluation of diaphragmatic function should be included in the post-operative assessment after lung transplantation.

Sympatho-Vagal Dysfunction in Patients with End-Stage Lung Disease Awaiting Lung Transplantation.

Although the literature demonstrates that cardiac autonomic control (CAC) might be impaired in patients with chronic pulmonary diseases, the interplay between CAC and disease severity in end-stage lung disease has not been studied yet. We investigated the effects of end-stage lung disease on CAC through the analysis of heart rate variability (HRV) among patients awaiting lung transplantation. Forty-nine patients on the waiting list for lung transplantation (LTx; 19 men, age 38 ± 15 years) and 49 healthy non-smoking controls (HC; 22 men, age 40 ± 16 years) were enrolled in a case-control study at Policlinico Hospital in Milan, Italy. LTx patients were divided into two groups, according to disease severity evaluated by the Lung Allocation Score (LAS). To assess CAC, electrocardiogram (ECG) and respiration were recorded at rest for 10 min in supine position and for 10 min during active standing. Spectral analysis identified low and high frequencies (LF, sympathetic, and HF, vagal). Symbolic analysis identified three patterns, i.e., 0V% (sympathetic) and 2UV% and 2LV% (vagal). Compared to HCs, LTx patients showed higher markers of sympathetic modulation and lower markers of vagal modulation. However, more severely affected LTx patients, compared to less severely affected ones, showed an autonomic profile characterized by loss of sympathetic modulation and predominant vagal modulation. This pattern can be due to a loss of sympathetic rhythmic oscillation and a subsequent prevalent respiratory modulation of heart rate in severely affected patients.

Early pulmonary function and mid-term outcome in lung transplantation after ex-vivo lung perfusion - a single-center, retrospective, observational, cohort study.

Outcomes after transplantation of lungs (LuTX) treated with ex-vivo lung perfusion (EVLP) are debated. In a single-center 8 years of retrospective analysis, we compared: donors' and recipients' characteristics, gas exchange and lung mechanics at ICU admission, 3, 6, and 12 months, and patients' survival of LuTX from standard donors compared with EVLP-treated grafts. A total of 193 LuTX were performed. Thirty-one LuTX, out of 50 EVLP procedures, were carried out: 7 from nonheart beating and 24 from extended criteria brain-dead donors. Recipients' characteristics were similar. At ICU admission, compared with standard donors, EVLP patients had worse PaO2 /FiO2 [276 (206; 374) vs. 204 (133; 245) mmHg, P < 0.05], more frequent extracorporeal support (18% vs. 32%, P = 0.053) and longer mechanical ventilation duration [28 days of ventilator-free days: 27 (24; 28) vs. 26 (19; 27), P < 0.05]. ICU length of stay [4 (2; 9) vs. 6 (3; 12) days, P = 0.208], 28-day survival (99% vs. 97%, P = 0.735), and 1-year respiratory function were similar between groups. Log-rank analysis (median follow-up 2.5 years) demonstrated similar patients' survival (P = 0.439) and time free of chronic lung allograft disease (P = 0.484). The EVLP program increased by 16% the number of LuTX. Compared to standard donors, EVLP patients had worse respiratory function immediately after LuTX but similar early and mid-term outcomes.

Effectiveness of chest physiotherapy and pulmonary rehabilitation in patients with non-cystic fibrosis bronchiectasis: a narrative review.

Respiratory physiotherapy and rehabilitation are important therapeutic options in non-cystic fibrosis bronchiectasis (NCFB). The aims of this review of clinical trials were to evaluate the safety and the effects on physiologic and clinical outcomes of airway clearance techniques (ACTs) and rehabilitation in NCFB patients, in comparison to usual care. The search was performed on March 2018 by using PubMed and PeDro databases. 33 studies were selected. The use of ACTs for NCFB were effective in increasing sputum volume although no benefit in quality of life (QoL) or pulmonary exacerbations were observed. There were no differences in effectiveness between the several techniques used. Humidification and saline inhalation were able to aid airway clearance. Hypertonic solution (HS) was more effective than isotonic solutions (IS) in improving expectoration and sputum viscosity. Pulmonary rehabilitation (PR) was found to be associated with short term benefits in exercise capacity, dyspnea and fatigue. Exercise training seems to improve quality of life and lower exacerbation rate, but long-term data are not available. Further studies are necessary to identify the most feasible long-term outcomes such as QoL and exacerbation rate.

Application of machine learning to predict obstructive sleep apnea syndrome severity.

INTRODUCTION: Obstructive sleep apnea syndrome has become an important public health concern. Polysomnography is traditionally considered an established and effective diagnostic tool providing information on the severity of obstructive sleep apnea syndrome and the degree of sleep fragmentation. However, the numerous steps in the polysomnography test to diagnose obstructive sleep apnea syndrome are costly and time consuming. This study aimed to test the efficacy and clinical applicability of different machine learning methods based on demographic information and questionnaire data to predict obstructive sleep apnea syndrome severity. MATERIALS AND METHODS: We collected data about demographic characteristics, spirometry values, gas exchange (PaO2, PaCO2) and symptoms (Epworth Sleepiness Scale, snoring, etc.) of 313 patients with previous diagnosis of obstructive sleep apnea syndrome. After principal component analysis, we selected 19 variables which were used for further preprocessing and to eventually train seven types of classification models and five types of regression models to evaluate the prediction ability of obstructive sleep apnea syndrome severity, represented either by class or by apnea-hypopnea index. All models are trained with an increasing number of features and the results are validated through stratified 10-fold cross validation. RESULTS: Comparative results show the superiority of support vector machine and random forest models for classification, while support vector machine and linear regression are better suited to predict apnea-hypopnea index. Also, a limited number of features are enough to achieve the maximum predictive accuracy. The best average classification accuracy on test sets is 44.7 percent, with the same average sensitivity (recall). In only 5.7 percent of cases, a severe obstructive sleep apnea syndrome (class 4) is misclassified as mild (class 2). Regression results show a minimum achieved root mean squared error of 22.17. CONCLUSION: The problem of predicting apnea-hypopnea index or severity classes for obstructive sleep apnea syndrome is very difficult when using only data collected prior to polysomnography test. The results achieved with the available data suggest the use of machine learning methods as tools for providing patients with a priority level for polysomnography test, but they still cannot be used for automated diagnosis.

The biology of pulmonary exacerbations in bronchiectasis.

Bronchiectasis is a heterogeneous chronic disease. Heterogeneity characterises bronchiectasis not only in the stable state but also during exacerbations, despite evidence on clinical and biological aspects of bronchiectasis, exacerbations still remain poorly understood.Although the scientific community recognises that bacterial infection is a cornerstone in the development of bronchiectasis, there is a lack of data regarding other trigger factors for exacerbations. In addition, a huge amount of data suggest a primary role of neutrophils in the stable state and exacerbation of bronchiectasis, but the inflammatory reaction involves many other additional pathways. Cole's vicious cycle hypothesis illustrates how airway dysfunction, airway inflammation, infection and structural damage are linked. The introduction of the concept of a "vicious vortex" stresses the complexity of the relationships between the components of the cycle. In this model of disease, exacerbations work as a catalyst, accelerating the progression of disease. The roles of microbiology and inflammation need to be considered as closely linked and will need to be investigated in different ways to collect samples. Clinical and translational research is of paramount importance to achieve a better comprehension of the pathophysiology of bronchiectasis, microbiology and inflammation both in the stable state and during exacerbations.

The effect of primary graft dysfunction after lung transplantation on parenchymal remodeling detected by quantitative computed tomography.

BACKGROUND: Regional analysis by computed tomography (CT) is an attractive technique to interpret lung patterns after transplantation (LTx). We evaluated the application of CT functional mask derived parameters to determine whether development of primary graft dysfunction (PGD) is associated with short and/or long-term postoperative evidences of pulmonary function alterations. METHODS: A total of 38 patients who underwent bilateral LTx were evaluated at 24, 48 and 72 hours after the end of surgery to establish PGD occurrence and grading. CT scans at 3 and 12 months after LTx were analyzed to measure specific gas volume (SVg) changes normalized on expiratory SVgEXP of the whole lung (ΔSVg/SVgEXP) and to obtain functional masks of density variation, namely maps of low ventilation (LV), consolidation (C), air trapping (AT) and healthy parenchyma (H). RESULTS: Our main result was the evidence of a marked decrease in ΔSVg/SVgEXP in all subjects, irrespectively on PGD, at each time point after LTx, indicating a high degree of ventilation defects versus healthy. High percentages of LV were found in all subjects while percentages of AT and C were negligible. CONCLUSIONS: We demonstrate that quantification of ventilation defects by CT functional mask offers insights into the correlation between PGD and pulmonary function after LTx at short and mid-term.

Successful preservation and transplant of warm ischaemic lungs from controlled donors after circulatory death by prolonged in situ ventilation during normothermic regional perfusion of abdominal organs.

OBJECTIVES: Donation after circulatory death (DCD) potentially provides transplantable lungs suitable for a transplant, but in Italy, the need for 20 min of a no-touch period after cardiac arrest for legal declaration of death poses real challenges to organ preservation. METHODS: This is a single-institution, retrospective study using data collected prospectively between October and December 2017. After the approval of the multidisciplinary DCD study group of Regione Lombardia, Maastricht category III DCD donors became eligible for combined procurement of lungs and abdominal organs. Our group subsequently established a dedicated technical protocol. Our protocol consists of a non-rapid normothermic open-lung procurement process that takes place during abdominal normothermic regional perfusion, namely without pleural topical cooling before the start of pneumoplegia. After the lung is procured according to the technique described in the article, lung function is evaluated by ex vivo lung perfusion, which is run with the low-flow, open atrium, low haematocrit technique. RESULTS: During the study, we managed 5 controlled DCDs. In 3 cases, the lungs were successfully transplanted. All 3 patients are alive after 1 year, with good respiratory function. CONCLUSIONS: Our approach resulted in adequate lung preservation and successful transplants without detrimental effects on abdominal organ procurement, confirming the possibility of overcoming the obstacle of a long no-touch period in a DCD setting.

Transplant options for end stage chronic obstructive pulmonary disease in the context of multidisciplinary treatments.

Lung transplantation (LTx) in advanced stage chronic obstructive pulmonary disease (COPD) patients is associated with significant improvement in lung function and exercise capacity. However, demonstration that the procedure also provides a survival benefit has been more elusive compared to other respiratory conditions. Identification of patients with increased risk of mortality is crucial: a low forced expiratory volume in 1 second (FEV1) is perhaps the most common reason for referral to a lung transplant center, but in itself is insufficient to identify which COPD patients will benefit from LTx. Many variables have to be considered in the selection of candidates, time for listing, and choice of procedure: age, patient comorbidities, secondary pulmonary hypertension, the balance between individual and community benefit. This review will discuss patient selection, transplant listing, potential benefits and critical issues of bilateral (BLTx) and single lung (SLTx) procedure, donor-to-recipient organ size-matching; furthermore, it will describe LTx outcomes and its effects on recipient survival and quality of life.

Infections after lung transplantation.

The good clinical result of lung transplantation is constantly undermined by the high incidence of infection, which negatively impacts on function and survival. Moreover, infections may also have immunological interactions that play a role in the acute rejection and in the development of chronic lung allograft dysfunction. There is a temporal sequence in the types of infection that affects lung allograft: in the first postoperative month bacteria are the most frequent cause of infection; following this phase, cytomegalovirus and Pneumocystis carinii are common. Fungal infections are particularly feared due to their association with bronchial complication and high mortality. Scrupulous postoperative surveillance is mandatory for the successful management of lung transplantation patients with respect to early detection and treatment of infections. This paper is aimed to address clinicians in the management of the major infectious complications that affect the lung transplant population.

Neutrophil elastase in bronchiectasis.

The role of neutrophil elastase (NE) is poorly understood in bronchiectasis because of the lack of preclinical data and so most of the assumptions made about NE inhibitor potential benefit is based on data from CF. In this context, NE seems to be a predictor of long-term clinical outcomes and a possible target of treatment. In order to better evaluate the role of NE in bronchiectasis, a systematic search of scientific evidence was performed.Two investigators independently performed the search on PubMed and included studies published up to May 15, 2017 according to predefined criteria. A final pool of 31 studies was included in the systematic review, with a total of 2679 patients. For each paper data of interest were extracted and reported in table.In this review sputum NE has proved useful as an inflammatory marker both in stable state bronchiectasis and during exacerbations and local or systemic antibiotic treatment. NE has also been associated with risk of exacerbation, time to next exacerbation and all-cause mortality. This study reviews also the role of NE as a specific target of treatment in bronchiectasis. Inhibition of NE is at a very early stage and future interventional studies should evaluate safety and efficacy for new molecules and formulations.