Search

Supported by the National Health and Medical Research Council Centre of Research Excellence in Pulmonary Fibrosis (GNT1116371), and by foundation partner, Boehringer Ingelheim, and program partners, Roche and Galapagos. Rationale : The interstitial lung disease (ILD) multidisciplinary meetings (MDM), composed of pulmonologists, radiologists, and pathologists, is integral to the rendering of an accurate ILD diagnosis. However, there is significant heterogeneity in the conduct of ILD MDMs, and questions regarding their best practices remain unanswered. Objectives : To achieve consensus among ILD experts on essential components of an ILD MDM. Methods : Using a Delphi methodology, semi-structured interviews with ILD experts were used to identify key themes and features of ILD MDMs. These items informed two subsequent rounds of online questionnaires that were used to achieve consensus among a broader, international panel of ILD experts. Experts were asked to rate their level of agreement on a five-point Likert scale. An a priori threshold for consensus was set at a median score 4 or 5 with an interquartile range of 0. Results : We interviewed 15 ILD experts, and 102 ILD experts participated in the online questionnaires. Five items and two exploratory statements achieved consensus on being essential for an ILD MDM following two questionnaire rounds. There was consensus that the presence of at least one radiologist, a quiet setting with a visual projection system, a high-quality chest high-resolution computed tomography, and a standardized template summarizing collated patient data are essential components of an ILD MDM. Experts also agreed that it would be useful for ILD MDMs to undergo an annual benchmarking process and a validation process by fulfilling a minimum number of cases annually. Twenty-seven additional features were considered to be either highly desirable or desirable features based on the degree of consensus. Although our findings on desirable features are similar to the current literature, several of these remain controversial and warrant further research. The study also showed an agreement among participants on several future concepts to improve the ILD MDM, such as performing regular self-assessments and conducting research into shared practices to develop an international expert guideline statement on ILD MDMs. Conclusions : This Delphi study showed consensus among international ILD experts on essential and desirable features of an ILD MDM. Our data represent an important step toward potential collaborative research into future standardization of ILD MDMs. Postprint

Background: Idiopathic pulmonary fibrosis (IPF) primarily affects old patients. Old age is a predictor of mortality. Nintedanib, the only antifibrotic drug approved in Italy for patients aged >80 years, can slow the progression of IPF by reducing the rate of decline in forced vital capacity (FVC) and the risk of exacerbations. Objectives: The primary aim of the study was to compare the decline of FVC after 12 months of nintedanib in patients aged >80 years versus younger patients. Differences related to other functional data, safety, tolerability, hospitalizations, exacerbations, and mortality were evaluated. Methods: An observational, retrospective, multicenter study was carried out in Italy. Results: 159 (122 [76.7%] males) patients were recruited: 106 (66.7%) aged ≤80 years and 53 (33.3%) aged >80 years. FVC decline after 12 months of therapy was not significantly different (−45 mL [−170; 75] vs. −20 mL [−138; 110] mL; p: 0.51). No differences were found for other functional data. Diarrhea was the most frequent adverse event (AE). Rate and type of any AEs, permanent/temporary dose reduction, or drug discontinuation were not significantly different between patients aged ≤80 vs. >80 years. Furthermore, acute exacerbations, hospitalization, and mortality were not significantly different. Conclusions: Nintedanib is effective and safe in patients with IPF aged >80 years, and no significant differences were found when clinical outcomes were compared with those of younger patients. Thus, older age should not be a barrier for the early prescription of antifibrotic treatment in IPF patients.

Study objective To assess the effects of a protective ventilation strategy during Trendelenburg pneumoperitoneum surgery on postoperative oxygenation.Parallel-group, randomized trial.Operating room of a university hospital, Italy.Morbidly obese patients undergoing Trendelenburg pneumoperitoneum gynaecological surgery.Participants were randomized to standard (SV: tidal volume = 10 ml/kg of predicted body weight, PEEP = 5 cmHPrimary outcome was PaOSixty patients were analyzed (31 in SV group, 29 in PV group). Median [IqR] tidal volume was 350 ml [300-360] in PV group and 525 [500-575] in SV group. Median PaOIn obese patients undergoing Trendelenburg pneumoperitoneum surgery, PV did not improve postoperative oxygenation nor day-2 respiratory function. PV was associated with intraoperative respiratory mechanics indicating less injurious ventilation. The high prevalence of complete airway closure may have affected study results.Prospectively registered on http://clinicaltrials.govNCT03157479 on May 17th, 2017.

Poster Abstract

A timely, confirmed diagnosis of Idiopathic Pulmonary Fibrosis (IPF) has a significant impact on the evolution of the disease. The current model of care in the Lazio region (in Italy) was assessed on the basis of real-world data provided by the four reference centers responsible for diagnosing and treating IPF. The 5-year, population-based, retrospective longitudinal study provided the data that is at the basis of the current proposal for a new clinical and therapeutic pathway (DTCP) and has been shared with regional decision makers. A DTCP must be defined and based on four pillars: GPs, pulmonologists, IPF centers, and telemedicine. Each must play a role within a sort of hub-and-spoke model. IPF centers remain the hubs, while spokes are identified in trained GPs and pulmonologists.

Fibrotic hypersensitivity pneumonitis is a complex interstitial lung disease that is not entirely understood. In its chronic and fibrotic form, hypersensitivity pneumonitis is one of the main mimickers of idiopathic pulmonary fibrosis (IPF). Distinguishing between these two conditions is challenging but is of particular clinical relevance. Two approved therapies are available for IPF, and a considerable number of clinical trials are now exploring newer pharmacological options. This impressive research effort is a consequence of new pathogenetic understanding, updated diagnostic criteria and a long history of pharmacological trials. Conversely, current knowledge gaps on pathogenesis of chronic hypersensitivity pneumonitis, coupled with lack of validated diagnostic criteria, make the management of this disease an unsolved clinical challenge. This also reflects the paucity of therapeutic clinical trials in this field. In this review, we describe the current evidence and the possible future options to approach this complex disease.

Background: The role of endoscopic ultrasound with bronchoscope fine-needle aspiration (EUS-B-FNA) in the diagnosis of suspected malignant pulmonary lesions adjacent to the esophagus has been poorly investigated. The aim of the present study was to assess the accuracy of EUS-B-FNA for the diagnosis and molecular profiling of paraesophageal pulmonary lesions, as well as its predictors of success. Materials and Methods: Patients who underwent EUS-B-FNA for the diagnosis of paraesophageal lesions were consecutively enrolled in four Italian centers. Demographic, clinical, procedural, pathological, and molecular characteristics of the malignant samples were collected. The primary outcome was the diagnostic accuracy for pulmonary malignancies. Secondary outcomes were diagnostic yield and predictors of success for diagnosis and molecular profiling. Results: 107 adult patients (60 [56.1%] males; median (interquartile range) age: 69 [60–70] years) were enrolled. The diagnostic accuracy of EUS-B-FNA was 95.3% in the overall cohort and 95.2% in the 99 patients with a final diagnosis of malignancy. Neither clinical nor procedural variables significantly affected the diagnostic accuracy, whereas rapid on-site evaluation (ROSE), performed by pathologists or trained pulmonologists, was a strong predictor for a complete molecular profiling (OR [95% CI]: 12.9 [1.2–137.4]; p value: 0.03). Conclusion: EUS-B-FNA is a safe and accurate method for the diagnosis of paraesophageal pulmonary lesions. The presence of ROSE is relevant for a complete molecular profiling in this selected cohort of patients with advanced lung cancer.

Background: Interstitial lung diseases (ILDs) are often associated with rheumatic diseases. Their early diagnosis and management are not only difficult, but also crucial, because they are associated with major morbidity and mortality and can be the first cause of death in autoimmune rheumatic diseases (ARDs).Objectives: By using methodologies, such as Nominal Group Technique (NGT) and Delphi Survey, the aims of this study were (1) to measure consensus between pulmonologists, radiologists, and rheumatologists experienced in the management of ARD-ILD; (2) to highlight the importance of a multidisciplinary approach; and (3) to provide clinicians with a practical tool aimed at improving the prompt recognition and follow-up of ILD associated with ARDs and of any possible rheumatic conditions underlying ILD.Results: During the NGT round, the Steering Committee defined 57 statements to be used in the Delphi survey. A total of 78 experts participated in the Delphi survey, namely 28 pulmonologists, 33 rheumatologists, and 17 radiologists. During this round, consensus on agreement was reached in 47 statements, while disagreement was not reached in any statements. A secondary questionnaire was drafted by the Steering Committee to obtain clearer indications on ILD-ARD “red-flags” and follow-up. Delphi Panelists took part also in the second-questionnaire survey. Answers from both surveys were used to draft two checklists of “red flags” sign or symptom suggestive of ILD and ARD, respectively, and two checklists on identification and monitoring of rheumatoid arthritis (RA) and systemic sclerosis (SSc) ILD.Limitations: This study is a consensus work, which cannot produce empiric data, and is limited to the Italian scenario.Conclusions: This work showed a high level of agreement, but also shows some divergent opinions between different experts. This underlines the importance of a multidisciplinary approach. Eventually, we believe the drafted checklists can help clinicians in the diagnosis and follow-up of ILD-ARD.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the novel coronavirus disease 2019 (COVID-19) pandemic, which spread throughout the world. Acute hypoxemic respiratory failure is the most dangerous complication of COVID-19 pneumonia. To date, no specific therapeutic drugs or vaccines have been proven efficacious. Ventilatory support is still a significant challenge for physicians facing COVID-19. The mechanisms underlying hypoxemia in those patients are not fully understood, but a new physiopathology model has been proposed. Oxygen therapy should be delivered to patients with mild to moderate hypoxemia. More severe patients could benefit from other treatments (high-flow nasal cannula, noninvasive ventilation or intubation, and invasive ventilation). Given the rapid evolution of COVID-19, there has been a paucity of the high-quality data that typically inform clinical practice guidelines from professional societies, and a worldwide consensus is still lacking. This chapter aims to illustrate the potentials of ventilatory support as therapeutic options for adult and pediatric patients affected by COVID-19 pneumonia.

Patient-reported outcome measures (PROMs), tools to assess patient self-report of health status, are now increasingly used in research, care and policymaking. While there are two well-developed disease-specific PROMs for interstitial lung diseases (ILD) and idiopathic pulmonary fibrosis (IPF), many unmet and urgent needs remain. In December 2019, 64 international ILD experts convened in Erice, Italy to deliberate on many topics, including PROMs in ILD. This review summarises the history of PROMs in ILD, shortcomings of the existing tools, challenges of development, validation and implementation of their use in clinical trials, and the discussion held during the meeting. Development of disease-specific PROMs for ILD including IPF with robust methodology and validation in concordance with guidance from regulatory authorities have increased user confidence in PROMs. Minimal clinically important difference for bidirectional changes may need to be developed. Cross-cultural validation and linguistic adaptations are necessary in addition to robust psychometric properties for effective PROM use in multinational clinical trials. PROM burden of use should be reduced through appropriate use of digital technologies and computerised adaptive testing. Active patient engagement in all stages from development, testing, choosing and implementation of PROMs can help improve probability of success and further growth.

Introduction: the Novel Coronavirus Disease (Covid-19) can infect the respiratory tract, causing mild to deadly respiratory impairment. It is still unknown whether patients recovering from Covid-19 will develop respiratory sequelae. This study aims to evaluate the respiratory and functional condition of Covid-19 recovered patients, stratified according to their worst p/F during hospitalization for Covid-19. Method: 86 Covid-19 recovered subjects performed, after 39 days on average, physical examination and arterial blood gas (ABG) examination, pulmonary function tests (PFTs) with diffusing capacity of the lung for carbon monoxide (DLco), and six-minute walk test (6MWT). Subjects also quantified their dyspnoea and cough using a visual analogic scale (VAS) at three-time points: previously than COVID infection, during COVID hospitalization, and currently. The 76 subjects with reliable ABG during the hospitalization were stratified in three groups according to their worst PaO2/FiO2 ratio (p/F): “mild”: p/F>300 (n = 38); “moderate”: 200Results: In this cohort, Covid-19 recovered subjects still reported significant residual dyspnoea at the visit time. The severe subjects group showed a lower Total Lung Capacity (TLC), a lower DLco, and a worse 6MWT performance. Conclusion: After Covid-19, respiratory and functional impairments may persist. These impairments seem to be more severe as much as minor was the patient worst p/F during hospitalization. These patients should receive a strict follow-up.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the novel coronavirus disease 2019 (COVID-19) pandemic, which spread throughout the world. Acute hypoxemic respiratory failure is the most dangerous complication of COVID-19 pneumonia. To date, no specific therapeutic drugs or vaccines have been proven efficacious. Ventilatory support is still a significant challenge for physicians facing COVID-19. The mechanisms underlying hypoxemia in those patients are not fully understood, but a new physiopathology model has been proposed. Oxygen therapy should be delivered to patients with mild to moderate hypoxemia. More severe patients could benefit from other treatments (high-flow nasal cannula, noninvasive ventilation or intubation, and invasive ventilation). Given the rapid evolution of COVID-19, there has been a paucity of the high-quality data that typically inform clinical practice guidelines from professional societies, and a worldwide consensus is still lacking. This chapter aims to illustrate the potentials of ventilatory support as therapeutic options for adult and pediatric patients affected by COVID-19 pneumonia.

Introduction: Idiopathic Pulmonary Fibrosis (IPF) is a fibrotic interstitial lung disease (ILD) with unknown pathogenesis and poor prognosis. Unpredictable events defined as Acute Exacerbations (AE-IPF) may be experienced up to one in five IPF patients. The hallmark is a rapid respiratory failure not fully explained by heart failure/infections and associated with new lung infiltrates. Guidelines recommended treatment with steroids despite a lack of solid evidence. Aims: To compare survival of AE-IPF patients treated with methylprednisolone to those not treated with steroids. Methods: Retrospective analysis of IPF patients admitted to the pulmonary ward from 1 Jan 2014 through 15 Jan 2020. A case-by-case record review was performed. Survival was analyzed using Cox regression and Kaplan-Meier. Results: We admitted 119 ILD patients due and 73 (61.3%) had IPF. We analyzed 26 (35.6%) AE-IPF subjects. Males were predominant (80.1%) with a mean age of 73.2 years and mostly smokers (63.2%). We administered steroid in 12 subjects (46.2%). 10 AE-IPFs died during hospitalization. No association between steroid and mortality was identified either during in-hospital stay (HR 0.81; CI 0.21-3.10; p=0.76). Conclusions: We found no association between corticosteroid use and improved survival in subjects with AE-IPF. Large, controlled-studies are needed to address this unsolved problem. To date, the decision to use steroids remains difficult

Multidisciplinary team (MDT) discussion is the gold standard in the management of interstitial lung disease (ILD). The rheumatologist is not routinely involved in MDT, even if up to 20% of ILD are related to systemic autoimmune rheumatic diseases (SARD). The study aims to assess the agreement and its variation over time between rheumatologists and pulmonologists in the screening of SARD and between rheumatologists and an MDT extended to rheumatologists (eMDT) in evaluating the progression of SARD. We computed the agreement between the pulmonologist and rheumatologist in the identification of red flags for SARDs of 81 ILD cases and between the rheumatologist alone and eMDT in the confirmation of 70 suspected SARD-ILD progressions. The agreement between rheumatologists and pulmonologists was moderate for the detection of autoimmunity test positivity (&kappa, = 0.475, p &lt, 0.001) and family history of SARD (&kappa, = 0.491, p &lt, 0.001) and fair for the identification of extrapulmonary symptoms (&kappa, = 0.225, p = 0.064) or routine laboratory abnormalities consistent with SARD. The average agreement between the rheumatologist and eMDT in the identification of ILD progression was moderate (&kappa, = 0.436, p &lt, 0.001). The class of agreement improved from the first to the third semester. The average agreement with the rheumatologist ranged from fair to moderate, suggesting that a shared evaluation of SARD-ILD in eMDT could improve the diagnostic work-up and the evaluation of ILD progression.

Medical guidelines on diagnosis and management of relevant diseases aim to recommend clinical practice while standardising patient care. However, evidence-based guideline development is laborious and challenging, the recommendations require nuanced wording, and the optimal approach remains controversial. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of interest: Dr. Funke-Chambour reports grants from roche, grants and personal fees from Boehringer Ingelheim, outside the submitted work;. Dr. Funke-Chambour reports grants from roche, grants and personal fees from Boehringer Ingelheim, outside the submitted work;. Conflict of interest: Dr. Albera reports personal fees from Roche, personal fees from Boheringer Ingelheim, personal fees from Fibrogen, personal fees from MSD, personal fees from Bayer, personal fees from GSK, grants from Roche, grants from Boheringer Ingelheim, during the conduct of the study;. Conflict of interest: Dr. Bendstrup reports grants, personal fees and non-financial support from Boehringer Ingelheim, grants, personal fees and non-financial support from Hoffmann la Roche, outside the submitted work;. Conflict of interest: Dr. Costabel reports personal fees and non-financial support from Boehringer, personal fees and non-financial support from Roche, personal fees from Fibrogen, personal fees from Pliant Therapeutics, personal fees from Bristol-Myers Squibb, personal fees from Astra Zeneca, personal fees from Novartis, outside the submitted work;. Conflict of interest: Dr. Grutters has nothing to disclose. Conflict of interest: Dr. Harari reports personal fees from Roche, grants and personal fees from Actelion and Boehringer Ingelheim, outside the submitted work;. Conflict of interest: Dr. Johannson reports personal fees, non-financial support and other from Boehringer-Ingelheim, personal fees from Hoffman-La Roche Ltd., grants from The Chest Foundation, grants from University of Calgary Cumming School of Medicine, personal fees from Blade Therapeutics, personal fees from Theravance, personal fees and non-financial support from Three Lakes Foundation, grants from UCB Biopharma SPRL, grants from Pulmonary Fibrosis Society of Calgary, outside the submitted work;. Conflict of interest: Dr. Kreuter reports grants and personal fees from Boehringer Ingelheim, grants and personal fees from Roche, personal fees from Galapagos, outside the submitted work;. Conflict of interest: Dr. Strambu reports personal fees from Boehringer Ingelheim, personal fees from Boehringer Ingelheim, personal fees from Roche Pharma, personal fees from Astra Zeneca, personal fees from Novartis, personal fees from Galapagos, outside the submitted work;. Conflict of interest: Dr. Vancheri reports grants and personal fees from Roche, grants and personal fees from Boehringer Ingelheim, outside the submitted work;. Conflict of interest: Dr. Varone reports personal fees from Boehringer Ingelheim and Roche, outside the submitted work. Conflict of interest: Dr. Vitulo has nothing to disclose. Conflict of interest: Dr. wuyts reports grants from roche, grants from Boehringer Ingelheim, outside the submitted work and payed to my institution;. Conflict of interest: Dr. Martinez reports personal fees, non-financial support and other from AtraZeneca, other from Afferent/Merck, personal fees, non-financial support and other from Boheringer Ingelheim, other from Bristol Myers Squibb, other from Chiesi, personal fees and non-financial support from Canadian Respiratory Society, personal fees and non-financial support from CME Outfitters, personal fees and non-financial support from CSL Behring, personal fees from Dartmouth University, personal fees from France Foundation, personal fees from Gala, personal fees and non-financial support from Genentech, grants, personal fees, non-financial support and other from GlaxoSmithKline, personal fees and non-financial support from Inova Fairfax, personal fees and non-financial support from MDMagazine, personal fees and non-financial support from NYP Methodist Hospital Brooklyn, personal fees and non-financial support from Miller Communications, personal fees and non-financial support from National Association for Continuing Education, other from Nitto, personal fees and non-financial support from Novartis, personal fees from New York University, personal fees and non-financial support from Patara/Respivant, personal fees from Pearl, personal fees and non-financial support from Peer View, personal fees from Physicians Education Resource, personal fees from ProMedior, personal fees and non-financial support from Rare Diseases Healthcare Communications, personal fees from Rockpointe Communications, personal fees and non-financial support from Sanofi/Regeneron, other from Biogen, personal fees and non-financial support from Sunovion, personal fees and non-financial support from Teva, other from twoXR, personal fees from University of Birmingham Alabama, personal fees from UpToDate, non-financial support from Veracyte, personal fees from Vindico, personal fees and non-financial support from WebMD/MedScape, non-financial support and other from Zambon, non-financial support from ProTerrix Bio, personal fees from IQVIA, outside the submitted work;. Conflict of interest: Dr. Raghu reports personal fees and other from Boerhinger Ingelheim, Roche, Respivant and Veracyte ;other from Avalyn, BMS, Biogen, Blade therapeutics Bellerophan, Fibrogen, Gilead, Genentech, Nitto, Promedior, and grants from NIH, outside the submitted work.

Objective Sleep disorders have a high prevalence among patients with idiopathic pulmonary fibrosis (IPF). The prevalence of restless legs syndrome (RLS) is not known in these patients, neither is its clinical impact as a comorbidity. We investigated the association of RLS with IPF and characterized the clinical features of RLS in a cohort of IPF patients. Methods Fifty patients with diagnosis of IPF were prospectively enrolled. RLS was diagnosed using the validated 5-item RLS criteria. Sleep quality was evaluated using the Pittsburgh Sleep Quality Index. The prevalence of RLS in the IPF group was compared to that observed in a group of 293 patients referred for suspect of sleep disorders. The relationships between RLS and clinical parameters were determined using multivariate logistic regression. Results Prevalence of RLS in the IPF group was significantly higher than in the control population of patients referred for sleep disorders (IPF: 24%, controls 10%: χ2 6.49, p = 0.011). Higher PSQI score confirmed to be associated with RLS after adjusting for demographics and clinical parameters of disease severity (OR = 1.38, 95%CI 1.08–1.76; p = 0.01). Conclusions RLS is highly prevalent in IPF and significantly worsen sleep quality in these patients. The benefit/risk ratio of a specific therapeutic intervention for RLS in IPF should be assessed in further prospective research.

Background and objectivesEvidence of mediastinal Lymph Node Enlargement (LNE) on CT scan is a common finding in idiopathic pulmonary fibrosis (IPF). We sought to investigate whether the involvement of mediastinal lymph nodes is associated with accelerated disease progression, and explored the changes occurring in mediastinal lymph nodes during the radiological follow up of these patients.MethodsThis retrospective study included IPF patients referred to a single ILD centre in Italy. A consensus-based assessment of mediastinal LNE on chest CT scan was performed by two thoracic radiologists. Kaplan-Meier curves and multivariate Cox proportional hazards regression were used to assess hazard ratios for mortality and disease progression (defined as categorical FVC decline ≥10%). The annualized rates of change in functional parameters for each patient were calculated using mixed linear models.ResultsThe study population consisted of 152 IPF patients, of whom 135 (89%) received antifibrotic treatment for IPF during the study follow up. Patients having evidence of 3 or more enlarged mediastinal lymph nodes on baseline CT scan showed increased rates of mortality (HR 5.03, 95% CI 1.86–13.62,p ≤ 0.001) and significant disease progression (HR 2.99, 95% CI 1.22–7.33,p = 0.17) as compared to patients without LNE, after adjusting for GAP stage. Among 62 patients with LNE who underwent a follow up CT scan of the chest and received antifibrotic treatment, 57 (92%) maintained evidence mediastinal LNE over time.ConclusionsDiffuse mediastinal lymph node involvement predicts clinically meaningful functional deterioration in patients with IPF.

Cytological endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) specimens of mediastinal lymph node metastasis are frequently used to perform concomitant diagnosis, staging and genetic testing in non-small-cell lung cancer (NSCLC). The purposes of this single-center retrospective study were to evaluate EBUS-TBNA samples’ adequacy for molecular testing of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), and to analyze the concordance between the cell block method and liquid-based cytology (LBC) in appraising the sample cellularity and in detecting EGFR mutation. We retrospectively examined 82 patients who underwent EBUS-TBNA from October 2012 to September 2015 and received a confirmed diagnosis of lymph node metastasis of lung adenocarcinoma. Each sample was processed using both cell block and LBC to carry out DNA analysis (adequacy criterion: tumor cell percentage > 25%) and EGFR mutation testing. Fifty-four patients were male, 66 were current or former-smokers, and the median age was 67 years. The median size of sampled lymph nodes was 14.8 mm. Seventy-one and 66 samples were adequate to perform cell block and LBC, respectively. The κ-statistic (0.78) showed an excellent concordance. EGFR mutation was detected in eight patients using cell block and in seven using LBC, with a simple percentage agreement of 87.5%. ALK translocation was found in two patients. This study demonstrates the feasibility of EGFR mutation analysis with both cell block and LBC, with an excellent concordance between the two methods. Considering that the majority of advanced NSCLCs are diagnosed on cytology specimens, LBC is feasible and needs to be implemented for ancillary tests (immunocytochemistry, molecular analysis).

Heart failure with preserved ejection fraction (HFpEF) has a poor prognosis, and an effective treatment is currently lacking. Increasing evidence suggests a prevailing pathogenic role of cardiac fibrosis in HFpEF, which generates the possibility of a mechanistic overlap with pulmonary fibrosis. Indeed, cardiac and pulmonary fibrosis share some characteristics and molecular pathways, such as that of transforming growth factor-β. If pulmonary and cardiac fibrosis share common pathways, we can hypothesize a beneficial effect of anti-fibrotic drugs used in idiopathic pulmonary fibrosis on cardiac outcomes. Of note, pirfenidone has been tested in animal models of cardiac fibrosis and was found to be effective in reducing ventricular remodelling. Yet, no results are hitherto available for humans. In this review article, we discuss the potential benefit of anti-fibrotic treatment in HFpEF. In particular, we propose to reappraise safety data collected in placebo-controlled trials of anti-fibrotic drugs in idiopathic pulmonary fibrosis, to explore the hypothesis that these might reduce cardiac fibrosis.

Idiopathic Pulmonary Fibrosis (IPF) is an interstitial lung disease characterized by the progressive loss of pulmonary function, ultimately leading to respiratory failure and death. Two novel compounds, nintedanib and pirfenidone, have shown efficacy in reducing the rate of decline of lung function in IPF patients. The multiple tyrosine kinase inhibitor nintedanib has extensively being studied as a potential angiogenesis inhibitor in clinical against various neoplastic disorders. Afterwards, this compound was successfully tested in IPF. Areas covered: Herein, the authors review the working mechanisms of nintedanib, its pharmacological profile, and its efficacy and safety for patients with IPF. Expert opinion: Nintedanib has shown to be safe and effective in patients with IPF, with a favorable long-term safety profile. There is a lack of comparative trials of pirfenidone and nintedanib, and the choice of treatment is left to the physicians' judgement. Future directions of nintedanib use are represented by the treatment of progressive fibrosing interstitial lung disease other than IPF, IPF with advanced functional impairment, and lung fibrosis secondary to connective tissue diseases. A promising safety profile for the combinational use of nintedanib and pirfenidone in IPF has also recently emerged.

Background Idiopathic pulmonary fibrosis (IPF) is a complex disease with a highly variable clinical course and generally poor prognosis. Classified as a rare disease, significant increases in incidence have been recorded worldwide in recent years. Left untreated IPF is extremely debilitating with substantial personal, social and economic implications. Objectives To discuss how IPF is diagnosed and managed in real life clinical practice with particular reference to Italy and to determine how new and effective therapies can be incorporated into a patient-centred management approach in order to improve the lives of patients with IPF. Outcomes Barriers to early diagnosis are discussed. Cited reasons for delays in diagnosing IPF in Italy include: inherent difficulties in diagnosis; lack of knowledge/awareness of the condition among point-of-contact healthcare professionals; delays in referral to centres of excellence and underestimation of symptoms by both patients and healthcare workers. Valid therapeutic options with demonstrated efficacy in slowing the decline in lung function are now available for patients with IPF. The ASCEND trial confirmed the effects of pirfenidone, approved for the treatment of IPF on the basis of the four phase III trials. Nintedanib, a tyrosine kinase inhibitor that targets the PDGF receptors α/β, FGF receptors 1 to 3, and VEGF receptors 1–3, is approved in the USA and the EU for the treatment of IPF. The TOMORROW and the INPULSIS placebo controlled trials in patients with IPF confirm the efficacy and safety of nintedanib and recent interim analyses endorse its long-term effects in slowing disease progression. Conclusions The importance of early and accurate diagnosis of IPF cannot be underestimated and it is the duty of all healthcare professionals to be vigilant to the symptoms of IPF and to involve a multidisciplinary team in diagnosing and managing IPF early in the course of disease.

BACKGROUND The bronchopleural fistula (BPF) is a rare but potentially fatal complication of major thoracic surgery. The purpose of this work is to investigate the risk factors associated with the development of fistulas after lobectomy and pneumonectomy. METHODS We retrospectively reviewed the records of 835 patients who underwent major anatomic lung resection at our centre from January 2003 to December 2013. Of these, 49 underwent pneumonectomy (P group) and 786 lobectomy (L group). RESULTS A total of 18 patients (2.6%) developed a BPF in the postoperative period, of which there were 11 in the L group (1.3%) and seven in the P group (14.28%). The 30-day mortality was 0.05% (one patient after right pneumonectomy). In the L group, three patients developed a fistula after a left lobectomy and eight after a right one, of which four developed after bilobectomy. Univariate analysis showed that induction therapy, lower lobectomy, manual suture of the bronchus, 'not covered' bronchial stump, empyema, postoperative anaemia and pulmonary infections and mechanical ventilation >24 h are associated with the development of fistulas after lobectomy. Multivariate analysis confirmed that induction therapy, manual closure of the bronchus, postoperative pulmonary infections and anaemia are the main risk factors involved in our series. In the P group, four patients developed a fistula after a right pneumonectomy and three after a left one. Postoperative empyema and pulmonary infections, mechanical ventilation >24 h and female gender emerged as the main risk factors on univariate analysis, while on multivariate analysis, only the female gender presented a trend towards significance. CONCLUSIONS Postoperative pulmonary infections, empyema and mechanical ventilation >24 h are strongly associated with the development of BPFs after both pneumonectomy and lobectomy in our series.

Background and objective In clinical practice, a working diagnosis of IPF may be performed to provide effective antifibrotic treatment to patients who cannot undergo SLB. In this study, we compared the disease course across IPF diagnostic categories in a real-life clinical setting to clarify the appropriateness of a working diagnosis of IPF and treatment initiation in these patients. Methods Longitudinal data from IPF patients receiving antifibrotic treatment (pirfenidone or nintedanib) were retrospectively collected at three tertiary centres in Italy. Univariate and multivariate analyses were performed to compare time to death and to a composite endpoint of disease progression between two diagnostic subgroups, that is, patients with UIP on HRCT and/or SLB, and patients with possible UIP and no histological confirmation. Results A total of 249 IPF patients were included in the analysis. Among patients with a possible UIP pattern on HRCT, 41 (55%) were prescribed antifibrotic treatment (either nintedanib or pirfenidone) despite absence of histological confirmation. This group demonstrated similar mortality and disease progression as compared to patients with a definite diagnosis of IPF as per diagnostic guidelines (log-rank test P = 0.771 and P = 0.139, respectively). Such findings were confirmed on multivariate analysis (HR: 1.19, 95% CI: 0.49-2.89, P = 0.7 for death; HR: 1.42, 95% CI: 0.83-2.44, P = 0.201 for disease progression). Conclusion In patients receiving antifibrotics following a working diagnosis of IPF, disease progression rates were similar to patients with a confident diagnosis of IPF according to consensus guidelines, supporting the rationale for treatment initiation in these patients by expert multidisciplinary teams.

Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Airway closure causes lack of communication between proximal airways and alveoli, making tidal inflation start only after a critical airway opening pressure is overcome. The authors conducted a matched cohort study to report the existence of this phenomenon among obese patients undergoing general anesthesia. Methods Within the procedures of a clinical trial during gynecological surgery, obese patients underwent respiratory/lung mechanics and lung volume assessment both before and after pneumoperitoneum, in the supine and Trendelenburg positions, respectively. Among patients included in this study, those exhibiting airway closure were compared to a control group of subjects enrolled in the same trial and matched in 1:1 ratio according to body mass index. Results Eleven of 50 patients (22%) showed airway closure after intubation, with a median (interquartile range) airway opening pressure of 9 cm H2O (6 to 12). With pneumoperitoneum, airway opening pressure increased up to 21 cm H2O (19 to 28) and end-expiratory lung volume remained unchanged (1,294 ml [1,154 to 1,363] vs. 1,160 ml [1,118 to 1,256], P = 0.155), because end-expiratory alveolar pressure increased consistently with airway opening pressure and counterbalanced pneumoperitoneum-induced increases in end-expiratory esophageal pressure (16 cm H2O [15 to 19] vs. 27 cm H2O [23 to 30], P = 0.005). Conversely, matched control subjects experienced a statistically significant greater reduction in end-expiratory lung volume due to pneumoperitoneum (1,113 ml [1,040 to 1,577] vs. 1,000 ml [821 to 1,061], P = 0.006). With airway closure, static/dynamic mechanics failed to measure actual lung/respiratory mechanics. When patients with airway closure underwent pressure-controlled ventilation, no tidal volume was inflated until inspiratory pressure overcame airway opening pressure. Conclusions In obese patients, complete airway closure is frequent during anesthesia and is worsened by Trendelenburg pneumoperitoneum, which increases airway opening pressure and alveolar pressure: besides preventing alveolar derecruitment, this yields misinterpretation of respiratory mechanics and generates a pressure threshold to inflate the lung that can reach high values, spreading concerns on the safety of pressure-controlled modes in this setting.

In Reply: We read with great interest the letter by Dr Karan Madan on the application of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for the evaluation of undiagnosed mediastinal lymphadenopathy and masses in children. This letter is a useful complement to our

Accurate diagnosis of idiopathic pulmonary fibrosis (IPF) is essential to ensure prompt initiation of appropriate treatment and enrolment in clinical trials. According to current international guidelines [1], in the appropriate clinical context the identification of the usual interstitial pneumonia (UIP) pattern on chest high-resolution computed tomography (HRCT) allows a confident diagnosis of IPF. Patients referred to tertiary centres for suspected interstitial lung disease (ILD) may provide CT images that do not fulfil recommended scanning protocols [1], therefore triggering the execution of another CT. However, the impact of suboptimal technical quality on the identification of the UIP pattern by thoracic radiologists is unknown. We assessed the quality of chest CT scans performed in the context of an ILD network including a tertiary ILD centre (hub) and the affiliated centres (spokes), and the impact on the identification of the UIP pattern. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of interest: Dr. Sgalla reports personal fees from Boehringer Ingelheim, outside the submitted work. Conflict of interest: Dr. LARICI has nothing to disclose. Conflict of interest: Dr. Re has nothing to disclose. Conflict of interest: Dr. Farchione has nothing to disclose. Conflict of interest: Dr. Cicchetti has nothing to disclose. Conflict of interest: Dr. Calandriello has nothing to disclose. Conflict of interest: Dr. Comes has nothing to disclose. Conflict of interest: Dr. Golfi has nothing to disclose. Conflict of interest: Dr. Iovene has nothing to disclose. Conflict of interest: Dr. Varone has nothing to disclose. Conflict of interest: Dr. Manfredi has nothing to disclose. Conflict of interest: Dr. Richeldi reports personal fees from Sanofi-Aventis, personal fees from Roche, personal fees from ImmuneWorks, personal fees from Shionogi, personal fees from Boehringer Ingelheim, personal fees from Celgene, personal fees from Nitto, personal fees from Fibrogen, personal fees from Promedior, personal fees from Bristol Myers Squibb, personal fees from DynaMed, outside the submitted work.

Idiopathic pulmonary fibrosis (IPF) is a chronic, debilitating, fibrotic lung disease leading to respiratory failure, and ultimately to death. It is characterized by marked heterogeneity regarding its clinical course. Despite significant progress in the understanding of its pathogenesis, the course of the disease and the response to treatment of an individual patient cannot be reliably predicted today. Areas covered: Non-invasive biomarkers, in particular serum biomarkers, for the (early) diagnosis, differential diagnosis, prognosis, and prediction of therapeutic response are described. The molecules are classified according to their involvement into alveolar epithelial cell injury, fibroproliferation, and matrix remodeling as well as immune regulation. Furthermore, genetic variants of TOLLIP, MUC-5B, and other genes associated with a differential response to treatment and with the development and/or the prognosis of IPF are reported. Expert commentary: The combination of multiple biomarkers may identify comprehensive biomarker signatures in IPF patients. This is a way to apply personalized medicine approach to patient affected by IPF in order to not only improve our ability to diagnose and treat disease but also offer the potential to detect disease at an earlier stage, when it is potentially easier to treat effectively.

IntroductionIdiopathic pulmonary fibrosis (IPF) is a fatal lung disease. Due to insufficient awareness of the disease, and the lack of specificity of clinical and physiological signs, the diagnosis of IPF is often delayed. In the Lazio Region (Italy) four reference centers manage patients with IPF. The objective of this analysis is to support the definition of a new regional care and therapeutic pathway (Percorso Diagnostico Terapeutico Assistenziale [PDTA]) for IPF to anticipate the moment of diagnosis by reference centers. The delayed referral to specialized centers has clinical consequences both in terms of survival and access to treatments.MethodsA survey collected aggregated evidence on factors associated with referral patterns to specialized centers for IPF. Its content was defined on the basis of a literature search, the experience of involved clinicians, and hospital data sources. The survey considered patients diagnosed with IPF by the network of reference centers from 2014 to 2018. Aggregated data on the pre-diagnosis pathway and evidence on organizational features of each reference center were collected.ResultsPatients with a confirmed diagnosis of IPF increased from 2014 (n = 81) to 2018 (n = 344). A similar trend emerged considering only older patients. Incidence rates reached 11.33 cases per 100,000 residents in 2018. The majority of patients had a diagnosis in time to access to available treatments (87% in 2018). The number of specialists in multidisciplinary teams didn't change in a significant way. GPs, pneumologists, and IPF centers emerged as the pillar of the de-facto PDTA.ConclusionsA new regional care and therapeutic pathway has been proposed to improve treatment of IPF. The first goal is to improve interaction among GPs, pneumologists, and IPF centers along the natural course of the disease. Criteria for referral to IPF centers has been defined (i.e. high-resolution computed tomography) as well as for adoption of a hub-and-spoke approach based on telemedicine.

Idiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive, fibrosing interstitial pneumonia associated with the histologic and/or radiologic pattern of usual interstitial pneumonia (UIP). Nowadays, the high-resolution computed tomography pattern of “definite UIP” is enough to define a diagnosis of UIP without histological proof. This is pivotal especially in elderly patients with comorbidities. Early recognition of IPF is relevant for its prognostic implication. Some pharmacological strategies have been proposing novel molecules that tend to slow lung function decline, even though without healing fibrosis. We report a case of ex-heavy smoker male with IPF showing clinical and radiological improvement after 11 months of treatment with Pirfenidone. The definite diagnosis was challenging and it was reached by a multidisciplinary approach.

We live in an era of respiratory medicine in which there is increasing awareness of interstitial lung diseases (ILDs). This is probably due to the publication of evidence-based guidelines [1, 2] and the discovery of newer drugs [3, 4]. These advances are particularly evident for idiopathic pulmonary fibrosis (IPF), which is to date the only fibrotic disease with specific pharmacologic-approved treatments. The burgeoning interest in pulmonary fibrosis has recently shifted its focus to the possibility of using therapeutic interventions available for IPF on other non-IPF ILDs, including pulmonary fibrosis secondary to systemic sclerosis (SSc). ILD represents one of the most relevant complications of SSc [5], but a standard treatment has yet to be achieved. Currently, the therapeutic management of SSc-ILD includes a “wait and see” approach in patients with a slow functional decay, and an immunosuppressive strategy (cyclophosphamide or mycophenolate) in patients with progressive ILD [6]. The Safety and Efficacy of Nintedanib in Systemic Sclerosis (SENSCIS) trial[7] explored the use of nintedanib, an intracellular inhibitor of tyrosine kinases currently approved for IPF, in scleroderma patients., Nintedanib shows a statistically significant effect on lung function decay in patients with ILD secondary to systemic sclerosis, but no effect on skin fibrosis and on health-related quality of life http://bit.ly/2vfJRj7

A proportion of patients with interstitial lung diseases (ILDs) are at risk of developing a progressive-fibrosing phenotype, which is associated with a deterioration in lung function and early mortality. In addition to idiopathic pulmonary fibrosis (IPF), fibrosing ILDs that may present a progressive phenotype include idiopathic nonspecific interstitial pneumonia, connective tissue disease-associated ILDs, hypersensitivity pneumonitis, unclassifiable idiopathic interstitial pneumonia, ILDs related to other occupational exposures and sarcoidosis. Corticosteroids and/or immunosuppressive therapies are sometimes prescribed to patients with these diseases. However, this treatment regimen may not be effective, adequate on its own or well tolerated, suggesting that there is a pressing need for efficacious and better tolerated therapies. Currently, the only approved treatments to slow disease progression in patients with IPF are nintedanib and pirfenidone. Similarities in pathobiological mechanisms leading to fibrosis between IPF and other ILDs that may present a progressive-fibrosing phenotype provide a rationale to suggest that nintedanib and pirfenidone may be therapeutic options for patients with the latter diseases.This review provides an overview of the therapeutic options currently available for patients with fibrosing ILDs, including fibrosing ILDs that may present a progressive phenotype, and explores the status of the randomised controlled trials that are underway to determine the efficacy and safety of nintedanib and pirfenidone.

In the everyday practice of respiratory physicians, ultrasound techniques play a key role by enabling several diagnostic and interventional procedures. The application of ultrasound to endoscopic procedures allows both a visualization and a guided sampling of mediastinal and hilar lymph nodes. Endobronchial ultrasound can be combined with transbronchial needle aspiration, and, similarly, endoscopic ultrasound can be combined with fine-needle aspiration to sample virtually all mediastinal nodal stations from the airways and the esophagus. Endobronchial ultrasound-transbronchial needle aspiration and endoscopic ultrasound-fine needle aspiration showed a complementary diagnostic yield, and, recently, endoscopic ultrasound with bronchoscope was introduced in clinical practice to perform a transesophageal needle aspiration by using an ultrasound bronchoscope. This technique allows a single operator to perform both transbronchial and transesophageal needle sampling with the same instrument during a single bronchoscopic procedure. Mediastinal staging impacts the management of patients affected by lung cancer, and the most recent guidelines clearly state that endobronchial ultrasound and endoscopic ultrasound should be the initial tissue sampling procedure over surgical staging. In addition, endoscopic ultrasound techniques demonstrated an excellent yield in diagnosing lymphoma and benign diseases, for example, sarcoidosis. The aim of this review was to discuss the current role and future perspectives of endosonography techniques available for the evaluation of the mediastinum. Special emphasis was placed on equipment and technical aspects, the diagnostic role, and future directions of development.

More than half of primary lung cancers are not resectable at diagnosis and 40% of deaths may be secondary to loco-regional disease. Many of these patients suffer from symptoms related to airways obstruction. Indications for therapeutic endoscopic treatment are palliation of dyspnea and other obstructive symptoms in advanced cancerous lesions and cure of early lung cancer. Bronchoscopic management is also indicated for all those patients suffering from benign or minimally invasive neoplasm who are not suitable for surgery due to their clinical conditions. Clinicians should select cases, evaluating tumor features (size, location) and patient characteristics (age, lung function impairment) to choose the most appropriate endoscopic technique. Laser therapy, electrocautery, cryotherapy and stenting are well-described techniques for the palliation of symptoms due to airway involvement and local treatment of endobronchial lesions. Newer technologies, with an established role in clinical practice, are endobronchial ultrasound (EBUS), autofluorescence bronchoscopy (AFB), and narrow band imaging (NBI). Other techniques, such as endobronchial intra-tumoral chemotherapy (EITC), EBUS-guided-transbronchial needle injection or bronchoscopy-guided radiofrequency ablation (RFA), are in development for the use within the airways. These endobronchial interventions are important adjuncts in the multimodality management of lung cancer and should become standard considerations in the management of patients with advanced lung cancer, benign or otherwise not approachable central airway lesions. We aimed at revising several endobronchial treatment modalities that can augment standard antitumor therapies for advanced lung cancer, including rigid and flexible bronchoscopy, laser therapy, endobronchial prosthesis, and photodynamic therapy (PDT).

IPF is a specific form of chronic fibrosing interstitial pneumonia of unknown cause, characterized by progressive worsening in lung function and an unfavorable prognosis. Current concepts on IPF pathogenesis are based on a dysregulated wound healing response, leading to an over production of extracellular matrix. Based on recent research however, several other mechanisms are now proposed as potential targets for novel therapeutic strategies. Areas covered: This review analyzes the current investigational strategies targeting extracellular matrix deposition, tyrosine-kinase antagonism, immune and autoimmune response, and cell-based therapy. A description of the pathogenic rationale implied in each novel therapeutic approach is summarized. Expert opinion: New IPF drugs are being evaluated in the context of phase 1 and 2 clinical trials. Nevertheless, many drugs that have shown efficacy in preclinical studies, failed to exhibit the same positive effect when translated to humans. A possible explanation for these failures might be related to the known limitations of animal models of the disease. The recent development of 3D systems composed of cells from individual patients that recreate an ex-vivo model of IPF, could lead to significant improvements in disease pathogenesis and treatment. New drugs could be tested on more genuine models and clinicians could tailor therapy based on patient's response.

Background The diagnostic yield of conventional transbronchial needle aspiration (TBNA) is characterized by a learning effect. The aim of this retrospective study was to verify whether a learning curve similarly affected the yield of endobronchial ultrasound-guided (EBUS)-TBNA. To this end, we evaluated the sensitivity and diagnostic accuracy of EBUS-TBNA during the first 3 years of activity. Methods EBUS-TBNA was performed by 2 operators with no previous experience in this technique. Cytologic samples were obtained from mediastinal and hilar lymph nodes enlarged at a chest computed tomography scan and/or with increased fluorodeoxyglucose uptake at computed tomography/positron emission tomography scan in patients with suspected lung cancer. The cytologic diagnosis of EBUS-TBNA samples has been compared with the final diagnosis obtained from further diagnostic procedures, surgery, or clinical-radiologic follow-up. Results From October 2012 to October 2015, we collected 408 EBUS-TBNA cytologic samples from 313 patients: 223 samples were positive for metastatic involvement and 185 were nonmetastatic. The latter included 137 true-negative and 48 false-negative results. The final diagnosis comprised 271 metastatic and 137 nonmetastatic lymph nodes. The overall sensitivity for cancer was 82% and diagnostic accuracy was 88%. Sensitivity and accuracy per year were as follows: first year, 78% and 82% in 90 nodal samples; second year, 83% and 89% in 144 nodal samples; third year, 85% and 91% in 174 nodal samples. Conclusions EBUS-TBNA can be considered as a reliable tool even if performed by operators without previous experience in this procedure, and the diagnostic yield continues to increase progressively over a long time.

The European Landscape Convention, with great determination, has placed as a priority target, the necessity to promote a high level of attention to the landscape, as a common asset. According to the Convention each part of the landscape conveys meanings: the areas of particular beauty, daily life landscapes and degraded ones. The evidence of this changed reading is the “Law on the Cultural Heritage and Landscape” (DLgs 22 n. 42 of 2004), which in the 2008 version (Dlgs. n. 63) embrace even the principles of the European Landscape Convention, which Italy ratified in 2006. If the Territorial Landscape Plan and the Territorial Coordination Plan have the useful role of containing guidelines, directives and safeguard provisions for the areas with landscape value, the Urban City Plans are the most appropriate tool to allow a planning which is respectful of landscape requirements. As a consequence, the urban city planning has to investigate the values of the landscape decoding both its specific and relational characters. The proposed landscape decoding method, already experimented with different scales of planning, offers a possible key to read and interpret the landscape in order to orient the Government projects on territorial-land transformations, which must be linked to protection, redevelopment and enhancement., UPLanD - Journal of Urban Planning, Landscape & environmental Design, Vol 2, No 1: GREEN

The bronchopleural fistula (BPF) is a rare but potentially fatal complication of major thoracic surgery. The purpose of this work is to investigate the risk factors associated with the development of fistulas after lobectomy and pneumonectomy.We retrospectively reviewed the records of 835 patients who underwent major anatomic lung resection at our centre from January 2003 to December 2013. Of these, 49 underwent pneumonectomy (P group) and 786 lobectomy (L group).A total of 18 patients (2.6%) developed a BPF in the postoperative period, of which there were 11 in the L group (1.3%) and seven in the P group (14.28%). The 30-day mortality was 0.05% (one patient after right pneumonectomy). In the L group, three patients developed a fistula after a left lobectomy and eight after a right one, of which four developed after bilobectomy. Univariate analysis showed that induction therapy, lower lobectomy, manual suture of the bronchus, 'not covered' bronchial stump, empyema, postoperative anaemia and pulmonary infections and mechanical ventilation24 h are associated with the development of fistulas after lobectomy. Multivariate analysis confirmed that induction therapy, manual closure of the bronchus, postoperative pulmonary infections and anaemia are the main risk factors involved in our series. In the P group, four patients developed a fistula after a right pneumonectomy and three after a left one. Postoperative empyema and pulmonary infections, mechanical ventilation24 h and female gender emerged as the main risk factors on univariate analysis, while on multivariate analysis, only the female gender presented a trend towards significance.Postoperative pulmonary infections, empyema and mechanical ventilation24 h are strongly associated with the development of BPFs after both pneumonectomy and lobectomy in our series.

Phagocytosis is a key mechanism of innate immunity, and promotion of phagosome maturation may represent a therapeutic target to enhance antibacterial host response. Phagosome maturation is favored by the timely and coordinated intervention of lipids and may be altered in infections. Here we used apoptotic body-like liposomes (ABL) to selectively deliver bioactive lipids to innate cells, and then tested their function in models of pathogen-inhibited and host-impaired phagosome maturation. Stimulation of macrophages with ABLs carrying phosphatidic acid (PA), phosphatidylinositol 3-phosphate (PI3P) or PI5P increased intracellular killing of BCG, by inducing phagosome acidification and ROS generation. Moreover, ABLs carrying PA or PI5P enhanced ROS-mediated intracellular killing of Pseudomonas aeruginosa, in macrophages expressing a pharmacologically-inhibited or a naturally-mutated cystic fibrosis transmembrane conductance regulator. Finally, we show that bronchoalveolar lavage cells from patients with drug-resistant pulmonary infections increased significantly their capacity to kill in vivo acquired bacterial pathogens when ex vivo stimulated with PA- or PI5P-loaded ABLs. Altogether, these results provide the proof of concept of the efficacy of bioactive lipids delivered by ABL to enhance phagosome maturation dependent antimicrobial response, as an additional host-directed strategy aimed at the control of chronic, recurrent or drug-resistant infections.

Background A restrictive lung function pattern is frequently observed in patients with diabetes mellitus (DM) and has been related to respiratory muscle dysfunction in type 1 DM or in mixed population. We aimed to verify whether such a relationship applies also to type 2 DM patients. Methods The respiratory muscle function was explored in 75 non-smoking patients with type 2 DM without pulmonary or cardiac diseases and compared with that of 40 healthy non-smoking control subjects matched by age and sex. Maximal inspiratory and expiratory pressures (MIP, MEP) and maximum voluntary ventilation (MVV), which reflect respiratory muscle strength and endurance, respectively, were measured, and a complete respiratory function assessment was recorded. Results Patients were in stable metabolic conditions and had, on average, normal total lung capacity and diffusing lung capacity for carbon monoxide. However, MIP and MVV were significantly reduced in comparison with those of control subjects. Both MIP/MEP and MVV significantly correlated with lung volumes and diffusing lung capacity for carbon monoxide. The multiple regression analysis identified age (beta coefficient = −0.238, p = 0.046), glycated haemoglobin (beta coefficient = −0.245, p = 0.047) and total lung capacity (beta coefficient = 0.430, p = 0.016) as independent correlates of MIP, whereas male sex (beta coefficient = 0.423, p = 0.004) and diabetic complications (beta coefficient = −0.248, p = 0.044) were independent correlates of MVV. Conclusions In type 2 DM, respiratory muscle strength was reduced and significantly related to lung volumes and quality of metabolic control, whereas impaired endurance of respiratory muscles prevailed in patients with microvascular complications. Copyright © 2012 John Wiley & Sons, Ltd.

Diabet. Med. 28, 1407–1411 (2011) Abstract Aims Decreased chemosensitivity to hypercapnia, a common finding in Type 1 diabetes mellitus, seems related to autonomic neuropathy. We proposed to verify whether simple neuroautonomic cardiovascular tests or indexes of severity of diabetes and respiratory impairment can identify patients with such a dysfunction, but no clinical evidence of autonomic neuropathy. Methods Forty patients with Type 1 diabetes, 20 with autonomic neuropathy according to the results of a standardized test battery, were studied and compared with 40 normal subjects matched by age and sex. Spirometry and pulmonary diffusing capacity for carbon monoxide were performed. The chemosensitivity to hypercapnia was tested by the rebreathing method. Results There was no significant difference between patients with and without autonomic neuropathy in chemosensitivity to hypercapnia, as expressed by the ventilation response to increasing end-tidal pressure of carbon dioxide; however, it was lower in the whole group of patients with diabetes than in control subjects (1.71 ± 0.80 vs. 2.45 ± 1.11 l−1 min−1 mmHg, respectively, P = 0.002). No significant correlation was found between ventilation response to increasing end-tidal pressure of carbon dioxide and the results of autonomic tests. In patients with diabetes mellitus, the ventilatory response to hypercapnia significantly correlated with pulmonary diffusing capacity for carbon monoxide (Spearman’s rho = 0.387, P = 0.013) and this was the only variable significantly associated with ventilation response to increasing end-tidal pressure of carbon dioxide in a multiple regression model. Conclusions Chemosensitivity to hypercapnia was depressed in patients with diabetes mellitus, irrespective of autonomic neuropathy, in comparison with control subjects. The correlation with pulmonary diffusing capacity for carbon monoxide suggests that microcirculatory damage might contribute to depress the central chemosensitivity.

Bronchopleural fistula is a rare but potentially fatal complication of pulmonary resections and proper management is essential for its resolution. In this study, we analyzed the incidence of fistula after pulmonary resection and reported data about endoscopic and conservative treatments of this complication. From January 2003 to December 2013, 835 patients underwent anatomic lung resections: 786 (94.1 %) had a lobectomy and 49 (5.9 %) a pneumonectomy. Bronchopleural fistula was suspected by clinical signs and confirmed by endoscopic visualization. Eighteen patients (2.2 %) developed a bronchopleural fistula, 11 in lobectomy group (1.4 %) and 7 in pneumonectomy group (14.3 %). The fistula size ranged between

Transbronchial needle aspiration (TBNA) is recognized as a valuable tool for the sampling of mediastinal lymph nodes. In this study, we report data about the diagnostic yield of conventional TBNA in the diagnosis and staging of lung cancer.All patients with suspected lung cancer who underwent bronchoscopy with conventional TBNA in the years 2008 to 2012 were evaluated. TBNA was performed on mediastinal lymph nodes enlarged at chest computed tomography scan and/or with increased fluorodeoxyglucose uptake on positron emission tomography/computed tomography scan. Cytologic results derived from TBNA have been compared, with the final diagnosis obtained with other more invasive procedures and/or with a clinical-radiologic follow-up of at least 12 months.TBNA was performed on 375 patients. However, 19 patients were lost to follow-up, and data from 356 patients with a total 459 TBNA specimens were analyzed. TBNA was positive for metastatic involvement of lymph nodes in 172 of 282 patients with cancer, with a sensitivity of 61%. Sensitivity achieved 65% when we considered the total of 459 TBNA specimens. The overall diagnostic accuracy of TBNA was 69%. The nodal stations more frequently examined were 7 (subcarinal: 190 TBNAs), 4R (right lower paratracheal: 147 TBNAs), and 10R (right hilar: 76 TBNAs), with a sensitivity of 66%, 66%, and 67%, respectively.Conventional TBNA remains a useful method for the diagnosis and staging of lung cancer, with a good diagnostic yield in several nodal stations.