Showing papers in "European Respiratory Review in 2020"

Protecting healthcare workers from SARS-CoV-2 infection: practical indications.

Abstract: The World Health Organization has recently defined the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection a pandemic. The infection, that may cause a potentially very severe respiratory disease, now called coronavirus disease 2019 (COVID-19), has airborne transmission via droplets. The rate of transmission is quite high, higher than common influenza. Healthcare workers are at high risk of contracting the infection particularly when applying respiratory devices such as oxygen cannulas or noninvasive ventilation. The aim of this article is to provide evidence-based recommendations for the correct use of "respiratory devices" in the COVID-19 emergency and protect healthcare workers from contracting the SARS-CoV-2 infection.

Updated guidance on the management of COVID-19: from an American Thoracic Society/European Respiratory Society coordinated International Task Force (29 July 2020).

Abstract: Background Coronavirus disease 2019 (COVID-19) is a disease caused by severe acute respiratory syndrome-coronavirus-2. Consensus suggestions can standardise care, thereby improving outcomes and facilitating future research. Methods An International Task Force was composed and agreement regarding courses of action was measured using the Convergence of Opinion on Recommendations and Evidence (CORE) process. 70% agreement was necessary to make a consensus suggestion. Results The Task Force made consensus suggestions to treat patients with acute COVID-19 pneumonia with remdesivir and dexamethasone but suggested against hydroxychloroquine except in the context of a clinical trial; these are revisions of prior suggestions resulting from the interim publication of several randomised trials. It also suggested that COVID-19 patients with a venous thromboembolic event be treated with therapeutic anticoagulant therapy for 3 months. The Task Force was unable to reach sufficient agreement to yield consensus suggestions for the post-hospital care of COVID-19 survivors. The Task Force fell one vote shy of suggesting routine screening for depression, anxiety and post-traumatic stress disorder. Conclusions The Task Force addressed questions related to pharmacotherapy in patients with COVID-19 and the post-hospital care of survivors, yielding several consensus suggestions. Management options for which there is insufficient agreement to formulate a suggestion represent research priorities.

Delphi consensus recommendations for a treatment algorithm in pulmonary sarcoidosis.

Abstract: Pulmonary sarcoidosis presents substantial management challenges, with limited evidence on effective therapies and phenotypes. In the absence of definitive evidence, expert consensus can supply clinically useful guidance in medicine. An international panel of 26 experts participated in a Delphi process to identify consensus on pharmacological management in sarcoidosis with the development of preliminary recommendations.The modified Delphi process used three rounds. The first round focused on qualitative data collection with open-ended questions to ensure comprehensive inclusion of expert concepts. Rounds 2 and 3 applied quantitative assessments using an 11-point Likert scale to identify consensus.Key consensus points included glucocorticoids as initial therapy for most patients, with non-biologics (immunomodulators), usually methotrexate, considered in severe or extrapulmonary disease requiring prolonged treatment, or as a steroid-sparing intervention in cases with high risk of steroid toxicity. Biologic therapies might be considered as additive therapy if non-biologics are insufficiently effective or are not tolerated with initial biologic therapy, usually with a tumour necrosis factor-α inhibitor, typically infliximab.The Delphi methodology provided a platform to gain potentially valuable insight and interim guidance while awaiting evidenced-based contributions.

Current and future applications of liquid biopsy in nonsmall cell lung cancer from early to advanced stages.

Abstract: Liquid biopsy refers to the analysis of any tumour-derived material circulating in the blood or any other body fluid. This concept is particularly relevant in lung cancer as the tumour is often difficult to reach and may need an invasive and potentially harmful procedure. Moreover, the multitude of anticancer drugs and their sequential use underline the importance of conducting an iterative assessment of tumour biology. Liquid biopsies can noninvasively detect any targetable genomic alteration and guide corresponding targeted therapy, in addition to monitoring response to treatment and exploring the genetic changes at resistance, overcoming spatial and temporal heterogeneity. In this article, we review the available data in the field, which suggest the potential of liquid biopsy in the area of lung cancer, with a particular focus on cell-free DNA and circulating tumour cells. We discuss their respective applications in patient selection and monitoring through targeted therapy, as well as immune checkpoint inhibitors. The current data and future applications of liquid biopsy in the early stage setting are also investigated. Liquid biopsy has the potential to help manage nonsmall cell lung cancer throughout all stages of lung cancer: screening, minimal residual disease detection to guide adjuvant treatment, early detection of relapse, systemic treatment initiation and monitoring of response (targeted or immune therapy), and resistance genotyping.

COVID-19 and COPD: a narrative review of the basic science and clinical outcomes

Abstract: The 2019 coronavirus disease (COVID-19) pandemic is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Clinical outcomes, including mortality, are worse in males, older individuals and patients with comorbidities. COPD patients are included in shielding strategies due to their susceptibility to virus-induced exacerbations, compromised pulmonary function and high prevalence of associated comorbidities. Using evidence from basic science and cohort studies, this review addresses key questions concerning COVID-19 and COPD. First, are there mechanisms by which COPD patients are more susceptible to SARS-CoV-2 infection? Secondly, do inhaled corticosteroids offer protection against COVID-19? And, thirdly, what is the evidence regarding clinical outcomes from COVID-19 in COPD patients? This up-to-date review tackles some of the key issues which have significant impact on the long-term outlook for COPD patients in the context of COVID-19.

Risk factors for all-cause hospital readmission following exacerbation of COPD: a systematic review and meta-analysis

Abstract: Background Readmission rates following hospitalisation for COPD exacerbations are unacceptably high, and the contributing factors are poorly understood. Our objective was to summarise and evaluate the factors associated with 30- and 90-day all-cause readmission following hospitalisation for an exacerbation of COPD. Methods We systematically searched electronic databases from inception to 5 November 2019. Data were extracted by two independent authors in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Study quality was assessed using a modified version of the Newcastle–Ottawa Scale. We synthesised a narrative from eligible studies and conducted a meta-analysis where this was possible using a random-effects model. Results In total, 3533 abstracts were screened and 208 full-text manuscripts were reviewed. A total of 32 papers met the inclusion criteria, and 14 studies were included in the meta-analysis. The readmission rate ranged from 8.8–26.0% at 30 days and from 17.5–39.0% at 90 days. Our narrative synthesis showed that comorbidities, previous exacerbations and hospitalisations, and increased length of initial hospital stay were the major risk factors for readmission at 30 and 90 days. Pooled adjusted odds ratios (95% confidence intervals) revealed that heart failure (1.29 (1.22–1.37)), renal failure (1.26 (1.19–1.33)), depression (1.19 (1.05–1.34)) and alcohol use (1.11 (1.07–1.16)) were all associated with an increased risk of 30-day all-cause readmission, whereas being female was a protective factor (0.91 (0.88–0.94)). Conclusions Comorbidities, previous exacerbations and hospitalisation, and increased length of stay were significant risk factors for 30- and 90-day all-cause readmission after an index hospitalisation with an exacerbation of COPD.

Developments in lung transplantation over the past decade.

Abstract: With an improved median survival of 6.2 years, lung transplantation has become an increasingly acceptable treatment option for end-stage lung disease. Besides survival benefit, improvement of quality of life is achieved in the vast majority of patients. Many developments have taken place in the field of lung transplantation over the past decade. Broadened indication criteria and bridging techniques for patients awaiting lung transplantation have led to increased waiting lists and changes in allocation schemes worldwide. Moreover, the use of previously unacceptable donor lungs for lung transplantation has increased, with donations from donors after cardiac death, donors with increasing age and donors with positive smoking status extending the donor pool substantially. Use of ex vivo lung perfusion further increased the number of lungs suitable for lung transplantation. Nonetheless, the use of these previously unacceptable lungs did not have detrimental effects on survival and long-term graft outcomes, and has decreased waiting list mortality. To further improve long-term outcomes, strategies have been proposed to modify chronic lung allograft dysfunction progression and minimise toxic immunosuppressive effects. This review summarises the developments in clinical lung transplantation over the past decade.

Minimal clinically important difference for asthma endpoints: An expert consensus report

Abstract: Minimal clinically important difference (MCID) can be defined as the smallest change or difference in an outcome measure that is perceived as beneficial and would lead to a change in the patient's medical management.The aim of the current expert consensus report is to provide a "state-of-the-art" review of the currently available literature evidence about MCID for end-points to monitor asthma control, in order to facilitate optimal disease management and identify unmet needs in the field to guide future research.A series of MCID cut-offs are currently available in literature and validated among populations of asthmatic patients, with most of the evidence focusing on outcomes as patient reported outcomes, lung function and exercise tolerance. On the contrary, only scant and partial data are available for inflammatory biomarkers. These clearly represent the most interesting target for future development in diagnosis and clinical management of asthma, particularly in view of the several biologic drugs in the pipeline, for which regulatory agencies will soon require personalised proof of efficacy and treatment response predictors.

Impact of CFTR modulator use on outcomes in people with severe cystic fibrosis lung disease

Abstract: Drug compounds that augment the production and activity of the cystic fibrosis (CF) transmembrane regulator (CFTR) have revolutionised CF care. Many adults and some children with CF suffer advanced and severe lung disease or await lung transplantation. While the hope is that these drug compounds will prevent lung damage when started early in life, there is an ongoing need to care for people with advanced lung disease. The focus of this review is the accumulating data from clinical trials and case series regarding the benefits of CFTR modulator therapy in people with advanced pulmonary disease. We address the impact of treatment with ivacaftor, lumacaftor/ivacaftor, tezacaftor/ivacaftor and elexacaftor/tezacaftor/ivacaftor on lung function, pulmonary exacerbations, nutrition and quality of life. Adverse events of the different CFTR modulators, as well as the potential for drug-drug interactions, are discussed.

Short-course systemic corticosteroids in asthma: striking the balance between efficacy and safety.

Abstract: Short courses of systemic corticosteroids (SCS), both oral and injectable, are very effective for the resolution of acute asthma symptoms, including exacerbations. However, the benefits of SCS, even short courses, must be balanced against the impact of their side-effects. While the adverse consequences of long-term use are widely recognised, there appears to be a perception in the medical community that short courses of SCS are safe. Limited but growing evidence in the literature suggests that even very brief dosing periods (3–7 days) of SCS are enough to cause significantly negative outcomes for patients. Short courses of SCS are associated with increased risk of adverse events including loss of bone density, hypertension and gastrointestinal ulcers/bleeds, in addition to serious impacts on mental health. Strategies to improve asthma control are recommended, including: 1) as-needed combination therapies in mild asthma; 2) risk factor reduction; 3) improving adherence/inhaler technique; 4) earlier initiation of add-on therapies; 5) use of biologics in appropriate patients; 6) development of new therapies to better control the disease; and 7) widespread education of the medical community. We propose that patients and primary care physicians should consider a cumulative SCS dose of 1 g per year as a highly relevant and easy-to-recall threshold.

The supportive care needs of people living with pulmonary fibrosis and their caregivers: a systematic review.

Abstract: Background People with pulmonary fibrosis often experience a protracted time to diagnosis, high symptom burden and limited disease information. This review aimed to identify the supportive care needs reported by people with pulmonary fibrosis and their caregivers. Methods A systematic review was conducted according to PRISMA guidelines. Studies that investigated the supportive care needs of people with pulmonary fibrosis or their caregivers were included. Supportive care needs were extracted and mapped to eight pre-specified domains using a framework synthesis method. Results A total of 35 studies were included. The most frequently reported needs were in the domain of information/education, including information on supplemental oxygen, disease progression and prognosis, pharmacological treatments and end-of-life planning. Psychosocial/emotional needs were also frequently reported, including management of anxiety, anger, sadness and fear. An additional domain of “access to care” was identified that had not been specified a priori; this included access to peer support, psychological support, specialist centres and support for families of people with pulmonary fibrosis. Conclusion People with pulmonary fibrosis report many unmet needs for supportive care, particularly related to insufficient information and lack of psychosocial support. These data can inform the development of comprehensive care models for people with pulmonary fibrosis and their loved ones.

α1-Antitrypsin deficiency and chronic respiratory disorders.

Abstract: α1-antitrypsin deficiency (AATD) is a hereditary disorder associated with a risk of developing liver disease and pulmonary emphysema, and other chronic respiratory disorders (mainly asthma and bronchiectasis); Z variant is the commonest deficient variant of AAT. Determining AAT concentration in serum or plasma and identifying allelic variants by phenotyping or genotyping are fundamental in the diagnosis of AATD. Initial evaluation and annual follow-up measurement of lung function, including post-bronchodilator forced expiratory volume in 1 s and gas transfer inform on disease progression. Lung densitometry is the most sensitive measure of emphysema progression, but must not be use in the follow-up of patients in routine clinical practice. The exogenous administration of purified human serum-derived AAT is the only approved specific treatment for AATD in PiZZ. AAT augmentation therapy is not recommended in PiSZ, PiMZ or current smokers of any protein phenotype, or in patients with hepatic disease. Lung volume reduction and endoscopic bronchial valve placement are useful in selected patients, whereas the survival benefit of lung transplant is unclear. There are several new lines of research in AATD to improve the diagnosis and evaluation of the response to therapy and to develop genetic and regenerative therapies and other treatments.

Subglottic secretion drainage for preventing ventilator-associated pneumonia: an overview of systematic reviews and an updated meta-analysis.

Abstract: Although several guidelines recommend subglottic secretion drainage as a strategy for prevention of ventilator-associated pneumonia (VAP), its use is not widespread. With the aim to assess the effectiveness of subglottic secretion drainage for preventing VAP and to improve other outcomes such as mortality, duration of mechanical ventilation and length of stay in the intensive care unit (ICU) or hospital, an electronic search of the Cochrane Library, MEDLINE, Web of Science and Embase was undertaken. Nine systematic reviews with meta-analysis (in the overview of reviews) and 20 randomised controlled trials (in the updated meta-analysis) were included.In the overview of reviews, all systematic reviews with meta-analysis included found a positive effect of subglottic secretion drainage in the reduction of incidence of VAP. In the updated meta-analysis, subglottic secretion drainage significantly reduced VAP incidence (risk ratio (RR) 0.56, 95% CI 0.48-0.63; I2=0%, p=0.841) and mortality (RR 0.88, 95% CI 0.80-0.97; I2=0%, p=0.888).This is the first study that has found a decrease of mortality associated with the use of subglottic secretion drainage. In addition, subglottic secretion drainage is an effective measure to reduce VAP incidence, despite not improving the duration of mechanical ventilation and ICU and/or hospital length of stay.

Mitochondrial dysfunction in lung ageing and disease.

Abstract: Mitochondrial biology has seen a surge in popularity in the past 5 years, with the emergence of numerous new avenues of exciting mitochondria-related research including immunometabolism, mitochondrial transplantation and mitochondria-microbe biology. Since the early 1960s mitochondrial dysfunction has been observed in cells of the lung in individuals and in experimental models of chronic and acute respiratory diseases. However, it is only in the past decade with the emergence of more sophisticated tools and methodologies that we are beginning to understand how this enigmatic organelle regulates cellular homeostasis and contributes to disease processes in the lung. In this review, we highlight the diverse role of mitochondria in individual lung cell populations and what happens when these essential organelles become dysfunctional with ageing and in acute and chronic lung disease. Although much remains to be uncovered, we also discuss potential targeted therapeutics for mitochondrial dysfunction in the ageing and diseased lung.

Birt–Hogg–Dubé syndrome

Abstract: Birt–Hogg–Dube syndrome (BHD) is a rare inherited autosomal dominant disorder caused by germline mutations in the tumour suppressor gene FLCN, encoding the protein folliculin. Its clinical expression typically includes multiple pulmonary cysts, recurrent spontaneous pneumothoraces, cutaneous fibrofolliculomas and renal tumours of various histological types. BHD has no sex predilection and tends to manifest in the third or fourth decade of life. Multiple bilateral pulmonary cysts are found on chest computed tomography in >80% of patients and more than half experience one or more episodes of pneumothorax. A family history of pneumothorax is an important clue, which suggests the diagnosis of BHD. Unlike other cystic lung diseases such as lymphangioleiomyomatosis and pulmonary Langerhans cell histiocytosis, BHD does not lead to progressive loss of lung function and chronic respiratory insufficiency. Renal tumours affect about 30% of patients during their lifetime, and can be multiple and recurrent. The diagnosis of BHD is based on a combination of genetic, clinical and/or skin histopathological criteria. Management mainly consists of early pleurodesis in the case of pneumothorax, periodic renal imaging for tumour detection, and diagnostic work-up in search of BHD in relatives of the index patient.

Artificial intelligence in pulmonary medicine: computer vision, predictive model and COVID-19

Abstract: Artificial intelligence (AI) is transforming healthcare delivery. The digital revolution in medicine and healthcare information is prompting a staggering growth of data intertwined with elements from many digital sources such as genomics, medical imaging and electronic health records. Such massive growth has sparked the development of an increasing number of AI-based applications that can be deployed in clinical practice. Pulmonary specialists who are familiar with the principles of AI and its applications will be empowered and prepared to seize future practice and research opportunities. The goal of this review is to provide pulmonary specialists and other readers with information pertinent to the use of AI in pulmonary medicine. First, we describe the concept of AI and some of the requisites of machine learning and deep learning. Next, we review some of the literature relevant to the use of computer vision in medical imaging, predictive modelling with machine learning, and the use of AI for battling the novel severe acute respiratory syndrome-coronavirus-2 pandemic. We close our review with a discussion of limitations and challenges pertaining to the further incorporation of AI into clinical pulmonary practice.

Community-acquired pneumonia in critically ill very old patients: a growing problem.

Abstract: Very old (aged ≥80 years) adults constitute an increasing proportion of the global population. Currently, this subgroup of patients represents an important percentage of patients admitted to the intensive care unit. Community-acquired pneumonia (CAP) frequently affects very old adults. However, there are no specific recommendations for the management of critically ill very old CAP patients. Multiple morbidities, polypharmacy, immunosenescence and frailty contribute to an increased risk of pneumonia in this population. CAP in critically ill very old patients is associated with higher short- and long-term mortality; however, because of its uncommon presentation, diagnosis can be very difficult. Management of critically ill very old CAP patients should be guided by their baseline characteristics, clinical presentation and risk factors for multidrug-resistant pathogens. Hospitalisation in intermediate care may be a good option for critical ill very old CAP patients who do not require invasive procedures and for whom intensive care is questionable in terms of benefit.

Prognosis of idiopathic pulmonary fibrosis without anti-fibrotic therapy: a systematic review

Abstract: In addition to facilitating healthcare delivery planning, reliable information about prognosis is essential for treatment decisions in patients with idiopathic pulmonary fibrosis (IPF). This review aimed to evaluate the prognosis of patients with IPF without anti-fibrotic therapy. We included all cohort studies and the placebo arms of randomised controlled trials (RCTs) in IPF and follow-up of ≥12 months. Two reviewers independently evaluated studies for inclusion, assessed risk of bias and extracted data. A total of 154 cohort studies and 16 RCTs were included. The pooled proportions of mortality were 0.12 (95% CI 0.09-0.14) at 1-2 years, 0.38 (95% CI 0.34-0.42) between 2-5 years, and 0.69 (95% CI 0.59-0.78) at ≥5 years. The pooled mean overall survival was 4 years (95% CI 3.7-4.6) for studies with a follow-up duration of 10 years. At <2 years, forced vital capacity and diffusing capacity of the lung for carbon monoxide declined by a mean of 6.76% predicted (95% CI -8.92 -4.61) and 3% predicted (95% CI -5.14 -1.52), respectively. Although heterogeneity was high, subgroup analyses revealed lower pooled proportions of mortality at 1 year in the RCT participants (0.07 (95% CI 0.05-0.09)) versus cohort study participants (0.14 (95% CI 0.12-0.17)). This review provides comprehensive information on the prognosis of IPF, which can inform treatment discussions with patients and comparisons for future studies with new therapies.

BNP/NT-proBNP in pulmonary arterial hypertension: time for point-of-care testing?

Abstract: Despite the advent of new therapies and improved outcomes in patients with pulmonary arterial hypertension (PAH), it remains a life-shortening disease and the time to diagnosis remains unchanged. Strategies to improve outcomes are therefore currently focused on earlier diagnosis and a treatment approach aimed at moving patients with PAH into a category of low-risk of 1-year mortality. B-type natriuretic peptide (BNP; or brain natriuretic peptide) and N-terminal prohormone of BNP (NT-proBNP) are released from cardiac myocytes in response to mechanical load and wall stress. Elevated levels of BNP and NT-proBNP are incorporated into several PAH risk stratification tools and screening algorithms to aid diagnosis of systemic sclerosis. We have undertaken a systematic review of the literature with respect to the use of BNP and NT-proBNP in PAH and the use of these biomarkers in the diagnosis and risk stratification of PAH, their relation to pulmonary haemodynamics and the potential for point-of-care testing to improve diagnosis and prognosis.

Noninfectious pulmonary complications of haematopoietic stem cell transplantation.

Abstract: Haematopoietic stem cell transplantation (HSCT) is an established treatment for a variety of malignant and nonmalignant conditions Pulmonary complications, both infectious and noninfectious, are a major cause of morbidity and mortality in patients who undergo HSCT Recent advances in prophylaxis and treatment of infectious complications has increased the significance of noninfectious pulmonary conditions Acute lung injury associated with idiopathic pneumonia syndrome remains a major acute complication with high morbidity and mortality On the other hand, bronchiolitis obliterans syndrome is the most challenging chronic pulmonary complication facing clinicians who are taking care of allogeneic HSCT recipients Other noninfectious pulmonary complications following HSCT are less frequent This review provides a clinical update of the incidence, risk factors, pathogenesis, clinical characteristics and management of the main noninfectious pulmonary complications following HSCT

How can we minimise the use of regular oral corticosteroids in asthma

Abstract: Options to achieve oral corticosteroid (OCS)-sparing have been triggering increasing interest since the 1970s because of the side-effects of OCSs, and this has now become achievable with biologics. The Societe de Pneumologie de Langue Francaise workshop on OCSs aimed to conduct a comprehensive review of the basics for OCS use in asthma and issue key research questions. Pharmacology and definition of regular use were reviewed by the first working group (WG1). WG2 examined whether regular OCS use is associated with T2 endotype. WG3 reported on the specificities of the paediatric area. Key "research statement proposals" were suggested by WG4. It was found that the benefits of regular OCS use in asthma outside episodes of exacerbations are poorly supported by the existing evidence. However, complete OCS elimination couldn't be achieved in any available studies for all patients and the panel felt that it was too early to conclude that regular OCS use could be declared criminal. Repeated or prolonged need for OCS beyond 1 g·year-1 should indicate the need for referral to secondary/tertiary care. A strategic sequential plan aiming at reducing overall exposure to OCS in severe asthma was then held as a conclusion of the workshop.

Respiratory viral sepsis: epidemiology, pathophysiology, diagnosis and treatment.

Abstract: According to the Third International Consensus Definition for Sepsis and Septic Shock, sepsis is a life-threatening organ dysfunction resulting from dysregulated host responses to infection. Epidemiological data about sepsis from the 2017 Global Burden of Diseases, Injuries and Risk Factor Study showed that the global burden of sepsis was greater than previously estimated. Bacteria have been shown to be the predominant pathogen of sepsis among patients with pathogens detected, while sepsis caused by viruses is underdiagnosed worldwide. The coronavirus disease that emerged in 2019 in China and now in many other countries has brought viral sepsis back into the vision of physicians and researchers worldwide. Although the current understanding of the pathophysiology of sepsis has improved, the differences between viral and bacterial sepsis at the level of pathophysiology are not well understood. Diagnosis methods that can broadly differentiate between bacterial and viral sepsis at the initial stage after the development of sepsis are limited. New treatments that can be applied at clinics for sepsis are scarce and this situation is not consistent with the growing understanding of pathophysiology. This review aims to give a brief summary of current knowledge of the epidemiology, pathophysiology, diagnosis and treatment of viral sepsis.

Fibrotic interstitial lung diseases and air pollution: a systematic literature review.

Abstract: Background Air pollution is hypothesised to be a risk factor for interstitial lung diseases (ILD). This study systematically reviewed the literature regarding the impact of air pollution on idiopathic pulmonary fibrosis (IPF) and fibrotic interstitial lung diseases (ILD). Methods A computer-assisted literature search of electronic databases was performed to identify studies focused on the association between ILDs and air pollution. Other inclusion criteria required that the article had to be: 1) original; 2) a prospective or retrospective study; and 3) fully published in English. Both randomised clinical trials and observational studies were considered. Results Only seven studies met the inclusion criteria. All studies investigated the relationship between pollution and IPF, except one that dealt with the relationship between pollution and hypersensitivity pneumonitis. Outcome measures included exacerbation of IPF, mortality, disease severity, prevalence of hypersensitivity pneumonitis, progression and incidence of IPF. On the whole, air pollution levels were negatively associated with outcomes in patients with IPF and fibrotic ILD outcome. The heterogeneity in the measurement and reporting of the end-points limited the performance of a quantitative synthesis of data. Conclusions This systematic review provides supporting evidence linking exposure to air pollution to poor outcomes in patients with IPF and fibrotic ILD.

Shared mechanisms of multimorbidity in COPD, atherosclerosis and type-2 diabetes: the neutrophil as a potential inflammatory target.

Abstract: Multimorbidity is increasingly common and current healthcare strategies are not always aligned to treat this complex burden of disease. COPD, type-2 diabetes mellitus (T2D) and cardiovascular disease, especially atherosclerosis, occur more frequently together than expected, even when risk factors such as smoking, obesity, inactivity and poverty are considered. This supports the possibility of unifying mechanisms that contribute to the pathogenesis or progression of each condition.Neutrophilic inflammation is causally associated with COPD, and increasingly recognised in the pathogenesis of atherosclerosis and T2D, potentially forming an aetiological link between conditions. This link might reflect an overspill of inflammation from one affected organ into the systemic circulation, exposing all organs to an increased milieu of proinflammatory cytokines. Additionally, increasing evidence supports the involvement of other processes in chronic disease pathogenesis, such as cellular senescence or changes in cellular phenotypes.This review explores the current scientific evidence for inflammation, cellular ageing and cellular processes, such as reactive oxygen species production and phenotypic changes in the pathogenesis of COPD, T2D and atherosclerosis; highlighting common mechanisms shared across these diseases. We identify emerging therapeutic approaches that target these areas, but also where more work is still required to improve our understanding of the underlying cellular biology in a multimorbid disease setting.

Chaotic activation of developmental signalling pathways drives idiopathic pulmonary fibrosis.

Abstract: Idiopathic pulmonary fibrosis (IPF) is characterised by an important remodelling of lung parenchyma. Current evidence indicates that the disease is triggered by alveolar epithelium activation following chronic lung injury, resulting in alveolar epithelial type 2 cell hyperplasia and bronchiolisation of alveoli. Signals are then delivered to fibroblasts that undergo differentiation into myofibroblasts. These changes in lung architecture require the activation of developmental pathways that are important regulators of cell transformation, growth and migration. Among others, aberrant expression of profibrotic Wnt-β-catenin, transforming growth factor-β and Sonic hedgehog pathways in IPF fibroblasts has been assessed. In the present review, we will discuss the transcriptional integration of these different pathways during IPF as compared with lung early ontogeny. We will challenge the hypothesis that aberrant transcriptional integration of these pathways might be under the control of a chaotic dynamic, meaning that a small change in baseline conditions could be sufficient to trigger fibrosis rather than repair in a chronically injured lung. Finally, we will discuss some potential opportunities for treatment, either by suppressing deleterious mechanisms or by enhancing the expression of pathways involved in lung repair. Whether developmental mechanisms are involved in repair processes induced by stem cell therapy will also be discussed.

Desquamative interstitial pneumonia: a systematic review of its features and outcomes.

Abstract: Background: Desquamative Interstitial Pneumonia (DIP) is a rare form of idiopathic interstitial pneumonia (IIP) Data on clinical features, aetiology, prognosis and effect of treatment strategies are limited We aimed to collect all published cases to better characterise DIP Methods: A systematic literature search was performed for all original cases of adult patients with histopathologically-confirmed DIP Individual patient data were extracted and summarised Results: We included 68 individual cases and 13 case series reporting on 294 cases Most common presenting symptoms were dyspnoea and cough Pulmonary function showed a restrictive pattern (71%) with decreased diffusion capacity We found a high incidence (81%) of ever smoking in patients with DIP and 22% of patients had other (occupational) exposures Characteristic features on high-resolution computed tomography (HRCT) scan were bilateral ground-glass opacities with lower lobe predominance (92%) Treatment and duration of treatment widely varied Initial response to treatment was generally good, but definitely not uniformly so A significant proportion of patients died (25% of individual cases) or experienced a relapse (18% of individual cases) Conclusion: DIP remains an uncommon disease, frequently but not always related to smoking or other exposures Furthermore, DIP behaves as a progressive disease more often than generally thought, possibly associated with different underlying aetiology

Prevalence of α1-antitrypsin PiZZ genotypes in patients with COPD in Europe: a systematic review.

Abstract: The percentage of α1-antitrypsin protease inhibitor ZZ (PiZZ) genotypes in patients with COPD is controversial, with large differences among various studies. We aimed to estimate the prevalence of PiZZ in COPD patients from 20 European countries with available data, according to the number of PiZZ and COPD individuals in each country. A systematic review was conducted to select European countries with reliable data on the prevalence of PiZZ and COPD. We created a database with the following data: 1) total population and population aged ≥40 years according to the Eurostat database; 2) number and 95% CI of PiZZ patients aged ≥40 years; 3) application of a conversion factor of genetic penetrance of 60%; 4) number of COPD individuals, with 95% CI, aged ≥40 years; and 5) calculation of the PiZZ/COPD ratio. Finally, results were presented using an Inverse Distance Weighted Interpolation map. We found 36 298 (95% CI 23 643–56 594) PiZZ individuals at high risk and 30 849 709 (95% CI 21 411 293–40 344 496) COPD patients, with a PiZZ/COPD ratio of 0.12% (range 0.08–0.24%), and a prevalence of 1 out of 408 in Northern, 1 out of 944 in Western, 1 out of 1051 in Central, 1 out of 711 in Southern, and 1 out of 1274 in Eastern Europe. These data may be useful to plan strategies for future research and diagnosis, and to rationalise the available therapeutic resources.

Schistosomiasis-associated pulmonary arterial hypertension: a systematic review.

Abstract: Schistosomiasis-associated pulmonary arterial hypertension (Sch-PAH) is a life-threatening complication of chronic hepatosplenic schistosomiasis. It is suggested to be the leading cause of pulmonary arterial hypertension (PAH) worldwide. However, pathophysiological data on Sch-PAH are scarce. We examined the hypothesis that there are pronounced similarities in pathophysiology, haemodynamics, and survival of Sch-PAH and idiopathic PAH (iPAH).This systematic review and meta-analysis was registered in the PROSPERO database (identifier CRD42018104066). A systematic search and review of the literature was performed according to PRISMA guidelines for studies published between 01 January 1990 and 29 June 2018.For Sch-PAH, 18 studies evaluating pathophysiological mechanisms, eight studies on haemodynamics (n=277), and three studies on survival (n=191) were identified. 16 clinical registries reporting data on haemodynamics and survival including a total of 5792 patients with iPAH were included for comparison. Proinflammatory molecular pathways are involved in both Sch-PAH and iPAH. The transforming growth factor (TGF)-β signalling pathway is upregulated in Sch-PAH and iPAH. While there was no difference in mean pulmonary artery pressure (54±17 mmHg versus 55±15 mmHg, p=0.29), cardiac output (4.4±1.3 L·min-1versus 4.1±1.4 L·min-1, p=0.046), and cardiac index (2.6±0.7 L·min-1·m-2versus 2.3±0.8 L·min-1·m-2, p<0.001) were significantly higher in Sch-PAH compared to iPAH, resulting in a lower pulmonary vascular resistance in Sch-PAH (10±6 Woods units versus 13±7 Woods units, p<0.001). 1- and 3-year survival were significantly better in the Sch-PAH group (p<0.001).Sch-PAH and iPAH share common pathophysiological mechanisms related to inflammation and the TGF-β signalling pathway. Patients with Sch-PAH show a significantly better haemodynamic profile and survival than patients with iPAH.

The promise of mTOR as a therapeutic target pathway in idiopathic pulmonary fibrosis.

Abstract: Idiopathic pulmonary fibrosis (IPF) is characterised by the progressive deposition of excessive extracellular matrix proteins within the lung parenchyma and represents the most rapidly progressive and fatal of all fibrotic conditions. Current anti-fibrotic drugs approved for the treatment of IPF fail to halt disease progression and have significant side-effect profiles. Therefore, there remains a pressing need to develop novel therapeutic strategies for IPF. Mammalian target of rapamycin (mTOR) forms the catalytic subunit of two complexes, mTORC1 and mTORC2. mTORC1 acts as critical cellular sensor which integrates intracellular and extracellular signals to reciprocally regulate a variety of anabolic and catabolic processes. The emerging evidence for a critical role for mTORC1 in influencing extracellular matrix production, metabolism, autophagy and senescence in the setting of IPF highlights this axis as a novel therapeutic target with the potential to impact multiple IPF pathomechanisms.

Management of tracheo-oesophageal fistula in adults.

Abstract: Tracheo-oesophageal fistula (TOF) is a pathological connection between the trachea and the oesophagus that is associated with various underlying conditions including malignancies, infections, inhalation injuries and traumatic damage. As the condition spans multiple organ systems with varying aetiologies and acuities, TOF poses unique diagnostic and management challenges to pulmonologists, gastroenterologists and thoracic surgeons alike. Although stents have been a cornerstone in the management of TOF, there exists a large gap in our understanding of their efficacy and precise methodology, making stenting procedure both art and science. TOFs relating to underlying oesophageal or tracheal malignancies require advanced understanding of the airway and digestive tract anatomy, dimensions of the fistula, stent characteristics and types, and the interplay between the oesophageal stent and the airway stent if dual stenting procedure is elected. In this review article, we review the most up-to-date data on risk factors, clinical manifestations, diagnostic approaches, management methods and prognosis. Consequently, this article serves to evaluate current therapeutic strategies and the future directions in the areas of 3D-printed stents, over-the-scope clipping systems, tissue matrices and atrial septal closure devices.