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  • ERJ September Podcast: The hidden burden of severe asthma
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-09-01
    European Respiratory Society

    As part of the September issue, the European Respiratory Journal presents the latest in its series of podcasts. Chief editor Marc Humbert discusses the publication of the results of a survey of patients with severe asthma with Prof. Helen K. Reddel from the University of Sydney, Sydney, and the NHMRC Centre for Research Excellence in Severe Asthma, Newcastle, Australia.

    更新日期:2017-09-21
  • Can epidemiological studies determine the productivity-related burden of COPD?
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-09-01
    Sanja Stanojevic

    The causal association between chronic airflow obstruction and unemployment is complex and requires further study http://ow.ly/INtD30eqgJJ

    更新日期:2017-09-21
  • 10 years since TORCH: shining a new light on the risks of inhaled corticosteroids in COPD
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-09-01
    James D. Chalmers; Holly R. Keir

    New research identifies an increased risk of NTM infection in inhaled steroid users http://ow.ly/Sk8130ej5Oa

    更新日期:2017-09-21
  • An invisible disease: severe asthma is more than just “bad asthma”
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-09-01
    Sally E. Wenzel; Sheila Brillhart; Kristin Nowack

    Severe asthma inflicts a tremendous burden on patients with this disease, which is often invisible to others http://ow.ly/RpGk30cTjIF

    更新日期:2017-09-21
  • New drug targets for chronic cough: research you can literally sink your teeth into!
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-09-01
    Caroline J. Jolley; Surinder S. Birring

    Human dental pulp stem cells and endocannabinoids: can preclinical models translate to effective antitussive drugs? http://ow.ly/RAJL30eq351

    更新日期:2017-09-21
  • Two valves in the pharynx
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-09-01
    Shiroh Isono

    The epiglottis and soft palate function as one-way valves limiting flow during inspiration and expiration http://ow.ly/85JB30epWOC

    更新日期:2017-09-21
  • Unemployment in chronic airflow obstruction around the world: results from the BOLD study
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-09-01
    Rune Grønseth; Marta Erdal; Wan C. Tan; Daniel O. Obaseki; Andre F.S. Amaral; Thorarinn Gislason; Sanjay K. Juvekar; Parvaiz A. Koul; Michael Studnicka; Sundeep Salvi; Peter Burney; A. Sonia Buist; William M. Vollmer; Ane Johannessen

    We aimed to examine associations between chronic airflow obstruction (CAO) and unemployment across the world. Cross-sectional data from 26 sites in the Burden of Obstructive Lung Disease (BOLD) study were used to analyse effects of CAO on unemployment. Odds ratios for unemployment in subjects aged 40–65 years were estimated using a multilevel mixed-effects generalised linear model with study site as random effect. Site-by-site heterogeneity was assessed using individual participant data meta-analyses. Out of 18 710 participants, 11.3% had CAO. The ratio of unemployed subjects with CAO divided by subjects without CAO showed large site discrepancies, although these were no longer significant after adjusting for age, sex, smoking and education. The site-adjusted odds ratio (95% CI) for unemployment was 1.79 (1.41–2.27) for CAO cases, decreasing to 1.43 (1.14–1.79) after adjusting for sociodemographic factors, comorbidities and forced vital capacity. Of other covariates that were associated with unemployment, age and education were important risk factors in high-income sites (4.02 (3.53–4.57) and 3.86 (2.80–5.30), respectively), while female sex was important in low- to middle-income sites (3.23 (2.66–3.91)). In the global BOLD study, CAO was associated with increased levels of unemployment, even after adjusting for sociodemographic factors, comorbidities and lung function.

    更新日期:2017-09-21
  • The risk of mycobacterial infections associated with inhaled corticosteroid use
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-09-01
    Sarah K. Brode; Michael A. Campitelli; Jeffrey C. Kwong; Hong Lu; Alex Marchand-Austin; Andrea S. Gershon; Frances B. Jamieson; Theodore K. Marras

    Inhaled corticosteroid (ICS) use is associated with an increased risk of pneumonia. This study was performed to determine if ICS use is associated with an increased risk of nontuberculous mycobacterial pulmonary disease (NTM-PD) or tuberculosis (TB). We conducted a population-based nested case–control study using linked laboratory and health administrative databases in Ontario, Canada, including adults aged ≥66 years with treated obstructive lung disease (i.e. asthma, chronic obstructive pulmonary disease (COPD) or asthma–COPD overlap syndrome) between 2001 and 2013. We estimated odds ratios comparing ICS use with nonuse among NTM-PD and TB cases and controls using conditional logistic regression. Among 417 494 older adults with treated obstructive lung disease, we identified 2966 cases of NTM-PD and 327 cases of TB. Current ICS use was associated with NTM-PD compared with nonuse (adjusted OR (aOR) 1.86, 95% CI 1.60–2.15) and was statistically significant for fluticasone (aOR 2.09, 95% CI 1.80–2.43), but not for budesonide (aOR 1.19, 95% CI 0.97–1.45). There was a strong dose–response relationship between incident NTM-PD and cumulative ICS dose over 1 year. There was no significant association between current ICS use and TB (aOR 1.43, 95% CI 0.95–2.16). This study suggests that ICS use is associated with an increased risk of NTM-PD, but not TB.

    更新日期:2017-09-21
  • “I have lost in every facet of my life”: the hidden burden of severe asthma
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-09-01
    Juliet M. Foster; Vanessa M. McDonald; Michael Guo; Helen K. Reddel

    People with severe asthma are thought to face a sizeable daily disease burden. This study aimed to explore the little-known life experiences of people living with severe asthma. Adults with severe asthma were invited for telephone interview. Semistructured interviews were conducted until no new themes emerged. The 25 interviews were recorded, transcribed and analysed thematically. Four themes emerged. 1) “The body as a hindrance”: severe asthma placed broad limits on life from daily chores to career, relationships and family life that left interviewees feeling emotionally distressed. 2) “Burden of treatment”: participants mostly accepted the need to take treatment, but were particularly concerned about side-effects of oral corticosteroids. 3) “Alone with asthma”: interviewees felt misunderstood and alone in their experience of breathlessness and frightening exacerbations; practical and emotional support needs were often lacking and the emotional distress of severe asthma was amplified in those with little support. 4) “Striving to adapt”: patients used both positive strategies (acquiring self-management skills) and less positive strategies (avoidance of physical exertion) in the process of adjustment to living with severe asthma. Severe asthma imposes long-term, debilitating burdens and should be considered differently to milder disease. There is an urgent need to improve practical and emotional support services for patients and their carers.

    更新日期:2017-09-21
  • Targeting fatty acid amide hydrolase as a therapeutic strategy for antitussive therapy
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-09-01
    Michael A. Wortley; John J. Adcock; Eric D. Dubuis; Sarah A. Maher; Sara J. Bonvini; Isabelle Delescluse; Ross Kinloch; Gordon McMurray; Christelle Perros-Huguet; Marianthi Papakosta; Mark A. Birrell; Maria G. Belvisi

    Cough is the most common reason to visit a primary care physician, yet it remains an unmet medical need. Fatty acid amide hydrolase (FAAH) is an enzyme that breaks down endocannabinoids, and inhibition of FAAH produces analgesic and anti-inflammatory effects. Cannabinoids inhibit vagal sensory nerve activation and the cough reflex, so it was hypothesised that FAAH inhibition would produce antitussive activity via elevation of endocannabinoids. Primary vagal ganglia neurons, tissue bioassay, in vivo electrophysiology and a conscious guinea pig cough model were utilised to investigate a role for fatty acid amides in modulating sensory nerve activation in vagal afferents. FAAH inhibition produced antitussive activity in guinea pigs with concomitant plasma elevation of the fatty acid amides N-arachidonoylethanolamide (anandamide), palmitoylethanolamide, N-oleoylethanolamide and linoleoylethanolamide. Palmitoylethanolamide inhibited tussive stimulus-induced activation of guinea pig airway innervating vagal ganglia neurons, depolarisation of guinea pig and human vagus, and firing of C-fibre afferents. These effects were mediated via a cannabinoid CB2/Gi/o-coupled pathway and activation of protein phosphatase 2A, resulting in increased calcium sensitivity of calcium-activated potassium channels. These findings identify FAAH inhibition as a target for the development of novel, antitussive agents without the undesirable side-effects of direct cannabinoid receptor agonists.

    更新日期:2017-09-21
  • TRPA1 activation in a human sensory neuronal model: relevance to cough hypersensitivity?
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-09-01
    Rebecca Clarke; Kevin Monaghan; Imad About; Caoimhin S. Griffin; Gerard P. Sergeant; Ikhlas El Karim; J. Graham McGeown; S. Louise Cosby; Timothy M. Curtis; Lorcan P. McGarvey; Fionnuala T. Lundy

    The cough reflex becomes hyperresponsive in acute and chronic respiratory diseases, but understanding the underlying mechanism is hampered by difficulty accessing human tissue containing both nerve endings and neuronal cell bodies. We refined an adult stem cell sensory neuronal model to overcome the limited availability of human neurones and applied the model to study transient receptor potential ankyrin 1 (TRPA1) channel expression and activation. Human dental pulp stem cells (hDPSCs) were differentiated towards a neuronal phenotype, termed peripheral neuronal equivalents (PNEs). Using molecular and immunohistochemical techniques, together with Ca2+ microfluorimetry and whole cell patch clamping, we investigated roles for nerve growth factor (NGF) and the viral mimic poly I:C in TRPA1 activation. PNEs exhibited morphological, molecular and functional characteristics of sensory neurons and expressed functional TRPA1 channels. PNE treatment with NGF for 20 min generated significantly larger inward and outward currents compared to untreated PNEs in response to the TRPA1 agonist cinnamaldehyde (p<0.05). PNE treatment with poly I:C caused similar transient heightened responses to TRPA1 activation compared to untreated cells. Using the PNE neuronal model we observed both NGF and poly I:C mediated sensory neuronal hyperresponsiveness, representing potential neuro-inflammatory mechanisms associated with heightened nociceptive responses recognised in cough hypersensitivity syndrome.

    更新日期:2017-09-21
  • Predicting epiglottic collapse in patients with obstructive sleep apnoea
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-09-01
    Ali Azarbarzin; Melania Marques; Scott A. Sands; Sara Op de Beeck; Pedro R. Genta; Luigi Taranto-Montemurro; Camila M. de Melo; Ludovico Messineo; Olivier M. Vanderveken; David P. White; Andrew Wellman

    Obstructive sleep apnoea (OSA) is characterised by pharyngeal obstruction occurring at different sites. Endoscopic studies reveal that epiglottic collapse renders patients at higher risk of failed oral appliance therapy or accentuated collapse on continuous positive airway pressure. Diagnosing epiglottic collapse currently requires invasive studies (imaging and endoscopy). As an alternative, we propose that epiglottic collapse can be detected from the distinct airflow patterns it produces during sleep. 23 OSA patients underwent natural sleep endoscopy. 1232 breaths were scored as epiglottic/nonepiglottic collapse. Several flow characteristics were determined from the flow signal (recorded simultaneously with endoscopy) and used to build a predictive model to distinguish epiglottic from nonepiglottic collapse. Additionally, 10 OSA patients were studied to validate the pneumotachograph flow features using nasal pressure signals. Epiglottic collapse was characterised by a rapid fall(s) in the inspiratory flow, more variable inspiratory and expiratory flow and reduced tidal volume. The cross-validated accuracy was 84%. Predictive features obtained from pneumotachograph flow and nasal pressure were strongly correlated. This study demonstrates that epiglottic collapse can be identified from the airflow signal measured during a sleep study. This method may enable clinicians to use clinically collected data to characterise underlying physiology and improve treatment decisions.

    更新日期:2017-09-21
  • Evaluation of criteria for exercise-induced pulmonary hypertension in patients with resting pulmonary hypertension
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-09-01
    Christopher J. Mullin; Steven Hsu; Kaushik Amancherla; Alison Wand; Parker Rhodes; Peter J. Leary; Monica Mukherjee; Rachel L. Damico; Todd M. Kolb; Stephen C. Mathai; Paul M. Hassoun; Ryan J. Tedford

    Owing to the lack of a suitable definition, exercise criteria for the diagnosis of pulmonary hypertension (PH) were removed from consensus guidelines following the 4th World Pulmonary Hypertension Symposium in 2008 [1] and have remained absent following the 5th World Symposium [2] and recent European Cardiology Society/European Respiratory Society guidelines [3]. Nonetheless, there remains significant interest in properly defining an abnormal pulmonary vascular response to exercise [4–6].Exercise-induced PH defined by the mPAP-CO relationship may lack sensitivity for detecting pulmonary vascular disease

    更新日期:2017-09-21
  • Determinants of diaphragm thickening fraction during mechanical ventilation: an ancillary study of a randomised trial
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-09-01
    Emmanuel Vivier; Ferran Roche-Campo; Laurent Brochard; Armand Mekontso Dessap

    Ultrasonography of the diaphragm is the subject of a growing interest in the intensive care unit (ICU) setting [1–6]. Observing the diaphragm in its zone of apposition allows measurement of its thickness and computation of its thickening fraction (TFdi), which depends on diaphragmatic activity [3] and reflects the diaphragm work of breathing [1]. A recent study showed that the TFdi correlated well with the endotracheal pressure variation generated by phrenic stimulation [6]. This index was also proposed for clinical evaluation of diaphragm weakness to detect ventilator-induced diaphragmatic dysfunction (VIDD) and predict difficult weaning [3, 4]. However, it remains unclear whether increased thickening in this setting only reflects a better intrinsic diaphragmatic strength, or if it also suggests enhanced work of breathing in response to increased cardiorespiratory workload. Furthermore, some authors suggested that VIDD could be thought as the “respiratory” manifestation of a global neuromuscular weakness [4, 7], but its relationship with ICU-acquired limb weakness is not straightforward [5]. The present study had a dual objective: first, to explore the correlation between ICU-acquired limb weakness (as assessed by the Medical Research Council (MRC) score) and diaphragm thickening (as assessed by TFdi); second, to assess the association of clinical variables with TFdi during mechanical ventilation.Diaphragm thickening does not correlate with ICUAW; it is influenced by cardiopulmonary load and residual sedation

    更新日期:2017-09-21
  • The validation of the sit-to-stand test for COPD patients
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-09-01
    Arnaud Chambellan; Simon Nusinovici; Trija Vaidya; Pierre-Antoine Gourraud; Claire de Bisschop

    We read with interest the publication by Crook et al. [1] on the validation and responsive properties of the 1-min sit-to-stand (STS) test in patients with chronic obstructive pulmonary disease (COPD) undergoing pulmonary rehabilitation. The authors performed a comprehensive evaluation of the minimal clinical meaningful difference of the 1-min STS test. In our own dataset of patients from a multicentre study, this STS test exhibited similar level of reliability, intra-subject repeatability [2], and responsiveness to pulmonary rehabilitation with an estimated minimal important difference (MID) of three repetitions [3]. In their study, Crook et al. [1] emphasised the change in STS repetitions, which is better related to change in subjective outcomes (feeling thermometer notably), rather than with physical capacity outcomes such as the 6-min walk distance (6MWD). It is, after all, largely accepted that health-related quality of life (HRQoL) tools are the most sensitive in pulmonary rehabilitation, given the multimodal and patient-tailored interventions addressed in order to optimise benefits, not only focused on exercise training, but also on change in education and behaviour [4].The change in the sit-to-stand test after a pulmonary rehabilitation is not influenced by the initial value

    更新日期:2017-09-21
  • The validation of the sit-to-stand test for COPD patients
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-09-01
    Sarah Crook; Milo A. Puhan; Anja Frei

    We thank A. Chambellan and colleagues for their interest in our study on the validation of the 1-min sit-to-stand (STS) test in chronic obstructive pulmonary disease (COPD) patients published in the European Respiratory Journal [1]. The authors highlighted some discrepancies between our study results and the results that they found in a similar study of COPD patients, raised questions over the possible cause of this difference and discuss results from their own study that they believe may provide additional information on the responsiveness of the 1-min STS test.Although evaluated in 3 different PR settings, the 1-min STS test shows consistent cross-sectional validity and MID

    更新日期:2017-09-21
  • After the asthmas: Star Wars and Star Trek
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-09-01
    Andrew Bush; Ian D. Pavord

    The Lancet commission on asthma proposes new paradgims; especially to ask “what asthma do I have?” http://ow.ly/YVpG30eaeN5

    更新日期:2017-09-12
  • Phase three studies of biologics for severe asthma: could do better?
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-09-01
    Douglas S. Robinson; Harsha H. Kariyawasam; Liam G. Heaney

    We need to reconsider how we assess biologics for severe asthma http://ow.ly/j7Mw30efCHb

    更新日期:2017-09-12
  • Treating anxious expectations can improve dyspnoea in patients with COPD
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-09-01
    Andreas von Leupoldt

    The detection and treatment of anxious expectations can improve dyspnoea in patients with COPD http://ow.ly/jnBR30efnhj

    更新日期:2017-09-12
  • Treating breathlessness via the brain: changes in brain activity over a course of pulmonary rehabilitation
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-09-01
    Mari Herigstad; Olivia K. Faull; Anja Hayen; Eleanor Evans; F. Maxine Hardinge; Katja Wiech; Kyle T.S. Pattinson

    Breathlessness in chronic obstructive pulmonary disease (COPD) is often discordant with airway pathophysiology (“over-perception”). Pulmonary rehabilitation profoundly affects breathlessness, without influencing lung function. Learned associations influence brain mechanisms of sensory perception. We hypothesised that improvements in breathlessness with pulmonary rehabilitation may be explained by changing neural representations of learned associations. In 31 patients with COPD, we tested how pulmonary rehabilitation altered the relationship between brain activity during a breathlessness-related word-cue task (using functional magnetic resonance imaging), and clinical and psychological measures of breathlessness. Changes in ratings of breathlessness word cues positively correlated with changes in activity in the insula and anterior cingulate cortex. Changes in ratings of breathlessness-anxiety negatively correlated with activations in attention regulation and motor networks. Baseline activity in the insula, anterior cingulate cortex and prefrontal cortex correlated with improvements in breathlessness and breathlessness-anxiety. Pulmonary rehabilitation is associated with altered neural responses related to learned breathlessness associations, which can ultimately influence breathlessness perception. These findings highlight the importance of targeting learned associations within treatments for COPD, demonstrating how neuroimaging may contribute to patient stratification and more successful personalised therapy.

    更新日期:2017-09-12
  • Bronchial hyperresponsiveness and obesity in middle age: insights from an Australian cohort
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-09-01
    John A. Burgess; Melanie C. Matheson; Fei Diao; David P. Johns; Bircan Erbas; Adrian J. Lowe; Lyle C. Gurrin; Caroline J. Lodge; Paul S. Thomas; Stephen Morrison; Bruce R. Thompson; Iain Feather; Jennifer L. Perret; Michael J. Abramson; Graham G. Giles; John L. Hopper; Shyamali C. Dharmage; Eugene H. Walters

    The association between obesity and bronchial hyperresponsiveness (BHR) is incompletely characterised. Using the 2006 follow-up of the Tasmanian Longitudinal Health Study, we measured the association between obesity and BHR and whether it was mediated by small airway closure or modified by asthma and sex of the patient. A methacholine challenge measured BHR. Multivariable logistic regression measured associations between body mass index (BMI) and BHR, adjusting for sex, asthma, smoking, corticosteroid use, family history and lung function. Mediation by airway closure was also measured. Each increase in BMI of 1 kg·m−2 was associated with a 5% increase in the odds of BHR (OR 1.05, 95% CI 1.01–1.09) and 43% of this association was mediated by airway closure. In a multivariable model, BMI (OR 1.06, 95% CI 1.00–1.16) was associated with BHR independent of female sex (OR 3.26, 95% CI 1.95–5.45), atopy (OR 2.30, 95% CI 1.34–3.94), current asthma (OR 5.74, 95% CI 2.79–11.82), remitted asthma (OR 2.35, 95% CI 1.27–4.35), low socioeconomic status (OR 2.11, 95% CI 1.03–4.31) and forced expiratory volume in 1 s/forced vital capacity (OR 0.86, 95% CI 0.82–0.91). Asthma modified the association with an increasing probability of BHR as BMI increased, only in those with no or remitted asthma. An important fraction of the BMI/BHR association was mediated via airway closure. Conflicting findings in previous studies could be explained by failure to consider this intermediate step.

    更新日期:2017-09-12
  • Macrophage dysfunction in the pathogenesis and treatment of asthma
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-09-01
    Michael Fricker; Peter G. Gibson

    Asthma is a chronic respiratory condition frequently associated with aberrant airway and systemic inflammation. Various inflammatory phenotypes in asthmatic airways have been described that relate to clinical phenotypes and impact on responses to conventional and novel asthma therapies. Macrophages are abundant immunocytes in the lung, capable of mounting diverse responses required for homeostasis and defence against pathogens. Here, we summarise the clinical evidence regarding macrophage dysfunction in asthma. We also describe evidence supporting the role of macrophages as therapeutic targets in asthma. We conclude that macrophage dysfunction in asthma is highly prevalent and heterogeneous, and hypothesise that macrophages may play roles in promoting the discrete inflammatory phenotypes of asthma. These clinical findings, along with recent ground-breaking insights into the ontogeny, behavioural complexity and longevity of pulmonary macrophages, support continued research into the role of macrophages as disease modifiers, biomarkers and therapeutic targets in asthma.

    更新日期:2017-09-12
  • Work productivity loss in mild to moderate COPD: lessons learned from the CanCOLD study
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-09-01
    Riany de Sousa Sena; Sara Ahmed; Wan C. Tan; Pei Z. Li; Laura Labonté; Shawn D. Aaron; Andrea Benedetti; Kenneth R. Chapman; B. Walker; J. Mark Fitzgerald; Paul Hernandez; François Maltais; Darcy D. Marciniuk; Denis E. O'Donnell; Don D. Sin; Jean Bourbeau

    Little attention has been given to the impact of chronic obstructive pulmonary disease (COPD) on work productivity loss. Individuals with COPD are at risk of reduced working hours, absenteeism, presenteeism and early retirement [1]. Studies have been focused mostly on patients attending outpatient clinics [2], which exclude individuals with undiagnosed COPD, thus limiting the external validity of the findings. There are very few population-based cohort studies [3–6], few reports on presenteeism [5], and a lack of objective measures to define COPD [6]. There would be value in knowing the extent of work productivity loss in individuals with mild COPD, or those who are yet undiagnosed. This could further translate into the allocation of health management programmes in the workplace.COPD patients with high symptom burden or CAT ≥10 have an increased likelihood of experiencing work productivity loss The authors thank the men and women who participated in the study and individuals in the CanCOLD Collaborative Research Group. Author contributions: R. de Sousa Sena contributed to the conception and implementation of the study, analysis of the data, and writing of the manuscript. J. Bourbeau contributed to the study conception and design, implementation and acquisition of the data, and writing and revision of the article. S. Ahmed contributed to the study conception and design and the writing and revision of the article. W.C. Tan, L. Labonté, S.D. Aaron, A. Benedetti, K.R. Chapman, B. Walker, J.M. Fitzgerald, P. Hernandez, F. Maltais, D.D. Marciniuk, D.E. O'Donnell and D.D. Sin contributed to the acquisition of data and revision of the article. P.Z. Li contributed to the analysis and interpretation of the data. All authors approved the final version of the manuscript.Members of the CanCOLD Collaborative Research Group are as follows. Executive Committee: Jean Bourbeau (McGill University, Montreal, Canada); Wan C. Tan, J. Mark FitzGerald; Don Sin (UBC, Vancouver, Canada); Darcy Marciniuk (University of Saskatoon, Saskatoon, Canada); Dennis E. O'Donnell (Queen's University, Kingston, Canada); Paul Hernandez (Dalhousie University, Halifax, Canada); Kenneth R. Chapman (University of Toronto, Toronto, Canada); Robert Cowie (University of Calgary, Calgary, Canada); Shawn Aaron (University of Ottawa, Ottawa, Canada); F. Maltais (University of Laval, Quebec City, Canada). International Advisory Board: Jonathon Samet (Keck School of Medicine of USC, Los Angeles, CA); Milo Puhan (John Hopkins School of Public Health, Baltimore, MD); Qutayba Hamid (McGill University, Montreal, Canada); James C. Hogg (UBC James Hogg Research Center, Vancouver, Canada). Operations Center: Jean Bourbeau (PI), Carole Jabet, Palmina Mancino, (McGill University, Montreal, Canada); Wan C. Tan (co-PI), Don Sin, Sheena Tam, Jeremy Road, Joe Comeau, Adrian Png, Harvey Coxson, Jonathon Leipsic, Cameron Hague (University of British Columbia James Hogg Research Center, Vancouver, Canada). Economic Core: Mohsen Sadatsafavi (University of British Columbia, Vancouver, Canada). Public Health Core: Teresa To, Andrea Gershon (University of Toronto, Toronto, Canada). Data Management and Quality Control: Wan C. Tan, Harvey Coxson (UBC, Vancouver, Canada); Jean Bourbeau, Pei Zhi Li, Zhi Song, Yvan Fortier, Andrea Benedetti, Dennis Jensen (McGill University, Montreal, Canada). Field Centers: Wan C. Tan (Vancouver PI), Christine Lo, Sarah Cheng, Cindy Fung, Nancy Haynes, Junior Chuang, Licong Li, Selva Bayat, Amanda Wong, Zoe Alavi, Catherine Peng, Bin Zhao, Nathalie Scott-Hsiung, Tasha Nadirshaw (UBC James Hogg Research Center, Vancouver, Canada); Jean Bourbeau (Montreal PI), Palmina Mancino, David Latreille, Jacinthe Baril, Laura Labonté (McGill University, Montreal, Canada); Kenneth Chapman (Toronto PI), Patricia McClean, Nadeen Audisho (University of Toronto, Toronto, Canada); R. Cowie and B. Walter (Calgary PI), Ann Cowie, Curtis Dumonceaux, Lisette Machado (University of Calgary, Calgary, Canada); Paul Hernandez (Halifax PI), Scott Fulton, Kristen Osterling (Dalhousie University, Halifax, Canada); Shawn Aaron (Ottawa PI), Kathy Vandemheen, Gay Pratt, Amanda Bergeron (University of Ottawa, Ottawa, Canada); Denis O'Donnell (Kingston PI), Matthew McNeil, Kate Whelan (Queen's University, Kingston, Canada); François Maltais (Quebec PI), Cynthia Brouillard (Université Laval, Quebec City, Canada); Darcy Marciniuk (Saskatoon PI), Ron Clemens, Janet Baran (University of Saskatoon, Saskatoon, Canada).

    更新日期:2017-09-12
  • Bosutinib-related pneumonitis
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-09-01
    Etienne-Marie Jutant; Véronique Meignin; David Montani; Abdellatif Tazi; Philippe Rousselot; Anne Bergeron

    We read with interest the recent correspondences from Hickey et al . [1] and Riou et al . [2] reporting bosutinib-associated pulmonary arterial hypertension (PAH) and pleural effusion. Tyrosine kinase inhibitors (TKIs) have revolutionised the treatment of chronic myeloid leukaemia (CML). However, TKIs are associated with potentially serious lung complications, which are particularly associated with dasatinib; the incidence of dasatinib-induced pleural effusion ranges from 15% to 35% [3, 4]. Dasatinib-related PAH has been reported in ∼0.45% of dasatinib-treated patients [5]. Bosutinib (developed by Pfizer (New York, NY, USA) in 2015) is a second-generation TKI approved for patients with CML that is resistant or intolerant to imatinib, nilotinib or dasatinib [6].Bosutinib can induce parenchymal, pleural and vascular lung disease

    更新日期:2017-09-12
  • Targeting bone morphogenic protein receptor 2 (BMPR2) signalling to treat pulmonary arterial hypertension
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-09-01
    Lewis J. Rubin

    BMPR signalling may be a therapeutic target for PAH, but further studies are needed http://ow.ly/KokP30efxbf

    更新日期:2017-09-11
  • Official ERS technical standards: Global Lung Function Initiative reference values for the carbon monoxide transfer factor for Caucasians
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-09-01
    Sanja Stanojevic; Brian L. Graham; Brendan G. Cooper; Bruce R. Thompson; Kim W. Carter; Richard W. Francis; Graham L. Hall

    There are numerous reference equations available for the single-breath transfer factor of the lung for carbon monoxide (T LCO); however, it is not always clear which reference set should be used in clinical practice. The aim of the study was to develop the Global Lung Function Initiative (GLI) all-age reference values for T LCO. Data from 19 centres in 14 countries were collected to define T LCO reference values. Similar to the GLI spirometry project, reference values were derived using the LMS (lambda, mu, sigma) method and the GAMLSS (generalised additive models for location, scale and shape) programme in R. 12 660 T LCO measurements from asymptomatic, lifetime nonsmokers were submitted; 85% of the submitted data were from Caucasians. All data were uncorrected for haemoglobin concentration. Following adjustments for elevation above sea level, gas concentration and assumptions used for calculating the anatomic dead space volume, there was a high degree of overlap between the datasets. Reference values for Caucasians aged 5–85 years were derived for T LCO, transfer coefficient of the lung for carbon monoxide and alveolar volume. This is the largest collection of normative T LCO data, and the first global reference values available for T LCO.

    更新日期:2017-09-11
  • Randomised placebo-controlled safety and tolerability trial of FK506 (tacrolimus) for pulmonary arterial hypertension
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-09-01
    Edda Spiekerkoetter; Yon K. Sung; Deepti Sudheendra; Valerie Scott; Patricia Del Rosario; Matthew Bill; Francois Haddad; Janel Long-Boyle; Haley Hedlin; Roham T. Zamanian

    Pulmonary arterial hypertension (PAH) is a devastating disease characterised by occlusive pulmonary vasculopathy. Activation of bone morphogenetic protein receptor 2 (BMPR2) signalling by FK506 (tacrolimus) reverses occlusive vasculopathy in rodent PAH models. Here, we determined the safety and tolerability of low-level FK506 therapy in stable PAH patients. We performed a randomised, double-blind, placebo-controlled, 16-week, single-centre, phase IIa trial in PAH patients with New York Heart Association functional class II/III symptoms using three FK506 target levels (<2, 2–3 and 3–5 ng·mL−1). 23 patients were randomised and 20 patients completed the trial. FK506 was generally well tolerated, with nausea/diarrhoea being the most commonly reported adverse event and no observation of line infections in patients on intravenous prostacyclin therapy. PAH patients had significantly lower BMPR2 expression in peripheral blood mononuclear cells versus healthy controls (n=13; p=0.005), which improved after FK506 treatment. While we observed that some patients responded with a pronounced increase in BMPR2 expression as well as improvement in 6-min walk distance, and serological and echocardiographic parameters of heart failure, these changes were not significant. Low-level FK506 is well tolerated and increases BMPR2 in subsets of PAH patients. These results support the study of FK506 in a phase IIb efficacy trial.

    更新日期:2017-09-11
  • The MUC5B promoter polymorphism is associated with specific interstitial lung abnormality subtypes
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-09-01
    Rachel K. Putman; Gunnar Gudmundsson; Tetsuro Araki; Mizuki Nishino; Sigurdur Sigurdsson; Elías F. Gudmundsson; Gudny Eiríksdottír; Thor Aspelund; James C. Ross; Raúl San José Estépar; Ezra R. Miller; Yoshitake Yamada; Masahiro Yanagawa; Noriyuki Tomiyama; Lenore J. Launer; Tamara B. Harris; Souheil El-Chemaly; Benjamin A. Raby; Michael H. Cho; Ivan O. Rosas; George R. Washko; David A. Schwartz; Edwin K. Silverman; Vilmundur Gudnason; Hiroto Hatabu; Gary M. Hunninghake

    The MUC5B promoter polymorphism (rs35705950) has been associated with interstitial lung abnormalities (ILA) in white participants from the general population; whether these findings are replicated and influenced by the ILA subtype is not known. We evaluated the associations between the MUC5B genotype and ILA in cohorts with extensive imaging characterisation. We performed ILA phenotyping and MUC5B promoter genotyping in 5308 and 9292 participants from the AGES-Reykjavik and COPDGene cohorts, respectively. We found that ILA was present in 7% of participants from the AGES-Reykjavik, 8% of non-Hispanic white participants from COPDGene and 7% of African-American participants from COPDGene. Although the MUC5B genotype was strongly associated (after correction for multiple testing) with ILA (OR 2.1, 95% CI 1.8–2.4, p=1×10−26), there was evidence of significant heterogeneity between cohorts (I2=81%). When narrowed to specific radiologic subtypes, (e.g. subpleural ILA), the MUC5B genotype remained strongly associated (OR 2.6, 95% CI 2.2–3.1, p=1×10−30) with minimal heterogeneity (I2=0%). Although there was no evidence that the MUC5B genotype influenced survival, there was evidence that MUC5B genotype improved risk prediction for possible usual interstitial pneumonia (UIP) or a UIP pattern in non-Hispanic white populations. The MUC5B promoter polymorphism is strongly associated with ILA and specific radiologic subtypes of ILA, with varying degrees of heterogeneity in the underlying populations.

    更新日期:2017-09-11
  • Mechanistic insight into the function of the microbiome in lung diseases
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-09-01
    Niki D.J. Ubags; Benjamin J. Marsland

    The lung harbours a diverse array of microbes whose dynamic composition is influenced by both host and environmental factors. Thus far, most studies have described the microbial composition of healthy or diseased lungs and provided an overview of the differences between topographical locations within the respiratory tract. However, insight into the functional mechanisms underlying host−microbe interactions and how they might drive lung health and disease are limited. This review provides an overview of the current mechanistic understanding of the microbiome, crosstalk between tissue compartments, and its involvement in respiratory diseases.

    更新日期:2017-09-11
  • Neither genotyping nor contact tracing allow correct understanding of multidrug-resistant tuberculosis transmission
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-09-01
    Arthur Fournier; Christine Bernard; Wladimir Sougakoff; Sylvie Quelet; Fadi Antoun; Cécile Charlois-Ou; Isabelle Dormant; Marie-Odile Dufour; Nora Hocine; Vincent Jarlier; Nicolas Veziris

    The control of tuberculosis (TB) is challenged by the progressive increase of cases of multi-drug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB). A recent European study underlined the need for data showing how TB control can be improved in terms of case finding, contact tracing, infection control and treatment to prevent further spread of MDR-/XDR-TB in the EU [1]. Even combined contact tracing and genotyping fail to explain how MDR-TB transmission occurs in one third of cases Author contributions: N. Veziris is the guarantor of the paper. A. Fournier, F. Antoun and N. Veziris designed the study, gathered data and wrote the manuscript. C. Bernard, W. Sougakoff and C. Charlois-Ou gathered data and corrected the manuscript. S. Quelet and V. Jarlier corrected the manuscript. I. Dormant, M-O. Dufour and N. Hocine gathered data.

    更新日期:2017-09-11
  • Do community demographics, environmental characteristics and access to care affect risks of developing ACOS and mortality in people with asthma?
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-09-01
    Teresa To; Jingqin Zhu; Christopher Carlsten; Kristian Larsen; Kandace Ryckman; Laura Y. Feldman; Eric Crighton; M. Diane Lougheed; Christopher Licskai; Paul J. Villeneuve; Yushan Su; Mohsen Sadatsafavi; Andrea Gershon

    Individuals with asthma and chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) have a more rapid decline in lung function, more frequent exacerbations and worse quality of life than those with asthma or COPD alone [1–3]. Various risk factors may be associated with the development of ACOS, such as smoking history and status, obesity, comorbidity and indoor and outdoor environmental exposures [1, 4–6]. The risk of developing ACOS may vary substantially by region, since demographic and environmental risk factors and community characteristics are not geographically homogeneous. Here, we use population-based data to estimate the incidence of ACOS in the asthma population and to measure the association between demographic factors, community-level characteristics and environmental factors and the risk of incident ACOS and all-cause mortality while accounting for spatial autocorrelation. Material deprivation increases ACOS and death risk in people with asthma; air pollution may also increase death risk Health administrative data were provided by the Institute for Clinical Evaluative Sciences (ICES) and air pollution data were provided by the Ministry of the Environment and Climate Change (MOECC). Neither ICES nor the MOECC had any role in study design, analysis, interpretation of data, or writing of the report. No endorsement by ICES or the MOECC is intended or should be inferred. Practice locations of currently certified respirologists were obtained from the website of the College of Physicians and Surgeons of Ontario ([www.cpso.on.ca/][1]). Practice location of currently certified asthma/COPD educators and certified respiratory therapists were provided by the College of Respiratory Therapists of Ontario. Finally, the geographic locations of pulmonary function testing laboratories or spirometry clinics were obtained from the Canadian Lung Association (). Kristian Larsen received a Postdoctoral Fellowship, in part, through the Hospital for Sick Children Research Training Centre and the CRRN. Andrea Gershon holds a New Investigator Career Award from CIHR and was also the recipient of 2015 Early Career Achievement Award of the Assembly on Behavioural Science and Health Services Research, American Thoracic Society. Teresa To was the recipient of the 2016 Meritorious Service Award of the Ontario Lung Association. Author contributions are as follows. T. To initiated and designed the study, conducted the spatial modelling and statistical analysis, interpreted findings and drafted the manuscript. J. Zhu compiled the data and conducted statistical analysis. K. Larsen compiled the geographical variables and conducted GIS mapping. L.Y. Feldman and K. Ryckman conducted a search of the literature, summarised relevant study findings and reviewed the manuscript. All authors interpreted findings, reviewed and commented on drafts, have seen and approved the final version. [1]: http://www.cpso.on.ca/

    更新日期:2017-09-11
  • Haemophilus influenzae biofilms in primary ciliary dyskinesia: a moving story
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-09-01
    Amelia Shoemark

    Impaired motile cilia function in the PCD cells results in susceptibility to NTHi biofilm development http://ow.ly/9D2u30eamR6

    更新日期:2017-09-10
  • Inhaled budesonide for acute mountain sickness
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-09-01
    Robert Naeije; Erik R. Swenson

    Inhaled corticosteroids are ineffective for the treatment of acute mountain sickness http://ow.ly/gz0i30eawqn

    更新日期:2017-09-10
  • International ERS/ESICM/ESCMID/ALAT guidelines for the management of hospital-acquired pneumonia and ventilator-associated pneumonia
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-09-01
    Antoni Torres; Michael S. Niederman; Jean Chastre; Santiago Ewig; Patricia Fernandez-Vandellos; Hakan Hanberger; Marin Kollef; Gianluigi Li Bassi; Carlos M. Luna; Ignacio Martin-Loeches; J. Artur Paiva; Robert C. Read; David Rigau; Jean François Timsit; Tobias Welte; Richard Wunderink

    The most recent European guidelines and task force reports on hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) were published almost 10 years ago. Since then, further randomised clinical trials of HAP and VAP have been conducted and new information has become available. Studies of epidemiology, diagnosis, empiric treatment, response to treatment, new antibiotics or new forms of antibiotic administration and disease prevention have changed old paradigms. In addition, important differences between approaches in Europe and the USA have become apparent. The European Respiratory Society launched a project to develop new international guidelines for HAP and VAP. Other European societies, including the European Society of Intensive Care Medicine and the European Society of Clinical Microbiology and Infectious Diseases, were invited to participate and appointed their representatives. The Latin American Thoracic Association was also invited. A total of 15 experts and two methodologists made up the panel. Three experts from the USA were also invited (Michael S. Niederman, Marin Kollef and Richard Wunderink). Applying the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) methodology, the panel selected seven PICO (population–intervention–comparison–outcome) questions that generated a series of recommendations for HAP/VAP diagnosis, treatment and prevention.

    更新日期:2017-09-10
  • Primary ciliary dyskinesia ciliated airway cells show increased susceptibility to Haemophilus influenzae biofilm formation
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-09-01
    Woolf T. Walker; Claire L. Jackson; Raymond N. Allan; Samuel A. Collins; Michael J. Kelso; Ardeshir Rineh; Nageshwar R. Yepuri; Ben Nicholas; Laurie Lau; David Johnston; Peter Lackie; Saul N. Faust; Jane S.A. Lucas; Luanne Hall-Stoodley

    Non-typeable Haemophilus influenzae (NTHi) is the most common pathogen in primary ciliary dyskinesia (PCD) patients. We hypothesised that abnormal ciliary motility and low airway nitric oxide (NO) levels on airway epithelial cells from PCD patients might be permissive for NTHi colonisation and biofilm development. We used a primary epithelial cell co-culture model to investigate NTHi infection. Primary airway epithelial cells from PCD and non-PCD patients were differentiated to ciliation using an air–liquid interface culture and then co-cultured with NTHi. NTHi adherence was greater on PCD epithelial cells compared to non-PCD cells (p<0.05) and the distribution of NTHi on PCD epithelium showed more aggregated NTHi in biofilms (p<0.001). Apart from defective ciliary motility, PCD cells did not significantly differ from non-PCD epithelial cells in the degree of ciliation and epithelial integrity or in cytokine, LL-37 and NO production. Treatment of PCD epithelia using exogenous NO and antibiotic significantly reduced NTHi viability in biofilms compared with antibiotic treatment alone. Impaired ciliary function was the primary defect in PCD airway epithelium underlying susceptibility to NTHi biofilm development compared with non-PCD epithelium. Although NO responses were similar, use of targeted NO with antibiotics enhanced killing of NTHi in biofilms, suggesting a novel therapeutic approach.

    更新日期:2017-09-10
  • Evaluation of severity score-guided approaches to macrolide use in community-acquired pneumonia
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-09-01
    Aran Singanayagam; Stefano Aliberti; Catia Cillóniz; Antoni Torres; Francesco Blasi; James D. Chalmers

    International guidelines including those in the UK, Japan, Australia and South Africa recommend the avoidance of macrolides in patients with low-severity community-acquired pneumonia (CAP). We hypothesised that severity scores are poor predictors of atypical pneumonia and response to macrolide therapy, and thus, inadequate tools for guiding antibiotic prescriptions. Secondary analysis of four independent prospective CAP datasets was conducted. The predictive values of the CURB-65 and pneumonia severity index (PSI) for clinically important groups of causative pathogens were evaluated. The effect of macrolide use according to risk class was assessed by multivariable analysis.  Patients (3297) were evaluated, and the predictive values of CURB-65 and PSI for atypical pathogens were poor (AUC values of 0.37 and 0.42, respectively). No significant differences were noted among the effects of macrolide use on mortality in patients with mild, moderate and severe CAP, according to either CURB-65 (interaction testing severe versus mild disease OR=0.74 (0.29–1.89)) or PSI (severe versus mild disease OR=3.4 (0.055–2.10)), indicating that severity scores were not significant modifiers of response to macrolide therapy. Severity scores did not accurately predict response to macrolide therapy in CAP, suggesting that current guidance to use these tools for empirical antibiotic choices might not be justified.

    更新日期:2017-09-10
  • Pain control in thoracic oncology
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-09-01
    Christine Peeters-Asdourian; Gilbert Massard; Paragi H. Rana; Paul Van Houtte; Andrew P. White; Bogdan Grigoriu; Dominique Lossignol; Mohammed Almalki; Jean Alexiou; Jean-Luc Engelholm; Jean-Paul Sculier

    This review of pain management in lung cancer is based on the presentation of four cases of thoracic oncology patients with pain at various stages of their disease. The approach will be multidisciplinary, involving a thoracic oncologist, radiologist, thoracic and orthopaedic spine surgeon, radiation therapist, pain medicine specialist, and palliative care specialist. This multispecialty approach to the management of different painful presentations in thoracic oncology will demonstrate the complexity of each case and the improved patient outcomes which result from the involvement of different disciplines working in concert. In the USA, Europe and other countries, palliative care specialists often become rapidly involved in the management of these patients, coordinating social care and providing psychological support. Thoracic and orthopaedic spine subspecialists provide surgical methods to control tumour invasion, and improve quality of life and preservation of function in settings of even diffuse metastatic disease. Similarly, thoracic oncology and radiation therapists utilise both therapeutic and palliative chemotherapeutic and radiation therapy regimens to prolong and improve quality of life. The pain medicine specialist can, in addition to medication management, offer a variety of interventional approaches including unique drug delivery systems such as epidural analgesia, regional anaesthesia techniques, and intrathecal pumps, as well as neuromodulation techniques and neurolytic or neuroablative procedures. In the USA, these specialists complete an additional fellowship year in pain medicine following the completion of an anaesthesiology, physical medicine and rehabilitation, neurology or psychiatry residency. These programmes are accredited by the Accreditation Council for Graduate Medical Education, or ACGME (www.acgme.org).

    更新日期:2017-09-10
  • Inhaled budesonide does not prevent acute mountain sickness after rapid ascent to 4559 m
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-09-01
    Marc Moritz Berger; Franziska Macholz; Mahdi Sareban; Peter Schmidt; Sebastian Fried; Daniel Dankl; Josef Niebauer; Peter Bärtsch; Heimo Mairbäurl

    Recent studies showed that inhaled budesonide (200 µg twice per day) reduced the incidence of acute mountain sickness (AMS) after passive ascent to 3700 and 3900 m [1, 2]. These findings raised the possibility that mediators released from the hypoxic lung transmit signals to the brain which contribute to the cerebral processes leading to AMS [3]. Because neither of these studies reflect alpine-style climbing, the present study was performed to test whether inhalation of budesonide at two different doses (200 and 800 µg twice per day) prior to active and rapid ascent (<20 h) to 4559 m prevents AMS in this high-risk setting. Prophylactic inhalation of budesonide does not prevent acute mountain sickness after rapid ascent to high-altitude

    更新日期:2017-09-10
  • Three years of experience with a novel “virtual” pneumonia follow-up clinic
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-09-01
    Christopher R. Wilcox; Jamie V. Krishnan; Claire Duffus; Ben G. Marshall

    Community-acquired pneumonia (CAP) remains the leading cause of adult mortality from infectious disease in the developed world, and carries a huge economic burden [1]. The annual expenditure attributable to CAP is estimated at 10 billion euros and 10 billion dollars for hospitals in Europe and the USA, respectively [2]. Furthermore, older people are disproportionally affected by CAP, and the projected increases in the elderly population over the coming years will put increasing strain on health services [2]. A virtual pneumonia follow-up service provides significant efficiency savings and retains high quality patient care

    更新日期:2017-09-10
  • Impact of alpha 1-antitrypsin deficiency and prior augmentation therapy on patients' survival after lung transplantation
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-09-01
    Anton Conrad; Sabina Janciauskiene; Thomas Köhnlein; Jan Fuge; Philipp Ivanyi; Igor Tudorache; Jens Gottlieb; Tobias Welte; Thomas Fuehner

    Alpha 1-antitrypsin (AAT) deficiency (AATD) is a genetic condition characterised by low serum levels of AAT and is associated with a high risk of developing early-onset pulmonary emphysema, especially in cigarette smokers [1]. The most common deficiency alleles among Caucasians are Pi*Z (Glu342Lys) and Pi*S (Glu264Val), and the majority of individuals with severe AATD are Pi type ZZ. According to available literature, PiZZ AATD comprises about 1–5% of all chronic obstructive pulmonary disease (COPD) cases [2]. Given the importance of the protease/anti-protease imbalance in causing Pi*Z-related emphysema [3], intravenous infusions of exogenous AAT are used as a specific augmentation therapy. Data from large interventional and observational studies suggest that decline in lung function and overall mortality decelerates in augmented compared to non-augmented patients [4]. Despite this therapy, it is impossible to halt the progression of emphysema in many patients and for those who develop end-stage lung disease, lung transplantation (LTx) remains the only option [5]. AATD is the fourth-most common reason for LTx, accounting for about 6% of all adult lung transplants [6]; however, there are only a few studies of post-LTx outcomes of patients with AATD [7, 8]. Evidence for the use of augmentation therapy after LTx is insufficient, and there is no consensus whether LTx recipients with AATD should receive augmentation therapy. According to the data, only 13–19% of AATD patients receive augmentation therapy after LTx [7]. Furthermore, the putative influence of previous augmentation therapy on lung recipients who discontinued this therapy following transplantation is entirely unknown. AATD patients who received augmentation therapy prior to LTx show worse survival rates

    更新日期:2017-09-10
  • Challenging the concept of adding more drugs in pulmonary arterial hypertension
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-09-01
    Caio J. C. dos Santos Fernandes; Marc Humbert; Rogerio Souza

    A “switch” strategy might represent an alternative for well-selected patients in PAH http://ow.ly/ppEt30enWo0

    更新日期:2017-09-09
  • In memoriam: Professor Philip H. Quanjer
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-09-01
    Janet Stocks; Irene Steenbruggen

    更新日期:2017-09-09
  • Prevention of COPD exacerbations: a European Respiratory Society/American Thoracic Society guideline
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-09-01
    Jadwiga A. Wedzicha; Peter M.A. Calverley; Richard K. Albert; Antonio Anzueto; Gerard J. Criner; John R. Hurst; Marc Miravitlles; Alberto Papi; Klaus F. Rabe; David Rigau; Pawel Sliwinski; Thomy Tonia; Jørgen Vestbo; Kevin C. Wilson; Jerry A. Krishnan

    This document provides clinical recommendations for the prevention of chronic obstructive pulmonary disease (COPD) exacerbations. It represents a collaborative effort between the European Respiratory Society and the American Thoracic Society. Comprehensive evidence syntheses were performed to summarise all available evidence relevant to the Task Force's questions. The evidence was appraised using the Grading of Recommendations, Assessment, Development and Evaluation approach and the results were summarised in evidence profiles. The evidence syntheses were discussed and recommendations formulated by a multidisciplinary Task Force of COPD experts. After considering the balance of desirable (benefits) and undesirable consequences (burden in the form of adverse effects and cost), quality of evidence, feasibility, and acceptability of various interventions, the Task Force made recommendations for mucolytic, long-acting muscarinic antagonist, phosphodiesterase-4 inhibitor (roflumilast) and macrolide therapy, as well as a conditional recommendation against fluoroquinolone therapy. All of the recommendations were conditional, except for a strong recommendation for the use of a long-acting antimuscarinic agent versus a long-acting β2-adrenergic, indicating that there was uncertainty about the balance of desirable and undesirable consequences of the intervention, and that well-informed patients may make different choices regarding whether to have or not have the specific intervention. The guideline summarises the evidence and provides recommendations for pharmacological therapy for the prevention of COPD exacerbations.

    更新日期:2017-09-09
  • European Respiratory Society guidelines for the management of adult bronchiectasis
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-09-01
    Eva Polverino; Pieter C. Goeminne; Melissa J. McDonnell; Stefano Aliberti; Sara E. Marshall; Michael R. Loebinger; Marlene Murris; Rafael Cantón; Antoni Torres; Katerina Dimakou; Anthony De Soyza; Adam T. Hill; Charles S. Haworth; Montserrat Vendrell; Felix C. Ringshausen; Dragan Subotic; Robert Wilson; Jordi Vilaró; Bjorn Stallberg; Tobias Welte; Gernot Rohde; Francesco Blasi; Stuart Elborn; Marta Almagro; Alan Timothy; Thomas Ruddy; Thomy Tonia; David Rigau; James D. Chalmers

    Bronchiectasis in adults is a chronic disorder associated with poor quality of life and frequent exacerbations in many patients. There have been no previous international guidelines. The European Respiratory Society guidelines for the management of adult bronchiectasis describe the appropriate investigation and treatment strategies determined by a systematic review of the literature. A multidisciplinary group representing respiratory medicine, microbiology, physiotherapy, thoracic surgery, primary care, methodology and patients considered the most relevant clinical questions (for both clinicians and patients) related to management of bronchiectasis. Nine key clinical questions were generated and a systematic review was conducted to identify published systematic reviews, randomised clinical trials and observational studies that answered these questions. We used the GRADE approach to define the quality of the evidence and the level of recommendations. The resulting guideline addresses the investigation of underlying causes of bronchiectasis, treatment of exacerbations, pathogen eradication, long term antibiotic treatment, anti-inflammatories, mucoactive drugs, bronchodilators, surgical treatment and respiratory physiotherapy. These recommendations can be used to benchmark quality of care for people with bronchiectasis across Europe and to improve outcomes.

    更新日期:2017-09-09
  • Inducible laryngeal obstruction: an official joint European Respiratory Society and European Laryngological Society statement
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-09-01
    Thomas Halvorsen; Emil Schwarz Walsted; Caterina Bucca; Andrew Bush; Giovanna Cantarella; Gerhard Friedrich; Felix J.F. Herth; James H. Hull; Harald Jung; Robert Maat; Leif Nordang; Marc Remacle; Niels Rasmussen; Janet A. Wilson; John-Helge Heimdal

    Inducible laryngeal obstruction (ILO) describes an inappropriate, transient, reversible narrowing of the larynx in response to external triggers. ILO is an important cause of a variety of respiratory symptoms and can mimic asthma. Current understanding of ILO has been hampered by imprecise nomenclature and variable approaches to assessment and management. A task force of the European Respiratory Society (ERS) and European Laryngological Society (ELS) was thus set up to address this, and to identify research priorities. A literature search identified relevant articles published until June 2016, using all identifiable terms for ILO, although including only articles using laryngoscopy. In total, 172 out of 252 articles met the inclusion criteria, summarised in sections on diagnostic approach, aetiology, comorbidities, epidemiology and treatment. The consensus taxonomy published by ERS, ELS and the American College of Chest Physicians (ACCP) in 2015 is used throughout this statement. We highlight the high prevalence of ILO and the clinical impact for those affected. Despite recent advances, most aspects of this condition unfortunately remain incompletely understood, precluding firm guidance. Specifically, validated diagnostic and treatment algorithms are yet to be established, and no randomised control studies were identified in this search; hence we also make recommendations for future research.

    更新日期:2017-09-09
  • RESPITE: switching to riociguat in pulmonary arterial hypertension patients with inadequate response to phosphodiesterase-5 inhibitors
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-09-01
    Marius M. Hoeper; Gérald Simonneau; Paul A. Corris; Hossein-Ardeschir Ghofrani; James R. Klinger; David Langleben; Robert Naeije; Pavel Jansa; Stephan Rosenkranz; Laura Scelsi; Ekkehard Grünig; Carmine Dario Vizza; MiKyung Chang; Pablo Colorado; Christian Meier; Dennis Busse; Raymond L. Benza

    A proportion of pulmonary arterial hypertension (PAH) patients do not reach treatment goals with phosphodiesterase-5 inhibitors (PDE5i). RESPITE investigated the safety, feasibility and benefit of switching from PDE5i to riociguat in these patients. RESPITE was a 24-week, open-label, multicentre, uncontrolled study. Patients in World Health Organization (WHO) functional class (FC) III, with 6-min walking distance (6MWD) 165–440 m, cardiac index <3.0 L·min−1·m−2 and pulmonary vascular resistance >400 dyn·s·cm−5 underwent a 1–3 day PDE5i treatment-free period before receiving riociguat adjusted up to 2.5 mg maximum t.i.d. Exploratory end-points included change in 6MWD, WHO FC, N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and safety. Of 61 patients enrolled, 51 (84%) completed RESPITE. 50 (82%) were receiving concomitant endothelin receptor antagonists. At week 24, mean±sd 6MWD had increased by 31±63 m, NT-proBNP decreased by 347±1235 pg·mL−1 and WHO FC improved in 28 patients (54%). 32 patients (52%) experienced study drug-related adverse events and 10 (16%) experienced serious adverse events (2 (3%) study drug-related, none during the PDE5i treatment-free period). Six patients (10%) experienced clinical worsening, including death in two (not study drug-related). In conclusion, selected patients with PAH may benefit from switching from PDE5i to riociguat, but this strategy needs to be further studied.

    更新日期:2017-09-09
  • Survival in individuals with severe alpha 1-antitrypsin deficiency (PiZZ) in comparison to a general population with known smoking habits
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-09-01
    Hanan A. Tanash; Magnus Ekström; Eva Rönmark; Anne Lindberg; Eeva Piitulainen

    Knowledge about the natural history of severe alpha 1-antitrypsin (AAT) deficiency (PiZZ) is limited. Our aim was to compare the survival of PiZZ individuals with randomly selected controls from the Swedish general population. The PiZZ subjects (n=1585) were selected from the Swedish National AATD Register. The controls (n=5999) were randomly selected from the Swedish population register. Smoking habits were known for all subjects. Median follow-up times for the PiZZ subjects (731 never-smokers) and controls (3179 never-smokers) were 12 and 17 years, respectively (p<0.001). During follow-up, 473 PiZZ subjects (30%), and 747 controls (12%) died. The PiZZ subjects had a significantly shorter survival time than the controls, p<0.001. After adjustment for gender, age, smoking habits and presence of respiratory symptoms, the risk of death was still significantly higher for the PiZZ individuals than for the controls, hazard ratio (HR) 3.2 (95% CI 2.8–3.6; p<0.001). By contrast, the risk of death was not increased in never-smoking PiZZ individuals identified by screening, compared to never-smoking controls, HR 1.2 (95% CI 0.6–2.2). The never-smoking PiZZ individuals identified by screening had a similar life expectancy to the never-smokers in the Swedish general population. Early diagnosis of AAT deficiency is of utmost importance.

    更新日期:2017-09-09
  • Interplay between cigarette smoking and pulmonary reverse lipid transport
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-09-01
    Éric Jubinville; Maude Talbot; Jean-Christophe Bérubé; Mélanie Hamel-Auger; Michaël Maranda-Robitaille; Marie-Josée Beaulieu; Sophie Aubin; Marie-Ève Paré; David G. Kallend; Benoit Arsenault; Yohan Bossé; Mathieu C. Morissette

    Reverse lipid transport is critical to maintain homeostasis. Smoking causes lipid accumulation in macrophages, therefore suggesting suboptimal reverse lipid transport mechanisms. In this study, we investigated the interplay between smoking and reverse lipid transport and the consequences on smoking-induced lung and peripheral alterations. To investigate the relationship between smoking and reverse lipid transport, we used a clinical lung gene expression dataset and a mouse model of cigarette smoke exposure. We also used ApoA-1−/− mice, with reduced reverse lipid transport capacity, and a recombinant ApoA-1 Milano/phospholipid complex (MDCO-216) to boost reverse lipid transport. Cellular and functional analyses were performed on the lungs and impact on body composition was also assessed. Smoking affects pulmonary expression of abca1, abcg1, apoe and scarb1 in both mice and humans, key genes involved in reverse lipid transport. In mice, the capacity of bronchoalveolar lavage fluid and serum to stimulate cholesterol efflux in macrophages was increased after a single exposure to cigarette smoke. ApoA-1−/− mice showed increased lung neutrophilia, larger macrophages and greater loss in lean mass in response to smoking, whereas treatment with MDCO-216 reduced the size of macrophages and increased the lean mass of mice exposed to cigarette smoke. Altogether, this study shows a functional interaction between smoking and reverse lipid transport, and opens new avenues for better understanding the link between metabolic and pulmonary diseases related to smoking.

    更新日期:2017-09-09
  • The paradoxes of asthma management: time for a new approach?
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-09-01
    Paul M. O'Byrne; Christine Jenkins; Eric D. Bateman

    Poor adherence to maintenance pharmacotherapy is a reality in asthma. Studies confirm that when symptoms worsen, most patients increase short-acting β2-agonist (SABA) use, instead of using controller medication. This behaviour might be attributable to several paradoxes in the current treatment approach. These paradoxes include the recommended use of a SABA bronchodilator alone at Global Initiative for Asthma (GINA) step 1, despite the fact that asthma is a chronic inflammatory disease. At step 1, the patient has autonomy and their perception of need and disease control is accepted, but at higher asthma treatment steps a fixed-dose approach is recommended, irrespective of symptom severity. The unintended consequence is the establishment of a pattern of early over-reliance on SABA. New approaches that avoid these paradoxes are needed, such as patient-adjusted therapy, in which patients adopt a symptom-driven approach using a combination reliever/controller. We propose that SABA reliever monotherapy should be replaced by a combination of inhaled corticosteroid (ICS) and formoterol, or similar rapid-onset bronchodilator, as reliever therapy for patients at GINA steps 1 or 2. This will ensure early and more regular administration of a controller medication. However, a significant body of clinical data will be needed before this approach can be approved by regulatory authorities.

    更新日期:2017-09-09
  • Nitrogen back-diffusion during multiple-breath washout with 100% oxygen
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-09-01
    Leanna Sullivan; Erick Forno; Knud Pedersen; Jørgen G. Nielsen; Daniel J. Weiner

    The lung clearance index (LCI) measured by multiple-breath washout (MBW) is defined as the number of lung volume turnovers needed to reduce the concentration of a blood-insoluble tracer gas by a factor of 40 during tidal breathing [1]. Over the past two decades, the MBW test has proven to be particularly useful in cystic fibrosis, and studies [2, 3] have demonstrated its superior sensitivity to that of forced expiratory volume in 1 s (FEV1). The ideal tracer gas for the LCI test is so insoluble in blood that any gas exchange effects are insignificant, and it can be measured in concentrations low enough that the tracer itself does not affect the physical properties of the respired air or gas mix. Historically, SF6 is the tracer gas that is most often used in the implementation of the MBW test [1]. However, it has been suggested that the LCI can instead be derived from the washout of nitrogen resident in the lungs using 100% oxygen, and this approach is being applied in a number of ongoing clinical trials. Nitrogen diffuses from blood into lung during nitrogen washout which can affect multiple breath washout results Author contributions: J.G. Nielsen and K. Pedersen initiated and designed the study. L. Sullivan, D.J. Weiner and K. Pedersen collected data and performed inert gas rebreathing and lung clearance index measurements. K. Pedersen and E. Forno analysed the data. All authors contributed to (participated in) the writing and reviewing of the manuscript.

    更新日期:2017-09-09
  • Are indexed values better for defining exercise pulmonary hypertension?
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-09-01
    Jason Weatherald; Athénaïs Boucly; Edmund Lau; Laurent Godinas; Laurent Savale; Xavier Jaïs; David Montani; Olivier Sitbon; Gérald Simonneau; Marc Humbert; Denis Chemla; Philippe Hervé

    Pulmonary hypertension (PH) is defined by resting mean pulmonary arterial pressure (mPAP) ≥25 mmHg [1]. Patients with pulmonary vascular disease (PVD) or left heart disease (LHD) may demonstrate abnormal haemodynamic responses to exercise even when resting mPAP is normal [2]. After the 4th World Symposium on PH in 2008, exercise PH, defined as mPAP >30 mmHg during exercise, was abandoned due to a lack of supportive evidence and the observation that mPAP frequently exceeds 30 mmHg in healthy individuals who attain high cardiac output (CO) [3, 4]. A disproportionate increase in mPAP relative to CO during exercise, however, reflects either an increase in pulmonary vascular resistance (PVR), as in PVD, or elevated left ventricular filling pressure in LHD. Therefore, attention to the mPAP/CO relationship, such as the mPAP/CO slope or the total pulmonary resistance (TPRmax) >3 Wood units (WU) at maximal exercise, could refine the definition of an abnormal haemodynamic response to exercise in order to reduce false positive diagnoses [5–7]. Indeed, combining mPAP (mPAPmax) >30 mmHg and the TPRmax >3 WU at maximal exercise has been demonstrated to have high accuracy in discriminating patients with PVD or LHD and resting mPAP ≤20 mmHg from controls or healthy volunteers [7]. Furthermore, these criteria have superior diagnostic performance compared to either the mPAP/CO slope or change in mPAP/CO during exercise [8]. No advantage to using indexed total pulmonary resistance in the definition of exercise pulmonary hypertension We would like to acknowledge Marie Line Goubet and Antoine Goineau from the Cardiac Catheterization Laboratory, Service de Pneumologie, Centre de Référence de l'Hypertension Pulmonaire Sévère, Hôpital de Bicêtre (Le Kremlin-Bicêtre, France) for their assistance in performing exercise haemodynamic testing.

    更新日期:2017-09-09
  • Overdosing on immediate-release morphine solution has predictable adverse effects
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-09-01
    David C. Currow; Magnus Ekström; Miriam J. Johnson

    Prescribing responsibility inherently includes adequate ongoing monitoring for medication. The adverse effects of an overdose of immediate-release morphine in a recent letter to the ERJ are well known

    更新日期:2017-09-09
  • Predictable adverse events such as respiratory depression highlight the need for caution when prescribing morphine for refractory breathlessness
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-09-01
    Natasha Smallwood; John Politis; Brian Le

    “A scientist's aim in a discussion with his colleagues is not to persuade, but to clarify” [1]. We therefore thank D.C. Currow and co-workers for both their comments and the opportunity to continue the discussion regarding the risks and benefits of using opioids to treat refractory chronic breathlessness. The purpose of our recent case report [2] is not to persuade clinicians to prescribe or not prescribe opioids for the off-licence indication of refractory breathlessness, but to highlight and clarify risks of prescribing opioids in this clinical setting and when practising real life medicine, which is so different from the carefully controlled and managed environment of clinical trials. Caution is needed when prescribing morphine for refractory breathlessness in the real world

    更新日期:2017-09-09
  • Clinical screening of oropharyngeal dysphagia: standard of care
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-08-01
    Eric Verin

    We were very interested in the comments made by I. Cavedies and co-workers regarding our paper entitled “Oropharyngeal dysphagia: when swallowing disorders meet respiratory diseases” [1]. Oropharyngeal dysphagia in respiratory disease: a submarine

    更新日期:2017-09-05
  • Clinical screening of oropharyngeal dysphagia: standard of care
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-08-01
    Ivan Caviedes; Sebastian Fernandez-Bussy; Gonzalo Labarca; Felix J.F. Herth

    We read with interest the paper by Verin et al. [1] related to oropharyngeal dysphagia and its importance in institutionalised neurological and head and neck patients, between others. Furthermore, this is a very common problem in the critical and intermediate care settings, and a similar situation occurs with other acute neurological diseases, such as amyotrophic lateral sclerosis, cerebral trauma, post-neurosurgical procedures and toxic metabolic encephalopathies [2, 3]. The authors emphasised the necessity of identifying risks factors for aspiration early and suggested that clinical screening methods are needed to recognise patients with oropharyngeal dysphagia. However, swallowing clinical screening performed by speech therapists and nurses is a standard of care in critical care units. This concept is particularly relevant, considering that in stroke patients, the prognosis is closely related to the medical complications, and aspiration is responsible for >50% of these and increases mortality for up to 33% at 6 months. Even more, after the acute phase of a stroke, swallowing dysfunction has a recovery capacity of 87% at 6 months [4–6]. The three-ounce water test is a well-known and useful bedside screening tool for oropharyngeal dysphagia

    更新日期:2017-09-05
  • DLCO: adjust for lung volume, standardised reporting and interpretation
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-08-01
    Brian L. Graham; Vito Brusasco; Felip Burgos; Brendan G. Cooper; Robert Jensen; Adrian Kendrick; Neil R. MacIntyre; Bruce R. Thompson; Jack Wanger

    D.C. Johnson proposed that an adjustment of the predicted value for the diffusing capacity of the lung for carbon monoxide ( D LCO) based on the measured and predicted lung volume be included in the report of D LCO test results. An interpretation algorithm is also proposed. A correction of the predicted value for D LCO based on the measured lung volume is not recommended

    更新日期:2017-09-05
  • DLCO: adjust for lung volume, standardised reporting and interpretation
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-08-01
    Douglas C. Johnson

    The American Thoracic Society (ATS) and European Respiratory Society (ERS) should be congratulated on updating standards for diffusing capacity of the lung for carbon monoxide ( D LCO) [1]. I agree that “Besides varying with age, sex, height and possible ethnicity, D LCO also changes with Hb, lung volume, COHb, P IO2 …, exercise and body position.” and that “adjustments for these factors be made in the predicted rather than the measured D LCO”. Reporting transfer coefficient of the lung for carbon monoxide ( K CO) rather than D LCO/alveolar volume ( V A) will help get away from the mistaken notion that D LCO/ V A “corrects” D LCO for lung volume [2]. While the new standards describe how to adjust predicted D LCO for haemoglobin (Hb), COHb and inspired oxygen tension ( P IO2), it does not discuss how to adjust predicted D LCO and K CO for lung volume. D LCO reports and interpretation should be standardised and include adjusting predicted D LCO and K CO for lung volume

    更新日期:2017-09-05
  • Serum sCD163 as a biomarker of adipose tissue inflammation in obstructive sleep apnoea patients: limits and perspectives
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-08-01
    Silke Ryan

    I thank D. Monneret and J-P. Bastard for their interest in our manuscript [1] and I could not agree more with their comment that the role of soluble CD163 (sCD163) in obstructive sleep apnoea (OSA) requires further detailed evaluation. As outlined in our article, the measurement of sCD163 in our patient cohort followed our results from the in vitro and in vivo studies demonstrating M1 polarisation of adipose tissue macrophages in response to intermittent hypoxia and thus, was not an a priori hypothesis of our study. Nonetheless, the detected independent association of sCD163 with OSA severity is intriguing. sCD163 in sleep apnoea requires further evaluation

    更新日期:2017-09-05
  • Serum sCD163 as a biomarker of adipose tissue inflammation in obstructive sleep apnoea patients: limits and perspectives
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-08-01
    Denis Monneret; Jean-Philippe Bastard

    Recently, Murphy et al. [1] demonstrated, through a challenging animal, cellular and human translational approach, that intermittent hypoxia induces a pro-inflammatory activation of adipose tissue macrophages (ATMs), promoting insulin resistance. They confirmed that intermittent hypoxia lowers insulin-mediated glucose uptake in 3T3-L1 adipocytes, and evidenced the interrelationship between inflammation and insulin resistance in the adipose tissue of mice exposed to intermittent hypoxia. They then measured the concentration of serum soluble CD163 (sCD163), an assumed pro-inflammatory biomarker reflecting macrophage activation, in obstructive sleep apnoea (OSA) patients classified according to their BMI and apnoea/hypopnoea index (AHI). This is the first time serum sCD163 has been evaluated in OSA patients, and its association with AHI is promising. With the aim of enhancing its relevance in further studies, we wish to discuss the following points. Serum sCD163 as a biomarker of adipose tissue inflammation in OSA patients: limits and perspectives The authors thank Vincent Fitzpatrick for the English rereading.

    更新日期:2017-09-05
  • Concern of underdiagnosing asthma–COPD overlap syndrome if age limit of 40 years for asthma is used
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-08-01
    Don D. Sin; Janice M. Leung; Michael E. Wechsler

    M. Tommola and colleagues raise an important and hotly debated diagnostic criterion of asthma–chronic obstructive pulmonary disease overlap syndrome (ACOS): an age threshold of 40 years for the asthma component of ACOS. We agree with their comment that asthma can develop later in life and these patients may respond well to inhaled corticosteroids and novel biologics, similar to those with childhood-onset asthma [1]. Thus, in the roundtable consensus report [2], we suggested that the asthma component of ACOS could be fulfilled by a clinical diagnosis of asthma before age 40 years or in those without a clinical diagnosis of asthma before 40 years by demonstrating an improvement in forced expiratory volume in 1 s (FEV1) of ≥400 mL following short-acting β2-agonist therapy. While a significant bronchodilatory response (BDR) is a common feature in both asthma and chronic obstructive pulmonary disease (COPD) [3], it is very unusual for COPD patients to demonstrate a BDR of ≥400 mL in FEV1 without a concomitant diagnosis of asthma [4]. To further improve the specificity of the asthma component of ACOS, we also suggested that in addition to all three major criteria, patients fulfil at least one of the three minor criteria: 1) a history of atopy or allergic rhinitis; 2) a BDR of ≥200 mL in FEV1 on two separate visits; or 3) peripheral eosinophil count of ≥300 cells per μL. While none of these criteria has been validated in ACOS, we believe that these criteria are clinically workable and may be useful in identifying patients with asthma with reasonable precision. Future work will be needed to refine these criteria based on high-grade data. While the ACOS criteria have not been validated, they are clinically workable and may identify asthma precisely

    更新日期:2017-09-05
Some contents have been Reproduced with permission of the American Chemical Society.
Some contents have been Reproduced by permission of The Royal Society of Chemistry.
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