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Phenotyping acute exacerbation of COPD: what more can we do for hospitalised patients?
Lai-Jian Cen, Xiao-xian Zhang, Wei-Jie Guan
doi : 10.1183/23120541.00362-2021
01 July 2021; volume 7, issue 3ERJ Open Res 7: 00362-2021
Prospective association between use of electronic cigarettes and use of conventional cigarettes: a systematic review and meta-analysis
Louise Adermark, Maria Rosaria Galanti, Charlotta Ryk, Hans Gilljam, Linnea Hedman
doi : 10.1183/23120541.00976-2020
01 July 2020; volume 7, issue 3ERJ Open Res 7: 00976-2020
Objective The aim of this systematic review and meta-analysis was to assess the association between e-cigarette use and subsequent initiation or recurrence of cigarette smoking.
The lower respiratory airway wall in children in health and disease
Michael Fayon, Fabien Beaufils
doi : 10.1183/23120541.00874-2020
01 July 2020; volume 7, issue 3ERJ Open Res 7: 00874-2020
Alone or in association with other lung or thorax component disorders, the airway wall (AWW) remains one of the most frequently involved elements in paediatric lung diseases. A myriad of AWW disorders will present with similar symptomatology. It is thus important for the clinician to reappraise the normal development and structure of the AWW to better understand the underlying disease patterns. We herein provide an overview of the structure of the AWW and a description of its development from the fetal period to adulthood. We also detail the most common AWW changes observed in several acute and chronic respiratory disorders as well as after cigarette smoke or chronic pollution exposure. We then describe the relationship between the AWW structure and lung function. In addition, we present the different ways of investigating the AWW structure, from biopsies and histological analyses to the most recent noninvasive airway (AW) imaging techniques. Understanding the pathophysiological processes involved in an individual patient will lead to the judicious choice of nonspecific or specific personalised treatments, in order to prevent irreversible AW damage.
Detection and diagnosis of large airway collapse: a systematic review
Alexandros Mitropoulos, Woo-Jung Song, Fatma Almaghlouth, Samuel Kemp, Michael Polkey, James H. Hull
doi : 10.1183/23120541.00055-2021
01 July 2021; volume 7, issue 3ERJ Open Res 7: 00055-2021
Large airway collapse (LAC) is a frequently encountered clinical problem, caused by tracheobronchomalacia +/? excessive dynamic airway collapse, yet there are currently no universally accepted diagnostic criteria. We systematically reviewed studies reporting a diagnostic approach to LAC in healthy adults and patients, to compare diagnostic modalities and criteria used. Electronic databases were searched for relevant studies between 1989 and 2019. Studies that reported a diagnostic approach using computed tomography (CT), magnetic resonance imaging or flexible fibreoptic bronchoscopy were included. Random effects meta-analyses were performed to estimate the prevalence of LAC in healthy subjects and in patients with chronic obstructive airway diseases. We included 41 studies, describing 10?071 subjects (47% female) with a mean±sd age of 59±9?years. Most studies (n=35) reported CT findings, and only three studies reported bronchoscopic findings. The most reported diagnostic criterion was a ?50% reduction in tracheal or main bronchi calibre at end-expiration on dynamic expiratory CT. Meta-analyses of relevant studies found that 17% (95% CI: 0–61%) of healthy subjects and 27% (95% CI: 11–46%) of patients with chronic airways disease were classified as having LAC, using this threshold. The most reported approach to diagnose LAC utilises CT diagnostics, and at a threshold used by most clinicians (i.e., ?50%) may classify a considerable proportion of healthy individuals as being abnormal and having LAC in a quarter of patients with chronic airways disease. Future work should focus on establishing more precise diagnostic criteria for LAC, relating this to relevant physiological and disease sequelae.
Diagnosis of COVID-19 by exhaled breath analysis using gas chromatography–mass spectrometry
Wadah Ibrahim, Rebecca L. Cordell, Michael J. Wilde, Matthew Richardson, Liesl Carr, Ananga Sundari Devi Dasi, Beverley Hargadon, Robert C. Free, Paul S. Monks, Christopher E. Brightling, Neil J. Greening, Salman Siddiqui
doi : 10.1183/23120541.00139-2021
01 July 2021; volume 7, issue 3ERJ Open Res 7: 00139-2021
Background The ongoing coronavirus disease 2019 (COVID-19) pandemic has claimed over two and a half million lives worldwide so far. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is perceived to be seasonally recurrent, and a rapid noninvasive biomarker to accurately diagnose patients early on in their disease course will be necessary to meet the operational demands for COVID-19 control in the coming years.
Post-anticoagulant D-dimer is a highly prognostic biomarker of COVID-19 mortality
Xiaoyu Song, Jiayi Ji, Boris Reva, Himanshu Joshi, Anna Pamela Calinawan, Madhu Mazumdar, Juan P. Wisnivesky, Emanuela Taioli, Pei Wang, Rajwanth R. Veluswamy
doi : 10.1183/23120541.00018-2021
01 July 2021; volume 7, issue 3ERJ Open Res 7: 00018-2021
Clinical biomarkers that accurately predict mortality are needed for the effective management of patients with severe coronavirus disease 2019 (COVID-19) illness. In this study, we determine whether changes in D-dimer levels after anticoagulation are independently predictive of in-hospital mortality.
The role of bronchoscopy in patients with SARS-CoV-2 pneumonia
Marisol Arenas-De Larriva, Roberto Mart?n-DeLeon, Blanca Urrutia Royo, Iker Fern?ndez-Navamuel, Andrés Gimenez Velando, Laura Nu?ez Garc?a, Carmen Centeno Clemente, Felipe Andreo Garc?a, Albert Rafecas Codern, Carmen Fern?ndez-Arias, Virginia Pajares Ruiz, Alfons Torrego Fern?ndez, Olga Rajas, Gorane Iturricastillo, Ricardo Garcia Lujan, Lorena Comeche Casanova, Albert S?nchez-Font, Ricardo Aguilar-Colindres, Roberto Larrosa-Barrero, Ruth Garc?a Garc?a, Rosa Cordovilla, Ana N??ez-Ares, Andrés Briones-G?mez, Enrique Cases Viedma, José Franco, Javier Cosano Povedano, Manuel Luis Rodr?guez-Per?lvarez, Jose Joaquin Cebrian Gallardo, Manuel Nu?ez Delgado, Mar?a Pav?n-Masa, Maria del Mar Valdivia Salas, Javier Flandes
doi : 10.1183/23120541.00165-2021
01 July 2021; volume 7, issue 3ERJ Open Res 7: 00165-2021
Background The role of bronchoscopy in coronavirus disease 2019 (COVID-19) is a matter of debate.Patients and methods This observational multicentre study aimed to analyse the prognostic impact of bronchoscopic findings in a consecutive cohort of patients with suspected or confirmed COVID-19. Patients were enrolled at 17 hospitals from February to June 2020. Predictors of in-hospital mortality were assessed by multivariate logistic regression.
Descriptive analysis of long COVID sequelae identified in a multidisciplinary clinic serving hospitalised and non-hospitalised patients
Stine Johnsen, Stefan M. Sattler, Kamilla Woznica Miskowiak, Keerthana Kunalan, Alan Victor, Lars Pedersen, Helle Frost Andreassen, Barbara Jolanta J?rgensen, Hanne Heeb?ll, Michael Brun Andersen, Lisbeth Marner, Carsten H?dersdal, Henrik Hansen, Sisse Bolm Ditlev, Celeste Porsbjerg, Thérèse S. Lapperre
doi : 10.1183/23120541.00205-2021
01 July 2021; volume 7, issue 3ERJ Open Res 7: 00205-2021
Background There are emerging data of long-term effects of coronavirus disease 2019 (COVID-19) comprising a diversity of symptoms. The aim of this study was to systematically describe and measure pulmonary and extra-pulmonary post-COVID-19 complications in relation to acute COVID-19 severity.
The sputum transcriptome better predicts COPD exacerbations after the withdrawal of inhaled corticosteroids than sputum eosinophils
Benedikt Ditz, Aartik Sarma, Huib A.M. Kerstjens, Jeroen J.W. Liesker, Erik Bathoorn, Judith M. Vonk, Victor Bernal, Peter Horvatovich, Victor Guryev, Saharai Caldera, Chaz Langelier, Alen Faiz, Stephanie A. Christenson, Maarten van den Berge
doi : 10.1183/23120541.00097-2021
01 July 2021; volume 7, issue 3ERJ Open Res 7: 00097-2021
Introduction Continuing inhaled corticosteroid (ICS) use does not benefit all patients with COPD, yet it is difficult to determine which patients may safely sustain ICS withdrawal. Although eosinophil levels can facilitate this decision, better biomarkers could improve personalised treatment decisions.
MULTI-PHACET: multidimensional clinical phenotyping of hospitalised acute COPD exacerbations
Martin I. MacDonald, Christian R. Osadnik, Lauren Bulfin, Elizabeth Leahy, Paul Leong, Eskandarain Shafuddin, Kais Hamza, Paul T. King, Philip G. Bardin
doi : 10.1183/23120541.00198-2021
01 July 2021; volume 7, issue 3ERJ Open Res 7: 00198-2021
Background The generic term “exacerbation” does not reflect the heterogeneity of acute exacerbations of COPD (AECOPD). We utilised a novel algorithmic strategy to profile exacerbation phenotypes based on underlying aetiologies.
Tongue strength and swallowing dynamics in chronic obstructive pulmonary disease
Isabella Epiu, Simon C. Gandevia, Claire L. Boswell-Ruys, Emma Wallace, Jane E. Butler, Anna L. Hudson
doi : 10.1183/23120541.00192-2021
01 July 2021; volume 7, issue 3ERJ Open Res 7: 00192-2021
Background Swallowing disorders occur in COPD, but little is known about tongue strength and mastication. This is the first assessment in COPD of tongue strength and a test of mastication and swallowing solids (TOMASS).Methods Anterior tongue strength measures were obtained in 18 people with COPD, aged 73±11?years (mean±sd), and 19 healthy age-matched controls, aged 72±6?years. Swallowing dynamics were assessed using an eating assessment tool (EAT-10), timed water swallow test (TWST), and TOMASS. Swallowing measures were compared to an inhibitory reflex (IR) in the inspiratory muscles to airway occlusion (recorded previously in the same participants).
Long-term Exercise After Pulmonary Rehabilitation (LEAP): a pilot randomised controlled trial of Tai Chi in COPD
Marilyn L. Moy, Peter M. Wayne, Daniel Litrownik, Douglas Beach, Elizabeth S. Klings, Roger B. Davis, Adlin Pinheiro, Gloria Y. Yeh
doi : 10.1183/23120541.00025-2021
01 July 2021; volume 7, issue 3ERJ Open Res 7: 00025-2021
Mind–body modalities are promising strategies to maintain the benefits gained after completion of conventional pulmonary rehabilitation in persons with COPD.In this pilot randomised controlled study we examined Tai Chi in persons with COPD after completing pulmonary rehabilitation. Participants were randomised 2:2:1 to Tai Chi (TC), usual care (UC) or group walking (GW) for 24?weeks. We assessed feasibility; primary outcome was exercise capacity measured by 6-min walk test (6MWT) distance at 24?weeks. Secondary outcomes included health-related quality of life measured by Chronic Respiratory Questionnaire (CRQ), dyspnoea, mood, stress, social support, self-efficacy, physical activity and exercise engagement. Effect size estimates and estimates from generalised estimating equations were calculated.
Haemoglobin as a biomarker for clinical outcomes in chronic obstructive pulmonary disease
Aparna Balasubramanian, Robert J. Henderson, Nirupama Putcha, Ashraf Fawzy, Sarath Raju, Nadia N. Hansel, Neil R. MacIntyre, Robert L. Jensen, Gregory L. Kinney, William W. Stringer, Craig P. Hersh, Russell P. Bowler, Richard Casaburi, MeiLan K. Han, Janos Porszasz, Barry J. Make, Meredith C. McCormack, Robert A. Wise
doi : 10.1183/23120541.00068-2021
01 July 2021; volume 7, issue 3ERJ Open Res 7: 00068-2021
In COPD, anaemia is associated with increased morbidity, but the relationship between haemoglobin over its entire observed range and morbidity is poorly understood. Such an understanding could guide future therapeutic targeting of haemoglobin in COPD management. Leveraging the COPDGene study, we conducted a cross-sectional analysis of haemoglobin from COPD participants, examining symptoms, quality of life, functional performance, and acute exacerbations of COPD (AECOPD). Haemoglobin was analysed both as a continuous variable and categorised into anaemia, normal haemoglobin, and polycythaemia groups. Fractional polynomial modelling was used for continuous analyses; categorical models were multivariable linear or negative binomial regressions. Covariates included demographics, comorbidities, emphysema, diffusing capacity, and airflow obstruction. From 2539 participants, 366 (14%) were identified as anaemic and 125 (5%) as polycythaemic. Compared with normal haemoglobin, anaemia was significantly associated with increased symptoms (COPD Assessment Test score: p=0.006, modified Medical Research Council (mMRC) Dyspnoea Score: p=0.001); worse quality of life (St. George's Respiratory Questionnaire (SGRQ) score: p<0.001; Medical Outcomes Study Short Form 36-item Questionnaire (SF-36) General Health: p=0.002; SF-36 Physical Health: p<0.001), decreased functional performance (6-min walk distance (6MWD): p<0.001), and severe AECOPD (p=0.01), while polycythaemia was not. Continuous models, however, demonstrated increased morbidity at both ends of the haemoglobin distribution (p<0.01 for mMRC, SGRQ, SF-36 Physical Health, 6MWD, and severe AECOPD). Evaluating interactions, both diffusing capacity and haemoglobin were independently associated with morbidity. We present novel findings that haemoglobin derangements towards either extreme of the observed range are associated with increased morbidity in COPD. Further investigation is necessary to determine whether haemoglobin derangement drives morbidity or merely reflects systemic inflammation, and whether correcting haemoglobin towards the normal range improves morbidity.
Challenging the obesity paradox: extreme obesity and COPD mortality in the SUMMIT trial
Emily P. Brigham, Julie A. Anderson, Robert D. Brook, Peter M.A. Calverley, Bartolome R. Celli, Nicholas J. Cowans, Courtney Crim, James E. Diserens, Fernando J. Martinez, Meredith C. McCormack, David E. Newby, Julie Yates, Jorgen Vestbo, Tianshi David Wu, Robert A. Wise
doi : 10.1183/23120541.00902-2020
01 July 2020; volume 7, issue 3ERJ Open Res 7: 00902-2020
Populations with COPD demonstrate higher survival in overweight and obese compared with normal weight; the “obesity paradox”. Relationships in less-severe COPD are unclear, as is the impact of cardiovascular risk, and few studies include individuals at extremes of obesity.We examined the relationship between body mass index (BMI; defined as underweight: <20?kg·m?2, normal: 20–25?kg·m?2, overweight: 25–?<30?kg·m?2, obese class I: 30–?<35?kg·m?2, class II: 35–?<40?kg·m?2 and class III: ?40?kg·m?2), morbidity, and mortality in the SUMMIT trial population (n=16?485), characterised by moderate COPD and heightened cardiovascular risk with a substantial proportion with class III obesity. The association between BMI category and time to event was modelled via proportional hazards (reference normal weight) adjusted for demographics and cardiorespiratory disease.
Efficacy and safety of single-inhaler triple therapy of glycopyrronium, formoterol and fluticasone in patients with COPD: a double-blind, randomised controlled trial
Sundeep Salvi, Akash Balki, Srikanth Krishnamurthy, Sagar Panchal, Saiprasad Patil, Rahul Kodgule, Hitesh Khandagale, Amol Pendse, Wen Wu, Shabbir Rangwala, Monika Tandon, Hanmant Barkate
doi : 10.1183/23120541.00255-2021
01 July 2021; volume 7, issue 3ERJ Open Res 7: 00255-2021
Background The aim of this work was to investigate the safety and efficacy of single-inhaler triple therapy with 12.5??g glycopyrronium (GB)/12??g formoterol fumarate (FF)/250??g fluticasone propionate (FP), compared to 50??g GB co-administered with a fixed dose of 12??g FF/250??g FP in subjects with COPD.
High serum granulocyte-colony stimulating factor characterises neutrophilic COPD exacerbations associated with dysbiosis
Arindam Chakrabarti, Jordan S. Mar, David F. Choy, Yi Cao, Nisha Rathore, Xiaoying Yang, Gaik W. Tew, Olga Li, Prescott G. Woodruff, Christopher E. Brightling, Michele Grimbaldeston, Stephanie A. Christenson, Mona Bafadhel, Carrie M. Rosenberger
doi : 10.1183/23120541.00836-2020
01 July 2020; volume 7, issue 3ERJ Open Res 7: 00836-2020
Introduction COPD exacerbations are heterogeneous and can be triggered by bacterial, viral, or noninfectious insults. Exacerbations are also heterogeneous in neutrophilic or eosinophilic inflammatory responses. A noninvasive peripheral biomarker of COPD exacerbations characterised by bacterial/neutrophilic inflammation is lacking. Granulocyte-colony stimulating factor (G-CSF) is a key cytokine elevated during bacterial infection and mediates survival, proliferation, differentiation and function of neutrophils.
The validity of shortened multiple-breath washout testing using sulfur hexafluoride in the assessment of patients with COPD
Enya Daynes, Neil Greening, John Owers-Bradley, Sally J. Singh, Salman Siddiqui
doi : 10.1183/23120541.00379-2020
01 July 2020; volume 7, issue 3ERJ Open Res 7: 00379-2020
Introduction COPD affects the small airways and is associated with ventilation heterogeneity. There are little data on the multiple-breath washout (MBW) in patients with COPD, particularly the variability over 8?weeks, using a shortened sulfur hexafluoride (SF6) washout. This work evaluated the repeatability of the lung clearance index (LCI)1/40 and LCI1/20 among subjects with COPD and compared to spirometry and clinical markers.
Upper airway symptoms associate with the eosinophilic phenotype of COPD
Nicolai Obling, Vibeke Backer, John R. Hurst, Uffe Bodtger
doi : 10.1183/23120541.00184-2021
01 July 2021; volume 7, issue 3ERJ Open Res 7: 00184-2021
Background There is growing evidence that upper airway symptoms coexist with lower airway symptoms in COPD. Still, the prevalence and impact of upper airway disease on the nature and course of COPD remain unclear. We aimed to describe this in a cross-sectional study.Methods We examined a cohort of COPD patients with pulmonary function tests, induced sputum, blood eosinophils, atopy tests and computed tomography (CT) of the paranasal sinuses. Lower airway symptoms were assessed using the COPD Assessment Test (CAT), and upper airway symptoms were assessed using the nasal subdomain of the 22-item Sino Nasal Outcome Test (SNOT22nasal). We recruited patients from five sites in Denmark and Sweden. We excluded patients with a history of asthma.
Accompanied versus unaccompanied walking for continuous oxygen saturation measurement during 6-min walk test in COPD: a randomised crossover study
Thomas F. Riegler, Anja Frei, Sarah R. Haile, Thomas Radtke
doi : 10.1183/23120541.00921-2020
01 July 2020; volume 7, issue 3ERJ Open Res 7: 00921-2020
The aim of this study was to determine if there is a difference in 6-min walk test (6MWT) distance when the assessor accompanies the patient to continuously measure peripheral oxygen saturation (SpO2) compared to the patient walking unaccompanied.
Sex-specific longitudinal association of DNA methylation with lung function
Shadia Khan Sunny, Hongmei Zhang, Caroline L. Relton, Susan Ring, Latha Kadalayil, Fawaz Mzayek, Susan Ewart, John W. Holloway, S. Hasan Arshad
doi : 10.1183/23120541.00127-2021
01 July 2021; volume 7, issue 3ERJ Open Res 7: 00127-2021
Investigating whether DNA methylation (DNA-M) at an earlier age is associated with lung function at a later age and whether this relationship differs by sex could enable prediction of future lung function deficit.A training/testing-based technique was used to screen 402?714 cytosine-phosphate-guanine dinucleotide sites (CpGs) to assess the longitudinal association of blood-based DNA-M at ages 10 and 18?years with lung function at 18 and 26?years, respectively, in the Isle of Wight birth cohort (IOWBC). Multivariable linear mixed models were applied to the CpGs that passed screening. To detect differentially methylated regions (DMRs), DMR enrichment analysis was conducted. Findings were further examined in the Avon Longitudinal Study of Parents and Children (ALSPAC). Biological relevance of the identified CpGs was assessed using gene expression data.
Awake or intubated surgery in diagnosis of interstitial lung diseases? A prospective study
Francesco Guerrera, Lorena Costardi, Giulio L. Rosboch, Paraskevas Lyberis, Edoardo Ceraolo, Paolo Solidoro, Claudia Filippini, Giulia Verri, Luca Brazzi, Carlo Albera, Enrico Ruffini
doi : 10.1183/23120541.00630-2020
01 July 2020; volume 7, issue 3ERJ Open Res 7: 00630-2020
Background Risks associated with video-assisted surgical lung biopsy (VASLB) for interstitial lung disease (ILD) with endotracheal intubation and mechanical ventilation are not nil. Awake video-assisted surgical lung biopsy (Awake-VASLB) has been proposed as a method to obtain a precise diagnosis in several different thoracic diseases.
High but stable incidence of adult-onset asthma in northern Sweden over the last decades
Petri R?is?nen, Helena Backman, Linnea Hedman, Martin Andersson, Caroline Stridsman, Hannu Kankaanranta, Pinja Ilmarinen, Heidi Andersen, P?ivi Piiril?, Anne Lindberg, Bo Lundb?ck, Eva R?nmark
doi : 10.1183/23120541.00262-2021
01 July 2021; volume 7, issue 3ERJ Open Res 7: 00262-2021
Background The prevalence of asthma has increased both among children and adults during the latter half of the 20th century. The prevalence among adults is affected by the incidence of asthma not only in childhood but also in adulthood. Time trends in asthma incidence have been poorly studied.
Incidence and predictors of asthma exacerbations in middle-aged and older adults: the Rotterdam Study
Emmely W. de Roos, Lies Lahousse, Katia M.C. Verhamme, Gert-Jan Braunstahl, Johannes C.C.M. in ‘t Veen, Bruno H. Stricker, Guy G.O. Brusselle
doi : 10.1183/23120541.00126-2021
01 July 2021; volume 7, issue 3ERJ Open Res 7: 00126-2021
Aim The aim of this study was to investigate occurrence and determinants of asthma exacerbations in an ageing general population.Methods Subjects aged 45?years or above with physician-diagnosed asthma in the Rotterdam Study, a population-based prospective cohort from January 1991 to May 2018, were assessed for asthma exacerbations. Exacerbations were defined as acute episodes of worsening asthma treated with oral corticosteroids. Cox proportional hazards analysis was used to investigate risk factors for a future exacerbation.
Airway monocyte modulation relates to tumour necrosis factor dysregulation in neutrophilic asthma
Natalie M. Niessen, Peter G. Gibson, Jodie L. Simpson, Hayley A. Scott, Katherine J. Baines, Michael Fricker
doi : 10.1183/23120541.00131-2021
01 July 2021; volume 7, issue 3ERJ Open Res 7: 00131-2021
Background Dysregulation of tumour necrosis factor-? (TNF-?) signalling is implicated in neutrophilic asthma. TNF-? signalling involves membrane-bound and soluble ligand (TNF-?) and receptors (TNFRs); however, little is known about how these proteins are altered in asthma. We hypothesised that intercompartment-, immune cell- and/or asthma inflammatory phenotype-dependent regulation could relate to TNF dysregulation in neutrophilic asthma.
Upregulation of interleukin-19 in severe asthma: a potential saliva biomarker for asthma severity
Fatemeh Saheb Sharif-Askari, Narjes Saheb Sharif-Askari, Swati Goel, Bassam Mahboub, Abdul Wahid Ansari, Mohamad-Hani Temsah, Adel M. Zakri, Elaref Ratemi, Rifat Hamoudi, Qutayba Hamid, Rabih Halwani
doi : 10.1183/23120541.00984-2020
01 July 2020; volume 7, issue 3ERJ Open Res 7: 00984-2020
Interleukin (IL)-19, a designated IL-20 subfamily cytokine, has been implicated in inflammatory disorders including rheumatoid arthritis, psoriasis and, lately, asthma. Here, through the analysis of transcriptomic datasets of lung tissue of large asthma cohorts, we report that IL-19 expression is upregulated in asthma and correlates with disease severity. The gene expression of IL-19 was significantly higher in lung tissue from patients with severe and mild/moderate asthma compared to healthy controls. IL-19 protein level, however, was significantly higher in the blood and saliva of patients with severe asthma compared to mild/moderate subgroups as measured by ELISA assay. IL-19 protein level was not affected by corticosteroid treatment in plasma. Our data provide insights into the potential use of IL-19 as a saliva marker for asthma severity and a potential therapeutic target.
Delivered dose with jet and mesh nebulisers during spontaneous breathing, noninvasive ventilation and mechanical ventilation using adult lung models
Arzu Ari, James B. Fink
doi : 10.1183/23120541.00027-2021
01 July 2021; volume 7, issue 3ERJ Open Res 7: 00027-2021
What is the delivered dose with jet and mesh nebulisers during spontaneous breathing (SB), noninvasive ventilation (NIV), and mechanical ventilation (MV) using an adult lung model with exhaled humidity (EH)?The delivery of salbutamol sulfate (2.5?mg per 3?mL) with jet (Mistymax10) and mesh nebulisers (Aerogen Solo) was compared during SB, NIV, and MV using breathing parameters (tidal volume 450?mL, respiratory rate 20?breaths per min, inspiratory:expiratory ratio 1:3) with three lung models simulating exhaled humidity. A manikin was attached to a sinusoidal pump via a filter at the bronchi to simulate an adult with SB. A ventilator (V60) was attached via a facemask to a manikin with a filter at the bronchi connected to a test lung to simulate an adult receiving NIV. A ventilator-dependent adult was simulated through a ventilator (Servo-i) operated with a heated humidifier (Fisher & Paykel) attached to an endotracheal tube (ETT) with a heated-wire circuit. The ETT was inserted into a filter (Respirgard II). A heated humidifier was placed between the filter and test lung to simulate exhaled humidity (35±2°C, 100% relative humidity). Nebulisers were placed at the Y-piece of the inspiratory limb during MV and positioned between the facemask and the leak-port during NIV. A mouthpiece was used during SB. The delivered dose was collected in an absolute filter that was attached to the bronchi of the mannequin during each aerosol treatment and measured with spectrophotometry.
The epidemiology of nontuberculous mycobacterial pulmonary disease in the Netherlands
Jodie Anne Schildkraut, Sanne Maria Henriëtte Zweijpfenning, Martijn Nap, Kun He, Elena Dacheva, Jetty Overbeek, Alma Tostmann, Heiman F.L. Wertheim, Wouter Hoefsloot, Jakko van Ingen
doi : 10.1183/23120541.00207-2021
01 July 2021; volume 7, issue 3ERJ Open Res 7: 00207-2021
Background Nontuberculous mycobacteria (NTM) are emerging opportunistic pathogens of humans. Because NTM pulmonary disease (PD) is not a notifiable disease in Europe, the epidemiology of NTM-PD is not well known. However, the prevalence of NTM-PD is thought to be increasing, particularly in countries where tuberculosis rates have decreased. Here we aim to determine the prevalence of NTM-PD in the Netherlands.
Chronic cough is associated with increased reporting of autonomic symptoms
Rachel J. Dockry, Carmen L. Farrelly, Joanne Mitchell, Douglas R. Corfield, Jaclyn A. Smith
doi : 10.1183/23120541.00105-2021
01 July 2021; volume 7, issue 3ERJ Open Res 7: 00105-2021
Background Patients with some neuronal hypersensitivity syndromes experience increased autonomic symptoms. Chronic cough is thought to be a neuronal hypersensitivity disorder and, therefore, may be associated with increased autonomic symptoms.
Adaptive study design to assess effect of TRPV4 inhibition in patients with chronic cough
Valerie J. Ludbrook, Kate E. Hanrott, James L. Kreindler, Joanna E. Marks-Konczalik, Nick P. Bird, Debbie A. Hewens, Misba Beerahee, David J. Behm, Alyn Morice, Lorcan McGarvey, Sean M. Parker, Surinder S. Birring, Jaclyn Smith
doi : 10.1183/23120541.00269-2021
01 July 2021; volume 7, issue 3ERJ Open Res 7: 00269-2021
Objective Airway sensory nerves involved in the cough reflex are activated by adenosine triphosphate (ATP) agonism of P2X purinoceptor 3 (P2X3) receptors. Transient receptor potential vanilloid 4 (TRPV4) channel activation causes ATP release from airway cells, and it is hypothesised that a TRPV4-ATP-P2X3 axis contributes to chronic cough. An adaptive study was run to determine if TRPV4 inhibition, using the selective TRPV4 channel blocker GSK2798745, was effective in reducing cough.
Clinical and research priorities for children and young people with bronchiectasis: an international roadmap
Anne B. Chang, Jeanette Boyd, Leanne Bell, Vikas Goyal, I. Brent Masters, Zena Powell, Christine Wilson, Angela Zacharasiewicz, Efthymia Alexopoulou, Andrew Bush, James D. Chalmers, Rebecca Fortescue, Adam T. Hill, Bulent Karadag, Fabio Midulla, Gabrielle B. McCallum, Deborah Snijders, Woo-Jung Song, Thomy Tonia, Keith Grimwood, Ahmad Kantar
doi : 10.1183/23120541.00122-2021
01 July 2021; volume 7, issue 3ERJ Open Res 7: 00122-2021
The global burden of children and young people (CYP) with bronchiectasis is being recognised increasingly. They experience a poor quality of life and recurrent respiratory exacerbations requiring additional treatment, including hospitalisation. However, there are no published data on patient-driven clinical needs and/or research priorities for paediatric bronchiectasis.
Prevalence of asymptomatic bronchiectasis and associations among the health screening population in South Korea
Soo Han Kim, Young Ju Jung, Myung-Su Ko, Sei Won Lee, Jae Seung Lee, Yeon-Mok Oh
doi : 10.1183/23120541.00188-2021
01 July 2021; volume 7, issue 3ERJ Open Res 7: 00188-2021
Despite the burden of bronchiectasis, there is little data from South Korea regarding asymptomatic bronchiectasis. We aimed to investigate the prevalence of bronchiectasis based on computed tomography (CT) findings, with emphasis on asymptomatic bronchiectasis (CT-proven) and its related factors.
Patients’ perspectives on bronchiectasis: findings from a social media listening study
Irisz Delestre-Levai, Stefano Aliberti, Marta Almagro, Chiara Carnini, James D. Chalmers, Sharath C. George, Soumya Shukla, Alan Timothy, Maria Carmela De Vuono
doi : 10.1183/23120541.00096-2021
01 July 2021; volume 7, issue 3ERJ Open Res 7: 00096-2021
Although it is of great importance for healthcare professionals to ensure that patients’ needs and concerns are valued and that they feel confident in the quality of the care they receive, there have been few studies specifically addressing the opinions, experiences and needs of patients with bronchiectasis, and more importantly the emotional impact of the disease, diagnosis and treatment.
Feasibility of comprehensive genotyping specimens from radial endobronchial ultrasonography and electromagnetic navigation bronchoscopy
Maxime Robin, Laurent Mhanna, Leonor Chaltiel, Gavin Plat, Valentin Héluain, Céline Basset, Julie Meilleroux, Thomas Filleron, Julien Mazières, Christophe Hermant, Nicolas Guibert
doi : 10.1183/23120541.00942-2020
01 July 2020; volume 7, issue 3ERJ Open Res 7: 00942-2020
Introduction Mini-invasive bronchoscopic techniques (such as radial endobronchial ultrasonography (rEBUS) and electromagnetic navigation (EMN)) have been developed to reach the peripheral lung but result in small samples. The feasibility of an adequate molecular testing from these specimens has been very little studied.
Reduced neutrophil elastase inhibitor elafin and elevated transforming growth factor-?1 are linked to inflammatory response in sputum of cystic fibrosis patients with Pseudomonas aeruginosa
Jan C. Thomassen, Tobias Trojan, Maxine Walz, Christina Vohlen, Gregor Fink, Ernst Rietschel, Miguel A. Alejandre Alcazar, Silke van Koningsbruggen-Rietschel
doi : 10.1183/23120541.00636-2020
01 July 2020; volume 7, issue 3ERJ Open Res 7: 00636-2020
Research question Pulmonary disease progression in patients with cystic fibrosis (CF) is characterised by inflammation and fibrosis and aggravated by Pseudomonas aeruginosa (Pa). We investigated the impact of Pa specifically on: 1) protease/antiprotease balance; 2) inflammation; and 3) the link of both parameters to clinical parameters of CF patients.
Cystic fibrosis in South Africa: spectrum of disease and determinants of outcome
Marco Zampoli, Janine Verstraete, Marlize Frauendorf, Reshma Kassanjee, Lesley Workman, Brenda M. Morrow, Heather J. Zar
doi : 10.1183/23120541.00856-2020
01 July 2020; volume 7, issue 3ERJ Open Res 7: 00856-2020
Introduction Little is known about cystic fibrosis (CF) in low- to middle-income settings. This study aimed to describe the spectrum and outcomes of CF in South Africa (SA) from the recently established SA CF registry (SACFR).
Development and validation of a mouse model of contemporary cannabis smoke exposure
Matthew F. Fantauzzi, Steven P. Cass, Joshua J.C. McGrath, Danya Thayaparan, Peiyao Wang, Martin R. Stampfli, Jeremy A. Hirota
doi : 10.1183/23120541.00107-2021
01 July 2021; volume 7, issue 3ERJ Open Res 7: 00107-2021
Cannabis is widely used for both recreational and medicinal purposes. Inhalation of combusted cannabis smoke is the most common mode of drug consumption, exposing the lungs to the pharmacologically active ingredients, including tetrahydrocannabinol (THC) and cannabidiol (CBD). While the relationship between cannabis smoke exposure and compromised respiratory health has yet to be sufficiently defined, previous investigations suggest that cannabis smoke may dysregulate pulmonary immunity. Presently, there exist few preclinical animal models that have been extensively validated for contemporary cannabis smoke exposure.
A novel approach to perioperative risk assessment for patients with pulmonary hypertension
Hussein J. Hassan, Traci Housten, Aparna Balasubramanian, Catherine E. Simpson, Rachel L. Damico, Stephen C. Mathai, Paul M. Hassoun, Jochen Steppan, Peter J. Leary, Todd M. Kolb
doi : 10.1183/23120541.00257-2021
01 July 2021; volume 7, issue 3ERJ Open Res 7: 00257-2021
Rationale Pulmonary hypertension (PH) is associated with significant perioperative morbidity and mortality. We hypothesised that pulmonary arterial hypertension (PAH) composite risk assessment scores could estimate perioperative risk for PH patients when adjusted for inherent procedural risk.
Early risk prediction in idiopathic versus connective tissue disease-associated pulmonary arterial hypertension: call for a refined assessment
Clara Hjalmarsson, Barbro Kjellstr?m, Kjell Jansson, Magnus Nisell, David Kylhammar, Mohammad Kavianipour, G?ran R?degran, Stefan S?derberg, Gerhard Wikstr?m, Dirk M. Wuttge, Roger Hesselstrand
doi : 10.1183/23120541.00854-2020
01 July 2020; volume 7, issue 3ERJ Open Res 7: 00854-2020
Despite systematic screening and improved treatment strategies, the prognosis remains worse in patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) compared to patients with idiopathic/hereditary pulmonary arterial hypertension (IPAH). We aimed to investigate differences in clinical characteristics, outcome and performance of the European Society of Cardiology (ESC)/ European Respiratory Society (ERS) risk stratification tool in these patient groups.
Lung ultrasound assessment for pneumothorax following transbronchial lung cryobiopsy
Christian B. Laursen, Pia I. Pietersen, Niels Jacobsen, Casper Falster, Amanda D. Juul, Jesper R. Davidsen
doi : 10.1183/23120541.00045-2021
01 July 2021; volume 7, issue 3ERJ Open Res 7: 00045-2021
Background Iatrogenic pneumothorax is a common and clinically important transbronchial cryobiopsy (TBCB) complication. A study was conducted to assess the diagnostic accuracy and clinical impact of immediate post-procedure lung ultrasound for diagnosing iatrogenic pneumothorax in patients suspected of interstitial lung disease (ILD) undergoing TBCB.
Quit attempts and tobacco abstinence in primary care patients: follow-up of a pragmatic, two-arm cluster randomised controlled trial on brief stop-smoking advice – ABC versus 5As
Sabrina Kastaun, Wolfgang Viechtbauer, Verena Leve, Jaqueline Hildebrandt, Christian Funke, Stephanie Klosterhalfen, Diana Lubisch, Olaf Reddemann, Tobias Raupach, Stefan Wilm, Daniel Kotz
doi : 10.1183/23120541.00224-2021
01 July 2021; volume 7, issue 3ERJ Open Res 7: 00224-2021
We developed a 3.5-h training for general practitioners (GPs) in delivering brief stop-smoking advice according to different methods (ABC, 5As). In a pragmatic, cluster randomised controlled trial our training proved effective in increasing GP-delivered rates of such advice (from 13% to 33%). In this follow-up analysis we examined the effect of the training and compared ABC versus 5As on patient-reported quit attempts and point prevalence abstinence at weeks 4, 12 and 26 following GP consultation.
Training general practitioners in the ABC versus 5As method of delivering stop-smoking advice: a pragmatic, two-arm cluster randomised controlled trial
Sabrina Kastaun, Verena Leve, Jaqueline Hildebrandt, Christian Funke, Stephanie Klosterhalfen, Diana Lubisch, Olaf Reddemann, Hayden McRobbie, Tobias Raupach, Robert West, Stefan Wilm, Wolfgang Viechtbauer, Daniel Kotz
doi : 10.1183/23120541.00621-2020
01 July 2020; volume 7, issue 3ERJ Open Res 7: 00621-2020
This study assessed the effectiveness of a 3.5-h training session for general practitioners (GPs) in providing brief stop-smoking advice and compared two methods of giving advice – ABC versus 5As – on the rates of delivery of such advice and of recommendations of evidence-based smoking cessation treatment during routine consultations.
Comparing individual and population differences in minute ventilation/carbon dioxide production slopes using centile growth curves and log-linear allometry
Alan M. Nevill, Jonathan Myers, Leonard A. Kaminsky, Ross Arena, Tony D. Myers
doi : 10.1183/23120541.00088-2021
01 July 2021; volume 7, issue 3ERJ Open Res 7: 00088-2021
Identifying vulnerable groups and/or individuals’ cardiorespiratory fitness (CRF) is an important challenge for clinicians/researchers alike. To quantify CRF accurately, the assessment of several variables is now standard practice including maximal oxygen uptake (V?CO2) and ventilatory efficiency, the latter assessed using the minute ventilation/carbon dioxide production (V?E/V?CO2) slope. Recently, reference values (centiles) for V?E/V?CO2 slopes for males and females aged 20 to 80 have been published, using cardiopulmonary exercise testing (CPX) data (treadmill protocol) from the Fitness Registry and the Importance of Exercise National Database (FRIEND Registry).
An adjusted and time-saving method to measure collateral ventilation with Chartis
T. David Koster, Karin Klooster, Hallie McNamara, Narinder S. Shargill, Sri Radhakrishnan, Ryan Olivera, Dirk-Jan Slebos
doi : 10.1183/23120541.00191-2021
01 July 2021; volume 7, issue 3ERJ Open Res 7: 00191-2021
Introduction Bronchoscopic lung volume reduction with endobronchial valves is an important treatment option in selected patients with severe emphysema and absence of collateral ventilation in the treatment target lobe. The Chartis system provides an important physiological assessment of the presence or absence of collateral ventilation. We aimed to evaluate a new feature and determine whether low flow during a Chartis measurement is predictive for the absence of collateral ventilation, and whether this allows for a procedure to be shortened by earlier terminating the Chartis measurement. This is measured with the “volume trend for the previous 20?s” (VT20).
Particle flow rate from the airways as fingerprint diagnostics in mechanical ventilation in the intensive care unit: a randomised controlled study
Filip Hallgren, Martin Stenlo, Anna Niroomand, Ellen Broberg, Snejana Hyllén, Malin Malmsj?, Sandra Lindstedt
doi : 10.1183/23120541.00961-2020
01 July 2020; volume 7, issue 3ERJ Open Res 7: 00961-2020
Introduction Mechanical ventilation can be monitored by analysing particles in exhaled air as measured by particle flow rate (PFR). This could be a potential method of detecting ventilator-induced lung injury (VILI) before changes in conventional parameters can be detected. The aim of this study was to investigate PFR during different ventilation modes in patients without lung pathology.
The role of noninvasive ventilation in the management of type II respiratory failure in patients with myotonic dystrophy
Vilma Rautemaa, Mark E. Roberts, Andrew Bentley, Timothy W. Felton
doi : 10.1183/23120541.00192-2020
01 July 2020; volume 7, issue 3ERJ Open Res 7: 00192-2020
Type 1 myotonic dystrophy (DM1) causes sleep disordered breathing and respiratory failure due to a combination of obstructive sleep apnoea, reduced central drive and respiratory muscle weakness. Noninvasive ventilation (NIV) is commonly used for treating respiratory failure in neuromuscular disease; however, there have been few studies assessing the role of NIV in DM1. The aim of this retrospective service evaluation was to investigate the impact of NIV adherence on hypercapnia and symptoms of hypoventilation in patients with DM1. Data on capillary carbon dioxide tension (PCO2), lung function, adherence to NIV and symptoms of hypoventilation were obtained from the records of 40 patients with DM1. Mean capillary PCO2 significantly reduced from 6.81±1.17?kPa during supervised inpatient set-up to 5.93±0.82?kPa after NIV set-up (p<0.001). NIV adherence reduced from 7.8 (range: 1.0–11.0) h per 24?h during supervised inpatient set-up to 2.9 (0–10.4) h per 24?h in the community. Overall 72% of patients used NIV <5?h per 24?h during follow-up, including 11% who discontinued NIV completely. There was no correlation between adherence to NIV and changes in capillary PCO2. Patients who reported symptomatic benefit (50%) had higher adherence than those who did not feel benefit (p<0.05). In conclusion, in patients with myotonic dystrophy with Type II respiratory failure maintaining adherence is challenging.
International BEAT-PCD consensus statement for infection prevention and control for primary ciliary dyskinesia in collaboration with ERN-LUNG PCD Core Network and patient representatives
June K. Marthin, Jane S. Lucas, Mieke Boon, Carmen Casaulta, Suzanne Crowley, Damien M.S. Destouches, Ernst Eber, Amparo Escribano, Eric Haarman, Claire Hogg, Bernard Maitre, Gemma Marsh, Vendula Martinu, Antonio Moreno-Gald?, Huda Mussaffi, Heymut Omran, Petr Pohunek, Bernhard Rindlisbacher, Phil Robinson, Deborah Snijders, Woolf T. Walker, Panayiotis Yiallouros, Helle Krogh Johansen, Kim G. Nielsen
doi : 10.1183/23120541.00301-2021
01 July 2021; volume 7, issue 3ERJ Open Res 7: 00301-2021
Introduction In primary ciliary dyskinesia (PCD) impaired mucociliary clearance leads to recurrent airway infections and progressive lung destruction, and concern over chronic airway infection and patient-to-patient transmission is considerable. So far, there has been no defined consensus on how to control infection across centres caring for patients with PCD. Within the BEAT-PCD network, COST Action and ERS CRC together with the ERN-Lung PCD core a first initiative has now been taken towards creating such a consensus statement.
Ventricular arrhythmia in heart failure patients with reduced ejection fraction and central sleep apnoea
Christoph Fisser, Jannis Bureck, Lara Gall, Victoria Vaas, J?rg Priefert, Sabine Fredersdorf, Florian Zeman, Dominik Linz, Holger W?hrle, Renaud Tamisier, Helmut Teschler, Martin R. Cowie, Michael Arzt
doi : 10.1183/23120541.00147-2021
01 July 2021; volume 7, issue 3ERJ Open Res 7: 00147-2021
Cheyne–Stokes respiration (CSR) may trigger ventricular arrhythmia in patients with heart failure with reduced ejection fraction (HFrEF) and central sleep apnoea (CSA). This study determined the prevalence and predictors of a high nocturnal ventricular arrhythmia burden in patients with HFrEF and CSA (with and without CSR) and to evaluate the temporal association between CSR and the ventricular arrhythmia burden.
Compatibility of a novel filter paper-based bio-safe sputum transport kit with line probe assay for diagnosing drug-resistant tuberculosis: a single-site evaluation study
Divya Anthwal, Rakesh Kumar Gupta, Ritu Singhal, Manpreet Bhalla, Ajoy Kumar Verma, Khalid Umar Khayyam, Vithal Prasad Myneedu, Rohit Sarin, Ashawant Gupta, Nalini Kant Gupta, Manjula Singh, Jaya Sivaswami Tyagi, Sagarika Haldar
doi : 10.1183/23120541.00137-2021
01 July 2021; volume 7, issue 3ERJ Open Res 7: 00137-2021
Background Near-patient access to appropriate tests is a major obstacle for the efficient diagnosis of tuberculosis (TB) and associated drug resistance.Methods We recently developed the “TB Concentration & Transport” kit for bio-safe, ambient-temperature transportation of dried sputum on Trans-Filter, and the “TB DNA Extraction” kit for DNA extraction from Trans-Filter for determining drug resistance by DNA sequencing. In the present study, we evaluated the compatibility of Kit-extracted DNA with Hain's line probe assays (LPAs), which are endorsed by National TB programmes for the detection of drug resistance in sputum collected from presumptive multidrug-resistant TB patients (n=207).
Vaping-induced metabolomic signatures in the circulation of mice are driven by device type, e-liquid, exposure duration and sex
Alexander Moshensky, Mulong Du, John Shin, Ira Advani, Deepti Gunge, Denzil Mathew, Rita Alkolla, Ashley Du, Christian Javier, Lauren Ma, Albert Tran, Nicholas Nguyen, Jarod Olay, Sedtavut Nilaad, Jeffrey Ding, Mahan Najhawan, Jeramie D. Watrous, Christine M. Bojanowksi, Mohit Jain, David C. Christiani, Laura E. Crotty Alexander
doi : 10.1183/23120541.00229-2021
01 July 2021; volume 7, issue 3ERJ Open Res 7: 00229-2021
COVID-19 6 months after hospital discharge: pulmonary function impairment and its heterogeneity
Manlio Milanese, Marco Anselmo, Sandra Buscaglia, Luca Garra, Riccardo Goretti, Lionello Parodi, Giovanni Riccio, Rodolfo Tassara, Paola Gnerre
doi : 10.1183/23120541.00196-2021
01 July 2021; volume 7, issue 3ERJ Open Res 7: 00196-2021
Swallow patterns associated with aspiration in COPD: a prospective analysis
Lydia Cvejic, Nadine Guiney, Kenneth K. Lau, Paul Finlay, Kais Hamza, Paul Leong, Martin MacDonald, Paul T. King, Philip G. Bardin
doi : 10.1183/23120541.00170-2021
01 July 2021; volume 7, issue 3ERJ Open Res 7: 00170-2021
A 3-month period of electronic monitoring can provide important information to the healthcare team to assess adherence and improve asthma control
Anja Jochmann, Luca Artusio, Jakob Usemann, Angela Jamalzadeh, Andrew Bush, Urs Frey, Louise J. Fleming
doi : 10.1183/23120541.00726-2020
01 July 2020; volume 7, issue 3ERJ Open Res 7: 00726-2020
Increased circulating levels of angiotensin-(1–7) in severely ill COVID-19 patients
Ana Luiza Valle Martins, Filipe Alex da Silva, Lucas Bolais-Ramos, Gisele Capanema de Oliveira, Renata Cunha Ribeiro, Danilo Augusto Alves Pereira, Filippo Annoni, Mirella Monique Lana Diniz, Thuanny Granato Fonseca Silva, Bruna Zivianni, Alexandre Carvalho Cardoso, Juliana Carvalho Martins, Daisy Motta-Santos, Maria José Campagnole-Santos, Fabio Silvio Taccone, Thiago Verano-Braga, Robson Augusto Souza Santos
doi : 10.1183/23120541.00114-2021
01 July 2021; volume 7, issue 3ERJ Open Res 7: 00114-2021
“Comparison between traditional and nontraditional add-on devices used with pressurised metered-dose inhalers”. Mina Nicola, Youssef M.A. Soliman, Raghda Hussein, Haitham Saeed and Mohamed Abdelrahim. ERJ Open Res 2020; 6: 00073-2020.
doi : 10.1183/23120541.50073-2020
01 July 2020; volume 7, issue 3ERJ Open Res 7: 50073-2020
