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Estação Científica (UNIFAP)
Number of Followers: 0  

  This is an Open Access Journal Open Access journal
ISSN (Print) 2179-1902
Published by Universidade Federal do Amapá Homepage  [10 journals]
  • Trimer IgG and neutralising antibody response to COVID-19 mRNA vaccination
           in individuals with sarcoidosis

    • Authors: Vagts, C. L; Chang, Y.-S, Ascoli, C, Lee, J. M, Huang, K, Huang, Y, Cherian, R. A, Sarup, N, Warpecha, S. R, Edafetanure-Ibeh, R, Amin, M.-R, Sultana, T, Ghassemi, M, Sweiss, N. J, Novak, R, Perkins, D. L, Finn, P. W.
      Pages: 00025-2022 - 25-2022
      Abstract: BackgroundIndividuals with sarcoidosis are at higher risk for infection owing to underlying disease pathogenesis and need for immunosuppressive treatment. Current knowledge as to how subjects with sarcoidosis respond to different forms of vaccination is limited. We examined quantitative and functional antibody response to COVID-19 vaccination in infection-naive subjects with and without sarcoidosis.MethodsOur prospective cohort study recruited 14 subjects with biopsy-proven sarcoidosis and 27 age–sex matched controls who underwent a two-shot series of the BNT162b2 mRNA vaccine at the University of Illinois at Chicago. Baseline, 4-week and 6-month trimer spike protein IgG and neutralising antibody (nAb) titres were assessed. Correlation and multivariate regression analysis was conducted.ResultsSarcoidosis subjects had a significant increase in short-term antibody production to a level comparable to controls; however, IgG titres significantly declined back to baseline levels by 6 months. Corresponding neutralising assays revealed robust nAb titres in sarcoidosis subjects that persisted at 6 months. A significant and strong correlation between IgG and nAb titres across all time points was observed in the control group. However within the sarcoidosis group, a significant but weak correlation between antibody levels was found. Overall, IgG levels were poor predictors of nAb titres at short- or long-term time points.ConclusionsSarcoidosis subjects exhibit nAb induced by the BNT162b2 mRNA SARS-CoV-2 vaccine at levels comparable to controls that persists at 6 months indicating conferred immunity. Trimer IgG levels are poor predictors of nAb in subjects with sarcoidosis. Studies of further antibody immunoglobulins and subtypes warrant investigation.
      Keywords: Interstitial and orphan lung disease, Respiratory infections and tuberculosis
      PubDate: 2023-01-03T00:29:59-08:00
      DOI: 10.1183/23120541.00025-2022
      Issue No: Vol. 9, No. 1 (2023)
  • The use of lung ultrasound in COVID-19

    • Authors: Blazic, I; Cogliati, C, Flor, N, Frija, G, Kawooya, M, Umbrello, M, Ali, S, Baranne, M.-L, Cho, Y.-J, Pitcher, R, Vollmer, I, van Deventer, E, del Rosario Perez, M.
      Pages: 00196-2022 - 196-2022
      Abstract: This review article addresses the role of lung ultrasound in patients with coronavirus disease 2019 (COVID-19) for diagnosis and disease management. As a simple imaging procedure, lung ultrasound contributes to the early identification of patients with clinical conditions suggestive of COVID-19, supports decisions about hospital admission and informs therapeutic strategy. It can be performed in various clinical settings (primary care facilities, emergency departments, hospital wards, intensive care units), but also in outpatient settings using portable devices.The article describes typical lung ultrasound findings for COVID-19 pneumonia (interstitial pattern, pleural abnormalities and consolidations), as one component of COVID-19 diagnostic workup that otherwise includes clinical and laboratory evaluation. Advantages and limitations of lung ultrasound use in COVID-19 are described, along with equipment requirements and training needs. To infer on the use of lung ultrasound in different regions, a literature search was performed using key words "COVID-19", "lung ultrasound" and "imaging".Lung ultrasound is a noninvasive, rapid and reproducible procedure; can be performed at the point of care; requires simple sterilisation; and involves non-ionising radiation, allowing repeated exams on the same patient, with special benefit in children and pregnant women. However, physical proximity between the patient and the ultrasound operator is a limitation in the current pandemic context, emphasising the need to implement specific infection prevention and control measures.Availability of qualified staff adequately trained to perform lung ultrasound remains a major barrier to lung ultrasound utilisation. Training, advocacy and awareness rising can help build up capacities of local providers to facilitate lung ultrasound use for COVID-19 management, in particular in low- and middle-income countries.
      Keywords: Lung imaging, Respiratory infections and tuberculosis
      PubDate: 2023-01-09T00:30:15-08:00
      DOI: 10.1183/23120541.00196-2022
      Issue No: Vol. 9, No. 1 (2023)
  • COVID-19 in patients with pulmonary alveolar proteinosis: a European
           multicentre study

    • Authors: Papiris, S. A; Campo, I, Mariani, F, Kallieri, M, Kolilekas, L, Papaioannou, A. I, Gonca Chousein, E, Cetinkaya, E, Bonella, F, Borie, R, Kokosi, M, Pickworth, T, Molina-Molina, M, Gasa, M, Radzikowska, E, Fijolek, J, Jouneau, S, Gomez, E, McCarthy, C, Bendstrup, E, Piotrowski, W. J, Pabary, R, Hadchouel, A, Coolen-Allou, N, Alfaro, T, Robalo Cordeiro, C, Antonogiannaki, E.-M, Tomos, I. P, Papakosta, D, Kontakiotis, T, Panagiotou, P, Douros, K, Schams, A, Lettieri, S, Papaevangelou, V, Kanaka-Gantenbein, C, Karakatsani, A, Loukides, S, Costabel, U, Crestani, B, Morgan, C, Tazawa, R, Bush, A, Griese, M, Manali, E. D.
      Pages: 00199-2022 - 199-2022
      Abstract: Granulocyte–macrophage colony-stimulating factor (GM-CSF) signalling is essential in both alveolar macrophage (AM) differentiation and activation of lung immune cells [1]. Differentiated AMs are crucial in both the elimination of alveolar microbes and surfactant clearance. The disruption of the GM-CSF axis in AMs leads to the development of pulmonary alveolar proteinosis (PAP) [1]. In the majority of patients, this relates to the presence of autoantibodies against GM-CSF (autoimmune (a)PAP) but there are multiple other causes [1–3]. GM-CSF-deficient animals may have impaired lung inflammatory response to commensal microbes and humans with PAP may occasionally develop opportunistic lung infections [4]. The mainstay of pharmacological treatment in aPAP is inhaled GM-CSF (iGM-CSF), which is off-label but increasingly used worldwide [5–9].
      Keywords: Interstitial and orphan lung disease, Respiratory infections and tuberculosis
      PubDate: 2023-01-03T00:29:59-08:00
      DOI: 10.1183/23120541.00199-2022
      Issue No: Vol. 9, No. 1 (2023)
  • All-cause admissions following a first ever exacerbation-related
           hospitalisation in COPD

    • Authors: Waeijen-Smit, K; Jacobsen, P. A, Houben-Wilke, S, Simons, S. O, Franssen, F. M. E, Spruit, M. A, Pedersen, C. T, Kragholm, K. H, Weinreich, U. M.
      Pages: 00217-2022 - 217-2022
      Abstract: BackgroundHospital admissions are important contributors to the overall burden of chronic obstructive pulmonary disease (COPD). Understanding the patterns and causes of hospital admissions will help to identify targets for preventive interventions. This study aimed to determine the 5-year all-cause hospital admission trajectories of patients with COPD following their first ever exacerbation-related hospitalisation.MethodsPatients with COPD were identified from the Danish national registries. Patients experiencing their first ever exacerbation-related hospitalisation, defined as the index event, between 2000 and 2014 were included. All-cause hospital admissions were examined during a subsequent 5-year follow-up period, and categorised using the International Classification of Diseases, 10th revision.ResultsIn total, 82 964 patients with COPD were included. The mean±sd age was 72±10 years and 48% were male. Comorbidities were present in 58%, and 65% of the patients collected inhalation medication ≤6 months prior to the index event. In total, 337 066 all-cause hospital admissions were identified, resulting in a 5-year admission rate of 82%. Most admissions were due to nonrespiratory causes (59%), amongst which cardiac events were most common (19%).ConclusionHospital admissions following a first exacerbation-related hospitalisation are common; nonrespiratory events constitute the majority of admissions. Besides the respiratory causes, treatment targeting the nonrespiratory causes of hospital admission should be considered to effectively decrease the burden of hospitalisation in COPD.
      Keywords: COPD and smoking
      PubDate: 2023-01-03T00:29:59-08:00
      DOI: 10.1183/23120541.00217-2022
      Issue No: Vol. 9, No. 1 (2023)
  • Characteristics and risk factors for post-COVID-19 breathlessness after
           hospitalisation for COVID-19

    • Authors: Daines, L; Zheng, B, Elneima, O, Harrison, E, Lone, N. I, Hurst, J. R, Brown, J. S, Sapey, E, Chalmers, J. D, Quint, J. K, Pfeffer, P, Siddiqui, S, Walker, S, Poinasamy, K, McAuley, H, Sereno, M, Shikotra, A, Singapuri, A, Docherty, A. B, Marks, M, Toshner, M, Howard, L. S, Horsley, A, Jenkins, G, Porter, J. C, Ho, L.-P, Raman, B, Wain, L. V, Brightling, C. E, Evans, R. A, Heaney, L. G, De Soyza, A, Sheikh, A, on behalf of the PHOSP-COVID Study Collaborative Group
      Pages: 00274-2022 - 274-2022
      Abstract: BackgroundPersistence of respiratory symptoms, particularly breathlessness, after acute coronavirus disease 2019 (COVID-19) infection has emerged as a significant clinical problem. We aimed to characterise and identify risk factors for patients with persistent breathlessness following COVID-19 hospitalisation.MethodsPHOSP-COVID is a multicentre prospective cohort study of UK adults hospitalised for COVID-19. Clinical data were collected during hospitalisation and at a follow-up visit. Breathlessness was measured by a numeric rating scale of 0–10. We defined post-COVID-19 breathlessness as an increase in score of ≥1 compared to the pre-COVID-19 level. Multivariable logistic regression was used to identify risk factors and to develop a prediction model for post-COVID-19 breathlessness.ResultsWe included 1226 participants (37% female, median age 59 years, 22% mechanically ventilated). At a median 5 months after discharge, 50% reported post-COVID-19 breathlessness. Risk factors for post-COVID-19 breathlessness were socioeconomic deprivation (adjusted OR 1.67, 95% CI 1.14–2.44), pre-existing depression/anxiety (adjusted OR 1.58, 95% CI 1.06–2.35), female sex (adjusted OR 1.56, 95% CI 1.21–2.00) and admission duration (adjusted OR 1.01, 95% CI 1.00–1.02). Black ethnicity (adjusted OR 0.56, 95% CI 0.35–0.89) and older age groups (adjusted OR 0.31, 95% CI 0.14–0.66) were less likely to report post-COVID-19 breathlessness. Post-COVID-19 breathlessness was associated with worse performance on the shuttle walk test and forced vital capacity, but not with obstructive airflow limitation. The prediction model had fair discrimination (concordance statistic 0.66, 95% CI 0.63–0.69) and good calibration (calibration slope 1.00, 95% CI 0.80–1.21).ConclusionsPost-COVID-19 breathlessness was commonly reported in this national cohort of patients hospitalised for COVID-19 and is likely to be a multifactorial problem with physical and emotional components.
      Keywords: Respiratory infections and tuberculosis
      PubDate: 2023-02-20T06:30:28-08:00
      DOI: 10.1183/23120541.00274-2022
      Issue No: Vol. 9, No. 1 (2023)
  • Validation of a small cough detector

    • Authors: Kuhn, M; Nalbant, E, Kohlbrenner, D, Alge, M, Kuett, L, Arvaji, A, Sievi, N. A, Russi, E. W, Clarenbach, C. F.
      Pages: 00279-2022 - 279-2022
      Abstract: Research questionThe assessment of cough frequency in clinical practice relies predominantly on the patient's history. Currently, objective evaluation of cough is feasible with bulky equipment during a brief time (i.e. hours up to 1 day). Thus, monitoring of cough has been rarely performed outside clinical studies. We developed a small wearable cough detector (SIVA-P3) that uses deep neural networks for the automatic counting of coughs. This study examined the performance of the SIVA-P3 in an outpatient setting.MethodsWe recorded cough epochs with SIVA-P3 over eight consecutive days in patients suffering from chronic cough. During the first 24 h, the detector was validated against cough events counted by trained human listeners. The wearing comfort and the device usage were assessed using a questionnaire.ResultsIn total, 27 participants (mean±sd age 50±14 years) with either chronic unexplained cough (n=12), COPD (n=4), asthma (n=5) or interstitial lung disease (n=6) were studied. During the daytime, the sensitivity of SIVA-P3 cough detection was 88.5±2.49% and the specificity was 99.97±0.01%. During the night-time, the sensitivity was 84.15±5.04% and the specificity was 99.97±0.02%. The wearing comfort and usage of the device was rated as very high by most participants.ConclusionSIVA-P3 enables automatic continuous cough monitoring in an outpatient setting for objective assessment of cough over days and weeks. It shows comparable sensitivity or higher sensitivity than other devices with fully automatic cough counting. Thanks to its wearing comfort and the high performance for cough detection, it has the potential for being used in routine clinical practice.
      PubDate: 2023-01-23T00:30:20-08:00
      DOI: 10.1183/23120541.00279-2022
      Issue No: Vol. 9, No. 1 (2023)
  • Artificial intelligence based software facilitates spirometry quality
           control in asthma and COPD clinical trials

    • Authors: Topole, E; Biondaro, S, Montagna, I, Corre, S, Corradi, M, Stanojevic, S, Graham, B, Das, N, Ray, K, Topalovic, M.
      Pages: 00292-2022 - 292-2022
      Abstract: RationaleAcquiring high-quality spirometry data in clinical trials is important, particularly when using forced expiratory volume in 1 s or forced vital capacity as primary end-points. In addition to quantitative criteria, the American Thoracic Society (ATS)/European Respiratory Society (ERS) standards include subjective evaluation which introduces inter-rater variability and potential mistakes. We explored the value of artificial intelligence (AI)-based software (ArtiQ.QC) to assess spirometry quality and compared it to traditional over-reading control.MethodsA random sample of 2000 sessions (8258 curves) was selected from Chiesi COPD and asthma trials (n=1000 per disease). Acceptability using the 2005 ATS/ERS standards was determined by over-reader review and by ArtiQ.QC. Additionally, three respiratory physicians jointly reviewed a subset of curves (n=150).ResultsThe majority of curves (n=7267, 88%) were of good quality. The AI agreed with over-readers in 91% of cases, with 97% sensitivity and 93% positive predictive value. Performance was significantly better in the asthma group. In the revised subset, n=50 curves were repeated to assess intra-rater reliability (=0.83, 0.86 and 0.80 for each of the three reviewers). All reviewers agreed on 63% of 100 unique tests (=0.5). When reviewers set the consensus (gold standard), individual agreement with it was 88%, 94% and 70%. The agreement between AI and "gold-standard" was 73%; over-reader agreement was 46%.ConclusionAI-based software can be used to measure spirometry data quality with comparable accuracy as experts. The assessment is a subjective exercise, with intra- and inter-rater variability even when the criteria are defined very precisely and objectively. By providing consistent results and immediate feedback to the sites, AI may benefit clinical trial conduct and variability reduction.
      Keywords: COPD and smoking, Asthma and allergy
      PubDate: 2023-01-03T00:29:59-08:00
      DOI: 10.1183/23120541.00292-2022
      Issue No: Vol. 9, No. 1 (2023)
  • Pulmonary Hypertension and Measurement of Exercise Capacity Remotely:
           Evaluation of the 1-min Sit-to-Stand Test (PERSPIRE) - a cohort study

    • Authors: Keen, C; Smith, I, Hashmi-Greenwood, M, Sage, K, Kiely, D. G.
      Pages: 00295-2022 - 295-2022
      Abstract: BackgroundMultiparameter risk assessment is recommended to aid treatment decisions in patients with pulmonary arterial hypertension. The 1-min sit-to-stand test (1MSTS) has been validated for use in other respiratory illnesses. The aim of this study was to evaluate its safety in the hospital setting and potential utility in remote assessment in patients with pulmonary hypertension.MethodsIn a prospective cohort study design patients performed the 1MSTS and incremental shuttle walk test (ISWT) on the same day. The primary aim of the study was to assess safety signals and correlations with other metrics used in risk assessment.Results60 patients with pulmonary arterial hypertension and 15 with chronic thromboembolic pulmonary hypertension were enrolled. No adverse events were recorded. Post-test change in physiological parameters was lower for the 1MSTS than for the ISWT in heart rate (mean±sd change +9.4±8.0 versus +38.3±25.9 beats per min, p
      Keywords: Pulmonary vascular disease
      PubDate: 2023-01-23T00:30:20-08:00
      DOI: 10.1183/23120541.00295-2022
      Issue No: Vol. 9, No. 1 (2023)
  • Multimorbidity in bronchiectasis: a systematic scoping review

    • Authors: Marsland, I; Sobala, R, De Soyza, A, Witham, M.
      Pages: 00296-2022 - 296-2022
      Abstract: IntroductionMultimorbidity, the coexistence of two or more chronic conditions, has been extensively studied in certain disease states. Bronchiectasis aetiology is complex and multimorbidity is insufficiently understood. We performed a scoping review, summarising the existing literature and identifying deficits.MethodA literature search of the electronic databases PubMed, CINAHL and EMBASE was conducted following PRISMA guidelines. Observational, interventional, qualitative, randomised control trials and systematic reviews were included. The main objective was to identify prevalence, prognosis, symptoms, quality of life and management in bronchiectasis multimorbidity. Key findings were analysed descriptively.Results40 studies (200 567 patients) met the inclusion criteria, the majority (68%) being cohort studies. Study size ranged from 25 to 57 576 patients, with mean age 30–69 years. 70% of studies investigated the prognosis of comorbidities and 68% prevalence; 70% analysed multiple comorbidities in bronchiectasis. The most frequent comorbid diseases evaluated were COPD (58%), cardiovascular disease (53%) and asthma (40%). COPD and hypertension were the most prevalent conditions (pooled mean 35% and 34% respectively). Multimorbidity was associated with increased mortality, exacerbations and hospitalisation rates. It had a negative impact on lung function. Mortality increased in the following comorbidities: COPD, gastro-oesophageal reflux disease and rheumatoid arthritis.ConclusionBronchiectasis multimorbidity is common. Research focuses on a few key aspects and favoured comorbidities (e.g. COPD). There is a deficit of research into symptoms, quality of life, interactions and management. High-resolution computed tomography diagnosis is not consistent, and there is no agreed multimorbidity screening questionnaire. Bronchiectasis multimorbidity is of importance; it is associated with morbidity and mortality.
      Keywords: CF and non-CF bronchiectasis
      PubDate: 2023-01-16T00:30:16-08:00
      DOI: 10.1183/23120541.00296-2022
      Issue No: Vol. 9, No. 1 (2023)
  • Biomarker-based clustering of patients with chronic obstructive pulmonary

    • Authors: Vanfleteren, L. E. G. W; Weidner, J, Franssen, F. M. E, Gaffron, S, Reynaert, N. L, Wouters, E. F. M, Spruit, M. A.
      Pages: 00301-2022 - 301-2022
      Abstract: RationaleCOPD has been associated repeatedly with single biomarkers of systemic inflammation, ignoring the complexity of inflammatory pathways. This study aimed to cluster patients with COPD based on systemic markers of inflammatory processes and to evaluate differences in their clinical characterisation and examine how these differences may relate to altered biological pathways.Methods213 patients with moderate-to-severe COPD in a clinically stable state were recruited and clinically characterised, which included a venous blood sample for analysis of serum biomarkers. Patients were clustered based on the overall similarity in systemic levels of 57 different biomarkers. To determine interactions among the regulated biomarkers, protein networks and biological pathways were examined for each patient cluster.ResultsFour clusters were identified: two clusters with lower biomarker levels (I and II) and two clusters with higher biomarker levels (III and IV), with only a small number of biomarkers with similar trends in expression. Pathway analysis indicated that three of the four clusters were enriched in Rage (receptor for advanced glycation end-products) and Oncostatin M pathway components. Although the degree of airflow limitation was similar, the clinical characterisation of clusters ranged from 1) better functional capacity and health status and fewer comorbidities; 2) more underweight, osteoporosis and static hyperinflation; 3) more metabolically deranged; and 4) older subjects with worse functional capacity and higher comorbidity load.ConclusionsThese new insights may help to understand the functionally relevant inflammatory interactions in the pathophysiology of COPD as a heterogeneous disease.
      Keywords: COPD and smoking
      PubDate: 2023-02-06T00:30:25-08:00
      DOI: 10.1183/23120541.00301-2022
      Issue No: Vol. 9, No. 1 (2023)
  • Use of inhaled ipratropium bromide to improve exercise-induced laryngeal
           obstruction cannot be recommended

    • Authors: Muralitharan, P; Carlsen, P, Hilland, M, Delestre-Levai, I, Vollsaeter, M, Hufthammer, K. O, Engan, M, Roksund, O. D, Halvorsen, T, Clemm, H. H.
      Pages: 00308-2022 - 308-2022
      Abstract: IntroductionExercise-induced laryngeal obstruction (EILO) is a common cause of exertional breathing problems in young adults. Current management generally consists of breathing advice, speech therapy, inspiratory muscle training or supraglottoplasty in highly motivated subjects with supraglottic collapse. Inhaled ipratropium bromide (IB) is a muscarinic receptor antagonist used to treat asthma that is suggested in a few reports to improve EILO symptoms. The aim of the present study was to investigate effects of inhaled IB in EILO diagnosed by continuous laryngoscopy exercise (CLE) test and classified by CLE scores.MethodsA randomised crossover trial was conducted at Haukeland University Hospital, Bergen, Norway, enrolling participants diagnosed with EILO defined by characteristic symptoms and CLE score ≥3 (range 0–12). Two consecutive CLE tests were performed within 2 weeks, one test with and one test without prior administration of inhaled IB in a randomised order. Main outcomes were the CLE score, dyspnoea measured using a modified BORG scale (range 0–10) and cardiopulmonary exercise data provided by the CLE test.Results20 participants (14 females) aged 12–25 years participated, and all ran to exhaustion on both tests. Mean CLE score, BORG score and peak oxygen consumption were similar in tests performed with and without IB; mean differences (95% confidence interval) were 0.08 (–0.28–0.43), 0.35 (–0.29–0.99) and –0.4 (–1.9–1.1) mL·kg–1·min–1, respectively.ConclusionInhaled IB did not improve CLE score, dyspnoea or exercise capacity in subjects with EILO. The study does not support the use of inhaled IB to treat EILO.
      Keywords: Pulmonary pharmacology and therapeutics
      PubDate: 2023-01-23T00:30:20-08:00
      DOI: 10.1183/23120541.00308-2022
      Issue No: Vol. 9, No. 1 (2023)
  • Exertional oscillatory ventilation in subjects without heart failure
           reporting chronic dyspnoea

    • Authors: Neder, J. A; Rocha, A, Arbex, F. F, Alencar, M. C. N, Sperandio, P. A, Hirai, D. M, Berton, D. C.
      Pages: 00324-2022 - 324-2022
      Abstract: The persistence of limiting breathlessness in a patient who is thought to be under the maximal available therapy for their underlying cardiovascular and/or respiratory disease(s) has been termed residual exertional dyspnoea (RED) [1]. RED remains a challenge to the modern pulmonologist because the patient (and the referring physician) assumes that the "lung doctor" should invariably provide an effective plan to fight the symptom. A sizable fraction of these subjects is eventually referred for cardiopulmonary exercise testing (CPET) in the hope that the test will shed light on the underlying mechanisms [2]. We herein report a series of carefully selected subjects with RED in whom CPET uncovered cycles of waxing and waning of ventilation (V'E) meeting the extant criteria for exertional oscillatory ventilation (EOV) [3]. Rather surprisingly, no subject had heart failure (HF) with reduced (r), mid-range or preserved ejection fraction (EF), i.e. the diseases traditionally related to EOV [4]. Although it is already known that EOV may occur in subjects without HF [5], the presence of EOV in non-HF subjects with RED has never been described.
      PubDate: 2023-01-30T00:30:21-08:00
      DOI: 10.1183/23120541.00324-2022
      Issue No: Vol. 9, No. 1 (2023)
  • Apnoea-hypopnoea index of 5 events{middle dot}h-1 as a metabolomic
           threshold in patients with sleep complaints

    • Authors: Kiens, O; Taalberg, E, Ivanova, V, Veeväli, K, Laurits, T, Tamm, R, Ottas, A, Kilk, K, Soomets, U, Altraja, A.
      Pages: 00325-2022 - 325-2022
      Abstract: BackgroundThe apnoea–hypopnoea index (AHI) forms the basis for severity of obstructive sleep apnoea (OSA), a condition expected to reprogramme metabolic pathways in humans. We aimed to identify the AHI breakpoint from which the majority of significant changes in the systemic metabolome of patients with sleep complaints occur.MethodsIn a prospective observational study on symptomatic individuals, who underwent polysomnography for the diagnosis of OSA, profiles of 187 metabolites including amino acids, biogenic amines, acylcarnitines, lysophosphatidylcholines, phosphatidylcholines and sphingomyelins were analysed with liquid chromatography mass spectrometry in peripheral blood drawn at three different time points overnight. Comparisons of rank-transformed data using a general linear model for repeated measures after dichotomising the study group at different AHI levels were applied to define the best cut-off based on Cohen's f.Results65 subjects were recruited with a median AHI of 15.6 events·h–1. The mean Cohen's f over the metabolites was highest (0.161) at an AHI level of 5 events·h–1 representing the metabolomic threshold. Of the particular between-group differences, eight phosphatidylcholines, nine acylcarnitines and one amino acid (threonine) had significantly lower concentrations in the individuals with an AHI level equal to or above the metabolomic threshold. The metabolomic changes at AHI levels defining moderate and severe OSA were smaller than at an AHI of 5 events·h–1.ConclusionsThe metabolomic threshold for patients with sleep complaints described in this report for the first time coincides with the AHI threshold required to confirm the diagnosis of OSA.
      Keywords: Sleep medicine
      PubDate: 2023-01-09T00:30:15-08:00
      DOI: 10.1183/23120541.00325-2022
      Issue No: Vol. 9, No. 1 (2023)
  • Inspiratory muscle strength and function in mechanically ventilated
           COVID-19 survivors 3 and 6 months after intensive care unit discharge

    • Authors: Nunez-Seisdedos, M. N; Valcarcel-Linares, D, Gomez-Gonzalez, M. T, Lazaro-Navas, I, Lopez-Gonzalez, L, Pecos-Martin, D, Rodriguez-Costa, I.
      Pages: 00329-2022 - 329-2022
      Abstract: BackgroundKnowledge regarding the long-term impact of invasive mechanical ventilation on the inspiratory muscles and functional outcomes in COVID-19 survivors is limited.MethodsIn this single-centre prospective cohort study, we evaluated invasively ventilated patients with COVID-19 pneumonia 3 and 6 months post-intensive care unit (ICU) discharge. Outcomes included: maximal inspiratory pressure (MIP), ultrasound parameters for diaphragm function, 6-min walk distance (6MWD), dyspnoea and quality of life. We evaluated associations between MIP and duration of mechanical ventilation with follow-up outcomes.Results50 COVID-19 survivors discharged from ICU between 15 October 2020 and 1 April 2021 were enrolled. Overall, survivors showed a recovery trajectory over time. However, impaired MIP remained in 24 (48%) and 12 (24%) at 3 and 6 months, respectively. Diaphragm dysfunction was not observed. At 3 months, 23 (46%) had impaired functional capacity versus 10 (20%) at 6 months. Dyspnoea persisted in 44 (88%) patients at 3 months and 38 (76%) at 6 months. Quality of life was slightly decreased at 3 months with further improvements at 6 months. MIP was correlated to 6MWD, 6MWD % predicted, dyspnoea across follow-up, and quality of life at 3 months. The duration of invasive ventilation was correlated with 6MWD and 6MWD % predicted.ConclusionIn invasively ventilated COVID-19 survivors, inspiratory muscle strength impairments persisted 6 months after ICU discharge, while maintaining normal diaphragm function. Decreased functional capacity, dyspnoea and slightly reduced health status were observed. Early screening of survivors is of utmost importance to identify those with impairments and at risk of delayed or incomplete recovery.
      Keywords: Respiratory infections and tuberculosis, Acute lung injury and critical care
      PubDate: 2023-01-16T00:30:16-08:00
      DOI: 10.1183/23120541.00329-2022
      Issue No: Vol. 9, No. 1 (2023)
  • Unravelling young COPD and pre-COPD in the general population

    • Authors: Cosio, B. G; Casanova, C, Soler-Cataluna, J. J, Soriano, J. B, Garcia-Rio, F, de Lucas, P, Alfageme, I, Rodriguez Gonzalez-Moro, J. M, Sanchez, G, Ancochea, J, Miravitlles, M.
      Pages: 00334-2022 - 334-2022
      Abstract: BackgroundChronic obstructive pulmonary disease (COPD) is commonly diagnosed when the airflow limitation is well established and symptomatic. We aimed to identify individuals at risk of developing COPD according to the concept of pre-COPD and compare their clinical characteristics with 1) those who have developed the disease at a young age, and 2) the overall population with and without COPD.MethodsThe EPISCAN II study is a cross-sectional, population-based study that aims to investigate the prevalence of COPD in Spain in subjects ≥40 years of age. Pre-COPD was defined as the presence of emphysema>5% and/or bronchial thickening by computed chromatography (CT) scan and/or diffusing capacity of the lung for carbon monoxide (DLCO) 0.70. Young COPD was defined as FEV1/FVC
      Keywords: COPD and smoking
      PubDate: 2023-02-20T06:30:28-08:00
      DOI: 10.1183/23120541.00334-2022
      Issue No: Vol. 9, No. 1 (2023)
  • Global burden of nontuberculous mycobacteria in the cystic fibrosis
           population: a systematic review and meta-analysis

    • Authors: Prieto, M. D; Alam, M. E, Franciosi, A. N, Quon, B. S.
      Pages: 00336-2022 - 336-2022
      Abstract: BackgroundPeople living with cystic fibrosis have an increased risk of lung infection with nontuberculous mycobacteria (NTM), the prevalence of which is reportedly increasing. We conducted a systematic review of the literature to estimate the burden (prevalence and incidence) of NTM in the cystic fibrosis population.MethodsElectronic databases, registries and grey literature sources were searched for cohort and cross-sectional studies reporting epidemiological measures (incidence and prevalence) of NTM infection or NTM pulmonary disease in cystic fibrosis. The last search was conducted in September 2021; we included reports published since database creation and registry reports published since 2010. The methodological quality of studies was appraised with the Joanna Briggs Institute tool. A random effects meta-analysis was conducted to summarise the prevalence of NTM infection, and the remaining results are presented in a narrative synthesis.ResultsThis review included 95 studies. All 95 studies reported on NTM infection, and 14 of these also reported on NTM pulmonary disease. The pooled estimate for the point prevalence of NTM infection was 7.9% (95% CI 5.1–12.0%). In meta-regression, sample size and geographical location of the study modified the estimate. Longitudinal analysis of registry reports showed an increasing trend in NTM infection prevalence between 2010 and 2019.ConclusionsThe overall prevalence of NTM infection in cystic fibrosis is 7.9% and is increasing over time based on international registry reports. Future studies should report screening frequency, microbial identification methods and incidence rates of progression from NTM infection to pulmonary disease.
      Keywords: CF and non-CF bronchiectasis, Respiratory infections and tuberculosis
      PubDate: 2023-01-03T00:29:59-08:00
      DOI: 10.1183/23120541.00336-2022
      Issue No: Vol. 9, No. 1 (2023)
  • Circulating dipeptidyl peptidase 3 and bio-adrenomedullin levels are
           associated with impaired outcomes in critically ill COVID-19 patients: a
           prospective international multicentre study

    • Authors: van Lier, D; Deniau, B, Santos, K, Hartmann, O, Dudoignon, E, Depret, F, Plaud, B, Laterre, P.-F, Mebazaa, A, Pickkers, P.
      Pages: 00342-2022 - 342-2022
      Abstract: IntroductionDipeptidyl peptidase-3 (DPP3) is a protease involved in the degradation of several cardiovascular mediators. Adrenomedullin (bio-ADM) is a peptide essential for regulation of endothelial barrier function. In different shock-pathologies, both biomarkers are associated with disease severity, organ dysfunction and mortality. Associations with outcome in critically ill COVID-19 patients are unknown. The objectives of the present study were to investigate associations of bio-ADM and "circulating DPP3" (cDPP3) with short-term outcome in critically ill COVID-19 patients (n=80).MethodsA multicentre prospective cohort study was performed. The primary end-point was 28-day mortality. Secondary end-points included different severities of acute kidney injury (AKI).ResultscDPP3 levels were mainly associated with 28-day mortality; Area under the receiver operating characteristics (AUROCs) of 0.69 (0.56–0.82, p=0.023), 0.77 (0.64–0.90, p
      Keywords: Respiratory infections and tuberculosis, Acute lung injury and critical care
      PubDate: 2023-01-09T00:30:15-08:00
      DOI: 10.1183/23120541.00342-2022
      Issue No: Vol. 9, No. 1 (2023)
  • Multidisciplinary rehabilitation in intensive care for COVID-19:
           randomised controlled trial

    • Authors: Carvalho, A. C; Moreira, J, Cubelo, P, Cantista, P, Aguiar Branco, C, Guimaraes, B.
      Pages: 00350-2022 - 350-2022
      Abstract: Coronavirus disease 2019 (COVID-19) has led to an increasing number of patients in intensive care units (ICUs). The size of this post-ICU cohort will be unprecedented, with many patients vulnerable to post-intensive care syndrome. We analysed the respiratory and functional effects of a multidisciplinary rehabilitation programme on functional performance, in patients hospitalised in the ICU due to COVID-19.We conducted a randomised controlled clinical trial. 96 patients who fulfilled the eligibility criteria were randomised into control or intervention group. The control group received standard of care in the ICU, and the intervention group received a functional and respiratory rehabilitation protocol that included medical, nursing, physiotherapy and occupational therapy interventions.At discharge, the intervention group showed significantly better muscular strength and respiratory capacity, and significantly fewer days of hospitalisation (12.90±5.8 versus 15.60±6.7 days, p=0.037). At the 4- and 12-week follow-up, we applied our main outcome measure, the 6-min walk test (6MWT). The intervention group had significantly better results than the control group on the 6MWT at the 4-week follow-up (604±67 versus 571±57 m, p=0.018) and at the 12-week follow-up (639±53 versus 611±67 m, p=0.025).These results support the role of a multidisciplinary rehabilitation programme in COVID-19 patients hospitalised in the ICU and adds evidence that the implementation of rehabilitation programmes in ICUs could result in beneficial outcomes for critically ill patients.
      Keywords: Respiratory infections and tuberculosis
      PubDate: 2023-01-09T00:30:15-08:00
      DOI: 10.1183/23120541.00350-2022
      Issue No: Vol. 9, No. 1 (2023)
  • Pulmonary hypertension: the hallmark of acute COVID-19 microvascular

    • Authors: Dintakurti, S. H; Kamath, S, Mahon, C, Singh, S, Rawal, B, Padley, S. P. G, Devaraj, A, Price, L. C, Desai, S. R, Semple, T, Ridge, C. A.
      Pages: 00389-2022 - 389-2022
      Abstract: There have been>481 million cases of COVID-19, caused by SARS-CoV-2, worldwide since December 2019 [1]. One of the hallmark features of acute COVID-19 pneumonia is pulmonary vascular involvement, most commonly manifesting as pulmonary artery thrombosis (PAT) [2, 3]. Post mortem data from 10 patients with COVID-19 pneumonia showed their central pulmonary arteries were free of thrombosis but all patients had small, firm thrombi in the peripheral parenchyma [4]. These findings raise the possibility that the computed tomography (CT) finding of isolated subsegmental PAT may reflect "the tip of the iceberg"; that small segmental thrombi may reflect downstream in situ thrombosis in the microvasculature. In patients with severe COVID-19 pneumonitis, dual-energy computed tomography pulmonary angiography (CTPA) has been used to demonstrate reduced pulmonary perfusion in the absence of any visible central thromboembolism [5, 6], further supporting the view that microscopic PAT is prevalent [6].
      Keywords: Respiratory infections and tuberculosis, Pulmonary vascular disease
      PubDate: 2023-02-06T00:30:25-08:00
      DOI: 10.1183/23120541.00389-2022
      Issue No: Vol. 9, No. 1 (2023)
  • Epidemiological characteristics of nontuberculous mycobacteriosis and
           bronchiectasis: comparative study using national mortality statistics from
           1970 to 2015 in Japan

    • Authors: Morimoto, K; Iwai, K, Yoshiyama, T, Ito, M, Uesugi, F, Asakura, T, Osawa, T, Furuuchi, K, Kurashima, A, Fujiwara, K, Hasegawa, N, Tanaka, Y, Shoji, K, Shiraishi, Y, Mitarai, S, Ato, M, Ohta, K.
      Pages: 00424-2022 - 424-2022
      Abstract: BackgroundThis study assessed longitudinal national data on mortality due to nontuberculous mycobacteriosis (NTMosis) and bronchiectasis and the association between the two diseases.MethodsWe analysed the national death statistics of Japan from 1970 to 2015. The International Classification of Disease (ICD) codes were used to extract the relevant data. Crude mortality, age-adjusted mortality and standardised mortality rates were calculated using vital statistics and the population in 2000. We also identified domestic publications related to NTMosis and bronchiectasis with an internet-based search system.ResultsThe total number of bronchiectasis-related deaths remained at the same level, which was approximately 1000, for 45 years, although the number of deaths has consistently decreased in males but increased in females since the mid-1990s. A substantial increasing trend in females was also observed for NTMosis in the same period. The age-adjusted mortality data showed an increase in mortality in women due to NTMosis and confirmed the trend in bronchiectasis in women. The patterns in the number of domestic reports showed a recent slight increase in bronchiectasis and a marked increase in NTMosis.ConclusionsThe trends in bronchiectasis-related mortality differed by sex. The epidemiological trends in the two diseases were associated, especially in elderly females since the mid-1990s. It is suggested that pulmonary NTMosis without pre-existing bronchiectasis might be a leading cause of postinfectious bronchiectasis in Japan.
      Keywords: CF and non-CF bronchiectasis, Respiratory infections and tuberculosis
      PubDate: 2023-02-20T06:30:28-08:00
      DOI: 10.1183/23120541.00424-2022
      Issue No: Vol. 9, No. 1 (2023)
  • At-home noninvasive ventilation initiation with telemonitoring in
           amyotrophic lateral sclerosis patients: a retrospective study

    • Authors: Reginault, T; Bouteleux, B, Wibart, P, Mathis, S, Le Masson, G, Pillet, O, Grassion, L.
      Pages: 00438-2022 - 438-2022
      Abstract: BackgroundNoninvasive ventilation (NIV) improves survival and quality of life in amyotrophic lateral sclerosis (ALS) patients. NIV initiation is mostly conducted at hospital, but a recurrent lack of hospital beds led to the necessity of exploring an at-home initiation process. Here, we report data from our NIV initiation cohort of ALS patients. Could our at-home NIV initiation process with telemonitoring in ALS patients be an efficient solution for adherence and nocturnal hypoxaemia correction'MethodsWe performed a retrospective analysis of data collected from 265 ALS patients treated at the Bordeaux ALS Centre for whom NIV initiation was carried out between September 2017 and June 2021, with two modalities: at-home initiation or in-hospital initiation. The primary outcome was adherence to NIV at 30 days. The secondary outcome was at-home NIV initiation process efficiency of nocturnal hypoxaemia correction.ResultsAt 30 days, NIV adherence (mean>4 h·day–1) was 66% of the total population, 70% of the at-home NIV initiation subgroup and 52% of the in-hospital NIV initiation subgroup. Nocturnal hypoxaemia correction was observed in 79% of adherent patients in the at-home NIV initiation subgroup. Mean delay of NIV prescription and at-home NIV initiation was 8.7 days (+/–6.5) versus 29.5 days in hospital.ConclusionOur study shows that our at-home NIV initiation process in ALS patients is a good option to provide rapid access to NIV with good adherence and efficiency. Further literature on the benefits of at-home NIV initiation is welcomed, especially to evaluate long-term efficiency and global cost analysis.
      PubDate: 2023-02-27T00:30:23-08:00
      DOI: 10.1183/23120541.00438-2022
      Issue No: Vol. 9, No. 1 (2023)
  • Adverse perception of cough in patients with severe asthma: a discrete
           choice experiment

    • Authors: Holmes, J; O'Neill, V, McGarvey, L. P, Heaney, L. G.
      Pages: 00442-2022 - 442-2022
      Abstract: BackgroundAsthma symptoms adversely impact quality of life in particular in those with poor disease control. Commonly used patient-reported measures for asthma used to assess asthma control often inadequately capture the impact of cough, despite evidence that cough is one of the most bothersome symptoms for patients with asthma. This study aims to improve our understanding of how patients with asthma perceive cough to better understand its clinical impact.MethodsA discrete choice experiment (DCE) was performed in two distinct adult asthma populations; those with severe asthma as defined by Global Initiative for Asthma (GINA) step 4/5 classification and those with moderate asthma (a GINA steps 2 or 3 classification of asthma severity).ResultsChoices were highly dominated by the cough attribute in the symptoms complexes; 48.4% of patients with severe asthma and 31.3% with moderate asthma consistently chose the alternative with the lowest level of cough. Furthermore, cough predominance was found to be significantly associated with severity of asthma (p=0.047). Patients with moderate asthma were not willing to accept any additional symptoms to reduce cough from severe to mild. However, these patients were willing to accept mild breathlessness, mild sleep disturbance, severe chest tightness and severe wheezing to remove coughing altogether.ConclusionsPatients with asthma prefer to have less cough and are willing to accept greater levels of other symptoms to achieve this. Additionally, asthma severity may influence an individual's perception of their symptoms; cough is a more important symptom for patients with severe asthma than those with a milder disease.
      Keywords: Asthma and allergy
      PubDate: 2023-01-03T00:29:59-08:00
      DOI: 10.1183/23120541.00442-2022
      Issue No: Vol. 9, No. 1 (2023)
  • Development and validation of a predictive model combining
           patient-reported outcome measures, spirometry and exhaled nitric oxide
           fraction for asthma diagnosis

    • Authors: Louis, G; Schleich, F, Guillaume, M, Kirkove, D, Nekoee Zahrei, H, Donneau, A.-F, Henket, M, Paulus, V, Guissard, F, Louis, R, Petre, B.
      Pages: 00451-2022 - 451-2022
      Abstract: IntroductionAlthough asthma is a common disease, its diagnosis remains a challenge in clinical practice with both over- and underdiagnosis. Here, we performed a prospective observational study investigating the value of symptom intensity scales alone or combined with spirometry and exhaled nitric oxide fraction (FENO) to aid in asthma diagnosis.MethodsOver a 38-month period we recruited 303 untreated patients complaining of symptoms suggestive of asthma (wheezing, dyspnoea, cough, sputum production and chest tightness). The whole cohort was split into a training cohort (n=166) for patients recruited during odd months and a validation cohort (n=137) for patients recruited during even months. Asthma was diagnosed either by a positive reversibility test (≥12% and ≥200 mL in forced expiratory volume in 1 s (FEV1)) and/or a positive bronchial challenge test (provocative concentration of methacholine causing a 20% fall in FEV1 ≤8 mg·mL–1). In order to assess the diagnostic performance of symptoms, spirometric indices and FENO, we performed receiver operating characteristic curve analysis and multivariable logistic regression to identify the independent factors associated with asthma in the training cohort. Then, the derived predictive models were applied to the validation cohort.Results63% of patients in the derivation cohort and 58% of patients in the validation cohort were diagnosed as being asthmatic. After logistic regression, wheezing was the only symptom to be significantly associated with asthma. Similarly, FEV1 (% pred), FEV1/forced vital capacity (%) and FENO were significantly associated with asthma. A predictive model combining these four parameters yielded an area under the curve of 0.76 (95% CI 0.66–0.84) in the training cohort and 0.73 (95% CI 0.65–0.82) when applied to the validation cohort.ConclusionCombining a wheezing intensity scale with spirometry and FENO may help in improving asthma diagnosis accuracy in clinical practice.
      Keywords: Asthma and allergy
      PubDate: 2023-02-06T00:30:25-08:00
      DOI: 10.1183/23120541.00451-2022
      Issue No: Vol. 9, No. 1 (2023)
  • Early selexipag initiation and long-term outcomes: insights from
           randomised controlled trials in pulmonary arterial hypertension

    • Authors: Coghlan, J. G; Gaine, S, Channick, R, Chin, K. M, du Roure, C, Gibbs, J. S. R, Hoeper, M. M, Lang, I. M, Mathai, S. C, McLaughlin, V. V, Mitchell, L, Simonneau, G, Sitbon, O, Tapson, V. F, Galie, N.
      Pages: 00456-2022 - 456-2022
      Abstract: Further understanding of when to initiate therapies in pulmonary arterial hypertension (PAH) is important to improve long-term outcomes. Post hoc analyses of GRIPHON (NCT01106014) and exploratory analyses of TRITON (NCT02558231) suggested benefit of early selexipag initiation on long-term outcomes, despite no additional benefit versus initial double combination on haemodynamic and functional parameters in TRITON. Post hoc analyses investigated the effect of early selexipag initiation on disease progression and survival in a large, pooled PAH cohort. Data from newly diagnosed (≤6 months) PAH patients from GRIPHON and TRITON were pooled. Patients on active therapy with selexipag (pooled selexipag group) were compared with those on control therapy with placebo (pooled control group). Disease progression end-points were defined as per the individual studies. Hazard ratios (HR) and 95% CI for time to first disease progression event up to end of double-blind treatment (selexipag/placebo) +7 days and time to all-cause death up to end of study were estimated using Cox regression models. The pooled dataset comprised 649 patients, with 44% on double background therapy. Selexipag reduced the risk of disease progression by 52% versus control (HR: 0.48; 95% CI: 0.35–0.66). HR for risk of all-cause death was 0.70 (95% CI: 0.46–1.10) for the pooled selexipag versus control group. Sensitivity analyses accounting for the impact of PAH background therapy showed consistent results, confirming the appropriateness of data pooling. These post hoc, pooled analyses build on previous insights, further supporting selexipag use within 6 months of diagnosis, including as part of triple therapy, to delay disease progression.
      Keywords: Pulmonary vascular disease
      PubDate: 2023-01-16T00:30:16-08:00
      DOI: 10.1183/23120541.00456-2022
      Issue No: Vol. 9, No. 1 (2023)
  • Bacterial DNA amplifies neutrophilic inflammation in IL-17-exposed airways

    • Authors: Mues, N; Martin, R. J, Alam, R, Schaunaman, N, Dimasuay, K. G, Kolakowski, C, Wright, C. J, Zheng, L, Chu, H. W.
      Pages: 00474-2022 - 474-2022
      Abstract: BackgroundNeutrophilic asthma (NA) is associated with increased airway interleukin (IL)-17 and abnormal bacterial community such as dominance of nontypeable Haemophilus influenzae (NTHi), particularly during asthma exacerbations. Bacteria release various products including DNA, but whether they cooperate with IL-17 in exaggerating neutrophilic inflammation is unclear. We sought to investigate the role of bacteria-derived DNA in airway neutrophilic inflammation related to IL-17-high asthma and underlying mechanisms (e.g. Toll-like receptor 9 (TLR9)/IL-36 signalling axis).MethodsBacterial DNA, IL-8 and IL-36 were measured in bronchoalveolar lavage fluid (BALF) of people with asthma and healthy subjects. The role of co-exposure to IL-17 and bacterial DNA or live bacteria in neutrophilic inflammation, and the contribution of the TLR9/IL-36 signalling axis, were determined in cultured primary human airway epithelial cells and alveolar macrophages, and mouse models.ResultsBacterial DNA levels were increased in asthma BALF, which positively correlated with IL-8 and neutrophil levels. Moreover, IL-36 increased in BALF of NA patients. Bacterial DNA or NTHi infection under an IL-17-high setting amplified IL-8 production and mouse lung neutrophilic inflammation. DNase I treatment in IL-17-exposed and NTHi-infected mouse lungs reduced neutrophilic inflammation. Mechanistically, bacterial DNA-mediated amplification of neutrophilic inflammation is in part dependent on the TLR9/IL-36 signalling axis.ConclusionsBacterial DNA amplifies airway neutrophilic inflammation in an IL-17-high setting partly through the TLR9 and IL-36 signalling axis. Our novel findings may offer several potential therapeutic targets including TLR9 antagonists, IL-36 neutralising antibodies and DNase I to reduce asthma severity associated with exaggerated airway neutrophilic inflammation.
      Keywords: Lung biology and experimental studies, Asthma and allergy
      PubDate: 2023-01-23T00:30:20-08:00
      DOI: 10.1183/23120541.00474-2022
      Issue No: Vol. 9, No. 1 (2023)
  • Computational platform for doctor-artificial intelligence cooperation in
           pulmonary arterial hypertension prognostication: a pilot study

    • Authors: Kheyfets, V. O; Sweatt, A. J, Gomberg-Maitland, M, Ivy, D. D, Condliffe, R, Kiely, D. G, Lawrie, A, Maron, B. A, Zamanian, R. T, Stenmark, K. R.
      Pages: 00484-2022 - 484-2022
      Abstract: BackgroundPulmonary arterial hypertension (PAH) is a heterogeneous and complex pulmonary vascular disease associated with substantial morbidity. Machine-learning algorithms (used in many PAH risk calculators) can combine established parameters with thousands of circulating biomarkers to optimise PAH prognostication, but these approaches do not offer the clinician insight into what parameters drove the prognosis. The approach proposed in this study diverges from other contemporary phenotyping methods by identifying patient-specific parameters driving clinical risk.MethodsWe trained a random forest algorithm to predict 4-year survival risk in a cohort of 167 adult PAH patients evaluated at Stanford University, with 20% withheld for (internal) validation. Another cohort of 38 patients from Sheffield University were used as a secondary (external) validation. Shapley values, borrowed from game theory, were computed to rank the input parameters based on their importance to the predicted risk score for the entire trained random forest model (global importance) and for an individual patient (local importance).ResultsBetween the internal and external validation cohorts, the random forest model predicted 4-year risk of death/transplant with sensitivity and specificity of 71.0–100% and 81.0–89.0%, respectively. The model reinforced the importance of established prognostic markers, but also identified novel inflammatory biomarkers that predict risk in some PAH patients.ConclusionThese results stress the need for advancing individualised phenotyping strategies that integrate clinical and biochemical data with outcome. The computational platform presented in this study offers a critical step towards personalised medicine in which a clinician can interpret an algorithm's assessment of an individual patient.
      Keywords: Pulmonary vascular disease
      PubDate: 2023-02-06T00:30:25-08:00
      DOI: 10.1183/23120541.00484-2022
      Issue No: Vol. 9, No. 1 (2023)
  • High-throughput functional assay in cystic fibrosis patient-derived
           organoids allows drug repurposing

    • Authors: Spelier, S; de Poel, E, Ithakisiou, G. N, Suen, S. W. F, Hagemeijer, M. C, Muilwijk, D, Vonk, A. M, Brunsveld, J. E, Kruisselbrink, E, van der Ent, C. K, Beekman, J. M.
      Pages: 00495-2022 - 495-2022
      Abstract: BackgroundCystic fibrosis (CF) is a rare hereditary disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Recent therapies enable effective restoration of CFTR function of the most common F508del CFTR mutation. This shifts the unmet clinical need towards people with rare CFTR mutations such as nonsense mutations, of which G542X and W1282X are most prevalent. CFTR function measurements in patient-derived cell-based assays played a critical role in preclinical drug development for CF and may play an important role to identify new drugs for people with rare CFTR mutations.MethodsHere, we miniaturised the previously described forskolin-induced swelling (FIS) assay in intestinal organoids from a 96-well to a 384-well plate screening format. Using this novel assay, we tested CFTR increasing potential of a 1400-compound Food and Drug Administration (FDA)-approved drug library in organoids from donors with W1282X/W1282X CFTR nonsense mutations.ResultsThe 384-well FIS assay demonstrated uniformity and robustness based on coefficient of variation and Z’-factor calculations. In the primary screen, CFTR induction was limited overall, yet interestingly, the top five compound combinations that increased CFTR function all contained at least one statin. In the secondary screen, we indeed verified that four out of the five statins (mevastatin, lovastatin, simvastatin and fluvastatin) increased CFTR function when combined with CFTR modulators. Statin-induced CFTR rescue was concentration-dependent and W1282X-specific.ConclusionsFuture studies should focus on elucidating genotype specificity and mode-of-action of statins in more detail. This study exemplifies proof of principle of large-scale compound screening in a functional assay using patient-derived organoids.
      Keywords: CF and non-CF bronchiectasis
      PubDate: 2023-01-30T00:30:21-08:00
      DOI: 10.1183/23120541.00495-2022
      Issue No: Vol. 9, No. 1 (2023)
  • Impact of computed tomographic patterns and extent on clinical management
           and outcomes of patients with organising pneumonia

    • Authors: Huang, T.-H; Wei, S.-H, Huang, L.-T, Er, H.-P, Yu, Y.-T, Lee, C.-T, Tseng, Y.-L, Wu, C.-L.
      Pages: 00505-2022 - 505-2022
      Abstract: BackgroundOrganising pneumonia (OP) has variable clinical and radiographic presentations and unstandardised treatments. Most patients with OP have favourable outcomes, but some develop respiratory insufficiency, experience recurrence or die. In this study we investigated the impact of computed tomographic (CT) patterns and extent of OP on the diagnostic and therapeutic management that patients received, and that on the therapeutic response and prognosis (particularly the risk of respiratory insufficiency and death).MethodsWe retrospectively studied 156 patients with OP followed at our hospital between 2010 and 2021. The diagnosis was confirmed histologically and verified by multidisciplinary specialists. We performed Firth's logistic regression to determine the relationship between CT features and aetiologies, management and outcomes including the risk of severe disease (defined as the need for supplemental oxygen or mechanical ventilation). We conducted Kaplan–Meier analyses to assess survival differences.ResultsPatients exhibiting multilobe involvement or mixed patterns, or both, were more likely to have secondary OP and receive immunosuppressants. Higher proportions of these patients experienced recurrence. Compared to patients with single-lobe involvement and single-pattern, they also had an enhanced risk of severe disease (the adjusted odds ratio for patients who simultaneously had multilobe involvement and mixed patterns was 27.64; 95% confidence interval 8.25–127.44). Besides, these patients had decreased survival probabilities.ConclusionDifferent CT features of OP impact patients’ management and prognosis. When treating patients with OP exhibiting multilobe involvement or mixed patterns, or both, it is important to identify the possible causative aetiology and follow closely for adverse outcomes.
      Keywords: Interstitial and orphan lung disease, Lung imaging
      PubDate: 2023-02-20T06:30:28-08:00
      DOI: 10.1183/23120541.00505-2022
      Issue No: Vol. 9, No. 1 (2023)
  • Dyspnoea in COVID-19 recovery beyond the intensive care unit: the
           potential impact of inspiratory muscle weakness

    • Authors: Bissett; B.
      Pages: 00521-2022 - 521-2022
      Abstract: It is now well-recognised that dyspnoea is a common feature of prolonged recovery from coronavirus disease 2019 (COVID-19). In their living systematic review, capturing the experiences of>10 000 people with "long COVID", Michelen et al. [1] report breathlessness in 25% of respondents, rendering it the fifth most common symptom. However, the impact of breathlessness on the disability associated with long COVID is less well understood. A recent study by Hodgson et al. [2] revealed that at 6 months following intensive care unit (ICU) discharge, 39% of survivors who had been critically ill with COVID-19 had new-onset disability and 11% could not return to work. The potential contribution of breathlessness to this disability deserves to be more deeply explored, not least because it could be treatable.
      Keywords: Respiratory infections and tuberculosis, Acute lung injury and critical care
      PubDate: 2023-01-16T00:30:16-08:00
      DOI: 10.1183/23120541.00521-2022
      Issue No: Vol. 9, No. 1 (2023)
  • It is time to end our love affair with short-acting {beta}2-agonists in
           asthma' Yes

    • Authors: Nannini; L. J.
      Pages: 00555-2022 - 555-2022
      Abstract: I read with interest the editorial by Crooks and Faruqi [1]. I agree with almost all of the concepts; however, given my experience, I must question why the scientific community does not take a drastic decision regarding short-acting β2-agonists (SABA) use in asthma. In 2019, Martin and Harrison [2] wrote a similar editorial. SABA overreliance was identified many times as the key issue [3–5]. But nothing happens. SABA's status quo has not been overcome for more than 30 years.
      Keywords: Asthma and allergy
      PubDate: 2023-02-27T00:30:23-08:00
      DOI: 10.1183/23120541.00555-2022
      Issue No: Vol. 9, No. 1 (2023)
  • Healthcare experiences of adults with COPD across community care settings:
           a meta-ethnography

    • Authors: Madawala, S; Osadnik, C. R, Warren, N, Kasiviswanathan, K, Barton, C.
      Pages: 00581-2022 - 581-2022
      Abstract: BackgroundStudies investigating lived experiences of patients with COPD raise important concerns about interactions with healthcare professionals. Patients often describe feelings of guilt and shame associated with their COPD and may experience stigma and poor patient experience of care. The aims and objectives of the present study were to systematically scope and synthesise findings from peer-reviewed qualitative studies describing healthcare experiences of patients living with COPD across community care settings.MethodsA meta-ethnography was undertaken. Database searches were performed in Ovid MEDLINE, PsychINFO, Ovid Emcare, CINAHL Plus and Sociological Abstracts. Eligible qualitative studies were included. Study screening and data extraction was performed by two independent reviewers. A "line-of-argument" synthesis and deductive and inductive analysis was used to identify key themes, where the deductive element aligned to Wong and Haggerty's six key dimensions of patient experiences.ResultsData from 23 studies were included. Experiences and their meaning to patients were explored within the context of six domains of patient experience including access, interpersonal communication, continuity and coordination, comprehensiveness and trust. Inductive coding revealed emotion, stigma, identity and vulnerability shaped healthcare experiences of adults with COPD.ImplicationsExperiences often fell short of what was expected and needed in community settings. Adopting strategies to improve experiences of care in the community can be expected to improve self-management and contribute to improved health outcomes and quality of life. These strategies should take account of vulnerability, stigma and emotions such as guilt and blame that are potent affective drivers of the experience of care for patients with COPD.
      Keywords: COPD and smoking
      PubDate: 2023-02-06T00:30:25-08:00
      DOI: 10.1183/23120541.00581-2022
      Issue No: Vol. 9, No. 1 (2023)
  • When more is more: the role of additional upfront therapy in pulmonary
           arterial hypertension

    • Authors: Niedermeyer, S; Hassoun, P.
      Pages: 00592-2022 - 592-2022
      Abstract: Pulmonary arterial hypertension (PAH) is a rare disease characterised by pulmonary vascular remodelling and related increased pulmonary vascular resistance. This disease, if left untreated, will ultimately lead to death from right ventricular failure [1]. Currently available therapies target one of three known pathogenic pathways: the endothelin, prostacyclin or nitric oxide pathway [2, 3]. The current treatment paradigm emphasises the role of upfront combination therapy, although the permutation and timing of which remain unclear [4]. Despite advances in the understanding and treatment of this disease, mortality from PAH remains unacceptably high [5]. Ongoing investigation into drug combination strategies and timing of therapy initiation provides clinicians and patients with the opportunity to maximise benefit from currently available therapies, as novel drug discovery can take decades.
      Keywords: Pulmonary vascular disease
      PubDate: 2023-01-16T00:30:16-08:00
      DOI: 10.1183/23120541.00592-2022
      Issue No: Vol. 9, No. 1 (2023)
  • ERJ Open Research receives its first impact factor and plans for the next

    • Authors: Song, W.-J; Barreiro, E.
      Pages: 00608-2022 - 608-2022
      Abstract: We are proud to announce that ERJ Open Research received its first impact factor (IF) of 4.2 in the 2021 Journal Citation Reports. ERJ Open Research is an open access, original research journal of the European Respiratory Society, and a sister journal of European Respiratory Journal, European Respiratory Review and Breathe. ERJ Open Research was launched in May 2015 [1]. It was initially led by Prof. Anita K. Simonds (Imperial College London, London, UK) in 2015–2018, followed by Prof. Alyn H. Morice (University of Hull, Hull, UK) in 2018–2021. Since early January 2022, Esther Barreiro is serving the journal as the Chief Editor and Woo-Jung Song continues his role as the Deputy Chief Editor (since June 2020), and we will continue to hold these positions up until the September 2024. Readers may have observed that ERJ Open Research has continued to build on its success, and is publishing more and more high-quality research articles. This achievement has come about through the joint efforts of its authors and peer reviewers, the international editorial board, the ERS Publications Office and the ERS Publications Committee. We thank everyone whose hard work and commitment have helped ERJ Open Research to continue to grow and succeed.
      PubDate: 2023-01-16T00:30:16-08:00
      DOI: 10.1183/23120541.00608-2022
      Issue No: Vol. 9, No. 1 (2023)
  • Triple therapy in COPD: understanding the data

    • Authors: Suissa; S.
      Pages: 00615-2022 - 615-2022
      Abstract: The recommended pharmacological treatment for a patient first diagnosed with COPD is a long-acting bronchodilator, either long-acting muscarinic antagonists (LAMA), long-acting β2-agonists (LABA) or their combination [1]. For patients with high blood eosinophil counts (>300 cells per μL), an inhaled corticosteroid (ICS) combined with a LABA (LABA-ICS) is considered. In follow-up management, dual (LAMA-LABA and LABA-ICS) and triple combinations (LAMA-LABA-ICS) of these drug classes are recommended if these initial treatments become ineffective, according to the degree of dyspnoea and the frequency of exacerbations. Currently, several single-inhaler combinations of these three treatment classes are available, including single-inhaler triple therapy.
      Keywords: COPD and smoking, Pulmonary pharmacology and therapeutics
      PubDate: 2023-01-30T00:30:21-08:00
      DOI: 10.1183/23120541.00615-2022
      Issue No: Vol. 9, No. 1 (2023)
  • ERJ Open Research, list of peer reviewers 2022

    • Pages: 10901-2023 - 10901-2023
      Abstract: ERJ Open Research is voluntarily reviewed. We are most grateful for the hard work and dedication of those listed below, who reviewed articles for ERJ Open Research in 2022.
      PubDate: 2023-01-16T00:30:16-08:00
      DOI: 10.1183/23120541.10901-2023
      Issue No: Vol. 9, No. 1 (2023)
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