Publications by authors named "Jesper Rømhild Davidsen"

57 Publications

Immunogenicity of SARS-CoV-2 mRNA vaccine in solid organ transplant recipients.

J Intern Med 2021 Jul 8. Epub 2021 Jul 8.

Department of Infectious Diseases, Odense University Hospital, Odense, Denmark.

Background: It is currently not well described if a two-dose regimen of a Covid-19 vaccine is sufficient to elicit an immune response in SOT recipients.

Results: A total of 80 solid organ transplant (SOT) recipients completed a two-dose regimen with SARS-CoV-2 messenger RNA vaccine. Only 35.0% (n = 28) were able to mount a positive IgG immune response six weeks after the second dose of vaccine.

Conclusion: This emphasizes that SOT recipients need continued use of personal protective measures. Future studies need to closely examine the cellular immune response in patients with compromised antibody response to Covid-19 vaccination. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/joim.13361DOI Listing
July 2021

Clusters of comorbidities in idiopathic pulmonary fibrosis.

Respir Med 2021 Jun 1;185:106490. Epub 2021 Jun 1.

Center for Rare Lung Diseases, Department of Respiratory Diseases and Allergy, Aarhus University Hospital, Aarhus, Denmark.

Introduction: Comorbidities are common in patients with idiopathic pulmonary fibrosis (IPF) and negatively impact health-related quality of life, health-care costs and mortality. Retrospective studies have focused on individual comorbidities, but clusters of multiple comorbidities have rarely been analysed. This study aimed to comprehensively and prospectively assess comorbidities in a multicentre, real-world cohort of patients with IPF, including prespecified conditions of special interest and to analyse clusters of comorbidities and examine characteristics, disease course and mortality of the clusters.

Methods: Several measurements, questionnaires, medications and medical history were combined to assess comorbidities. Using self-organizing maps, clusters of comorbidities were identified and phenotypes characterized. Disease course was assessed using mixed effects models and mortality using Cox regression.

Results: One-hundred and fifty IPF patients were included prospectively. All except one patient suffered from at least one comorbidity and multimorbidity was common. Arterial hypertension, gastro-oesophageal reflux disease, hypercholesterolemia, emphysema and obstructive sleep apnea were most prevalent. Four comorbidity clusters were identified. Each cluster had distinct comorbidity profiles, patient characteristics, symptom burden and disease severity. Patients with fewer comorbidities had better exercise capacity and less dyspnea at baseline, but a trend towards faster deterioration was observed. Mortality analyses showed no significant differences between clusters.

Conclusions: Multimorbidity is prevalent in patients with IPF. Four specific clusters of comorbidities may represent phenotypes in IPF. A trend towards faster decline in exercise capacity and dyspnea was observed in patients with fewer comorbidities. Increased knowledge of comorbidities facilitates prevention and treatment of comorbidities in patients with IPF.
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http://dx.doi.org/10.1016/j.rmed.2021.106490DOI Listing
June 2021

Lung ultrasound may be a valuable aid in decision making for patients admitted with COVID-19 disease.

Eur Clin Respir J 2021 Apr 7;8(1):1909521. Epub 2021 Apr 7.

Department of Respiratory Medicine, Odense University Hospital, Odense, Denmark.

COVID-19 is associated with a risk of severe pneumonia and acute respiratory distress syndrome (ARDS), requiring treatment at an intensive care unit (ICU). Since clinical deterioration may occur rapidly, a simple, fast, bedside, non-invasive method for assessment of lung changes is warranted. The primary aim of this study was to investigate whether lung ultrasound (LUS) findings within 72 hours of admission were predictive of clinical deterioration in hospitalized patients with confirmed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Patients admitted to a dedicated COVID-19 unit were subject to daily LUS examinations. Number of present consolidations and pleural effusions were registered and a Mongodi score was calculated. These findings were correlated with initial chest x-ray and clinical deterioration, defined as ICU-admission, ARDS diagnosis, death. In total, 29 of 83 patients had LUS performed during admission, 18 within 72 h of admission. Of these, four patients died during admission, six were transferred to the ICU and 13 were diagnosed with ARDS. Initial Mongodi-score did not differ significantly between patients with and without clinical deterioration (p = 0.95). Agreement between initial LUS and chest x-ray findings were fair with Cohen's Kappa at 0.21. LUS performed within 72 h in patients admitted to a dedicated COVID-19 unit could not predict ARDS, ICU admission or death. However, consecutive investigations may be of value, as sudden substantial changes may herald disease progression, enabling earlier supplementary diagnostics and treatment initiation.
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http://dx.doi.org/10.1080/20018525.2021.1909521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032333PMC
April 2021

Lung Ultrasound to Phenotype Chronic Lung Allograft Dysfunction in Lung Transplant Recipients. A Prospective Observational Study.

J Clin Med 2021 Mar 5;10(5). Epub 2021 Mar 5.

Department of Cardiology, Section for Lung Transplantation, Copenhagen University Hospital, Rigshospitalet, 2100 Copenhagen, Denmark.

Background: Bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS) are two distinct phenotypes of chronic lung allograft dysfunction (CLAD) in lung transplant (LTx) recipients. Contrary to BOS, RAS can radiologically present with a pleuroparenchymal fibroelastosis (PPFE) pattern. This study investigates lung ultrasound (LUS) to identify potential surrogate markers of PPFE in order to distinguish CLAD phenotype RAS from BOS.

Methods: A prospective cohort study performed at a National Lung Transplantation Center during June 2016 to December 2017. Patients were examined with LUS and high-resolution computed tomography of the thorax (HRCT).

Results: Twenty-five CLAD patients (72% males, median age of 54 years) were included, corresponding to 19/6 BOS/RAS patients. LUS-identified pleural thickening was more pronounced in RAS vs. BOS patients (5.6 vs. 2.9 mm) compatible with PPFE on HRCT. LUS-identified pleural thickening as an indicator of PPFE in RAS patients' upper lobes showed a sensitivity of 100% (95% CI; 54-100%), specificity of 100% (95% CI; 82-100%), PPV of 100% (95% CI; 54-100%), and NPV of 100% (95% CI; 82-100%).

Conclusion: Apical pleural thickening detected by LUS and compatible with PPFE on HRCT separates RAS from BOS in patients with CLAD. We propose LUS as a supplementary tool for initial CLAD phenotyping.
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http://dx.doi.org/10.3390/jcm10051078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961975PMC
March 2021

Implementation of transbronchial lung cryobiopsy in a tertiary referral center for interstitial lung diseases: a cohort study on diagnostic yield, complications, and learning curves.

BMC Pulm Med 2021 Feb 25;21(1):67. Epub 2021 Feb 25.

Department of Respiratory Medicine, Odense University Hospital, Odense, Denmark.

Background: Transbronchial lung cryobiopsy (TBLC) has been introduced as an alternative to surgical lung biopsy (SLB) in the diagnostics of interstitial lung diseases (ILD). Despite controversy on safety, TBLC is increasingly implemented in ILD centers with an apparent diagnostic yield comparable to SLB. The aim of this study was to assess TBLC implementation experiences from a tertiary Danish ILD center regarding diagnosis, complications, and learning curves for TBLC performance.

Methods: TBLC was prospectively performed in a cohort of patients with unclassifiable ILD based on a preceding multidisciplinary clinical and radiological revision. TBLC was performed as an outpatient procedure with the patients in general anesthesia using a flexible bronchoscope with 1.9 or 2.4 mm cryoprobes. Learning curves for TBLC performance were calculated using cumulated sum (CUSUM) scores for diagnostic yield, pneumothorax, and bleeding.

Results: From February 2017 to March 2020 141 patients (86 (61%) men, median age 69 years [IQR, 60-74 years]) had TBLC performed. A histological and confirmative diagnosis was made in 101 patients (75.2%) and 124 patients (87.9%, i.e. clinical diagnostic yield), respectively, in whom idiopathic interstitial pneumonias constituted the majority (67.3%) of the clinical diagnoses. We observed 2 deaths (1.4%) within 30 days of TBLC, but no procedure-related mortality or severe bleeding. Moderate bleeding occurred in 23 patients (16.3%), pneumothorax in 21 patients (14.9%) with only 14 patients (9.9%) requiring a pleural drain. Based on the CUSUM score analysis, the diagnostic yield obtained was satisfactory throughout the period.

Conclusion: This study reports experiences of outpatient TBLC implementation in a tertiary referral ILD center from the largest investigated TBLC cohort in Scandinavia The diagnostic yield and prevalence of complications obtained by TBLC from this single center study on unclassifiable ILD support outpatient TBLC as a valuable and safe alternative to SLB to diagnose ILD in well-selected patients. The learning curves for TBLC were acceptable in the hands of experienced bronchoscopists.
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http://dx.doi.org/10.1186/s12890-021-01438-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7908747PMC
February 2021

Altered retinal oxygen metabolism in patients with combined ocular and central nervous system sarcoidosis.

Rheumatology (Oxford) 2021 Jul;60(7):3301-3306

Department of Ophthalmology, Odense University Hospital, Odense, Denmark.

Objective: To evaluate retinal oxygen metabolism by retinal oximetry for ocular and CNS diseases in a cross-sectional study of sarcoidosis.

Methods: Overall 201 eyes from 103 biopsy-verified sarcoidosis patients were included and divided into four groups depending on the organ affection: (i) sarcoidosis without ocular or CNS affection, (ii) ocular sarcoidosis, (iii) CNS sarcoidosis, and (iv) combined ocular and CNS sarcoidosis. Retinal oximetry was obtained and analysed, with the mean retinal arteriolar and venular saturation as well as arteriovenous difference as principal outcomes. Comparison between groups was done in a multi linear regression model adjusted for age, sex, duration of sarcoidosis, best corrected visual acuity and retinal oximetry quality.

Results: Mean (s.d.) age was 50.5 (13.4) (95% CI: 47.9, 53.1) years and 52.2% were males. Eyes of the combined Ocular/CNS group had a higher retinal arteriovenous difference than eyes of the Non-ocular/no-CNS group (42.1% vs 37.7%, P = 0.012) but did not differ between other groups. Eyes in the four groups (Non-ocular/no-CNS, Ocular, CNS and Ocular/CNS) did not differ according to retinal arterial (94.5%, 93.5%, 93.5% and 94.5%, respectively) or venular (57.5%, 56.4%, 55.0% and 52.5%, respectively) oxygen saturation.

Conclusions: The results of this study suggest that eyes of sarcoidosis patients with combined ocular and CNS affection have an altered oxygen metabolism indicating a subclinical eye affection that is not recognized by conventional screening methods.
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http://dx.doi.org/10.1093/rheumatology/keaa781DOI Listing
July 2021

Dynamics in diagnoses and pharmacotherapy before and after diagnosing idiopathic pulmonary fibrosis.

ERJ Open Res 2020 Oct 10;6(4). Epub 2020 Nov 10.

Clinical Pharmacology and Pharmacy, Dept of Public Health, University of Southern Denmark, Odense, Denmark.

Background: Idiopathic pulmonary fibrosis (IPF) is a well-characterised interstitial lung disease. Typically, IPF diagnosis is delayed due to nonspecific symptoms, but can also be delayed due to treatment attempts on false indication or due to treatment targeting common comorbidities. This observational study aimed to assess the dynamics in the medication and diagnosis patterns in the period before and after an IPF diagnosis.

Methods: We identified all Danish patients with IPF between 2002 and 2017. We evaluated new and ongoing drug treatments and incident diagnoses 36 months before and 12 months after an IPF diagnosis by use of Danish nationwide registries. To aid interpretation, 10 random controls were recruited for each case.

Results: A total of 650 IPF patients were identified (median age 73 years (interquartile range 65-78), 70.3% males). Prior to the IPF diagnosis, the most prevalent diagnoses were dyspnoea and non-IPF interstitial lung diseases. For drug use, IPF patients had higher initiation rates for antibiotics, oral corticosteroids and mucolytics. In terms of drug volume, IPF patients used more respiratory drugs, antibiotics, immunosuppressants, corticosteroids, proton pump inhibitors, benzodiazepines and opium alkaloids within the 6 months preceding their IPF diagnosis, compared to the controls. Overall drug use decreased after an IPF diagnosis, mainly due to a reduced glucocorticoid and cardiovascular drug use.

Conclusion: Among IPF patients, an increased drug use was observed for diagnoses with symptoms overlapping those of IPF, particularly this was observed during the last 6 months before an IPF diagnosis. This emphasises the need for an increased IPF awareness.
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http://dx.doi.org/10.1183/23120541.00479-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7682713PMC
October 2020

Economic Burden and Management of Systemic Sclerosis-Associated Interstitial Lung Disease in 8 European Countries: The BUILDup Delphi Consensus Study.

Adv Ther 2021 01 6;38(1):521-540. Epub 2020 Nov 6.

Boehringer Ingelheim, Amsterdam, The Netherlands.

Introduction: Systemic sclerosis (SSc) is a rare chronic autoimmune disease characterised by microvascular damage, immune dysregulation and fibrosis, affecting the skin, joints and internal organs. Interstitial lung disease (ILD) is frequently associated with systemic sclerosis (SSc-ILD), leading to a poor prognosis and a high mortality rate. The aim of the BUILDup study (BUrden of Interstitial Lung Disease Consensus Panel) was to investigate the overall disease management and to estimate the social and economic burden of SSc-ILD across 8 European countries.

Methods: A modified Delphi method was used to obtain information on the management of SSc-ILD patients among 40 specialists (panellists) from 8 European countries. Average annual costs per patient and country were estimated by means of a direct cost-analysis study.

Results: The panellists had managed 805 SSc-ILD patients in the last year, 39.1% with limited (L-SSc-ILD) and 60.9% with extensive (E-SSc-ILD) disease. Of these, 32.8% of the panellists started treatment at diagnosis, 42.3% after signs of deterioration/progression and 24.7% when the disease had become extensive. The average annual cost of SSc-ILD per patient ranged from €6191 in Greece to €25,354 in Sweden. Main cost drivers were follow-up procedures, accounting for 80% of the total annual costs. Hospitalisations were the most important cost driver of follow-up costs. Healthcare resource use was more important for E-SSc-ILD compared to L-SSc-ILD. Early retirement was taken by 40.4% of the patients with an average of 11.9 years before the statutory retirement age.

Conclusions: SSc-ILD entails not only a clinical but also a social and economic burden, and is higher for E-SSc-ILD.
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http://dx.doi.org/10.1007/s12325-020-01541-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7854393PMC
January 2021

European Respiratory Society statement on thoracic ultrasound.

Eur Respir J 2021 03 4;57(3). Epub 2021 Mar 4.

Academic Respiratory Unit, University of Bristol, Bristol, UK.

Thoracic ultrasound is increasingly considered to be an essential tool for the pulmonologist. It is used in diverse clinical scenarios, including as an adjunct to clinical decision making for diagnosis, a real-time guide to procedures and a predictor or measurement of treatment response. The aim of this European Respiratory Society task force was to produce a statement on thoracic ultrasound for pulmonologists using thoracic ultrasound within the field of respiratory medicine. The multidisciplinary panel performed a review of the literature, addressing major areas of thoracic ultrasound practice and application. The selected major areas include equipment and technique, assessment of the chest wall, parietal pleura, pleural effusion, pneumothorax, interstitial syndrome, lung consolidation, diaphragm assessment, intervention guidance, training and the patient perspective. Despite the growing evidence supporting the use of thoracic ultrasound, the published literature still contains a paucity of data in some important fields. Key research questions for each of the major areas were identified, which serve to facilitate future multicentre collaborations and research to further consolidate an evidence-based use of thoracic ultrasound, for the benefit of the many patients being exposed to clinicians using thoracic ultrasound.
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http://dx.doi.org/10.1183/13993003.01519-2020DOI Listing
March 2021

CPAnet Registry-An International Chronic Pulmonary Aspergillosis Registry.

J Fungi (Basel) 2020 Jun 29;6(3). Epub 2020 Jun 29.

Department of Respiratory Medicine, Ghent University Hospital, B-9000 Ghent, Belgium.

Chronic pulmonary aspergillosis (CPA) is a chronic fungal infection of the lung associated with high morbidity and mortality. The CPA Research network (CPAnet) registry established in 2018 is an international multicenter collaboration aiming to improve CPA knowledge and patient care. This study's aim was to describe the data collection process and content of CPAnet registry with preliminary clinical data. In the CPAnet registry, clinical data are collected through a web-based questionnaire. Data include CPA phenotype, comorbidities, treatment, outcome, and follow-up from several international centers. An exemplary descriptive analysis was performed on 74 patients, who were registered online before April 2020. CPA patients were predominantly (72%) male, 39% had chronic obstructive pulmonary disease, and 68% had a history of smoking. Chronic cavitary pulmonary aspergillosis was the most common CPA subtype (62%). In 32 patients (52%), voriconazole was the preferred first-line therapy. The multicenter multinational CPAnet registry is a valuable approach to gather comprehensive data on a large study population and reflects real-world clinical practice rather than focusing on specific patient populations in more specialized centers. Additional CPA reference centers are being encouraged to join this promising clinical research collaboration.
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http://dx.doi.org/10.3390/jof6030096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7559693PMC
June 2020

The Burden of Progressive Fibrosing Interstitial Lung Disease: A DELPHI Approach.

Adv Ther 2020 07 22;37(7):3246-3264. Epub 2020 May 22.

Boehringer Ingelheim, Amsterdam, The Netherlands.

Introduction: The term progressive fibrosing interstitial lung disease (ILD) describes patients with fibrotic ILDs who, irrespective of the aetiology of the disease, show a progressive course of their disease despite current available (and non-licensed) treatment. Besides in idiopathic pulmonary fibrosis, little is known about management and the burden of patients with fibrotic ILD, particularly those with a progressive behaviour.

Methods: Using the Delphi method, 40 European experts in ILD management delivered information on management of (progressive) fibrosing ILD and on the impact of the disease on patients' quality of life (QoL) and healthcare resource utilisation (HCRU). Annual costs were calculated for progressive and non-/slow-progressive fibrosing ILD for diagnosis, follow-up management, exacerbation management, and end-of-life care based on the survey data.

Results: Physicians reported that progression in fibrosing ILD worsens QoL in both patients and their caregivers. Progression of fibrosing ILD was associated with a greater use of HCRU for follow-up visits and maintenance treatment compared with the non-/slow progression. The number of patients who suffered at least one acute exacerbation was reported to be more than three times higher in progressive fibrosing ILD patients than in patients with non-/slow-progressive fibrosing ILD. On average, annual estimated costs of progressive fibrosing ILD per patient were 1.8 times higher than those of the non-/slow-progressive form of the disease.

Conclusions: Progression in fibrosing ILD causes a significant impact on QoL and HCRU and costs. These survey data underline the need for safe and effective therapies to slow the disease progression.
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http://dx.doi.org/10.1007/s12325-020-01384-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7467418PMC
July 2020

Responsiveness and minimal clinically important difference of SGRQ-I and K-BILD in idiopathic pulmonary fibrosis.

Respir Res 2020 Apr 21;21(1):91. Epub 2020 Apr 21.

Center for Rare Lung Diseases, Department of Respiratory Diseases and Allergy, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, DK-8200, Aarhus N, Denmark.

Background: Idiopathic pulmonary fibrosis (IPF) specific version of St. George's Respiratory Questionnaire (SGRQ-I) and King's Brief Interstitial Lung Disease questionnaire (K-BILD) are validated health-related quality of life (HRQL) instruments, but no or limited data exist on their responsiveness and minimal clinically important difference (MCID). The objectives of this study were to assess responsiveness of SGRQ-I and K-BILD and determine MCID separately for deterioration and improvement in a large, prospective cohort of patients with IPF in a real-world setting.

Methods: Consecutive patients with IPF were recruited. SGRQ-I, K-BILD, SGRQ, Shortness of Breath Questionnaire, pulmonary function tests and 6-min walk test measurements were obtained at baseline and at six and 12 months; at six and 12 months, patients also completed Global Rating of Change Scales. Responsiveness was assessed using correlation coefficients and linear regression. Cox regression was used for mortality analyses. MCID was estimated using receiver operating characteristic curves with separate analyses for improvement and deterioration.

Results: A total of 150 IPF patients were included and 124 completed the 12-month follow-up. Based on all HRQL anchors and most physiological anchors, responsiveness analyses supported the evidence pointing towards SGRQ-I and K-BILD as responsive instruments. Multivariate analyses showed an association between SGRQ-I and mortality (HR: 1.18, 95% CI: 1.02 to 1.36, p = 0.03) and a trend was found for K-BILD (HR: 0.82, 95% CI: 0.64 to 1.05, p = 0.12). MCID was estimated for all domains of SGRQ-I and K-BILD. MCID for improvement differed from deterioration for both SGRQ-I Total (3.9 and 4.9) and K-BILD Total (4.7 and 2.7).

Conclusions: SGRQ-I and K-BILD were responsive to change concerning both HRQL and most physiological anchors. MCID was determined separately for improvement and deterioration, resulting in different estimates; especially a smaller estimate for deterioration compared to improvement in K-BILD.

Trial Registration: Clinicaltrials.gov, no. NCT02818712. Registered 30 June 2016.
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http://dx.doi.org/10.1186/s12931-020-01359-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7175493PMC
April 2020

Recurrent respiratory papillomatosis with lower airway involvement in a young woman.

Eur Clin Respir J 2020 12;7(1):1740567. Epub 2020 Mar 12.

Department of Respiratory Medicine, Odense University Hospital, Denmark.

Radiological presentation of bronchiectasis should prompt the respiratory physician to investigate various differential diagnosis leading to this condition. This case report describes a young non-smoking woman with HPV11 induced laryngeal Recurrent Respiratory Papillomatosis (RRP) since early childhood, who developed progressive exertional dyspnea. A thorough diagnostic process revealed HPV11 infection in the lung parenchyma consistent with RRP in the lower airways, an HPV infection that was most likely obtained from the patient´s mother during vaginal birth. This case report illustrates that also respiratory physicians should keep RRP in mind in persons with the radiological presentation of bronchiectasis previously diagnosed RRP in the upper airways.
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http://dx.doi.org/10.1080/20018525.2020.1740567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144305PMC
March 2020

Validation of the King's Brief Interstitial Lung Disease questionnaire in Idiopathic Pulmonary Fibrosis.

BMC Pulm Med 2019 Dec 19;19(1):255. Epub 2019 Dec 19.

Department of Respiratory Diseases and Allergy, Aarhus University Hospital, Aarhus, Denmark.

Background: Health-related quality of life (HRQL) is impaired in patients with idiopathic pulmonary fibrosis (IPF). The King's Brief Interstitial Lung Disease questionnaire (K-BILD) is a validated measure of HRQL, but no previous studies have focused on the validity of K-BILD in IPF. Moreover, the relationship between K-BILD and dyspnoea or the 6-min walk test (6MWT) has not been assessed. The aim of this study was to validate K-BILD in the largest cohort of patients with IPF to date and assess how K-BILD correlates to dyspnoea and 6MWT.

Methods: Firstly, K-BILD was translated into Danish using validated translation procedures. Consecutive patients with IPF were recruited. At baseline, patients completed K-BILD, the IPF-specific version of St. Georges Respiratory Questionnaire, University of California, San Diego Shortness of Breath Questionnaire (SOBQ) Short Form-36, and pulmonary function tests and 6MWT were performed. After 14 days, K-BILD and Global Rating of Change Scales were completed. Internal consistency, concurrent validity, test-retest reliability and known groups validity were assessed. Analyses were also performed in subgroups of patients with different time since diagnosis.

Results: At baseline, 150 patients with IPF completed the questionnaires, and 139 patients completed the questionnaires after 14 days. K-BILD had a high internal consistency (Cronbach's α = 0.92). The concurrent validity was strong compared to SOBQ (r = - 0.66) and moderate compared to 6MWT (r = 0.43). Intraclass correlation coefficients (ICC = 0.91) and a Bland Altman plot demonstrated a good reliability. K-BILD was also able to discriminate between patients with different stages of disease (p < 0.002, Δscore > 7.4) and most results were comparable in patients with different time since diagnosis.

Conclusion: K-BILD is a valid and reliable instrument in patients with IPF and in patients with different time since diagnosis. To a major extent, K-BILD scores reflected the impact of dyspnoea on HRQL and the impact of physical functional capacity measured by the 6MWT to a moderate degree. Compared to PFTs alone, K-BILD provides additional information on the burden of living with IPF, and importantly, K-BILD is simple to implement in both research and clinical contexts.

Trial Registration: Clinicaltrials.org (NCT02818712) on 30 June 2016.
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http://dx.doi.org/10.1186/s12890-019-1018-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6924069PMC
December 2019

Validation of the IPF-specific version of St. George's Respiratory Questionnaire.

Respir Res 2019 Aug 28;20(1):199. Epub 2019 Aug 28.

Department of Respiratory Diseases and Allergy, Aarhus University Hospital, Aarhus, Denmark.

Background: Patients with idiopathic pulmonary fibrosis (IPF) have impaired health-related quality of life (HRQL). To measure HRQL, an IPF-specific version of the St. George's Respiratory Questionnaire (SGRQ-I) was developed, but not sufficiently validated. This study aimed to assess the validity (i.a. known-groups validity and concurrent validity) and test-retest reliability of SGRQ-I in IPF patients with different disease durations.

Methods: Patients with IPF were consecutively recruited and completed SGRQ, SGRQ-I, King's Brief Interstitial Lung Disease questionnaire (K-BILD), University of California, San Diego Shortness of Breath Questionnaire (SOBQ) and Short Form-36 (SF-36) along with pulmonary function tests and a 6-min walk test (6MWT) at baseline. After two weeks, SGRQ-I and Global Rating of Change Scales (GRCS) were completed.

Results: At baseline and after two weeks, 150 and 134 patients completed the questionnaires, respectively. The internal consistency of SGRQ-I was high (Cronbach's α = 0.92). Good concurrent validity was demonstrated by high intraclass correlation coefficients (ICC = 0.97), Bland-Altman plots and moderate to strong correlations to K-BILD, SOBQ and SF-36 (r = - 0.46 to 0.80). High ICC (0.92) and a Bland-Altman plot indicated good test-retest reliability. SGRQ-I was good at discriminating between patients with different stages of disease (Δscore > 18.1, effect sizes > 0.10). Validity was similar across groups of different disease duration.

Conclusions: SGRQ-I proved to be valid at distinguishing between different disease severities, valid compared to other HRQL instruments, applicable across different disease durations and reliable upon repetition. SGRQ-I is a valid option for measuring HRQL in patients with IPF.

Trial Registration: The study was registered at clinicaltrials.org ( NCT02818712 ) on 15 June 2016.
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http://dx.doi.org/10.1186/s12931-019-1169-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6714302PMC
August 2019

[The first 25 years of lung transplantations in Denmark].

Ugeskr Laeger 2019 Apr;181(15)

Lung transplantation (LTx) has been performed in Denmark since 1992, and chronic obstructive pulmonary disease and interstitial lung diseases are the major indications. All candidates are subject to an intensive evaluation before being accepted for LTx. Follow-up after transplantation is life-long and includes immunosuppressive medication with a high risk of side effects. The median survival in Denmark is 7.0 years. Chronic rejection is common, diagnosed by declining lung function, and it is the most important factor for morbidity and mortality. LTx requires dedicated personnel in an interdisciplinary organisation.
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April 2019

Pulmonary alveolar proteinosis - a crazy presentation of dyspnea.

Eur Clin Respir J 2019 4;6(1):1552065. Epub 2018 Dec 4.

Department of Respiratory Medicine, Odense University Hospital, Odense, Denmark.

This case report demonstrates 44-year old man, presenting with recurring clinical pneumonias during a period of over 1 year. The patient was clinically affected with, i.a., weight loss, finger clubbing and severely reduced diffusion capacity. Repetitive chest x-rays showed bilateral and consolidating infiltrates, and a high-resolution computed tomography of the thorax (HRCT) exposed ground glass opacities superimposed on a reticular pattern as the so-called 'crazy paving' pattern. A bronchoscopic alveolar lavage revealed alveolar proteinaceous material compatible with the diagnosis pulmonary alveolar proteinosis (PAP). PAP is a rare syndrome where surfactant is accumulated in the alveoli, causing respiratory disease in typically young to middle-aged patients with male predominance. Both symptoms and prognosis are variable, and range from spontaneous remission to terminal respiratory failure. The standard treatment is whole lung lavage, where surfactant is mechanically rinsed from the lungs. The lack of specific clinical symptoms makes it easy to overlook the diagnosis, as supported by this case report. It serves as a reminder, that the findings of a crazy paving pattern on HRCT in young adults should alert of this rare disease, and advises on the further examinations required to make the diagnosis.
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http://dx.doi.org/10.1080/20018525.2018.1552065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6282426PMC
December 2018

Lung Ultrasound in the Assessment of Pulmonary Complications After Lung Transplantation.

Ultraschall Med 2020 Apr 9;41(2):148-156. Epub 2018 Nov 9.

Department of Respiratory Medicine, Odense University Hospital, Odense, Denmark.

Introduction:  Lung ultrasound (LUS) has a high diagnostic accuracy for identifying frequent conditions in the post-operative phase after lung transplantation (LTx). This study aimed to investigate the feasibility and clinical ability of LUS to identify pulmonary complications such as pleural effusions and pneumonias in the early postoperative phase after LTx.

Methods:  A prospective cohort study of lung transplant recipients who consecutively underwent single LTx (SLTx) or double LTx (DLTx) at the National Lung Transplantation Center in Denmark from May 1 to October 31, 2015 was conducted. LUS was performed at four time points corresponding to post-transplant day 3, and weeks 2, 6, and 12 (LUS #1-4) to detect and monitor variation in pathological LUS findings over time. Concurrent with LUS #4, a high-resolution computed tomography examination of the thorax (HRCT) was also performed.

Results:  14 patients (1 SLTx/13 DLTx, 7 (50 %) women, mean age: 50.4 years) who had undergone the four prespecified LUS examinations were included. Pleural effusion was the most common condition and most pronounced at post-LTx week 2. Findings consistent with pneumonia increased during week 2 and subsequently decreased. Corresponding to LUS #1, 2, 3, and 4, pleural effusion occurred in 85.7 %, 92.9 %, 85.7 %, and 78.6 %, and pneumonia in 21.4 %, 28.6 %, 14.3 %, and 14.3 %, respectively. HRCT findings at post-LTx week 12 were predominantly presented by unspecific ground glass opacities.

Conclusion:  In a post-LTx setting, LUS represents a clinical novelty as a feasible diagnostic and monitoring tool to identify pathological pulmonary complications in the early post-operative phase.
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http://dx.doi.org/10.1055/a-0783-2466DOI Listing
April 2020

Cryoablation: a potential treatment option for renal metastasis from lung cancer?

BMJ Case Rep 2018 Nov 1;2018. Epub 2018 Nov 1.

Research Unit at the Department of Radiology, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.

Cryoablation is successfully performed as a treatment for small renal cancers. The occurrence of a solitary renal metastasis from lung cancer is an uncommon finding entailing a limited knowledge on the choice of its optimal treatment. We present two patients diagnosed with non-small cell lung cancer, who were initially treated with curatively intended chemoradiotherapy. In the follow-up period, a non-symptomatic solitary renal metastasis was found in both patients. Both received CT-guided cryoablation of their renal metastases. One patient was successfully treated with no relapse, whereas the other patient received re-cryoablation due to development of a new renal metastasis. In both patients, no residual tumour was found at the 3 months' follow-up examination. Whether the minimally invasive procedure of cryoablation is a feasible treatment in the management of solitary renal metastases from lung cancer is still undetermined. The recurrence and incomplete treatment are concerns requiring further research.
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http://dx.doi.org/10.1136/bcr-2018-225841DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6214398PMC
November 2018

Nationwide use of theophylline among adults-A 20-year Danish drug utilisation study.

Respir Med 2018 07 25;140:57-62. Epub 2018 May 25.

Department of Respiratory Medicine, Odense University Hospital, Denmark; Department of Clinical Research, University of Southern Denmark, Denmark.

Background: Theophylline, a dimethylxanthine, has been used the last 100 years to treat airway disease. Although it is one of the most widely prescribed medicines to treat asthma and chronic obstructive pulmonary disease (COPD) throughout the years, the utilisation patterns are not well-described.

Methods: Using the Danish Register of Medicinal Products Statistics, we identified adults above 18 years redeeming one or more prescriptions of theophylline between 1997 up to 2017, with a 2-year run-in period from 1995 to 1997. Using descriptive statistics, we reported the development in prevalence, incidence, and a measure of treatment duration (proportion of patients covered).

Results: In total, 55,636 individuals redeemed 1,066,475 prescriptions of theophylline, 30,619 women (55%) and 25,017 men (45%). The prevalence decreased from 401 per 100,000 individuals in 1997 to 26 per 100,000 individuals in 2016. The incidence rate decreased throughout the entire study period (105 per 100,000 person-years in 1997 to 5 per 100,000 person-years in 2016). In total, 52% were still current users three months after theophylline initiation, 33%, 27%, and 23% were current users after 6 months, one year, and two years.

Conclusions: Although newer and more efficient medicines to treat asthma and COPD has been developed, theophylline is still prescribed and used in 2016, but the incidence and prevalence have decreased markedly since 1997.
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http://dx.doi.org/10.1016/j.rmed.2018.05.015DOI Listing
July 2018

[Asbestosis and pleural plaques].

Ugeskr Laeger 2018 Jun;180(25)

Asbestos was used in numerous products until its total ban in Denmark in 1988. The prevalence of asbestosis and pleural plaques does not yet appear to be falling. Unfortunately the statistics are unreliable due to errors in the Danish translation of the ICD-10 codes of the disease. In this review, clinical and radiologic diagnostic criteria of asbestosis and pleural plaques and recommendations for follow-up of patients are described. Typical changes on a high-resolution CT scan combined with relevant asbestos exposure is essential for the diagnosis. Asbestosis and pleural plaques are both notifiable in Denmark.
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June 2018

Determinants of persistent asthma in young adults.

Eur Clin Respir J 2018 5;5(1):1478593. Epub 2018 Jun 5.

Department of Occupational Medicine, Hospital of South West Jutland, Esbjerg, Denmark.

The aim of the study was to evaluate determinants for the prognosis of asthma in a population-based cohort of young adults. The study was a nine-year clinical follow up of 239 asthmatic subjects from an enriched population-based sample of 1,191 young adults, aged 20-44 years, who participated in an interviewer-administered questionnaire and clinical examination at baseline in 2003-2006. From the interview, an asthma score was generated as the simple sum of affirmative answers to five main asthma-like symptoms in order to analyse symptoms of asthma as a continuum. The clinical examination comprised spirometry, bronchial challenge or bronchodilation, and skin prick test. : Among the 239 individuals with asthma at baseline 164 (69%) had persistent asthma at follow up, while 68 (28%) achieved remission of asthma and seven (3%) were diagnosed with COPD solely. Determinants for persistent asthma were use of medication for breathing within the last 12 months: Short-acting beta-adrenoceptor agonists (SABA) only (OR 3.39; 95%CI: 1.47-7.82) and inhaled corticosteroids (ICS) and/or long-acting beta-adrenoceptor agonists (LABA) (8.95; 3.87-20.69). Stratified by age of onset determinants for persistence in individuals with early-onset asthma (age less than 16 years) were FEV₁ below predicted (7.12; 1.61-31.50), asthma score at baseline (2.06; 1.15-3.68) and use of ICS and/or LABA within 12 months (9.87; 1.95-49.98). In individuals with late-onset asthma the determinant was use of ICS and/or LABA within 12 months (6.84; 2.09-22.37). : Pulmonary function below predicted, severity of disease expressed by asthma score and use of ICS and/or LABA were all determinants for persistent early-onset asthma, whereas only use of ICS and/or LABA was a determinant in late-onset asthma. A high asthma score indicated insufficient disease control in a substantial proportion of these young adults.
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http://dx.doi.org/10.1080/20018525.2018.1478593DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5990946PMC
June 2018

Roflumilast Usage from 2010 to 2016: A Danish Nationwide Drug Utilization Study.

Basic Clin Pharmacol Toxicol 2018 Sep 4;123(3):314-319. Epub 2018 May 4.

Department of Respiratory Medicine, Odense University Hospital, Odense, Denmark.

Roflumilast, a phosphodiesterase-4-inhibitor, is marketed as add-on treatment to inhaled bronchodilators and corticosteroids in COPD patients with frequent exacerbations. Although marketed since 2010, usage pattern of roflumilast for an entire nation has not previously been explored. This study aimed to estimate the total utilization of roflumilast in Denmark during 2010 to 2016, using the Danish nationwide health registers. We identified 1573 individuals (47% males) who used roflumilast during the study period, of whom 705 (45%) redeemed only one prescription. Of all patients initiating roflumilast, 67% discontinued treatment within the first year. The rate of treatment initiation decreased 73% from 2011 (7.5/100,000 person-years) to 2016 (2.0/100,000 person-years) concurrent with a stable prevalence of 3.0-4.0/100,000 persons throughout the study period. The median duration of roflumilast use was 76 days. Patients with severe comorbidity tended to exhibit a lower degree of early discontinuation (Charlson Comorbidity Index 3+: odds ratio [OR]: 0.59; 95% confidence interval [CI] 0.33-1.04), as well as patients with a COPD-related admission within a year prior to roflumilast initiation (OR 0.62; 95% CI 0.49-0.80). The decreasing incidence and high level of early roflumilast discontinuation could be due to lack of benefit, a low awareness of romiflulast's indication among physicians, secondary to a challenging prescribing procedure or to adverse effects.
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http://dx.doi.org/10.1111/bcpt.13014DOI Listing
September 2018

Seventeen-Year Nationwide Trends in Use of Long-acting Bronchodilators and Inhaled Corticosteroids among Adults - A Danish Drug Utilization Study.

Basic Clin Pharmacol Toxicol 2018 Jul 25;123(1):58-64. Epub 2018 Mar 25.

Department of Respiratory Medicine, Odense University Hospital, Odense, Denmark.

Long-acting bronchodilators and inhaled corticosteroids (ICS) are the cornerstones in treatment of chronic obstructive and inflammatory pulmonary diseases. However, non-adherence to guidelines is widespread. Detailed information on real-life treatment patterns is needed to promote rational use. We aimed to investigate nationwide time trends in individual-level treatment patterns of long-acting bronchodilators and ICS. Using nationwide Danish health registries, we identified all Danish adults with a prescription for long-acting bronchodilators and/or ICS from 2000 to 2016. We investigated the total use of long-acting bronchodilators and ICS, the proportion of current users and the rate of new users over time. Finally, we assessed treatment persistence. We included 23,061,681 prescriptions for long-acting bronchodilators and ICS issued to 805,860 individuals from 2000 to 2016. Over this period, the total annual amount of prescribed long-acting bronchodilators and ICS increased by 39%. Similarly, the proportion of adult users increased from 2.6% to 4.5%, mainly driven by the introduction of combination therapy and long-acting muscarinic antagonist (LAMA). Although the rate of new users of fixed-dose combination drugs increased substantially over time, the overall rate of new users was stable. In general, the proportion of patients on therapy after 1 year was low (25-53%), especially among young individuals and users of ICS. We document a pronounced increase in the total use of long-acting bronchodilators and ICS over time, mainly driven by the introduction of combination drugs and LAMA. Special attention should be paid to the low level of persistence, especially among young individuals and users of ICS.
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http://dx.doi.org/10.1111/bcpt.12978DOI Listing
July 2018

[Chronic pulmonary aspergillosis].

Ugeskr Laeger 2018 01;180(5)

Chronic pulmonary aspergillosis (CPA) is an overlooked disease category in which delay of diagnosis and treatment is associated with increased mortality. A prerequisite for prognostic optimization of CPA is an increased focus on predisposing factors and patients at risk. Diagnosis of CPA is challenging and requires a systematic approach to assessment and interpretation of findings, both of which are necessary for correct disease classification and selection of targeted antifungal treatment and duration.
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January 2018

Lung Ultrasound - A Novel Diagnostic Tool To Phenotype Chronic Lung Allograft Dysfunction?

Ultrasound Int Open 2017 Jun 23;3(3):E117-E119. Epub 2017 Aug 23.

Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Unit of lung transplantation, Copenhagen, Denmark.

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http://dx.doi.org/10.1055/s-0043-116489DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5568532PMC
June 2017

Appropriate selection for omalizumab treatment in patients with severe asthma?

Eur Clin Respir J 2017 7;4(1):1359477. Epub 2017 Aug 7.

Department of Respiratory Medicine, Odense University Hospital, Odense C, Denmark.

: Omalizumab improves asthma control in patients with uncontrolled severe allergic asthma; however, appropriate patient selection is crucial. Information in this field is sparse. : We aimed to estimate whether potential omalizumab candidates were appropriately selected according to guidelines, and the clinical effect of omalizumab treatment over time. : We performed a retrospective observational study on adult patients with asthma treated with omalizumab during 2006-2015 at the Department of Respiratory Medicine at Odense University Hospital (OUH), Denmark. Data were obtained from the Electronic Patient Journal of OUH and Odense Pharmaco-Epidemiological Database. Guideline criteria for omalizumab treatment were used to evaluate the appropriateness of omalizumab candidate selection, and the Asthma Control Test (ACT) to assess the clinical effects of omalizumab at weeks 16 and 52 from treatment initiation. : During the observation period, 24 patients received omalizumab, but only 10 patients (42%) fulfilled criteria recommended by international guidelines. The main reasons for not fulfilling the criteria were inadequately reduced lung function, insufficient number of exacerbations, and asthma standard therapy below Global Initiative for Asthma (GINA) step 4-5. Seventeen and 11 patients completed treatment at weeks 16 and 52, with a statistically significant increase in ACT score of 5.1 points [95% confidence interval (CI) 3.1-7.2,  = 0.0001] and 7.7 points (95% CI 4.3-11.1,  = 0.0005), respectively. : Only 42% of the omalizumab-treated patients were appropriately selected according to current guidelines. Still, as omalizumab showed significant improvement in asthma control over time, it is important to keep this drug in mind as an add-on to asthma therapy in well-selected patients.
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http://dx.doi.org/10.1080/20018525.2017.1359477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5553102PMC
August 2017

Silicone implant incompatibility syndrome (SIIS) in a 57-year-old woman with unilateral silicone breast implant.

BMJ Case Rep 2017 Jul 24;2017. Epub 2017 Jul 24.

Department of Plastic Surgery, Odense University Hospital, Odense, Denmark.

Since the 1960s, silicone implants have been used for breast augmentations, both cosmetically and in reconstructive surgery. Tissue exposed to silicone can react with multiple adverse advents. Autoimmune/inflammatory syndrome induced by adjuvants due to silicone exposure from ruptured silicone implants can lead to different interstitial lung manifestations predominantly with granuloma evolvement, leading to the so-called silicone implant incompatibility syndrome (SIIS). This case describes a 57-year-old woman with multiple lung infiltrations and a left-sided breast implant. The implant had been replaced twice, once due to implant rupture 36 years ago. The nodular infiltrates could not be related to infection, malignancy, interstitial lung disease, vasculitis or connective tissue disorder, and it was concluded that the nodular infiltrations were of inflammatory origin due to an autoimmune response secondary to the silicone implants (SIIS). After explantation, the patient's symptoms subsided and her physical condition has remarkably improved.
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http://dx.doi.org/10.1136/bcr-2016-218709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5612359PMC
July 2017

Fibrocyte measurement in peripheral blood correlates with number of cultured mature fibrocytes in vitro and is a potential biomarker for interstitial lung disease in Rheumatoid Arthritis.

Respir Res 2017 07 18;18(1):141. Epub 2017 Jul 18.

Department Clinical Immunology, Odense University Hospital, Odense, Denmark.

Background: Interstitial lung disease (ILD) can be a severe extra-articular disease manifestation in Rheumatoid Arthritis (RA). A potential role of fibrocytes in RA associated ILD (RA-ILD) has not previously been described. We present a modified faster method for measuring circulating fibrocytes, without intracellular staining. The results are compared to the traditional culture method, where the number of monocytes that differentiate into mature fibrocytes in vitro are counted. The results are following compared to disease activity in patients with severe asthma, ILD, RA (without diagnosed ILD) and RA with verified ILD (RA-ILD).

Method: CD45 CD34 CD11b (7-AAD CD3 CD19 CD294) cells were isolated by cell sorting and stained for pro-collagen type 1. Thirty-nine patients (10 RA, 9 ILD and 10 with severe asthma, 10 with RA-ILD) and 10 healthy controls (HC) were included. Current medication, disease activity, pulmonary function test and radiographic data were collected. Circulating fibrocytes were quantified by flow cytometry. Peripheral blood mononuclear cells were isolated and cultured for 5 days and the numbers of mature fibrocytes were counted.

Results: 90.2% (mean, SD = 1.5%) of the sorted cells were pro-collagen type 1 positive and thereby fulfilled the criteria for being circulating fibrocytes. The ILD and RA-ILD groups had increased levels of circulating fibrocytes compared to HC (p < 0.05). Levels of circulating fibrocytes correlated overall to number of monocytes that subsequently in vitro differentiated to mature fibrocytes (r = 0.81, p < 0.001). RA patients with pathologically reduced diffusion capacity for carbon monoxide adjusted for hemoglobin (DLCO) in both the RA and in the combined RA + RA-ILD group, had significantly higher levels of both circulating and number of cultured mature fibrocytes (both p < 0.05). In both groups, the level of circulating fibrocytes and number of mature fibrocytes in culture also correlated to a reduction in DLCO (r = -0.61 an r = -0.58 both p < 0.05).

Conclusions: We presented a fast and valid method for measuring circulating fibrocytes using flow cytometry on lysed peripheral blood. Further, we showed for the first time, that the level of circulating fibrocytes correlated with the number of peripheral blood mononuclear cells, that differentiated into mature fibrocytes in vitro. Reduced DLCO was correlated with high levels of circulating and mature fibrocytes in RA, which have not been reported previously. In such, this study suggests that fibrocytes may exhibit an important role in the pathogenesis of RA-ILD, which requires further clarification in future studies.

Trial Registration: ClinicalTrials.gov : NCT02711657 , registered 13/3-2016, retrospectively registered.
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http://dx.doi.org/10.1186/s12931-017-0623-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5516315PMC
July 2017