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Background Health-related quality of life (HRQoL) is impaired in patients with pulmonary hypertension (PH). The EmPHasis-10 and CAMPHOR questionnaires are developed to evaluate HRQoL specifically in patients with PH. Data on the longitudinal use of both questionnaires are still limited. Purpose This paper will evaluate and compare the longitudinal value of two health-related quality of life questionnaires specific for patients with pulmonary hypertension (CAMPHOR and EmPHasis-10 questionnaires) using a broad spectrum of clinical anchor points. Furthermore we will establish minimal clinically important differences (MCID) for both questionnaires. Methods Sixty-one treatment naïve pulmonary arterial hypertension or chronic thromboembolic patients were prospectively included. Patients were treated according to the current ESC/ERS guidelines. We compared EmPHasis-10 and CAMPHOR scores between baseline, 6 and 12 months of follow-up and evaluated the correlation between these scores and a 5-scale symptom severity score, 5-scale overall health score, NYHA-classification, six minute walk test distance (6MWD), NT-proBNP and echocardiographic parameters. MCIDs were calculated using distribution and anchor based calculations. Results After one year of treatment a significant reduction in EmPHasis-10 score and CAMPHOR QoL and symptoms domain score was observed. Moderate to good correlations were observed between the questionnaires and the overall-health and symptom severity score and 6MWD. No relevant correlations were seen between the questionnaires and NT-pro-BNP and echocardiographic parameters. EmPHasis-10 scores showed strong correlations with all CAMPHOR domains. The MCID for the EmPHasis-10 questionnaire was −8. The MCIDs for the CAMPHOR domains were: activity −3, symptoms −4, QoL −3. Conclusion The EmPHasis-10 and CAMPHOR questionnaires are valid tools for the longitudinal measurement of HRQoL in patients with PH. The much shorter EmPHasis-10 correlates well with the CAMPHOR domain scores and with the clinical endpoints and it may be easier to use in daily practice. We established acceptable MCIDs. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): This research project was supported by an unrestricting grant by Actelion pharmaceuticals.

Background Recent studies have provided evidence for an important contribution of the immune system in the pathophysiology of pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). In this report, we investigated whether the inflammatory profile of pulmonary hypertension patients changes over time and correlates with patient WHO subgroups or survival. Methods 50 PAH patients (16 idiopathic (I)PAH, 24 Connective Tissue Disease (CTD)-PAH and 10 Congenital Heart Disease (CHD)-PAH), 37 CTEPH patients and 18 healthy controls (HCs) were included in the study. Plasma inflammatory markers at baseline and after 1-year follow-up were measured using ELISAs. Subsequently, correlations with hemodynamic parameters and survival were explored and data sets were subjected to unbiased multivariate analyses. Results At diagnosis, we found that plasma levels of interleukin-6 (IL-6) and the chemokines (C-X3-C) motif legend CXCL9 and CXCL13 in CTD-PAH patients were significantly increased, compared with HCs. In idiopathic PAH patients the levels of tumor growth factor-β (TGFβ), IL-10 and CXCL9 were elevated, compared with HCs. The increased CXCL9 and IL-8 concentrations in CETPH patients correlated significantly with decreased survival, suggesting that CXCL9 and IL-8 may be prognostic markers. After one year of treatment, IL-10, CXCL13 and TGFβ levels changed significantly in the PAH subgroups and CTEPH patients. Unbiased multivariate analysis revealed clustering of PH patients based on inflammatory mediators and clinical parameters, but did not separate the WHO subgroups. Importantly, these multivariate analyses separated patients with 3 years survival, in particular when inflammatory mediators were combined with clinical parameters. Discussion Our study revealed elevated plasma levels of inflammatory mediators in different PAH subgroups and CTEPH at baseline and at 1-year follow-up, whereby CXCL9 and IL-8 may prove to be prognostic markers for CTEPH patients. While this study is exploratory and hypothesis generating, our data indicate an important role for IL-8 and CXCL9 in CHD and CTEPH patients considering the increased plasma levels and the observed correlation with survival. Conclusion In conclusion, our studies identified an inflammatory signature that clustered PH patients into WHO classification-independent subgroups that correlated with patient survival.

Additional file 1: Figure 1. Effects of CXCL9 and IL-8 plasma levels on patient survival. Figure 2. Plasma concentrations of IL-1β and IL-6 Inflammatory markers in plasma of PAH and CTEPH patients at diagnosis and 1-year follow up. Figure 3. Inflammatory marker concentration of PH patients at diagnosis and at 1-year follow up are not separated by principal component analysis. Figure 4. Contribution of inflammatory markers and clinical parameters to multivariate analyses. Figure 5. Combination of inflammatory markers and clinical parameters leads to the best separation of survival in PAH patients. Table 1. Antibody kits used for ELISA.

Electronic cigarettes have rapidly attracted interest as a method to help people quit smoking, on the premise that e-cigarettes are less harmful than tobacco. However, so far studies have not provided convincing evidence that using electronic cigarettes is a better method of smoking cessation than other methods such as motivational counselling, either with or without nicotine replacement therapy. In addition, there is an alarming growth in the popularity of vaping among young people who find e-cigarettes attractive. Recent studies show the harmful effects of the ingredients of the e-cigarette fluid have resulted in acute pulmonary complications such as organizing pneumonia, asthma attacks and diffuse alveolar bleeding. The long-term effects of e-cigarettes are largely unknown, but one doesn't need to be a soothsayer to predict that the long-term damage will be significant. In conclusion, as pulmonologists, we find it necessary to give a serious warning to the Dutch population and would summarize the recommendations for vaping with one simple word - "Don't".

Objectives Sarcoidosis is a chronic, multisystem disease with often a major impact on quality of life. Information on unmet needs of patients and their partners is lacking. We assessed needs and perceptions of sarcoidosis patients and their partners. Methods During patient information meetings in 2015 and 2017 in the Erasmus University Medical Center, we interviewed patients and partners using interactive voting boxes. Patients responded anonymously to 17 questions. Answers were projected directly on the screen in the room. Results 210 patients and 132 partners participated. Sarcoidosis has a subjective significant impact on lives of both patients and partners. The vast majority of patients and partners feel regularly misunderstood because of the general unawareness of sarcoidosis. Many patients and partners experience anxiety. Three-quarters of patients would like to see more attention and support for their psychological problems. Additionally, more supportive care for partners of sarcoidosis patients is warranted. Interactive interviewing was considered educational (91%) and pleasant (84%). Discussion This study improves awareness of needs and perceptions of patients with sarcoidosis and their partners. Sarcoidosis leads to anxiety and psychological distress and impairs well-being of patients and their partners. Attention for psychological support, better disease education, and more supportive care for partners is warranted.

BackgroundPatients with sarcoidosis often experience fatigue and psychological distress, but little is known about the etiology of these conditions. While serum and saliva steroid hormones are used to monitor acute steroid levels, scalp hair analysis is a relatively new method enabling measurement of long-term steroid levels, including hair cortisol reflecting chronic stress. We investigated whether scalp hair cortisol and testosterone levels differ between sarcoidosis patients both with and without fatigue and general population controls. Additionally, we studied if these hormones could serve as objective biomarkers for psychological distress in patients with sarcoidosis.MethodsWe measured hair steroid levels using liquid chromatography-tandem mass spectrometry in glucocorticoid naïve sarcoidosis patients. Patients completed the Perceived Stress Scale, Fatigue Assessment Scale, Hospital Anxiety and Depression Scale and Short Form 36 (SF-36). Hair steroid levels from 293 participants of the population-based Lifelines cohort study served as controls.ResultsThirty-two patients (14 males) were included. Hair cortisol, but not testosterone, concentrations were significantly higher in patients with sarcoidosis than in general population controls (mean 6.6 versus 2.7 pg/mg, pConclusionsPatients with sarcoidosis have chronically higher levels of the stress hormone cortisol than the normal population, while testosterone levels in hair did not differ. Hair cortisol levels were positively related to subjective measures of psychological distress, but not to fatigue. Our study shows that hair cortisol is a promising non-invasive biomarker for psychological distress in patients with sarcoidosis.Trial registrationClinicalTrials.gov: NCT03108547. Registered 31 March 2017, retrospectively registered.

The Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) is the first disease-specific instrument for pulmonary arterial hypertension (PAH) to assess patient-perceived symptoms, activity limitations and quality of life. To be able to use this questionnaire in the Netherlands, the aim of the study was to translate and validate this instrument for the Dutch-speaking population.First the CAMPHOR was translated into Dutch (by means of a bilingual and a lay panel) and field-tested by means of cognitive debriefing interviews with ten PAH patients. For psychometric evaluation, 80 patients with PAH or chronic thromboembolic pulmonary hypertension (CTEPH) were asked to complete the CAMPHOR twice over a two-week period. To test for construct validity, participants also completed the Nottingham Health Profile (NHP).The Dutch version of the CAMPHOR showed high internal consistency for all scales (Cronbach's alpha 0.89-0.91) and excellent reproducibility over two weeks (reliability coefficients 0.87-0.91). Concurrent validity showed that the CAMPHOR scales correlated as expected with the NHP scales. The CAMPHOR was able to distinguish between patient groups based on self-reported general health status, disease severity and NYHA classification demonstrating evidence of known group validity. The CAMPHOR activity limitations scale correlated moderately with the distance walked during the 6‑minute walk test (r = -0.47, p 0.01) and the symptoms scale with the Borg dyspnoea score (r = 0.51, p 0.01).The Dutch version of the CAMPHOR is a reliable and valid measure of quality of life and health status in patients with PAH and CTEPH is recommended for use in routine care and in clinical research.

Background The Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) is the first disease-specific instrument for pulmonary arterial hypertension (PAH) to assess patient-perceived symptoms, activity limitations and quality of life. To be able to use this questionnaire in the Netherlands, the aim of the study was to translate and validate this instrument for the Dutch-speaking population. Methods First the CAMPHOR was translated into Dutch (by means of a bilingual and a lay panel) and field-tested by means of cognitive debriefing interviews with ten PAH patients. For psychometric evaluation, 80 patients with PAH or chronic thromboembolic pulmonary hypertension (CTEPH) were asked to complete the CAMPHOR twice over a two-week period. To test for construct validity, participants also completed the Nottingham Health Profile (NHP). Results The Dutch version of the CAMPHOR showed high internal consistency for all scales (Cronbach’s alpha 0.89–0.91) and excellent reproducibility over two weeks (reliability coefficients 0.87–0.91). Concurrent validity showed that the CAMPHOR scales correlated as expected with the NHP scales. The CAMPHOR was able to distinguish between patient groups based on self-reported general health status, disease severity and NYHA classification demonstrating evidence of known group validity. The CAMPHOR activity limitations scale correlated moderately with the distance walked during the 6‑minute walk test (r = −0.47, p

Background Fibrocytes are implicated in Idiopathic Pulmonary Fibrosis (IPF) pathogenesis and increased proportions in the circulation are associated with poor prognosis. Upon tissue injury, fibrocytes migrate to the affected organ. In IPF patients, circulating fibrocytes are increased especially during exacerbations, however fibrocytes in the lungs have not been examined. Therefore, we sought to evaluate if fibrocytes can be detected in IPF lungs and we compare percentages and phenotypic characteristics of lung fibrocytes with circulating fibrocytes in IPF. Methods First we optimized flow cytometric detection circulating fibrocytes using a unique combination of intra- and extra-cellular markers to establish a solid gating strategy. Next we analyzed lung fibrocytes in single cell suspensions of explanted IPF and control lungs and compared characteristics and numbers with circulating fibrocytes of IPF. Results Using a gating strategy for both circulating and lung fibrocytes, which excludes potentially contaminating cell populations (e.g. neutrophils and different leukocyte subsets), we show that patients with IPF have increased proportions of fibrocytes, not only in the circulation, but also in explanted end-stage IPF lungs. These lung fibrocytes have increased surface expression of HLA-DR, increased intracellular collagen-1 expression, and also altered forward and side scatter characteristics compared with their circulating counterparts. Conclusions These findings demonstrate that lung fibrocytes in IPF patients can be quantified and characterized by flow cytometry. Lung fibrocytes have different characteristics than circulating fibrocytes and represent an intermediate cell population between circulating fibrocytes and lung fibroblast. Therefore, more insight in their phenotype might lead to specific therapeutic targeting in fibrotic lung diseases. Electronic supplementary material The online version of this article (10.1186/s12931-018-0798-8) contains supplementary material, which is available to authorized users.

Background Nasal nitric oxide (nNO) values are reduced in patients with cystic fibrosis (CF). Humming during nNO measurement increases nNO values in healthy subjects. Nasal NO is reduced in patients with CF, sinus disease or nasal polyps. Humming nNO values have not been reported in CF patients yet. Our aim was to explore humming nNO values in CF patients and assess whether nNO during humming is a better discriminator than silent nNO measurements in this patient group. Materials and methods In a cross sectional study we measured nNO concentrations in healthy controls (HC) and in CF patients (n = 23 and 31, respectively). The participants held their breath for 10 s while air was passively extracted from one nostril with 700 mL min−1 for direct NO measurements (NIOX chemiluminescence analyser). Subsequently nNO was measured during humming with the mouth closed for 10 s. Results Mean nNO in parts per billion (p.p.b.) (SD) during breath hold was 499 (164) and 240 (139), respectively. The median nNO peak (p.p.b., minimum–maximum) during humming was 1500 (425–4100) for HC and 120 (23–500) for CF. There was a highly significant difference between nNO both with and without humming between CF and HC (P

Introduction: Stress, depression, anxiety and fatigue are major problems in sarcoidosis. Little is known about the etiology of psychological distress in sarcoidosis. Serum and saliva cortisol tests are commonly used to monitor acute stress. Scalp hair cortisol is a novel biomarker of long-term cortisol levels, and may reveal biological stress and its relationship with psychopathology in sarcoidosis patients. Aim: To study the relationships between hair cortisol concentrations (HCC) and psychological and fatigue measures in patients with sarcoidosis. Methods: We measured HCC using liquid chromatography–tandem mass spectrometry in glucocorticoid naive sarcoidosis patients. All patients completed the Hospital Anxiety and Depression Scale (HADS), Fatigue Assessment Scale (FAS), Perceived Stress Scale (PSS) and Short Form 36 (SF-36). Results: We included 32 patients with sarcoidosis (14 male). Mean (ranges) questionnaire scores were respectively PSS 26 (4-55), FAS 29 (10-46), HADS anxiety 6 (0-19), HADS depression 7 (0-21) and SF-36 mental field 60 (36-75); no significant sex differences were observed. In women, elevated HCC were associated with decreased psychological wellbeing, as measured by PSS (r=0.588, p=0.01), SF-36 mental (r=-0.553, p=0.017) and HADS anxiety (r=0.716, p=0.001), HADS depression (r=0.655,p=0.003). No significant correlations were found in men. HCC did not correlate with the FAS. Conclusion: Long-term increased cortisol measured in scalp hair is associated with decreased psychological wellbeing in women with sarcoidosis, but not with fatigue. Hair cortisol analysis seems a promising non-invasive biomarker of distress in sarcoidosis. Sex differences need further evaluation.

A 19-year-old man presented with dyspnoea, a non-productive cough and subfebrile temperature. Chest radiography showed a diffuse nodular pattern and a pneumomediastinum. HR-CT revealed a diffuse ‘tree in bud’ pattern (figure 1). An infectious bronchiolitis was suspected. Despite treatment with moxifloxacin he developed hypercapnic respiratory failure requiring mechanical ventilation. Extensive microbiological investigations did not reveal a pathogenic microorganism. Continued treatment with antibiotics, low-dose steroids and neomacrolides was not effective, and an open lung biopsy was performed. Histology showed an organising pneumonia (OP) with extensive endobronchiolar granulation tissue (figure 2). The treatment was converted …

A role for inflammatory processes in the pathogenesis of pulmonary arterial hypertension (PAH) has been proposed, since inflammatory infiltrates surrounding remodelled vessels in human and experimental PAH have been described by several groups 1, 2. Increased levels and expression of cytokines, chemokines and lipid mediators have been found in the blood, lung parenchyma and affected pulmonary vessels. The higher prevalence of PAH in connective tissue disorders and the successful treatment with immunosuppressive therapy in some forms of PAH support the concept of inflammatory pathways in the development and/or modulation of the disease. Although data are scarce, the infiltrates found in plexiform lesions consist mainly of lymphocytes and macrophages, whereas neutrophilic inflammation has not traditionally been described. The presence of lymphocytes in the vessel wall suggests that these cells might control the disease process by secretion of pleiotropic cytokines, analogous to what has been described in other T-cell-mediated diseases, such as asthma, auto-immune disorders or transplant rejection. In these diseases, effector T-lymphocytes are activated locally by antigen-presenting dendritic cells (DCs) to mediate disease 3, 4. A report by Perros et al. 5 in the current issue of the European Respiratory Journal describes an increase in these DCs in plexiform lesions of idiopathic PAH (IPAH) patients and rats with monocrotaline-induced PAH. This strongly suggests that these DCs present some form of (auto-)antigen to T-cells that might initiate or perpetuate inflammation. DCs are professional antigen-presenting cells that are located throughout the body but particularly at the boundaries of the body, such as mucosal surfaces and the skin, where they are known as Langerhans' cells. In these peripheral sites, they are specialised in recognising foreign antigens that invade across the natural barrier of the skin and mucosa 3, 4. At this stage, they are in a so-called immature …

Symptoms of atopic asthma often disappear around puberty. The authors recently demonstrated that this clinical remission is accompanied with ongoing airways inflammation in most subjects. The discrepancy between lack of symptoms and persistent airway inflammation suggests that perception of the symptoms is unclear. In the present study, young adults in clinical remission of atopic asthma assigned themselves a modified Borg score during methacholine and adenosine-5'-monophosphate induced bronchoconstriction. Borg scores of subjects in clinical remission were compared with those of symptomatic asthmatic subjects. A marked variation in the Borg scores at a 20% fall in the forced expiratory volume in one second was found. Significant differences in Borg scores between remission patients and asthmatics could not be detected. It was concluded that perception of dyspnoea, induced with methacholine and adenosine challenge, is similar in young adults in clinical remission of atopic asthma compared to that of patients with symptomatic asthma. Hence, an unclear perception seems to be an unlikely explanation for the discrepancy between lack of symptoms and ongoing inflammation. Other factors, including both physical and psychological ones, may play a role in the apparent absence of symptoms, thereby potentially leading to undertreatment.