79 research outputs found

    Severe T2-high asthma in the biologics era: European experts' opinion

    Get PDF
    The European Respiratory Biologics Forum gathered participants from 21 countries in Madrid, Spain, to discuss the management and treatment of severe asthma in the era of biologics. The current insights on the pathophysiology of severe asthma were discussed, as well as the role of respiratory biologics in clinical practice and strategies for eliminating chronic use of oral corticosteroids. The participants also highlighted the key challenges in identifying patients with severe asthma based on phenotypes, biomarkers and treatable traits, and the existing problems in patient referral to specialist care. The monitoring of treatment was debated and the need for a change towards precision medicine and personalised care was emphasised throughout the meeting. This review provides a summary of the discussions and highlights important concerns identified by the participants regarding the current management of severe asthma

    Quality of life assessment in interstitial lung diseases:a comparison of the disease-specific K-BILD with the generic EQ-5D-5L

    Get PDF
    Background: Patients with interstitial lung diseases (ILD) have impaired health-related quality of life (HRQL). Little is known about the applicability of the disease-specific King’s Brief Interstitial Lung Disease questionnaire (K-BILD) and the generic EQ-5D-5L in a German setting. Methods: We assessed disease-specific (K-BILD) and generic HRQL (EQ-5D experience based value set (EBVS) and Visual Analog Scale (VAS)) in 229 patients with different ILD subtypes in a longitudinal observational study (HILDA). Additionally, we assessed the correlation of the HRQL measures with lung function and comorbidities. In a linear regression model, we investigated predictors (including age, sex, ILD subtype, FVC percentage of predicted value (FVC%pred), DLCO percentage of predicted value, and comorbidities). Results: Among the 229 patients mean age was 63.2 (Standard deviation (SD): 12.9), 67.3% male, 24.0% had idiopathic pulmonary fibrosis, and 22.3% sarcoidosis. Means scores were as follows for EQ-5D EBVS 0.66(SD 0.17), VAS 61.4 (SD 19.1) and K-BILD Total 53.6 (SD 13.8). K-BILD had good construct validity (high correlation with EQ-5D EBVS (0.71)) and good internal consistency (Cronbach’s alpha 0.89). Moreover, all HRQL measures were highly accepted by patients including low missing items and there were no ceiling or floor effects. A higher FVC % pred was associated with higher HRQL in all measures meanwhile comorbidities had a negative influence on HRQL. Conclusions: K-BILD and EQ-5D had similar HRQL trends and were associated similarly to the same disease-related factors in Germany. Our data supports the use of K-BILD in clinical practice in Germany, since it captures disease specific effects of ILD. Additionally, the use of the EQ-5D-5L could provide comparison to different disease areas and give an overview about the position of ILD patients in comparison to general population

    Prognosis and longitudinal changes of physical activity in idiopathic pulmonary fibrosis

    Get PDF
    Background: Physical activity (PA) is associated with disease severity in idiopathic pulmonary fibrosis (IPF), but longitudinal studies evaluating its prognostic value and changes over time are lacking. Methods: We measured PA (steps per day, SPD) in a cohort of 46 IPF-patients (mean age, 67 years; mean FVC, 76.1%pred.) by accelerometry at baseline, recorded survival status during 3 years follow-up and repeated measurements in survivors. We compared the prognostic value of PA to established mortality predictors including lung function (FVC, DLCO) and 6-min walking-distance (6MWD). Results: During follow-up (median 34 months) 20 patients (43%) died. SPD and FVC best identified non-survivors (AUROC-curve 0.79, p < 0.01). After adjustment for confounders (sex, age, therapy), a standardized increase (i.e. one SD) in SPD, FVC%pred. or DLCO%pred. was associated with a more than halved risk of death (HR < 0.50; p < 0.01). Compared to baseline, SPD, FVC, and 6MWD annually declined in survivors by 973 SPD, 130 ml and 9 m, resulting in relative declines of 48.3% (p < 0.001), 13.3% (p < 0.001) and 7.8% (p = 0.055), respectively. Conclusion: While PA predicts mortality of IPF patients similar to established functional measures, longitudinal decline of PA seems to be disproportionally large. Our data suggest that the clinical impact of disease progression could be underestimated by established functional measures

    Small Airway Dysfunction Links Asthma Severity with Physical Activity and Symptom Control.

    Get PDF
    BACKGROUND Little is known about the role of small airway dysfunction (SAD) and its complex relation with asthma control and physical activity (PA). OBJECTIVE To investigate the interrelations among SAD, risk factors for asthma severity, symptom control, and PA. METHODS We assessed SAD by impulse oscillometry and other sophisticated lung function measures including inert gas washout in adults with asthma (mild to moderate, n = 140; severe, n = 128) and 69 healthy controls from the All Age Asthma Cohort. We evaluated SAD prevalence and its interrelation with risk factors for asthma severity (older age, obesity, and smoking), type 2 inflammation (sputum and blood eosinophils, fractional exhaled nitric oxide), systemic inflammation (high-sensitivity C-reactive protein), asthma control (AC), and PA (accelerometer for 1 week). We applied a clinical model based on structural equation modeling that integrated causal pathways among these clinical variables. RESULTS The prevalence of SAD ranged from 75% to 90% in patients with severe asthma and from 53% to 64% in mild to moderate asthma. Severe SAD was associated with poor AC and low PA. Structural equation modeling indicated that age, obesity, obesity-related systemic inflammation, T2 inflammation, and smoking are independent predictors of SAD. Small airway dysfunction was the main determinant factor of AC, which in turn affected PA. Obesity affected AC directly and through its contribution to SAD and low PA. In addition, PA had bidirectional associations with obesity, SAD, and AC. Structural equation modeling also indicated interrelations among distal airflow limitation, air trapping, and ventilation heterogeneity. CONCLUSIONS Small airway dysfunction is a highly prevalent key feature of asthma that interrelates a spectrum of distal lung function abnormalities with risk factors for asthma severity, asthma control, and physical activity

    Ocular manifestations in patients with COVID-19

    Get PDF
    Background There are only few reports on ocular symptoms and manifestations in association with coronavirus disease 2019 (COVID-19). Objective The aim of this study is to describe ocular manifestations in the anterior and posterior segments of the eye and to analyze viral prevalence in tears of patients with COVID-19. Methods Hospitalized COVID-19 patients treated from 16 April 2020 to 7 January 2021 at this hospital were screened for ocular manifestations in the anterior and posterior segments. Conjunctival swabs were analyzed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA. Results A total of 37 patients were enrolled in this study. In the anterior segment we found chemosis of the conjunctiva (5), hyposphagma (2) and conjunctivitis (1). In 11 patients vascular alterations and potentially disease-specific manifestations of the fundus were found in one or both eyes: retinal hemorrhages (5), cotton wool spots (5) and tortuosity (5). One patient demonstrated branch artery occlusion, one had branch retinal vein occlusion and two patients had positive conjunctival swab results in one or both eyes. Conclusion Our findings of the anterior segment are commonly known, although not specific for COVID-19. Various vascular fundus abnormalities were found in the study; however, it is unclear whether these were correlated to systemic comorbidities or whether they were caused or exacerbated by COVID-19. This study suggests that the risk of viral transmission via tears is low

    Increased breath naphthalene in children with asthma and wheeze of the All Age Asthma Cohort (ALLIANCE).

    Get PDF
    Background&#xD;Exhaled breath contains numerous volatile organic compounds (VOCs) known to be related to lung disease like asthma. Its collection is non-invasive, simple to perform and therefore an attractive method for the use even in young children. We analysed breath in children of the multicenter All Age Asthma Cohort (ALLIANCE) to evaluate if "breathomics" have the potential to phenotype patients with asthma and wheeze, and to identify extrinsic risk factors for underlying disease mechanisms.&#xD;Methods&#xD;A breath sample was collected from 142 children (asthma: 51, pre-school wheezers: 55, healthy controls: 36) and analysed using gas chromatography-mass spectrometry (GC/MS). Children were diagnosed according to GINA guidelines and comprehensively examined each year over up to seven years. Forty children repeated the breath collection after 24 or 48 months. &#xD;Results&#xD;Most breath VOCs differing between groups reflect the exposome of the children. We observed lower levels of lifestyle-related VOCs and higher levels of the environmental pollutants, especially naphthalene, in children with asthma or wheeze. Naphthalene was also higher in symptomatic patients and in wheezers with recent inhaled corticosteroid use. No relationships with lung function or TH2 inflammation were detected.&#xD;Conclusion&#xD;Increased levels of naphthalene in asthmatics and wheezers and the relationship to disease severity could indicate a role of environmental or indoor air pollution for the development or progress of asthma. Breath VOCs might help to elucidate the role of the exposome for the development of asthma.&#xD;The study was registered at ClinicalTrials.gov (NCT02496468).&#xD;&#xD

    A serological biomarker of type I collagen degradation is related to a more severe, high neutrophilic, obese asthma subtype

    Get PDF
    BACKGROUND: Asthma is a heterogeneous disease; therefore, biomarkers that can assist in the identification of subtypes and direct therapy are highly desirable. Asthma is a chronic inflammatory disease that leads to changes in the extracellular matrix (ECM) by matrix metalloproteinases (MMPs) degradation causing fragments of type I collagen that is released into circulation. OBJECTIVE: Here, we asked if MMP-generated type I collagen (C1M) was associated with subtypes of asthma. METHODS: C1M was serologically assessed at baseline in the adult participants of the All Age Asthma study (ALLIANCE) (n = 233), and in The Prospective Epidemiological Risk Factor study (PERF) (n = 283). In addition, C1M was assessed in mice sensitized to ovalbumin (OVA) and challenged with OVA aerosol. C1M was evaluated in mice with and without acute neutrophilic inflammation provoked by poly(cytidylic-inosinic) acid and mice treated with CP17, a peptide inhibiting neutrophil accumulation. RESULTS: Serum C1M was significantly increased in asthmatics compared to healthy controls (p = 0.0005). We found the increased C1M levels in asthmatics were related to blood neutrophil and body mass index (BMI) in the ALLIANCE cohort, which was validated in the PERF cohort. When patients were stratified into obese (BMI > 30) asthmatics with high neutrophil levels and uncontrolled asthma, this group had a significant increase in C1M compared to normal-weight (BMI < 25) asthmatics with low neutrophil levels and controlled asthma (p = 0.0277). C1M was significantly elevated in OVA mice with acute neutrophilic inflammation compared to controls (P = 0.0002) and decreased in mice treated with an inhibitor of neutrophil infiltration (p = 0.047). CONCLUSION & CLINICAL RELEVANCE: C1M holds the potential to identify a subtype of asthma that relates to severity, obesity, and high neutrophils. These data suggest that C1M is linked to a subtype of overall inflammation, not only derived from the lung. The link between C1M and neutrophils were further validated in in vivo model. TRIAL REGISTRATION: (ALLIANCE, NCT02419274). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40733-022-00084-6

    In vitro neutrophil migration is associated with inhaled corticosteroid treatment and serum cytokines in pediatric asthma.

    Get PDF
    Background: Different asthma phenotypes are driven by molecular endotypes. A Th1-high phenotype is linked to severe, therapy-refractory asthma, subclinical infections and neutrophil inflammation. Previously, we found neutrophil granulocytes (NGs) from asthmatics exhibit decreased chemotaxis towards leukotriene B4 (LTB4), a chemoattractant involved in inflammation response. We hypothesized that this pattern is driven by asthma in general and aggravated in a Th1-high phenotype. Methods: NGs from asthmatic nd healthy children were stimulated with 10 nM LTB4/100 nM N-formylmethionine-leucyl-phenylalanine and neutrophil migration was documented following our prior SiMA (simplified migration assay) workflow, capturing morphologic and dynamic parameters from single-cell tracking in the images. Demographic, clinical and serum cytokine data were determined in the ALLIANCE cohort. Results: A reduced chemotactic response towards LTB4 was confirmed in asthmatic donors regardless of inhaled corticosteroid (ICS) treatment. By contrast, only NGs from ICS-treated asthmatic children migrate similarly to controls with the exception of Th1-high donors, whose NGs presented a reduced and less directed migration towards the chemokines. ICS-treated and Th1-high asthmatic donors present an altered surface receptor profile, which partly correlates with migration. Conclusions: Neutrophil migration in vitro may be affected by ICS-therapy or a Th1-high phenotype. This may be explained by alteration of receptor expression and could be used as a tool to monitor asthma treatment

    COL4A3 is degraded in allergic asthma and degradation predicts response to anti-IgE therapy.

    Get PDF
    BACKGROUND Asthma is a heterogeneous syndrome substantiating the urgent requirement for endotype-specific biomarkers. Dysbalance of fibrosis and fibrolysis in asthmatic lung tissue leads to reduced levels of the inflammation-protective collagen 4 (COL4A3). OBJECTIVE To delineate the degradation of COL4A3 in allergic airway inflammation and evaluate the resultant product as a biomarker for anti-IgE therapy response. METHODS The serological COL4A3 degradation marker C4Ma3 (Nordic Bioscience, Denmark) and serum cytokines were measured in the ALLIANCE cohort (pediatric cases/controls: 134/35; adult cases/controls: 149/31). Exacerbation of allergic airway disease in mice was induced by sensitising to OVA, challenge with OVA aerosol and instillation of poly(cytidylic-inosinic). Fulacimstat (chymase inhibitor, Bayer) was used to determine the role of mast cell chymase in COL4A3 degradation. Patients with cystic fibrosis (CF, n=14) and CF with allergic broncho-pulmonary aspergillosis (ABPA, n=9) as well as severe allergic, uncontrolled asthmatics (n=19) were tested for COL4A3 degradation. Omalizumab (anti-IgE) treatment was assessed by the Asthma Control Test. RESULTS Serum levels of C4Ma3 were increased in asthma in adults and children alike and linked to a more severe, exacerbating allergic asthma phenotype. In an experimental asthma mouse model, C4Ma3 was dependent on mast cell chymase. Serum C4Ma3 was significantly elevated in CF plus ABPA and at baseline predicted the success of the anti-IgE therapy in allergic, uncontrolled asthmatics (diagnostic odds ratio 31.5). CONCLUSION C4Ma3 level depend on lung mast cell chymase and are increased in a severe, exacerbating allergic asthma phenotype. C4Ma3 may serve as a novel biomarker to predict anti-IgE therapy response
    • …
    corecore