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Purpose To evaluate the optimal tracer uptake time, the minimal amount of radioactivity and the inter-observer agreement for 11C-choline positron emission tomography/computed tomography (PET/CT) in patients with primary hyperparathyroidism (pHPT). Methods Twenty-one patients with biochemically proven pHPT were retrospectively studied after injection of 6.3 ± 1.2 MBq/kg 11C-choline. PET data of the first nine patients, scanned for up to 60 min, were reconstructed in 10-min frames from 10- to 60-min postinjection (p.i.), mimicking varying 11C-choline uptake times. Parathyroid adenoma to background contrast ratios were calculated and compared, using standardized uptake values (SUVs). Data was reconstructed with varying scan durations (1, 2.5, 5, and 10 min) at 20–30-min p.i. (established optimal uptake time), mimicking less administered radioactivity. To establish the minimal required radioactivity, the SUVs in the shorter scan durations (1, 2.5, and 5 min) were compared to the 10-min scan duration to determine whether increased variability and/or statistical differences were observed. Four observers analyzed the 11C-choline PET/CT in four randomized rounds for all patients. Results SUVpeak of the adenoma decreased from 30 to 40 p.i. onwards. All adenoma/background contrast ratios did not differ from 20- to 30-min p.i. onwards. The SUVs of adenoma in the scan duration of 1, 2.5, and 5 min all differed significantly from the same SUV in the 10-min scan duration (all p = 0.012). However, the difference in absolute SUV adenoma values was well below 10% and therefore not considered clinically significant. The inter-observer analysis showed that the Fleiss’ kappa of the 1-min scan were classified as “moderate,” while these values were classified as “good” in the 2.5-, 5-, and 10-min scan duration. Observers scored lower certainty scores in the 1- and 2.5-min scans compared to the 5- and 10-min scan durations. Conclusion The optimal time to start PET/CT scanning in patients with pHPT is 20 min after mean injection of 6.3 MBq/kg 11C-choline, with a recommended scan duration of at least 5 min. Alternatively, the radioactivity dose can be lowered by 50% while keeping a 10-min scan duration without losing the accuracy of 11C-choline PET/CT interpretation. Electronic supplementary material The online version of this article (10.1186/s13550-019-0534-5) contains supplementary material, which is available to authorized users.

Parametric response mapping can distinguish small airway disease, emphysema and parenchymal disease on pulmonary CT http://ow.ly/Neuw6

Nasal gene expression profiling is a promising method to characterize COPD non-invasively. We aimed to identify a nasal gene expression profile to distinguish COPD patients from healthy controls. We investigated whether this COPD-associated gene expression profile in nasal epithelium is comparable with the profile observed in bronchial epithelium. Genome wide gene expression analysis was performed on nasal epithelial brushes of 31 severe COPD patients and 22 controls, all current smokers, using Affymetrix Human Gene 1.0 ST Arrays. We repeated the gene expression analysis on bronchial epithelial brushes in 2 independent cohorts of mild-to-moderate COPD patients and controls. In nasal epithelium, 135 genes were significantly differentially expressed between severe COPD patients and controls, 21 being up- and 114 downregulated in COPD (false discovery rate

Introduction: Nasal gene expression profiling is a promising method to characterize COPD non-invasively. First, we aimed to identify a nasal gene expression profile that distinguishes COPD patients from healthy controls. Next, we investigated whether this COPD-associated gene expression profile in nasal epithelium is comparable with the profile in the lower airways, i.e. the bronchial epithelium. Methods: Genome wide gene expression analysis was performed on nasal epithelial brushes of 76 COPD patients and 39 healthy controls, using Affymetrix Human Gene 1.0 ST Arrays. To compare findings in nasal and bronchial epithelium, we repeated the gene expression analysis on bronchial epithelial brushes in 2 independent cohorts of COPD patients and controls. Results: We found 2673 genes to be significantly differentially expressed in nasal epithelium between COPD patients and controls, 1158 being up- and 1515 downregulated in COPD (false discovery rate Conclusion: We identified a nasal gene expression profile that differentiates individuals with and without COPD. Of interest, part of the nasal gene expression changes in COPD is comparable to differentially expressed genes in the bronchus. These findings indicate that nasal gene expression has the potential to be developed as a non-invasive biomarker in COPD.

Background. Cigarette smoking is the main cause of chronic obstructive pulmonary disease (COPD) inducing oxidative stress and local tissue injury, resulting in pulmonary inflammation. Advanced glycation end products (AGEs) are produced by glycation and oxidation processes and their formation is accelerated in inflammatory conditions. In this study we assessed whether AGE accumulation in the skin is elevated in COPD and associates with disease severity.Methods. 202 mild-to-very-severe COPD patients and 83 old (40-75 years) and 110 young (18-40 years) healthy smokers and never-smokers were included. AGEs were measured by skin autofluorescence (SAF). Demographic variables, smoking habits, co-morbidities and lung function values were obtained.Results. COPD patients (FEV1 = 55% predicted) had significantly higher SAF values than old and young healthy controls: 2.5 vs. 1.8 and 1.2 (arbitrary units, p Conclusions. SAF is increased in mild-to-very severe COPD patients compared with healthy controls. Interestingly, SAF was not associated with disease severity as values were comparable between different GOLD stages (stage I-IV) of COPD. This may suggest that AGEs play a role in the induction phase of COPD in susceptible smokers. Future studies should further investigate the mechanisms underlying AGEs formation and accumulation in COPD. (C) 2014 Elsevier Inc. All rights reserved.

Background We hypothesised that increased oxidative stress, as present in the airways of asthma and chronic obstructive pulmonary disease (COPD) patients, induces epithelial damage and reduces epithelial responsiveness to suppressive effects of corticosteroids on proinflammatory cytokine production and barrier function.Methods We induced oxidative stress by H2O2 and/or cigarette smoke extract (CSE) in human bronchial epithelial 16HBE cells and primary bronchial epithelial cells (PBEC) derived by brushings from asthma patients, COPD patients, and smoking and non-smoking control individuals. We investigated effects of budesonide on barrier function (electrical resistance) and TNF-alpha-induced proinflammatory cytokine production (IL-8/CXCL8, granulocyte macrophage-colony stimulating factor (GM-CSF)).Results We observed that H2O2 and CSE reduce epithelial resistance. Budesonide significantly counteracted this effect, likely by protection against epidermal growth factor receptor-dependent cell-cell contact disruption. Furthermore, budesonide suppressed proinflammatory cytokine production. H2O2 pretreatment reduced this effect of budesonide on cytokine production in both 16HBE cells and PBECs. Importantly, PBECs from asthma and COPD patients were less sensitive to budesonide with respect to cytokine production and barrier function than PBECs from control subjects.Conclusions Together, our data indicate that budesonide suppresses epithelial proinflammatory responses and barrier dysfunction and that oxidative stress reduces these effects in airway epithelium from asthma and COPD patients. Therefore, restoration of corticosteroid responsiveness in asthma and COPD may act to improve the airway epithelial barrier.

To the Editor: Bronchial hyperresponsiveness (BHR), i.e. increased narrowing of the airways after exposure to non-allergic stimuli, is a hallmark of asthma. BHR is a risk factor for asthma development and, additionally, a marker of worse disease outcome in asthma [1, 2]. It is generally acknowledged that obstruction of the large airways due to inflammation and remodelling contributes to more severe BHR. This is plausible, given that BHR is expressed as the concentration or dose of a stimulus that induces a 20% fall in forced expiratory volume in 1 s (FEV1). Recent studies suggest that asthmatics with BHR have more severe small airways obstruction [3, 4]. However, little is known about the converse, i.e. the association between small airways obstruction and the severity of BHR. Our aim was to assess: 1) whether asthma patients with small airways obstruction express more severe BHR than those without small airways obstruction; and 2) whether small airways obstruction is associated with more severe BHR independently of FEV1. We analysed data from patients with mild-to-moderate asthma who were included in a previously published study on inhaled corticosteroids (ICS) in primary care [5]. All subjects underwent spirometry before and after 1 mg terbutaline, measuring FEV1, forced vital capacity (FVC) and mean expiratory flow at 50% of FVC (MEF50). BHR was assessed using a histamine challenge test, measuring the provocative dose causing a 20% fall in FEV1 (PD20) (histamine). All patients were hyperresponsive to histamine (PD …

Rationale: Cigarette smoke is the major risk factor in the development of chronic obstructive pulmonary disease (COPD). Lipidomics is a novel and emerging research field that may provide new insights in the origins of chronic inflammatory diseases, such as COPD.Objectives: To investigate whether expression of the sputum lipidome is affected by COPD or cigarette smoking.Methods: Lipid expression was investigated with liquid chromatography and high-resolution quadrupole time-of-flight mass spectrometry in induced sputum comparing smokers with and without COPD, and never-smokers. Changes in lipid expression after 2-month smoking cessation were investigated in smokers with and without COPD.Measurements and Main Results: More than 1,500 lipid compounds were identified in sputum. The class of sphingolipids was significantly higher expressed in smokers with COPD than in smokers without COPD. At single compound level, 168 sphingolipids, 36 phosphatidylethanolamine lipids, and 5 tobacco-related compounds were significantly higher expressed in smokers with COPD compared with smokers without COPD. The 13 lipids with a high fold change between smokers with and without COPD showed high correlations with lower lung function and inflammation in sputum. Twenty (glyco)sphingolipids and six tobacco-related compounds were higher expressed in smokers without COPD compared with never-smokers. Two-month smoking-cessation reduced expression of 26 sphingolipids in smokers with and without COPD.Conclusions: Expression of lipids from the sphingolipid pathway is higher in smokers with COPD compared with smokers without COPD. Considering their potential biologic properties, they may play a role in the pathogenesis of COPD.

The management of bronchiolitis obliterans syndrome (BOS) after hematopoietic cell transplantation presents many challenges, both diagnostically and therapeutically. We developed a computed tomography (CT) voxel-wise methodology termed parametric response mapping (PRM) that quantifies normal parenchyma, functional small airway disease (PRMfSAD,) emphysema, and parenchymal disease as relative lung volumes. We now investigate the use of PRM as an imaging biomarker in the diagnosis of BOS. PRM was applied to CT data from 4 patient cohorts: acute infection (n = 11), BOS at onset (n = 34), BOS plus infection (n = 9), and age-matched, nontransplant control subjects (n = 23). Pulmonary function tests and bronchoalveolar lavage were used for group classification. Mean values for PRMfSAD were significantly greater in patients with BOS (38% +/- 2%) when compared with those with infection alone (17% +/- 4%, P 28% highly indicative of BOS occurrence. PRM may provide a major advance in our ability to identify the small airway obstruction that characterizes BOS, even in the presence of concurrent infection. (C) 2014 American Society for Blood and Marrow Transplantation.

Background It has been suggested that smoking asthmatics benefit less from corticosteroid treatment than never-smoking asthmatics. We investigated differences in blood and sputum inflammatory profiles between ex-, current-, and never-smokers and assessed their ICS treatment response after 2-week and 1-year treatment. Methods We analyzed FEV1, PC20 methacholine and PC20 AMP, (differential) cell counts in sputum and blood in ex-, current- and never-smokers at baseline (n=114), after 2-week treatment with fluticasone 500 or 2000 μg/day (n=76) and after 1-year treatment with fluticasone 500 μg/day or a variable dose of fluticasone based on a self-management plan (n=64). Results A total of 114 patients were included (29 ex-, 30 current- and 55 never-smokers. At baseline, ex- and current-smokers had less eosinophils in sputum and blood than never-smokers. Blood neutrophil counts were higher in current- than in never-smokers. A higher number of cigarettes smoked daily was associated with lower blood and sputum eosinophils. After 2-week ICS treatment, FEV1 %predicted improved less in current-smokers than never-smokers (2.4% versus 8.1%, p=0.010) and ex-smokers tended to improve less than never-smokers (4.1%, p=0.067). In contrast, no differences in ICS treatment response in lung function or inflammatory cells were found between the three groups after 1 year. Conclusions Ex- and current-smokers have less eosinophils and more neutrophils in their sputum and blood than never-smokers. Although ex- and current-smokers have a reduced short-term corticosteroid treatment response, we did not find a difference in their long-term treatment response.

BackgroundBronchial hyperresponsiveness (BHR) can be present in subjects without any respiratory symptoms. Little is known about the role of the small airways in asymptomatic subjects with BHR.MethodsWe investigated small airway function assessed by spirometry and impulse oscillometry, as well as Borg dyspnea scores at baseline and during a methacholine provocation test in 15 subjects with asymptomatic BHR, 15 asthma patients, and 15 healthy controls.ResultsAt baseline, small airway function (R-5-R-20 and X-5) was comparable between subjects with asymptomatic BHR and healthy controls, whereas asthma patients showed small airway dysfunction as reflected by higher R-5-R-20 and lower X-5 values. During methacholine provocation, small airway dysfunction was more severe in asthma patients than in subjects with asymptomatic BHR. Interestingly, a higher increase in small airway dysfunction during methacholine provocation was associated with a higher increase in Borg dyspnea scores in subjects with asymptomatic BHR, but not in asthma patients.ConclusionSubjects with asymptomatic BHR may experience fewer symptoms in daily life because they have less small airway dysfunction.