Diagnostic value of bronchoalveolar lavage in interstitial lung diseases

Bronchoalveolar lavage (BAL) is currently widely applied to sample cells and proteins present in the bronchoalveolar space for subsequent studies. Moreover, this limited invasive technique is a sensitive indicator of infectious and non-infectious inflammatory disorders, such as interstitial lung diseases. The aim of this study was to investigate the clinical applications of BAL, in particular the diagnostic value of this method with a view to preventing more invasive procedures. The studies presented in this thesis are based on BAL fluid data obtained from patients during a ten-year period between 1980 and 1990. Cells and proteins, ie, albumin and immunoglobulins, determined in those BAL fluid samples, have been analyzed. Retrospectively, we searched for specific features in the data from the BAL fluid analyses, which distinguish between various interstitial lung diseases. This thesis describes the diagnostic value of BAL fluid sample analyses in patients suffering from various interstitial lung diseases. Emphasis is put on patients with sarcoidosis, extrinsic allergic alveolitis (EAA), or idiopathic pulmonary fibrosis

Informatieproblemen oplossen: een digitale en leerzame toets

In dit verslag wordt een advies gegeven over de bruikbaarheid van een Amerikaanse toets informatievaardigheden voor het Nederlands Hoger onderwijs. Deze toets is geëvalueerd binnen het DU-project Instrumentatie van Onderwijs in Kenniscompetenties (IOK). In de eerste fase van het project is gebleken dat deze toets deels bruikbaar lijkt binnen de Nederlandse onderwijscontext. In de tweede fase van het project is een selectie van de items vertaald en aangepast aan de Nederlandse context. De op basis hiervan ontwikkelde toets is afgenomen bij tweehonderd studenten in het hoger beroepsonderwijs en wetenschappelijk onderwijs. Uit de resultaten blijkt dat de toets in te zetten is als een diagnostisch meetinstrument. Daarbij blijken studenten door het gebruik van het instrument bewuster te worden van hun eigen (on) bekwaamheid op het gebied van informatievaardigheden. De studenten zijn met name positief over de in het instrument geïntegreerde feedback. Op basis van de reacties van studenten en inhoudsdeskundigen blijkt wel dat de toets nog voor verbetering vatbaar is

Benefit of wearing an activity tracker in sarcoidosis

Sarcoidosis causes many disabling symptoms, including fatigue and exercise limitations, which have been shown to improve by physical activity programs. The aim of this study was to estimate the effect of continuous activity monitoring using an electronic activity tracker (AT) on exercise performance and fatigue of sarcoidosis patients, compared to controls (cohort study), and the effect of additional personal coaching (randomized trial) over a period of 3 months. Fifty-four sarcoidosis patients received an AT (Group Ia: 27 with coaching and Group Ib: 27 without). A historical group of sarcoidosis patients (Group II;n= 41) who did not follow a physical activity program served as controls. Exercise performance of patients wearing an AT (Group I) improved compared with controls (Group II), including the 6MWD, % predicted ( increment 4.4 +/- 9.1 versus increment 0.7 +/- 5.0, respectively), and fatigue levels decreased ( increment -3.9 +/- 5.7 versus increment -1.8 +/- 5.3). Patients with coaching (Group Ia) showed greater improvement of exercise capacity over time than patients without coaching (Group Ib) as shown by the Steep Ramp Test results (watts: increment 20.2 +/- 33.8 versus increment 5.7 +/- 26.4; and SRT, VO(2)max, % predicted: increment 1.6 +/- 2.6 versus increment 0.7 +/- 2.3). Sarcoidosis patients wearing an AT achieved improvement of exercise performance and reduction of fatigue. We therefore recommend encouraging sarcoidosis patients to wear an AT to stimulate physical activity and reduce fatigue. The additional benefit of coaching needs to be explored in future studies

Potential biomarkers for diagnosis of sarcoidosis using proteomics in serum

SummaryBackgroundSarcoidosis is a multi-systemic inflammatory disorder, which affects the lungs in 90% of the cases. The main pathologic feature is chronic inflammation resulting in non-caseating granuloma formation. Until now there is no satisfying biomarker for diagnosis or prognosis of sarcoidosis. This study is focused on the detection of potential biomarkers in serum for the diagnosis of sarcoidosis using surface-enhanced laser desorption ionization-time of flight-mass spectrometry (SELDI-TOF-MS).MethodsFor detection of potential biomarkers, protein profiles of anion exchange fractionated serum of 35 sarcoidosis patients and 35 healthy controls were compared using SELDI-TOF-MS. Sensitivities and specificities of the potential biomarkers obtained with SELDI-TOF-MS, generated with decision tree algorithm, were compared to the conventional markers angiotensin converting enzyme (ACE) and soluble interleukin-2 receptor (sIL-2R).ResultsOptimal classification was achieved with metal affinity binding arrays. A single marker with a mass-to-charge (m/z) value of 11,955 resulted in a sensitivity and specificity of 86% and 63%, respectively. A multimarker approach of two peaks, m/z values of 11,734 and 17,377, resulted in a sensitivity and specificity of 74% and 71%, respectively. These sensitivities and specificities were higher compared to measurements of ACE and sIL-2R. Identification of the peak at m/z 17,377 resulted in the α-2chain of haptoglobin.ConclusionsThis study acts as a proof-of-principle for the use of SELDI-TOF-MS in the detection of new biomarkers for sarcoidosis. The peak of the multimarker at m/z 17,377 was identified as the α-2chain of haptoglobin

Clara cell protein in bronchoalveolar lavage fluid: a predictor of ventilator-associated pneumonia?

INTRODUCTION: Clara cell protein 10 (CC-10) has been associated with inflammatory and infectious pulmonary diseases. This study evaluates CC-10 concentrations in bronchoalveolar lavage (BAL) fluid as a potential marker of ventilator-associated pneumonia (VAP). METHODS: Between January 2003 and December 2007, BAL fluid samples obtained from critically ill patients at the intensive care unit of the Maastricht University Medical Centre clinically suspected of having VAP were included. Patients were divided into two groups: (1) microbiologically confirmed VAP (the VAP group) and (2) microbiologically unconfirmed VAP (the non-VAP group). The concentration of CC-10 was measured by means of a commercially available enzyme-linked immunosorbent assay kit, and retrospective analysis was performed. Areas under the curve of receiver operating characteristic curves were calculated for CC-10 concentrations. RESULTS: A total of 196 patients (122 men, 74 women) were included. A total of 79 (40%) of 196 cases of suspected VAP were microbiologically confirmed. The median CC-10 concentration in the VAP group was 3,019 ng/mL (range, 282 to 65,546 ng/mL) versus 2,504 ng/mL (range, 62 to 30,240 ng/mL) in the non-VAP group (P = 0.03). There was no significant difference in CC-10 concentrations between patients treated with or without corticosteroids (P = 0.26) or antibiotic therapy (P = 0.9). The CC-10 concentration did not differ significantly between patients with Gram-positive versus Gram-negative bacteria that caused the VAP (P = 0.06). However, CC-10 concentrations did differ significantly between the late-onset VAP group and the non-VAP group. CONCLUSIONS: The CC-10 concentration in BAL fluid yielded low diagnostic accuracy in confirming the presence of VAP

Quantitative ultrasound does not identify patients with an inflammatory disease at risk of vertebral deformities

<p>Abstract</p> <p>Background</p> <p>Previous studies from our group have shown that a high prevalence of vertebral deformities suggestive of fracture can be found in patients with an inflammatory disease, despite a near normal bone mineral density (BMD). As quantitative ultrasound (QUS) of the heel can be used for refined assessment of bone strength, we evaluated whether QUS can be used to identify subjects with an inflammatory disease with an increased chance of having a vertebral fracture.</p> <p>Methods</p> <p>246 patients (mean age: 44 ± 12.4 years) with an inflammatory disease (sarcoidosis or inflammatory bowel disease (IBD)) were studied. QUS of the heel and BMD of the hip (by dual X-ray absorptiometry (DXA)) were measured. Furthermore lateral single energy densitometry of the spine for assessment of vertebral deformities was done. Logistic regression analysis was performed to assess the strength of association between the prevalence of a vertebral deformity and BMD and QUS parameters, adjusted for gender and age.</p> <p>Results</p> <p>Vertebral deformities (ratio of <0.80) were found in 72 vertebrae of 54 subjects (22%). In contrast to the QUS parameters BUA (broadband ultrasound attenuation) and SOS (speed of sound), T-score of QUS and T-scores of the femoral neck and trochanter (DXA) were lower in the group of patients with vertebral deformities. Logistic regression analysis showed that the vertebral deformity risk increases by about 60 to 90% per 1 SD reduction of BMD (T-score) determined with DXA but not with QUS.</p> <p>Conclusion</p> <p>Our findings imply that QUS measurements of the calcaneus in patients with an inflammatory condition, such as sarcoidosis and IBD, are likely of limited value to identify patients with a vertebral fracture.</p

Increased circulating desmosine and age-dependent elastinolysis in idiopathic pulmonary fibrosis

Abstract Although chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) seem to be opposite entities from a clinical perspective, common initial pathogenic steps have been suggested in both lung diseases. Emphysema is caused by an elastase/anti-elastase imbalance leading to accelerated elastin degradation. Elastinolysis is however, also accelerated in the IPF patients’ lungs. The amino acids desmosine and isodesmosine (DES) are unique to elastin. During the degradation process, elastases liberate DES from elastin fibers. Blood DES levels consequently reflect the rate of systemic elastinolysis and are increased in COPD. This is the first report describing elevated DES levels in IPF patients. We also demonstrated that the age-related increment of DES concentrations is enhanced in IPF. Our current study suggests that elastinolysis is a shared pathogenic step in both COPD and IPF. Further investigation is required to establish the relevance of accelerated elastin degradation in IPF and to determine whether decelerating this process leads to slower progression of lung fibrosis and better survival for patients with IPF.https://deepblue.lib.umich.edu/bitstream/2027.42/142803/1/12931_2018_Article_747.pd