Test-retest repeatability for Fatigue Assessment Scale, Short-Form 6-Dimension and King's Sarcoidosis Questionnaire in people with sarcoidosis associated fatigue.

BACKGROUND AND AIM: Patient related outcomes are important in sarcoidosis but the medium-term repeatability of the key patient reported outcome measure is not known. We aimed to test the repeatability of the Fatigue Assessment Scale (FAS), Short Form 6-Dimension (SF-6D), and King's Sarcoidosis Questionnaire (KSQ) in free living people with sarcoidosis associated fatigue. METHODS: Twelve people with sarcoidosis associated fatigue completed the FAS, short form 36 questionnaire (SF-36) and the KSQ at baseline and 12 weeks. The SF-6D utility was calculated from the SF-36. The difference between baseline and 12 week assessments was measured. RESULTS: The interclass correlation (95% confidence interval) showed good agreement between the baseline and 3 months measurements: FAS 0.91 (0.74, 0.71), SF-36 0.98 (0.94, 1), KSQ 0.98 (0.93, 0.99), SF-6D utility 0.98 (0.93, 0.99). The baseline (standard deviation) FAS was 27.83 (5.86) and at 12 weeks was 27.25 (7.55) representing 0.58 difference (95% CI for difference (-1.89, 3.06)), SF-6D utility was 0.69 (0.16) at baseline and 0.68 (0.17) after 3 months representing at 0.00 (-0.03, 0.03) difference and corresponding values for KSQ were 59.12 (18.68) and 56.91 (27.26) with a difference of -1.87 (5.49,1.76). CONCLUSIONS: There was good repeatability of FAS, SF-36, SF-6D and KSQ in free living people with sarcoidosis associated fatigue. Fatigue, general and disease specific health related quality of life showed no significant change over a 12 week period. Studies identifying changes in these outcomes can confidently report a true change and not measurement error or regression to the mean.

Soluble interleukin-2 receptor in exhaled breath condensate in pulmonary sarcoidosis: a cross-sectional pilot study.

INTRODUCTION: Sarcoidosis is a chronic granulomatous disease of unknown aetiology with a variable clinical course and prognosis. There is an urgent need to identify new and novel biomarkers to help differentiate between clinical phenotypes and guide clinical decisions with respect to commencing and monitoring treatment. Across the spectrum of respiratory disease there has been a growing interest in the role of breath-based biomarkers given their non-invasive nature and ability to repeat sampling with ease for serial monitoring. Soluble interleukin-2 receptor (sIL2R) in bronchoalveolar lavage and serum correlates with disease activity in sarcoidosis; however, no previous study has evaluated sIL2R in exhaled breath. OBJECTIVES: The main aim of this cross-sectional case-controlled pilot study was to determine the concentration of sIL2R in exhaled breath condensate (EBC) from patients with recently diagnosed sarcoidosis compared to healthy volunteers and to establish, if present, if this correlated with markers of disease activity, pulmonary function tests and serological markers used in current clinical practice. METHODS: Paired serum and EBC samples were collected from twelve treatment naïve patients with histologically proven sarcoidosis diagnosed during the previous six months and compared to twelve healthy volunteers matched for age and gender. RESULTS: Mean concentration of serum sIL2R was significantly elevated in participants with sarcoidosis compared to healthy controls (1584.3 ± 489.1 versus 874.2 ± 235.7 pg mL-1; p = 0.001). Soluble interleukin-2 receptor in EBC was detectable in only five subjects including three participants with sarcoidosis. The range of sIL2R across all five samples was 148.0-288.2 pg mL-1 with the two highest concentrations observed in two participants with sarcoidosis. There was no significant difference observed in EBC sIL2R between sarcoidosis and healthy controls (p = 0.71). No apparent correlations were observed between EBC sIL2R and radiological stage, pulmonary function tests or serological markers. CONCLUSION: Soluble interleukin-2 receptor is detectable in EBC; however, the findings from our study do not support its role as a diagnostic marker in sarcoidosis. Further research is required to evaluate its prognostic utility.

The role of measuring exhaled breath biomarkers in sarcoidosis: a systematic review.

INTRODUCTION: Sarcoidosis is a chronic granulomatous disease of unknown aetiology with a variable clinical course and prognosis. There is a growing need to identify non-invasive biomarkers to differentiate between clinical phenotypes, identify those at risk of disease progression and monitor response to treatment. OBJECTIVES: We undertook a systematic review and meta-analysis to evaluate the utility of breath-based biomarkers in discriminating sarcoidosis from healthy controls, alongside correlation with existing non breath-based biomarkers used in clinical practice, radiological stage, markers of disease activity and response to treatment. METHODS: Electronic searches were undertaken during November 2017 using PubMed, Ebsco, Embase and Web of Science to capture relevant studies evaluating breath-based biomarkers in adult patients with sarcoidosis. RESULTS: 353 papers were screened; 21 met the inclusion criteria and assessed 25 different biomarkers alongside VOCs in exhaled breath gas or condensate. Considerable heterogeneity existed amongst the studies in terms of participant characteristics, sampling and analytical methods. Elevated biomarkers in sarcoidosis included 8-isoprostane, carbon monoxide, neopterin, TGF-ß1, TNFα, CysLT and several metallic elements including chromium, silicon and nickel. Three studies exploring VOCs were able to distinguish sarcoidosis from controls. Meta-analysis of four studies assessing alveolar nitric oxide showed no significant difference between sarcoidosis and healthy controls (2.22 ppb; 95% CI -0.83, 5.27) however, a high degree of heterogeneity was observed with an I 2 of 93.4% (p < 0.001). Inconsistent or statistically insignificant results were observed for correlations between several biomarkers and radiological stage, markers of disease activity or treatment. CONCLUSIONS: The evidence for using breath biomarkers to diagnose and monitor sarcoidosis remains inconclusive with many studies limited by small sample sizes and lack of standardisation. VOCs have shown promising potential but further research is required to evaluate their prognostic role.

Breath biomarkers in idiopathic pulmonary fibrosis: a systematic review.

BACKGROUND: Exhaled biomarkers may be related to disease processes in idiopathic pulmonary fibrosis (IPF) however their clinical role remains unclear. We performed a systematic review to investigate whether breath biomarkers discriminate between patients with IPF and healthy controls. We also assessed correlation with lung function, ability to distinguish diagnostic subgroups and change in response to treatment. METHODS: MEDLINE, EMBASE and Web of Science databases were searched. Study selection was limited to adults with a diagnosis of IPF as per international guidelines. RESULTS: Of 1014 studies screened, fourteen fulfilled selection criteria and included 257 IPF patients. Twenty individual biomarkers discriminated between IPF and controls and four showed correlation with lung function. Meta-analysis of three studies indicated mean (± SD) alveolar nitric oxide (CalvNO) levels were significantly higher in IPF (8.5 ± 5.5 ppb) than controls (4.4 ± 2.2 ppb). Markers of oxidative stress in exhaled breath condensate, such as hydrogen peroxide and 8-isoprostane, were also discriminatory. Two breathomic studies have isolated discriminative compounds using mass spectrometry. There was a lack of studies assessing relevant treatment and none assessed differences in diagnostic subgroups. CONCLUSIONS: Evidence suggests CalvNO is higher in IPF, although studies were limited by small sample size. Further breathomic work may identify biomarkers with diagnostic and prognostic potential.

A 31-year-old female with a rare cause of recurrent lower lobar collapses.

Can you diagnose this patient presenting to the emergency department with a short history of productive cough and breathlessness and a history of recurrent admission for chest infections? http://ow.ly/PoHQ30kmGPi.

Management of Septated Malignant Pleural Effusions.

PURPOSE OF REVIEW: We review recent studies of patients with septated malignant pleural effusions, to understand what the clinical implications for patients are and what evidence-based methods should be used to manage these effusions. RECENT FINDINGS: Fibrinolytics improve effusion size assessed radiologically in patients with a chest drain inserted for septated malignant pleural effusions but this does not translate into an improvement in breathlessness relief or pleurodesis success. Fibrinolytics have also been used in patients with septated effusions associated with indwelling pleural catheters, but dyspnoea relief has not been assessed in this population. Patients with septated effusions or extensive adhesions appear to have a worse prognosis. SUMMARY: Patients with septated malignant pleural effusions have a poor prognosis and do not gain clinical benefit from fibrinolytics via chest drain. The role of fibrinolytics for septated effusions associated with indwelling pleural catheters requires further study.