Christopher Atkins

Managing fatigue in sarcoidosis – a systematic review of the evidence

Fatigue is a common manifestation of sarcoidosis, often persisting without evidence of disease activity. First-line therapies for sarcoidosis have limited effect on fatigue. This review aimed to assess the treatment options targeting sarcoidosis-associated fatigue. Medline and Web of Science were searched in November 2015; the bibliographies of these papers, and relevant review papers, were also searched. Studies were included if they reported on the efficacy of interventions (both pharmacological and non-pharmacological) on fatigue scores in sarcoidosis patients. Eight studies were identified that fulfilled the inclusion criteria. These studies evaluated six different interventions (infliximab, adalimumab, ARA 290, methylphenidate, armodafinil and exercise programmes). There is evidence to support a treatment effect of anti-tumour necrosis factor (TNF)-αtherapies (adalimumab and infliximab) and neurostimulants (methylphenidate and armodafinil), but within five of the studies, the risk of bias was high within most domains and the remaining three studies included only small numbers of participants and were short in duration. Trial evidence for treating fatigue as a manifestation of sarcoidosis is limited and requires further investigation. Anti-TNF-α therapies may be beneficial in patients with organ-threatening disease. Neurostimulants have some trial evidence supporting improvements in fatigue but further investigation is needed before they can be recommended.

Measuring sedentary behaviors in patients with idiopathic pulmonary fibrosis using wrist-worn accelerometers

Idiopathic pulmonary fibrosis (IPF) patients suffer increasing functional limitation with disease worsening disease. Increasing time in sedentary behavior has been associated with poorer quality of life. Determining thresholds for activity in patients with respiratory disease is difficult due to variable cardiorespiratory limitations between individuals. Measuring sedentary behavior is not confounded by this limitation and may be a better measurement of activity in patients with respiratory disease.

Feasibility study of a randomised controlled trial to investigate the treatment of sarcoidosis-associated fatigue with methylphenidate (FaST-MP): a study protocol

Introduction Fatigue is a frequent and troublesome manifestation of chronic sarcoidosis. This symptom can be debilitating and difficult to treat, with poor response to the treatment. Symptomatic management with neurostimulants, such as methylphenidate, is a possible treatment option. The use of such treatment strategies is not without precedent and has been trialled in cancer-related fatigue. Their use in sarcoidosis requires further evaluation before it can be recommended for clinical practice. Methods and analysis The Fatigue and Sarcoidosis—Treatment with Methylphenidate study is a randomised, controlled, parallel-arm and feasibility trial of methylphenidate for the treatment of sarcoidosis-associated fatigue. Patients are eligible if they have a diagnosis of sarcoidosis, significant fatigue (measured using the Fatigue Assessment Scale) and have stable disease. Up to 30 participants will be randomly assigned to either methylphenidate (20 mg two times per day) or identical placebo in a 3:2 ratio for 24 weeks. The primary objective is to collect data determining the feasibility of a future study powered to determine the clinical efficacy of methylphenidate for sarcoidosis-associated fatigue. The trial is presently open and will continue until July 2018. Ethics and dissemination Ethical approval for the study was granted by the Cambridge Central Research Ethics Committee on 21 June 2016 (reference 16/EE/0087) and was approved and sponsored by the Norfolk and Norwich University Hospital (reference 190280). Clinical Trial Authorisation (EudraCT number 2016-000342-60) from the Medicines and Healthcare products Regulatory Agency (MHRA) was granted on 19 April 2016. Results will be presented at relevant conferences and submitted to appropriate journals following trial closure and analysis. Trial registration number NCT02643732; Pre-results.

P277 Measuring sedentary behaviours in patients with idiopathic pulmonary fibrosis using wrist-worn accelerometers

Introduction Idiopathic pulmonary fibrosis (IPF) patients suffer increasing functional limitation as the disease progresses. Increasing sedentary behaviour (SB) time has been associated with poorer health-related quality of life. Determining thresholds for activity vigour in patients with respiratory disease is difficult due to variability in cardiorespiratory limitations between individuals. SB time is not confounded by this limitation and may be a more reliable measurement of activity in patients with severe exercise limitation such as IPF. Methods Thirty-nine IPF patients wore a GENEActiv actiwatch continually for 7 days. Participants underwent measurement of forced vital capacity (FVC), diffusion capacity of carbon monoxide (DLCO), 6 minute walk distance (6MWD) Results Valid data was downloaded from 35 of the 39 participants (89.7%). Mean acceleration intensity recorded in the most active 5 hours of each day (M5; in milli-g) were 43.8 milli-g and time spent in SB was 551.7 minutes per day, higher than estimates of time in SB in similar age demographics in previous studies. Daily SB time correlated moderately with M5 values (pearson correlation −0.366, p = 0.030). Only M5 values predicted time in SB. No variability in SB time was seen by day of the week. There was a trend towards higher one and two year mortality with greater periods of time in SB. Conclusions Wrist-worn accelerometers reliably collected data and were well tolerated. IPF patients spent long periods of time in sedentary behaviours. Of the standard clinical measures used, 6MWD predicted daily activity but not SB time; no clinical measures predicted SB time. Increased time in SB may be associated with poorer outcomes in IPF patients; replacing time in SB with light activity may be a more achievable goal than increasing moderate or vigorous activity levels in IPF patients and improve outcomes. Abstract P277 Figure 1 2-year survival analysis by tercile of sedentary behaviour

Plasma Vascular Endothelial Growth Factor Concentration and Alveolar Nitric Oxide as Potential Predictors of Disease Progression and Mortality in Idiopathic Pulmonary Fibrosis.

Background: Declining lung function signifies disease progression in idiopathic pulmonary fibrosis (IPF). Vascular endothelial growth factor (VEGF) concentration is associated with declining lung function in 6 and 12-month studies. Alveolar nitric oxide concentration (CANO) is increased in patients with IPF, however its significance is unclear. This study investigated whether baseline plasma VEGF concentration and CANO are associated with disease progression or mortality in IPF. Methods: 27 IPF patients were studied (maximum follow-up 65 months). Baseline plasma VEGF concentration, CANO and pulmonary function tests (PFTs) were measured. PFTs were performed the preceding year and subsequent PFTs and data regarding mortality were collected. Disease progression was defined as one of: death, relative decrease of ≥10% in baseline forced vital capacity (FVC) % predicted, or relative decrease of ≥15% in baseline single breath diffusion capacity of carbon monoxide (TLCO-SB) % predicted. Results: Plasma VEGF concentration was not associated with progression-free survival or mortality. There was a trend towards shorter time to disease progression and death with higher CANO. CANO was significantly higher in patients with previous declining versus stable lung function. Conclusion: The role of VEGF in IPF remains uncertain. It may be of value to further investigate CANO in IPF.