Tag: longitudinal study

Longitudinal investigation of natural killer cells and cytokines in chronic fatigue syndrome/myalgic encephalomyelitis

Abstract:

BACKGROUND: Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) is an etiologically unexplained disorder characterised by irregularities in various aspects of the immunological function. Presently, it is unknown whether these immunological changes remain consistent over time. This study investigates Natural Killer (NK) cell cytotoxic activity, NK cell subsets (CD56brightCD16- and CD56dimCD16+) and cytokines, over the course of a12 month period in patients with CFS/ME.

METHODS: The participants in the study comprised 65 (47.2 ± 11.5 years) CFS/ME participants and 21 (45.2 ± 9.3 years) non-fatigued controls. Flow cytometry protocols were used to assess NK subsets and NK cytotoxic activity at various time points that included baseline (T1), 6 (T2) and 12 months (T3). Cytokine secretions were measured following mitogenic stimulation of peripheral blood mononuclear cells.

RESULTS: NK cytotoxic activity was significantly decreased in the CFS/ME patients at T1, T2 and T3 compared to the non-fatigued group. Additionally, in comparison to the non-fatigued controls, the CFS/ME group had significantly lower numbers of CD56brightCD16- NK cells at both T1 and T2. Interestingly, following mitogenic stimulation, cytokine secretion revealed significant increases in IL-10, IFN-γ and TNF-α at T1 in the CFS/ME group. A significant decrease was observed at T2 in the CFS/ME group for IL-10 and IL-17A while at T3, IL-2 was increased in the CFS/ME group in comparison to the non-fatigued controls. Overall cytotoxic activity was significantly decreased at T3 compared to T1 and T2. CD56brightCD16- NK cells were much lower at T2 compared to T1 and T3. IL-10 and IL-17A secretion was elevated at T2 in comparison to T1 and T3.

CONCLUSION: These results confirm decreases in immune function in CFS/ME patients, suggesting an increased susceptibility to viral and other infections. Furthermore, NK cytotoxic activity may be a suitable biomarker for diagnosing CFS/ME as it was consistently decreased during the course of the 12 months study.

 

Source: Brenu EW, van Driel ML, Staines DR, Ashton KJ, Hardcastle SL, Keane J, Tajouri L, Peterson D, Ramos SB, Marshall-Gradisnik SM. Longitudinal investigation of natural killer cells and cytokines in chronic fatigue syndrome/myalgic encephalomyelitis. J Transl Med. 2012 May 9;10:88. doi: 10.1186/1479-5876-10-88. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3464733/ (Full article)

 

Fatigue severity remains stable over time and independently associated with orthostatic symptoms in chronic fatigue syndrome: a longitudinal study

Abstract:

OBJECTIVES: to examine fatigue variability over time in chronic fatigue syndrome (CFS) and the effect of other symptoms on its predictability.

DESIGN: longitudinal cohort study of patients with CFS (Fukuda criteria).

SETTING: specialist CFS clinical service.

SUBJECTS: phase 1: 100 patients who participated in a study of CFS symptoms in 2005 were revisited in 2009. Phase 2: 25 patients completed fatigue diaries to address intra- and inter-day variability in perceived fatigue.

MAIN OUTCOME MEASURES: phase 1: subjects completed fatigue impact scale (FIS), Epworth sleepiness scale (ESS), orthostatic grading scale (OGS) and hospital anxiety and depression scale (HADS). Changes in variables represented the differences between 2005 and 2009. Phase 2: subjects rated fatigue on a scale of 0 (no fatigue) to 10 (severe fatigue) four times a day for 5 weeks.

RESULTS: symptom assessment tools were available in both 2005 and 2009 for 74% of patients. FIS and HADS depression (HAD-D) and anxiety (HAD-A) scores significantly improved during follow-up whereas ESS and OGS remained stable. FIS improved in 29/74 (39%) subjects, and by ≥ 10 points in 19 (26%). FIS worsened by ≥ 10 points in 33/74 (45%) subjects. On multivariate analysis, independent predictors of current fatigue (FIS in 2009) were FIS in 2005, HAD-D in 2009, OGS in 2009 and change in HAD-A. Reported fatigue was stable from week to week and from day to day. Patients reported higher fatigue in the morning (mean ± SD; 6.4 ± 2), becoming significantly lower at lunchtime (6.2 ± 2; P < 0.05) and increasing again to 7 ± 2 at bedtime.

CONCLUSIONS: current fatigue is independently associated with current autonomic symptom burden, current depression and change in anxiety during follow-up. These findings have implications for targeted symptom management in CFS.

 

Source: Jones DE, Gray J, Frith J, Newton JL. Fatigue severity remains stable over time and independently associated with orthostatic symptoms in chronic fatigue syndrome: a longitudinal study. J Intern Med. 2011 Feb;269(2):182-8. doi: 10.1111/j.1365-2796.2010.02306.x. Epub 2010 Nov 14. http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2796.2010.02306.x/full (Full article)

 

Illness trajectories in the chronic fatigue syndrome: a longitudinal study of improvers versus non-improvers

Abstract:

The natural progression of chronic fatigue syndrome (CFS) in adults is not well established. The aims of this longitudinal study were to (a) compare CFS Improvers and Non-Improvers; (b) determine whether an initial diagnosis of fibromyalgia (FM) was associated with CFS nonimprovement; and (c) determine whether this effect could be explained by the presence of nonspecific physical symptoms.

Consecutive referrals to a tertiary clinic that satisfied case criteria for CFS were invited to enroll in a longitudinal study. After an initial on-site physical examination and psychiatric interview, a total of 94 female care-seekers completed biannual telephone surveys, including the Short Form-36 physical functioning (PF) scale, over a period of 2(1/2) years. There were very few differences between Improvers and Non-Improvers at baseline but at final assessment Improvers had less disability, less fatigue, lower levels of pain, fewer symptoms of depressed mood, and fewer nonspecific physical complaints.

Participants with FM at baseline were 3.23 times (p < 0.05) more likely to become Non-Improvers than those without FM. Participants identified initially as Somatizers were 3.33 times (p < 0.05) more likely to become Non-Improvers. Patients with CFS who bear the added burden of FM are at greater risk of a negative outcome than patients with CFS alone. This effect could not be explained by the presence of multiple, nonspecific symptoms.

 

Source: Ciccone DS, Chandler HK, Natelson BH. Illness trajectories in the chronic fatigue syndrome: a longitudinal study of improvers versus non-improvers. J Nerv Ment Dis. 2010 Jul;198(7):486-93. doi: 10.1097/NMD.0b013e3181e4ce0b. https://www.ncbi.nlm.nih.gov/pubmed/20611051

 

Nurse led, home based self help treatment for patients in primary care with chronic fatigue syndrome: randomised controlled trial

Abstract:

OBJECTIVE: To evaluate the effectiveness of home delivered pragmatic rehabilitation-a programme of gradually increasing activity designed collaboratively by the patient and the therapist-and supportive listening-an approach based on non-directive counselling-for patients in primary care with chronic fatigue syndrome/myalgic encephalomyelitis or encephalitis (CFS/ME).

DESIGN: Single blind, randomised, controlled trial.

SETTING: 186 general practices across the north west of England between February 2005 and May 2007.

PARTICIPANTS: 296 patients aged 18 or over with CFS/ME (median illness duration seven years) diagnosed using the Oxford criteria.

INTERVENTIONS: Participants were randomly allocated to pragmatic rehabilitation, supportive listening, or general practitioner treatment as usual. Both therapies were delivered at home in 10 sessions over 18 weeks by one of three adult specialty general nurses who had received four months’ training, including supervised practice, in each of the interventions. GP treatment as usual was unconstrained except that patients were not to be referred for systematic psychological therapies during the treatment period. Main outcome measures The primary clinical outcomes were fatigue and physical functioning at the end of treatment (20 weeks) and 70 weeks from recruitment compared with GP treatment as usual. Lower fatigue scores and higher physical functioning scores denote better outcomes.

RESULTS: A total of 257 (87%) of the 296 patients who entered the trial were assessed at 70 weeks, the primary outcome point. Analysis was on an intention to treat basis, with robust treatment effects estimated after adjustment for missing data using probability weights. Immediately after treatment (at 20 weeks), patients allocated to pragmatic rehabilitation (n=95) had significantly improved fatigue (effect estimate -1.18, 95% confidence interval -2.18 to -0.18; P=0.021) but not physical functioning (-0.18, 95% CI -5.88 to +5.52; P=0.950) compared with patients allocated to treatment as usual (n=100). At one year after finishing treatment (70 weeks), there were no statistically significant differences in fatigue or physical functioning between patients allocated to pragmatic rehabilitation and those on treatment as usual (-1.00, 95% CI -2.10 to +0.11; P=0.076 and +2.57, 95% CI 3.90 to +9.03; P=0.435). At 20 weeks, patients allocated to supportive listening (n=101) had poorer physical functioning than those allocated to treatment as usual (-7.54, 95% CI -12.76 to -2.33; P=0.005) and no difference in fatigue. At 70 weeks, patients allocated to supportive listening did not differ significantly from those allocated to treatment as usual on either primary outcome.

CONCLUSIONS: For patients with CFS/ME in primary care, pragmatic rehabilitation delivered by trained nurse therapists improves fatigue in the short term compared with unconstrained GP treatment as usual, but the effect is small and not statistically significant at one year follow-up. Supportive listening delivered by trained nurse therapists is not an effective treatment for CFS/ME.

Trial registration International Standard Randomised Controlled Trial Number IRCTN74156610.

Comment in:

Pragmatic rehabilitation for chronic fatigue syndrome. [BMJ. 2010]

Nurse-delivered, home-based pragmatic rehabilitation has a short-term effect on improving fatigue in people with chronic fatigue syndrome compared with usual GP care, but effects were not sustained at 1 year. [Evid Based Nurs. 2010]

 

Source: Wearden AJ, Dowrick C, Chew-Graham C, Bentall RP, Morriss RK, Peters S, Riste L, Richardson G, Lovell K, Dunn G; Fatigue Intervention by Nurses Evaluation (FINE) trial writing group and the FINE trial group and 23 Collaborators. Nurse led, home based self help treatment for patients in primary care with chronic fatigue syndrome: randomised controlled trial. BMJ. 2010 Apr 23;340:c1777. doi: 10.1136/bmj.c1777. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2859122/ (Full article)

 

Longitudinal MRI shows no cerebral abnormality in chronic fatigue syndrome

Abstract:

MRI has previously provided conflicting results when used to search for brain abnormalities in sufferers of chronic fatigue syndrome (CFS). Eighteen CFS patients and nine healthy volunteers each underwent MRI on two occasions, one year apart. The resulting images were examined for abnormalities in brain atrophy, deep white matter hyperintensities (WMH) and cerebral blood and cerebrospinal fluid (CSF) flow.

Mean proportionate CSF volume was not significantly different between subject groups. All participants showed a slight increase in CSF between scans, but no significant difference was found between those with CFS and those without. Between-group comparisons of ventricular volume revealed no significant differences at study commencement and no significant change over the year. No significant inter-group differences were found for any of the cerebral blood and CSF flow parameters. Low levels of WMH were found in all participants. Objective scoring of WMH using Scheltens’ scale revealed no change in summary components (prosencephalic deep white matter hyperintensities, basal ganglia hyperintensities and infratentorial hyperintensities) or in individual component variables between the baseline and 1 year follow-up scans. No abnormal patterns in rate and extent of brain atrophy, ventricle volume, white matter lesions, cerebral blood flow or aqueductal CSF flow were detected in the CFS population.

These results throw open the debate into whether MRI scanning can reveal diagnostic signs of CFS and clinically questions the diagnoses of CFS made on the basis of previous research conclusions.

 

Source: Perrin R, Embleton K, Pentreath VW, Jackson A. Longitudinal MRI shows no cerebral abnormality in chronic fatigue syndrome. Br J Radiol. 2010 May;83(989):419-23. doi: 10.1259/bjr/85621779. Epub 2010 Mar 11. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3473570/ (Full article)

 

Serum Cytokine Levels in Postinfective Fatigue Syndrome

TO THE EDITOR—Previous studies have sought evidence for a role of abnormal cytokine activity in patients with chronic fatigue syndrome and have had conflicting results [1–3]. These ambiguous results may reflect heterogeneity in groups of patients considered to have chronic fatigue syndrome and variations in assay systems.

We established postinfective fatigue syndrome as the only well-characterized model of the onset and evolution of chronic fatigue syndrome in a prospective cohort of individuals followed up from the onset of acute infection (Dubbo Infection Outcomes Study [DIOS]) [4]. Longitudinally collected clinical data and blood samples from participants in DIOS provide a unique opportunity for nested case-control studies examining the pathophysiology of chronic fatigue syndrome.

We previously reported the lack of association between cytokine production from cultured peripheral blood mononuclear cells and the postinfective fatigue syndrome- related illness in participants in DIOS [5]. We now report a masked analysis of a longitudinal case-control series from DIOS that extended the number of cytokines tested and focused on serum levels.

Twenty patients with acute infection were selected, including 5 patients with serologically confirmed acute Epstein-Barr virus (EBV) infection followed by postinfective fatigue syndrome lasting ⩾6 months, 5 patients with acute infection (not primary EBV but seropositive for EBV) followed by postinfective fatigue syndrome, and 10 matched control subjects with acute EBV infection followed by prompt recovery. Serum samples and clinical data from baseline and from 3–6 months and 9–12 months after onset of infection were analyzed. Serum samples were coded according to case-control status before transfer to the cytokine analysis laboratory.

Thirty-five analytes were measured in serum samples with use of amultiplex immunoassay, including the chemokines leptin, epithelial cell-derived neutrophil-activating peptide 78, eotaxin, growth-regulated oncogene α, interleukin (IL)-8, interferon (IFN)-inducible protein 10, monocyte chemotactic protein 3, monokine induced by gamma IFN, macrophage inflammatory protein 1α, macrophage inflammatory protein 1β, and regulated upon activation normal T cell expressed and secreted; the cytokines IFN-γ, IL-1α, IL-1β, IL-1Ra, IL-4, IL-5, IL-6, IL-7, IL-2, IL-10, IL-12p40, IL-12p70, IL-13, IL-15, IL-17, IL-17F, tumor necrosis factor α, tumor necrosis factor β; and the growth factors nerve growth factor, plate-let-derived growth factor β, transforming growth factor β, vascular endothelial growth factor, fibroblast growth factor β, granulocyte colony-stimulating factor, and granulocyte-macrophage colony-stimulating factor.

All of the study groups were predominantly female and were matched for both sex distribution (by χ2 test, P = .670) and age (by analysis of variance, P = .597). Cytokine data were analyzed by 2-way analysis of variance examining the effects of time and type of case (EBV postinfective fatigue syndrome, non-EBV postinfective fatigue syndrome, or control) and by Spearman’s correlation between symptom scores and cytokine levels. Because of the number of parameters tested, a conservative threshold for statistical significance (P < .005) was used. Results are shown in Table 1

You can read the rest of this article here: http://cid.oxfordjournals.org/content/50/2/278.full

 

Source: Cameron B, Hirschberg DL, Rosenberg-Hassan Y, Ablashi D, Lloyd AR. Serum cytokine levels in postinfective fatigue syndrome. Clin Infect Dis. 2010 Jan 15;50(2):278-9. doi: 10.1086/649546. http://cid.oxfordjournals.org/content/50/2/278.full (Full article)

 

Longitudinal change in chronic fatigue syndrome: what home-based assessments reveal

Abstract:

The purpose of this 2-year prospective study was to compare standard self-report and ecologically-based outcome measures in patients with chronic fatigue syndrome (CFS). Standard measures assessed physical function, fatigue impact, psychological variables, and global impression of change ratings. Ecological measures included actigraphy, a structured activity record, and an electronic fatigue/energy diary.

Results for this high functioning sample (N = 75) revealed that self-report global improvement was significantly associated with lower momentary fatigue and fatigue impact, and a higher frequency of standing up (at home), but not with actigraphy or psychological variables. However, actigraphy change was significantly correlated with change in self-report physical function. At follow-up, only a small minority (<20%) scored in the healthy adult range for fatigue impact and physical function.

The findings suggest that home-based measures of symptom severity and physical functioning may provide evidence of change (or lack of change) that is important for interpreting standard self-report outcomes in CFS.

 

Source: Friedberg F, Sohl SJ. Longitudinal change in chronic fatigue syndrome: what home-based assessments reveal. J Behav Med. 2009 Apr;32(2):209-18. doi: 10.1007/s10865-008-9189-9. Epub 2008 Dec 20. https://www.ncbi.nlm.nih.gov/pubmed/19101789

 

Longitudinal analysis of pro- and anti-inflammatory cytokine production in severely fatigued adolescents

Abstract:

In the adolescent population, fatigue is associated with somatic complaints, unrefreshing sleep, cognitive disturbances and symptoms of depression and anxiety. This pattern of symptoms resembles the one described in chronic fatigue syndrome (CFS). Since immunological alterations have been reported in CFS patients, we wondered whether also severely fatigued girls from a healthy population would show comparable alterations in psychological and immunological parameters. We tested this hypothesis in a longitudinal design, allowing a reliable assessment of the participants’ characteristic immune status. Groups of severely fatigued (N=67) and non-fatigued (N=61) participants were selected. Severely fatigued girls reported more depressive symptoms, anxiety, reduced sleep quality, and somatic and CFS-related symptoms than non-fatigued participants across three measurements during one year (T1: spring, T2: autumn, T3: spring). In contrast, no group differences in mitogen-induced cytokine production or T-cell proliferation in vitro or in leukocyte subset counts were observed. Although absolute cytokine production and cell counts were affected by seasonal variation, the within-subject values, relatively to the rest of the participants, were fairly stable. Data from a small group of CFS patients (N=11) showed similarities in self-reported complaints between CFS patients and fatigued participants. Interestingly, CFS patients showed a distinct immune profile when compared to the severely fatigued or non-fatigued participants, i.e. increased levels of anti-inflammatory cytokines (IL-10, decreased IFN-gamma/IL-10 ratio) and reduced levels of pro-inflammatory cytokines (IL-6, TNF-alpha) over all three time points analyzed. These results show that, although overlap in symptomatology between the general population and patients with CFS was observed, only CFS patients show a skewing of the cytokine balance towards an anti-inflammatory profile.

 

Source: ter Wolbeek M, van Doornen LJ, Kavelaars A, van de Putte EM, Schedlowski M, Heijnen CJ. Longitudinal analysis of pro- and anti-inflammatory cytokine production in severely fatigued adolescents.Brain Behav Immun. 2007 Nov;21(8):1063-74. Epub 2007 Jun 1. https://www.ncbi.nlm.nih.gov/pubmed/17544255

A longitudinal study of the relationship between psychological distress and recurrence of upper respiratory tract infections in chronic fatigue syndrome

Abstract:

OBJECTIVES: Previous research has found that chronic fatigue syndrome (CFS) patients report increased susceptibility to upper respiratory tract illnesses (URTIs) when compared with healthy volunteers. This study aimed to replicate and extend this research by investigating the role of psychological distress (stress and negative mood) in the recurrence of URTIs in CFS patients as well as its role in the recurrence of CFS symptoms.

DESIGN: A 15-week diary study.

METHODS: Measures of psychological stress, negative mood, recurrence of URTIs and symptoms were recorded each week for a 15-week period. CFS patients (N=21), who had been assessed and diagnosed according to the Oxford criteria, were recruited from the Cardiff Chronic Fatigue Clinic and compared with a matched group of healthy controls (N=18). Frequency of occurrence of infectious illness and the relationship between psychological stress/negative mood and occurrence of illness were assessed.

RESULTS: CFS patients reported more URTIs than the controls. Stress scores (and negative mood) were significantly higher in the week prior to the occurrence of URTIs than in weeks when no subsequent illness occurred. High levels of psychological stress also preceded the severity of reported symptoms of fatigue in the CFS group.

CONCLUSIONS: CFS patients reported more frequent URTIs than healthy controls and these recurrences were preceded by high levels of psychological stress. High levels of stress were also associated with greater subsequent fatigue. Possible explanations of these results are discussed.

 

Source: Faulkner S, Smith A. A longitudinal study of the relationship between psychological distress and recurrence of upper respiratory tract infections in chronic fatigue syndrome. Br J Health Psychol. 2008 Feb;13(Pt 1):177-86. https://www.ncbi.nlm.nih.gov/pubmed/17535488

 

Long-term outcomes of an integrative rehabilitation program on quality of life: a follow-up study

Abstract:

OBJECTIVE: To assess the long-term effects of an integrative rehabilitation program on the overall quality of life of individuals with chronic fatigue syndrome (CFS).

METHODS: This study utilized a within-subjects, repeated measures cohort design. Twenty-three subjects diagnosed with CFS attended eight sessions of an illness-management group followed by 7 months of goal-oriented, individualized counseling that occurred once weekly for 30 min per session. Quality of life was assessed at five time points (baseline, following the group phase, following the one-on-one phase, and 4 and 12 months following program completion).

RESULTS: A within-subjects repeated measures ANOVA revealed significant increases in overall quality of life for up to 1 year following program completion [F(4, 21)=23.5, P<.001].

CONCLUSIONS: Definitive conclusions about program efficacy are limited by design issues. However, findings suggest that the program may have led to improvement in quality of life for up to 1 year following program completion.

 

Source: Taylor RR, Thanawala SG, Shiraishi Y, Schoeny ME. Long-term outcomes of an integrative rehabilitation program on quality of life: a follow-up study. J Psychosom Res. 2006 Dec;61(6):835-9. https://www.ncbi.nlm.nih.gov/pubmed/17141674