Associations between bronchial hyperresponsiveness and immune cell parameters in patients with chronic fatigue syndrome

Abstract:

STUDY OBJECTIVE: To examine whether bronchial hyperresponsiveness (BHR) in patients with chronic fatigue syndrome (CFS) is caused by immune system abnormalities.

DESIGN: Prospective comparative study.

SETTING: A university-based outpatient clinic (Vrije Universiteit; Brussels, Belgium).

PARTICIPANTS: One hundred thirty-seven CFS patients and 27 healthy volunteers.

MEASUREMENTS: Pulmonary function testing, histamine bronchoprovocation test, immunophenotyping, and ribonuclease (RNase) latent determination.

RESULTS: Seventy-three of 137 patients presented with BHR, of whom 64 had normal results of the histamine bronchoprovocation test. No significant differences were found in age or sex characteristics between the groups. There were no differences in the RNase L ratio, total lung capacity, or FEV(1)/FVC ratio between CFS patients with or without BHR. The group of patients in whom BHR was present (BHR+) differs most significantly from the control group with eight differences in the immunophenotype profile in the cell count analysis and seven differences in the percentage distribution profile. The group of patients in whom no BHR was detected (BHR-) only differed from the control subjects in CD25+ count and in the percentage of CD25+ cells. We observed a significant increase in cytotoxic T-cell count and in the percentage of BHR+ patients compared to BHR- patients, which is consistent with the significant reduction in percentage naïve T cells.

CONCLUSIONS: These results refute any association between the cleaving of 80 kd RNase L and BHR. Immunophenotyping of our sample confirmed earlier reports on (chronic) immune activation in patients with CFS, compared to healthy control subjects. BHR+ CFS patients have more evidence of immune activation compared to BHR- patients. Inflammation and the consequent IgE-mediated activation of mast cells and eosinophils, as seen in asthma patients, is unlikely to be responsible for the presence of BHR in patients with CFS.

 

Source: Nijs J, De Becker P, De Meirleir K, Demanet C, Vincken W, Schuermans D, McGregor N. Associations between bronchial hyperresponsiveness and immune cell parameters in patients with chronic fatigue syndrome. Chest. 2003 Apr;123(4):998-1007. http://www.ncbi.nlm.nih.gov/pubmed/12684286

 

The relationship between illness attributions and attributional style in Chronic Fatigue Syndrome

Abstract:

OBJECTIVE: To examine the relationship between illness attributions and general attributional style in Chronic Fatigue Syndrome (CFS).

METHOD: Participants with CFS answered questions on their explanation for their illness and completed the Attributional Style Questionnaire (parallel form).

RESULTS: Of the participants, 58.3% attributed their illness to predominantly physical factors. A significant relationship was found between the presence of a self-serving attributional style and illness attributions.

CONCLUSION: Illness attributions were associated with an individual’s general attributional style. It is suggested that illness attributions may be less important with regards prognosis than, for example, other variables which influence a person’s general view of the world.

 

Source: Creswell C, Chalder T. The relationship between illness attributions and attributional style in Chronic Fatigue Syndrome. Br J Clin Psychol. 2003 Mar;42(Pt 1):101-4. http://www.ncbi.nlm.nih.gov/pubmed/12675983

 

Perceived exertion in fatiguing illness: Gulf War veterans with chronic fatigue syndrome

Abstract:

PURPOSE: It has been reported that ratings of perceived exertion (RPE) are elevated in chronic fatigue syndrome (CFS). We have challenged this notion by examining perceived exertion in civilian females with CFS and expressing the data relative to exercise capacity (%[OV0312]O(2max)). The purpose of the present investigation was to further examine RPE during exercise in a unique population of CFS patients, Gulf veterans (GV).

METHODS: Thirty-four GV (N = 15 CFS, 42 +/- 8 yr; N = 19 healthy, 43 +/- 5 yr) performed a maximal exercise test on a cycle ergometer. After a 3-min warm-up, exercise intensity increased by 30 W every minute until exhaustion. RPE were obtained during the last 15 s of each minute using Borg’s CR-10 scale.

RESULTS: With the exception of peak [OV0312]E, there were no significant differences in any peak exercise variables. Repeated measures ANOVA revealed significantly higher RPE at each power output examined (F(1,32) = 16.4, P < 0.001). Group differences in RPE remained significant when analyzed relative to peak [OV0312]O(2) (F(1,32) = 7.2, P = 0.01). Both group main effects and the interaction were eliminated when self-reported fatigue symptoms were controlled for in the analyses. Power functions for RPE as a function of relative oxygen consumption were not different between groups and were significantly greater than a linear value of 1.0 (1.6 +/- 0.3 for both groups, P < 0.02).

CONCLUSIONS: Our results show that RPE are greater in GV with CFS regardless of whether the data were expressed in terms of absolute or relative exercise intensity. However, self-reported fatigue associated with CFS eliminated the group differences. These results suggest that GV with CFS were unique compared with their civilian counterparts. Future research aimed at determining the influence of preexisting fatigue on RPE during exercise is warranted.

 

Source: Cook DB, Nagelkirk PR, Peckerman A, Poluri A, Lamanca JJ, Natelson BH. Perceived exertion in fatiguing illness: Gulf War veterans with chronic fatigue syndrome. Med Sci Sports Exerc. 2003 Apr;35(4):569-74. http://www.ncbi.nlm.nih.gov/pubmed/12673138

 

Perceived exertion in fatiguing illness: civilians with chronic fatigue syndrome

Abstract:

PURPOSE: It has been reported that ratings of perceived exertion (RPE) are elevated in chronic fatigue syndrome (CFS). However, methodological limitations have rendered this conclusion suspect. The purpose of the present investigation was to examine RPE during exercise in civilians with CFS by comparing subjects at both absolute exercise stage and relative oxygen consumption reference criteria.

METHODS: A sample of 39 civilian females (N = 19 CFS, 34 +/- 7 yr; N = 20 healthy controls, 33 +/- 7 yr) underwent a maximal exercise test on a treadmill. RPE were obtained during the last 15 s of each 3-min stage using Borg’s 6-20 scale.

RESULTS: There were no significant differences in peak [OV0312]O(2), RER, or RPE. However, controls exercised longer (20.0 +/- 1.1 vs 15.9 +/- 1.1 min, P = 0.01, healthy vs CFS) and had higher peak HR (183 +/- 3 vs 174 +/- 2 bpm, P = 0.03, healthy vs CFS). Civilians with CFS reported higher RPE at stages 3 through 5 compared with controls (F(3,111)= 3.6,P = 0.017). Preexercise fatigue ratings were not a significant predictor of perceived exertion during exercise. There were no group differences (F(1,37)= 1.9, P = 0.17) when RPE were expressed relative to peak [OV0312]O(2).

CONCLUSIONS: Our results show that RPE are greater in civilians with CFS when the data are expressed in terms of absolute exercise intensity. However, by examining RPE relative to a common maximum (i.e., peak [OV0312]O(2)) no differences were observed. The findings of the present investigation challenge the notion that RPE are dysregulated in CFS.

 

Source: Cook DB, Nagelkirk PR, Peckerman A, Poluri A, Lamanca JJ, Natelson BH. Perceived exertion in fatiguing illness: civilians with chronic fatigue syndrome. Med Sci Sports Exerc. 2003 Apr;35(4):563-8. http://www.ncbi.nlm.nih.gov/pubmed/12673137

 

Financial, occupational, and personal consequences of disability in patients with chronic fatigue syndrome and fibromyalgia compared to other fatiguing conditions

Abstract:

OBJECTIVE: To examine the nature and degree of self-reported disability in patients with chronic fatigue syndrome (CFS) and its associated conditions, fibromyalgia (FM) and subsyndromal fatigue (CF), compared with a chronically fatiguing but unrelated medical condition (MED).

METHODS: Six hundred and thirty patients evaluated at the University of Washington Chronic Fatigue Clinic were sent questionnaires asking them to identify the financial, occupational, and personal consequences of their fatiguing illness. Thorough medical evaluations had previously applied accepted criteria for defining CFS, FM, and CF.

RESULTS: The FM groups (those with and without CFS) were among the least employed. Likewise, the FM and CFS groups, more frequently than the other groups, endorsed loss of material possessions (such as car), loss of job, and loss of support by friends and family, as well as recreational activities as a result of their fatiguing illness. There were no reliable differences between groups in use of disability benefits.

CONCLUSION: There is substantial illness-related disability among those evaluated at a specialized chronic fatigue clinic. Those reporting the most pervasive disability met criteria for FM either alone or in conjunction with CFS. Employers and personal relations of patients with chronic fatigue should make a greater effort to accommodate the illness-related limitations of these conditions, especially for those with FM and CFS.

 

Source: Assefi NP, Coy TV, Uslan D, Smith WR, Buchwald D. Financial, occupational, and personal consequences of disability in patients with chronic fatigue syndrome and fibromyalgia compared to other fatiguing conditions. J Rheumatol. 2003 Apr;30(4):804-8. http://www.ncbi.nlm.nih.gov/pubmed/12672203

 

Comparative study of anxiety, depression, somatization, functional disability, and illness attribution in adolescents with chronic fatigue or migraine

Abstract:

OBJECTIVE: To compare adolescents with migraine, unexplained profound chronic fatigue of >6 months duration, and normal school controls on measures of anxiety, depression, somatization, functional disability, and illness attribution.

METHODS: Adolescents referred to Children’s Hospital and Regional Medical Center for behavioral treatment of migraine (n = 179) or evaluation of chronic fatigue (n = 97) were compared with a group of healthy controls of similar age and sex from a middle school (n = 32). Subjects completed the Spielberger State-Trait Anxiety Inventory-Trait Form, the Children’s Depression Inventory, the Childhood Somatization Inventory, and estimated the number of school days missed in the past 6 months because of illness. Migraine and fatigued subjects completed an illness attribution questionnaire.

RESULTS: Subjects in the 3 groups were 56% to 70% female and ranged from 11 years old to 18 years old with a mean age of 14.0 +/- 2.0. Forty-six of the 97 chronically fatigued adolescents met 1994 Centers for Disease Control and Prevention (CDC) criteria for chronic fatigue syndrome (CDC-CFS), while 51 had idiopathic chronic fatigue syndrome (I-CFS) that did not meet full CDC criteria. Adolescents with migraine had significantly higher anxiety scores than those with I-CFS or controls and higher somatization scores than controls. Adolescents with CDC-CFS had significantly higher anxiety scores than those with I-CFS or controls, and higher depression and somatization scores than all other groups. There were significant differences between all groups for school days missed with CDC-CFS more than I-CFS more than migraine more than controls. Parents of adolescents with unexplained I-CFS had significantly lower attribution scores relating illness to possible psychological or stress factors than parents of adolescents with CDC-CFS or migraine.

CONCLUSIONS: Adolescents referred to an academic center for evaluation of unexplained chronic fatigue had greater rates of school absenteeism than adolescents with migraine or healthy controls. Those meeting CDC-CFS criteria had higher anxiety scores than controls and higher depression and somatization scores than migraineurs or controls. Parents of adolescents with I-CFS were less likely to endorse psychological factors as possibly contributing to their symptoms than parents of adolescents with CDC-CFS or migraine.

 

Source: Smith MS, Martin-Herz SP, Womack WM, Marsigan JL. Comparative study of anxiety, depression, somatization, functional disability, and illness attribution in adolescents with chronic fatigue or migraine. Pediatrics. 2003 Apr;111(4 Pt 1):e376-81. http://www.ncbi.nlm.nih.gov/pubmed/12671155

 

Correlates of illness worry in chronic fatigue syndrome

Abstract:

BACKGROUND: Anxiety about illness leading to restriction of activity and physical deconditioning has been hypothesized to contribute to the chronicity of fatigue. Pathological symptom attributions, personality traits, and depression have all been hypothesized to contribute to illness worry.

METHODS: We compared 45 chronic fatigue syndrome (CFS) and 40 multiple sclerosis (MS) outpatients using a battery of psychometric instruments comprising the 12-item Illness Worry scale, the Symptom Interpretation Questionnaire (SIQ), the NEO Five-Factor Inventory (NEO-FFI), and a modified version of the SCL-90R Depression scale.

RESULTS: There was no difference between the two diagnostic groups on neuroticism, depressive symptoms, as well as the three scales of the SIQ. On the illness worry index, the CFS group had significantly higher scores than the MS group. This difference was due to items tapping vulnerability to illness and the perception that others are not taking their illness seriously. Somatic attributional style, neuroticism, depressive symptoms, and age were all significant predictors of illness worry in both CFS and MS patients.

CONCLUSIONS: Somatic attributions, neuroticism, and depression all contribute to illness worry in chronic illness. However, these factors do not account for the higher levels of illness worry in CFS as opposed to MS, which may be due to other specific cognitive and social interactional processes.

 

Source: Taillefer SS, Kirmayer LJ, Robbins JM, Lasry JC. Correlates of illness worry in chronic fatigue syndrome.  J Psychosom Res. 2003 Apr;54(4):331-7. http://www.ncbi.nlm.nih.gov/pubmed/12670610

 

Unexplained fatigue syndromes in a multinational primary care sample: specificity of definition and prevalence and distinctiveness from depression and generalized anxiety

Abstract:

OBJECTIVE: The authors investigated whether narrow definitions of unexplained fatigue syndromes that require additional minor somatic symptoms are more strongly associated with psychiatric morbidity than wider ones.

METHOD: This was a secondary analysis of the World Health Organization Collaborative Project on Psychological Problems in General Health Care. A total of 5,438 primary care patients from 14 countries were assessed with the Composite International Diagnostic Interview.

RESULTS: The prevalence of fatigue syndromes fell from 7.99 to 1.69 as somatic criteria were added. Patients with depression or anxiety were more likely to report unexplained fatigue, but this association was stronger for definitions of unexplained fatigue with more somatic criteria.

CONCLUSIONS: Definitions of unexplained fatigue syndromes that require more somatic criteria selected more patients with psychiatric disorders in this culturally diverse sample. These findings might have implications for the revision of existing international diagnostic criteria for neurasthenia or chronic fatigue syndrome.

 

Source: Skapinakis P, Lewis G, Mavreas V. Unexplained fatigue syndromes in a multinational primary care sample: specificity of definition and prevalence and distinctiveness from depression and generalized anxiety. Am J Psychiatry. 2003 Apr;160(4):785-7. http://www.ncbi.nlm.nih.gov/pubmed/12668371

 

Use of IVIG in secondary immunodeficiencies

Abstract:

The research connects usefulness of intravenous preparates of immunoglobulins in patients with secondary immunodeficiencies. Basing on the data of literature there was discussed the using IVIG in patients with HIV infection and with the chronic fatigue syndrome. There was also discussed the matter of using IVIG after multiorgans traumas, burns and operations with high risk complications.

 

Source: Zeman K, Lewandowicz-Uszyńska A. Use of IVIG in secondary immunodeficiencies. Postepy Hig Med Dosw. 2002;56 Suppl:91-102. [Article in Polish] http://www.ncbi.nlm.nih.gov/pubmed/12661419

 

 

Lessons from macrophagic myofasciitis: towards definition of a vaccine adjuvant-related syndrome

Abstract:

Macrophagic myofasciitis is a condition first reported in 1998, which cause remained obscure until 2001. Over 200 definite cases have been identified in France, and isolated cases have been recorded in other countries. The condition manifests by diffuse myalgias and chronic fatigue, forming a syndrome that meets both Center for Disease Control and Oxford criteria for the so-called chronic fatigue syndrome in about half of patients.

One third of patients develop an autoimmune disease, such as multiple sclerosis. Even in the absence of overt autoimmune disease they commonly show subtle signs of chronic immune stimulation, and most of them are of the HLADRB1*01 group, a phenotype at risk to develop polymyalgia rheumatica and rheumatoid arthritis.

Macrophagic myofasciitis is characterized by a stereotyped and immunologically active lesion at deltoid muscle biopsy. Electron microscopy, microanalytical studies, experimental procedures, and an epidemiological study recently demonstrated that the lesion is due to persistence for years at site of injection of an aluminum adjuvant used in vaccines against hepatitis B virus, hepatitis A virus, and tetanus toxoid. Aluminum hydroxide is known to potently stimulate the immune system and to shift immune responses towards a Th-2 profile.

It is plausible that persistent systemic immune activation that fails to switch off represents the pathophysiologic basis of chronic fatigue syndrome associated with macrophagic myofasciitis, similarly to what happens in patients with post-infectious chronic fatigue and possibly idiopathic chronic fatigue syndrome. Therefore, the WHO recommended an epidemiological survey, currently conducted by the French agency AFSSAPS, aimed at substantiating the possible link between the focal macrophagic myofasciitis lesion (or previous immunization with aluminium-containing vaccines) and systemic symptoms.

Interestingly, special emphasis has been put on Th-2 biased immune responses as a possible explanation of chronic fatigue and associated manifestations known as the Gulf war syndrome. Results concerning macrophagic myofasciitis may well open new avenues for etiologic investigation of this syndrome. Indeed, both type and structure of symptoms are strikingly similar in Gulf war veterans and patients with macrophagic myofasciitis. Multiple vaccinations performed over a short period of time in the Persian gulf area have been recognized as the main risk factor for Gulf War syndrome.

Moreover, the war vaccine against anthrax, which is administered in a 6-shot regimen and seems to be crucially involved, is adjuvanted by aluminium hydroxide and, possibly, squalene, another Th-2 adjuvant. If safety concerns about long-term effects of aluminium hydroxide are confirmed it will become mandatory to propose novel and alternative vaccine adjuvants to rescue vaccine-based strategies and the enormous benefit for public health they provide worldwide.

 

Source: Gherardi RK. Lessons from macrophagic myofasciitis: towards definition of a vaccine adjuvant-related syndrome. Rev Neurol (Paris). 2003 Feb;159(2):162-4. [Article in French] http://www.ncbi.nlm.nih.gov/pubmed/12660567