ArticlePDF Available

Whole-Body Cryotherapy Decreases the Levels of Inflammatory, Oxidative Stress, and Atherosclerosis Plaque Markers in Male Patients with Active-Phase Ankylosing Spondylitis in the Absence of Classical Cardiovascular Risk Factors

Authors:

Abstract

Objective The aim of the study was to estimate the impact of whole-body cryotherapy (WBC) on cardiovascular risk factors in patients with ankylosing spondylitis (AS). Material and Methods We investigated the effect of WBC with subsequent kinesiotherapy on markers of inflammation, oxidative stress, lipid profile, and atherosclerosis plaque in male AS patients (WBC group). To assess the disease activity, the BASDAI and BASFI were also calculated. The results from the WBC group were compared with results from the kinesiotherapy (KT) group. Results The results showed that in the WBC group, the plasma hsCRP level decreased without change to the IL-6 level. The ICAM-1 level showed a decreasing tendency. The CER concentration, as well as the BASDAI and BASFI, decreased in both groups, but the index changes of disease activity were higher in the WBC than KT patients. Additionally, in the WBC group, we observed a decrease in oxidative stress markers, changes in the activity of some antioxidant enzymes and nonenzymatic antioxidant parameters. In both groups, the total cholesterol and LDL cholesterol, triglycerides, sCD40L, PAPP-A, and PLGF levels decreased, but the parameter changes were higher in the WBC group. Conclusion WBC appears to be a useful method of atherosclerosis prevention in AS patients.
Research Article
Whole-Body Cryotherapy Decreases the Levels of Inflammatory,
Oxidative Stress, and Atherosclerosis Plaque Markers in
Male Patients with Active-Phase Ankylosing Spondylitis in the
Absence of Classical Cardiovascular Risk Factors
Agata Stanek ,
1
Armand Cholewka,
2
Tomasz Wielkoszyński ,
3
Ewa Romuk ,
3
and Aleksander Sieroń
1
1
School of Medicine with the Division of Dentistry in Zabrze, Department of Internal Medicine, Angiology and Physical Medicine,
Medical University of Silesia, Batorego Street 15, 41-902 Bytom, Poland
2
Department of Medical Physics, Chełkowski Institute of Physics, University of Silesia, 4 Uniwersytecka St., 40-007 Katowice, Poland
3
School of Medicine with the Division of Dentistry in Zabrze, Department of Biochemistry, Medical University of Silesia, Jordana 19
St., 41-808 Zabrze, Poland
Correspondence should be addressed to Agata Stanek; astanek@tlen.pl
Received 26 August 2017; Accepted 19 October 2017; Published 1 February 2018
Academic Editor: Adrian Doroszko
Copyright © 2018 Agata Stanek et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Objective. The aim of the study was to estimate the impact of whole-body cryotherapy (WBC) on cardiovascular risk factors in
patients with ankylosing spondylitis (AS). Material and Methods. We investigated the eect of WBC with subsequent
kinesiotherapy on markers of inammation, oxidative stress, lipid prole, and atherosclerosis plaque in male AS patients (WBC
group). To assess the disease activity, the BASDAI and BASFI were also calculated. The results from the WBC group were
compared with results from the kinesiotherapy (KT) group. Results. The results showed that in the WBC group, the plasma
hsCRP level decreased without change to the IL-6 level. The ICAM-1 level showed a decreasing tendency. The CER
concentration, as well as the BASDAI and BASFI, decreased in both groups, but the index changes of disease activity were
higher in the WBC than KT patients. Additionally, in the WBC group, we observed a decrease in oxidative stress markers,
changes in the activity of some antioxidant enzymes and nonenzymatic antioxidant parameters. In both groups, the total
cholesterol and LDL cholesterol, triglycerides, sCD40L, PAPP-A, and PLGF levels decreased, but the parameter changes were
higher in the WBC group. Conclusion. WBC appears to be a useful method of atherosclerosis prevention in AS patients.
1. Introduction
Patients with ankylosing spondylitis (AS) have a higher risk
of cardiovascular morbidity and mortality in comparison to
the general population, which may be connected with the
diseases activity, the functional and mobility limitations,
structural damage, and inammation [1, 2]. Even AS patients
without concomitant classical cardiovascular risk factors
yet, but in an active phase of the disease, are characterized
by increased levels of oxidative stress, inammatory states,
higher serum concentrations of soluble CD40 ligand
(sCD40L), and increased carotid intima-media thickness
(IMT) in comparison to the general population. These
factors may accelerate atherosclerosis in this group of
patients [3, 4].
Fortunately, over the last several years, a revolution in the
treatment of AS has taken place through the introduction of
biological and disease-modifying antirheumatic drugs
(DMARDs). Despite these advances, exercise and physio-
therapy still play a very important role [5, 6].
A relatively new physiotherapeutic method used in the
rheumatic disease treatment is whole-body cryotherapy
Hindawi
Mediators of Inflammation
Volume 2018, Article ID 8592532, 11 pages
https://doi.org/10.1155/2018/8592532
(WBC), which is based on the therapeutic exposure of the
entire human body to very low temperatures (below 100
°
C)
for 120180 seconds [7].
Recent studies have conrmed the anti-inammatory,
antianalgesic, and antioxidant eects of extremely low tem-
peratures in athletes [8]. WBC procedures also have had a
benecial inuence on lipid proles in healthy subjects [9]
and in obese people [10].
In addition, noticeably positive eects on the mental
state [11] and antioxidant status of patients with multiple
sclerosis [12] and seropositive rheumatoid arthritis [13] have
been observed when low temperatures were applied to the
entire body.
Little is still known about the role of WBC in the manage-
ment of AS patients. So far, the studies have shown that WBC
procedures in AS patients do not inuence ejection fraction,
late ventricular potentials, nor QT dispersion. However, they
do have a benecial eect on the adaptive processes of the
vegetative nervous system in patients without a signicant
pathology in the circulatory system [14].
It has also been proved that in AS patients, WBC proce-
dures with subsequent kinesiotherapy may improve BAS-
DAI (Bath Ankylosing Spondylitis Diseases Activity Index)
and BASFI (Bath Ankylosing Spondylitis Functional Index)
and some spinal mobility parameters and help to decrease
pain [15, 16].
In our preliminary study [17], we showed that WBC may
also have a benecial inuence on some specicinamma-
tory parameters in AS patients.
In light of the above ndings, the primary aim of the
study was to assess the inuence of WBC on cardiovascular
risk factors in AS patients with active phase and without
any concomitant classical cardiovascular risk factors.
2. Materials and Methods
2.1. Participants. The study protocol had been reviewed and
approved by the Bioethical Committee of the Medical
University of Silesia in Katowice (permission number: NN-
6501-93/I/07), and all analyzed patients were informed
about the trial and provided written consent for inclusion
in the study. All clinical investigations were conducted
according to the principles expressed in the Declaration of
Helsinki (1964).
The study involved a total of 32 nonsmoking male
patients with ankylosing spondylitis who were divided ran-
domly by a physician into two groups with an allocation ratio
1 : 1. The rst group consisted of 16 AS patients exposed to
whole-body cryotherapy procedures with subsequent kine-
siotherapy (WBC group, mean age 46.63 ±1.5 years). The
second group consisted of 16 AS patients exposed only to
kinesiotherapy procedures (KT group, mean age 45.94 ±1.24
years). There was no signicant dierence in the mean age,
BMI, carotid IMT, BASDAI, BASFI, and comorbiding disor-
ders and distribution of classical cardiovascular risk factors
between these groups.
Computer-generated random numbers were sealed in
sequentially numbered envelopes, and the group allocation
was independent of the time and person delivering the
treatment. The physician (main coordinator) who allocated
the patients to groups had 32 envelopes, each containing a
piece of paper marked with either group WBC or KT. The
physician selected and opened each envelope in the presence
of a physiotherapist to see the symbol and would then direct
the subject to the corresponding group.
Male patients who successfully enrolled in the study had
adenite diagnosis of AS, did not suer from any other dis-
eases, had no associated pathologies, and had an attending
physician who did not apply disease-modifying antirheu-
matic drugs (DMARDs), biologic agents, or steroids. The
AS patients were treated with doses of nonsteroidal anti-
inammatory drugs (NSAIDs), which were not altered
within one month before the beginning of the study and dur-
ing it. All the patients included in the trial fullled the mod-
ied New York Criteria for denite diagnosis of AS, which
serves as the basis for the ASAS/EULAR recommendations
[18]. The nal selection for the study included only HLA
B27-positive patients, who exhibited II and III radiographic
grades of sacroiliac joint disease and attended a consulting
unit in a health resort in the period of subsidence of acute
clinical symptoms, in order to qualify for sanatorium treat-
ment (physiotherapy). The demographic data of the subjects
is shown in Table 1.
The patients from both groups were asked to abstain
from alcohol, drugs and any immunomodulators, immunos-
timulators, hormones, vitamins, minerals, or other sub-
stances with antioxidant properties for 4 weeks before the
study. All the patients were also asked to refrain from the
consumption of caeine 12 hours prior to laboratory analy-
ses. The diet of the patients was not modied.
Before the study, each patient was examined by a physi-
cian to exclude any coexisting diseases as well as any contra-
indications for WBC procedures. Prior to the study, a resting
electrocardiogram was performed on all the patients, and
before each session of cryotherapy, the blood pressure was
measured for each patient.
2.2. Whole-Body Cryotherapy and Kinesiotherapy Procedures.
Depending on the group, the AS patients were exposed either
to a cycle of WBC procedures lasting 3 minutes a day with a
subsequent 60-minute session of kinesiotherapy or to a 60-
minute session of kinesiotherapy only, for 10 consecutive
days excluding the weekend.
The WBC procedures were performed in a cryochamber
with cold retention and cooled by synthetic liquid air (pro-
duced by Metrum Cryoex, Poland), which consists of two
compartments: the antechamber and the proper chamber,
which were connected by a door. In the trial, the tempera-
ture in the antechamber was 60
°
C, whereas in the proper
chamber, it reached 120
°
C. After a 30-second adaptation
process in the antechamber, the patients were exposed to
cryogenic temperatures in the proper chamber for 3
minutes. During the WBC procedure, all the patients were
dressed in swimsuits, cotton socks and gloves, and
wooden shoes and their mouths and noses were protected
by surgical masks and their ears by ear protectors. All
jewelry, glasses, and contact lenses were removed before
entry into the chamber. During the WBC procedure, the
2 Mediators of Inammation
patients were walking round the chamber without touching
each other.
Immediately after leaving the cryogenic chamber and
changing into track suits and trainers, the AS patients under-
went kinesiotherapy lasting one hour. The program of kine-
siotherapy was the same for all the patients in both groups.
Kinesiotherapy procedures included range-of-motion exer-
cises of the spine and major joints (including the ankle, knee,
hip, wrist, elbow, and shoulder). Chest expansion and breath-
ing exercises were also included. Apart from range-of-
motion exercise, the AS patients received strengthening exer-
cises of the muscles of the major joints (including the ankle,
knee, hip, wrist, elbow, shoulder, thoracolumbar spine, and
cervical spine) as well as aerobic exercise (including cycling
and fast walking). All the exercises were carried out under
the supervision of physical therapists.
All the patients completed the study and no complications
or side eects related to the WBC procedures were observed.
2.3. Blood Sample Collection. Blood samples of all the subjects
were collected in the morning before the rst meal. Samples
of whole blood (5 ml) were drawn from the basilic vein of
each subject and then collected into tubes containing ethyl-
enediaminetetraacetic acid (Sarstedt, S-Monovette with
1.6 mg/ml EDTA-K
3
) and into tubes with a clot activator
(Sarstedt, S-Monovette). The blood samples were centrifuged
(10 min, 900gat 4
°
C), and then the plasma and serum were
immediately separated and stored at the temperature of
75
°
C, until biochemical analyses could be performed. In
turn, the red blood cells retained from the removal of EDTA
plasma were rinsed with isotonic salt solution and then 10%
of the hemolysates were prepared for further analyses. The
hemoglobin concentration in the hemolysates was deter-
mined by the standard cyanmethemoglobin method. The
inter- and intra-assay coecients of variations (CV) were
1.1% and 2.4%, respectively.
2.4. Biochemical Analyses
2.4.1. Determination of Inammatory-State Parameters.
High-sensitivity C-reactive protein (hs-CRP) concentration
in the serum was determined by the latex immunoturbidi-
metric method (BioSystems, Spain) and expressed in mg/l.
The inter- and intra-assay coecients of variations (CV)
were 2.3% and 5.5%, respectively.
The serum ceruloplasmin (CER) oxidase activity was
measured using the p-phenylenediamine kinetic method by
Richterich [19] and expressed in mg/dl after a calibration
with pure ceruloplasmin isolated from a healthy donor serum
pool. The inter- and intra-assay coecients of variations
(CV) were 3.1% and 6.1%, respectively.
The plasma interleukin 6 (IL-6) and soluble intercellular
adhesion molecule-1 (sICAM-1) concentrations were deter-
mined using the ELISA method from R&D Systems (USA).
The concentrations of IL-6 and sICAM-1 were expressed in
pg/ml and ng/ml. The inter- and intra-assay coecients of
variations (CV) were 5.1% and 8.8%, respectively, for IL-6
and 4.8% and 9.1%, respectively, for sICAM-1.
2.4.2. Oxidative Stress Marker Analyses
(1) Determination of Lipid Peroxidation Products, Total
Oxidative Status, and Oxidative Stress Index. The intensity
of lipid peroxidation in the plasma and the erythrocytes
was measured spectrouorimetrically as thiobarbituric acid-
reactive substances (TBARS) according to Ohkawa et al.
[20]. The TBARS concentrations were expressed as malon-
dialdehyde (MDA) equivalents in μmol/l in plasma or in
nmol/gHb in erythrocytes. The inter- and intra-assay coe-
cients of variations (CV) were 2.1% and 8.3%, respectively.
The serum concentrations of oxidized low-density lipo-
protein (ox-LDL) and antibodies to ox-LDL (ab-ox-LDL)
were measured with the use of ELISA kits (Biomedica,
Poland). The ox-LDL and the ab-ox-LDL concentrations
were expressed in ng/ml and mU/ml, respectively. The inter-
and intra-assay coecients of variations (CV) for ox-LDL
were 5.8% and 9.4%, respectively, and 4.1% and 8.7% for
ab-ox-LDL, respectively.
The serum total oxidant status (TOS) was determined
with the method described by Erel [21] and expressed in
μmol/l. The inter- and intra-assay coecients of variations
(CV) were 2.2% and 6.4%, respectively.
The oxidative stress index (OSI), an indicator of the
degree of oxidative stress, was expressed as the ratio of total
oxidant status (TOS) to total antioxidant capacity (FRAP)
in arbitrary units [22].
(2) Determination of Activity of Antioxidant Enzymes. The
plasma and erythrocytes superoxide dismutase (SOD -
E.C.1.15.1.1) activity was determined by the Oyanagui
method [23]. Enzymatic activity was expressed in nitrite unit
(NU) in each mg of hemoglobin (Hb) or ml of blood plasma.
One nitrite unit (1 NU) means a 50% inhibition of nitrite ion
production by SOD in this method. SOD isoenzymes (SOD-
Table 1: Demographic data of the study subjects.
Characteristic
WBC
group
(n=16)
Kinesiotherapy
group
(n=16)
Pvalue
Age (years), mean (SD) 46.63 ±1.5 45.94 ±1.24 0.114
Sex (M/F) 16/0 16/0
BMI (kg/m
2
), mean (SD) 24.24 ±4.4 23.76 ±6.8 0.880
BASDAI 5.43 ±1.61 5.28 ±1.71 0.720
BASFI 5.20 ±2.29 5.01 ±2.06 1.00
Carotid IMT (mm) 1.1 ±0.13 1.0 ±0.14 0.925
Smoking (yes/no) 0/16 0/16
Medication
NSAID (yes/no) 16/0 16/0
DMARD (yes/no) 0/16 0/16
Biological agents
(yes/no) 0/16 0/16
SD: standard deviation; BMI: body mass index; BASDAI: the Bath
Ankylosing Spondylitis Diseases Activity Index; BASFI: the Bath
Ankylosing Spondylitis Functional Index; IMT: intima-media thickness;
NSAID: nonsteroidal anti-inammatory drug; DMARD: disease-modifying
antirheumatic drug.
3Mediators of Inammation
Mn and SOD-ZnCu) were measured using potassium cya-
nide as the inhibitor of the SOD-ZnCu isoenzyme. The inter-
and intra-assay coecients of variations (CV) were 2.8% and
5.4%, respectively.
The catalase (CAT - E.C.1.11.1.6.) activity in erythrocytes
was measured by the Aebi [24] kinetic method and expressed
in IU/mgHb. The inter- and intra-assay coecients of varia-
tions (CV) were 2.6% and 6.1%, respectively.
The erythrocyte glutathione peroxidase (GPx - E.C.1.11.
1.9.) activity was assayed by Paglia and Valentines kinetic
method [25], with t-butyl peroxide as a substrate and
expressed as micromoles of NADPH oxidized per minute
and normalized to one gram of hemoglobin (IU/gHb). The
inter- and intra-assay coecients of variations (CV) were
3.4% and 7.5%, respectively.
The activity of glutathione reductase in erythrocytes
(GR - E.C.1.6.4.2) was assayed by Richterichs kinetic method
[19], expressed as micromoles of NADPH utilized per min-
ute and normalized to one gram of hemoglobin (IU/gHb).
The inter- and intra-assay coecients of variations (CV)
were 2.1% and 5.8%, respectively.
(3) Determination of Nonenzymatic Antioxidant Status. The
total antioxidant capacity of plasma was measured as the
ferric-reducing ability of plasma (FRAP) according to Benzie
and Strain [26] and calibrated using Trolox and expressed in
(μmol/l). The inter- and intra-assay coecients of variations
(CV) were 1.1% and 3.8%, respectively.
The serum concentration of protein sulfhydryl (PSH)
was determined by Kosters method [27], using dithionitro-
benzoic acid (DTNB) and expressed in (μmol/l). The inter-
and intra-assay coecients of variations (CV) were 2.6%
and 5.4%, respectively.
The serum concentration of uric acid (UA) was deter-
mined by a uricase-peroxidase method [28] on the Cobas
Integra 400 plus analyzer and expressed as (mg/dl). The
inter- and intra-assay coecients of variations (CV) were
1.4% and 4.4%, respectively.
2.4.3. Determination of Lipid Prole. The total, HDL, and
LDL cholesterol (T-Chol, HDL-Chol, and LDL-Chol, resp.)
and triglyceride (TG) concentrations in serum were esti-
mated using routine techniques (Cobas Integra 400 plus ana-
lyzer, Roche Diagnostics, Mannheim, Germany). The
concentrations were expressed in (mg/dl). The inter- and
intra-assay coecients of variations (CV) were 2.8% and
5.4%, respectively, for T-Chol; 3.2% and 5.4%, respectively,
for HDL-Chol; 2.6% and 6.5%, respectively, for LDL-Chol;
and 2.5% and 7.6%, respectively, for TG. The triglyceride/
HDL cholesterol (TG/HDL) ratio was calculated.
2.4.4. Determination of Atherosclerosis Plaque Instability
Markers and Atherosclerosis Plaque Markers. Serum
pregnancy-associated plasma protein-A (PAPP-A), soluble
CD40 ligand (sCD40L), and placental growth factor (PLGF)
concentrations were assayed by ELISA methods with DRG
Instruments GmbH (Germany). The PAPP-A and sCD40L
concentrations were expressed in ng/ml and the PLGF con-
centration in pg/ml. The inter- and intra-assay coecients
of variations (CV) were 6.8% and 10.2%, respectively, for
PAPPA-A; 5.1% and 9.4%, respectively, for sCD40L; and
6.2% and 12.1%, respectively, for PLGF.
2.5. Assay of Activity of Ankylosing Spondylitis. The activity of
ankylosing spondylitis was measured by the Bath Ankylosing
Spondylitis Diseases Activity Index (BASDAI) and the Bath
Ankylosing Spondylitis Functional Index (BASFI).
The BASDAI has six questions related to fatigue, back
pain, peripheral pain, peripheral swelling, local tenderness,
and morning stiness (degree and length). Other than the
issues relating to morning stiness, all questions were scored
from 0 (none) to 10 (very severe) using a visual analogue
scale (VAS). The sum was calculated as the mean of two
morning stiness issues and the four remaining issues [29].
The BASFI is the mean score of ten questions address-
ing functional limitations and the level of physical activity
at home and work, assessed on VAS scales (0 = easy,
10 = impossible) [30].
2.6. Assay of Intima-Media Thickness. A high-resolution
Doppler ultrasonography was performed with a Logic-5
device with a high-frequency (11 MHz, 15 MHz) linear
probe. The sonographer was an angiologist who was unaware
of subjects clinical state. The measurement of intima-media
thickness (IMT) was performed in the right and left common
carotid arteries, and the average of the 2 measurements was
calculated. The IMT was expressed in mm.
2.7. Statistical Analyses. Statistical analyses were undertaken
using the statistical package of Statistica 10 Pl software. For
each parameter, the indicators of the descriptive statistics
were determined (mean value and standard deviation
(SD)). The normality of the data distribution was checked
using the Shapiro-Wilk test, while the homogeneity of the
variance was checked by applying Levenes test. In order
to compare the dierences between the groups, an indepen-
dent sample Student t-test was used or alternatively the
MannWhitney Utest. In the case of dependent samples,
the Student t-test was used or alternatively the Wilcoxon
test. Correlations between particular parameters were statis-
tically veried by means of Spearmans nonparametric cor-
relation test. Dierences at the signicance level of P<0 05
were considered as statistically signicant.
3. Results
3.1. Inammatory-State Parameters, BASDAI, and BASFI. In
the WBC group of AS patients, who underwent a ten-day-
long cycle of WBC procedures with subsequent kinesiother-
apy, it was found that after the completion of the treatment,
the levels of hsCRP and CER decreased signicantly. In the
case of hsCRP, the dierence prior to post treatment values
in the WBC group was signicantly higher in comparison
to those in the KT group patients. Also, in the WBC group,
the level of sICAM-1 showed a decreasing trend. Moreover,
after the completion of the WBC cycle, the level of sICAM-
1 was signicantly lower in comparison to the KT group.
But the level of IL-6 did not change signicantly in the
4 Mediators of Inammation
WBC group with subsequent kinesiotherapy after the com-
pletion of treatment.
After the completion of treatment, only the level of CER
decreased signicantly from the estimated inammatory
parameters in AS patients from the KT group who under-
went a cycle of kinesiotherapy only, without being preceded
by WBC procedures. The levels of hsCRP and sICAM-1 did
not change signicantly in the KT group. Also, as in the
WBC group, no statistically signicant changes in the level
of IL-6 were observed in the KT group.
In turn, the BASDAI and BASFI decreased signicantly
in both groups, but in the WBC group with subsequent kine-
siotherapy after the completion of the treatment, the decrease
of these parameters was signicantly higher in comparison to
that in the KT group. Moreover, only in the WBC group after
the completion of the treatment, the value of both BASDAI
and BASFI was below 4 (inactive phase of AS disease)
(Table 2).
3.2. Oxidative Stress. We observed that patients in the WBC
group had, after the completion of the treatment, a statisti-
cally signicant decrease in erythrocyte levels of MDA,
serum anti-ox-LDL ab, serum TOS, and value of OSI in com-
parison to initial values. What is more, the dierences of these
parameters prior to post treatment values in the WBC group
were signicantly higher in comparison to the KT group.
The levels of plasma MDA and serum ox-LDL did not change
signicantly in the WBC group. In turn, in the KT group, no
signicant changes in the levels of plasma and erythrocyte
MDA, serum ox-LDL, serum anti-ox-LDL ab, and serum
TOS and OSI were observed after the completion of the treat-
ment, in comparison to the initial values before the beginning
of the kinesiotherapy cycle (Table 3).
In the WBC group patients, we observed a statistically
signicant decrease in erythrocyte activity of GPx after
the completion of a cycle of cryotherapy procedures with
subsequent kinesiotherapy. However, the activity of plasma
and erythrocyte total SOD, plasma SOD-Mn, plasma SOD-
CuZn, erythrocyte CAT, and GR did not change signi-
cantly in the WBC group after treatment. But in the
WBC group, the activity of plasma SOD-Mn after treat-
ment was signicantly higher in comparison to the KT
group. In turn, in the KT group, the activity of erythrocyte
total SOD, GPx, and GR decreased signicantly after
Table 2: Levels of inammatory parameters as well as the value of BASDAI and BASFI (mean value ±standard deviation (SD)) in AS
patients before and after the completion of a cycle of ten whole-body cryotherapy procedures with subsequent kinesiotherapy (WBC
group) or a cycle of ten kinesiotherapy procedures only (KT group), with statistical analyses. (p): plasma; (s): serum; Δ:dierence prior to
post treatment.
Parameters WBC group KT group P
hsCRP (s) (mg/l)
Before 13.5 ±16.3 13.9 ±15.2 0.942
After 9.2 ±15.3 13.6 ±16.2 0.438
P0.002 0.623
Δ4.24 ±5.68 0.27 ±3.25 0.023
CER (s) (mg/dl)
Before 62.83 ±12.61 67.57 ±12.60 0.296
After 51.32 ±10.74 53.51 ±14.26 0.628
P0.006 0.003
Δ11.51 ±16.6 14.06 ±14.47 0.646
IL-6 (p) (pg/ml)
Before 41.6 ±8.86 41.8 ±10.5 0.957
After 36.6 ±7.89 41.0 ±10.4 0.191
P0.121 0.301 0.216
Δ4.94 ±11.9 0.74 ±5.71
sICAM-1 (p) (ng/ml)
Before 79.0 ±15.5 84.3 ±21.9 0.432
After 69.2 ±14.2 83.9 ±20.0 0.023
P0.088 0.642
Δ9.84 ±23.0 0.41 ±16.1 0.191
BASDAI
Before 5.43 ±1.61 5.28 ±1.71 0.720
After 3.29 ±0.91 4.53 ±1.62 <0.05
P<0.001 <0.001
Δ2.14 ±1.23 0.74 ±0.38 0.001
BASFI
Before 5.20 ±2.29 5.01 ±2.06 1.00
After 3.81 ±2.20 4.35 ±2.23 0.497
P<0.001 <0.001
Δ1.39 ±1.03 0.66 ±0.39 <0.01
P: statistical signicance of dierences between both groups of patients; P: statistical signicance of dierences between values before and after treatment in
particular groups of patients.
5Mediators of Inammation
treatment in comparison to the WBC group. Additionally,
the activity of plasma SOD-CuZn showed also a decreased
tendency in the KT group. Similarly as in the WBC group
patients, the activity of plasma total SOD and erythrocyte
CAT did not change signicantly in the KT group after
treatment (Table 4).
What is more, in the WBC group, the parameters of non-
enzymatic antioxidants, FRAP values, and UA concentration
increased signicantly after treatment. The levels of those
parameters were signicantly higher in the WBC group in
comparison to the KT group after the completion of the
treatment. The level of PSH did not change signicantly in
the WBC group after treatment. In turn, in the KT group,
the FRAP values and PSH level decreased signicantly, but
the level of UA did not change signicantly after treatment
(Table 5).
3.3. Markers of Lipid Prole, Atherosclerosis Plaque, and
Atherosclerosis Plaque Instability. The levels of T-Chol,
LDL, TG, sCD40L, PLGF, and PAPP-A decreased signi-
cantly after treatment in both groups, but the dierences
prior to post treatment values in the WBC group were signif-
icantly higher in comparison to the KT group, except for T-
Chol. But the TG dierence prior to post treatment values
in the WBC group was higher in comparison to the KT
group. The level of HDL-Chol did not change signicantly
in both groups. The TG/HDL ratio showed a decreasing ten-
dency in the WBC group in comparison to the KT group
(Table 6).
3.4. Signicant Relationships among the Estimated Parameters
in AS Patients Who Underwent WBC Procedures. After treat-
ment, we noticed signicant relationships in the WBC group
between changes of serum hsCRP concentration and erythro-
cyte MDA concentration (r=06). Also, a positive correlation
between serum hsCRP change and plasma FRAP activity
change (r=0 6) was observed. Additionally, a negative corre-
lation between serum hsCRP concentration and plasma
SOD-CuZn activity was found (r=062). In the case of
the analysis of serum oxLDL-ab, we observed a negative cor-
relation with CAT and SOD activities in erythrocytes (rcoef-
cients: 0.51 and 0.53, resp.). Furthermore, the ratio of
Table 3: Levels of lipid peroxidation parameters, total oxidative status (TOS), and oxidative stress index (OSI) (mean value ±standard
deviation (SD)) in AS patients before and after the completion of a cycle of ten whole-body cryotherapy procedures with subsequent
kinesiotherapy (WBC group) or a cycle of ten kinesiotherapy procedures only (KT group), with statistical analyses. (p): plasma; (s): serum;
(e): erythrocyte lysates; Δ:dierence prior to post treatment.
Parameters WBC group KT group P
MDA (p) (μmol/l)
Before 2.54 ±0.52 2.32 ±0.60 0.272
After 2.30 ±0.75 2.41 ±0.83 0.715
P0.278 0.959
Δ0.24 ±0.81 0.09 ±1.04 0.331
MDA (e) (nmol/gHb)
Before 0.17 ±0.04 0.18 ±0.02 0.418
After 0.15 ±0.03 0.18 ±0.04 0.007
P0.013 0.642
Δ0.02 ±0.03 0.00 ±0.04 0.043
ox-LDL (s) (ng/ml)
Before 249 ±77.6 298 ±122 0.191
After 223 ±100 288±133 0.132
P0.301 0.84
Δ25.9 ±123 9.6 ±149 0.738
Anti-oxLDL ab (s) (mU/ml)
Before 465 ±209 571±426 0.382
After 347 ±139 490±316 0.111
P0.013 0.379
Δ118 ±178 80.5 ±323 0.687
TOS (s) (μmol/l)
Before 26.54 ±4.45 23.94 ±11.60 0.414
After 12.09 ±2.55 24.41 ±6.24 <0.001
P<0.001 0.605
Δ14.45 ±4.83 0.46 ±9.11 <0.001
OSI (p/s) (arbitrary unit)
Before 24.10 ±15.94 18.87 ±11.30 0.294
After 8.20 ±6.76 23.65 ±15.68 0.002
P0.003 0.301
Δ15.90 ±16.82 4.78 ±13.88 0.001
P: statistical signicance of dierences between both groups of patients; P: statistical signicance of dierences between values before and after treatment in
particular groups of patients.
6 Mediators of Inammation
TG/HDL was positively correlated with the PLGF serum
concentration after WBC procedures (r=0 58). We also
observed a positive correlation between plasma concentra-
tions of sICAM-1 and MDA (r=066) in the WBC group
after treatment. In the case of erythrocyte GPx activity in
AS patients who underwent WBC procedures with subse-
quent kinesiotherapy, a positive correlation with plasma
PSH (r=054) was visible and a negative correlation was
found with plasma MDA concentration. All the correlations
mentioned above were signicant (p<005).
4. Discussion
In our study, we observed that, after the completion of the
treatment, the WBC group of AS patients who underwent a
ten-day-long cycle of WBC procedures with subsequent
kinesiotherapy had signicantly decreased levels of hsCRP
and CER. The level of sICAM-1 showed a decreasing trend
in the WBC group. But the level of IL-6 did not change
signicantly.
The results of the inammatory parameters in this study
are consistent with our previous preliminary study [17], in
which AS patients who underwent WBC procedures were
observed to have a decrease in CRP, brinogen, mucoprotein,
and sICAM levels.
However, in another study [31], the authors have
observed a decrease in TNF-αand an increase in IL-6 in ten-
nis players after a 5-day exposure to WBC twice a day.
Banet al. [32] have also conrmed that a decreased level
of sICAM-1 is induced by WBC treatment and is linked to an
anti-inammatory response. In another paper, Pournot et al.
[33] have found that WBC (110
°
C) decreased IL-1βand
CRP levels and increased the IL-1ra level after intense exercise.
But the levels of TNF-α, IL-10, and IL-6 remained unchanged.
Similarly, in our study, we did not observe any changes in
serum IL-6 in AS patients who underwent WBC.
Table 4: Activities of antioxidant enzymes (mean value ±standard deviation (SD)) in AS patients before and after the completion of a cycle
of ten whole-body cryotherapy procedures with subsequent kinesiotherapy (WBC group) or a cycle of ten kinesiotherapy procedures only
(KT group), with statistical analyses. (p): plasma; (e): erythrocyte lysates; Δ:dierence prior to post treatment.
Parameters WBC group KT group P
Total SOD (p) (NU/ml)
Before 13.4 ±2.13 12.3 ±1.85 0.145
After 12.1 ±1.88 1.7 ±2.49 0.632
P0.233 0.301
Δ1.28 ±3.13 0.60 ±2.65 0.512
SOD-Mn (p) (NU/ml)
Before 5.37 ±2.75 4.56 ±1.86 0.336
After 6.27 ±0.99 5.02 ±1.64 0.015
P0.163 0.642
Δ0.90 ±2.80 0.46 ±2.46 0.642
SOD-CuZn (p) (NU/ml)
Before 8.09 ±2.74 7.80 ±2.21 0.749
After 7.15 ±1.32 7.05 ±3.09 0.902
P0.326 0.063
Δ0.93 ±2.77 0.75 ±2.72 0.854
Total SOD (e) (NU/mgHb)
Before 85.5 ±17.3 128.0 ±11.2 <0.001
After 90.5 ±11.9 111.0 ±15.6 <0.001
P0.438 0.001
Δ5.02 ±17.3 17.1 ±11.8 <0.001
CAT (e) (IU/mgHb)
Before 385.0 ±70.3 425.0 ±53.6 0.084
After 375.0 ±58.3 412.0 ±58.6 0.088
P0.535 0.352
Δ9.9 ±57.0 13.0 ±54.0 0.876
GPx (e) (IU/gHb)
Before 31.2 ±4.90 29.9 ±2.84 0.363
After 29.1 ±2.97 20.4 ±5.05 <0.001
P0.039 0.001
Δ2.09 ±3.61 9.49 ±6.74 0.001
GR (e) (IU/gHb)
Before 1.72 ±0.56 2.07 ±0.52 0.043
After 1.54 ±0.60 1.65 ±0.59 0.078
P0.469 0.002
Δ0.18 ±0.80 0.42 ±0.41 0.622
P: statistical signicance of dierences between both groups of patients; P: statistical signicance of dierences between values before and after treatment in
particular groups of subjects.
7Mediators of Inammation
In the present study, we also saw a signicant decrease in
the BASDAI and BASFI after the completion of the WBC
treatment in a cryochamber with cold retention. Similar
results were observed in a closed cryochamber of a type called
Wrocławski, cooled by liquid nitrogen [15]. In the both
studies, after the completion of a cycle consisting of ten daily
3-minute-long WBC procedures with subsequent kine-
siotherapy (120
°
C, with a weekend break), the BASDAI
and BASFI decreased below 4. This indicates that the AS dis-
ease entered an inactive phase after the completion of treat-
ment. Our results are also consistent with a study [16], in
which the AS patients underwent 8 daily WBC procedures
(110
°
C, 3 minutes).
There are not many reports on the impact of WBC on
the prooxidant-antioxidant balance. It has been noticed that
WBC procedures may have a benecial inuence on antiox-
idant status. In the study performed by Dugué et al. [34], a
signicant increase has been seen in the TAS value in healthy
men at the end of a cycle of 45 procedures of WBC (110
°
C,
2 minutes, coolant liquid nitrogen) performed three times a
week. In another study, Miller et al. [12] have noticed an
increase in total antioxidant status, SOD activity, and uric
acid level in the plasma of multiple sclerosis patients who
underwent WBC treatment (110
°
temperature, daily 10
procedures with weekend break, coolant medium liquid
nitrogen). What is more, WBC was advocated to possibly
enhance antioxidant capacities and, thus, counteract the
exercise-induced reactive oxygen species production [12].
However, in a dierent study [13], patients with seropos-
itive rheumatoid were observed by the authors to have only a
short-term increase in TRAP during the rst treatment ses-
sion of WBC (110
°
C, three times daily for 7 consecutive
days) and the cold treatment did not cause any signicant
oxidative stress or adaptation.
In our study, we observed a signicant decrease in oxida-
tive stress, which may also be linked to the decrease in
systemic inammation in AS patients who underwent WBC
treatment. After treatment, in the WBC group, we observed
positive correlations between plasma concentrations of
sICAM-1 and MDA as well as serum hsCRP and erythrocyte
MDA concentrations. In addition, negative correlations
between serum hsCRP concentration and plasma SOD-
CuZn activity were found.
Furthermore, we observed the similar results in healthy
subjects who underwent WBC procedures performed in a
cryochamber with cold retention [35].
The dierences in the results of various studies may be
related to the type of cryochamber being used and the
coolant medium, in addition to the time of exposure to
cryogenic temperatures.
Only a few papers have estimated the impact of WBC on
lipid prole. In rats exposed to WBC for 5 or 10 days, HDL
and LDL cholesterol fraction decreased and total cholesterol
levels in animals subjected to 60
°
C sessions for 10 days
remained unchanged. The authors have also observed an
increase in triglycerides in the blood serum of animals sub-
jected to cryostimulation compared to control. A decrease
in HDL cholesterol in rats after cryostimulation can be
explained by the fact that HDL is the main fraction transport-
ing cholesterol in rats, while in humans, most cholesterol is
found in low-density lipoproteins [36].
In another study [9], the authors have observed reducing
T-Chol, LDL-Chol, and TG and increasing HDL-Chol after
20 sessions of WBC in healthy men, but after 10 sessions of
WBC, only LDL-Chol decreased, while a simultaneous
HDL-Chol increase was observed in healthy men (cryogenic
temperature 130
°
C).
In another study by these authors [14], a signicant
decrease in the level of LDL-Chol and TG has been
observed, with a slight increase in high-density lipoprotein
concentration after WBC treatment, including two cryosti-
mulation treatments of 20 daily sessions in the second and
Table 5: Levels of nonenzymatic antioxidants (mean value ±standard deviation (SD)) in AS patients before and after the completion of a
cycle of ten whole-body cryotherapy procedures with subsequent kinesiotherapy (WBC group) or a cycle of ten kinesiotherapy procedures
only (KT group), with statistical analyses. (p): plasma; (s): serum; Δ:dierence prior to post treatment.
Parameters WBC group KT group P
FRAP (μmol/l)
Before 587.1 ±58.3 550.0 ±91.3 0.183
After 636.1 ±62.3 499.3 ±74.6 <0.001
P0.010 0.001
Δ49.0 ±31.7 50.8 ±39.4 <0.001
PSH (s) (μmol/l)
Before 402.6 ±91.7 393.2 ±90.0 0.772
After 392.6 ±87.4 364.7 ±28.4 0.239
P0.836 0.017
Δ9.9 ±108.1 28.5 ±92.6 0.605
UA (s) (mg/dl)
Before 5.40 ±1.39 4.34 ±1.15 0.025
After 6.62 ±2.07 4.61 ±1.25 0.003
P0.011 0.196
Δ1.22 ±1.70 0.27 ±0.70 0.052
P: statistical signicance of dierences between both groups of patients; P: statistical signicance of dierences between values before and after treatment in
particular groups of patients.
8 Mediators of Inammation
the last month of intervention, without diet modication in
obese subjects.
In our study, we also observed a signicant decrease
in T-Chol, LDL-Chol, and TG. But the HDL-Chol level
did not change after completing WBC procedures in the
AS patients. What is more, in our study, we observed a sig-
nicant decrease in the levels of sCD40, PAPP-A, and
PLGF. Additionally, in the present study, the ratio of TG/
HDL was positively correlated with the PLGF serum con-
centration after WBC procedures. The impact of WBC on
these markers in AS patients has been estimated for the
rst time.
A signicant decrease in lipid prole, atherosclerotic
plaque and oxidative stress, and inammatory parameters,
as well as a reduction in the proportion of TG cholesterol
to HDL cholesterol (TG/HDL ratio), seems benecial enough
to consider WBC treatment as a useful method for athero-
sclerosis prevention in AS patients.
The present study has some limitations. First, the
study did not provide long-term follow-up (at least 3
months), and thus, we do not know how long the bene-
cial eect of WBC with subsequent kinesiotherapy would
be maintained after the completion of a WBC cycle. Sec-
ond, the cycle of WBC with subsequent kinesiotherapy
Table 6: Levels of lipid prole parameters, atherosclerosis plaque markers, and atherosclerosis plaque instability and values of TG/HDL ratio
(mean value ±standard deviation (SD)) in AS patients before and after the completion of a cycle of ten whole-body cryotherapy procedures
with subsequent kinesiotherapy (WBC group) or a cycle of ten kinesiotherapy procedures only (KT group), with statistical analyses.
(p): plasma; (s): serum; (e): erythrocyte lysates; Δ:dierence prior to post treatment.
Parameters WBC group KT group P
T-Chol (s) (mg/dl)
Before 221.3 ±39.17 200.33 ±21.33 0.074
After 202.40 ±24.40 190.70 ±22.57 0.51
P0.0006 0.04
Δ18.90 ±20.54 9.63 ±18.38 0.20
LDL-Chol (s) (mg/dl)
Before 125.2 ±32.6 145.3 ±28.3 0.073
After 93.3 ±36.9 132.4 ±24.7 0.002
P<0.001 0.005
Δ31.9 ±28.6 12.9 ±15.1 0.027
HDL-Chol (s) (mg/dl)
Before 50.5 ±14.1 58.0 ±18.0 0.198
After 47.0 ±9.0 56.4 ±18.2 0.078
P0.079 0.109
Δ3.5 ±9.1 1.7 ±10.1 0.590
TG (s) (mg/dl)
Before 185.1 ±18.9 178.6 ±15.9 0.299
After 156.7 ±11.2 165.2 ±20.4 0.158
P0.001 0.001
Δ28.4 ±22.4 13.4 ±19.7 0.053
TG/HDL ratio
Before 3.95 ±1.18 3.32 ±0.96 0.150
After 3.44 ±0.60 3.18 ±0.99 0.320
P0.055 0.250
Δ0.51 ±0.92 0.14 ±0.43 0.190
sCD40L(s) (mg/ml)
Before 9.21 ±3.88 7.25 ±2.20 0.180
After 5.01 ±2.55 5.85 ±2.06 0.171
P0.0004 0.006
Δ4.19 ±2.17 1.4 ±1.78 0.0001
PLGF(s) (pg/ml)
Before 30.17 ±10.23 21.69 ±3.54 0.007
After 19.32 ±5.53 18.31 ±2.91 0.641
P0.001 0.004
Δ10.84 ±7.05 3.38 ±2.13 0.0001
PAPP-A (s) (ng/ml)
Before 17.74 ±7.78 14.48 ±4.52 0.162
After 11.24 ±3.12 11.79 ±3.72 0.920
P0.0004 0.003
Δ6.51 ±8.40 2.69 ±3.65 0.008
P: statistical signicance of dierences between both groups of patients; P: statistical signicance of dierences between values before and after treatment in
particular groups of patients.
9Mediators of Inammation
consisted of only ten procedures. A greater number of
procedures (e.g., 2030) could probably increase the treat-
ment eect. Third, the study should involve a larger num-
ber of AS patients.
5. General Conclusion
Whole-body cryotherapy with subsequent kinesiotherapy
facilitates a decrease in oxidative stress, lipid prole, athero-
sclerosis plaque, and its instability, as well as inammatory
parameters, and appears to be a useful method of atheroscle-
rosis prevention in AS patients.
Conflicts of Interest
The authors declare that there is no conict of interests
regarding the publication of this paper.
Acknowledgments
This work was supported by grants from the Medical Uni-
versity of Silesia (KNW-1-045/K/7/K and KNW-640-2-1-
376/17).
References
[1] A. Bremander, I. F. Petersson, S. Bergman, and M. Englund,
Population-based estimates of common comorbidities and
cardiovascular disease in ankylosing spondylitis,Arthritis
Care & Research, vol. 63, no. 4, pp. 550556, 2011.
[2] N. Bodnar, G. Kerekes, I. Seres et al., Assessment of subclini-
cal vascular disease associated with ankylosing spondylitis,
The Journal of Rheumatology, vol. 38, no. 4, pp. 723729, 2011.
[3] A. Stanek, A. Cholewka, T. Wielkoszyński, E. Romuk,
K. Sieroń, and A. Sieroń,Increased levels of oxidative stress
markers, soluble CD40 Ligand and carotid intima-media thick-
ness reect acceleration of atherosclerosis in male patients with
ankylosing spondylitis in active phase and without the classical
cardiovascular risk factors,Oxidative Medicine and Cellular
Longevity, vol. 2017, Article ID 9712536, 8 pages, 2017.
[4] D. van der Heijde, S. Ramiro, R. Landewé et al., 2016 update
of the ASAS-EULAR management recommendations for axial
spondyloarthritis,Annals of the Rheumatic Diseases, vol. 76,
no. 6, pp. 978991, 2017.
[5] L. A. Passalent, Physiotherapy for ankylosing spondylitis: evi-
dence and application,Current Opinion in Rheumatology,
vol. 23, no. 2, pp. 142147, 2011.
[6] J. Tyrrell, W. Schmidt, D. H. Williams, and C. H. Redshaw,
Physical activity in ankylosing spondylitis: evaluation and
analysis of an eHealth tool,Journal of Innovation in Health
Informatics, vol. 23, no. 2, pp. 510522, 2016.
[7] X. Guillot, N. Tordi, L. Mourot et al., Cryotherapy in inam-
matory rheumatic diseases: a systematic review,Expert Review
of Clinical Immunology, vol. 10, no. 2, pp. 281294, 2014.
[8] G. Lombardi, E. Ziemann, and G. Ban,Whole-body cryo-
therapy in athletes: from therapy to stimulation. An updated
review of the literature,Frontiers in Physiolology, vol. 8,
no. 258, pp. 116, 2017.
[9] A. Lubkowska, G. Ban, B. Dolegowska, G. V. dEril, J. Łuczak,
and A. Barrasi, Changes in lipid prole in response to three
dierent protocols of whole-body cryostimulation treat-
ments,Cryobiology, vol. 61, no. 1, pp. 2226, 2010.
[10] A. Lubkowska, W. Dudzińska, I. Bryczkowska, and
B. Dołęgowska, Body composition, lipid prole, adipokine
concentration, and antioxidant capacity changes during inter-
ventions to treat overweight with exercise programme and
whole-body cryostimulation,Oxidative Medicine and Cellu-
lar Longevity, vol. 2015, Article ID 803197, 13 pages, 2015.
[11] J. Rymaszewska, D. Ramsey, and S. Chładzińska-Kiejna,
Whole-body cryotherapy as adjunct treatment of depressive
and anxiety disorders,Archivum Immunologiae et Therapiae
Experimentalis, vol. 56, no. 1, pp. 6368, 2008.
[12] E. Miller, M. Mrowiecka, K. Malinowska, K. Zołynski, and
J. Kedziora, Eects of the whole-body cryotherapy on a total
antioxidative status and activities of some antioxidative
enzymes in blood of patients with multiple sclerosis-
preliminary study,The Journal of Medical Investigation,
vol. 57, no. 1,2, pp. 168173, 2010.
[13] H. Hirvonen, H. Kautiainen, E. Moilanen, M. Mikkelsson, and
M. Leirisalo-Repo, The eect of cryotherapy on total antioxi-
dative capacity in patients with active seropositive rheumatoid
arthritis,Rheumatology International, vol. 37, no. 9,
pp. 14811487, 2017.
[14] L. Jagodziński, A. Stanek, J. Gmyrek, G. Cieślar, A. Sielańczyk,
and A. Sieroń,Evaluation of whole-body cryotherapy on the
circulatory system in patients with ankylosing spondylitis by
analysis of duration and QT interval dispersion,Polish Jour-
nal of Physiotherapy, vol. 7, no. 3, pp. 362369, 2007.
[15] A. Stanek, A. Cholewka, J. Gaduła, Z. Drzazga, A. Sieroń, and
K. Sieroń-Stołtny, Can whole-body cryotherapy with subse-
quent kinesiotherapy procedures in closed type cryogenic
chamber improve BASDAI, BASFI, some spine mobility
parameters and decrease pain intensity in patients with anky-
losing spondylitis?,BioMed Research International, vol. 2015,
Article ID 404259, 11 pages, 2015.
[16] M. W. Romanowski, W. Romanowski, P. Keczmer,
M. Majchrzycki, W. Samborski, and A. Straburzynska-Lupa,
Whole body cryotherapy in rehabilitation of patients with
ankylosing spondylitis. A randomised controlled study,Phys-
iotherapy, vol. 101, article e1294, Supplement 1, 2015.
[17] A. Stanek, G. Cieślar, K. Strzelczyk et al., Inuence of cryo-
genic temperatures on inammatory markers in patients with
ankylosing spondylitis,Polish Journal of Environmental
Study, vol. 19, no. 1, pp. 167175, 2010.
[18] S. van der Linden, H. A. Valkenburg, and A. Catts, Evaluation
of diagnostic criteria for ankylosing spondylitis,Arthritis &
Rheumatology, vol. 27, no. 4, pp. 361368, 1984.
[19] R. Richterich, Clinical Chemistry: Theory and Practice, Aca-
demic Press, New York, 1969.
[20] H. Ohkawa, N. Ohishi, and K. Yagi, Assay for lipid peroxides
in animal tissues by thiobarbituric acid reaction,Analytical
Biochemistry, vol. 95, no. 2, pp. 351358, 1979.
[21] O. Erel, A new automated colorimetric method for measuring
total oxidant status,Clinical Biochemistry, vol. 38, no. 12,
pp. 11031111, 2005.
[22] M. Harma, M. Harma, and O. Erel, Increased oxidative stress
in patients with hydatidiform mole,Swiss Medical Weekly,
vol. 133, no. 41-42, pp. 563566, 2003.
[23] Y. Oyanagui, Reevaluation of assay methods and establish-
ment of kit for superoxide dismutase activity,Analytical Bio-
chemistry, vol. 142, no. 2, pp. 290296, 1984.
10 Mediators of Inammation
[24] H. Aebi, [13] Catalase in vitro,Methods in Enzymology,
vol. 105, pp. 121126, 1984.
[25] D. Paglia and W. Valentine, Studies on the quantitative and
qualitative characterization of erythrocyte glutathione peroxi-
dase,The Journal of Laboratory and Clinical Medicine,
vol. 70, no. 1, pp. 158169, 1967.
[26] I. F. F. Benzie and J. J. Strain, The ferric reducing ability of
plasma (FRAP) as a measure of antioxidant power: the FRAP
assay,Analytical Biochemistry, vol. 239, no. 1, pp. 7076,
1996.
[27] J. F. Koster, P. Biemond, and A. J. Swaak, Intracellular and
extracellular sulphydryl levels in rheumatoid arthritis,Annals
of the Rheumatic Diseases, vol. 45, no. 1, pp. 4446, 1986.
[28] Y. Zhao, X. Yang, W. Lu, H. Liao, and F. Liao, Uricase based
methods for determination of uric acid in serum,Microchi-
mica Acta, vol. 164, no. 1-2, pp. 16, 2009.
[29] S. Garrett, T. Jenkinson, L. G. Kennedy, H. Whitelock,
P. Gaisford, and A. Calin, A new approach to dening disease
status in ankylosing spondylitis: the Bath Ankylosing Spondy-
litis Disease Activity Index,Journal of Rheumatology, vol. 21,
no. 12, pp. 22862291, 1994.
[30] A. Calin, S. Garrett, H. Whitelock et al., A new approach to
dening functional ability in ankylosing spondylitis: the devel-
opment of the Bath Ankylosing Spondylitis Functional Index,
The Journal of Rheumatology, vol. 21, no. 12, pp. 22812285,
1984.
[31] E. Ziemann, R. A. Olek, S. Kujach et al., Five-day whole-body
cryostimulation, blood inammatory markers, and perfor-
mance in high-ranking professional tennis players,Journal
of Athletic Training, vol. 47, no. 6, pp. 664672, 2012.
[32] G. Ban, M. Melegati, A. Barassi et al., Eects of whole-body
cryotherapy on serum mediators of inammation and serum
muscle enzymes in athletes,Journal of Thermal Biology,
vol. 34, no. 2, pp. 5559, 2009.
[33] H. Pournot, F. Bieuzen, J. Louis et al., Time-course of changes
in inammatory response after whole-body cryotherapy multi
exposures following severe exercise,PLoS One, vol. 6, no. 7,
article e22748, 2011.
[34] B. Dugué, J. Smolander, T. Westerlund et al., Acute and long-
term eects of winter swimming and whole-body cryotherapy
on plasma antioxidative capacity in healthy women,Scandi-
navian Journal of Clinical and Laboratory Investigation,
vol. 65, no. 5, pp. 395402, 2005.
[35] A. Stanek, K. Sieroń-Stołtny, E. Romuk et al., Whole-body
cryostimulation as an eective method of reducing oxidative
stress in healthy men,Advances in Clinical and Experimental
Medicine, vol. 25, no. 6, pp. 12811291, 2016.
[36] B. Skrzep-Poloczek, E. Romuk, and E. Birkner, The eect of
whole-body cryotherapy on lipids parameters in experimental
rat model,Polish Journal of Balneology, vol. 44, no. 14, pp. 7
13, 2002.
11Mediators of Inammation
... Another promising method of non-pharmacological treatment of cognitive decline is called Whole-Body Cryotherapy or Cryostimulation (WBC). WBC involves a repetitive, short-term (up to 3 min) exposure to extremely low temperatures, and is nowadays widely used to relieve symptoms of various ailments in the course of which inflammation, muscle spasms, chronic pain, and swelling are observed (17)(18)(19)(20). Systematic review revealed that WBC may exert beneficial effects on the lipid profile in terms of lowering the levels of total cholesterol, LDL, and triglycerides (21). ...
... Preliminary studies suggest that it may also be an effective method of improving cognitive functioning, especially memory processes (22). According to current knowledge, vascular malfunction, mitochondrial damage, oxidative stress and inflammatory response contribute to the development of cognitive deterioration, and WBC might be a response to these processes (20,(23)(24)(25)(26). Recent studies suggest anti-inflammatory, anti-analgesic, metabolic, hormonal, and anti-oxidant effects of this therapy based on the underlying physiological responses (21,27,28). ...
Article
Full-text available
Objectives: Subjective Cognitive Decline (SCD) and Mild Cognitive Impairment (MCI) are common in elderly population, and constitute a high-risk group for progression to dementia. Innovative, complex, and engaging non-pharmacological methods of cognitive stimulation, implementable at this stage, are needed. The aim of the study was to determine the effect of Computerized Cognitive Training (CCT) combined with Whole Body Stimulation (WBC) on cognitive functions of older adults with SCD and MCI. Methods: A 9-week single-blind pre/post case control trial was conducted. The study enrolled 84 adults aged 60 or older, allocated to one of two intervention groups: EG; CCT with psychoeducation, EG2; CCT with psychoeducation and 10 WBC sessions, or the control group (CG), which comprised patients receiving usual care. The primary outcome measures were cognitive functions evaluated with MoCA scale and several other neuropsychological tools. Depressive symptoms assessed with the GDS scale constituted the secondary outcome measures. Results: The results show evidence for increased performance in the assessment of general cognitive functioning in both EGs ( p ≤ 0.05). Significant improvement was also visible in several cognitive domains, such as verbal fluency (EG1 & EG2), learning ability and immediate memory (EG1 & EG2), delayed memory (EG2), attentional control (EG1), and information processing (EG2) ( p ≤ 0.05). However, only in the group with combined interventions (CCT + WBC) the participants presented significantly less depressive symptoms ( p ≤ 0.05). Conclusions: The results of the study suggest that CCT, especially in combination with WBC, might be a practical and effective method of improving cognitive performance. Moreover, this combination leads to a reduction of depressive symptoms.
... It provides improved pain control and is used to increase regeneration rate. [6] As per standard protocol, a minimally dressed subject enters a vestibule chamber at -60°C, where he stays for about 30 seconds for body adaptation and then passes into a cryochamber at -110° to -140°C, where he or she remains for no more than three minutes. [6] Although stent thrombosis has been previously reported as a complication of cryotherapy, occurrence of PVT has not been described in the literature yet. ...
... [6] As per standard protocol, a minimally dressed subject enters a vestibule chamber at -60°C, where he stays for about 30 seconds for body adaptation and then passes into a cryochamber at -110° to -140°C, where he or she remains for no more than three minutes. [6] Although stent thrombosis has been previously reported as a complication of cryotherapy, occurrence of PVT has not been described in the literature yet. This case represents a case of acute PVT in a previously healthy young male athlete with no known risk factors. ...
... The new finding of the present study is that local cryotherapy exerted positive effects remoted from the joint, improving all the aspects of AIA-induced systemic vascular pathology. Of note, a previous study in patients with ankylosing spondylitis showed that a cycle of 10 wholebody cryotherapy procedures with subsequent kinesiotherapy reduced plasma ICAM-1 levels as compared to kinesiotherapy alone [36], suggesting a positive effect on EA. Importantly, whether the effects of cryotherapy on the systemic vasculature would be maintained in the longterm after completion of the treatment was not investigated in the present study. ...
Article
Full-text available
Aim This study explored the systemic vascular effects of local cryotherapy with a focus on endothelial changes and arterial inflammation in the model of rat adjuvant-induced arthritis (AIA). Methods Cryotherapy was applied twice a day on hind paws of AIA rats from the onset of arthritis to the acute inflammatory phase. Endothelial activation was studied in the aorta by measuring the mRNA levels of chemokines (CXCL-1, MCP-1 (CCL-2), MIP-1α (CCL-3)) and adhesion molecules (ICAM-1, VCAM-1) by qRT-PCR. Endothelial dysfunction was measured in isolated aortic and mesenteric rings. Aortic inflammation was evaluated via the mRNA expression of pro-inflammatory cytokines (TNF-α, IL-6) by qRT-PCR and leucocyte infiltration analysis (flow cytometry). Plasma levels of TNF-α, IL-6, IL-1β, IL-17A, and osteoprotegerin (OPG) were measured using Multiplex/ELISA. Results AIA was associated with an increased aortic expression of CXCL-1 and ICAM-1 as well as an infiltration of leucocytes and increased mRNA expression of IL-6, IL-1β, and TNF-α. Local cryotherapy, which decreased arthritis score and structural damages, reduced aortic mRNA expression of CXCL-1, IL-6, IL-1β, and TNF-α, as well as aortic infiltration of leucocytes (T lymphocytes, monocytes/macrophages, neutrophils) and improved acetylcholine-induced vasorelaxation in the aorta and mesenteric arteries. Plasma levels of IL-17A and OPG were significantly reduced by cryotherapy, while the number of circulating leucocytes was not. IL-17A levels positively correlated with endothelial activation and dysfunction. Conclusion In the AIA model, local cryotherapy reduced systemic endothelial activation, immune cell infiltration, and endothelial dysfunction. Mechanistically, the reduction of circulating levels of IL-17A appears as the possible link between joint cooling and the remote vascular effects.
... Despite the very low temperatures, the procedure is considered safe and has few contraindications. The method was first applied in rheumatoid arthritis patients [2] and is currently involved in the management of various disease including ankylosing spondylitis [3] and depression [4], while it is an increasingly popular tool for the recovery of athletes [5]. Only a limited number of studies have addressed the effects of WBC in respiratory and cardiovascular parameters in healthy individuals (not athletes). ...
Chapter
Introduction: Whole-body cryostimulation (WBC) refers to the therapeutic application of extremely cold dry air for a short period of time. The method has beneficial results in various diseases as well as the recovery of athletes. The effects of WBC in healthy individuals have not been extensively investigated. Purpose: We aim to explore differences in the effects of WBC on blood pressure (BP), oxygen saturation (SpO2), and heart rate (HR) in healthy adults (not athletes) as well as differences according to gender and smoking status. Materials and methods: Fifty adults (male/female: 32/18) smokers/nonsmokers: 26/24) were included in the study. WBC was performed in a cryochamber at -85 °C for 3 min. Systolic BP (SBP) and diastolic BP (DBP), HR, and SpO2 were measured before and immediately after WBC. Results: Males and females differed significantly in SBP after WBC (138.1 ± 13.0 vs 128.5 ± 17.0 mmHg, respectively, p = 0.029), SpO2 after WBC (96.6 ± 1.8 vs 98.3 ± 1.5%, respectively, p = 0.001) and HR after WBC (60.1 ± 9.6 vs 70.2 ± 7.7 bpm, respectively, p < 0.001). In males, SpO2 remained unchanged before and after WBC, whereas in women SpO2 increased by 1.0 ± 1.4% (p = 0.038) (Table 2). HR after WBC displayed a downward trend by -9.8 ± 5.9% in males compared to an upward trend by 3.6 ± 15.1 in females (p < 0.001). Nonsmokers displayed higher increase in SBP after WBC (4.3 ± 9.0% in smokers compared to 13.3 ± 13.2% in nonsmokers, p = 0.007). Smokers presented an increase by 1.0 ± 1.6% in SpO2, while in nonsmokers, SpO2 decreased by 0.8 ± 2.1% following WBC (p = 0.001). Conclusions: Our results suggest that WBC affects the cardiovascular and the respiratory system differently in males versus females and smokers versus nonsmokers. More studies are needed in order to fully explore the effects of WBC in these population groups in order to design individualized treatment protocols.
... Stanek et al. reported in two different studies a significantly reduced mean pain (VAS) score following WBC at -120°C and rehab, along with a significantly greater reduction compared to the control group with just rehab [28,31]. Stanek et al. also reported in two additional studies a significant decrease in disease activity as measured by BASDAI, and the WBC (-120°C) and rehab groups had a significantly greater reduction in BASDAI than the control groups that just received rehab [24,32]. A decrease in BASDAI was also reported by Straburzynska-Lupa et al. in all their study groups (WBC at Randomized RA None reported -110°C ? ...
Article
Full-text available
Background Cryotherapy has been used to reduce chronic pain for many years due in part to its ease of use, affordability, and simplicity. It can be applied either locally (e.g., ice packs) or non-locally (e.g., partial and whole-body cryotherapy) depending on the location of the pain.Objectives To determine the overall effectiveness of cryotherapy at reducing chronic pain by characterizing the currently available evidence supporting the use and effects of cryotherapy on chronic pain associated with chronic diseases.Study DesignA narrative review of original research studies assessing the efficacy of cryotherapy in alleviating chronic pain.MethodsA PubMed database search was performed to find human studies between the years 2000 and 2020 that included the application of cryotherapy in patients with chronic pain associated with chronic diseases. A review of the relevant references was also performed to gather more articles. Data was extracted, summarized into tables, and qualitatively analyzed.ResultsTwenty-five studies (22 randomized controlled trials, one prospective analysis, 1 one-group pretest/posttest study, and one case–control study) were included after the literature search. Both local and non-local cryotherapy applications show promise in reducing chronic pain associated with various chronic diseases including those of rheumatic and degenerative origin. Cryotherapy appears to be a safe therapy in carefully selected patients, with only minimal adverse effects reported in the literature.LimitationsMeta-analysis was not possible given the many differences between studies. Cross-study data homogenization and comparison between studies proved fairly difficult due to the lack of standardized studies, various uses and practice types of cryotherapy, and lack of control groups in some studies.Conclusions Local and non-local cryotherapy can be low-risk and easy treatment options to add in the management of chronic pain in carefully selected patients. However, long-term effects, a standardized approach, and careful study of other chronic pain syndromes should be considered in future research to further support the use of cryotherapy in the management of chronic pain.
... In another paper Banfi et al. [17] presented that WBC procedures performed once daily for 5 days caused a rise of anti-inflammatory cytokine (IL-10) and a drop of proinflammatory cytokines (Il-2 and IL-8) in athletes. Moreover, the beneficial impact of WBC procedures on inflammatory parameters was also observed in patients with rheumatoid arthritis [33] and ankylosing spondylitis [7,34]. ...
Article
Full-text available
Background: The purpose of this study was to estimate the effect of whole-body cryostimulation (WBC) and subsequent kinesiotherapy on inflammatory endothelium and oxidative stress parameters in healthy subjects. Methods: The effects of ten WBC procedures lasting 3 min per day and followed by a 60-min session of kinesiotherapy on oxidative stress and inflammatory endothelium parameters in healthy subjects (WBC group n = 32) were analyzed. The WBC group was compared to a kinesiotherapy only (KT; n = 16) group. The following parameters were estimated one day before the start, and one day after the completion of the studies: oxidative stress parameters (the total antioxidant capacity of plasma (FRAP), paraoxonase-1 activity (PON-1), and total oxidative status (TOS)) and inflammatory endothelium parameters (myeloperoxidase activity (MPO), serum amyloid A (SAA), and sCD40L levels). Results: A significant decrease of PON-1 and MPO activities and TOS, SAA, and sCD40L levels as well as a significant FRAP increase were observed in the WBC group after the treatment. In addition, the SAA levels and PON-1 activity decreased significantly after the treatment in both groups, but the observed decrease of these parameters in the WBC group was higher in comparison to the KT group. Conclusion: WBC procedures have a beneficial impact on inflammatory endothelium and oxidative stress parameters in healthy subjects, therefore they may be used as a wellness method.
... Importantly, these patients were not burdened with classic cardiovascular risk factors [59]. Whole-body cryotherapy decreases the levels of Inflammatory, oxidative stress, and atherosclerosis plaque markers in male patients with active phase ankylosing spondylitis in the absence of classical cardiovascular risk factors [60]. Chronic inflammatory state in these patients cause increased cardiovascular and cerebrovascular mortality [61]. ...
Article
While the recent literature on Whole-Body Cryotherapy pointed to its beneficial systemic effects on inflammatory markers in rheumatoid arthritis, it was not clear whether it could also have more localized effects, with the attainment of analgesic thresholds on hands that are usually protected during protocols. Twenty-five young, healthy subjects (12 males aged 25.1 ± 3.5 years and 13 females aged 23.5 ± 2.6 years) agreed to participate in this study. Two study groups were defined: (1) a control group with a hand fully gloved and (2) an experimental group with a partially ungloved hand during the WBC session. In both groups, the achievement of analgesic thresholds of skin temperature was established through thermal imaging, focused on the measurement of temperatures at the different joint locations. Using a new protocol with direct exposure of the hands during the last 40 s of a standard WBC session of 3 min at −110 °C made it possible to respect this risk/benefit balance. Infrared thermography analyses revealed that for all regions of interest (except MCP and IP, CMP for thumb), there was a clinically meaningful reduction of skin temperature in participants from the experimental group. The thermal analysis suggests that a protocol of Whole-Body Cryotherapy at −110 °C where hands must be ungloved during 40 s could be a useful tool for the management of hand rheumatoid arthritis by achieving local antalgic thresholds.
Article
Purpose Whole-body cryotherapy (WBC) is an already proven method of supportive therapy in somatic medicine. Emerging evidence suggests that WBC might exert beneficial effects on lipid profile; however, studies in this field have provided mixed findings. Objective We aimed to perform a systematic review and meta-analysis of studies investigating the impact of WBC on lipid profile. Methods Electronic databases (the MEDLINE, the ERIC, the CINAHL Complete, the International Pharmaceutical Abstracts as well as the Academic Search Ultimate and the Health Source: Nursing/Academic Edition) were searched from their inception until 25th April 2020. Meta-analysis was performed using random-effects models and Hedges g’ was calculated as the effect size estimate. Results We identified seven eligible studies. Pooled data analysis revealed significantly lower levels of triglycerides after WBC. Sensitivity analysis also demonstrated significantly lower levels of total cholesterol and low-density lipoproteins (LDL) after removing single studies. Meta-regression analysis showed that lower baseline body mass index (BMI) was significantly associated with greater changes in the levels of total cholesterol and LDL during WBC. Conclusions Our findings imply that WBC may exert beneficial effects on the lipid profile in terms of lowering the levels of total cholesterol, LDL and triglycerides. Lower BMI may predict a greater improvement of lipid profile during WBC. However, caution should be taken as to the way our results are being interpreted due to low number of studies and considerable methodological heterogeneity of studies included in our meta-analysis.
Article
Full-text available
Objective The primary aim of the study was to assess levels of oxidative stress markers, soluble CD40 ligand (sCD40L), serum pregnancy-associated plasma protein-A (PAPP-A), and placental growth factor (PlGF) as well as carotid intima-media thickness (IMT) in patients with ankylosing spondylitis (AS) with active phase without concomitant classical cardiovascular risk factors. Material and methods The observational study involved 96 male subjects: 48 AS patients and 48 healthy ones, who did not differ significantly regarding age, BMI, comorbid disorders, and distribution of classical cardiovascular risk factors. In both groups, we estimated levels of oxidative stress markers, lipid profile, and inflammation parameters as well as sCD40L, serum PAPP-A, and PlGF. In addition, we estimated carotid IMT in each subject. Results The study showed that markers of oxidative stress, lipid profile, and inflammation, as well as sCD40L, PlGF, and IMT, were significantly higher in the AS group compared to the healthy group. Conclusion Our results demonstrate that ankylosing spondylitis may be associated with increased risk for atherosclerosis.
Article
Full-text available
Patients with rheumatoid arthritis (RA) have increased oxidative stress, decreased antioxidant levels, and impaired antioxidant capacity. Cold treatments are used to relieve joint inflammation and pain. Therefore, we measured the effect of cold treatments on the antioxidative capacity of RA patients with active disease. Sixty patients were randomized to (1) whole body cryotherapy at -110 °C, (2) whole body cryotherapy at -60 °C, or (3) local cryotherapy. Each treatment was given three times daily for 7 consecutive days in addition to the conventional rehabilitation. Blinded rheumatologist evaluated disease activity before the first and after the last cryotherapy. We collected plasma samples daily immediately before the first and after the second cryotherapy and measured total peroxyl radical trapping antioxidant capacity of plasma (TRAP), which reflects global combined antioxidant capacity of all individual antioxidants in plasma. Baseline morning TRAP levels (mean, 95% CI), adjusted for age, body mass index, disease activity, and dose of prednisolone, were 1244 (1098-1391) µM/l in the local cryotherapy, 1133 (1022-1245) µM/l in the cryotherapy at -60 °C, and 989 (895-1082) µM/l in the cryotherapy at -110 °C groups (p = 0.006). After the first treatment, there was a rise in 1-h TRAP of 14.2 (-4.2 to 32.6) µM/l, 16.1 (-7.4 to 39.6) µM/l, and 23.6 (4.1-43.2) µM/l, respectively. The increase was significant in the whole-body cryotherapy -110 °C group (p < 0.001) but not significant between the groups (p = 0.78). When analyzed for the whole week, the daily morning TRAP values differed significantly between the treatment groups (p = 0.021), but there was no significant change within each treatment group. Whole-body cryotherapy at -110 °C induced a short-term increase in TRAP during the first treatment session with but not during other treatment modalities. The effect was short and the cold treatments did not cause a significant oxidative stress or adaptation during 1 week.
Article
Full-text available
Nowadays, whole-body cryotherapy is a medical physical treatment widely used in sports medicine. Recovery from injuries (e.g., trauma, overuse) and after-season recovery are the main purposes for application. However, the most recent studies confirmed the anti-inflammatory, anti-analgesic, and anti-oxidant effects of this therapy by highlighting the underlying physiological responses. In addition to its therapeutic effects, whole-body cryotherapy has been demonstrated to be a preventive strategy against the deleterious effects of exercise-induced inflammation and soreness. Novel findings have stressed the importance of fat mass on cooling effectiveness and of the starting fitness level on the final result. Exposure to the cryotherapy somehow mimics exercise, since it affects myokines expression in an exercise-like fashion, thus opening another possible window on the therapeutic strategies for metabolic diseases such as obesity and type 2 diabetes. From a biochemical point of view, whole-body cryotherapy not always induces appreciable modifications, but the final clinical output (in terms of pain, soreness, stress, and post-exercise recovery) is very often improved compared to either the starting condition or the untreated matched group. Also, the number and the frequency of sessions that should be applied in order to obtain the best therapeutic results have been deeply investigated in the last years. In this article, we reviewed the most recent literature, from 2010 until present, in order to give the most updated insight into this therapeutic strategy, whose rapidly increasing use is not always based on scientific assumptions and safety standards.
Article
Full-text available
Background. Whole-body cryostimulation (WBC) is the therapeutic exposure of the total human body (without underwear) to a very low temperature (below –100°C) for 120–180 s. Currently, WBC is used more frequently not only in the treatment of patients suffering from various diseases, but also by healthy people as a wellness method. Objectives. The aim of this research is to evaluate the impact of WBC procedures on oxidative stress parameters in healthy men. Material and Methods. The study involved 32 healthy male subjects who were randomly divided into 2 groups: 16 men exposed to WBC procedures with subsequent kinesiotherapy (WBC group) and 16 men exposed only to kinesiotherapy procedures (KT group). Depending on the group, the subjects were exposed to 10 daily WBC procedures lasting 3 min, with a subsequent 60-min of kinesiotherapy, or exclusively to kinesiotherapy. In subjects from both groups, a day before the beginning of a cycle of treatment and a day after its completion, the level of selected indicators of oxidative stress and non-enzymatic antioxidants, as well as the activity of antioxidant enzymes in serum, plasma and erythrocyte lysates were determined. Results. In the WBC group subjects, we recorded a statistically significant decrease in the concentrations of most of the parameters of oxidative stress with an accompanying increase in plasma concentrations of non-enzymatic antioxidants (total antioxidant status and uric acid). We recorded no significant changes in the activities of antioxidant enzymes (plasma total superoxide dismutase (SOD) and its isoenzymes SOD-Mn and SOD-ZnCu, erythrocyte catalase, glutathione peroxidase and glutathione reductase). Conclusions. The results we obtained confirmed that WBC decreases oxidative stress in healthy men.
Article
Full-text available
Background: Ankylosing spondylitis (AS) is a chronic inflammatory condition characterised by spinal arthritis and exercise is often recommended to reduce the symptoms and improve mobility. However, very little evidence exists for the value of exercise in AS. Objectives: Firstly, this pilot study aimed to evaluate an eHealth tool, the AS Observer, specifically designed to monitor symptoms, quality of life and physical activity in AS, in terms of patient experience and suitability in generating data for epidemiological studies. Secondly, it also investigated the collected data to determine if physical activity benefited individuals with AS. Methods: The AS Observer was designed to enable weekly monitoring of AS symptoms and exercise using a web based platform. Participants with AS (n = 223) were recruited to use the AS observer. They provided baseline data and completed online weekly data entry for 12 weeks (e.g. Bath Ankylosing Spondylitis Activity Index (BASDAI), howRu, International Physical Activity Questionnaire (IPAQ)). Panel data analysis with fixed effects models investigated associations between variables. Activity type data and exit questionnaires were subjected to qualitative thematic analysis. Results: In general, the AS Observer was well received and considered useful by participants, with 66% providing a positive response. The collected data suggested that IPAQ is inversely associated with total BASDAI, stiffness, tenderness and pain, but not fatigue. Stratified analysis demonstrated differential associations between BASDAI, IPAQ and howRU based on sex, HLA-B27 status and disease duration. Approximately half of the participants frequently did therapy and three-quarters undertook at least some vigorous activity ranging from formal exercise to recreation and (house) work. Despite some technical challenges, tool evaluation suggested that the AS Observer was a useful self-monitoring tool for participants. Conclusions: This pilot study demonstrated that increased exercise intensity and duration were associated with an improved BASDAI symptom score in a cohort of participants with AS. Furthermore, it provided further evidence of the value of using eHealth tools for clinical purposes and data collection for research, inclusive of the development of treatment pathways and disease management strategies.
Article
To update and integrate the recommendations for ankylosing spondylitis and the recommendations for the use of tumour necrosis factor inhibitors (TNFi) in axial spondyloarthritis (axSpA) into one set applicable to the full spectrum of patients with axSpA. Following the latest version of the European League Against Rheumatism (EULAR) Standardised Operating Procedures, two systematic literature reviews first collected the evidence regarding all treatment options (pharmacological and non-pharmacological) that were published since 2009. After a discussion of the results in the steering group and presentation to the task force, overarching principles and recommendations were formulated, and consensus was obtained by informal voting. A total of 5 overarching principles and 13 recommendations were agreed on. The first three recommendations deal with personalised medicine including treatment target and monitoring. Recommendation 4 covers non-pharmacological management. Recommendation 5 describes the central role of non-steroidal anti-inflammatory drugs (NSAIDs) as first-choice drug treatment. Recommendations 6–8 define the rather modest role of analgesics, and disprove glucocorticoids and conventional synthetic disease-modifying antirheumatic drugs (DMARDs) for axSpA patents with predominant axial involvement. Recommendation 9 refers to biological DMARDs (bDMARDs) including TNFi and IL-17 inhibitors (IL-17i) for patients with high disease activity despite the use (or intolerance/contraindication) of at least two NSAIDs. In addition, they should either have an elevated C reactive protein and/or definite inflammation on MRI and/or radiographic evidence of sacroiliitis. Current practice is to start with a TNFi. Switching to another TNFi or an IL-17i is recommended in case TNFi fails (recommendation 10). Tapering, but not stopping a bDMARD, can be considered in patients in sustained remission (recommendation 11). The final two recommendations (12, 13) deal with surgery and spinal fractures. The 2016 Assessment of SpondyloArthritis international Society-EULAR recommendations provide up-to-date guidance on the management of patients with axSpA.