Long‐term efficacy of radon spa therapy in rheumatoid arthritis—a randomized, sham‐controlled study and follow‐up

Authors: Franke A (1) , Reiner L (2) , Pratzel HG (3) , Franke T (1) , Resch KL (1)
Affiliations:
(1) Balneology and Rehabilitation Sciences Research Institute (FBK), Bad Elster, Maximilians University (2) In‐patient rehabilitation hospital (Dr Ebel Fachklinik) Bad Brambach (3) Institute of Medical Balneology and Climatology, Ludwig Maximilians University
Source: Rheumatology, Volume 39, Issue 8, August 2000, Pages 894–902
DOI: 10.1093/rheumatology/39.8.894 Publication date: 2000 Aug E-Publication date: Aug. 1, 2000 Availability: full text Copyright: © British Society for Rheumatology
Language: English Countries: Germany Location: Bad Brambach Correspondence address: Not specified

Keywords

Article abstract

Objective. To quantify the efficacy of a series of baths containing natural radon and carbon dioxide (1.3 kBq/l, 1.6 g carbon dioxide/l on average) versus artificial carbon dioxide baths alone in patients with rheumatoid arthritis.

Subjects. Sixty patients participating in an in‐patient rehabilitation programme including a series of 15 baths were randomly assigned to two groups.

Design. Pain intensity (100 mm visual analogue scale) and functional restrictions [Keitel functional test, Arthritis Impact Measurement Scales (AIMS questionnaire)] were measured at baseline, after completion of treatment and 3 and 6 months thereafter. To investigate whether the overall value of the outcomes was the same in both groups, the overall mean was analysed by Student's t‐test for independent samples.

Results. The two groups showed a similar baseline situation. After completion of treatment, relevant clinical improvements were observed in both groups, with no notable group differences. However, the follow‐up revealed sustained effects in the radon arm, and a return to baseline levels in the sham arm. After 6 months, marked between‐group differences were found for both end‐points (pain intensity: −16.9%, 95% confidence interval −27.6 to −6.2%; AIMS score: 0.57, 95% confidence interval 0.16 to 0.98). The between‐group differences were statistically significant for both overall means (pain intensity, P = 0.04; AIMS, P = 0.01).

Conclusion. Marked short‐term improvements in both groups at the end of treatment may have masked potential specific therapeutic effects of radon baths. However, after 6 months of follow‐up the effects were lasting only in patients of the radon arm. This suggests that this component of the rehabilitative intervention can induce beneficial long‐term effects.

Article content

Rheumatoid arthritis (RA) is an inflammatory rheumatic disease for which there is neither prophylaxis nor cure. Treatment regimens are complex and include, besides disease‐modulating and symptomatic drug therapy, specific exercises, physical and/or occupational therapy, surgery, rehabilitative treatment and orthopaedic aids, together with psychological care [1]. Most treatment concepts concern long‐term disease management.

RA rehabilitation aims particularly to inhibit the inflammatory processes, to relieve pain, to preserve the remaining functions and to develop or stabilize compensatory functions and suitable coping strategies. Spa therapy is used as an integral part of physical therapy for RA [2].

The inert natural radioactive gas radon has been used since the beginning of the century in the treatment of rheumatic diseases. The most famous European health resort where radon is used therapeutically is Badgastein in Austria. Evidence from empirical experience and from clinical observational studies [36] suggests that radon has analgesic [78], anti‐inflammatory [9] and immune‐stimulating [1011] effects. Patients' compliance with radon treatment is usually high. However, because of its intrinsic radioactivity the therapeutic use of radon is still controversial [e.g. 1213]. The dosages used in radon therapy are very small. Hofmann [14] compared target organ doses in medical X‐ray diagnosis with those of several radon treatment schemes used at Badgastein. For instance, the dose equivalents for an X‐ray examination of the lumbosacral spine are typically about 40 mSv and almost twice as much as this for computed tomography, whereas a typical series of thermal baths in Badgastein results in a cumulative exposure of 0.8 mSv to the skin, which receives the highest organ‐specific dose. Although there are differences in radiation quality, exposure time and the distribution of radiation, the organ doses are similar for the two exposure modes, and therefore the radiation hazards may also be supposed to be similar [14].

We undertook a study of the efficacy of baths with natural spring water containing radon and carbon dioxide in comparison with baths containing artificially produced carbon dioxide at the same concentration as in the spring water, but without radon. The evaluation of efficacy was based on the hypotheses that: (1) the complex treatment regimen in our study (including the baths) is effective in relieving pain, in increasing mobility and in decreasing functional and psychosocial limitations; and (2) with radon–carbon dioxide baths but not with carbon dioxide baths (despite the comprehensive co‐intervention) treatment effects are maintained for a clinically relevant period of time (long‐term effects).

Methods

This study was designed to evaluate, under controlled conditions, the efficacy of baths with natural spring water containing, on average, radon 1.3 kBq/l and carbon dioxide 1.6 g/l vs artificially produced carbon dioxide baths of the same carbon dioxide concentration. Patients with classical or definite RA who were participating in a multi‐modality in‐patient rehabilitation programme of 4 weeks' duration in Bad Brambach were invited to enter the trial. The springs at this health resort, situated in the south‐west of Saxony, Germany, contain both radon and carbon dioxide in therapeutic concentrations.

Patients and therapy

The setting for this study—an in‐patient rehabilitation programme offered in a health resort—represents a therapeutic option of high treatment intensity (in comparison with out‐patient physical therapy) for patients with mild to moderate disease activity but worsening overall health status. German health insurance companies agree to patients' participation, based on a medical certificate, if this treatment promises to stabilize the patients' living conditions with as little external support as possible.

Patients referred to the rehabilitation hospital were invited to participate if they met the inclusion and exclusion criteria. The inclusion criteria were based on the 1987 revised American College of Rheumatology (ACR) criteria for RA [15]. Patients receiving disease‐remitting drugs must have started this treatment at least 6 months before the start of the study. Participation was restricted to patients younger than 75 yr.

Exacerbation of the inflammatory process requiring an injection of cortisone led to the exclusion of a patient. Further exclusion criteria included concomitant musculoskeletal diseases possibly affecting measurement of the outcome measures, i.e. advanced osteoarthritis, endoprosthesis of the hip or knee, spinal disc syndrome or muscular dystrophy. Patients with central nervous system diseases such as epilepsy or with systemic inflammatory diseases such as collagen diseases and gout, patients with general contraindications to immersion in water and patients with advanced malignancies were also excluded.

To enrol 60 patients, 84 patients who fulfilled the inclusion/exclusion criteria were asked to participate. Among those who refused, three patients did not agree with the study procedures, three were to stay in Bad Brambach for only 3 weeks, and 18 objected to exclusion from radon therapy if they were allocated to the control treatment.

The recruitment period was 16 months and ended in October 1996.

The treatment regimen is described in Table 1. The only systematic difference in treatment between the two groups was the therapeutic bath used: either radon–carbon dioxide water or artificially enriched carbon dioxide water.

Participants in the study were not restricted with regard to additional offers (leisure time sport, relaxation therapy), in order to maximize the patients' compliance. As expected, demand was similar in the two groups (Table 1). All patients continued to receive their regular drug treatment without any change in type or dose.

 

 

 

 




     
     
     
     
     




 


   





       
       
       
       
       
       
       
       

 

 

 
TABLE 1.

Components of therapeutic intervention during in‐patient rehabilitation

  Absolute frequency in 4 weeks

Therapy
Planned
Provided: median (25%, 75%)
Radon–carbon dioxide bathsa  15 per patient,  15 (15, 15) 
  20 min each, subsequent 30‐min  Min. 14, max. 15 
  rest, between 10 and 12 a.m.   
Artificially generated  15 per patient,  15 (15, 15) 
   carbon dioxide bathsb  20 min each, subsequent 30‐min  Min. 14, max. 15 

rest, between 10 and 12 a.m.


  Absolute frequency in 4 weeks


    Provided: median (25%, 75%)

Further treatment procedures not evaluated
Planned
Radon group
Control group
RA‐specific exercises  10–12  10 (9, 11)  10 (10, 11) 
   and/or physiotherapy  30 min each     
Classical massage  8–10   8 (8, 9)  8 (8, 9) 
  25 min each     
Hydrogalvanic partial baths  6–8   7 (7, 8)  7 (7, 8) 
Occupational therapy  On request   7.5 (0, 9)  8 (5, 10) 
Leisure time sports  On request   1 (0, 11)  0 (0, 6) 
Relaxation therapy  On request   0 (0, 2)  0 (0, 0) 

a250 l, 35°C, on average 1.3 kBq/l, 1.6 g CO2/l.

b250 l, 35°C, 1.6 g CO2/l.

Randomization and blinding

After they had given informed consent, the patients were randomized into the treatment groups. The patients, therapists and investigator were unaware of group allocation.

A randomization list was generated by means of a random number table, and was used to produce one bar code card for each patient in the study. An automated device constructed for the purpose and activated by the patient's bar code card guaranteed the correct filling of the bath according to group assignment [16]. Because of relocation of the hospital during the course of the study, bath fillings had to be prepared manually for approximately two‐thirds of the patients. This was done by a single therapist, who was instructed not to interfere with the patients otherwise or to disclose any patient's group allocation to any other person.

End‐points

The outcome criteria of the study were focused on the patient‐centred core symptoms in RA, i.e. pain and functional limitations.

Pain intensity.

Pain intensity (PI) was measured on a visual analogue scale (VAS) from 0 mm = no pain to 100 mm = pain as bad as it can be; VAS are regarded as reliable, valid and sensitive to changes [1718].

Keitel functional test.

The Keitel functional test [19] was performed to evaluate limitations of functioning; its index (KFI) ranges from 0 to 100 points (100 = no functional limitations). Because of known diurnal variations, measurements were always taken at the same time of day. The validity and reliability of the KFI have been shown to be satisfactory [2021].

Arthritis Impact Measurement Scales.

A validated German version of the Arthritis Impact Measurement Scales (AIMS), the MOPO (measurement of patient outcome) [22], was used to describe the physical and psychosocial consequences of RA. This questionnaire has been shown to have good reliability, validity, sensitivity and practicability [22]. Scores range from 0 to 10. However, in contrast to the original AIMS, a score of 10 represents good health status for the overall score as well as the subscales measuring mobility, physical activity, dexterity, household activity, social activity and activities of daily living. Only the pain, depression and anxiety subscales follow the convention of associating good health status with low scores. These three scales had to be transformed in order to summarize the AIMS (MOPO) overall score.

In addition, to describe disease activity the erythrocyte sedimentation rate (ESR; Westergren method), the serum concentration of C‐reactive protein (CRP), pain frequency and morning stiffness (on rating scales) were recorded.

Short‐term and long‐term treatment effects were evaluated. Data were collected at admission, on completion of treatment and 3 and 6 months thereafter. Longitudinal changes were analysed within and between groups.

Analysis

The target sample size was 60 patients. This number yields a power of 90% to detect large differences in effect size between treatment groups according to Cohen [23] when one‐sided α is limited to 0.05. One‐sided hypothesis formulation seemed to be justified because there was considerable empirical evidence concerning the larger effects attainable with radon intervention [24]. Assuming moderate group differences and using 30 patients per group, the power of the trial would be 0.6.

All analyses were based on intention to treat as initially assigned. Data missing because of loss to follow‐up were handled by means of the last‐observation carry‐forward approach. No interim analyses were done.

Measures that were distributed fairly normally were expressed as mean and S.D. and as mean change with the 95% confidence interval (CI). Measures with a discrete distribution were expressed as counts (k/n cases) and as odds ratios for improvement.

For all outcome measures, effect sizes were calculated according to Cohen [23].

To determine whether the overall value of the outcomes was the same in both treatment groups, the simple mean of repeated measurements was calculated. With equal intervals between successive observations (as in this study), this is considered to be closely related to the area under the curve [25]. Thereafter, between‐group t‐tests were performed for confirmatory analysis. Summary measures like the above simple mean are recommended by Matthews et al. [25] for the analysis of serial measurements, provided they are meaningful (e.g. to quantify an ‘overall treatment difference’).

A sensitivity analysis was carried out to estimate the robustness of the results.

Multivariate analyses with the outcome criteria (see above) as dependent variables were used to test whether imbalance in prognostic factors between the two groups may have affected the results despite randomization. Predictive variables included were treatment group, sex, age, body mass index, socioeconomic status, disease duration, radiological damage and baseline scores describing disease activity such as pain, stiffness and laboratory measures.

For statistical analysis, SPSS 8.0 for windows (SPSS, Chicago, IL, USA) was used.

Course of the trial

The study was conducted according to a protocol that was approved by the ethics committee of the Ludwig Maximilians University, Munich, Germany. At the initial examination, sociodemographic and clinical characteristics and all baseline data were documented. After completion of treatment, all measures were taken again except for the AIMS (because of lack of comparability of the patients' situation at home with that in the hospital).

Follow‐ups were carried out 3 and 6 months after the completion of treatment by means of a postal questionnaire. It addressed all measures suitable for self‐assessment by the patients, including questions about modification of medication. Furthermore, patients were asked to report the actual ESR determined by their general practitioners. If necessary, patients were reminded by telephone to send back the questionnaire.

The patients' level of adherence to the treatment protocol was high (Table 1).

Results

Sample characteristics

Table 2 summarizes the characteristics of the treatment groups at baseline. Almost three‐quarters of the study participants were women. For approximately two‐thirds of the patients, X‐rays revealed marked erosions of joints, cysts or lesions, or subluxation [26a26b]. Eighty per cent reported daily or continuous pain. Almost all patients suffered from morning stiffness lasting at least 1 h. Every second participant was retired or had retired early. Only 12 patients (20%) were actively employed at the beginning of the study. The age of the study participants ranged from 21 to 75 yr, the mean age at onset of RA was 48 yr, and the duration of disease ranged from 1 to 46 yr (median 6 yr). The mean body mass index was 25.7 kg/m2 (S.D. = 3.7). The drug prescription profile varied markedly, and included disease‐modifying anti‐rheumatic drugs, non‐steroidal anti‐inflammatory drugs (NSAIDs), steroids and combinations (Table 2). Only 11 patients were not on continuous medication. The patients' basic medication was kept unchanged during the in‐patient rehabilitation period. An attempt was made to maintain this medication during the follow‐up period by informing the patients' general practitioners about their participation in the study. The short‐term use of drugs on demand (exclusively NSAIDs) was not recorded.

Table 3 provides a descriptive summary of the main outcome measures at baseline and during the course of the study, according to group allocation. In the multiple regression models, the two treatment groups did not differ significantly at baseline (pain intensity, P = 0.55; KFI, P = 0.89; AIMS, P = 0.32).

 

 

 





       
       
       
       
       
       
       
       
       
       
       
       
       
       
       
       

 

 

 

 
TABLE 2.

Patient characteristics of the treatment groups at baseline

Feature
Radon group (n = 30)
Control group (n = 30)
Total
Sex (F/M)a  22/8  24/6  46/14 
Age (yr)b  58.1 (9.9)  58.6 (11.9)  58.3 (10.9) 
Body mass index (kg/m2)b  25.7 (3.3)  25.7 (4.0)  25.7 (3.7) 
Duration of disease (yr)b  11.1 (12.2)   9.9 (9.8)  10.5 (11.0) 
Occupational statusa       
   Working/sick leave/retired   8/7/15   4/5/21  12/12/36 
Radiograph classificationa,c   4/21/5   5/21/4   9/42/9 
Medicationa       
   DMARDs   4   2   6 
   Steroids   1   1   2 
   NSAIDs   6   6  12 
   DMARDs + steroids   1   2   3 
   DMARDs + NSAIDs   8   8  16 
   Steroids + NSAIDs   1   3   4 
   DMARDs + steroids + NSAIDs   2   4   6 
   None   7   4  11 

aNumber of patients.

bMean (S.D.).

cDorso‐palmar/plantar view of both hands and feet: no or insignificant erosion of joints; only slight decalcification/clear signs of erosion of joints; cysts, osseous lesions subluxation/atrophy, destruction of joints.

 

 

 







           
           
           
           
           
           
           
           
           
           
           
           
           
           
           
           
           
           
           
           

 

 

 

 

 
TABLE 3.

Baseline measures [mean (S.D.) or absolute frequency] and mean changes with 95% confidence interval or improvement rates (compared with baseline measures) during the course of the study; n = 30 in each group unless indicated otherwise

Measure

Baseline
End of rehabilitation
3‐month follow‐up
6‐month follow‐up
Pain intensity  Radon  44.8 (25.0)  − 14.9 (− 24.6 to −5.1)  − 6.0 (− 16.5 to 4.5)  − 6.5 (− 17.8 to 4.8)b 
  Control  38.6 (20.2)  − 11.8 (− 19.2 to −4.4)  4.8 (− 5.0 to 14.7)b  9.7 (2.0 to 17.4)a 
Keitel functional index  Radon  70.5 (18.0)  5.2 (2.2 to 7.7)  –  – 
  Control  71.1 (13.2)  2.3 (−0.4 to 5.1)  –  – 
AIMS (MOPO) score  Radon  6.27 (1.33)  –  0.41 (0.06 to 0.75)  0.41 (0.06 to 0.74) 
  Control  6.60 (1.10)  –  − 0.06 (− 0.34 to 0.23)a  − 0.18 (− 0.56 to 0.20)a 
ESR (1st h, mm)  Radon  18.6 (15.8)  2.1 (−2.9 to 7.0)  5.2 (−0.7 to 11.0)a  3.3 (− 3.4 to 9.9)c 
  Control  22.0 (15.6)  − 3.1 (− 7.9 to 1.7)  − 0.3 (− 7.2 to 6.5)d  1.2 (− 5.2 to 7.7)d 
C‐reactive protein (g/ml)  Radon  12.2 (14.4)  1.2 (− 2.0 to 4.4)  –  – 
  Control  18.4 (17.0)  − 4.9 (− 10.1 to 0.3)  –  – 
Pain frequency           
   No pain/sporadic/  Radon  1/2/13/14       
   daily/continuous  Control  2/3/18/7       
   improvement of  Radon    47% (14/30)  37% (11/30)  57% (16/28) 
   ≥ 1 category  Control    37% (11/30)  28% (8/29)  24% (7/29) 
Morning stiffness           
   None/≤1h/  Radon  1/15/8/6       
   ≤2 h/until noon  Control  4/16/7/3       
   Improvement of  Radon    33% (10/30)  40% (12/30)  28% (8/29) 
   ≥1 category  Control    27% (8/30)  14% (4/29)  24% (7/29) 

an = 29.

bn = 28.

cn = 27.

dn = 26.

Losses to follow‐up

For one patient in the control group, no follow‐up data were available for unknown reasons. After rehabilitation, her outcome measures showed only small restrictions in comparison with healthy persons. Three other patients returned their follow‐up questionnaire incomplete (one subject from the control group after 3 months, and two subjects from the radon group after 6 months). The AIMS score was available for 59 of the 60 patients at both follow‐ups.

Treatment effects

Both groups showed marked treatment effects at discharge (Table 3). Pain intensity was reduced by 14.9% (95% CI, 5.1 to 24.6%) in the radon group and by 11.8% (95% CI, 4.4 to 19.2%) in the control group. There was virtually no difference between groups (Table 4). The KFI improved more in the radon group than in the control group (Table 3), but the difference (ΔKFI = 2.6, 95% CI, −0.5 to 5.8) did not reach statistical significance (Pdescriptive = 0.09).

Despite a decrease in treatment effects during the follow‐up period, the radon group had better values 3 and 6 months after the end of rehabilitation compared with baseline, whereas the control group had already declined to values below the baseline level after 3 months (Table 3, Fig. 1). Lasting effects of small and moderate size, respectively, according to Cohen [23] were observed only in patients of the radon group (Fig. 2). Group differences increased continuously (Table 4). Whereas the AIMS score indicated superiority of the radon treatment at both 3‐ and 6‐month follow‐ups, this was true for pain relief only at 6 months.

For pain intensity, the overall treatment effect was 9.5% (95% CI, 2.1 to 16.9%) in the radon group and no effect was found (−0.7%; 95% CI, −6.1 to 4.8%) in the control group. A similar situation was observed for the AIMS score, which remained improved (0.40; 95% CI, 0.14 to 0.67) in the radon group compared with the control group (−0.11; 95% CI, −0.36 to 0.13).

The confirmatory analysis of the overall treatment differences (Δpain intensity = 10.1 [95% CI, 0.9 to 19.3; ΔAIMS = 0.52; 95% CI 0.15 to 0.88) revealed significant superiority of the radon bath series over the sham treatment for both outcome criteria (Table 4). No side‐effects were observed in either group.

 

 

FIG. 1.

Longitudinal mean changes in pain intensity and 95% confidence intervals for both treatment groups.

 
Longitudinal mean changes in pain intensity and 95% confidence intervals for both treatment groups.
 

 

 

 

FIG. 2.

Treatment effects of pain and functional capacity/disability. Effect sizes according to Cohen [23]. The KFI was assessed at baseline and after completion of treatment by the investigator; AIMS score was measured at baseline and at follow‐ups by self‐assessment.

 
Treatment effects of pain and functional capacity/disability. Effect sizes according to Cohen [23]. The KFI was assessed at baseline and after completion of treatment by the investigator; AIMS score was measured at baseline and at follow‐ups by self‐assessment.
 

 

 

 

 






         
         
         
         
         
         
         
         
         
         
         
       

 

 

 
TABLE 4.

Between‐group differences in longitudinal changes in outcome criteria

Measure
End of treatment
3‐month follow‐up
6‐month follow‐up
Overall mean
Pain intensity, Δma  − 3.0  − 10.5  − 16.9  − 10.1, P = 0.04 
  (− 13.0 to 7.0)  (− 21.8 to 0.9)  (− 27.6 to −6.2)  (− 19.3 to −0.9) 
Keitel functional index, Δma  2.6      2.6, P = 0.09 
  (− 0.5 to 5.8)      (− 0.5 to 5.8) 
AIMS score, Δma    0.46  0.57  0.52, P = 0.01 
    (0.10 to 0.82)  (0.16 to 0.98)  (0.15 to 0.88) 
ESR, Δma  5.1  5.5  2.1   
  (− 1.6 to 11.9)  (− 3.3 to 14.3)  (− 7.0 to 11.1)   
Pain frequency, ORb  1.5  1.5  4.2   
  (0.5 to 4.2)  (0.5 to 4.6)  (1.3 to 13.0)   
Morning stiffness, ORb  1.4  4.2  1.2   
  (0.5 to 4.2)  (1.2 to 15.0)  (0.4 to 3.9) 

aMean group difference (95% confidence interval) (treatment minus reference group).

bOdds ratio (95% confidence limits) of improvement rate (treatment vs reference group).

Sensitivity analysis

In 27 patients (11 of the radon group and 16 of the control group), drug consumption changed during the follow‐up period. Therefore, a sensitivity analysis was carried out to estimate the influence of changes in medication during the follow‐up period on the study results. A two‐way analysis of variance was done using group allocation and changes in medication as independent factors (55 of 60 patients with complete information included). For both outcome criteria, neither a significant influence of changes in medication nor a significant interaction between the two factors was found at the 6‐month follow‐up. On the other hand, the differences between the treatment groups remained significant (Table 5). These results validated those of the confirmatory analysis.

 

 

 







           
           
           
           
           
           
           
           
           
           
           
           
           
           
           
           
           
           
 
TABLE 5.

Effect of changes in drug consumption during the follow‐up period on the results of the trial (two‐way analysis of variance; SS/MS: sum/mean of squares; DF: degrees of freedom)

Source of variation
SS
DF
MS
F
Significance
Pain intensity after 6 months (n = 53)           
Main effects           
   Treatment group  4467.06   1  4467.06  7.16  0.010 
   Change in medication    45.50   1  45.50  0.07  0.788 
Interaction           
   Group × medication   234.61   1  234.61  0.38  0.543 
Residuals           
   Within observations  30571.44  49  623.91     
Total  35231.02  52  677.52     
AIMS score after 6 months (n = 55)           
Main effects           
   Treatment group      6.22   1    6.22  6.68  0.013 
   Change in medication      0.02   1    0.02  0.02  0.894 
Interaction           
   Group × medication      1.35   1    1.35  1.45  0.234 
Residuals           
   Within observations     47.48  51    0.93     
Total     55.00  54    1.02     

Discussion

Perceived pain relief and increased joint mobility led to the common acceptance of radon treatment in musculoskeletal diseases in Central Europe, although the evidence for its efficacy was only empirical. Since 1990, however, controlled randomized trials using up‐to‐date methods have been performed. Positive effects have been reported for tendomyopathy, osteoarthritis and ankylosing spondylitis [82729]. The present trial confirmed these effects for RA.

Basic research in the last two decades has revealed some of the potential therapeutic mechanisms of radon in the human organism. It has been suggested that it is the skin that is primarily responsible for the incorporation of radon [9]. Within its morphological structures, radiation may activate local processes that are similar to the effects of topical steroids [30]. In animal experiments it has been demonstrated that the accumulation of incorporated radon, enhanced by its lipophilia, stimulates the secretion of corticoids from the adrenal cortex [31]. The normalization of killer cell activity, which is reduced in rheumatic diseases, has been found under radon therapy [32]. At the cellular level, the forced generation of free radicals has been observed along the α‐traces, resulting in increased activity of scavenger enzymes such as superoxide dismutase. An increase in these enzymes may contribute to the improvement of symptoms of the disease, e.g. by inhibiting rheumatic inflammation [33]. The DNA repair capacity of the cell nucleus increases with small radiation doses, suggesting that disease‐related DNA damage may be repaired more quickly and effectively [1334]. Both the response of the organism to the generation of free radicals and the increase in the DNA repair capacity represent adaptive, health‐supporting reactions which may also offer increased protection against other, non‐radiation induced, health‐threatening influences [3536].

In this study, the radon spa therapy was part of a complex rehabilitation programme in an in‐patient rehabilitation hospital. Random allocation of the patients seemed to be successful, since it resulted in groups that were comparable in their sociodemographic and disease features as well as in their initial status with respect to the outcome criteria. Because the specific spa treatment was the only systematic difference in treatment between the groups, it can be assumed to have been the cause for the differences observed.

The rehabilitation regimen was apparently effective with regard to pain relief and the improvement of functional capacity, but no relevant difference was found after completion of treatment. This result was not surprising because in both groups the rehabilitation programme focused on the specific problems of RA patients. The resulting marked improvements in both groups at the end of the treatment may have masked specific therapeutic effects of radon baths. However, between‐group differences increased during the follow‐up period in favour of the radon group, and long‐term effects were observed only in the radon group, not least the significant group differences in the overall treatment effect. These findings agree with those of other trials [82729] and confirm the suggestion that radon baths induce beneficial long‐term effects in rheumatic diseases, although the underlying mechanisms are not yet fully understood.

Regarding the outcomes in RA clinical trials, the last decade has been characterized by efforts to achieve better standardization of effect measures [3744]. Recommendations have been published by the ACR and by the participants in the OMERACT conference(s) with the aim of improving the comparability of study results. Both the ACR [40] and the WHO/ILAR [41] core set of end‐points included pain, patients' and physicians' global assessments and physical disability, as well as joint indices and acute‐phase reactants.

To deal with the multiplicity of end‐points that have been used in previous RA studies, it was recommended [47] either that a few high‐quality outcome measures fulfilling the known validity criteria should be selected, or that various measures should be pooled into a single composite index. Although pooling single measures is considered to be a valid way [45] of increasing sensitivity to change and is favoured by various authors [e.g. 4648], only a few RA studies [e.g. 4649] have used this approach.

In our study we limited the number of end‐points to three validated outcome measures reflecting relevant patient‐centred dimensions of chronic diseases: impairment and disability/activity [50]. Because the patients came from all parts of Germany and it would therefore have been impossible for the clinical investigator (L.R.) to carry out follow‐up examinations, we chose outcomes that could be obtained by self‐assessment by the patients. Self‐reports of pain, functional capacity, activities of daily living and health‐related quality of life obtained by means of validated scales and questionnaires such as the AIMS [51], the Health Assessment Questionnaire [52], the Functional Questionnaire Hanover (FFbH) [5354] and others are appropriate for the evaluation of rehabilitation programmes because they indicate the somatic, function‐related and psychosocial effects of interventions. Regarding the follow‐ups in our study, the AIMS score was more sensitive to differences in effect than the visual analogue scale for pain.

Because the patients' typical living conditions could not be compared with their situation in the rehabilitation hospital (especially with respect to their psychosocial state and personal interactions), we decided not to assess the AIMS at the end of rehabilitation. Instead, the KFI, performed by the clinical investigator, was used to evaluate functional deficits. In contrast to the AIMS score, the KFI measures impairment rather than disability, yet correlates well with the AIMS physical function score [55]. This was shown in our sample; the observed correlation coefficients were r = 0.80 (Pearson) and r = 0.76 (Spearman).

In accordance with other studies in typical in‐patient rehabilitation settings [5456], effect sizes after completion of treatment were moderate.

Considering that most patients had long‐standing disease, that the duration of treatment was relatively short, and that the treatment had good tolerability, no side‐effects and long‐term benefits, this complex rehabilitation programme, including a series of radon baths, may be an interesting option for RA patients.

 

Correspondence to: A. Franke, Balneology and Rehabilitation Sciences Research Institute (FBK), Lindenstrasse 5, 08645 Bad Elster, Germany.

 

References

1

Scott DL, Shipley M, Dawson A, Edwards S, Symmons DPM, Woolf AD. The clinical management of RA and OA: strategies for improving clinical effectiveness. 

Br J Rheumatol
1998
;
37
:
546
–54.

 

2

Verhagen AP, de Vet HCW, de Bie RA, Kessels AGH, Boers M, Knipschild PG. Taking baths: the efficacy of balneotherapy in patients with arthritis. A systematic review. 

J Rheumatol
1997
;
24
:
1964
–71.

 

3

Callies R. Radonbädertherapie bei entzündlichen rheumatischen Erkrankungen. In: Jordan H, ed. Abhandlungen der Sächsischen Akademie der Wissenschaften zu Leipzig, Mathematisch‐Naturwissenschaftliche Klasse, Bd. 57, Heft 1. Berlin: Akademie, 

1989
;
133
–4.

 

4

Vulpe B, Zielke A, Häntzschel H, Tautenhahn B. Klinische Langzeitbeobachtungen nach Kur‐orttherapie auf Radonbasis bei Rheumatoid Arthritis (RA) und Spondylitis ankylosans (SPA). In: Jordan H, ed. Abhandlungen der Sächsischen Akademie der Wissenschaften zu Leipzig, Mathematisch‐Naturwissenschaftliche Klasse, Bd. 57, Heft 1. Berlin: Akademie, 

1989
;
139
–42.

 

5

Zielke A, Vulpe B. Was leistet eine Radon‐CO2‐Bäder‐Monotherapie bei Rheumatoid Arthritis und Spondylitis ankylosans? In: Jordan H, ed. Abhandlungen der Sächsischen Akademie der Wissenschaften zu Leipzig, Mathematisch‐Naturwissenschaftliche Klasse, Bd. 57, Heft 1. Berlin: Akademie, 

1989
;
135
–8.

 

6

Griessmayer H, Tripathi R, Falkenbach A. Development of RA during a radon thermal cure treatment. 

Br J Rheumatol
1997
;
36(Suppl.1)
:
187
.

 

7

Pratzel HG, Schnizer W. Handbuch der Medizinischen Bäder: Indikationen‐ Anwendungen‐ Wirkungen. Heidelberg: Karl F. Haug, 

1992
.

 

8

Bernatzky G, Graf AH, Sarai A et al. Schmerzhemmende Wirkung einer Kurbehandlung bei Patienten mit Spondylarthritis Ankylopoetica. In: Pratzel HG, Deetjen P, eds. 

Radon in der Kurortmedizin
. Geretsried: ISMH, 
1997
:
144
–57.

 

9

Jöckel H. Praktische Erfahrungen mit der Radontherapie. In: Pratzel HG, Deetjen P, eds. 

Radon in der Kurortmedizin
. Geretsried: ISMH, 
1997
:
84
–91.

 

10

Peter A, Vulpe B. Reaktionsdynamik von Entzündungsproteinen und T‐Lymphozyten unter einer Radonkur. 

Z Physiother
1989
;
41
:
211
–4.

 

11

Soto J. Effects of radon on the immune system. In: Pratzel HG, Deetjen P, eds. 

Radon in der Kurortmedizin
. Geretsried: ISMH, 
1997
:
103
–13.

 

12

Seichert N. Zur Problematik der Radon‐Balneotherapie. 

Phys Rehab Kur Med
1992
;
2
:
157
–60.

 

13

Deetjen P. Radon‐Balneotherapie—neue Aspekte. 

Phys Rehab Kur Med
 ;
2
:
100
–3.

 

14

Hofmann W. Radon doses compared to X‐ray doses. In: Pratzel HG, Deetjen P, eds. 

Radon in der Kurortmedizin
. Geretsried: ISMH, 
1997
:
57
–67.

 

15

Arnett FC, Edworthy SM, Bloch DA et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. 

Arthritis Rheum
1988
;
31
:
315
–23.

 

16

Pratzel HG. Die Wirksamkeit von Radonbädern ist bewiesen. 

Heilbad und Kurort
1992
;
44
:
343
–7.

 

17

Price DB, McGrawth PH, Rafii A, Buckingham B. The validation of visual analogue scales as ratio scales measures for chronic and experimental pain: 

Pain
1983
;
17
:
45
–56.

 

18

Jensen MP, Karoly P, Braver S. The measurement of clinical pain intensity: a comparison of six methods. 

Pain
1986
;
27
:
117
–26.

 

19

Keitel W, Hoffmann H, Weber G, Krieger U. Ermittlung der prozentualen Funktionsverminderung der Gelenke durch einen Bewegungsfunktionstest in der Rheumatologie. 

Dtsch Gesundheitswes
1971
;
26
:
1901
–3.

 

20

Keitel W. Das Messen in der Rheumatologie—Probleme der Standardisierung und Verlässlichkeit. 

Akt Rheumatol
1988
;
13
:
43
–6.

 

21

Kohlmann T, Raspe H. Die patientennahe Diagnostik von Funktionseinschränkungen im Alltag. 

Psychomed
1994
;
6
:
21
–7.

 

22

Jäckel W, Cziske R, Schochat T, Jacobi E. Messung der körperlichen Beeinträchtigung und der psychologischen Konsequenzen (patient outcome) bei rheumatoider Arthritis. 

Akt Rheumatol
1985
;
10
:
43
–52.

 

23

Cohen J. 

Statistical power analysis for behavioral sciences
. New York: Academic Press, 
1977
.

 

24

Pratzel HG, Deetjen P, eds. 

Radon in der Kurortmedizin
. Geretsried: ISMH, 
1997
.

 

25

Matthews JNS, Altman DG, Campbell MJ, Royston P. Analysis of serial measurements in medical research. 

Br Med J
1990
;
300
:
230
–5.

 

26a.

Otto W, Seidel K, Wessel G. 

Rheumatische Erkrankungen, Vol. 2
. Berlin: Verlag Volk und Gesundheit, 
1977
;
S.44
.

 

26b.

Treutler H. 

Röntgenologische Diagnostik
. In: Häntzschel H, Otto W, Nassonova V, eds. Rheumatoid‐Arthritis: eine systemische Erkrankung. Leipzig: Johann Ambrosius Barth, 
1992
;
208
–16.

 

27

Pratzel HG, Legler B, Aurand K, Baumann K, Franke T. Wirksamkeitsnachweis von Radonbädern im Rahmen einer kurortmedizinischen Behandlung des zervikalen Schmerzsyndroms. 

Phys Rehab Kur Med
1993
;
3
:
76
–82.

 

28

Lind‐Albrecht G. 

Einfluss der Radonstollentherapie auf Schmerzen und Verlauf bei Spondylitis ankylosans (M. Bechterew)—eine randomisierte prospektive Studie
. Mainz: Johannes Gutenberg University, 
1994
.

 

29

Heisig S. 

Zur analgetischen Wirksamkeit von Radonbädern bei Patienten mit degenerativen Erkrankungen von Wirbelsäule und Gelenken
. München: Ludwig Maximilians University, 
1997
.

 

30

Pratzel HG, Artmann C. Das Immunorgan Haut im Rahmen der Balneologie. 

Z Phys Med Baln Med Klimatol
1990
;
19
:
325
–31.

 

31

Pfaller W. Subzelluläre Veränderungen der Nebennierenrinde nach Inhalation von Radon. Z Angew Bäder‐u. 

Klimaheilkd
1979
;
26
:
384
–90.

 

32

Gastl G, Egg D, Herold M et al. Influence of Finnish bath and radon balneotherapy on the frequency and activity of natural killer cells in peripheral blood. 

Z Phys Med Baln Med Klimatol
1988
;
17(Sonderheft 1)
:
47
–53.

 

33

Frick W, Pfaller W. Die Auswirkung niedriger α‐Strahlendosis auf epitheliale Zellkulturen. 

Z Phys Med Baln Med Klimatol
1988
;
17(Sonderheft 1)
:
23
–31.

 

34

Feinendegen LE, Loken MK, Booz J, Bond VP. Reasons why beneficial effects from irradiation shown in single cells may be advantageous to complex systems. In: Pratzel HG, Deetjen P, eds. 

Radon in der Kurortmedizin
. Geretsried: ISMH, 
1997
:
40
–56.

 

35

Schüttmann, W. Radonbalneologie im Spannungsfeld der Strahlenschutzpolitik. In: Pratzel HG, Deetjen P, eds. 

Radon in der Kurortmedizin
. Geretsried: ISMH, 
1997
;
9
–32.

 

36

Burkart W. Die adaptive Reaktion menschlicher Lymphozyten auf kleine Strahlendosen. 

Z Phys Med Baln Med Klimatol
1990
:
19(Suppl.2)
:
19
–27.

 

37

Anderson JJ, Felson DT, Meenan RF, Williams J. Which traditional measures should be used in rheumatoid arthritis clinical trials? 

Arthritis Rheum
1989
;
32
:
1093
–9.

 

38

Felson DT, Anderson JJ, Meenan RF. Time for changes in the design, analysis, and reporting of rheumatoid arthritis clinical trials. 

Arthritis Rheum
1990
;
33
:
140
–9.

 

39

Van der Heijde DMFM, van Riel PLCM, van't Hof MA, van de Putte LBA. Comment on the article by Felson et al

Arthritis Rheum
1991
;
34
:
124
–5.

 

40

Felson DT, Andersson JJ, Boers M et al. The American College of Rheumatology preliminary core set of disease activity measures for rheumatoid arthritis clinical trials. 

Arthritis Rheum
1993
;
36
:
729
–40.

 

41

Boers M, Tugwell P, Felson DT et al. WHO and International League of Associations for Rheumatology core endpoints for symptom modifying antirheumatic drugs in RA clinical trials. 

J Rheumatol
1994
41(Suppl.)
:
86
–9.

 

42

Buchbinder R, Bombardier C, Yeung M, Tugwell P. Which outcome measures should be used in rheumatoid arthritis clinical trials? Clinical and quality‐of‐life measures' responsiveness to treatment in a randomised controlled trial. 

Arthritis Rheum
1995
;
38
:
1568
–80.

 

43

Pillemer SR, Fowler SE, Tilley BC et al. (MIRA Trial Group). Meaningful improvement criteria sets in a rheumatoid arthritis clinical trial. 

Arthritis Rheum
1997
40
:
419
–25.

 

44

Boers M, Brooks P, Strand CV. Tugwell P. The OMERACT filter for outcome measures in rheumatology. 

J Rheumatol
1998
;
25
:
198
–9.

 

45

Smythe HA, Helewa A, Goldmith CH. ‘Independent assessor’ and ‘pooled index’ as technique for measuring treatment effects in rheumatoid arthritis. 

J Rheumatol
1977
;
4
:
144
–52.

 

46

Van der Heijde DMFM, van't Hof MA, van Riel PLCM, van Leeuwen MA, van Rijswijk MH, van de Putte LBA. Judging disease activity in clinical practice in rheumatoid arthritis: first step in the development of a ‘disease activity score’. 

Ann Rheum Dis
1990
;
49
:
916
–20.

 

47

Roberts RS. Pooled outcome measures in arthritis—the pros and cons. 

J Rheumatol
1993
:
20
:
566
–7.

 

48

Boers M, Tugwell P. The validity of pooled outcome measures (indices) in RA clinical trials. 

J Rheumatol
1993
;
20
:
568
–74.

 

49

Boers M, Verhoeven AC, Markusse HM et al. Randomised comparison of combined step‐down prednisolone, methotrexate and sulphasalazine with sulphasalazine alone in early rheumatoid arthritis. 

Lancet
1997
;
350
:
309
–18.

 

50

WHO. 

International classification of impairments, disabilities and handicaps
. (a) ICIDH‐1 1980, (b) ICIDH‐2 (beta‐1 version). Geneva: World Health Organization, 
1997
.

 

51

Meenan RF,Gertman PM, Mason JM. Measurement of patient outcome in arthritis. 

Arthritis Rheum
1980
;
23
:
146
–52.

 

52

Fries JF, Spitz P, Kraines RG, Holman HR. Measurement of patient outcome in arthritis. 

Arthritis Rheum
1980
23
:
137
–45.

 

53

Raspe HH, Hagedorn U, Kohlmann T, Mattusek S. Der Funktionsfragebogen Hannover (FFbH): Ein Instrument zur Funktionsdiagnostik bei polyartikulären Gelenkerkrankungen. In: Siegrist J, ed. Wohnortnahe Betreuung Rheumakranker—Ergebnisse sozialwissenschaftlicher Evaluation eines Modellversuchs. Stuttgart: Schattauer, 

1990
:
164
–82.

 

54

Kohlmann T, Raspe H. Der Funktionsfragebogen Hannover zur alltagsnahen Diagnostik der Funktionsbeeinträchtigungen durch Rückenschmerzen (FFbH‐R). 

Rehabilitation
1996
;
35(Suppl.)
:I–VIII.

 

55

Mason JH, Anderson JJ, Meenan RF. A model of health status for rheumatoid arthritis—a factor analysis of the Arthritis Impact Measurement Scales. 

Arthritis Rheum
1988
;
31
:
714
–20.

 

56

Gerdes N, Jäckel WH. Der IRES‐Fragebogen für Klinik und Forschung. 

Rehabilitation
1995
;
34(Suppl)
XIII
–XXIV.
Download the file : 390894.pdf (128.1 KB) Find it online