Action mechanisms of complex spa therapy (swimming training in a hot spring pool, inhalation with iodine salt solution, and fango therapy) were studied in relation to patient age, clinical asthma type, and airway inflammation. Actions of spa therapy were observed by two clinical effects : direct and indirect effects. Improvement of subjective symptoms, ventilatory function, and bronchial hyperresponsiveness was observed as direct effects of spa therapy, and improvement of suppressed function of adrenocortical glands as indirect effects of the therapy. The clinical effects of spa therapy were higher in patients over the age of 40. Regarding clinical asthma type, the effects were larger in patients with type Ib and type II asthma than in those with type Ia. The efficacy of spa therapy was closely related with airway inflammation in patients with type Ib and type II asthma.複合温泉療法(温泉プール水泳訓練,ヨードゾル吸入,鉱泥湿布療法)の作用機序が,年齢,臨床病型,気道炎症反応との関連のもとに検討された｡温泉療法の作用機序は,2種類の臨床効果,すなわち,直接効果と間接効果により観察された｡自,他覚症状の改善,換気機能の改善,そして,気道過敏性の改善などが,温泉療法の直接効果として,また,副腎皮質機能の改善が間接効果とし
て観察された｡温泉療法の臨床効果は,40才以上の症例においてより有効であり,また,臨床病型別では､Ia型に比べ,Ib型およびⅡ型においてより有効であった｡Ib型やⅡ型の気管支喘息では,温泉療法の作用機序と気道炎症反応との間に密接な関連が認められた

Ashida, Kozo

Harada, Hideo

Hosaki, Yasuhiro

Mifune, Takashi

Mitsunobu, Fumihiro

Nawa, Yuichiro

Ochi, Koji

Takeuchi, Kazuaki

Tanizaki, Yoshiro

Tsugeno, Hirofumi

Yokota, Satoshi

Okayama University Digital Information Repository

気管支喘息に対する複合温泉療法の作用機序 1.温泉療法の評価方法との関連

Okayama University Scientific Achievement Repository

Action mechanisms of spa therapyAction mechanisms of complex spa therapy onbronchial asthma. 1. Relationship to evaluation ofspa therapyFumihiro Mitsunobu, Takashi Mifune, Yasuhiro Hosaki,Kouzou Ashida, Satoshi Yokota, Hirofumi Tsugeno,Kazuaki Takeuchi, Yuichiro Nawa, Yoshiro Tanizaki, KojiOchi I ) and Hideo Harada I )Division of Medicine, Misasa Medical Branch, 1) Depart-ment of Laboratory Medicine, Okayama UniversityMedical SchoolAbstract: Action mechanisms of complex spa therapy (swimming training in a hotspring pool, inhalation with iodine salt solution, and fango therapy) were studied inrelation to patient age, clinical asthma type, and airway inflammation. Actions of spatherapy were observed by two clinical effects: direct and indirect effects. Improvementof subjective symptoms, ventilatory function, and bronchial hyperresponsiveness wasobserved as direct effects of spa therapy, and improvement of suppressed function ofadrenocortical glands as indirect effects of the therapy. The clinical effects of spatherapy were higher in patients over the age of 40. Regarding clinical asthma type, theeffects were larger in patients with type Ib and type II asthma than in those with typela. The efficacy of spa therapy was closely related with airway inflammation inpatients with type Ib and type II asthma.Key words: complex spa therapy, clinical asthma type, ventilatory function, bronchialhyperresponsiveness, adrenocortical glands85IntroductionBronchial asthma is characterized by wheez-ing and transient dyspnea. The new conceptthat airway inflammation plays a major rolein bronchial asthmal-3), even in mild asth-rna" 5), has been widely accepted in recentyears. Cells such as lymphocytes, neutrophils,eosinophils and basophils that are observed inbronchoalveolar lavage (BAL) fluid have beenidentified as inflammatory cells 6-10) •In view of medication, asthma can becontrolled with the usual antiasthma drugs.However, despite newly developed drugs forthe treatment of asthma, there are somepatients whose asthma attacks cannot be86 Action mechanisms of spa therapyEfficacy 0 10 20 30 40 50 60 70 80Patient age. yearsFig. 1. Clinical effects of spa therapy onbronchial asthma and patient ageFig. 2. Clinical effects of spa therapy onbronchial asthma and age at onsetof the disease• ~.p.•• •- -• •II.z : :.~!:.• ....IZ_ __: "·11• I·~··..s.1•• • _.11• I-:. •Age at onset. yearsEfficacy 0 10 20 30 40 50 60 70MarKed •• • •• • ~Z~!eff: 10. •I=. '~Moderate _ .. ..:.U _ .: _.,I -Slight • ~~.II. S .:- •No-~ • •ModerateSlightNoMarkedtraining in a hot spring pool, inhalation ofiodine salt solution and fango therapy2l).Swimming training is carried out in a hotspring pool for 30 min a day and 5 times aweek. Inhalation of 1.0 mP of iodine saltsolution (kP 135mg/.e, NaCI 14.664 g/.e) isperformed twice a day. Clinical symptomsand ventilatory function are improved byinhalation of iodine salt solution for 2weeks22). In fango therapy, fango taken fromNingyo pass and heated to 70-80°C is packedwith cloth (40-43°C). The back of patientsThe efficacy of spa therapy correlates withpatient age. Spa therapy is more effective inpatients over the age of 41 compared to thoseunder the age of 4019), as shown in Fig. 1.Regarding age at onset of the disease, spatherapy is less effective in patients whose ageat onset is under 30 years (Fig. 2). Ourstudies on clinical effects of spa therapy on30 elderly patients (over the age of 65) withasthma have shown that spa efficacy isobserved in all patients with type Ia - 2, Iband IT. Of the 21 patients with type Ia - 1 .however, 17 (81.0%) showed marked ormoderate efficacy of spa therapy, suggestingthat spa therapy is more effective in patientswith type Ia - 2, Ib and IT than in thosewith type Ia - 1 (simple bronchoconstriction)In the elderli1(I).Comples spa therapyComplex spa therapy comprises swimmingSpa effects and patient agecontrolled without resorting to gluco-corticoids. In these steroid-dependent intracta-ble asthma (SDIA) subjects, efforts to reducethe dose of glucocorticoids have been made toavoid the adverse side effects of the drugs,but most of these efforts have beenunsuccrssful except patients whose attackscan be controlled with a large dose of inhaledglucocorticoid (Beclomethason).Our previous studies have shown that spatherapy, i.e., swimming training in a hotspring pool, is effective in patients withbronchial asthma: improvement in clinicalsymptoms and findings U- 15), in ventilatoryfunctionl~17), and in adrenocortical functiontogether with a reduced necessity forglucocorticoids is usually observed after spatherapylS) .Action mechanisms of spa therapy 877 1 - _:;:;:;:;:;:;:;:;:;'.Fig. 3. Clinical efficacy; marked (.),moderate (fa ), slight ( ~ ) andno efficacy ( 0 ), of complex spatherapy on patients with SDIA inrelation to age.FEV LO(+~~}~FVCType nFEV 1.0 "20(+29.3~ FEV,»PEF'R ito. PEFRMMFFVCMMF(+34.1%)Fig. 4. %Improvement of ventilatoryfunction in each clinical asthmaAction of spa therapytherapy (1990-).FVCtype after spa therapy. The valueof parameter showing maximum %improvement is presented as 100%.Type IaAction of spa therapy is clinically observedby direct effects for airways and indirecteffects for the other organs except a1rways.1. Direct effects of spa therapy1) Ventilatory functionIn addition to improvement of clinicalsymptoms, ventilatory function is alsoimproved by spa therapy26). In type la,not so high increase in FEV1.0% and.moderate increase in %MMF, %V50 and.%V25 are observed after spa therapy.The highest increase in FEV1.0% amongthree asthma types, accompanied with.marked improvement of %MMF, %V50.and %V25, is found in type lb. In type.II, the improvement of %V25 is morepredominant after spa therapy, comparedto the improvement of %MMF and%V50 (Fig. 4).Type I b100Percent50Ageyears 0I20-4041-5051-6061-70The clinical effects of spa therapy differsaccording to the type of therapy used25). Themean efficacy rate of spa therapy A (swim-ming training in a hot spring pool) (adminis-tered from 1982 to 1985) was 68.2% ; therate was 87.5% for spa therapy B (swimmingtraining+inhalation of iodine salt solution)(1986 to 1989) and 94.3% in complex spa1S covered with the fango, and warmed for30 mm 5 times a week. The valuesof ventilatory parameters except %FVCare increased by fango therapy23). Of .sixventilatory parameters, the values of %V50.and %V25 tend to show the highest increaseafter fango therapy.Complex spa therapy 1S effective inpatients with bronchial asthma, particularlyin those with steroid-dependent intractableasthma (SDIA)'" 24) • Our studies on 52 patientswith SDIA, Clinical effects of the therapywere found in 36 of the 52 (69.2%) patientswith SDIA. The efficacy was higher in thepatients between the ages of 41 and 50(87.5%) and between 51 and 60 (84.2%) thanin those in the other age groups (Fig. 3).88 Action mechanisms of spa therapyReferencesSpa therapyFig. 5. Increase in serum cortisol levels afterspa therapy in patients withbronchial asthma. B: before, A: after.AA BA BA BA BSerum cortisol level (."9/<12)0-1.9 2.0-2.9 3.0-4.9 5.0-9.9 10.0-~~B15~Cl-3iii 10>.2!"0en'f00Eil/lvanes according to the level before spatherapy. In patients with low serumcortisol levels, a marked and significantincrease is found compared to the levelsbefore therapy. No significant increase is,however, observed in patients with thelevels of more than 10.0M/de (Fig. 5).1. Nadel JA : Inflammation and asthma. JAllergy Clin lmmunol 73 : 651-653, 1984.2. Pauwels R : The relationship betweenairway inflammation and bronchial hyper-responSIveness. Clin Exp Allergy 19 : 395-398, 1989.ConclusionAction of spa therapy is observed as twokinds of clinical effects; direct effects forairways and indirect effects for the otherorgans except airways. Direct effects ofspa therapy are evaluated by improvementof symptoms, ventilatory function, andbronchial hyperresponsiveness. In contrast,indirect effects of the therapy are estimatedby improvement of suppressed function ofadrenocortical glands.2) Bronchial hyperresponsivenessBronchial hyperresponsiveness ISestimated by bronchial reactivity tomethacholine. Different concentrations ofmethacholine (49, 98, 195, 390, 781, 1563,3125, 6250, 12500 and 25000 J1. g / m£) arechallenged to airways. The increase oftotal respiratory resistance (Rrs) aftermethacholine inhalation is measured bythe oscillation methodZ/J. A methacholineconcentration causing a significantincrease in Rrs is assessed as Cmin(minimum concentration). Spa efficacyIS evaluated by exammmg bronchialreactivity to methacholine before andafter the therapy2JlJ. The mean Cmin(minimum concentration of methacholineinducing bronchospasm) in 16 patientswith asthma was clearly decreased from470 J1. g / mR before spa therapy to 1514J1. g / mR after the therapy. The cleardecrease in Cmin of methacholine wasobserved in 4 of the 9 patients (44.4%)under the age of 59, and in 2 of the 7subjects (28.6%) over age 60.2. Indirect effects of spa therapy1) Function of adrenocortical glandsDespite adverse side effects of gluco-corticoids, it is very difficult to stopor reduce the drugs in pa tien ts withsteroid-dependent intractable asthma(SDIA). Among the side effects ofglucocorticoids29. 30), suppression of adreno-cortical glands, and of humoral andcellular immunity are very important3l-33J,since they are closely related to thepathology of the asthmatic airways, andmcrease complexity and severity of thedisease. The increase in serum cortisollevels is observed by spa therapy. Thedegree of the increase in cortisol levelsAction mechanisms of spa therapy 893. Holgate ST, Djukannovic R, Wilson J, etal. : Inflammatory process and bronchialhyperresponsiveness. Clin Exp Allergy 21 :30-38, 1991.4. Lozewicz S, Gomez E, Fergyuson H, etal. : Inflammatory cells in the airways inmild asthma. Br Med J 297 : 1515 -1516,1988.5. Beasely RM, Roche WR, and Holgate ST :Cellular events in the bronchi in mildasthma and after bronchial provocation.Am Rev Respir Dis 139 : 806 ~817, 1989.6. Gonzalez MC, Diaz P, Gallenguillos FR,et al. : Allergen-induced recruitment ofbronchoalveolar helper (OKT 4) andsuppressor (OKT 8) T cells in asthma. AmRev Respir Dis 136 : 600~604, 1987.7. Kelly CA, Ward C, Stenton CS, et al. :Numbers and activity of inflammatory cellin bronchoalveolar lavage in asthma, andtheir relationship to airway responsiveness.Thorax 43: 684-692, 1988.8. Kelly CA, Stenton SC, Ward C, et al. :Lymphocyte subsets in bronchoalveolarlavage fluid from bronchial responsiveness.Clin Exp Allergy 19 : 169 -185, 1989.9. Wardlaw AJ and Kay AB : The role ofthe eosinophil m the pathogenesis ofasthma. Allergy 42 : 321-335, 1987.10. Kirby JG, Hargreave FE, Gleich GJ, etal. : Bronchoalveolar cell profiles of asth-matics and nonasthmatic subjects. Am RevRespir Dis 136: 379-383, 1987.11. Tanizaki Y, Komagoe H, Sudo M, et al. :Swimming training in a hot spring pool astherapy for steroid-dependent asthma. JpnJ Allergol 33: 389-395, 1984.12. Tanizaki Y, Komagoe H, Sudo M, et al. :Intractable asthma and swimming trainingin a hot spring pool. J Jpn Assoc PhysMed Balneol Climatol 47 : 115-122, 1984.13. Tanizaki Y, Komagoe H, Sudo M, et al. :Clinical effects of spa therapy on patientswith bronchial asthma and characteristicsof its action mechanisms. J Jpn AssocPhys Med Balneol Climatol 48 : 99 - 103,1985.14. Tanizaki Y, Komagoe H, Sudo M, et a1. :Clinical effects of spa therapy on steroid-dependent intractable asthma. J Physiother377 : 425-438, 1985.15. Tanizaki Y, Kitani H, Okazaki M, et al. :Eight-year study on spa therapy for pa-tients with chronic respiratory disease.Annual changes in background and charac-teristics of asthmatics. J Jpn Assoc PhysMed Balnrol Climatol 54: 161-167, 1991.16. Tanizaki Y, Komagoe H, Sudo M, et al. :Changes of ventilatory function in patientswith bronchial asthma during swimmingtraining in a hot spring poo1. J Jpn AssocPhys Med Balneol Climatol47 : 99 - 104,1984.17. Tanizaki Y : Improvement of ventilatoryfunction by spa therapy in patients withintractable asthma. Acta Med Okayama 39: 441-446, 1985.18. Tanizaki Y, Sudo M, Kitani H, et al. :Spa therapy for bronchial asthma. Effectsof spa therapy on adrenal gland function.Papers of the Institute for EnvironmentalMedicine, Okayama University MedicalSchool 60 : 14-18, 1989.19. Tanizaki Y, Kitani H, Okazaki M, et a1. :Clinical effects of spa therapy on bronchialasthma. 1. Relationship to clinical asthmatypes and patient age. J Jpn Assoc PhysMed Balneol Climatol 55 : 77 -81, 1992.20. Tanizaki Y, Kitani H, Okazaki M, et al. :Clinical effects of spa therapy on bronchialasthma. 11. Efficacy on asthma in theelderly. J Jpn Assoc Phys Med Balneol90 Action mechanisms of spa therapyClimatol 56 : 195-205, 1993.21. Tanizaki Y, Kitani H, Okazaki M, et al. :Clinical effects of complex spa therapy onpatients with steroid-dependent intractableasthma (SDIA). Jpn J Allergol 42 : 219-227, 1993.22. Tanizaki Y, Kitani H, Okazaki M, et al. :Clinical effects of spa therapy on bronchialasthma. 5. Effects of inhalation withiodine salt solution. J Jpn Assoc Phys MedBalneol Climatol 55: 179-184, 1992.23. Kitani H, Mifune T, Mitsunobu F, et al. :Clinical effects of spa therapy on bronchialasthma. 3. Efficacy of fango therapy. JJpn Assoc Phys Med Balneol Climatol 55 :133-147, 1992.24. Mitsunobu F, Kitani H, Okazaki M, et al. :Clinical effects of spa therapy on bronchialasthma. 6. Comparison among three kindsof spa therapies. J Jpn Assoc Phys MedBalneol Climatol 55 : 185-190, 1992.25. Tanizaki Y, Kitani H, Mifune T, et al. :Ten-year study on spa therapy in 329 pa-tients with bronchial asthma. J Jpn AssocPhys Med Balneol Climatol 57 : 142 - 150,1994.26. Tanizaki Y, Kitani H, Okazaki M, et al. :Clinical effects of spa therapy on bronchialasthma. 2. Relationship to ventilatoryfunction. J Jpn Assoc Phys Med BalneolClimatol 55 : 82-86, 1992.27. Grimby G, Takashima T, Graham W, etal. : Frequency dependence of flow resist-ance in patients with obstructive lungdisease. J Clin Invest 47: 1455-1465, 1986.28. Tanizaki Y, Kitani H, Okazaki M, et al. :Clinical effects of spa therapy on bronchialasthma. 9. Suppression of bronchial hyper-responsiveness. J Jpn Assoc Phys MedBalnrol Climatol 56 : 135-142, 1993.29. Tanizaki Y, Kitani H, Okazaki M, et al. :Clinical effects of spa therapy on bronchialasthma. 8. Effects on suppressed functionof adrenocortical glands. J Jpn Assoc PhysMed Balneol Climatol 56 : 87 -94, 1993.30. Tanizaki Y, Kitani H, Okazaki M, et al. :Clinical effects of spa therapy on bronchialasthma. 4. Effects on steroid-dependentintractable asthma (SDIA). J Jpn AssocPhys Med Balneol Climatol 55 : 134 - 138,1992.31. Mifune T, Mitsunobu F, Hosaki T, et al. :Spa therapy and function of adrenocorticalglands in patients with steroid-dependentintractable asthma (SDIA). Relationship toclinical asthma type, patient age and clini-cal efficacy. J Jpn Assoc Phys Med BalneolClimatol 59 : 133-146, 1996.32. Tanizaki Y, Kitani H, Okazaki M, et al. :Effects of long-term glucocorticoid therapyon bronchoalveolar cells in adult patientswith bronchial asthma. J Asthma 30 : 309-318, 1993.33. Tanizaki Y, Kitani H, Mifune T, et al. :Effects of glucocorticoids on humoral andcellular immunity and on airway inflamma-tion in patients with steroid-dependentintractable asthma. J Asthma 30 : 485-492, 1993.34. Tanizaki Y, Kitani H, Okazaki M, et al. :Changes in the proportions of bronchoa-lveolar lymphocytes, neutrophils and baso-philic cells and the release of histamine andleukotrienes from bronchoalveolar cells inpatients with steroid-dependent intractableasthma. Int Arch Allergy Immunol 101 :196-202, 1993.35. Tanizaki Y, Kitani H, Mifune T, et al. :Effects of spa therapy on psychologicalfactors in patients with bronchial asthma.J Jpn Assoc Phys Med Balneol Climatol 58: 153-159, 1995.Actionmechanismsofspatherapy気管支噂息に対する複合温泉療法の作用機序1.温泉療法の評価方法との関連光延文裕,御船尚志,保崎泰弘,芦田耕三,横田 聡,柘野浩史,竹内一昭,名和由一郎,谷崎勝朗,越智浩二1),原田英雄 1)岡山大学医学部附属病院三朝分院内科, 1)医学部臨床検査医学複合温泉療法 (温泉プール水泳訓練,ヨードゾル吸入,鉱泥湿布療法)の作用機序が,年齢,臨床病型,気道炎症反応との関連のもとに検討された｡温泉療法の作用機序は,2種類の臨床効果,91すなわち,直接効果と間接効果により観察された｡白,他覚症状の改善,換気機能の改善,そして,気道過敏性の改善などが,温泉療法の直接効果として,また,副腎皮質機能の改善が間接効果として観察された｡温泉療法の臨床効果は,40才以上の症例においてより有効であり,また,臨床病型別では､Ia型に比べ,Ib型およびE型においてより有効であった｡Ib型やⅡ型の気管支暗息では,温泉療法の作用機序と気道炎症反応との間に密接な関連が認められた｡索引用語 :複合温泉療法,臨床病型,換気機能,気道過敏性,副腎皮質

気管支喘息に対する複合温泉療法の作用機序 1.温泉療法の評価方法との関連

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