気管支喘息の臨床分類とその細胞性および液性因子の特徴

Characteristics of each asthma type classified by clinical symptoms and　findings were studied in 72 patients with bronchial asthma. 1. Ventilatory function tests showed that the values of % MMF, % V(50) and % V(25) were significantly lower in patients with bronchiolar obstruction (type II) compared to the values of those with simple bronchoconstriction type (type Ia) and those with bronchoconstriction + hypersecretion (type Ib). 2. The proportion of neutrophils in bronchoalveolar lavage (BAL) fluid was significantly higher in type II than in type Ia and type Ib. Several　patients with type Ib showed higher proportion of BAL eosinophils. 3. The release of LTC(4) from leucocytes was significantly lower in type II compared with type Ia and type Ib. There was no significant difference in the release of histamine and LTB(4) among the three asthma types.気管支喘息72例を対象に,その臨床病態の特徴を,気道炎症性の細胞および化学伝達物質の観察により検討した｡1.気道反応の特徴を換気機能の面から検討すると,II細気管支閉塞型において,MMF,V(50)やV(25)などの小ないし細気管支領域の換気障害を示すパラメーターの値は,Ia型,Ib型に比べ 有意の低下を示した｡2.気道細胞反応では,II型において,他の臨床病型に比べ,BAL液中好中球の出現頻度の有意の増加が観察された(Ia, p<0.001 ; Ib, p<0.01)｡好酸球の出現頻度は,Ib過分泌型において著しい増加傾向を示す症例が見られたが,その平均出現頻度には3病型間に有意の差は見られなかった｡3.好中球からのメジェー夕ー遊離では,ヒスタミン遊離は,Ia単純性気管支撃縮型において最も高い値が示されたが,推計学的には3病型間に有意の差は見られなかった｡ロイコトリエンC(4)では,Ia型においてII型に比べ有意に高い遊離が観察された(p<0.05)｡ロイコトリエンB(4)遊離には,3病型間に差は見られなかった

気管支喘息における気道の反応性および炎症反応におよぼす加齢の影響について

Ventilatory function, cellular composition in bronchoalveolar lavage (BAL) fluid and release of chemical mediators from leucocytes were examined in 25 older asthmatics (mean age 66.7 years) and 25 younger asthmatics (mean age 45.1 years) in relation to clinical asthma types. 1. Ventilatory function tests showed that the values of ventilatory parameters such as % MMF, % V(50) and % V(25) were lower in older subjects than in younger subjects, and a significant difference was found in the % V(50) value between the two age groups. Regarding clinical asthma types, the values of % MMF, % V(50), and V(25) were significantly lower in both younger and older subjects with type II. 2. In analysis of cellular composition in BAL fluid, the proportion of BAL lymphocytes was significantly lower in type II older subjects than in younger subjects with the same type. A significantly increased proportion of BAL neutrophils was observed in both younger and older subjects with type II. 3. The release of leukotriene C(4) (LTC(4)) from leucocytes was significantly lower in type II older subjects than in younger subjects with the same type, and LTC(4) release in patients with type II was also significantly lower than that in those with other asthma types in both younger and older subjects. The release of histamine and leukotriene B(4) (LTB(4)) from leucocytes was not significantly different between the two age groups. These results demonstrate that ventilatory function, cellular composition in BAL fluid, and the release of chemical mediators from leucocytes are affected by aging and clinical asthma types.25例の老年者気管支喘息と25例の若壮年者喘息症例を対象に,換気機能,気道内細胞成分の頻度,白血球からの化学伝達物質遊離などの気道反応と関連した要素について,喘息の臨床病型との関連のもとに検討を加えた｡ 1. % MMF, % V(50), % V(25)などの換気パラメーターは老年症例において全般的に低く, % V(50)では若壮年症例に比べ有意の低値を示した｡臨床病型別では,II型喘息において,両年齢群とも他の病型に比べ% MMF, % V(50)及び% V(25)値は有意に低い傾向が見られた｡ 2. 気管支肺胞洗浄(BAL)液中のリンパ球頻度は,II型の老年症例において若壮年症例に比べ有意に低い値を示した｡BAL液中好中球頻度は,いずれの年齢群においても,他の病型に比べ有意に高い値を示した｡ 3. 白血球からのLTC(4)遊離は,II型の老年症例において若壮年症例に比べ,また他の臨床病型に比べ有意に低い値を示した｡ヒスタミンおよびLTB(4)遊離には両年歯群間に有意の差は見られなかった｡これらの結果は,換気機能,気道内細胞成分の頻度,白血球からの化学伝達物質遊離などが,加齢や臨床病態により影響を受けることをある程度示しているものと考えられた

Pathogenic significance of IgG and IgG(4) antibodies against Candida albicans in bronchial asthma

カレジダ特異的IgG及びIgG(4)抗体が,気管支喘息の発症病態に関与しているかどうかについて検討を加えた。カンジダ特異的IgGおよびIgG(4)抗体は, 0-30才の年齢層の症例ではアトピー性素因の強い症例で,また,31-60才の年齢層の症例ではストロイド依存性重症難治性喘息症例で,さらに61才以上の高年令の症例で,その産生亢進が観察される｡これらの症例におけるIgG及びIgG(4)抗体産生は,0-30才の年齢ではアトピーとの関連で,また31-60才の年齢では副腎皮質ホルモンの長期投与と関連して,さらに61才以上の症例では加齢と関連して,細胞性免疫能が低下し,そのためカンジダの発育が促進され,その結果として,IgG及びIgG(4)抗体の産生亢進が見られることが明らかにされている｡すなわち,気管支喘息におけるカンジダに対するIgG系抗体の産生亢進は,cell-mediated immunityの低下と言う共通の基盤を有しており,病因的意義とは必ずしも関連していないことを述べた。Pathogenic significance of IgG and IgG(4) antibodies against Candida albicans was discussed in patients with bronchial asthma. An increased production of IgG and IgG(4) antibodies against Candida albicans has been observed in patients with atopic between the ages of 0 and 30, those with steroid-dependent intractable asthma between 31 and 61, and elderly patients over the age of 61. The mechanism of an increased production of IgG and IgG(4) antibodies seems to be related to atopy in patients between 0 and 30, long-term glucocorticoid therapy in those with steroid-dependent intractable asthma between 31 and 60, and aging in elderly patients over age 61. Atopy, glucocorticoid therapy and aging in general suppress cell-mediated immunity, and suppressed cell-mediated immunity increases growth of C. albicans in patient's body, leading to an increased production of IgG and IgG(4) antibodies against C. albicans. These results show that an increased production of IgG and IgG(4) antibodies against C. albicans is not always related to the pathogenesis of bronchial asthma

老年者気管支喘息における気道炎症細胞.喘息重症度と関連した気道細胞反応の特徴

Cellular composition of bronchoalveolar lavage (BAL) fluid was examined in 11 elderly asthmatics over the age of 70, and the results were compared with those of 11 younger asthmatics under the age of 50. In the subjects with mild asthma, the proportion of BAL cells in the elderly subjects was 86.2% macrophages, 11.0% lymphocytes, 1.9% neutrophils, 0.9% eosinophils and 0.08% basophilic cells. The proportion of neutrophils and eosinophils in the BAL fluid was slightly higher in younger subjects with mild asthma compared with that in elderly subjects, although no significant difference was found between the two groups. In subjects with severe asthma, the proportions of lymphocytes, neutrophils, eosinophils and basophilic cells were more increased in both younger and older patients compared to those with mild asthma, and a significant increase in the number of BAL eosinophils was found in younger subjects with severe asthma compared to those with mild asthma (p < 0.05). However, no significant difference was present in the proportion of BAL cells between younger and older patients with severe asthma. The results reveal that BAL cells are more increased in subjects with suvere asthma than in those with mild asthma in both younger and older subjects, and show the possibility that this increase is more predominant in neutrophils in older subjects and in eosinophils in younger subjects.70才以上の老年者気管支喘息11例(平均年齢71.4才)を対象に,重症度と気道細胞反応との関連について検討を加えた｡なお,対照として50才以下の喘息症例11例(平均年齢33.5才)を選んだ｡1.老年者の軽症型喘息における気管支肺胞洗浄(BAL)液中の出現細胞の頻度は,マクロファージが86.2%,リンパ球が11.0%,好中球が1.9%,好酸球が0.9%,好塩基性細胞が0.08%であった｡BAL液中の好中球,好酸球の頻度は若青年症例でやや高い傾向が見られたが,両群間に有意の差は見られなかった｡重症例では,老年症例,若青年症例とも,軽症例に比べリンパ球,好中球,好酸球などのBAL細胞の出現頻度が増加しており,特に好酸球では若青年症例の重症例で軽症例に比べ有意に高い頻度が観察された｡これらの結果は, リンパ球,好中球,好酸球などのBAL細胞は,軽症例に比べ重症例で増加してくること,そして,その増加は老年症例では好中球,若青年症例では好酸球の増加が特徴的であることを示唆しているものと考えられた

気管支喘息における副腎皮質ホルモン長期投与による免疫抑制と気管支肺胞洗浄液中好中球増多との関連

Cellular composition of bronchoalveolar lavage (BAL) fluid was compared　between two age-matched steroid-dependent　intractable asthma (SDIA) groups : 17 group A patients (serum IgG level 1200mg/dℓ). 1. The levels of serum IgA and IgM were significantly decreased in group A compared to the levels in group B patients. 2. The number of blood lymphocytes was also significantly lower in group A than in group B patients. However, the number of blood neutrophils was not different between the two asthma groups. 3.The number of BAL lymphocytes was significantly lower in group A than in group B patients. 4. BAL neutrophilia (more than 1.5×10 (4)/mℓ) was observed in 6 of the 17(35.3%) patients in group A, but not observed in any patients in group B. The number of BAL neutrophils was significantly greater in group A than in group B　patients. These results suggest that there is a correlation between immunosuppression by glucocorticoids and BAL neutrophilia in patients with bronchial asthma.ステロイド依存性重症難治性喘息を,免疫抑制の見られる症例(血清IgG値1000mg/dℓ以下)(グループA)と抑制の見られない症例(血清IgG値1200mg/dℓ以上)(グループB)の2群に分け,気管支肺胞洗浄液中の細胞成分について比較検討した｡1.血清IgAおよびIgM値は,グループBに比べ免疫抑制の見られるグループAにおいて有意に低い値であった｡2.末梢血リンパ球数は,グループAにおいて,グループBに比べ有意に少ない傾向が見られた｡しかし,末梢血好中球数は両群間に有意の差は見られなかった｡3.BAL液中リンパ球数は,グループBに比べ免疫抑制の見られるグループAにおいて有意に少 ない数であった｡4.BAL液中好中球増多(1.5×10(4)/mℓ以上)を示す症例は, グループAの17例中6例(35.3%)に見られたが,グループBでは全く 見られなかった｡また,BAL液中好中球数は,グループAにおいてグループBに比べ有意に多い数であった｡以上の結果により,副腎皮質ホルモン長期投与 による免疫抑制とBAL液中好中球増多とはある程度関連があることが明らかにされた

気管支喘息におけるActivated Tリンパ球について,喘息発作との関連

The number of CD4(+) T-Iymphocytes, CD4/CD8 ratio, and the number of IL2R(+) T-Iymphocytes (CD25) were examined in 14 patients with bronchial asthma, and the results were compared in three different asthma stages : symptom-free stage, wheeze stage, and attack stage. 1. The proportion of blood CD4(+) T-lymphocytes was more decreased in patients with asthma attacks than in those without symptoms. The CD4/CD8 ratio was also more　decreased in patients with attacks than in those without symptoms. However, these differences were not significant. 2. The proportion of blood activated T cells (IL2R(+) cells, CD25) was significantly increased in patients with attacks than in those without symptoms. The proportion of activated T cells in 5 asthma patients was 2.9±0.8% in　symptom-free stage and 6.6±1.1% in attack stage(p<0.001). These findings show that numbers of activated T-lymphocytes in peripheral blood were increased during asthma attacks, and this increase suggests the participation of　activated T cells in the pathogenesis of asthma.気管支喘息14例を対象に,末梢血CD4(+)リンパ球の頻度,CD4／CD8比およびIL2R(+)Tリンパ球の頻度について,喘息発作との関連のもとに検討を加えた｡1.CD4(+)リンパ球の頻度は,非発作時の症例で最も高く,喘鳴のみの症例,発作の見られる症例へと順次低くなる傾向が見られたが,推計学的には有意の差は見られなかった｡CD4/CD8比も同様に,非発作時に最も高く,発作を有する症例では非発作時に比べ低い値を示したが,推計学的には有意の差は見られなかった｡2.IL2R(+)Tリンパ球(activated Tリンパ球)の頻度は,非発作時の症例で最も低く(3.5±1.1%),喘鳴のみをともなう症例(3.8±1.1%),発作の見られる症例(5.8±1.9%)へと順次高くなる傾向を示し,発作のある症例では,非発作および喘鳴のみの症例に比べ有意に高い値 を示した｡また,非発作時と発作のある時期にIL2R(+)Tリンパ球を観察し得た5症例では,非発作時2.9±0.8%,発作のある時期6.6±1.1%であり,発作のある時期に有意の高値を示した(p<0.001)。これらの結果は,発作のある時期にはactivated Tリンパ球の頻度が増加すること,そして,この増加はactivated Tリンパ球が喘息発作の病態と密接な関連を有していることを示唆するものと考えられた

気管支喘息におけるハウスダストアレルギー. 血清IgE値とIgE抗体価と年齢との関連

Serum IgE levels and IgE antibody values in relation to patient age were examined in 50 patients with house dust mite (HDm) sensitive asthma, 1. IgE antibody values to HDm were highest in patients between the ages of 10 and 19, and the　values generally low in those over the age of 40. 2. High IgE antibody values to HDm　were accompanied by high serum IgE levels in patients between 10 and 19. IgE antibody values and serum IgE levels were in general low in patients over age 40. In patient under　age 9, serum IgE levels were less than 500 IU/ml in 5 of the 10 subjects despite an increased value of IgE antibodies to HDm. These results suggest that an increased　production of IgE antibodies to HDm is usually accompanied by an increased production of total IgE in younger subjects. However, an increase in production of IgE antibodies is not always related to an increase in production of total IgE in patients under age 9. The results also show that production of IgE antibodies to HDm and total IgE is in general low in older patients despite the hyperreactivity to HDm.ハウスダストが原因抗原であるアトピー型気管支喘息50例を対象に,血清IgE値とIgE抗体価を年齢との関連のもとに検討した｡1.IgE抗体価は10-19才の年齢層の症例において最も高く,一方40才以上の症例では全般的に低い傾向が見られた｡2.10-19才の年齢層の症例では,IgE抗体価の高値と同時に血清IgE値も高い値を示したが,40才以上の症例では,IgE抗休価および血清IgE値いずれも10-19才の症例に比べ全般的に低い値を示した｡9才以下の症例では,IgE抗体価の高値にもかかわらず,血清IgE値は比較的低く,500IU/ml以下を示した症例が10例中5例に観察された｡これらの結果は,若年症例では,IgE抗体の産生亢進と総IgEの産生亢進が同時に見られること が多いが,9才以下ではIgE抗体産生亢進に総IgE産生亢進が必ずしもともなわない場合があることを示している｡また,40才以上の症例では,ハウスダストに対する過敏性は有しているものの,IgE抗体価および血清IgEは全般的に低い値を示す傾向が示唆された

気管支肺胞洗浄液中に一過性の好中球増多をきたしたアトピー型喘息

Clinical course of one asthma patient (64 years old, female), who had an increased proportion of neutrophils in bronchoalveolar lavage (BAL) fluid, was observed in relation to the proportion of BAL cells and ventilatory function. The patient had large asthma attacks two times during her clinical course for 15 months observed. 1. An increased proportion of BAL neutrophils and suppression of ventilatory function were found after her first large asthma attacks. The increased proportion of BAL neutrophils continued for more than 5 months. A reduction in the proportion of BAL neutrophils was found 3 months after her second large asthma attack, accompanied by improvement of clinical symptoms and ventilatory function. The numbers of total cells and neutrophils in BAL fluid were also reduced. Transient increase in number of BAL lymphocytes was found 13 months after the first large attack when the number of BAL neutrophils was markedly decreased. The number of BAL eosinophils did not change during her clinical course.経過中に気管支肺胞洗浄(BAL)液中に一過性の好中球増多が観察されたアトピー型喘息症例について,若干の臨床的観察を加えた｡症例は,64才の女性で,臨床症状,および血清IgE高値,ハウスダストに対するIgE抗体陽性などから,アトピー型喘息と診断された｡なお,経過観察し得た15ヵ月の間に2回の大発作が観察された｡1.第1回の大発作後,BAL液中好中球増多と換気機能の低下が観察された｡そして,このBAL液中好中球頻度は明らかな改善が見られた｡BAL液中の総細胞数および好中球の絶対数も徐々に減少傾向を示し,好中球頻度と同様,第2回目の大発作3ヵ月後には著明な減少が観察された｡同時にこの時期には,BAL液中リンパ球の増加も見られた｡しかし,BAL液中好酸球数は15ヵ月の経過観察中ほとんど変化は見られなかった

気管支喘息における気道炎症反応の臨床的意義｡慢性閉塞性細気管支炎との比較検討

Clinical significanoce of airway inflammation was assessed in 28 patients with bronchial asthma, and the results were compared with those in 9 patients with chronic obstructive bronchiolitis (COB). 1. Total cell number in bronchoalveolar lavage(BAL) fluid was markedly increased in patients with COB (51.0×10(6)), which was significantly greater than that in those with bronchial asthma (9.6×10(6) ). 2. The proportion of BAL macrophages was significantly higher in patients with bronchial asthma than in those with COB. However, the, absolute number of BAL macrophages was not significantly different between them. 3. The proportion of BAL lymphocytes was higher in patients with bronchial asthma than in those with COB, but this difference was not signifcant. In contrast, the absolute number of BAL lymphocytes was significantly greater in patients with COB than in those with bronchial asthma. 4. The proportion and the number of BAL neutrophils were markedly increased in patients with COB compared to those with bronchial asthma. 5. The proportion and the number of BAL eosinophils were higher in patients with bronchial asthma than in those with COB, although these defferences were not significant. The results suggest that airway inflammation in bronchial asthma is not so intensive as that in COB.気管支喘息28例および慢性閉塞性細気管支炎9例を対象に,気道炎症反応の臨床的意義について検討を加えた｡1.気管支肺胞洗浄(BAL)液中の総細胞数は,慢性閉塞性細気管支炎において著明に増加しており(51.0×10(6)),気管支喘息(9.6×10(6))との間に有意の差が見られた｡2.BAL液中マクロファージの頻度は気管支喘息において,慢性閉塞性細気管支炎に比べ有意に高い値を示したが,絶対数での比較では両疾患群間に有意の差は見られなかった｡ 3.BAL液中リンパ球の頻度は,気管支喘息においてやや高い傾向が見られたが,絶対数の比較では慢性閉塞性細気管支炎において有意に高い値であった｡ 4.BAL液中の好中球は,その頻度および絶対数とも慢性閉塞性細気管支炎において著明に増加しており,これは気管支喘息と比べ有意に高い値であった｡ 5.BAL液中好酸球の頻度および絶対数は,気管支喘息においてやや高い値であったが,両疾患群間に有意の差は見られなかった｡以上の結果より,気管支喘息における気道炎症反応は,慢性閉塞性細気管支炎ほど高度ではない ことが明らかにされた

老年者気管支喘息における液性および細胞性免疫反応について

Humoral and cellular immune responses in bronchial asthma were examined by comparing the results of older asthmatics (group OA) with those of older healthy subjects (group OH) and of younger asthmatics (group YA). In humoral immune response, IgE-mediated immune system expressed by elevated serum IgE levels and IgE antibodies for house dust mite (HDm) and/or Candida albicans was clearly found in older asthmatics, while there was no finding showing the presence of IgE-mediated immune response in older healthy subjects. There was no significant difference in levels of serum IgG and IgA among the three groups. However, the serum IgM level was significantly lower in older asthmatics than in younger asthmatics. IgE antibodies to HDm and/or Candida albicans were more frequently found in older asthmatics compared with older healthy subjects. In contrast, IgG(4) antibodies to HDm were not different among the three groups. IgG(4) antibodies to Candida albicans were significantly higher in both older groups than in younger group. However, there was no significant difference between asthmatic and healthy subjects in the elderly. Delayed skin reaction to PPD was significantly more decreased in older asthmatics. These results show that bronchial asthma in the elderly is characterized by the presence of IgE-mediated immune response and by the changes of immune response with aging.気管支喘息における液性および細胞性免疫反応について,老年者気管支喘息,老年者健常人,および若年者気管支喘息の間で比較検討を行った｡1.まず,液性免疫では,血清IgE値高値,ハウスダストやカンジダに対するIgE抗体陽性などのIgE系反応は,老年者気管支喘息においては明らかに観察されたが,老年者健常人では全く観察されなかった｡血清IgGおよびIgA値には3者間に有意の差は見られなかったが,血清IgMは,若年者喘息に比べ老年者喘息で有意に低い値を示した｡2.ハウスダストやカンジダに対するIgE抗体は老年者喘息において老年者健常人に比べより高い頻度で陽性であったが,一方,ハウスダストに対するIgG(4)抗体は3者聞に有意の差は見られなかった｡また,カンジダに対するIgG(4)抗体は,老年者喘息および健常人において,若年者喘息に比べ有意の高値を示した｡しかし,老年者の喘息と健常人との間には有意の差は見られなかった｡3.PPDによる遅延型皮膚反応は,若年者喘息に比べ老年者喘息において有意の減弱傾向を示した｡これらの結果は,老年者喘息はIgE系反応を有していること,そして,加齢による免疫反応の変化の影響を受けること,を示している