pulmonary tuberculosis

Japanese: 肺結核

What kind of disease is it?

●The main symptoms and progression are slight fever, cough, phlegm, bloody phlegm, sweating, dyspnea (shortness of breath), weight loss, and loss of appetite. Since these symptoms are not unique to pulmonary tuberculosis, diagnosis is often delayed. On an X-ray, in mild cases, a faint shadow resembling a flower blooming in the bronchus or a pneumonia-like shadow can be seen on the upper part of the lungs. Only when the symptoms have progressed significantly will the cavities characteristic of tuberculosis be visible on an X-ray. The diagnosis is made by confirming the presence of tuberculosis bacteria through sputum culture.
As a rule, patients are hospitalized in a tuberculosis ward and receive oral medication. Because the treatment period is long, lasting from six months to a year, patients are hospitalized only in the early stages of treatment, and once tuberculosis bacteria are no longer excreted in sputum, they are transferred to outpatient treatment. If the initial treatment is not carried out properly, the tuberculosis bacteria may develop drug resistance, making future treatment extremely difficult.

● Causes of the disease and how symptoms developIf you are unaware that you have tuberculosis , you may infect those around you. However, if you are not excreting the bacteria (if there are no bacteria in your phlegm), you are unlikely to infect others, and even if you come into contact with the tuberculosis bacteria, you do not necessarily get tuberculosis.
Tuberculosis bacteria are relatively non-toxic, and the initial symptoms are mild, so caution is required as it is often the case that people do not notice the disease until it has progressed. Also, elderly people who are infected but have no symptoms may develop the disease due to factors such as a decline in physical strength.
When droplets containing tuberculosis bacteria that have been coughed up are inhaled and the bacteria reach the alveoli, they multiply in that area, creating lesions and causing infection.
In many cases, the infection is suppressed by the immune system, but if the immune system is weak or the amount of bacteria is high, tuberculous nodules will form.
Later, when the patient's physical strength declines, the disease may spread within the lungs, causing pulmonary tuberculosis, or the patient may develop other diseases such as tuberculous pleurisy or lymph node tuberculosis.

●Characteristics of the disease People of all ages can develop this disease, from young people to the elderly. The number of cases had been steadily declining since the 1950s, but the incidence rate started to increase for the first time in 43 years, and in July 1999, the Ministry of Health and Welfare (now the Ministry of Health, Labour and Welfare) issued a "Tuberculosis Emergency Declaration." Since then, the number of newly registered cases has been decreasing and then leveling off, but there are still more than 20,000 new tuberculosis cases registered each year.

EBM checks on common treatments and care

[Treatment and care] Help patients understand the importance of early treatment [Rating] ☆☆☆☆☆
[Evaluation points] It has been found that drug treatment during the first six months after the onset of the disease is extremely important in achieving a complete recovery. There are highly reliable clinical studies that show that educating patients on the importance of this treatment makes them more cooperative with the treatment. (1)(2)

[Treatment and care] Provide initial intensive short-term therapy with tuberculosis drugs [Rating] ☆☆☆
[Evaluation points] For the initial treatment of tuberculosis, one of the following drug therapies is selected. These drug therapies are prescriptions based on the experience of many experts and are strongly recommended in clinical guidelines. (5)-(12)
Isoniazid + rifampicin + pyrazinamide Isoniazid + rifampicin + pyrazinamide + ethambutol hydrochloride Isoniazid + rifampicin + pyrazinamide + streptomycin sulfate

[Treatment and care] In cases of liver dysfunction or hyperuricemia, initial intensive short-term therapy should be performed using a prescription that does not contain pyrazinamide. [Evaluation] ☆☆☆
[Evaluation Points] Pyrazinamide is known to sometimes cause severe liver damage. It is also known that people who drink a lot of alcohol or have liver damage are more likely to have their liver function deteriorated by tuberculosis medications. For these reasons, people with liver damage should avoid using pyrazinamide. It is also known that pyrazinamide can cause hyperuricemia, but it is not clear whether this causes complications such as gout. Some experts say that even if you have hyperuricemia, it is okay to use pyrazinamide for up to two months, while monitoring your condition. (13)

[Treatment and care] To prevent infection, the patient will be admitted to a tuberculosis ward. [Rating] ☆☆☆☆
[Evaluation points] The results of many reliable studies have shown that hospital-acquired infections occur through close contact with tuberculosis-infected patients. Therefore, patients who have been diagnosed with tuberculosis or are suspected of having tuberculosis must be hospitalized in a tuberculosis ward until it is proven that they are not shedding the bacteria, until they are discharged from the hospital, and until it is proven that they are not infected. (14)

Checking commonly used drugs with EBM

Drugs used in initial therapy (3)(4)
[Drug name] Iscotin (isoniazid) + Rifadin (rifampicin) + Pyramide (pyrazinamide) + Streptomycin sulfate (streptomycin sulfate) or Ethambutol/Ebutol (ethambutol hydrochloride)
[Rating] ☆☆☆
[Evaluation points] A combination of isoniazid, rifampicin, and pyrazinamide with streptomycin sulfate or ethambutol hydrochloride is usually used. This combination has been confirmed by clinical studies and is recommended in the guidelines.

Drugs to be used in patients with liver disorder or hyperuricemia (3)(4)
[Drug name] Iscotin (isoniazid) + Rifadin (rifampicin) + Streptomycin sulfate (streptomycin sulfate)
[Rating] ☆☆☆
[Evaluation points] Clinical studies have confirmed that both drugs are effective in combination therapy.

Medications to be used in mild cases (3)(4)
[Drug name] Iscotin (isoniazid) + Rifadin (rifampicin)
[Rating] ☆☆☆
[Evaluation points] Clinical studies have confirmed that both drugs are effective in combination therapy.

Overall, it is currently the most reliable treatment method. <br /> Patients who are emitting tuberculosis bacteria must be hospitalized in a tuberculosis ward. Patients who are emitting tuberculosis bacteria will first be hospitalized in a tuberculosis ward and receive oral drug therapy. However, it is usually not necessary to be hospitalized for the entire 6-month oral treatment period or until completely cured, and patients can switch to outpatient treatment once they no longer emit bacteria.

Four-drug combination therapy is effective. Usually, treatment is with four drugs: Isoniazid (isoniazid), Rifadin (rifampicin), Pyramide (pyrazinamide), and streptomycin sulfate (streptomycin sulfate) or Ethambutol/Ebutol (ethambutol hydrochloride). Isoniazid can cause side effects that cause nerve abnormalities, so vitamin _B6 (pyridoxine) is taken at the same time as a preventative measure.

Beware of drug resistance If you do not take the necessary medicines exactly as instructed by your doctor in the initial treatment, the drug-resistant tuberculosis bacteria will multiply, making future treatment very difficult. This is called drug resistance, and is one of the most important points in the treatment of pulmonary tuberculosis.
In particular, since the period of taking the medicine is often long, from six months to a year, please be careful not to stop taking the medicine on your own judgment. If you feel that it is difficult to take the medicine due to side effects, etc., it is necessary to consult a doctor.

It is important to understand the meaning of taking medication The World Health Organization's (WHO) Global TB Programme recommends DOTS (Directly Observed Therapy, Short-course). This is a program in which governments actively work to detect the disease and ensure a stable supply of drugs, while health care workers observe patients taking the medication and record it to ensure treatment is carried out. It can be said to be a program to ensure that patients take their tuberculosis medication.
DOTS is mainly implemented in developing countries, but the importance of taking medicines reliably is the same in Japan. Medical professionals such as doctors and pharmacists need to provide sufficient information and education/guidance.
At the same time, it is important for patients to fully understand the meaning of their medication and engage in treatment accordingly.

(1)Essential components of a tuberculosis prevention and control program. Recommendations of the Advisory Council for the Elimination of Tuberculosis. MMWR Recomm Rep. 1995;44(RR-11):1-16.
(2)White MC, Tulsky JP, Goldenson J, et al. Randomized controlled trial of interventions to improve follow-up for latent tuberculosis infection after release from jail. Arch Intern Med. 2002;162:1044-1050.
(3)Blumberg HM, Burman WJ, Chaisson RE, et al. American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: treatment of tuberculosis. Am J Respir Crit Care Med 2003; 167:603.
(4)Hopewell PC, Pai M, Maher D, et al. International standards for tuberculosis care. Lancet Infect Dis 2006; 6:710.
(5)Controlled clinical trial of four short-course (6-month) regimens of chemotherapy for treatment of pulmonary tuberculosis. Second report. Lancet 1973; 1:1331.
(6)Controlled trial of 6-month and 9-month regimens of daily and intermittent streptomycin plus isoniazid plus pyrazinamide for pulmonary tuberculosis in Hong Kong. The results up to 30 months. Am Rev Respir Dis 1977; 115:727.
(7)Short-course chemotherapy in pulmonary tuberculosis. A controlled trial by the British Thoracic and Tuberculosis Association. Lancet 1976; 2:1102.
(8)British Thoracic Association. A controlled trial of six months chemotherapy in pulmonary tuberculosis. Second report: results during the 24 months after the end of chemotherapy. Am Rev Respir Dis 1982; 126:460.
(9)Hong Kong Chest Service/British Medical Research Council. Five-year follow-up of a controlled trial of five 6-month regimens of chemotherapy for pulmonary tuberculosis. Am Rev Respir Dis 1987; 136:1339.
(10)Hong Kong Chest Service/British Medical Research Council. Controlled trial of 2, 4, and 6 months of pyrazinamide in 6-month, three-times-weekly regimens for smear-positive pulmonary tuberculosis, including an assessment of a combined preparation of isoniazid, rifampin, and pyrazinamide. Results at 30 months. Am Rev Respir Dis 1991; 143:700.
(11)Johnson JL, Hadad DJ, Dietze R, et al. Shortening treatment in adults with noncavitary tuberculosis and 2-month culture conversion. Am J Respir Crit Care Med 2009; 180:558.
(12)Combs DL, O'Brien RJ, Geiter LJ. USPHS Tuberculosis Short-Course Chemotherapy Trial 21: Effectiveness, toxicity, and acceptability. The report of final results. Ann Intern Med 1990; 112:397.
(13)Sharma SK, Balamurugan A, Saha PK, et al. Evaluation of clinical and immunogenetic risk factors for the development of hepatotoxicity during antituberculosis treatment. Am J RespirCrit Care Med. 2002;166:916-919.
(14)Bass JB Jr, Farer LS, Hopewell PC, et al. Treatment of tuberculosis and tuberculosis infection in adults and children. American Thoracic Society and The Centers for Disease Control and Prevention. Am J RespirCrit Care Med. 1994;149:1359-1374.

Source: "EBM: A book that explains correct treatment" Information about the book "EBM: A book that explains correct treatment"

Japanese:

どんな病気でしょうか?

●おもな症状と経過
　症状は微熱、せき、痰(たん)、血痰(けったん)、発汗、呼吸困難（息苦しさ）、体重減少、食欲不振などで、肺結核(はいけっかく)にしかみられない症状ではないため、しばしば診断が遅れてしまいます。レントゲン写真では、軽症であれば気管支に花が咲いたような淡い陰影や、肺炎のような影を肺の上側に認めます。結核に特徴的な空洞(くうどう)がレントゲン写真に写るのは、かなり症状が進行した場合です。痰の培養で結核菌を確認して診断します。
　治療は原則として結核病棟に入院して内服薬による治療を受けます。治療期間が半年から1年と長いので、入院は治療初期のみとして、痰に結核菌が排出されなくなれば外来治療に移行します。最初の治療をきちんと行わないと、結核菌の薬剤耐性化(やくざいたいせいか)を招き、のちのちの治療が非常に困難となります。

●病気の原因や症状がおこってくるしくみ
　結核にかかったことに気がつかずにいると、周囲の人を感染させることもあります。ただし、排菌していなければ（痰のなかに菌がいなければ）他人を感染させることはまずありませんし、結核菌に触れても必ず結核にかかるわけではありません。
　結核菌は比較的毒性の弱い菌で、初期症状が軽く、病状が進行してから気がつくことが多いため注意が必要です。また、お年寄りでは、感染していても症状のなかった人が、体力の低下などをきっかけに発病することもあります。
　せきとともに吐きだされた結核菌を含む飛沫(ひまつ)を吸い込み、肺胞に結核菌が付着するとその部分で菌が増殖し、病巣(びょうそう)をつくって感染が生じます。
　多くの場合、免疫力によって感染は抑えられますが、免疫力が弱い場合や菌の量が多い場合は、結核結節をつくります。
　その後、体力が低下した際に肺内に病巣が拡大して肺結核となったり、結核性胸膜炎(けっかくせいきょうまくえん)、リンパ節結核などの病気になったりします。

●病気の特徴
　若年者からお年寄りまで、年齢にかかわりなく発病します。1950年代から発生患者数は低下の一途をたどってきましたが、43年ぶりに患者発生率が増加に転じたため、1999年7月に当時の厚生省（現・厚生労働省）から「結核緊急事態宣言」が発せられました。その後、新規登録患者数は減少から横ばいの傾向ですが、未だ年間2万人以上の結核患者が新たに登録されています。

よく行われている治療とケアをEBMでチェック

［治療とケア］初期治療の重要性を患者さんに理解させる
［評価］☆☆☆☆☆
［評価のポイント］　発病後最初の6カ月の薬物治療が完全に治癒させるうえで非常に重要であることがわかっています。患者さんに対してこの治療の重要性を理解してもらうための教育を行うと、治療に協力的になるという非常に信頼性の高い臨床研究があります。(1)(2)

［治療とケア］結核治療薬による初期強化短期療法を行う
［評価］☆☆☆
［評価のポイント］　結核の初期治療は、次にあげる薬物療法のなかから一つを選択します。これらの薬物療法は、多くの専門家の経験に基づいてつくられた処方であり、診療ガイドラインなどで強く推奨されています。(5)～(12)
　イソニアジド＋リファンピシン＋ピラジナミド
　イソニアジド＋リファンピシン＋ピラジナミド＋エタンブトール塩酸塩
　イソニアジド＋リファンピシン＋ピラジナミド＋ストレプトマイシン硫酸塩

［治療とケア］肝障害、高尿酸血症(こうにょうさんけっしょう)がある場合には、ピラジナミドの入っていない処方で初期強化短期療法を行う
［評価］☆☆☆
［評価のポイント］　ピラジナミドは、ときに重症の肝障害をおこすことが知られています。またアルコール類をよく飲む人や肝障害のある人は、結核治療薬によって肝機能が悪化しやすいことが知られています。以上の理由から、肝障害のある人は、ピラジナミドの使用を避けたほうがよいでしょう。またピラジナミドにより高尿酸血症がおこることが知られていますが、それが痛風などの合併症の原因になるかどうかは、はっきりとわかっていません。高尿酸血症があっても、2カ月までならようすを見ながらピラジナミドを使用してもよいという専門家の意見もあります。(13)

［治療とケア］感染防止のため、結核病棟に入院する
［評価］☆☆☆☆
［評価のポイント］　結核に感染した患者さんと濃厚に接触することにより院内感染がおこることが、多くの信頼性の高い研究の結果によってわかっています。したがって、①排菌していないことが証明されるまで、②退院するまで、③感染していないことが証明されるまで、結核と診断された患者さんおよび結核の疑いのある患者さんは結核病棟に入院する必要があります。(14)

よく使われている薬をEBMでチェック

初回療法に使用する薬剤(3)(4)
［薬名］イスコチン（イソニアジド）＋リファジン（リファンピシン）＋ピラマイド（ピラジナミド）＋硫酸ストレプトマイシン（ストレプトマイシン硫酸塩）またはエサンブトール／エブトール（エタンブトール塩酸塩）
［評価］☆☆☆
［評価のポイント］　ふつうはイソニアジド、リファンピシン、ピラジナミドの3剤にストレプトマイシン硫酸塩またはエタンブトール塩酸塩を組み合わせた4剤が用いられます。この処方は臨床研究によって確認され、ガイドラインでも推奨されています。

肝障害、高尿酸血症がある場合に使用する薬剤(3)(4)
［薬名］イスコチン（イソニアジド）＋リファジン（リファンピシン）＋硫酸ストレプトマイシン（ストレプトマイシン硫酸塩）
［評価］☆☆☆
［評価のポイント］　いずれの薬も併用療法で有効であることが臨床研究によって確認されています。

軽症の場合に使用する薬剤(3)(4)
［薬名］イスコチン（イソニアジド）＋リファジン（リファンピシン）
［評価］☆☆☆
［評価のポイント］　いずれの薬も併用療法で有効であることが臨床研究によって確認されています。

総合的に見て現在もっとも確かな治療法
排菌者は結核病棟に入院が必要
　結核菌を排菌している患者さんは、まず、結核病棟に入院して内服による薬物療法を受けることになります。ただし、ふつう6カ月間の内服治療の全期間あるいは完全に治癒するまで入院する必要はなく、排菌さえなくなれば外来治療に移行しても大丈夫です。

4剤併用療法が有効
　ふつうはイスコチン（イソニアジド）＋リファジン（リファンピシン）＋ピラマイド（ピラジナミド）＋硫酸ストレプトマイシン（ストレプトマイシン硫酸塩）またはエサンブトール／エブトール（エタンブトール塩酸塩）の4剤による治療を行います。イソニアジドには神経に異常を感じる副作用がみられることがあるので、予防のためにビタミンB₆（ピリドキシン）を同時に服用してもらいます。

薬剤耐性化に注意
　最初の治療において必要な薬を医師の指示通りにきちんと服用しないと、薬剤の効かない結核菌が増えてしまい、のちのちの治療が非常に難しくなります。これを薬剤耐性化といい、肺結核の治療で非常に重要なポイントの一つです。
　とくに薬の服用期間が半年から1年と長期にわたることが多いので、自己判断で薬を中止しないように注意してください。副作用などで薬が飲みにくいと感じたときは、医師に相談することが必要です。

服薬の意味を理解することが大切
　WHO（世界保健機関）の世界結核計画では、DOTS（Directly Observed Therapy, Short-course：直接監視下服薬、短期コース）を推奨しています。これは病気の発見や薬剤の安定供給に対して政府が積極的に取り組むとともに、患者さんが治療薬を服用するところを保健医療従事者が見届け、そのことを記録して、治療を確実に行おうとするものです。結核治療薬を患者さんが確実に服用することができるようにするためのプログラムといえるでしょう。
　DOTSはおもに開発途上国で実施されていますが、薬を確実に服用することの重要性はわが国でも同じです。医師や薬剤師など医療関係者は、十分な情報提供と教育・指導をしていく必要があります。
　同時に患者さんも、服薬の意味をよく理解して治療に取り組むことが大切です。

(1)Essential components of a tuberculosis prevention and control program. Recommendations of the Advisory Council for the Elimination of Tuberculosis. MMWR Recomm Rep. 1995;44(RR-11):1-16.
(2)White MC, Tulsky JP, Goldenson J, et al. Randomized controlled trial of interventions to improve follow-up for latent tuberculosis infection after release from jail. Arch Intern Med. 2002;162:1044-1050.
(3)Blumberg HM, Burman WJ, Chaisson RE, et al. American Thoracic Society/Centers　for Disease Control and Prevention/Infectious Diseases Society of America: treatment of tuberculosis. Am J Respir Crit Care Med 2003; 167:603.
(4)Hopewell PC, Pai M, Maher D, et al. International standards for tuberculosis care. Lancet Infect Dis 2006; 6:710.
(5)Controlled clinical trial of four short-course (6-month) regimens of chemotherapy for treatment of pulmonary tuberculosis. Second report. Lancet 1973; 1:1331.
(6)Controlled trial of 6-month and 9-month regimens of daily and intermittent streptomycin plus isoniazid plus pyrazinamide for pulmonary tuberculosis in Hong Kong. The results up to 30 months. Am Rev Respir Dis 1977; 115:727.
(7)Short-course chemotherapy in pulmonary tuberculosis. A controlled trial by the British Thoracic and Tuberculosis Association. Lancet 1976; 2:1102.
(8)British Thoracic Association. A controlled trial of six months chemotherapy in pulmonary tuberculosis. Second report: results during the 24 months after the end of chemotherapy. Am Rev Respir Dis 1982; 126:460.
(9)Hong Kong Chest Service/British Medical Research Council. Five-year follow-up of a controlled trial of five 6-month regimens of chemotherapy for pulmonary tuberculosis. Am Rev Respir Dis 1987; 136:1339.
(10)Hong Kong Chest Service/British Medical Research Council. Controlled trial of 2, 4, and 6 months of pyrazinamide in 6-month, three-times-weekly regimens for smear-positive pulmonary tuberculosis, including an assessment of a combined preparation of isoniazid, rifampin, and pyrazinamide. Results at 30 months. Am Rev Respir Dis 1991; 143:700.
(11)Johnson JL, Hadad DJ, Dietze R, et al. Shortening treatment in adults with noncavitary tuberculosis and 2-month culture conversion. Am J Respir Crit Care Med 2009; 180:558.
(12)Combs DL, O'Brien RJ, Geiter LJ. USPHS Tuberculosis Short-Course Chemotherapy Trial 21: effectiveness, toxicity, and acceptability. The report of final results. Ann Intern Med 1990; 112:397.
(13)Sharma SK, Balamurugan A, Saha PK, et al. Evaluation of clinical and immunogenetic risk factors for the development of hepatotoxicity during antituberculosis treatment. Am J RespirCrit Care Med. 2002;166:916-919.
(14)Bass JB Jr, Farer LS, Hopewell PC, et al. Treatment of tuberculosis and tuberculosis infection in adults and children. American Thoracic Society and The Centers for Disease Control and Prevention. Am J RespirCrit Care Med. 1994;149:1359-1374.