Bronchial asthma

Japanese: 気管支喘息

What kind of disease is it?

●Main symptoms and progression Bronchial asthma is a disease in which chronic inflammation occurs in the airways, obstructing the flow of air. The main symptoms are paroxysmal coughing, wheezing (the wheezing sound that occurs with each breath), and dyspnea (shortness of breath), and it is characterized by repeated attacks.
Attacks tend to occur more frequently in the middle of the night or early morning than during the day, and it has long been known that they are more likely to occur during seasonal changes and periods of unstable weather. Even when an attack is not occurring, the mucous membrane of the bronchi is inflamed, and attacks occur due to hypersensitivity to even the slightest stimuli. The throat and chest feel tight, and then wheezing occurs, making it difficult to breathe, and in addition, severe coughing and phlegm are produced.
These symptoms will subside naturally or will return to normal with appropriate treatment, but in patients who have continued to suffer from attacks for a long time, the airway walls will thicken and become more difficult to return to normal as inflammation and repair processes are repeated, further increasing airway hyperresponsiveness.
If we can stay as attack-free as possible and prevent these changes in the airways, we can lead an almost identical daily life to a healthy person. However, if the condition is not well controlled and the disease worsens with repeated attacks, it can even lead to death.
Along with a proper diagnosis by a specialist, self-management is also essential for the treatment of asthma. A peak flow meter is used to check the severity of asthma. A peak flow meter is a device that reads the value when you blow into the air as hard as you can, and because it is a simple device, it can also be used by patients themselves to understand their symptoms and condition.
The severity of asthma is classified as follows:
● Step 1 (mild intermittent type)
Peak flow is 80 percent or more of predicted, morning and evening peak flow varies by less than 20 percent, and wheezing, coughing, or dyspnea occurs less than once a week.
● Step 2 (Mild persistent symptoms)
Peak flow is 80 percent or more of predicted, fluctuates between 20-30 percent, symptoms occur at least once a week but not every day, daily activities or sleep are disrupted at least once a month, and nocturnal symptoms occur at least twice a month.
● Step 3 (moderate persistent type)
Peak flow is 60 to 80 percent of predicted, fluctuates by 30 percent or more, chronic symptoms are present, inhaled beta- ₂ agonists are required almost daily, daily activities or sleep are disrupted at least once a week, and nocturnal symptoms occur at least once a week.
● Step 4 (severe persistent type)
Peak flow is less than 60 percent of the predicted value, fluctuates by more than 30 percent, and symptoms often worsen despite treatment. Symptoms persist, restricting daily life, and often worsening at night. Continuous use of oral corticosteroids and bronchodilators are required.
The severity of acutely worsening attacks is classified as follows:
Mild symptoms (minor attacks)
When a patient who usually has mild symptoms or is well-controlled develops an attack due to cold, overwork, or exposure to an antigen. The symptoms are relatively mild and do not interfere with daily life. The peak flow value is 80% or more of the predicted value.
Moderate symptoms (moderate attacks)
The cough, phlegm, and dyspnea have become much worse, and although the inhalation of the beta ₂ agonist I have on hand has been effective, it is not lasting very long. My peak flow has dropped to 60-80% of the predicted value, and I am in a state where I am unable to lie down due to the strain (orthopnea).
Severe symptoms (grand mal seizures)
Moderate to severe patients may experience seizures due to catching a cold or overwork, but may continue to struggle without adequate treatment and may experience a major seizure. Peak flow is less than 60 percent of the predicted value.
●Severe symptoms/emergencies (severe attacks)
This condition often occurs when a patient with a grand mal attack neglects treatment. Breath sounds are reduced, the sense of dyspnea is very strong, cold sweat drips from the face, and the patient is unable to walk or speak. Peak flow cannot be measured.

● How the disease causes and symptoms develop Bronchial asthma is thought to be caused by a combination of genetic and environmental factors, but the exact cause is still unknown. It is divided into atopic asthma, which is thought to develop because patients are genetically predisposed to allergies, and non-atopic asthma, which develops regardless of a patient's natural constitution. It is said that atopic asthma involves an immediate allergic reaction, while non-atopic asthma involves a delayed allergic reaction. In both cases, the airways of people with this condition are more sensitive than those of the average person, and more susceptible to irritation.
In addition to contact with antigens that cause attacks (such as dust mites, mold, pollen, etc.), various factors can be cited as causes, such as colds, overwork, stress, pets, weather, exercise, cigarette smoke, strong odors, cold air, drinking alcohol, menstruation, etc. If the condition is severe and unstable, some trigger can cause a sudden change in the condition, leading to cyanosis and loss of consciousness, and even death from asthma (suffocation).

●Characteristics of the disease In the 1960s, the number of asthma patients was said to be around 1% of the population, but in a survey conducted in the 2010s, it had increased to about 3-5%. A recent trend has been an increase in the number of children and elderly people in urban areas.

EBM checks on common treatments and care

There are several guidelines for bronchial asthma, but the international guidelines "GINA 2014" and the Japanese Society of Allergology's "Asthma Prevention and Management Guidelines" continue to emphasize the importance of inhaled corticosteroids, positioning them as the central long-term control medication, as in the past.

■ Step 1 (mild intermittent type)
[Treatment and care] Suppresses inflammation in the airways, maintains lung function, and reduces the likelihood of attacks in the long term. [Rating] ☆☆☆☆☆
[Evaluation points] For patients with mild intermittent allergies, the use of low-dose inhaled corticosteroids, sustained-release theophylline, or anti-allergy medications including leukotriene receptor antagonists will be considered depending on the frequency of symptoms, etc.
The most reliable clinical studies in patients with mild asthma have shown that inhaled corticosteroids are effective in improving peak flow rates.
Anti-allergy drugs have been shown to be effective for patients with mild to moderate allergies. If no effect is seen within 6 to 10 weeks, some clinical studies recommend switching to another anti-allergy drug or other treatment. The effectiveness of leukotriene receptor antagonists has been almost established. (1)-(17)

■ Step 2 (mild persistent symptoms)
[Treatment and care] Suppresses inflammation in the airways, maintains lung function, and reduces the likelihood of attacks in the long term. [Rating] ☆☆☆☆☆
[Evaluation points] Patients with mild persistent allergy symptoms are given low-dose inhaled corticosteroids, long-acting bronchodilators (such as theophylline sustained-release preparations or beta- ₂ agonists), or anti-allergy drugs including leukotriene receptor antagonists, either alone or in combination, daily.
Even in patients with mild persistent asthma, highly reliable clinical studies have shown that inhaled corticosteroids are effective in improving peak flow values. In addition, the effectiveness of long-acting bronchodilators (sustained-release theophylline preparations) is said to be equal to or slightly inferior to inhaled corticosteroids, and in the long term, inhaled corticosteroids are clearly more effective.
Transdermal _β2 agonists have also been reported to be effective in improving peak flow values in patients with mild to moderate BP. (1)-(18)

■ Step 3 (moderate persistent)
[Treatment and care] Suppresses inflammation in the airways, maintains lung function, and reduces the likelihood of attacks in the long term. [Rating] ☆☆☆☆☆
[Evaluation points] For patients with moderate to persistent bronchitis, medium to high doses of inhaled corticosteroids, long-acting bronchodilators (sustained-release theophylline, _β2 agonists, etc.), anti-allergy drugs with anti-inflammatory properties (leukotriene receptor antagonists, etc.), and long-acting anticholinergics are used daily in combination. The effectiveness of these drugs has been confirmed by highly reliable clinical studies.
When asthma symptoms do not stabilize despite the use of medium or higher doses of inhaled corticosteroids, it has been reported that the effect is the same or slightly better when combined with sustained-release theophylline instead of doubling the dose of inhaled corticosteroids. (1)-(18)(45)

■ Step 4 (severe persistent)
[Treatment and care] Suppresses inflammation in the airways, maintains lung function, and reduces the likelihood of attacks in the long term. [Rating] ☆☆☆☆☆
[Evaluation points] For patients with severe persistent allergies, high doses of inhaled corticosteroids, long-acting bronchodilators (sustained-release theophylline, _β2 agonists, etc.), and long-acting anticholinergics are used daily. If symptoms remain unstable and frequently worsen, oral corticosteroids may be used for a short period of time, or anti-IgE antibody injections may be administered if the patient is positive for perennial inhaled allergens and has a serum IgE level of 30-1500 IU/ml. In addition, the use of anti-allergy drugs may be considered in combination to suppress symptoms as much as possible and allow the patient to continue with daily life. The effectiveness of these treatments has been confirmed by highly reliable clinical studies. (19)-(21)(45)(46)

■ Steps 1 to 4
[Treatment and care] Use anti-seizure medication during seizures [Rating] ☆☆☆☆☆
[Evaluation points] For patients with mild to severe symptoms, attacks can be suppressed with the use of short-acting bronchodilators (inhaled _β2 agonists) as needed. However, for severe patients whose condition is unstable and attacks occur frequently, oral corticosteroids may be used for a short period of time. The effectiveness of these drugs has been confirmed by highly reliable clinical studies.
As for inhaled _β2 agonists, they should be used up to 3-4 times a day. If more than this is required, it is determined that the symptoms are not being controlled with the current treatment, and the treatment will be strengthened (stepped up from step 1 to step 2, etc.). On the other hand, if symptoms have been stable for at least 3 months, the treatment may be lowered (stepped down) and the use of medication may be reduced. (1)-(21)

■Mild symptoms (minor attacks)
[Treatment and care] Add inhaled bronchodilators as needed [Rating] ☆☆☆☆☆
[Evaluation Points] For mild attacks, add a short-acting inhaled _β2 agonist as needed. Highly reliable clinical studies have confirmed that spacer and nebulizer inhalation are almost equally effective. However, in patients with mild intermittent attacks, regular use of _β2 agonists without inhaled corticosteroids is said to worsen airway hyperresponsiveness and pulmonary function. Intravenous infusion of theophylline (aminophylline hydrate) has also been shown to improve the condition. (16)(22)-(24)

■ Moderate symptoms (moderate attacks)
[Treatment and care] Repeated inhalation of bronchodilators, drip infusion, subcutaneous injection, and intravenous injection of corticosteroids are performed. [Evaluation] ☆☆☆☆☆
[Evaluation points] Patients with moderate attacks should visit the emergency room. First, they will be given a nebulized _β2 agonist. If symptoms improve within an hour, they can go home.
If the condition does not improve, we will administer subcutaneous injections of _β2 agonists, infusions of theophylline (aminophylline hydrate), intravenous injections of corticosteroids, etc. The effectiveness of these treatments has been confirmed by highly reliable clinical studies.
If the patient does not respond to treatment for 2 to 4 hours, or if there is no response at all, hospitalization may be necessary. (22)-(25)

■ Severe symptoms (grand mal seizures)
[Treatment and care] Repeated inhalation of bronchodilators, intravenous drip, subcutaneous injection, intravenous injection of corticosteroids, and oxygen were used. [Evaluation] ☆☆☆☆☆
[Evaluation points] Patients with major attacks should visit the emergency room. Repeated inhalation of _β2 agonists using a nebulizer is performed, and subcutaneous injections of _β2 agonists, infusion of theophylline (aminophylline hydrate), and intravenous injection of corticosteroids are also administered. The effectiveness of these treatments has been confirmed by highly reliable clinical studies.
If the condition does not improve within an hour, hospitalization is usually considered. (23)-(28)(38)

■ Severe symptoms/emergencies (severe attacks)
[Treatment and care] Immediate hospitalization and continued treatment for grand mal seizures in the ICU [Rating] ☆☆☆☆☆
[Evaluation points] Patients with severe attacks may have severe breathing difficulties and may have cyanosis or impaired consciousness. Immediate hospitalization is required.
Repeated inhalation of _β2 agonists with a nebulizer, subcutaneous injection of _β2 agonists, drip infusion of theophylline (aminophylline hydrate), intravenous injection of corticosteroids, etc. are performed, but if there is no response or the condition worsens, artificial respiration, inhalation and washing of the airway are performed. In addition, anesthetics with bronchodilatory effects (isoflurane, sevoflurane, enflurane, etc.) may be used.
The effectiveness of these treatments has been confirmed by highly reliable clinical studies. (20)(23)-(28)(38)

Checking commonly used drugs with EBM

As a long-term control medication [Drug use] Inhaled corticosteroid [Drug name] Cuvar (beclomethasone propionate) (4)(7)(29)
[Rating] ☆☆☆☆☆
[Drug name] Flutide (fluticasone propionate ester) (4) (29)
[Rating] ☆☆☆☆☆
[Drug name] Pulmicort (Budesonide) (4) (29) (30)
[Rating] ☆☆☆☆☆
[Drug name] Alvesco (ciclesonide) (4) (29) (30)
[Rating] ☆☆☆☆☆
[Drug name] Azmanex (mometasone furoate) (4) (31)
[Rating] ☆☆☆☆☆

[Evaluation points] Inhaled corticosteroids have excellent local anti-inflammatory effects and have little systemic effect, and are currently considered to be the most effective asthma treatment. By properly administering drug therapy centered on inhaled corticosteroids, the frequency of hospitalization due to asthma attacks and death from asthma has decreased. Inhaled corticosteroids improve airway inflammation in asthma patients, which in turn improves subjective symptoms, lung function, and airway hyperresponsiveness. Early use in particular can improve airway remodeling and prevent a decline in lung function. Patients who use high doses of inhaled corticosteroids may experience effects on bones, adrenal function, etc. When used for a long period of time, the amount used should be minimized. Attention should also be paid to effects on the eyes, skin, etc. These facts have been confirmed by highly reliable clinical studies.

[Drug use] Long-acting bronchodilator [Drug name] Unifil LA/Theodur/Unicon (theophylline sustained-release formulation) (5)-(7)
[Rating] ☆☆☆☆
[Evaluation points] Reliable clinical studies have confirmed the effectiveness of sustained-release theophylline in improving asthma symptoms and pulmonary function in patients with mild to moderate asthma. However, its effectiveness is said to be equivalent to or slightly inferior to inhaled corticosteroids, and in the long term, it has been reported that inhaled corticosteroids are clearly more effective. If asthma symptoms do not stabilize despite the use of medium or higher doses of inhaled corticosteroids, the effect is equivalent or slightly better when theophylline sustained-release is used in combination with the inhaled corticosteroid instead of doubling the dose.

[Drug name] Spiropent (Clenbuterol hydrochloride) (5)-(7)
[Rating] ☆☆☆☆
[Drug name] Meptin (Procaterol hydrochloride hydrate) (17)(22)(23)(33)～(37)
[Rating] ☆☆☆☆☆
[Drug name] Hokunarin Tape (Tulobuterol) (17)(22)(23)(33)～(37)
[Rating] ☆☆☆☆☆
[Drug name] Serevent (salmeterol xinafoate)
[Rating] ☆☆☆☆
[Evaluation Points] Long-acting _β2 agonists are available as oral medications, patches, and inhaled medications. They have been confirmed by reliable clinical studies to have a long-lasting bronchodilator effect, reduce asthma symptoms, enable exercise and daily life to be maintained, and improve the quality of life (QOL) of patients. They are particularly effective in reducing early morning and pre-dawn symptoms and exercise-induced asthma. However, because _β2 agonists do not have an anti-inflammatory effect, their use alone is inappropriate as a treatment, and it has been proven that their use in combination with drugs such as inhaled corticosteroids that have anti-inflammatory effects is very effective and appropriate.

[Medicinal use] Inhaled steroid/long-acting beta ₂ agonist combination [Medicinal name] Adoair (salmeterol xinafoate/fluticasone propionate) (39)
[Rating] ☆☆☆☆☆
[Drug name] Symbicort (budesonide-formoterol fumarate hydrate) (40)
[Rating] ☆☆☆☆☆

[Drug name] Flutiform (fluticasone propionate, formoterol fumarate hydrate) (32) (41)
[Rating] ☆☆☆☆
[Drug name] Relvar (vilanterol triphenylacetate/fluticasone furoate) (42)(43)
[Rating] ☆☆☆☆☆
[Evaluation points] Reliable clinical studies have confirmed that combining an inhaled corticosteroid with a long-acting _β2 agonist produces a synergistic effect, making it more effective than inhaling each drug individually, and that it also makes it possible to reduce the amount of steroid used. Currently, the above four types of inhaled combination drugs are on the market in Japan.

[Medicinal use] Long-acting anticholinergic drug [Drug name] Spiriva (tiotropium bromide hydrate) (45)
[Rating] ☆☆☆☆☆
[Evaluation points] Highly reliable clinical studies have proven that it is effective when used in combination with inhaled corticosteroids as a long-term control medication.

[Medicinal use] Anti-IgE antibody [Drug name] Xolair (omalizumab) (46) (47)
[Rating] ☆☆☆☆☆
[Key points] High-quality clinical studies have demonstrated that this drug is effective for patients in whom high-dose inhaled corticosteroids are insufficiently controlled.

[Medicinal use] Antiallergic drug [Drug name] Singulair (montelukast sodium) (44)
[Rating] ☆☆☆☆☆
[Drug name] Onon (Pranlukast hydrate) (9)(10)
[Rating] ☆☆☆☆☆
[Drug name] Intal (sodium cromoglycate) (8)
[Rating] ☆☆☆
[Drug name] Alesion (Epinastine hydrochloride) (8)
[Rating] ☆☆☆
[Drug name] IPD (suplatast tosilate) (8)
[Rating] ☆☆☆
[Evaluation Points] Antiallergic drugs are generally considered appropriate for use in atopic or mixed asthma, and mild to moderate asthma. These drugs should not be used as treatments for attacks, but are recommended for long-term management. In such cases, they are used in combination with anti-inflammatory drugs such as long-acting bronchodilators and inhaled corticosteroids. It takes 4 to 8 weeks or more for the effects to appear. However, the effectiveness of pranlukast hydrate has been confirmed by highly reliable clinical studies.

[Medicinal use] Antihistamine [Drug name] Celestamine (betamethasone/d-chlorpheniramine maleate combination drug)
[Rating] ☆☆
[Evaluation points] Expert opinion and experience support the idea that allergic symptoms can be effectively suppressed by combining with inhaled corticosteroids. The aim is to reduce the dose of inhaled corticosteroids.

As a treatment for attacks [Medicinal use] Short-acting bronchodilator [Drug name] Venetrin (salbutamol sulfate) (17)(22)(23)(33)～(37)
[Rating] ☆☆☆☆☆
[Drug name] Neophylline (aminophylline hydrate) (22)-(25)
[Rating] ☆☆☆☆☆
[Evaluation points] For temporary exacerbation of asthma symptoms, short-acting inhaled _β2 agonists are used as needed. The effectiveness of this has been confirmed by highly reliable clinical studies.
Depending on the severity of the attack (moderate or severe), it may be administered by injection.

As a treatment for moderate to severe attacks [Medicinal use] Corticosteroid [Drug name] Rinderon (betamethasone) (20)(21)(26)-(28)(38)
[Rating] ☆☆☆☆☆
[Drug name] Sol-Cortef (hydrocortisone sodium succinate) (20)(21)(26)-(28)(38)
[Rating] ☆☆☆☆☆
[Drug name] Solu-Medrol (methylprednisolone sodium succinate) (20)(21)(26)-(28)(38)
[Rating] ☆☆☆☆☆
[Evaluation points] The effectiveness of intravenous corticosteroids for treating moderate to severe attacks has been confirmed by highly reliable clinical studies.

Overall, it is currently the most reliable treatment <br /> Inhaled corticosteroids are the core of treatment Treatment for bronchial asthma can be broadly divided into two categories: everyday prevention to suppress inflammation in the airways, and treatment during attacks. Traditionally, medications that dilate the bronchi (bronchodilators) were the main treatment, but recently the main goal of treatment has been to use inhaled corticosteroids to suppress inflammation and make attacks less likely to occur in the long term.

If you gargle, you don't have to worry about side effects. Corticosteroids can cause side effects if absorbed into the bloodstream, but with inhalation therapy for bronchial asthma, if you gargle properly and wash away any corticosteroids remaining in your mouth, you don't have to worry about side effects like you would with oral or injected medications. In addition, the effectiveness of bronchodilators (theophylline sustained-release preparations, oral _β2 agonists, inhaled _β2 agonists, transdermal _β2 agonists, etc.) and anti-allergy drugs is also well established.
Treatment is based on a combination of these medications depending on the severity of the symptoms.

Use of a peak flow meter A peak flow meter is used to check the severity of asthma. A peak flow meter is a simple device that records the speed of air flow when you breathe in with all your might, and is also used by patients themselves to understand their symptoms and condition.
Subjective symptoms such as difficulty breathing may not appear until respiratory function has decreased by 40% or more, but by using a peak flow meter, even the slightest changes in respiratory function can be detected. Patients and their families may become accustomed to asthma attacks and tend to underestimate the symptoms, so by managing the condition based on the objective data obtained from a peak flow meter, appropriate treatment can be administered before the attack becomes severe.

Self-management is also important. Inhaled _β2 agonists are particularly effective when used in the early stages of an attack, but if the attack becomes severe, the patient may not be able to inhale enough, and the number of inhalations may increase, resulting in stronger side effects. It is important to predict attacks early based on changes in respiratory function.
Taking the symptoms lightly and neglecting treatment can lead to the aggravation of attacks. In the worst case, it can be life-threatening. Daily self-management, such as keeping an asthma diary, is an important part of treatment.

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(40)Rabe KF, Pizzichini E, Ställberg B, et al. Budesonide/formoterol in a single inhaler for maintenance and relief in mild-to-moderate asthma: a randomized, double-blind trial. Chest 2006; 129:246.
(41)Devillier P, Salvator H, Grassin-Delyle S, et al. A new fixed dose combination of fluticasone and formoterol in a pressurised metered-dose inhaler for the treatment of asthma. Rev Mal Respir. 2014;31(8):700-713. doi: 10.1016/j.rmr.2014.04.102. Epub 2014 May 20.
(42)Busse WW, Bleecker ER, Bateman ED, et al. Fluticasone furoate demonstrates efficacy in patients with asthma symptomatic on medium doses of inhaled corticosteroid therapy: an 8-week, randomised, placebo-controlled trial. Thorax. 2012 Jan;67(1):35-41. doi: 10.1136/thoraxjnl-2011-200308. Epub 2011 Aug 9.
(43)Lin J, Kang J, Lee SH, et al. Fluticasone furoate/vilanterol 200/25 mcg in Asian asthma patients: A randomized trial.Respir Med. 2014 Oct 31. pii: S0954-6111(14)00362-X. doi: 10.1016/j.rmed.2014.10.012. [Epub ahead of print]
(44)Price DB, Hernandez D, Magyar P, et al. Clinical Outcomes with Montelukast as a Partner Agent to Corticosteroid Therapy (COMPACT) International Study Group. Randomised controlled trial of montelukast plus inhaled budesonide versus double dose inhaled budesonide in adult patients with asthma. Thorax. 2003 Mar;58(3):211-6.
(45)Kew KM, Dahri K. et al. Long-acting muscarinic antagonists (LAMA) added to combination long-acting beta2-agonists and inhaled corticosteroids (LABA/ICS) versus LABA/ICS for adults with asthma. Cochrane Database Syst Rev. 2016 Jan 21;1:CD011721. [Epub ahead of print]
(46)Abraham I, Alhossan A, Lee CS, Kutbi H, MacDonald K. "Real-life" effectiveness studies of omalizumab in adult patients with severe allergic asthma: systematic review. Allergy. 2015 Dec 8. doi: 10.1111/all.12815. [Epub ahead of print]
(47)Rodrigo GJ, Neffen H. et al. Systematic review on the use of omalizumab for the treatment of asthmatic children and adolescents. Pediatr Allergy Immunol. 2015 Sep;26(6):551-6. doi: 10.1111/pai.12405. Epub 2015 Jul 1.

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
　気管支喘息(きかんしぜんそく)は気道に慢性の炎症がおこり、空気の流れが妨げられる病気です。発作性のせき、喘鳴(ぜんめい)（呼吸のたびに「ぜいぜい」という音がでること）や呼吸困難（息苦しさ）などがおもな症状であり、発作がくり返されるのが特徴です。
　発作は昼間より夜半から明け方におこる特徴があり、季節の変わり目、気候の不安定な時期におこりやすいことも昔からよく知られています。発作がおこっていないときでも気管支の粘膜には炎症がおきていて、ちょっとした刺激にも過敏に反応して発作が現れることになります。のどや胸がつまる感じになって、やがて喘鳴がおこり、呼吸が苦しくなり、さらに、激しいせきや痰(たん)がでます。
　このような症状は自然におさまったり、適切な治療をしたりすることで元に戻ります。しかし、長期にわたって発作の続く患者さんでは、炎症とその修復過程がくり返されるうちに気道の壁が厚くなって元に戻りにくくなり、さらに気道の過敏性が増加してしまいます。
　そこでなるべく発作のない状態を保ち、そうした気道の変化を防げれば、ほとんど健康な人と変わらない日常生活を送ることができます。しかし、病状のコントロールがうまくいかず、発作をくり返しながら重症化が進むと、死に至ることもあります。
　専門医の適切な診断とともに、自己管理も喘息の治療に欠かせないものです。喘息の重症度を確認するためにピークフローメーターが使用されます。ピークフローメーターは、思いきり息を吹き込んだ際の値を読み取るもので、簡便な装置のため患者さん自身が症状や病態を把握するためにも使用します。
　気管支喘息の重症度分類は次のようになっています。
　●ステップ1（軽症間欠型）
　　ピークフロー値は予測値の80パーセント以上、朝と晩のピークフロー値の変動は20パーセント未満、喘鳴、せき、呼吸困難は週に1回未満。
　●ステップ2（軽症持続型）
　　ピークフロー値は予測値の80パーセント以上、変動は20～30パーセント、症状は週1回以上であるが毎日ではない、日常生活や睡眠が妨げられることが月に1回以上、夜間症状が月に2回以上。
　●ステップ3（中等症持続型）
　　ピークフロー値は予測値の60以上80パーセント未満、変動は30パーセント以上、慢性的に症状がある。吸入β₂刺激薬がほとんど毎日必要。日常生活や睡眠が妨げられることが週1回以上、夜間症状が週1回以上。
　●ステップ4（重症持続型）
　　ピークフロー値は予測値の60パーセント未満、変動は30パーセント以上、治療を行っていてもしばしば増悪(ぞうあく)し、症状が持続し、日常生活が制限され、しばしば夜間症状の増悪などがみられ、経口副腎皮質(ふくじんひしつ)ステロイド薬連用、気管支拡張薬が必要である。
　急性に増悪する発作の重症度分類は以下のようになります。
　●軽度症状（小発作）
　　いつもは軽症あるいは良好にコントロールされている患者さんが、かぜや過労あるいは抗原曝露(こうげんばくろ)などで発作をおこした場合。比較的症状も軽く、日常生活に支障はない。ピークフロー値は予測値の80パーセント以上。
　●中等度症状（中発作）
　　せき、痰、呼吸困難の程度はかなり強くなり、手持ちのβ₂刺激薬の吸入では効果はあるが、あまり長続きしない状態になっている。ピークフロー値は予測値の60～80パーセントに低下し、苦しくて横になれない（起座(きざ)呼吸）状態。
　●高度症状（大発作）
　　中等症～重症の患者がかぜや過労をきっかけとして発作状態に至り、それでも十分な治療を受けずにがんばっているうちに大発作に陥ることがある。ピークフロー値は予測値の60パーセント未満。
　●重篤(じゅうとく)症状・エマージェンシー（重篤発作）
　　大発作の患者が治療をおろそかにした場合に出現することが多い。呼吸音は減弱し、呼吸困難感は非常に強く、顔面から冷や汗がしたたり落ち、歩くことも口をきくこともできない状態。ピークフロー値は測定不可能。

●病気の原因や症状がおこってくるしくみ
　気管支喘息は遺伝的な要素と環境的な要素が関係しておこると考えられていますが、明確な原因はいまだに不明です。遺伝的には患者さんが生まれつきアレルギーをおこしやすい体質をもっているために発病すると考えられるアトピー性喘息と、生まれつきの体質とは関係なく発病する非アトピー性喘息とに分けられます。アトピー性喘息は即時型アレルギーという反応が、非アトピー性喘息は遅発型アレルギーという反応が関与しているといわれています。いずれもふつうの人より気道の過敏性が強く、刺激を受けやすくなっています。
　発作をおこす原因となっている抗原（ダニ・カビ・花粉など）との接触のほか、かぜ、過労、ストレス、ペット、天候、運動、たばこの煙、強いにおい、冷気、飲酒、月経などさまざまなものが原因としてあげられます。重症で不安定な状態であれば、なんらかのきっかけで病態が激変し、チアノーゼや意識障害をおこし、喘息死（窒息死）に至る場合もあります。

●病気の特徴
　1960年代には人口の1パーセント前後といわれていた気管支喘息の患者さんの数は2010年代の調査では約3～5パーセントと増加しています。とくに最近の傾向として都市部の子どもとお年寄りに増加傾向がみられています。

よく行われている治療とケアをEBMでチェック

　気管支喘息には、いくつかガイドラインが存在しますが、国際指針となっている「GINA2014」や日本アレルギー学会の「喘息予防・管理ガイドライン」では、これまで同様に、吸入副腎皮質ステロイド薬の重要性が強調され、長期管理薬の中心的な薬として位置付けられています。

■ステップ1（軽症間欠型）
［治療とケア］気道の炎症を抑えて肺機能を維持し、長期的に発作をおこりにくくする
［評価］☆☆☆☆☆
［評価のポイント］　軽症間欠型の患者さんでは、症状の回数などに応じて、低用量の吸入副腎皮質ステロイド薬、テオフィリン徐放剤、またはロイコトリエン受容体拮抗(きっこう)薬を含む抗アレルギー薬を用いるかどうかを検討します。
　軽症喘息の患者さんを対象とした非常に信頼性の高い臨床研究により、吸入副腎皮質ステロイド薬がピークフロー値の改善に有効であることが示されています。
　抗アレルギー薬は、軽症から中等症までの患者さんに対して効果が認められています。6～10週で効果が認められない場合は、ほかの抗アレルギー薬に変更するか、ほかの治療法に変更するよう勧めている臨床研究もあります。ロイコトリエン受容体拮抗薬の有効性はほぼ確立しています。(1)～(17)

■ステップ2（軽症持続型）
［治療とケア］気道の炎症を抑えて肺機能を維持し、長期的に発作をおこりにくくする
［評価］☆☆☆☆☆
［評価のポイント］　軽症持続型の患者さんでは、低用量の吸入副腎皮質ステロイド薬、長時間作用性の気管支拡張薬（テオフィリン徐放剤、β₂刺激薬など）、ロイコトリエン受容体拮抗薬を含む抗アレルギー薬のいずれかを単独あるいは併用で、毎日用います。
　軽症持続型の患者さんにおいても、非常に信頼性の高い臨床研究により、吸入副腎皮質ステロイド薬は、ピークフロー値の改善に有効であるとされています。また、長時間作用性の気管支拡張薬（テオフィリン徐放剤）の効果は、吸入副腎皮質ステロイド薬と同等であるかやや劣るとされ、長期的には、吸入副腎皮質ステロイド薬のほうが明らかに有効であるとされています。
　経皮吸収型のβ₂刺激薬も軽症から中等症の患者さんに対して、ピークフロー値を改善する効果があると報告されています。(1)～(18)

■ステップ3（中等症持続型）
［治療とケア］気道の炎症を抑えて肺機能を維持し、長期的に発作をおこりにくくする
［評価］☆☆☆☆☆
［評価のポイント］　中等症持続型の患者さんでは、中～高用量の吸入副腎皮質ステロイド薬、長時間作用性の気管支拡張薬（テオフィリン徐放剤、β₂刺激薬など）、炎症を抑制する作用のある抗アレルギー薬（ロイコトリエン受容体拮抗薬など）、長時間作用性抗コリン薬を併用で毎日用います。これらの効果は非常に信頼性の高い臨床研究によって確認されています。
　中用量以上の吸入副腎皮質ステロイド薬を使用しているにもかかわらず、喘息症状が安定しない場合、吸入副腎皮質ステロイド薬を倍量にするかわりにテオフィリン徐放剤を併用すると、その効果は同等かテオフィリン徐放剤併用のほうが若干まさるとの報告があります。(1)～(18)(45)

■ステップ4（重症持続型）
［治療とケア］気道の炎症を抑えて肺機能を維持し、長期的に発作をおこりにくくする
［評価］☆☆☆☆☆
［評価のポイント］　重症持続型の患者さんでは、高用量の吸入副腎皮質ステロイド薬、長時間作用性の気管支拡張薬（テオフィリン徐放剤、β₂刺激薬など）、長時間作用性抗コリン薬を毎日用います。それでも症状が安定せず、しばしば増悪することがある場合は、経口副腎皮質ステロイド薬を短期で用いたり、通年性吸入アレルゲンに対して陽性かつ血清IgE値が30～1500IU/mlの場合に抗IgE抗体の注射を行うこともあります。さらに、抗アレルギー薬の併用も考慮するなどして、できるだけ症状を抑え、日常生活を続けられるようにします。これらの治療の効果については非常に信頼性の高い臨床研究によって確認されています。(19)～(21)(45)(46)

■ステップ1～4
［治療とケア］発作時には発作治療薬を用いる
［評価］☆☆☆☆☆
［評価のポイント］　軽症～重症いずれの患者さんでも、発作に対しては短時間作用性の気管支拡張薬（吸入β₂刺激薬）の頓用で抑えます。ただし、重症の患者さんで状態が不安定で発作がしばしばおこる場合には、短期間だけ経口副腎皮質ステロイド薬を用いることがあります。これらの効果は、非常に信頼性の高い臨床研究によって確認されています。
　吸入β₂刺激薬の頓用については、1日3～4回までとし、それ以上必要になる場合は、現在の治療では症状がコントロールできていないと判断し、治療を強化します（ステップ1から2へというようにステップアップする）。一方、少なくとも3カ月以上症状が安定している場合には、治療の段階を下げ（ステップダウン）、薬の使用を軽減することもあります。(1)～(21)

■軽度症状（小発作）
［治療とケア］吸入気管支拡張薬の頓用を追加する
［評価］☆☆☆☆☆
［評価のポイント］　軽度の発作には、短時間作用性の吸入β₂刺激薬の頓用を追加します。スペーサーとネブライザー吸入で、ほぼ同等の効果があることが非常に信頼性の高い臨床研究によって確認されています。ただし、軽症間欠型の患者さんに、吸入副腎皮質ステロイド薬を用いないで、β₂刺激薬を常用することは、むしろ、気道過敏性や肺機能をさらに悪化させるとされています。テオフィリン薬（アミノフィリン水和物）の点滴の静脈注射でも状態が改善することが示されています。(16)(22)～(24)

■中等度症状（中発作）
［治療とケア］気管支拡張薬の吸入の反復、点滴、皮下注射、副腎皮質ステロイド薬の静脈注射を行う
［評価］☆☆☆☆☆
［評価のポイント］　中発作の患者さんでは、救急外来の受診が必要です。まず、β₂刺激薬のネブライザー吸入を行い、1時間程度で症状が改善すれば、帰宅可能です。
　改善しない場合は、β₂刺激薬の皮下注射、テオフィリン薬（アミノフィリン水和物）の点滴、副腎皮質ステロイド薬の静脈注射などを行います。これらの治療の効果は非常に信頼性の高い臨床研究によって確認されています。
　2～4時間程度治療しても反応が不十分であったり、反応がなければ入院治療が必要な場合もありえます。(22)～(25)

■高度症状（大発作）
［治療とケア］気管支拡張薬の吸入の反復、点滴、皮下注射、副腎皮質ステロイド薬の静脈注射、酸素の使用を行う
［評価］☆☆☆☆☆
［評価のポイント］　大発作の患者さんでは、救急外来の受診が必要です。β₂刺激薬のネブライザー吸入を反復して行い、β₂刺激薬の皮下注射、テオフィリン薬（アミノフィリン水和物）の点滴、副腎皮質ステロイド薬の静脈注射などを追加します。これらの治療の効果は非常に信頼性の高い臨床研究によって確認されています。
　通常、1時間程度で改善しなければ入院を考慮します。(23)～(28)(38)

■重篤症状・エマージェンシー（重篤発作）
［治療とケア］ただちに入院し、ICUで大発作の治療を継続する
［評価］☆☆☆☆☆
［評価のポイント］　重篤発作の患者さんでは、呼吸困難も強く、チアノーゼや意識障害をおこしている場合もあります。ただちに入院が必要となります。
　β₂刺激薬のネブライザー吸入を反復して行い、β₂刺激薬の皮下注射、テオフィリン薬（アミノフィリン水和物）の点滴、副腎皮質ステロイド薬の静脈注射などを行いますが、反応しない、あるいはさらに悪化するような場合は人工呼吸や気道内の吸入や洗浄を行います。また、気管支拡張作用のある麻酔薬（イソフルラン、セボフルラン、エンフルレンなど）を用いる場合もあります。
　これらの治療の効果は非常に信頼性の高い臨床研究によって確認されています。(20)(23)～(28)(38)

よく使われている薬をEBMでチェック

長期管理薬として
［薬用途］吸入副腎皮質ステロイド薬
［薬名］キュバール（ベクロメタゾンプロピオン酸エステル）(4)(7)(29)
［評価］☆☆☆☆☆
［薬名］フルタイド（フルチカゾンプロピオン酸エステル）(4)(29)
［評価］☆☆☆☆☆
［薬名］パルミコート（ブデソニド）(4)(29)(30)
［評価］☆☆☆☆☆
［薬名］オルベスコ（シクレソニド）(4)(29)(30)
［評価］☆☆☆☆☆
［薬名］アズマネックス（モメタゾンフランカルボン酸エステル）(4)(31)
［評価］☆☆☆☆☆

［評価のポイント］　吸入副腎皮質ステロイド薬は局所抗炎症効果にすぐれ、全身的な影響が少ない薬剤で、現在もっとも効果的な喘息治療薬であると考えられています。吸入副腎皮質ステロイド薬中心の薬物療法を適切に行うことで、発作による入院、喘息死の頻度が減少してきています。吸入副腎皮質ステロイド薬は喘息患者さんの気道炎症を改善し、その結果自覚症状、肺機能、気道過敏性を改善させます。とくに早期に用いれば気道リモデリングを改善し、肺機能の低下を防止できる可能性があります。高用量の吸入副腎皮質ステロイド薬を用いた患者さんでは、骨、副腎機能などへの影響が出現する可能性があります。長期に使用する場合には、使用量を最少限にするべきです。目、皮膚などへの影響にも注意する必要があります。これらのことは、非常に信頼性の高い臨床研究によって確認されています。

［薬用途］長時間作用性の気管支拡張薬
［薬名］ユニフィルLA／テオドール／ユニコン（テオフィリン徐放剤）(5)～(7)
［評価］☆☆☆☆
［評価のポイント］　軽症、中等症の患者さんに対する、テオフィリン徐放剤の喘息症状および肺機能の改善効果については信頼性の高い臨床研究によって確認されています。ただし、その効果は吸入副腎皮質ステロイド薬と同等であるか少し劣るとされ、長期的には、明らかに吸入副腎皮質ステロイド薬のほうが有効であると報告されています。中用量以上の吸入副腎皮質ステロイド薬を使用しているにもかかわらず、喘息症状が安定しない場合、吸入副腎皮質ステロイド薬を倍量にするかわりにテオフィリン徐放剤を併用すると、その効果は同等かテオフィリン徐放剤併用のほうが少しまさります。

［薬名］スピロペント（クレンブテロール塩酸塩）(5)～(7)
［評価］☆☆☆☆
［薬名］メプチン（プロカテロール塩酸塩水和物）(17)(22)(23)(33)～(37)
［評価］☆☆☆☆☆
［薬名］ホクナリンテープ（ツロブテロール）(17)(22)(23)(33)～(37)
［評価］☆☆☆☆☆
［薬名］セレベント（サルメテロールキシナホ酸塩）
［評価］☆☆☆☆
［評価のポイント］　長時間作用性のβ₂刺激薬には経口薬、貼付薬、吸入薬があり、長時間にわたる気管支拡張効果をもたらし、喘息症状を軽減し、運動や日常生活が維持でき、患者さんの生活の質（QOL）を改善することが信頼性の高い臨床研究によって確認されています。とくに早朝・未明の症状や運動誘発喘息の軽減に有効です。しかし、β₂刺激薬は抗炎症作用をもたないため、単独使用は治療としては不適切であり、抗炎症作用をもつ吸入副腎皮質ステロイド薬などの薬剤との併用が非常に有効で適切であることが証明されています。

［薬用途］吸入ステロイド薬／長時間作用性β₂刺激薬配合剤
［薬名］アドエア（サルメテロールキシナホ酸塩・フルチカゾンプロピオン酸エステル）(39)
［評価］☆☆☆☆☆
［薬名］シムビコート（ブデソニド・ホルモテロールフマル酸塩水和物）(40)
［評価］☆☆☆☆☆

［薬名］フルティフォーム（フルチカゾンプロピオン酸エステル・ホルモテロールフマル酸塩水和物）(32)(41)
［評価］☆☆☆☆
［薬名］レルベア（ビランテロールトリフェニル酢酸塩・フルチカゾンフランカルボン酸エステル）(42)(43)
［評価］☆☆☆☆☆
［評価のポイント］　吸入副腎皮質ステロイド薬と長時間作用性β₂刺激薬を組み合わせることにより、相乗効果をきたして、個々に吸入するより有効性の高いこと、および、ステロイド薬の減量が可能になることが信頼性の高い臨床研究によって確認されています。現在わが国では、上記4種類の吸入薬配合剤が発売されています。

［薬用途］長時間作用性抗コリン薬
［薬名］スピリーバ（チオトロピウム臭化物水和物）(45)
［評価］☆☆☆☆☆
［評価のポイント］　長期管理薬として吸入副腎皮質ステロイド薬と併用することにより効果が得られることが、非常に信頼性の高い臨床研究によって証明されています。

［薬用途］抗IgE抗体
［薬名］ゾレア（オマリズマブ）(46)(47)
［評価］☆☆☆☆☆
［評価のポイント］　高用量の吸入副腎皮質ステロイド薬でもコントロールが不十分な患者さんに有効であることが、質の高い臨床研究によって証明されています。

［薬用途］抗アレルギー薬
［薬名］シングレア（モンテルカストナトリウム）(44)
［評価］☆☆☆☆☆
［薬名］オノン（プランルカスト水和物）(9)(10)
［評価］☆☆☆☆☆
［薬名］インタール（クロモグリク酸ナトリウム）(8)
［評価］☆☆☆
［薬名］アレジオン（エピナスチン塩酸塩）(8)
［評価］☆☆☆
［薬名］アイピーディ（スプラタストトシル酸塩）(8)
［評価］☆☆☆
［評価のポイント］　抗アレルギー薬は、一般にアトピー性喘息または混合型喘息、軽症および中等症喘息に用いることが適当と考えられています。これらの薬剤は発作治療薬として用いるべきではなく、長期管理薬として用いることが推奨されています。その際、長時間作用性の気管支拡張薬や、吸入副腎皮質ステロイド薬などの抗炎症薬と併用します。効果が現れるまでには4～8週以上を要します。ただし、プランルカスト水和物の有効性は非常に信頼性の高い臨床研究によって確認されています。

［薬用途］抗ヒスタミン薬
［薬名］セレスタミン（ベタメタゾン・ｄ-クロルフェニラミンマレイン酸塩配合剤）
［評価］☆☆
［評価のポイント］　吸入副腎皮質ステロイド薬との併用によりアレルギー症状を効果的に抑制ができることは、専門家の意見と経験によって支持されています。吸入副腎皮質ステロイド薬の用量の削減が目的となります。

発作治療薬として
［薬用途］短時間作用性の気管支拡張薬
［薬名］ベネトリン（サルブタモール硫酸塩）(17)(22)(23)(33)～(37)
［評価］☆☆☆☆☆
［薬名］ネオフィリン（アミノフィリン水和物）(22)～(25)
［評価］☆☆☆☆☆
［評価のポイント］　喘息症状の一時的な増悪には短時間作用性の吸入β₂刺激薬の頓用を行います。この効果は非常に信頼性の高い臨床研究によって確認されています。
　発作の重症度によっては（中発作以上）、注射で用いることもあります。

中等度以上の発作治療薬として
［薬用途］副腎皮質ステロイド薬
［薬名］リンデロン（ベタメタゾン）(20)(21)(26)～(28)(38)
［評価］☆☆☆☆☆
［薬名］ソル・コーテフ（ヒドロコルチゾンコハク酸エステルナトリウム）(20)(21)(26)～(28)(38)
［評価］☆☆☆☆☆
［薬名］ソル・メドロール（メチルプレドニゾロンコハク酸エステルナトリウム）(20)(21)(26)～(28)(38)
［評価］☆☆☆☆☆
［評価のポイント］　中等度以上の発作に対する副腎皮質ステロイド薬の静脈注射の有効性は、非常に信頼性の高い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
吸入副腎皮質ステロイド薬が治療の中心
　気管支喘息の治療は、気道の炎症を抑える日常的な予防と発作時の治療の二つに大別されます。従来は気管支を広げる薬（気管支拡張薬）が主体でしたが、最近は吸入副腎皮質ステロイド薬を用いて炎症を抑制し、長期的に発作をおこしにくくすることが治療の主目的となってきました。

うがいをすれば副作用の心配はない
　副腎皮質ステロイド薬は血液に吸収されれば副作用をおこす可能性がありますが、気管支喘息での吸入療法では、うがいをきちんとして口に残った副腎皮質ステロイド薬を洗い流せば、内服薬や注射薬による場合のような心配はいりません。そのほかに、気管支拡張薬（テオフィリン徐放剤、経口β₂刺激薬、吸入β₂刺激薬、経皮β₂刺激薬など）、抗アレルギー薬なども、有効性は十分確立されていると考えられます。
　これらの薬を組み合わせながら、症状の重症度に応じて治療が行われます。

ピークフローメーターの活用
　喘息の重症度を確認するためにはピークフローメーターが使用されます。ピークフローメーターは、思いっきり息を吹き込んだ際の空気の流れる速度を記録する簡便な装置で、患者さん自身が症状や病態を把握するためにも使用します。
　呼吸困難感などの自覚症状は、呼吸機能が40パーセント以上低下しなければ現れてこないこともありますが、ピークフローメーターを用いれば、わずかな呼吸機能の変化を知ることができます。患者さん自身、また家族も喘息発作に慣れてしまっていて、症状を軽く見てしまうこともありますので、ピークフローメーターで得られる客観的なデータに基づいて管理すれば、発作が重症化する前に適切な治療を行うことができます。

自己管理も重要
　とくに吸入β₂刺激薬は発作の初期に用いると効果的ですが、発作が強くなってしまうと十分に吸入できずに、吸入回数が増え、副作用が強くでることになってしまいます。呼吸機能の変化から早めに発作を予測することは大切です。
　症状を軽くみて治療を怠ることは発作の重症化を招きかねません。最悪の場合は生命にかかわることもあります。喘息日記をつけるなど毎日の自己管理は重要な治療の一部となります。

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