Therapeutic agent for asthmatic attack and prophylactic agent for plastic bronchitis

Abstract

To provide a therapeutic agent for asthmatic attacks associated with viral infection, and a prophylactic agent for plastic bronchitis associated with viral or bacterial infection.SOLUTION: A therapeutic agent for asthmatic attacks associated with viral infection or a prophylactic agent for plastic bronchitis associated with viral or bacterial infection is prepared that comprises an antibody that binds to immunoglobulin E (IgE) as an active ingredient. Here, a representative example of the virus is influenza virus (A(H1N1)pdm09).SELECTED DRAWING: Figure 1A

Description

[Technical field]

[0001] The present invention relates to a therapeutic agent for bronchial asthma attacks accompanied by viral infections, and a preventive agent for plastic bronchitis accompanied by viral or bacterial infections. [Background technology]

[0002] The A(H1N1)pdm09 influenza virus (hereinafter, simply referred to as "A(H1N1)pdm09"), which caused a global pandemic in 2009, caused sudden respiratory failure requiring intensive care management, and had a significant impact on humanity. The present inventors retrospectively examined cases of acute respiratory failure associated with A(H1N1)pdm09 infection and found that compared with seasonal influenza virus infection, there were more respiratory complications such as pneumonia and atelectasis, and severe bronchial asthma attacks were more likely to occur. Furthermore, they found that serum total IgE levels were significantly elevated in cases with these complications (see Non-Patent Document 1). Furthermore, the present inventors infected asthma model mice with A(H1N1)pdm09 and found that, compared with non-asthmatic mice, the bronchoalveolar lavage fluid (BAL fluid) of the infected asthmatic mice had significantly higher levels of interleukin (IL)-6, IL-10, and TNF-α, whereas the IFN-γ concentration was significantly lower (see Non-Patent Document 2). Many aspects of the mechanism by which the disease worsens remain unclear, and no studies have been conducted on preventive or therapeutic methods for severe respiratory complications due to A(H1N1)pdm09 infection. The present inventors clarified through infection experiments using bronchial asthma model mice that bronchial asthma is involved in the aggravation of the disease (see Non-Patent Document 2). However, it remains unclear why the disease aggravates, and no effective preventive or therapeutic method has been established for preventing or treating severe respiratory complications triggered by infection.

[0003] In this context, the present inventors have proposed a leukotriene receptor antagonist as a prophylactic or ameliorating agent for bronchial asthma caused by A(H1N1)pdm09 infection (see Patent Document 1). However, this has not yet been put to practical use.

[0004] Plastic bronchitis has been attracting attention as a factor that causes severe respiratory failure due to influenza infection (Non-Patent Document 3). Regarding the mechanism of development of plastic bronchitis, Yoshida et al. reported the involvement of a special cell death of eosinophils (ETosis) from the analysis of mucus plugs collected from patients with plastic bronchitis (see Non-Patent Documents 4 and 5). However, elucidation of the mechanism of development of plastic bronchitis, including the mechanism of ETosis, is an important subject for future study, and prevention or treatment of plastic bronchitis has not been clarified. Furthermore, Yamaoka et al. reported that existing influenza drug treatments cannot prevent or treat plastic bronchitis triggered by influenza infection, and that treatment with a positive-negative extracorporeal ventilator (BCV) together with multiple drug treatments could promote expectoration, expectorate mucus plugs, and inhibit further progression of atelectasis (see Non-Patent Document 6). Although methods thought to be effective in removing mucus plugs have been reported, it was thought to be difficult to develop a drug that was sufficiently effective in preventing the occurrence of mucus plugs, which are the root cause of plastic bronchitis.

[0005] Meanwhile, in domestic and international guidelines, a clear distinction is made between long-term control drugs for basic and additional treatment of bronchial asthma and drugs for treating asthma attacks. Here, this guideline states that antibodies that bind to IgE (anti-IgE antibodies) are to be used only as long-term control drugs for asthma. In other words, it is only assumed that they are to be used as long-term control drugs for asthma patients who are not experiencing asthma attacks and to prevent attacks. On the other hand, the effect of anti-IgE antibodies on asthma attacks has not been shown, and they are not applicable as influenza treatment drugs (see Non-Patent Documents 7-9). In addition, anti-IgE antibodies are disclosed as treatment drugs for allergic bronchial asthma and rhinitis (see Patent Documents 2-4), but they are only intended for allergic bronchial asthma and do not take into account the treatment of asthma attacks. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] JP 2016-175866 A [Patent Document 2] Japanese Patent Application Publication No. 11-510172 [Patent Document 3] Special Publication No. 2001-505181 [Patent Document 4] Special Publication No. 2001-529180 [Non-patent literature]

[0007] [Non-Patent Document 1] Hasegawa S, et al. Pediatr Allergy Immunol 22: 119-123, 2011 [Non-Patent Document 2] Okada S, et al. Cytokine 63:194-200, 2013 [Non-Patent Document 3] Zhang J, et al., Int J Pediatr Otorhinolaryngol. 2015 Apr;79(4):481-6. doi: 10.1016 / j.ijporl.2015.01.002. [Non-Patent Document 4] Yoshida M, et al. Chest Infections Research Letters 160(3):854-857, 2021 [Non-Patent Document 5] National Research and Development Agency National Center for Child Health and Development NEWS RELEASE May 18, 2021 URL:www.ncchd.go.jp / press / 2021 / 0518.pdf [Non-Patent Document 6] Akiko Yamaoka et al. Pediatric Infection and Immunology Vol.24 No.3 269-273, 2012 [Non-Patent Document 7] Jun Tamaki Allergy 67(9), 1263-1268, 2018(Heisei 30) [Non-Patent Document 8] Global Initiative for Asthma, 2006 Medical Communications Resources, Inc., p 58-59 URL: ginasthma.org / wp-content / uploads / 2019 / 01 / 2006-GINA.pdf [Non-Patent Document 9] Pediatric Asthma Treatment and Management Guidelines 2020, Japan Society of Pediatric Allergy, pp. 131-133, 152-155 Summary of the Invention [Problem to be solved by the invention]

[0008] As typified by A(H1N1)pdm09 infection, acute respiratory failure triggered by influenza virus infection is associated with bronchial asthma attacks and plastic bronchitis, and it was thought that methods for preventing or treating these were necessary. At present, existing influenza treatment drugs are not effective against bronchial asthma attacks or plastic bronchitis. Drug treatment with inhaled β-agonists and steroids, which are recommended for bronchial asthma attacks, has little effect on improving respiratory conditions, and there is no drug therapy for plastic bronchitis itself. For severely ill patients who require intensive care, extracorporeal positive-negative pressure ventilators (BCV) and extracorporeal membrane oxygenation (ECMO) are sometimes used as emergency measures. However, the use of extracorporeal positive-negative pressure ventilators and extracorporeal membrane oxygenation can be a physical and economic burden on the patient, and a treatment system involving many medical staff members must be established. In addition, direct aspiration of mucus plugs is sometimes performed using a bronchoscope, but there are concerns that there are areas where mucus plugs cannot be aspirated, and that the burden on the lungs of pediatric patients is large. The desired effect of a drug against plastic bronchitis is to prevent the formation of mucus plugs. It is essential to clarify the mechanism of plastic bronchitis formation, but the mechanism has not been fully elucidated, and no drug that is considered to be effective has been put into practical use. Therefore, the object of the present invention is to provide a therapeutic agent for bronchial asthma attacks associated with viral infection, and a preventive agent for plastic bronchitis associated with viral or bacterial infection. [Means for solving the problem]

[0009] In order to solve the above problems, the present inventors have been searching for a therapeutic agent for bronchial asthma attacks associated with the above-mentioned viral infections and a preventive agent for plastic bronchitis associated with viral or bacterial infections. They discovered that when an anti-IgE antibody was administered to a bronchial asthma model mouse after infection with influenza virus (A(H1N1)pdm09), the administration of the anti-IgE antibody suppressed the airway contraction response to methacholine stimulation as compared to a control antibody, and also had an inhibitory effect on the formation of mucus plugs in the bronchi, thereby completing the present invention.

[0010] That is, the present invention is as follows. [1] A treatment for bronchial asthma attacks associated with viral infections, the active ingredient of which is an antibody that binds to immunoglobulin E (IgE). [2] The therapeutic agent for an asthma attack described in [1] above, for administration to a subject who has a history of an asthma attack or who has been diagnosed with bronchial asthma. [3] The therapeutic agent for bronchial asthma attack according to [1] or [2] above, characterized in that the virus is influenza virus (A(H1N1)pdm09). [4] The therapeutic agent for bronchial asthma attacks according to [1] or [2] above, wherein the antibody that binds to IgE is omalizumab. [5] A preventive agent for plastic bronchitis associated with viral or bacterial infection, which contains as an active ingredient an antibody that binds to immunoglobulin E (IgE). [6] The preventive agent for mold bronchitis described in [5] above, for administration to a subject who has a history of bronchial asthma attacks or who has been diagnosed with bronchial asthma. [7] The preventive agent for plastic bronchitis according to [5] or [6] above, characterized in that the virus is influenza virus (A(H1N1)pdm09). [8] The preventive agent for plastic bronchitis according to [5] or [6] above, characterized in that the antibody that binds to IgE is omalizumab.

[0011] Other aspects of the present invention include (I) a method for treating bronchial asthma attacks associated with viral infection, comprising administering an effective amount of an antibody that binds to immunoglobulin E (IgE) to a subject who has developed bronchial asthma attacks associated with viral infection, (II) an antibody that binds to immunoglobulin E (IgE) for use in treating bronchial asthma attacks associated with influenza virus infection, and (III) use of an antibody that binds to immunoglobulin E (IgE) for preparation of a therapeutic agent for bronchial asthma attacks associated with viral infection. Note that the "effective amount" in (I) above means an amount that is effective for treating bronchial asthma attacks when administered to a subject who has developed bronchial asthma attacks associated with viral infection. Further, other aspects of the present invention include (IV) a method for preventing plastic bronchitis associated with viral or bacterial infection, comprising administering an effective amount of an antibody that binds to immunoglobulin E (IgE) to a subject in whom plastic bronchitis associated with viral or bacterial infection is to be prevented, (V) an antibody that binds to immunoglobulin E (IgE) for use in preventing plastic bronchitis associated with viral or bacterial infection, and (IV) use of an antibody that binds to immunoglobulin E (IgE) for preparation of a preventive agent for plastic bronchitis associated with viral or bacterial infection. Note that the "effective amount" in the above (VI) means an amount effective for preventing plastic bronchitis associated with viral or bacterial infection, to be administered to a subject in whom plastic bronchitis associated with viral or bacterial infection is to be prevented. Effect of the Invention

[0012] The present invention makes it possible to treat bronchial asthma attacks caused by viral infections and to prevent plastic bronchitis caused by viral or bacterial infections. [Brief description of the drawings]

[0013] [Figure 1A]In Example 1, bronchial asthma model mice were infected with influenza virus A(H1N1)pdm09, and anti-IgE antibody was administered one hour after infection, and methacholine was inhaled on the seventh day after infection. The results show the results of examining total airway resistance (Rrs). [Figure 1B] In Example 1, bronchial asthma model mice were infected with influenza virus A(H1N1)pdm09, and anti-IgE antibody was administered 24 hours after infection, and methacholine was inhaled on the 7th day after infection. The results show the total airway resistance (Rrs) measured. [Figure 1C] In Example 1, bronchial asthma model mice were infected with influenza virus A(H1N1)pdm09, and anti-IgE antibody was administered 48 hours after infection, and methacholine was inhaled on the 7th day after infection. The results show the total airway resistance (Rrs) measured. [Diagram 2] In Example 2, bronchial asthma model mice were infected with influenza virus A(H1N1)pdm09, and then anti-IgE antibody was administered. On the seventh day, the bronchial tissue was stained with periodic acid-Schiff (PAS) and observed under a microscope. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0014] The therapeutic agent for bronchial asthma attacks associated with viral infection of the present invention is not particularly limited as long as it is a therapeutic agent for bronchial asthma attacks associated with viral infection that contains an antibody that binds to immunoglobulin E (IgE) as an active ingredient, and is hereinafter also referred to as "the therapeutic agent for bronchial asthma attacks of the present invention". Also, the prophylactic agent for plastic bronchitis associated with viral or bacterial infection of the present invention is not particularly limited as long as it is a prophylactic agent for plastic bronchitis associated with viral or bacterial infection that contains an antibody that binds to immunoglobulin E (IgE) as an active ingredient, and is hereinafter also referred to as "the prophylactic agent for plastic bronchitis of the present invention".

[0015] In this specification, bronchial asthma attack means a state in which airway hyperresponsiveness is increased, and some kind of stimulation causes the contraction of bronchial smooth muscle or the thickening of mucous membrane, causing the narrowing of the airway, and causing coughing, wheezing, and dyspnea.In this specification, bronchial asthma means a state in which the above-mentioned transient coughing, wheezing, and dyspnea do not occur, and is clearly distinguished from bronchial asthma attack in this specification.In addition, in this specification, "treatment of bronchial asthma attack" means a means for the purpose of not only suppressing the progression and aggravation of bronchial asthma attack, but also slowing down, reducing, or stopping bronchial asthma attack.

[0016] Examples of the above viruses include influenza viruses such as influenza A virus and influenza B virus, respiratory syncytial virus, human rhinovirus, parainfluenza, human metapneumovirus, enterovirus, adenovirus, human bocavirus, coxsackievirus, and echovirus, as well as viruses described in the literature by Abe N et al. (Pediatr Allergy Immunol. 2019 Nov; 30(7): 724-731.). Examples of the above influenza A viruses include influenza (A(H1N1)) viruses such as influenza (A(H1N1)pdm09) virus, influenza (A(H3N2)) viruses, and influenza (A(H5N1)) viruses as representative epidemic viruses. The influenza (A(H1N1)pdm09) virus is the name given to the novel influenza virus that emerged in 2009, as determined by the World Health Organization (WHO) on October 18, 2011 (see URL: www.who.int / influenza / gisrs_laboratory / terminology_ah1n1pdm09 / en / ).

[0017] In this specification, the term "plastic bronchitis" refers to a disease in which the mucus plug of the plastic clogging the bronchi leads to respiratory failure. The plastic bronchitis is caused by infection with the above-mentioned virus or bacteria. Note that the above-mentioned plastic bronchitis does not include asthma attacks without mucus plugs. The above-mentioned bacteria can include Streptococcus pneumoniae or Haemophilus influenzae.

[0018] Diagnosis of whether or not a subject requires prophylaxis against plastic bronchitis can be made by checking for the presence of mucus plugs in sputum, by checking for mucus plugs using CT or MRI imaging, or by checking for mucus plugs using a bronchoscope.

[0019] The present therapeutic agent for asthma attack is preferably a therapeutic agent for asthma attack to be administered to a subject who has developed an asthma attack due to infection with influenza virus such as influenza A virus or B virus, more preferably influenza (A(H1N1)pdm09) virus. The present prophylactic agent for plastic bronchitis is preferably a prophylactic agent for plastic bronchitis to be administered to a subject who needs to prevent plastic bronchitis due to infection with influenza virus such as influenza A virus or B virus, more preferably influenza (A(H1N1)pdm09) virus. Infection with influenza A virus or B virus can be determined using a commercially available influenza test kit. Subtype and antigenicity can be confirmed in detail by known methods such as hemagglutination inhibition test and genetic testing, and infection with influenza (A(H1N1)pdm09) virus can be confirmed by the above-mentioned known methods.

[0020] The present therapeutic agent for bronchial asthma attacks or the present preventive agent for plastic bronchitis is preferably a therapeutic agent for bronchial asthma attacks or a preventive agent for plastic bronchitis to be administered to a subject who has a history of bronchial asthma attacks or has been diagnosed with bronchial asthma. A history of bronchial asthma attacks can be determined by comprehensively considering information obtained by interviewing parents and siblings or the subject himself / herself about allergy diseases, regardless of the severity (minor attacks, moderate attacks, major attacks, respiratory failure). Symptoms of bronchial asthma can be confirmed by known methods such as respiratory function measurement using testing equipment such as a spirometer, and exhaled nitric oxide tests.

[0021] As used herein, "immunoglobulin (IgE)" refers to one of the classes of immunoglobulins. It binds with high affinity to FcεRI on the surface of cells such as mast cells and basophils, and when an antigen binds to the Fab portion of IgE, an intracellular signal is transmitted inside the cell, causing an allergic response.

[0022] The anti-IgE antibody, which is an active ingredient of the present therapeutic agent for bronchial asthma attacks or the present prophylactic agent for template bronchitis, may be any antibody that binds to IgE and inhibits the binding of IgE to FcεRI, and examples of such antibodies include monoclonal antibodies, polyclonal antibodies, human antibodies, chimeric antibodies, and humanized antibodies. The above-mentioned anti-IgE antibody is preferably an anti-IgE antibody that specifically binds to IgE. The above-mentioned antibodies also include antibody fragments consisting of a part of antibodies such as F(ab')2, Fab, diabody, Fv, ScFv, and Sc(Fv)2. The classes and subclasses of the above-mentioned monoclonal antibodies include IgG such as IgG1, IgG2, IgG3, and IgG4; IgA such as IgA1 and IgA2; IgD; IgE; IgM; and among these, IgG and IgM are preferably mentioned. Preferred examples of the anti-IgE antibody include a humanized anti-human IgE monoclonal antibody, more preferably a humanized antibody that specifically binds to the binding site of IgE with the high affinity receptor FcεRI, such as the Cε3 domain, and even more preferably omalizumab. In addition, the anti-IgE antibody described in JP-A-2004-529180 is incorporated herein by reference.

[0023] Methods for producing monoclonal antibodies include a method using a hybridoma, a method using genetic engineering techniques to transform a host with an expression vector containing an antibody gene, and a method of immunizing a transgenic animal with a desired antigen.

[0024] The present agent for treating bronchial asthma attacks or the present agent for preventing mold bronchitis can be made into a pharmaceutical composition by adding various compounding ingredients for preparations such as pharma- ceutical acceptable ordinary carriers, binders, stabilizers, excipients, diluents, pH buffers, disintegrants, solubilizers, dissolution aids, isotonicity agents, etc. Specific examples of the compounding ingredients include water, physiological saline, animal fats and oils, vegetable oils, lactose, starch, gelatin, crystalline cellulose, gum, talc, magnesium stearate, hydroxypropyl cellulose, polyalkylene glycol, polyvinyl alcohol, and glycerin.

[0025] The method of administration of the present therapeutic agent for asthma attacks or the present preventive agent for mold bronchitis is not particularly limited, but includes parenteral administration in which a dosage form such as a solution, emulsion, or suspension is injected subcutaneously, into a vein or an artery, or administered intranasally as a spray, and oral administration in the form of a powder, granules, tablets, capsules, syrup, or suspension, among which intravenous administration is preferred. It may also be self-administered as an autoinjector. The dosage of the present therapeutic agent for asthma attacks or the present preventive agent for mold bronchitis may vary depending on the age, weight, sex, health condition, etc. of the subject, but is usually 0.1 to 1000 mg, preferably 1 to 100 mg per kg of body weight per day for adults, and may be administered once or in several divided doses. The administration interval may be 1 week, 6 days, 5 days, 4 days, 3 days, 2 days, 1 day, 12 hours, 8 hours, 4 hours, 2 hours, 1 hour, or 30 minutes.

[0026] The subject of administration of the present therapeutic agent for bronchial asthma attacks or the present preventive agent for plastic bronchitis is preferably a mammal, and among such mammals, human, mouse, dog, rat, guinea pig, rabbit, bird, sheep, pig, cow, horse, cat, monkey, chimpanzee are more preferably exemplified, and human is particularly preferably exemplified. In addition, when the subject of administration is a human, there is no particular limit to the age, and it may be a child or an adult. EXAMPLES

[0027] The present invention will be described in detail below with reference to examples, but the technical scope of the present invention is not limited to these examples.

[0028] [Example 1] Airway resistance induced by administration of anti-IgE antibody to a mouse model of bronchial asthma First, Balb / c mice (6-8 weeks old: Chiyoda Kaihatsu) were subcutaneously injected with ovalbumin (OVA: Sigma-Aldrich) (day 0 when the subcutaneous injection started, and day 14 after the subcutaneous injection) and inhaled (days 22, 24, 26, and 28 after the subcutaneous injection) to induce bronchial asthma model mice. These bronchial asthma model mice were inoculated with 1×10 influenza virus A(H1N1)pdm09 (mouse-adapted strain: provided by the National Institute of Infectious Diseases). 5 The mice were intranasally infected with approximately pfu / 20μl. Next, 1 hour, 24 hours, and 48 hours after infection, anti-IgE antibody (Purified Rat Anti-Mouse IgE: BD Pharmingen) was administered intraperitoneally at approximately 4mg / kg to create the anti-IgE antibody administration group. Similarly, control antibody (Purified Rat IgG1, κ Isotype Control: BD Pharmingen) was administered intraperitoneally at approximately 4mg / kg to create the control antibody administration group at 1 hour, 24 hours, and 48 hours after infection.

[0029] Seven days after infection, the mice in the anti-IgE antibody and control antibody groups were aerosolized and inhaled methacholine to induce asthma attacks (0, 3, 6, 12, or 24 mg / mL in PBS: Sigma-Aldrich), and total airway resistance (Rrs) was measured using flexiVent (registered trademark: Emka Technologies). The results of total airway resistance (Rrs) 1 hour, 24 hours, and 48 hours after infection are shown in Figures 1A-C, respectively. Note that methacholine can induce a state of airway hyperresponsiveness, i.e., an asthma attack, by contracting bronchial smooth muscle and closing the bronchi.

[0030] The results in Figures 1A-C show that total airway resistance increased in both the anti-IgE antibody and control antibody groups depending on the methacholine inhalation concentration. However, administration of anti-IgE antibody tended to suppress the increase in airway resistance compared to the control antibody group. Therefore, it was confirmed that asthma attacks caused by A(H1N1)pdm09 infection were suppressed by administration of anti-IgE antibody.

[0031] [Example 2] Lung pathological characteristics To confirm the occurrence of mucus plugs in the bronchi, bronchial asthma model mice were induced in the same manner as in Example 1, and A(H1N1)pdm09 was inoculated at 1 × 10 5 About pfu / 20μl was intranasally infected. Next, 1 hour after infection, anti-IgE antibody (Purified Rat Anti-Mouse IgE: BD Pharmingen) was intraperitoneally administered at about 0.1mg per dose to create an anti-IgE antibody administration group. The group using the control antibody described in Example 1 was used as a control group. Bronchial tissues on the 7th day after infection were fixed with formalin, paraffin blocks were prepared, and specimens were prepared using 5μm sections, and periodic acid Schiff (PAS) staining was performed. The results of microscopic observation are shown in Figure 2. In Figure 2, the scale bar in the upper right corner is 100μm. Note that mucin secreted by mucus cells and lung cells containing mucin are stained reddish purple by PAS staining, but in this specification, they are represented in grayscale. Note that when infected with A(H1N1)pdm09, mucus plugs are likely to accumulate in the bronchi, narrowing the airways.

[0032] As shown in Figure 2, the formation of mucus plugs blocking the bronchi, which is a characteristic of plastic bronchitis, was observed in many cases in the control administration group. Therefore, bronchial asthma model mice were induced by the method of Example 1, and then A(H1N1)pdm09 was administered at 1 × 10 5 It was confirmed that by infecting mice intranasally with approximately 20 μl of pfu, it was possible to reproduce in mice the same condition as that caused by A(H1N1)pdm09 infection in patients with bronchial asthma, which leads to plastic bronchitis.

[0033] In addition, the formation of mucus plugs in the plastic bronchitis state was suppressed by administration of anti-IgE antibody alone compared to the control group, indicating that anti-IgE antibody can prevent plastic bronchitis caused by influenza virus infection.

[0034] (summary) When patients with a history of asthma attacks or patients diagnosed with asthma become infected with A(H1N1)pdm09, the airways become extremely narrow due to both the contraction of bronchial smooth muscle and the accumulation of mucus plugs, resulting in severe respiratory complications. In conventional asthma treatments, it was extremely difficult to treat asthma in subjects who had developed plastic bronchitis. However, considering the results of Figures 1A-C and 2 above comprehensively, it became clear that administration of anti-IgE antibodies can treat asthma attacks caused by influenza virus infection and prevent plastic bronchitis caused by influenza virus infection. It was also surprising that one drug had the effects of both treating asthma attacks caused by influenza virus infection and preventing plastic bronchitis caused by influenza virus infection. [Industrial Applicability]

[0035] The present invention makes it possible to treat asthma attacks caused by infection with viruses such as influenza virus, and to prevent plastic bronchitis caused by infection with viruses such as influenza virus or bacteria, and can be applied in the medical and pharmaceutical fields.

Claims

1. A therapeutic agent for bronchial asthma attacks associated with viral infections, the active ingredient of which is an antibody that binds to immunoglobulin E (IgE).

2. The therapeutic agent for an asthma attack according to claim 1, which is for administration to a subject who has a history of an asthma attack or who has been diagnosed with bronchial asthma.

3. 3. The therapeutic agent for bronchial asthma attack according to claim 1 or 2, wherein the virus is influenza virus (A(H1N1)pdm09).

4. 3. The therapeutic agent for bronchial asthma attack according to claim 1 or 2, wherein the antibody that binds to IgE is omalizumab.

5. A preventive agent for plastic bronchitis caused by viral or bacterial infection, which contains as an active ingredient an antibody that binds to immunoglobulin E (IgE).

6. The preventive agent for mold bronchitis according to claim 5, for administration to a subject who has a history of bronchial asthma attacks or who has been diagnosed with bronchial asthma.

7. 7. The preventive agent for plastic bronchitis according to claim 5 or 6, wherein the virus is influenza virus (A(H1N1)pdm09).

8. The preventive agent for plastic bronchitis according to claim 5 or 6, wherein the antibody that binds to IgE is omalizumab.

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