Inhaled Inactivated Mycobacterium Phlei in Moderate Asthma
Inhaled Inactivated Mycobacterium Phlei in Moderate Asthma
The most effective drugs for asthma control are inhaled corticosteroids (ICS). Patients with moderate persistent asthma require continuous treatment with ICS, alone or in combination with long-acting beta-agonists. In patients requiring high-dose and continuous treatment, side effects of glucocorticoids have become a serious concern. The mycobacterial vaccine can be used to control Th2 responses such as asthma, probably via two major immunologic mechanisms. First, the mycobacterial vaccine may induce Tregs that secrete suppressive cytokines, IL-10 and TGF-β, which prevent the development of Th2 effector cells. Second, many studies have shown that immunization with mycobacterial products established a Th1-type immune response that suppressed Th2 cytokines, AHR and airway inflammation in murine asthma models.Mycobacterium bovis BCG suppresses ovalbumin-induced airway eosinophilia via IFN-γ. Recent research suggests that multiple BCG vaccinations of neonates reduced metrics characteristic of allergen-induced airway remodeling and this decrease was correlated with an increase of IFN-γ-producing T cells. It appears that the degree of Mycobacterium suppression is dependent on the mycobacterial strain and its preparation (live or dead microorganisms), dose, timing and route of administration.
We use inactivated M. phlei by a way of atomizing inhalation via the mucosa to treat adult asthma. M. phlei is a nonpathogenic bacteria to humans. It is possible that vaccines delivered by mucosal surfaces would stimulate even more vigorous cell-mediated immune responses. In animal models, evidence shows that vaccines administered via the mucosa are able to elicit neutralizing serum antibodies and cell-mediated immune responses as well as mucosal secretory IgA antibodies. In addition, we explored the course of treatment. In this investigation, we used a 5-day therapy and repeated the procedure once a month. Our study demonstrated that inhaled inactivated M. phlei to a certain extent improved asthma symptoms, reduced the need for rescue medication, reduced acute exacerbation of asthma and it plays the same role as inhaled Seretide in reducing AHR. Results from this research suggest that this course of treatment is efficient in adult asthma. We speculated that aerosol inhalation of inactivated M. phlei may attenuate airway inflammation and AHR in asthma through regulating airway local immune balance. Such a course of treatment does not require long-term daily administration as ICS or fixed combinations of ICS and long-acting β2-adrenoceptor agonists, so it is more convenient for patients to comply with. However, this experimental procedure seemed to have small effect and was less effective than the standard treatment, indicating that a larger dose and longer time course of inactivated M. phlei should be considered.
Thus, inactivated-M. phlei inhalation may be accepted as an alternative method with less risk of adverse reactions, more convenience and better compliance in treatment of asthma. However, the potential toxicity of inhaled whole mycobacteria, which might be expected to be granulomagenic, need to be taken into consideration, especially over a long period as the treatment for asthma. In China there has been a long history of repeated injections of inactivated BCG in the treatment of asthma. There may still be some side effects such as sclerosis, ulcer, fever and even tuberculosis diffusion. As a species of nonpathogenic Mycobacterium, M. phlei vaccine delivered by mucosal surfaces reduce the probability of side effects. Still, more observations are needed to understand the duration of its protective effect and more studies would still focus on its course of treatment in asthma.
Dicussion
The most effective drugs for asthma control are inhaled corticosteroids (ICS). Patients with moderate persistent asthma require continuous treatment with ICS, alone or in combination with long-acting beta-agonists. In patients requiring high-dose and continuous treatment, side effects of glucocorticoids have become a serious concern. The mycobacterial vaccine can be used to control Th2 responses such as asthma, probably via two major immunologic mechanisms. First, the mycobacterial vaccine may induce Tregs that secrete suppressive cytokines, IL-10 and TGF-β, which prevent the development of Th2 effector cells. Second, many studies have shown that immunization with mycobacterial products established a Th1-type immune response that suppressed Th2 cytokines, AHR and airway inflammation in murine asthma models.Mycobacterium bovis BCG suppresses ovalbumin-induced airway eosinophilia via IFN-γ. Recent research suggests that multiple BCG vaccinations of neonates reduced metrics characteristic of allergen-induced airway remodeling and this decrease was correlated with an increase of IFN-γ-producing T cells. It appears that the degree of Mycobacterium suppression is dependent on the mycobacterial strain and its preparation (live or dead microorganisms), dose, timing and route of administration.
We use inactivated M. phlei by a way of atomizing inhalation via the mucosa to treat adult asthma. M. phlei is a nonpathogenic bacteria to humans. It is possible that vaccines delivered by mucosal surfaces would stimulate even more vigorous cell-mediated immune responses. In animal models, evidence shows that vaccines administered via the mucosa are able to elicit neutralizing serum antibodies and cell-mediated immune responses as well as mucosal secretory IgA antibodies. In addition, we explored the course of treatment. In this investigation, we used a 5-day therapy and repeated the procedure once a month. Our study demonstrated that inhaled inactivated M. phlei to a certain extent improved asthma symptoms, reduced the need for rescue medication, reduced acute exacerbation of asthma and it plays the same role as inhaled Seretide in reducing AHR. Results from this research suggest that this course of treatment is efficient in adult asthma. We speculated that aerosol inhalation of inactivated M. phlei may attenuate airway inflammation and AHR in asthma through regulating airway local immune balance. Such a course of treatment does not require long-term daily administration as ICS or fixed combinations of ICS and long-acting β2-adrenoceptor agonists, so it is more convenient for patients to comply with. However, this experimental procedure seemed to have small effect and was less effective than the standard treatment, indicating that a larger dose and longer time course of inactivated M. phlei should be considered.
Thus, inactivated-M. phlei inhalation may be accepted as an alternative method with less risk of adverse reactions, more convenience and better compliance in treatment of asthma. However, the potential toxicity of inhaled whole mycobacteria, which might be expected to be granulomagenic, need to be taken into consideration, especially over a long period as the treatment for asthma. In China there has been a long history of repeated injections of inactivated BCG in the treatment of asthma. There may still be some side effects such as sclerosis, ulcer, fever and even tuberculosis diffusion. As a species of nonpathogenic Mycobacterium, M. phlei vaccine delivered by mucosal surfaces reduce the probability of side effects. Still, more observations are needed to understand the duration of its protective effect and more studies would still focus on its course of treatment in asthma.
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