Contribution of Kazal-Like Domains of the Serine Protease Inhibitor-1 from Toxoplasma gondii in Asthma Therapeutic Vaccination Effectiveness

<b><i>Background:</i></b> We have previously showed rTgPI-1 tolerogenic adjuvant properties in asthma treatment, turning it a promising candidate for allergen-specific immunotherapy. This therapy is an alternative treatment to control asthma that still presents several concerns related to its formulation. rTgPI-1 contains independent inhibitory domains able to inhibit trypsin and neutrophil elastase, both involved in asthma pathology. <b><i>Objectives:</i></b> In view of the need to design rational therapies, herein we investigated the contribution of the different inhibitory domains in rTgPI-1 therapeutic effectiveness. <b><i>Methods:</i></b> BALB/c mice were rendered allergic by intraperitoneal OVA-alum sensitization and airway challenged. Once the asthmatic phenotype was achieved, mice were intranasally treated with OVA combined with the full-length recombinant protein rTgPI-1 or its truncated versions, Nt (containing trypsin-inhibitory domains) or Ct (containing neutrophil elastase-inhibitory domains). Afterward, mice were aerosol re-challenged. <b><i>Results:</i></b> Asthmatic mice treated with the neutrophil elastase- or the trypsin-inhibitory domains separately failed to improve allergic lung inflammation. Only when all inhibitory domains were simultaneously administered, an improvement was achieved. Still, a better outcome was obtained when mice were treated with the full-length rTgPI-1. <b><i>Conclusions:</i></b> Adjuvant ability depends on the presence of all its inhibitory domains in a single entity, so it should be included in potential asthma treatment formulations as a full-length protein.

Implication of Buteyko Breathing Technique in Asthmatic Population: A Literature Review

Background: Complementary and experimental medicine is gaining interest in the treatment of asthma around the world. This study summarizes the literature on complementary and alternative medicine approaches that use breathing retraining, i.e Buteyko breathing technique (BBT) as a primary component. Aim: The aim of this research is to provide background for BBT, analyse the available evidence for its efficacy and evaluate the physiological framework behind it. Methods: The analysis of literature is carried out by studying papers from electronic databases such as Cochrane, Medline, Embase, AMED, PEDro, Google Scholar, Elsevier, APTA, Campbell, Web of Science, and Research Gate. Conclusion: Individual studies using BBT consistently showed a reduction in asthma medication use. In either of the BBT experiments, no significant difference in lung ability was found. BBT detractors argue that drug reduction can be due to the physicians' influence, which is difficult to determine. Longer follow-up is needed to show that the improvement in asthma treatment as measured by drug usage is sustained over a clinically appropriate time span.

Investigation of two treatment regimens in adults with mild asthma

<p>Introduction In adults with mild-moderate asthma, poor adherence to daily maintenance inhaled corticosteroids (ICS) leads to increased asthma symptoms and risk of asthma exacerbations. There is evidence that symptom-driven use of a combination ICS plus a fast-onset long-acting beta2-agonist (LABA) inhaler taken as needed may be an alternative to daily maintenance ICS plus as-needed short-acting beta2-agonists (SABA). Through four studies: The PRACTICAL study (a randomised controlled trial) and three sub-studies nested within it, this thesis aims to investigate the efficacy of as-needed ICS-formoterol (a fast-onset LABA), exposure to and patterns of ICS and beta2-agonist use, and patient preferences for and priorities concerning their asthma management. Methods The PRACTICAL study was a 52 week, open label, parallel group, multicentre, superiority, randomised controlled trial conducted at 15 sites throughout New Zealand. Adults aged 18-75 with a diagnosis of asthma who were taking SABA for symptom relief with or without low dose maintenance ICS were recruited. Participants were randomised 1:1 to either as-needed budesonide-formoterol (200/6mcg) one actuation for symptom relief or budesonide (200mcg) one actuation twice a day plus as-needed terbutaline (250mcg) two actuations for symptom relief. A sub-group of 110 participants had electronic inhaler monitors attached to their study inhalers which captured the time and date of every inhaler actuation. At their final study visit a total of 407 participants were eligible to complete a survey on their treatment preferences and experiences of their study randomised treatment, and a discrete choice experiment to determine their priorities for attributes of asthma management including; treatment regimen, shortness of breath, steroid dose and likelihood of an asthma flare-up. Results The PRACTICAL study found the rate of severe exacerbations per patient per year was lower in participants randomised to as-needed budesonide-formoterol than participants randomised to maintenance budesonide (absolute rate per patient per year 0.119 vs 0.172; relative rate 0.69; 95%CI 0.48-1.00; p=0.049). Within the electronic monitoring sub-study, exposure to ICS was significantly lower in the group randomised to as-needed budesonide-formoterol with a mean daily ICS dose of 176.0mcg versus 302.5mcg in those randomised to maintenance budesonide (difference -126.5mcg per day; 95%CI -171.0 to -81.9; p<0.001). Use of as-needed budesonide-formoterol was associated with extended periods of no ICS use (median 156 days vs 22 days respectively) and more days where ≥4, 6 or 8 actuations of ICS were taken than maintenance budesonide. Participants’ preference for either as-needed or maintenance treatment was strongly associated with randomised treatment; 90% randomised to as-needed budesonideformoterol preferred their randomised treatment compared to 60% of those randomised to maintenance budesonide, odds ratio for association between randomised treatment and preference was 13.3 (95%CI 7.1 to 24.7; p<0.001). The DCE found that amount of shortness of breath was the most important attribute of asthma treatment to all participants. However, the relative importance of other attributes, particularly type of treatment regimen, varied depending on whether the participants had previously stated a preference for as-needed or maintenance treatment. Discussion In adults with mild-moderate asthma, as-needed budesonide-formoterol is more effective at preventing severe asthma exacerbations than maintenance budesonide at a significantly lower exposure to ICS, despite long periods of no ICS use. This suggests that timing of ICS dose and titrating it in response to symptoms is more important than total dose. If participants have experienced as-needed budesonide-formoterol, they prefer it over maintenance budesonide suggesting this new approach to asthma treatment will be acceptable to patients. Control of shortness of breath was the most important attribute of asthma treatment to all patients. However, participants who preferred as-needed treatment were more willing to trade-off likelihood of an asthma flare up and steroid dose for their preferred treatment regimen. Knowledge of patient preferences and priorities for treatment, together with knowledge of regimen characteristics can be used in discussion with patients to determine the most appropriate regimen for them.</p>

Investigation of two treatment regimens in adults with mild asthma

<p>Introduction In adults with mild-moderate asthma, poor adherence to daily maintenance inhaled corticosteroids (ICS) leads to increased asthma symptoms and risk of asthma exacerbations. There is evidence that symptom-driven use of a combination ICS plus a fast-onset long-acting beta2-agonist (LABA) inhaler taken as needed may be an alternative to daily maintenance ICS plus as-needed short-acting beta2-agonists (SABA). Through four studies: The PRACTICAL study (a randomised controlled trial) and three sub-studies nested within it, this thesis aims to investigate the efficacy of as-needed ICS-formoterol (a fast-onset LABA), exposure to and patterns of ICS and beta2-agonist use, and patient preferences for and priorities concerning their asthma management. Methods The PRACTICAL study was a 52 week, open label, parallel group, multicentre, superiority, randomised controlled trial conducted at 15 sites throughout New Zealand. Adults aged 18-75 with a diagnosis of asthma who were taking SABA for symptom relief with or without low dose maintenance ICS were recruited. Participants were randomised 1:1 to either as-needed budesonide-formoterol (200/6mcg) one actuation for symptom relief or budesonide (200mcg) one actuation twice a day plus as-needed terbutaline (250mcg) two actuations for symptom relief. A sub-group of 110 participants had electronic inhaler monitors attached to their study inhalers which captured the time and date of every inhaler actuation. At their final study visit a total of 407 participants were eligible to complete a survey on their treatment preferences and experiences of their study randomised treatment, and a discrete choice experiment to determine their priorities for attributes of asthma management including; treatment regimen, shortness of breath, steroid dose and likelihood of an asthma flare-up. Results The PRACTICAL study found the rate of severe exacerbations per patient per year was lower in participants randomised to as-needed budesonide-formoterol than participants randomised to maintenance budesonide (absolute rate per patient per year 0.119 vs 0.172; relative rate 0.69; 95%CI 0.48-1.00; p=0.049). Within the electronic monitoring sub-study, exposure to ICS was significantly lower in the group randomised to as-needed budesonide-formoterol with a mean daily ICS dose of 176.0mcg versus 302.5mcg in those randomised to maintenance budesonide (difference -126.5mcg per day; 95%CI -171.0 to -81.9; p<0.001). Use of as-needed budesonide-formoterol was associated with extended periods of no ICS use (median 156 days vs 22 days respectively) and more days where ≥4, 6 or 8 actuations of ICS were taken than maintenance budesonide. Participants’ preference for either as-needed or maintenance treatment was strongly associated with randomised treatment; 90% randomised to as-needed budesonideformoterol preferred their randomised treatment compared to 60% of those randomised to maintenance budesonide, odds ratio for association between randomised treatment and preference was 13.3 (95%CI 7.1 to 24.7; p<0.001). The DCE found that amount of shortness of breath was the most important attribute of asthma treatment to all participants. However, the relative importance of other attributes, particularly type of treatment regimen, varied depending on whether the participants had previously stated a preference for as-needed or maintenance treatment. Discussion In adults with mild-moderate asthma, as-needed budesonide-formoterol is more effective at preventing severe asthma exacerbations than maintenance budesonide at a significantly lower exposure to ICS, despite long periods of no ICS use. This suggests that timing of ICS dose and titrating it in response to symptoms is more important than total dose. If participants have experienced as-needed budesonide-formoterol, they prefer it over maintenance budesonide suggesting this new approach to asthma treatment will be acceptable to patients. Control of shortness of breath was the most important attribute of asthma treatment to all patients. However, participants who preferred as-needed treatment were more willing to trade-off likelihood of an asthma flare up and steroid dose for their preferred treatment regimen. Knowledge of patient preferences and priorities for treatment, together with knowledge of regimen characteristics can be used in discussion with patients to determine the most appropriate regimen for them.</p>

METODE INTERPRETATIVE PHENOMENOLOGICAL ANALYSIS (IPA): PERSEPSI TENAGA KESEHATAN DAN PASIEN TERHADAP PENGOBATAN ASMA

Pharmaceutical care by pharmacists in the management have an important role of treatment monitoring. Optimal asthma treatment for patients requires cooperation between patients, healthcares, involving doctors, nurses, and pharmacists. Therefore the purpose of this study is to know the perception of healthcares and patients about asthma treatment and pharmaceutical cares on asthma mangement. The method of this study is based on phenomenological perspective with interpretative phenomenological analysis (IPA) on pulmonologist, outpatient asthma, pharmacist and nurse who directly correlated with asthma treatment at a hospital in Surabaya conducted for two years using purposive sampling. The results of this study indicate that asthma patients know how to manage asthma and use asthma drugs well. In addition it is known that asthma patients feel the role of doctors in the treatment of asthma is very dominating; pulmonologists and nurses perceive that the role of pharmacists is limited to drug delivery; and pharmacists assume that their role has been well done although not all patients get the same asthma treatment education. It is therefore necessary to evaluate the role of pharmacist in performing its role in the treatment of this asthma in order for a more harmonious collaboration.