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Beta agonist use during asthma exacerbations: How much is too much?
Abstract
Overuse of inhaled beta agonist therapy is associated with risk in adult asthmatics. We report on a case of excessive short-acting and long-acting beta agonist use in the setting of a severe exacerbation of asthma, which highlights some important good practice points.
... Some studies have shown that glucocorticoids treatment, even though associated to bronchodilators, do not always revert all these asthmatic features (Baraket et al., 2012). In addition, the significant incidence of adverse effects related to corticosteroids and bronchodilators, particularly b2-agonists, have been described (Miller et al., 2011;Patel et al., 2011;Ernst and Suissa, 2012). For this reason, the search for a potent antiinflammatory and nontoxic compound is inevitable in the asthma treatment. ...
... Some studies have shown that glucocorticoids treatment, even though associated to bronchodilators, do not always revert all these asthmatic features (Baraket et al., 2012). In addition, the significant incidence of adverse effects related to corticosteroids and bronchodilators, particularly b2-agonists, have been described (Miller et al., 2011;Patel et al., 2011;Ernst and Suissa, 2012). For this reason, the search for a potent antiinflammatory and nontoxic compound is inevitable in the asthma treatment. ...
Asthma is an inflammatory disease that involves airway hyperresponsiveness and remodelling. Flavonoids have been associated to anti-inflammatory and antioxidant activities and may represent a potential therapeutic treatment of asthma. Our aim was to evaluate the effects of the sakuranetin treatment in several aspects of experimental asthma model in mice.
Male BALB/c mice received ovalbumin (i.p.) on days 0 and 14, and were challenged with aerolized ovalbumin 1% on days 24, 26 and 28. Ovalbumin-sensitized animals received vehicle (saline and dimethyl sulfoxide, DMSO), sakuranetin (20 mg kg–1 per mice) or dexamethasone (5 mg kg–1 per mice) daily beginning from 24th to 29th day. Control group received saline inhalation and nasal drop vehicle. On day 29, we determined the airway hyperresponsiveness, inflammation and remodelling as well as specific IgE antibody. RANTES, IL-5, IL-4, Eotaxin, IL-10, TNF-α, IFN-γ and GMC-SF content in lung homogenate was performed by Bioplex assay, and 8-isoprostane and NF-kB activations were visualized in inflammatory cells by immunohistochemistry.
We have demonstrated that sakuranetin treatment attenuated airway hyperresponsiveness, inflammation and remodelling; and these effects could be attributed to Th2 pro-inflammatory cytokines and oxidative stress reduction as well as control of NF-kB activation.
These results highlighted the importance of counteracting oxidative stress by flavonoids in this asthma model and suggest sakuranetin as a potential candidate for studies of treatment of asthma.
Multiple health behavior change can ameliorate adverse effects of cancer.
The purpose of this study was to determine the effects of a multiple health behavior change intervention (CanChange) for colorectal cancer survivors on psychosocial outcomes and quality of life.
A total of 410 colorectal cancer survivors were randomized to a 6-month telephone-based health coaching intervention (11 sessions using acceptance and commitment therapy strategies focusing on physical activity, weight management, diet, alcohol, and smoking) or usual care. Posttraumatic growth, spirituality, acceptance, mindfulness, distress, and quality of life were assessed at baseline, 6 and 12 months.
Significant intervention effects were observed for posttraumatic growth at 6 (7.5, p < 0.001) and 12 months (4.1, p = 0.033), spirituality at 6 months (1.8, p = 0.011), acceptance at 6 months (0.2, p = 0.005), and quality of life at 6 (0.8, p = 0.049) and 12 months (0.9, p = 0.037).
The intervention improved psychosocial outcomes and quality of life (physical well-being) at 6 months with most effects still present at 12 months. (Trial Registration Number: ACTRN12608000399392).
Purpose
We have a limited understanding of the objectively determined physical activity levels of cancer survivors at the population level. Further, we have even less of an understanding of this behavior by weight status (i.e., normal weight, overweight, and obese). Therefore, the purpose of this study was to describe accelerometer-assessed physical activity levels among US cancer survivors and to do so across weight status.
Methods
Data from the 2003–2006 NHANES was used. One hundred twenty-six adult cancer survivors wore an accelerometer for ≥4 days, with weight status determined from measured body mass index.
Results
Approximately 13 % of cancer survivors were sufficiently active (i.e., met current physical activity guidelines). Results were not significant for light-intensity physical activity; however, results showed that obese cancer survivors engaged in 47 % less MVPA than normal weight cancer survivors (rate ratio = 0.53; 95 % CI, 0.29–0.93).
Conclusion
Most adult cancer survivors are insufficiently active and obese cancer survivors engage in less MVPA than their counterparts.
Implications for Cancer Survivors
Health care professionals are encouraged to increase cancer survivors’ awareness of the minimum levels of MVPA needed for optimal health, particularly among obese cancer survivors. Additionally, cancer survivors should also be informed of the positive health outcomes associated with light-intensity physical activity.
Background and objective:
Measuring adherence to inhaled asthma treatment is a key priority for asthma care. The aim of this study was to determine the relationship between self-report and actual medication use as measured by electronic monitoring for single and combination inhaled corticosteroid (ICS) and long-acting beta-agonist (LABA) metered-dose inhaler therapy.
Methods:
In this retrospective analysis from a previously completed prospective 24-week randomized, controlled trial of single or combination ICS/LABA therapy, medication use in the week prior to study visits determined by self-report questionnaire and electronic monitoring was compared. One hundred eleven participants received 125 µg fluticasone dipropionate and 25 µg salmeterol, two actuations twice daily, by either separate or combination ICS/LABA inhalers. Paired data for self-report and electronic monitoring were analysed. Measurement of agreement was by Bland-Altman-like plots by visit with calculation of limits of agreement.
Results:
For single and combination ICS/LABA therapy, self-report consistently overestimated actual inhaler use assessed by electronic monitoring by a mean of 2.2-8.4 inhalations over a 1-week period, with limits of agreement ranging from ±15.8 to 25.6 inhalations. Participants who underused their inhalers tended to overreport their use, while those who overused tended to underreport their medication use. The greater the degree of underuse, the greater the magnitude of overreport, and likewise, the greater the degree of overuse, the greater the magnitude of underreport.
Conclusions:
Self-report is inaccurate in measuring actual use of inhaled asthma treatment with patients who underuse their maintenance therapy overreporting their use and those who overuse their therapy underreporting their use.
The use of a combination inhaler containing budesonide and formoterol as both maintenance and quick relief therapy (SMART) has been recommended as an improved method of using inhaled corticosteroid/long-acting beta agonist (ICS/LABA) therapy. Published double-blind trials show that budesonide/formoterol therapy delivered in SMART fashion achieves better asthma outcomes than budesonide monotherapy or lower doses of budesonide/formoterol therapy delivered in constant dosage. Attempts to compare budesonide/formoterol SMART therapy with regular combination ICS/LABA dosing using other compounds have been confounded by a lack of blinding and unspecified dose adjustment strategies. The asthma control outcomes in SMART-treated patients are poor; it has been reported that only 17.1% of SMART-treated patients are controlled. In seven trials of 6-12 months duration, patients using SMART have used quick reliever daily (weighted average 0.92 inhalations/day), have awakened with asthma symptoms once every 7-10 days (weighted average 11.5% of nights), have suffered asthma symptoms more than half of days (weighted average 54.0% of days) and have had a severe exacerbation rate of one in five patients per year (weighted average 0.22 severe exacerbations/patient/year). These poor outcomes may reflect the recruitment of a skewed patient population. Although improvement from baseline has been attributed to these patients receiving additional ICS therapy at pivotal times, electronic monitoring has not been used to test this hypothesis nor the equally plausible hypothesis that patients who are non-compliant with maintenance medication have used budesonide/formoterol as needed for self-treatment of exacerbations. Although the long-term consequences of SMART therapy have not been studied, its use over 1 year has been associated with significant increases in sputum and biopsy eosinophilia. At present, there is no evidence that better asthma treatment outcomes can be obtained by moment-to-moment symptom-driven use of ICS/LABA therapy than conventional physician-monitored and adjusted ICS/LABA therapy.
There is concern long-acting beta-agonist (LABA) drugs may increase the risk of asthma mortality. We undertook a systematic review which included the AstraZeneca Formoterol Clinical Trial Safety Database and Novartis Food and Drug Administration Formoterol Briefing Document. Randomised controlled clinical trials of duration > or = 4 weeks that compared formoterol with a non-LABA comparator treatment in asthma were included in a meta-analysis of the risk of all-cause mortality and asthma death. Simple contingency tables, Peto's one-step method and a Bayesian analysis were used. There were 42 deaths (nine from asthma) recorded in 62 studies with 49,327 subjects. The simple contingency table odds ratio for risk of all-cause mortality with formoterol was 1.1 (95% CI 0.6-2.2) and for asthma death was 2.7 (95% CI 0.5-26.7). Analyses by the other methods using both "as randomised" and "as exposed" classifications of treatment gave similar risk estimates with wide confidence and credible intervals. We conclude that there was insufficient power to determine whether formoterol increases the risk of mortality. However, the point estimates of a 2.0- to 3.2-fold increased risk of asthma death are not reassuring and add weight to evidence that LABA use in certain circumstances may increase the risk of asthma mortality.
Although both inhaled corticosteroids and beta-agonists have been the mainstay of inhaled pharmacotherapy in the management of asthma for many years, as "preventers" and "relievers", the advent of combination inhalers has prompted a revision of how these drugs ought to be used in practice. Studies to investigate their role, not only as regular treatment but also "as required" for relief of breakthrough symptoms, have recently been reported. The results are prompting a paradigm shift as to how inhaler therapy should be prescribed. In this review, the Executive of the Thoracic Society of Australia and New Zealand (New Zealand Branch) provide recommendations on maintenance and relief strategies based on currently available evidence. It is recognised that with further data these recommendations may require revision after three years.
A case-control study has previously been reported of asthma deaths in people aged 5-45 years who had a hospital admission for asthma (the index admission) in New Zealand during 1981-1987. The study has been re-analysed to examine the association between markers of asthma severity and risk of asthma death or hospital admission; patients prescribed fenoterol were excluded from this re-analysis because of the previously reported interaction between fenoterol, asthma severity, and asthma deaths. The re-analysis included 39 patients who died of asthma during the 12 months after their index admission, 226 patients who had a readmission for asthma during the 12 months after their index admission, and 263 controls chosen from all index admissions. An admission in the previous 12 months was the strongest marker of subsequent risk of death (odds ratio (OR) = 3.5, 95% confidence interval (CI): 1.8-6.9, P less than 0.01), and was also a strong marker of subsequent risk of readmission (OR = 3.0, 95% CI: 2.1-4.2, P less than 0.01); the risk increased with the number of previous admissions. Three or more categories of prescribed asthma drugs was also associated with subsequent death (OR = 1.7, 95% CI: 0.9-3.3, P = 0.13) or readmission (OR = 1.9, 95% CI: 1.3-2.7, P less than 0.01); prescribed oral corticosteroids was only weakly associated with subsequent death (OR = 1.3, 95% CI: 0.6-2.8, P = 0.59), but was more strongly associated with subsequent readmission (OR = 1.9, 95% CI: 1.2-2.8, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
The cardiovascular and metabolic effects of the long-acting beta 2-agonist formoterol were compared with those of salbutamol, fenoterol and placebo in 12 healthy volunteers, using a randomised, double-blind, cross-over design. On the study days, the subjects inhaled either formoterol (24 micrograms), salbutamol (400 micrograms), fenoterol (400 micrograms) or placebo, at 30 min intervals for five doses. Heart rate (HR) total electromechanical systole (Q-S2I) (a measure of inotropy), the corrected QT interval (QTc), systolic and diastolic blood pressure, plasma glucose and plasma potassium (K+) were measured prior to drug administration, 10 min after each inhalation and at 30 min intervals for 3 h after the last inhalation. All of the active agents significantly increased HR, QTc and plasma glucose, and decreased Q-S2I, diastolic blood pressure and plasma K+ compared to placebo. Fenoterol had a significantly greater maximum effect on HR, QTc and Q-S2I than either salbutamol or formoterol. Formoterol and fenoterol caused a similar maximum reduction in plasma K+, greater than that due to salbutamol. We conclude that formoterol is a more selective beta 2-agonist than fenoterol, and has similar cardiovascular effects to salbutamol when inhaled repeatedly by normal volunteers.
The development of self-management plans arose as clinicians tried to design better methods by which they could deliver asthma care and reduce the significant mortality and morbidity associated with this disease. The basic principles that resulted have been widely endorsed, and self-management plans are now recommended in the long-term management of adult asthma. Self-management plans essentially focus on the early recognition of unstable or deteriorating asthma, by monitoring peak flow or symptoms. Through the use of written guidelines, patients are then able to determine when it is necessary to adjust therapy or obtain medical assistance. There is now convincing evidence that the use of self-management plans by patients with asthma leads to a marked reduction in morbidity and a reduced requirement for acute medical treatment including hospital admissions. Recent research has also clarified many of the different issues concerning their structure and implementation. In some respects the skill in the use of the asthma self-management plan system of care is the ability to modify the standard plans to meet the particular needs of the individual asthmatic patient, including their preferences.