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1.  Asthma in adults 
Clinical Evidence  2010;2010:1501.
Introduction
About 10% of adults have suffered an attack of asthma, and up to 5% of these have severe disease that responds poorly to treatment. Patients with severe disease have an increased risk of death, but patients with mild-to-moderate disease are also at risk of exacerbations. Most guidelines about the management of asthma follow stepwise protocols. This review does not endorse or follow any particular protocol, but presents the evidence about specific interventions.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments for chronic asthma? What are the effects of treatments for acute asthma? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2008 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 99 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions. For acute asthma: beta2 agonists (plus ipratropium bromide, pressured metered-dose inhalers, short-acting continuous nebulised, short-acting intermittent nebulised, and short-acting intravenous); corticosteroids (inhaled); corticosteroids (single oral, combined inhaled, and short courses); education about acute asthma; generalist care; helium-oxygen mixture (heliox); magnesium sulphate (intravenous and adding isotonic nebulised magnesium to inhaled beta2 agonists); mechanical ventilation; oxygen supplementation (controlled 28% oxygen and controlled 100% oxygen); and specialist care. For chronic asthma: beta2 agonists (adding long-acting inhaled beta2 agonists when asthma is poorly controlled by inhaled corticosteroids, or short-acting inhaled beta2 agonists as needed for symptom relief); inhaled corticosteroids (low dose and increasing dose); leukotriene antagonists (with or without inhaled corticosteroids); and theophylline (when poorly controlled by inhaled corticosteroids).
Key Points
About 10% of adults have suffered an attack of asthma, and up to 5% of these have severe disease that responds poorly to treatment. These people have an increased risk of death.
Most guidelines about the management of asthma follow stepwise protocols. This review does not endorse or follow any particular protocol, but presents the evidence about specific interventions.
Taking short-acting beta2 agonists as needed is as likely to relieve symptoms and improve lung function as a regular dosing schedule in adults with chronic asthma.
Adding long-acting beta2 agonists to inhaled corticosteroids decreases the number of exacerbations and improves symptoms, lung function, and quality of life in people with mild-to-moderate persistent asthma that is poorly controlled with corticosteroids.
CAUTION: Long-acting beta2 agonists have been associated with increased asthma-related mortality, and should always be used with inhaled corticosteroids.
Low-dose inhaled corticosteroids improve symptoms and lung function in persistent asthma compared with placebo or regular inhaled beta2 agonists. Leukotriene antagonists are more effective than placebo at reducing symptoms, but we don't know if adding leukotriene antagonists to inhaled corticosteroids is of benefit in people with chronic asthma.CAUTION: Leukotriene antagonists have been associated with a possible increased risk of neuropsychiatric events.Adding theophylline to inhaled corticosteroids may improve lung function in people with mild or moderate chronic asthma that is poorly controlled with inhaled corticosteroids, but we don't know if they are of benefit compared with long-acting beta2 agonists or leukotriene antagonists.
In people with an acute attack of asthma, supplementation of beta2 agonists with 28% oxygen, systemic corticosteroids (short courses), additional beta2 agonists (various routes of administration), or ipratropium bromide improve symptoms. Inhaled corticosteroids seem to improve lung function in people with acute asthma. However, we don't know whether inhaled corticosteroids are as effective as systemic corticosteroids at improving symptom severity, lung function, and hospital admissions. Inhaled plus oral corticosteroids and oral corticosteroids alone may have similar effects in preventing relapse and improving lung function.Beta2 agonists delivered from a metered-dose inhaler using a spacer are as effective at improving lung function as those given by a nebuliser or given intravenously. Giving beta2 agonists intravenously is more invasive than giving beta2 agonists by nebuliser.In people with severe acute asthma, continuous nebulised short-acting beta2 agonists may also improve lung function more than intermittent nebulised short-acting beta2 agonists.We don't know if intravenous magnesium sulphate, nebulised magnesium alone, or adding nebulised magnesium to inhaled beta2 agonists improves lung function in people with acute asthma.We don't know whether helium-oxygen mixture (heliox) is more effective at improving lung function compared with usual care. Mechanical ventilation may be life saving in severe acute asthma, but it is associated with high levels of morbidity. Specialist care of acute asthma may lead to improved outcomes compared with generalist care.We don't know whether education to help self-manage asthma improves symptom severity, lung function, or quality of life, but it may reduce hospital admissions.
PMCID: PMC2907598  PMID: 21718577
2.  Relationship between recent short-acting β-agonist use and subsequent asthma exacerbations 
Background
US national guidelines recommend assessing short-acting β-agonist (SABA) medication use as a marker of asthma severity and control. However, the relationship between recent SABA use and asthma exacerbations is not currently known.
Objective
To evaluate the proximal relationship between the type and frequency of SABA use and asthma-related outcomes.
Methods
We evaluated SABA use among patients with asthma ages 5 to 56 years who were members of a large health maintenance organization in southeast Michigan. Frequency of use was estimated from pharmacy data assessing the timing and amount of SABA fills. Cox proportional hazards models were used to examine the prospective relationship between average daily SABA use for 3 months and outcomes associated with poor asthma control (ie, oral corticosteroids use, asthma-related emergency department visits, and asthma-related hospitalizations). We separately accounted for SABA metered-dose inhaler (MDI) and SABA nebulizer use.
Results
Of the 2,056 patients who met study criteria, 1,569 (76.3%) had used a SABA medication in their baseline year. After adjusting for potential confounders, SABA nebulizer use was associated with asthma-related emergency department visits (adjusted hazard ratio [aHR], 6.32; 95% confidence interval [CI], 2.38 to 16.80) and asthma-related hospitalizations (aHR, 21.62; 95% CI, 3.17 to 147.57). In contrast, frequency of SABA MDI use was not associated with these outcomes.
Conclusions
Frequency of SABA use during a 3-month period was associated with poor asthma outcomes. The relationship with poor asthma outcomes was strongest for SABA nebulizer use, suggesting that the type of SABA used is also of prognostic importance.
PMCID: PMC2646829  PMID: 19055201
3.  379 Adverse Drug Reactions to Anti-asthmatics in Patients with Bronchial Asthma 
Background
The number of self-reported adverse drug reactions (ADRs) has been rapidly increased with the active pharmacovigilance activities in Korea. However, there has been few data on ADRs to anti-asthmatics in Korea. This study was conducted to investigate the clinical characteristics of ADRs to anti-asthmatics in adult patients with bronchial asthma.
Methods
ADRs to anti-asthmatics reported to Regional Pharmacovigilance Center of Inha University Hospital by 2 physicians were collected from January 2011 to April 2011. Causality assessment of adverse events was performed by using WHO-UMC criteria and Naranjo's probability scale. Clinical information was additionally collected from electronic medical records.
Results
Twenty five ADRs to anti-asthmatics were reported in 19 (male 5, female 14) out of 228 patients with asthma. The most common offending anti-asthmatics were inhaled glucocorticoids combined with inhaled long-acting beta agonist (LABA) (12 of 19 subjects, 63.2%), theobromine (10.5%), oral LABA (10.5%), doxofylline (5.3%), acetylcysteine (5.3%), and montelukast (5.3%). Severity of ADRs was mild in most patients (13 of 19, 68.5%), and no severe ADR was detected. By frequency, oral LABA was the commonest drug associated with ADRs (2 in 17 prescription, 11.8%). ADR frequency was not different according to asthma control status. But ADRs to simultaneously prescribed drugs were more frequently detected in patients with combined upper airway diseases (ADRs to antihistamines) or patients with combined infection (ADRs to anti-infective drugs, mucolytics, oral LABA, or to SABA), or older patients with asthma.
Conclusions
Although the severity is usually mild, ADRs are relatively common in patients with bronchial asthma. Physician should monitor ADRs to anti-asthmatics or related drugs in patients with asthma, especially in older patients or in patients with multiple drug treatment for combined conditions.
doi:10.1097/01.WOX.0000412142.81425.50
PMCID: PMC3512811
4.  Asthma in adults (acute) 
Clinical Evidence  2011;2011:1513.
Introduction
About 10% of adults have suffered an attack of asthma, and up to 5% of these have severe disease that responds poorly to treatment. Patients with severe disease have an increased risk of death, but patients with mild to moderate disease are also at risk of exacerbations. Most guidelines about the management of asthma follow stepwise protocols. This review does not endorse or follow any particular protocol, but presents the evidence about specific interventions.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for acute asthma? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 100 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: beta2 agonists (plus ipratropium bromide, pressured metered-dose inhalers, short-acting continuous nebulised, short-acting intermittent nebulised, short-acting iv, and inhaled formoterol); corticosteroids (inhaled); corticosteroids (single oral, combined inhaled, and short courses); education about acute asthma; generalist care; helium–oxygen mixture (heliox); magnesium sulphate (iv and adding isotonic nebulised magnesium to inhaled beta2 agonists); mechanical ventilation; oxygen supplementation (controlled 28% oxygen and controlled 100% oxygen); and specialist care.
Key Points
About 10% of adults have suffered an attack of asthma, and up to 5% of these have severe disease that responds poorly to treatment. These people have an increased risk of death.
Most guidelines about the management of asthma follow stepwise protocols. This review does not endorse or follow any particular protocol, but presents the evidence about specific interventions.
Inhaled short-acting beta2 agonists are considered the mainstay of treatment for acute asthma.
In people with an acute attack of asthma, supplementation of beta2 agonists with low oxygen concentrations, systemic corticosteroids (short courses), additional beta2 agonists (various routes of administration), or ipratropium bromide improves symptoms. Inhaled corticosteroids seem to improve lung function in people with acute asthma. However, we don't know whether inhaled corticosteroids are as effective as systemic corticosteroids at improving symptom severity, lung function, and hospital admissions. Inhaled plus oral corticosteroids and oral corticosteroids alone may have similar effects in preventing relapse.Beta2 agonists delivered from a metered-dose inhaler using a spacer are as effective at improving lung function as those given by a nebuliser or given iv. Giving beta2 agonists iv is more invasive than giving beta2 agonists by nebuliser.In people with severe acute asthma, continuous nebulised short-acting beta2 agonists may also improve lung function more than intermittent nebulised short-acting beta2 agonists.The inhaled long-acting beta2 agonist formoterol seems to be at least equivalent to the short-acting beta2 agonists salbutamol and terbutaline in terms of pulmonary function in moderate to severe acute asthma treatment. On the basis of research undertaken in people with chronic asthma, the FDA has recommended minimising the use of long-acting beta agonists because of an increased risk of asthma exacerbations, hospital admissions, and death. The FDA acknowledges that they do have an important role in helping some patients control asthma symptoms.We don't know if iv magnesium sulphate, nebulised magnesium alone, or adding nebulised magnesium to inhaled beta2 agonists improves lung function in people with acute asthma.We don't know whether helium–oxygen mixture (heliox) is more effective at improving lung function compared with usual care.Mechanical ventilation may be life saving in severe acute asthma, but it is associated with high levels of morbidity. Specialist care of acute asthma may lead to improved outcomes compared with generalist care.We don't know whether education to help self-manage asthma improves symptom severity, lung function, or quality of life, but it may reduce hospital admissions.
PMCID: PMC3661228  PMID: 21463536
5.  Knowledge of Asthma among Doctors Practicing in Three South Eastern States of Nigeria 
Background:
Asthma is a chronic airway disease that has a significant impact on patients with substantial global socioeconomic burden. Appropriate knowledge by health care practitioners is important in the management of asthma.
Aim:
The aim was to assess the knowledge of asthma among doctors practicing in health care facilities in three South-Eastern states of Nigeria.
Subjects and Methods:
This was a descriptive cross-sectional study. The participants were selected using multi-staged sampling method and interviewed with structured, self-administered questionnaires. Comparison of the different outcome variables using the Chi-square (categorical) and Student's t-test (noncategorical) with the characteristics of the participants were done.
Result:
A total of 283 doctors were interviewed. Eighty-eight percent of them identified asthma as a common disease in our environment, (P = 0.04) but unrelated to socioeconomic status. Knowledge of epidemiology was poor among medical officers and registrars (P = 0.04). Most of the doctors (80%)(226/283) recognized the pathogenic significance of bronchospasm in exacerbation, while 58.6% (166/283) of them considered chronic inflammation as a significant factor in asthma pathogenesis P < 0.001. Majority of the doctors (84.1%) (238/283) were aware of the use of steroids in acute exacerbation, while 59.4% (168/283) considered aminophylline as the first line medication in exacerbation (P = 0.02). Knowledge about the use of steroids as controller medication was noted in 1.7% (5/283) of the respondents. Only 47.3% (134/283) of the participants were aware of the Global Initiative on Asthma guideline, (P = 0.03).
Conclusion:
There was good knowledge of epidemiology and clinical features of asthma, but a small number of the doctors had knowledge of pathophysiology and treatment of the disease. For best practices in asthma management, there is a need for further education.
doi:10.4103/2141-9248.141968
PMCID: PMC4212386  PMID: 25364598
Asthma knowledge; Doctors; Nigeria; Southeast
6.  Sex differences in the use of asthma drugs: cross sectional study 
BMJ : British Medical Journal  1998;317(7170):1434-1437.
Objectives
To assess the use of asthma drugs by men and women with asthma and to identify sex specific predictors for the use of oral steroids.
Design
Cross sectional study.
Setting
Six general practices in East Anglia.
Subjects
103 men and 134 women aged 20-54 with asthma.
Main outcome measures
Self reported use of β agonists, inhaled steroids, and oral steroids.
Results
No sex difference was found in use of β agonists or inhaled steroids. However a strong association existed between sex and oral steroid use. 40 (30%) women reported using oral steroids compared with nine (9%) men. Women were more than five times (odds ratio=5.5, 95% confidence interval 2.2 to 13.7) more likely to report use of oral steroids than men after asthma symptoms, age, visits to the general practitioner in previous six months, and time since diagnosis of asthma were controlled for. Women who had visited the general practitioner for asthma one or more times in the previous six months were four times (3.9, 1.6 to 9.5) as likely to report use of oral steroids. In addition, more frequent visits to the general practitioner for asthma were related in a dose-response manner to a greater likelihood of using oral steroids among women after asthma symptoms, age, and time since diagnosis were controlled for. This relation was not observed among men.
Conclusion
Women used oral steroids more than men. The more frequent consultations with a doctor by women may result in more requests for oral steroids or doctors may preferentially prescribe oral steroids to women.
Key messagesWomen tend to take more prescription drugs than menIn this study men and women reported similar use of β agonists and inhaled steroids for asthma but women used significantly more oral steroidsWomen who had visited their general practitioner for asthma in the past six months were four times more likely to take oral steroids than those who had not visitedA dose-response relation was found between number of visits to the general practitioner and use of oral steroidsWomen may be making more requests for steroids or doctors may be preferentially prescribing them to women
PMCID: PMC28725  PMID: 9822401
7.  Self-Management of Acute Asthma among Low-Income Urban Adults 
One approach to address asthma disparities has been to create evidence-based guidelines to standardize asthma care and education. However, the adoption of these recommendations has been suboptimal among many providers. As a result, low-income minority patients may not be receiving adequate instruction in asthma self-management. In addition, these patients may fail to follow guideline-based recommendations. We conducted 25 interviews to identify the extent to which urban low-income adults have received training in, and implement, self-management protocols for acute asthma. Twenty-five adults (92% female; 76% African American; mean age 39) were enrolled. Only one subject had received asthma self-management training and only 10 (40%) used short-acting beta-2 agonist-based (SABA) self-management protocols for the early treatment of acute asthma. No subject used a peak flow meter or an asthma action plan. Most (52%) chose to initially treat acute asthma with complementary and alternative medicine (CAM) despite the availability of SABAs. Importantly, 21 (84%) preferred an integrated approach using both conventional and CAM treatments. Four themes associated with acute asthma self-management emerged from the qualitative analysis. The first theme safety reflected subjects’ perception that CAM was safer than SABA. Severity addressed the calculation that subjects made in determining if SABA or CAM was indicated based on the degree of symptoms they were experiencing. The third theme speed and strength of the combination described subjects’ belief in the superiority of integrating CAM and SABA for acute asthma self-management. The final themesense of identity spoke to the ability of CAM to provide a customized self-management strategy that subjects desired. It is unclear if subjects’ greater use of CAM or delays in using SABA-based self-management protocols were functions of inadequate instruction or personal preference. Regardless, delays in, or under use of, conventional self-management protocols may increase the risk for an untoward outcome. To that end, all patents’ acute asthma self-management strategies should be evaluated for their timeliness and appropriateness. This would be of particular importance for vulnerable populations who bear a disproportionate burden of the disease and who have the fewest resources.
doi:10.1080/02770900903029788
PMCID: PMC2751633  PMID: 19657906
acute asthma; self-management; complementary and alternative medicine (CAM); minority; health disparities; qualitative
8.  Asthma in adults (chronic) 
Clinical Evidence  2011;2011:1512.
Introduction
About 10% of adults have suffered an attack of asthma, and up to 5% of these have severe disease that responds poorly to treatment. Patients with severe disease have an increased risk of death, but patients with mild-to-moderate disease are also at risk of exacerbations. Most guidelines about the management of asthma follow stepwise protocols. This review does not endorse or follow any particular protocol, but presents the evidence about specific interventions.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for chronic asthma? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 54 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: adding anti-IgE treatment; beta2 agonists (adding long-acting inhaled beta2 agonists when asthma is poorly controlled by inhaled corticosteroids, or short-acting inhaled beta2 agonists as needed for symptom relief); inhaled corticosteroids (low dose and increasing dose); leukotriene antagonists (with or without inhaled corticosteroids); and theophylline (when poorly controlled by inhaled corticosteroids).
Key Points
About 10% of adults have suffered an attack of asthma, and up to 5% of these have severe disease that responds poorly to treatment. These people have an increased risk of death.
Most guidelines about the management of asthma follow stepwise protocols. This review does not endorse or follow any particular protocol, but presents the evidence about specific interventions.
Taking short-acting beta2 agonists as needed is as likely to relieve symptoms and improve lung function as a regular dosing schedule in adults with chronic asthma.
Adding long-acting beta2 agonists to inhaled corticosteroids decreases the number of exacerbations and improves symptoms, lung function, and quality of life in people with mild-to-moderate persistent asthma that is poorly controlled with corticosteroids.
CAUTION: Long-acting beta2 agonists have been associated with increased asthma-related mortality, and should always be used with inhaled corticosteroids.
Low-dose inhaled corticosteroids improve symptoms and lung function in persistent asthma compared with placebo or regular inhaled beta2 agonists. Leukotriene antagonists are more effective than placebo at reducing symptoms, but we don't know if adding leukotriene antagonists to low-dose inhaled corticosteroids is of benefit in people with chronic asthma.CAUTION: Leukotriene antagonists have been associated with a possible increased risk of neuropsychiatric events.Adding theophylline to inhaled corticosteroids may improve lung function in people with mild or moderate chronic asthma that is poorly controlled with inhaled corticosteroids, but we don't know if they are of benefit compared with long-acting beta2 agonists or leukotriene antagonists. Anti-IgE treatment (omalizumab) as an adjunct to treatment with inhaled and oral corticosteroids improves symptom severity, decreases exacerbation frequency, and may decrease hospital admission rates in people with chronic moderate to severe asthma.
PMCID: PMC3275169  PMID: 21749735
9.  Clustered randomised trial of an intervention to improve the management of asthma: Greenwich asthma study 
BMJ : British Medical Journal  1999;318(7193):1251-1255.
Objectives
To evaluate the effectiveness of an asthma resource centre in improving treatment and quality of life for asthmatic patients.
Design
Community based randomised controlled trial.
Setting
41 general practices in Greenwich with a practice nurse.
Subjects
All registered patients aged 15-50 years.
Intervention
Nurse specialists in asthma who educated and supported practice nurses, who in turn educated patients in the management of asthma according to the British Thoracic Society's guidelines.
Main outcome measures
Quality of life of asthmatic patients, attendance at accident and emergency departments, admissions to local hospitals, and steroid prescribing by general practitioners.
Results
Of 24 400 patients randomly selected and surveyed in 1993, 12 238 replied; 1621 were asthmatic of whom 1291 were sent a repeat questionnaire in 1996 and 780 replied. Of 24 400 patients newly surveyed in 1996, 10 783 (1616 asthmatic) replied. No evidence was found for an improvement in asthma related quality of life among newly surveyed patients in intervention practices compared with control practices. Neither was there evidence of an improvement in other measures of the quality of asthma care. Weak evidence was found for an improvement in quality of life in intervention practices among asthmatics registered with study practices in 1993 and followed up in 1996. Neither attendances at accident and emergency departments nor admissions for asthma showed any tendency to diverge in intervention and control practices over the study period. Steroid prescribing rates rose steadily during the study period. The average annual increase in steroid prescribing was 3% per year higher in intervention than control practices (95% confidence interval −1% to 6%, P=0.10).
Conclusions
This model of service delivery is not effective in improving the outcome of asthma in the community. Further development is required if cost effective management of asthma is to be introduced.
Key messagesSmall randomised trials suggest that implementation of management guidelines can improve outcomes for asthmatic patients treated in specialist unitsRandomised trials also suggest that guidelines can improve the process of care in general practiceAn intervention in which specialist nurses trained and supported practice nurses in running asthma clinics on the basis of British Thoracic Society guidelines failed to improve asthma outcomes for patients over a 3 year periodFactors that may have reduced the potential impact of the measures include the large number of asthmatic patients that need to be cared for in primary care, and the high turnover of practice nurses in inner city areasFurther research is required on how best to implement good practice in inner city areas if cost effective interventions are to be devised
PMCID: PMC27864  PMID: 10231256
10.  Appropriate prescribing in asthma and its related cost in east London. 
BMJ : British Medical Journal  1995;310(6972):97-100.
OBJECTIVES--To determine the patterns of preventive to reactive prescribing for asthma among general practices in the City and East London Family Health Services Authority area and their relation to prescribing cost. DESIGN--Descriptive study of asthma prescribing during April 1992 to March 1993. Prescribing data were linked with general practice and population data on one database. SETTING--City and East London Family Health Services Authority area, including all general practices in contract with the authority, which covers the inner city London Boroughs of Hackney, Tower Hamlets, and Newham and the Corporation of the City of London. SUBJECTS--All 163 general practices as at 1 June 1993. MAIN OUTCOME MEASURES--Ratios of prescribed inhaled corticosteroids plus cromoglycates (prophylactic treatment) to bronchodilators; distribution of the cost of asthma prescribing; distribution of overall generic prescribing; proportion of asthma generic prescribing; distribution of cost of overall drugs prescribed per prescribing unit. RESULTS--Practices approved for band 3 health promotion or asthma surveillance and those with a general practitioner trainer had on average higher ratios of prophylactic to bronchodilator treatment and significantly higher asthma drug costs than other practices. Those practices with high levels of overall generic prescribing had significantly higher prophylactic to bronchodilator ratios than those with lower levels of generic prescribing. Practices with higher levels of asthma drug generic prescribing also had significantly higher prophylactic prescribing. However, the proportion of generically prescribed asthma drugs was lower than overall generic prescribing. There was no correlation between the ratio of prophylactic to bronchodilator asthma prescribing and the proportion of overall drugs expenditure, but high spending practices spent significantly more on asthma drugs. CONCLUSIONS--Pressure to reduce the cost of asthma prescribing may lead to a lowering of the ratio of prophylactic to bronchodilator treatments. However, reducing prophylactic prescribing would run contrary to the British Thoracic Society guidelines and might worsen the quality of asthma care.
PMCID: PMC2548501  PMID: 7833736
11.  Which patients are prescribed inhaled anti-asthma drugs? 
Thorax  1994;49(11):1090-1095.
BACKGROUND--Prescribing rates for inhaled anti-asthmatic drugs in the UK vary considerably from area to area and between individual practices. The objectives of this study were to determine the prevalence of patients prescribed inhaled steroids and beta agonist bronchodilators, the indications for these prescriptions, and to relate prescribing to the recorded levels of morbidity for specific respiratory disease. METHODS--Anonymised patient-specific prescription and diagnostic data were extracted from computerised general practice records for the 41 practices in the Northern region (total population 330,749) whose data had been validated for inclusion in a research databank. Patients were included if they were either prescribed an inhaled steroid or bronchodilator during a 12 month period, or had a recorded diagnosis of asthma, bronchitis or chronic obstructive pulmonary disease. Prescribing of inhalers per 1000 population was determined within age, sex, and diagnostic groups. Respiratory diagnosis rates within different patient groups were used to measure the underlying level of morbidity in the population. RESULTS--Inhaled anti-asthma drugs were prescribed for 5% of the study population. Prescribing prevalences peaked at ages 5-14 (steroids 40 per 1000 population; bronchodilators 68 per 1000) and at ages 65-74 (steroids 53 per 1000; bronchodilators 79 per 1000). Prescribing frequency for both drugs increased from two or three items per patient annually at age 0-14 to about six in the over 65 age group. Of the 39,424 respiratory patients 38% received inhalers and 7% only non-inhaler medication. Inhaler therapy was used in only 6% of patients with bronchitis, but in 66% of those with asthma, though the proportions varied with patient age and gender. Study practices differed in their overall levels of both inhaler prescribing and respiratory diagnosis, and had lower prescribing patterns of these drugs than other practices in the Northern region. CONCLUSIONS--Inhaled steroid and bronchodilator prescribing have age-related and gender-related prevalences. Treatment for respiratory diagnoses varies with patient age and gender, and with the diagnosis. Prescribing differences between practices are attributable to variation in both diagnostic rates for respiratory disease and therapeutic intervention patterns. For asthma patients study practices show consensus in approach, perhaps illustrating the value of clear guidelines for asthma prescribing.
Images
PMCID: PMC475267  PMID: 7831622
12.  Guidelines for the emergency management of asthma in adults. CAEP/CTS Asthma Advisory Committee. Canadian Association of Emergency Physicians and the Canadian Thoracic Society. 
OBJECTIVE: To develop a set of comprehensive, standardized evidence-based guidelines for the assessment and treatment of acute asthma in adults in the emergency setting. OPTIONS: The use of medications was evaluated by class, dose, route, onset of action and optimal mode of delivery. The use of objective measurements and clinical features to assess response to therapy were evaluated in relation to the decision to admit or discharge the patient or arrange for follow-up care. OUTCOMES: Control of symptoms and disease reflected in hospital admission rates, frequency of treatment failures following discharge, resolution of symptoms and improvement of spirometric test results. EVIDENCE: Previous guidelines, articles retrieved through a search of MEDLINE, emergency medical abstracts and information from members of the expert panel were reviewed by members of the Canadian Association of Emergency Physicians (CAEP) and the Canadian Thoracic Society. Where evidence was not available, consensus was reached by the expert panel. The resulting guidelines were reviewed by members of the parent organizations. VALUES: The evidence-based methods and values of the Canadian Task Force on the Periodic Health Examination were used. BENEFITS, HARMS AND COSTS: As many as 80% of the approximate 400 deaths from asthma each year in Canada are felt to be preventable. The use of guidelines, aggressive emergency management and consistent use of available options at discharge are expected to decrease the rates of unnecessary hospital admissions and return visits to emergency departments because of treatment failures. Substantial decreases in costs are expected from the use of less expensive drugs, or drug delivery systems, fewer hospital admissions and earlier return to full activity after discharge. RECOMMENDATIONS: Beta2-agonists are the first-line therapy for the management of acute asthma in the emergency department (grade A recommendation). Bronchodilators should be administered by the inhaled route and titrated using objective and clinical measures of airflow limitation (grade A). Metered-dose inhalers are preferred to wet nebulizers, and a chamber (spacer device) is recommended for severe asthma (grade A). Anticholinergic therapy should be added to beta 2 agonist therapy in severe and life-threatening cases and may be considered in cases of mild to moderate asthma (grade A). Aminophylline is not recommended for use in the first 4 hours of therapy (grade A). Ketamine and succinylcholine are recommended for rapid sequence intubation in life-threatening cases (grade B). Adrenaline (administered subcutaneously or intravenously), salbutamol (administered intravenously) and anesthetics (inhaled) are recommended as alternatives to conventional therapy in unresponsive life-threatening cases (grade B). Severity of airflow limitation should be determined according to the forced expiratory volume at 1 second or the peak expiratory flow rate, or both, before and after treatment and at discharge (grade A). Consideration for discharge should be based on both spirometric test results and assessment of clinical risk factors for relapse (grade A). All patients should be considered candidates for systemic corticosteroid therapy at discharge (grade A). Those requiring corticosteroid therapy should be given 30 to 60 mg of prednisone orally (or equivalent) per day for 7 to 14 days; no tapering is required (grade A). Inhaled corticosteroids are an integral component of therapy and should be prescribed for all patients receiving oral corticosteroid therapy at discharge (grade A). Patients should be given a discharge treatment plan and clear instructions for follow-up care (grade C). VALIDATION: The guidelines share the same principles of those from the British Thoracic Society and the National Institutes of Health. Two specific validation initiatives have been undertaken: (a) several Canadian centres have been involved in the collection of comprehensive administrative data to assess compliance and outcome measures and (b) a survey of Canadian emergency physicians conducted to gather baseline informaton of treatment patterns, was conducted before development of the guidelines and will be repeated to re-evaluate emergency management of asthma.
PMCID: PMC1487869  PMID: 8673983
13.  Prescription pattern and prevalence of potentially inappropriate medications among elderly patients in a Nigerian rural tertiary hospital 
Introduction
Polypharmacy and inappropriate prescriptions are prominent prescribing issues with elderly patients. Beers criteria and other guidelines have been developed to assist in the reduction of potentially inappropriate medications prescribed to elderly patients. The objectives of this study were to assess the prescribing pattern for elderly Nigerian outpatients and estimate the prevalence of potentially inappropriate medications among them using the Beers criteria.
Methodology
This was a prospective cross-sectional study of elderly patients (65 years and above) who were attending the general outpatients clinic of a rural Nigerian hospital. For the drug utilization aspect of the study, drug-use indicators were assessed using established World Health Organization guidelines, while the Beers criteria was used to screen for potentially inappropriate medications.
Result
The medical records of 220 patients aged 65 years and above were utilized for the study. A total of 837 drugs were prescribed for the patients, giving an average of 3.8 ± 1.3 drugs per person. Antihypertensive drugs accounted for 30.6% of the prescriptions, followed by multivitamins/food supplements (11.5%) and analgesics (10.8%). A review of the prescribed medications using the 2012 Updated Beers Criteria by the American Geriatric Society identified 56 patients with at least one potentially inappropriate medication prescribed giving a rate of 25.5%. The drug groups identified were nonsteroidal anti-inflammatory drugs, antihistamines, and amitriptyline.
Conclusion
Polypharmacy and prescription of potentially inappropriate medications are major therapeutic issues in Nigeria. There is a need for prescriber training and retraining with emphasis on the geriatric population.
doi:10.2147/TCRM.S40120
PMCID: PMC3601648  PMID: 23516122
drug utilization pattern; elderly patients; rational use of medicines; adverse drug reactions; Beers criteria
14.  Asthma and other recurrent wheezing disorders in children (chronic) 
Clinical Evidence  2012;2012:0302.
Introduction
Childhood asthma is the most common chronic paediatric illness. There is no cure for asthma but good treatment to palliate symptoms is available. Asthma is more common in children with a personal or family history of atopy, increased severity and frequency of wheezing episodes, and presence of variable airway obstruction or bronchial hyperresponsiveness. Precipitating factors for symptoms and acute episodes include infection, house dust mites, allergens from pet animals, exposure to tobacco smoke, and exercise.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of single-agent prophylaxis in children taking as-needed inhaled beta2 agonists for asthma? What are the effects of additional prophylactic treatments in childhood asthma inadequately controlled by standard-dose inhaled corticosteroids? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 48 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: beta2 agonists (long-acting), corticosteroids (inhaled standard or higher doses), leukotriene receptor antagonists (oral), omalizumab, and theophylline (oral).
Key Points
Childhood asthma can be difficult to distinguish from viral wheeze and can affect up to 20% of children.
Regular monotherapy with inhaled corticosteroids improves symptoms, reduces exacerbations, and improves physiological outcomes in children with asthma symptoms requiring regular short-acting beta2 agonist treatment. Their effect on final adult height is minimal and when prescribed within recommended doses have an excellent safety record. Regular monotherapy with other treatments is not superior to low-dose inhaled corticosteroids.
Leukotriene receptor antagonists may have a role as first-line prophylaxis in very young children.
There is consensus that long-acting beta2 agonists should not be used for first-line prophylaxis. CAUTION: Monotherapy with long-acting beta2 agonists does not reduce asthma exacerbations but may increase the chance of severe asthma episodes.
Theophylline was used as first-line prevention before the introduction of inhaled corticosteroids. Although there is weak evidence that theophylline is superior to placebo, theophylline should no longer be used as first-line prophylaxis in childhood asthma because of clear evidence of the efficacy and safety of inhaled corticosteroids. Theophylline has serious adverse effects (cardiac arrhythmia, convulsions) if therapeutic blood concentrations are exceeded.
When low-dose inhaled corticosteroids fail to control asthma, most older children will respond to one of the add-on options available, which include addition of long-acting beta2 agonists, addition of leukotriene receptor antagonists, addition of theophylline, or increased dose of inhaled corticosteroid. However, we don't know for certain how effective these additional treatments are because we found no/limited RCT evidence of benefit compared with adding placebo/no additional treatments. Addition of long-acting beta2 agonists may reduce symptoms and improve physiological measures compared with increased dose of corticosteroids in older children. Long-acting beta2 agonists are not currently licensed for use in children under 5 years of age.Consensus suggests that younger children are likely to benefit from addition of leukotriene receptor antagonists. Although there is weak evidence that addition of theophylline to inhaled corticosteroids does improve symptom control and reduce exacerbations, theophylline should only be added to inhaled corticosteroids in children aged over 5 years when the addition of long-acting beta2 agonists and leukotriene receptor antagonists have both been unsuccessful.
Omalizumab may be indicated in the secondary care setting for older children (aged over 5 years) with poorly controlled allergic asthma despite use of intermediate- and high-dose inhaled corticosteroids once the diagnosis is confirmed and compliance and psychological issues are addressed. However, we need more data to draw firm conclusions.
PMCID: PMC3285219  PMID: 22305975
15.  Asthma and other wheezing disorders in children 
Clinical Evidence  2006;2006:0302.
Introduction
Asthma is more common in children with a personal or family history of atopy, increased severity and frequency of wheezing episodes, and presence of variable airway obstruction or bronchial hyperresponsiveness. Precipitating factors for symptoms and acute episodes include infection, house dust mites, allergens from pet animals, exposure to tobacco smoke, and anxiety.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments for acute asthma in children? What are the effects of single-agent prophylaxis in children taking as-needed inhaled beta agonists for asthma? What are the effects of additional prophylactic treatments in childhood asthma inadequately controlled by standard-dose inhaled corticosteroids? What are the effects of treatments and of prophylactic treatments for acute wheezing in infants? We searched: Medline, Embase, The Cochrane Library and other important databases up to October 2005 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 84 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: beta2 agonists (high-dose nebulised, long-acting [inhaled salmeterol], short-acting [oral salbutamol or by nebuliser, or metered-dose inhaler/spacer versus nebuliser]), corticosteroids (oral prednisolone, systemic, inhaled higher or lower doses [beclometasone]), ipratropium bromide (single or multiple dose inhaled), leukotriene receptor antagonists (oral montelukast), nedocromil (inhaled), oxygen, sodium cromoglycate (inhaled), or theophylline (oral or intravenous).
Key Points
Childhood asthma can be difficult to distinguish from viral wheeze and can affect up to 20% of children.
The consensus is that oxygen, high dose nebulised beta2 agonists and systemic corticosteroids should be used to treat an acute asthma attack. High dose beta2 agonists may be equally effective when given intermittently or continuously via a nebuliser, or from a metered dose inhaler using a spacer, in children with an acute asthma attack.Admission to hospital may be averted by adding ipratropium bromide to beta2 agonists, or by using high dose nebulised or oral corticosteroids.
Prophylactic inhaled corticosteroids improve symptoms and lung function in children with asthma. Their effect on final adult height is unclear. Inhaled nedocromil, inhaled long acting beta2 agonists, oral theophylline and oral leukotriene receptor antagonists are less effective than corticosteroids.Inhaled sodium cromoglycate does not seem to improve symptoms.
CAUTION: Monotherapy with long acting beta2 agonists reduces the frequency of asthma episodes, but may increase the chance of severe asthma episodes and death when those episodes occur. Intravenous theophylline may improve lung function in children with severe asthma, but can cause cardiac arrhythmias and convulsions.
We don't know whether adding higher doses of corticosteroids, long acting beta2 agonists, oral leukotriene receptor antagonists or oral theophylline to standard treatment improves symptoms or lung function in children with uncontrolled asthma.
In infants with acute wheeze, short acting beta2 agonists via a nebuliser or a spacer may improve symptoms, but we don't know whether high dose inhaled or oral corticosteroids or inhaled ipratropium bromide are beneficial.
Oral short acting beta2 agonists and inhaled high dose corticosteroids may prevent or improve wheeze in infants but can cause adverse effects. We don't know whether lower dose inhaled or oral corticosteroids, inhaled ipratropium bromide or inhaled short acting beta2 agonists improve wheezing episodes in infants.
PMCID: PMC2907635
16.  Double trouble: impact of inappropriate use of asthma medication on the use of health care resources 
Background
There is considerable controversy about the regular use of short- acting β-agonists for the treatment of asthma. Although case–control studies have suggested that excessive use of these drugs may worsen asthma control and increase the risk of fatal or near-fatal asthma, the controversy remains unresolved because of the confounding that exists among disease control, disease severity and the use of short-acting β-agonists. Whatever the cause-and-effect relation between the use of short-acting β-agonists and disease severity, we hypothesized that their excessive use, in conjunction with underuse of inhaled corticosteroids, would be a marker for poorly controlled asthma and excessive use of health care resources.
Methods
To characterize the pattern of health services utilization among asthmatic patients taking various doses of inhaled β-agonists and corticosteroids in British Columbia, we linked the relevant health administrative databases. All patients between 5 and 50 years of age for whom a prescription for a short-acting β-agonist was filled in 1995 and whose prescription data were captured through the provincial drug plan were included in a retrospective analysis of prescriptions for asthma drugs, physician prescribing patterns and health services utilization. Patients' use of asthma medication was classified as appropriate (low doses of short-acting β-agonist and high doses of inhaled corticosteroid) or inappropriate (high doses of short-acting β-agonist and low doses of inhaled corticosteroid), and the 2 resulting groups were compared, by means of logistic, Poisson and gamma regression, for differences in prescribing patterns, physician visits and use of hospital resources.
Results
A total of 23 986 patients were identified as having filled a prescription for a short-acting β-agonist (for inhalation) in 1995. Of these, 3069 (12.8%) filled prescriptions for 9 or more canisters of β-agonist, and of this group of high-dose β-agonist users, 763 (24.9%) used no more than 100 μg/day of inhaled beclomethasone. On average, those with inappropriate use of β-agonists visited significantly more physicians for their prescriptions (1.8 v. 1.4), and each of these physicians on average wrote significantly more prescriptions for asthma medications per patient than the physicians who prescribed to appropriate users (5.2 v. 2.5 prescriptions). Patients with inappropriate use were more likely to be admitted to hospital (adjusted relative risk [RR] 1.68, 95% confidence interval [CI] 1.25–2.26), were admitted to hospital more frequently (adjusted RR 1.81, 95% CI 1.41–2.32) and were more likely to require emergency admission (adjusted RR 1.93, 95% CI 1.35–2.77).
Interpretation
Despite the widespread distribution of guidelines for asthma pharmacotherapy, inappropriate use of asthma medications persists (specifically excessive use of inhaled short-acting β-agonists combined with underuse of inhaled corticosteroids). Not only are patients who use medication inappropriately at higher risk for fatal or near-fatal asthma attacks, but, as shown in this study, they use significantly more health care resources than patients with appropriate medication use.
PMCID: PMC80815  PMID: 11258208
17.  Risk of severe life threatening asthma and beta agonist type: an example of confounding by severity. 
Thorax  1996;51(11):1093-1099.
BACKGROUND: A study was undertaken to test the hypothesis that a particular inhaled beta agonist, fenoterol, increases the incidence of severe life threatening asthma. METHODS: A retrospective cohort was assembled comprising 655 patients with asthma aged 15-55 years who attended a single Auckland hospital for acute asthma between 1 January 1986 and 31 December 1987 (the "index event"). Patients were followed for the occurrence of death from asthma or admission to the intensive care unit for asthma, until death or 31 May 1989. Data on asthma medications and asthma severity were obtained from forms used specifically for managing patients with acute asthma in the emergency department and maintained as part of the hospital record and/or from the hospital record (when patients were admitted). RESULTS: Following the index event 90 admissions to the intensive care unit (ICU) and 15 asthma deaths were identified. Before adjusting for asthma severity, patients using inhaled fenoterol had a greater incidence of severe life threatening asthma than patients using inhaled salbutamol (RR = 2.1, 95% CI 1.4 to 3.1). After controlling for two markers of severe asthma used in previous studies-a hospital admission in the previous year and prescribed oral corticosteroids-the relative risk estimate declined to 1.5 (95% CI 1.0 to 2.3). After controlling further for the number of hospital admissions during the study period, continuous oral corticosteroid use rather than short courses of treatment, severity of the previous attack requiring a hospital visit, and race, fenoterol was not associated with severe life threatening asthma at the time of attendance for a previous hospital visit (RR = 1.0, 95% CI 0.6 to 1.7). CONCLUSION: Fenoterol is used more often by patients with severe asthma and, after adjusting for differences in baseline risk, it does not increase the risk of severe life threatening asthma.
PMCID: PMC1090519  PMID: 8958891
18.  Challenges in the Management of Bronchial Asthma Among Adults in Nigeria: A Systematic Review 
Inadequate attention given to the management of asthma and ways of improving bronchial asthma control could be an important factor for the rising morbidity and mortality from asthma despite major advances in our understanding of the disease process. There is a paucity of data concerning the challenges faced in the management of asthma in Africa. This review was aimed at highlighting the challenges facing asthma management and to discuss various strategies in improving asthma control in Nigeria. Data were sourced from PubMed, Medline, African Journals Online, Google Scholar, SCOPUS, and by reviewing the references of relevant literature. Additional articles were obtained via communications with colleagues and reviewing the Abstract Books of Nigeria Thoracic Society Annual Scientific Conference from 2005 to 2012. The data search was up-to-date as of December 31, 2012. Challenges in asthma management were found during diagnosis, treatment, and follow-up. There are wide variations in diagnostic criteria for bronchial asthma and lack of standard diagnostic equipment leading to under or misdiagnosis. Treatment challenges include poor communication gap between the health-care providers and the patients, a high-cost and unavailability of essential asthma medications. Poor technique uses for medication devices, especially the inhalational drugs and Lack of National/hospital protocol or guidelines for treating asthma. Several challenges affect asthma management in developing countries, which borders on poverty, inadequate resources, weak health systems, and poor infrastructure. Efforts should be made to address these challenges by the Nigerian government, Nigerian Thoracic Society, pharmaceutical industries, and the health-care workers in general.
doi:10.4103/2141-9248.117927
PMCID: PMC3793433  PMID: 24116307
Asthma; Challenges; Diagnosis; Follow-up; Nigeria; Treatment
19.  Medication prescribing for asthma and COPD: a register-based cross-sectional study in Swedish primary care 
BMC Family Practice  2014;15:54.
Background
There is a gap between prescribed asthma medication and diagnosed asthma in children and adolescents. However, few studies have explored this issue among adults, where asthma medication is also used for the treatment of chronic obstructive pulmonary disease (COPD). The aim of this study was to examine the relationship between prescribing of medications indicated for asthma and COPD and the recorded diagnosis for these conditions.
Method
In a register-based study, individuals prescribed a medication indicated for asthma and COPD during 2004-2005 (Group A; n = 14 101) and patients with diagnoses of asthma or COPD recorded during 2000-2005 (Group B; n = 12 328) were identified from primary health care centers in Skaraborg, Sweden. From a 5% random sample of the medication users (n = 670), the written medical records were accessed. Primary outcomes: prevalence of medication and diagnoses, reasons for prescription. Secondary outcomes: type and number of prescribed drugs and performance of peak expiratory flow or spirometry.
Results
Medications indicated for asthma and COPD was prescribed to 5.6% of the population in primary care (n = 14 101). Among them, an asthma diagnosis was recorded for 5876 individuals (42%), 1116 (8%) were diagnosed with COPD and 545 (4%) had both diagnoses. The remaining 6564 individuals (46%) were lacking a recorded diagnosis. The gap between diagnosis and medication was present in all age-groups. Medication was used as a diagnostic tool among 30% of the undiagnosed patients and prescribed off-label for 54%. Missed recording of ICD-codes for existing asthma or COPD accounted for 16%.
Conclusion
There was a large discrepancy between prescribing of medication and the prevalence of diagnosed asthma and COPD. Consequently, the prevalence of prescriptions of medications indicated for asthma and COPD should not be used to estimate the prevalence of these conditions. Medication was used both as a diagnostic tool and in an off-label manner. Therefore, the prescribing of medications for asthma and COPD does not adhere to national clinical guidelines. More efforts should be made to improve the prescribing of medication indicated for asthma and COPD so that they align with current guidelines.
doi:10.1186/1471-2296-15-54
PMCID: PMC3987171  PMID: 24666507
Asthma; COPD; Prescribing; Off-label; Guidelines; Cross-sectional study
20.  Utilization, Spending, and Price Trends for Short- and Long-Acting Beta-Agonists and Inhaled Corticosteroids in the Medicaid Program, 1991–2010 
American Health & Drug Benefits  2011;4(3):140-149.
Background
Asthma is a chronic respiratory disease that afflicts millions of people and accounts for substantial utilization of healthcare resources in most industrialized countries, including in the United States. However, the exact cost and utilization of anti-asthma medications in Medicaid in the past 2 decades have not been well studied. Considering the safety issues surrounding the long-acting beta-agonists, guideline updates, and the increase in asthma prevalence, understanding anti-asthma medication prescribing trends is important to payers and patients.
Goal
The purpose of this study was to analyze the utilization and spending trends for anti-asthmatic agents in the US Medicaid program over the past 2 decades.
Methods
This study was based on a retrospective, descriptive analysis of trends in utilization of and spending on anti-asthma medications, including short-acting beta-agonists, inhaled corticosteroids, long-acting beta-agonists, and inhaled corticosteroid/long-acting beta-agonist combinations. Quarterly utilization and expenditure data were obtained from the national Medicaid pharmacy files provided by the Centers for Medicare & Medicaid Services from quarter 1 of 1991 through quarter 2 of 2010. Average reimbursement per prescription was calculated each quarter as a proxy for drug price.
Results
The total number of prescriptions for the studied anti-asthma medications rose from 8.9 million in 1991 to 15.6 million in 2009, peaking at 20.8 million in 2005, the year before Medicare and Medicaid dual-eligible beneficiaries were moved to Medicare Part D. From 1991 to 2009, Medicaid spending on anti-asthma medications overall rose from $180.7 million to $1.3 billion, and spending on inhaled corticosteroid/long-acting beta-agonist combinations rose from $52.8 million in 2001—their first year on the market—to $411.7 million in 2009. The average price per prescription has risen in all the anti-asthma drug classes: overall, spending per prescription has increased 4-fold between 1991 and 2009, significantly faster than the consumer price index (57.5%) over the same period. In quarter 2 of 2010, Medicaid spent more on the combination medication fluticasone-salmeterol—$60 million—than on any other anti-asthma medication.
Conclusion
Anti-asthma medications are a major and growing expense for state Medicaid programs and can be expected to be the same for Medicare Part D in the future. Increased disease prevalence has in part contributed to the rise in pharmacotherapy cost. Nevertheless, drug therapy is crucial for managing asthma and asthma exacerbations.
PMCID: PMC4105711  PMID: 25126346
21.  Bronchial reversibility with a short-acting β2-agonist predicts the FEV1 response to administration of a long-acting β2-agonist with inhaled corticosteroids in patients with bronchial asthma 
A long-acting β2-agonist (LABA) combined with an inhaled corticosteroid (ICS) is frequently prescribed as initial therapy in steroid-naïve asthma patients because of its effective control of symptoms and improvement of pulmonary function. However, it is unclear which patients will be responsive to LABAs and whether bronchial responsiveness to LABAs is similar to that to short-acting β2-agonists (SABAs) in a clinical setting. Therefore, the goal of the present study was to compare the changes in spirometric parameters after SABA (salbutamol) inhalation to those after 1-month LABA/ICS (salmeterol/fluticasone propionate) therapy. Spirometric changes were evaluated as absolute values, as the percentage of predicted normal values and as the percentage of baseline values after salbutamol inhalation or 1-month LABA/ICS therapy in 45 patients with asthma. Compared to SABA inhalation, LABA/ICS therapy produced significant improvements in forced expiratory volume in 1 sec (FEV1), peak expiratory flow (PEF), forced expiratory flow at 50% of vital capacity expired (FEF50%) from baseline (expressed as the percentage predicted) in all patients. FEV1 and the FEV1/forced vital capacity (FVC) ratio after SABA or LABA/ICS therapy were inversely related to the corresponding baseline values. Analysis of spirometric changes after SABA inhalation showed that FEV1 was the best among spirometric parameters, such as PEF, correlated with responsiveness to LABA/ICS therapy. Reversibility of FEV1 with SABA inhalation predicts the spirometric response to LABA/ICS as initial therapy in patients with bronchial asthma. LABA/ICS therapy had a greater effect on bronchial reversibility in asthmatic patients, compared to SABA inhalation. This suggested that evaluation of bronchial reversibility after LABA/ICS therapy would be superior to that after SABA inhalation.
doi:10.3892/etm.2011.268
PMCID: PMC3440754  PMID: 22977550
bronchial asthma; short-acting β2-agonist; long-acting β2-agonist; bronchial reversibility; lung function test
22.  The predictive value of asthma medications to identify individuals with asthma--a study in German general practices. 
BACKGROUND: The assessment of prescribing performance by aggregated measures mainly developed from automated databases is often helpful for general practitioners. For asthma treatment, the frequently applied ratio of anti-inflammatory to bronchodilator drugs may, however, be misleading if the specificity of a drug for the treatment of asthma, compared with other diseases, is unknown. AIM: To test the association of specific drugs with the diagnosis of asthma compared with other diagnoses. DESIGN OF STUDY: Cross-sectional study analysing prescription data from a retrospective chart review. SETTING: Eight general practices and one community respiratory practice in a town in Northern Germany. METHOD: All patients in the participating practices who received at least one of the 50 asthma drugs most frequently prescribed in Germany within the past 12 weeks were identified. Odds ratios (ORs) with 95% confidence intervals (ClI) were calculated to reveal any association between a specific drug and the diagnosis of asthma. The unit of analysis was the item prescribed. RESULTS: Topical betamimetics (e.g salbutamol, fenoterol) were the most often prescribed asthma drugs in the general practices (52.1 ) and in the respiratory practice (57.6%). Inhaled steroids accounted for 15% and 13%; systemic steroids accounted for 10% and 13%, respectively. In the general practices, inhaled betamimetics had a moderate marker function for asthma (OR = 2.0; 95% CI = 1.14-3.58). A fixed oral combination drug of clenbuterol plus ambroxol was a marker drug against asthma (OR = 0.35; 95% CI = 0.20-0.61). In the respiratory practice, the diagnosis of asthma was strongly marked by fixed combinations of cromoglycate plus betamimetics (OR = 29.0; 95% CI = 6.86-122.24) and moderately by inhaled betamimetics (OR = 2.6; 95% CI = 1.28-5.14). In contrast, systemic steroids (OR = 0.24; 95% CI 0.10-0.57) and even inhaled steroids (OR = 0.46; 95% ClI= 0.22-0.96) proved to contradict the diagnosis of asthma. CONCLUSION: Only betamimetics were markers for asthma patients in both types of practices; inhaled steroids, however, were not. Combinations of cromoglycate were markers in the respiratory practice only. Limited specificity of drugs for a disease (e.g asthma) should be taken into account when analysing prescribing data that are not diagnosis linked.
PMCID: PMC1314143  PMID: 11761200
23.  Switching patients from other inhaled corticosteroid devices to the Easyhaler®: historical, matched-cohort study of real-life asthma patients 
Purpose
To investigate the clinical and cost effectiveness of switching real-life asthma patients from other types of inhalers to the Easyhaler® (EH) for the administration of inhaled corticosteroids (ICS).
Patients and methods
Historical, matched-cohort study of 1,958 asthma patients (children and adults) treated in UK primary-care practices, using data obtained from the Optimum Patient Care Research Database and Clinical Practice Research Datalink. Other inhalers (OH) included pressurized metered-dose inhalers, breath-actuated inhalers, and dry-powder inhalers, delivering beclomethasone, budesonide, fluticasone, or ciclesonide. Patients remaining on OH unchanged (same drug, dosage, and device; n=979) were matched 1:1 with those switched to the EH (beclomethasone or budesonide) at the same or lower ICS dosage (n=979), based on age, sex, year of index patient review/switch, most recent ICS drug, dosage, and device, and the number of severe exacerbations and average daily short-acting β2 agonist (SABA) dosage in the preceding year. Clinical outcomes and health care costs were compared between groups for 12 months before and after the switch. Co-primary clinical outcomes were: 1) risk domain asthma control (RDAC) – no asthma-related hospitalization, acute oral steroid use, or lower respiratory tract infection (LRTI); 2) exacerbation rate (American Thoracic Society [ATS] definition) – where exacerbation is asthma-related hospitalization or acute oral steroid use; 3) exacerbation rate (clinical definition) – where exacerbation is ATS exacerbation or LRTI; and 4) overall asthma control (OAC) – RDAC plus average salbutamol-equivalent SABA dosage ≤200 μg/day. Non-inferiority (at least equivalence) of EH was tested against OH for the four co-primary outcomes in order (hierarchical approach) by comparing the difference in proportions of patients [EH-OH] achieving asthma control or having no exacerbations in the outcome year, using a limit of 10% difference.
Results
Non-inferiority was shown for the EH for all four co-primary outcomes. There were no significant differences between groups for RDAC or exacerbation rates, but EH patients were significantly more likely to achieve OAC (adjusted odds ratio [95% confidence interval]: 1.26 [1.05, 1.52]), as significantly more EH than OH patients had an average SABA dosage of ≤200 μg/day (52% versus 47%, respectively; P<0.001). Mean asthma-related health care costs increased from baseline to outcome years in both groups, but SABA costs increased significantly more in OH than EH patients (mean difference £5.5/patient/year) and consultation costs decreased significantly more in EH than OH patients (mean difference £13.5/patient/year).
Conclusion
Typical asthma patients may be switched from other ICS devices to the Easyhaler® with no reduction in clinical effectiveness or increase in cost.
doi:10.2147/JAA.S59386
PMCID: PMC3986277  PMID: 24748807
asthma; ICS; inhaler; Easyhaler; cost
24.  Influence of ethnic group on asthma treatment in children in 1990-1: national cross sectional study. 
BMJ : British Medical Journal  1996;313(7050):148-152.
OBJECTIVE--To examine the extent to which the prescription of drugs for asthma adhered to recommended guidelines in 1990-1 and to assess the influence of ethnic group on prescription. DESIGN--Cross sectional. SETTING--Primary schools in England and Scotland in 1990-1. SUBJECTS--Children aged mainly 5-11 years. The representative samples included 10628 children. The inner city sample included 7049 children, 4866 (69%) from ethnic minority groups. For the prevalence estimation 14490 children were included in the analysis (82% of the eligible children). For the treatment analysis a subgroup of 5494 children with respiratory symptoms was selected. MAIN OUTCOME MEASURES--Prevalence of respiratory symptoms and drugs commonly prescribed for asthma, method of administration, inappropriate treatment, and odds ratios to assess the effect of ethnic group on rate of prescription and method of administration. RESULTS--Children with respiratory symptoms in the inner city sample were less likely to be diagnosed as having asthma. Of children with reported asthma attacks, those in inner city areas had a higher risk of not having been prescribed any drug for asthma (odds ratio 1.87 (95% confidence interval 1.26 to 2.77). Overall, 773 (75%) of these children had received a beta 2 agonist, 259 (25%) had received steroids, 148 (14%) had received sodium cromoglycate, and 194 (19%) had received no drug treatment in the previous year. When prescribed, beta 2 agonists were inhaled in 534 (69%) of cases, and this percentage was even lower in ethnic minority groups. Children of Afro-Caribbean and Indian subcontinent origin who had asthma were less likely to receive beta 2 agonists, and those from the Indian subcontinent were less likely to receive anti-inflammatory drugs. Antibiotics were less prescribed and antitussives more prescribed in children from ethnic minority groups than in white children. CONCLUSION--In 1990-1 the risk of underdiagnosis and undertreatment of asthma was higher in children from ethnic minority groups. The implementation of indicators and targets to monitor inequalities in the treatment of asthma in ethnic groups could improve equity and effectiveness in the NHS.
PMCID: PMC2351536  PMID: 8688777
25.  Adequate Levels of Adherence with Controller Medication Is Associated with Increased Use of Rescue Medication in Asthmatic Children 
PLoS ONE  2012;7(6):e39130.
Background
The role of asthma controller medication adherence and the level of asthma control in children is poorly defined.
Aims
To assess the association between asthma controller medication adherence and asthma control in children using routinely acquired prescribing data.
Methods
A retrospective observational study of children aged 0–18 years prescribed inhaled corticosteroids only (ICS), leukotriene receptors antagonists (LTRA), or long-acting β2 agonists (LABA) and ICS prescribed as separate or combined inhalers, between 01/09/2001 and 31/08/2006, registered with primary care practices contributing to the Practice Team Information database. The medication possession ratio (MPR) was calculated and associations with asthma control explored. Poor asthma control was defined as the issue of prescriptions for ≥1 course of oral corticosteroids (OCS) and/or ≥6 short-acting β2 agonists (SABA) canisters annually.
Results
A total of 3172 children prescribed asthma controller medication were identified. Of these, 15–39% (depending on controller medication) demonstrated adequate MPR. Adequate MPR was associated with male gender, good socio-economic status, and oral LTRA therapy. Adequate MPR was more likely to be associated with increased use of rescue medication. However logistic regression only identified a significant relationship for ICS only (odds ratio [OR], 1.89; 95% confidence interval [CI], 1.35–2.48; p<0.001), LTRA (OR, 2.11; 95% CI, 1.27–3.48; p = 0.004) and LABA/ICS (OR, 2.85; 95% CI, 1.62–5.02; p<0.001).
Conclusion
Poor adherence was observed for all asthma controller medications, although was significantly better for oral LRTA. In this study adequate adherence was not associated with the use of less rescue medication, suggesting that adherence is a complex issue.
doi:10.1371/journal.pone.0039130
PMCID: PMC3384638  PMID: 22761728

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