Asthma Management Handbook

Planning asthma review and follow-up

Recommendations

Set up a system to help identify patients with asthma and to schedule asthma reviews.

How this recommendation was developed

Consensus

Based on clinical experience and expert opinion (informed by evidence, where available).

Assess recent asthma symptom control at all the following times:

  • when the person presents with uncontrolled asthma symptoms
  • at follow-up after an asthma flare-up
  • at follow-up 1–3 months after beginning preventer treatment or adjusting the dose
  • at scheduled asthma review visits
  • opportunistically at non-asthma visits
  • every 4–6 weeks during pregnancy.
How this recommendation was developed

Consensus

Based on clinical experience and expert opinion (informed by evidence, where available).

Validated checklists or questionnaires can be used at each visit to assess recent asthma symptom control or to screen for poor asthma control, e.g:

Table. Primary care Asthma Control Screening tool (PACS)

Have you experienced any of the following more than once a week in the last month? Yes No
Symptoms of asthma, cough, wheeze, shortness of breath
  •  
  •  
Waking at night because of asthma
  •  
  •  
Chest tightness on waking
  •  
  •  
Difficulty in performing vigorous activity like running, lifting heavy objects, exercise
  •  
  •  
Difficulty in performing moderate activities like vacuuming, climbing flights of stairs
  •  
  •  

Interpretation: ‘Yes’ to any question indicates that the person may have poorly controlled asthma, so more detailed assessment is needed.

Source: LeMay KS, Armour CL, Reddel HK. Performance of a brief asthma control screening tool in community pharmacy: a cross-sectional and prospective longitudinal analysis. Prim Care Respir J; 2014. Available from: http://dx.doi.org/10.4104/pcrj.2014.00011

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How this recommendation was developed

Consensus

Based on clinical experience and expert opinion (informed by evidence, where available).

Plan regular review of risk factors for flare-ups, accelerated decline in lung function, or treatment-related adverse effects.

Table. Risk factors for adverse asthma outcomes in adults and adolescents Opens in a new window Please view and print this figure separately: https://www.asthmahandbook.org.au/table/show/40

Table. Management of risk factors for adverse asthma outcomes in adults

Risk factor

Clinical action †

Any risk factor for flare-ups

Check patient has an appropriate action plan

Carefully check inhaler technique and adherence, and identify any barriers to good adherence

Review frequently (e.g. every 3 months)

Hospitalisation or ED visit for asthma or any asthma flare-up during the previous 12 months

Ask about triggers for flare-ups, and lead time

History of intubation or intensive care unit admission for asthma

Ensure action plan recommends early medical review when asthma worsens

Hospitalisation or ED visit for asthma in the past month

Emphasise importance of maintaining regular ICS use after symptoms improve

Confirm that patient has resumed using SABA only when needed for symptoms

High SABA use (>2 canisters per month)

Check lung function

If SABA use appears to be habitual, investigate causes and consider alternative strategies, e.g. short-term substitution of ipratropium for SABA

Long-term high-dose ICS

Consider gradual reduction of ICS dose if symptoms stable

Monitor regularly (e.g. assessment of bone density, regular eye examinations)

For local side-effects, ensure inhaler technique is appropriate

Poor lung function (even if few symptoms)

Consider 3-month trial of higher ICS dose, then recheck lung function

Consider referral for detailed specialist investigation

Sensitivity to unavoidable allergens (e.g. Alternaria species of common moulds)

Refer for further investigation and management

Exposure to cigarette smoke (smoking or environmental exposure)

Emphasise the importance of avoiding smoke

Provide quitting strategies

Consider increasing ICS dose (higher dose of ICS likely to be necessary to control asthma)

Refer for assessment of asthma–COPD overlap

Difficulty perceiving airflow limitation or the severity of exacerbations

Regular PEF monitoring

Action plan should recommend early review and measurement of lung function

No current written asthma action plan

Provide and explain written asthma action plan

† In addition to actions applicable to all risk factors

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How this recommendation was developed

Adapted from existing guidance

Based on reliable clinical practice guideline(s) or position statement(s):

  • Global Initiative for Asthma, 20121

Review each patient’s written asthma action plan at least once a year.

How this recommendation was developed

Consensus

Based on clinical experience and expert opinion (informed by evidence, where available).

When altering the medication or dose, flag the patient’s medical record with a reminder to ask at next visit:

  • whether they thought the treatment change was helpful
  • whether they are still taking that dose.
How this recommendation was developed

Consensus

Based on clinical experience and expert opinion (informed by evidence, where available).

For patients who need long-term high-dose inhaled corticosteroids to maintain good asthma control or need frequent courses of oral corticosteroids, arrange monitoring of bone mineral density and glucose metabolism status.

Advise patients to:

  • have regular eye examinations
  • do regular weight-bearing physical activity
  • have adequate dietary calcium intake
  • maintain adequate vitamin D levels. 

Table. Definitions of ICS dose levels in adults

Inhaled corticosteroid Daily dose (mcg)
Low Medium High
Beclometasone dipropionate † 100–200 250–400 >400
Budesonide 200–400 500–800 >800
Ciclesonide 80–160 240–320 >320
Fluticasone furoate* 100 200
Fluticasone propionate 100–200 250–500 >500

† Dose equivalents for Qvar (TGA-registered CFC-free formulation of beclometasone dipropionate).

*Fluticasone furoate is not available as a low dose. TGA-registered formulations of fluticasone furoate contain a medium or high dose of fluticasone furoate and should only be prescribed as one inhalation once daily.

Note: The potency of generic formulations may differ from that of original formulations. Check TGA-approved product information for details.

Sources

Respiratory Expert Group, Therapeutic Guidelines Limited. Therapeutic Guidelines: Respiratory, Version 4. Therapeutic Guidelines Limited, Melbourne, 2009.

GlaxoSmithKline Australia Pty Ltd. Product Information: Breo (fluticasone furoate; vilanterol) Ellipta. Therapeutic Goods Administration, Canberra, 2014. Available from: https://www.ebs.tga.gov.au/

GlaxoSmithKline Australia Pty Ltd. Product Information: Arnuity (fluticasone furoate) Ellipta. Therapeutic Goods Administration, Canberra, 2016. Available from: https://www.ebs.tga.gov.au/

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How this recommendation was developed

Consensus

Based on clinical experience and expert opinion (informed by evidence, where available), with particular reference to the following source(s):

  • Etminan et al. 20082
  • Suissa et al. 20103
  • Weatherall et al. 20094
  • Wisniewski et al. 19975

When dispensing asthma medicines in pharmacies, routinely ask when was the person’s last asthma review. Encourage them to visit their GP for comprehensive review as soon as possible if any of the following apply:

  • Last review was 6 months ago or earlier.
  • The person has recently experienced poor asthma control or worsening asthma.
  • The person does not have a current written asthma action plan.
  • The person is experiencing acute asthma.
How this recommendation was developed

Consensus

Based on clinical experience and expert opinion (informed by evidence, where available).

More information

Inhaled corticosteroids for adults: adverse effects

Local adverse effects

Hoarseness (dysphonia) and candidiasis are the most common local adverse effects of inhaled corticosteroids with both pressurised metered-dose inhalers and dry-powder inhalers:6

  • The rate of of dysphonia among patients taking inhaled corticosteroids has been estimated at 5–20%.7 However, higher rates of up to 58% have been reported in some studies.8 The risk varies with the device used.
  • The rate of oropharyngeal candidiasis among adults using inhaled corticosteroids has been estimated at 5–7%, with positive mouth culture for Candida albicans in approximately 25% of patients. However, higher rates of up to 70% have been reported in some studies. The risk depends on the formulation, dose and dose frequency.7

When taking inhaled corticosteroids via pressurised metered-dose inhalers, the use of a spacer reduces the risk of dysphonia and candidiasis.9 Spacers improve delivery of the medicine to the airways.

Rinsing the mouth with water after inhaling reduces the risk of oropharyngeal candidiasis.9 Quick mouth rinsing immediately after inhaling effectively removes a high proportion of remaining medicine.10

The incidence of dysphonia and candidiasis is significantly lower with ciclesonide than with equivalent doses of fluticasone propionate.11 This may an important consideration for patients who experience dysphonia, particularly for those for whom voice quality is important (e.g. singers, actors, teachers). With ciclesonide, the rate of adverse effects may not differ when taken with or without a spacer.12

Systemic adverse effects

Cross-sectional population studies have reported lower bone mineral density with long-term use of high doses of inhaled corticosteroid,5 but the effect on fracture risk in patients with asthma is unclear.

A meta-analysis of randomised controlled trials in adults older than 40 years with COPD (in which osteoporosis is more common) or asthma found no association between the use of inhaled corticosteroid and fracture risk overall, but found a slight increase in facture risk among those using high doses.2

Cross-sectional studies show a dose–response relationship between inhaled corticosteroid use for asthma or COPD, and risk of cataracts in adults.4

Long-term inhaled corticosteroid use for asthma or COPD is associated with a small increase in the risk of developing diabetes, and in the risk of diabetes progression. These risks are greatest at higher doses (equivalent to fluticasone propionate 1000 mcg/day or higher).3

The incidence of osteoporosis, cataracts and diabetes increases with age, and these conditions are also more common in smokers and in patients with COPD. Few studies have assessed risk specifically in patients with asthma.

Patients at risk of osteoporosis should be referred for bone density screening, screened for vitamin D and/or calcium deficiency, and provided with advice about maintaining bone health.

Patient concerns about adverse effects

The prevalence of side effects that patients consider troubling increases with increasing dose of inhaled corticosteroids.13 Mid and high doses are consistently associated with a higher intensity and a higher prevalence of reported adverse effects, after controlling for other factors.13

A high proportion of people with asthma may have misunderstandings and fears about using inhaled corticosteroids,1415 such as fears about weight gain, unwanted muscle development, bone fractures, susceptibility to infections and reduction of efficacy of the medicine over time.14 Most people do not discuss their concerns about inhaled corticosteroid treatment with health professionals.14 Safety concerns are a major reason for poor adherence, particularly general concerns about corticosteroids rather than concerns about specific adverse effects.16

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Ongoing monitoring of asthma in adults

Asthma monitoring includes both self-monitoring by patients and periodic assessments by the clinician.

Asthma management in primary care should include periodic reassessment of (both):17

  • recent asthma symptom control based on symptoms over the previous 4 weeks, with or without lung function testing. In many patients in primary care, symptoms, reliever use and lung function are useful surrogate measures of the degree to which the underlying disease process is controlled.
  • risk factors that predict poor asthma outcomes (e.g. flare-ups, accelerated decline in lung function, or treatment-related adverse effects) independent of the person’s level of recent asthma symptom control.

Planned asthma check-ups should be made at intervals determined by both the individual’s level of recent asthma symptom control and risk factors. The following is a guide:

  • 1–3 months after each adjustment to medications
  • yearly for a person with no flare-up in the past 12 months and good symptom control for at least a year
  • every 6 months for a person who has had a flare-up within the past 12 months or who has other risk factors for flare-ups or life-threatening asthma (e.g. smoking, previous recording of poor lung function on spirometry, history of admission to an intensive care unit for asthma)
  • at least every 3 months for a person with severe asthma, work-exacerbated asthma, poor perception of airflow limitation, frequent rhinosinusitis symptoms, or other comorbid conditions that affect asthma control
  • every 4–6 weeks for pregnant women.

Note: For patients with occupational asthma, management and follow-up by a specialist with experience in occupational asthma is recommended.

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Assessing recent asthma control in adults: symptoms

Questionnaires

Questionnaire-based tools can be used to standardise review of asthma symptoms, e.g.:

  • Primary care Asthma Control Screening tool (also known as Pharmacy Asthma Control Screening tool)18 – a quick screening test to detect poor asthma control, developed and validated for use with Australian patients attending primary care
  • UK Royal College of Physicians ‘3 Questions’19
  • Asthma Score (also known as Asthma Control Test).20
  • Asthma Control Questionnaire (ACQ)

The questionnaires can be completed on paper in the waiting room and scored by the practice nurse. They have also been administered via an application on hand-held personal electronic devices,2122 or by telephone.23

Note: Clinicians and researchers should only use the versions of the ACQ and Asthma Score that have been validated for use in the Australian population. The wording and layout of questionnaires must not be changed.
 

Table. Primary care Asthma Control Screening tool (PACS)

Have you experienced any of the following more than once a week in the last month? Yes No
Symptoms of asthma, cough, wheeze, shortness of breath
  •  
  •  
Waking at night because of asthma
  •  
  •  
Chest tightness on waking
  •  
  •  
Difficulty in performing vigorous activity like running, lifting heavy objects, exercise
  •  
  •  
Difficulty in performing moderate activities like vacuuming, climbing flights of stairs
  •  
  •  

Interpretation: ‘Yes’ to any question indicates that the person may have poorly controlled asthma, so more detailed assessment is needed.

Source: LeMay KS, Armour CL, Reddel HK. Performance of a brief asthma control screening tool in community pharmacy: a cross-sectional and prospective longitudinal analysis. Prim Care Respir J; 2014. Available from: http://dx.doi.org/10.4104/pcrj.2014.00011

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Table. UK Royal College of Physicians ‘3 Questions’ screening tool

In the last month: Yes No
Have you had difficulty sleeping because of your asthma symptoms (including cough)?
  •  
  •  
Have you had your usual asthma symptoms during the day (cough, wheeze, chest tightness or breathlessness)?
  •  
  •  
Has your asthma interfered with your usual activities (e.g. housework, work/school etc)?
  •  
  •  

Inerpetation:

No to all three questions indicates good control.

Yes to 2 or 3 questions indicates poor control.

Yes to 1 question indicates that more detailed questioning is needed to assess level of asthma control (using another validated questionnaire or by asking about frequency of daytime symptoms, reliever requirement, limitation of activities and symptoms at night or on waking during the previous month).

Note: This test provides a quick and easy way of confirming someone’s asthma control is good, or identifying those who need more assessments.

Sources

Thomas M, Gruffydd-Jones K, Stonham C et al. Assessing asthma control in routine clinical practice: use of the Royal College of Physicians ‘3 Questions’. Prim Care Respir J 2009; 18: 83-8. Available from: http://www.nature.com/articles/pcrj200845

Pinnock H, Burton C, Campbell S et al. Clinical implications of the Royal College of Physicians three questions in routine asthma care: a real-life validation study. Prim Care Respir J 2012; 21: 288-94. Available from: http://www.nature.com/articles/pcrj201252

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Symptom-guided management

Data from one UK study suggest that, for the majority of patients attending primary care, asthma symptoms are concordant with eosinophilic airway inflammation, and that symptoms can therefore be used as a guide to changing anti-inflammatory treatment.24

However, if symptoms do not improve as expected after a change in treatment, or if the person continues to experience flare-ups, it is necessary to measure lung function and consider other possible causes:

  • Respiratory symptoms in a person with asthma may be due to non-asthma factors (e.g. cough due to post-nasal drip, shortness of breath due to obesity). Increasing the preventer treatment in such patients could result in unnecessarily high doses. A careful history (with lung function measurement in some patients) is necessary to confirm that symptoms are due to asthma, before deciding to change a person’s treatment.
  • Patients vary in their ability to perceive airflow limitation, so symptoms may be an unreliable measure of asthma control in some patients. Spirometry can help identify if the person is a poor perceiver of airflow limitation (e.g. person is unable to feel the difference when FEV1 increases or decreases by 15%).
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Assessing asthma control in adults: spirometry

Spirometry is necessary when making the diagnosis of asthma and when establishing the patient’s baseline and personal best status.

In ongoing asthma management, spirometry is useful in the following clinical situations:

  • During a flare-up, spirometry provides objective evidence about the severity of bronchoconstriction.
  • After a dose adjustment (either an increase or a decrease), change in lung function measured by spirometry provides additional information about the response to treatment.
  • Spirometry can help identify if the person’s symptoms may be due to non-asthma conditions (e.g. for a patient with frequent respiratory symptoms, FEV1 above 80–90% predicted should prompt consideration of an alternative cause).
  • Spirometry can help identify if the person is a poor perceiver of airflow limitation (e.g. person is unable to feel the difference when FEV1 increases or decreases by 15%).
  • Repeating spirometry over time may identify lung function decline that is more rapid than expected decline due to ageing alone, so the person can be referred for specialist review. (Spirometry should be repeated approximately every 1–2 years in most patients but more frequently as indicated by individual needs.)

There are limits to the amount of information that can be gained from spirometry alone:

  • For an individual, spirometry readings are not closely reproducible between visits, so only a change in FEV1 of greater than 0.2 L and 12% from baseline can be considered clinically meaningful in adults.25
  • Older people with long-standing asthma may develop fixed (irreversible or incompletely reversible) airflow limitation. Reliance solely on lung function expressed as percentage predicted value as a guide to adjusting preventer treatment would risk dose-escalation and over-treatment in these patients.
  • At the population level, spirometry correlates poorly with symptom-based measures of asthma control,26 so in individual patients it is not possible to predict lung function from symptoms or vice versa.

To obtain reliable, good-quality readings, the spirometer must be well maintained and correctly calibrated, and the operator must be adequately trained and experienced.

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Self-monitoring in adults using peak expiratory flow

Peak flow monitoring is no longer routinely used in Australia, but is recommended for patients with severe asthma, a history of frequent flare-ups, or poor perception of airflow limitation.

Peak expiratory flow can be monitored at home using a mechanical or electronic peak flow meter, either regularly every day or when symptoms are worse. For patients who are willing to measure peak flow regularly, morning and evening readings can be plotted on a graph or recorded in a diary.

When peak flow monitoring results are recorded on a graph, the same chart should be used consistently so that patterns can be recognised. Flare-ups are easier to detect when the chart or image has a low ratio of width to height (aspect ratio), i.e. is compressed horizontally.27

When a person’s written asthma action plan is based on peak expiratory flow, instructions should be based on personal best, rather than predicted values. Personal best can be determined as the highest reading over the previous 2 weeks. When a person begins high-dose inhaled corticosteroid treatment, personal best peak expiratory flow reaches a plateau within a few weeks with twice daily monitoring.28

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Assessing risk factors for adverse asthma outcomes in adults

Predicting poor asthma outcomes

As well as assessing recent asthma symptom control, it is necessary to assess each patient’s risk of future asthma events or adverse treatment effects. (Recent asthma symptom control and risk of adverse events are both components of overall asthma control.)

Table. Risk factors for adverse asthma outcomes in adults and adolescents Opens in a new window Please view and print this figure separately: https://www.asthmahandbook.org.au/table/show/40

Table. Management of risk factors for adverse asthma outcomes in adults

Risk factor

Clinical action †

Any risk factor for flare-ups

Check patient has an appropriate action plan

Carefully check inhaler technique and adherence, and identify any barriers to good adherence

Review frequently (e.g. every 3 months)

Hospitalisation or ED visit for asthma or any asthma flare-up during the previous 12 months

Ask about triggers for flare-ups, and lead time

History of intubation or intensive care unit admission for asthma

Ensure action plan recommends early medical review when asthma worsens

Hospitalisation or ED visit for asthma in the past month

Emphasise importance of maintaining regular ICS use after symptoms improve

Confirm that patient has resumed using SABA only when needed for symptoms

High SABA use (>2 canisters per month)

Check lung function

If SABA use appears to be habitual, investigate causes and consider alternative strategies, e.g. short-term substitution of ipratropium for SABA

Long-term high-dose ICS

Consider gradual reduction of ICS dose if symptoms stable

Monitor regularly (e.g. assessment of bone density, regular eye examinations)

For local side-effects, ensure inhaler technique is appropriate

Poor lung function (even if few symptoms)

Consider 3-month trial of higher ICS dose, then recheck lung function

Consider referral for detailed specialist investigation

Sensitivity to unavoidable allergens (e.g. Alternaria species of common moulds)

Refer for further investigation and management

Exposure to cigarette smoke (smoking or environmental exposure)

Emphasise the importance of avoiding smoke

Provide quitting strategies

Consider increasing ICS dose (higher dose of ICS likely to be necessary to control asthma)

Refer for assessment of asthma–COPD overlap

Difficulty perceiving airflow limitation or the severity of exacerbations

Regular PEF monitoring

Action plan should recommend early review and measurement of lung function

No current written asthma action plan

Provide and explain written asthma action plan

† In addition to actions applicable to all risk factors

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Poor clinical control, as indicated by frequent asthma symptoms and frequent reliever use, is a very strong predictor of the risk of flare-ups in the future. Any asthma flare-up during the previous 12 months indicates higher risk of flare-up over the next 12 months. A history  of artificial ventilation due to acute asthma, and admission to an intensive care unit due to acute asthma have been associated with increased risk of near-fatal asthma,29 but there is not enough evidence to indicate how long this risk may persist over a person’s lifetime. Other risk factors indicate increased probability of future flare-ups or accelerated decline in lung function, independent of the person’s level of recent asthma symptom control. 12030

Other factors may increase a person’s risk of treatment-associated adverse effects. The most important of these are prescription of high dose treatment and frequent courses of oral steroids.

People with risk factors need more frequent asthma review, a carefully tailored written asthma action plan, and close attention to adherence and correct inhaler technique.

Inflammatory markers

Inflammatory markers, such as sputum eosinophil percentage or exhaled nitric oxide, are used in research and for managing severe asthma in patients attending secondary or tertiary care. Elevated sputum eosinophil levels and, to a lesser extent, elevated exhaled nitric oxide, are associated with increased risk of flare-ups. At present, treatment based on inflammatory markers is not recommended for routine use in primary care.

The value of inflammatory markers is being evaluated:

  • Adjusting asthma treatment by monitoring exhaled nitric oxide does not reduce the rate of flare-ups or improve asthma control in adults and children, compared with adjusting treatment according to clinical symptoms or spirometry, based on a meta-analysis of randomised controlled clinical trials.31 However, many of the studies were not optimally designed to answer this question,32 and some comparator regimens did not match current recommended treatment options.
  • In some studies, asthma treatment algorithms based on monitoring sputum eosinophil counts reduced flare-ups, compared with control-based management.17, 33 However, most studies assessing treatment guided by sputum eosinophilia have been conducted in selected populations in a few research centres, and therefore may not apply to the general community population. Assessment of sputum inflammatory cells is not generally available at present even in secondary care.
  • Limited evidence24 suggests that patients whose symptoms do not match their degree of eosinophilic inflammation may benefit more from treatment monitoring using sputum eosinophil count than other patients.
  • Monitoring inflammatory markers might enable safer down-titration of maintenance inhaled corticosteroid doses.
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Health system initiatives that support asthma care

Chronic Disease Management Medicare items

Patients with asthma are eligible for Chronic Disease Management Medicare items.34 These include:

  • Preparation of a GP Management Plan (Item 721)
  • Review of a GP Management Plan (Item 732)
  • Coordination of Team Care Arrangements (Item 723) for patients who need ongoing care from a multidisciplinary team of at least three health or care providers
  • Coordination of a Review of Team Care Arrangements (Item 732)
  • Contribution to a multidisciplinary care plan being prepared by another health or care provider (Item 729)
  • Contribution to a multidisciplinary care plan being prepared for a resident of an aged care facility (Item 731).

GPs can be assisted by practice nurses, Aboriginal and Torres Strait Islander health practitioners, Aboriginal health workers and other health professionals.34

Asthma cycle of care

The Asthma cycle of care is an Australian Government initiative to support primary care health professionals (GPs, other medical practitioners and trainees) to provide asthma care. It is implemented through the Practice Incentives Program (PIP) Asthma Incentive and applies to the clinical care of people with moderate-to-severe asthma, generally defined as people with (any of):35

  • symptoms on most days
  • use of preventative medication
  • bronchodilator use at least three times per week
  • hospital attendance or admission following an acute asthma flare-up.

The Asthma cycle of care involves at least two asthma-related consultations within 12 months for a patient with moderate-to-severe asthma, of which at least one visit is a planned asthma review. Each consultation includes:

  • documenting the diagnosis, assessing asthma severity and assessing level of recent asthma symptom control
  • reviewing the patient’s use of and access to asthma medicines and inhaler devices
  • providing a written asthma action plan (or documented alternative, if the patient is unable to use a written action plan)
  • providing asthma self-management education
  • reviewing the written or documented asthma action plan.

The Personally Controlled eHealth Record System

The eHealth record is an electronic record for a patient that contains a summary of their health information. Patients can choose to register for an eHealth record. Authorised healthcare professionals can access a patient’s record and upload information to the record if their healthcare organisation has registered for the eHealth record system.

Health system initiatives for Aboriginal and Torres Strait Islander people

Health system initiatives to support the care of Aboriginal and Torres Strait Islander people include:

  • Health Assessment Medicare items
  • The Indigenous Chronic Disease Package
  • The Asthma Spacer Ordering System.
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References

  1. Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention. GINA, 2012. Available from: http://www.ginasthma.org
  2. Etminan M, Sadatsafavi M, Ganjizadeh ZS, et al. Inhaled corticosteroids and the risk of fractures in older adults: a systematic review and meta-analysis. Drug Saf. 2008; 31: 409-14. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18422381
  3. Suissa S, Kezouh A, Ernst P. Inhaled Corticosteroids and the Risks of Diabetes Onset and Progression. Am J Med. 2010; 123: 1001-1006. Available from: http://www.amjmed.com/article/S0002-9343(10)00648-0/fulltext
  4. Weatherall M, Clay J, James K, et al. Dose-response relationship of inhaled corticosteroids and cataracts: a systematic review and meta-analysis. Respirology. 2009; 14: 983-90. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19740259
  5. Wisniewski AF, Lewis SA, Green DJ, et al. Cross sectional investigation of the effects of inhaled corticosteroids on bone density and bone metabolism in patients with asthma. Thorax. 1997; 52: 853-60. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1758420/
  6. Rachelefsky GS, Liao Y, Faruqi R. Impact of inhaled corticosteroid-induced oropharyngeal adverse events: results from a meta-analysis. Ann Allergy Asthma Immunol. 2007; 98: 225-38. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17378253
  7. Buhl R. Local oropharyngeal side effects of inhaled corticosteroids in patients with asthma. Allergy. 2006; 61: 518-526. Available from: http://onlinelibrary.wiley.com/doi/10.1111/j.1398-9995.2006.01090.x/full
  8. Galvan CA, Guarderas JC. Practical considerations for dysphonia caused by inhaled corticosteroids. Mayo Clin Proc. 2012; 87: 901-4. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3496982/
  9. National Asthma Council Australia. Inhaler technique in adults with asthma or COPD. An information paper for health professionals. National Asthma Council Australia, Melbourne, 2008. Available from: http://www.nationalasthma.org.au/publication/inhaler-technique-in-adults-with-asthma-or-copd
  10. Yokoyama H, Yamamura Y, Ozeki T, et al. Effects of mouth washing procedures on removal of budesonide inhaled by using Turbuhaler. Yakugaku Zasshi. 2007; 127: 1245-1249. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17666876
  11. Bateman ED, Linnhof AE, Homik L, et al. Comparison of twice-daily inhaled ciclesonide and fluticasone propionate in patients with moderate-to-severe persistent asthma. Pulm Pharmacol Ther. 2008; 21: 264-275. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17604664
  12. Engelstatter R, Szlavik M, Gerber C, Beck E. Once-daily ciclesonide via metered-dose inhaler: Similar efficacy and safety with or without a spacer. Respir Med. 2009; 103: 1643-50. Available from: http://www.resmedjournal.com/article/S0954-6111(09)00195-4/fulltext
  13. Forster JM, Aucott L, van der Werf RH, et al. Higher patient perceived side effects related to higher daily doses of inhaled corticosteroids in the community: a cross-sectional analysis. Respir Med. 2006; 100: 1318-1336. Available from: http://www.resmedjournal.com/article/S0954-6111(05)00520-2/fulltext
  14. Boulet LP. Perception of the role and potential side effects of inhaled corticosteroids among asthmatic patients. Chest. 1998; 113: 587-92. Available from: http://www.ncbi.nlm.nih.gov/pubmed/9515829
  15. Boulet LP, Vervloet D, Mager Y, Forster J. Adherence: the goal to control asthma. Clin Chest Med. 2012; 33: 405-417. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22929091
  16. Foster JM, Smith L, Bosnic-Anticevich SZ, et al. Identifying patient-specific beliefs and behaviours for conversations about adherence in asthma. Intern Med J. 2012; 42: e136-e144. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21627747
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