Asthma Management Handbook

Assessing and managing asthma in adolescents and young adults

Recommendations

By mid-adolescence (around 14–16 years), consider applying asthma management guidance for adults in most situations.

Note: Whether the individual is considered to be a child or adult for the purposes of prescribing will depend on the individual’s size and clinical factors, TGA-approved product information for medicines, and PBS subsidisation criteria.

How this recommendation was developed

Consensus

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

For patients who report the diagnosis of asthma made in the past or elsewhere, confirm the diagnosis if possible.

Table. Confirming the diagnosis of asthma in a person using preventer treatment Opens in a new window Please view and print this figure separately: https://www.asthmahandbook.org.au/table/show/9

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):

  • Aaron et al. 20081
  • Lucas et al. 20082
  • Luks et al. 20103
  • Marklund et al. 19994

Consider whether exercise-related symptoms may be due to a non-asthma cause such as poor cardiopulmonary fitness (particularly in obese patients), upper airway dysfunction, hyperventilation or anxiety.

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):

  • British Thoracic Society and Scottish Intercollegiate Guidelines Network, 20085
  • Tilles, 20106
  • Rietveld et al. 19997

Plan regular asthma review as for adults. Explain that asthma often changes during these years so it is important to keep adjusting the treatment to maintain good control at the lowest effective dose.

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

How this recommendation was developed

Consensus

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

For adolescents taking regular inhaled corticosteroid whose asthma has been well controlled for at least 3 months, try reducing the dose or stepping down by one step while monitoring. If well controlled for at least 3 months on the lowest dose, consider a trial cessation of inhaled corticosteroid.

Note: For those in mid-to-late adolescence, follow the guidance for adults

Figure. Stepped approach to adjusting asthma medication in children Opens in a new window Please view and print this figure separately: https://www.asthmahandbook.org.au/figure/show/18

Figure. Stepped approach to adjusting asthma medication in adults Opens in a new window Please view and print this figure separately: https://www.asthmahandbook.org.au/figure/show/31

How this recommendation was developed

Consensus

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

When assessing the causes of poor asthma control, consider psychosocial and behavioural factors such as non-adherence to preventer medicines, smoking or exposure to other people’s tobacco smoke.

How this recommendation was developed

Consensus

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

If adherence to preventer medicines is inadequate, explore barriers and motivating factors.

How this recommendation was developed

Consensus

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

Explain to young people that asthma medicines do not have any effects on sexual activity or fertility in the short-term or long-term.

How this recommendation was developed

Consensus

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

Assess and manage comorbid conditions, lifestyle and psychosocial factors that could affect asthma:

  • encourage adequate physical activity and healthy eating
  • repeatedly assess smoking status and offer help to quit
  • manage obesity according to national guidelines
  • identify and manage allergic rhinitis, mental health conditions (e.g. depression and anxiety), gastro-oesophageal reflux disease and sleep disorders
  • identify and manage psychosocial risk factors.

Table. Interrelated psychosocial risk factors for poor asthma control in adolescents

Poor adherence to treatment

Denying or disregarding asthma symptoms

Avoiding regular review appointments

Life events (new school, moving house, family disruption, absent parent)

Family problems (e.g. family conflict, family dysfunction)

Psychological distress (e.g. feelings of hopelessness, bereavement or recent loss)

Mental health problems (e.g. depression, emerging mood disorders)

Risky use of alcohol/other substances

Communication problems

Risk behaviours or disregard of symptoms may indicate emerging mental health problems. Poor adherence can be an indicator of family problems, life events and psychological distress.

Source: Bender BG. Risk taking, depression, adherence, and symptom control in adolescents and young adults with asthma. Am J Respir Crit Care Med 2006; 173: 953-957. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16424441

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How this recommendation was developed

Consensus

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

For girls and women, assess whether flare-ups are affected by the menstrual cycle. For girls and woman with predictable perimenstrual worsening of asthma symptoms, consider hormonal management or refer for investigation.

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):

  • Boulet, 20098
  • Rao et al. 20139

In pharmacies, ask adolescents and young adults buying non-prescription relievers when they last saw their doctor, and encourage asthma check-ups.

How this recommendation was developed

Consensus

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

If the person has been seeing a paediatric respiratory physician, arrange a new referral to a respiratory physician who treats adults, when appropriate. Discuss the transition to adult health care and check that the young person is satisfied with the adult services.

How this recommendation was developed

Consensus

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

More information

Diagnostic difficulties when investigating asthma-like symptoms in adolescents

Asthma is commonly misdiagnosed in young people presenting with exercise-related symptoms or cough.10 Conditions associated with dyspnoea include hyperventilation, anxiety, and poor cardiopulmonary fitness.11

Both denial and overplay of symptoms has been observed among adolescents.10 Adolescents with new or re-emerging asthma symptoms may deny their symptoms.10 US data suggest that risk factors for undiagnosed asthma among adolescents include female sex, smoking (current smoking and exposure to others’ smoke), low socioeconomic status, family problems, low physical activity and high body mass.12

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Exercise-related symptoms in adolescents

In adolescents, exercise-related wheezing and breathlessness are poor predictors of exercise-induced bronchoconstriction. Only a minority of adolescents referred for assessment of exercise-induced respiratory symptoms show objective evidence of exercise-induced bronchoconstriction.13

For adolescents with exercise-related symptoms, common conditions that should be considered in the differential diagnosis include poor cardiopulmonary fitness, exercise-induced upper airway dysfunction and exercise-induced hyperventilation.106

In addition to spirometry, other objective tests (e.g. cardiopulmonary fitness testing, bronchial provocation tests) may be helpful to clarify the diagnosis and inform management.

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Physiological and psychological changes

Stress, anxiety and extreme emotions

Some patients report asthma flare-ups and asthma symptoms in response to stress and extreme emotions.1415

Adolescents with asthma may experience breathlessness in response to stress (without changes in lung function or other asthma symptoms).7

Laughter

Laughing is a common trigger for wheeze in infants. In children, the presence of respiratory symptoms that are triggered by laughter increases the probability of symptoms being due to asthma.

Hormonal changes

Asthma may worsen during the premenstrual phase in up to 40% of women, possibly due to a reduced response to corticosteroids and bronchodilators.8 However, this rarely causes severe flare-ups.8

Perimenstrual worsening asthma may be relatively common among women with severe or poorly controlled asthma, and may share risk factors with aspirin-exacerbated respiratory disease.9

Asthma control worsens during pregnancy in about one third of women with asthma.16 During pregnancy, approximately 6% of women with asthma are hospitalised with a severe asthma flare-up.1718

Sexual activity

Sexual activity may trigger asthma symptoms possibly due to physical exertion (exercise-induced bronchoconstriction), heightened emotion, or a combination of these factors. Exposure to dust mite allergens in bedding may also be a trigger for people who are sensitised.

People with asthma may experience limitation to sexual activity due to asthma or be concerned about the effect of their asthma on their sex life.1920 However, patients are unlikely to mention concerns about sexual activity to their doctor.20

Practical information for patients about sex and asthma is available from Asthma Australia.

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Impact of puberty on asthma

In the past, it was thought that children typically 'outgrew' asthma due to maturation of the autonomic and central nervous systems under the effect of sex steroids during puberty.21 However, there is little evidence to support this assumption.21 Puberty does not predict remission of asthma. Almost two-thirds of children with chronic asthma have persistent symptoms throughout puberty.21

Early puberty has been reported to be an independent risk factor for the persistence of asthma into adolescence, and for the severity of asthma in adulthood.21 The mechanism for this association is unclear, and might involve the effects of hormonal changes on reactivity of airways or risk factors that are common to both asthma and early puberty.21

Increased BMI in girls has been associated with both early puberty and increased asthma risk.

Australian data show that more boys than girls experience remission of asthma during adolescence (based on 2007–2008 data):22

  • the prevalence of current asthma is higher for boys than girls among children aged 0–14 years, and higher for women among people aged 15 years and over
  • the prevalence of current asthma in children aged 10–14 years is approximately 12% for boys and 7% for girls
  • the prevalence of current asthma in adolescents and young adults aged 15–24 years is approximately 11% in both sexes.

Asthma can worsen or improve during adolescence; close monitoring is necessary so that medicines can be adjusted to maintain good asthma control at the lowest effective doses. If attempted back-titration of an adolescent’s preventer dose or step-down in the treatment regimen results in worsening of asthma symptoms, this experience can help the person understand why it is necessary to take these medicines regularly. Health professionals can make unsuccessful back-titration an opportunity to reinforce self-management education.

Asthma can occur for the first time during adolescence, more commonly in girls than boys.10 The true prevalence of asthma in adolescents is difficult to estimate because of under- and over-diagnosis.

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Transition to adult asthma care

The late teens and early twenties can be a dangerous period for young people with asthma because GPs and parents often assume that the parent’s good management of their child’s asthma will automatically continue as the child grows up. Good self-management cannot be assumed, and health professionals need to carefully check the patient’s understanding of their asthma and its treatment.

Equipping and supporting an adolescent with a chronic disease to take over self-management of their condition as they grow up and make a smooth transition to adult health services requires planning. Some experts consider this in three phases:

  • early stage (12–14 years) – the adolescent begins to participate in his or her own care
  • middle stage (15–16 years) – the adolescent gains skills and information to take over self-care
  • late stage (17–18 years) – the young person moves into the adult system.
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Resources for health professionals working with adolescents
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Stepping down regular asthma medicines in adults

The main aim of medical treatment for asthma is to achieve good asthma control and minimise the risks of asthma with the lowest effective dose of preventer medicines for each individual.

Stepping down is considered when the patient has experienced good asthma control for 2–3 months and is at low risk of flare-ups.

Figure. Stepped approach to adjusting asthma medication in adults Opens in a new window Please view and print this figure separately: https://www.asthmahandbook.org.au/figure/show/31

General tips

It is important to ascertain the person’s actual treatment regimen before stepping down, because many patients may already be taking their preventer only intermittently.

Those who deliberately avoid taking their preventer due to concerns about inhaled corticosteroids may accept regular daily treatment at a lower dose, with an action plan to deal with flare-ups.

Steps down should be planned before the patient has finished their current inhaler, so that the previous dose can be resumed immediately if asthma control deteriorates.

Patients should be advised to step back up if they or their clinician judge that their asthma is worse overall (not just after the first time they experience asthma symptoms after stepping down). Patients and clinicians should agree beforehand on criteria for worsening asthma control.

Some patients are very concerned about reducing their dose (despite the risk of treatment-related adverse effects) and may prefer to stay on high doses for long periods. To enable early detection of deterioration in control during step-down, patients can be asked to monitor their peak flow for 2 weeks before, and 3–4 weeks after, the dose reduction.

Stepping down inhaled corticosteroid dose

For many patients with well-controlled asthma taking inhaled corticosteroid/long-acting beta2 agonist combinations or inhaled corticosteroids alone, the inhaled corticosteroid dose can be reduced without loss of asthma control if downward dose adjustments are made gradually.2324

The dose can be reduced by stepping down through the available formulations.

Note: TGA-registered fluticasone furoate/vilanterol combinations contain moderate-to-high doses of inhaled corticosteroid (100/25 mcg and 200/25 mcg respectively).

Ceasing inhaled corticosteroid

Patients with well-controlled asthma who stop taking regular low-dose inhaled corticosteroid treatment have an increased risk of flare-ups, compared with those who continue inhaled corticosteroids.25

It may sometimes be necessary to stop treatment temporarily in order to confirm the diagnosis of asthma in a person taking inhaled corticosteroids. In this situation, close monitoring of symptom control is needed.

Table. Confirming the diagnosis of asthma in a person using preventer treatment Opens in a new window Please view and print this figure separately: https://www.asthmahandbook.org.au/table/show/9

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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Ceasing long-acting beta2 agonist

Patients whose asthma is well controlled with an inhaled corticosteroid/long-acting beta2 agonist combination (either as conventional maintenance treatment plus short-acting beta2 agonist reliever, or as budesonide/formoterol maintenance-and-reliever therapy) can continue taking this regimen long-term. The dose can be reduced by stepping down through the available formulations.

Alternatively, for patients taking an inhaled corticosteroid/long-acting beta2 agonist combination as maintenance treatment, the combination can be replaced with an inhaled corticosteroid inhaler at the same dose. However, a meta-analysis of several studies reported deterioration in asthma control after ceasing long-acting beta2 agonist treatment in patients with asthma previously stabilised on inhaled corticosteroid/long-acting beta2 agonist combination. Therefore, if inhaled corticosteroid/long-acting beta2 agonist is replaced by inhaled corticosteroid only, patients should be advised to start taking their old combination inhaler again if asthma worsens within the first few days after switching.

Note: For patients taking fluticasone furoate/vilanterol, no studies are available to guide stepping down. Options include stepping down to inhaled corticosteroid alone (recommended in the TGA-approved Product Information),26 or stepping down to a different inhaled corticosteroid/long-acting beta2 agonist combination that will achieve a lower inhaled corticosteroid dose. (e.g. Stepping down from treatment with once-daily medium dose fluticasone furoate/vilanterol [100/25 mcg] can be achieved by switching to twice-daily low-dose fluticasone propionate/salmeterol [100/50 mcg or 50/25 mcg]). With either option, patients need careful explanation, including clear written instructions, to avoid potential confusion when changing between inhaler devices and dosing frequencies.

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Definition of variable expiratory airflow limitation

Most of the tests for variable expiratory airflow limitation are based on showing variability in FEV1. While reduced FEV1 may be seen with many other lung diseases (or due to poor spirometric technique), a reduced ratio of FEV1 to FVC indicates airflow limitation.27 Normal FEV1/FVC values derived from population studies vary,2829 but are usually greater than:28

  • 0.85 in people aged up to 19 years
  • 0.80 in people aged 20–39 years
  • 0.75 in people aged 40–59 years
  • 0.70 in people aged 60–80 years.

In children, it is less useful to define expiratory airflow limitation according to a specific cut-off for FEV1/FVC ratio, because normal values in children change considerably with age.29

Some spirometers provide predicted normal values specific to age group. If these are available, a FEV1/FVC ratio less than the lower limit of normal (i.e. less than the 5th percentile of normal population) indicates airflow limitation.

Variable expiratory airflow limitation (beyond the range seen in healthy populations) can be documented if any of the following are recorded:

  • a clinically important increase in FEV1 (change in FEV1 of at least 200 mL and 12% from baseline for adults, or at least 12% from baseline for children) 10–15 minutes after administration of bronchodilator
  • clinically important variation in lung function (at least 20% change in FEV1) when measured repeatedly over time (e.g. spirometry on separate visits)
  • a clinically important reduction in lung function (decrease in FEV1 of at least 200 mL and 12% from baseline on spirometry, or decrease in peak expiratory flow rate by at least 20%) after exercise (formal laboratory-based exercise challenge testing uses different criteria for exercise-induced bronchoconstriction)
  • a clinically important increase in lung function (at least 200 mL and 12% from baseline) after a trial of 4 or more weeks of treatment with an inhaled corticosteroid
  • clinically important variation in peak expiratory flow (diurnal variability of more than 10%)
  • a clinically important reduction in lung function (15–20%, depending on the test) during a test for airway hyperresponsiveness (exercise challenge test or bronchial provocation test) measured by a respiratory function laboratory.

Notes

Patients referred to a respiratory function laboratory may be asked not to take certain medicines within a few hours to days before a spirometry visit.

A clinically important increase or decrease in lung function is defined as a change in FEV1 of at least 200 mL and 12% from baseline for adults, or at least 12% from baseline for children, or a change in peak expiratory flow rate of at least 20% on the same meter.3027 A clinically important increase in FVC after administering bronchodilator may also indicate reversible airflow limitation, but FVC is a less reliable measure in primary care because FVC may vary due to factors such as variation in inspiratory volume or expiratory time.

The finding of ‘normal’ lung function during symptoms reduces the probability that a patient has asthma, but a clinically important improvement in response to bronchodilator or inhaled corticosteroid can occur in patients whose baseline value is within the predicted normal range.

The greater the variation in lung function, the more certain is the diagnosis of asthma. However, people with longstanding asthma may develop fixed airflow limitation.

Reversibility in airflow limitation may not be detected if the person is already taking a long-acting beta2 agonist or inhaled corticosteroid.

Airflow limitation can be transient and does not necessarily mean that the person has asthma (e.g. when recorded during a severe acute infection of the respiratory tract). Ideally, airflow limitation should be confirmed when the patient does not have a respiratory tract infection. Reduction in lung function during a respiratory tract infection with improvement in lung function after its resolution, commonly occurs in people with asthma, but can also be seen in patients with COPD or in healthy people without either asthma or COPD.31,32

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References

  1. Aaron SD, Vandemheen KL, Boulet LP, et al. Overdiagnosis of asthma in obese and nonobese adults. CMAJ. 2008; 179: 1121-1131. Available from: http://www.cmaj.ca/content/179/11/1121.full
  2. Lucas AE, Smeenk FW, Smeele IJ, van Schayck CP. Overtreatment with inhaled corticosteroids and diagnostic problems in primary care patients, an exploratory study. Fam Pract. 2008; 25: 86-91. Available from: http://fampra.oxfordjournals.org/content/25/2/86.full
  3. Luks VP, Vandemheen KL, Aaron SD. Confirmation of asthma in an era of overdiagnosis. Eur Respir J. 2010; 36: 255-260. Available from: http://erj.ersjournals.com/content/36/2/255.full
  4. Marklund B, Tunsäter A, Bengtsson C. How often is the diagnosis bronchial asthma correct?. Fam Pract. 1999; 16: 112-116. Available from: http://fampra.oxfordjournals.org/content/16/2/112.full
  5. British Thoracic Society (BTS) Scottish Intercollegiate Guidelines Network (SIGN). British Guideline on the Management of Asthma. Quick Reference Guide. Revised May 2011. BTS, SIGN, Edinburgh, 2008.
  6. Tilles SA. Exercise-induced respiratory symptoms: an epidemic among adolescents. Ann Allergy Asthma Immunol. 2010; 104: 361-7; 368-70, 412. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20486325
  7. Rietveld S, van Beest I, Everaerd W. Stress-induced breathlessness in asthma. Psychol Med. 1999; 29: 1359-66. Available from: http://www.ncbi.nlm.nih.gov/pubmed/10616941
  8. Boulet LP. Influence of comorbid conditions on asthma. Eur Respir J. 2009; 33: 897-906. Available from: http://erj.ersjournals.com/content/33/4/897.long
  9. Rao CK, Moore CG, Bleecker E, et al. Characteristics of perimenstrual asthma and its relation to asthma severity and control: data from the Severe Asthma Research Program. Chest. 2013; 143: 984-92. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23632943
  10. Towns SJ, van Asperen PP. Diagnosis and management of asthma in adolescents. Clin Respir J. 2009; 3: 69-76. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20298380
  11. Weinberger M, Abu-Hasan M. Pseudo-asthma: when cough, wheezing, and dyspnea are not asthma. Pediatrics. 2007; 120: 855-864. Available from: http://pediatrics.aappublications.org/content/120/4/855.full
  12. Yeatts K, Davis KJ, Sotir M, et al. Who gets diagnosed with asthma? Frequent wheeze among adolescents with and without a diagnosis of asthma. Pediatrics. 2003; 111: 1046-54. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12728087
  13. British Thoracic Society (BTS), Scottish Intercollegiate Guidelines Network (SIGN). British Guideline on the Management of Asthma. A national clinical guideline. BTS, SIGN, Edinburgh, 2012. Available from: https://www.brit-thoracic.org.uk/guidelines-and-quality-standards/asthma-guideline/
  14. Busse WW. The brain and asthma: what are the linkages?. Chem Immunol Allergy. 2012; 98: 14-31. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22767055
  15. Theoharides TC, Enakuaa S, Sismanopoulos N, et al. Contribution of stress to asthma worsening through mast cell activation. Ann Allergy Asthma Immunol. 2012; 109: 14-9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22727152
  16. Murphy VE, Gibson PG. Asthma in pregnancy. Clin Chest Med. 2011; 32: 93-110. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21277452
  17. Murphy VE, Clifton VL, Gibson PG. Asthma exacerbations during pregnancy: incidence and association with adverse pregnancy outcomes. Thorax. 2006; 61: 169-76. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2104591/
  18. Ali Z, Ulrik CS. Incidence and risk factors for exacerbations of asthma during pregnancy. J Asthma Allergy. 2013; 6: 53-60. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3650884/
  19. Meyer IH, Sternfels P, Fagan JK, Ford JG. Asthma-related limitations in sexual functioning: an important but neglected area of quality of life. Am J Public Health. 2002; 92: 770-2. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1447159/
  20. Kaptein AA, van Klink RC, de Kok F, et al. Sexuality in patients with asthma and COPD. Respir Med. 2008; 102: 198-204. Available from: http://www.resmedjournal.com/article/S0954-6111(07)00400-3/fulltext
  21. Patton GC, Viner R. Pubertal transitions in health. Lancet. 2007; 369: 1130-1139. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17398312
  22. Australian Centre for Asthma Monitoring. Asthma in Australia 2011: with a focus chapter on chronic obstructive pulmonary disease. Asthma series no. 4. Cat. no ACM 22. Australian Institute of Health and Welfare, Canberra, 2011. Available from: http://www.aihw.gov.au/publication-detail/?id=10737420159
  23. Reddel HK, Gibson PG, Peters MJ, et al. Down-titration from high-dose combination therapy in asthma: removal of long-acting. Respir Med. 2010; 104: 1110-1120. Available from: http://www.resmedjournal.com/article/S0954-6111(10)00156-3/fulltext
  24. Hagan JB, Samant SA, Volcheck GW, et al. The risk of asthma exacerbation after reducing inhaled corticosteroids: a systematic review and meta-analysis of randomized controlled trials. Allergy. 2014; 69: 510-6. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24571355
  25. Rank MA, Hagan JB, Park MA, et al. The risk of asthma exacerbation after stopping low-dose inhaled corticosteroids: a systematic review and meta-analysis of randomized controlled trials. J Allergy Clin Immunol. 2013; 131: 724-9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23321206
  26. GlaxoSmithKline Australia Pty Ltd. Product Information: Breo (fluticasone furoate; vilanterol) Ellipta. Therapeutic Goods Administration, Canberra, 2014. Available from: https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf
  27. Pellegrino R, Viegi G, Brusasco V, et al. Interpretative strategies for lung function tests. Eur Respir J. 2005; 26: 948-968. Available from: http://erj.ersjournals.com/content/26/5/948
  28. National Heart Lung and Blood Institute (NHLBI) National Asthma Education and Prevention Program. Expert Panel Report 3: guidelines for the diagnosis and management of asthma. Full report 2007. US Department of Health and Human Services National Institutes of Health, Bethesda, 2007. Available from: http://www.nhlbi.nih.gov/health-pro/guidelines/current/asthma-guidelines/full-report
  29. Quanjer PH, Stanojevic S, Cole TJ, et al. Multi-ethnic reference values for spirometry for the 3-95-yr age range: the global lung function 2012 equations. Eur Respir J. 2012; 40: 1324-43. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22743675
  30. Levy ML, Quanjer PH, Booker R, et al. Diagnostic Spirometry in Primary Care: Proposed standards for general practice compliant with American Thoracic Society and European Respiratory Society recommendations. Prim Care Respir J. 2009; 18: 130-147. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19684995
  31. Collier AM, Pimmel RL, Hasselblad V, et al. Spirometric changes in normal children with upper respiratory infections. Am Rev Respir Dis. 1978; 117: 47-53. Available from: http://www.ncbi.nlm.nih.gov/pubmed/619724
  32. Melbye H, Kongerud J, Vorland L. Reversible airflow limitation in adults with respiratory infection. Eur Respir J. 1994; 7: 1239-1245. Available from: http://www.ncbi.nlm.nih.gov/pubmed/7925901