Asthma Management Handbook

Management considerations for patients with asthma–COPD overlap

Recommendations

For patients with features of COPD and any features of asthma, prescribe regular long-term inhaled corticosteroids (at a low dose, if possible, or at the lowest effective dose) to reduce the risk of serious flare-ups, even if asthma symptoms appear to be mild or infrequent.

  • Monitor closely for lower respiratory tract infections, and advise patients to get medical advice immediately if they develop symptoms of a lower respiratory tract infection.

How this recommendation was developed

Adapted from existing guidance

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

  • Abramson et al. 20121
  • GINA and GOLD, 20172
  • NACA, 20173

Consider adding a long-acting bronchodilator (long-acting muscarinic antagonist [anticholinergic] or LABA), if symptoms and/or flare-ups are not well controlled. Options include:

  • combination inhaled corticosteroid/long-acting beta2 agonist in a single inhaler (or separate inhalers if the preferred combination is not available in a single inhaler)
  • concomitant treatment with an inhaled corticosteroid and a long-acting muscarinic antagonist (anticholinergic)
  • the combination of an inhaled corticosteroid, a long-acting muscarinic antagonist and a long-acting beta2 agonist (with at least two of the agents in a single inhaler).

Ensure all patients have a short-acting beta2 agonist to use as needed for symptom relief.

Table. Long-acting bronchodilators for asthma–COPD overlap

Class

Dosing frequency

Agent

Brand name

ICS–LABA combinations

Once daily

Fluticasone furoate + vilanterol

Breo Ellipta#

Twice daily

Budesonide + formoterol

Symbicort Rapihaler

Symbicort Turbuhaler

Twice daily

Fluticasone propionate + formoterol

Flutiform

Twice daily

Fluticasone propionate + salmeterol

Fluticasone and Salmeterol Cipla

Seretide Accuhaler

Seretide MDI

LABAs*

Once daily

Indacaterol

Onbrez Breezhaler

Twice daily Formoterol

Oxis

Foradile

Twice daily Salmeterol

Serevent Accuhaler

LAMAs* Once daily Glycopyrronium

Seebri Breezhaler

Once daily

Tiotropium

Spiriva

Spiriva Respimat

Once daily

Umeclidinium

Incruse Ellipta

Twice daily Aclidinium

Bretaris Genuair

LABA–LAMA combinations*

Once daily

Indacaterol + glycopyrronium

Ultibro Breezhaler

Once daily

Olodaterol + tiotropium

Spiolto Respimat

Once daily

Vilanterol + umeclidinium

Anoro Ellipta

Twice daily

Formoterol + aclidinium

Brimica Genuair

  • * Ensure that patient is also using regular long-term ICS. LABAs and LAMAs should not be used by people with asthma or asthma–COPD overlap unless they are also taking an ICS, in combination or separately)

# Only the 100/25 mcg dose of fluticasone furoate/vilanterol is TGA-approved for treatment of COPD. The higher dose (200/25 mcg) is not TGA-approved for the treatment of COPD, so it should not be used in people with asthma–COPD overlap.

High doses of ICS (alone or in combination) are not recommended in patients with COPD and should therefore be used with caution in patients with asthma-COPD overlap, because of the risk of pneumonia.

Refer to PBS status before prescribing.

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Note: The use of separate inhalers for concomitant treatment with an inhaled corticosteroid and a long-acting bronchodilator (long-acting beta2-agonist or long-acting muscarinic antagonist) in patients with asthma–COPD overlap should be avoided due to the risk of selective non-adherence with the inhaled corticosteroid. If no combination product is available for the desired combination, carefully explain to the patient that it is very important that they continue taking the inhaled corticosteroid, to reduce the risk of hospitalisation or death. 

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):

  • Abramson et al. 20121

Consider pulmonary rehabilitation for patients with asthma–COPD overlap, manage comorbidities, and provide advice on physical activity, vaccinations, and self-management. Provide a written action plan. Choose an asthma action plan or a COPD action plan template, depending on the person’s dominant clinical features.

How this recommendation was developed

Consensus

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

Advise patients to follow their action plan or get medical advice within 24 hours if they develop symptoms that suggest a lower respiratory tract infection (e.g. fever, increased sputum production, worsening shortness of breath).

How this recommendation was developed

Consensus

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

Consider specialist referral for patients with atypical symptoms or symptoms that suggest an alternative diagnosis, persistent symptoms or flare-ups despite treatment, or complex comorbidities.

How this recommendation was developed

Consensus

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

More information

Asthma–COPD overlap

Distinguishing between typical allergic asthma (childhood-onset allergic asthma) and typical COPD (emphysema in a heavy smoker) is straightforward.4 However, it can be difficult to distinguish COPD from asthma in adults who have features of both conditions.2, 5These people are described as having asthma–COPD overlap.2, 4, 6

Asthma–COPD overlap is not a single, well-defined disease entity, but includes a range of airway disease phenotypes with different causal mechanisms.2, 7 Features of both asthma and COPD have been described in:6, 8, 9, 10

  • people with current asthma (allergic or non-allergic) who have had significant exposure to tobacco smoke
  • people with longstanding asthma or late-onset asthma who have become persistently short of breath over time
  • people significant smoking history and symptoms consistent with COPD who also have a history of childhood asthma
  • people who present in middle age or later with shortness of breath, with a history of childhood asthma but no or few symptoms in between, and little smoking history.

Figure. Development of asthma, COPD and asthma–COPD overlap Opens in a new window Please view and print this figure separately: https://www.asthmahandbook.org.au/figure/show/108

People with asthma–COPD overlap often have poor disease outcomes, including:2, 10, 11, 12, 13, 14

  • high need for healthcare services
  • worse quality of life, more wheezing, dyspnoea, cough and sputum production, and more frequent and severe respiratory exacerbations and hospitalisations, than people with COPD or asthma alone
  • worse lung function demonstrated by spirometry than those with COPD alone, despite lower average exposure to tobacco smoke.

Features of asthma, COPD and asthma–COPD overlap

If several features of both asthma and COPD are present and neither condition is strongly favoured, respiratory disease should be managed according to recommendations for asthma–COPD overlap.

Table. Features that, when present, favour asthma or COPD

Clinical feature (if measured/relevant)

Asthma more likely

COPD more likely

Age of onset

Before 20 After 40

Pattern of symptoms

Variation in respiratory symptoms:

  • changes over minutes, hours or days
  • worse at night or early morning
  • triggered by exercise, emotions, airborne pollutants or allergens

Persistence of respiratory symptoms despite treatment

Symptoms every day, including exertional dyspnoea

History of chronic cough and sputum unrelated to specific triggers, before onset of dyspnoea

Lung function

Expiratory airflow limitation* is variable#

Lung function normal between symptoms

Expiratory airflow limitation* is persistent

Lung function abnormal between symptoms

History

Previous diagnosis of asthma

Family history of asthma and allergies§ (allergic rhinitis or eczema)

Previous diagnosis of COPD, chronic bronchitis or emphysema

Heavy exposure to tobacco smoke or biomass fuels

Long-term disease trajectory

Seasonal or yearly variation in symptoms

Improvements (spontaneously or in response to medication) last for weeks

Slowly worsens over years

Relief in response to medication is limited and short term

Chest X-ray

Normal Severe hyperinflation

Features that, when present, increase the probability of either typical asthma or typical COPD. None of these features is essential to make the diagnosis of asthma or COPD, with the exception of persistent airflow limitation for making the diagnosis of COPD.

* Expiratory airflow limitation: indicated by a reduced ratio of forced expiratory volume in one second (FEV1) to forced vital capacity (FVC) on spirometry (FEV1/FVC less than the lower limit of normal (i.e. less than the 5th percentile of normal population). Typical FEV1/FVC values derived from population studies are > 0.75 in people aged 40–59 years and > 0.70 in people aged 60–80 years.

# Variable expiratory airflow limitation: variation beyond the range seen in healthy populations. It is indicated in adults by any of the following:

  • a clinically important increase in FEV1 (change in FEV1 of at least 200 mL and 12% from baseline) 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 increase in lung function (at least 200 mL and 12% from baseline) after ≥ 4 weeks’ treatment trial with an ICS
  • clinically important variation in peak expiratory flow (diurnal variability of more than 10%, calculated over 1–2 weeks as the average of daily amplitude per cent mean)
  • 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 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.

The greater the variations, or the more occasions excess variation is seen, the more confidently the diagnosis of variable expiratory airflow limitation consistent with asthma can be made.

† Persistent expiratory airflow limitation is indicated by reduced post-bronchodilator FEV1/FVC*

§ Lack of history of atopy does not exclude non-allergic asthma.

‡ Chest X-ray may be normal in a patient with COPD

Adapted from

Global Initiative for Asthma, Global Initiative for Obstructive Lung Disease. Diagnosis and initial treatment of asthma, COPD and asthma-COPD overlap. Updated April 2017. Global Initiative for Asthma and Global Initiative for Obstructive Lung Disease; 2017. Available from: http://ginasthma.org/gina-reports

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Table. Spirometry findings in asthma, COPD and asthma–COPD overlap

Finding

Consistent with

Asthma COPD Asthma–COPD overlap

Normal FEV1 /FVC before of after bronchodilator

  Yes   No   No *

Abnormal lung function

(post-bronchodilator reduced FEV1/FVC and FEV1 < lower limit of normal)

  Yes #   Yes   Yes

Airflow limitation with greater bronchodilator reversibility than in healthy population

(post-bronchodilator FEV1 increase ≥ 12% and 200mL from baseline)

  Yes   Yes   Yes

Marked bronchodilator reversibility

(FEV1 increase ≥ 12% and 400mL from baseline)

  Yes   Possible but unusual   Possible §

FEV1/FVC: ratio of forced expiratory volume in one second (FEV1) to forced vital capacity (FVC), either before or after bronchodilator

* Normal FEV1/FVC is not consistent with COPD unless there is other evidence of chronic non-reversible expiratory airflow limitation.

# This finding is consistent with asthma that is poorly controlled or measured during a flare-up, or can be seen in some patients with longstanding asthma.

‡ The greater the variation, and the more times variation is seen, the more likely the diagnosis of asthma. However, some patients with longstanding asthma may develop persistent airflow limitation.

† Marked reversibility strongly favours asthma and is generally inconsistent with COPD, but does not rule out asthma–COPD overlap.

§ This finding may be seen in patients with asthma–COPD overlap, or occasionally in COPD, especially when FEV1 is low.

Sources

Global Initiative for Asthma, Global Initiative for Obstructive Lung Disease. Diagnosis and initial treatment of asthma, COPD and asthma-COPD overlap. Updated April 2017. Global Initiative for Asthma and Global Initiative for Obstructive Lung Disease; 2017. Available from: http://ginasthma.org/gina-reports

Woodruff P, van den Berge M, Boucher R et al. ATS-NHLBI Asthma COPD Overlap (ACO) Workshop Report. Am J Respir Crit Care Med 2017; 196:375-381. Available from: https://www.ncbi.nlm.nih.gov/pubmed/28636425

 

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Treatment for patients with asthma–COPD overlap

Inhaled corticosteroid treatment at low–moderate doses is essential to reduce the risk of potentially life-threatening flare-ups, even if asthma symptoms appear mild or infrequent.2, 15

Most patients also need treatment with a long-acting bronchodilator (either long-acting beta2 agonist or long-acting muscarinic antagonist) in addition to an inhaled corticosteroid. Long-acting beta2 agonists and long-acting muscarinic antagonists should not be used by people with asthma or asthma–COPD overlap unless they are also taking an inhaled corticosteroid (either in combination or separately).

Table. Long-acting bronchodilators for asthma–COPD overlap

Class

Dosing frequency

Agent

Brand name

ICS–LABA combinations

Once daily

Fluticasone furoate + vilanterol

Breo Ellipta#

Twice daily

Budesonide + formoterol

Symbicort Rapihaler

Symbicort Turbuhaler

Twice daily

Fluticasone propionate + formoterol

Flutiform

Twice daily

Fluticasone propionate + salmeterol

Fluticasone and Salmeterol Cipla

Seretide Accuhaler

Seretide MDI

LABAs*

Once daily

Indacaterol

Onbrez Breezhaler

Twice daily Formoterol

Oxis

Foradile

Twice daily Salmeterol

Serevent Accuhaler

LAMAs* Once daily Glycopyrronium

Seebri Breezhaler

Once daily

Tiotropium

Spiriva

Spiriva Respimat

Once daily

Umeclidinium

Incruse Ellipta

Twice daily Aclidinium

Bretaris Genuair

LABA–LAMA combinations*

Once daily

Indacaterol + glycopyrronium

Ultibro Breezhaler

Once daily

Olodaterol + tiotropium

Spiolto Respimat

Once daily

Vilanterol + umeclidinium

Anoro Ellipta

Twice daily

Formoterol + aclidinium

Brimica Genuair

  • * Ensure that patient is also using regular long-term ICS. LABAs and LAMAs should not be used by people with asthma or asthma–COPD overlap unless they are also taking an ICS, in combination or separately)

# Only the 100/25 mcg dose of fluticasone furoate/vilanterol is TGA-approved for treatment of COPD. The higher dose (200/25 mcg) is not TGA-approved for the treatment of COPD, so it should not be used in people with asthma–COPD overlap.

High doses of ICS (alone or in combination) are not recommended in patients with COPD and should therefore be used with caution in patients with asthma-COPD overlap, because of the risk of pneumonia.

Refer to PBS status before prescribing.

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Management should also include smoking cessation, treatment of comorbid conditions, physical activity, pulmonary rehabilitation, vaccinations, self-management (including a regularly updated action plan) and regular follow-up.2

Respiratory tract infections should be monitored carefully because people with asthma–COPD overlap have high morbidity rates and because ICS treatment is associated with increased risk of non-fatal pneumonia in people with COPD.16 Most of the available evidence is from patients treated with fluticasone propionate, particularly at higher doses. Increased pneumonia rates have also been observed in studies of patients with COPD using fluticasone furoate/vilanterol. The higher dose of fluticasone furoate/vilanterol (Breo Ellipta 200/25 mcg) is not approved for patients with COPD, so it should also not be used in patients with asthma–COPD overlap.

Specialist referral should be considered for patients with atypical symptoms or symptoms that suggest an alternative diagnosis, persistent symptoms or flare-ups despite treatment, or complex comorbidities.

For information on diagnosis and management of COPD, refer to the COPD-X Concise Guide for Primary Care.17

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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.18 Normal FEV1/FVC values derived from population studies vary,1920 but are usually greater than:19

  • 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.20

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.2118 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.22,23

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References

  1. Abramson MJ, Crockett AJ, Dabscheck E, et al. The COPD-X Plan: Australian and New Zealand guidelines for the management of chronic obstructive pulmonary disease. Version 2.34. The Australian Lung Foundation and The Thoracic Society of Australia and New Zealand, 2012. Available from: http://www.copdx.org.au/
  2. Global Initiative for Asthma,, Global Initiative for Obstructive Lung Disease,. Diagnosis and initial treatment of asthma, COPD and asthma-COPD overlap. Updated April 2017. Global Initiative for Asthma and Global Initiative for Obstructive Lung Disease, 2017.
  3. National Asthma Council Australia,, Lung Foundation Australia,. Asthma–COPD overlap. National Asthma Council Australia, Melbourne, 2017.
  4. Reddel, H. K.. Treatment of overlapping asthma-chronic obstructive pulmonary disease: Can guidelines contribute in an evidence-free zone?. J Allergy Clin Immunol Pract. 2015; 136: 546-52. Available from: https://www.ncbi.nlm.nih.gov/pubmed/26343938
  5. Bateman, E. D., Reddel, H. K., van Zyl-Smit, R. N., Agusti, A.. The asthma-COPD overlap syndrome: towards a revised taxonomy of chronic airways diseases?. Lancet Respir Med. 2015; 3: 719-28.
  6. Gibson PG, Simpson JS. The overlap syndrome of asthma and COPD: what are its features and how important is it?. Thorax. 2009; 64: 728-735. Available from: http://thorax.bmj.com/content/64/8/728.full
  7. Gibson, P. G., McDonald, V. M.. Asthma-COPD overlap 2015: now we are six. Thorax. 2015; 70: 683-91.
  8. McDonald VM, Higgins I, Gibson PG. Managing older patients with coexistent asthma and chronic obstructive pulmonary disease. Drugs Aging. 2013; 30: 1-17. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23229768
  9. Reed CE. Asthma in the elderly: diagnosis and management. J Allergy Clin Immunol. 2010; 126: 681-7; quiz 688-9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20673985
  10. Gelb, A. F., Christenson, S. A., Nadel, J. A.. Understanding the pathophysiology of the asthma-chronic obstructive pulmonary disease overlap syndrome. Curr Opin Pulm Med. 2016; 22: 100-5.
  11. Nielsen, M., Barnes, C. B., Ulrik, C. S.. Clinical characteristics of the asthma-COPD overlap syndrome – a systematic review. Int J Chron Obstruct Pulmon Dis. 2015; 10: 1443-54.
  12. Tho, N. V., Park, H. Y., Nakano, Y.. Asthma-COPD overlap syndrome (ACOS): A diagnostic challenge. Respirology. 2016; 21: 410-8.
  13. Alshabanat, A., Zafari, Z., Albanyan, O., et al. Asthma and COPD Overlap Syndrome (ACOS): A Systematic Review and Meta Analysis. PloS one. 2015; 10: e0136065.
  14. Lange, P., Halpin, D. M., O'Donnell, D. E., MacNee, W.. Diagnosis, assessment, and phenotyping of COPD: beyond FEV(1). Int J Chron Obstruct Pulmon Dis. 2016; 11 Spec Iss: 3-12.
  15. Gershon, A. S., Campitelli, M. A., Croxford, R., et al. Combination long-acting beta-agonists and inhaled corticosteroids compared with long-acting beta-agonists alone in older adults with chronic obstructive pulmonary disease. JAMA. 2014; 312: 1114-21. Available from: https://www.ncbi.nlm.nih.gov/pubmed/25226477
  16. Kew, K. M., Seniukovich, A.. Inhaled steroids and risk of pneumonia for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2014; Issue 3: . Available from: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD010115.pub2/full
  17. Abramson, M, Frith, P, Yang, I, et al. COPD-X concise guide for primary care. Lung Foundation Australia, Brisbane, 2017.
  18. 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
  19. 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
  20. 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
  21. 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
  22. 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
  23. 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