Asthma Management Handbook

General considerations for further investigations in adults

Recommendations

Consider arranging further investigations and referral to appropriate specialists if the diagnosis cannot be made with confidence from clinical features, spirometry and response to treatment.

How this recommendation was developed

Consensus

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

Consider investigation for conditions that may affect or mimic asthma symptoms (e.g. coronary heart disease, obstructive sleep apnoea, gastro-oesophageal reflux disease or aspirin-exacerbated respiratory disease).

How this recommendation was developed

Consensus

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

Consider and investigate the possibility of work-related asthma if (any of):

  • the timing of asthma symptoms is associated with work activities (especially if symptoms improve when the person is away from the workplace)
  • the person is exposed to substances known to cause occupational asthma
  • co-workers have respiratory symptoms.

Note: Do not rule out the possibility of work-related asthma if the person’s occupation is not among those commonly associated with asthma triggers (e.g. bakers, vehicle spray painters, electronics manufacturing workers who perform soldering, woodworkers, healthcare workers, laboratory animal workers, agriculture workers), because many substances and occupations have been associated with asthma and more are being identified continually.

How this recommendation was developed

Adapted from existing guidance

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

  • Dykewics, 2009 1
  • Henneberger et al. 2011 2
  • Hoy et al. 2010 3
  • Tarlo et al. 2008 4

Consider referral in the following circumstances:

  • if the diagnosis is uncertain (consider referral for diagnostic assessment and further investigation by a respiratory physician or general physician)
  • if signs and symptoms do not respond to a treatment trial (consider further investigations or referral to an appropriate specialist)
  • if work-related asthma is suspected (consider referral to a respiratory physician, occupational physician and/or allergist, or allergist with experience in work-related asthma, if possible. Investigation is complex and involves a very detailed history, detailed lung function testing, site visits and sometimes challenge testing).
How this recommendation was developed

Consensus

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

More information

Spirometry in diagnosis and monitoring

Spirometry is the best lung function test for diagnosing asthma and for measuring lung function when assessing asthma control. Spirometry can:

  • detect airflow limitation
  • measure the degree of airflow limitation compared with predicted normal airflow (or with personal best)
  • demonstrate whether airflow limitation is reversible.

It should be performed by well-trained operators with well-maintained and calibrated equipment.5, 6

Before performing spirometry, check if the person has any contraindications (e.g. myocardial infarction, angina, aneurysm, recent surgery, suspected pulmonary embolism, suspected pneumothorax, fractured ribs). Advise them to stop if they become dizzy.

Clearly explain and physically demonstrate correct spirometry technique: 7

  • Sit upright with legs uncrossed and feet flat on the floor and do not lean forward.
  • Breathe in rapidly until lungs feel absolutely full. (Coaching is essential to do this properly.)
  • Do not pause for more than 1 second.
  • Place mouthpiece in mouth and close lips to form a tight seal.
  • Blast air out as hard and fast as possible and for as long as possible, until the lungs are completely empty or you are unable to blow out any longer.
  • Remove mouthpiece.

Repeat the test until you obtain three acceptable tests and these meet repeatability criteria.

Acceptability of test

A test is acceptable if all the following apply:

  • forced expiration started immediately after full inspiration
  • expiration started rapidly
  • maximal expiratory effort was maintained throughout the test, with no stops
  • the patient did not cough during the test
  • the patient did not stop early (before 6 seconds for adults and children over 10 years, or before 3 seconds for children under 10 years).

Record the highest FEV1 and FVC result from the three acceptable tests, even if they come from separate blows.7

Repeatability criteria

Repeatability criteria for a set of acceptable tests are met if both of the following apply:5

  • the difference between the highest and second-highest values for FEV1 is less than 150 mL
  • the difference between the highest and second-highest values for FVC is less than 150 mL.

For most people, it is not practical to make more than eight attempts to meet acceptability and repeatability criteria.7

Testing bronchodilator response (reversibility of airflow limitation)

Repeat spirometry 10-15 minutes after giving 4 separate puffs of salbutamol (100 mcg/actuation) via a pressurised metered-dose inhaler and spacer.7 (For patients who have reported unacceptable side-effects with 400 mcg, 2 puffs can be used.)

For adults and adolescents, record a clinically important bronchodilator response if FEV1 increases by ≥ 200 mL and ≥ 12%.7

For children, record a clinically important bronchodilator response if FEV1 increases by
≥ 12%.7

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Cough and asthma in adults

When no other asthma symptoms are present, chronic cough (present for more than 8 weeks) is unlikely to indicate asthma.

Chronic cough may be due to asthma if:8

  • cough is episodic
  • cough with exercise is associated with other symptoms that suggest airflow limitation (expiratory wheeze or breathlessness)
  • spirometry confirms reversible airflow limitation.

If cough is due to asthma, it should respond to treatment with an inhaled corticosteroid preventer taken regularly and reliever as needed).8

Findings that suggest a serious alternative or comorbid diagnosis that requires further investigation include:8

  • haemoptysis
  • smoker with > 20 pack–year smoking history
  • smoker aged over 45 years with a new cough, altered cough, or cough with voice disturbance
  • prominent dyspnoea, especially at rest or at night
  • substantial sputum production
  • hoarseness
  • fever
  • weight loss
  • complicated gastro-oesophageal reflux disease
  • swallowing disorders with choking or vomiting
  • recurrent pneumonia
  • abnormal clinical respiratory examination.
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Asthma–COPD overlap

Distinguishing between typical allergic asthma (childhood-onset allergic asthma) and typical COPD (emphysema in a heavy smoker) is straightforward.9 However, it can be difficult to distinguish COPD from asthma in adults who have features of both conditions.10, 11These people are described as having asthma–COPD overlap.10, 9, 12

Asthma–COPD overlap is not a single, well-defined disease entity, but includes a range of airway disease phenotypes with different causal mechanisms.10, 13 Features of both asthma and COPD have been described in:12, 14, 15, 16

  • 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:10, 16, 17, 18, 19, 20

  • 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.10, 21

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.10

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.22 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.23

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Other diagnostic tests in adults

For patients with incompletely reversible airflow limitation, a careful history will often clarify which investigation is most appropriate. Lung volume tests and diffusing capacity tests may be helpful to identify emphysema or pulmonary fibrosis. High-resolution computed tomography is useful if bronchiectasis is suspected.

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References

  1. Dykewics MS. Occupational asthma: Current concepts in pathogenesis, diagnosis, and management. J Allergy Clin Immunol. 2009; 123: 519-528. Available from: http://www.jacionline.org/article/S0091-6749(09)00214-0/fulltext
  2. Henneberger PK, Redlich CA, Callahan DB, et al. An official american thoracic society statement: work-exacerbated asthma. Am J Respir Crit Care Med. 2011; 184: 368-78. Available from: http://ajrccm.atsjournals.org/content/184/3/368.long
  3. Hoy RF, Abramson MJ, Sim MR. Work related asthma - diagnosis and management. Aust Fam Physician. 2010; 39: 39-42. Available from: http://www.racgp.org.au/afp/201001/35841
  4. Tarlo SM, Balmes J, Balkissoon R, et al. Diagnosis and management of work-related asthma: American College Of Chest Physicians Consensus Statement. Chest. 2008; 134(3 Suppl): 1S-41S. Available from: http://journal.publications.chestnet.org/article.aspx?articleid=1044851
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  7. Johns DP, Pierce R. Pocket guide to spirometry. 3rd edn. McGraw Hill, North Ryde, 2011.
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  11. 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.
  12. 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
  13. Gibson, P. G., McDonald, V. M.. Asthma-COPD overlap 2015: now we are six. Thorax. 2015; 70: 683-91.
  14. 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
  15. 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
  16. 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.
  17. 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.
  18. Tho, N. V., Park, H. Y., Nakano, Y.. Asthma-COPD overlap syndrome (ACOS): A diagnostic challenge. Respirology. 2016; 21: 410-8.
  19. 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.
  20. 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.
  21. 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
  22. 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
  23. Abramson, M, Frith, P, Yang, I, et al. COPD-X concise guide for primary care. Lung Foundation Australia, Brisbane, 2017.