Asthma Management Handbook

Considering alternative diagnoses in adults


Consider other possible causes of respiratory symptoms, including:

  • poor cardiopulmonary fitness
  • other respiratory conditions (e.g. bronchiectasis, chronic obstructive pulmonary disease, hyperventilation/dysfunctional breathing, inhaled foreign body, large airway stenosis, pleural effusion, pulmonary fibrosis, rhinitis/rhinosinusitis, upper airway dysfunction)
  • cardiovascular disease (e.g. chronic heart failure, pulmonary hypertension)
  • comorbid conditions (e.g. obesity, gastro-oesophageal reflux)
  • lung cancer.

Table. Findings that increase or decrease the probability of asthma in adults

Asthma is more likely to explain the symptoms if any of these apply

Asthma is less likely to explain the symptoms if any of these apply

More than one of these symptoms:

  • wheeze
  • breathlessness
  • chest tightness
  • cough

Symptoms recurrent or seasonal

Symptoms worse at night or in the early morning

History of allergies (e.g. allergic rhinitis, atopic dermatitis)

Symptoms obviously triggered by exercise, cold air, irritants, medicines (e.g. aspirin or beta blockers), allergies, viral infections, laughter

Family history of asthma or allergies

Symptoms began in childhood

Widespread wheeze audible on chest auscultation

FEV1 or PEF lower than predicted, without other explanation

Eosinophilia or raised blood IgE level, without other explanation

Symptoms rapidly relieved by a SABA bronchodilator

Dizziness, light-headedness, peripheral tingling

Isolated cough with no other respiratory symptoms

Chronic sputum production

No abnormalities on physical examination of chest when symptomatic (over several visits)

Change in voice

Symptoms only present during upper respiratory tract infections

Heavy smoker (now or in past)

Cardiovascular disease

Normal spirometry or PEF when symptomatic (despite repeated tests)

Adapted from:

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

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:

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How this recommendation was developed


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

Consider the possibility of upper airway dysfunction when FEV1/FVC ratio on spirometry is normal or when symptoms of breathlessness or wheeze do not improve after taking short acting beta2 agonist.

How this recommendation was developed


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

  • Benninger et al. 2011 1
  • Deckert and Deckert, 2010 2
  • Weinberger and Abu-Hasan, 2007 3
  • Morris and Christopher, 2010 4
  • Kenn and Balkissoon, 2011 5

Investigate cough thoroughly if there are findings that might indicate a serious alternative or comorbid diagnosis.

How this recommendation was developed


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

  • Gibson et al. 2010 6

If expiratory airflow limitation is not completely reversible, consider the possibility of COPD as an alternative diagnosis or of asthma–COPD overlap, especially in smokers and ex-smokers over 35 years old and in people over 65 years old.

How this recommendation was developed


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

  • Abramson et al. 2012 7

Consider the possibility of adult-onset asthma in people with dyspnoea, wheeze or cough, even if they have no previous diagnosis of asthma.

How this recommendation was developed


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

More information

Upper airway dysfunction

Upper airway dysfunction is intermittent, abnormal adduction of the vocal cords during respiration, resulting in variable upper airway obstruction. It often mimics asthma12 and is commonly misdiagnosed as asthma.34 It can cause severe acute episodes of dyspnoea that occur either unpredictably or due to exercise.3 Inspiratory stridor associated with vocal cord dysfunction is often described as ‘wheezing’,3 but symptoms do not respond to asthma treatment.25

Upper airway dysfunction can coexist with asthma.1 People with asthma who also have upper airway dysfunction experience more symptoms than those with asthma alone and this can result in over-treatment if vocal cord dysfunction is not identified and managed appropriately.1

Upper airway dysfunction probably has multiple causes.1 In some people it is probably due to hyperresponsiveness of the larynx in response to intrinsic and extrinsic triggers.18 Triggers can include exercise, psychological conditions, airborne irritants, rhinosinusitis, gastro-esophageal reflux disease, and medicines.24

Upper airway dysfunction should be considered when spirometry shows normal FEV1/FVC ratio in a patient with suspected asthma4 or symptoms do not respond to short-acting beta2 agonist reliever. The shape of the maximal respiratory flow loop obtained by spirometry may suggest the diagnosis.3 Direct observation of the vocal cords is the best method to confirm the diagnosis of upper airway dysfunction.1

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:

People with asthma–COPD overlap often have poor disease outcomes, including:10, 1718, 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


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:

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


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.


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:

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:


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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


Dosing frequency


Brand name

ICS–LABA combinations

Once daily

Fluticasone furoate + vilanterol

Breo Ellipta 100/25 microg

  • Do not prescribe 200/25 microg formulation#
Twice daily

Budesonide + formoterol

Symbicort Rapihaler

Symbicort Turbuhaler

Twice daily

Fluticasone propionate + formoterol


Twice daily

Fluticasone propionate + salmeterol

Fluticasone and Salmeterol Cipla

Seretide Accuhaler

Seretide MDI


Once daily


Onbrez Breezhaler

Twice daily Formoterol



Twice daily Salmeterol

Serevent Accuhaler

LAMAs* Once daily Glycopyrronium

Seebri Breezhaler

Once daily



Spiriva Respimat

Once daily


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)
  • Advise patients/carers that inhalers should be stored below 30°C and should not be left in cars.

The inhaler must be discarded 1 month after opening the package and removing device from tray. When first opened, patients should write the discard date on the label in the space provided. If stored in the refrigerator, inhaler should be taken out and allowed to return to room temperature for at least an hour before use.

The inhaler must be discarded 6 weeks after opening the package and removing device from tray. When first opened, patients should write the discard date on the label in the space provided. If stored in the refrigerator, inhaler should be taken out and allowed to return to room temperature for at least an hour before use.

# Only the 100/25 microg dose of fluticasone furoate/vilanterol is TGA-approved for treatment of COPD. The higher dose (200/25 microg) 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 microg) 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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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:6

  • 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).6

Findings that suggest a serious alternative or comorbid diagnosis that requires further investigation include:6

  • 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.
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.24, 25

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: 26

  • 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.26

Repeatability criteria

Repeatability criteria for a set of acceptable tests are met if both of the following apply:24

  • 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.26

Testing bronchodilator response (reversibility of airflow limitation)

Repeat spirometry 10-15 minutes after giving 4 separate puffs of salbutamol (100 microg/actuation) via a pressurised metered-dose inhaler and spacer.26 (For patients who have reported unacceptable side-effects with 400 microg, 2 puffs can be used.)

For adults and adolescents, record a clinically important bronchodilator response if FEV1 increases by ≥ 200 mL and ≥ 12%.26

For children, record a clinically important bronchodilator response if FEV1 increases by
≥ 12%.26

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