Approaches to the assessment of severe asthma: barriers and strategies

Figures & data

Figure 1 Checklist for the multidimensional assessment of severe asthma.

Note: Figure reproduced with permission from the Centre of Excellence in Severe Asthma, originally developed as part of the Severe Asthma Toolkit © (http://www.severeasthma.org.au).³⁰

Table 1 Pulmonary function tests to consider in severe asthma

Assessment	Rationale	Outcome	Advantages	Disadvantages
Lung function
Spirometry	An objective test that measures the air that is expired and inspired.^Citation18	Confirms airflow limitation.^Citation18 Determines the reversibility of airflow limitation after the administration of short-acting bronchodilator drug.^Citation18	Reproducible.^Citation18 Non-invasive.^Citation18	Spirometers may not be readily accessible in some health care settings.^Citation19 Caution is needed in interpreting results as bronchodilator reversibility lacks sensitivity.^Citation18 Training and equipment costs.^Citation18
Airway hyper-responsiveness (AHR)	Direct Stimuli: Methacholine. Challenge or Indirect Stimuli: Hypertonic Saline/Mannitol is utilized to determine the presence of AHR and aid in the clinical diagnosis.^Citation20	Defines the presences and degree of AHR.^Citation20	Reproducible.^Citation21 Safe.^Citation21	Requires technical expertise.^Citation20
Exhaled nitric oxide measurements	A surrogate marker of Type 2 airway inflammation. Can be used to measure adherence.^Citation22	Determines the presence of Type 2 inflammation.^Citation22	Easy to perform compared to induced sputum analysis.^Citation22 Convenient and portable.^Citation22 Highly reproducible.^Citation22 Cost effective.^Citation22 Non-invasive.^Citation23	Unreliable in current smokers and lacks sufficient sensitivity and specificity to measure asthma control. Readings are influenced by ICS or oral corticosteroid therapy.^Citation23 Single breath technique is not feasible in preschool children.^Citation23
Lung volume assessment	An accurate and well-established method to determine the total lung capacity.^Citation24	Confirms the presence of restrictive lung disease.^Citation24 Confirms the presence of hyperinflation.^Citation24	Non-invasive.^Citation25 Reproducible.^Citation25	Requires technical expertise.^Citation25 Equipment is heavy and space demanding.^Citation25 Expensive.^Citation25 Not ideal for patients with claustrophobia or skeletal abnormalities.^Citation25 Overestimate lung volumes in patients with obstruction.^Citation25
Carbon monoxide diffusion capacity	Measures the ability of the lungs to transfer gas and evaluates issues with gas transfer.^Citation26	Diagnoses emphysema.^Citation27	Non-invasive.^Citation26 Reproducible.^Citation27	Results are sensitive to errors due to physiologic variation, test technique, errors in gas analysis and computation algorithms.^Citation26

Abbreviations: AHR, airway hyper-responsiveness; FeNO, exhaled fraction of nitric oxide; ICS, inhaled corticosteroids.

Table 2 Criteria for uncontrolled asthma

Poor symptom control	Consistent ACQ score of >1.5, ACT score of <20, classified as “not well controlled.”^Citation7
Frequent severe exacerbations	Requiring two or more bursts of systemic corticosteroids in the previous year (>3 days each).^Citation7
Serious exacerbations	At least one hospitalization, life-threatening episode or the need for mechanical ventilation in the preceding year.^Citation7
Airflow limitation	Following applicable bronchodilator withhold (FEV1<80% predicted (in the presence of reduced FEV1/FVC) defined as less than lower limit of normal.^Citation7

Abbreviations: ACQ, Asthma Control Questionnaire; ACT, asthma control test; FEV1, forced expiratory volume in one second; FVC, forced vital capacity.

Table 3 Asthma definitions and characteristics

	Under-treated asthma	Difficult-to-treat asthma	Severe treatment-refractory asthma
Symptoms	++	++	++
Medication: prescribed adequate ICS	_	+	+
Asthma skills	May be suboptimal	May be suboptimal	Optimized
Comorbidity		Not managed	Managed
Recommended management	ICS ± LABA	ICS ± LABA Optimize skills and manage comorbidities	Phenotype and use of targeted therapy in addition to ICS/LABA Optimize skills and manage comorbidities

Note: Table has been reproduced with permission from John Wiley & Sons, McDonald VM, Maltby S, Reddel HK, et al. Severe asthma: current management, targeted therapies and future directions-Aroundtable report. Respirology. 2017;22(1):53–60.¹⁰

Abbreviations: ICS, inhaled corticosteroids; LABA, long-acting beta agonist; -, absent; +, present.

Table 4 Checklist of important contributory factors in severe asthma

Panel	Assessment
Self-management skills	Optimal inhaler technique Minimization of inhaler device polypharmacy Self-monitoring of symptoms or peak flow monitoring Adherence Written action plan Disease knowledge
Comorbidities	Pulmonary or airway assessments: Allergic & non-allergic rhinitis Chronic rhinosinusitis Dysfunctional breathing Vocal cord dysfunction Chronic obstructive pulmonary disease Bronchiectasis Obstructive sleep apnea Extrapulmonary Obesity Anxiety & depression Gastro-esophageal reflux disease (GORD) Osteoporosis Cardiovascular disease & metabolic disease
Triggers	Allergens Cigarette smoke Respiratory viral infection Emotional stress Mould or dampness Medications Patient-reported triggers
Risk factors	Smoking Physical inactivity Poor nutrition leading to obesity Poor self-management skills

Table 5 Useful tools for assessing adherence

Assessment Tool	Description	Advantage	Disadvantage
Canister weighing	An objective method to assess the number of doses remaining in a pressurized metered dose inhaler (pMDI).^Citation34	A reproducible technique that can assess patient adherence to medication based on the accurate weight of the canister.^Citation34,Citation35	Can overestimate adherence.^Citation36 Cannot reveal full patterns of medication used over time.^Citation36 Can be confounded by test doses or dumping.^Citation36
Dose counter	A dose counter counts the number of doses in the inhaler to determine the remaining amount of medication.^Citation35	Improves the tracking of adherence to treatment and increases patients’ awareness of remaining doses.^Citation34,Citation35	Can be confounded by test doses or dumping.^Citation36
Electronic inhaler monitoring	An electronic device used to accurately assess and record adherence to inhaled therapies.^Citation37	Unique features include audio-visual reminders, date and time tracker of each actuation of the inhaler device.^Citation37 Benefits clinician in distinguishing poor treatment response.^Citation37	Expensive.^Citation36 Subject to mechanical failures.^Citation38 Self-monitoring could alter patients’ behaviour (Hawthorne Effect).^Citation36
FeNO suppression test	An objective method to distinguish non-adherence to ICS.^Citation35 FeNO testing after directly observed inhaled corticosteroid treatment. This facilitates stratification of non-adherent patients with difficult asthma.^Citation39	Non-invasive.^Citation35 Correlates with Type 2 inflammation.^Citation35 Feasible.^Citation39	Limited to patients with elevated baseline FeNO.^Citation35 Devices not available in all clinics.^Citation10
Serum prednisolone/cortisol	A direct serum prednisolone or cortisol evaluation can be performed on patients taking prescribed prednisolone.^Citation40 Lower level indicates low adherence with oral prednisolone or poor absorption.^Citation40	Provides direct measurement of non-adherence to prednisolone through prednisolone or cortisol assay.^Citation40 Reproducible.^Citation40	Requires specialized equipment.^Citation40 Expensive.^Citation40
Prescription/pharmacy records	Objective method to compare the dispensing ratio of preventer medication to reliever medication.^Citation40,Citation41 Dispensing record showing large amounts of reliever medication indicates poor asthma control.^Citation35,Citation40,Citation41	Simple and economical way of obtaining patients’ medication information.^Citation35	Does not provide direct measures of medication adherence.^Citation35 No assurance that the dispensed medication is actually taken.^Citation17 Prescription records may not be available in all health care settings.^Citation17

Abbreviations: pMDI, pressurized metered dose inhaler; FeNO, exhaled fraction of nitric oxide.

Figure 2 Clinical domains in the phenotyping of severe refractory asthma.

Note: Figure reproduced with permission from the Centre of Excellence in Severe Asthma, originally developed as part of the Severe Asthma Toolkit © (http://www.severeasthma.org.au).³⁰

Figure 3 Barriers to assessment of severe asthma by stakeholders.

Centre of Excellence in Severe Asthma. The severe asthma toolkit. Available from: https://toolkit.severeasthma.org.au/. Accessed 715, 2019.

 Google Scholar

Moore VC. Spirometry: step by step. Breathe. 2012;8(3):232. doi:10.1183/20734735.0021711

 Google Scholar

Ayuk AC, Uwaezuoke SN, Ndukwu CI, et al. Spirometry in asthma care: a review of the trends and challenges in pediatric practice. Clin Med Insights Pediatr. 2017;11:1179556517720675. doi:10.1177/117955651772067528781518

 PubMedGoogle Scholar

Brannan JD, Lougheed MD. Airway hyperresponsiveness in asthma: mechanisms, clinical significance, and treatment. Front Physiol. 2012;3:460. doi:10.3389/fphys.2012.0046023233839

 PubMed Web of Science ®Google Scholar

Sanguinetti CM. When to perform a bronchial challenge with mannitol? Multidiscip Respir Med. 2011;6(2):76–78. doi:10.1186/2049-6958-6-2-7622958857

 PubMed Web of Science ®Google Scholar

Taylor DR, Pijnenburg MW, Smith AD, De Jongste JC. Exhaled nitric oxide measurements: clinical application and interpretation. Thorax. 2006;61(9):817–827. doi:10.1136/thx.2005.05609316936238

 PubMed Web of Science ®Google Scholar

Pijnenburg MW. The role of FeNO in predicting asthma. Front Pediatr. 2019;7:41. doi:10.3389/fped.2019.0004130847334

 PubMed Web of Science ®Google Scholar

Ruppel GL. What is the clinical value of lung volumes? Respir Care. 2012;57(1):26–38. doi:10.4187/respcare.0137422222123

 PubMed Web of Science ®Google Scholar

Ritz T, Dahme B, Dubois AB, et al. Guidelines for mechanical lung function measurements in psychophysiology. Psychophysiology. 2002;39(5):546–567.12236321

 PubMed Web of Science ®Google Scholar

Graham BL, Brusasco V, Burgos F, et al. 2017 ERS/ATS standards for single-breath carbon monoxide uptake in the lung. Eur Respir J. 2017;49(1):1600016. doi:10.1183/13993003.00016-201628049168

 PubMed Web of Science ®Google Scholar

Bailey KL. The importance of the assessment of pulmonary function in COPD. Med Clin North Am. 2012;96(4):745–752. doi:10.1016/j.mcna.2012.04.01122793942

 PubMed Web of Science ®Google Scholar

Chung KF, Wenzel SE, Brozek JL, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J. 2014;43(2):343–373. doi:10.1183/09031936.0020201324337046

 PubMed Web of Science ®Google Scholar

McDonald VM, Maltby S, Reddel HK, et al. Severe asthma: current management, targeted therapies and future directions-A roundtable report. Respirology. 2017;22(1):53–60. doi:10.1111/resp.1295727905186

 PubMed Web of Science ®Google Scholar

Chuenjit W, Engchuan V, Yuenyongviwat A, Sangsupawanich P. Achieving good adherence to inhaled corticosteroids after weighing canisters of asthmatic children. F1000Res. 2017;6:266. doi:10.12688/f1000research.10710.128868133

 PubMedGoogle Scholar

McNicholl DM, Stevenson M, McGarvey LP, Heaney LG. The utility of fractional exhaled nitric oxide suppression in the identification of nonadherence in difficult asthma. Am J Respir Crit Care Med. 2012;186(11):1102–1108. doi:10.1164/rccm.201204-0587OC23024023

 PubMed Web of Science ®Google Scholar

Lindsay JT, Heaney LG. Nonadherence in difficult asthma - facts, myths, and a time to act. Patient Prefer Adherence. 2013;7:329–336. doi:10.2147/PPA.S3820823723690

 PubMed Web of Science ®Google Scholar

Taylor TE, Zigel Y, Egan C, et al. Objective assessment of patient inhaler user technique using an audio-based classification approach. Sci Rep. 2018;8(1):2164. doi:10.1038/s41598-018-20523-w29391489

 PubMed Web of Science ®Google Scholar

Lavorini F, Fontana GA, Usmani OS. New inhaler devices-the good, the bad and the ugly. Respiration. 2014;88(1):3–15. doi:10.1159/00036339024902629

 PubMed Web of Science ®Google Scholar

Faruqi S, Thompson J, Robinson T, et al. Fractional exhaled nitric oxide (FeNO) suppression with directly observed inhaled corticosteroid therapy: does it make a difference to patient outcomes? Eur Respir J. 2018;52(suppl62):PA4453. doi:10.1183/13993003.01675-2018

 Web of Science ®Google Scholar

Gamble J, Stevenson M, McClean E, Heaney LG. The prevalence of nonadherence in difficult asthma. Am J Respir Crit Care Med. 2009;180(9):817–822. doi:10.1164/rccm.200902-0166OC19644048

 PubMed Web of Science ®Google Scholar

Murphy AC, Proeschal A, Brightling CE, et al. The relationship between clinical outcomes and medication adherence in difficult-to-control asthma. Thorax. 2012;67(8):751–753. doi:10.1136/thoraxjnl-2011-20109622436168

 PubMed Web of Science ®Google Scholar

Tay TR, Lee JW-Y, Hew M. Diagnosis of severe asthma. Med J Aust. 2018;209(2 Suppl):S3–S10.

 Web of Science ®Google Scholar