Resistant asthma in primary care: assessment, pitfalls and when to refer

Respiratory physicians Dr Hannah Petty and Dr Nita Sehgal discuss management of treatment resistant asthma in primary care

One cause of apparently resistant asthma is ‘wrong diagnosis’ – what are the differentials we should be aware of, and how can we distinguish them from true asthma?

Resistant asthma is asthma that remains poorly controlled despite maximal medical therapy. However, poor control can reflect an array of other factors such as uncertain diagnosis, treatment adherence, ongoing exposure to triggers or co-existing conditions that can exacerbate or mimic asthma symptoms.

A review of patients labelled as having severe/resistant asthma has shown that a considerable proportion have additional factors contributing to poor symptom control.¹ Reassessment in primary care is often paramount to review the need for escalation of treatment, referral to secondary care or to review the diagnosis itself.

Diagnostic uncertainty – asthma mimics or co-existing conditions

Before labelling asthma as treatment-resistant or severe, clinicians should ensure the diagnosis is robust. Asthma remains a clinical diagnosis based on the history and is supported by evidence of raised biomarkers; elevated fractional exhaled nitric oxide (FeNO), eosinophils and often variable airflow obstruction – objective testing should be sought wherever possible.²

If the diagnosis is in doubt or uncertain then clinicians should be aware of alternative diagnoses that can often mimic asthma symptoms or can co-exist alongside asthma and if untreated, can result in patients being labelled as having resistant asthma. Around 12-50% of patients diagnosed with severe asthma do not have asthma.³

Inducible laryngeal obstruction

Inducible laryngeal obstruction (ILO) is characterised by paradoxical adduction of the vocal cords during respiration, most commonly on inspiration. Patients typically present with episodic breathlessness, throat tightness, globus pharyngeus, inspiratory wheeze or stridor, and a poor response to bronchodilators.⁴

ILO frequently coexists with asthma and should be suspected when symptoms appear disproportionate to lung function testing or fail to improve to escalating therapy. Early recognition is important, as management involves speech and language therapy and breathing techniques rather than escalation of treatment.

Tip: Think ILO when the patient reports episodes of shortness of breath especially upon inspiration that is triggered by exercise, strong smells, emotions, talking or laughing. Throat tightness, voice change/hoarseness should also prompt consideration/referral to the speech and language team or the airways team.

Disordered breathing pattern

Disordered breathing pattern (DBP), including hyperventilation syndrome, can both mimic and exacerbate asthma. Identification and referral for physiotherapy, can result in substantial improvement in symptoms and quality of life. DBP can be more common in patients with musculoskeletal problems and those with nasal congestion/mouth breathers.

Tip: Think DBP when the patient complains of chest tightness/pain, tingling in the hands or fingers, air hunger, frequent reliever use that does not improve symptoms, dizziness, frequent yawning or sighing with normal spirometry.⁵

What other factors might lead to treatment resistance?

Upper airway disease and post-nasal drip

Upper airway disease, including allergic rhinitis and chronic rhinosinusitis is often an under-recognised contributor to poor asthma control. The concept of the ‘united airway’ highlights the close relationship between nasal and bronchial inflammation.⁶ Ongoing upper airway inflammation can worsen lower airway symptoms and increase bronchial hyper-responsiveness.

Nasal obstruction can lead to mouth breathing, increasing exposure of the lower airways to cold, dry and irritant air. Treatment with intranasal corticosteroids, antihistamines, and saline nasal sprays can improve asthma control and reduce the need for treatment escalation.

Tip: Consider upper airway disease in patients who report chronic cough, throat clearing, globus, hoarseness or a sensation of mucus in the throat.

Gastro-oesophageal reflux disease

Gastro-oesophageal reflux disease (GORD) is common in patients with asthma and may contribute to poor symptoms control. There have been studies which correlate the increasing frequency of GORD, hiatus hernia, and oesophagitis in patients with asthma in comparison to the general population and micro-aspiration can lead to increased bronchial hyperresponsiveness, leading to cough, wheeze, and nocturnal symptoms.⁷

Reflux at night can be particularly problematic, contributing to night-time asthma symptoms and frequent reliever use. Identification and management through lifestyle modification (earlier and lighter meals, using more pillows to prop oneself up and avoiding tight clothes around the abdomen for example), weight management and medical management of acid suppression where appropriate can improve respiratory symptoms and reduce apparent treatment resistance.

Tip: Consider GORD in patient with predominant nocturnal symptoms or those that consider their symptoms worse after eating. Ask about chest discomfort, waterbrash, or bloating.

Physical deconditioning

Physical deconditioning is a reduction in cardiovascular fitness and reduced muscle strength usually as a consequence of inactivity. In patients with asthma, this can lead to disproportionate breathlessness on exertion, inefficient breathing patterns, and early symptom limitation. It can often be a vicious cycle and difficult to break; encouraging exercise, pulmonary rehabilitation, and reassurance can benefit patients.

Tip: Think deconditioning in patients when they report breathlessness with minimal activity out of keeping with their spirometry. Always ask about muscle fatigue and weight gain.

Environmental and occupational triggers

Environmental and occupational exposures remain important contributors to poor asthma control. Common triggers include smoking, exposure to allergens, cold air, pollution and workplace irritants. Occupational asthma should be suspected when symptoms improve on days away from work or during holidays.^8,9

Tip: Ask the patient what triggers their symptoms, do they get better when they are away from work?

How can we establish treatment adherence?

Poor treatment adherence is one of the most common causes of uncontrolled asthma. Contributing factors include misunderstanding the role of preventer therapy, concerns regarding corticosteroid side effects, complex treatment regimens, and incorrect inhaler technique.

A patient’s relationship with inhaler therapy often begins in primary care, where education is fundamental.¹⁰ Common questions encountered within severe asthma services include: ‘Why am I prescribed an inhaled corticosteroid (ICS)?’; ‘Are there long-term side effects?’; ‘Do I need to take this every day?’. Addressing these concerns early is essential to support adherence.

Careful consideration of the inhaled regimen, whether AIR therapy, once daily dosing, or MART, as well as the choice between dry powder inhalers (DPIs) and metered-dose inhalers (MDIs), can significantly influence adherence and clinical outcomes. While clinicians have a responsibility to consider environmental impact and may favour DPIs, device selection should be guided by what provides the greatest clinical benefit for the patient. Potential issues such as oral thrush, sore throat, or inhaler-related embarrassment should be actively explored, alongside assessment of the patient’s ability to generate sufficient inspiratory flow to use a DPI effectively. If provided with an MDI, the patient should be given a spacer. Shared decision-making should underpin inhaler selection, and inhaler technique reviewed and optimised at every opportunity.

Encouraging patients to link inhaler use to established daily habits can improve consistency and adherence. For example, if a patient routinely checks their phone on waking, keeping the inhaler nearby can help reinforce regular use. Similarly, for patients who make a cup of tea every morning, placing the inhaler next to the kettle can function as a simple and effective reminder. Integrating inhaler therapy into familiar routines supports adherence by embedding treatment into daily life rather than presenting it as an additional task. Adherence can be assessed using the Medicines Possession Ratio (MPR), calculated as the number of doses prescribed divided by the number of doses expected.¹¹ An MPR greater than 75% is considered to be good adherence.

Implementing a personalised asthma action plan is associated with improved asthma control, reduced exacerbations, and fewer acute health visits.¹² In primary care, ensuring that every patient has a written or digital action plan and understands when and how to adjust treatment is a highly effective intervention.

How should we escalate treatment in resistant asthma and at what point should we refer this patient to the asthma service?

Severe asthma represents a subset of patients with apparent difficult-to-treat asthma. It is persistent symptoms and/or frequent exacerbations despite treatment with high-dose ICS and long-acting beta-agonist (ICS/LABA) therapy plus additional add-on treatments, in the presence of good inhaler technique, good adherence and optimal management of comorbid or contributory conditions.²

Both GINA (Global initiative for asthma) and BTS/NICE/SIGN have clear guidance for implementation of inhaled therapy and escalation using a step wise approach.³

When escalating a patient’s treatment especially to high dose ICS/LABA or add on therapies such as a LAMA or Leukotriene receptor antagonist (LRA) it is imperative that the response to treatment be reviewed.

The HASTE tool (summarised in the box below)¹¹ is a useful checklist for clinicians when assessing patients with asthma, if you have answered yes to all the questions, then refer the patient to the severe asthma service. All patients on maintenance oral steroids should be referred.

What are the secondary care options in truly resistant asthma?

In the severe asthma service, assessment often begins from first principles. This includes a review of the asthma diagnosis, identification of potential co-existing or exacerbating conditions, and evaluation of biomarkers and lung function with spirometry +/– bronchodilator reversibility. Patients undergo an asthma screening panel, including total and specific IgE to common allergens, and may benefit from further imaging such as a repeat chest X-ray or high-resolution CT where indicated. Bone health is also considered as part of the assessment. All patients are reviewed by an asthma specialist nurse, with inhaler technique routinely assessed and optimised.

If the patient is optimised on medical therapy and their clinical history is consistent with a diagnosis of asthma, they are referred to the multidisciplinary team (MDT) for consideration of biologic therapy. Biologic therapies are add-on injectable treatments for patients with severe asthma, used in addition to regular inhaled therapy, and target specific immune pathways that drive airway inflammation. These therapies can reduce exacerbation frequency, improve symptom control and lung function, and reduce the need for systemic corticosteroids.

Dr Hannah Petty is specialist registrar (ST7) in respiratory medicine and Dr Nita Sehgal is consultant respiratory physician at North Manchester General Hospital

References

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3. Global Initiative for Asthma (GINA). Global Strategy for Asthma Management and Prevention. Updated 15 November 2025  
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6. Bousquet J et al. Allergic rhinitis and its impact on asthma. J Allergy Clin Immunol. 2001;108(5 Suppl):S147–334
7. Havemann B et al. The association between gastro-oesophageal reflux disease and asthma: a systematic review. Gut 2007;56(12):1654–64
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10. Price D et al. Inhaler competence in asthma: common errors, barriers to use and recommended solutions. Respir Med 2013;107(1):37–46
11. AAC Consensus Pathway. Rapid uptake products: asthma biologics – management of uncontrolled asthma in adults. June 2022
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