Table 2. Current therapeutic options in type-2 low asthma.

Treatable trait	Phenotype	Potential Biomarkers	Investigations	Therapeutic option	Comments
Fixed airflow obstruction	Persistent airflow obstruction despite ICS+LABA use.		Spirometry with reduced post-bronchodilator FEV1/FVC ratio.	Long acting antimuscarinics.	Effect small and may worsen cough so assess response and discontinue if no benefit.
Chronic bacterial airway colonisation	Persistent mucopurulent cough, frequent infective exacerbations.	Typical organisms on sputum culture.	Sputum culture.	Long term, low dose azithromycin.	Research needed into optimal patient selection, duration of therapy, potential use of other macrolides.
	Bacterial colonisation with potentially pathogenic bacteria (e.g. Haemophilus influenzae).	Pathogenic specific quantitative PCR.	Exclude mycobacteria with sputum culture.
			Consider CT to exclude bronchiectasis.
Cough reflex hypersensitivity	Female predominant, adult onset.	Capsaicin hypersensitivity.		Discontinue ACEi, treat GORD.	Research needed into cough suppressants including P2X3 inhibitors.
Airway hyperreactivity	Marked airway hyperreactivity and inadequate response to other therapies.	Paucigranulocytic.	Reversibility / bronchial hyperresponsiveness testing, CT to exclude bronchiectasis and tracheobronchomalacia.	Consider bronchial thermoplasty in highly-selected patients.	Optimal phenotype, long term outcomes and efficacy of retreatment remain to be defined.
Steroid over use	Non-eosinophilic, patient reports symptoms are slow to improve after initiation of systemic steroids.		Peripheral blood eosinophil count.	Consider a steroid holiday: cautiously stopping systemic steroids.	Care to avoid iatrogenic adrenal insufficiency.
Vocal cord dysfunction (ILO)	Episodic, symptoms predominantly inspiratory, inspiratory stridor, minimal response to pharmacotherapy.	Flattened inspiratory flow loop, normal expiratory spirometry.	Laryngoscopy during provocation.	Specialist speech and language therapy.	Often coexists with asthma, triggers include inhalational irritants, exercise, and psychosocial disorders.

ACEi, angiotensin converting enzyme inhibitor; CT, computed tomography; GORD, gastro-oesophageal reflux; ILO, inducible laryngeal obstruction; LABA, long-acting beta-2 agonist; PCR, polymerase chain reaction.