Table (3).

Modifiable factors that, in patients with severe asthma, may contribute to poor symptom control and/ or exacerbations, with diagnostic investigations, and effective intervention strategies (11)

	Modifiable risk factors	Diagnosis	Intervention strategies
Medication & Delivery	Incorrect inhaler technique Poor adherence with controller therapy	Check technique against a device specific checklist	Physical demonstration and regular rechecking Identify adherence barriers including cost; simplify treatment regimen; electronic inhaler reminders for missed doses; refill reminders
Exposure	Smoking or environmental tobacco smoke; biomass fuel exposure Allergen exposure in sensitized patients (house dust mite, cat, mold, cockroach)	History, urinary cotinine Skin prick testing, history	Smoking cessation advice; alternative cooking or heating methods Selected avoidance strategies if shown to be effective
	Indoor or outdoor air pollution, extreme weather	Specific questioning, seasonal or event related	Ventilate dwelling; alternative cooking/heating methods; avoid running during outdoor air pollution or extreme weather
	Occupational exposure to allergens or irritants	Occupational history, peak expiratory flow on work/non-work days	Early withdrawal from exposure
	Respiratory viruses including rhinovirus, respiratory syncytial virus, influenza	History, serology	Consider avoiding close contact with children when they have respiratory infections; influenza vaccination
Comorbidities	Obesity Gastro-esophageal reflux disease (GERD) Rhinosinusitis ± nasal polyposis COPD (i.e. asthma-COPD overlap) Anxiety, depression Vocal cord dysfunction Bronchiectasis Allergic bronchopulmonary aspergillosis (ABPA) Pregnancy	Body mass index Usually only relevant when symptomatic; 24-hour pH monitoring including acid and non-acid reflux ENT evaluation, nasal endoscopy and/or CT sinuses Smoking history, diffusing capacity, lung volumes, ± HRCT chest Inspiratory/expiratory flow-volume loops, functional laryngoscopy (± with exercise), HRCT larynx HRCT chest, sputum culture, investigate for immunodeficiency and ABPA Serum IgE, skin test/specific IgE for Aspergillus, IgG Aspergillus precipitins. Pregnancy test	Diet and exercise; bariatric surgery Lifestyle changes, proton pump inhibitor, reduce medications that predispose to reflux; treatment of asymptomatic reflux may not improve asthma control Nasal corticosteroids (spray or wash), surgery if needed; consider leukotriene modifier if aspirin exacerbated respiratory disease Smoking cessation, pulmonary rehabilitation, long-acting muscarinic antagonist, check for cardiac
Social	Socioeconomic problems Illicit drug use At-risk populations (adolescents, elderly)	Empathic questioning about cost barriers to adherence; social work consultation Blood/urine testing Assess adherence, inhaler technique, comorbidities (especially in elderly), medication interactions	Community/government support; medication samples; choose lowest cost medication regimen Refer for withdrawal strategies and support

Data from From Israel E, Reddel HK. Severe and Difficult-to-Treat Asthma in Adults. N Engl J Med. 2017;377(10):965-76