Can Asthma Be Managed in Smokers?

Smokers with Asthma: An Understudied Population. Smokers may have up to 4 times the risk of poorly controlled asthma, compared to nonsmokers(1): Asthma guidelines generally do not provide advice for treating the population. Smokers are often excluded from randomized controlled trials, limiting evidence about effective management of asthma in smokers. Some evidence comes from observational studies and trials in routine clinical practice

Steroid Resistance in Smokers.(2) Smokers often have poor response to corticosteroid therapy, possibly explained by: Smoking-induced tissue damage, increased neutrophils and macrophages in the sputum, increased oxidative stress. Smokers also have increased inflammation: Increased levels of certain leukotrienes linked to microvascular permeability, mucus hypersecretion, and smooth muscle contraction; increased inflammatory infiltrates in small airways; increased growth factor production in airway walls, causing increased small-airway remodeling.

Asthma Management in Smokers: Smoking cessation is *highly* recommended. Studies suggest tissue damage is reversible with smoking cessation. Use higher-dose inhaled corticosteroids: Multicenter randomized, double-blind study of 95 people with mild asthma suggested beclomethasone 2000 µg daily may improve control; after 12 weeks of therapy, there were no significant differences in peak expiratory flow or exacerbation rates in smokers compared with non-smokers.(3)

Asthma management tips in smokers: Target the small airways with extra-fine ICS formulationsNewer MDIs that use hydrofluoroalkane (HFA) generate aerosolized particles that are about 2 to 4 times smaller than traditional dry powder inhalers. Extra-fine particles penetrate more deeply into small airways; improved deposition, more uniform treatment of inflammation/bronchoconstriction throughout bronchial tree.

Leukotriene Receptor Antagonists (LTRA): Alternative to ICS for smokers with asthma. Largest RCT of smokers with asthma (31 countries)4 randomized patients to: Montelukast 10 mg daily (n=347), fluticasone propionate 250 μg twice daily (n=336), placebo (n=336). At 6 months: fluticasone and montelukast groups had significantly improved asthma control vs placebo (44.97% vs 39.05%, respectively, P=.04).

Both drugs significantly improved daytime symptom score vs placebo (P=.0004 and P=.001); no significant differences. Montelukast significantly improved mean morning PEF vs placebo (P ≤ .001), while fluticasone did not (P=.117). Patients with history of ≤11 pack years showed more improvement with fluticasone; those with ≥11 pack years showed more improvement with montelukast.

Limited Data for Combination Therapy. Options include: Extra-fine ICS combined with long-acting beta-agonist or LTRA therapy. Prospective observational trial included 619 participants and 123 smokers with moderate to severe persistent asthma.(5) Treated with extra-fine beclomethasone dipropionate 100 μg/formoterol 6 μg pressurized metered dose inhaler. After 1 year, both smokers and non-smokers had significant improvements in pulmonary function (+7.1% in FEV1% pred), asthma control (per GINA criteria).

Take Home Points: Smokers may have up to 4x the risk of poorly controlled asthma compared with nonsmokers yet are understudied, which limits evidence about effective management. Smokers often have poor response to corticosteroid therapy. Smoking cessation is *highly* recommended. Management options include: higher-dose inhaled corticosteroids, targeting the small airways with extra-fine ICS formulations, leukotriene receptor antagonists, and combination therapy.