Challenges in the management of asthma associated with smoking-induced airway diseases

ABSTRACT

Introduction: Smoking-induced airway diseases such as chronic bronchitis, emphysema, and small airway dysfunction contribute to the chronic respiratory symptoms experienced by adults with asthma, including those with spirometric chronic obstructive pulmonary disease (COPD), termed asthma-COPD overlap (ACO). Drug treatment of symptomatic smokers with asthma or ACO is uncertain due to their exclusion from most clinical trials.

Areas covered: This review summarizes evidence for the efficacy of small molecule drugs used in the clinic to treat current and former smokers with a diagnostic label of asthma or ACO. Other therapeutic interventions are reviewed, including smoking cessation and biologics.

Expert opinion: Clinical trials and observational studies suggest that smoking cessation and approved drugs used to treat non-smokers with asthma produce clinical benefits in smokers with asthma or ACO, although the overall quality of evidence is low. The efficacy of some treatments for asthma is altered in current smokers, including reduced responsiveness to short-term inhaled corticosteroids and possibly improved responsiveness to leukotriene receptor antagonists. Preliminary findings suggest that low-dose theophylline, statins, and biologics, such as omalizumab, mepolizumab, and dupilumab, may improve clinical outcomes in smokers with asthma or ACO. Improved phenotyping and endotyping of asthma and smoking-induced airway diseases should lead to better targeted therapies.

KEYWORDS:

• Asthma
• Asthma-COPD overlap (ACO)
• biologics
• cigarette smokers
• COPD
• inhaled corticosteroid
• leukotriene-receptor antagonist
• long-acting beta₂-agonist
• long-acting muscarinic antagonist
• macrolide
• phosphodiesterase inhibitor
• small airway dysfunction
• smoking cessation
• statin
• theophylline
• thiol antioxidant
• tobacco smoke

Article highlights

• Smoking cessation is a central component of the management of current smokers with asthma and asthma-COPD overlap (ACO) and associated co-morbidities.

• Clinical trials and observational studies suggest that approved drugs used to treat non-smokers with asthma produce clinical benefits in smokers with asthma or ACO, although the quality of evidence is low.

• The efficacy of some drug treatments for asthma is influenced by smoking status, such as reduced responsiveness to short-term ICSs and possibly improved responsiveness to leukotriene receptor antagonists in current smokers with asthma.

• Preliminary findings suggest that low-dose theophylline, statins, and biologics, such as omalizumab, mepolizumab, and dupilumab, may improve clinical outcomes in smokers with asthma or ACO.

• In the future, improved phenotyping and endotyping of asthma and smoking-induced airway diseases should lead to better targeted therapies.

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Declaration of Interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This manuscript was not funded.