Systemic Inflammation in Asthma: What Are the Risks and Impacts Outside the Airway?

Abstract

Airway inflammation in asthma has been well recognized for several decades, with general agreement on its role in asthma pathogenesis, symptoms, propensity toward exacerbation, and decline in lung function. This has led to universal recommendation in asthma management guidelines to incorporate the use of inhaled corticosteroid as an anti-inflammatory therapy for all patients with persistent asthma symptoms. However, there has been limited attention paid to the presence and potential impact of systemic inflammation in asthma. Accumulating evidence from epidemiological observations and cohort studies points to a host of downstream organ dysfunction in asthma especially among patients with longstanding or more severe disease, frequent exacerbations, and underlying risk factors for organ dysfunction. Most studies to date have focused on cognitive impairment, depression/anxiety, metabolic syndrome, and cardiovascular abnormalities. In this review, we summarize some of the evidence demonstrating these abnormalities and highlight the proposed mechanisms and potential benefits of treatment in limiting these extrapulmonary abnormalities in patients with asthma. The goal of this commentary is to raise awareness of the importance of recognizing potential extrapulmonary conditions associated with systemic inflammation of asthma. This area of treatment of patients with asthma is a large unmet need.

Keywords: Alzheimer’s disease; Anxiety; Asthma; Cardiovascular events; Cognitive impairment; Dementia; Depression; Severe asthma; Systemic inflammation.

Figure 1:

The extra-pulmonary manisfestations of asthma. This figure highlights the organ systems affected by asthma. Arrows indicate the directionality of the relationships that have been described between asthma and the organ systems.

Figure 2.

Data from the Multi-Ethnic Study of Atherosclerosis (MESA) demosntrating the Kaplan-Meier curves depicting cardiovascular-free survival estimates based on asthma status (no asthma, intermittent asthma and persistent asthma). The persistent asthma participants in this cohort also had higher levels of serum inflammatory markers (IL-6, CRP) and blood coagulation (Fibrinogen and D-Dimer) compared to the non-asthma and intermittent asthma groups.

Figure 3.

Visualization of the spectrum of arterial injury using ultrasound. Panel A. Carotid plaque identification at the carotid bifurcation in a 58-year-old woman with asthma. The arrows indicated carotid plaque presence on the near wall of the carotid bifurcation. Panel B. Carotid ultrasound of age-sex matched control without asthma showing no carotid plaque.

Figure 4.

Clinical approaches to diagnose and treat the extra-pulmonary manisfestations of asthma. This figure demonstrates established and emerging strategies to address the extra-pulmonary manisfestations fo asthma.