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Overview

A comorbid diagnosis of asthma is a negative prognostic factor for patients with sickle cell disease (SCD). It is associated with increased frequency of acute chest syndrome (ACS) episodes in children and adolescents, progression of disease, and an increased mortality rate.1-8 Given these findings, the concept of asthma as a modifiable risk factor in SCD developed.3 Simply making an earlier diagnosis of asthma seemed to be an opportunity by which to significantly improve outcomes in SCD. It turns out that the pathophysiology, diagnosis, and treatment of asthma in individuals with SCD is far from straightforward, but recognizing and treating the airway disease in individuals with SCD remains crucial to improving patient outcomes.

Asthma in SCD

An appreciation of the complex interplay of asthma and sickle cell airway pathophysiology begins with a definition of asthma. Yet, asthma itself is not easily defined because it is actually a heterogeneous disease.9,10 Broadly speaking, asthma involves airway hyperreactivity (AHR) and inflammation in addition to a constellation of recognized signs and symptoms. These signs and symptoms may be persistent or intermittent and even completely absent for months at a time. The consensus put forth by the Global Initiative for Asthma (GINA) is that asthma is characterized by chronic airway inflammation and defined by a history of respiratory symptoms such as wheeze, shortness of breath, chest tightness, and cough, together with variable expiratory airflow limitation.9 Meanwhile, asthma and airway pathophysiology in SCD are entangled, but not synonymous. Multiple studies have shown that the correlations between symptoms, pulmonary function, and biomarkers typically found in asthma do not uniformly apply to the airway disease that occurs in SCD.11-15 Although there are numerous overlapping mechanisms common to both classic asthma and SCD, there are also some paradigms unique to SCD (Figure 11-1). Herein lies the diagnostic and therapeutic conundrum that we are confronted with as clinicians.

FIGURE 11-1

The Asthma-Like Condition of Sickle Cell Disease. There are numerous overlapping mechanisms in both classic asthma and sickle cell disease. Mechanisms unique to “asthma” in sickle cell disease are also listed. PlGF, placental growth factor; NO, nitric oxide; LTB4, leukotriene B4; IL-13, interleukin-13 (TH2 pathway); iNKTs, invariant natural killer T cells; IFN-gamma, interferon-gamma (pro-inflammatory); DAMPs, damage associated molecular patterns; V/Q, ventilation-to-perfusion ratio; NOS, nitric oxide synthase; IL-1 beta, interleukin-1 beta (pro-inflammatory); IL-18, interleukin-18 (TH1 pathway).

Epidemiology

Asthma has a significant global disease burden. It is estimated that >300 million individuals worldwide are affected. The existing data show an international asthma prevalence of approximately 5% to 18%.10,16

There is not yet a consensus definition of what qualifies as a diagnosis of asthma within the context of SCD, but “asthma” or airway obstruction and hyperreactivity in patients with SCD is ...

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