Convergence of Inflammatory Pathways in Allergic Asthma and Sickle Cell Disease

Abstract

The underlying pathologies of sickle cell disease and asthma share many characteristics in terms of respiratory inflammation. The principal mechanisms of pulmonary inflammation are largely distinct, but activation of common pathways downstream of the initial inflammatory triggers may lead to exacerbation of both disease states. The altered inflammatory landscape of these respiratory pathologies can differentially impact respiratory pathogen susceptibility in patients with sickle cell disease and asthma. How these two distinct diseases behave in a comorbid setting can further exacerbate pulmonary complications associated with both disease states and impact susceptibility to respiratory infection. This review will provide a concise overview of how asthma distinctly affects individuals with sickle cell disease and how pulmonary physiology and inflammation are impacted during comorbidity.

In-Depth Immunological Typization of Children with Sickle Cell Disease: A Preliminary Insight into Its Plausible Correlation with Clinical Course and Hydroxyurea Therapy

“…Further, our study confirmed a higher mean IgE level among SCD HU− pediatric patients, consistent with an adaptive cellular immunity skewed towards a T-helper 2 phenotype; however, this was without statistical significance, ascribable to the small cohort size. An increase in IgE levels occurs much more frequently in children affected by SCD than in the general pediatric population, being associated with a higher risk for both asthma and acute chest syndrome, as a result of an imbalance between type 1 and 2 helper T cells, with adaptive cellular immunity dominated by the latter [ 35 ].…”

Hidden Comorbidities in Asthma: A Perspective for a Personalized Approach

“…A broad spectrum of lung clinical manifestations, such as acute chest syndrome (ACS), asthma and recurrent wheezing, venous thromboembolic disease and sleep-disordered breathing, commonly coexist with SCD [ 60 ]. The association between asthma and SCD has long since been recognized; however, the frequent wheezing that characterizes SCD patients may perhaps account for overdiagnosis of asthma in such a condition [ 61 ]. Of note is that the presence of wheezing, even in the absence of an asthma diagnosis, has been recently proposed as a risk factor for the severity of sickle cell related clinical manifestations [ 62 ].…”

“…Of note is that the presence of wheezing, even in the absence of an asthma diagnosis, has been recently proposed as a risk factor for the severity of sickle cell related clinical manifestations [ 62 ]. This is of interest since children with SCD and asthma have increased rates of VOCs and ACS and have an increased risk of premature death [ 61 , 63 ]. Epidemiologic studies report a higher prevalence of asthma in the SCD population compared to matched healthy controls.…”

“…In this scenario, the design of population-based studies comparing SCD patients and healthy control subjects in terms of asthma incidence and prevalence are required to drive consistent conclusions on asthma in SCD, particularly considering that recurrent wheezing is a common feature in patients with SCD, even without a personal or familiar asthma history. In a study on 939 patients experiencing ACS, 11% of them presented with wheezing on admission to the hospital [ 61 ]. Similar findings have been confirmed by different research groups, describing an equally common wheezing presentation of ACS among children and adults [ 66 , 67 ].…”

Apolipoprotein E in Asthmatic Inflammatory Response: Friend or Foe?

“…This inflammation is often accompanied by increased airway responsiveness, which causes recurrent wheezing, shortness of breath, chest tightness, and/or cough ( 1 ). Allergic asthma threatens the lives and health of 300 million people worldwide, with more than 26 million people being affected each year in the United States alone ( 2 ). Despite intense efforts at understanding pathogenic mechanisms and developing strategies to contain this disease in recent decades, the high morbidity and mortality of asthma and subsequent airway remodeling are still difficult to control.…”