Aeroallergen sensitization predicts acute chest syndrome in children with sickle cell anaemia

Willen, Shaina M.; Rodeghier, Mark; Strunk, Robert C.; Bacharier, Leonard B.; Rosen, Carol L.; Kirkham, Fenella J.; DeBaun, Michael R.; Cohen, Robyn T.

doi:10.1111/bjh.15076

Cited by 8 publications

(4 citation statements)

References 28 publications

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“…While some microorganisms are particularly virulent because of the functional asplenia that develops in infancy in sickle cell anemia, the lung, in general, is more vulnerable to infection in children with SCD. Bronchial hyper-reactivity, asthma, and chronic airway inflammation (209) are highly prevalent in children with SCD and may result in a proinflammatory milieu that amplifies cellular and humoral immunity to airway pathogens, thus leading to a paroxysmal, detrimental response (210,211).…”

Section: Convergence Of Multiple Pathogenic Pathways: Acute Chest Syndromementioning

confidence: 99%

Pathophysiology of Sickle Cell Disease

Sundd

Gladwin

Novelli

2019

Annu. Rev. Pathol. Mech. Dis.

495

397

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Since the discovery of sickle cell disease (SCD) in 1910, enormous strides have been made in the elucidation of the pathogenesis of its protean complications, which has inspired recent advances in targeted molecular therapies. In SCD, a single amino acid substitution in the β-globin chain leads to polymerization of mutant hemoglobin S, impairing erythrocyte rheology and survival. Clinically, erythrocyte abnormalities in SCD manifest in hemolytic anemia and cycles of microvascular vaso-occlusion leading to end-organ ischemia-reperfusion injury and infarction. Vaso-occlusive events and intravascular hemolysis promote inflammation and redox instability that lead to progressive small- and large-vessel vasculopathy. Based on current evidence, the pathobiology of SCD is considered to be a vicious cycle of four major processes, all the subject of active study and novel therapeutic targeting: ( a) hemoglobin S polymerization, ( b) impaired biorheology and increased adhesion-mediated vaso-occlusion, ( c) hemolysis-mediated endothelial dysfunction, and ( d) concerted activation of sterile inflammation (Toll-like receptor 4– and inflammasome-dependent innate immune pathways). These molecular, cellular, and biophysical processes synergize to promote acute and chronic pain and end-organ injury and failure in SCD. This review provides an exhaustive overview of the current understanding of the molecular pathophysiology of SCD, how this pathophysiology contributes to complications of the central nervous and cardiopulmonary systems, and how this knowledge is being harnessed to develop current and potential therapies.

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Section: Convergence Of Multiple Pathogenic Pathways: Acute Chest Syndromementioning

confidence: 99%

Pathophysiology of Sickle Cell Disease

Sundd

Gladwin

Novelli

2019

Annu. Rev. Pathol. Mech. Dis.

495

397

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“…In contrast, other studies have found significant associations between elevated IgE levels and a diagnosis of asthma in patients with SCD . Further, high IgE levels and aeroallergen sensitization in patients with SCD have been reported as risk factors for ACS episodes . The relationship between atopy and SCD needs to be further understood.…”

Section: Discussionmentioning

confidence: 79%

A physicians survey assessing management of pulmonary airway involvement in sickle cell disease

Agrawal

Burton

Manwani

et al. 2019

Pediatric Pulmonology

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Background: Airway involvement in patients with sickle cell disease (SCD) involves recurrent episodes of acute chest syndrome (ACS), co-existent asthma, lower airway obstruction (LAO), or airway hyper-responsiveness/ bronchodilator response (AHR/ BDR). With increased recognition that sickle cell (SC) airway inflammation may be distinct from asthma, our aim was to study regional and individual practices among pediatric pulmonologists and elucidate the patient characteristics that determine the diagnosis of asthma or SC airway inflammation. Methods:A cross-sectional web-based survey including 6 case scenarios on diagnosis and management of pulmonary manifestations of pediatric SC airway disease was conducted.The case scenarios, combined different risk factors for airway inflammation: history of recurrent ACS, atopy, family history of asthma, LAO, or AHR/BDR, with possible responses including − diagnosis of asthma, SC airway inflammation, both or neither.

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“…In addition, recurrent episodes of ACS can lead to the development of debilitating chronic lung disease. 76 Several risk factors such as young age, low HbF, high baseline hemoglobin, steady-state leukocytosis, 74 asthma/ airway hyperresponsiveness, 77 and aeroallergen sensitization 78 have been associated with the development ACS. ACS is an ideal target for biomarker development, as two-thirds of ACS episodes occur in patients who are hospitalized for other reasons (primarily VOCs).…”

Section: Acs and Multiorgan Failure Syndrome (Mofs)mentioning

confidence: 99%

Measuring success: utility of biomarkers in sickle cell disease clinical trials and care

Kalpatthi

Novelli

2018

Hematology

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Progress in the care of sickle cell disease (SCD) has been hampered by the extreme complexity of the SCD phenotype despite its monogenic inheritance. While epidemiological studies have identified clinical biomarkers of disease severity, with a few exceptions, these have not been routinely incorporated in clinical care algorithms. Furthermore, existing biomarkers have been poorly apt at providing objective parameters to diagnose sickle cell crisis, the hallmark, acute complication of SCD. The repercussions of these diagnostic limitations are reflected in suboptimal care and scarcity of adequate outcome measures for clinical research. Recent progress in molecular and imaging diagnostics has heralded a new era of personalized medicine in SCD. Precision medicine strategies are particularly timely, since molecular therapeutics are finally on the horizon. This chapter will summarize the existing evidence and promising data on biomarkers for clinical care and research in SCD.

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Aeroallergen sensitization predicts acute chest syndrome in children with sickle cell anaemia

Cited by 8 publications

References 28 publications

Pathophysiology of Sickle Cell Disease

Pathophysiology of Sickle Cell Disease

A physicians survey assessing management of pulmonary airway involvement in sickle cell disease

Measuring success: utility of biomarkers in sickle cell disease clinical trials and care

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