Asthma is a Distinct Comorbid Condition in Children With Sickle Cell Anemia With Elevated Total and Allergen-specific IgE Levels

Ross, Jerlinda; Bernaudin, Françoise; Strunk, Robert C.; Kamdem, Annie; Hervé, M. Emilia; Delacourt, Christophe; DeBaun, Michael R.

doi:10.1097/mph.0b013e31820db7b1

Cited by 18 publications

(18 citation statements)

References 19 publications

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“…For example, total IgE is increased in chi-SCD mice compared with chi-HbA mice whether or not the mice are sensitized to OVA. This is similar to reports in humans, where IgE is increased in individuals with SCD (with or without asthma) compared with the general population (20,21). IgE production is stimulated by IL-13 (22).…”

Section: Discussionsupporting

confidence: 78%

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Effects of Experimental Asthma on Inflammation and Lung Mechanics in Sickle Cell Mice

Pritchard

Feroah²,

Nandedkar³

et al. 2012

Am J Respir Cell Mol Biol

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Experimental asthma increases eosinophil and collagen deposition in the lungs of sickle cell disease (SCD) mice to a greater extent than in control mice. However, the effects of asthma on inflammation and airway physiology remain unclear. To determine effects of asthma on pulmonary inflammation and airway mechanics in SCD mice, hematopoietic stem cell transplantation was used to generate chimeric SCD and hemoglobin A mice. Experimental asthma was induced by sensitizing mice with ovalbumin (OVA). Airway mechanics were assessed using forced oscillation techniques. Mouse lungs were examined histologically and physiologically. Cytokine, chemokine, and growth factors in bronchoalveolar lavage fluid were determined by multiplex. IgE was quantified by ELISA. LDH was quantified using a colorimetric enzymatic assay. At baseline (nonsensitized), chimeric SCD mice developed hemolytic anemia with sickled red blood cells, mild leukocytosis, and increased vascular endothelial growth factor and IL-13 compared with chimeric hemoglobin A mice. Experimental asthma increased perialveolar eosinophils, plasma IgE, and bronchoalveolar lavage fluid IL-1b, IL-4, IL-6, and monocyte chemotactic protein 1 in chimeric hemoglobin A and SCD mice. IFN-g levels were reduced in both groups. IL-5 was preferentially increased in chimeric SCD mice but not in hemoglobin A mice. Positive end-expiratory pressures and methacholine studies revealed that chimeric SCD mice had greater resistance in large and small airways compared with hemoglobin A mice at baseline and after OVA sensitization. SCD alone induces a baseline lung pathology that increases large and small airway resistance and primes the lungs to increased inflammation and airway hyperresponsiveness after OVA sensitization.

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Section: Discussionsupporting

confidence: 78%

“…In sensitized mice, total IgE in the OVA-Sen chi-SCD mice was further increased compared with OVA-Sen chi-HbA mice ( Figure 3). These data suggest that SCD specifically contributes to total circulating IgE levels at baseline or after OVA sensitization, similar to humans with SCD (20,21).…”

Section: Total Ige Levelsmentioning

confidence: 70%

Effects of Experimental Asthma on Inflammation and Lung Mechanics in Sickle Cell Mice

Pritchard

Feroah²,

Nandedkar³

et al. 2012

Am J Respir Cell Mol Biol

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“…Respiratory morbidity, including asthma2 3 and acute chest syndrome (ACS),4–6 is common in children with SCD. Elevated total IgE in SCD is associated with increased wheeze and cough and is an independent risk factor for ACS 7.…”

Section: Introductionmentioning

confidence: 99%

“…Airway hyper-responsiveness (AHR) measured using cold air or exercise has been reported in 20–64% in children with SCD3 8 9 but is not associated with symptoms of reactive airway disease8 or ACS 9. AHR to methacholine is no more frequent in SCD children reporting asthma symptoms than unselected SCD children,10 11 suggesting that AHR may be a component of SCD8 while asthma may represent a distinct coexisting condition 2. Ethnicity may be an important factor though, since AHR has been reported in 42% of young, healthy, African-American children, despite a doctor diagnosis of asthma in only 10% 12.…”

Section: Introductionmentioning

confidence: 99%

Reduced forced expiratory flow but not increased exhaled nitric oxide or airway responsiveness to methacholine characterises paediatric sickle cell airway disease

Chaudry

Rosenthal

Bush

et al. 2014

Thorax

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“…Studies looking at whether IgE levels can be used to discriminate between those with and without asthma have been inconsistent. While some studies have demonstrated that children and adults with SCD and asthma have higher IgE levels than those without asthma, [21, 42, 43] Strunk et al found that there was no difference in IgE levels between those with and without a physician diagnosis of asthma among children in the SAC cohort [3]. Having ≥ 2 positive skin tests to aeroallergens was more common among those with asthma compared to those without asthma in the SAC cohort, but skin test reactivity did not add much to a predictive model for discriminating “asthma” from “no asthma” in this cohort [3].…”

Section: Introductionmentioning

confidence: 99%

Sickle cell disease: wheeze or asthma?

Cohen

Klings

Strunk

2015

asthma res and pract

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Sickle cell disease (SCD) is the most common life-limiting genetic disease among African Americans, affecting more than 100,000 people in the United States. Respiratory disorders in patients with sickle cell disease have been associated with increased morbidity and mortality. Associations between asthma and pain, acute chest syndrome (ACS), and even death have long been reported. More recently wheezing, even in the absence of an asthma diagnosis, has gained attention as a possible marker of SCD severity. Several challenges exist with regards to making the diagnosis of asthma in patients with SCD, including the high prevalence of wheezing, evidence of airway obstruction on pulmonary function testing, and/or airway hyperresponsiveness among patients with SCD. These features often occur in isolation, in the absence of other clinical criteria necessary for an asthma diagnosis. In this review we will summarize: 1) Our current understanding of the epidemiology of asthma, wheezing, airway obstruction, and airway responsiveness among patients with SCD; 2) The evidence supporting associations with SCD morbidity; 3) Our understanding of the pathophysiology of airway inflammation in SCD; 4) Current approaches to diagnosis and management of asthma in SCD; and 5) Future directions.

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Asthma is a Distinct Comorbid Condition in Children With Sickle Cell Anemia With Elevated Total and Allergen-specific IgE Levels

Cited by 18 publications

References 19 publications

Effects of Experimental Asthma on Inflammation and Lung Mechanics in Sickle Cell Mice

Effects of Experimental Asthma on Inflammation and Lung Mechanics in Sickle Cell Mice

Reduced forced expiratory flow but not increased exhaled nitric oxide or airway responsiveness to methacholine characterises paediatric sickle cell airway disease

Sickle cell disease: wheeze or asthma?

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