Elevation of IgE in children with sickle cell disease is associated with doctor diagnosis of asthma and increased morbidity

doi:10.1016/j.jaci.2010.12.1114

Journal of Allergy and Clinical Immunology

Volume 127, Issue 6, June 2011, Pages 1440-1446

https://doi.org/10.1016/j.jaci.2010.12.1114 Get rights and content

Background

A doctor’s diagnosis of asthma is associated with increased morbidity (pain and acute chest syndrome [ACS]) among children with sickle cell disease (SCD). An association between IgE levels and asthma and morbidity has not been investigated in children with SCD.

Objective

We tested the hypothesis that elevated total and allergen-specific IgE levels are associated with asthma and SCD morbidity in children with SCD.

Methods

A cross-sectional study of children with SCD who participated in the Silent Cerebral Infarct Trial was conducted. Logistic regression and negative binomial regression were used to investigate potential associations of total and allergen-specific IgE levels with asthma diagnosis and SCD morbidity, both confirmed by medical record review. Elevation of total IgE level was defined as age-adjusted and sex-adjusted IgE level exceeding the 90th percentile compared with a nonatopic reference population. IgE antibody positivity to Alternaria alternata (mold), Blattella germanica (cockroach), and Dermatophagoides pteronyssinus (dust mite) was assessed by ImmunoCAP analysis.

Results

Children with SCD (140 with asthma; 381 without asthma) were evaluated. Elevations in total IgE level (P = .04) and IgE antibody specific for Alternaria alternata (P = .0003), Blattella germanica (P = .008), and Dermatophagoides pteronyssinus (P = .01) were associated with asthma. ACS (P = .048) but not pain (P = .20) was associated with total IgE level, but neither was associated with specific IgE levels.

Conclusion

Significantly increased levels of total and allergen-specific IgE levels are associated with asthma in SCD. High IgE levels are a risk factor for ACS but not pain rates.

Section snippets

Patient population

The Silent Cerebral Infarct Transfusion (SIT) Trial includes 29 North American (US and Canadian) and European (United Kingdom and French) clinical sites, a clinical coordinating center, and a statistical data coordinating center to test the following hypothesis: prophylactic blood transfusion therapy in children with SCD will result in at least an 86% reduction in the rate of subsequent overt strokes or new or progressive cerebral infarcts as defined by magnetic resonance imaging of the brain.

Demographics

A total of 521 children with SCD had complete clinical data and measured total IgE levels for this analysis (Fig 1; Table II). One hundred forty of 521 (27%) children met the criterion of having a physician diagnosis of asthma, with statistically significantly (P = .01) higher asthma prevalence in boys (32%; 86/271) than in girls (22%; 54/250)—that is, boys accounted for 61% (86/140) of subjects with asthma and 49% (185/381) of subjects without asthma. Hemoglobin SS distribution was not

Discussion

Previously, our group6, 11, 14 and others7, 8, 9, 10, 12, 13 have demonstrated that children with SCD and asthma are at increased risk for ACS6, 7, 8, 9, 10, 11, 12, 13, 14 and pain¹¹ episodes compared with children with SCD alone; however, there has been limited evaluation of asthma risk factors. In the current analysis, we tested 2 hypotheses: first, whether the asthma risk factors of total and allergen-specific IgE levels are associated with a physician diagnosis of asthma, and second,

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Cited by (42)

Pulmonary Manifestations of Hematologic and Oncologic Diseases in Children
2021, Pediatric Clinics of North America
Citation Excerpt :
The use of antiinflammatory, antipolymerization, and antiadhesive medications offers potential beneficial approaches to treat ACS. Asthma is seen in 15% to 28% of patients with SCD and is associated with increased morbidity and mortality.85 In a cohort of 521 children with SCD, those having asthma had higher incidence rates of ACS episodes (19 vs12 episodes per 100 patient years; P = .02) as well as more vasoocclusive pain episodes than those without asthma.85
Sickle Cell Disease: Monitoring, Current Treatment, and Therapeutics Under Development
2019, Hematology/Oncology Clinics of North America
Citation Excerpt :
Silent cerebral infarcts occur in up to 39% of children with SCD and 43% of adults,4,29–32 and are associated with neurocognitive deficits33–35 and increased risk for overt strokes (Box 4).36 Asthma is common in SCD40–43 and is associated with a higher incidence of acute chest syndrome,44–46 vasoocclusive episodes (VOE), and mortality (Box 5).47–50 Common underlying pathophysiology includes dysregulation of arginine metabolism and nitric oxide.7,51
Exhaled nitric oxide: Not associated with asthma, symptoms, or spirometry in children with sickle cell anemia
2016, Journal of Allergy and Clinical Immunology
The significance of fractional exhaled nitric oxide (Feno) levels in children with sickle cell anemia (SCA) is unclear, but increased levels can be associated with features of asthma and thus increased morbidity.
We sought to determine factors associated with Feno and whether Feno levels are associated with increased rates of acute chest syndrome (ACS) and pain.
All participants had SCA, were part of the prospective observational Sleep and Asthma Cohort study, and had the following assessments: Feno levels, spirometry, blood samples analyzed for hemoglobin, white blood cell counts, eosinophil counts and total serum IgE levels, questionnaires about child medical and family history, and review of medical records.
The analytic sample included 131 children with SCA (median age, 11.2 years; age range, 6-18 years) followed for a mean of 16.2 years, including a mean of 5.1 years after baseline Feno data measurements. In multivariable analyses higher Feno levels were associated with ln(IgE) levels (P < .001) and the highest quartile of peripheral eosinophil counts (P = .03) but not wheezing symptoms, baseline spirometric indices, or response to bronchodilator. Multivariable analyses identified that the incident rate of ACS was associated with ln(Feno) levels (P = .03), as well as male sex (P = .025), wheezing causing shortness of breath (P = .002), and ACS at less than 4 years of age (P < .001). Feno levels were not associated with future pain episodes.
Steady-state Feno levels were not associated with an asthma diagnosis, wheezing symptoms, lung function measures, or prior sickle cell morbidity but were associated with markers of atopy and increased risk of future ACS events.
Improved guideline adherence with integrated sickle cell disease and asthma care
2016, American Journal of Preventive Medicine
In children with sickle cell disease (SCD), concomitant asthma is associated with increased morbidity and mortality when compared with children with SCD without asthma. Despite the well-established burden of asthma in children with SCD, no paradigm of care exists for the co-management of these two diseases.
To address this gap, an integrated SCD and asthma clinic was created in a community health center that included (1) a dual respiratory therapist/asthma case manager; (2) an SCD nurse practitioner with asthma educator certification; (3) an onsite pulmonary function test laboratory; (4) a pediatric hematologist with expertise in managing SCD and asthma; and (5) application of the National Asthma Education and Prevention Program guidelines. A before (2010–2012) and after (2013–2014) study design was used to assess for improved quality of care with implementation of an integrative care model among 61 children with SCD and asthma followed from 2010 to 2014.
Asthma action plan utilization after initial diagnosis increased with the integrative care model (n=16, 56% before, 100% after, p=0.003), as did the use of spirometry in children aged ≥5 years (n=41, 65% before, 95% after, p<0.001) and correction of lower airway obstruction (n=10, 30% before, 80% after, p=0.03).
Although the use of an integrative care model for SCD and asthma improved evidence-based asthma care, longer follow-up and evaluation will be needed to determine the impact on SCD-related morbidity.
Ischemia-reperfusion injury in sickle cell anemia: Relationship to acute chest syndrome, endothelial dysfunction, arterial vasculopathy, and inflammatory pain
2014, Hematology/Oncology Clinics of North America
Citation Excerpt :
So, it seems plausible that the adverse effects of smoke exposure on both vessel wall and airways would increase lung susceptibility to ALI/ACS as ROI from an inciting I/R event. Asthma association with ACS is particularly intriguing, because both are associated with increased levels of total and allergen-specific IgE.68 The sickle milieu includes other (allergen-independent) mast cell activators (superoxide, PAF), and one wonders if this total IgE includes hidden cytokinergic IgE.69
Acute pulmonary complications of sickle cell disease
2014, Paediatric Respiratory Reviews
Acute pulmonary problems in sickle cell disease (SCD) patients, in particular acute chest syndrome (ACS), cause significant mortality and morbidity. It is important to differentiate ACS from pneumonia to avoid inappropriate or inadequate treatment. Asthma may increase the risk of ACS and co-morbid asthma and SCD are associated with worse patient outcomes and, in preclinical models, more severe inflammation. Recurrent wheezing, however, can occur in the absence of a diagnosis of asthma; it is likely due to SCD related inflammation and additional therapies than those that treat asthma may be required. Further research is merited to clarify these issues.

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: Supported by the National Institute of Neurological Disorders and Stroke (U01 NS042804) and the National Heart, Lung, and Blood Institute (RO1-HL079937).

: Disclosure of potential conflict of interest: J. Casella receives research support from the National Institutes of Health. The rest of the authors have declared that they have no conflict of interest.

View full text

Asthma and lower airway diseaseElevation of IgE in children with sickle cell disease is associated with doctor diagnosis of asthma and increased morbidity

Background

Objective

Methods

Results

Conclusion

Section snippets

Patient population

Demographics

Discussion

J Pediatr Health Care

Blood

J Allergy Clin Immunol

J Allergy Clin Immunol

J Pediatr

Outcome of sickle cell anemia: a 4-decade observational study of 1056 patients

Medicine

Mortality in sickle cell disease: life expectancy and risk factors for early death

N Engl J Med

Causes and outcomes of the acute chest syndrome in sickle cell disease. National Acute Chest Syndrome Study Group

N Engl J Med

Methacholine challenge in children with sickle cell disease: a case series

Pediatr Pulmonol

Asthma and acute chest in sickle cell disease

Pediatr Pulmonol

Minor hemoglobinopathies: a risk factor for asthma

Eur Ann Allergy Clin Immunol

Asthma is a risk factor for acute chest syndrome and cerebral vascular accidents in children with sickle cell disease

Clin Mol Allergy

Asthma in children with sickle cell disease and its association with acute chest syndrome

Thorax

Asthma and lower airway disease
Elevation of IgE in children with sickle cell disease is associated with doctor diagnosis of asthma and increased morbidity