Wheezing in children with sickle cell disease

Abstract

Purpose of review: The purpose of this article is to provide a comprehensive review of wheezing in sickle cell disease (SCD), including epidemiology, pathophysiology, associations between wheezing and SCD morbidity and finally the clinical approach to evaluation and management of individuals with SCD who wheeze.

Recent findings: Wheezing is common in SCD and in some individuals represents an intrinsic component of SCD-related lung disease rather than asthma. Emerging data suggest that, regardless of the cause, individuals with SCD and with recurrent wheezing are at increased risk for subsequent morbidity and premature mortality. We believe individuals who acutely wheeze and have respiratory symptoms should be managed with a beta agonist and short-term treatment of oral steroids, typically less than 3 days to attenuate rebound vaso-occlusive disease. For those who wheeze and have a history or examination associated with atopy, we consider asthma treatment and monitoring per National Heart, Lung and Blood Institute asthma guidelines.

Summary: Wheezing in SCD should be treated aggressively both in the acute setting and with controller medications. Prospective SCD-specific clinical trials will be necessary to address whether anti-inflammatory asthma therapies (leukotriene antagonists, inhaled corticosteroids) can safely mitigate the sequelae of wheezing in SCD.

Figure 1

Conceptual model to explain the association between wheezing and SCD mortality. Wheezing is common in SCD and in some individuals represents an intrinsic component of SCD related lung disease rather than asthma. Both etiologies of wheeze likely create ventilation-perfusion mismatch which increases regional hypoxia, red cell sickling, membrane damage and inflammation leading to increased systemic complications of SCD.

Figure 2

Sample questions which may assist in the identification of clinically important respiratory symptoms in individuals with SCD. A yes to any one question indicates that clinically significant respiratory symptoms are present and that further evaluation and treatment are indicated. Adapted from the National Asthma Education and Prevention Program (NAEPP) 2007 guidelines (http://www.nhlbi.nih.gov/guidelines/asthma/).

Figure 3

NAEPP schema for classification of asthma severity. We recommend using the NAEPP schema to classify the severity of symptoms in individuals with SCD who report wheezing cough or shortness of breath regardless of whether or not the patient carries a diagnosis of asthma. The severity of symptoms then dictates the level of treatment which is described in figure 4. Adapted from the National Asthma Education and Prevention Program (NAEPP) 2007 guidelines (http://www.nhlbi.nih.gov/guidelines/asthma/).

Figure 4

NAEPP stepwise management schema. The level of therapy is dictated by the severity of the patient’s symptoms as classified in figure 3. Any patient who requires step 3 or higher should be referred to an asthma specialist. Adapted from the National Asthma Education and Prevention Program (NAEPP) 2007 guidelines (http://www.nhlbi.nih.gov/guidelines/asthma/).