INTRODUCTION
Sickle Cell Disease (SCD) affects about one in every 400
African-Americans in the United States1 with significant
complications including recurrent severe pain
episodes2 and acute
chest syndrome (ACS)3for
which each episode carries a 4% chance of death4. Pulmonary
complications are the cause of death in over 50% of autopsies in SCD
patients yet reliable and sensitive tests to detect early lung disease
are not available. An estimated 30-70% of children with SCD have
wheezing and airway hyper-reactivity (AHR) and air trapping5-11 and those with
asthma have higher rates of pain and ACS as well as premature death12-17. Ultimately,
patients with multiple episodes of ACS and wheezing develop Sickle Cell
Lung Disease (SCLD), which is a restrictive lung disorder18, often associated
with pulmonary hypertension.
Diagnosis of early lung disease in SCD is delayed as spirometry and
plethysmography, measures of obstructive or restrictive lung disease,
cannot often be reliably performed in children under the age of 5 years.
Additionally, spirometry is relatively insensitive in identifying and
assessing early lung disease in the smaller, more distal airways until
significant disease has developed19,20.
The multiple breath washout (MBW) technique, which measures the Lung
Clearance Index (LCI), is a novel noninvasive measurement of ventilation
inhomogeneity that is simple, involves no risk or hazardous exposures
and can be used in children, including preschoolers. LCI has been shown
to be a sensitive tool in detecting lung disease in cystic fibrosis and
asthma before any changes are apparent on spirometry21,22and has been demonstrated to be abnormal in patients with normal lung
function on spirometry23,24.
To date, MBW has not been studied in children with SCD. One study
explored the potential relationship between nitrogen single-breath
washout (N2SBW) and exercise intolerance in 38 adults with SCD (median
age of 28 years) 25.
Results suggested that phase III slope (SIIIN2) values correlated with
hemoglobin level, forced vital capacity (FVC), diffusing capacity and
SpO2 after exercise. Given this, assessing the ability of MBW to detect
potential ventilation inhomogeneity may prove beneficial and allow for
earlier intervention in patients where the disease may go unrecognized.
Since pulmonary complications such as ACS, wheezing and airway
hyper-reactivity (AHR) often start early in
SCD11,26we hypothesized that children with SCD (with or without asthma) would
have an abnormal and elevated LCI compared to healthy controls. Findings
of abnormal LCI in children with SCD during which time spirometry may be
normal would be useful in initiating early intervention and more
in-depth diagnostic screening.