Wheezing Is Associated with Increased Rates of Acute Chest Syndrome and Pain Episodes In Adults with Sickle Cell Disease

Among children with sickle cell disease (SCD), a physician diagnosis of asthma has been associated with increased rates of acute chest syndrome (ACS), pain and mortality. Respiratory symptoms, including wheezing, occur in individuals with SCD independent of an asthma diagnosis. Few studies have evaluated the significance of asthma or respiratory symptoms in adults with SCD.

The primary objective of this study was to determine whether adults with SCD and a physician-diagnosis of asthma have more ACS and pain episodes compared to adults with SCD but without asthma. A secondary objective was to evaluate the relationship between asthma-like symptoms and ACS and pain among adults with SCD.

This was an observational cohort study of adults (≥ 19 years) with SCD who received care exclusively in the Washington University/Barnes Jewish Hospital system and completed baseline questionnaires including the ATS-DLD respiratory symptom survey. The questionnaires documented the frequency, severity and precipitants of symptoms such as wheezing, cough and shortness of breath. Enrollment into the study began August 2006. Hospitalizations for ACS and pain were determined from retrospective and prospective review of electronic medical records from January 1, 2004 to March 1, 2010 and analyzed using adjusted negative binomial regression models. Cox proportional hazards models were used to determine survival rates from date of consent through March 1, 2010. Spirometry was obtained from 69% of the study cohort.

Of 114 adults with SCD, those with a physician diagnosis of asthma (n=34) were more likely to have classic features of asthma including cough and wheeze, history of eczema, parental history of asthma, and an IgE level >150 kU/L (all p<0.05); however, there were no differences in rates of ACS or pain (table 1), lung function (table 2), or risk of death between adults with and without asthma. In contrast, those adults who reported recurrent episodes of severe wheezing (defined as ≥ 2 episodes of wheezing that progressed to shortness of breath) (n=34), with or without a diagnosis of asthma, had twice the rates of ACS and pain (table 1), significantly decreased lung function (table 2), and a trend towards increased risk of death (unadjusted HR 4.2, p=.046; adjusted HR 3.5, p=.09) compared to adults without a history of recurrent, severe wheezing. Notably, of 80 patients without a diagnosis of asthma, 30 reported multiple, persistent asthma-like symptoms at least monthly including nighttime cough/wheeze, daytime cough/wheeze even in the absence of exercise, and recurrent episodes of severe wheezing progressing to shortness of breath.

While a physician diagnosis of asthma was not associated with an increased risk of morbidity/mortality or decreased lung function in this cohort of adults with SCD, a history of recurrent, severe wheezing was associated with an increased rate of ACS, pain and decreased lung function. These findings may represent a misclassification of asthma diagnoses or SCD-associated wheezing, a clinical observation that is not well-defined. This study highlights the need for careful assessment of respiratory symptoms by physicians caring for adults with SCD.

Blinder:Novartis: Honoraria, Research Funding, Speakers Bureau. Field:Novartis: Honoraria.