563A irway hyperresponsiveness (AHR) is believed to refl ect infl ammation in the airways that is relatively specifi c for asthma. 1 The diagnostic evaluation for asthma includes measures of AHR, most commonly using methacholine provocation. In children with sickle cell disease (SCD), AHR is present in up to 78% of those tested, 2,3 whereas the prevalence of asthma in children with SCD is 20% to 48%. [4][5][6] Given that AHR is more prevalent than asthma in children with SCD, mechanisms other than asthmarelated infl ammation may be causing this high rate of AHR. Among children with HbSS or sickle cell anemia (SCA), a doctor diagnosis of asthma has been associated with an increased rate of pain, acute chest syndrome, and death. 4,5,7,8 Although these data imply that asthma has a signifi cant disease-modifying effect in children with SCA, characteristics of SCA, such as episodes of acute chest syndrome, 9 pulmonary function abnormalities, 10-12 and chronic respiratory symptoms, add complexity to the diagnosis of asthma. Thus, it is not clear if descriptions of asthma in these children refl ect the presence of two distinct comorbid conditions or an asthma-like phenotype secondary Background: The high prevalence of airway hyperresponsiveness (AHR) among children with sickle cell anemia (SCA) remains unexplained. Methods: To determine the relationship between AHR, features of asthma, and clinical characteristics of SCA, we conducted a multicenter, prospective cohort study of children with SCA. Dose response slope (DRS) was calculated to describe methacholine responsiveness, because 30% of participants did not achieve a 20% decrease in FEV 1 after inhalation of the highest methacholine concentration, 25 mg/mL. Multiple linear regression analysis was done to identify independent predictors of DRS. Results: Methacholine challenge was performed in 99 children with SCA aged 5.6 to 19.9 years (median, 12.8 years). Fifty-four (55%) children had a provocative concentration of methacholine producing a 20% decrease in FEV 1 , 4 mg/mL. In a multivariate analysis, independent associations were found between increased methacholine responsiveness and age ( P , .001), IgE ( P 5 .009), and lactate dehydrogenase (LDH) levels ( P 5 .005). There was no association between methacholine responsiveness and a parent report of a doctor diagnosis of asthma ( P 5 .986). Other characteristics of asthma were not associated with methacholine responsiveness, including positive skin tests to aeroallergens, exhaled nitric oxide, peripheral blood eosinophil count, and pulmonary function measures indicating airfl ow obstruction.

Dyspnea on exertion is prevalent in otherwise healthy obese women, which seems to be strongly associated with an increased oxygen cost of breathing. Exercise capacity is not reduced in obese women with dyspnea on exertion.

We tested the hypothesis that the exercise ventilatory response (EVR) differed between otherwise healthy obese women with and without dyspnea on exertion (DOE). In fourteen obese women we determined EVR (defined as slope of VE vs. VCO2) during cycling at 30W and 60W, O2 cost of breathing (from measurements of VO2 and VE at rest and during eucapnic voluntary hyperpnea at 40 and 60 L/min; slope was calculated in ml/L) and O2 uptake of the respiratory muscles (VO2RESP) at 30W and 60W (calculated from O2 cost multiplied by VE at each exercise level). Subjects were grouped according to RPB (Borg 0–10) during cycling at 60W (Control, n = 7, RPB ≤ 2; DOE, n = 7, RPB ≥ 4). Age, ht, wt and % body fat were similar between groups. RPB and O2 cost of breathing were significantly higher in DOE than Control (p<0.05). The EVR at 30W and 60W was similar between groups. VO2RESP was significantly higher in DOE than Control at 30W and 60W (30W 66±19 and 37±6, 60W 115±44 and 63±12 ml/min, respectively; p<0.02). There were significant correlations between RPB at 60W and VO2RESP at 30W and 60W (30W r = 0.91, 60W r = 0.88; p<0.01). The EVR did not differ between groups, and hence did not appear to account for the DOE. However, VO2RESP during exercise was significantly higher in obese women with DOE, suggesting that VO2RESP may play an important role in DOE. Support: American Heart Association, The King Foundation, The Cain Foundation, Presbyterian Hospital of Dallas