Airway and alveolar nitric oxide production, lung function, and pulmonary blood flow in sickle cell disease

Abstract

Background: Children with sickle cell disease (SCD) often have obstructive lung function abnormalities which could be due to asthma or increased pulmonary blood volume; it is important to determine the underlying mechanism to direct appropriate treatment. In asthmatics, exhaled nitric oxide (F eNO ) is elevated. F eNO , however, can also be raised due to increased alveolar production. Our aim, therefore, was to determine if airway or alveolar NO production differed between SCD children and ethnic and age-matched controls. Methods: Lung function, airway NO flux and alveolar NO production, and effective pulmonary blood flow were assessed in 18 SCD children and 18 ethnic and age-matched controls. results: The SCD children compared to the controls had a higher respiratory system resistance (P = 0.0008), alveolar NO production (P = 0.0224), and pulmonary blood flow (P < 0.0001), but not airway NO flux. There was no significant correlation between F eNO and respiratory system resistance in either group, but in the SCD children, there were correlations between alveolar NO production (P = 0.0006) and concentration (P < 0.0001) and pulmonary blood flow. conclusion: Airway NO flux was not elevated in the SCD children nor correlated with airways obstruction, suggesting that airways obstruction, at least in some SCD children, is not due to asthma.

Exhaled nitric oxide: Not associated with asthma, symptoms, or spirometry in children with sickle cell anemia

“…Furthermore, FeNO measured at 50ml/sec was positively correlated with pulmonary blood flow but was not correlated with measures of airway obstruction or resistance, suggesting that some component of the FeNO of a SCD patient is due to increased alveolar NO production resulting from chronic anemia rather than airway inflammation from asthma. 40 In contrast, utilizing flow-independent methods, Radhakrishnan et al were able to determine that elevated FeNO levels among non-atopic children with SCD were higher compared to healthy controls, but their results showed that increase in FeNO originated in the bronchial tree and not from alveolar sources. 17 Further studies of FeNO in larger cohorts of SCD patients of varying ages and disease severity, with and without atopy, may clarify the relative contribution of airway and alveolar FeNO and possible associations with other markers of disease severity, such as endothelial dysfunction and markers of pulmonary hypertension.…”

“…19,39 Pawar et al noted that FeNO levels among patients during an acute VOC pain episode were no different than among those at steady state. 19 A recent study of FeNO measured at variable flow rates 40 found elevated alveolar NO concentration and production among SCD patients compared to healthy race-matched controls. They also found significant positive correlations between alveolar NO and pulmonary blood flow in the SCD group, suggesting that alveolar NO production is related to the chronic hyperdynamic circulation found in patients with SCD.…”

Pulmonary Complications and Lung Function Abnormalities in Children with Sickle Cell Disease

“…Furthermore, in a study of 18 SCD children compared to 18 ethnic and age-matched controls, the SCD children had a significantly higher respiratory system resistance, alveolar NO production and pulmonary blood flow, but not airway NO flux. There was a significant correlation between alveolar NO production and pulmonary blood flow, but not between airway NO flux and respiratory system resistance [66]. SCD patients have an increased pulmonary capillary blood volume resulting from their chronic anaemia.…”

Asthma and the outcome of sickle cell disease

“…Exhaled nitric oxide, a marker of asthma and steroid response, is reduced in SCD patients [72]. Comparison of SCD children with age-and ethnicity-matched controls demonstrated the former did not have elevated airway nitric oxide flux nor did the levels correlate with airways obstruction [73].…”