Original Article
Lower Airway Nitric Oxide is Increased in Children with Sickle Cell Disease

https://doi.org/10.1016/j.jpeds.2011.06.048Get rights and content

Objectives

To determine alveolar and airways nitric oxide (NO) levels in children with sickle cell disease (SCD).

Study design

Multiple flows fractional exhaled NO (FENO), bronchial NO flux (J’awNO), and alveolar NO concentration (CaNO) were determined prospectively in 16 non-atopic children with SCD in a tertiary ambulatory clinic and compared with those in 10 children with primary ciliary dyskinesia and 22 healthy control subjects. Differences in FENO, J’awNO, and CaNO were compared with mixed model analysis and Mann-Whitney tests.

Results

Children with SCD had reference range FENO at 50 mL/sec, but FENO was elevated across all flows compared with healthy control subjects (mean difference = 2.10 ± 0.91 parts per billion, P = .03). Subjects with SCD had increased J’awNO (1177 ± 533 picoliters per second versus 833 ± 343 picolitres per second, P = .03), and CaNO was no different from control subjects. In contrast, children with primary ciliary dyskinesia had decreased FENO (mean difference = 3.36 ± 1.24 parts per billion, P < .01) and J’awNO (507 ± 259 picoliters per second versus 833 ± 343 picoliters per second, P < .01).

Conclusions

Lower airways NO is increased in children with SCD. Elevation of J’awNO may represent dysregulation of NO metabolism or subclinical airways inflammation.

Section snippets

Methods

Ethics approval for this study was obtained from the Hospital for Sick Children institutional research ethics board. A convenience sample of patients with either SCD or PCD were consecutively recruited during routine ambulatory clinic visits at the Hospital for Sick Children, Toronto, Ontario, Canada. Children with SCD included those with hemoglobin “sickle” “sickle” (HbSS), hemoglobin “sickle”/beta thalassemia (HbSβthal), or hemoglobin “sickle”/Caribbean (HbSC) on hemoglobin electrophoresis.

Results

Forty-eight subjects were included in the study; 16 with SCD, 10 with PCD, and 22 healthy control subjects (Table). All children with SCD, but none of the patients with PCD, were of African descent. The healthy control group included 15 Caucasian subjects, 5 subjects of African descent, and two subjects of Southeast Asian ethnicity. There was no difference in FENO, J’awNO, and CaNO between the 5 subjects of African descent and the remaining healthy control subjects. In the subjects with SCD, 13

Discussion

We assessed NO in subjects with SCD by using multiple exhalation flows and comprehensive methods to measure flow-dependent and -independent airway NO parameters. This study showed that when using standard techniques (exhalation flow of 50 mL/sec), FENO in children with SCD without atopy or asthma was well within published reference ranges.33, 34 However, with multiple flow analyses, FENO was revealed to be significantly higher in patients with SCD compared with healthy control subjects.

There

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  • Cited by (16)

    • Lower Airway Nitrogen Oxide Levels in Children with Primary Ciliary Dyskinesia Is Linked to Neutrophilic Inflammation

      2022, Journal of Pediatrics
      Citation Excerpt :

      This may be related to the severity of the PEx events and/or the intensity of the therapeutic intervention. Other investigators have shown that nasal and exhaled NO are decreased in PCD,8,9 but NO deficiency could not be explained by the absence of NOS in airway epithelium or cilia.10,11 However, one study suggested absent or delayed expression of inducible NOS (NOS2) in airway epithelium during early infection in PCD.12

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

      2016, Journal of Allergy and Clinical Immunology
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      This study has a number of strengths, including ascertainment of Feno levels by using standardized ATS criteria, use of objective measurements of lung function with centralized standardized overreading of lung function, and prospective ascertainment of SCA-specific morbidity. Although this is the largest study to date of Feno in patients with SCA, a limitation is measuring Feno levels at one flow rate.17,40 SAC chose to measure Feno levels according to current ATS guidelines because this is the method widely available to clinicians rather than using methods available only as part of a research protocol.

    • Airway Inflammation and Lung Function in Sickle Cell Disease

      2019, Pediatric, Allergy, Immunology, and Pulmonology
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    Funded by the Hospital for Sick Children pediatric consultants. The authors declare no conflicts of interest.

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