US EPA

2265382 

Journal Article 

Abstract 

Nasal nitric oxide & ciliary function in patients with non-heterotaxy congenital heart disease 

Kureshi, S; Nakhleh, N; Setton, M; Giese, R; Francis, R; Chatterjee, B; Sami, I; Kuehl, K; Olivier, KN; Jonas, R; Tian, X; Leigh, MW; Knowles, MR; Leatherbury, L; Lo, C 

2010 

Yes 

American Journal of Respiratory and Critical Care Medicine
ISSN: 1073-449X
EISSN: 1535-4970 

181 

A3323 

English 

10.1164/ajrccm-conference.2010.181.1_MeetingAbstracts.A3323 

WOS:000208771002434 

is part of a larger document 3452678 Proceedings of the American Thoracic Society 2010 International Conference, May 14-19, 2010, New Orleans

RATIONALE: Heterotaxy is a rare disorder characterized by discordant abdominal/thoracic organ situs due to aberrant left-right patterning, a developmental process dependent on motile cilia in the embryonic node. Ciliary dysfunction is implicated in complex congenital heart disease (CHD) associated with heterotaxy. We previously found 40% incidence of CHD associated with heterotaxy in a murine model of primary ciliary dyskinesia (PCD). In a study of 45 patients with CHD associated with heterotaxy, we observed 42% incidence of ciliary dysfunction defined by nasal nitric oxide (nNO) level that is low (<100 nl/min for ≥6 years or <50 nl/min for 1-6 years) or borderline low (< 2 standard deviations below the mean) and abnormal ciliary motion as observed by videomicroscopy. We refer to this as vCD (variant ciliary dysfunction). Significantly, patients with vCD have more chronic respiratory symptoms, suggesting the possibility that diminished mucociliary clearance may contribute to increased respiratory complications and higher postsurgical morbidity of heterotaxy patients.

METHODS AND RESULTS: To examine whether vCD may have broader relevance to CHD, we expanded our study to include CHD patients without heterotaxy. As in our previous study, nNO was measured utilizing a chemiluminescence nNO analyzer, and we also performed nasal biopsy and conducted ciliary motion analysis of the respiratory epithelia using high-speed videomicroscopy. Of 5 non-heterotaxy CHD patients examined ranging from 2 months to 19 years old, one 17-year old male with double chambered right ventricle and ventricular septal defect exhibited vCD. His nNO was 142 nl/min and his nasal biopsy showed asynchronous ciliary motion with incomplete stroke. With the ready availability of CHD patients, we expect to recruit many more CHD patients in the coming months to assess the prevalence of vCD in CHD patients without heterotaxy.

CONCLUSION: Ciliary dysfunction was previously shown to be closely linked to CHD associated with heterotaxy. Preliminary findings suggest ciliary dysfunction may also have a role to play in CHD without heterotaxy, a possibility we will further evaluate in our ongoing studies. 

American Thoracic Society 2010 International Conference 

New Orleans, LA 

May 14-19, 2010