TY - JOUR
T1 - Laterality defects other than situs inversus totalis in primary ciliary dyskinesia
T2 - Insights into situs ambiguus and heterotaxy
AU - Shapiro, Adam J.
AU - Davis, Stephanie D.
AU - Ferkol, Thomas
AU - Dell, Sharon D.
AU - Rosenfeld, Margaret
AU - Olivier, Kenneth N.
AU - Sagel, Scott D.
AU - Milla, Carlos
AU - Zariwala, Maimoona A.
AU - Wolf, Whitney
AU - Carson, Johnny L.
AU - Hazucha, Milan J.
AU - Burns, Kimberlie
AU - Robinson, Blair
AU - Knowles, Michael R.
AU - Leigh, Margaret W.
N1 - Funding Information:
FUNDING/SUPPORT: Funding for this research was provided to Drs Shapiro, Davis, Ferkol, Dell, Rosenfeld, Olivier, Sagel, Milla, Zariwala, Carson, Hazucha, Knowles, and Leigh and Mss Wolf and Burns by National Institutes of Health (NIH), Office of Rare Diseases Research, National Heart, Lung, and Blood Institute (NHLBI) [Grant 5US54HL096458-06] and to Drs Zariwala and Knowles by NIH, NHLBI [Grant 5R01HL071798] and NIH, National Center for Advancing Translational Science (NCATS) [Grant UL1TR000083]. Funding for Dr Rosenfeld was provided by NIH/NCATS [Grant UL1TR000423]. Funding for Dr Olivier was provided by the Intramural Research Program of the NIH, National Institute of Allergy and Infectious Diseases. Funding for Dr Sagel was by NIH/NCATS Colorado Clinical and Translational Sciences Institute [Grant UL1TR000154]. The Genetic Disorders of Mucociliary Clearance Consortium [U54HL096458] is a part of the NIH Rare Diseases Clinical Research Network supported through collaboration between the NIH Office of Rare Diseases Research at the NCATS and the National Heart, Lung, and Blood Institute.
Publisher Copyright:
© 2014 American College of Chest Physicians.
PY - 2014/11/1
Y1 - 2014/11/1
N2 - BACKGROUND: Motile cilia dysfunction causes primary ciliary dyskinesia (PCD), situs inversus totalis (SI), and a spectrum of laterality defects, yet the prevalence of laterality defects other than SI in PCD has not been prospectively studied. METHODS: In this prospective study, participants with suspected PCD were referred to our multisite consortium. We measured nasal nitric oxide (nNO) level, examined cilia with electron microscopy, and analyzed PCD-causing gene mutations. Situs was classifi ed as (1) situs solitus (SS), (2) SI, or (3) situs ambiguus (SA), including heterotaxy. Participants with hallmark electron microscopic defects, biallelic gene mutations, or both were considered to have classic PCD. RESULTS: Of 767 participants (median age, 8.1 years, range, 0.1-58 years), classic PCD was defi ned in 305, including 143 (46.9%), 125 (41.0%), and 37 (12.1%) with SS, SI, and SA, respectively. A spectrum of laterality defects was identified with classic PCD, including 2.6% and 2.3% with SA plus complex or simple cardiac defects, respectively; 4.6% with SA but no cardiac defect; and 2.6% with an isolated possible laterality defect. Participants with SA and classic PCD had a higher prevalence of PCD-associated respiratory symptoms vs SA control participants (year-round wet cough, P<.001; year-round nasal congestion, P=.015; neonatal respiratory distress, P=.009; digital clubbing, P=.021) and lower nNO levels (median, 12 nL/min vs 252 nL/min; P<.001). CONCLUSIONS: At least 12.1% of patients with classic PCD have SA and laterality defects ranging from classic heterotaxy to subtle laterality defects. Specifi c clinical features of PCD and low nNO levels help to identify PCD in patients with laterality defects.
AB - BACKGROUND: Motile cilia dysfunction causes primary ciliary dyskinesia (PCD), situs inversus totalis (SI), and a spectrum of laterality defects, yet the prevalence of laterality defects other than SI in PCD has not been prospectively studied. METHODS: In this prospective study, participants with suspected PCD were referred to our multisite consortium. We measured nasal nitric oxide (nNO) level, examined cilia with electron microscopy, and analyzed PCD-causing gene mutations. Situs was classifi ed as (1) situs solitus (SS), (2) SI, or (3) situs ambiguus (SA), including heterotaxy. Participants with hallmark electron microscopic defects, biallelic gene mutations, or both were considered to have classic PCD. RESULTS: Of 767 participants (median age, 8.1 years, range, 0.1-58 years), classic PCD was defi ned in 305, including 143 (46.9%), 125 (41.0%), and 37 (12.1%) with SS, SI, and SA, respectively. A spectrum of laterality defects was identified with classic PCD, including 2.6% and 2.3% with SA plus complex or simple cardiac defects, respectively; 4.6% with SA but no cardiac defect; and 2.6% with an isolated possible laterality defect. Participants with SA and classic PCD had a higher prevalence of PCD-associated respiratory symptoms vs SA control participants (year-round wet cough, P<.001; year-round nasal congestion, P=.015; neonatal respiratory distress, P=.009; digital clubbing, P=.021) and lower nNO levels (median, 12 nL/min vs 252 nL/min; P<.001). CONCLUSIONS: At least 12.1% of patients with classic PCD have SA and laterality defects ranging from classic heterotaxy to subtle laterality defects. Specifi c clinical features of PCD and low nNO levels help to identify PCD in patients with laterality defects.
UR - http://www.scopus.com/inward/record.url?scp=84910018969&partnerID=8YFLogxK
U2 - 10.1378/chest.13-1704
DO - 10.1378/chest.13-1704
M3 - Article
C2 - 24577564
AN - SCOPUS:84910018969
VL - 146
SP - 1176
EP - 1186
JO - Chest
JF - Chest
SN - 0012-3692
IS - 5
ER -