Transcript Scientific Power Point Poster for ARPKD

Screening for Respiratory Ciliary Dysfunction in Autosomal Recessive Polycystic Kidney Disease
Root H1, Gunay-Aygun M2, Holland SM1, Olivier KN1
1Laboratory
of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases and 2Medical Genetics Branch, National Human Genome Research Institute, Bethesda, MD
Background
Results
*p<0.0008
33
108.8
2
6
115.3
3
12
132.3
4
5
136.2
5
6
136.2
6
9
138.8
7
4
151.6
8
4
155.8
9
14
165.7
10 15
172.2
11 29
174.1
12 18
178.1
13
5
179.9
14 13
180.7
15
182.1
6
16 13
198
17 28
199.7
18 28
200.1
19
9
215.6
20
8
222.4
21 18
243.6
22 11
249.6
23 10
261
24 10
267.7
25 10
290.5
26 50
329.3
27 33
353
28
373
7
Pneumothorax at History of Lower Respiratory
Epistaxis Otitis Media
Birth
Asthma
Infections
PET* (1)
X
premature birth
X
400
• Six ARPKD patients (21%) had a history of recurring
respiratory tract infections including 3 out of 4 with otitis media
requiring myringotomy tubes (nNO: 115, 132, 182 nL/min).
200
PET* (3)
X
• Air trapping on lung volume measurements was noted in 8
(n=22, 36%) and abnormal diffusion was noted in 16 (n=21,
76%) patients.
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K
P
R
A
D
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A
NI
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o
C
ls
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tr
C
N
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• Three patients had available high resolution chest CT
scans; no evidence of bronchiectasis was seen.
X
Figure 1. Nasal Nitric Oxide Levels in ARPKD patients and
2 sets of controls: healthy volunteers from NIAID (age 32±2
years) and from UNC (age 14±1).
X
X
X
X
premature birth
X
PET* (2)
X
X
premature birth
premature birth
*PET = Pressure Equalization Tubes
X
X
X
Conclusions
• None of the ARPKD patients had nNO levels in the range
seen with PCD (<100 nL/min).
X
• However, the values were significantly lower than both
older, same-site controls and age appropriate controls from
UNC with lower levels in those with more respiratory
problems.
150
100
• Respiratory infections and respiratory tract abnormalities in
ARPKD indicate further investigation of respiratory ciliary
dysfunction is warranted.
50
References
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O
1
nNo Values
(nL/min)
nNO (nL/min)
# Age
Neonatal
Respiratory
Distress
1. Harris PC, Torres VE. Polycistic Kidney Disease. Annu. Rev. Med. 2009.
60:321-37.
LC
Records of patients enrolled in a natural history study of
ARPKD/CHF at the NIH were reviewed for a history of
respiratory symptoms for a history of respiratory symptoms
and/or respiratory tract infections, prior pulmonary function test
results, and chest imaging. Sampling of nNO was performed
through a foam nasal probe during exhalation through a resistor
and was measured in real-time via a NiOx (Aerocrine)
chemiluminescense analyzer. Values from ARPKD patients
were compared to the nNO measurements from healthy
volunteers.
Table 1. Respiratory Symptoms of ARPKD Patients
D
Methods
• The average age and nNO of the ARPKD patients (n=28)
were 15±(SEM)2 years and 204±13 nL/min respectively
compared to 32±2 years (p<0.0001) and 289±16 nL/min
(p<0.0001) in the NIAID controls (n=25) and 14±1 years
(p>0.7) and 272±11 nL/min (p<.0008) in the UNC controls
(n=79).
TL
C
To screen for respiratory ciliary dysfunction in ARPKD by
assessing nNO production and to look for evidence of respiratory
tract abnormalities in ARPKD patients.
Summary
*p<0.0001
FE
V1
Objectives
600
% Predicted
Autosomal recessive polycystic kidney disease (ARPKD) is a
rare sensory ciliopathy characterized by enlarged kidneys due
to renal cysts and associated congenital hepatic fibrosis
(CHF).1 Recent data have suggested a possible connection
between sensory ciliopathies and respiratory ciliary
dysmotility. Bronchiectasis was seen on chest CT scans in
37% of autosomal dominant polycystic kidney disease
patients vs. 12% of control chronic kidney disease patients
suggesting possible respiratory ciliary abnormalities.2 In vivo
measurement of nasal nitric oxide (nNO) production has been
used as an easily performed, sensitive screen for primary
ciliary dyskinesia (PCD).
X
Figure 2. Lung Function Tests results of ARPKD patients. These
are the % predicted values of Forced Expiratory Volume in 1
second (FEV1), Total Lung Capacity (TLC) and Diffusing Capacity
of the Lung for Carbon Monoxide (DLCO).
2. Driscoll JA, Bhalla S, Liapis H, Ibricevic A, Brody SL. Autosomal Dominant
Polycistic Kidney Disease is Associated with an Increased Prevalence of
Radiographic Bronchiectasis. 2008. Chest. 133:1181-1188.
Supported in part by intramural funds of the NIAID and NHGRI and by the Genetic Diseases of
Mucociliary Clearance Consortium, NIH 9 U54 HL096458-06 funded by Office of the Director, and
supported by ORDR and NHLBI, NIH.