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Source of Exhaled Nitric Oxide in Primary Biliary Cirrhosis^*

^* From the Allergologia e Immunologia Clinica (Dr. Rolla), Ospedale Mauriziano, the Divisions of Internal Medicine and Respiratory Physiology (Drs. Brussino, Scappaticci, and Bucca), and Cardiology (Dr. Morello), Molinette Hospital, University of Torino, and the Division of Gastroenterology (Drs. Innarella and Rosina), Gradenigo Hospital, Torino, Italy.

Correspondence to: Giovanni Rolla, MD, FCCP, Allergologia e Immunologia Clinica, Ospedale Mauriziano Umberto I, Largo Turati 62, 10126 Torino, Italy; e-mail: grolla{at}mauriziano.it

Background: Exhaled nitric oxide (NO) levels may be elevated in patients with liver cirrhosis and autoimmune diseases. Primary biliary cirrhosis (PBC) is often associated with keratoconjunctivitis sicca (Sjögren syndrome [SS]), an extrahepatic autoimmune manifestation. The aim of this study was to evaluate the source of increased exhaled NO (ie, alveolar vs airway) in patients with PBC, whether associated with SS or not, and to evaluate its impact on oxygenation abnormalities.

Design: Observational controlled study.

Setting: University hospital.

Methods: The fractional alveolar NO concentration (FANO) and airway flux of NO (QbrNO) were measured by the multiple flows technique in 34 patients with PBC, 12 with associated SS, and were compared to 20 control subjects and 12 patients with primary SS.

Results: FANO was significantly higher in patients with PBC, associated with SS (mean [± SEM], 8.9 ± 0.8 parts per billion [ppb]) or not (mean, 7.7 ± 0.7 ppb) compared to healthy control subjects (mean, 4.6 ± 0.5 ppb; p < 0.001) and to patients with primary SS (mean, 4.3 ± 0.5 ppb; p < 0.001). FANO was significantly higher in cirrhotic patients with increased alveolar-arterial oxygen pressure difference (P[A-a]O₂) compared to patients with normal P(A-a)O₂ values (9.8 ± 0.8 vs 7.3 ± 0.7, respectively; p = 0.018). When compared with control subjects and with patients with PBC not associated with SS, QbrNO was significantly increased in patients with both primary SS and SS associated with PBC.

Conclusions: Increased exhaled NO levels found in PBC are from both alveolar and airway sources in patients with associated SS, but only FANO is associated with oxygenation impairment.

Key Words: exhaled nitric oxide • hepatopulmonary syndrome • liver cirrhosis • Sjögren syndrome

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