High-dose acetylcysteine in idiopathic pulmonary fibrosis.
BACKGROUND
Idiopathic pulmonary fibrosis is a chronic progressive disorder with a poor prognosis.


METHODS
We conducted a double-blind, randomized, placebo-controlled multicenter study that assessed the effectiveness over one year of a high oral dose of acetylcysteine (600 mg three times daily) added to standard therapy with prednisone plus azathioprine. The primary end points were changes between baseline and month 12 in vital capacity and in single-breath carbon monoxide diffusing capacity (DL(CO)).


RESULTS
A total of 182 patients were randomly assigned to treatment (92 to acetylcysteine and 90 to placebo). Of these patients, 155 (80 assigned to acetylcysteine and 75 to placebo) had usual interstitial pneumonia, as confirmed by high-resolution computed tomography and histologic findings reviewed by expert committees, and did not withdraw consent before the start of treatment. Fifty-seven of the 80 patients taking acetylcysteine (71 percent) and 51 of the 75 patients taking placebo (68 percent) completed one year of treatment. Acetylcysteine slowed the deterioration of vital capacity and DL(CO): at 12 months, the absolute differences in the change from baseline between patients taking acetylcysteine and those taking placebo were 0.18 liter (95 percent confidence interval, 0.03 to 0.32), or a relative difference of 9 percent, for vital capacity (P=0.02), and 0.75 mmol per minute per kilopascal (95 percent confidence interval, 0.27 to 1.23), or 24 percent, for DL(CO) (P=0.003). Mortality during the study was 9 percent among patients taking acetylcysteine and 11 percent among those taking placebo (P=0.69). There were no significant differences in the type or severity of adverse events between patients taking acetylcysteine and those taking placebo, except for a significantly lower rate of myelotoxic effects in the group taking acetylcysteine (P=0.03).


CONCLUSIONS
Therapy with acetylcysteine at a dose of 600 mg three times daily, added to prednisone and azathioprine, preserves vital capacity and DL(CO) in patients with idiopathic pulmonary fibrosis better than does standard therapy alone.
Demedts
Maurits
M
University Hospital, Katholieke Universiteit Leuven, Leuven, Belgium. maurits.demedts@uz.kuleuven.ac.be
Behr
Juergen
J
Buhl
Roland
R
Costabel
Ulrich
U
Dekhuijzen
Richard
R
Jansen
Henk M
HM
MacNee
William
W
Thomeer
Michiel
M
Wallaert
Benoit
B
Laurent
François
F
Nicholson
Andrew G
AG
Verbeken
Eric K
EK
Verschakelen
Johny
J
Flower
Christopher D R
CD
Capron
Frédérique
F
Petruzzelli
Stefano
S
De Vuyst
Paul
P
van den Bosch
Jules M M
JM
Rodriguez-Becerra
Eulogio
E
Corvasce
Giuseppina
G
Lankhorst
Ida
I
Sardina
Marco
M
Montanari
Mauro
M
D000111:Acetylcysteine / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000975:Antioxidants / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D001379:Azathioprine / Q000627:therapeutic use; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D017079:Exercise Tolerance / Q000187:drug effects; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000627:therapeutic use; D011653:Pulmonary Diffusing Capacity / Q000187:drug effects; D011658:Pulmonary Fibrosis / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D014797:Vital Capacity / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D007166:Immunosuppressive Agents; D001379:Azathioprine; D011241:Prednisone; D000111:Acetylcysteine