SummaryBackground. Increased oxidative stress and inflammation has a role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Drugs with antioxidant and anti-inflammatory properties, such as N-acetylcysteine, might provide a useful therapeutic approach for COPD. We aimed to assess whether N-acetylcysteine could reduce the rate of exacerbations in patients with COPD. Methods. In our prospective, randomised, double-blind, placebo-controlled, parallel-group study, we enrolled patients aged 40-80 years with moderate-to-severe COPD (post-bronchodilator forced expiratory volume in 1 s (FEV1) / forcedvital capacity < 0.7 and FEV1 of 30-70 % of predicted) at 34 hospitals in China. We stratified patients according to use of inhaled corticosteroids (regular use or not) at baseline and randomly allocated them to receive N-acetylcysteine (one 600 mg tablet, twice daily) or matched placebo for 1 year. The primary endpoint was the annual exacerbation rate in patients who received at least one dose of study drug and had at least one assessment visit after randomisation. This study is registered with the Chinese Clinical Trials Registry, ChiCTR-TRC-09000460. Findings. Between June 25, 2009, and Dec 29, 2010, we screened 1 297 patients, of whom 1 006 were eligible for randomisation (504 to N-acetylcysteine and 502 to placebo). After 1 year, we noted 497 acute exacerbations in 482 patients in the N-acetylcysteine group who received at least one dose and had at least one assessment visit (1.16 exacerbations per patient-year) and 641 acute exacerbations in 482 patients in the placebo group (1.49 exacerbations per patient-year; risk ratio 0.78, 95% CI 0.67-0.90; p = 0.0011). N-acetylcysteine was well tolerated: 146 (29 %) of 495 patients who received at least one dose of N-acetylcysteine had adverse events (48 serious), as did 130 (26 %) of 495 patients who received at least one dose of placebo (46 serious). The most common serious adverse event was acute exacerbation of COPD, occurring in 32 (6 %) of 495 patients in the N-acetylcysteine group and 36 (7 %) of 495 patients in the placebo group. Interpretation. Our findings show that in Chinese patients with moderate-to-severe COPD, long-term use of N-acetylcysteine 600 mg twice daily can prevent exacerbations, especially in disease of moderate severity. Future studies are needed to explore efficacy in patients with mild COPD (GOLD I). Key words: chronic obstructive pulmonary disease, acute exacerbation, antioxidant therapy, N-acetylcysteine, high dose. РезюмеУсиление воспалительных и окислительных процессов играет важную роль в патогенезе хронической обструктивной болезни легких (ХОБЛ). При этом заболевании может быть эффективно применение лекарств с противовоспалительной и антиоксидантной актив-

INTRODUCTION Cigarette smoking is the most important risk factor for Crohn's disease (CD). The effectiveness of smoking cessation programs (SCPs) in patients with CD is still poorly understood. METHODS This was a retrospective, observational, single-centre, cohort study of 136 active smokers with mean age 55 years (SD=11), 58% males, including 27 (19.8%) patients with CD who entered the multidisciplinary SCP of the Luigi Sacco University Hospital of Milan from January 2017 through January 2019. A pulmonologist was responsible for the clinical and pharmacological management, while a psychiatrist and a psychologist conducted the counselling and assessed the motivation to quit, anxiety and depression using the Brief Psychiatric Rating Scale (BPRS) and the nicotine dependence with the Fagerström test. Patients were defined as quitters after 12 months. RESULTS Demographic and clinical characteristics, and Fagerström score, did not differ in patients with and without CD. At baseline, patients with CD had a higher BPRS (median: 27, IQR: 22-32; vs 25 and 22-28.5; p=0.03), and a lower motivation to quit score (median: 10, IQR: 9-13; vs 14 and 12-15; p<0.001). After 12 months, the quitting rate of smokers with CD was significantly lower (14.8% vs 36.7%; p<0.022) and the chance of quitting was negatively associated with the baseline BPRS (r=-0.256; p<0.003). Varenicline and nicotine replacement therapy tended to be less effective in patients with CD. CONCLUSIONS The lower efficacy of SCPs in patients with CD might be secondary to a higher prevalence of anxiety and depression. Psychological issue recognition and support should be enhanced to increase SCP effectiveness in CD.

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