Treatment with N-acetylcysteine, a mucus-dissolving and anti-inflammatory agent, reduces the frequency of acute worsening episodes and improves the quality of life of patients with bronchiectasis, results from a randomized trial in China show. Trial findings were reported in the study, “Effect of N-acetylcysteine on exacerbations of bronchiectasis (BENE): a randomized controlled trial,” published in the journal Respiratory Research. Hallmark clinical features of bronchiectasis, such as bronchi dilation and enlargement of mucus-secreting glands, commonly lead to excessive secretion of mucus into the airways. This ultimately triggers disease-associated symptoms including chronic coughing. Although approximately 27% of bronchiectasis patients have a form of the disease called dry bronchiectasis, which is not associated with excessive production of sputum (saliva and mucus), most patients do experience overproduction of sputum accompanied by chronic bacterial infections. As a result, mucus-reducing (mucoactive) therapies such as concentrated saline products or mannitol can be beneficial for the treatment of bronchiectasis. An earlier large-cohort study named PANTHEON (ChiCTR-TRC-09000460) showed that the mucus-loosening (mucolytic) medication N-acetylcysteine could reduce the exacerbation rate and improve the quality of life of patients with chronic obstructive pulmonary disease (COPD). The therapeutic compound not only lowered the viscosity of the sputum but also exhibited anti-inflammatory and antioxidant effects. Given that COPD and bronchiectasis share similar clinical features, investigators decided to explore the long-term impact of N-acetylcysteine in patients with bronchiectasis experiencing daily sputum production. The study called BENE (NCT02088216) included 161 patients with bronchiectasis enrolled at five hospitals across the Shandong province in China. Participants were randomized to receive orally 600 mg N-acetylcysteine twice daily (81 patients; mean age 53.3 years) or to take as-needed therapy (80 control patients; mean age 56.6 years) over a 12-month period. Researchers assessed changes in the frequency of exacerbations over one year, defined as the study's primary goal. Exacerbations describe acute episodes of at least three bronchiectasis-associated symptoms lasting for two or more days, the management of which requires a change in treatment. Trial data showed a lower incidence of exacerbations in the N-acetylcysteine-treated group than in the on-demand treatment group — 1.31 versus 1.98 exacerbations per patient-years. Overall, treatment with N-acetylcysteine was associated with a 59% lower risk of bronchiectasis exacerbations. Further analyses showed that 24.7% of patients treated with N-acetylcysteine remained exacerbation-free during the study period, compared with 11.3% in the control group. While the time to the first exacerbation was similar between the two groups, time to the second exacerbation was significantly longer in the N-acetylcysteine treated group. In addition, 24-hour sputum volumes were significantly lower in N-acetylcysteine-treated patients. Patients' quality of life, measured by a new questionnaire called the COPD assessment test, was also found to be significantly better among those treated with N-acetylcysteine. Still, researchers found no significant differences between the groups in Pseudomonas aeruginosa colonies in the sputum (a common source of difficult-to-treat lung infections), inflammatory markers, or lung infections. Based on these results and the anti-inflammatory properties previously associated with N-acetylcysteine, the team believes this therapeutic agent can be beneficial for treating bronchiectasis. However, they highlight the need for larger randomized and placebo-controlled trials to confirm these findings. In general, the therapeutic intervention was found to be safe and well-tolerated, with no serious adverse effects reported. Three patients experienced mild elevation of liver enzymes and two patients had a rash. Also, five patients in the treatment group complained of body odor. “In conclusion, the long-term use of N-acetylcysteine is able to reduce the risk of exacerbations for bronchiectasis patients,” the researchers wrote. “This trial may lead to larger international multicenter research in the field."