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Effect of N-acetylcysteine on Bronchietasis

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I recently diagnosed bronchiectasis in a patient, with the help of a pulmonologist, so I was especially interested in this condition and this study. Bronchiectasis is a chronic lung disease that is described as permanent dilation of the bronchi and bronchioles and enlargement of mucus-secreting glands. Patients experience chronic excessive mucus secretions into the airway that results in a chronic cough and constant desire to expel the mucus. Inflammation, injury and changes to the shape of the bronchi, mucus collection and respiratory infections are the four major aspects that underlie bronchiectasis. 

The treatment of bronchiectasis is focused on managing the symptoms and reducing the number of respiratory infections. Mucoactive agents such as hypertonic saline, mannitol and erdosteine can bring about some improvements in some patients. Studies on inhaling dry powder of mannitol for 12 weeks reduced sputum in these patients, and short term use of erdosteine plus chest physical therapy reduced mucus secretion, but sample size has been small and duration is too short to conclude anything definitive. Long term antibiotic regimens are also used to reduce the frequency of exacerbations, although this approach can increase the risk of bacterial resistance and adverse events.

N-acetylcysteine (NAC) is a dietary supplement used to thin the mucus, amongst many other uses, and reduces the viscosity and elasticity of sputum as well as having anti-inflammatory and anti-oxidant activity. This action of thinning the mucus and reducing inflammation, plus a clinical trial using NAC 1200 mg/day that reduced the rate of exacerbations and improved quality of life in chronic obstructive pulmonary disease patients suggests that it could be helpful for those with bronchiectasis as well.

The purpose of the current study was to assess whether NAC 600 mg twice daily might reduce the number of exacerbations and improve quality of life.(1)  An exacerbation is defined as the increase in three or more key symptoms: cough, sputum volume and/or consistency, sputum purulence, breathlessness and /or exercise intolerance, fatigue, and coughing up blood for at least 48 hours.

A total of 161 patients were randomized with 81 receiving oral NAC 600 mg twice daily and 80 in the control group. Due to drop outs and deaths in both the treatment and control groups, there were in the end, 69 patients taking NAC and 70 in the control group. To emphasize the potential seriousness of bronchiectasis, one patient died of an acute exacerbation of bronchiectasis in the NAC group and 2 died of the same cause, in the control group.

The incidence of exacerbations in the NAC group was significantly lower than in the control group (1.31 vs 1.98 exacerbations per patient-year. The average number of exacerbations in the NAC group was 1, compared with 2 in the control group. A total of 24.7% in the NAC group and 11.3% in the control group remained free of any exacerbation during the 12 month period. In addition, while the time to the first exacerbation did not differ between the NAC group and the control group, the time to the second exacerbation was longer in the NAC group.

Commentary: This study is very encouraging in light of a disease with no known cure. Not only did it reduce the number of exacerbations, it also reduced the volume of sputum and improved quality of life.

NAC was also very well tolerated with a low incidence of adverse reactions and long term use of a year was found to be safe. It should be noted that there are subtypes of bronchiectasis, one being a dry bronchiectasis, and it is not clear if these individuals would benefit from NAC. While this study used NAC in oral encapsulated delivery, nebulized NAC might be a more effective way to deliver the medicine. I will be curious to learn if anyone has experience with that.

Reference:
1. Qi, Q., et al. Respiratory Research 2019: 20:73