Lung Disease and NAC

Dr. Weeks’ Comment: Glutathione is very beneficial for people with lung problems but it tastes like rotten eggs and it is transient and it is expensive.  But NAC (N-acetylcysteine) converts to glutathione so oral or IV NAC is very valuable. 


“…. In humans NAC had been proven to improve idiopathic pulmonary fibrosis (IPF)…”

“…Inhalation of N-acetylcysteine (NAC) has been carried out in our department since 1994 for treating interstitial pneumonia such as idiopathic pulmonary fibrosis (IPF)…”

Intern Med. 2010;49(21):2289-96. Epub 2010 Nov 1.

Long-term efficacy of inhaled N-acetylcysteine in patients with idiopathic pulmonary fibrosis.


Inhalation of N-acetylcysteine (NAC) has been carried out in our department since 1994 for treating interstitial pneumonia such as idiopathic pulmonary fibrosis (IPF). In this study, the clinical efficacy and safety of long-term NAC inhalation monotherapy for IPF was investigated.


NAC inhalation was carried out in 23 of 34 cases diagnosed as IPF by surgical lung biopsy in our department between 1994 and 2008. The treatment was continued for one year or longer in 14 cases. In these 14 cases and in 11 cases without treatment, the clinical courses, prognosis, lung function (%FVC, %DLco, and %TLC), and changes in serum markers for interstitial pneumonia (KL-6 and SP-D) were examined.


There were no significant differences in survival curves between the two groups. Acute exacerbation was observed in 4 of 14 cases (28.6%) receiving NAC inhalation. Compared with the results just before the beginning of NAC inhalation, Δ%FVC and Δ%DLco in the treated cases were -4.7% and -2.9% one year later and -4.0% and -5.8% two years later, respectively. In cases without treatment, Δ%FVC and Δ%DLco were -3.5% and +5.3% one year later and +0.2% and +1.0% two years later, respectively.


Since this study is an open case-control study in a single institute and the number of cases is not large, its use in evaluating the efficacy of NAC inhalation monotherapy is limited. In addition, the role of NAC inhalation in combination with a steroid, an immunosuppressive agent, and a new anti-fibrosis drug should also be investigated.



Int J Immunopathol Pharmacol. 2011 Jul-Sep;24(3):727-33.

Long-term N-acetylcysteine therapy in systemic sclerosis interstitial lung disease: a retrospective study.


Systemic sclerosis (SSc) is associated with interstitial lung diseases. The primary endpoints of this study were changes between baseline and month 24 in single-breath carbon monoxide diffusing capacity (DLco). The secondary endpoints were: vital capacity (VC), forced expired volume in 1 sec (FEV1), total lung capacity (TLC), scores of high resolution computed tomography (HRCT) of the chest, number of adverse effects. In this study, we retrospectively investigated data from SSc patients who had undergone therapy with high-dose intravenous N-acetylcysteine (NAC) at a dosage of 15 mg/Kg/h for 5 consecutive hours every 14 days. After NAC therapy median values of DLco (69.5 vs 77.7%), VC (99 vs 101.3%) and TLC (93 vs 98.3%) significantly increased. We did not observe any significant changes from baseline in FEV1 value and HRTC score. The improvement in lung function was more evident in SSc patients without radiological signs of pulmonary fibrosisthan in patients with pulmonary fibrosis. In SSc patients with mild-moderate pulmonary fibrosis intravenous NAC administration slows the rate of deterioration of DLco, VC and TLC. In conclusion, this retrospective study demonstrates that long-term therapy with intravenous NAC ameliorates pulmonary function tests in SSc patients.

Pneumologie. 2011 Sep;65(9):549-57. doi: 10.1055/s-0030-1256592. Epub 2011 Jul 14.

[Anti-inflammatory efficacy of N-acetylcysteine and therapeutic usefulness].


N-acetylcyteine (NAC) is a thiol containing compound which by providing Sulfhydryl groups, can act both as a precursor or reduced glutathione and as a direct scavenger of reactive oxygen species. By regulation the redox status in cells, it can interfere with several signaling pathways that play a role in regulation apoptosis, angiogenesis, cell growth, nuclear transcription and cytokine production. In humans NAC had been proven to improve idiopathic pulmonary fibrosis (IPF), various forms of alveolitis and to avoid hepatoxic effects of paracetamol and paraquate through binding these compounds enabling biliary excretion. Overall, the anti-inflammatory action of NAC is well documented in vitro as well as in vivo. This review summarizes the biochemical effects of NAC and hints proven and likely diseases where NAC have or might have a beneficial effect.


Health Technol Assess. 2015 Mar;19(20):i-xxiv, 1-336. doi: 10.3310/hta19200.

The clinical effectiveness and cost-effectiveness of treatments for idiopathic pulmonary fibrosis: a systematic review and economic evaluation.


Idiopathic pulmonary fibrosis (IPF) is a life-limiting lung disease that generally affects people over 60 years old. The main symptoms are shortness of breath and cough, and as the disease progresses there is a considerable impact on day-to-day life. Few treatments are currently available.


Few interventions have any statistically significant effect on IPF and a lack of studies on palliative care approaches was identified. Research is required into the effects of symptom control interventions, in particular pulmonary rehabilitation and thalidomide. Other research priorities include a well-conducted randomised controlled trial on inhaled NAC therapy and an updated evidence synthesis once the results of ongoing studies are reported.


Pharmacol Rep. 2010 Jan-Feb;62(1):131-8.

N-acetylcysteine inhibits IL-8 and MMP-9 release and ICAM-1 expression by bronchoalveolar cells from interstitial lung disease patients.


N-acetylcysteine (NAC), owing to its antioxidant, mucolytic and anti-inflammatory properties, is used in the treatment of various pulmonary disorders. However, the direct effects of NAC on bronchoalveolar lavage (BAL) cells from patients suffering from interstitial lung diseases have not yet been studied. Therefore, the aim of the present work was to evaluate the effect of NAC on interleukin-8 (IL-8) and matrix metalloproteinase-9 (MMP-9) production as well as intercellular cell adhesion molecule-1 (ICAM-1) expression by BAL cells from interstitiallung diseases. The study was performed on BAL cells from nine patients with interstitial lung disease: four patients with idiopathic pulmonary fibrosis (IPF) and five patients with sarcoidosis. Cultured unstimulated BAL cells were treated with increasing doses of NAC (1-30 mM). Production of IL-8 and MMP-9 was evaluated by specific enzyme-linked immuno-sorbent assays and ICAM-1 expression was studied by immunohistochemistry. NAC exerted a dose-dependent inhibitory effect on IL-8 and MMP-9 release and ICAM- expression by BAL macrophages and lymphocytes from patients with IPF and sarcoidosis. In conclusion, NAC inhibits production of factors playing a key role in the etiopathogenesis of interstitial lung diseases, thus suggesting its possible therapeutic potency in the treatment of these disorders.

Am J Respir Crit Care Med. 2000 Jul;162(1):225-31.

Aerosolized administration of N-acetylcysteine attenuates lung fibrosis induced by bleomycin in mice.


Reactive oxygen species (ROS) play an important role in the pathogenesis of pulmonary fibrosis. We previously demonstrated that N-acetylcysteine (NAC), an antioxidant, inhibited adhesion molecule expression and cytokine production in lung cells. When NAC is inhaled into the alveolar space, it is expected to directly interact with inflammatory cells and to elevate glutathione levels in the epithelial lining fluids. We therefore examined whether inhaled NAC inhibits lung fibrosis induced by bleomycin (BLM). Male ICR mice were given a single intravenous injection of BLM (150 mg/ kg). Thirty milliliters of NAC (70 mg/ml) or saline were inhaled twice a day for 28 d using an ultrasonic nebulizer. In the inflammatory phase (Day 7), NAC administration attenuated the cellular infiltration in both bronchoalveolar lavage fluid (BALF) and alveolar tissues. At Day 28, the fibrotic changes estimated by Aschroft’s criteria and hydroxyproline content in the NAC inhalation group were significantly decreased compared with the BLM-only group (p < 0.05). CXC chemokines, macrophage inflammatory protein-2 (MIP-2), cytokine-induced neutrophil chemoattractant (KC), and CC chemokines, macrophage inflammatory protein-1alpha (MIP-1alpha), in BALF were mostly elevated on Day 7 in the BLM-only group; however, these elevations were significantly repressed by NAC inhalation (p < 0.05). Lipid hydroperoxide (LPO) was also quantified in BALF. LPO was markedly increased on Day 3 in the BLM-only group, and this increase was significantly decreased by NAC inhalation (p < 0.05). These results revealed that aerosolized NAC ameliorated acute pulmonary inflammation induced by BLM injection via the repression of chemokines and LPO production, resulting in the attenuation of subsequent lung fibrosis. These findings are limited to the BLM-induced lung fibrosis animal model. However, NAC inhalation will be expected to be a potential therapy for patients with other interstitial pneumonias because ROS are involved in the pathogenesis of lung injury in most interstitial pneumonia.




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