The cone-shaped lungs are sponge-like organs that fill the chest cavity and make up most of the lower respiratory tract. Their most important job is providing oxygen to capillaries so they can oxygenate blood. Each lung is divided into lobes. The right lung has three, but the left lung has only two, thus allowing room to accommodate the heart.Together, the lungs’ tissue surface is almost 40 times greater than the body’s outer surface, making the lungs (together) one of the largest organs in the body.Each lung houses a bronchial tree, which gets its name from the intricate network of air passages that supply the lungs with air. The air-filled sacs in the lungs called alveoli resemble grape clusters. White blood cells known as macrophages, located inside each alveolus, ingest and destroy airborne irritants that enter the lungs. After you exhale, the lungs stay partly inflated because of a fluid called surfactant that is produced by special cells and secreted within the alveoli. Surfactant contains fatty proteins and helps to prevent lung infections. Suffering from a respiratory disorder is one of the most common reasons for doctor visits in industrialized countries, where the air is filled with chemicals, pollutants, dust, pollen, bacteria, and viruses. The billions of microorganisms — bacteria, viruses, and fungi — in the air you breathe can enter the lungs, they make respiratory infections quite common. Some infections, such as the common cold or sinusitis, affect the upper respiratory tract. Others, such as bronchitis and pneumonia, affect the lower respiratory tract.
JOBS OF GLUTATHIONE:
A : MASTER ANTIOXIDANT
I : IMMUNE SYSTEM BALANCE AND STRENGTHENING
D : DETOXIFICATION
AS WELL THE BODIES MOST EFFECTIVE ANTI- INFLAMMATORY
Although oxidation is a natural chemical reaction that takes place in your body, chronic exposure to air pollution and toxins can dramatically increase your level of oxidation and the production of free radicals. Free radicals are unstable molecules that gain stability by ‘stealing’ electrons from other molecules such as your proteins, DNA or cell membranes via the oxidation process. When oxidation occurs, important elements of the cells are damaged, lose their ability to function normally and may eventually lead to cell death. Glutathione in the epithelial lining fluid (ELF) of the lower respiratory tract is thought to be the first line of defense against oxidative stress. The ELF concentration of GSH is 140 times that of serum concentrations. In fact, alternations in alveolar and lung GSH metabolism are widely recognized as a central feature among many inflammatory lung diseases. In healthy lungs, the oxidant burden is balanced by local antioxidant defenses. However, in lung diseases, cellular damage and injury are mediated by an increased oxidant burden and/or decreased antioxidant defenses.
Antioxidants donate molecules to stabilize free radicals and reduce oxidative damage, so they help to protect your lungs and respiratory tract from exposure to air pollution and toxins.
Maintaining a healthy antioxidant network can help protect your lungs from damage and detoxify air pollution and toxins.
Constant exposure to air pollution and toxins leads to oxidation and free radical damage to tissues. This adversely affects your health through reduced lung function, inflammation of the respiratory tract and uncomfortable respiratory symptoms such as:
~Dr. S. Jill James, PhD  Arkansas Childrens Research Institute
BACKGROUND: Oxidative stress is an important hallmark of asthma and much research has therefore focused on the predominant antioxidant in the lungs, namely the tripeptide Glutathione.
MAJOR CONCLUSIONS: In lung samples of patients with asthma increased levels of Glutathione are typically observed, which appear to relate to the level of pulmonary inflammation and are therefore regarded as an adaptive response to the associated oxidative stress. Also in blood samples increased total GSH levels have been reported, representing the systemic inflammatory component of the disease. In addition, a number of the antioxidant enzymes involved in the maintenance of the GSH/GSSG ratio as well as enzymes that utilize GSH have been found to be altered in the lungs and the blood of asthmatics. Important in this respect is the physiological role of the GSH redox equilibrium in determining the outcome of immune responses, which could be deregulated in asthmatics and contribute to the disease.
2011 : Severe asthma in children is characterized by altering airway and intracellular AM (airway macrophages) GSH homeostasis that translate to impaired AM function. Interventions to restore airway GSH homeostasis may be warranted in children with severe asthma.
2006: Oxidative stress is an important feature in the pathogenesis of COPD. Targeting oxidative stress with antioxidants or boosting the endogenous levels of antioxidants is likely to be beneficial in the treatment of COPD.
Clear evidence that oxidants in cigarette smoke markedly decrease plasma antioxidants, which may play an important role in the pathogenesis of COPD.
Studies support the concept that dietary antioxidant supplementation including polyphenols may be a possible therapy to prevent or inhibit oxidative stress and inflammatory responses, which are key features in the development of COPD.
2007: The major contribution to oxidant related lung damage in COPD is from the oxidant/antioxidant imbalance and possibly impaired antioxidant defence. Glutathione (GSH) is one of the most important antioxidants in human lung and lung secretions.
Conclusion: GSTO1-1 is abundant in the alveolar macrophages, but it is also present in extracellular fluids and in airway secretions, the levels being decreased in COPD.
2008 : Part of the altered alveolar environment in lung fibrosis involves oxidative stress that is driven by an imbalance between oxidant production and antioxidant defenses. Inadequate antioxidant adaptive responses play a key role in lung fibrosis.
Antioxidants have been defined many different ways, and in a very broad sense, they are agents that decrease steady-state ROS levels and protect cellular macromolecules from oxidative modification.
• Thiol-based antioxidants (GSH) have protective effects of the radiation-induced lung injury and fibrosis.
• Thiol-based antioxidants (GSH) also have protective effects in the silica-induced injuries.
In addition to its well-known association with lung infection (i.e., pneumonia), alcohol abuse now is recognized as an independent factor that increases by three- to fourfold the incidence of the acute respiratory distress syndrome, a severe form of acute lung injury with a mortality rate of 40 to 50 percent.
Seeking to verify that the relationship between alcohol intake and pulmonary Glutathione deficiency in the rat were relevant for humans, Moss and colleagues (2000) measured lung Glutathione levels in 19 otherwise healthy alcoholic subjects. Lung Glutathione levels in the alcoholic subjects were approximately 80 percent lower than those of nonalcoholic subjects (Moss et al. 2000). These findings, taken together with the findings reported above linking oxidative stress and decreased Glutathione in the lungs of alcohol-fed experimental animals, illustrate that the alcoholic lung observed in humans, even in the absence of apparent disease, shows evidence of severe oxidative stress.
The Glutathione “deficiency” observed in ELF in CF patients is not limited to the site of the inflammation but is systemic.
Data reporting that Glutathione levels in the lung epithelial lining fluid of patients with cystic fibrosis are low, and that cystic fibrosis lung disease is associated with increased oxidative damage. In addition, more recent studies have also demonstrated that the cystic fibrosis transmembrane conductance regulator (CFTR), which is defective in cystic fibrosis, regulates a substantial portion of Glutathione efflux into the epithelial lining fluid.
A mother’s story: Hudson is willing to discuss her sons’ GSH treatments when asked. John, whose CF before GSH she described as severe, started GSH at age two. “Because his salivary glands were obstructed, he had no saliva and he could only eat wet foods. After we started GSH, he actually began to drool,” she says. His frequent loose bowel movements have stopped, and his growth jumped from 35% below average for his age to 10% above average after three months of treatment. “But what delighted us the most is he routinely cultured staph and influenza B in his sputum. Now he cultures, nothing, and that is without antibiotic treatment. That’s unheard of,” she says.
2008 : Abstract: CFTR mutation, which causes cystic fibrosis (CF), has also recently been identified as causing Glutathione system dysfunction and systemic deficiency of reduced Glutathione (GSH). Such dysfunction and deficiency regarding GSH may contribute to the pathophysiology of CF. We followed 13 patients (age range 1–27 years) with cystic fibrosis who were using a regimen of reduced Glutathione (GSH), including oral Glutathione and inhaled buffered Glutathione in an uncontrolled, observational study. Dosage ranged from 66–148 mg/kg/day in divided doses, and the term examined was the initial 5.5 months of GSH use (45 days of incrementally adjusted dose, plus 4 months of use at full dosage). Baseline and post-measurements of FEV1 percent predicted, BMI percentile, and weight percentile were noted, in addition to bacterial status and pulmonary exacerbations. Significant improvement in the following clinical parameters was observed: average improvement in FEV1 percent predicted (N = 10) was 5.8 percentage points (p < 0.0001), average weight percentile (N = 13) increased 8.6 points (p < 0.001), BMI percentile (N = 11) improved on average 1.22 points (p < 0.001). All patients improved in FEV1 and BMI, if measured in their case; 12 of 13 patients improved in weight percentile. Positive sputum cultures of bacteria in 11 patients declined from 13 to 5 (p < 0.03) with sputum cultures of Pseudomonas aeruginosa becoming negative in 4 of 5 patients previously culturing PA, including two of three patients chronically infected with PA as determined by antibody status. Use of a daily GSH regimen appears to be associated in CF patients with significant improvement in lung function and weight, and a significant decline in bacteria cultured in this uncontrolled study.
An exaggerated inflammatory response is also involved in the pathogenesis or complications of pulmonary infections such as tuberculosis, severe acute respiratory syndrome, influenza, and acute respiratory distress syndrome (ARDS).
It can be seen that there is an overlap between the list of pulmonary diseases associated with inflammation and those where GSH repletion is protective, indirectly supporting the hypothesis of an anti-inflammatory role of GSH.
The functions of GSH are not only inhibitory as described above in the inflammatory response. In fact, GSH is essential for some functions of the immune system, both innate and adaptive, including T-lymphocyte proliferation, phagocytic activity of polymorphonuclear neutrophils (PMN), and dendritic cell functions, and is also important for the first step of adaptive immunity, consisting of the antigen presentation by antigen-presenting cells.
This essential role of GSH in immunity might explain why in many diseases, not only AIDS, decreased GSH levels are associated with an increased susceptibility to infection. These include COPD, cystic fibrosis, influenza infection, and alcoholism, as ethanol impairs Th1/Th2 balance via GSH depletion.
The role of oxidative stress in the pulmonary damage by the influenza virus is well characterized in the mouse model. Mice infected with influenza show pulmonary damage associated with a dramatic decrease in pulmonary GSH levels as well as an increase of oxidative stress markers such as oxidized Glutathione.
Mycobacterium tuberculosis is an intracellular pathogen that grows in the phagosomes, where it is protected from immune system effectors such as antibodies and T lymphocytes. Although the literature showing that GSH levels are lower in patients with tuberculosis, both GSH and GSNO have direct bactericidal activity against these pathogens.77.