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Pulmonary Conditions--Breathing, the Highest Consideration in the Hierarchy of Health.

Many of us are paying attention to the food we ingest, shopping for organic meat and produce items, or filtering our water to reduce our exposure to toxins. But how often do we pay attention to the air we're breathing? Yet, what we breathe in can have as important effect on our bodies as the food we're eating and the water we're drinking. To name one example, exposure to air pollution is associated with development and worsening of asthma and other allergic diseases. (1)

Whether caused by exposure to air pollution, genetic susceptibility, a viral or bacterial infection, exposure to cigarette smoke, or gastroesophageal reflux, impaired pulmonary health can have systemic effects. Therefore, it is critical to ensure the strength and health of our lungs. In this article, we'll discuss a number of lung diseases, their risk factors including the role that gastroesophageal reflux plays in several lung disorders, the role of the gut microbiota in cystic fibrosis, and natural solutions for optimal lung health.

Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF), a type of idiopathic interstitial pneumonia, is a chronic, debilitating lung disorder that results in a progressive worsening of lung capacity over time. It is characterized by scarring (fibrosis) and inflammation. The course of the disease can progress in varying ways, with some individuals undergoing periods of relative stability while others experience a steady reduction in lung function or periods of acute exacerbation. Rarely, some patients may remain symptom free for two to three years after diagnosis. (2)

In the United States, using narrow definitions, the prevalence is 14 to 27.9 cases of the disease per 100,000 population. Using a broader definition, the prevalence is 42.7 to 63 cases per 100,000 population. (3) IPF is slightly more common in males compared with females with a medium age of onset of 66 years. (4) Symptoms include shortness of breath and a cough, leading to marked declines in health-related quality of life. The survival rate is approximately two to five years. (3)

Conventional treatment for IPF usually includes corticosteroids or immunosuppressants, but this therapy does not markedly improve the survival of patients with IPF. (3) Balancing the benefits versus adverse effects of standard pharmaceutical therapies such as nintedanib, etanercept, warfarin (which is generally contraindicated), Gleevec, and bosentan is a very real clinical challenge. (5)

Cystic Fibrosis

Cystic fibrosis is a genetic disease involving chronic inflammation and oxidative stress impacting primarily the respiratory and digestive systems. Cystic fibrosis is the most common life-shortening autosomal recessive disorder, affecting 30,000 people in the US and 70,000 globally. (6,7) Although 75 percent of people with the disease are diagnosed by age 2, (7) Dr. Meletis recently had a 12-year-old boy in his clinical practice diagnosed that was quite athletically active whose sole presentation was frequent congestion and phlegm particularly in the morning. This reminds us as clinicians to test patients with unique presentations.

A mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, leading to expression of impaired Cl-ion transport proteins in epithelial cells, is responsible for the development of cystic fibrosis. (6) This mutation results in insufficient hydration in the lungs and colon, leading to build up of viscous mucus on epithelial surfaces. (6,8) This accumulation of mucus leads to increased risk of infection in this group of individuals. Specifically, the lungs of cystic fibrosis patients are usually predisposed to colonization with Pseudomonas aeruginosa resistant to eradication by the immune system and medications. (9) The bacteria in the lungs of the cystic fibrosis patients often develops a biofilm to shield the microorganisms from host defenses and antibacterial drugs. (9) This biofilm combined with higher lung mucus viscosity and persistence in cystic fibrosis patients inhibits the effectiveness of antibiotics. (9)

Airway inflammation plays an important role in poor clinical outcomes in cystic fibrosis patients. (10) Inflammation markers are higher in the sputum of people with cystic fibrosis while anti-inflammatory markers are decreased. (11,12) Impaired fatty acid metabolism, including low linoleic acid and docosahexaenoic acid levels, have been observed in patients with cystic fibrosis. (13) Human and animal studies indicate that impaired fatty acid metabolism in cystic fibrosis patients may be associated with greater inflammation via an elevation in prostaglandin synthesis. (14)

Dysbiosis of the gut microbiota is another contributing factor in cystic fibrosis. We will discuss this in more detail later in the article.

Asthma

Asthma is a chronic respiratory disease characterized by bronchial airway inflammation leading to increased generation of mucus and hyper-responsiveness of the airway to asthma triggers. Symptoms of asthma include wheezing, coughing, and shortness of breath. According to the Centers for Disease Control and Prevention, 18.4 million adults (7.6%) in the US have asthma. (15)

Genetic, allergic, environmental, infectious, emotional, and nutritional factors all play a role in asthma. Airway inflammation is a driving force behind the pathophysiology of the disease. The cause of this inflammation is thought to be an abnormal or poorly regulated CD4+ T-cell immune response. (16) The T-helper 2 (Th2) subset of immune cells generate proteins known as cytokines including interleukin-4 (IL-4), IL-5, IL-6, IL-9, IL-10, and IL-13. These cytokines enhance the growth, differentiation, and recruitment of mast cells, basophils, eosinophils, and B-cells. Each of these cells play an important role in humoral immunity, inflammation, and allergic response.

Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is comprised of two conditions: emphysema and/or chronic bronchitis. Chronic infections are common in COPD patients, who have heightened inflammatory responses and a progressive reduction in respiratory function. Chronic cough, respiratory secretions, and progressive difficult or labored breathing and fibrosis are all hallmarks of COPD. Nearly 15.7 million people in the US (6.4%) have COPD, although half of adults with low pulmonary function are unaware they have COPD so the actual number of people who have the disease may be higher. (17)

The primary cause of COPD is chronic exposure to cigarette smoke (CS), and the risk of disease is proportionally correlated to the number of cigarettes smoked daily. (18) However, other contributing factors to the disease include high exposure to dust laden with toxins, contact with chemicals, and mutations in the [[alpha].sub.1]-antitrypsin gene. (19,20)

Other Risk Factors for Development and Exacerbation of Lung Disorders

In addition to the other risk factors mentioned above, there are several important contributors to the development or worsening of lung diseases.

Viral and Bacterial Infections

An association exists between infections with certain viruses and lung diseases, especially IPF and asthma. Studies using lung samples have established a possible association between the hepatitis C (HCV) family of viruses and IPF, acute exacerbations of IPF, or patients at risk for familial IPF, indicating these viruses may be involved in the development and/or worsening of IPF. (21) In one of those studies, HCV antibodies were present in 28% of patients with IPF compared with only 3.6% of controls. (22) In another study, researchers found a greater incidence of IPF at 10 and 20 years after HCV infection compared with hepatitis B virus patients. (23) Other researchers observed a greater prevalence of HCV in many forms of lung disease, indicating the association may not be limited to IPF. (24)

Scientists have also found the presence of herpes simplex virus (HSV-1) in bronchoalveolar lavage fluid and lung tissue biopsy from patients with IPF and nonspecific idiopathic interstitial pneumonia. (25) Epstein-Barr virus (EBV), which belongs to the herpes virus family, is also common in patients with IPF and may be involved in the development of pulmonary hypertension in these patients. (26-29)

Other viruses are implicated in the development or exacerbation of IPF. There is a high prevalence of the Torque-Teno (Transfusion-Transmitted) virus (TTV) in patients with IPF. (30) Furthermore, in one study, the three-year survival rate of patients with IPF who were infected with TTV was markedly lower. (30) The same trial also found higher TTV levels in patients with IPF who develop lung cancer compared to patients who did not develop cancer. (30) Additionally, TTV was the most common virus in a group of individuals with IPF suffering from acute exacerbation. (31) Scientists have also observed this virus in people with lung cancer and acute lung injury. (21)

Viral infections acquired early in life are also triggers for the development of asthma. A newly discovered virus family known as Anelloviridae are contracted in childhood and replicate continuously without causing any symptoms. (32) This virus modifies the innate and adaptive immune systems and plays a role in the development of asthma. (32)

Asthma may be associated with other types of viral infections including EBV33 and adenovirus. (34,35)

Bacterial infections may also play a role in lung diseases. Interestingly, reports have identified Chlamydia pneumoniae infection as a trigger for the development of asthma and improvement in asthma occurred after antibiotics eradicated the bacteria. (36) Chlamydia infections may also worsen smoking-associated inflammation in COPD patients. (36) Another study in adults found that higher levels of Chlamydia antibodies correlated with greater asthma severity. (37)

Pseudomonas aeruginosa is another bacterial infection implicated in lung disease, specifically cystic fibrosis. Individuals with cystic fibrosis are vulnerable to P. aeruginosa infections of the lungs and these infections are often resistant to clearance by the immune system and antibiotics. (9)

Gastroesophageal Reflux Disease

Gastroesophageal reflux disease (GERD) is characterized by reflux and regurgitation leading to symptoms such as heartburn, pain in the upper abdomen, difficulty swallowing, and aerodigestive symptoms including asthma, chronic cough, or recurrent pneumonia. GERD often occurs together with IPF and may play a role in progression and worsening of the disease. (38) Some evidence suggests that treatment of GERD leads to lower IPF-related mortality but not overall mortality. (38) Researchers have also observed an increased incidence of GERD in asthma patients, (39) although it has not been firmly established whether these two disorders simply occur together, whether GERD causes asthma, or whether asthma causes GERD. (16) It is estimated that 75% of asthma patients have GERD symptoms, 80% have abnormal acid reflux, 60% have a hiatal hernia, and 40% have esophageal erosions or ulcerations. (39)

Increased bronchoconstriction occurs with esophageal acid infusion. (16) In a human study, this bronchoconstriction was eliminated after antacid treatment. (40) The mechanism of action linking GERD to asthma may involve the vagus nerve creating a reflex from the irritated esophagus to the lungs, leading to bronchoconstriction. (16) Another explanation is that gastric acid from the esophagus may seep into the lungs, causing injury, irritation, and increased production of mucus. (16)

There is some indication, as observed by Jonathan Wright, that asthma patients actually have a reduced gastric acid output, which results in impaired protein digestion and nutrient absorption as well as increased food allergies. (16)

Dysbiosis of the Gut Microbiota

An imbalance (dysbiosis) in the gut microbiota--the population of microbes residing in the intestinal tract--is associated with airway diseases such as cystic fibrosis and asthma. In cystic fibrosis, abnormal intestinal mucosa is associated with alterations in gut microbiota. (41) Patients with cystic fibrosis have a reduced overall bacterial abundance and lower species diversity compared with healthy people. (41) Researchers conducted one study of 43 individuals with cystic fibrosis and 69 controls without the disorder. (42) Although the greatest differences in diversity of the intestinal microbiota occurred between cystic fibrosis patients and healthy controls, alterations in the gut microbiota were also observed between individuals with cystic fibrosis when divided into groups based upon different parameters including the percent predicted [FEV.sup.1] (a measurement of lung dysfunction) and the amount of intravenous antibiotic courses received in the previous year. Patients with cystic fibrosis who had severe lung impairment had markedly lower gut microbiota diversity compared with patients who had mild or moderate impairment. Additionally, greater number of IV antibiotic courses was significantly associated with lower diversity of the gut microbiota.

There is also a relationship between the gut microbiota and asthma. Infants given antibiotics have an altered gut microbiota and immune development and an increased risk of childhood asthma. (43) However, in one study similar associations were found for maternal antibiotic use before and after pregnancy. This indicated the correlation is either not directly causal or it's not specific to pregnancy. (43) Furthermore, researchers have observed a difference in the microbiota profile of people with asthma compared with healthy controls. (44)

In mice with a predisposition to develop allergic airway diseases, oral administration of the live probiotic Bifidobacterium adolescentis ATCC 15703 alleviated allergic airway inflammation and decreased levels of eosinophils in the airway, hallmarks of allergic asthma. (45) In humans, supplementation with [10.sup.8] ()CFU per day of the probiotic L. reuterii was effective in reducing bronchial inflammation in children with well-controlled asthma. (46)

Another study evaluated the effects of supplementation with the prebiotic Bimuno-galactooligosaccharide (B-GOS) on exercise-induced bronchoconstriction and airway inflammation. (47) Ten adults with asthma and bronchoconstriction caused by hyperpnea (increased depth and rate of breathing) and eight healthy controls randomly received either 5.5 grams/day of B-GOS or a placebo for three weeks separated by a two-week washout period. The prebiotic intervention resulted in reduced airway hyperresponsiveness along with reductions in markers of airway inflammation.

Air Pollution and Environmental Exposures

Epidemiological evidence indicates there is a significant association between air pollution and the development and worsening of asthma and COPD. The primary components of pollution responsible are ozone ([O.sub.3]) and nitrogen dioxide (N[O.sub.2]), as well as particulate matter (PM) derived from car exhaust and industry. (1,48) Diesel exhaust particulate (DEP) can bind proteins and may act as a carrier of allergens, allowing them to penetrate deep into the respiratory tract. (1,48) Furthermore, acute flare ups and worsening of idiopathic pulmonary fibrosis correlate with exposure to [O.sub.3], N[O.sub.2], and particulate matter. (49) In addition, chronic exposure to air pollution might actually cause the development of IPF. (49)

Indoor pollution including secondhand cigarette smoke and emissions from wood-burning stoves can also exacerbate asthma symptoms. (16) Secondhand smoke up-regulatestheTh2 immune response in animal studies. (50) Exposure to cigarette smoke is also responsible for most cases of COPD. (51) Gas appliances can increase the level of nitrogen dioxide breathed in, impairing lung function. (16) Offgasing of volatile organic compounds and formaldehyde emitted from paints, adhesives, furniture, carpet, and building materials are also associated with an increased risk of asthma attacks. (16)

Environmental exposure is also linked to IPF. A meta-analysis found that smoking at any time throughout life or exposure to agriculture/farming, livestock, wood dust, metal dust, and stone/sand were each considered significant risk factors for IPF. (19)

Natural Support for Lung Conditions

A number of nutritional and lifestyle options exist for patients with pulmonary concerns. Here are some suggestions based on both clinical practice and research.

Idiopathic Pulmonary Fibrosis. Animal studies have reported on the promising effects of a number of botanicals. In a rat model, rosemary extract, which contains rosmarinic and carnosic acids, reduced and cured pulmonary fibrosis even when it was administered after fibrosis occurred. (52) Similar results were achieved with rosemary extract in other animal studies. (53,54)Green tea is another botanical that has demonstrated antifibrotic activity in animal studies. In one of those studies, a rat model of pulmonary fibrosis, green tea extract reduced oxidative stress and suppressed endothelin-1 expression, a mediator of pulmonary fibrosis. (55) In another rodent model of pulmonary fibrosis, a combination of green tea extract and curcumin exhibited powerful, synergistic anti-inflammatory effects. (56)

Gingko biloba and carnitine were also studied in rats exposed to a substance that causes pulmonary fibrosis. (57) Researchers induced pulmonary fibrosis in the animals then administered ginkgo or carnitine. Ginkgo decreased the collagen content in the lungs of the rats and reduced inflammation and oxidative stress. Carnitine did not reduce the collagen content but did lower oxidative stress and inflammation.

Additionally, promising results were achieved using Rhodiola rosea L. in a rat model of pulmonary fibrosis. (58) Rhodiola protected against fibrotic lung damage through its anti-inflammatory, antioxidant, and anti-fibrotic actions.

Furthermore, a combination of the botanicals Astragali Radix, Angelicae Sinensis Radix, Paeoniae Radix Alba, Pheretima, Chuanxiong Rhizoma, Carthami Flos, and Persicae Semen (known as a Buyang Huanwu decoction) alleviated pulmonary fibrosis of rats by improving lung tissue morphology and reducing levels of serum collagen types I and III. (59)

Human studies of dietary supplements and IPF have focused on the use of N-acetylcysteine (NAC). A meta-analysis found that although NAC did not have a beneficial effect on changes in forced vital capacity, changes in predicted carbon monoxide diffusing capacity, rates of adverse events, or death rates, it did significantly improve decreases in percentage of predicted vital capacity and 6 minutes walking test distance. (60) Inhalation of NAC is a promising route of administration as noted in a study where patients with early stage IPF experienced enhanced forced vital capacity after exposed to NAC in an aerosol form. (61)

Cystic Fibrosis. In addition to supplementation with probiotics, as noted earlier in this article, there is also justification for support with other nutraceuticals in patients with cystic fibrosis. An imbalance in omega-6/omega-3 polyunsaturated fatty acids is common in cystic fibrosis (CF) patients. (62) Consequently, researchers have explored the effects of omega-3 fatty acid supplementation in these individuals. One randomized, placebo-controlled study found that compared to the previous year, cystic fibrosis patients given omega-3 fatty acids experienced a decline in pulmonary exacerbations at 12 months. (63) In addition, the subjects receiving the omega-3 fatty acids took antibiotics for a shorter period of time (26.5 days compared with 60 days in participants not receiving the fatty acids.)

NAC is another nutraceutical studied in patients with cystic fibrosis. When combined in an inhaled form together with an aerosol form of an antibiotic drug, it has synergistic effects against P. aeruginosa infections in this group of patients. (9) NAC is known for its ability to break down mucus. Therefore, combining it with the drug enhanced the ability of the antibiotic to diffuse into the mucus, compared to when the drug was used alone.

There's also indication that vitamin A may play a role in the health of cystic fibrosis patients. After excluding subjects with acute pulmonary exacerbations, researchers found that cystic fibrosis patients with a moderately high retinol level (up to 110 [micro]g/dL) had the best respiratory function without any signs of toxicity. (64)

Asthma. Since oxygen radicals play a prominent role in the development of asthma, antioxidant supplementation is important. In one study, levels of the antioxidant vitamins C and E were low in the lung lining fluid of individuals with asthma, despite normal or increased plasma concentrations of the vitamins. (65) Furthermore, vitamins E and C may be able to prevent air pollution damage in patients with asthma. Four randomized, controlled trials found that vitamin E combined with vitamin C protected against bronchoconstriction caused by ozone in people with and without asthma. (66-69) Furthermore, the gamma tocopherol isoform of vitamin E suppressed markers of inflammation in subjects with asthma and reduced acute airway response. (70)

Vitamin D is another nutrient of interest to asthmatics. Although not all studies have found an association between vitamin D and asthma, enough evidence exists to warrant its use. Three population-based studies demonstrated a correlation between lower serum vitamin D concentrations and severe asthma exacerbations or core measures of exacerbations such as hospitalizations. (71-73) For example, one of these studies observed that vitamin D insufficiency or deficiency in Puerto Rican children is linked to increased likelihood of having had one or more severe asthma exacerbation in the previous year. (71)

Other nutrients that may be important for individuals with asthma include pyridoxine (vitamin B6), magnesium, and omega-3 fatty acids. (74-76)

One botanical showing promise in supporting asthma patients is Boswellia serrata, which suppresses the formation of leukotrienes, inflammatory metabolites of arachidonic acid. One double-blind, placebo-controlled trial investigated the effects of 300 mg Boswellia extract three times daily for six weeks in 40 subjects with asthma. (77) Symptoms such as difficulty breathing, number of attacks, and wheezing improved in 70% of the participants given Boswellia compared to only 27% of the placebo group. Measurements of lung function also improved in the patients given Boswellia and eosinophilia was reduced.

Due to the connection between GERD and asthma and the finding that stomach acid is low in asthmatics, some clinicians have successfully used hydrochloric acid in asthma patients, indicating there may be justification for its use. (16) Moreover, in some people with asthma, aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) can trigger an attack, so avoiding this class of drugs is important. (16) By blocking the cyclooxygenase enzyme, NSAIDs lead to production of leukotrienes, which in turn promote inflammation and bronchial constriction. (16) Dehydration may also play a role in asthma symptoms. (78) Cautioning asthma patients to stay well-hydrated is therefore important. Acupuncture, biofeedback, yoga breathing, and chiropractic care may offer other solutions. (16)

Chronic Obstructive Pulmonary Disease. Dietary supplements can offer support to COPD patients. Carotenoids and vitamins D and E help suppress lung injury after pollution exposure. (79) Furthermore, nitric oxide (NO) modulates lung function and low serum NO concentrations are associated with COPD severity. (80) This indicates that NO-balancing supplements such as L-citrulline and beetroot juice may be beneficial.

Additionally, NAC may be beneficial in COPD. In patients with COPD who were at high risk for exacerbations, a randomized, placebo-controlled trial showed that 600 mg twice per day of NAC was associated with a reduction in exacerbations and increased the time to the first exacerbation. (81) In another trial, Chinese patients with moderate-to-severe COPD given 600 mg of NAC twice daily for a year experienced a reduced number of exacerbations, especially in the patients with moderate disease severity. (82)

Conclusion

Our lungs are vulnerable to an onslaught of toxins including cigarette smoke and indoor and outdoor pollution. Lung disorders can seriously affect quality of life and in the case of idiopathic pulmonary fibrosis significantly increase mortality. Incorporating specific nutraceuticals into the regimens of patients with pulmonary concerns and in some cases implementing lifestyle solutions can have a beneficial impact on lung health.

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by Chris D. Meletis, ND, and Kimberly Wilkes

Dr. Chris D. Meletis is an educator, international author, and lecturer. His personal mission is "Changing America's Health One Person at a Time." He believes that when people become educated about their bodies, that is the moment when true change and wellness begins. Dr. Meletis served as dean of naturopathic medicine and chief medical officer for 7 years at National College of Natural Medicine (NCNM) and was awarded the 2003 Physician of the Year award by the American Association of Naturopathic Physicians.

www.DrMeletis.com

Kimberly Wilkes is a freelance writer specializing in health, science, nutrition, and complementary medicine. She has written more than 300 articles covering a variety of topics from the dangers of homocysteine to sugar's damaging effects on the heart. She is the editor of ProThera[R] Inc.'s practitioner newsletter and enjoys scouring the medical literature to find the latest health-related science.
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Date:Apr 1, 2019
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