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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.
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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 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 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 α1-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
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