Pulmonary Fibrosis
What is Pulmonary Fibrosis?
With each inhalation, air travels through two tubes called bronchi into the left and right lung. Within each lung, the
bronchi branches into thousands of smaller airways, or bronchioles, and then even further, splitting into millions of
tiny air sacs called alveoli. Oxygen exchange occurs within the alveoli. Each air sac is lined with a paper-thin membrane
(interstitium) and surrounded by capillaries. As air enters the alveoli, oxygen is absorbed through the membrane and
into the blood stream. Carbon dioxide, a waste product of metabolism, is removed.
In pulmonary fibrosis, microscopic damage to the alveoli causes inflammation and the development of fibrous scar
tissue on the interstitium. This scar tissue changes the anatomy of the air sacs, transforming them from being highly
elastic to stiff and thick, causing restriction to the flow of oxygen into the blood. This abnormal scarring is permanent,
and improper inflammatory responses do not regulate the amount of fibrin deposited on the affected sites.1
While scarring mechanisms are vital for proper healing, the uncontrolled deposition of fibrin and formation of scar
tissue around the alveoli is detrimental, even lethal. In humans, plasmin functions as the body’s natural fibrindegrading enzyme, circulating in the blood as plasminogen until activated. In most people, less plasminogen is
produced by the body over time. Research indicates that patients with pulmonary fibrosis not only produce less
plasminogen, but also have excessive amounts of plasminogen activator inhibitor-1 (PAI-1)2. PAI-1 prevents the
conversion of the enzyme precursor plasminogen into plasmin, drastically reducing the body’s innate ability to dissolve
fibrin.
Furthermore, excess fibrin can prevent other protective mechanisms from functioning properly. New blood vessels,
formed to increase oxygen delivery, are obstructed by the scar tissue. This progression limits the amount of oxygen
that reaches the brain and other organs, which may lead to more serious problems.3
Pulmonary Fibrosis Causes and Risk Factors
There are about 100 types of interstitial lung diseases (ILD) with similar characteristics which can result in lung scarring.
This scarring is referred to as Pulmonary Fibrosis. Sometimes the scarring can be linked to a particular cause, such as
environmental factors or radiation; however, many times no known cause can be identified. When no cause can be
identified, the condition is called idiopathic pulmonary fibrosis (IPF).1
Hundreds of factors have been recognized to cause lung damage that can lead to pulmonary fibrosis. The most
common causes include:
-
Occupational or environmental exposures: metal or wood dust, pesticides, asbestos, silica dust, etc.
Radiation: ionizing radiation used to treat tumors of the chest
Medications: certain chemotherapy drugs, antiarrhythmic drugs, psychiatric drugs or antibiotics
Acid reflux disease or GERD
Other medical conditions: lung infections such as pneumonia or tuberculosis; chronic inflammatory conditions
such as rheumatoid arthritis, sarcoidosis, etc.
Additional risk factors which can make someone more susceptible to idiopathic pulmonary fibrosis include:
-
Cigarette smoking
-
Viral infection
A family history of pulmonary fibrosis
Pulmonary Fibrosis Symptoms
The most common symptoms of pulmonary fibrosis include:
-
Shortness of breath
A dry cough
Diminished exercise tolerance
Fatigue
Unexplained weight loss
Chest discomfort
Clubbing, or enlargement of the ends of the fingers due to a buildup of tissue
Often times, symptoms do not appear until the disease state advances and scarring has already occurred. The severity
of symptoms and their worsening over time can vary and are at least partially dependent on the cause of the
interstitial fibrosis.
Pulmonary Fibrosis Complications and Prognosis
The progression of pulmonary fibrosis and the severity of symptoms can vary significantly from person to person.
While some maintain moderate symptoms that gradually worsen over months or years, others may become severely ill
quickly. The average life expectancy after diagnosis is 3 years.
As inflammation persists and scar tissue continues to build up around the alveoli, the exchange of gases lessens and
oxygen levels in the blood decrease.4 As pulmonary fibrosis worsens, low blood oxygen levels, or hypoxemia, can lead
to many other serious conditions, which may include:
-
Chronic hypoxemia: low blood oxygen level
Pneumothorax: collection of air in chest cavity surrounding lungs
Polycythemia: abnormally high levels of red blood cells
Pulmonary hypertension: elevated pressure in pulmonary artery, which carries blood from the heart to the
lungs
Cor pulmonale: failure of the right side of the heart
Respiratory failure
Additionally, some evidence suggests those with pulmonary fibrosis are at greater risk of developing a pulmonary
embolism, or a blood clot which travels to the lungs. Blood thinning therapy may be recommended.
Pulmonary Fibrosis Treatment
Pulmonary fibrosis causes permanent scarring on the lungs, limiting treatment options. There is no medication or
procedure available to remove scarring, and no known cure for idiopathic pulmonary fibrosis.1,2 However, some
treatments are available to help alleviate or improve symptoms, slow the progression of disease and improve quality
of life.
The pathology of some lung diseases presenting interstitial fibrosis is linked to the body’s inflammatory response
mechanisms. Hence, immunosuppressant drugs, such as Prednisone, are sometimes prescribed to reduce the
processes leading to fibrosis.3 Immunosuppressant drugs, however, carry the possibility of contracting very serious side
effects, including skin cancer, lymphoma, diabetes and glaucoma. The use of corticosteroids and immunosuppressant
medications does not seem to show improvement in those with idiopathic pulmonary fibrosis.1
Lung transplantation remains a last resort for those with advanced pulmonary fibrosis.
Other treatment options such as oxygen therapy and lung rehabilitation are available to help with ease of living with
pulmonary fibrosis. Both therapies are designed to improve the amount of oxygen taken in and help prevent or lessen
complications from low blood-oxygen levels.
References:
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3.
4.
Katzenstein AL, Myers JL. Idiopathic pulmonary fibrosis: clinical relevance of pathologic classification. Am J Respir Crit Care Med. 1998;
157:1301-1315.
Idell S, et al. Local abnormalities in coagulation and fibrinolytic pathways predispose to alveolar fibrin deposition in the adult
respiratory distress syndrome. J Clin Invest. 1989; 84(2):695-705.
Crystal RG, Bitterman PB, Mossman B, et al. Future research directions in idiopathic pulmonary fibrosis: summary of a national heart,
lung, and blood institute working group. Am J Respir Crit Care Med. 2002; 166:236-246.
Bals R, Hiemstra PS. Innate immunity in the lung: how epithelial cells fight against respiratory pathogens. Eur Respir J. 2004; 23(2):327333.
The contents of inflammation-systemicenzymes.com website, including images, graphics, text and other material, are for informational purposes
only. The Content on the site is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of
your healthcare professional with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay
in seeking it because of something you have read on the inflammation-systemicenzymes.com website. If you think you may have a medical
emergency, call your doctor or 911 immediately.
Pulmonary Fibrosis and Systemic Enzymes
Limited treatment options and a bleak prognosis have led to an increasing use of systemic enzyme therapy as a means
to alleviate symptoms and improve quality of life. Certain proteolytic (protein digesting) enzymes have been identified
to have extremely beneficial actions when applied to the inflammation and fibrin buildup related to this condition.
Systemic enzymes, typically taken orally and on an empty stomach, enter directly into the blood stream. Enzymes can
then circulate throughout the body, acting upon complexes in the blood as well as in tissues and organs.
Pulmonary Fibrosis and Scar Tissue
Supplementing with fibrinolytic (fibrin digesting) enzymes can be beneficial in limiting and even reducing the amount
of scar tissue. The most notable fibrinolytic enzymes are nattokinase, an enzyme extracted from the Japanese
fermented soybean food Nattō, and serrapeptase, an enzyme extracted from silkworms.1,2
Nattokinase is particularly effective because it enhances the body's natural ability to fight excess fibrin deposits in
several different ways. It dissolves fibrin directly and appears to enhance the body's natural production of both
plasmin and other clot-dissolving enzymes such as urokinase. An in vivo study was undertaken to demonstrate the
thrombolytic activity of nattokinase, plasmin and elastase on an induced clot in the common carotid artery of
laboratory rats. The results indicate that the thrombolytic activity of nattokinase is stronger than that of plasmin or
elastase in vivo in this model.3 Nattokinase appears to reduce the formation of dangerous clots and inhibit arterial
thickening, not only by direct fibrinolysis of clots but also by inhibition of the plasma protein plasminogen activator
inhibitor.4
The efficacy of serrapeptase was evaluated in a multicenter, double-blind, placebo-controlled study of 193 subjects
suffering from acute or chronic ear, nose or throat disorders. After 3-4 days' treatment, significant symptom regression
was observed in serrapeptase treated patients. Statistical comparison confirmed the greater efficacy of serrapeptase
against all the symptoms examined. It was concluded that serrapeptase has anti-inflammatory, anti-edemic and
fibrinolytic activity and acts rapidly on localized inflammation.5
Pulmonary Fibrosis and Inflammation
Reducing the amount of fibrin is only one aspect of how systemic enzymes can function. Chronic inflammation is often
the root cause of a number of conditions and controlling the process can help alleviate symptoms.
One research trial in Japan investigated the effect of serrapeptase on sputum properties and symptoms in patients
with chronic airway diseases. After 4 weeks of serrapeptase treatment, sputum output, viscosity and sputum
neutrophil count decreased significantly. In addition, the frequency of coughing and of expectoration also decreased.
The researchers concluded serrapeptase may exert a beneficial effect on mucus clearance by reducing neutrophil
(white blood cell) numbers and altering the viscoelasticity of sputum in patients with chronic airway diseases.6
Research on nattokinase demonstrates the enzyme may help avoid or reduce the likelihood of deep vein thrombosis,
cardiac infarction, pulmonary emboli and stroke. Nattokinase appears to accomplish this via its fibrinolytic, antiinflammatory and modulating effect on blood pressure. Studies on hypertension demonstrate an average drop of
10.9% in Systolic Blood Pressure and a 9.7 percent drop in Diastolic Blood Pressure.7,8,9
Bromelain, a proteolytic enzyme extracted from pineapple, has also been found effective in reducing inflammation by
blocking chemical signals called cytokines which promote and increase inflammation.10,11 Research has shown that
bromelain disrupts the migration of neutrophils to an inflamed area, where they would otherwise propagate the
process. One study measured a 50-85% decrease in the migration of neutrophils after bromelain treatment.12
Researchers hypothesize neutrophils contribute to the onset of idiopathic pulmonary fibrosis.13 Another study
investigating lung injury in mice due to asthma displayed a qualitative reduction in pulmonary injury after taking oral
bromelain.11
Pulmonary Fibrosis and Blood Cleansing
Blood viscosity is an important consideration when assessing blood pressure concerns which arise during disease
progression. Studies suggest enzymes such as nattokinase can help reduce red blood cell aggregation and improve flow
rates.14 Serrapeptase has demonstrated the ability to cleanse blood by removing excess fibrin from circulation, thus
reducing blood stickiness and the threat of blood clot formation. Additionally, toxic substances and remnant food
particles can be further degraded in the blood by serrapeptase, and prepared for filtration through the liver and
expulsion.15
References:
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12.
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14.
15.
Fujita M, Nomura K, Hong K, et al. Purification and characterization of a strong fibrinolytic enzyme (nattokinase) in the vegetable
cheese natto, a popular soybean fermented food in Japan. Biochem Biophys Res Commun. 1993; 197:1340-1347.
Moriya N, Nakata M, Nakamura M, et al. Intestinal absorption of serrapeptase (TSP) in rats. Biotechnol Appl Biochem. 1994; 20(1):101108.
Fujita M, Hong K, Ito Y, et al. Thrombolytic Effect of Nattokinase on a Chemically Induced Thrombosis Model in Rat. Biol Pharm Bull.
1995; 18(10):1387-1391.
Hiroyuki S, Tomohiro S, Chieko Y, Yasutaka K. Determination and Properties of the Fibrinolysis Accelerating Substance (FAS) in Japanese
Fermented Soybean "Natto". Nippon Nogeikagaku Kaishi. 2000; 74(11):1259-1264.
Mazzone A, Catalani M, Costanzo M, et al. Evaluation of Serratia peptidase in acute or chronic inflammation of otorhinolaryngology
pathology: a multicentre, double-blind, randomized trial versus placebo. J Int Med Res. 1990; 18(5):379-88.
Nakamura S, Hashimoto Y, Mikami M, et al. Effect of the proteolytic enzyme serrapeptase in patients with chronic airway disease.
Respirology. 2003; 8(3):316-20.
Prevent Heart Attack and Stroke with Potent Enzyme that Dissolves Deadly Blood Clots in Hours. Health Sciences Institute, 2002.
Maruyama M, Sumi H. Effect of Natto Diet on Blood Pressure. JTTAS, 1995.
Kim JY, Gum SN, Paik JK. Effects of Nattokinase on Blood Pressure: A Randomized, Controlled Trial. Hypertension Research. 2008;
31:1583–1588.
Onken JE, Greer PK, Calingaert B, et al. Bromelain treatment decreases secretion of pro-inflammatory cytokines and chemokines by
colon biopsies in vitro. Clin Immunol. 2008; 126(3):345-352.
Secor ER, Carson WF, Singh A, et al. Oral bromelain attenuates inflammation in an ovalbumin-induced murine model of asthma. Evid
Based Complement Alternat Med. 2008; 5(1):61-69.
Fitzhugh DJ, Shan S, Dewhirst MW et al. Bromelain treatment decreases neutrophil migration to sites of inflammation. Clin Immunol.
2008; 128:66-74.
Mukae H, Iiboshi H, Nakazato M, et al. Raised plasma concentration of alpha-defensins in patients with idiopathic pulmonary fibrosis.
Thorax. 2002; 57:623-628.
Pais E, Alexy T, Holsworth RE, Meiselman HJ. Effects of nattokinase, a pro-fibrinolytic enzyme, on red blood cell aggregation and whole
blood viscosity. Clin Hemorheol Microcirc. 2006; 35(1-2):139-42.
Ernst E., Matrai A. Oral Therapy with proteolytic enzymes for modifying blood rheology. Klin Wschr. 1987; 65:994.
The contents of inflammation-systemicenzymes.com website, including images, graphics, text and other material, are for informational purposes
only. The Content on the site is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of
your healthcare professional with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay
in seeking it because of something you have read on the inflammation-systemicenzymes.com website. If you think you may have a medical
emergency, call your doctor or 911 immediately.