Idiopathic Pulmonary Fibrosis

Sally Sanchez

Philadelphia College of Osteopathic Medicine

Abstract

Idiopathic pulmonary fibrosis (IPF) is a respiratory disease that is rare and, effects 13 to 20 per 100,000 people.  Researchers noted that prevalence and incidence rates have risen over the last decades.  IPF is considered to be a chronic condition that impacts lung tissue and respiratory abilities.  The disease is known to be more prevalent amongst the elderly, as it typically effects people ages 50 and older.  The process of fibrosis causes irreversible damage, and physical changes to the structure of the lungs.  Patients with IPF generally present with increase dyspnea, persistent and uncontrollable dry cough, fatigue, and finger clubbing.  There are significant risk factors that increase the risk to develop IPF including smoking, exposure to environmental toxins, genetic factors, viral infections, and more.  Pirfenidone and nintedanib contain anti-fibrotic qualities that assist in the preservation of healthy lung tissue.  Quality of life is severely impacted by IPF and, many IPF patients present with signs of depression and/or anxiety.  Future research studies should focus extensively on identifying any epigenetic considerations that may lead to the production of fibrosis in the lungs.

Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a respiratory disease that is rare and, effects 13 to 20 per 100,000 people (U.S. Department of Health & Human Services, 2019).  The National Institute of Health (NIH) (2019), estimated that in the United States, there are approximately 100,000 people affected by IPF.  Additionally, the NIH (2019), determined that there are between 30,000 and 40,000 new cases of IPF diagnosed each year.  Although researchers have considered IPF to be a rare disease, they noted that prevalence and incidence rates have risen over the last decades (Sauleda, Nuñez, Sala, & Soriano, 2018).  Lipsi et al., (2018) reported similar findings regarding prevalence rates; however, they mentioned that incidence rates remained constant.  Researchers indicated that prevalence and incidence rates are higher amongst males (Sauleda et el., 2018).  Moreover, IPF is known to be a disease that is more prevalent amongst the elderly, as it typically effects people ages 50 and above (Sauleda et al., 2018; U.S. Department of Health & Human Services, 2019).

IPF is considered to be a chronic condition that impacts lung tissue and respiratory abilities (U.S. Department of Health & Human Services, 2019).  Although there have been several risk factors identified as potential contributors to the development of IPF, it has not been attributed to a direct cause (Sauleda et al., 2018).  Moreover, IPF has been associated with a high mortality rate and, very poor prognosis (Lipsi et al., 2018; Swigris, Brown, Make, & Wambolt, 2008).  The progression of the disease involves limited abilities to deliver oxygen to parts of the body and, ultimately leads to death (Vega-Olivo & Criner, 2018).  Patients diagnosed with IPF live for an average of 2 to 5 years after being diagnosed with IPF (Lipsi et al., 2018; Sauleda et el., 2018; Swigris et al., 2008).  The poor prognosis and high mortality rate are not only attributed to a lack of cure, but also to a lack of effective pharmacological treatment options (Sauleda et al., 2018).

What is Idiopathic Pulmonary Fibrosis?

IPF is deemed to be the most prevalent subtype of idiopathic interstitial pneumonias (Lipsi et al., 2018; Sauleda et el., 2018; Swigris et al., 2008).  Interstitial pneumonias belong to a broader category of disease known as interstitial lung diseases (Swigris et al., 2008).  One of the essential features of interstitial lung disease is the scarring of lung tissue (Lipsi et al., 2018).  Throughout the development of IPF, lung tissue becomes thick and tough which often leads to the formation of scar tissue in the lungs (U.S. Department of Health & Human Services, 2019).  The scarring is considered to be the fibrosis (U.S. Department of Health & Human Services, 2019).

Fibrosis is defined as, “The overgrowth, hardening and/or scarring of various tissues and is attributed to excess deposition of extracellular matrix components including collagen” (Wynn, 2008, p. 199).  According to researchers, IPF is a byproduct of altered healing processes that occur during the cycle of cell damage and repair, specifically in the lungs (U.S. Department of Health & Human Services, 2019).  The result is, the formation of scar tissue that prevents the lungs from accomplishing its main function of delivering oxygen to other areas of the body (U.S. Department of Health & Human Services, 2019).  In essence, IPF makes it very difficult to breathe, as oxygen does not pass through the thick walls of the alveoli with ease (Kolahian, Fernandez, Eickelberg, & Hartl, 2016).  The fibrosis prevents the oxygen in the lungs from fluently passing through the cell walls and, into the thin blood vessels that surround the cells (Kolahian et al., 2016).

There are a number of events that must occur in order for IPF to develop.  There must be a presence of an abnormal tissue healing process in the lungs as well as, constant microinjuries to the alveoli (Todd, Luzina, & Atamas, 2012).  This leads to an excessive deposition of extracellular matrix components which include hyaluronan, fibronectin, and interstitial collagens which ultimately compromise gas exchange abilities at the cellular level (Todd, Luzina, & Atamas, 2012).  The process causes irreversible damage to the lungs as well as physical changes to the structure of the lungs (Kolahian et al., 2016).

Patients with IPF generally present with increase dyspnea or difficulty breathing (Ryu et al., 2014).  Other symptoms include dyspnoea or shortness of the breath and persistent and uncontrollable dry cough, and finger clubbing (Ryu et al., 2014; Swigris et al., 2008; U.S. Department of Health & Human Services, 2019).  Patients may also present with fatigue, fevers, and weight loss as a result of the progressive respiratory failure (Ryu et al., 2014).  It is also common to observe declines in walking distance when completing a 6-minute walk test (Vega-Olivo & Criner, 2018).  Furthermore, patients with IPF often complain about sleeping difficulties (as breathing may become difficult even at rest), gastrointestinal problems, anxiety, and depression (Vega-Olivo & Criner, 2018).  Researchers have noted that the presentation of IPF can be very similar to the presentation of other respiratory diseases and can be comorbid with other conditions such as emphysema, pulmonary hypertension, and lung cancer amongst others (Ryu et al., 2014).  Comparably, Vega-Olivo and Criner (2018) discussed the importance of ruling out other respiratory disorders before diagnosing IPF.

Diagnostic

Vega-Olivo and Criner (2018) encouraged the use of a multidisciplinary framework when working with a patient who is suspected to have IPF.  They highlighted the benefits of working collaboratively in order to reliably diagnose IPF.  Typically, high resolution computed tomography (HRCT) scans allow physicians to screen for recognizable patterns of usual interstitial pneumonia (UIP) (Vega-Olivo & Criner, 2018).  HRCT scans help physicians and diagnostic teams view distinguishable patterns that are similar to the pattern of a honeycomb (U.S. Department of Health & Human Services, 2019).  Whereas some researchers consider that a HRCT scan is sufficient to fulfill a diagnosis of IPF (Vega-Olivo & Criner, 2018), others consider that HRCT scans can conceal IPF (Lipsi et al., 2018).  It was noted that honeycombing may only be observed in the upper lungs although a majority of the damage may be in the periphery of the lungs (Lipsi et al., 2018).  Therefore, Lipsi et al., (2018) suggest that a lung biopsy is required to make a diagnosis of IPF.

Causes and Risk Factors

Researchers have not yet found a direct cause of IPF (Ryu et al., 2014).  Idiopathic is a term used to describe disease that do not have a direct cause.  Although researchers have not yet found a direct cause of IPF, many factors have been linked to the development of IPF (Ryu et al., 2014).  Researchers have found relationships between IPF and smoking, exposure to environmental toxins, pharmacological therapies, respiratory disease, medical conditions, viral infections, autoimmune disorders, genetic mutations, and more (Kolahian et al., 2016; Ryu et al., 2014; Vega-Olivo & Criner, 2018).  Amongst the most profound contributions are genetic factors and exposure to environmental pollutants (Li et al., 2019; Renzoni, Srihari, & Sestini, 2014; Ryu et al., 2014).

Multiple researchers have referenced the role of genetics in the development of IPF (Kolahian et al., 2016; Ryu et al., 2014; Vega-Olivo & Criner, 2018).  Kolhian et al., (2016) reported that the gene MUC5B is highly correlated with IPV.  Ryu et al., 2014 discussed that the MUC5B gene is present in almost 40% of patients with IPV.  Researchers believe that MUC5B is related to a higher chance of survival and, it is hypothesized that MUC5B may actually decrease the rate of advancement of IPF (Renzoni, Drihari, & Sestini, 2014; Ryu et al., 2018).  Additionally, researchers have noted that particular chromosomes suffer structural damage as they are observed to have shorter telomeres, specifically AEC1 and AEC2 (Richeldi, Collard, and Jones, 2017).  AEC1 and AEC2 are suspected to be instrumental in the development of fibrosis and restructuring of the lungs (Richeldi, Collard, and Jones, 2017).  Overall, researchers have proposed that IPF is a byproduct of an interplay between genetics and exposure to environmental toxins (Renzoni, Srihari, & Sestini, 2014).

Scientists have largely credited exposure to environmental toxins as a prime factor in the etiology of IPF (Li et al., 2019; Renzoni, Drihari, & Sestini, 2014;


Richeldi, Collard, and Jones, 2017; Ryu et al., 2018).  Exposure to metals, silica, and wood dust have been linked to IPF (Richeldi, Collard, and Jones, 2017).  Moreover, researchers examined the incidence of IPF in world trade center respondents who were exposed to high levels of environmental toxins that have been linked to IPF (Li et al., 2019).  The findings indicated that first respondents who were exposed to environmental toxins from 9/11, had a higher incidence rate than non-respondents (Li et al., 2019).  Additionally, older age groups, males, and smokers were more likely to develop IPF (Li et al., 2019).  Overall exposure to environmental toxins from 9/11 was a significant factor in the development of IPF.  Li et al., (2019) hypothesize that exposure to metals, alkaline, silica, and wood dust may have triggered inflammatory responses in the cell.  Scientists propose that the inflammatory responses may have triggered abnormal healing processes, which may have led to the development of IPF (Li et al., 2019).  Other studies should continue to investigate how exposure to environmental toxins may have influenced the development of IPF.

Treatment

Over the years, treatment options for IPF have been scarce and limited (Lipsi et al., 2018).  However, researchers have explored the use of pharmacological options such as pirfenidone and nintedanib (Lipsi et al., 2018; Vega-Olivo & Criner, 2018).  Although the medications that are currently available are not intended to cure IPF, they have been found to be effective at limiting the advancement of IPF (Lipsi et al., 2018).  Pirfenidone and nintedanib contain anti-fibrotic qualities that assist in the preservation of healthy lung tissue and ultimately prolong lung functioning (Lipsi et al., 2018).  Vega-Olivo and Criner (2018) noted that there are minimal differences between each drug’s effectiveness in treating IPF.  Vega-Olivo and Criner (2018), advise that treatment of IPF should be guided by the current stage of IPF.  Patients with severe IPF experiencing the last stages of the disease may resort to other treatment modalities such as oxygen therapy to increase oxygen levels, lung transplant, or palliative care (Lipsi et al., 2018).  Oxygen therapy alleviates dyspnea and increases quality of life (Vega-Olivo & Criner, 2018).  In relation to accessibility, oxygen therapy may be more accessible than lung transplants as lung transplants often involve waiting lists, require patients to complete multiple examinations, and can require patients to wait long periods of time (Akhtar, Ali, & Smith, 2013).

Impact on Quality of Life

Patients with IPF are very limited with the activities that they can engage in due to the symptoms presented in IPF (Swigris et al., 2008).  Patients with IPF often present with difficulty breathing upon exertion (Swigris et al., 2008).  Throughout the progression of the disease, breathing becomes difficult even at rest.  According to Swigris et al., (2008) patients with IPF reported having to pace themselves during physical activities, needing to rest more often, and required more time to recover after completing an activity that requires energy (Swigris et al., 2008).  Moreover, oxygen therapy can be a barrier to engaging in pleasurable activities and hobbies if the patient is confined to carrying a large oxygen tank along with him or her.

Swigris et al., (2008) noted that the limitations presented with IPF, can be accompanied with symptoms associated with depression and/or anxiety.  Investigators who examined the relationship between IPF and depression discovered that symptoms of depression were prevalent in almost 50% of the participants (Akhtar, Ali, & Smith, 2013).  Multiple researchers attribute the depression symptoms to the changes in daily living and, they noted that IPF has multiple social and psychological implications (Akhtar, Ali, & Smith, 2013).  Akhtar, Ali, and Smith (2013) recommend that patients with IPF be screened for depression.

Conclusion

IPF is a chronic respiratory condition that severely affects the elderly and is more common amongst males.  Researchers estimated that the prevalence and incidence rates of IPF has increased throughout the years (Sauleda et al., 2018).  IPF is characterized by fibrosis in the lungs, which prevent the lungs from carrying out their responsibilities.  Overtime, the respiratory disease leads to respiratory failure, and ultimately death.  Researchers have mentioned that several factors play a key role in the development of IPF.  Such factors include genetic factors, environmental factors, and comorbidity with other disorders (Li et al., 2019; Renzoni, Drihari, & Sestini, 2014; Richeldi, Collard, and Jones, 2017; Ryu et al., 2018).  Specific genes have been identified and, thought to be involved in the development of IPF (Li et al., 2019).

It has also been noted that exposure to metals, wood dust, silica, and other toxins plays a pivotal role in the development of IPF (Li et al., 2019).  Although there have been multiple studies exploring IPF, more research is needed to clearly understand the underlying markers of IPF.  Future research studies should focus extensively on identifying any epigenetic considerations that may lead to the production of fibrosis in the lungs, in attempts to identify the genesis of IPF.  Superior treatment modalities for IPF can significantly enhance the life of patients with IPF as currently, there is no cure for IPF (Ryu et al., 2014).   Systematic investigations evaluating the origin of IPF can lead to better treatment modalities and, essentially better treatment outcomes for patients with IPF.

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