Pulmonary Fibrosis

Original Editor - Lydia Xenou

Top Contributors - Alfred Chan, Jenna Aiuto, Lydia Xenou, Evan Thomas and Michelle Lee  

Definition

Pulmonary Fibrosis (PF) describes a condition in which the lung tissue becomes thickened, stiff, and scarred. The medical terminology used to describe this scar tissue is fibrosis. The alveoli and the blood vessels within the lungs are responsible for delivering oxygen to the body, including the brain, heart, and other organs. As lung tissue becomes scarred and thicker, it is more difficult for the lungs to transfer oxygen into the bloodstream. As a result, the brain, heart, and other organs do not get the oxygen they need to function properly. In some cases, doctors can determine the cause of the fibrosis, but in many cases the cause remains unknown. When there is no known cause for the development of pulmonary fibrosis (and certain radiographic and/or pathologic criteria are met), the disease is called idiopathic pulmonary fibrosis or IPF. More specifically, consensus treatment guidelines from international lung societies define IPF as “a specific form of chronic, progressive fibrosing interstitial pneumonia of unknown cause, occurring primarily in older adults, limited to the lungs, and associated with the histopathologic and/or radiologic pattern of UIP [usual interstitial pneumonia]

Normal Lung vs Lung affected by IPF


The confirmation of diagnosis of PF involves the exclusion of other IPP's and interstitial lung disease that may be caused or associated with drug use, environmental exposure, or other systematic diseases. [1] The diagnois of this disease requires the use of a multidisciplinary team which will include pulmonologists, radiologists, and pathologists. [1]

If there is a clear association with another illness or the lung fibrosis is the result of a side effect from a medication or an exposure to an agent known to cause PF, then the cause of the disease is no longer considered idiopathic. PF clearly associated with another disease, such as scleroderma or rheumatoid arthritis, would be referred to as pulmonary fibrosis secondary to scleroderma or secondary to rheumatoid arthritis.[2]

Idiopathic pulmonary fibrosis portends a poor prognosis, with an estimated mean survival of 2-5 years from the time of diagnosis.Estimated mortality rates are 64.3 deaths per million in men and 58.4 deaths per million in women.[3] The most common cause of death associated with PF is respiratory failure and will account for an estimated 80% of all fatalities associated with the disease. Other causes of death are likely to be heart failure and disease, bronchogenic carcinoma, ischemic heart disease, infections, as well as pulmonary embolism. [4]

Signs and Symtoms

Individuals with long term Idiopathic Pulmonary Fibrosis (IPF) may not show any symptoms but as scarring continues to progress within the lungs, patient might have:

  • Diffculity in breathing (Dyspnea)
  • An unproductive cough that is persistent
  • Shortness of breath (especially when engaging in activities such as walking)
  • Greater levels of fatigue
  • low-grade fevers
  • Muscular pain (myalgias)
  • Joint pain (arthralgias)
  • Unexplained weight loss
  • Clubbing in fingers and toes

Epidemiology

There are no reliable data to determine how many people are affected by PF, possibly due to the large number of conditions under which it can arise.

According to the ATS, the incidence of IPF was estimated at 10.7 cases per 100,000 per year for men and 7.4 cases per 100,000 per year for women in a population-based study from the county of Bernalillo, New Mexico. A study from the United Kingdom reported an overall incidence rate of only 4.6 per 100,000 person-years, but estimated that the incidence of IPF increased by 11% annually between 1991 and 2003. This increase was not felt to be attributable to the aging of the population or increased ascertainment of milder cases. A third study from the United States estimated the incidence of IPF to be between 6.8 and 16.3 per 100,000 persons using a large database of healthcare claims in a health plan.

Prevalence estimates for IPF have varied from 2 to 29 casesper 100,000 in the general population. The wide range in these numbers is likely explained by the previous lack of uniform definition used in identifying cases of IPF, as well as by differences in study designs and populations. A recent analysis based on healthcare claims data of a large health plan in the United States yielded a prevalence estimate of between 14.0 and 42.7 per 100,000 persons depending on the case definition used. It is unknown if the incidence and prevalence of IPF are
influenced by geographic, ethnic, cultural, or racial factors.[5] Studies have shown a higher overall prevalence of the disease among men compared to women, but the cause of this correlation is unknown. [4]

Causes

  • Idiopathic Disorders: Idiopathic Pulmonary Fibrosis(IPF), acute interstitial pneumonia(AIP), idiopathic non-specific interstitial pneumonia(NSIP), sarcoidosis.
  • Connective tissue and Autoimmune disease: Sleroderma/Progressive systemic sclerosis, Lupus, Rheumatoid arthritis(RA), polyomyositis/dermatomyositis.
  • Occupational and Environmental: Inorganic dust, organic dust, gases and fumes, radiation.
  • Drug Induced: Chemotherapeutic agent, radiation therapy, antiarrythmics, antibiotics, anticonvulsants.
  • Infections: Viral and bacterial.
  • Genetic/Inherited: Familial pulmonary fibrosis, Hermansky-Pudlak syndrome.

Other factors associated with the disease is heavy smoking and acid reflux disease(GERD).[2]

Causes.png


Future Research for PF

In patients presenting with PF, the development and progression of the healing response has slipped out of control, disrupting many delicate cycles occuring in the body's respiratory system. Although there are a number of compensatory and redundant processes which occur in the body to contribute to proficient healing and remodeling, there is a lack of therapeutic intervention and new therapies to treat the diease. Further studies are required to understand the role of chemical mediators in patients presenting with PF, so that theraputic interventions can be progressed in years to come to limit the burden of this prevalent health condition. [6]

Pathophysiology

The pathogenesis of IPF has been heavily debated among health professionals, yet two main considerations for the pathology of this disease have been widely recognized.

1.) The involvement of an inflammatory stimulus is involved, with recurring inflammation leading to immunopathology, tissue destruction and the propagation of a wound-healing response

2.)The initial or absent inflammatory stage is quickly followed by an uncontrolled wound-healing response

Controversy surrounding the pathogenesis of IPF reflects the lack of understanding among health professionals to understand the complexity and depth of this condition.  [6]

Although the pathologial mechanism involved in PF is still unclear, health professionals recognize that the the condition appears to involve the cells that line the tiny air sacs in the lungs (alveoli). These are called alveolar epithelial cells (AECs).
In IPF, these cells appear to become damaged and begin to die. The body tries to repair the damage by releasing another type of cell known as fibroblasts. The production of these fibroblasts goes out of control and they cause scarring and hardening (fibrosis) of the delicate tissues of the lungs. This leads to difficulty of expansion of the lung tissue- making breathing difficult in the affected patient. The lung tissue also has issues transferring oxygen to the rest of the body.
As this scarring gets worse the lungs find it even more difficult to work properly, resulting in the rest of the symptoms of IPF. The reason the AECs become damaged in the first place is still unknown. [7]


The alveoli in your lungs are responsible for gas exchange- they move oxygen to the capillaries and pick up carbon dioxide from the blood to the breathed out. Due to the scarring of the lung tissue in IPF, this process can not be carried out properly. This leads to the many symptoms of IPF including shortness of breath and a dry cough. [8]

How fibrosis in IPF affects the air sacs in your lungs


Diagnostic Procedures

  • Laboratory studies: Reportedly, up to 30% of patients with idiopathic pulmonary fibrosis (IPF) have positive tests for antinuclear antibodies or rheumatoid factor; however, these titers are generally not high.
  • Chest Radiography: The typical findings are peripheral reticular opacities (netlike linear and curvilinear densities) predominantly at the lung bases (see image below). Honeycombing (coarse reticular pattern) and lower lobe volume loss can also be seen.
  • High resolution Computing tomography.
  • 6 minute walk test:  Desaturation below the threshold of 88% during the 6MWT has been associated with an increased mortality.
  • Pulmonary function testing: In patients with idiopathic pulmonary fibrosis, a restrictive ventilatory defect is typically present. Vital capacity, functional residual capacity, total lung capacity, and forced vital capacity (FVC) all are reduced. Additionally, the static pressure-volume curve is shifted downward and to the right as a result of decreased lung compliance. Obstructive ventilatory defects are not common; however, if present, they may suggest the coexistence of chronic obstructive pulmonary disease.
  • Bronchoalveolar lavage.
  • Transthoracic echocardiography.
  • Surgical lung biopsy.

In order to diagnose Idiopathic Pulmonary Fibrosis, which is the most common type, the following diagnostic criteria have to be present:

  • The exclusion of other known causes of interstitial lung disease (ILD), including domestic and occupational environmental exposures, connective tissue disease, and drug toxicity.
  • The presence of a UIP pattern on HRCT in patients not subjected to a surgical lung biopsy.
  • Specific combinations of HRCT and surgical lung biopsy pattern in patients subjected to surgical lung biopsy.[3]


Treatment

Treatment courses for pulmonary fibrosis are highly variable and difficult to predict. Each therapy strategy is individualized according to the patient's history and symptoms. 

The pharmacologic treatment options include Cyclophosphamide, Azathioprine, N-acetylcysteine, Pirfenidone. They medications may stabilize their disease and there may be a benefit to continuing usage. Further, some of these medications may be prescribed to manage symptoms when a patient has an acute exacerbation or period of worsening. Medications may be used alone or in combination. Also,  as fibrosis inhibits an adequate transfer of oxygen into the bloodstream, some patients may require supplemental oxygen. This helps to reduce breathlessness, enabling the patient to be more active. Some patients may need oxygen therapy all the time while others may only need it during sleep and exercise. [2]

The non-pharmacologic treatment option is pulmonary rehabilitation. Pulmonary rehabilitation programs involve aerobic conditioning, strength and flexibility training, educational lectures, nutritional interventions, and psychosocial support. Pulmonary rehabilitation has recently been studied in patients with ILD. Two controlled trials of pulmonary rehabilitation in IPF have demonstrated an improvement in walk distance and symptoms or quality of life. Other uncontrolled studies have found similar findings. The beneficial effects of pulmonary rehabilitation may be more pronounced in patients with worse baseline functional status. Pulmonary rehabilitation may not be reasonable in a minority.[5]

Lung transplantation for Idiopathic Pulmonary Fibrosis patients confer a survival benefit over medical therapy. Due to the use of the Lung Allocation Score(LAS) IPF has now replaces COPD as the most common indication for lung transplantation in the United States.[3]

Prevention

Due to the unknown cause of idiopathic pulmonary fibrosis, prevention of the respiratory disease is difficult. Higher prevalence of the disease is attributed with certain family genetics and cigarette smokers. As such, a physiotherapist can advise patients to avoid or stop smoking in order to decrease the chance of idiopathic pulmonary fibrosis.

Physiotherapy in Pulmonary Fibrosis Management

The goals of physiotherapy management in Pulmonary fibrosis include the following:

  1. Maximize the patient's quality of life, general health and wellbeing.
  2. Educate the patient about PF, self management, ceasing of smoking, prevention of infections.
  3. Optimize alveolar ventilation.
  4. Optimize lung volumes and capacities.
  5. Reduce the work of breathing.
  6. Maximize aerobic capacity and efficiency of oxygen transport.
  7. Optimize physical endurance and exercise capacity.
  8. Optimize general muscle strength and thereby peripheral oxygen extraction.

Patient monitoring includes dyspnea, respiratory distress, breathing pattern(depth and frequency), arterial saturation, heart rate, blood pressure, and rate pressure product. patients with cardiac dysfunction or low arterial oxygen tensions require ECG monitoring, particularly during exercise. Breathlessness is accessed using a modified version of the Borg scale of perceived exertion.

The primary interventions for maximizing cardiopulmonary function and oxygen transport in patients with PF include some combination of education, aerobic exercise, strengthening exercises, chest wall mobility exercises, body positioning, coughing, relaxation techniques, pacing and energy and energy conservation. An ergonomic assessment of home and work environments may be indicated to maximize function in these settings.

Education includes information in preventative health practices, such as removing from the causative environment, flu shots, smoking reduction and cessation, weight control, hydration, relaxation, energy conservation.

During aerobic exercise, patients with PF are prone to arterial desaturation. Patients who desaturate during sleep, require supplemental oxygen during exercise. [9]

Multidisciplinary Team in Pulmonary Fibrosis Management 

General Practitioner

  • Manage and educate patients with comorbid medical conditions associated with idiopathic pulmonary fibrosis.
  • These conditions include:

o Chronic Obstructive Pulmonary Disease
o Obstructive Sleep Apnea
o Gastroesophageal Reflux Disease
o Coronary Artery Disease

  • Encourage idiopathic pulmonary fibrosis patients to take vaccination against influenza and pneumococcal infections

Surgeon

  • Evaluate patients with idiopathic pulmonary fibrosis and determine whether they require lung transplantation .
  • Evaluation guidelines is based on:

o a diffusion capacity of carbon monoxide (DLCO) less than 39%
o a 10% or greater decrement in forced vital capacity during six months of follow-up
o a decrease in pulse oximetry below 88% during a 6-minute walk test (6MWT)
o honeycombing on high-resolution computed tomography (HRCT) imaging with a fibrosis score of less than 2

  • Establish an operational waiting list using the Lung Allocation Score (LAS) that prioritize patients based on the difference between post-transplant 1-year survival and pre-transplant urgency.[10]

Dietician

  • Educate patients with food nutrition and proper dieting.
  • Encourage obese patients with idiopathic pulmonary fibrosis to achieve ideal body weight.

Personal Trainer

  • Responsible for improving quality of life and preventing functional impairment.
  • Aid idiopathic pulmonary fibrosis patient with weight and disease management through musculoskeletal and cardiorespiratory conditioning.

References

  1. 1.0 1.1 Prasad R, Gupta N, Singh A, Gupta P. Diagnosis of idiopathic pulmonary fibrosis: Current Issues. Intractable Rare Dis Res 2015;4:65-69.
  2. 2.0 2.1 2.2 Pulmonary fibrosis foundation. About pulmonary fibrosis. [1] (accessed 25 March 2014).
  3. 3.0 3.1 3.2 Medscape. Idiopathic pulmonary fibrosis. [2] (accessed 25 March 2014).
  4. 4.0 4.1 Raghu G, Weycker D, Edelsberg J, Bradford W, Oster G. Incidence and Prevalence of Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med 2015;174:810-816.
  5. 5.0 5.1 American Thoracic Society documents. An official ATS/ERS/JRS/ALAT Statement: idiopathic pulmonary fibrosis: evidence based guidelines for diagnosis and management. Am J Respir Crit Care Med 2011; 183:788-824.
  6. 6.0 6.1 Wilson M, Wynn T. Pulmonary Fibrosis: pathogenesis, etiology and regulation. Mucosal Immunology 2009;2: 103-121.
  7. NHS. Disease fact sheet: Pulmonary fibrosis (idiopathic). http://www.nhs.uk/conditions/pulmonary-fibrosis/Pages/Introduction.aspx (accessed 20 May 2015).
  8. British Lung Foundation. Disease Fact sheet: What is IPF?.http://www.blf.org.uk/Page/What-is-IPF (accessed 18 May 2015).
  9. Frowfelter D, Dean E. Principles and practice of Cardiopulmonary physical therapy. 3rd ed. St.Louis: Mosby-Year book, 1996.
  10. Prasad R, Gupta N, Singh A, Gupta P. Diagnosis of idiopathic pulmonary fibrosis: Current Issues. Intractable Rare Dis Res 2015;4:65-69.