IDIOPATHIC PULMONARY FIBROSIS

(IPF)Kimberly A Smith

Liberty University Advanced Pathophysiology NURS 506

Introduction A progressive, irreversible, devastating

interstitial lung disease

Etiology unknown (duBois, Weycker, Albera, Bradford, & Costabel ,2011)

Disease of the basal and peripheral lungs that progresses centrally and toward apices of the lungs over time (Leslie, 2012)

Lungs contain excessive amount of fibrous or connective tissue

Fibrotic process causes lungs to become stiff and difficult to ventilate (McCance & Heuther, 2010)

X-ray of fibrotic lung evidencing

excessive amount of fibrotic tissue

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Incidence and Prevalence of

IPF• Incidence• No differentiation found among ethnicities• Rising• Estimated to be between 4.6 and 16.3 per

100,000• Median survival post diagnosis is 2 to 4 years

• Prevalence• More predominant in men than women (1.7:1)• Frequency increases with age• Occurs in middle aged and elderly adults (median

age at diagnosis-66 years old, range 55-75) (King, Pardo, Selman, 2011)

Assessment

Probable Causes: Exposure to inhaled harmful substances (toxic fumes, organic/inorganic dusts, smoking) (McCance & Huether, 2010)

• Signs & Symptoms• Slow progressive breathlessness, especially with

exertion• Non-productive cough• Decreased oxygen saturation with exercise• Diffuse inspiratory crackles (Leslie, 2012)

• Clubbing of fingers (King et al., 2011)

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Assessment (continued)

Diagnostics Lab studies—reveal mild non-specific

elevation of antinuclear antibodies Pulmonary Function Test

Decreased lung capacity Decreased forced vital capacity Diffusing capacity for CO2

Arterial Blood Gas Decreased oxygen (pO2) levels Increased carbon dioxide (pCO2) levels (Leslie, 2012)

Assessment (continued)

Chest X-Ray Will demonstrate fibrotic patches Computed Tomography more definitive

High Resolution Computed Axial Tomography (HRCT) Patchy, coarse, subpleural reticulation Distortion of lung architecture Presence of pleural-based cysts (required

feature for a confident diagnosis) Subpleural “honeycombing” at bases (Leslie,

2012)

Assessment (continued)

Lung Biopsy Partially or completely scarred lobules devoid

of alveolar spaces Coarse peripheral lobar fibrosis Scar tissue demonstrates small cysts lined by

respiratory epithelium Fibroblast foci exist at the interface between

fibrosis and uninvolved lung tissue Microscopic “honeycombing” nearly always

present (Leslie, 2012)

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Pathophysiology of IPF

A heterogenous disease

The result of abnormal behavior of alveolar epithelial cells that: Provoke migration, proliferation, and activation of

mesenchymal cells Initiate formation of fibroblast and myofibroblast

foci

Activated fibroblasts secrete exaggerated amounts of extracellular matrix molecules

Subsequent destruction of lung architecture with alveolar collapse (King, Pardo, & Selman, 2011)

Pathophysiology (continued)

Gene expression of CCNA2 and {alpha}-Defensins up-regulated in patients with exacerbation of IPF, localized in the alveolar epithelium

{Alpha}-Defensin and ST2 protein levels in serum found to be elevated (Bhatti, Girdhar, Usman, & Abubakr, 2013)

Pathological Process of IPF & Activation of

Coagulation Cascade and Procoagulant

Signaling

Tissue factor-Factor VIIa-Factor X complex assembles on alveolar epithelium

Factor X activation stimulates fibroblasts within underlying fibrotic regions

Thrombin and activated Factor X induce differentiation of lung fibroblasts to myofibroblasts via the proteinase-activated receptor (King, Pardo, & Selman, 2011)

Proposed Pathological Sequence (Leslie, 2012)

1. Stretch injury to

epithelial-mesenchymal

transition

2. Formation of the Fibroblastic Reticulum-Type 2 cells proliferate over tear and

reconstitute the alveolar interface with air

3. Local alveolar collapse

4. Collagen deposition

5. Vascular growth

6. “Simplification” of lobules-devoid of alveoli, consist only of terminal

airways and dilate over time

7. Honeycomb lung

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Genetic/Genomic Implications for Care & Treatment

Genetics/Genomics Genetic transmission occurs in approximately 0.5-

3.7% of patients with IPF Effected families have autosomal dominant vertical

transmission patters of inheritance with reduced penetrance

In some familial cases, alterations in unfolded protein response occur with mutations in surfactant protein C– a hydrophobic protein expressed exclusively by AEC type II (King, Pardo, Selman, 2011)

Genetic/Genomic Implications for Care & Treatment (continued)

A genome wide scan of several families with familial IPF identified shared haplotype on chromosome 4g31 that harbored ELMOD2—a gene expressed in the lung ELMOD2 expressed slightly less in IPF lung when

compared to healthy lung ELMOD2 essential for cellular process

Mutations of telomerase also implicated in familial IPF (King, Pardo,& Selman, 2011)

50% of asymptomatic members have evidence of alveolar inflammation—a possible precursor to IPF (Doyle, Hunninghake, & Rosas, 2012)

Genetic/Genomic Implications for Care & Treatment (continued)

Some suggest that increased levels of matrix metalloproteinase-7 (MMP7) predict disease progression and mortality

Biomarker serum CC-chemokine ligand 18 as well as CXCL9 & CXCL10 have shown to be a predictive value in IPF

Others suggest further study of biomarkers neutrophilelastase, KL-6, and lactate dehydrogenase for disease determinant (Doyle, Hunninghake,& Rosas, 2012)

Care & Treatment of Patients with IPF

Pharmacological Corticosteroids (Methylprednisolone,

Prednisolone) Immuno-suppressants (Cyclosporin A,

Cyclophosphamide) Antifibrotic compounds (Pirfenidone—not yet

available in the United States for Rx) Efficacy unknown

Antioxidant Amino Acid/Mucolytic (Acetylcysteine) (Lee,

McLaughlin, & Collard, 2011)

Care & Treatment of Patients with IPF

Non-pharmacological Non-invasive ventilation (NIV)

High-flow oxygen for patients with resting hypoxia Continuous positive airway pressure (CPAP)

Mechanical Ventilation Once patient advances to mechanical ventilation,

probability of ventilator removal is poor, as is prognosis

<15% of patients requiring mechanical ventilation survive to hospital discharge (Lee, McLaughlin, & Collard, 2011)

Care & Treatment of Patients with IPF

Surgical – Lung Transplantation

Only therapy proven to increase long-term survival Problems:

Not all patients qualify for transplant Few hospitals have the capability for

transplantation Donor lungs not readily available (Bharri et al., 2012)

Patient Education

Disease Management Initial Teaching

Disease Pathophysiology Types of Diagnostic testing, indications Prognosis Disease- and symptom-centered management

Oxygen therapy Medications (indications, actions, possible

complications/side effects) (Lee, McLaughlin, & Collard, 2011)

Goal: Maintain maximal level of wellness and quality of life

Patient Education

Supplemental teaching Advanced Care Planning

Goal set within context of patient’s values and preferences

Initiated at a non-critical time (when death is imminent)

Palliative care/End-of-Life care Symptom control Relief of suffering (Lee, McLaughlin, & Collard, 2011)

Continual Reassessment

Patient Education

Cultural Teaching specific to language of patient Utilizing language-appropriate materials

and interpretive modalities AT&T language line Language Services Associates (LSA)

video communicator Providing care according to cultural

beliefs (Lever, 2011)

Patient Education

Spiritual Considerations Significant when dealing with advanced

planning and end-of-life care Encourage support of church family (if

affiliated with a church/religious organization) Provide pastoral care if requested Allow patient to express concerns and initiate

interdisciplinary modalities

NOTE: All education will utilize teach-back method to enhance/confirm understanding.

ReferencesBhatti, H., Girdhar, A., Usman, F., Cury, J. Bajwa, A. (2013). Approach to acute exacerbation of idiopathic pulmonary fibrosis. Annals of Thoracic Medicine, 8(2), 71-77. doi: 10.4103/1817-1737.109815

Doyle, T. Hunninghake, G., Rosas, I. (2012). Subclinical interstitial lung disease: Why you should care. American Journal of Respiratory and Critical Care Medicine, 185 (11), 1147-1153. doi: 10218100114

duBois, R., Weycker, D., Albera, C., Bradford, W., Costabel, U. (2011). Ascertainment of individual risk of mortality for patients with idiopathic pulmonary fibrosis. American Journal of Respiratory and Critical Care Medicine, 184(4), 459-466. doi: 884295098

King, T., Pardo, A., Selman, M. (2011). Idiopathic pulmonary fibrosis. The Lancet, 378(9807) , 1949-1961. doi: 910067528

Lee, J., McLaughlin, S., Collard, H. (2011). Comprehensive care of the patient with idiopathic pulmonary fibrosis. Current Opinion in Pulmonary Medicine, 17, 348-354. doi: 10.1097/MCP.ob013e328349721b

Leever, M. (2011). Cultural competence: Reflections on patient autonomy and patient good. Nursing Ethics, 18(4), 560-670. doi: 10.1177/0969733011405936

Leslie, K. (2012). Idiopathic pulmonary fibrosis may be a disease of recurrent, tractional injury to the periphery of the aging lung. Archives of Pathology & Laboratory Medicine, 136(6), 591-600. doi: 10.5858/arpa.2011-0511-OA

McCance, K., Huether, S. (2010). Pathophysiology: The biological basis for disease in adults and children (6th ed.). Maryland Hieghts, MO: Mosby.