Idiopathic Pulmonary Fibrosis: An Overview

Idiopathic pulmonic Fibrosis An OverviewJennifer BeardsleyAbstractIdiopathic pneumonic fibrosis (IPF) is a ravage interstitial lung disease that has no cure. The term fibrosis refers to scarring, in IPF particularly the scarring of the lungs. The scarring shits irreversible destruction and set aheadive decline of the lungs. When the tissue thickens, the lungs potnot properly exchange oxygen. The term idiopathic, in medicine, means that the origin of the disease is unknown. The exact cause of IPF is unknown, however, certain luck factors much(prenominal) as ingest, exposure to inhaled toxins such as asbestos, lung injury, viral, and bacterial infections, acid wane and genetics associated with the disease. IPF mainly affects people ages 50 and up. Many people live only about 3 to 5 socio-economic classs after diagnosis. The most joint cause of death related to IPF is respiratory failure (What Is Idiopathic pulmonic Fibrosis? NHLBI, NIH, n.d.). 40,000 people die each year t o IPF, the same as to breast crabby person (Facts About Idiopathic pulmonic Fibrosis Coalition For Pulmonary FibrosisCoalition For Pulmonary Fibrosis, n.d.), yet IPF is still an unknown disease to many people. This paper will discuss the take chances factors, disease process, complications, management, and new drug therapy clinical trials.Idiopathic Pulmonary Fibrosis An OverviewEtiologyIdiopathic Pulmonary Fibrosis first started to become recognizable around the late 1800s (Noble Homer, 2005). While currently the exact cause is unknown, there have been several risk factors that are recognized to contri only whene to the disease. As mentioned above, smoking, exposure to inhaled toxins such as asbestos, lung injury, viral and bacterial infections, acid reflux and genetics are associated with the disease (Noble Homer, 2005).Smoking urge ons the bolshy of lung function by destroying the cilia inhibiting the lungs natural susceptibility to clean and speed up itself (Oh, Murr ay, Molfino, 2012). Smoking to a fault damages alveoli, causing poor gas exchange. The chemicals in cigarettes contribute to lung decline and disease and coat the lungs with tar and toxins (Oh et al., 2012).Inhaled substance and toxins such as asbestos are hypothesized to increase IPF probability (Meltzer Noble, 2008). When toxins invade the lungs, they interfere with the alveoli gas exchange process (Meltzer Noble, 2008).Lung injury can cause permanent damage. Acute lung injury has been hypothesized to accelerate an underlying progression of IPF. When cells of the lungs are damaged, it can be irreversible (Kottmann, Hogan, Phipps, Sime, 2009).Viral and bacterial infections cause a build of mucus in the lungs. When the alveoli get clotted they cannot properly exchange oxygen and carbon dioxide. Each infection acquired can cause more damage and can lead to permanent damage. When the lungs lose their ability to exchange gas, oxygen is inhibited from reaching the bodys indispensab le organs (Kottmann et al., 2009).GER, commonly known as acid reflux, clears when acid is aspired into the esophagus. Researchers have make up that 9 out of 10 people who have IPF also have gastroesophageal reflux disease (What Causes Idiopathic Pulmonary Fibrosis? NHLBI, NIH, n.d.)Recent research has run aground that genetics may play an important role in the risk factor of developing IPF. Over the past decade, one aspect that has held great contract in helping the medical community to better define the pathogenesis of IPF is the recognition that genetic factors may play a role in this disease (Lawson, Loyd, Degryse, 2011).PathophysiologyThe cause of IPF is unknown. Despite considerable advancement in understanding the progression of IPF, the knowledge of the beginning stages of IPF re still inadequately understood (Noble Homer, 2005). Originally, in the 1970s, it was thought that inflaming of the alveoli was the cause (Noble Homer, 2005). It was believed that untreated in flammation leads to the scarring of the lungs. Anti-inflammatory and cortico steroid hormones were widely used to treat the inflammation. However, those therapies have proven ineffective, making it evident that inflammation was not the cause (Dempsey, Kerr, Gomersall, Remmen, Currie, 2006).The due south theory that came about in the 1980s suggesting growth termed alveolar macrophage-derived growth factor (Noble Homer, 2005). Known as the growth factor hypothesis, it is believed that abnormal improve of trauma within the lungs exaggerates the response and growth of profibrogenic causing the scarring of IPF (Noble Homer, 2005). This theory still proves to be a highly important discovery in the pathophysiology of IPF (Dempsey et al., 2006).A trine theory also came out of the 1980s, known as the epithelial-mesenchymal hypothesis, suggests that tissue death of alveolar epithelial cells can lead to alveolar collapse (Noble Homer, 2005). The epithelial- mesenchymal cell metempsycho sis can alter and change motility and the ability to heal. Imbalance of the normal homeostatic microenvironment might be, per se, a cause of fibroblast proliferation and myofibroblast differentiation leading to fibrosis (Prunotto et al., 2012).Clinical verbalismAccording to the Coalition for Pulmonary Fibrosis, Idiopathic pulmonary fibrosis (IPF) is a progressive and generally fatal disease characterized by scarring of the lungs that thickens the lining of the lungs, causing an irreversible loss of the tissues ability to transport oxygen. IPF ultimately robs a patient of the ability to breathe(Facts About Idiopathic Pulmonary Fibrosis Coalition For Pulmonary Fibrosis, n.d.). IPF unremarkably occurs in older adults in their 50s or 60s, and tends to occur more in men than in women (Lawson, Loyd, Degryse, 2011). According to the Coalition For Pulmonary Fibrosis, IPF affects about 128,100 people in the United States, with 48,000 new cases diagnosed annually (Facts About Idiopathic P ulmonary Fibrosis Coalition For Pulmonary Fibrosis, n.d.). IPF has been reported to occur throughout the area in many different racial and ethnic groups. Studies in the United States have suggested that Caucasians are more likely to be diagnosed with IPF and have higher mortality rate rates from IPF than African Americans. It is unclear if these findings are due to real differences in racial characteristics or to an under-diagnosis of this condition in minority populations (Siegel, 2011).IPF symptoms develop over m and usually are not diagnosed until serious damage has already been done to the lungs (What Are the Signs and Symptoms of Idiopathic Pulmonary Fibrosis? NHLBI, NIH, n.d.). Patients are often misdiagnosed with diseases that present similar symptoms such as Chronic Obstructive Pulmonary Disorder (Facts About Idiopathic Pulmonary Fibrosis Coalition For Pulmonary Fibrosis, n.d.). Idiopathic pulmonary fibrosis usually present in stages with a nonproductive cough and dys pnea. (Hyzy, Huang, Myers, Flaherty, Martinez, 2007). The main symptom patients complain of being shortness of breath (Noble Homer, 2005). Other common symptoms include dry, hacking cough rapid, shallow public discussion gradual, unintended weight loss Fatigue (tiredness) or malaise (a general feeling of being unwell) clubbing, which is the widening and rounding of the tips of the fingers and toes (What Are the Signs and Symptoms of Idiopathic Pulmonary Fibrosis? NHLBI, NIH, n.d.).The amber standard for diagnosis of patients with IPF is a surgical lung biopsy (SLB), however critical risk for these patients usually prevent a high-risk surgical procedure (Kaarteenaho, 2013). The mortality, which can occur shortly after the procedure, has probably been the major reason to refrain from performing SLB (Kaarteenaho, 2013). With that in mind, diagnosis of IPF includes clinical, radiologic and histopathologic aspects (Wolters, Collard, Jones, 2014). The American Thoracic Society states , in the absence of a definitive lung biopsy, the presence of all four major criteria and three minor criteria, as set forth in the current guidelines, increases the likelihood of a sort out diagnosis of IPFMajor CriteriaExclusion of other known causes of interstitial lung diseases, such as certain drug toxicities, environmental exposures, and connective tissue diseasesAbnormal pulmonary function studies that include evidence of restriction (reduced vital capacity often with an increased FEVFVC ratio) and impaired gas exchange (increased AaPO2 with rest or exercise or decreased DLCO)HRCT scan showing bibasilar reticular abnormalities with minimal ground-glass opacitiesTransbronchial lung biopsy or BAL showing no features to support another diagnosisMinor CriteriaAge 50 years pestilent onset of otherwise unexplained dyspnea on exertionDuration of illness greater than or equal to 3 monthsBibasilar inspiratory crackles (dry or Velcro-like in quality)(Raghu et al., 2011).The physical a ssessment is an important part of diagnosis, however, symptoms can mimic other diseases and make it hard to differentiate (Meltzer Noble, 2008). Attention should be paid to key risk factors such as work related inhaled chemical exposure and smoking. Fine inspiratory Velcro-like crackles can be heard upon examination and advance towards the upper air duct as the disease progresses (Meltzer Noble, 2008).Clubbing of the fingers and toes is found in 50% of patients (Meltzer Noble, 2008). Lab results are often inconclusive to IPF, but as part of a puzzle can help to identify the disease. An ABG will more than likely read normal (Meltzer Noble, 2008).The pulmonary function test (PFT) can lend valuable information to name IPF. While IPF is a restrictive disease, it can often imitate obstructive disorders or congestive heart failure (CHF) (Meltzer Noble, 2008). Routine spirometry reveals decreased measures of forced vital capacity (FVC) and forced expiratory volume in one second (FEV 1). The ratio of FEV1/FVC remains normal (or increased) in IPF, consistent with restrictive physiology (Meltzer Noble, 2008). Subsequently, the PFT can also reveal reduced TLC, RC, and RV. Reduced gas transfer may also be noted with a DLCO (Meltzer Noble, 2008).Almost every patient with Idiopathic Pulmonary Fibrosis will have abnormal radiological findings (Meltzer Noble, 2008). The imaging modality of choice in diagnosing IPF is High-resolution computed tomography (HRCT) (Hospenthal, 2006). Patchy, predominantly peripheral, subpleural, bibasal reticular opacities, often associated with handle bronchiectasis (Harari Caminati, 2005). A phenomenon referred to as honeycombing is a prevalent finding in IPF, seen below is figure 3.Figure 1 thorax radiograph of a patient with IPF. Chest radiograph reveals peripheral, subpleural reticular opacities, most profuse at the lung bases (Harari Caminati, 2005).Figure 2 Chest HRCT in a patient with IPF. HRCT shows patchy, predominantly peri pheral, subpleural, bibasal reticular abnormalities, traction bronchiectasis and bronchiolectasis and unorthodox septal thickening. There is also ground glass (Harari Caminati, 2005).Figure 3 Chest HRCT in a patient with IPF. HRCT shows predominantly peripheral and subpleural fibrosis with honeycombing (Harari Caminati, 2005).ComplicationsIdiopathic pulmonary fibrosis is a highly progressive disease. Because the tissues in the lungs are scarred, they cannot properly exchange gas and the low amount of oxygen delivered to the body causes several complications and puts strain on the right side of the heart. According to the America Thoracic Society, There is an increasing awareness of complications and comorbid conditions frequently associated with IPF (Raghu et al., 2011). Some of the most common complications are Pulmonary hypertension, cor pulmonale, respiratory failure and lung cancer (Daniels, Yi, Ryu, 2008). Depression is also often seen in people with IPF because of its deva stating prognosis (Living With Idiopathic Pulmonary Fibrosis NHLBI, NIH, n.d.). Acute exacerbations (unexplained worsening of dyspnea) of IPF present the most destructive and deadly complication (Raghu et al., 2011). It is presently unclear if acute exacerbation of IPF is simply a manifestation of an unidentified respiratory complication (such as pulmonary emboli, infection) contributing to an acute worsening in a patient with IPF or represents an inherent acceleration in the pathobiological processes involved in IPF (Raghu et al., 2011).Medical anxietyThere is currently not a cure for idiopathic pulmonary fibrosis (What Is Idiopathic Pulmonary Fibrosis? NHLBI, NIH, n.d.). Until recently, primary methods of management have been anti-inflammatories and lung transplants (Dempsey, Kerr, Gomersall, Remmen, Currie, 2006). While Anti-inflammatory are still used today it is not due to the effectiveness of treatment, but lack thereof for alternatives (Dempsey et al., 2006).Immunosuppre ssive or cytotoxic agents are used among steroid nonresponders, patients experiencing serious adverse effects from corticosteroids, and patients at high risk for corticosteroid complications (Harari Caminati, 2005). Single-lung transplantation results in an actuarial survival of 73% at 1 year and 57% at 3 years (Harari Caminati, 2005). Unfortunately, most patients are not eligible for transplant due to age or comorbidity factors (Harari Caminati, 2005).In the spring of 2014 the FDA inform two new drugs for the management of IPF (CPF Celebrates Historic Year of Progress in Pulmonary Fibrosis Coalition For Pulmonary Fibrosis Coalition For Pulmonary Fibrosis, n.d.). Ofev (nintedanib) and Esbriet (pirfenidone) were both shown to slow the progress of IPF in clinical trials. Pirfenidone is a transforming growth factor-beta inhibitor and tumor necrosis factor-alpha inhibitor (Gohil, 2015). Ofev is a fibroblast growth factor receptor (FGFR) antagonist, platelet-derived growth factor re ceptor (PDGFR) antagonist, and vascular endothelial growth factor receptor (VEGFR) antagonist (Gohil, 2015). The two treatments are still in the early stages with little known about their effectiveness.PrognosisPrognosis for IPF is dim. It is a fatal disease (Meltzer Noble, 2008). The median survival rate is 3 years after diagnosis (Peljto et al., 2013). Factors associated with shortened survival time include older age, smoking history, lower body mass index (BMI), more severe physiologic impairment, greater radiologic extent of disease, and the development of other complications or conditions, in particular, pulmonary hypertension, emphysema, and bronchogenic cancer (Ley, Collard, King, 2011).Clinical TrialsDuring the past decade, there has been a notable amount of research into the treatment of idiopathic pulmonary fibrosis. IPF is no longer believed to be due to inflammation, but multiple injuries with atypical cell repair. According to The Coalition for Pulmonary Fibrosis, the re are many therapies under investigation in clinical trials that includeAntifibrotic or antifibrogenic agents (such as Pirfenidone, interferon and certain blood-pressure-lowering medications) to suppress the scarring processAntioxidants (such as N-acetylcysteine) to prevent damage to lung tissueMonoclonal antibodies to inhibit bad cytokines (protein growth factors, such as TGF-beta, TNF-Alpha, or CTGF, that activate inflammation)(Active Clinical Trials and Investigational Research in IPF Coalition For Pulmonary FibrosisCoalition For Pulmonary Fibrosis, n.d.).ReferencesActive Clinical Trials and Investigational Research in IPF Coalition For Pulmonary FibrosisCoalition For Pulmonary Fibrosis. (n.d.). Retrieved February 17, 2015, from http//www.coalitionforpf.org/active-clinical-trials-and-investigational-research-in-ipf/Facts About Idiopathic Pulmonary Fibrosis Coalition For Pulmonary FibrosisCoalition For Pulmonary Fibrosis. (n.d.). Retrieved February 17, 2015, from http//www.coa litionforpf.org/facts-about-idiopathic-pulmonary-fibrosis/Hospenthal. (2006). Diagnosis and management of idiopathic pulmonary fibrosis Implications for respiratory care. Respir Care, 51, 382391. Retrieved from http//www.ncbi.nlm.nih.gov/pubmed/16563193Hyzy, R., Huang, S., Myers, J., Flaherty, K., Martinez, F. (2007). Acute exacerbation of idiopathic pulmonary fibrosis. Chest, 132, 16521658. inside10.1378/chest.07-0299Kaarteenaho, R. (2013). The current position of surgical lung biopsy in the diagnosis of idiopathic pulmonary fibrosis. respiratory Research, 14, 43. doi10.1186/1465-9921-14-43Lawson, W. E., Loyd, J. E., Degryse, A. L. (2011). Genetics in pulmonary fibrosisfamilial cases provide clues to the pathogenesis of idiopathic pulmonary fibrosis. The American Journal of the Medical Sciences, 341(6), 43943. doi10.1097/MAJ.0b013e31821a9d7aLey, B., Collard, H. R., King, T. E. (2011). Clinical course and prediction of survival in idiopathic pulmonary fibrosis. American Journal o f Respiratory and precise Care Medicine, 183(3), 431440. doi10.1164/rccm.201006-0894CIMeltzer, E. B., Noble, P. W. (2008). Idiopathic pulmonary fibrosis. Orphanet Journal of Rare Diseases, 3, 8. doi10.1186/1750-1172-3-8Noble, P. W., Homer, R. J. (2005). Back to the future Historical perspective on the pathogenesis of idiopathic pulmonary fibrosis. American Journal of Respiratory Cell and Molecular Biology, 33(8), 113120. doi10.1165/rcmb.F301Peljto, A. L., Zhang, Y., Fingerlin, T. E., Ma, S.-F., Garcia, J. G. N., Richards, T. J., Schwartz, D. A. (2013). Association between the MUC5B promoter polymorphism and survival in patients with idiopathic pulmonary fibrosis. JAMA, 309(21), 22329. doi10.1001/jama.2013.5827Raghu, G., Collard, H. R., Egan, J. J., Martinez, F. J., Behr, J., Brown, K. K., Schnemann, H. J. (2011). An Official ATS/ERS/JRS/ALAT Statement Idiopathic pulmonary fibrosis Evidence-based guidelines for diagnosis and management. American Journal of Respiratory and Critic al Care Medicine, 183, 788824. doi10.1164/rccm.2009-040GLSiegel, M. D. (2011). Breathing in America Diseases, Prognosis, and Hope. Critical Care Medicine, 39, 1857. doi10.1097/CCM.0b013e31821b1e92What Are the Signs and Symptoms of Idiopathic Pulmonary Fibrosis? NHLBI, NIH. (n.d.). Retrieved February 17, 2015, from http//www.nhlbi.nih.gov/health/health-topics/topics/ipf/signsWhat Is Idiopathic Pulmonary Fibrosis? NHLBI, NIH. (n.d.). Retrieved February 14, 2015, from http//www.nhlbi.nih.gov/health/health-topics/topics/ipfWolters, P. J., Collard, H. R., Jones, K. D. (2014). Pathogenesis of idiopathic pulmonary fibrosis. Annual Review of Pathology, 9, 15779. doi10.1146/annurev-pathol-012513-104706