Idiopathic pulmonary fibrosis - Essay Example

?Idiopathic pulmonary fibrosis The lungs take in air through the wind pipe called trachea to its branching airway called bronchi. These branch down into very smaller bronchioles and then into millions of air sacs called as alveoli. Oxygen passes through these tiny walls of alveoli into the tiny blood vessels that are present near to them. Similarly the carbon-di-oxide is transferred from the blood vessels to the alveoli which are then removed out of the lungs through the process of exhalation. Thus the oxygen required by the blood vessels is taken in by the cells. The most important part of respiration is the alveoli. These alveoli are sometimes damaged by unknown causes and results in the thickening of the walls. As the wall thickens the transfer of oxygen to the blood vessels decrease, this result in the increase of the blood pressure inside the blood vessels and finally leads to the heart failure. Such a condition is called as Idiopathic pulmonary fibrosis. The process by which these alveoli cells are damaged is unknown. This damage is passed to the epithelial cells and the changes in these muscles causes serious abnormalities. Idiopathic pulmonary fibrosis is a serious chronic disease of the respiratory system. Here the alveoli present in the lung tissues becomes damaged and scarred. It is also called as cryptogenic fibrosing alveolitis. The main reason for the cause of this disease was thought to be inflammation that occurs in the alveoli of the lungs and that inflammation was thought to increase and cause scarring and fibrosis. Recently it is called as one type of idiopathic interstitial pneumonia and a distinct clinical disorder. The words idiopathic and cryptogenic means “of unknown cause”, that is the occurrence of this disease is unknown. , pulmonary means “affecting the lungs”, as the alveoli of the lungs re affected it is called so. Fibrosis means “thickening”, here the thickening of the walls of the alveoli occurs and Alveolitis means “inflammation of the alveoli”. The main causative agent for this disease is unknown. It is suggested that either drug toxicities, environmental factors such as pollutants in the environment, cigarette smoking, viral infections and the presence of reflux diseases or vascular diseases can be the causative agent for this disease. Some genetic factors are also found to be involved in the occurrence of this disease. The mutations at the surfactant protein C and the polymorphisms at the tumor necrosis factor alpha are also found to cause IPF. The over expression of this disease is found to occur at mutations at the transforming growth factor Beta 1. The pulmonary function studies performed to analysis IPF has concluded that the oxygen and air supply is very much reduced in this case because of the thickening of the alveoli due to inflammation. (Noth, 2007). This disease is a very rare disease. 3 among 10,000 people are prone for this disease. This can occur at any age but the persons between 50 – 70 years are developing this disease more commonly. This disease is more common among men than women. The environmental factors are found to play a major role in the incorporation of this disease. The dusts from the diamond polishing, the pollen grains, the heavy industrial smoke. Industrial car cleaning, the people working in the mines, and those who are exposed to very finite particles are having more risk for the IPF to occur. Pathophysiology: The pathophysiology of this disease is less understood. The alveolar epithelial cell injury and the apoptosis of the cells are the earlier pathogenesis for this disease. (Horowitz, 2006). The interactions between the epithelial and mesenchymal cells are interrupted at the basement. The key control point for the pathogenesis was found to be basement membrane and the extra cellular matrix. The changes in the alveoli cells include alterations in type II alveolar epithelial cells, proliferation of the infected cells and the damage, bronchiolarization, regenerative hyperplasia and bronchiolarization. These regions are found to secrete large amount of extra cellular matrix proteins (ECM). (King et al. 2000). The ECM proteins are secreted by the activated contractile myofibroblasts. The myofibroblasts are found to be involved in cell death and regeneration. Because of the dysregulated interactions between the epithelial cells and mesenchymal cells, the cells get damaged and they develop injuries to the alveoli that results in the thickening of the alveoli and finally less oxygen supply to the lungs. This lack in the supply of oxygen to the cells and carbon – di – oxide outside the lungs results in the chronic condition. (Bouros et al. 2006). The phenotypic change in the epithelial cells elaborates the soluble factors to activate the underlying mesenchymal cells. (Horowitz, 2006).Epithelial cell apoptosis was found to occur in the patients with the IPF. This apoptosis is found to induce pulmonary fibrosis. Some mediators are also found to induce the apoptosis in the epithelial cells such as angiotensin II, oxidative stress, Fas activation and TGF- beta 1. The animal model studies have also concluded that TGF- beta 1 is found to induce apoptosis in the epithelial cells. (Horowitz, 2006). (King et al. 2000). Oxidative stress was also found to induce apoptosis. The relative oxygen stress (ROS) release by the activated phagocytic cells is found to induce apoptosis. The failure in the migration of the impaired epithelial cells is found to induce fibrosis by preventing reconstitution of the alveolar epithelium. Angiogenesis in IPF: The recent models, the change in the pulmonary vascular system of the lung causes neovascularisation of the lungs. Angiogenic” ELR+ CXC chemokines (IL-8/CXCL8, ENA-78/CXCL5, MIP-2/CXCL2) and the “angiostatic” interferon (IFN)-inducible ELR? CXC chemokines (IP10/CXCL10) expression levels were found to vary between these two. The angiogenic ELR plus CXC chemokines were found to be increased and decreased level of angiostatic chemokines in the IPF. Some studies have also concluded that increase in the endostatin was found to occur in the IPF patients, an inhibitor of angiogenesis. The Pulmonary hypertension was an important risk factor in the IPF patients. The mortality rate was found to be high. Many pharmacotherapy targeting IPF are in the clinical trial stage. Some of the drugs include interferon gamma- 1b, pirfenidone, Zileuton, N-acetyle cysteine and Etanercept . (Horowitz , 2006). Symptoms: 1. Shortening of breath as time proceeds is the worst case and is the most important symptom. 2. The development of dry cough. 3. Painless swellings at the base of the nails. 4. The presence of tiredness. 5. The increased risk of chest infections. 6. Unexplained and worsening of dypsnea with in 30 days from onset. 7. Worsening hypoxemia is the next important case. This is identified by the arterial blood gas measurement. 8. No infection due to the endo tracheal aspiration and also due to braonchoalveolar lavage (BAL). (infectious etiologies presence can be identified in BAL). As the symptoms progress, the heart failure may reach up. The oxygen level gets educed up in the blood and the lung tissues get deformed and increases pressure in the blood vessels of the lungs. This leads to heart failure which results in breathlessness and fluid retention. (patient.co.uk) Figure 1: Normal lung geographic heterogeneity. Figure 2: Geographic heterogeneity showing the changes that have taken place in the lung. Diagnosis of IPF: 1. Physical Examination: presence of fine cracks when listening to the internal sounds of the body is the first symptom. These crackles can be observed throughout the inspiration process. The next diagnostic symptom is hypoxia and the presence of the “ pink puffer” pattern. The best clue for a patient ot have this disease is the presence of prominent inspiratory squeaks. 2. Chest X-Ray – The Chest radiography will show the presence of nodular regions at the lower part of the lungs. The presence of abnormalities in the lungs can be clearly identified for the IPF patients and this is not possible for the rheumatological lung disorders. The presence of honey combing can be easily found at the chest radiography. The increase in the size of the lungs in the picture clearly indicated that there is some problem in the lung. (Godfrey et al. 2007). Figure 3: Chest X-ray of the patients with IPF. 3. Blood tests: The blood test is done to check the level of oxygen present in the blood. The low concentration of oxygen is an indication of IPF. The erythrocyte sedimentation rate (ESR) is checked for the IPF patients. ESR is higher for the IPF patients. Hyper gamma globulinaemia is very common in these patients. The level of precipitin is also measured for these patients. 4. High resolution Computed Tomography (HRCT): HRCT scanning is a series of X-rays that are taken at 360 degrees of the patient body. The X-ray is taken from the top, bottom and sides of the body to look for the changes occurred in the body parts. These pictures are arranged in a series with different positions to give an idea about the disease condition. Accurate diagnosis is possible with this HRCT. The presence of a vast network reticular pattern of the cells is a clear indication of microcystic spaces. (Landefeld, 2004).(Webb, 2010). Figure 4: HRCT imaging of the IPF patient. 5. Lung biopsy is the next diagnostic procedure – Here the sample is taken through the key hole method of open or thoracoscopic lung biopsy method. The sample can be looked under the microscope and the typical appearance of the lung alveoli is observed. (Baughman 2008). Figure 5: This figure shows the IPF patients CAT scan showing bilateral plural effusions. 6. The Echocardiogram can also detect the prevalence of IPF. (patient.co.uk) 7. Bronchoalveolar lavage (BAL) : IN this method the lower tract respiratory cells are taken and diagnosed. This method is better than lung biopsy method. The elevated levels of basophils and eosinophils at the lung tissue are an indicator of lung disease. The BAL neutrophilia increases gradually as the disease progresses. Treatment/Management of IPF: 1.Steriod Medication: This is the first positive method that can be sued to treat the IPF. The use of steroid has reduced the symptoms in 1 out of 4 patients. The steroids were started with a high dose and then reduced to the lower dose. If there is no improvement for the patients then the treatment can be stopped. 2.Immunosuppresant drugs: these drugs are used to reduce the inflammation. Commonly used drugs are azathioprine and cyclophosphamide. 3. Oxygen treatment: this can be sued as one method of treatment , if the symptom is very severe. 4. Immunization: the immunization against pneumonia and influenza is another way to protect against infections. 5. The lung transplant is the next option that can be tried. Lung transplant is the best option for the cure if the patient is very young. (Noth and Martinez 2007). Apart from these newer treatment methods such as the use of interferon, N-acetylcysteine and pirfenidone can also be tried. The newer drugs were found to reduce the fibrosis and thus reduce the disease. Other therapies such as corticosteroid therapy, azathioprine therapy and cyclophosphamide therapy are also tried to cure IPF. (George 2005). Corticosteroid therapy: In this method, prednisone is given at a dose of 0.5mg/kg orally for four weeks and then gradually reduced to 0.25mg/kg and finally to 0.125mg/kg as the initial therapy for 8 weeks. The inclusion criterion for this therapy is that the body of the patient should be very lean. Prolonged treatment for one or two years will improve the condition of the patient. (Lynch, 2004). Azathioprine: 2-3mg.kg of the body weight is preferred for a time interval of one – two weeks. Cyclophosphamide: the therapy can be started from 2-3 mg/kg and finally increased to 150 mg/day. The drug concentration can be increased by 25mg/day increment and can be extended for two weeks. The results of this treatment is not so impressive. (Gribbin et al. 2006). Cyclosporin A was tried first but had only a very less effect. Methotrexate was also used as a successful therapy for the immune mediated pulmonary disorders but it was not suitable for the IPF. Glutathione, Taurine and niacin were found to inhibit the development of experimental fibrosis. The use of antibiotics to reduce the adhesion property of the leukocytes in the lungs was also tried. They were not clinically proven but are in the positive approach. (King et al., 2000). These therapies can be used until the following improvements in the patients are noted. 1. Decrease in the difficulty of breathing 2. Reduction of the abnormalities in the lungs. This can be found through the chest radiograph or HRCT scan. 3. 10 – 15% increase in the TLC or VC and single breath DLco 4. A good increase in the oxygen saturation level. (King et al., 2000). Discussion: The idiopathic pulmonary fibrosis is a very chronic disease and the pathophysiology is this disease is very less known. The air sacs of the lungs get thickened by some unknown factors. environmental factors, drugs are said to be the main reason for the prevalence of this disease. The patients must be encouraged to go for pulmonary rehabilitation and regular exercise to maintain the same conditions of musculoskeletal conditions. Apart from these regular monitoring of the lung physiology, gas exchange in the lungs, the heart conditions and the HRCT scanning must be done. This will enable us to look for the positive aspects of the patients and their life. Anti inflammatory and immunosuppressive agents are becoming less effective for this disease. Till now there is no proven or approved drug therapy for IPF. (Lynch 2004). References: Baughman,RP. 2008, Pulmonary Arterial hypertension and Interstitial Lung diseases: A clinical guide, Springer. Bouros D, Antoniou KM, and Tzouvelekis Al 2006, “Interferon-gamma1b for the treatment of idiopathic pulmonary fibrosis”, Expert Opinion on Biological Therapy, vol. 6, no.10, pp.1051-60 George, RP 2005, Chest medicine: essentials of pulmonary and critical care medicine, Lippincott Williams and Willkins. Godfrey, A., Ouelette, DR and Peters, SP 2010, Idiopathic Pulmonary Fibrosis, eMedicine, viewed on April 16, 2011 http://emedicine.medscape.com/article/301226 Gribbin J, Hubbard, RB and Le Jeune, I 2006, The incidence and mortality of idiopathic pulmonary fibrosis and sarcoidosis in the UK, Thorax, vol. 61, no.11, pp.980-985. Horowitz, JC and Thannickal, VJ 2006, “Idiopathic pulmonary fibrosis: New concepts in pathogenesis and implications for drug therapy,” Treatments in Respiratory Medicine, vol.5, no.5, pp.325 – 342. King, TE., Costabel, U., Cordier, JF., Dopico, GA., Du Bios, RM., Lynch, JP., Myers, J., Panos, R., Raghu, G., Schwartz, D., and Smith, CM., 2000, “Idiopathic Pulmonary Fibrosis: Daignosis and Treatment,” American Journal of Respiratory and Critical care Medicine, vol.161, no. 2, 646-664. Landefeld, CS 2004, Current geriatric diagnosis and treatment, McGraw- Hill Professional. Lynch, JP 2004, Idiopathic Pulmonary Fibrosis, CRC press. Noth, I and Martinez, FJ 2007, “Recent advances in idiopathic pulmonary fibrosis”, Chest, vol.132, No.2, pp.637-50. patient.co.uk 2010, Idiopathic pulmonary fibrosis, viewed on April 16, 2011 http://www.patient.co.uk/health/Idiopathic-Pulmonary-Fibrosis.htm Webb, WR and Higgins, CB 2010, Thoracic imaging: Pulmonary and Cardiovascular Radiology, North American Edition, Lippincott Williams and Willkins. Read More