1. Pulmonary Fibrosis

2. What is Pulmonary Fibrosis? Formation or development of excess fibrous connective tissue in the lungs. ● “Scarring of the lungs” ● Restrictive lung disease ● 5 million people worldwide affected ● Usually affects middle-aged and older adults ● Has been known by other names (i.e. cryptogenic fibrosing alveolitis)

3. Symptoms ● Fatigue, weakness, aching muscles and joints ● SOB ● Chest discomfort ● Chronic dry, hacking coughing ● Loss of appetite, rapid unintended weight loss ● Clubbing of fingertips ● Crackles on auscultation ● Fig. 1: Clubbing of fingertips ● (google images)

4. Diagnosis ● Can be diagnosed quicker now due to research conducted ● X-Rays / High Resolution CT Scans ● Spirometry ● Lung biopsy ● Misdiagnosis common ● Fig. 2: Chest X-Ray demonstrating ● Pulmonary Fibrosis due to ● Amiodarone. (Wiki)

5. Causes.. ● Secondary effect of other diseases – Interstitial Lung Diseases - Inhalation of environmental/occupational pollutants (asbestosis, silicosis) - Cigarette smoking - Some typical connective tissue diseases (rheumatoid arthritis, scleroderma, SLE) - Other diseases involving connective tissue (sarcoidosis, Wegener's Granulomatosis) - Infections - Radiation therapy to the chest - Certain medications (Amiodarone, Bleomycin, Busulfan, Methotrexate, Nitrofurantoin)

6. ● No known cause – Idiopathic Pulmonary Fibrosis (IPF) ● GERD (Raghu et al., 2006) ● Genetic predisposition? - Surfactant protein C (SP-C) mutation (Nogee et al., 2001; Thomas et al., 2002) - Familial IPF – when more than one member of family has IPF..Causes continued

7. Prognosis ● Affects people differently – some sudden onset, slow onset or stay same for years ● Currently no cure ● Many people live 3-5 years after diagnosis ● Hypoxia → Pulmonary hypertension → heart failure of right ventricle

8. Treatments ● Drug Therapy ● Oxygen Therapy ● Pulmonary Rehabilitation

9. Drug Therapy.. ● Currently no medicines proven to slow progression ● Prednisone, azathioprine and N-acetylcysteine have been used to treat IPF either alone or in combination. However, there is not enough evidence to support their use. Another drug also used: Cyclophosphamide.

10. ..Prednisone ● Anti-inflammatory, corticosteroid ● Mimics action of cortisol ● Problems: - Prolonged use can cause adrenal glands to stop producing own cortisol - Potentially increase severity/frequency of infections - Side effects: sugar intolerance, weight gain, swelling, depression, anxiety, fatigue, peptic ulcers ● Usually prescribed 3-6 months or less at first due to side effects

11. ..Azathioprine (or 'Imuran') ● Also suppresses immune system ● Also has serious side effects ● May be prescribed with prednisone for only 3-6 months ● Although some successful reports in small number of individuals, its effectiveness not yet confirmed in RCT

12. ..N-acetylcysteine ('NAC') ● Naturally occurring antioxidant ● Reduces inflammation and theoretically prevent some oxidative injury that precedes fibroproliferation ● Small non-randomised trial demonstrated some improvement ● Number of ongoing studies investigating NAC with other drugs

13. The common treatment for IPF (combination of prednisone, azathioprine, and N-acetylcysteine) recently found harmful in a study funded by the National Heart, Lung, and Blood Institute (NHLBI)

14. ..Cyclophosphamide (or Cytoxan) ● Anti-cancer drug ● Used for its immune suppression properties ● Often given in conjunction with Prednisone or may be given alone

15. Oxygen Therapy ● From large oxygen machines to small lightweight portable oxygen cylinders – adaptable for person ● Fear – addiction to oxygen

16. Pulmonary Rehabilitation ● Standard treatment for chronic (ongoing) lung disease ● Teaches person to manage their condition and function at their best ● Does not replace medical therapy but used alongside ● Can include: ● Exercise training Nutritional counselling Education Energy-conserving techniques Breathing strategies Psychological counselling and/or group support

17. Other Treatments ● Flu/Pneumonia vaccinations ● Cough medicines ● Vitamin D, Calcium and bone building medicine for those taking corticosteroids ● Anti-reflux therapy for GERD

18. Research and New Treatments? ● Clinical trials – medication to reduce inflammation and prevent/reduce scarring (Klingsberg, Mutsaers & Lasky, 2009) ● Organisations taking advantage – false health benefit claims – HealthWatch UK ● Some drugs being looked at: Cyclosporin A., Methotrexate, Chlorambucil, Colchicine, D-Penicillamine Other anti-fibrotic agents : Interferon γ, interferon ß, relaxin, pirfenidone, halfuginone, suramin and prostaglandin E2. (Paz & Shoenfeld, 2010) Possibility of pulmonary toxicity, patient toleration and severe side effects cause issues for testing effectiveness.

19. Organisations and Useful Websites British Lung Foundation (BLF)- http://www.lunguk.org/you-and-your- lungs/conditions-and- diseases/Idiopathic+pulmonaryfibrosis%28fibrosingalveolitis%29#What treatment is available? BLF helpline 08458 50 50 20/ 03000 030 555 to find nearest Pulmonary rehabilitation course. HealthWatch UK http://www.healthwatch-uk.org/newsletters/nlett78.htm Patient.co.uk - http://www.patient.co.uk/doctor/Pulmonary-Fibrosis.htm Pulmonary Fibrosis Foundation http://www.pulmonaryfibrosis.org/http://www.lunguk.org/you-and-your- lungs/conditions-and- diseases/Idiopathic+pulmonaryfibrosis%28fibrosingalveolitis%29#What treatment is available?http://www.healthwatch-uk.org/newsletters/nlett78.htmhttp://www.patient.co.uk/doctor/Pulmonary-Fibrosis.htmhttp://www.pulmonaryfibrosis.org/ Pulmonary Fibrosis UK - http://www.pulmonaryfibrosis.org.uk/http://www.pulmonaryfibrosis.org.uk/ National Heart Lung and Blood Institute (NHLBI)- http://www.nhlbi.nih.gov/health/health-topics/topics/ipf/ http://www.nhlbi.nih.gov/health/health-topics/topics/ipf/ NHS Choices - http://www.nhs.uk/Conditions/pulmonary- fibrosis/Pages/Treatment.aspxhttp://www.nhs.uk/Conditions/pulmonary- fibrosis/Pages/Treatment.aspx PILOT (Pulmonary fibrosis Identification: Lessons for Optimising Treatment) - http://www.pilotforipf.org/ http://www.pilotforipf.org/

20. References Klingsberg, Mutsaers & Lasky (2009) 'Current clinical trials for the treatment of Idiopathic pulmonary fibrosis', Respirology, 15(1), 19-31 http://onlinelibrary.wiley.com/doi/10.1111/j.1440-1843.2009.01672.x/full http://onlinelibrary.wiley.com/doi/10.1111/j.1440-1843.2009.01672.x/full Nogee et al. (2001) 'A Mutation in the Surfactant Protein C Gene associated with Familial Interstitial Lung Disease', The New England Journal of Medicine, 344, 573-579. http://www.nejm.org/doi/full/10.1056/NEJM200102223440805 http://www.nejm.org/doi/full/10.1056/NEJM200102223440805 Paz & Shoenfeld (2010) 'Antifibrosis: To reverse the irreversible', Clinical Reviews in Allergy and Immunology, 38(2-3), 276-286 http://www.springerlink.com/content/7j740131k32jn103/ http://www.springerlink.com/content/7j740131k32jn103/ Raghu et al (2006) 'High prevalence of abnormal acid gastro-oesophageal reflux in idiopathic pulmonary fibrosis', European Respiratory Journal, 27(1), 136-142. http://www.ersj.org.uk/content/27/1/136.shorthttp://www.ersj.org.uk/content/27/1/136.short Thomas et al. (2002) 'Heterozygosity for a Surfactant Protein C Gene Mutation Associated with Usual Interstitial Pneumonitis and Cellular Nonspecific Interstitial Pneumonitis in One Kindred', American Journal of Respiratory and Critical Care Medicine, 165(9), 1322-1328 http://ajrccm.atsjournals.org/content/165/9/1322.shorthttp://ajrccm.atsjournals.org/content/165/9/1322.short

21. Other interesting papers.. International Consensus Statement (2000), 'Idiopathic Pulmonary Fibrosis: Diagnosis and Treatment', American Journal of Respiratory and Critical Care Medicine, 161(2), 646- 664 http://ajrccm.atsjournals.org/content/161/2/646.full – This was a joint statement made by The American Thoracic Society (ATS) and The European Respiratory Society (ERS).http://ajrccm.atsjournals.org/content/161/2/646.full Richeldi et al. (2010) 'Corticosteroids for idiopathic pulmonary fibrosis (Review)', The Cochrane Collaboration, Issue 2 http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD002880/ pdf/standard http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD002880/ pdf/standard

22. Hope we find a cure for you soon Nan - Love you lots!! :) xxxx