Idiopathic Pulmonary Fibrosis Clinical Presentation

  • Author: Amanda Godfrey, MD; Chief Editor: Zab Mosenifar, MD   more...
 
Updated: May 23, 2012
 

History

The clinical symptoms of idiopathic pulmonary fibrosis are nonspecific. Most patients present with exertional dyspnea and a nonproductive cough. Such symptoms can be shared with a variety of pulmonary and cardiac diseases. Dyspnea, which is the most prominent symptom in idiopathic pulmonary fibrosis (IPF), usually begins insidiously and is often progressive. Associated systemic symptoms can occur but are not common. Some of these systemic symptoms include weight loss, low-grade fevers, fatigue, arthralgias, or myalgias.

The reported median duration of symptoms before the diagnosis of idiopathic pulmonary fibrosis is made is 1-2 years.[5] Most patients are referred to a cardiologist for evaluation of exertional dyspnea prior to being referred to a pulmonologist. Approximately 5% of patients have no presenting symptoms when idiopathic pulmonary fibrosis is diagnosed. Among asymptomatic patients with idiopathic pulmonary fibrosis (diagnosed by radiographic abnormalities found on routine chest radiograph screening and lung biopsy showing usual interstitial pneumonia), symptoms developed approximately 1000 days after the recognition of the radiographic abnormality.[5]

It is critical to obtain a complete history, including medication history, social history, occupational history, exposure history, and review of systems, to ensure other causes of interstitial lung disease are excluded. Amiodarone, bleomycin, and nitrofurantoin are notable medications associated with pulmonary fibrosis. Oxidant stress from smoking may damage alveolar epithelial cells and contribute to the pathogenesis of idiopathic pulmonary fibrosis.[18] Any patient with idiopathic pulmonary fibrosis who is a current smoker should be encouraged to quit. Any prior exposure to asbestos, silica, heavy metals, contaminated ventilation systems, moldy foliage, and/or pigeon droppings should be investigated. Evidence of arthralgia, arthritis, photosensitivity, Raynaud phenomenon, dry eyes, and/or dry mouth on review of systems may indicate the presence of a collagen-vascular disease.

Physicians should pay attention to historical clues that may suggest the presence of obstructive sleep apnea (OSA) because a 2009 study demonstrated the high prevalence of OSA in patients with idiopathic pulmonary fibrosis. Fifty outpatients with stable idiopathic pulmonary fibrosis were prospectively evaluated for the presence of OSA. OSA was defined as an apnea-hypopnea index (AHI) of greater than 5 events per hour. Ten subjects (20%) had mild OSA (AHI of 5-15 events per hour) and 34 subjects (68%) had moderate-to-severe OSA (AHI of >15 events per hour).[19] Therefore, the prevalence of OSA in this sample was 88%, suggesting that OSA in patients with idiopathic pulmonary fibrosis may have been previously underrecognized.

Next

Physical

In most patients with idiopathic pulmonary fibrosis, the physical examination reveals fine bibasilar inspiratory crackles (Velcro crackles). Additionally, digital clubbing is seen in 25-50% of patients with idiopathic pulmonary fibrosis (IPF).[5] Extrapulmonary involvement does not occur with idiopathic pulmonary fibrosis, and, therefore, physical examination findings do not help to confirm the diagnosis.

Pulmonary hypertension is a common comorbidity in patients with idiopathic pulmonary fibrosis, and an estimated 20-40% of patients with idiopathic pulmonary fibrosis who are evaluated or listed for lung transplantation have pulmonary hypertension at rest.[20] Physical examination findings may be suggestive of the presence of pulmonary hypertension. Patients may have a loud P2 component of the second heart sound, a fixed split S2, a holosystolic tricuspid regurgitation murmur, and pedal edema. As right ventricular hypertrophy ensues, a right ventricular heave may be palpated at the lower left sternal border and increased right atrial pressure may cause elevation of the jugular venous pressure.[21]

Previous
Next

Causes

The etiology of idiopathic pulmonary fibrosis remains undefined; however, in the current hypothesis regarding the pathogenesis of idiopathic pulmonary fibrosis (IPF), exposure to an inciting agent (eg, smoke, environmental pollutants, environmental dust, viral infections, gastroesophageal reflux disease, chronic aspiration) in a susceptible host may lead to the initial alveolar epithelial damage.[9] This damage may lead to activation of the alveolar epithelial cells, which provokes the migration, proliferation, and activation of mesenchymal cells with the formation of fibroblastic/myofibroblastic foci, leading to the exaggerated accumulation of extracellular matrix with the irreversible destruction of the lung parenchyma.[9]

Other potential causes of idiopathic pulmonary fibrosis have been recognized through the study of familial pulmonary fibrosis. Familial pulmonary fibrosis, affecting 2 or more members of the same primary biological family, accounts for less than 5% of total patients with idiopathic pulmonary fibrosis.[22]

Genetic mutations in serum surfactant protein C have been discovered in some individuals with familial pulmonary fibrosis.[22] These mutations in serum surfactant protein C may damage type II alveolar epithelial cells.[22] Additionally, a common variant in the putative promoter of the gene encoding mucin 5B (MUC5B) has been associated with the development of both familial interstitial pneumonia and sporadic pulmonary fibrosis.[13]

Finally, mutant telomerase is associated with familial idiopathic pulmonary fibrosis.[12] Pulmonary fibrosis in patients with short telomeres is provoked by a loss of alveolar epithelial cells. Telomere shortening also occurs with aging and can also be acquired. This telomere shortening could promote the loss of alveolar epithelial cells, resulting in aberrant epithelial cell repair, and therefore should be considered as another potential contributor to the pathogenesis of idiopathic pulmonary fibrosis.[12]

Respiratory viruses have been considered a particularly likely cause of AE-IPF based on the similarities in clinical and radiologic presentation between and AE-IPF and viral pneumonitis and the poor sensitivity of standard methods of viral detection. A study by Wootton et al used genomics-based discovery methods to define the role of viral infections in AE-IPF. Initial multiplex polymerase chain reaction (PCR) revealed common respiratory viral infection in only 4 of 43 patients with AE-IPF. Pan-viral microarrays revealed torque teno virus (TTV) in 12 patients with AE-IPF. The pathogenic significance of TTV in AE-IPF is unclear. Overall, viral infection was not detected in most cases of AE-IPF.[23]

Previous
Proceed to Differential Diagnoses
 
 
Contributor Information and Disclosures
Author

Amanda Godfrey, MD  Fellow, Pulmonary and Critical Care Medicine, Henry Ford Hospital

Amanda Godfrey, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Medical Association, American Thoracic Society, and Michigan State Medical Society

Disclosure: Nothing to disclose.

Coauthor(s)

Daniel R Ouellette, MD, FCCP  Associate Professor of Medicine, Wayne State University School of Medicine; Consulting Staff, Pulmonary Disease and Critical Care Medicine Service, Henry Ford Health System

Daniel R Ouellette, MD, FCCP is a member of the following medical societies: American College of Chest Physicians and American Thoracic Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Stephen P Peters, MD, PhD, FACP, FAAAAI, FCCP, FCPP  Professor of Genomics and Personalized Medicine Research, Internal Medicine, and Pediatrics, Associate Director, Center for Genomics and Personalized Medicine Research, Director of Research, Section on Pulmonary, Critical Care, Allergy and Immunologic Diseases, Wake Forest University School of Medicine

Stephen P Peters, MD, PhD, FACP, FAAAAI, FCCP, FCPP is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Association of Immunologists, American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, American Thoracic Society, and Sigma Xi

Disclosure: See below for list of all activities None None

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Daniel R Ouellette, MD, FCCP  Associate Professor of Medicine, Wayne State University School of Medicine; Consulting Staff, Pulmonary Disease and Critical Care Medicine Service, Henry Ford Health System

Daniel R Ouellette, MD, FCCP is a member of the following medical societies: American College of Chest Physicians and American Thoracic Society

Disclosure: Nothing to disclose.

Timothy D Rice, MD  Associate Professor, Departments of Internal Medicine and Pediatrics and Adolescent Medicine, St Louis University School of Medicine

Timothy D Rice, MD is a member of the following medical societies: American Academy of Pediatrics and American College of Physicians

Disclosure: Nothing to disclose.

Chief Editor

Zab Mosenifar, MD  Director, Division of Pulmonary and Critical Care Medicine, Director, Women's Guild Pulmonary Disease Institute, Professor and Executive Vice Chair, Department of Medicine, Cedars Sinai Medical Center, University of California, Los Angeles, David Geffen School of Medicine

Zab Mosenifar, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, and American Thoracic Society

Disclosure: Nothing to disclose.

Additional Contributors

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous authors, Rajesh G. Patel, MD, and Javier I. Diaz, MD, to the development and writing of this article.

References

  1. Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, Brown KK. An Official ATS/ERS/JRS/ALAT Statement: Idiopathic Pulmonary Fibrosis: Evidence-based Guidelines for Diagnosis and Management. Am J Respir Crit Care Med. Mar 15 2011;183(6):788-824. [Medline].

  2. American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias. This joint statement of the American Thoracic Society (ATS), and the European Respiratory Society (ERS) was adopted by the ATS board of directors, June 2001 and by the ERS Executive Committee, June 2001. Am J Respir Crit Care Med. Jan 15 2002;165(2):277-304. [Medline].

  3. Frankel SK, Schwarz MI. Update in idiopathic pulmonary fibrosis. Curr Opin Pulm Med. Sep 2009;15(5):463-9. [Medline].

  4. Ley B, Collard HR, King TE Jr. Clinical course and prediction of survival in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. Feb 15 2011;183(4):431-40. [Medline].

  5. Kim DS, Collard HR, King TE Jr. Classification and natural history of the idiopathic interstitial pneumonias. Proc Am Thorac Soc. Jun 2006;3(4):285-92. [Medline]. [Full Text].

  6. Misumi S, Lynch DA. Idiopathic pulmonary fibrosis/usual interstitial pneumonia: imaging diagnosis, spectrum of abnormalities, and temporal progression. Proc Am Thorac Soc. Jun 2006;3(4):307-14. [Medline].

  7. Visscher DW, Myers JL. Histologic spectrum of idiopathic interstitial pneumonias. Proc Am Thorac Soc. Jun 2006;3(4):322-9. [Medline].

  8. Verma S, Slutsky AS. Idiopathic pulmonary fibrosis--new insights. N Engl J Med. Mar 29 2007;356(13):1370-2. [Medline].

  9. Harari S, Caminati A. IPF: new insight on pathogenesis and treatment. Allergy. May 2010;65(5):537-53. [Medline].

  10. Thannickal VJ, Horowitz JC. Evolving concepts of apoptosis in idiopathic pulmonary fibrosis. Proc Am Thorac Soc. Jun 2006;3(4):350-6. [Medline]. [Full Text].

  11. Maher TM, Evans IC, Bottoms SE, Mercer PF, Thorley AJ, Nicholson AG. Diminished prostaglandin E2 contributes to the apoptosis paradox in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. Jul 1 2010;182(1):73-82. [Medline].

  12. Armanios MY, Chen JJ, Cogan JD, et al. Telomerase mutations in families with idiopathic pulmonary fibrosis. N Engl J Med. Mar 29 2007;356(13):1317-26. [Medline].

  13. Seibold MA, Wise AL, Speer MC, Steele MP, Brown KK, Loyd JE. A common MUC5B promoter polymorphism and pulmonary fibrosis. N Engl J Med. Apr 21 2011;364(16):1503-12. [Medline].

  14. Wang XM, Zhang Y, Kim HP, et al. Caveolin-1: a critical regulator of lung fibrosis in idiopathic pulmonary fibrosis. J Exp Med. Dec 25 2006;203(13):2895-906. [Medline]. [Full Text].

  15. Fernandez Perez ER, Daniels CE, Schroeder DR, et al. Incidence, prevalence, and clinical course of idiopathic pulmonary fibrosis: a population-based study. Chest. Jan 2010;137(1):129-37. [Medline]. [Full Text].

  16. Olson AL, Swigris JJ, Lezotte DC, Norris JM, Wilson CG, Brown KK. Mortality from pulmonary fibrosis increased in the United States from 1992 to 2003. Am J Respir Crit Care Med. Aug 1 2007;176(3):277-84. [Medline].

  17. Raghu G, Weycker D, Edelsberg J, Bradford WZ, Oster G. Incidence and prevalence of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. Oct 1 2006;174(7):810-6. [Medline].

  18. Antoniou KM, Hansell DM, Rubens MB, et al. Idiopathic pulmonary fibrosis: outcome in relation to smoking status. Am J Respir Crit Care Med. Jan 15 2008;177(2):190-4. [Medline].

  19. Lancaster LH, Mason WR, Parnell JA, et al. Obstructive sleep apnea is common in idiopathic pulmonary fibrosis. Chest. Sep 2009;136(3):772-8. [Medline]. [Full Text].

  20. Patel NM, Lederer DJ, Borczuk AC, Kawut SM. Pulmonary hypertension in idiopathic pulmonary fibrosis. Chest. Sep 2007;132(3):998-1006. [Medline].

  21. Fishman A, Elias J, Fishman J, Grippi M, Senior R, Pack A. Idiopathic Pulmonary Fibrosis. In: Fishman AP. Fishman's Pulmonary Diseases and Disorders. Vol 1. 4th ed. The McGraw-Hill Companies, Inc.; 2008:1143-60.

  22. Lawson WE, Loyd JE. The genetic approach in pulmonary fibrosis: can it provide clues to this complex disease?. Proc Am Thorac Soc. Jun 2006;3(4):345-9. [Medline]. [Full Text].

  23. Wootton SC, Kim DS, Kondoh Y, et al. Viral infection in acute exacerbation of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. Jun 15 2011;183(12):1698-702. [Medline]. [Full Text].

  24. Flaherty KR, Thwaite EL, Kazerooni EA, et al. Radiological versus histological diagnosis in UIP and NSIP: survival implications. Thorax. Feb 2003;58(2):143-8. [Medline]. [Full Text].

  25. Martinez FJ, Flaherty K. Pulmonary function testing in idiopathic interstitial pneumonias. Proc Am Thorac Soc. Jun 2006;3(4):315-21. [Medline]. [Full Text].

  26. Tzilas V, Koti A, Papandrinopoulou D, Tsoukalas G. Prognostic factors in idiopathic pulmonary fibrosis. Am J Med Sci. Dec 2009;338(6):481-5. [Medline].

  27. du Bois RM, Weycker D, Albera C, Bradford WZ, Costabel U, Kartashov A, et al. Forced vital capacity in patients with idiopathic pulmonary fibrosis: test properties and minimal clinically important difference. Am J Respir Crit Care Med. Dec 15 2011;184(12):1382-9. [Medline].

  28. Flaherty KR, Andrei AC, Murray S, et al. Idiopathic pulmonary fibrosis: prognostic value of changes in physiology and six-minute-walk test. Am J Respir Crit Care Med. Oct 1 2006;174(7):803-9. [Medline]. [Full Text].

  29. Swigris JJ, Swick J, Wamboldt FS, et al. Heart rate recovery after 6-min walk test predicts survival in patients with idiopathic pulmonary fibrosis. Chest. Sep 2009;136(3):841-8. [Medline]. [Full Text].

  30. Bois RM, Weycker D, Albera C, et al. Six-minute-walk test in idiopathic pulmonary fibrosis: test validation and minimal clinically important difference. Am J Respir Crit Care Med. May 1 2011;183(9):1231-7. [Medline].

  31. Ohshimo S, Bonella F, Cui A, et al. Significance of bronchoalveolar lavage for the diagnosis of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. Jun 1 2009;179(11):1043-7. [Medline].

  32. Kinder BW, Brown KK, Schwarz MI, Ix JH, Kervitsky A, King TE Jr. Baseline BAL neutrophilia predicts early mortality in idiopathic pulmonary fibrosis. Chest. Jan 2008;133(1):226-32. [Medline].

  33. Lee JS, Ryu JH, Elicker BM, Lydell CP, Jones KD, Wolters PJ, et al. Gastroesophageal reflux therapy is associated with longer survival in patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. Dec 15 2011;184(12):1390-4. [Medline].

  34. Kozower BD, Meyers BF, Smith MA, et al. The impact of the lung allocation score on short-term transplantation outcomes: a multicenter study. J Thorac Cardiovasc Surg. Jan 2008;135(1):166-71. [Medline].

  35. Weiss ES, Allen JG, Merlo CA, Conte JV, Shah AS. Survival after single versus bilateral lung transplantation for high-risk patients with pulmonary fibrosis. Ann Thorac Surg. Nov 2009;88(5):1616-25; discussion 1625-6. [Medline].

  36. Orens JB, Estenne M, Arcasoy S, et al. International guidelines for the selection of lung transplant candidates: 2006 update--a consensus report from the Pulmonary Scientific Council of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant. Jul 2006;25(7):745-55. [Medline].

  37. Behr J, Kolb M, Cox G. Treating IPF--all or nothing? A PRO-CON debate. Respirology. Nov 2009;14(8):1072-81. [Medline].

  38. Demedts M, Behr J, Buhl R, et al. High-dose acetylcysteine in idiopathic pulmonary fibrosis. N Engl J Med. Nov 24 2005;353(21):2229-42. [Medline].

  39. Prednisone, Azathioprine, and N-Acetylcysteine for Pulmonary Fibrosis. N Engl J Med. May 20 2012;[Medline].

  40. National Heart, Lung, and Blood Institute. Clinical Alert: Commonly Used Three-Drug Regimen for Pulmonary Fibrosis Found Harmful. NIH Stops One Treatment Arm of Trial; Other Two Treatments to Continue. US National Library of Medicine: National Institutes of Health; October 21, 2011. [Full Text].

  41. Raghu G, Brown KK, Bradford WZ, et al. A placebo-controlled trial of interferon gamma-1b in patients with idiopathic pulmonary fibrosis. N Engl J Med. Jan 8 2004;350(2):125-33. [Medline].

  42. Raghu G, Brown KK, Costabel U, et al. Treatment of idiopathic pulmonary fibrosis with etanercept: an exploratory, placebo-controlled trial. Am J Respir Crit Care Med. Nov 1 2008;178(9):948-55. [Medline].

  43. King TE Jr, Albera C, Bradford WZ, et al. Effect of interferon gamma-1b on survival in patients with idiopathic pulmonary fibrosis (INSPIRE): a multicentre, randomised, placebo-controlled trial. Lancet. Jul 18 2009;374(9685):222-8. [Medline].

  44. King TE Jr, Behr J, Brown KK, et al. BUILD-1: a randomized placebo-controlled trial of bosentan in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. Jan 1 2008;177(1):75-81. [Medline].

  45. The Idiopathic Pulmonary Fibrosis Clinical Research Network, Zisman DA, Schwarz M, Anstrom KJ, Collard HR, Flaherty KR. A controlled trial of sildenafil in advanced idiopathic pulmonary fibrosis. N Engl J Med. Aug 12 2010;363(7):620-8. [Medline].

  46. Daniels CE, Lasky JA, Limper AH, Mieras K, Gabor E, Schroeder DR. Imatinib treatment for idiopathic pulmonary fibrosis: Randomized placebo-controlled trial results. Am J Respir Crit Care Med. Mar 15 2010;181(6):604-10. [Medline].

  47. Richeldi L, Costabel U, Selman M, et al. Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosis. N Engl J Med. 365:1079-1087.

  48. Azuma A, Nukiwa T, Tsuboi E, et al. Double-blind, placebo-controlled trial of pirfenidone in patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. May 1 2005;171(9):1040-7. [Medline].

  49. Taniguchi H, Ebina M, Kondoh Y, et al. Pirfenidone in idiopathic pulmonary fibrosis. Eur Respir J. Apr 2010;35(4):821-9. [Medline].

  50. Noble PW, Albera C, Bradford WZ, et al. Pirfenidone in patients with idiopathic pulmonary fibrosis (CAPACITY): two randomised trials. Lancet. May 21 2011;377(9779):1760-9. [Medline].

  51. Hyzy R, Huang S, Myers J, Flaherty K, Martinez F. Acute exacerbation of idiopathic pulmonary fibrosis. Chest. Nov 2007;132(5):1652-8. [Medline].

  52. Song JW, Hong SB, Lim CM, Koh Y, Kim DS. Acute exacerbation of idiopathic pulmonary fibrosis: incidence, risk factors and outcome. Eur Respir J. Feb 2011;37(2):356-63. [Medline].

  53. du Bois RM, Weycker D, Albera C, Bradford WZ, Costabel U, Kartashov A, et al. Ascertainment of individual risk of mortality for patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. Aug 15 2011;184(4):459-66. [Medline].

  54. Ley B, Ryerson CJ, Vittinghoff E, et al. A Multidimensional Index and Staging System for Idiopathic Pulmonary Fibrosis. Annals of Internal Medicine. 2012/05;156:684-691.

  55. Fang A, Studer S, Kawut SM, Ahya VN, Lee J, Wille K. Elevated Pulmonary Artery Pressure Is a Risk Factor for Primary Graft Dysfunction Following Lung Transplantation for Idiopathic Pulmonary Fibrosis. Chest. Apr 2011;139(4):782-787. [Medline].

  56. Kinder BW, Brown KK, McCormack FX, et al. Serum surfactant protein-A is a strong predictor of early mortality in idiopathic pulmonary fibrosis. Chest. Jun 2009;135(6):1557-63. [Medline]. [Full Text].

  57. American Thoracic Society. Idiopathic pulmonary fibrosis: diagnosis and treatment. International consensus statement. American Thoracic Society (ATS), and the European Respiratory Society (ERS). Am J Respir Crit Care Med. Feb 2000;161(2 Pt 1):646-64. [Medline].

  58. Patel AS, Siegert RJ, Brignall K, Gordon P, Steer S, Desai SR. The development and validation of the King's Brief Interstitial Lung Disease (K-BILD) health status questionnaire. Thorax. May 3 2012;[Medline].

 
Previous
Next
 
Chest radiograph of a patient with idiopathic pulmonary fibrosis showing bilateral lower lobe reticular opacities (red circles).
Classic subpleural honeycombing (red circle) in a patient with a diagnosis of idiopathic pulmonary fibrosis.
A patient with IPF and a confirmed histologic diagnosis of usual interstitial pneumonia. Note the reticular opacities (red circle) distributed in both lung bases and the minimal ground-glass opacities (blue circle).
A patient with nonspecific interstitial pneumonia. Note the predominance of ground-glass opacities (blue circles) and a few reticular lines (red arrow).
Patchwork distribution of abnormalities in a classic example of usual interstitial pneumonia (low-magnification photomicrograph; hematoxylin and eosin stain; original magnification, X4). Courtesy of Chad Stone, MD.
Table 1. Scoring for mortality risk in IPF.
PredictorPoints
SexFemale0
Male1
Age (years)≥600
61-651
>652
FVC (% predicted)>750
50-751
< 502
DLCO (% predicted)>550
36-551
≤352
Cannot perform3
Table 2. Staging and mortality risk for IPF.
StageIIIIII
Points0-34-56-8
Mortality
1-year5.616.239.2
2-year10.929.962.1
3-year16.342.176.8
Previous
Next
 
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.