Medscape is available in 5 Language Editions – Choose your Edition here.


Interstitial (Nonidiopathic) Pulmonary Fibrosis Clinical Presentation

  • Author: Eleanor M Summerhill, MD, FACP, FCCP; Chief Editor: Zab Mosenifar, MD, FACP, FCCP  more...
Updated: Aug 09, 2016


The clinical history offered by patients with a DPLD is variable and related to the underlying disease process. Many patients with DPLD, particularly IPF/UIP, may experience acute exacerbations of the disease with subsequent persistent decrement in lung function, which has become increasingly recognized.

In general, all manifest primarily with respiratory symptoms that may be erroneously attributed to aging, obesity, deconditioning, or recent respiratory tract infection. Note the following:

  • Dyspnea is the most frequent symptom, but chronic cough, wheezing, hemoptysis, and chest pain can occur.
  • Digital clubbing is common with some diagnoses (eg, IPF and asbestosis) and may first be noted by the patient. When it develops in a patient with known interstitial lung disease, it is usually indicative of advanced fibrosis. However, it may also herald an underlying bronchogenic carcinoma.

Clinical history may include the following:

  • Incidental diagnosis may be made from a chest radiograph or abnormal screening spirometry findings obtained for unrelated reasons.
  • Diagnosis may occur as a result of screening for high-risk occupational exposure, such as asbestos.
  • Medical attention may be sought for other manifestations of systemic illness that also affect the lungs.

Broadly, the manifestations of fibrotic lung disease can be grouped as follows:

  • They may be chronic, insidious, and slowly progressive.
  • They may be subacute, with a resolving, remitting, relapsing, or progressive course.
  • They may be acute, with a fulminant, progressive, remitting, or resolving course.

Disorders with chronic, insidious, and slowly progressive courses are those that clinically resemble IPF and usually share a common pathology (ie, UIP). Note the following:

  • Many of the rheumatologic/connective-tissue diseases (eg, rheumatoid arthritis; calcinosis cutis, Raynaud phenomenon, esophageal motility disorder, sclerodactyly, and telangiectasia (CREST) syndrome/progressive systemic scleroderma; systemic lupus erythematosus; mixed connective-tissue disease; the pneumoconioses (eg, asbestosis, silicosis); chronic hypersensitivity pneumonitis; and drug-related pulmonary fibrosis (eg, due to bleomycin) generally fit into this category.
  • Development of clinically apparent lung diseases related to occupational exposures (eg, pneumoconiosis) generally occurs many years after the exposure. Radiation fibrosis often develops months to years after radiation exposure.
  • A lag time of months or years can occur between the use of pulmonary toxic medications and the development of fibrotic disease. The effect can be dose-dependent (eg, bleomycin), although, in other cases, the relationship is less clear.
  • Pulmonary manifestations of rheumatologic/connective-tissue disease may develop in advance of, coincident with, or many years after the onset of articular disease.
  • Pulmonary sarcoidosis, although sometimes acute or subacute in onset, in some cases may present insidiously over time.

Subacute presentations with a variable course are typified by COP. Note the following:

  • COP often develops weeks or months after the onset of a flulike illness.
  • Patients can present to medical attention with dyspnea or exercise intolerance.
  • The course is variable and may either spontaneously remit or progress.
  • The disorder is thought to be very responsive to steroid therapy, although it may recur when steroids are withdrawn or tapered.
  • In some cases, COP may progress to end-stage fibrotic lung disease.

Disorders with an acute onset are typified by AIP, which is an idiopathic form of severe lung injury. Note the following:

  • The histopathology is that of adult respiratory distress syndrome with diffuse alveolar damage.
  • Patients present either with no antecedent history of lung disease or as part of an accelerated phase of underlying interstitial disease.
  • Most patients progress rapidly to respiratory failure.
  • Some patients may improve with steroids or other immunosuppressive therapy.


Varied etiologies make generalization of physical examination findings difficult for patients with DPLD. However, clinical examination findings noted in patients with idiopathic pulmonary fibrosis are frequently noted in patients with other DPLDs. Note the following:

  • Patients frequently are dyspneic, which may be more pronounced with activity and generally is associated with an accompanying tachypnea.
  • Central cyanosis may be present if significant hypoxemia and arterial oxygen desaturation are present.
  • Fine end-inspiratory pulmonary rales (Velcro rales) are a common finding and may be difficult to distinguish from those auscultated in patients with congestive heart failure. Pulmonary sarcoidosis and other granulomatous disorders are often an exception.
  • Wheezes may be heard and reflect airway involvement, as in sarcoidosis.
  • A pulmonary squawk has been described with HSP.
  • A right-sided gallop (S3), an accentuated second heart sound (P2) with fixed or paradoxic splitting, and a right ventricular lift may be present. These indicate the presence of cor pulmonale.
  • Digital clubbing may accompany many of these disorders, as previously discussed.

Disease-specific findings include the following:

  • Generalized lymphadenopathy often occurs with sarcoidosis.
  • Cutaneous and articular findings are associated with rheumatologic disease.
  • Gastrointestinal manifestations occur with inflammatory bowel disease.


Numerous causes/diagnoses are included among the DPLDs, many of which can be grouped as shown below.

DPLDs that mimic interstitial lung disease in clinical presentation and chest radiographic findings include the following:

  • Congestive heart failure
  • Atypical pneumonia (including Pneumocystis species)
  • Lymphangitic spread of cancer

DPLDs associated with environmental or occupational exposures include the following:

  • Pneumoconioses (a group of occupational lung diseases related to inhalational exposures to inorganic dusts [eg, silicosis, asbestosis, berylliosis, coal worker's pneumoconiosis {black lung}])
  • HSP caused by exposure to protein antigens (eg, farmer's lung, pigeon-breeder's lung, hot-tub lung)
  • Fibrotic lung disease due to exposure to toxic gases, fumes, aerosols, and vapors (eg, silo-filler's disease)
  • Radiation exposure (ionizing radiation, frequently used in medical therapeutics)

DPLDs associated with rheumatologic/connective-tissue diseases include the following:

  • Scleroderma (CREST syndrome/progressive systemic scleroderma)
  • Rheumatoid arthritis
  • Mixed connective-tissue disease
  • Systemic lupus erythematosus
  • The pulmonary-renal syndromes (ie, Wegner or Goodpasture disease) - Often included with this group; however, predominant manifestation is vasculitis rather than fibrosis

DPLDs related to drug exposure include the following:

  • Cytotoxic agents (eg, bleomycin, busulfan, methotrexate)
  • Antibiotics (eg, nitrofurantoin, sulfasalazine)
  • Antiarrhythmics (eg, amiodarone, tocainide)
  • Anti-inflammatory medications (eg, gold, penicillamine)
  • Illicit drugs (eg, crack cocaine, heroin)
  • Sarcoidosis and other granulomatous diseases (eg, berylliosis)

DPLDs related to other systemic illnesses include the following:

  • Hepatitis C
  • Inflammatory bowel disease
  • Acquired immunodeficiency syndrome

Idiopathic or rare DPLDs include the following:

  • COP (idiopathic)
  • PLCH (rare)
  • Eosinophilic pneumonia

Inherited DPLDs include the following:

  • Familial IPF or sarcoidosis
  • Tuberous sclerosis
  • Neurofibromatosis
  • Niemann-Pick disease
  • Gaucher disease
  • Hermansky-Pudlak syndrome

Certain DPLDs, such as RBILD, DIP, and PLCH, are largely or only seen in current or former smokers.

Contributor Information and Disclosures

Eleanor M Summerhill, MD, FACP, FCCP Associate Professor of Medicine, Division of Pulmonary and Critical Care Medicine, Warren Alpert Medical School of Brown University; Director, Internal Medicine Residency Program, Memorial Hospital of Rhode Island

Eleanor M Summerhill, MD, FACP, FCCP is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Thoracic Society, Rhode Island Medical Society, Association of Program Directors in Internal Medicine

Disclosure: Nothing to disclose.

Specialty Editor Board

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

Disclosure: Received salary from Medscape for employment. for: Medscape.

Daniel R Ouellette, MD, FCCP Associate Professor of Medicine, Wayne State University School of Medicine; Chair of the Clinical Competency Committee, Pulmonary and Critical Care Fellowship Program, Senior Staff and Attending Physician, Division of Pulmonary and Critical Care Medicine, Henry Ford Health System; Chair, Guideline Oversight Committee, American College of Chest Physicians

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

Disclosure: Nothing to disclose.

Chief Editor

Zab Mosenifar, MD, FACP, FCCP Geri and Richard Brawerman Chair in Pulmonary and Critical Care Medicine, Professor and Executive Vice Chairman, Department of Medicine, Medical Director, Women's Guild Lung Institute, Cedars Sinai Medical Center, University of California, Los Angeles, David Geffen School of Medicine

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

Disclosure: Nothing to disclose.

Additional Contributors

Stephen P Peters, MD, PhD, FACP, FAAAAI, FCCP, FCPP Thomas H Davis Chair in Pulmonary Medicine, Chief, Section on Pulmonary, Critical Care, Allergy and Immunologic Diseases, Professor of Internal Medicine, Pediatrics, and Translational Science, Associate Director, Center for Genomics and Personalized Medicine Research, Wake Forest University School of Medicine; Executive Director of the Respiratory Service Line, Wake Forest Baptist Medical Center

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, Sigma Xi

Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: Integrity CE, Merck<br/>Received income in an amount equal to or greater than $250 from: – Array Biopharma, AstraZeneca, Aerocrine, Airsonett AB, Boehringer-Ingelheim, Experts in Asthma, Gilead, GlaxoSmithKline, Merck, Novartis, Ono Pharmaceuticals, Pfizer, PPD Development, Quintiles, Sunovion, Saatchi & Saatichi, Targacept, TEVA, Theron.


The authors and editors of eMedicine gratefully acknowledge the contributions of previous author Robert S. Crausman, MD, MMS, to the development and writing of this article.

  1. Belloli EA, Beckford R, Hadley R, Flaherty KR. Idiopathic non-specific interstitial pneumonia. Respirology. 2016 Feb. 21(2):259-68. [Medline].

  2. Coultas DB, Zumwalt RE, Black WC, Sobonya RE. The epidemiology of interstitial lung diseases. Am J Respir Crit Care Med. 1994 Oct. 150(4):967-72. [Medline].

  3. Seibold MA, Smith RW, Urbanek C, et al. The idiopathic pulmonary fibrosis honeycomb cyst contains a mucocilary pseudostratified epithelium. PLoS One. 2013. 8(3):e58658. [Medline]. [Full Text].

  4. Elliot TL, Lynch DA, Newell JD Jr, et al. High-resolution computed tomography features of nonspecific interstitial pneumonia and usual interstitial pneumonia. J Comput Assist Tomogr. 2005 May-Jun. 29(3):339-45. [Medline].

  5. Lynch DA, Godwin JD, Safrin S, et al for the Idiopathic Pulmonary Fibrosis Study Group. High-resolution computed tomography in idiopathic pulmonary fibrosis: diagnosis and prognosis. Am J Respir Crit Care Med. 2005 Aug 15. 172(4):488-93. [Medline].

  6. Borie R, Quesnel C, Phin S, et al. Detection of alveolar fibrocytes in idiopathic pulmonary fibrosis and systemic sclerosis. PLoS One. 2013. 8(1):e53736. [Medline]. [Full Text].

  7. Hunninghake GW, Zimmerman MB, Schwartz DA, et al. Utility of a lung biopsy for the diagnosis of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2001 Jul 15. 164(2):193-6. [Medline].

  8. Katzenstein AL, Myers JL. Idiopathic pulmonary fibrosis: clinical relevance of pathologic classification. Am J Respir Crit Care Med. 1998 Apr. 157(4 Pt 1):1301-15. [Medline].

  9. Nicholson AG, Addis BJ, Bharucha H, et al. Inter-observer variation between pathologists in diffuse parenchymal lung disease. Thorax. 2004 Jun. 59(6):500-5. [Medline].

  10. Lettieri CJ, Veerappan GR, Parker JM, et al. Discordance between general and pulmonary pathologists in the diagnosis of interstitial lung disease. Respir Med. 2005 Nov. 99(11):1425-30. [Medline].

  11. Egan JJ, Martinez FJ, Wells AU, Williams T. Lung function estimates in idiopathic pulmonary fibrosis: the potential for a simple classification. Thorax. 2005 Apr. 60(4):270-3. [Medline].

  12. 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. 2004 Jan 8. 350(2):125-33. [Medline].

  13. 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. 2005 May 1. 171(9):1040-7. [Medline].

  14. Demedts M, Behr J, Buhl R, Costabel U, Dekhuijzen R, Jansen HM. High-dose acetylcysteine in idiopathic pulmonary fibrosis. N Engl J Med. 2005 Nov 24. 353(21):2229-42. [Medline].

  15. 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. 2008 Jan 1. 177(1):75-81. [Medline].

  16. Kim R, Meyer KC. Therapies for interstitial lung disease: past, present and future. Ther Adv Respir Dis. 2008 Oct. 2(5):319-38. [Medline].

  17. Alalawi R, Whelan T, Bajwa RS, Hodges TN. Lung transplantation and interstitial lung disease. Curr Opin Pulm Med. 2005 Sep. 11(5):461-6. [Medline].

  18. Mason DP, Brizzio ME, Alster JM, et al. Lung transplantation for idiopathic pulmonary fibrosis. Ann Thorac Surg. 2007 Oct. 84(4):1121-8. [Medline].

  19. Meyer DM, Edwards LB, Torres F, Jessen ME, Novick RJ. Impact of recipient age and procedure type on survival after lung transplantation for pulmonary fibrosis. Ann Thorac Surg. 2005 Mar. 79(3):950-7; discussion 957-8. [Medline].

  20. Abe M, Tsushima K, Matsumura T, et al. Efficacy of thrombomodulin for acute exacerbation of idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia: a nonrandomized prospective study. Drug Des Devel Ther. 2015. 9:5755-62. [Medline].

  21. Raghu G, Nyberg F, Morgan G. The epidemiology of interstitial lung disease and its association with lung cancer. Br J Cancer. 2004 Aug. 91 Suppl 2:S3-10. [Medline].

  22. American Thoracic Society, European Respiratory Society. 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. 2002 Jan 15. 165(2):277-304. [Medline].

  23. King TE Jr. Clinical advances in the diagnosis and therapy of the interstitial lung diseases. Am J Respir Crit Care Med. 2005 Aug 1. 172(3):268-79. [Medline].

  24. King TE Jr, Schwarz MI, Brown K, et al. Idiopathic pulmonary fibrosis: relationship between histopathologic features and mortality. Am J Respir Crit Care Med. 2001 Sep 15. 164(6):1025-32. [Medline].

  25. King TE Jr, Tooze JA, Schwarz MI, Brown KR, Cherniack RM. Predicting survival in idiopathic pulmonary fibrosis: scoring system and survival model. Am J Respir Crit Care Med. 2001 Oct 1. 164(7):1171-81. [Medline].

  26. Martinez FJ, Keane MP. Update in diffuse parenchymal lung diseases 2005. Am J Respir Crit Care Med. 2006 May 15. 173(10):1066-71. [Medline].

  27. Philit F, Etienne-Mastroianni B, Parrot A, Guerin C, Robert D, Cordier JF. Idiopathic acute eosinophilic pneumonia: a study of 22 patients. Am J Respir Crit Care Med. 2002 Nov 1. 166(9):1235-9. [Medline].

  28. Quigley M, Hansell DM, Nicholson AG. Interstitial lung disease--the new synergy between radiology and pathology. Histopathology. 2006 Oct. 49(4):334-42. [Medline].

  29. Schwarz MI, King TE, Raghu G. Approach to the evaluation and diagnosis of interstitial lung disease. King TE, Schwarz MI, eds. Interstitial Lung Disease. Ontario, Canada: BC Decker; 2003. 1-30.

Frontal chest radiograph demonstrating bilateral reticular and nodular interstitial infiltrates with upper zone predominance.
High-resolution chest CT scan of patient with bilateral reticular and nodular interstitial infiltrates with upper zone predominance.
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.