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A brief overview of IPF and NSIP.

The diffuse parenchymal lung diseases (DPLDs), also called interstitial lung diseases (ILDs), are a heterogeneous group of rare disorders that cause expansion of the interstitial compartment by varying degrees of inflammation and fibrosis, resulting in parenchymal damage. This group of lung diseases is subdivided into four categories, one of which is the idiopathic interstitial pneumonias (IIPs) (Table 1). (1) The IIPs account for 25 - 30% of all DPLDs, each with distinct clinicopathological and radiological features. Within this subgroup, idiopathic pulmonary fibrosis (IPF) and idiopathic nonspecific interstitial pneumonia (iNSIP) account for 55% and 25% of cases, respectively. (2-4)
Table 1. Classification of diffuse parenchymal lung diseases
(DPLDs) (1)

Category Examples

1. DPLD of known cause Drug toxicity
or association

 Associated connective tissue
 disease (CTD)

 Hypersensitivity pneumonitis


2. Granulomatous DPLD Sarcoidosis

3. Rare DPLD with Lymphangioleiomyomatosis (LAM)
well-defined features

 Langerhans' cell histiocytosis

4. Idiopathic Idiopathic pulmonary fibrosis
interstitial pneumonia (IPF)

 Nonspecific interstitial pneumonia

 Cryptogenic organising pneumonia

 Acute interstitial pneumonia (AIP)

 Desquamative interstitial pneumonia

 Lymphocytic interstitial pneumonia

 Respiratory bronchiolitis
 interstitial lung disease (RBILD)

Accurate diagnosis determines both the appropriate management and the prognosis of DPLDs, and is based on an integrated assessment of clinical, radiological and histological data, preferably by a team experienced in the evaluation of these disorders. (1), (3), (5)

Other conditions associated with similar pathoradiological patterns must be excluded (Table 2), especially in patients presenting with an NSIP pattern, as 39% are subsequently found to have an underlying condition, usually connective tissue disease (CTD). (6) In addition, human immunodeficiency virus (HIV) infection is an important consideration in the work-up of NSIP. (7) A thorough history and clinical examination, together with judicious use of laboratory investigations (e.g. full blood count, electrolytes and renal function, urinalysis, antinuclear antibody and rheumatoid factor), are invaluable in excluding these associated disorders. (1-3), (8)
Table 2. Clinical conditions associated with UIP and NSIP
patterns (1)


Connective tissue disease Connective tissue disease
Drug toxicities Drug toxicities
Occupational exposures (e.g. asbestos) HIV infection
Chronic hypersensitivity pneumonitis Hypersensitivity pneumonitis
Familial idiopathic pulmonary fibrosis Idiopathic NSIP
Idiopathic pulmonary fibrosis

UIP = usual interstitial pneumonia; NSIP = nonspecific
interstitial pneumonia.


IPF is a progressive, fibrotic lung disease, which carries a distinctly poor prognosis with a 5-year mortality of 50 - 80%. (2) It typically affects older patients (age range 55 - 75 years), with a male predominance. Cigarette smoking has been implicated in its development. (4), (5) In contrast, iNSIP usually occurs among non-smoking women in the sixth decade of life (median age of onset 52 years). (9) Although the course of iNSIP is variable, the long-term outcome is more favourable than for IPF, with a 5-year mortality <20%. (2), (10)

Clinical presentation

Classically, patients report a chronic, non-productive cough and exertional dyspnoea that progresses over months. Fever and weight loss are unusual in IPF, but are seen in a minority of iNSIP patients who follow a subacute course with prominent constitutional symptoms. (1) Digital clubbing is found more commonly in IPF (25 - 66%) than iNSIP (8%). (1), (11) Although they are nonspecific, bibasilar crackles are the cardinal feature on respiratory examination. (1), (3)

The chest X-ray usually reveals nonspecific changes, including reduced lung volumes and bilateral, predominantly lower-zone, reticular opacities. (1), (3)

During early disease, lung function tests may be normal, but with disease progression restriction develops. Among smokers and ex-smokers, IPF and chronic obstructive pulmonary disease may co-exist (combined pulmonary fibrosis and emphysema (CPFE)). In patients with CPFE, lung volumes are typically preserved compared with non-smokers with IPF. (1) Most patients demonstrate impaired gas exchange, as evidenced by low oxygen-haemoglobin saturation at rest or on exercise; hypoxaemia on arterial blood gas sampling; or impaired diffusing capacity (DLCO). (1) Serial lung functions are used to monitor IPF and iNSIP, with a declining forced vital capacity (FVC), DLCO and exercise capacity reflecting disease progression. (12)


Identification of a characteristic usual interstitial pneumonia (UIP) or NSIP pattern on high-resolution computerised tomography (HRCT) scan is the initial step in making a definitive diagnosis of IPF and iNSIP, respectively (Table 3). (1-3), (11)
Table 3. UIP and NSIP patterns on HRCT scan (1-3)


Bilateral reticular opacities Bilateral reticular opacities

Ground-glass opacities not Bilateral ground-glass
prominent opacities

Basal and subpleural Basal predominance, diffuse or
predominance subpleural

Fibrosis and honeycombing Honeycombing minimal or absent

With or without traction With or without traction
bronchiectasis bronchiectasis

UIP = usual interstitial pneumonia; NSIP = nonspecific interstitial
pneumonia; HRCT = high-resolution computerised tomography.

Lung biopsy is not required in patients with a typical clinical picture and a definite UIP pattern on HRCT. However, unless specifically contraindicated, surgical lung biopsy (SLB) is recommended for patients with atypical features of IPF (e.g. extensive ground-glass opacities, nodules, consolidation and discrete cysts) or an NSIP pattern on imaging, as radiological and pathological correlation is inconsistent in these situations. (1), (3), (4), (9)

Bronchoalveolar lavage and/or transbronchial biopsies are not required for the diagnosis of an IIP, but may be helpful in excluding differential diagnoses under consideration. (13)

Clinical course and management

Most patients with IPF follow a chronic course, steadily declining over several years. However, subgroups of patients experience either rapid progression or acute exacerbations--defined as periods of rapid deterioration without an identifiable precipitant--both of which portend a poor prognosis. (5)

Unfortunately, despite active research, there is currently no pharmacotherapy with proven benefit in the management of IPF. Consequently, supportive measures (vaccination against pneumococcus and influenza, domiciliary oxygen therapy, pulmonary rehabilitation, management of right heart failure and treatment of gastro-oesophageal reflux) form the mainstay of therapy. However, lung transplantation may offer improved survival for appropriately selected patients. (14)

Although the course of iNSIP differs among individuals, it is generally more responsive to pharmacotherapy than IPF, especially for patients with predominantly inflammatory disease (cellular NSIP), as opposed to predominant fibrosis (fibrotic NSIP). (1), (3), (10) Since prospective, randomised, controlled data in iNSIP are lacking, the therapeutic approach is largely extrapolated from studies of ILD complicating CTD. It employs immunosuppression with corticosteroids, alone or in combination with steroid-sparing cytotoxic agents, such as azathioprine, cyclophosphamide and mycophenolate mofetil. (9) For the minority of iNSIP patients who progress despite pharmacotherapy, supportive measures, similar to those employed in the management of IPF, can be used.


(1.) American Thoracic Society, European Respiratory Society. American Thoracic Society/European Respiratory Society international multi-disciplinary consensus classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med 2002;165:277-304. []

(2.) King TE. Clinical advances in the diagnosis and therapy of interstitial lung diseases. Am J Respir Crit Care Med 2005;172:268-279. []

(3.) Martinez FJ. Idiopathic interstitial pneumonias: Usual interstitial pneumonia versus nonspecific interstitial pneumonia. Proc Am Thorac Soc 2006; 3:81-95. []

(4.) Wells AU. Managing diagnostic procedures in idiopathic pulmonary fibrosis. Eur Respir Rev 2013;22:128,158-162. []

(5.) King TE, Pardo A, Selman M. Idiopathic pulmonary fibrosis. Lancet 2011;378:1949-1961. []

(6.) Katzenstein AL, Fiorelli RF. Nonspecific interstitial pneumonia/fibrosis. Histologic features and clinical significance. Am J Surg Pathol 1994;18:2,136-147.

(7.) Doffman SR, Miller RF. Interstitial lung disease in HIV. Clin Chest Med 2013;34:2, 293-306. []

(8.) Tzelepis GE, Toya SP, Moutsopoulos HM. Occult connective tissue diseases mimicking idiopathic interstitial pneumonias. Eur Respir J 2008;31:11-20. []

(9.) Kinder BW. Nonspecific interstitial pneumonia. Clin Chest Med 2012;33:111-121. []

(10.) Travis WD, Hunninghake G, King TE, et al. Idiopathic nonspecific interstitial pneumonia: Report of an American Thoracic Society Project. Am J Respir Crit Care Med 2008;177:1338-1347. []

(11.) Glaspole I, Goh NSL. Differentiating between IPF and NSIP. Chronic Respir Dis 2010;7:3,187-195. []

(12.) Cottin V. Changing the idiopathic pulmonary fibrosis treatment approach and improving patient outcomes. Eur Respir Rev 2012;21:124,161-167. []

(13.) Raghu G, Collard HR, Egan JJ, et al. An official ATS/ERS/JRS/ALAT statement. Idiopathic pulmonary fibrosis: Evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med 2011;183:788-824. [http://dx.doi.org10.1164/rccm.2009-040GL]

(14.) Behr J. Evidence-based treatment strategies in idiopathic pulmonary fibrosis. Eur Respir Rev 2013;22:128,163-168. []

B Schar, MB ChB, FCP (SA), Cert Pulmonology (SA)

Division of Pulmonology, Department of Medicine, University of the Witwatersrand, Johannesburg, South Africa

Corresponding author: B Schar (
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Title Annotation:More about ... Pulmonology
Author:Schar, B.
Publication:CME: Your SA Journal of CPD
Date:Sep 1, 2013
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