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A brief overview of IPF and NSIP
Division of Pulmonology, Department of Medicine, University of the Witwatersrand, Johannesburg, South Africa
Corresponding author: B Schär (bronwynschar@gmail.com)
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
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
Epidemiology
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
Diagnosis
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
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.
References
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2. King TE. Clinical advances in the diagnosis and therapy of interstitial lung diseases. Am J Respir Crit Care Med 2005;172:268-279. [http://dx.doi.org/10.1164/rccm.200503-483OE]
3. Martinez FJ. Idiopathic interstitial pneumonias: Usual interstitial pneumonia versus nonspecific interstitial pneumonia. Proc Am Thorac Soc 2006; 3:81-95. [http://dx.doi.org/10.1513/pats.200511-123JH]
4. Wells AU. Managing diagnostic procedures in idiopathic pulmonary fibrosis. Eur Respir Rev 2013;22:128,158-162. [http://dx.doi.org/10.1183/09059180.00001213]
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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. [http://dx.doi.org/10.1164/rccm.200611-1685OC]
11. Glaspole I, Goh NSL. Differentiating between IPF and NSIP. Chronic Respir Dis 2010;7:3,187-195. [http://dx.doi.org/10.1177/1479972310376205]
12. Cottin V. Changing the idiopathic pulmonary fibrosis treatment approach and improving patient outcomes. Eur Respir Rev 2012;21:124,161-167. [http://dx.doi.org/10.1183/09059180.00001112]
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.org 10.1164/rccm.2009-040GL]
14. Behr J. Evidence-based treatment strategies in idiopathic pulmonary fibrosis. Eur Respir Rev 2013;22:128,163-168. [http://dx.doi.org/10.1183/09059180.00001013]
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