ReviewIdiopathic Pulmonary Fibrosis: Current Concepts
Section snippets
DEFINITION
Currently, a universally accepted definition of IPF is lacking. The clinician, the radiologist, the physiologist, and the pathologist all have different points of view and frames of reference. IPF is generally considered a pulmonary disease of unknown cause, characterized by parenchymal inflammation (“alveolitis”) and progressive interstitial fibrosis.8, 9, 18, 19 Usually, it affects middle-aged and older persons.6, 7, 20 In most patients, IPF is slowly progressive and results in death.6, 7, 20
HISTORICAL PERSPECTIVE
More than 50 years ago, Hamman and Rich30, 31 described four patients dying of diffuse interstitial fibrosis of the lungs of unknown cause. The duration of illness ranged from 4 to 24 weeks.30, 31 These investigators referred to this condition as “interstitial fibrosis” and described “the remarkable proliferation of connective tissue that occurs within the alveolar walls.”31 Although this report is frequently referred to as the initial description of IPF, the rapidly fatal course of their
EPIDEMIOLOGY
The prevalence of IPF is not precisely known but has been estimated to be 3 to 29 cases per 100,000 population.5, 6, 7 The wide range of this estimate is likely explained by the lack of uniform definition used in identifying cases of IPF, the differences in study designs and populations, and the fact that the incidence may be increasing (see subsequent discussion). The most recent prevalence estimates are from a population-based registry of patients with ILDs from 1988 to 1990 in Bernalillo
PATHOGENESIS
The cause of IPF remains unknown. A general theory is that a triggering agent or event induces an inflammatory reaction in the lung that perpetuates itself and causes progressive parenchymal fibrosis.9, 18, 37 Reports have described familial cases of IPF for which an autosomal dominant pattern of inheritance has been suggested.51, 52 No clear evidence exists for a viral cause.59 A few cases of IPF have been described after viral or mycoplasmal infections, but some of these probably represented
PATHOLOGY
Although most investigators currently consider IPF synonymous with idiopathic UIP, IPF (and CFA) has historically been used to refer to a heterogeneous group of disorders in patients with various histologic pattems.10, 12, 21, 25 The histologic modifications in the classification of idiopathic interstitial pneumonias have occurred in recent years and have confused clinicians, radiologists, and pathologists. The results of reclassification of a series of cases diagnosed as IPF during the 1970s
CLINICAL FEATURES
Most patients with a clinical diagnosis of IPF have increasing exertional breathlessness and a chronic cough, which may produce sputum but often is dry.19, 21, 25 These symptoms may be preceded by an influenza-like illness.19, 21, 25 About 5% of patients are asymptomatic at the time of diagnosis.20 Almost all patients have bibasilar crackles, and about one-half to two-thirds have digital clubing20, 21, 25, 26, 44, 71 Additional symptoms can include chest pain or constitutional symptoms such as
Chest Radiograph
Most symptomatic patients have abnormal findings on chest radiographs. Rarely, patients may have abnormal findings on chest radiographs in the absence of respiratory symptoms.20 A previous chest radiograph (if available) for comparison is extremely helpful in the assessment of the activity of the disease. The most common chest radiographic abnormalities are bilateral reticular (linear) interstitial infiltrates with a predilection for the lower lung zones.9, 19, 21, 26 As the disease advances,
MEDIASTINAL IMAGING
Mediastinal lymph nodes are commonly detected by CT in patients with UIP.83, 84 Usually, only a few nodes are enlarged; maximal diameter is less than 15 mm.84 In late disease, pneumomediastinum may be detected by CT.85
GALLIUM SCANNING
Ga67 lung scanning previously had been recommended as a noninvasive method of distinguishing active cellular disease from fibrotic disease by assessment of the degree of active inflammation in the lung of patients with IPF and other ILDs.8667Ga citrate is taken up by activated macro-phages. Unfortunately, the validity of this test has not been adequately demonstrated, and interpretation has been difficult. Subjective visual index is generally used and is not always reproducible.67Ga lung
PULMONARY FUNCTION TESTING
As with most types of ILDs, pulmonary function testing in patients with IPF usually shows a restrictive impairment, with reduced lung volumes and decreased diffusing capacity.87, 88 In early stages, an isolated reduction in diffusing capacity may be seen with normal lung volumes. The ratio of the forced expiratory volume in 1 second to the forced vital capacity is normal or increased, a finding consistent with a restrictive dysfunction. Gas exchange is usually impaired with an increased
DIAGNOSIS
During the initial assessment of a patient with suspected IPF, elicitation of the history is the most important step in identifying clues to possible occupational and environmental causes (Table 4). The history should include a review of not only previous occupations but also the home environment, including presence of birds, pets, humidifiers, air conditioners, and hot tubs. A review of the family history and the list of medications may also yield the cause of lung disease. Known causes of
TREATMENT
The traditional mainstay of treatment of patients with IPF has been corticosteroids, but this type of therapy is unproved in prospective and randomized studies. Corticosteroid therapy is based on current knowledge of the pathogenic mechanisms of this disease—that is, chronic active inflammation leading to progressive, irreversible fibrosis. Thus, the attempt is made to control the inflammatory and immune cell response with corticosteroid therapy in conjunction with other immunosuppressive
PROGNOSIS
The median survival for patients with IPF has been estimated to be 3 to 6 years, but the clinical course of IPF has been noted to vary considerably.21, 24, 26, 27, 42, 43, 71 This variability in clinical course and prognosis is likely due, in part, to the heterogeneity of patients included in earlier series of IPF. For example, in a recent study by Bjoraker and associates,12 patients with an initial diagnosis of IPF based on open-lung biopsy were shown to have various histologic lesions,
SUMMARY
- 1.
IPF (or CFA) as originally defined was a clinical concept. Cases previously classified as IPF are currently heterogeneous and include several clinicopathologic entities.
- 2.
The most common histologic pattern in cases previously diagnosed as IPF is UIP. UIP is associated with a worse prognosis (median survival of less than 3 years) and response to corticosteroid therapy in comparison with other types of chronic interstitial pneumonia including DIP, NSIP, RB-ILD, and BOOP.
- 3.
Inclusion of several
CONCLUSION
Assessment and management of patients with IPF remain challenging. A need exists for a consensus on the defining diagnostic criteria of IPF. Many of the currently available studies describe patient populations that have been inadequately characterized and are not entirely comparable. Thus, we recommend that, in the future, the term “idiopathic pulmonary fibrosis” be used only in reference to patients with known or suspected UIP histology.
Treatment options remain limited and unsatisfactory for
Acknowledgment
We thank Drs. William W. Douglas and David E. Midthun for their critique and thoughtful suggestions regarding the submitted manuscript.
References (127)
Diagnostic and management strategies of diffuse interstitial lung disease
Chest
(1998)Diffuse interstitial pulmonary disease from the perspective of the clinician
Chest
(1987)- et al.
Colchicine versus prednisone as treatment of usual interstitial pneumonia
Mayo Clin Proc
(1997) - et al.
Survival in patients with cryptogenic fibrosing alveolitis: a population-based cohort study
Chest
(1998) - et al.
Hamman-Rich syndrome revisited
Mayo Clin Proc
(1990) - et al.
Pathologic manifestations of bronchiolitis, constrictive bronchiolitis, cryptogenic organizing pneumonia, and diffuse panbronchiolit is
Clin Chest Med
(1993) - et al.
Respiratory bronchiolitisassociated interstitia l lung disease and its relationship to desquamative inter st iti al pneumoni a
Mayo Cli n Ptoc
(1989) - et al.
Cryptogenic fibrosing alveolitis: assessment by graded trephine lung biopsy histology compared with clinical, radiographic, and physiologic features
Br J Dis Chest
(1981) - et al.
Diffuse interstitial pneumonit is: clinicopathologic correlations in 20 patients treated with prednisone/azathioprine
AmJ Med
(1978) - et al.
Disease progression in usual interstitial pneumonia compared with desquamative interstitia l pneumonia: assessment with serial CT
Chest
(1996)
Chronic intersti tial pulmonary fibrosis following Mycoplasma pneumoniae pneumonia
Am J Med
Pulmonary hypertension in the interstitial lung diseases [editori al]
Chest
The concept of classic interstitial pneumonitis-fibrosis (CIP-F) as a clinicopathologic syndrome
Chest
Pulmonary fibrosis as an unusual clinical manifestation of a pulmonary-renal vasculitis in elderly patients
Mayo Clin Proc
Acute exacerbation in idiopathic pulmonary fibrosis: analysis of clin ica l and path ol ogic f indi ngs in t hree cases
Chest
Pneumomediastinum in pulmonary fibrosis: detection by computed tomography
Chest
Clinical significance of pulmonary function tests: pulmonary function testing in interstitial pulmonary disease; what does it tell us?
Chest
Correlation of chest roentgenograms with pulmonary function and bronchoalveolar lavage in interstitial lung disease
Chest
Changes in pulmonary function test results after 1 year of therapy as predictors of survival in patients with idiopathic pulmonary fibrosis
Chest
Lung function tests in patients with idiopathic pulmonary fibrosis: are they helpful in predicting outcome?
Chest
The sensitivity of high-resolution CT in detecting idiopathic pulmonary fibrosis proved by open lung biopsy: a prospective study
Chest
The diagnostic and therapeutic utility of thoracoscopy: a review
Chest
Anatomic distribution of histopathologic patterns in diffuse lung disease: correlation with HRCT (published erratum appears in J Thorac Imaging 1996:11:163]
J Thorac Imaging
Interstitial lung diseases of unknown cause: disorders characterized by chronic inflammation of the lower respiratory tract
N Engl J Med
The epidemiology of interstitial lung diseases
Am J Respir Crit Care Med
What causes cryptogenic fibrosing alveolitis? A case-control study of environmental exposure to dust
BMJ
Idiopathic pulmonary fibrosis: current clinical concepts and challenges in management
Semin Respir Crit Care Med
Idiopathic pulmonary fibrosis
Idiopathic pulmonary fibrosis: clinical relevance of pathologic classification
Am J Respir Crit Care Med
Nonspecific interstitial pneumonia
Clin Pulm Med
Prognostic significance of histopathologic subsets in idiopathic pulmonary fibrosis
Am J Respir Crit Care Med
Nonspecific interstitial pneumonia/fibrosis: histologic features and clinical significance
Am J Surg Pathol
Idiopathic interstitial pneumonia: classification and diagnosis
Monogr Pathol
Respiratory bronchiolitis causing interstitial lung disease: a clinicopathologic study of six cases
Am Rev Respir Dis
Bronchiolitis obliterans organizing pneumonia
N Engl J Med
Acute interstitial pneumonia: a clinicopathologic, ultrastructural and cell kinetic study
Am J Surg Pathol
Current concepts in idiopathic pulmonary fibrosis: a road map for the future
Am Rev Respir Dis
Idiopathic pulmonary fibrosis: clinical, histologic, radiographic, physiologic, scintigraphic, cytologic, and biochemical aspects
Ann Intern Med
British Thoracic Society study of cryptogenic fibrosing alveolitis: current presentation and initial management
Thorax
Cryptogenic fibrosing alveolitis: clinical features and their influence on survival
Thorax
Determinants of survival in idiopathic pulmonary fibrosis
Am J Respir Crit Care Med
Quantitative assessment of lung pathology in idiopathic pulmonary fibrosis
Am Rev Respir Dis
The prognosis of cryptogenic fibrosing alveolitis
Thorax
Diffuse fibrosing alveolitis (diffuse interstitial fibrosis of the lungs): correlation of histology at biopsy with prognosis
Thorax
Diffuse interstitial pulmonary fibrosis: a clinical, radiological, and pathological study based on 45 patients
Q J Med
Natural history and treated course of usual and desquamative interstitial pneumonia
N Engl J Med
Fulminating diffuse interstitial fibrosis of the lungs
Trans Am Clin Climatol Assoc
Acute diffuse interstitial fibrosis of the lungs
Bull Johns Hopkins Hosp
Alveolar diseases
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