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Idiopathic Pulmonary Fibrosis*: A Practical Approach for Diagnosis and Management FREE TO VIEW

Jeffrey E. Michaelson, MD; Samuel M. Aguayo, MD, FCCP; Jesse Roman, MD
Author and Funding Information

*From the Division of Pulmonary and Critical Care Medicine (Drs. Michaelson and Roman), Departments of Medicine, Atlanta Veterans Affairs Medical Center, Emory University School of Medicine; and Morehouse School of Medicine (Dr. Aguayo), Atlanta, GA.

Correspondence to: Jesse Roman, MD, Atlanta VA Medical Center, Pulmonary Section, Rm 12C191, 1670 Clairmont Rd, Decatur, GA 30033; e-mail: ROMAN-RODRIGUEZ.JESSE@ATLANTA.VA.GOV



Chest. 2000;118(3):788-794. doi:10.1378/chest.118.3.788
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Published online

Idiopathic pulmonary fibrosis (IPF) is a challenging clinical entity because virtually every aspect of the disease (ie, pathogenesis, diagnosis, management) remains controversial. While the resolution of these controversies will require further investigations, the purpose of this clinical commentary is to integrate recent advances described in the literature in an effort to delineate a practical clinical approach for the diagnosis and management of IPF. As such, our commentary is not meant to be an exhaustive review, but rather a focused discussion dealing specifically with terminology, diagnosis, and treatment of this condition.

Our clinical commentary on IPF is timely because recent epidemiologic data suggest that IPF may be more common than originally suspected. For instance, Coultas and colleagues,1 studied all diagnoses of interstitial lung disease (ILD) from 1988 to 1990 in a population of almost 500,000 in Bernadillo County, NM. In that study, IPF was the most common form of ILD, accounting for 39% of all ILD cases. Of note, only a minority of such diagnoses were proven by open lung biopsy specimens, and this may contribute to the relatively high prevalence, compared to previous estimates. At any rate, among male subjects, the prevalence of IPF was 30.3/100,000 and the incidence was 27.5/100,000/yr. Rates among female subjects were approximately half that of male subjects, with a prevalence and incidence of 14.6/100,000 and 11.5/100,000/yr, respectively. IPF rates increased with advancing age, such that for those > 75 years old, the prevalence was 250/100,000, with an incidence of 160/100,000/yr. Another limitation of the study by Coultas and colleagues1is that, compared to the general population of North America, the disproportionate representations of African Americans (reduced) and Hispanics (increased) in New Mexico may have partly accounted for the increased rates of IPF relative to other forms of ILD such as sarcoidosis. Nevertheless, the results suggest that IPF is indeed a clinical entity of considerable impact. Along those same lines, Mannino and coworkers2 have observed that in the United States, disease-related mortality for IPF increased from 1979 to 1991. Again, although increased awareness and, perhaps, misdiagnoses may have contributed to this observation, the work of Mannino and coworkers2 underscores how little progress has been made in the treatment of this complex disorder.

Diagnostic uncertainties created in part by the multiple different ways in which physicians have approached IPF (ie, the availability of appropriate lung biopsy specimens and accurate medical histories) and the variability in the natural history and response to therapy of IPF have contributed to the confusion inherent in this topic. Historically, IPF (or cryptogenic fibrosing alveolitis, as it has been known in Europe) was originally presumed to be a single clinical entity distinguished by a constellation of symptoms and signs that include cough, dyspnea, and inspiratory rales on physical examination; evidence of restrictive physiology with reduced diffusion capacity for carbon monoxide and abnormal gas exchange; and the appearance of diffuse interstitial infiltrates on chest imaging. Unfortunately, there is nothing specific about this clinical-radiographic syndrome that would distinguish an idiopathic form of pulmonary fibrosis from other forms of ILD (eg, asbestosis, collagen vascular disease-associated lung disease, chronic hypersensitivity pneumonitis, bronchiolitis obliterans and organizing pneumonia), for which we may have more specific information about etiology, pathogenesis, and course of the illness. It is critical then to remember that, when reviewing and integrating the medical literature, some confusion is likely to be generated by many of the early clinical studies of IPF because of the inclusion of patients with ILD secondary to other illnesses (eg, collagen vascular disease), in which the clinical course has been demonstrated more recently to be more benign than that of IPF. Furthermore, it should be recognized that in patients in whom other causes of ILD have been carefully considered and discarded, histologic analysis of their lungs may still reveal several patterns that differ in the distribution, intensity, and nature of their fibrosis and inflammation. Liebow3was the first to classify these patterns of idiopathic interstitial pneumonias based on morphologic criteria. Katzenstein and Myers4revised this scheme and described the following four major histologic patterns of idiopathic interstitial pneumonia: usual interstitial pneumonitis (UIP), desquamative interstitial pneumonitis (DIP), acute interstitial pneumonitis (AIP), and nonspecific interstitial pneumonitis (NSIP; Table 1 ). Of these four patterns, UIP appears to be the most common, followed by NSIP, DIP, and AIP.5 The existence of these different histologic subsets is perhaps what best explains the variable clinical manifestations of the clinical-radiographic syndrome of IPF (see below). Accordingly, the clinical diagnosis of idiopathic interstitial pneumonia without an open lung biopsy specimen may include any of these histologic patterns, with a probability that is determined by the prevalence of each condition (Table 1). However, the firm diagnosis of IPF should be reserved only for the idiopathic interstitial pneumonia that has been classified as UIP by histology or other means (see below).

One of the most difficult decisions in the evaluation of a patient suspected of suffering from IPF is whether a lung biopsy should be performed to confirm the diagnosis.6 Our short answer is that histologic confirmation is not necessary in every single patient with suspected IPF, but that it is desirable to have histologic confirmation whenever possible. However, this is a very complicated decision that needs to incorporate factors such as the desire for diagnostic and prognostic certainty, both from the patient’s and the physician’s perspective; the overall health status and age of the patient, as these relate to possible complications and expected outcomes; the availability of surgical and pathology expertise that would minimize complications and maximize the usefulness of the biopsy, respectively; and the disposition of the patient to adhere to the available therapeutic regimens after considering the prognosis and other issues, like side effects and quality of life.

Those who strongly advocate for histologic confirmation have done so based on the assumption that, under most circumstances, it provides clinically useful information about prognosis that can affect patient management. This assumption is for the most part supported by the literature. The review by Carrington and colleagues7 was one of the first to clearly demonstrate the differences in prognosis and survival of separate histologic diagnoses in a group of patients suspected of having IPF. They evaluated mortality and response to therapy in 53 patients with UIP, compared to 40 patients with DIP. After an observation period of 24 years, they found that those with UIP had a 66% mortality rate, as opposed to a 27.5% mortality rate in patients with DIP. More recently, Katzenstein and Myers4 evaluated all such trials that have adequate histologic data, and have defined those clinical characteristics that accompany the various histologic patterns (Table 2 ). Of note, UIP is still associated with having a poor response to corticosteroids and a high mortality rate. This is in contrast to DIP and NSIP, which are more likely to respond to corticosteroids and have lower mortality rates. Furthermore, DIP, AIP, and NSIP all tend to occur in patients at a younger age than does UIP.

In addition to the qualitative methodology of Katzenstein and Myers,4 in which an overall histologic pattern is specific for a diagnosis, another method of relating histology to prognosis and survival among patients with the clinical-radiographic syndrome of IPF is the semiquantitative histologic analysis.89 Semiquantitative analysis utilizes a scoring system that takes into account the extent and severity of four factors (fibrosis, cellularity, desquamation, and granulation/connective tissue) and does not rely on the overall pattern. Results from studies using this method have demonstrated an improved survival and response to therapy in those patients with greater cellularity and less fibrosis.1015 The earliest of these studies were limited by lack of sufficient biopsy material and the lack of standard methods of histologic analysis. However, more recent and rigorous studies using this technique continue to demonstrate that those with greater cellularity respond better to corticosteroids and survive longer.7,1617 Survival rates related to qualitative vs semiquantitative methods of histologic analyses have not been compared.

Regardless of the method of analysis, the available data suggest that histologic review of lung biopsy specimens may indeed provide distinct information regarding prognosis, survival, and response to therapy, information that could affect management. And, because transbronchial biopsies do not provide sufficient amount of tissue for this type of analysis, an open or thoracoscopic lung biopsy is still the procedure of choice for obtaining tissue from patients suspected of having IPF. Unfortunately, open or thoracoscopic lung biopsies can be expensive and have associated morbidity and, very rarely, mortality. Consequently, many have searched for a less invasive means of obtaining the same type of diagnostic and prognostic information. Among the many unsuccessful attempts to validate less invasive diagnostic techniques, those that have proved unreliable, impractical, or not consistent with histology include sophisticated pulmonary function testing,16,1820 BAL analysis,15,21 gallium scanning,7 and the use of a combined clinical-radiologic-physiologic scoring system.22 More recently, high-resolution CT (HRCT) has shown some promise as a noninvasive test that could obviate the need for lung biopsy in many patients suspected of suffering from IPF.

Diagnostically, HRCT scanning is too nonspecific, not only for ILD in general, but also for IPF in particular.2324 Some would argue that even its sensitivity is questionable. Orens and colleagues25prospectively found HRCT scanning to be only 88% sensitive in detecting IPF that was proven by open lung biopsy in 25 patients. The specificity of HRCT is raised only in conjunction with clinical information, but once the ILD diagnoses that are more easily identified on clinical grounds are eliminated from the differential, one is left simply with a descriptive modality. Investigators have used such descriptive findings to correlate the HRCT appearance with pathology.2627 Overall, these studies suggest that a ground-glass appearance correlates with “cellular inflammation” or“ active alveolitis,” whereas a reticular pattern reflects fibrosis. Although these types of correlations seem enticing, they continue to be challenged.2829 For instance, Remy-Jardin and colleagues29retrospectively demonstrated that ground-glass attenuation by HRCT corresponded to actual histologic inflammation only 65% of the time, with fibrosis being the predominating pattern seen in the biopsy specimen in the rest. Furthermore, many studies that have attempted to correlate HRCT appearance with histologic appearance and prognosis are biased by their retrospective nature, usually have small number of subjects, may lack consistent histologic diagnoses, and have variable therapy and follow-up.3031

A study published in 1998 by Gay and colleagues16 may have overcome some of these limitations. They prospectively demonstrated in 38 patients with biopsy-proven IPF, all of whom were treated with 1 mg/kg/d of corticosteroids, that a patient with a pretreatment HRCT showing an “interstitial score” ≥ 2 had a decreased survival. An interstitial score of 2 was defined as honeycombing involving at most 25% of the lung (Table 3 ). At a mean follow-up of 34 months, 60% of patients with a score > 2 had died, compared to 15% of those patients with a score ≤ 2. Such a pattern predicted death with 80% sensitivity and 85% specificity, as determined by receiver operating characteristics analysis. Interestingly, the HRCT ground-glass score was not found to be an independent predictor of death during follow-up, consistent with the findings of Remy-Jardin and colleagues,29 described above, reaffirming the inaccuracy of the ground-glass appearance to correlate with pathology.

In summary, the best literature on the use of HRCT to date suggests that it is the predominantly fibrotic appearance, rather than the ground-glass attenuation, that provides the most useful information regarding prognosis. Patients with fibrosis involving > 25% of the lungs, as determined by HRCT, have the worst prognosis and will likely progress despite treatment.32 In these patients, an open lung biopsy is unlikely to provide further useful information. In contrast, in those patients with a predominantly ground-glass-appearing HRCT, any of the four idiopathic interstitial pneumonias could be present, suggesting that such patients could benefit the most from the information provided by an open lung biopsy.

The early reviews that evaluated response to corticosteroids found that < 30% of patients with IPF responded to treatment.7,1114,33 As alluded to earlier, these trials were limited by the small number of cases or by their lack of consistent histologic and clinical criteria for diagnosis of IPF.7,1214,33 Hence, many of those who responded could have been patients with ILD of secondary causes, such as hypersensitivity pneumonitis or collagen vascular disease; therefore, the true rate of response to steroids was probably much < 30%. Additionally, Bjoraker and colleagues5 demonstrated that when current histologic criteria were used to retrospectively review open lung biopsy specimens of patients with diagnosed IPF, various lesions other than UIP were found, including NSIP, DIP, and bronchiolitis—histologic patterns that are associated with a better response to corticosteroids and improved survival.

Carrington et al7 noted the relative amounts of histologic fibrosis in all of their patients with UIP and DIP, and compared the two groups depending on whether they were treated with high-dose corticosteroids or untreated. Two interesting findings resulted. First, those patients who responded to therapy, regardless of diagnosis, had only mild to moderate amounts of fibrosis. When UIP patients in particular were scrutinized, however, only three patients responded: one with nitrofurantoin toxicity, another with systemic sclerosis, and still another with polymyositis—entities that are not classified as idiopathic interstitial pneumonitis. If these patients are excluded from the analysis, one finds that none of the patients with UIP responded to treatment. Second, those patients with severe amounts of fibrosis, regardless of diagnosis, did not have improved conditions. These findings are consistent with the observation of Gay et al (1998),16 described above, which demonstrated the value of a fibrotic-appearing HRCT in predicting death and lack of long-term response to therapy in patients with UIP. Based on this information, one would predict that patients with UIP (as determined by histology) or a picture consistent with IPF associated with a predominant fibrotic pattern on HRCT would not benefit from corticosteroids.

To date and to our knowledge, only three trials have ever attempted to evaluate the treatment of UIP prospectively.3436 The first trial, by Johnson and colleagues34 in 1989, compared the effect of prednisolone and cyclophosphamide vs prednisolone alone. Biases and limitations of earlier reports also apply to this study. Limited by the inclusion of patients with collagen vascular disease, inadequate numbers of open lung biopsies, a histologic grading system based on needle biopsies, and dissimilar baseline characteristics, this study did not find any significant difference in survival between the two groups. Nor was there a significant long-term response to either treatment in those who did survive, as measured by pulmonary function testing.

The next trial, by Raghu and colleagues35 in 1991, evaluated the efficacy of azathioprine and prednisone vs prednisone and placebo in 27 patients, 23 of whom had IPF diagnosed by open lung biopsy specimens, graded only in terms of the severity of fibrosis. This study was somewhat limited by its ill-defined histologic criteria, since the investigators did not use either semiquantitative analysis or the histologic subsetting proposed by Katzenstein and Myers.4 They did, however, exclude patients with associated collagen vascular diseases. This study also found no significant difference in overall survival between the two groups. Furthermore, no patient in either group experienced a significant improvement with any treatment.

The third trial, by Douglas and colleagues36in 1998, evaluated the efficacy of colchicine vs prednisone in 26 patients with UIP diagnosed by clinical criteria, supported by HRCT and/or open lung biopsy. Prior retrospective evaluations of colchicine by the same investigators3738 did not show any significant advantage over prednisone. Only one patient had an open lung biopsy. This fact, however, is not necessarily a limitation to the study, since they based their HRCT criteria of UIP on a predominantly fibrotic appearance. As noted previously, a predominantly fibrotic-appearing HRCT carries the worst prognosis, and is an independent predictor of death in these patients.16 Likewise, biopsy-proven UIP had been shown not to respond long-term to therapy with high-dose corticosteroids.7 As would be expected, no difference in survival was seen between the two groups in their prospective evaluation. In fact, not one patient responded to either treatment.

Of note, Douglas and colleagues36 observed that those patients receiving prednisone experienced significantly more serious side effects than those receiving colchicine. This last finding complements results from a preliminary report39that prospectively assessed adverse effects associated with corticosteroids therapy in patients with biopsy-proven IPF. Only 1 of 16 patients treated with high-dose corticosteroids (prednisone, 1 mg/kg/d) experienced an improvement in clinicoradiologic physiologic score after 4 months of treatment. However, virtually all patients were noted to have significant side effects, including diabetes mellitus requiring insulin therapy, avascular necrosis, corticosteroid myopathy, insomnia, irritability, fatigue, cushingoid features, blurred vision, depression, acne, and peptic ulcer disease. These results suggest that the host of side effects associated with high-dose corticosteroid therapy may cause more harm than good for many of these patients. Furthermore, it should be emphasized that each of the trials used prednisone as the “standard therapy,” but only the last trial evaluated prednisone against an alternate drug alone (rather than a combination of prednisone and the alternate drug), and none compared prednisone vs placebo. With the lack of randomized placebo-controlled trials of corticosteroids in a population-based sample of patients with UIP, we cannot definitively say whether corticosteroids truly have a beneficial effect in these patients.40 None of these drugs have shown an unequivocal advantage in survival. In fact, based on historical data, one might even conclude that they are as effective as no treatment at all. In view of these findings, one has to wonder why corticosteroids remain the standard of care for patients with UIP. We argue that indiscriminate long-term treatment with high-dose corticosteroids (> 10 mg/d of prednisone for > 3 months) in IPF should be discouraged, and that corticosteroids should be used mainly when a more corticosteroid-responsive lesion (eg, DIP or NSIP) is identified histologically. Beyond lung transplantation, which should be considered early in those patients who are eligible, the results of these trials indicate that there is currently no treatment available that will unequivocally benefit patients with UIP. We suggest that when confronted with such a patient, perhaps the most appropriate action to take is to explain the pros and cons of available agents, in view of the limited data, and help each patient decide what is best for him or her.

In summary, the term IPF should be reserved for the clinical syndrome associated with the histologic pattern of UIP, the most common of the idiopathic interstitial pneumonias. Several reviews detail the distinguishing histologic features of these pneumonitides.4,41A recently published consensus statement provides detailed recommendations about diagnosis and management of IPF.42 We propose that when evaluating a patient with suspected IPF, the physician must consider the risks and benefits of histologic confirmation of the diagnosis. Figure 1 depicts a suggested algorithm for decision making regarding open lung biopsy in patients presenting with the clinical syndrome of ILD. Histologic confirmation should be pursued in all patients with progressive disease who show a predominantly ground-glass appearance by HRCT. Conversely, those immunocompetent patients with a predominantly fibrotic-appearing HRCT and, hence, likely to have UIP, are less likely to benefit from an open lung biopsy, since this may not provide any additional prognostic information. Such patients have been shown not to respond well to corticosteroid therapy. In fact, if these patients are treated with high-dose corticosteroids indiscriminately, there are data to suggest that not only will they not respond, but that they may also do worse than if they had not been treated at all. Thus, by succumbing to the argument that “no patient with IPF should be denied a trial of corticosteroids,” clinicians run the risk of doing their patients a disservice. When appropriate, transplantation should be an early consideration. Educating the patient regarding the risks and benefits of treatment is paramount. Communication is of the essence when dealing with a disease with limited therapeutic options.

Abbreviations: AIP = acute interstitial pneumonitis; DIP = desquamative interstitial pneumonitis; HRCT = high-resolution CT; ILD = interstitial lung disease; IPF = idiopathic pulmonary fibrosis; NSIP = nonspecific interstitial pneumonitis; UIP = usual interstitial pneumonitis

Dr. Aguayo is recipient of a Career Investigator Award from the American Lung Association, and Dr. Roman is recipient of an Established Investigator Award from the American Heart Association. This work was also supported in part by Merit Review Grants from the Department of Veterans Affairs (S.M.A. and J.R.) and by grant NHLBI UO1-HL60263 (S.M.A.).

Table Graphic Jump Location
Table 1. Pathologic Classification of the Interstitial Pneumonias*
* 

The pathologic classification schemes are based on histomorphometric analysis. Note that the last three in the scheme of Liebow,3 (bronchiolitis obliterans with interstitial pneumonia, lymphocytic interstitial pneumonia, and giant cell interstitial pneumonia) are not necessarily idiopathic.

Table Graphic Jump Location
Table 2. Pathologic and Clinical Features of the Interstitial Pneumonias*
* 

Adapted from Katzenstein and Myers.4

 

According to Bjoraker et al.5

Table Graphic Jump Location
Table 3. HRCT Interstitial Score*
* 

Adapted from Gay et al.16 The HRCT scoring system is based upon the relative quantity of honeycombing. Final score is mean of scores from each lobe. A score> 2 predicts mortality with 80% sensitivity and 85% specificity.

Figure Jump LinkFigure 1. Diagnosis and management of IPF: suggested algorithm. CXR = chest x-ray; PFT = pulmonary function testing; Bx = biopsy; TBBx = transbronchial biopsy.Grahic Jump Location

We are indebted to Dr. Jeffrey L. Myers (Mayo Clinic, Rochester, MN), Dr. Talmadge E. King, Jr. (University of California at San Francisco, San Francisco, CA), and Dr. Roland H. Ingram, Jr. (Emory University School of Medicine, Atlanta, GA) for their helpful discussions and for their critical review of this article.

Coultas, DB, Zumwalt, RE, Black, WC, et al (1994) The epidemiology of interstitial lung diseases.Am J Respir Crit Care Med150,967-972. [PubMed]
 
Mannino, DM, Etzel, RA, Parrish, RG Pulmonary fibrosis deaths in the United States, 1979–1991: an analysis of multiple-cause mortality data.Am J Respir Crit Care Med1996;153,1548-1552. [PubMed]
 
Liebow, AA Definition and classification of interstitial pneumonias in human pathology.Prog Respir Res1975;8,1-31
 
Katzenstein, A-LA, Myers, JL Idiopathic pulmonary fibrosis: clinical relevance of pathologic classification.Am J Respir Crit Care Med1998;157,1301-1315. [PubMed]
 
Bjoraker, JA, Ryu, JH, Edwin, MK, et al Prognostic significance of histopathologic subsets in idiopathic pulmonary fibrosis.Am J Respir Crit Care Med1998;157,199-203. [PubMed]
 
Raghu, G Interstitial lung disease: a diagnostic approach; are CT scan and lung biopsy indicated in every patient?Am J Respir Crit Care Med1995;151,909-914. [PubMed]
 
Carrington, CB, Gaensler, EA, Coutu, RE, et al Natural history and treated course of usual and desquamative interstitial pneumonia.N Engl J Med1978;298,801-809. [CrossRef] [PubMed]
 
Cherniack, RM, Colby, TV, Flint, A, et al Quantitative assessment of lung pathology in idiopathic pulmonary fibrosis.Am Rev Respir Dis1991;144,892-900. [CrossRef] [PubMed]
 
Hyde, DM, King, TE, McDermott, T, et al Idiopathic pulmonary fibrosis: quantitative assessment of lung pathology; comparison of a semiquantitative and a morphometric histopathologic scoring system.Am Rev Respir Dis1992;146,1042-1047. [PubMed]
 
Turner-Warwick, M, Burrows, B, Johnson, A Cryptogenic fibrosing alveolitis: clinical features and their influence on survival.Thorax1980;35,171-180. [CrossRef] [PubMed]
 
Scadding, JG, Hinson, KFW Diffuse fibrosing alveolitis (diffuse interstitial fibrosis of the lungs): correlation of histology at biopsy with prognosis.Thorax1967;27,291-304
 
Stack, BHR, Choo-Kang, YF, Heard, BE The prognosis of cryptogenic fibrosing alveolitis.Thorax1972;27,535-542. [CrossRef] [PubMed]
 
DeRemee, RA, Harrison, JR, Andersen, HA The concept of classic interstitial pneumonitis-fibrosis (CIP-F) as a clinicopathologic syndrome.Chest1972;61,213-220. [CrossRef] [PubMed]
 
Tukiainen, P, Taskinen, E, Holsti, P, et al Prognosis of cryptogenic fibrosing alveolitis.Thorax1983;38,349-355. [CrossRef] [PubMed]
 
Watters, LC, King, TE, Schwarz, MI, et al A clinical, radiographic, and physiologic scoring system for the longitudinal assessment of patients with idiopathic pulmonary fibrosis.Am Rev Respir Dis1986;133,97-103. [PubMed]
 
Gay, SE, Kazerooni, EA, Toews, GB, et al Idiopathic pulmonary fibrosis: predicting response to therapy and survival.Am J Respir Crit Care Med1998;157,1063-1072. [PubMed]
 
Katzenstein, A-LA, Fiorelli, RF Non-specific interstitial pneumonia/fibrosis: histologic patterns and clinical significance.Am J Surg Pathol1994;18,136-147. [CrossRef] [PubMed]
 
Cherniack, RM, Colby, TV, Flint, A, et al Correlation of structure and function in idiopathic pulmonary fibrosis.Am J Respir Crit Care Med1995;151,1180-1188. [PubMed]
 
Schwartz, DA, Helmers, RA, Galvin, JR, et al Determinants of survival in idiopathic pulmonary fibrosis.Am J Respir Crit Care Med1994;149,450-454. [PubMed]
 
Erbes, R, Schaberg, T, Loddenkemper, R Lung function tests in patients with idiopathic pulmonary fibrosis: are they helpful for predicting outcome.Chest1997;111,51-57. [CrossRef] [PubMed]
 
Haslam, PL, Turton, CWG, Heard, B, et al Bronchoalveolar lavage in pulmonary fibrosis: comparison of cells obtained with lung biopsy and clinical features.Thorax1980;35,9-18. [CrossRef] [PubMed]
 
Watters, LC, Schwarz, MI, Cherniack, RM, et al Idiopathic pulmonary fibrosis: pretreatment bronchoalveolar lavage cellular constituents and their relationships with lung histopathology and clinical response to therapy.Am Rev Respir Dis1987;135,696-704. [PubMed]
 
Lynch, DA, Newell, JD, King, TE, et al Can CT distinguish hypersensitivity pneumonitis from idiopathic pulmonary fibrosis?AJR Am J Roentgenol1995;165,807-811. [PubMed]
 
Tung, KT, Wells, AU, Rubens, MB, et al Accuracy of the typical computed tomographic appearances of fibrosing alveolitis.Thorax1993;48,334-338. [CrossRef] [PubMed]
 
Orens, JB, Kazerooni, EA, Martinez, FJ, et al The sensitivity of high-resolution CT in detecting idiopathic pulmonary fibrosis proved by open lung biopsy: a prospective study.Chest1995;108,109-115. [CrossRef] [PubMed]
 
Muller, NL, Miller, RR, Webb, WR, et al Fibrosing alveolitis: CT-pathologic correlation.Radiology1986;160,585-588. [PubMed]
 
Muller, NL, Staples, CA, Miller, RR, et al Disease activity in idiopathic pulmonary fibrosis: CT and pathologic correlation.Radiology1987;165,731-734. [PubMed]
 
Kazerooni, E, Martinez, FJ, Flint, A, et al Thin-section CT obtained at 10 mm increments versus three-level thin-section CT for idiopathic pulmonary fibrosis: correlation with pathologic scoring.AJR Am J Roentgenol1997;169,977-983. [PubMed]
 
Remy-Jardin, M, Giraud, F, Remy, J, et al Importance of ground-glass attenuation in chronic diffuse infiltrative lung disease: pathologic-CT correlation.Radiology1993;189,693-698. [PubMed]
 
Wells, AU, Hansell, DM, Rubens, MB, et al The predictive value of appearances on thin-section computed tomography in fibrosing alveolitis.Am Rev Respir Dis1993;148,1076-1082. [CrossRef] [PubMed]
 
Lee, J, Im, J, Ahn, J, et al Fibrosing alveolitis: prognostic implication of ground-glass attenuation at high-resolution CT.Radiology1992;184,451-454. [PubMed]
 
Hartman, TE, Primack, SL, Kang, EY, et al Disease progression in usual interstitial pneumonia compared with desquamative interstitial pneumonia: assessment with serial CT.Chest1996;110,378-382. [CrossRef] [PubMed]
 
Turner-Warwick, M, Burrows, B, Johnson, A Cryptogenic fibrosing alveolitis: response to corticosteroid treatment and its effect on survival.Thorax1980;35,593-599. [CrossRef] [PubMed]
 
Johnson, MA, Kwan, S, Snell, NJ, et al Randomised controlled trial comparing prednisolone with cyclophosphamide and low dose prednisolone in combination in cryptogenic fibrosing alveolitis.Thorax1989;44,280-288. [CrossRef] [PubMed]
 
Raghu, G, Depaso, WJ, Cain, K, et al Azathioprine combined with prednisone in the treatment of idiopathic pulmonary fibrosis: a prospective double-blind, randomized, placebo-controlled clinical trial.Am Rev Respir Dis1991;144,291-296. [CrossRef] [PubMed]
 
Douglas, WW, Ryu, JH, Swensen, SJ, et al Colchicine versus prednisone in the treatment of idiopathic pulmonary fibrosis: a randomized prospective study.Am J Respir Crit Care Med1998;158,220-225. [PubMed]
 
Peters, SG, McDougall, JC, Douglas, WW, et al Colchicine in the treatment of pulmonary fibrosis.Chest1993;103,101-104. [CrossRef] [PubMed]
 
Douglas, WW, Ryu, JH, Swensen, SJ, et al Colchicine versus prednisone as treatment of usual interstitial pneumonia.Mayo Clin Proc1997;72,201-209. [CrossRef] [PubMed]
 
Hampton, J, Martinez, F, Orens, J, et al Corticosteroids in idiopathic pulmonary fibrosis: toxicity may outweigh benefits [abstract]. Am Rev Respir Dis. 1994;;149 ,.:A878
 
Mapel, DW, Samet, JM, Coultas, DB Corticosteroids and the treatment of idiopathic pulmonary fibrosis: past, present, and future.Chest1996;110,1058-1067. [CrossRef] [PubMed]
 
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King, TE, Costabel, U, Cordier, J-F, et al International consensus statement on idiopathic pulmonary fibrosis: diagnosis and treatment.Am J Respir Crit Care Med2000;161,646-664. [PubMed]
 

Figures

Figure Jump LinkFigure 1. Diagnosis and management of IPF: suggested algorithm. CXR = chest x-ray; PFT = pulmonary function testing; Bx = biopsy; TBBx = transbronchial biopsy.Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1. Pathologic Classification of the Interstitial Pneumonias*
* 

The pathologic classification schemes are based on histomorphometric analysis. Note that the last three in the scheme of Liebow,3 (bronchiolitis obliterans with interstitial pneumonia, lymphocytic interstitial pneumonia, and giant cell interstitial pneumonia) are not necessarily idiopathic.

Table Graphic Jump Location
Table 2. Pathologic and Clinical Features of the Interstitial Pneumonias*
* 

Adapted from Katzenstein and Myers.4

 

According to Bjoraker et al.5

Table Graphic Jump Location
Table 3. HRCT Interstitial Score*
* 

Adapted from Gay et al.16 The HRCT scoring system is based upon the relative quantity of honeycombing. Final score is mean of scores from each lobe. A score> 2 predicts mortality with 80% sensitivity and 85% specificity.

References

Coultas, DB, Zumwalt, RE, Black, WC, et al (1994) The epidemiology of interstitial lung diseases.Am J Respir Crit Care Med150,967-972. [PubMed]
 
Mannino, DM, Etzel, RA, Parrish, RG Pulmonary fibrosis deaths in the United States, 1979–1991: an analysis of multiple-cause mortality data.Am J Respir Crit Care Med1996;153,1548-1552. [PubMed]
 
Liebow, AA Definition and classification of interstitial pneumonias in human pathology.Prog Respir Res1975;8,1-31
 
Katzenstein, A-LA, Myers, JL Idiopathic pulmonary fibrosis: clinical relevance of pathologic classification.Am J Respir Crit Care Med1998;157,1301-1315. [PubMed]
 
Bjoraker, JA, Ryu, JH, Edwin, MK, et al Prognostic significance of histopathologic subsets in idiopathic pulmonary fibrosis.Am J Respir Crit Care Med1998;157,199-203. [PubMed]
 
Raghu, G Interstitial lung disease: a diagnostic approach; are CT scan and lung biopsy indicated in every patient?Am J Respir Crit Care Med1995;151,909-914. [PubMed]
 
Carrington, CB, Gaensler, EA, Coutu, RE, et al Natural history and treated course of usual and desquamative interstitial pneumonia.N Engl J Med1978;298,801-809. [CrossRef] [PubMed]
 
Cherniack, RM, Colby, TV, Flint, A, et al Quantitative assessment of lung pathology in idiopathic pulmonary fibrosis.Am Rev Respir Dis1991;144,892-900. [CrossRef] [PubMed]
 
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