MEDLINE Abstracts: Idiopathic Pulmonary Fibrosis

November 10, 2003

What's new concerning idiopathic pulmonary fibrosis? Find out in this easy-to-navigate collection of recent MEDLINE abstracts compiled by the editors at Medscape Pulmonary Medicine.

Copley SJ, Wells AU, Sivakumaran P, et al
Radiology. 2003 Oct 23 [Epub ahead of print]

Purpose: To identify differences, if any, in thin-section computed tomographic (CT) features between asbestosis and idiopathic pulmonary fibrosis (IPF) and to test the findings in a subset of histopathologically proved cases of usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP).
Materials and Methods: Consecutive patients with a diagnosis of IPF (n = 212) or asbestosis (n = 74) were included. The relationships derived from the initial comparison were tested in a separate group of biopsy-proved UIP (n = 30) and NSIP (n = 23) cases. Two observers independently scored thin-section CT images for extent, distribution, and coarseness of fibrosis; proportion of ground-glass opacification; severity of traction bronchiectasis; and extent of emphysema.
Results: After controlling for extent of fibrosis, patients with asbestosis had coarser fibrosis than those with IPF (odds ratio, 1.52; 95% CI: 1.25, 1.84; P < .001). Compared with the biopsy-proved cases, the asbestosis cases involved coarser fibrosis (after controlling for disease extent) than the NSIP cases (odds ratio, 2.48; 95% CI: 1.49, 4.11; P < .001), but fibrosis similar to that in the UIP cases. A basal and subpleural distribution of disease was usual in all subgroups, but significantly more prevalent (P < .01 to .001) with asbestosis than with UIP or NSIP.
Conclusion: The thin-section CT pattern of asbestosis closely resembles that of biopsy-proved UIP and differs markedly from that of biopsy-proved NSIP.

Geiser T
Swiss Med Wkly. 2003;133:405-411

Idiopathic pulmonary fibrosis (IPF) is a chronic and usually progressive lung disorder of unknown etiology. Conventional management of patients with IPF has been primarily based on the concept that suppressing inflammation would prevent progression to fibrosis. Although the pathogenesis is incompletely understood, it is here suggested that IPF is a disease of abnormal wound repair and remodeling in the lung rather than an inflammatory disease. Therefore, treatment strategies are no longer aimed at reducing inflammation, but rather at preventing or inhibiting the fibroproliferative responses and enhancing efficient alveolar epithelial repair. So far, no cell-specific drugs for these purposes are clinically available. However, novel promising molecules or drugs are being studied in experimental models or ongoing clinical trials in patients with IPF. Evolving hypotheses on the pathogenesis of IPF are reviewed, focusing on possible implications for future therapies. A better understanding of the sequence of the pathogenic mechanisms that control the fibrotic response will hopefully lead to efficient therapies and finally a favorable outcome in patients with this disease.

Tajima S, Oshikawa K, Tominaga S, Sugiyama Y
Chest. 2003;124:1206-1214

Background: The human ST2 gene can be specifically induced by growth stimulation in fibroblastic cells, and the soluble ST2 protein (ST2) is expressed preferentially in T-helper type 2 (Th2) cells. Furthermore, ST2 is induced by proinflammatory stimuli such as tumor necrosis factor-alpha and interleukin-1 beta. It has been reported that the inflammatory response in idiopathic pulmonary fibrosis (IPF) is thought to be associated with proinflammatory cytokines and Th2 immune response.
Study Objective: The objective of this study was to evaluate the relevance of the serum ST2 levels in the pathogenesis of IPF.
Design: Retrospective study.
Setting: Inpatients in a college hospital.
Participants: Forty-nine patients with IPF admitted to our hospital 64 times: 36 patients were admitted once, 11 patients were admitted twice, and 2 patients were admitted three times. The participants also included 200 healthy control volunteers.
Measurements and Results: Among 64 events in 49 patients with IPF, 50 of the events occurred in a stable state, and 14 events occurred during acute exacerbation. An acute exacerbation of IPF was defined as an accelerated phase of IPF. The serum ST2 levels were measured by enzyme-linked immunosorbent assay. The serum levels of ST2 in the stable state group did not differ from those in the healthy control group, while the serum levels of ST2 in the acute exacerbation group were significantly higher than those in the stable state group or the healthy control group (P < .001, acute exacerbation group vs stable state group or healthy control group; acute exacerbation group, 2.76 ± .56 ng/mL; stable state group, .44 ± .07 ng/mL; healthy control group, .42 ± .03 ng/mL). Furthermore, serum ST2 statistically correlated with lactate dehydrogenase (r = .344, P = .005) and C-reactive protein (r = .496, P < .001), and inversely correlated with PaO2 (r = - .356, P = .018) and the percentage of predicted vital capacity (r = - .346, P = .026).
Conclusions: These results suggest that ST2 protein may increase in the serum, reflecting severity in the inflammatory process and Th2 immune response in the IPF lung.

Kurup RK, Kurup PA
Int J Neurosci. 2003;113:1427-1443

The isoprenoid pathway produces 3 key metabolites--endogenous digoxin, dolichol, and ubiquinone. This was assessed in patients with idiopathic pulmonary fibrosis and in individuals of differing hemispheric dominance to find out the role of hemispheric dominance in the pathogenesis of idiopathic pulmonary fibrosis. All 15 cases of interstitial lung disease were right-handed/left hemispheric dominant by the dichotic listening test. The isoprenoidal metabolites--digoxin, dolichol, and ubiquinone, RBC membrane Na+-K+ ATPase activity, serum magnesium, tyrosine/tryptophan catabolic patterns, free radical metabolism, glycoconjugate metabolism, and RBC membrane composition--were assessed in idiopathic pulmonary fibrosis as well as in individuals with differing hemispheric dominance. In patients with idiopathic pulmonary fibrosis there was elevated digoxin synthesis, increased dolichol and glycoconjugate levels, and low ubiquinone and elevated free radical levels. There was also an increase in tryptophan catabolites and a reduction in tyrosine catabolites. There was an increase in cholesterol phospholipid ratio and a reduction in glycoconjugate level of RBC membrane in patients with idiopathic pulmonary fibrosis. Isoprenoid pathway dysfunction contributes to the pathogenesis of idiopathic pulmonary fibrosis. The biochemical patterns obtained in interstitial lung disease are similar to those obtained in left-handed/right hemispheric chemically dominant individuals by the dichotic listening test. However, all the patients with interstitial lung disease were right-handed/left hemispheric dominant by the dichotic listening test. Hemispheric chemical dominance has no correlation with handedness or the dichotic listening test. Interstitial lung disease occurs in right hemispheric chemically dominant individuals and is a reflection of altered brain function.

Petkova DK, Clelland CA, Ronan JE, Lewis S, Knox AJ
Histopathology. 2003;43:381-386

Aims: To test the hypothesis that cyclooxygenase (COX)-1 or COX-2 expression is defective in lungs in idiopathic pulmonary fibrosis (IPF) and to characterize the cellular distribution. IPF is a progressive inflammatory lung disorder with an adverse prognosis. Previous work has shown that prostaglandin E2 (PGE2) regulates collagen deposition and fibroblast proliferation and a defect in COX regulation may contribute to the fibrosis that occurs in IPF.
Methods: Immunohistochemistry was utilized to determine COX immunoreactivity in lung sections from 25 IPF, 6 sarcoidosis and 14 control subjects.
Results: COX-1 and COX-2 expression in bronchiolar epithelial cells was significantly lower in IPF and sarcoidosis than in controls. No significant difference was found in COX-2 expression between macrophages in IPF and control sections, but COX-2 was reduced in macrophages in sarcoidosis compared with controls.
Conclusions: These studies confirm COX-2 loss in bronchial epithelial cells but not macrophages in IPF, and show for the first time reduced constitutive COX-1 expression in epithelial cells and macrophages. Similar abnormalities were observed in sarcoidosis.

Wynes MW, Riches DW
J Immunol. 2003;171:3550-3559

Macrophage-derived insulin-like growth factor-I (IGF-I) has long been implicated in the pathogenesis of the interstitial lung disease, idiopathic pulmonary fibrosis, in part, by its ability to 1. stimulate the proliferation and survival of fibroblasts and myofibroblasts, and 2. promote collagen matrix synthesis by these cells. However, little is known about the mechanisms that stimulate the expression of IGF-I by macrophages. Previous studies have shown that the development of pulmonary fibrosis is accompanied by enhanced expression of Th2-profile cytokines, especially IL-4, and diminished expression of Th1 cytokines, including IFN-gamma. In addition, in vitro studies have shown that IFN-gamma down-regulates the expression of IGF-I. Thus, the paucity of IFN-gamma in the fibrotic lung may favor increased growth factor production by allowing Th2 cytokines to predominate. In view of these findings, we investigated the hypothesis that Th2 cytokines stimulate the expression of IGF-I by macrophages. Incubation with IL-4 or IL-13 led to concentration- and time-dependent increases in the expression of IGF-I mRNA and the secretion of IGF-I protein by mouse macrophages as a consequence of increased transcription of IGF-I pre-mRNA. Exposure of macrophages to IL-4 in the presence of IFN-gamma inhibited the increase in the expression of IGF-I. Studies using STAT6-deficient macrophages indicated that the increase in IGF-I expression was dependent on STAT6. In addition, the down-regulation of IGF-I expression by IFN-gamma was absent in STAT1-deficient macrophages. Collectively, these findings define a homeostatic mechanism in which Th2 cytokines promote, and Th1 cytokines inhibit, the expression of IGF-I by macrophages.

Lappi-Blanco E, Kaarteenaho-Wiik R, Salo S, et al
Am J Respir Crit Care Med. 2003 Sep 18 [Epub ahead of print]

Insufficient re-epithelialization of injured alveolar walls is suspected to be important in the pathogenesis of IPF. Laminin-5 is expressed in epithelial cells of healing wounds promoting cell attachment and migration. In this study we have studied the extent of re-epithelialization of newly formed intraluminal connective tissue, the immunohistochemical expression and ultrastructural localization of laminin-5 gamma2 chain protein, and the synthesis of laminin-5 gamma2 chain mRNA in regenerating epithelial cells in cryptogenic organizing pneumonia (COP) and IPF. The results show that the mean extent of re-epithelialization of intraluminal connective tissue lesions was 76% (SD ± 27%) in COP, and 54% (SD ±23%) in IPF (P < .025). The laminin-5 gamma2 chain was synthesized and widely expressed in regenerating epithelial cells in both diseases. Immunohistochemistry for surfactant-associated protein A suggests a pneumocyte origin for the regenerating epithelial cells in IPF. It is concluded that both in COP and IPF, the regenerating epithelial cells are capable of synthesizing the laminin-5 gamma2 chain needed for adhesive connections to the underlying BM. However, in IPF, the re-epithelialization seems to be disturbed or delayed.

Selman M, Lin HM, Montano M, et al
Hum Genet. 2003;113:542-550. Epub 2003 Sep 06

Derangement in pulmonary surfactant or its components and alveolar collapse are common findings in IPF. Surfactant proteins play important roles in innate host defense and normal function of the lung. We examined associations between IPF and genetic polymorphic variants of surfactant proteins, SP-A1, SP-A2, SP-B, SP-C, and SP-D. One SP-A1 (6A(4)) allele and single nucleotide polymorphisms (SNPs) that characterize the 6A(4) allele, and one SP-B (B1580_C) were found with higher frequency (P ≤ .01) in nonsmoker and smoker IPF (n = 84) subgroups, respectively, compared with healthy controls (n = 194). To explore whether a tryptophan (present in 6A(4)) or an arginine (present in other SP-A1 alleles and in all SP-A2 alleles) at amino acid 219 alters protein behavior, two truncated proteins that varied only at amino acid 219 were oxidized by exposure to ozone. Differences in the absorption spectra (310-350 nm) between the two truncated recombinant SP-A proteins were observed both before and after protein oxidation, suggesting allele-specific aggregation differences attributable to amino acid 219. The SP-B SNP B1580_C (odds ratio:7.63; confidence interval:1.64-35.4; P ≤ .01), to be a risk factor for IPF smokers, has also been shown to be a risk factor for other pulmonary diseases. The SP-C and SP-D SNPs and SP-B-linked microsatellite markers studied did not associate with IPF. These findings indicate that surfactant protein variants may serve as markers to identify subgroups of patients at risk, and we speculate that these contribute to IPF pathogenesis.

Wittram C, Mark EJ, McLoud TC
Radiographics. 2003;23:1057-1071

The American Thoracic Society and the European Respiratory Society 2002 classification defines the histologic patterns that provide the basis for a clinico-radiologic-pathologic diagnosis of an idiopathic interstitial pneumonia. IPF is the clinical term for usual interstitial pneumonia, the characteristic histologic pattern is interstitial fibrosis with temporal heterogeneity, and the radiologic pattern is basal and subpleural areas of ground-glass and reticular attenuation and honeycomb pattern. Nonspecific interstitial pneumonia has cellular or fibrosing patterns of chronic inflammation with temporal homogeneity; the radiologic pattern is subpleural and basal areas of ground-glass and reticular attenuation. Lymphoid interstitial pneumonia results from lymphocyte interstitial infiltration; CT demonstrates ground-glass attenuation and nodular interlobular septal thickening. Respiratory bronchiolitis-associated interstitial lung disease is characterized by bronchiolocentric alveolar macrophage accumulation; CT shows centrilobular ground-glass attenuation. Desquamative interstitial pneumonia is characterized by alveolar macrophage accumulation with predominantly lower zone ground-glass attenuation seen on CT scans. Cryptogenic organizing pneumonia is characterized radiologically by peribronchial ground-glass attenuation and subpleural consolidation. Acute interstitial pneumonia is the clinical term for idiopathic diffuse alveolar damage; the exudative phase is characterized radiologically by diffuse ground-glass attenuation and dependent consolidation, with the additional feature of lung architectural distortion in the organizing phase. Ideally, diagnosis of an idiopathic interstitial pneumonia should be rendered only after all clinico-radiologic-pathologic data have been reviewed.

Kalra S, Utz JP, Ryu JH; Mayo Clinic Interstitial Lung Diseases Group
Mayo Clin Proc. 2003;78:1082-1087

Objective: To report on observations made in a group of patients with idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP) who were treated with interferon gamma-1b.
Patients and Methods: We reviewed the clinical records, radiological studies, and pulmonary function data of all patients treated with interferon gamma-1b between January 2000 and March 2002 at the Mayo Clinic in Rochester, Minn.
Results: Twenty-one patients (mean age, 68 years; range, 52 to 80 years) were treated with interferon gamma-1b for a mean duration of 82 months (range, 3-21 months). All patients had been diagnosed previously as having IPF/UIP based on clinical, pulmonary function, and chest high-resolution CT scan criteria; 12 patients had also undergone video-assisted thoracoscopic surgical lung biopsy. Baseline pulmonary function data (mean ± SEM percent predicted) were as follows: total lung capacity, 57.3 ± 2.5; vital capacity, 55.0 ± 3.3; diffusing capacity of lung for carbon monoxide, 39.7 ± 2.8; and forced expiratory volume in 1 second, 58.1 ± 3.6. Only 1 patient showed symptomatic and functional improvement, and 7 discontinued treatment because of a perceived lack of benefit. Eleven patients (52%) died after a mean of 6.4 months of treatment, and follow-up pulmonary function data suggested continued worsening in all but 1 patient.
Conclusion: These observations do not support the use of interferon gamma-lb therapy for patients with advanced IPF/UIP.

Veeraraghavan S, Latsi PI, Wells AU, et al
Eur Respir J. 2003;22:239-244

Idiopathic pulmonary fibrosis (IPF), which has the histological pattern of usual interstitial pneumonia (UIP), is a progressive interstitial lung disease with a poor prognosis. Idiopathic interstitial pneumonias with a histological pattern of nonspecific interstitial pneumonia (NSIP) have a better prognosis than UIP, and may present with a clinical picture identical to IPF. The authors hypothesized that bronchoalveolar lavage (BAL) findings may distinguish between UIP and NSIP, and have prognostic value within disease subgroups. BAL findings were studied retrospectively in 54 patients with histologically proven (surgical biopsy) idiopathic UIP (n = 35) or fibrotic NSIP (n = 19), all presenting clinically as IPF. These findings were also compared with the BAL profile of patients with other categories of idiopathic interstitial pneumonias. BAL total and differential cell counts did not differ between the 2 groups. Survival was better in NSIP. In neither group were BAL findings predictive of survival or changes in lung function at 1 year, even after adjustment for disease severity, smoking, and treatment. BAL differential counts in fibrotic NSIP differed from respiratory bronchiolitis-associated interstitial lung disease, but not from desquamative interstitial pneumonia or cellular NSIP. The authors conclude that bronchoalveolar lavage findings do not discriminate between usual interstitial pneumonia and nonspecific interstitial pneumonia in patients presenting with clinical features of IPF, and have no prognostic value, once the distinction between the two has been made histologically.

Knight DA, Ernst M, Anderson GP, Moodley YP, Mutsaers SE
Pharmacol Ther. 2003;99:327-338

Cryptogenic fibrosing alveolitis (CFA), also known as idiopathic pulmonary fibrosis (IPF), is the end stage of a heterogeneous group of disorders in which the deposition of excessive amounts of collagen results in the loss of lung function and premature death. The molecular mechanisms underlying the disease are unknown. Accordingly, there is much debate as to whether pulmonary fibrosis is the end result of 1. a chronic inflammatory process or 2. a disturbance in normal epithelium-fibroblast cross talk, or both. In addition, it appears increasingly likely that there is a genetic component in the development of pulmonary fibrosis. The IL-6 cytokine family is a group of pleiotropic mediators produced by a variety of cells in response to an inflammatory stimuli. These cytokines are grouped together on the basis of weak structural homology, overlapping functions, and shared use of the transmembrane glycoprotein beta-subunit gp130 as part of their multimeric receptor complexes. Activation of these receptor complexes results in the recruitment and phosphorylation of specific transcription factors. In addition, membrane-proximal tyrosine residues act as docking sites for molecules involved in the activation of extracellular signal-related kinase (ERK). However, studies in genetically engineered mice that overexpress members of this family have shown that while overlapping biological activities exist, there are effects specific to individual cytokines. Data from both human and animal studies are now emerging to suggest that members of this cytokine family play an important role in the pathogenesis of fibroproliferative diseases and thus represent a novel group of cytokines implicated in pulmonary fibrosis. Importantly, manipulation of signaling pathways activated by these cytokines may suppress fibrosis but leave innate cellular mechanisms necessary for host defense largely untouched. This may provide guides for the development of novel pharmacological treatment for fibroproliferative diseases.

Marchand-Adam S, Marchal J, Cohen M, et al
Am J Respir Crit Care Med. 2003 Aug 28 [Epub ahead of print]

Hepatocyte growth factor (HGF) is a growth factor for alveolar epithelial cells that protects from pulmonary fibrosis in different animal models. We compared in vitro HGF production by human lung fibroblasts from patients with IPF (n = 8) and from controls (n = 6). Basal HGF secretion by IPF fibroblasts was decreased by 50% when compared with control fibroblasts (P < .05). HGF was mainly secreted in the cleaved mature form, both in IPF and control fibroblasts. HGF mRNA levels were reduced in IPF fibroblasts. Prostaglandin E2 secretion by IPF fibroblasts was very low when compared with controls (P < .05). After the addition of PGE2 (10-6 M) or dibutyryl cyclic AMP (10-3 M), HGF secretion by IPF fibroblasts reached the level of controls. Inhibition of PGE2 synthesis with indomethacin reduced HGF secretion by control fibroblasts but had no effect on IPF fibroblasts. HGF secretion by control fibroblasts was also slightly inhibited by TGFb1 and stimulated by anti-TGFb antibody, whereas both agents had no effect on IPF fibroblasts. Our results demonstrate a defect in HGF production by IPF fibroblasts that seems secondary to a defect in PGE2 secretion.

Thabut G, Mal H, Castier Y, et al
J Thorac Cardiovasc Surg. 2003;126:469-475

Objective: Although lung transplantation is viewed as an acceptable option for patients with end-stage IPF, the survival benefit of this approach is still debated. This study examined whether there was a survival benefit of lung transplantation in a cohort of patients referred to our transplant center with a diagnosis of IPF according to American Thoracic Society criteria.
Methods: Forty-six patients accepted for lung transplantation during a 12-year period with a diagnosis of IPF form the basis of this study. Survival benefit offered by lung transplantation was assessed using Cox proportional-hazards modeling, with patients on a waiting list as the control group.
Results: Twenty-eight patients underwent lung transplantation (27 single and 1 double), 16 patients died while waiting, and 2 patients remained on the active waiting list. Diagnosis of IPF was made on histologic examination of the explanted lung or lung biopsy before lung transplantation. There was a pattern of usual interstitial pneumonia in 31 cases (67%). The 15 remaining patients fulfilled all American Thoracic Society criteria for IPF. The median waiting time for organs was 51 days. Survival after lung transplantation was 79.4% at 1 year, 63.5% at 2 years, and 39% at 5 years. The multivariable analysis showed that lung transplantation reduced the risk of death by 75% (95% confidence interval, 8%-86%; P = .03) after adjustment on potential confounding variables.
Conclusion: Lung transplantation is effective in improving the survival of selected patients affected by IPF.

Davies HR, Richeldi L, Walters EH
Cochrane Database Syst Rev. 2003;(3):CD003134

Background: Idiopathic Pulmonary Fibrosis (IPF) or Usual Interstitial Pneumonia (UIP) is a form of chronic fibrosing interstitial pneumonia of unknown aetiology, with progressively deteriorating respiratory function and ultimately death from respiratory failure. Most treatments are intended to suppress inflammation, but none has been proven to alter this process. The most widespread approach uses oral corticosteroids; others use immunosuppressive, immunomodulatory, or anti-fibrotic agents, alone or with corticosteroids. A Cochrane review of corticosteroids in IPF has found no evidence that they are of benefit.
Objectives: To determine the effect of non-corticosteroid immunosuppressive, anti-fibrotic and immunomodulatory agents in the treatment of IPF(UIP).
Search Strategy: We searched the Cochrane Central Register of Controlled Trials (CENTRAL - The Cochrane Library, Issue 2 2003), MEDLINE (January 1966 to April 2003), EMBASE (January 1985 to April 2003) and with additional handsearching.
Selection Criteria: RCTs/CCTs utilizing non-corticosteroid immunosuppressive, anti-fibrotic or immunomodulatory agents versus either placebo or corticosteroids alone in adult patients with histological evidence of IPF (UIP) or with a diagnosis consistent with published American Thoracic Society guidelines were included.
Data Collection and Analysis: We retrieved abstracts of identified articles and reviewed those possibly fulfilling inclusion criteria and included or excluded. Two reviewers assessed the studies for inclusion in the review. Where doubt existed a third reviewer re-assessed the article and consensus was obtained. Methodological quality was assessed using the Jadad scale and the Cochrane assessment of allocation of concealment.
Main Results: 59 studies were identified. Quality was generally poor. Only three RCT/CCTs were suitable for meta-analysis, two lesser quality RCTs were included in discussion only, 52 studies were excluded and two ongoing trials were identified. Each high-quality trial used a different agent (azathioprine, colchicine, interferon-gamma 1b) and meaningful comparisons are not possible. Azathioprine and interferon were studied as additional therapy, while colchicine was compared with oral corticosteroids. Only interferon was shown to produce any significant improvement in pulmonary function and arterial oxygenation. There may be a small (but undefined) long-term survival advantage for azathioprine. One of the lower quality studies showed a marginal benefit for cyclophosphamide and prednisone over prednisone alone; the other showed no benefit for azathioprine and prednisone over prednisone alone. There are no high quality studies utilizing cyclophosphamide.
Reviewer's Conclusions: There is little good quality information regarding the efficacy of non-corticosteroid agents in IPF(UIP). The older agents have generally not been well evaluated. A number of new agents require further evaluation. Currently, there is little to justify the routine use of any non-corticosteroid agent in the management of IPF (UIP).

Richeldi L, Davies HR, Ferrara G, Franco F
Cochrane Database Syst Rev. 2003;(3):CD002880

Background: IPF, also called cryptogenic fibrosing alveolitis (CFA), is a lethal form of diffuse lung disorder of unknown origin; the mean survival being 2 to 4 years. Currently recommended and most prescribed therapy for IPF is based on the use of systemic corticosteroids, even if no formal demonstration of efficacy of this treatment of IPF is available. Furthermore, new insights from pathological studies have produced a new hypothesis, based upon the central role played by aberrant wound healing following repeated lung injury, weakening the rationale basis of the use of corticosteroids in IPF, previously considered simply a chronic inflammatory disease.
Objectives: The objective of the review was to determine the efficacy of corticosteroids in the treatment of adults with IPF.
Search Strategy: We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 2, 2002), MEDLINE (January 1966 to May 2002) and EMBASE (January 1985 to December 2002), and reference lists of articles. We searched reference lists of published articles to identify trials.
Selection Criteria: Randomized controlled trials (RCT) and controlled clinical trials (CCT) using corticosteroids alone for the treatment of adults with IPF.
Data Collection and Analysis: Abstracts of identified articles were retrieved and articles possibly fulfilling inclusion criteria were retrieved in full. Two reviewers would have independently assessed trial quality if there had been any included studies.
Main Results: Fifteen studies were selected as potentially eligible for meta-analysis. After further analysis of full text papers, no RCTs or CCTs were identified as suitable and therefore no data was available for inclusion in any meta-analysis. All studies were excluded due to inadequate methodologies.
Reviewer's Conclusions: At present, there is no evidence for an effect of corticosteroid treatment in patients with IPF/usual interstitial pneumonia (UIP). Given developments in understanding of the pathogenesis of IPF, randomized controlled trials designed to test the efficacy of corticosteroids will probably never be designed. As other forms of pulmonary fibrosis, such as non-specific interstitial pneumonia, are reported to show a better response to corticosteroids, it is crucial to make an accurate diagnosis in each patient. Moreover, therapies with immunomodulatory rather than anti-inflammatory or immunosuppressive effects may be more promising for the effective treatment of IPF/UIP.

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