Course Of Idiopathic Pulmonary Fibrosis Research Articles

The Red Cell Distribution Width as a Prognostic Indicator in Idiopathic Pulmonary Fibrosis

BackgroundThe course of idiopathic pulmonary fibrosis (IPF) is characterized by variable patterns of disease progression. The red cell distribution width (RDW) is a parameter that is routinely reported with all CBC counts. We sought to test the prognostic usefulness of this parameter in a well-defined cohort of patients with IPF. MethodsCBCs, demographics, and pulmonary function data from patients with IPF evaluated between January 1997 and June 2011 were collated. Patient outcomes were ascertained from the program's database and the Social Security Death Index. ResultsThere were 319 patients with IPF evaluated in whom baseline CBCs were available. The range in the RDW was 11.9 to 21.9 (median 14.1). There were 228 subjects with RDW values ≤ 15 (normal) and 91 patients with RDW values > 15. Patients with normal RDW values had a median survival of 43.1 months compared with 16.3 months for those whose RDW was > 15 (P = .001). There were 198 patients with available serial RDW data. Those patients who had a change in the RDW of less or greater than +0.010/mo had median survivals of 43.0 and 23.9 months, respectively (P = .0246). ConclusionsThe RDW is a readily available laboratory test result that may provide important, independent prognostic information at baseline and follow-up in patients with IPF. Further studies are warranted to validate this as a biomarker for IPF outcomes, as well as to define the biologic basis for this association.

Blood Biomarkers MMP-7 and SP-A: Predictors of Outcome in Idiopathic Pulmonary Fibrosis

Because of the variable course of idiopathic pulmonary fibrosis (IPF), it is important to generate an accurate prognosis at the time of diagnosis. The aim of this study was to investigate the prognostic value of blood biomarkers in IPF.The plasma level of the biomarkers, matrix metalloproteinase-7 (MMP-7), Krebs von den Lungen-6 antigen, and surfactant protein (SP)-A and SP-D were retrospectively compared with the clinical course of 118 patients with IPF, 68 of whom had biopsy-proven IPF.The median follow-up period was 24 months. Multivariate Cox analysis showed MMP-7 (HR, 1.056; P = .0063) and SP-A (HR, 1.011; P = .0001) were significant predictors of survival along with age, FVC, and extent of honeycombing. The patients with high levels of both MMP-7 (≥ 12.1 ng/mL) and SP-A (≥ 80.3 ng/mL) had shorter survival (1-year survival rate: 59%) and higher frequency (42%) of lung function decline (> 10% reduction in FVC in 6 months) compared with those with high levels of one biomarker (1-year survival rate: 81%; FVC decline: 27%) or low levels of both (1-year survival rate: 83.3%; FVC decline: 9%). Multivariate models demonstrated marginal improvement in the prediction of mortality (concordance index [C-index]: 0.731; P = .061) when MMP-7 and SP-A were included and compared with standard clinical predictors only (C-index: 0.686); however, it became significant with addition of MMP-7, SP-A, and Krebs von den Lungen-6 antigen (C-index: 0.730; P = .037).Our retrospective study suggested that at least three biomarkers are necessary to improve predictability of mortality in IPF compared with clinical parameters. Further study in a greater number of patients is warranted.

Interstitial lung disease

This article reviews the most important articles published in interstitial lung disease, as reviewed during the Clinical Year in Review session at the 2012 annual European Respiratory Society Congress in Vienna, Austria. Since the recent international guidelines for the management of idiopathic pulmonary fibrosis (IPF), important new evidence is available. The anti-fibrotic drug pirfenidone has been recently approved in Europe. Other pharmacological agents, especially nintedanib, are still being tested. The so-called triple combination therapy, anticoagulation therapy and endothelin receptor antagonists, especially ambrisentan, are either harmful or ineffective in IPF and are not recommended as treatment. Although the clinical course of IPF is highly variable, novel tools have been developed for individual prediction of prognosis. Acute exacerbations of IPF are associated with increased mortality and may occur with higher frequency in IPF patients with associated pulmonary hypertension. Interstitial lung disease associated with connective tissue disease has been definitely established to have a better long-term survival than IPF. A subset of patients present with symptoms and/or biological autoimmune features, but do not fulfil diagnostic criteria for a given autoimmune disease; this condition is associated with a higher prevalence of nonspecific interstitial pneumonia pattern, female sex and younger age, although survival relevance is unclear.

Incidence of myeloperoxidase anti-neutrophil cytoplasmic antibody positivity and microscopic polyangitis in the course of idiopathic pulmonary fibrosis

Pulmonary fibrosis is a manifestation of microscopic polyangitis (MPA), and often precedes the detection of MPA. The prevalence and sequence of myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) and MPA in patients initially diagnosed with idiopathic pulmonary fibrosis (IPF) have not been precisely elucidated. We enrolled 61 consecutive patients with IPF and measured the MPO-ANCA titers at initial presentation and during the follow-up period. Clinical, radiologic and histologic features of MPO-ANCA-positive cases were examined. Of 61 patients, 3 (4.9%) had positive MPO-ANCA titers at the initial presentation of IPF. During the disease course, MPO-ANCA-positive conversion occurred in 6 patients and the prevalence of ANCA increased to 14.8%. Among the nine patients positive for MPO-ANCA, two patients developed MPA during follow-up. Histologic features of MPO-ANCA-positive pulmonary fibrosis were compatible with the usual interstitial pneumonia pattern in which alveolar hemorrhage and capillaritis were not observed. The patients with MPO-ANCA-positive conversion showed increased percentages of bronchoalveolar lavage eosinophils and more frequent complication of pulmonary emphysema compared to those with MPO-ANCA-negative IPF. The findings of the present study demonstrated that patients with an initial diagnosis of IPF occasionally acquire MPO-ANCA, which develops to MPA during the disease course of IPF. The presence of pulmonary eosinophilia and low attenuation areas on computed tomography scans might be predictive of MPO-ANCA positive conversion.

Acute exacerbations in patients with idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a chronic, fibrosing interstitial lung disease that primarily affects older adults. Median survival after diagnosis is 2–3 years. The clinical course of IPF may include periods of acute deterioration in respiratory function, which are termed acute exacerbations of IPF (AEx-IPF) when a cause cannot be identified. AEx-IPF may represent a sudden acceleration of the underlying disease process of IPF, or a biologically distinct pathological process that is clinically undiagnosed. An AEx-IPF can occur at any time during the course of IPF and may be the presenting manifestation. The incidence of AEx-IPF is hard to establish due to variation in the methodology used to assess AEx-IPF in different studies, but AEx-IPF are believed to occur in between 5 and 10% of patients with IPF every year. Risk factors for AEx-IPF are unclear, but there is evidence that poorer lung function increases the risk of an AEx-IPF and reduces the chances of a patient surviving an AEx-IPF. The presence of comorbidities such as gastroesophageal reflux disease (GERD) and pulmonary hypertension may also increase the risk of an AEx-IPF. AEx-IPF are associated with high morbidity and mortality. Patients who experience an AEx-IPF show a worsened prognosis and AEx-IPF are believed to reflect disease progression in IPF. Current treatments for AEx-IPF have only limited data to support their effectiveness. The latest international treatment guidelines state that supportive care remains the mainstay of treatment for AEx-IPF, but also give a weak recommendation for the treatment of the majority of patients with AEx-IPF with corticosteroids. There is emerging evidence from clinical trials of investigational therapies that chronic treatment of IPF may reduce the incidence of AEx-IPF. Additional clinical trials investigating this are underway.

Silent gastro-oesophageal reflux and microaspiration in IPF: mounting evidence for anti-reflux therapy?

Idiopathic pulmonary fibrosis (IPF) is a distinct clinical entity that generally affects people who are over 60 yrs of age, and median survival ranges from 3 to 5 yrs after the diagnosis is ascertained. The natural course of IPF is well known: the majority of patients with IPF display steady decline in lung function, some patients remain stable for prolonged periods of time, a subgroup of patients rapidly decline, and a subset of patients manifest acute exacerbations of IPF preceding death [1]. While several key cellular and molecular events that are thought to follow “injury” have been identified in the pathogenesis of IPF [2], the ultimate cause of IPF and the triggering factor(s) that injure the lung remain elusive, and none of the currently available pharmacological agents have demonstrated improved outcomes and survival in patients with IPF. The incidence and prevalence of IPF is highly linked to advanced age with an estimated incidence and prevalence of 71 and 271 per 100,000 per year for males and 67 and 266 per 100,000 per year for females aged 75 yrs or greater versus an overall incidence and prevalence of 16.3 and 42.7 per 100,000 per year using broad diagnostic criteria [3]. Interestingly, many observations suggest that the aged lung is more susceptible to injury and fibrosis induced by a variety of stimuli, and this susceptibility may be linked to age-associated changes in gene expression or genetic polymorphisms such as age-associated telomerase dysfunction [4–7]. Advanced age is also accompanied by a decline in oesophageal and gastric motility, diminished upper oesophageal sphincter pressure, and an increase in oesophageal acid exposure [8]. Hiatal hernias appear with advancing age and have been detected in up to 60% of individuals older than 60 yrs [ …

Retrospective analysis of the prognosis factors in patients with idiopathic pulmonary fibrosis

To investigate the prognostic implications of clinical and physiological variables, and the cellular classification of bronchoalveolar lavage fluid (BALF) in patients with idiopathic pulmonary fibrosis (IPF). The effect of treatment with glucocorticoids with or without cytotoxic drugs was also evaluated. The significances of clinical, arterial blood gas analysis, pulmonary function test, lung high-resolution computed tomography, echocardiography and BALF in the prognosis of patients with IPF were assessed in 65 patients with IPF at diagnosis. Univariate Cox proportional-hazards regression analysis was used to evaluate the various parameters associated with hazard ratio. The survival rates of all groups were compared using the Kaplan-Meier method. In 38 months of average follow-up time, the survival rate of the patients was 43.1%, and the median survival time was 39 months after diagnosis. Univariate Cox proportional-hazards regression analysis showed that body mass index, clubbing fingers, ESR, PaO(2)/FiO(2), SaO(2), TLC%, D(L)CO%, pulmonary arterial pressure and the percent of neutrophil in BALF were factors that affected the prognosis of the patients with IPF (HR 0.842 - 1.945, Wald 3.782 - 12.963, P < 0.05). In the meanwhile, the patients were divided into 2 groups by the median of significant variables in univariate Cox proportional-hazards regression analysis (the cut off point value), and the survival rate group comparison showed statistically significant difference in body mass index, clubbing fingers, ESR, TLC% as well as D(L)CO% (Log-rank 3.907 - 10.452, P < 0.05), while glucocorticoids with or without cytotoxic drugs for patients with IPF did not change the prognosis (Log-rank 2.405, P > 0.05). Body mass index, clubbing fingers, ESR, PaO(2)/FiO(2), TLC%, and D(L)CO% maybe the factors affecting the prognosis of patients with IPF, while glucocorticoids with or without cytotoxic drugs did not change the course of IPF.

Intérêt pronostique de l’exploration fonctionnelle à l’exercice (EFX) au cours de la fibrose pulmonaire idiopathique

Current guidelines for referring patients with idiopathic pulmonary fibrosis (IPF) for lung transplantation, based on resting parameters, are insufficient to predict 3-year mortality. The aim of this study was to determine the prognostic value of cardio-pulmonary exercise testing (CPET) in patients with IPF. A multicentre retrospective study of 3-year outcome was made on 63 adult patients with IPF who underwent CPET with blood gas analysis. Demographic data, resting pulmonary function and CPET parameters were collected to perform a univariate survival analysis. To estimate prognosis at 3 years, a multivariate logistic regression analysis by Kaplan-Meier curves and log-rank tests was performed. Forty-four patients (70%) were alive without lung transplant at the end of the 3-year follow-up: 19 patients (30%) were dead (n=14) or transplanted (n=5). Univariate analysis indicated that: at rest lower TLC, FVC, DLCO and PaCO(2), higher alveolo-arterial gradient for oxygen [P(A-a)O(2)] and pH; at ventilatory threshold (VT) higher VE/VO(2) and VE/VCO(2) and at peak exercise higher VE/VO(2) and VE/VCO(2), higher pH and ΔP(A-a)O(2)/ΔVO(2) (mmHg/L), lower VO(2) peak, PaO(2) and VO(2)/FC were associated with a significantly lower survival at 3 years. The multivariate logistic regression analysis showed that CPT (<65%) and VE/VO(2) at VT (>45) were independently associated with a lower survival at 3 years. Restriction and hyperventilation at ventilatory threshold are major prognostic factors in the course of IPF. CPET with blood gas analysis may have a prognostic value in these patients and initial evaluation of these parameters can help to predict disease progression.

Tacrolimus and Steroid Treatment for Acute Exacerbation of Idiopathic Pulmonary Fibrosis

Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) occurs during the chronic progressive course of idiopathic pulmonary fibrosis. Mortality is estimated to be >70%, because no effective treatment has been established. We evaluated the effectiveness of combination therapy of tacrolimus and methylprednisolone for AE-IPF. Patients of AE-IPF treated with methylprednisolone pulse therapy with or without tacrolimus (targeting 20 ng/mL) during the period between January 2001 and April 2010 were retrospectively reviewed. The primary endpoints were survival rate and duration. We also observed lactate dehydrogenase levels, partial pressure of arterial oxygen/fraction of inspired oxygen ratio (P/F ratio), KL-6, occurrence of re-exacerbation, and computed tomography score. Fifteen Japanese patients [tacrolimus group aged 74.2±6.0 years old (n=5), non-tacrolimus group aged 75.1±12.8 years old (n=10)] were identified. Pre-treatment clinical parameters were not significantly different between the two groups. Four of 5 tacrolimus group patients and 1 of 10 non-tacrolimus group patients survived (p<0.05). The median survival durations were >92 days (tacrolimus group) and 38 days (non-tacrolimus group) (p<0.05). Lactate dehydrogenase levels and the P/F ratio were also significantly favorable in the tacrolimus group. KL-6 and CT score were not significantly different in both groups. Four re-acute exacerbations were observed only in the non-tacrolimus group. Combined tacrolimus and methylprednisolone pulse therapy mitigates AE-IPF, prevents re-acute exacerbation, and contributes to a better prognosis.

Acute exacerbations of interstitial lung diseases

This review aims to highlight recent advances in pathogenesis, clinical presentation and treatment of interstitial lung diseases (ILDs). Acute exacerbation is increasingly recognized as a major complication in the course of idiopathic pulmonary fibrosis. It is precipitated by a variety of intrinsic and extrinsic factors. Moreover, acute exacerbation is an apparently equally frequent event in hypersensitivity pneumonitis and collagen-vascular diseases associated ILDs, especially the rheumatoid pulmonary fibrosis. Treatment of acute exacerbations is unsatisfactory and prognosis extremely poor. In a critically ill patient proper recognition of an acute exacerbation and of the underlying chronic ILD is warranted because treatment approach varies with the type of ILD. Advances in the understanding of the pathogenesis and treatment of this 'idiopathic' phenomenon are reviewed.

High-resolution computed tomography in the diagnosis and follow-up of idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is the most common interstitial lung disease and is associated with a fatal prognosis. Familiarity with the typical appearances of IPF on high-resolution computed tomography (HRCT) is important, as in the appropriate clinical setting, it is often sufficient for establishing a confident diagnosis of IPF without the need for surgical biopsy. Moreover, HRCT can provide important prognostic information in IPF. This is noteworthy, as the course of IPF is variable, and many patients develop complications leading to respiratory failure and death. The purpose of this paper is to review the progress made towards a better understanding of the HRCT patterns of IPF.

Cyclosporin A in the Treatment of Acute Exacerbation of Idiopathic Pulmonary Fibrosis

Acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) is considered to be a nearly fatal condition during the clinical course of IPF, as it is unresponsive to most conventional therapies. To evaluate the efficacy of cyclosporin A (CsA) for AE of IPF, we conducted a retrospective study on autopsied IPF cases who developed AE and were treated with corticosteroids (CS) combined with CsA. The subjects comprised 11 males with a mean age of 69.9 years. The clinical features and prognosis of the CsA-treated group was compared to a group of 11 autopsied IPF cases with a mean age of 68.7 years who developed AE and were treated with CS alone (non-CsA-treated group). CS pulse therapy followed by CS maintenance treatment were conducted in all cases of AE. Patients in the CsA-treated group received in addition a low dosage of CsA (100-150 mg). Although 7 out of 11 patients in the CsA-treated group died of AE per se, 4 patients survived the AE. Only 2 patients died during the first episode of AE. In comparison, 7 out of 11 patients in the non-CsA-treated group died during the first episode of AE. The mean survival period after the first onset of AE was 285 days in the CsA-treated group and 60 days in the non-CsA-treated group. The prognosis of the CsA-treated group therefore was significantly better than that of non-CsA-treated group after AE of IPF. Administration of CsA combined with CS may be efficacious in the treatment of AE of IPF.

Incidence, Prevalence, and Clinical Course of Idiopathic Pulmonary Fibrosis: A Population-Based Study

Limited data exist regarding the population-based epidemiology of idiopathic pulmonary fibrosis (IPF). The objective of the study was to describe the trends in the incidence, prevalence, and clinical course of IPF in the community. We conducted a population-based study of adult patients with IPF in Olmsted County, Minnesota, from 1997 to 2005. Two methods were used to identify IPF cases, as defined by the 2002 American Thoracic Society/European Respiratory Society consensus statement: (1) usual interstitial pneumonia (UIP) on a surgical lung biopsy specimen or a definite UIP pattern on a high-resolution CT image (narrow criteria) and (2) UIP on a surgical lung biopsy specimen or a definite or possible UIP pattern on CT image (broad criteria). Of 596 patients screened for the possibility of pulmonary disease or pulmonary fibrosis over 9 years of follow-up, 47 cases had IPF. Of these, 24 met the narrow criteria. The age- and sex-adjusted incidence was 8.8/100,000 and 17.4/100,000 person-years, for narrow and broad criteria, respectively. The age-adjusted incidence was higher in men than in women, and among patients aged 70-79 years. During the study period, the incidence of IPF decreased (P < .001). On December 31, 2005, the age- and sex-adjusted prevalence was 27.9/100,000 and 63/100,000 persons by narrow and broad criteria, respectively. Thirty-seven patients experienced a total of 53 respiratory exacerbations (26 IPF related, 27 non-IPF related), and 34 (72%) patients died. The primary cause of death was IPF related in 16 (47%) patients. Median survival for narrow-criteria and broad-criteria incidence cases was 3.5 and 4.4 years, respectively. The incidence of IPF in Olmsted County decreased over the study period. Nonprimary IPF respiratory exacerbations are as frequent as primary IPF respiratory exacerbations and an important cause of death.

Acute exacerbation of idiopathic pulmonary fibrosis as the initial presentation of the disease

The clinical course of patients with idiopathic pulmonary fibrosis (IPF) is generally marked by a decline in pulmonary function over time, although recently there is increasing recognition that fatal deterioration from acute exacerbation can occur at any stage. The patient described in the present case study was a 65-yr-old male who presented with exertional dyspnoea and fever of 2&emsp14;weeks' duration. He had no history of chronic lung disease or physiological or radiological hallmarks of pre-existing disease. He underwent surgical lung biopsy and the histological examination showed a background pattern of usual interstitial pneumonia (UIP) with a pattern of focal acute diffuse alveolar damage (DAD) in the area where normal lung architecture was preserved. It is notable that the pathological diagnosis of this rapidly progressive interstitial pneumonia was DAD on UIP, which is typically seen in acute exacerbations of IPF. Unusual findings on high-resolution computed tomography scan were also noted. We presume that in this case acute exacerbation developed in the very early course of IPF. Given the possibility that similar cases may have arisen among patients diagnosed with acute interstitial pneumonia or acute respiratory distress syndrome, the histopathology of rapidly progressive interstitial pneumonia may need to be revisited.

The 15-Step Oximetry Test: a Reliable Tool to Identify Candidates for Lung Transplantation Among Patients With Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a relentlessly progressive disease with a median survival of approximately 3 years. Measurements of lung volumes and diffusion capacity at rest are generally used to monitor the clinical course of IPF. Due to its high mortality, identification of patients at high risk is crucial for treatment strategies such as lung transplantation. This study was design to determine whether the simple 15-step climbing exercise oximetry test accurately characterizes disease severity and survival in patients with IPF. The study population consisted of 51 patients with progressive IPF. Findings on the 15-step climbing test, pulmonary function tests, cardiopulmonary exercise test and 6-minute walk distance test were assessed at baseline. Participants were prospectively followed for >or=2 years to determine the relationship between the test parameters and survival. On univariate analysis, there were strong correlations between the 15-stair climbing test parameters and survival. On stepwise linear regression analysis, independent significant predictors of mortality were lowest saturation levels on the 15-step test and the 6-minute walk distance test. The lowest saturation and desaturation areas on the 15-step oximetry test are significantly associated with long-term outcome in patients with IPF. We suggest that the 15-step test be used as a simple and reliable tool to predict severity and prognosis in IPF and to identify candidates for lung transplantation.

Investigation of effects of antibiotics on experimental bleomycin-induced pulmonary fibrosis

Several reports have shown results of antifibrotic action of antibiotics in experimental models of idiopathic pulmonary fibrosis (IPF). Effects of antibiotics on course of IPF has been also investigated in the present work. IPF model was created in male rats Vistar (n = 41) using intratracheal instillations of bleomycin 10 mg/kg followed by intramuscular injections of cefotaxime (n = 10) or erythromycin (n = 10) after the 5th day during 8 days. We evaluated bronchoalveolar lavage fluid (BALF) cell count and differentiation, oxidative activity of alveolar macrophages (AM) using luminol-dependent chemiluminescence, and histological changes in the lung tissue. Both the antimicrobials decreased total cell count in BALF, increased AM and lymphocyte numbers and decreased neutrophil number. Erythromycin increased oxidative activity of AM and cefotaxime reduced it in some degree. Structure of the lung tissue after 14 days of administration of antibiotics did not differ from that seen in rats received bleomycin alone but the formers had more severe vascular lesions such as vasculitis, perivascular fibrosis, full-blooded capillaries. Therefore, antibiotics inhibited neutrophil-related inflammation, heterogeneously affected oxidative activity of AM, caused vascular lesions and did not influence fibrosis. These results do not suggest antibiotics to be used as therapeutic drugs in IPF.

A Role for the Receptor for Advanced Glycation End Products in Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a severely debilitating disease associated with a dismal prognosis. There are currently no effective therapies for IPF, thus the identification of novel therapeutic targets is greatly needed. The receptor for advanced glycation end products (RAGE) is a member of the immunoglobulin superfamily of cell surface receptors whose activation has been linked to various pathologies. In healthy adult animals, RAGE is expressed at the highest levels in the lung compared to other tissues. To investigate the hypothesis that RAGE is involved in IPF pathogenesis, we have examined its expression in two mouse models of pulmonary fibrosis and in human tissue from IPF patients. In each instance we observed a depletion of membrane RAGE and its soluble (decoy) isoform, sRAGE, in fibrotic lungs. In contrast to other diseases in which RAGE signaling promotes pathology, immunohistochemical and hydroxyproline quantification studies on aged RAGE-null mice indicate that these mice spontaneously develop pulmonary fibrosis-like alterations. Furthermore, when subjected to a model of pulmonary fibrosis, RAGE-null mice developed more severe fibrosis, as measured by hydroxyproline assay and histological scoring, than wild-type controls. Combined with data from other studies on mouse models of pulmonary fibrosis and human IPF tissues indicate that loss of RAGE contributes to IPF pathogenesis.

Idiopathic Pulmonary Fibrosis and Pulmonary Hypertension

Idiopathic pulmonary fibrosis (IPF) has a poor prognosis and a course that is unpredictable. Pulmonary hypertension may complicate the course of IPF and potentially impact prognosis. There are multiple factors that might influence the onset and severity of pulmonary hypertension in IPF. The relationship between the physiologic and pathobiologic manifestations of the progressive fibrotic process and interceding pulmonary hypertension has not been well defined. This article serves to explore these relationships and to hypothesize about the possible linkage between these entities. From a prognostic standpoint, recent evidence suggests this to be important to assess for pulmonary hypertension in patients with IPF. The appropriate triggers for evaluating for pulmonary hypertension and the best method of detection require further study. Despite the relative ease of noninvasive methods, such as echocardiography, right-heart catheterization remains the best diagnostic test. The appeal of pulmonary hypertension in IPF is that it may be an enticing therapeutic target in a disease that otherwise does not have any proven effective therapies. Which agent(s) might be useful and when they should be implemented mandate the appropriate studies being performed. Some of the data presented in this article have previously been reported in abstract form only.

Chemokine/Cytokine Cocktail in Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible fibrosing lung disease of unknown etiology and with an unfavorable outcome, leading ultimately to death due to respiratory failure. To date, no treatment strategies have been effective in modifying the natural course of IPF and its fatal outcome. The aberrant parenchymal remodeling is characterized by the expansion of fibroblasts/myofibroblasts, which form characteristic subepithelial foci, and by the abnormal deposition of extracellular matrix in the lung parenchyma. Although the pathophysiology underlying this disease has not yet been fully elucidated, animal models of pulmonary fibrosis have provided contributions in dissecting the molecular basis of this disease, focusing on the role of cytokines and chemokines as important pathogenetic mediators of lung fibrosis. Starting with the data obtained from animal models, this article provides a comment on a number of findings that suggest the possible role of the chemokine/cytokine system in the pathogenesis of IPF.

Current Perspectives on the Treatment of Idiopathic Pulmonary Fibrosis

The clinical course of idiopathic pulmonary fibrosis (IPF) is variable; however, the long-term survival in IPF is poor. Prednisone has been the mainstay of therapy since its release for clinical use in 1948. Recently, prednisone combined with azathioprine or cyclophosphamide has been used. A number of other drug combinations have been tried with prednisone (e.g., methotrexate, colchicine, penicillamine, or cyclosporine) but have failed or are not well tolerated by the patient. Few high quality, prospective, controlled clinical trials have been performed. Thus, there is no good evidence to support the routine use of any specific therapy in the management of IPF. Additional large clinical trials are needed to confirm the potential usefulness of the newer agents (e.g., IFN-gamma1b, pirfenidone, N-acetylcysteine, coumadin, bosentan, or etanercept). This article examines the body of evidence supporting the current therapies and reviews the newer agents being tested in patients with IPF.