Harold R Collard

University of California, San Francisco, San Francisco, California, United States

Are you Harold R Collard?

Claim your profile

Publications (133)902.86 Total impact

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: IL-13 can bind to two distinct receptors: a heterodimer of IL-13Rα1/IL-4Rα and IL-13Rα2. Whereas IL-13Rα1/IL-4Rα engagement by IL-13 leads to the activation of STAT6, the molecular events triggered by IL-13 binding to IL-13Rα2 remain incompletely understood. IL-4 can bind to and signal through the IL-13Rα1/IL-4Rα complex but does not interact with IL-13Rα2. Idiopathic pulmonary fibrosis is a progressive and generally fatal parenchymal lung disease of unknown etiology with no current pharmacologic treatment options that substantially prolong survival. Preclinical models of fibrotic diseases have implicated IL-13 activity on multiple cell types, including macrophages and fibroblasts, in initiating and perpetuating pathological fibrosis. In this study, we show that IL-13, IL-4, IL-13Rα2, and IL-13-inducible target genes are expressed at significantly elevated levels in lung tissue from patients with idiopathic pulmonary fibrosis compared with control lung tissue. IL-4 and IL-13 induce virtually identical transcriptional responses in human monocytes, macrophages, and lung fibroblasts. IL-13Rα2 expression can be induced in lung fibroblasts by IL-4 or IL-13 via a STAT6-dependent mechanism, or by TNF-α via a STAT6-independent mechanism. Endogenously expressed IL-13Rα2 decreases, but does not abolish, sensitivity of lung fibroblasts to IL-13 and does not affect sensitivity to IL-4. Genome-wide transcriptional analyses of lung fibroblasts stimulated with IL-13 in the presence of Abs that selectively block interactions of IL-13 with IL-13Rα1/IL-4Rα or IL-13Rα2 show that endogenously expressed IL-13Rα2 does not activate any unique IL-13-mediated gene expression patterns, confirming its role as a decoy receptor for IL-13 signaling.
    The Journal of Immunology 05/2014; 193(1). DOI:10.4049/jimmunol.1301761 · 5.36 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: Nintedanib (formerly known as BIBF 1120) is an intracellular inhibitor that targets multiple tyrosine kinases. A phase 2 trial suggested that treatment with 150 mg of nintedanib twice daily reduced lung-function decline and acute exacerbations in patients with idiopathic pulmonary fibrosis. METHODS: We conducted two replicate 52-week, randomized, double-blind, phase 3 trials (INPULSIS-1 and INPULSIS-2) to evaluate the efficacy and safety of 150 mg of nintedanib twice daily as compared with placebo in patients with idiopathic pulmonary fibrosis. The primary end point was the annual rate of decline in forced vital capacity (FVC). Key secondary end points were the time to the first acute exacerbation and the change from baseline in the total score on the St. George's Respiratory Questionnaire, both assessed over a 52-week period. RESULTS: A total of 1066 patients were randomly assigned in a 3:2 ratio to receive nintedanib or placebo. The adjusted annual rate of change in FVC was -114.7 ml with nintedanib versus -239.9 ml with placebo (difference, 125.3 ml; 95% confidence interval [CI], 77.7 to 172.8; P<0.001) in INPULSIS-1 and -113.6 ml with nintedanib versus -207.3 ml with placebo (difference, 93.7 ml; 95% CI, 44.8 to 142.7; P<0.001) in INPULSIS-2. In INPULSIS-1, there was no significant difference between the nintedanib and placebo groups in the time to the first acute exacerbation (hazard ratio with nintedanib, 1.15; 95% CI, 0.54 to 2.42; P=0.67); in INPULSIS-2, there was a significant benefit with nintedanib versus placebo (hazard ratio, 0.38; 95% CI, 0.19 to 0.77; P=0.005). The most frequent adverse event in the nintedanib groups was diarrhea, with rates of 61.5% and 18.6% in the nintedanib and placebo groups, respectively, in INPULSIS-1 and 63.2% and 18.3% in the two groups, respectively, in INPULSIS-2. CONCLUSIONS: In patients with idiopathic pulmonary fibrosis, nintedanib reduced the decline in FVC, which is consistent with a slowing of disease progression; nintedanib was frequently associated with diarrhea, which led to discontinuation of the study medication in less than 5% of patients.
    New England Journal of Medicine 05/2014; 370(22):2071-82. · 54.42 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Published data for the epidemiology of idiopathic pulmonary fibrosis in the USA are scarce. We sought to estimate the incidence, prevalence, and mortality risk of idiopathic pulmonary fibrosis among US Medicare beneficiaries.
    05/2014; DOI:10.1016/S2213-2600(14)70101-8
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: Nintedanib (formerly known as BIBF 1120) is an intracellular inhibitor that targets multiple tyrosine kinases. A phase 2 trial suggested that treatment with 150 mg of nintedanib twice daily reduced lung-function decline and acute exacerbations in patients with idiopathic pulmonary fibrosis. METHODS: We conducted two replicate 52-week, randomized, double-blind, phase 3 trials (INPULSIS-1 and INPULSIS-2) to evaluate the efficacy and safety of 150 mg of nintedanib twice daily as compared with placebo in patients with idiopathic pulmonary fibrosis. The primary end point was the annual rate of decline in forced vital capacity (FVC). Key secondary end points were the time to the first acute exacerbation and the change from baseline in the total score on the St. George's Respiratory Questionnaire, both assessed over a 52-week period. RESULTS: A total of 1066 patients were randomly assigned in a 3:2 ratio to receive nintedanib or placebo. The adjusted annual rate of change in FVC was -114.7 ml with nintedanib versus -239.9 ml with placebo (difference, 125.3 ml; 95% confidence interval [CI], 77.7 to 172.8; P<0.001) in INPULSIS-1 and -113.6 ml with nintedanib versus -207.3 ml with placebo (difference, 93.7 ml; 95% CI, 44.8 to 142.7; P<0.001) in INPULSIS-2. In INPULSIS-1, there was no significant difference between the nintedanib and placebo groups in the time to the first acute exacerbation (hazard ratio with nintedanib, 1.15; 95% CI, 0.54 to 2.42; P=0.67); in INPULSIS-2, there was a significant benefit with nintedanib versus placebo (hazard ratio, 0.38; 95% CI, 0.19 to 0.77; P=0.005). The most frequent adverse event in the nintedanib groups was diarrhea, with rates of 61.5% and 18.6% in the nintedanib and placebo groups, respectively, in INPULSIS-1 and 63.2% and 18.3% in the two groups, respectively, in INPULSIS-2. CONCLUSIONS: In patients with idiopathic pulmonary fibrosis, nintedanib reduced the decline in FVC, which is consistent with a slowing of disease progression; nintedanib was frequently associated with diarrhea, which led to discontinuation of the study medication in less than 5% of patients.
    New England Journal of Medicine 05/2014; 370(22):2071-82. DOI:10.1056/NEJMoa1402584 · 54.42 Impact Factor
  • 05/2014; 2(5):e5. DOI:10.1016/S2213-2600(14)70075-X
  • [Show abstract] [Hide abstract]
    ABSTRACT: Rheumatoid arthritis (RA) is a systemic inflammatory disorder affecting approximately 1.3 million adults in the United States. Approximately 10% of these individuals with RA have clinically evident interstitial lung disease (RA-ILD), and an additional one-third demonstrate subclinical ILD on chest CT scan. The risk of death for individuals with RA-ILD is three times higher than for patients with RA without ILD, with a median survival after ILD diagnosis of only 2.6 years. Despite the high prevalence and mortality of RA-ILD, little is known about its molecular features and its natural history. At present, we lack a standard validated approach to the definition, diagnosis, risk stratification, and management of RA-ILD. In this perspective, we discuss the importance of clinical and translational research and how ongoing research efforts can address important gaps in our knowledge over the next few years. Furthermore, recommendations are made to design multicenter collaborative studies that will expedite the development of clinical trials designed to decrease the significant morbidity and mortality associated with RA-ILD.
    Chest 03/2014; 145(3):454-63. DOI:10.1378/chest.13-2408 · 7.13 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Interstitial lung disease (ILD) is the leading cause of morbidity and mortality in patients with systemic sclerosis (SSc), however prognostication of SSc-ILD remains challenging. We conducted a systematic review to identify variables that predict mortality and ILD progression in SSc-ILD. Three databases were searched to identify all studies relating to predictors of mortality or ILD progression in SSc-ILD. Eligible studies were published in English and included 10 or more adults with SSc-ILD. Two authors independently reviewed and extracted data from acceptable studies. The initial search identified 3145 unique citations. Twenty-seven studies met inclusion criteria, including 6 abstracts. A total of 1616 patients with SSc-ILD were included. Patient-specific, ILD-specific and SSc-specific variables predicted mortality and progression, however most predictors were identified in only one study. Most studies did not fully account for potential confounders and none of the studies included a validation cohort. Older age, lower forced vital capacity and lower diffusing capacity of carbon monoxide predicted mortality in more than one study. Male sex, extent of disease on high-resolution computed tomography (HRCT), presence of honeycombing, elevated KL-6 and increased alveolar epithelial permeability were identified as predictors of both mortality and ILD progression on unadjusted analysis. Extent of disease on HRCT was the only variable that independently predicted both mortality and ILD progression. Mortality and ILD progression were predicted by several patient-specific, ILD-specific and SSc-specific factors. Additional prospective studies are required to validate these preliminary findings and identify combinations of variables that accurately predict prognosis of SSc-ILD.
    Chest 02/2014; 146(2). DOI:10.1378/chest.13-2626 · 7.13 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Interstitial lung diseases (ILD), including those related to connective tissue disease (CTD), and idiopathic pulmonary fibrosis (IPF) carry high morbidity and mortality. Great efforts are under way to develop and investigate meaningful treatments in the context of clinical trials. However, efforts have been challenged by a lack of validated outcome measures and by inconsistent use of measures in clinical trials. Lack of consensus has fragmented effective use of strategies in CTD-ILD and IPF, with a history of resultant difficulties in obtaining agency approval of treatment interventions. Until recently, the patient perspective to determine domains and outcome measures in CTD-ILD and IPF had never been applied. Efforts described here demonstrate unequivocally the value and influence of patient involvement on core set development. Regarding CTD-ILD, this is the first OMERACT working group to directly address a manifestation/comorbidity of a rheumatic disease (ILD) as well as a disease not considered rheumatic (IPF). The OMERACT 11 proceedings of the CTD-ILD Working Group describe the forward and lateral process to include both the medical and patient perspectives in the urgently needed identification of a core set of preliminary domains and outcome measures in CTD-ILD and IPF.
    The Journal of Rheumatology 02/2014; · 3.17 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Patients with interstitial lung disease (ILD) have poor health-related quality of life (HRQL). However, whether HRQL differs among different subtypes of ILD is unclear. The aim of this study was to determine whether HRQL was different among patients with idiopathic pulmonary fibrosis (IPF) and chronic hypersensitivity pneumonitis (CHP). We identified patients from an ongoing longitudinal cohort of ILD patients. HRQL was assessed using the SF-36v2 medical outcomes form. Regression analysis was used to determine the association between clinical co-variates and HRQL, primarily the physical component summary (PCS) and mental component summary (MCS) score. A multivariate regression model was created to identify potential co-variates that could help explain the association between the ILD subtype and HRQL. IPF patients (n=102) were older, more likely to be men, and to have smoked. Pulmonary function was similar between the groups. The CHP patients (n=69) had worse HRQL across all eight domains of the SF-36, as well as the PCS and MCS, compared to IPF (p-value <0.01-0.09). This pattern remained after controlling for age and pulmonary function (p-value <0.01-0.02). Co-variates explaining part of the relationship between disease subtype and PCS score included severity of dyspnea (p-value <0.01) and fatigue (p-value 0.01). Co-variates explaining part of the relationship between disease subtype and MCS score included severity of dyspnea (p-value <0.01), female sex (p-value 0.02), and fatigue (p-value 0.02). HRQL is worse in CHP compared to IPF. HRQL differences between ILD subtypes are explained in part by differences in gender, dyspnea, and fatigue.
    Chest 01/2014; 145(6). DOI:10.1378/chest.13-1984 · 7.13 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) has a heterogeneous clinical presentation and disease course. Establishing prognosis for these patients is challenging. Identifying the factors that predict mortality in patients with RA-ILD could help guide management. A detailed systematic review was conducted in order to identify individual variables that predict mortality in RA-ILD. A literature review was performed using keywords and medical subject headings to identify all articles relating to the prognosis of RA-ILD. Studies were included if they identified predictors of mortality in adults with RA-ILD, were published in English, and included at least 10 patients with RA-ILD. Two authors independently reviewed each citation and extracted data from all studies meeting inclusion criteria. Any differences were then resolved by consensus. A total of 10 studies met our inclusion criteria. All were observational cohort studies of variable quality. Mean age of reported patients ranged from 55 to 69 years, and 41.7% of all patients were male. Median survival ranged from 3.2 to 8.1 years. Significant predictors of mortality on multivariate analysis were older age, male gender, lower diffusion capacity for carbon monoxide, extent of fibrosis, and the presence of usual interstitial pneumonia pattern. Mortality in RA-ILD is associated with several patient- and ILD-specific variables; however, previous studies are of low quality.
    Respirology 12/2013; 19(4). DOI:10.1111/resp.12234 · 3.50 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Clinical trial design in interstitial lung diseases (ILDs) has been hampered by lack of consensus on appropriate outcome measures for reliably assessing treatment response. In the setting of connective tissue diseases (CTDs), some measures of ILD disease activity and severity may be confounded by non-pulmonary comorbidities. The Connective Tissue Disease associated Interstitial Lung Disease (CTD-ILD) working group of Outcome Measures in Rheumatology-a non-profit international organisation dedicated to consensus methodology in identification of outcome measures-conducted a series of investigations which included a Delphi process including >248 ILD medical experts as well as patient focus groups culminating in a nominal group panel of ILD experts and patients. The goal was to define and develop a consensus on the status of outcome measure candidates for use in randomised controlled trials in CTD-ILD and idiopathic pulmonary fibrosis (IPF). A core set comprising specific measures in the domains of lung physiology, lung imaging, survival, dyspnoea, cough and health-related quality of life is proposed as appropriate for consideration for use in a hypothetical 1-year multicentre clinical trial for either CTD-ILD or IPF. As many widely used instruments were found to lack full validation, an agenda for future research is proposed. Identification of consensus preliminary domains and instruments to measure them was attained and is a major advance anticipated to facilitate multicentre RCTs in the field.
    Thorax 12/2013; · 8.56 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: PURPOSE To determine the performance and interobserver variability of radiologists with different levels of experience for the high-resolution CT (HRCT) diagnosis of Idiopathic Pulmonary Fibrosis according to ATS/ERS/JRS/ALAT criteria. METHOD AND MATERIALS HRCT scans of 219 randomly selected patients from the UCSF interstitial lung disease database were analyzed by a senior attending radiologist, a junior attending radiologist and a 1st year radiology resident according to ATS/ERS/JRS/ALAT criteria. Each case was interpreted as "definite UIP", "possible UIP" or "inconsistent with UIP." In cases that were “inconsistent with UIP”, the inconsistent criteria were identified. Agreement was assessed with a Kappa statistic and a 1-tail test against the null (p-value of 0.05 considered significant). RESULTS 33% of patients in the total cohort had a final multidisciplinary diagnosis of IPF. Overall agreement for “definite UIP” was 0.639 (p < 0.001). The overall sensitivity and specificity, respectively, of each reader for the diagnosis of IPF was as follows: senior attending radiologist (48%, 96%), junior attending radiologist (81%, 84%) and 1st year radiology resident (73%, 85%). Similar results were obtained when subset analysis only included patients with HRCT signs of fibrosis or patients ≥50 years of age. 6 false positive “definite UIP” interpretations were made by the senior attending radiologist whereas 22 false positive interpretations were made by the junior attending radiologist, including 14 connective tissue disease, 4 hypersensitivity pneumonitis, 1 drug toxicity and 3 idiopathic nonspecific interstitial pneumonia patients. The senior radiologist described mosaic perfusion/air trapping more often and honeycombing less often than the other two readers. CONCLUSION The radiologist with greater experience had a lower sensitivity and greater specificity in the HRCT diagnosis of IPF using ATS/ERS/JRS/ALAT criteria. Most false positives in the radiologists with less experience were in patients with connective tissue disease and hypersensitivity pneumonitis. CLINICAL RELEVANCE/APPLICATION Experience improves the specificity of a HRCT diagnosis of IPF. Since a "definite UIP" pattern on HRCT is often considered sufficient evidence for diagnosing IPF, maintaining specificity is paramount.
    Radiological Society of North America 2013 Scientific Assembly and Annual Meeting; 12/2013
  • [Show abstract] [Hide abstract]
    ABSTRACT: Pulmonary rehabilitation improves outcomes in patients with interstitial lung disease (ILD), however it is unclear whether these effects are long lasting and which patients benefit most. Patients with ILD were recruited into this prospective cohort study from three pulmonary rehabilitation programs. Patients completed functional assessments (6-minute walk distance (6MWD), and 4-meter walk time) and surveys (quality of life, dyspnea, depression, and physical activity) before rehabilitation, after rehabilitation, and at six months. Changes from baseline were compared using a paired t-test. Independent predictors of change in 6MWD and quality of life were determined using multivariate analysis. Fifty-four patients were recruited (22 with idiopathic pulmonary fibrosis), 50 patients (93%) completed the rehabilitation program, and 39 returned for six-month follow-up. 6MWD improved 57.6 m immediately after rehabilitation (95% confidence interval (CI) 40.2-75.1 m, p < 0.0005), and remained 49.8 m above baseline at six months (95%CI 15.0-84.6 m, p = 0.005). The majority of patients achieved the minimum clinically important difference for quality of life (51%), dyspnea (65%), and depression score (52%) immediately after rehabilitation, and improvements were still significant at 6-month follow-up for quality of life, depression, and physical activity. A low baseline 6MWD was the only independent predictor of improvement in 6MWD during rehabilitation (r = -0.49, p < 0.0005). Change in 6MWD was an independent predictor of change in quality of life (r = -0.36, p = 0.01). Pulmonary rehabilitation improved multiple short- and long-term outcomes in patients with ILD. While all patients appear to benefit, ILD patients with a low baseline 6MWD had greater benefit from rehabilitation. NCT01055730 (clinicaltrials.gov).
    Respiratory medicine 12/2013; 108(1). DOI:10.1016/j.rmed.2013.11.016 · 2.33 Impact Factor
  • Kerri A. Johannson, Harold R Collard
    [Show abstract] [Hide abstract]
    ABSTRACT: Acute exacerbation of idiopathic pulmonary fibrosis (IPF) occurs in roughly 10% of patients annually, and is a leading cause of morbidity and mortality in this disease. While currently defined as idiopathic acute worsenings, acute exacerbations of IPF may in fact have a variety of causes, in particular infection and aspiration. Central to the pathobiology of clinically meaningful events is a diffuse injury to the IPF lung manifest histopathologically as diffuse alveolar damage, and biologically as accelerated alveolar epithelial cell injury or repair. Based on these recent observations, we propose a new paradigm for acute exacerbation of IPF that removes the idiopathic requirement and focuses on the pathophysiological mechanism involved.
    12/2013; 2(4). DOI:10.1007/s13665-013-0065-x
  • [Show abstract] [Hide abstract]
    ABSTRACT: Acute exacerbations of idiopathic pulmonary fibrosis are associated with high mortality and are of unknown cause. The effect of air pollution on exacerbations of interstitial lung disease is unknown. This study aims to define the association of air pollution exposure with acute exacerbation of idiopathic pulmonary fibrosis.Patients with idiopathic pulmonary fibrosis and corresponding air pollution data were identified from a longitudinal cohort. Air pollution exposures were assigned to each patient for ozone, nitrogen dioxide, particulate matter, sulfur dioxide and carbon monoxide based on geo-coded residential addresses. Cox proportional hazards models were used to estimate the association of air pollution exposures and acute exacerbations.Acute exacerbation was significantly associated with antecedent 6 week increases in mean level, maximum level, and number of exceedances above accepted standards of ozone (Hazard Ratio=1.57, 95% CI=1.09-2.24; 1.42, 95% CI=1.11-1.82; and 1.51, 95% CI=1.17-1.94, respectively) and nitrogen dioxide (Hazard Ratio=1.41, 95% CI=1.04-1.91; 1.27, 95% CI=1.01-1.59; and 1.20, 95% CI=1.10-1.31, respectively).Increased ozone and nitrogen dioxide exposure over the preceding 6 weeks was associated with an increased risk of acute exacerbation of idiopathic pulmonary fibrosis, suggesting that air pollution may contribute to the development of this clinically meaningful event.
    European Respiratory Journal 10/2013; 43(4). DOI:10.1183/09031936.00122213 · 7.13 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The median survival of patients with idiopathic pulmonary fibrosis continues to be approximately 3 years from the time of diagnosis, underscoring the lack of effective medical therapies for this disease. In the United States alone, approximately 40,000 patients die of this disease annually. In November 2012, the National Heart, Lung and Blood Institute held a workshop aimed at coordinating research efforts and accelerating the development of idiopathic pulmonary fibrosis therapies. Basic, translational and clinical researchers gathered with representatives from the National Heart Lung and Blood Institute, patient advocacy groups, pharmaceutical companies and the Food and Drug Administration to review the current state of idiopathic pulmonary fibrosis research and identify priority areas, opportunities for collaborations and directions for future research. The workshop was organized into groups that were tasked with assessing and making recommendations to promote progress in one of the following six critical areas of research: 1) biology of alveolar epithelial injury and aberrant repair, 2) role of extracellular matrix, 3) preclinical modeling, 4) the role of inflammation and immunity, 5) genetic, epigenetic and environmental determinants, 6) translation of discoveries into diagnostics and therapeutics. The workshop recommendations provide a basis for directing future research and strategic planning by scientific, professional and patient communities and the National Heart Lung and Blood Institute.
    American Journal of Respiratory and Critical Care Medicine 10/2013; DOI:10.1164/rccm.201306-1141WS · 11.04 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Purpose:To determine the accuracy of computed tomography (CT) in identifying the histopathologic usual interstitial pneumonia (UIP) pattern in rheumatoid arthritis-associated interstitial lung disease (RA-ILD).Materials and Methods:All patients were enrolled into institutional review board-approved longitudinal cohorts at their respective institution, and informed consent was obtained at the time of enrollment. Images of patients with surgical lung biopsy-proved RA-ILD (n = 69) were collected from three tertiary care centers. Two experienced thoracic radiologists independently reviewed the CT scans. The CT pattern was categorized as definite UIP, possible UIP, or inconsistent with UIP in accordance with published criteria. Findings of biopsies were reviewed by an experienced lung pathologist. The sensitivity and specificity of definite CT UIP pattern to histopathologic UIP pattern were determined. The agreement between radiologists was assessed by calculating a κ score.Results:The histopathologic UIP pattern was present in 42 of 69 (61%) patients. Men were more likely than women to have a histopathologic UIP pattern (P = .02). Twenty patients (29%, 20 of 69) had a definite UIP pattern on CT scans. The specificity of CT UIP pattern was 96% (26 of 27; 95% confidence interval [CI]: 81%, 100%), with a negative predictive value of 53% (26 of 49). The sensitivity of CT UIP pattern was 45% (19 of 42; 95% CI: 30%, 61%), with a positive predictive value of 95% (19 of 20). The agreement between radiologists for definite UIP pattern versus not was 87% (κ = 0.67, P < .0001).Conclusion:Definite UIP pattern on a CT scan in RA-ILD is highly specific and moderately sensitive for histopathologic UIP pattern. CT can therefore help accurately identify the UIP pattern in RA-ILD.© RSNA, 2013Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.13130187/-/DC1.
    Radiology 10/2013; 270(2). DOI:10.1148/radiol.13130187 · 6.21 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Risk prediction is challenging in chronic interstitial lung disease because of heterogeneity in disease-specific and patient-specific variables. Our objective was to determine whether mortality is accurately predicted in patients with chronic interstitial lung disease using the GAP model, a clinical prediction model based on gender, age, and lung physiology, that was previously validated in patients with idiopathic pulmonary fibrosis. Patients with idiopathic pulmonary fibrosis (n=307), chronic hypersensitivity pneumonitis (n=206), connective tissue disease-associated interstitial lung disease (n=281), idiopathic nonspecific interstitial pneumonia (n=45), or unclassifiable interstitial lung disease (n=173) were selected from an ongoing database (total n=1012). Performance of the previously validated GAP model was compared to novel prediction models in each interstitial lung disease subtype and the combined cohort. Patients with follow-up pulmonary function data were used for longitudinal model validation. The GAP model had good performance in all interstitial lung disease subtypes (c-index 74.6 in the combined cohort), which was maintained at all stages of disease severity and during follow-up evaluation. The GAP model had similar performance compared to alternative prediction models. A modified ILD-GAP Index was developed for application across all ILD subtypes to provide disease-specific survival estimates using a single risk prediction model. This was done by adding a disease subtype variable that accounted for better adjusted survival in connective tissue disease-associated interstitial lung disease, chronic hypersensitivity pneumonitis, and idiopathic nonspecific interstitial pneumonia. The GAP model accurately predicts risk of death in chronic interstitial lung disease. The ILD-GAP model accurately predicts mortality in major chronic ILD subtypes and at all stages of disease.
    Chest 10/2013; 145(4). DOI:10.1378/chest.13-1474 · 7.13 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: In 2002 the American Thoracic Society/European Respiratory Society (ATS/ERS) classification of idiopathic interstitial pneumonias (IIPs) defined seven specific entities, and provided standardized terminology and diagnostic criteria. In addition, the historical "gold standard" of histologic diagnosis was replaced by a multidisciplinary approach. Since 2002 many publications have provided new information about IIPs. Purpose: The objective of this statement is to update the 2002 ATS/ERS classification of IIPs. Methods: An international multidisciplinary panel was formed and developed key questions that were addressed through a review of the literature published between 2000 and 2011. Results: Substantial progress has been made in IIPs since the previous classification. Nonspecific interstitial pneumonia is now better defined. Respiratory bronchiolitis-interstitial lung disease is now commonly diagnosed without surgical biopsy. The clinical course of idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia is recognized to be heterogeneous. Acute exacerbation of IIPs is now well defined. A substantial percentage of patients with IIP are difficult to classify, often due to mixed patterns of lung injury. A classification based on observed disease behavior is proposed for patients who are difficult to classify or for entities with heterogeneity in clinical course. A group of rare entities, including pleuroparenchymal fibroelastosis and rare histologic patterns, is introduced. The rapidly evolving field of molecular markers is reviewed with the intent of promoting additional investigations that may help in determining diagnosis, and potentially prognosis and treatment. Conclusions: This update is a supplement to the previous 2002 IIP classification document. It outlines advances in the past decade and potential areas for future investigation.
    American Journal of Respiratory and Critical Care Medicine 09/2013; 188(6):733-48. DOI:10.1164/rccm.201308-1483ST · 11.04 Impact Factor
  • Paul J Wolters, Harold R Collard, Kirk D Jones
    [Show abstract] [Hide abstract]
    ABSTRACT: Idiopathic pulmonary fibrosis (IPF) is a fibrosing interstitial lung disease associated with aging that is characterized by the histopathological pattern of usual interstitial pneumonia. Although an understanding of the pathogenesis of IPF is incomplete, recent advances delineating specific clinical and pathologic features of IPF have led to better definition of the molecular pathways that are pathologically activated in the disease. In this review we highlight several of these advances, with a focus on genetic predisposition to IPF and how genetic changes, which occur primarily in epithelial cells, lead to activation of profibrotic pathways in epithelial cells. We then discuss the pathologic changes within IPF fibroblasts and the extracellular matrix, and we conclude with a summary of how these profibrotic pathways may be interrelated. Expected final online publication date for the Annual Review of Pathology: Mechanisms of Disease Volume 9 is February 28, 2014. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.
    Annual Review of Pathology Mechanisms of Disease 09/2013; DOI:10.1146/annurev-pathol-012513-104706 · 22.13 Impact Factor

Publication Stats

4k Citations
902.86 Total Impact Points

Institutions

  • 2003–2015
    • University of California, San Francisco
      • • Division of Hospital Medicine
      • • Department of Medicine
      San Francisco, California, United States
    • University of Colorado
      • Department of Medicine
      Denver, CO, United States
  • 2013
    • CSU Mentor
      Long Beach, California, United States
  • 2006–2013
    • University of Ulsan
      • Asan Medical Center
      Urusan, Ulsan, South Korea
    • University of Michigan
      • Department of Internal Medicine
      Ann Arbor, MI, United States
  • 2012
    • University of British Columbia - Vancouver
      • Department of Medicine
      Vancouver, British Columbia, Canada
    • University of Washington Seattle
      • Division of Pulmonary and Critical Care Medicine
      Seattle, WA, United States
    • Università degli Studi di Modena e Reggio Emilia
      Modène, Emilia-Romagna, Italy
  • 2007
    • Duke University
      Durham, North Carolina, United States
  • 2005
    • University of Wisconsin, Madison
      • Department of Medicine
      Madison, MS, United States