Harold R Collard

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

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Publications (125)899.69 Total impact

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    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; · 7.13 Impact Factor
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    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; · 3.50 Impact Factor
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    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
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    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; · 2.33 Impact Factor
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    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
  • Kerri Johannson, Harold R Collard
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    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.
    Current respiratory care reports. 12/2013; 2(4).
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    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; · 7.13 Impact Factor
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    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; · 11.04 Impact Factor
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    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; · 6.21 Impact Factor
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    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; · 7.13 Impact Factor
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    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. · 11.04 Impact Factor
  • Paul J Wolters, Harold R Collard, Kirk D Jones
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    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; · 22.13 Impact Factor
  • Christopher J Ryerson, Harold R Collard
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    ABSTRACT: The purpose of this review is to provide an update on the diagnosis and classification of interstitial lung disease (ILD), with a specific focus on newly described ILD subtypes and phenotypes. In addition, the strengths and limitations of the current approach to ILD diagnosis and management are discussed. Idiopathic pleuroparenchymal fibroelastosis and acute fibrinous and organizing pneumonia are new entities that have been described in small case series. Undifferentiated connective tissue disease-associated ILD, smoking-related interstitial fibrosis, familial ILD, unclassifiable ILD, and subclinical ILD have also been better characterized in recent publications. New data regarding these conditions are summarized in this review. The multidisciplinary approach to ILD is reviewed, and complementary classification schemes are described that may help direct the management and improve prognostication of some ILDs. ILDs are a large and heterogeneous group of diseases with several newly characterized subtypes and phenotypes. The current approach to ILD classification has limitations in some patients that can be minimized by considering complementary classification schemes.
    Current opinion in pulmonary medicine 07/2013; · 2.96 Impact Factor
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    ABSTRACT: Acute exacerbation of idiopathic pulmonary fibrosis has become an important outcome measure in clinical trials. This study aimed to explore the concept of suspected acute exacerbation as an outcome measure. Three investigators retrospectively reviewed subjects enrolled in the Sildenafil Trial of Exercise Performance in IPF who experienced a respiratory serious adverse event during the course of the study. Events were classified as definite acute exacerbation, suspected acute exacerbation, or other, according to established criteria. Thirty-five events were identified. Four were classified as definite acute exacerbation, fourteen as suspected acute exacerbation, and seventeen as other. Definite and suspected acute exacerbations were clinically indistinguishable. Both were most common in the winter and spring months and were associated with a high risk of disease progression and short-term mortality. In this study one half of respiratory serious adverse events were attributed to definite or suspected acute exacerbations. Suspected acute exacerbations are clinically indistinguishable from definite acute exacerbations and represent clinically meaningful events. Clinical trialists should consider capturing both definite and suspected acute exacerbations as outcome measures.
    Respiratory research 07/2013; 14(1):73. · 3.38 Impact Factor
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    ABSTRACT: Abnormal acid gastro-oesophageal reflux is common in patients with idiopathic pulmonary fibrosis (IPF) and is considered a risk factor for development of IPF. Retrospective studies have shown improved outcomes in patients given anti-acid treatment. The aim of this study was to investigate the association between anti-acid treatment and disease progression in IPF. In an analysis of data from three randomised controlled trials, we identified patients with IPF assigned to receive placebo. Case report forms had been designed to prospectively obtain data about diagnosis and treatment of abnormal acid gastro-oesophageal reflux in each trial. The primary outcome was estimated change in forced vital capacity (FVC) at 30 weeks (mean follow-up) in patients who were and were not using a proton-pump inhibitor or histamine-receptor-2 (H2) blocker. Of the 242 patients randomly assigned to the placebo groups of the three trials, 124 (51%) were taking a proton-pump inhibitor or H2 blocker at enrolment. After adjustment for sex, baseline FVC as a percentage of predicted, and baseline diffusing capacity of the lung for carbon monoxide as a percentage of predicted, patients taking anti-acid treatment at baseline had a smaller decrease in FVC at 30 weeks (-0·06 L, 95% CI -0·11 to -0·01) than did those not taking anti-acid treatment (-0·12 L, -0·17 to -0·08; difference 0·07 L, 95% CI 0-0·14; p=0·05). Anti-acid treatment could be beneficial in patients with IPF, and abnormal acid gastro-oesophageal reflux seems to contribute to disease progression. Controlled clinical trials of anti-acid treatments are now needed. National Institutes of Health.
    The lancet. Respiratory medicine. 07/2013; 1(5):369-76.
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    ABSTRACT: Pulmonary fibrosis is the ultimate outcome of various interstitial lung diseases, many of which have a dismal prognosis. Pulmonary fibrosis therefore represents a critical unmet medical need. Progress in research over the last 30 years has been encouraging. This work, which has been funded by governments, charitable trusts, industries and patient groups, has resulted in clinical trials testing novel drugs, giving hope to patients. In late September 2012, representatives from across academics, industry, and funding agencies met at the 17(th) International Colloquium on Airway and Lung Fibrosis Meeting to discuss state-of-the-art knowledge of pulmonary fibrosis. This manuscript summarizes the outcome of the meeting, highlighting the most relevant results and discoveries. It also attempts to provide a roadmap for future studies. It is hoped that such a roadmap may help all interested parties to generate new research, which will be vital to continued progress. We are encouraged by the commitment expressed by all participants at this meeting and the shared vision of promoting future progress through international collaboration, the pooling of valuable resources, and the involvement of new generation of physicians and scientists.
    European Respiratory Journal 05/2013; · 7.13 Impact Factor
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    ABSTRACT: BACKGROUND: Lung disease is the leading cause of death in systemic sclerosis (SSc). The diagnosis of SSc-related lung disease (SSc-LD) is often a contraindication to lung transplantation (LT) due to concerns that extrapulmonary involvement will yield worse outcomes. We sought to evaluate posttransplantation outcomes in persons with SSc-LD with esophageal involvement compared with persons with nonconnective tissue disease-related interstitial lung disease (nCTD-ILD). METHODS: From 1998 to 2012, persons undergoing LT for SSc-LD were age and gender matched in a 2:1 fashion to controls undergoing LT for nCTD-ILD. Esophageal function was assessed by pH testing and manometry. We defined esophageal dysfunction as the presence of a DeMeester score >14 or dysmotility more severe than "mild nonspecific disorder". The primary outcome was posttransplantation survival. Secondary outcomes included freedom from bronchiolitis obliterans syndrome (fBOS) and rates of acute rejection. Survival and fBOS were estimated with Kaplan-Meier methods. Acute rejection was compared with Student's t test. RESULTS: Survival was similar in 23 persons with SSc-LD and 46 controls who underwent LT (P=0.47). For the SSc-LD group, 1- and 5-year survival was 83% and 76% compared with 91% and 64% in the nCTD-ILD group, respectively. There were no differences in fBOS (P=0.83). Rates of acute rejection were less in SSc-ILD (P=0.05). Esophageal dysfunction was not associated with worse outcomes (P>0.55). CONCLUSIONS: Persons with SSc-LD appear to have similar survival and fBOS as persons transplanted for nCTD-ILD. The risk of acute rejection after transplantation may be reduced in persons with SSc-LD. Esophageal involvement does not appear to impact outcomes.
    Transplantation 04/2013; 95(7):975-980. · 3.78 Impact Factor
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    ABSTRACT: We performed a genome-wide association study of non-Hispanic, white individuals with fibrotic idiopathic interstitial pneumonias (IIPs; n = 1,616) and controls (n = 4,683), with follow-up replication analyses in 876 cases and 1,890 controls. We confirmed association with TERT at 5p15, MUC5B at 11p15 and the 3q26 region near TERC, and we identified seven newly associated loci (Pmeta = 2.4 × 10(-8) to 1.1 × 10(-19)), including FAM13A (4q22), DSP (6p24), OBFC1 (10q24), ATP11A (13q34), DPP9 (19p13) and chromosomal regions 7q22 and 15q14-15. Our results suggest that genes involved in host defense, cell-cell adhesion and DNA repair contribute to risk of fibrotic IIPs.
    Nature Genetics 04/2013; · 29.65 Impact Factor
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    ABSTRACT: ABSTRACT BACKGROUND: It is unknown whether the radiographic fibrosis score predicts mortality in persistent hypersensitivity pneumonitis (HP) and if survival is similar to that observed in idiopathic pulmonary fibrosis (IPF) when adjusting for the extent of radiographic fibrosis. METHODS: We reviewed records from 177 HP and 224 IPF patients whose diagnoses were established by multidisciplinary consensus. Two thoracic radiologists scored high-resolution computed tomography (HRCT) lung images. Independent predictors of transplant-free survival were determined using a Cox proportional hazards analysis. Kaplan-Meier survival curves were constructed stratified by disease as well as fibrosis score. RESULTS: HRCT fibrosis score and radiographic reticulation independently predicted time to death or lung transplantation. Clinical predictors included a history of cigarette smoking, auscultatory crackles on lung examination, baseline FVC, and FEV1/FVC ratio. The majority of HP deaths occurred in patients with both radiographic reticulation and auscultatory crackles on exam, compared to patients with only one of these manifestations (p<0.0001). Patients with IPF had worse survival than HP patients at any given degree of radiographic fibrosis (hazard ratio 2.31, p<0.01). CONCLUSIONS: Survival in HP was superior to that of IPF patients with similar degrees of radiographic fibrosis. The combination of auscultatory crackles and radiographic reticulation identified HP patients with a particularly poor outcome.
    Chest 02/2013; · 7.13 Impact Factor
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    ABSTRACT: ABSTRACT BACKGROUND: Combined pulmonary fibrosis and emphysema (CPFE) is increasingly recognized, but its prevalence and prognosis remain unclear. We sought to determine the prevalence, clinical features, and prognosis of CPFE in idiopathic pulmonary fibrosis (IPF) using a standardized and reproducible definition. METHODS: Patients with IPF were identified from two ongoing cohorts. Two radiologists scored emphysema and fibrosis severity on high-resolution computed tomography (HRCT). CPFE was defined as ≥10% emphysema on HRCT. Clinical characteristics and outcomes of CPFE and non-CPFE IPF patients were compared with unadjusted analysis followed by adjustment for HRCT fibrosis score. Mortality was compared using competing risks regression to handle lung transplantation. Sensitivity analyses were performed using Cox proportional hazards, including time to death (transplantation censored) and time to death or transplant. RESULTS: CPFE criteria were met in 29 of 365 IPF patients (8%), with high agreement between radiologists (kappa 0.74). Patients with CPFE had less HRCT fibrosis and higher forced vital capacity, but greater oxygen requirements (p≤0.01 for all comparisons). Findings were maintained with adjustment for fibrosis severity. Inhaled therapies for chronic obstructive pulmonary disease were used in 53% of patients with CPFE. There was no significant difference in mortality comparing CPFE to non-CPFE IPF patients (hazard ratio 1.14, 95% confidence interval 0.61-2.13, p=0.69). CONCLUSIONS: CPFE was identified in 8% of patients with IPF and is a distinct clinical phenotype with potential therapies that remain underutilized. CPFE and non-CPFE IPF patients have similar mortality.
    Chest 01/2013; · 7.13 Impact Factor

Publication Stats

3k Citations
899.69 Total Impact Points

Institutions

  • 2006–2014
    • University of California, San Francisco
      • Division of Hospital Medicine
      San Francisco, California, United States
    • University of Michigan
      • Department of Internal Medicine
      Ann Arbor, MI, United States
  • 2013
    • CSU Mentor
      Long Beach, California, United States
  • 2006–2013
    • University of Ulsan
      • Asan Medical Center
      Urusan, Ulsan, South Korea
  • 2012
    • University of British Columbia - Vancouver
      Vancouver, British Columbia, Canada
    • Università degli Studi di Modena e Reggio Emilia
      Modène, Emilia-Romagna, Italy
    • University of Washington Seattle
      • Division of Pulmonary and Critical Care Medicine
      Seattle, WA, United States
  • 2011
    • University of California, Berkeley
      Berkeley, California, United States
  • 2010
    • University of Cincinnati
      • Division of Pulmonary, Critical Care & Sleep Medicine
      Cincinnati, OH, United States
  • 2007
    • University of California, Los Angeles
      • Center for Culture and Health
      Los Angeles, CA, United States
  • 2006–2007
    • San Francisco VA Medical Center
      San Francisco, California, United States
  • 2005
    • National Institutes of Health
      • Critical Care Medicine Department
      Bethesda, MD, United States
    • University of Wisconsin, Madison
      • Department of Medicine
      Madison, MS, United States
  • 2003–2004
    • University of Colorado
      • Department of Medicine
      Denver, CO, United States