Harold R Collard

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

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Publications (91)652.01 Total impact

  • Source
    Brett Ley, Harold R Collard
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    ABSTRACT: Idiopathic pulmonary fibrosis is a chronic fibrotic lung disease of unknown cause that occurs in adults and has a poor prognosis. Its epidemiology has been difficult to study because of its rarity and evolution in diagnostic and coding practices. Though uncommon, it is likely underappreciated both in terms of its occurrence (ie, incidence, prevalence) and public health impact (ie, health care costs and resource utilization). Incidence and mortality appear to be on the rise, and prevalence is expected to increase with the aging population. Potential risk factors include occupational and environmental exposures, tobacco smoking, gastroesophageal reflux, and genetic factors. An accurate understanding of its epidemiology is important, especially as novel therapies are emerging.
    Clinical Epidemiology 01/2013; 5:483-492.
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    ABSTRACT: To determine the prevalence, characteristics, and outcomes of patients with unclassifiable interstitial lung disease (ILD) and develop a simple method of predicting disease behaviour.Unclassifiable ILD patients were identified from an ongoing longitudinal cohort. Unclassifiable ILD was diagnosed when multidisciplinary review did not secure a specific ILD diagnosis. Clinical characteristics and outcomes were compared with idiopathic pulmonary fibrosis (IPF) and non-IPF ILDs. Independent predictors of mortality were determined using Cox proportional hazards analysis to identify subgroups with distinct disease behaviour.Unclassifiable ILD was diagnosed in 10% of the ILD cohort (132 of 1370 patients). The most common reason for being unclassifiable was missing histopathological assessment due to a high risk of surgical lung biopsy. Demographic and physiologic features of unclassifiable ILD were intermediate between IPF and non-IPF disease controls. Unclassifiable ILD had longer survival compared to IPF on adjusted analysis (hazard ratio 0.62, p=0.04) and similar survival compared to non-IPF ILDs (hazard ratio 1.54, p=0.12). Independent predictors of survival in unclassifiable ILD included DL,CO (p=0.001) and radiological fibrosis score (p=0.02).Unclassifiable ILD represents approximately 10% of ILD cases and has a heterogeneous clinical course that can be predicted using clinical and radiological variables.
    European Respiratory Journal 12/2012; · 6.36 Impact Factor
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    ABSTRACT: BACKGROUND: The clinical significance of circulating autoantibodies in idiopathic pulmonary fibrosis is unclear. The objective of this study was to determine the frequency and clinical significance of circulating autoantibodies in idiopathic pulmonary fibrosis. METHODS: We measured an extensive panel of autoantibodies (including rheumatoid factor, anti-cyclic citrullinated peptide, and anti-nuclear antibodies by immunofluorescence) associated with connective tissue disease or vasculitis in a cohort of well-characterized patients with idiopathic pulmonary fibrosis (n = 67). The prevalence of circulating autoantibodies was compared between idiopathic pulmonary fibrosis patients and healthy controls (n = 52). We compared the clinical characteristics of patients with and without circulating autoantibodies, and analyzed the relationship between autoantibody positivity and transplant-free survival time. RESULTS: Positive autoantibodies were found in 22% of patients with IPF and 21% of healthy controls. There were no differences in the types of autoantibodies found between patients with idiopathic pulmonary fibrosis and healthy controls. Among patients with idiopathic pulmonary fibrosis, there were no significant differences in clinical characteristics between those with and without circulating autoantibodies. The presence of circulating autoantibodies was associated with longer transplant-free survival time on adjusted analysis, however the significance varied depending on which statistical model was used (HR 0.22-0.47, p value 0.02-0.17). CONCLUSIONS: The frequency of circulating autoantibodies in patients with idiopathic pulmonary fibrosis is no different compared to healthy controls, but may be associated with longer survival.
    Respiratory medicine 11/2012; · 2.33 Impact Factor
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    ABSTRACT: BACKGROUND: Stress of the endoplasmic reticulum (ER) leading to activation of the unfolded protein response (UPR) and alveolar epithelial cell (AEC) apoptosis may play a role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Our objectives were to determine whether circulating caspase-cleaved cytokeratin-18 (cCK-18) is a marker of AEC apoptosis in IPF, define the relationship of cCK-18 with activation of the UPR, and assess its utility as a diagnostic biomarker. METHODS: IPF and normal lung tissues were stained with the antibody (M30) that specifically binds cCK-18. The relationship between markers of the UPR and cCK-18 was determined in AECs exposed in vitro to thapsigargin to induce ER stress. cCK-18 was measured in serum from subjects with IPF, hypersensitivity pneumonitis (HP), nonspecific interstitial pneumonia (NSIP), and control subjects. RESULTS: cCK-18 immunoreactivity was present in AECs of IPF lung, but not in control subjects. Markers of the UPR (phosphorylated IRE-1alpha and spliced XBP-1) were more highly expressed in IPF type II AECs than in normal type II AECs. Phosphorylated IRE-1alpha and cCK-18 increased following thapsigargin-induced ER stress. Serum cCK-18 level distinguished IPF from diseased and control subjects. Serum cCK-18 was not associated with disease severity or outcome. CONCLUSIONS: cCK-18 may be a marker of AEC apoptosis and UPR activation in patients with IPF. Circulating levels of cCK-18 are increased in patients with IPF and cCK-18 may be a useful diagnostic biomarker.
    Respiratory research 11/2012; 13(1):105. · 3.64 Impact Factor
  • Proceedings of the American Thoracic Society 10/2012; 9(4):204-9.
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    ABSTRACT: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease with an overall poor prognosis. A simple-to-use staging system for IPF may improve prognostication, help guide management, and facilitate research. To develop a multidimensional prognostic staging system for IPF by using commonly measured clinical and physiologic variables. A clinical prediction model was developed and validated by using retrospective data from 3 large, geographically distinct cohorts. Interstitial lung disease referral centers in California, Minnesota, and Italy. 228 patients with IPF at the University of California, San Francisco (derivation cohort), and 330 patients at the Mayo Clinic and Morgagni-Pierantoni Hospital (validation cohort). The primary outcome was mortality, treating transplantation as a competing risk. Model discrimination was assessed by the c-index, and calibration was assessed by comparing predicted and observed cumulative mortality at 1, 2, and 3 years. Four variables were included in the final model: gender (G), age (A), and 2 lung physiology variables (P) (FVC and Dlco). A model using continuous predictors (GAP calculator) and a simple point-scoring system (GAP index) performed similarly in derivation (c-index of 70.8 and 69.3, respectively) and validation (c-index of 69.1 and 68.7, respectively). Three stages (stages I, II, and III) were identified based on the GAP index with 1-year mortality of 6%, 16%, and 39%, respectively. The GAP models performed similarly in pooled follow-up visits (c-index ≥71.9). Patients were drawn from academic centers and analyzed retrospectively. The GAP models use commonly measured clinical and physiologic variables to predict mortality in patients with IPF.
    Annals of internal medicine 05/2012; 156(10):684-91. · 13.98 Impact Factor
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    ABSTRACT: Definitive evidence of clinical efficacy in a Phase 3 trial is best shown by a beneficial impact on a clinically meaningful endpoint-that is, an endpoint that directly measures how a patient feels (symptoms), functions (the ability to perform activities in daily life), or survives. In idiopathic pulmonary fibrosis (IPF), we believe the endpoints that best meet these criteria are all-cause mortality and all-cause nonelective hospitalization. There are no validated measures of symptoms or broader constructs such as health status or functional status in IPF. A surrogate endpoint is defined as an indirect measure that is intended to substitute for a clinically meaningful endpoint. Surrogate endpoints can be appropriate outcome measures if validated. However, validation requires substantial evidence that the effect of an intervention on a clinically meaningful endpoint is reliably predicted by the effect of an intervention on the surrogate endpoint. For patients with IPF, there are currently no validated surrogate endpoints.
    American Journal of Respiratory and Critical Care Medicine 04/2012; 185(10):1044-8. · 11.04 Impact Factor
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    ABSTRACT: Idiopathic pulmonary fibrosis is a life-threatening condition, and few data concerning the impact on healthcare utilization and associated costs are available. The objective of this study was to describe the burden of illness (comorbidity, healthcare resource utilization, and associated costs) in patients with idiopathic pulmonary fibrosis. Two cohorts (patients with idiopathic pulmonary fibrosis and matched controls) were retrospectively identified from US claims databases between January 1, 2001 and September 30, 2008. Cases with idiopathic pulmonary fibrosis were defined by age of 55 years or older and either two or more claims with a code for idiopathic fibrosing alveolitis (ICD-9 516.3), or one claim with ICD 516.3 and a subsequent claim with a code for post-inflammatory pulmonary fibrosis (ICD-9 515). The prevalence and incidence of pre-selected comorbidities, healthcare resource utilization (hospital, outpatient, drugs), and direct medical costs were assessed in each cohort. A total of 9286 patients with idiopathic pulmonary fibrosis were identified. When compared with age- and gender-matched controls, these patients were at significantly increased risk for comorbidities including pulmonary hypertension and emphysema. The all-cause hospital admission rate (0.5 per person-year) and the all-cause outpatient visit rate (28.0 per person-year) were both ∼2-fold higher than in controls. Total direct costs for patients with idiopathic pulmonary fibrosis were $26,378 per person-year; the incremental costs over controls were $12,124 (2008 value). Patients with idiopathic pulmonary fibrosis experience increased comorbidity, healthcare resource utilization, and direct medical costs compared to controls.
    Journal of Medical Economics 03/2012; 15(5):829-35.
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    ABSTRACT: In a case-control analysis comparing 303 patients with diabetes and 303 without (matched on age, race, sex and height), diabetics had reduced lung diffusion (DLCO) independent of smoking, obesity, clinical heart failure, asymptomatic left ventricular systolic and diastolic dysfunction: DLCO (mean±SE: 15.5±0.9 vs. 16.4 ±0.9, p=0.01).
    Diabetes research and clinical practice 03/2012; 96(3):e73-5. · 2.74 Impact Factor
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    ABSTRACT: Decline in forced vital capacity (FVC) over time reliably predicts mortality in patients with idiopathic pulmonary fibrosis. The use of this measure in clinical practice is recommended by current evidence-based guidelines. It is unknown if the method of calculating decline in FVC (relative vs. absolute change) impacts its frequency or its ability to predict mortality. Patients with idiopathic pulmonary fibrosis from two prospective cohorts were included if they had a baseline and 12-month follow-up FVC. A ≥10% decline in FVC from baseline was calculated in two ways: a relative decline of 10% (e.g., from 60% predicted to 54% predicted) and an absolute decline of 10% (e.g., from 60% predicted to 50% predicted). The frequency of a ≥10% decline in FVC and its ability to predict 2-year transplant-free survival were compared between these two methods. Declines in FVC of ≥5% and ≥15% were similarly compared. Analyses were performed unadjusted and adjusted for age, gender, use of oxygen, baseline FVC and baseline diffusion capacity for carbon monoxide. The frequency of any given FVC decline was significantly greater using the relative change in FVC method. For ≥10% decline, both methods predicted 2-year transplant-free survival with similar accuracy, and remained significant predictors after adjusting for baseline characteristics. The absolute change method appeared more predictive for ≥5% decline. Using the relative change in FVC maximises the chance of identifying a ≥10% decline in FVC without sacrificing prognostic accuracy. This may not hold true for ≥5% decline in FVC. These findings have important implications for clinical practice and the design of clinical trials.
    Thorax 03/2012; 67(5):407-11. · 8.38 Impact Factor
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    ABSTRACT: The relationship of mast cells to the pathogenesis of lung fibrosis remains undefined despite recognition of their presence in the lungs of patients with pulmonary fibrosis. This study was performed to characterize the relationship of mast cells to fibrotic lung diseases. Lung tissues from patients with idiopathic pulmonary fibrosis (IPF), chronic hypersensitivity pneumonitis (HP), systemic sclerosis (SSc)-related interstitial lung disease (ILD) and normal individuals were subjected to chymase immunostaining and the mast cell density quantified. Eosinophils were quantified by immunostaining for eosinophil peroxidase. Changes in lung function were correlated with mast cell density. Lung tissue obtained from IPF patients had a higher density of chymase-immunoreactive mast cells than that from patients with HP, SSc-related ILD or normal lungs. IPF lung tissue had a higher density of eosinophils than normal lung. There was no correlation between mast cell density and eosinophil density in IPF lung. IPF patients with high mast cell density had a slower rate of decline in forced vital capacity (FVC) than IPF patients with low mast cell density. Mast cell density in IPF lungs is higher than in other fibrotic lung diseases and normal lungs. Increased mast cell density in IPF may predict slower disease progression.
    Histopathology 03/2012; 61(1):98-106. · 2.86 Impact Factor
  • Talmadge E King, Harold R Collard, Luca Richeldi
    Clinics in chest medicine 03/2012; 33(1):xiii. · 2.51 Impact Factor
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    ABSTRACT: Little is known about the treatment and correlates of dyspnea in idiopathic pulmonary fibrosis (IPF). The objective of this systematic review was to summarize the literature regarding the treatment and correlates of dyspnea in IPF. MEDLINE, EMBASE, and all Evidence-Based Medicine Reviews were searched for publications that evaluated treatment or correlates of dyspnea in IPF. Reference lists and recent review articles also were searched. The heterogeneity of included studies did not permit meta-analysis. Dyspnea improved in studies of sildenafil, pulmonary rehabilitation, and prednisone with colchicine. Additional studies of these three treatments, however, found discordant results. One study suggested that assisted ventilation delivered by facemask improved exertional dyspnea. Oxygen and opioids improve dyspnea in other chronic lung diseases, but data in IPF are limited. Correlates of dyspnea included functional and physiological measures and comorbid diseases. Sildenafil and pulmonary rehabilitation should be considered as potential therapies for dyspnea in selected patients with IPF. Supplemental oxygen and opioids may be additional potential therapies; however, the evidence supporting their use is weak. Additional research should focus on the management of functional status and comorbidities as potential treatments for dyspnea.
    Journal of pain and symptom management 01/2012; 43(4):771-82. · 2.42 Impact Factor
  • Brett Ley, Harold R Collard
    American Journal of Respiratory and Critical Care Medicine 01/2012; 185(1):6-7. · 11.04 Impact Factor
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    ABSTRACT: Little is known about depression in interstitial lung disease (ILD). The aim of this study was to determine the prevalence of depression, characterize the association of depression with clinical variables and describe the natural history of depression in patients with ILD. In this prospective cohort study, clinical variables were recorded at baseline and 6 months. Depression was measured with the Centre for Epidemiologic Studies Depression scale. Depression prevalence was determined using the established threshold of >15 points. Multivariate linear regression was used to determine the baseline features that independently correlated with baseline depression score and that predicted depression severity at follow-up. Fifty-two subjects were enrolled, and 45 returned for follow-up (three deaths, one lung transplant). Prevalence of depression was 21% at baseline. Independent predictors of depressive symptoms at baseline included dyspnoea severity, pain severity, sleep quality and forced vital capacity (R(2) 0.67). The odds of clinically meaningful depression at follow-up were 34-fold higher for subjects who had clinically meaningful depression at baseline compared with those who were not (95% confidence interval 3.5-422, P < 0.0005). Baseline depression score was the strongest predictor of depression score at follow-up (r 0.59, P < 0.00005). Depressive symptoms in ILD are common, persistent, and strongly and independently correlated with dyspnoea, pain, sleep quality and forced vital capacity. Clinically meaningful depression at baseline is the most important predictor of depressive symptoms at follow-up. Patients with ILD should routinely be screened for depression.
    Respirology 12/2011; 17(3):525-32. · 2.78 Impact Factor
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    ABSTRACT: Some patients with idiopathic pulmonary fibrosis experience acute exacerbations in their respiratory status leading to substantial morbidity and mortality. Occult aspiration of gastric contents has been proposed as one possible mechanism leading to these acute exacerbations. We sought to determine whether pepsin, a marker of gastric aspiration, is elevated in bronchoalveolar lavage fluid obtained from patients during acute exacerbation of idiopathic pulmonary fibrosis, compared with that obtained in stable disease. Lavage samples were obtained in a case-control study of well-characterised patients. Acute exacerbation was defined using standard criteria. Levels of lavage pepsin were compared in cases and controls, and were correlated with clinical features and disease course. 24 cases with acute exacerbations and 30 stable controls were identified. There were no significant differences in baseline demographics between the two groups. Pepsin level was an indicator of acute exacerbation status (p=0.04). On average, pepsin appeared higher in patients with acute exacerbations compared with stable controls. This difference was driven by a subgroup of eight patients (33%) with pepsin levels ≥70 ng·mL(-1). Pepsin level was not an independent predictor of survival time. These results suggest occult aspiration may play a role in some cases of acute exacerbation of idiopathic pulmonary fibrosis.
    European Respiratory Journal 12/2011; 39(2):352-8. · 6.36 Impact Factor
  • Source
    C J Ryerson, H R Collard
    Sarcoidosis, vasculitis, and diffuse lung diseases: official journal of WASOG / World Association of Sarcoidosis and Other Granulomatous Disorders 10/2011; 28(2):83-4. · 1.63 Impact Factor
  • Joyce S Lee, Sally McLaughlin, Harold R Collard
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    ABSTRACT: Recently, an expert committee endorsed by the American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and the Latin American Thoracic Society published an evidence-based guideline on the management of idiopathic pulmonary fibrosis (IPF). In the current document, we summarize and supplement this recent expert document and propose a comprehensive approach to the care and management of patients with IPF. We propose three pillars of care for the patient with IPF titled 'disease-centered management', 'symptom-centered management', and 'education and self-management'. Disease-centered management involves both pharmacological and nonpharmacological approaches. Palliative care should be an integral and routine component of the care of patients with IPF. Education and self-management strengthens the provider-patient partnership by enabling patients to set realistic goals, remain in control of his or her care, and prepare for the future. The comprehensive care of the patient with IPF involves balancing the three pillars of disease-centered management, symptom-centered management, and patient education and self-management upon a solid foundation of provider-patient partnership. Constant reassessment of the individual patient's goals of care, based on their values and preferences, is essential to the constant recalibration of these various interventions.
    Current opinion in pulmonary medicine 09/2011; 17(5):348-54. · 3.12 Impact Factor
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    ABSTRACT: Gastroesophageal reflux (GER) is highly prevalent in patients with idiopathic pulmonary fibrosis (IPF). Chronic microaspiration secondary to GER may play a role in the pathogenesis and natural history of IPF. To investigate the relationship between GER-related variables and survival time in patients with IPF. Regression analysis was used to investigate the relationship between GER-related variables and survival time in a retrospectively identified cohort of patients with well-characterized IPF from two academic medical centers. Two hundred four patients were identified for inclusion. GER-related variables were common in this cohort: reported symptoms of GER (34%), a history of GER disease (45%), reported use of GER medications (47%), and Nissen fundoplication (5%). These GER-related variables were significantly associated with longer survival time on unadjusted analysis. After adjustment, the use of GER medications was an independent predictor of longer survival time. In addition, the use of gastroesophageal reflux medications was associated with a lower radiologic fibrosis score. These findings were present regardless of center. The reported use of GER medications is associated with decreased radiologic fibrosis and is an independent predictor of longer survival time in patients with IPF. These findings further support the hypothesis that GER and chronic microaspiration may play important roles in the pathobiology of IPF.
    American Journal of Respiratory and Critical Care Medicine 06/2011; 184(12):1390-4. · 11.04 Impact Factor
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    ABSTRACT: The clinical associations and prognostic value of cough in IPF have not been adequately described. The objective of this study was to describe the characteristics and prognostic value of cough in IPF. Subjects with IPF were identified from an ongoing longitudinal database. Cough and other clinical variables were recorded prospectively. Logistic regression was used to determine predictors of cough and predictors of disease progression, defined as 10% decline in FVC, 15% decline in DL(CO) , lung transplantation or death within 6 months of clinic visit. The relationship of cough with time to death or lung transplantation was analysed using Cox proportional hazards analysis. Two hundred and forty-two subjects were included. Cough was reported in 84% of subjects. On multivariate analysis, cough was less likely in previous smokers (OR 0.07, 95% CI: 0.01-0.55, P = 0.01), and more likely in subjects with exertional desaturation (OR 2.56, 95% CI: 1.15-5.72, P = 0.02) and lower FVC (OR 0.76, 95% CI: 0.60-0.96, P = 0.02). Cough predicted disease progression (OR 4.97, 95% CI: 1.25-19.80, P = 0.02) independent of disease severity, and may predict time to death or lung transplantation (HR 1.78, 95% CI: 0.94-3.35, P = 0.08). Cough in IPF is more prevalent in never-smokers and patients with more advanced disease. Cough is an independent predictor of disease progression and may predict time to death or lung transplantation.
    Respirology 05/2011; 16(6):969-75. · 2.78 Impact Factor

Publication Stats

2k Citations
1k Downloads
652.01 Total Impact Points

Institutions

  • 2006–2013
    • University of California, San Francisco
      • Division of Hospital Medicine
      San Francisco, CA, United States
    • University of Michigan
      • Department of Internal Medicine
      Ann Arbor, MI, United States
    • University of Ulsan
      • Asan Medical Center
      Ulsan, Ulsan, South Korea
  • 2012
    • University of British Columbia - Vancouver
      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
  • 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
    • University of Wisconsin, Madison
      • Department of Medicine
      Madison, MS, United States
    • National Institutes of Health
      • Critical Care Medicine Department
      Bethesda, MD, United States
  • 2003–2004
    • University of Colorado
      • Department of Medicine
      Denver, CO, United States