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Sharon Chao Wootton,
Dong Soon Kim,
Yasuhiro Kondoh,
Eunice Chen,
Joyce S Lee,
Jin Woo Song,
Jin Won Huh,
Hiroyuki Taniguchi,
Charles Chiu,
Homer Boushey,
Lisa H Lancaster,
Paul J Wolters,
Joseph DeRisi,
Don Ganem, Harold R Collard
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ABSTRACT: Idiopathic pulmonary fibrosis is a progressive, uniformly fatal interstitial lung disease. An acute exacerbation of idiopathic pulmonary fibrosis is an episode of acute respiratory worsening without an identifiable etiology. Occult viral infection has been proposed as a possible cause of acute exacerbation.
To use unbiased genomics-based discovery methods to define the role of viruses in acute exacerbation of idiopathic pulmonary fibrosis.
Bronchoalveolar lavage and serum from patients with acute exacerbation of idiopathic pulmonary fibrosis, stable disease, and acute lung injury were tested for viral nucleic acid using multiplex polymerase chain reaction, pan-viral microarray, and high-throughput cDNA sequencing.
Four of forty-three patients with acute exacerbation of idiopathic pulmonary fibrosis had evidence of common respiratory viral infection (parainfluenza [n = 1], rhinovirus [n = 2], coronavirus [n = 1]); no viruses were detected in the bronchoalveolar lavage from stable patients. Pan-viral microarrays revealed additional evidence of viral infection (herpes simplex virus [n = 1], Epstein-Barr virus [n = 2], and torque teno virus [TTV] [n = 12]) in patients with acute exacerbation. TTV infection was significantly more common in patients with acute exacerbation than stable controls (P = 0.0003), but present in a similar percentage of acute lung injury controls. Deep sequencing of a subset of acute exacerbation cases confirmed the presence of TTV but did not identify additional viruses.
Viral infection was not detected in most cases of acute exacerbation of idiopathic pulmonary fibrosis. TTV was present in a significant minority of cases, and cases of acute lung injury; the clinical significance of this finding remains to be determined.
American Journal of Respiratory and Critical Care Medicine 02/2011; 183(12):1698-702. · 11.08 Impact Factor
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ABSTRACT: Idiopathic pulmonary fibrosis (IPF) is a progressive, life-threatening, interstitial lung disease of unknown etiology. The median survival of patients with IPF is only 2 to 3 years, yet some patients live much longer. Respiratory failure resulting from disease progression is the most frequent cause of death. To date we have limited information as to predictors of mortality in patients with IPF, and research in this area has failed to yield prediction models that can be reliably used in clinical practice to predict individual risk of mortality. The goal of this concise clinical review is to examine and summarize the current data on the clinical course, individual predictors of survival, and proposed clinical prediction models in IPF. Finally, we will discuss challenges and future directions related to predicting survival in IPF.
American Journal of Respiratory and Critical Care Medicine 10/2010; 183(4):431-40. · 11.08 Impact Factor
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Chest 07/2010; 138(1):240-1; author reply 241-2. · 5.25 Impact Factor
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ABSTRACT: Idiopathic pulmonary fibrosis is a diffuse fibrotic lung disease of unknown etiology with no effective treatment. Emerging data support a role for chronic microaspiration (ie, subclinical aspiration of small droplets) in the pathogenesis and natural history of idiopathic pulmonary fibrosis. However, the precise relationship between chronic microaspiration and idiopathic pulmonary fibrosis remains unknown. Gastroesophageal reflux, a presumed risk factor for microaspiration, has been strongly associated with idiopathic pulmonary fibrosis with an estimated prevalence of up to 90%. This review aims to describe the relationship between chronic microaspiration and idiopathic pulmonary fibrosis by laying out the clinical and biologic rationale for this relationship and exploring the scientific evidence available. The gaps in our current understanding of the diagnosis of chronic microaspiration and idiopathic pulmonary fibrosis and the ongoing uncertainties in management and treatment will be highlighted. Defining the role of chronic microaspiration in idiopathic pulmonary fibrosis is essential as it has potential clinical, pathobiological, and treatment implications for this deadly disease.
The American journal of medicine 04/2010; 123(4):304-11. · 4.47 Impact Factor
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Harold R Collard,
Carolyn S Calfee,
Paul J Wolters,
Jin Woo Song,
Sang-Bum Hong,
Sandra Brady,
Akitoshi Ishizaka,
Kirk D Jones,
Talmadge E King,
Michael A Matthay,
Dong Soon Kim
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ABSTRACT: Little is known about the pathobiology of acute exacerbation of idiopathic pulmonary fibrosis (IPF), a condition that shares clinical and histopathological features with acute lung injury. Plasma biomarkers have been well studied in acute lung injury and have provided insight into the underlying disease mechanism. The objective of this study was to determine the plasma biomarker profile of acute exacerbation of IPF and compare this profile with that of stable IPF and acute lung injury. Plasma was collected from patients with stable IPF, acute exacerbation of IPF, and acute lung injury for measurement of biomarkers of cellular activity/injury (receptor for advanced glycation endproducts, surfactant protein D, KL-6, von Willebrand factor), systemic inflammation (IL-6), and coagulation/fibrinolysis (protein C, thrombomodulin, plasminogen activator inhibitor-1). Plasma from patients with acute exacerbation of IPF showed significant elevations in markers of type II alveolar epithelial cell injury and/or proliferation, endothelial cell injury, and coagulation. This profile differed from the biomarker profile in patients with acute lung injury. These findings support the hypothesis that type II alveolar epithelial cells are centrally involved in the pathobiology of acute exacerbation of IPF. Furthermore, they suggest that acute exacerbation of IPF has a distinct plasma biomarker profile from that of acute lung injury.
AJP Lung Cellular and Molecular Physiology 04/2010; 299(1):L3-7. · 3.66 Impact Factor
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ABSTRACT: Undifferentiated connective tissue disease (UCTD) is a distinct clinical entity that may be accompanied by interstitial lung disease (ILD). The natural history of UCTD-ILD is unknown. We hypothesized that patients with UCTD-ILD would be more likely to have improvement in lung function than those with idiopathic pulmonary fibrosis (IPF) during longitudinal follow-up. We identified subjects enrolled in the UCSF ILD cohort study with a diagnosis of IPF or UCTD. The primary outcome compared the presence or absence of a > or = 5% increase in percent predicted forced vital capacity (FVC) in IPF and UCTD. Regression models were used to account for potential confounding variables. Ninety subjects were identified; 59 subjects (30 IPF, 29 UCTD) had longitudinal pulmonary function data for inclusion in the analysis. After accounting for baseline pulmonary function tests, treatment, and duration between studies, UCTD was associated with substantial improvement in FVC (odds ratio = 8.23, 95% confidence interval, 1.27-53.2; p = 0.03) during follow-up (median, 8 months) compared with IPF. Patients with UCTD-ILD are more likely to have improved pulmonary function during follow-up than those with IPF. These findings demonstrate the clinical importance of identifying UCTD in patients presenting with an "idiopathic" interstitial pneumonia.
Beiträge zur Klinik der Tuberkulose 04/2010; 188(2):143-9. · 1.90 Impact Factor
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ABSTRACT: Dyspnea is the most common symptom in interstitial lung disease, yet little is known about its management. This review summarizes the available evidence for the treatment of dyspnea in interstitial lung disease.
The management of dyspnea in interstitial lung disease remains a challenge, with few effective therapies. Limited evidence suggests that pulmonary rehabilitation is an effective treatment of dyspnea. In patients with interstitial lung disease, dyspnea severity is associated with measures of ventilatory restriction, gas exchange, functional status, mental health, and some comorbid diseases. Treatment directed toward these modifiable correlates of dyspnea might be effective in dyspnea management; however, the outcome of this strategy has not been adequately studied.
Studies support pulmonary rehabilitation as an effective treatment for dyspnea in interstitial lung disease and pulmonary rehabilitation should be considered in all dyspneic patients. Several investigational agents have been developed and evaluated for potential use in fibrotic interstitial lung disease; however, these agents have not been shown to improve dyspnea.
Current opinion in supportive and palliative care 04/2010; 4(2):69-75.
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ABSTRACT: Interstitial lung disease (ILD) is a frequent extraarticular manifestation of rheumatoid arthritis (RA). While the nonspecific interstitial pneumonia pattern predominates in most forms of connective tissue-associated ILD, studies in patients with RA-associated ILD (RA-ILD) suggest that the usual interstitial pneumonia (UIP) pattern is more common in this patient population. High-resolution CT (HRCT) scans appear accurate in identifying UIP pattern in many patients with RA-ILD. Although the data are limited, UIP pattern appears to predict worse survival in RA-ILD patients. Larger, prospective, multicenter studies are needed to confirm this finding. We propose that the evaluation of patients with RA-ILD should focus on identifying those with UIP pattern on HRCT scans, as these patients are likely to carry a worse prognosis. In patients in whom the underlying pattern cannot be determined by HRCT scanning, surgical lung biopsy should be considered.
Chest 11/2009; 136(5):1397-405. · 5.25 Impact Factor
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ABSTRACT: From 1984 to 2006, studies of sleep in patients with interstitial lung disease revealed disturbed sleep, frequent nocturnal desaturations, nocturnal cough, and obstructive sleep apnea (OSA). Our goal was to analyze OSA in an outpatient population of stable patients with idiopathic pulmonary fibrosis (IPF).
Patients with IPF who had been followed up in the Vanderbilt Pulmonary Clinic were asked to participate. All patients were given a diagnosis of IPF by the 2000 American Thoracic Society consensus statement criteria. Subjects completed an Epworth sleepiness scale (ESS) questionnaire and a sleep apnea scale of sleep disorders questionnaire (SA-SDQ) before undergoing nocturnal polysomnography (NPSG). OSA was defined as an apnea-hypopnea index (AHI) of > 5 events per hour.
Fifty subjects enrolled and completed a NPSG. The mean age was 64.9 years, and the mean BMI was 32.3. OSA was diagnosed in 88% of subjects. Ten subjects (20%) had mild OSA (AHI, 5 to 15 events per hour), and 34 subjects (68%) had moderate-to-severe OSA (AHI, > 15 events per hour). Only 6 subjects (12%) had a normal AHI. One patient was asymptomatic as determined by ESS and SA-SDQ, but had an AHI of 24 events per hour. The sensitivity of the ESS was 75% with a specificity of 15%, whereas the SA-SDQ had a sensitivity of 88% with a specificity of 50%. BMI did not correlate strongly with AHI (r = 0.30; p = 0.05).
OSA is prevalent in patients with IPF and may be underrecognized by primary care providers and specialists. Neither ESS nor SA-SDQ alone or in combination was a strong screening tool. Given the high prevalence found in our sample, formal sleep evaluation and polysomnography should be considered in patients with IPF.
Chest 07/2009; 136(3):772-8. · 5.25 Impact Factor
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ABSTRACT: Data examining the role of pulmonary rehabilitation (PR) in interstitial lung disease (ILD) are limited. We tested the hypothesis that PR can improve functional status and dyspnea in a large group of patients with ILD, and that certain baseline patient variables can predict this improvement.
Data from patients who were referred to PR with a diagnosis of ILD were included. Baseline and post-PR variables were recorded, and changes in 6-min walk test (6MWT) distance and dyspnea were evaluated. The impact of baseline variables on change in 6MWT distance and dyspnea were analyzed.
A statistically significant difference was seen in both the change in Borg score and 6MWT distance after PR (p < 0.0001). These changes were consistent with previously established clinically significant differences. Baseline 6MWT distance was a significant predictor of change in 6MWT distance (p < 0.0001), with increasing baseline 6MWT distance predicting a smaller improvement after PR.
These results suggest that PR should be considered as a standard of care for patients with ILD.
Chest 10/2008; 135(2):442-7. · 5.25 Impact Factor
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ABSTRACT: Dyspnea is a common complication of interstitial lung disease, yet little is known about its cause and effective management. This review attempts to summarize the current state of the art in this area.
Dyspnea is a near-universal finding in people with interstitial lung disease, predominantly due to neuromechanical abnormalities. Several well studied metrics exist for the measurement of dyspnea in this population, and its severity has been linked to quality of life and survival. The management of dyspnea in interstitial lung disease remains a challenge, with no proven pharmacological options. Pulmonary rehabilitation shows therapeutic promise, and aggressive treatment of physical and psychiatric comorbidities is important.
Dyspnea remains a common and difficult to treat symptom for people with interstitial lung disease. More research is sorely needed.
Current opinion in supportive and palliative care 07/2008; 2(2):100-4.
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ABSTRACT: Up to 80% of patients with scleroderma have lung disease, with interstitial lung disease (ILD) being the most common manifestation. Currently, there is no definitive therapy for this condition. The objective of the study is to investigate the use of mycophenolate mofetil (MMF) to treat scleroderma interstitial ILD. We report a retrospective chart review of 17 patients with scleroderma ILD treated with MMF (2g/day) for at least 12 months. Demographics, bronchoalveolar lavage (BAL) findings, pulmonary physiology and high-resolution computed tomography were recorded at baseline and after 12 and 24 months of therapy. Baseline BAL (n=12) showed alveolitis (median of 18% neutrophils). Ninety-four percent of subjects had either improved or stable lung function after 12 months of treatment: four improved, 12 were stable and only one worsened. All patients had radiographic abnormalities consistent with ILD. After 12 months of therapy, radiological findings (n=15) were stable in 11 patients, worse in three, and improved in one. There were no side effects attributable to MMF therapy recorded. Treatment of patients with scleroderma ILD for up to 24 months with MMF was generally associated with stable pulmonary function. These data argue for a prospective trial using MMF to treat scleroderma ILD.
Respiratory Medicine 02/2008; 102(1):150-5. · 2.47 Impact Factor
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ABSTRACT: The American Thoracic Society/European Respiratory Society International Consensus Classification panel identified the clinical entity idiopathic nonspecific interstitial pneumonia (NSIP) as a provisional diagnosis and recommended further study.
We hypothesized that idiopathic NSIP is an autoimmune disease and the lung manifestation of undifferentiated connective tissue disease (UCTD), a recently described, distinct entity.
We studied 28 consecutive patients with idiopathic interstitial pneumonia (IIP) enrolled in the University of California, San Francisco Interstitial Lung Disease Center who met prespecified criteria for UCTD, as follows: at least one clinical manifestation of connective tissue disease, serologic evidence of systemic inflammation in the absence of clinical infection, and absence of sufficient American College of Rheumatology criteria for another connective tissue disease. Medical record reviews, evaluation of radiographs, and scoring of lung biopsies were performed. The control group consisted of all other patients (n = 47) with IIP who did not meet the UCTD criteria.
The patients with UCTD were more likely to be women, younger, and nonsmokers than the IIP control subjects. Compared with the control group, patients with UCTD-ILD were significantly more likely to have ground-glass opacity on high-resolution computed tomography (HRCT) and NSIP pattern on biopsy, and less likely to have honeycombing on HRCT or usual interstitial pneumonia on biopsy. At our center, the majority of patients classified as idiopathic NSIP (88%) met the criteria for UCTD.
Most patients diagnosed with idiopathic NSIP meet the case definition of UCTD. Furthermore, these results show that the clinical entity idiopathic NSIP is different from idiopathic pulmonary fibrosis and appears to be an autoimmune disease.
American Journal of Respiratory and Critical Care Medicine 11/2007; 176(7):691-7. · 11.08 Impact Factor
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Harold R Collard,
Bethany B Moore,
Kevin R Flaherty,
Kevin K Brown,
Robert J Kaner,
Talmadge E King,
Joseph A Lasky,
James E Loyd,
Imre Noth,
Mitchell A Olman, [......],
Dong Soon Kim,
Yasuhiro Kondoh,
David A Lynch,
Joachim Müller-Quernheim,
Jeffrey L Myers,
Andrew G Nicholson,
Moisés Selman,
Galen B Toews,
Athol U Wells,
Fernando J Martinez
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ABSTRACT: The natural history of idiopathic pulmonary fibrosis (IPF) has been characterized as a steady, predictable decline in lung function over time. Recent evidence suggests that some patients may experience a more precipitous course, with periods of relative stability followed by acute deteriorations in respiratory status. Many of these acute deteriorations are of unknown etiology and have been termed acute exacerbations of IPF. This perspective is the result of an international effort to summarize the current state of knowledge regarding acute exacerbations of IPF. Acute exacerbations of IPF are defined as acute, clinically significant deteriorations of unidentifiable cause in patients with underlying IPF. Proposed diagnostic criteria include subjective worsening over 30 days or less, new bilateral radiographic opacities, and the absence of infection or another identifiable etiology. The potential pathobiological roles of infection, disordered cell biology, coagulation, and genetics are discussed, and future research directions are proposed.
American Journal of Respiratory and Critical Care Medicine 11/2007; 176(7):636-43. · 11.08 Impact Factor
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ABSTRACT: Little is known about practice patterns regarding the diagnosis and management of idiopathic pulmonary fibrosis (IPF). This study attempts to define the practice patterns of academic pulmonologists caring for patients with IPF. Academic pulmonologists in the United States were surveyed electronically. Completed surveys were received from 272 respondents (representing approximately 10% of academic pulmonologists). The majority agreed that high-resolution computed tomography can establish the diagnosis of IPF, and that surgical lung biopsy is indicated when the diagnosis remains unclear. Bronchoscopy is little utilized. Most respondents treat patients with medications, but there is no consensus regarding treatment regimen. These results suggest there is general consensus regarding the approach to diagnosis, but that there is no consensus about medical management in IPF.
Respiratory Medicine 10/2007; 101(9):2011-6. · 2.47 Impact Factor
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ABSTRACT: Amiodarone is commonly used to treat supraventricular and ventricular arrhythmias in various inpatient and outpatient settings. Over- and under-use of amiodarone is common, and data regarding patterns of use are sparse and largely anecdotal. Because of adverse drug reactions, proper use is essential to deriving optimal benefits from the drug with the least risk. This guide updates an earlier version published in 2000, reviews indications for use of amiodarone and recommends strategies to minimize adverse effects. The recommendations included herein are based on the best available data and the collective experience of the member of the writing committee.
Heart Rhythm 10/2007; 4(9):1250-9. · 4.10 Impact Factor
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ABSTRACT: This survey describes the experiences of patients diagnosed with pulmonary fibrosis, focusing on the issues of patient education and resources. A survey of 52 defined-choice and open-ended questions regarding the diagnosis and management of pulmonary fibrosis was delivered. A total of 1448 respondents comprised the study group. Two-thirds of respondents reported a clear lack of information and resources on pulmonary fibrosis at the time of diagnosis. Less than half of respondents reported they felt well-informed about treatment options, the role of supplemental oxygen, pulmonary rehabilitation, and transplantation. These results suggest there is a substantial need for improved patient education regarding the diagnosis and management of pulmonary fibrosis.
Respiratory Medicine 07/2007; 101(6):1350-4. · 2.47 Impact Factor
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American Journal of Infection Control 06/2007; 35(4):284-5. · 2.40 Impact Factor
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ABSTRACT: Pulmonary hypertension is a common finding in patients with idiopathic pulmonary fibrosis (IPF), and is associated with increased morbidity and mortality. Therapy with sildenafil has been shown to decrease pulmonary vascular resistance in patients with pulmonary fibrosis and may improve functional status. Patients with IPF and documented pulmonary hypertension were followed up in an open-label study of sildenafil. The 6-min walk test distance (6MWD) was obtained before and after 3 months of sildenafil therapy. Fourteen patients were followed up in the study; 11 patients completed both 6-min walk tests. The mean improvement in walk distance was 49.0 m (90% confidence interval, 17.5 to 84.0 m). When all 14 patients were dichotomized into groups of "responders" (ie, >/= 20% improvement in 6MWD) or "nonresponders" (ie, < 20% change or unable to complete), 57% were classified as responders. Sildenafil is a promising and well-tolerated therapeutic agent for use in patients with IPF and pulmonary hypertension, and should be studied in a large, well-controlled trial.
Chest 03/2007; 131(3):897-9. · 5.25 Impact Factor
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Chest 08/2006; 130(1):302-3. · 5.25 Impact Factor
