Dr. Rishi Raj is a Clinical Professor of Medicine at Stanford University, where he directs the Interstitial Lung Disease program. He has practiced pulmonary and critical care medicine for over two decades and specializes in the diagnosis and treatment of interstitial lung diseases.
His primary clinical interest encompasses a range of interstitial lung diseases, including idiopathic pulmonary fibrosis, other idiopathic interstitial lung diseases, drug-induced interstitial lung diseases, interstitial lung disease associated with connective tissue diseases such as scleroderma, rheumatoid arthritis, dermatomyositis, sarcoidosis, hypersensitivity pneumonitis, and other various interstitial lung diseases.
Dr. Raj's clinical research explores the use of radiologic biomarkers to predict outcomes in various interstitial lung diseases. He is a principal investigator and co-investigator in numerous clinical trials, examining new therapies for treating idiopathic pulmonary fibrosis and other interstitial lung diseases.
- Idiopathic Pulmonary Fibrosis
- Other Idiopathic Interstitial Lung Diseases
- Connective Tissue Associated Interstitial Lung Disease (RA, Scleroderma, Myosites, others)
- Drug Induced Interstitial Lung Diseases
- Hypersensitivity Pneumonitis
- Other Interstitial Lung Diseases
- Pulmonary Disease
Clinical Professor, Medicine - Pulmonary, Allergy & Critical Care Medicine
Director, Interstitial Lung Disease Program, Stanford (2017 - Present)
Fellowship: Baylor College of Medicine (2002) TX
Board Certification: American Board of Internal Medicine, Critical Care Medicine (2003)
Board Certification: American Board of Internal Medicine, Pulmonary Disease (2002)
Residency: Texas Tech University Health Sciences Center (1999) TX
Medical Education: Christian Medical College/Vellor (1995)
A Study Measuring the Effectiveness, Safety, and Tolerability of BMS-986278 in Participants With Lung Fibrosis
The purpose of this study is to provide an initial evaluation of the effectiveness of BMS-986278 in participants with lung fibrosis, to demonstrate the safety of BMS-986278, and provide information on the drug levels of BMS-986278 in these participants.
Prospective Treatment Efficacy in IPF Using Genotype for Nac Selection (PRECISIONS) Trial
The purpose of this study is to compare the effect of n-acetylcysteine (NAC) plus standard care with matched placebo plus standard of care in patients diagnosed with idiopathic pulmonary fibrosis (IPF) who have the TOLLIP rs3750920 TT genotype. The study will compare the time to a composite endpoint of relative decline in lung function [10% relative decline in forced vital capacity (FVC), first respiratory hospitalization, lung transplantation, or all-cause mortality] The secondary objectives will be to examine the effect of NAC on the components of the primary composite endpoint, the rates of clinical events, change in physiology, change in health status, and change in respiratory symptoms.
Pulmonary Fibrosis Foundation Patient Registry
The Pulmonary Fibrosis Foundation Patient Registry will collect data on at least 2,000 patients with interstitial lung disease (ILD) at approximately 40 clinical sites in the US. The Registry is targeting enrollment of approximately 60% of the 2,000 ILD participants to have idiopathic pulmonary fibrosis (IPF). The aim of the Registry is to create a cohort of well-characterized patients with interstitial lung disease (ILD) for participation in retrospective and prospective research
Study of Efficacy and Safety of Inhaled Treprostinil in Subjects With Idiopathic Pulmonary Fibrosis
Study RIN-PF-301 is designed to evaluate the superiority of inhaled treprostinil against placebo for the change in absolute forced vital capacity (FVC) from baseline to Week 52.
Idiopathic Pulmonary Fibrosis and Interstitial Lung Disease Prospective Outcomes Registry
This registry will collect data on the strategies used to achieve a diagnosis of Idiopathic Pulmonary Fibrosis (IPF) and Chronic Fibrosing Interstitial Lung Disease with Progressive Phenotype (ILD) and the treatment and management efforts applied throughout study follow-up, clinical outcome events and patient reported outcome data. Blood samples will be collected periodically throughout the study for use in future research efforts. For participants with non-IPF, chronic fibrosing ILD with progressive phenotype, HRCT images will be collected throughout the study for use in future research efforts.
Stanford is currently not accepting patients for this trial. For more information, please contact Kim Nguyen, 650-723-0291.
Prospective Validation of Cough, Dyspnea, and Quality of Life Questionnaires in Patients With IPF
The purpose of this study is to test cough, dyspnea (shortness of breath), and quality of life (QOL) questionnaires for their accuracy, sensitivity, and ability to reliably measure the severity of cough, breathlessness, and changes in cough and disease-related quality of life over time in Idiopathic Pulmonary Fibrosis (IPF) patients. These questionnaires have been used in other types of disease, but have not all been tested and validated in patients with cough due to IPF. Our hypothesis is that worsening of cough, dyspnea, and cough-related QOL questionnaire scores will correlate with physiologic markers of IPF severity and worsening of disease. Written, valid questionnaires measuring cough, dyspnea, and QOL are important to assess the benefit of investigational drugs under development to treat patients with IPF.
Stanford is currently not accepting patients for this trial.
Safety and Efficacy of a Lysophosphatidic Acid Receptor Antagonist in Idiopathic Pulmonary Fibrosis
The purpose of this study is to determine if study drug (BMS-986020) dose of 600 mg once daily or 600 mg twice daily for 26 weeks compared with placebo will reduce the decline in forced vital capacity (FVC) and will be well tolerated in subjects with idiopathic pulmonary fibrosis (IPF).
Stanford is currently not accepting patients for this trial.
Zephyrus I: Evaluation of Efficacy and Safety of Pamrevlumab in Participants With Idiopathic Pulmonary Fibrosis (IPF)
This is a Phase 3 trial to evaluate the efficacy and safety of 30 milligrams (mg)/kilogram (kg) intravenous (IV) infusions of pamrevlumab administered every 3 weeks as compared to placebo in participants with IPF.
Stanford is currently not accepting patients for this trial.
Lung function trajectories in patients with idiopathic pulmonary fibrosis.
2023; 24 (1): 209
Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease characterised by decline in lung function. We evaluated trajectories of forced vital capacity (FVC) and diffusing capacity (DLco) in a cohort of patients with IPF.Patients with IPF that was diagnosed or confirmed at the enrolling centre in the previous 6 months were enrolled into the IPF-PRO Registry between June 2014 and October 2018. Patients were followed prospectively, with lung function data collected as part of routine clinical care. Mean trajectories of FVC and DLco % predicted in all patients and in subgroups by characteristics assessed at enrolment were estimated using a joint model that accounted for factors such as disease severity and visit patterns.Of 1002 patients in the registry, 941 had ≥ 1 FVC and/or DLco measurement after enrolment. The median (Q1, Q3) follow-up period was 35.1 (18.9, 47.2) months. Overall, mean estimated declines in FVC and DLco % predicted were 2.8% and 2.9% per year, respectively. There was no evidence that the mean trajectories of FVC or DLco had a non-linear relationship with time at the population level. Patients who were male, white, had a family history of ILD, were using oxygen, or had prior/current use of antifibrotic therapy at enrolment had greater rates of decline in FVC % predicted. Patients who were male or white had greater rates of decline in DLco % predicted.Data from the IPF-PRO Registry suggest a constant rate of decline in lung function over a prolonged period, supporting the inexorably progressive nature of IPF. A graphical abstract summarising the data in this manuscript is available at: https://www.usscicomms.com/respiratory/IPF-PRORegistry_LungFunctionTrajectories .NCT01915511.
View details for DOI 10.1186/s12931-023-02503-5
View details for PubMedID 37612608
View details for PubMedCentralID 9851481
A double-blind, placebo-controlled, randomized withdrawal trial of sarilumab for the treatment of glucocorticoid-dependent sarcoidosis.
Rheumatology (Oxford, England)
Effective steroid-sparing therapies for the treatment of sarcoidosis are lacking; interleukin-6 (IL-6) antagonists may reduce sarcoidosis disease activity. This study assessed the safety and efficacy of the IL-6 receptor antagonist, sarilumab, in subjects with glucocorticoid-dependent sarcoidosis.This phase II, double-blind, placebo-controlled, randomized withdrawal trial enrolled 15 subjects with biopsy-proven sarcoidosis at Stanford University from November 2019 to September 2022. In Period 1, subjects were treated with open-label sarilumab 200mg subcutaneously every two weeks for 16 weeks, with predefined tapering of prednisone. Subjects who completed Period 1 without a sarcoidosis flare entered Period 2 and were randomized to continue sarilumab or to receive matching placebo for 12 weeks. Endpoints included flare-free survival, as well as changes in pulmonary function tests, chest imaging, patient reported outcomes, and laboratory values.Fifteen subjects were enrolled in the study (median age 57 years, 80% male, 73.3% White), and 10 subjects successfully completed Period 1. During Period 1, 4 of 15 subjects (26.7%) discontinued due to worsening of their sarcoidosis, and CT chest imaging worsened in 5 of 15 subjects (35.7%). During Period 2, 0 of 2 subjects in the sarilumab group and 1 of 8 subjects (12.5%) in the placebo group had a flare. Treatment with sarilumab 200 mg was generally well tolerated in subjects with sarcoidosis.In this double-blind, placebo-controlled, randomized withdrawal trial, a meaningful signal for improvement in subjects with sarcoidosis treated with sarilumab was not observed. Given the small numbers in this study, no definitive conclusions can be drawn.ClinicalTrials.gov Identifier: NCT04008069.
View details for DOI 10.1093/rheumatology/kead373
View details for PubMedID 37471590
Integrative multi-omics analysis reveals novel idiopathic pulmonary fibrosis endotypes associated with disease progression.
2023; 24 (1): 141
Idiopathic pulmonary fibrosis (IPF) is characterized by the accumulation of extracellular matrix in the pulmonary interstitium and progressive functional decline. We hypothesized that integration of multi-omics data would identify clinically meaningful molecular endotypes of IPF.The IPF-PRO Registry is a prospective registry of patients with IPF. Proteomic and transcriptomic (including total RNA [toRNA] and microRNA [miRNA]) analyses were performed using blood collected at enrollment. Molecular data were integrated using Similarity Network Fusion, followed by unsupervised spectral clustering to identify molecular subtypes. Cox proportional hazards models tested the relationship between these subtypes and progression-free and transplant-free survival. The molecular subtypes were compared to risk groups based on a previously described 52-gene (toRNA expression) signature. Biological characteristics of the molecular subtypes were evaluated via linear regression differential expression and canonical pathways (Ingenuity Pathway Analysis [IPA]) over-representation analyses.Among 232 subjects, two molecular subtypes were identified. Subtype 1 (n = 105, 45.3%) and Subtype 2 (n = 127, 54.7%) had similar distributions of age (70.1 +/- 8.1 vs. 69.3 +/- 7.6 years; p = 0.31) and sex (79.1% vs. 70.1% males, p = 0.16). Subtype 1 had more severe disease based on composite physiologic index (CPI) (55.8 vs. 51.2; p = 0.002). After adjusting for CPI and antifibrotic treatment at enrollment, subtype 1 experienced shorter progression-free survival (HR 1.79, 95% CI 1.28,2.56; p = 0.0008) and similar transplant-free survival (HR 1.30, 95% CI 0.87,1.96; p = 0.20) as subtype 2. There was little agreement in the distribution of subjects to the molecular subtypes and the risk groups based on 52-gene signature (kappa = 0.04, 95% CI= -0.08, 0.17), and the 52-gene signature risk groups were associated with differences in transplant-free but not progression-free survival. Based on heatmaps and differential expression analyses, proteins and miRNAs (but not toRNA) contributed to classification of subjects to the molecular subtypes. The IPA showed enrichment in pulmonary fibrosis-relevant pathways, including mTOR, VEGF, PDGF, and B-cell receptor signaling.Integration of transcriptomic and proteomic data from blood enabled identification of clinically meaningful molecular endotypes of IPF. If validated, these endotypes could facilitate identification of individuals likely to experience disease progression and enrichment of clinical trials.NCT01915511.
View details for DOI 10.1186/s12931-023-02435-0
View details for PubMedID 37344825
View details for PubMedCentralID 9851481
Ziritaxestat, a Novel Autotaxin Inhibitor, and Lung Function in Idiopathic Pulmonary Fibrosis: The ISABELA 1 and 2 Randomized Clinical Trials.
2023; 329 (18): 1567-1578
There is a major need for effective, well-tolerated treatments for idiopathic pulmonary fibrosis (IPF).To assess the efficacy and safety of the autotaxin inhibitor ziritaxestat in patients with IPF.The 2 identically designed, phase 3, randomized clinical trials, ISABELA 1 and ISABELA 2, were conducted in Africa, Asia-Pacific region, Europe, Latin America, the Middle East, and North America (26 countries). A total of 1306 patients with IPF were randomized (525 patients at 106 sites in ISABELA 1 and 781 patients at 121 sites in ISABELA 2). Enrollment began in November 2018 in both trials and follow-up was completed early due to study termination on April 12, 2021, for ISABELA 1 and on March 30, 2021, for ISABELA 2.Patients were randomized 1:1:1 to receive 600 mg of oral ziritaxestat, 200 mg of ziritaxestat, or placebo once daily in addition to local standard of care (pirfenidone, nintedanib, or neither) for at least 52 weeks.The primary outcome was the annual rate of decline for forced vital capacity (FVC) at week 52. The key secondary outcomes were disease progression, time to first respiratory-related hospitalization, and change from baseline in St George's Respiratory Questionnaire total score (range, 0 to 100; higher scores indicate poorer health-related quality of life).At the time of study termination, 525 patients were randomized in ISABELA 1 and 781 patients in ISABELA 2 (mean age: 70.0 [SD, 7.2] years in ISABELA 1 and 69.8 [SD, 7.1] years in ISABELA 2; male: 82.4% and 81.2%, respectively). The trials were terminated early after an independent data and safety monitoring committee concluded that the benefit to risk profile of ziritaxestat no longer supported their continuation. Ziritaxestat did not improve the annual rate of FVC decline vs placebo in either study. In ISABELA 1, the least-squares mean annual rate of FVC decline was -124.6 mL (95% CI, -178.0 to -71.2 mL) with 600 mg of ziritaxestat vs -147.3 mL (95% CI, -199.8 to -94.7 mL) with placebo (between-group difference, 22.7 mL [95% CI, -52.3 to 97.6 mL]), and -173.9 mL (95% CI, -225.7 to -122.2 mL) with 200 mg of ziritaxestat (between-group difference vs placebo, -26.7 mL [95% CI, -100.5 to 47.1 mL]). In ISABELA 2, the least-squares mean annual rate of FVC decline was -173.8 mL (95% CI, -209.2 to -138.4 mL) with 600 mg of ziritaxestat vs -176.6 mL (95% CI, -211.4 to -141.8 mL) with placebo (between-group difference, 2.8 mL [95% CI, -46.9 to 52.4 mL]) and -174.9 mL (95% CI, -209.5 to -140.2 mL) with 200 mg of ziritaxestat (between-group difference vs placebo, 1.7 mL [95% CI, -47.4 to 50.8 mL]). There was no benefit with ziritaxestat vs placebo for the key secondary outcomes. In ISABELA 1, all-cause mortality was 8.0% with 600 mg of ziritaxestat, 4.6% with 200 mg of ziritaxestat, and 6.3% with placebo; in ISABELA 2, it was 9.3% with 600 mg of ziritaxestat, 8.5% with 200 mg of ziritaxestat, and 4.7% with placebo.Ziritaxestat did not improve clinical outcomes compared with placebo in patients with IPF receiving standard of care treatment with pirfenidone or nintedanib or in those not receiving standard of care treatment.ClinicalTrials.gov Identifiers: NCT03711162 and NCT03733444.
View details for DOI 10.1001/jama.2023.5355
View details for PubMedID 37159034
View details for PubMedCentralID PMC10170340
- Diffuse Panbronchiolitis in a Patient With Ulcerative Colitis Treated With Ustekinumab. ACG case reports journal 2023; 10 (5): e01062
Exploring the Versatility of Zero-Shot CLIP for Interstitial Lung Disease Classification
Interstitial lung diseases (ILD) present diagnostic challenges due to their varied manifestations and overlapping imaging features. To address this, we propose a machine learning approach that utilizes CLIP, a multimodal (image and text) self-supervised model, for ILD classification. We extensively integrate zero-shot CLIP throughout our workflow, starting from the initial extraction of image patches from volumetric CT scans and proceeding to ILD classification using "patch montages". Furthermore, we investigate how domain adaptive pretraining (DAPT) CLIP with task-specific images (CT "patch montages" extracted with ILD-specific prompts for CLIP) and/or text (lung-specific sections of radiology reports) affects downstream ILD classification performance. By leveraging CLIP-extracted "patch montages" and DAPT, we achieve strong zero-shot ILD classification results, including an AUROC of 0.893, without the need for any labeled training data. This work highlights the versatility and potential of multimodal models like CLIP for medical image classification tasks where labeled data is scarce.Exploring the Versatility of Zero-Shot CLIP for Interstitial Lung Disease Classification
- COVID-19 mRNA Vaccines and ILD Exacerbation: Causation or Just a Temporal Association? American journal of respiratory and critical care medicine 2022
The Role of Surgical Lung Biopsy in the Diagnosis of Fibrotic Interstitial Lung Disease: Perspective from the Pulmonary Fibrosis Foundation.
Annals of the American Thoracic Society
Diagnosis of interstitial lung disease (ILD) requires a multidisciplinary diagnosis (MDD) approach that includes clinicians, radiologists, and pathologists. Surgical lung biopsy (SLB) is currently the recommended standard in obtaining pathological specimens for patients with ILD requiring a tissue diagnosis. The increased diagnostic confidence and accuracy provided by microscopic pathology assessment of SLB specimens must be balanced with the associated risks in ILD patients. This document was developed by the Surgical Lung Biopsy Working Group of the Pulmonary Fibrosis Foundation, composed of a multidisciplinary group of ILD physicians including pulmonologists, radiologists, pathologists, and thoracic surgeons. In this document, we present an up-to-date literature review of the indications, contraindications, risks, and alternatives to SLB in the diagnosis of fibrotic ILD, outline an integrated approach to the decision-making around SLB in the diagnosis of fibrotic ILD, and provide practical information to maximize the yield and safety of SLB.
View details for DOI 10.1513/AnnalsATS.202009-1179FR
View details for PubMedID 34004127
Prescription Patterns for Pulmonary Vasodilators in the Treatment of Pulmonary Hypertension Associated With Chronic Lung Diseases: Insights From a Clinician Survey.
Frontiers in medicine
1800; 8: 764815
Background: Pulmonary hypertension is a complication of chronic lung diseases (PH-CLD) associated with significant morbidity and mortality. Management guidelines for PH-CLD emphasize the treatment of the underlying lung disease, but the role of PH-targeted therapy remains controversial. We hypothesized that treatment approaches for PH-CLD would be variable across physicians depending on the type of CLD and the severity of PH. Methods and Results: Between May and July 2020, we conducted an online survey of PH experts asking for their preferred treatment approach in seven hypothetical cases of PH-CLD of varying severity. We assessed agreement amongst clinicians for initial therapy choice using Fleiss' kappa calculations. Over 90% of respondents agreed that they would treat cases of severe PH in the context of mild lung disease with some form of PH-targeted therapy. For cases of severe PH in the context of severe lung disease, over 70% of respondents agreed to use PH-targeted therapy. For mild PH and mild lung disease cases, <50% of respondents chose to start PH-specific therapy. There was overall poor agreement between respondents in the choice to use mono-, double or triple combination therapy with PH-specific agents in all cases. Conclusion: Although management guidelines discourage the routine use of PH-targeted therapies to treat PH-CLD patients, most physicians choose to treat patients with some form of PH-targeted therapy. The choice of therapy and treatment approach are variable and appear to be influenced by the severity of the PH and the underlying lung disease.
View details for DOI 10.3389/fmed.2021.764815
View details for PubMedID 34926507
- Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH): clinical characteristics and progression to carcinoid tumor. The European respiratory journal 2021
Disease Severity and Quality of Life in Patients With Idiopathic Pulmonary Fibrosis: A Cross-Sectional Analysis of the IPF-PRO Registry.
2020; 157 (5): 1188-1198
Limited data are available on the association between clinically measured disease severity markers and quality of life (QOL) in idiopathic pulmonary fibrosis (IPF). The study examined the associations between objective disease severity metrics and QOL in a contemporary IPF population.This study evaluated baseline data from patients enrolled in the multicenter, US-based Idiopathic Pulmonary Fibrosis Prospective Outcomes Registry between June 2014 and July 2018. Disease severity metrics included FVC % predicted, diffusing capacity for carbon monoxide (Dlco) % predicted, supplemental oxygen use with activity, supplemental oxygen use at rest, and two summary scores (the Gender-Age-Lung Physiology index, based on gender, age, and % predicted values for Dlco and FVC; and the Composite Physiologic Index, based on % predicted values for Dlco, FVC, and FEV1). Multivariable adjusted regression models were used to examine cross-sectional associations between each severity measure and St. George's Respiratory Questionnaire (SGRQ) total score.Among 829 patients with complete SGRQ data, the median (interquartile range) SGRQ score at enrollment was 40 (26-53), with higher scores indicating worse QOL. Modest SGRQ impairments were observed with increasing Gender-Age-Lung Physiology score (2.9 [1.8-4.0] per 1-point increase] and with increasing Composite Physiologic Index scores (3.0 [2.4-3.6] per 5-point increase). Substantial SGRQ impairments were observed for oxygen use with activity (15.6 [12.9-18.2]), oxygen use at rest (16.2 [13.0-19.4]), and decreasing Dlco (5.0 [4.0-6.1] per 10% decrease in % predicted).Objective measures of disease severity, including severity scores, physiologic parameters, and supplemental oxygen use, are associated with worse QOL in patients with IPF.ClinicalTrials.gov; No.: NCT01915511; URL: www.clinicaltrials.gov.
View details for DOI 10.1016/j.chest.2019.11.042
View details for PubMedID 31954102
Sleep Patterns and Health Behaviors in Healthcare Students.
Southern medical journal
2020; 113 (3): 104–10
OBJECTIVES: Personal health behavior can influence the academic development of healthcare students. This study was designed to evaluate the personal health behavior, including sleep time, of healthcare students at a large health sciences center.METHODS: An anonymous online survey based on standardized questionnaires about sleep, insomnia, depression, alcohol use, and exercise was sent to all of the healthcare students (including medical, nursing, pharmacy, graduate biomedical science, and allied health students) in the Texas Tech University Health Sciences Center graduate education programs in Lubbock.RESULTS: In total, 412 students replied to this survey. Their mean sleep duration during the weekday was 7.5 ± 1.2 hours; 16.5% were short sleepers (<7 hours) during weekdays; 33% of the students woke up "feeling tired or worn out" >15 days during the last month. Many students were either moderately or severely bothered by "the lack of energy" because of poor sleep, and 56.6% of students rated their sleep as either fair or poor. Approximately 35% of students had drinking patterns that qualified as hazardous drinking, 6.3% of students smoked, and 23% of students did not do even mild exercise during the week. Eighty-nine percent of students reported stress in their life, including family stress, job stress, financial stress, legal stress, and other stress. Thirty-five percent of students considered their health as either poor or fair. Approximately 50% of students did not expect any change in their situation during the next 3 to 6 months.CONCLUSIONS: Although most healthcare students report adequate sleep times, more than half of them rate their sleep as fair or poor. In addition, some have poor health habits, including excessive alcohol use. Health science centers should introduce programs to promote healthy behaviors and reduce stress in healthcare students.
View details for DOI 10.14423/SMJ.0000000000001077
View details for PubMedID 32123923
Rituximab Versus Mycophenolate in the Treatment of Recalcitrant Connective Tissue Disease-Associated Interstitial Lung Disease.
ACR open rheumatology
Interstitial lung disease (ILD) is a major cause of morbidity and mortality in connective tissue diseases (CTDs). We aimed to assess the effect of rituximab ± mycophenolate mofetil (MMF) compared with MMF on pulmonary function and prednisone dosage in patients with CTD-related ILD (CTD-ILD).This retrospective study included 83 patients from Stanford and Centre Hospitalier de l'Universite de Montreal. Fifteen patients received rituximab ± MMF (rituximab group), and 68 patients received MMF only (control group).Median ILD duration at the start of treatment was longer in the rituximab group at 47 months (range: 4-170) versus 6.5 months (range: 0-164) in controls. Forced vital capacity (FVC) decreased by 3.0% (range: 11%-21%) after treatment in the rituximab group, whereas it increased by 2.0% (range: 14%-25%) in the control group (p = 0.025). Diffusing capacity of carbon monoxide (DLCO) decreased by 3.0% (range: 10%-12%) after treatment in the rituximab group, whereas it increased by 4.5% (range: 30%-36%) in the control group (p = 0.046). Mixed model analysis controlling for ILD duration, baseline DLCO, systemic sclerosis, pulmonary hypertension, and prednisone use showed no significant difference in FVC or DLCO between groups at 6 months or 1 year. The average daily prednisone dose score decreased after treatment in the rituximab group, whereas it remained unchanged in the control group (p = 0.017).Rituximab ± MMF did not significantly change pulmonary function compared with MMF alone, but it did result in a relative decrease in average daily prednisone dose in a population with recalcitrant CTD-ILD.
View details for DOI 10.1002/acr2.11210
View details for PubMedID 33274857
Vaping-related Acute Parenchymal Lung Injury: A Systematic Review.
The ongoing U.S. outbreak of vaping-related acute lung injury, recently named EVALI (E-cigarette or vaping product use associated acute lung injury), has reignited concerns about the health effects of vaping. Initial case reports of vaping-related lung injury date back to 2012, but the ongoing outbreak of EVALI began in the summer of 2019 and has been implicated in 2,807 cases and 68 deaths as of this writing. Review of the scientific literature reveals 216 patient cases spanning 41 reports of parenchymal lung injury attributed to vaping. In this review, we detail the clinical, radiographic, pathologic patterns of lung injury attributable to vaping, as well as provide an overview of the scientific literature to date on the effects of vaping on respiratory health. Tetrahydrocannabinol was the most common vaped substance and Vitamin E acetate was found in bronchoalveolar lavage specimens from many affected individuals, however no specific component or contaminant has conclusively been identified as the cause for the injury to date. Patients present with cough, dyspnea, constitutional symptoms, and gastrointestinal symptoms. Radiology and histopathology demonstrate a spectrum of nonspecific acute injury patterns. A high index of suspicion combined with a good history are the key to an accurate diagnosis. Treatment is supportive, mortality is low, and most patients recover. Corticosteroids have been used with apparent success in patients with severe disease but more rigorous studies are needed to clarify their role in treating vaping related lung injury.
View details for DOI 10.1016/j.chest.2020.03.085
View details for PubMedID 32442559
Peripheral blood proteomic profiling of idiopathic pulmonary fibrosis biomarkers in the multicentre IPF-PRO Registry
2019; 20 (1): 227
Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease for which diagnosis and management remain challenging. Defining the circulating proteome in IPF may identify targets for biomarker development. We sought to quantify the circulating proteome in IPF, determine differential protein expression between subjects with IPF and controls, and examine relationships between protein expression and markers of disease severity.This study involved 300 patients with IPF from the IPF-PRO Registry and 100 participants without known lung disease. Plasma collected at enrolment was analysed using aptamer-based proteomics (1305 proteins). Linear regression was used to determine differential protein expression between participants with IPF and controls and associations between protein expression and disease severity measures (percent predicted values for forced vital capacity [FVC] and diffusion capacity of the lung for carbon monoxide [DLco]; composite physiologic index [CPI]). Multivariable models were fit to select proteins that best distinguished IPF from controls.Five hundred fifty one proteins had significantly different levels between IPF and controls, of which 47 showed a |log2(fold-change)| > 0.585 (i.e. > 1.5-fold difference). Among the proteins with the greatest difference in levels in patients with IPF versus controls were the glycoproteins thrombospondin 1 and von Willebrand factor and immune-related proteins C-C motif chemokine ligand 17 and bactericidal permeability-increasing protein. Multivariable classification modelling identified nine proteins that, when considered together, distinguished IPF versus control status with high accuracy (area under receiver operating curve = 0.99). Among participants with IPF, 14 proteins were significantly associated with FVC % predicted, 23 with DLco % predicted, 14 with CPI. Four proteins (roundabout homolog-2, spondin-1, polymeric immunoglobulin receptor, intercellular adhesion molecule 5) demonstrated the expected relationship across all three disease severity measures. When considered in pathways analyses, proteins associated with the presence or severity of IPF were enriched in pathways involved in platelet and haemostatic responses, vascular or platelet derived growth factor signalling, immune activation, and extracellular matrix organisation.Patients with IPF have a distinct circulating proteome and can be distinguished using a nine-protein profile. Several proteins strongly associate with disease severity. The proteins identified may represent biomarker candidates and implicate pathways for further investigation.ClinicalTrials.gov (NCT01915511).
View details for DOI 10.1186/s12931-019-1190-z
View details for Web of Science ID 000492020100001
View details for PubMedID 31640794
View details for PubMedCentralID PMC6805665
- Survival implications of pulmonary hypertension in end-stage COPD EUROPEAN RESPIRATORY SOC JOURNALS LTD. 2019
- Elevated pulmonary vascular resistance is associated with increased risk of death in IPF EUROPEAN RESPIRATORY SOC JOURNALS LTD. 2019
Predictors of death or lung transplant after a diagnosis of idiopathic pulmonary fibrosis: insights from the IPF-PRO Registry
2019; 20: 105
Idiopathic pulmonary fibrosis (IPF) is a progressive disease with a variable clinical course and high mortality. We used data from a large national US registry of patients with IPF to investigate relationships between patient characteristics, including markers of disease severity, and mortality.The analysis cohort comprised patients enrolled in the IPF-PRO Registry from its inception on 5 June 2014 to 26 October 2017. The primary criterion for inclusion in this registry is that patients must be diagnosed or confirmed with IPF at the enrolling centre within 6 months. Associations between patient characteristics and markers of disease severity at enrolment and mortality outcomes were investigated using univariable, multivariable and adjustment models.Among 662 patients enrolled, 111 patients died or had a lung transplant over a follow-up period of 30 months. The probability of being free of both events at month 30 was 50.6% (95% CI: 40.0, 60.2). When patient characteristics and markers of disease severity were jointly examined in a multivariable analysis, oxygen use at rest (hazard ratio [HR] 2.44 [95% CI: 1.45, 4.10]), lower forced vital capacity (FVC) % predicted (HR 1.28 [95% CI: 1.10, 1.49] per 10% decrease) and diffusion capacity for carbon monoxide (DLco) % predicted (HR 1.25 [95% CI: 1.04, 1.51] per 10% decrease) were significantly associated with increased risk of death or lung transplant. The risk of death or lung transplant increased with increasing age in patients ≥62 years old (HR 1.18 [95% CI: 0.99, 1.40] per 5-year increase), and decreased with increasing age in patients <62 years old (HR 0.60 [95% CI: 0.39, 0.92] per 5-year increase).In an observational US registry of patients with IPF, oxygen use at rest, lower FVC % predicted, and lower DLco % predicted were associated with risk of death or lung transplant. An audio podcast of the lead author discussing these data can be downloaded from: http://www.usscicomms.com/respiratory/snyder/IPF-PROsurvival1/ .ClinicalTrials.gov number: NCT01915511 .
View details for DOI 10.1186/s12931-019-1043-9
View details for Web of Science ID 000469504900001
View details for PubMedID 31142314
View details for PubMedCentralID PMC6542049
Tissue Continues to Be the Issue: Role of Histopathology in the Context of Recent Updates in the Radiologic Classification of Interstitial Lung Diseases.
Archives of pathology & laboratory medicine
2019; 143 (1): 30-33
High-resolution computed tomography (HRCT) imaging has an increasingly important role in clinical decision-making in patients with interstitial lung diseases. The recent Fleischner Society white paper on the diagnostic criteria for idiopathic pulmonary fibrosis highlights the advances in our understanding of HRCT imaging in interstitial lung diseases.To discuss the evidence and recommendations outlined in the white paper as it pertains to the radiologic diagnosis of interstitial lung disease, specifically highlighting the current limitations of HRCT in confidently predicting histopathologic findings.The recent Fleischner Society white paper and other studies pertaining to the role of HRCT in predicting histopathology in interstitial lung diseases are reviewed.High-resolution computed tomography is highly predictive of a usual interstitial pneumonia (UIP) pattern on histopathology when the HRCT shows a typical UIP pattern on a "confident" read by the radiologist. A probable UIP pattern is also very predictive of a UIP pattern on histopathology, and histopathologic confirmation is not needed for most patients demonstrating this pattern in the appropriate clinical setting. A UIP pattern may be seen in a substantial proportion of patients with an "indeterminate UIP" pattern on HRCT and in many patients for whom the HRCT suggests an alternative diagnosis; histopathologic confirmation should be considered in patients demonstrating these patterns whenever feasible.
View details for DOI 10.5858/arpa.2018-0134-RA
View details for PubMedID 30785335
- Tissue Continues to Be the Issue Role of Histopathology in the Context of Recent Updates in the Radiologic Classification of Interstitial Lung Diseases ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE 2019; 143 (1): 30–33
Rituximab Versus Mycophenolate Mofetil in Interstitial Lung Disease Secondary to Connective Tissue Disease
View details for Web of Science ID 000447268902402
Surgical Lung Biopsy for Interstitial Lung Diseases.
2017; 151 (5): 1131-1140
This review addresses common questions regarding the role of surgical lung biopsy (SLB) in the diagnosis and treatment of interstitial lung disease (ILD). We specifically address when a SLB can be diagnostic as well as when it may be avoided; for example, when the combination of the clinical context and the imaging pattern seen on high-resolution CT (HRCT) chest scans can provide a confident diagnosis. Existing studies on the diagnostic utility as well as the complications associated with SLB are reviewed; also reviewed are the performance characteristics and reliability of HRCT scans of the chest in predicting the underlying histopathologic findings of the lung. The review is formatted in the form of answers to questions that clinicians regularly ask when considering an SLB in a patient with ILD.
View details for DOI 10.1016/j.chest.2016.06.019
View details for PubMedID 27471113
- Mortality Related to Surgical Lung Biopsy in Patients with Interstitial Lung Disease. The Devil Is in the Denominator. American journal of respiratory and critical care medicine 2016; 193 (10): 1082-4
- Hyperacute Methotrexate Pneumonitis in a Patient With Crohn's Disease. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association 2016; 14 (3): A29-30
The Frequency of Frailty in Ambulatory Patients With Chronic Lung Diseases.
Journal of primary care & community health
2016; 7 (1): 10–15
To determine the prevalence of frailty in patients with chronic lung diseases.We studied 120 patients with chronic lung disease using Fried's criteria (gait speed, weight loss, exhaustion, grip strength, and physical activity).The study population (56% women) had a mean age of 64 ± 13 years, mean body mass index of 31± 9 kg/m(2), and a mean FEV(1) (forced expiratory volume in 1 second) of 60% ± 25% of predicted. The average gait speed was 52.1 ± 14.3 m/min; 18% were frail, 64% prefrail, and 18% robust. Gait speed correlated with frailty status and decreased as frailty worsened (57 m/min in robust subjects and 41 m/min in frail subjects). Slow gait speeds (<60 m/min) had a 95% sensitivity and 34% specificity to predict frailty.Patients with chronic lung disease frequently meet Fried's criteria for frailty. Gait speed can be used to screen these patients to determine if a more detailed evaluation is needed.
View details for DOI 10.1177/2150131915603202
View details for PubMedID 26333537
View details for PubMedCentralID PMC5932671
Peripheral lung adenocarcinomas with KRAS mutations are more likely to invade visceral pleura.
Archives of pathology & laboratory medicine
2015; 139 (2): 189-93
Kirsten-RAS (KRAS) mutations play an important role in the carcinogenesis of a subset of lung adenocarcinomas and are associated with poorer prognosis.To investigate the relationship of KRAS mutation status to the histologic subtype of adenocarcinoma according to the recent classification, patient demographics, tumor size, predominant histologic subtype, nodal status, and visceral pleural invasion, in an attempt to uncover the reason for the worse prognosis associated with KRAS mutation.A total of 187 consecutive resected lung adenocarcinomas from our institution from 2008 to 2011 that were diagnosed according to the new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification and screened for KRAS mutations were included in the study.A total of 32% of the adenocarcinomas harbored the KRAS mutation. The median age in the KRAS mutation group was 69 years (range, 43-86 years), and male to female ratio was 1:2.3. The proportion of heavy smokers was significantly higher in tumors with KRAS mutation compared with wild type (83% versus 62%; P = .01). A total of 27% of tumors with KRAS mutation had pleural invasion versus 11% of tumors without KRAS mutation (P = .009). A total of 59 tumor samples were positive for KRAS mutation (25 for G12C, 14 for G12A, 8 for G12V, 7 for G12D, 3 for G12S, and 1 for G12T), and only 3 tumors harbored codon 13 mutations (G13C). Two tumors had double mutations.KRAS mutations are more common in heavy smokers, and lung adenocarcinomas with KRAS mutation are more likely to invade the visceral pleura. Increased frequency of visceral pleural invasion may explain in part the worse prognosis associated with KRAS mutations.
View details for DOI 10.5858/arpa.2013-0759-OA
View details for PubMedID 24694341
Bladder Pressure Measurements in Patients Admitted to a Medical Intensive Care Unit.
The American journal of the medical sciences
2015; 350 (3): 181–85
Intra-abdominal hypertension is identified as an independent risk factor for death. However, this pathophysiological state is not always considered in patients in medical intensive care units and is frequently underdiagnosed.Serial bladder pressure measurements were recorded in patients admitted to the medical intensive care units to determine the frequency of intra-abdominal hypertension.This study included 53 patients with a mean age of 59.0 ± 17.7 years. The average admission intra-abdominal pressure was 10.0 ± 5.4 mm Hg with a range of 0 to 28 mm Hg. Eleven patients (21%) had an initial pressure reading above normal (>12 mm Hg). Peak airway pressures were higher, and PaO2/FiO2 ratios were lower in patients with an initial pressure >12 mm Hg.Bladder pressure measurements provide an easy method to estimate intra-abdominal pressures and provide an additional tool for the physiologic assessment of critically ill patients.
View details for DOI 10.1097/MAJ.0000000000000543
View details for PubMedID 26309180
Correlation of EGFR mutation status with predominant histologic subtype of adenocarcinoma according to the new lung adenocarcinoma classification of the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society.
Archives of pathology & laboratory medicine
2014; 138 (10): 1353-7
Epidermal growth factor receptor (EGFR) mutations have been identified as predictors of response to EGFR tyrosine kinase inhibitors in non-small cell lung cancer.To investigate the relationship of EGFR mutation status to the histologic subtype of adenocarcinoma according to the new International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) classification.We screened EGFR mutation in 200 consecutive lung adenocarcinoma resection specimens diagnosed between 2008 and 2011.Among 200 lung adenocarcinomas, EGFR mutations were identified in 41 tumors (20.5%). The mean age in the EGFR-mutant group was 64.8 years and this group consisted of 78% females and 22% males. Most patients with EGFR-positive lung cancers were never-smokers (51%) as compared to 8% with EGFR-negative cancers (P < .001). The most common mutations identified in our population were deletions in exon 19 (22 patients) and L858R in exon 21 (12 patients). Five patients had double mutations. The predominant pattern of adenocarcinoma was lepidic (44%) in EGFR-mutant lung cancers as compared to 69% with acinar pattern in EGFR wild-type lung cancers (P < .001). Of 22 minimally invasive adenocarcinomas, 8 (36%) had EGFR mutations, accounting for 20% of adenocarcinomas with EGFR mutations (P < .05).Based on the new IASLC/ATS/ERS classification, the predominant subtype of adenocarcinoma was lepidic (44%) in EGFR-mutant lung cancers (P < .001). However, histologic subtype should not be used to exclude patients from tyrosine kinase inhibitor therapy, since EGFR mutations are found in lung adenocarcinomas of other subtypes.
View details for DOI 10.5858/arpa.2013-0376-OA
View details for PubMedID 24571650
- Refractory IgG4-related lung disease with constitutional symptoms and severe inflammation. American journal of respiratory and critical care medicine 2014; 189 (3): 374-5
- Reply: Refractory IgG4-related lung disease with constitutional symptoms and severe inflammation. American journal of respiratory and critical care medicine 2014; 189 (3): 375-6
The repeatability of gait speed and physiological cost index measurements in working adults.
Journal of primary care & community health
2014; 5 (2): 128–33
To determine the performance characteristics of gait speed measurements and the physiological cost index (PCI; heart rate change/gait speed) in working adults.Gait speeds, heart rate changes, and non-steady state PCIs were calculated in 61 volunteers who worked in our health sciences center. These subjects completed 9 separate 100-foot walk tests in 3 separate sessions.The mean heart rate change after a 100-foot walk was 16.6 ± 8.1 beats per minute. The mean gait speed was 76.1 ± 9.6 meters per minute, and the mean PCI was 0.22 ± 0.11 beats per meter. There were highly significant correlations among all measurements on the 9 separate tests (correlation coefficients 0.41-0.95); gait speed measurements had the highest correlations (0.91-0.95). In a multivariable model hypertension and arthritis were associated with reduced gait speeds.Gait speed, heart rate changes, and non-steady state PCIs have good repeatability when measured over short walks. This information provides a rapid physiological assessment and a method for measuring changes in functional status in healthy subjects and most patients.
View details for DOI 10.1177/2150131913506226
View details for PubMedID 24327593
- Numerical Simulations of High-Frequency Respiratory Flows in 2D and 3D Lung Bifurcation Models INTERNATIONAL JOURNAL FOR COMPUTATIONAL METHODS IN ENGINEERING SCIENCE & MECHANICS 2014; 15 (4): 337–44
Accelerometer-based devices can be used to monitor sedation/agitation in the intensive care unit.
Journal of critical care
2014; 29 (5): 748–52
Monitoring sedation/agitation levels in patients in the intensive care unit (ICU) are important to direct treatment and to improve outcomes. This study was designed to determine the potential use of accelerometer-based sensors/devices to objectively measure sedation/agitation in patients admitted to the ICU.Accelerometer-based devices (actigraphs) were placed on nondominant wrists of 86 patients in the ICU after informed consent. The sedation/agitation levels were classified as deep sedation, light sedation, alert and calm, mild agitation and severe agitation, and measured at regular intervals. The sedation/agitation levels were correlated with the accelerometer data (downloaded raw actigraphy data).The sedation/agitation levels correlated strongly with the accelerometer readings represented by mean actigraphy counts (r = 0.968; P = .007) and the proportion of time spent moving as determined by actigraphy (r = 0.979; P = .004).Accelerometer data correlate strongly with the sedation/agitation levels of patients in the ICUs, and appropriately designed accelerometer-based sensors/devices have the potential to be used for automating objective and continuous monitoring of sedation/agitation levels in patients in the ICU.
View details for DOI 10.1016/j.jcrc.2014.05.014
View details for PubMedID 24973100
Modeling the relation between obesity and sleep parameters in children referred for dietary weight reduction intervention.
Southern medical journal
2014; 107 (8): 473–80
Cross-sectional and longitudinal studies have demonstrated that short sleep periods increase the likelihood of obesity in children. This study was designed to identify other less-clearly defined sleep and behavioral patterns associated with changes in body mass index (BMI) in obese children referred for interventions.We retrospectively reviewed the clinic records of children with obesity and children at risk for developing obesity who were referred for counseling and weight loss. Information on sleep habits, pediatric quality of life, pediatric sleep questionnaire (PSQ), and the pediatric daytime sleepiness scale were analyzed, and children were distributed into three behavior groups using cluster analysis.Our sample contained 48 girls and 29 boys with an age range of 2.7 to 16.8 years. The mean BMI was 33.08 ± 7.37 kg/m(2), and mean sleep duration was 9.09 ± 1.09 hours. Multivariate analysis revealed a significant interaction between sleep duration and age when the child was older than 12 years. A 1-hour increase in sleep in older children was associated with a decrease in BMI of 1.263 kg/m(2). Higher (more abnormal) pediatric quality-of-life school scores, higher PSQ1 and PSQ2 scores, and higher pediatric daytime sleepiness scale scores were associated with an increased BMI in univariate analyses but not in the multivariate analysis using the behavior group as an independent predictor. Children who shared a bedroom had a lower BMI in univariate analysis but not in the multivariate analysis.Longer sleep periods are associated with a decreased BMI, even in children who already meet the criteria for obesity. These children have poor-quality sleep, diurnal behavioral problems, and increased diurnal sleepiness. This study suggests that studies in obese children using questionnaires about sleep habits and quality of life provide useful information that could lead to better weight loss intervention studies.
View details for DOI 10.14423/SMJ.0000000000000145
View details for PubMedID 25084183
Characterization of sleep patterns and problems in healthcare workers in a tertiary care hospital.
Southern medical journal
2014; 107 (1): 11–16
Restrictions in sleep can have important adverse effects on health and job performance. We collected information about sleep from US healthcare workers to determine whether they had sleep difficulties.We used an Internet-based survey to collect information on sleep patterns and sleep quality in healthcare workers at a tertiary care hospital. We classified these workers into short sleepers (<7 hours), normal sleepers (7-8 hours), and long sleepers (≥9 hours). We compared these three groups using simple descriptive statistics. We used logistic regression to identify factors associated with short sleep times.Of 3012 questionnaires distributed, 376 healthcare workers (12.5%) replied to this survey. The median age was 38 years, the median body mass index was 28 kg/m, and 76% were women. The median sleep duration on weekdays was 7 hours. Sixty-nine respondents (18.4%) were short sleepers, 269 of the respondents (71.5%) were normal sleepers, and 38 respondents (10.1%) were long sleepers. A total of 113 (30.1%) had sleep difficulties more than 50% of the time and 140 respondents (37.3%) were bothered by lack of energy from poor sleep. Short sleepers were less likely than other types of sleepers to have normal bedtimes and regular mealtimes. Eighty-four respondents (22.3%) went to bed between 2 AM and 2 PM. These workers were younger; slept less on the weekdays and weekends; and reported more difficulty with sleeping, feeling depressed, overconsumption of alcoholic beverages, and personal stressors.Most healthcare workers have healthy sleep patterns; however, many workers have poor sleep quality. Workers with "odd" bedtimes have abnormal sleep patterns and abnormal sleep quality; these workers need additional evaluation to understand the causes and consequences of their sleep patterns.
View details for DOI 10.1097/SMJ.0000000000000041
View details for PubMedID 24389779
Leflunomide-induced interstitial lung disease (a systematic review).
Sarcoidosis, vasculitis, and diffuse lung diseases : official journal of WASOG
2013; 30 (3): 167-76
Leflunomide, a disease modifying anti-rheumatic drug in use since 1998, causes interstitial lung disease (ILD) and other pulmonary complications.We undertook a systematic review of literature of PubMed (March 2013) to identify the published literature pertaining to pulmonary toxicity associated with leflunomide.We identified 41 relevant articles detailing four population studies and case reports/series on an additional 42 patients. Available data were reviewed and summarized.Leflunomide can cause ILD. Most of these patients present within three months of starting leflunomide with acute symptoms for a week or less. Bilateral ground glass opacities and diffuse alveolar damage are the most common radiologic and histopathologic findings, respectively. Patients with pre-existing ILD are particularly at risk for this complication, and leflunomide should be avoided in this population. Activated charcoal and cholestyramine significantly decrease the half-life of the drug because of its enterohepatic circulation and should be considered in cases with acute toxicity.
View details for PubMedID 24284289
- IgG4-related lung disease. American journal of respiratory and critical care medicine 2013; 188 (5): 527-9
Oropharyngeal flora in patients admitted to the medical intensive care unit: clinical factors and acid suppressive therapy.
Journal of medical microbiology
2013; 62 (Pt 5): 778–84
Acid suppression therapy in critically ill patients significantly reduces the incidence of stress ulceration and gastrointestinal (GI) bleeding; however, recent studies suggest that proton pump inhibitors (PPIs) increase the risk of pneumonia. We wanted to test the hypothesis that acid suppressive therapy promotes alteration in the bacterial flora in the GI tract and leads to colonization of the upper airway tract with pathogenic species, potentially forming the biological basis for the observed increased incidence of pneumonia in these patients. This was a prospective observational study on patients (adults 18 years or older) admitted to the medical intensive care unit (MICU) at a tertiary care centre. Exclusion criteria included all patients with a diagnosis of pneumonia at admission, with infection in the upper airway, or with a history of significant dysphagia. Oropharyngeal cultures were obtained on day 1 and days 3 or 4 of admission. We collected data on demographics, clinical information, and severity of the underlying disease using APACHE II scores. There were 110 patients enrolled in the study. The mean age was 49±16 years, 50 were women, and the mean APACHE II score was 9.8 ± 6.5. Twenty per cent of the patients had used a PPI in the month preceding admission. The first oropharyngeal specimen was available in 110 cases; a second specimen at 72-96 h was available in 68 cases. Seventy-five per cent of the patients admitted to the MICU had abnormal flora. In multivariate logistic regression, diabetes mellitus and PPI use were associated with abnormal oral flora on admission. Chronic renal failure and a higher body mass index reduced the frequency of abnormal oral flora on admission. Most critically ill patients admitted to our MICU have abnormal oral flora. Patients with diabetes and a history of recent PPI use are more likely to have abnormal oral flora on admission.
View details for DOI 10.1099/jmm.0.053066-0
View details for PubMedID 23378561
Risk factors of Candida colonization in the oropharynx of patients admitted to an intensive care unit.
Journal de mycologie medicale
2012; 22 (4): 301-7
Candida colonization is an important precursor for candidiasis. However, there is little information about its risk factors in critically ill patients. We aimed to identify risk factors for oropharyngeal Candida colonization in critically ill patients.This is a prospective observational study of 110 patients admitted to a medical intensive care unit (MICU). Oropharyngeal swabs were obtained on day one and day four. Characteristics of patients colonized with Candida species at admission or not colonized were compared. In addition, patients becoming colonized during their ICU stay were compared to patients who did not.Independent risk factors for a positive Candida sample at the time of admission were: a history of proton pump inhibitor (PPI) use before admission (OR: 5.24, 95% CI: 1.36-20.19), the presence of diabetes mellitus (OR: 2.84, 95%CI: 1.02-7.92) and a lower BMI (OR: 0.9, 95% CI: 0.84-0.97). Chronic kidney disease was associated with a decreased frequency of Candida colonization (OR: 0.26, 95% CI: 0.01-0.46). No independent risk factors could be identified for patients who gained Candida during their ICU hospitalization. Patients with Candida colonization frequently had abnormal oral bacterial flora.Diabetes mellitus, PPI use and a lower BMI are risk factors for Candida colonization in critically ill patients being admitted to the MICU.
View details for DOI 10.1016/j.mycmed.2012.08.001
View details for PubMedID 23518163
- Vagus nerve stimulator-induced apneas and hypopneas in a child with refractory seizures JOURNAL OF PEDIATRIC NEUROLOGY 2012; 10 (1): 53–56
Patterns of use of prophylaxis for stress-related mucosal disease in patients admitted to the intensive care unit.
Journal of intensive care medicine
2012; 29 (2): 96–103
Morbidity associated with stress ulcer-related bleeding, the cost of medications, and the possible complications associated with stress ulcer prophylaxis are important considerations when prescribing prophylaxis. We prospectively studied the prescription patterns for stress ulcer prophylaxis in patients admitted to our ICU.We prospectively recorded the indications for stress ulcer prophylaxis and prescription patterns for use based on the American Society of Healthcare Pharmacists criteria and other indications for 99 new intensive care unit (ICU) admissions to a tertiary referral center.In all 51 patients had no indication for stress ulcer prophylaxis, 32 had 1 indication, 14 had 2 indications, and 2 patients had 3 indications for receiving stress ulcer prophylaxis in the ICU. Eighty-two percent of patients without any indications received stress ulcer prophylaxis; 81% of patients with 1 indication, 79% of patients with 2 indication, and 50% of patients with 3 indications received stress ulcer prophylaxis. Overall, 53% of patients either received stress ulcer prophylaxis when none was indicated or did not receive stress ulcer prophylaxis when it was indicated. We also review the recent literature on stress-related mucosal disease and the use of prophylaxis for stress-related mucosal disease.Stress ulcer prophylaxis administration in this ICU is inconsistent and includes both underutilization and overutilization. Educating physicians and implementing hospital protocols could improve use patterns.
View details for DOI 10.1177/0885066612453542
View details for PubMedID 22786980
Sirolimus induced granulomatous interstitial pneumonitis.
Respiratory medicine case reports
2012; 7: 8–11
Report a case of sirolimus induced granulomatous pneumonitis.Sirolimus is used in clinical transplantation as an immunosuppressive agent. Pulmonary toxicity does occur, but only a few cases of sirolimus associated granulomatous interstitial pneumonitis have been reported.Case report and literature review.This 53-year-old woman with ESRD from polycystic kidney disease status post deceased donor kidney transplantation presented with fever, progressive dyspnea, and hypoxia for two weeks. She had been switched to sirolimus two months before admission. A CT scan of the chest revealed bilateral ill-defined patchy ground glass opacities. Extensive investigations were negative for infection. Video-assisted thoracoscopic biopsy showed granulomatous interstitial pneumonitis. Her symptoms and infiltrates resolved after sirolimus discontinuation and corticosteroid treatment.Drugs induced pneumonitis should always be considered in transplant patients after infectious or other etiologies have been excluded. Sirolimus can cause granulomatous infiltrates in the lung possibly secondary to T-cell mediated hypersensitivity.
View details for DOI 10.1016/j.rmcr.2012.09.002
View details for PubMedID 26029599
View details for PubMedCentralID PMC3920426
Obstructive sleep apnea and respiratory complications associated with vagus nerve stimulators.
Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine
2011; 7 (4): 401–7
Intermittent vagus nerve stimulation can reduce the frequency of seizures in patients with refractory epilepsy. Stimulation of vagus nerve afferent fibers can also cause vocal cord dysfunction, laryngeal spasm, cough, dyspnea, nausea, and vomiting. Vagus nerve stimulation causes an increase in respiratory rate, decrease in respiratory amplitude, decrease in tidal volume, and decrease in oxygen saturation during periods of device activation. It usually does not cause an arousal, or a change in heart rate or blood pressure. Most patients have an increase in their apnea-hypopnea index (AHI). Patients with VNS can have central apneas, obstructive hypopneas, and obstructive apneas. These respiratory events can be reduced with changes in the vagus nerve stimulator operational parameters or with the use of CPAP. In summary, there are complex relationships between epilepsy and obstructive sleep apneas. In particular, patients with refractory epilepsy need assessment for undiagnosed and untreated obstructive sleep apnea before implantation of vagus nerve stimulator devices. Patients with vagus nerve stimulators often have an increase in apneic events after implantation, and these patients need screening for sleep apnea both before and after implantation.
View details for DOI 10.5664/JCSM.1204
View details for PubMedID 21897779
View details for PubMedCentralID PMC3161774
- Low-dose oral interferon α possibly retards the progression of idiopathic pulmonary fibrosis and alleviates associated cough in some patients. Thorax 2011; 66 (5): 446–47
Hyperthyroidism and pulmonary hypertension: an important association.
The American journal of the medical sciences
2011; 342 (6): 507–12
Pulmonary hypertension is a complex disorder with multiple etiologies. The World Health Organization Group 5 (unclear multifactorial mechanisms) includes patients with thyroid disorders. The authors reviewed the literature on the association between hyperthyroidism and pulmonary hypertension and identified 20 publications reporting 164 patients with treatment outcomes. The systolic pulmonary artery (PA) pressures in these patients ranged from 28 to 78 mm Hg. They were treated with antithyroid medications, radioactive iodine and surgery. The mean pretherapy PA systolic pressure was 39 mm Hg; the mean posttreatment pressure was 30 mm Hg. Pulmonary hypertension should be considered in hyperthyroid patients with dyspnea. All patients with pulmonary hypertension should be screened for hyperthyroidism, because the treatment of hyperthyroidism can reduce PA pressures, potentially avoid the side-effects and costs with current therapies for pulmonary hypertension and limit the consequences of untreated hyperthyroidism. However, the long-term outcome in these patients is uncertain, and this issue needs more study. Changes in the pulmonary circulation and molecular regulators of vascular remodeling likely explain this association.
View details for DOI 10.1097/MAJ.0b013e31821790f4
View details for PubMedID 22112709
Prolonged acute care in a 52-year-old man with respiratory failure: lessons learned from 70-day intensive care unit hospitalization.
Journal of critical care
2011; 26 (5): 532.e9–532.e16
This study was undertaken to record the experiences of a patient who survived prolonged intensive care unit (ICU) care secondary to acute respiratory failure.The patient's medical record was summarized, and the patient was interviewed with audio recording and transcription. He completed several surveys, including the ICU memory tool, the 14-question Posttraumatic Stress Syndrome Questionnaire, the Impact of Event Scale-Revised Questionnaire, and the Hospital Anxiety and Depression Scale Questionnaire.The patient had little factual recall of his prolonged ICU care but had multiple delusional memories from this period. The Impact of Event Scale-Revised results indicate that this hospitalization had significant impact. However, his scores on the 14-question Posttraumatic Stress Syndrome and Hospital Anxiety and Depression Scale questionnaires indicate that his risk for posttraumatic stress disorder, anxiety, and depression is low. These outcomes were attributed, in part, to his willingness to discuss his ICU care and experiences with health care workers, family, and friends.Patient debriefing may improve outcomes after prolonged acute care. Current survey instruments provide a good estimate of a patient's mental status. Patients themselves can provide important information about hospital care and areas needing improvement.
View details for DOI 10.1016/j.jcrc.2010.11.006
View details for PubMedID 21439761
- Abdominal Wall Hematoma Following Paracentesis NATURE PUBLISHING GROUP. 2010: S278–S279
Amiodarone-induced loculated pleural effusion: case report and review of the literature.
2010; 30 (2): 218
Pleural effusion is an uncommon manifestation of amiodarone toxicity and is usually associated with amiodarone-induced interstitial pneumonitis. We describe a 70-year-old woman who came to the emergency department with bilateral pleuritic chest pain and malaise 4 weeks after her amiodarone dose was increased from 200 mg/day to 600 mg/day. She had bilateral exudative pleural effusions without associated pneumonitis. She was diagnosed with amiodarone-induced pleural effusions after a thorough workup during her hospitalization excluded other causes for the effusions. Due to intractable arrhythmias, the patient's amiodarone was not discontinued, and she was discharged home. Four days later at a follow-up visit at the pulmonary clinic, the patient complained of worsening chest pain as well as dyspnea and cough. A computed tomography scan showed left-sided pleural effusion with multiple loculations. She underwent a pulmonary vein isolation procedure, and amiodarone was discontinued. She was treated with prednisone 40 mg/day, tapered over the next 2 weeks. Three weeks after the amiodarone was stopped, the patient was asymptomatic, and a chest radiograph showed complete resolution of the effusions. Review of the patient's medical records revealed that she had experienced similar symptoms and exudative pleural effusions 2 years earlier after a similar dose escalation of amiodarone; the symptoms and pleural effusions resolved after the amiodarone dosage was reduced. Use of the Naranjo adverse drug reaction probability scale indicated that the association between the pleural effusions and amiodarone was highly probable (score of 9). This case report emphasizes that amiodarone should be considered in the differential diagnosis of patients with exudative effusions after a thorough workup has excluded other causes. Amiodarone should be replaced with alternative antiarrhythmic therapy if clinically feasible, and corticosteroids may be beneficial.
View details for DOI 10.1592/phco.30.2.218
View details for PubMedID 20099996
Lenalidomide-induced interstitial lung disease.
2010; 30 (3): 325
Lenalidomide is a more potent and less toxic oral analog of thalidomide. The drug is indicated for treatment of multiple myeloma and other hematologic disorders and has rarely been associated with pulmonary toxicity. We describe a 73-year-old woman who received lenalidomide therapy for multiple myeloma. Nine weeks after starting the drug, she developed progressive dyspnea, cough, and constitutional symptoms, and was found to be hypoxic. A computed tomography scan of the chest showed bilateral interstitial infiltrates. Bronchoalveolar lavage was negative for infection, but transbronchial biopsy showed an organizing pneumonia. The patient was diagnosed with lenalidomide-induced interstitial lung disease after other causes were excluded. Clinical and radiologic resolution occurred after lenalidomide was discontinued and a tapering course of corticosteroids was begun. Use of the Naranjo adverse drug reaction probability indicated a high probability (score of 7) that this adverse drug reaction was caused by lenalidomide. Lenalidomide inhibits prostaglandin E(2) (PGE(2)) secretion by cells. If fibroblast PGE(2) synthesis is impaired in the lung, the mitogenic action of cysteinyl leukotrienes may be unmasked, promoting fibroblast proliferation and collagen synthesis, eventually leading to interstitial lung disease. Another potential mechanism may be an immunologic one similar to that seen in the interstitial pulmonary process in patients with hypersensitivity pneumonitis. To our knowledge, only one other case of lenalidomide-induced pulmonary toxicity has been reported in the literature. Although lenalidomide-induced pulmonary toxicity is uncommon, clinicians should consider this potential adverse drug reaction in the differential diagnosis in patients receiving lenalidomide who present with symptoms of interstitial lung disease for which alternative causes have been excluded.
View details for DOI 10.1592/phco.30.3.325
View details for PubMedID 20180616
- Advanced locally invasive squamous cell carcinoma. The American journal of the medical sciences 2009; 338 (1): 68
Novel swine-origin (S-OIV) H1N1 influenza A pneumonia in a lung transplant patient: a case report and review of the literature on performance characteristics of rapid screening tests for the S-OIV.
The American journal of the medical sciences
2009; 338 (6): 506–8
Rapid screening tests are insensitive for detecting the novel swine-origin influenza A (H1N1) virus (S-OIV), and false negatives can delay the diagnosis and initiation of appropriate antiviral therapy. The case of a 26-year-old double lung transplant recipient presenting with fever, bilateral pulmonary infiltrates, and a negative influenza direct immunofluorescent antibody on bronchoalveolar lavage is presented. A diagnosis was made, and antiviral therapy was started 10 days after the initial bronchoalveolar lavage on receipt of a positive culture for S-OIV. The published literature on the performance characteristics of rapid screening tests for S-OIV is reviewed in this clinical context.
View details for DOI 10.1097/MAJ.0b013e3181c78a64
View details for PubMedID 20010157
One hundred-foot walk test for functional assessment of clinic patients.
The American journal of the medical sciences
2009; 338 (5): 361–67
Gait velocity measurements provide functional assessment of patients with diverse diseases and allow predictions about future adverse events. The optimal distance for patient classification is uncertain.Participants were identified in internal medicine clinics and had to be independently ambulatory. Study investigators collected medical information, used a qualitative test to assess gait and balance (G and B score), and measured gait velocity with a timed 100-foot walk.One hundred eighty-four patients participated in this study. The mean age was 57.8 +/- 12.7 years; 50% of the participants were men. The mean gait speed was 3.33 +/- 0.71 ft/sec. Gait speed decreased with age and with body mass index (BMI) and increased with height and male sex. Patients with more comorbidities had decreased speed (P < 0.01). There were significant correlations between gait speed and grip strength (P < 0.01) and between lower G and B scores and slower gait speeds (P < 0.01). G and B scores were negatively correlated with age, BMI, and certain diagnoses. They also predicted risk for past falls. The mean heart rate change during the test was 8 beats per minute. Patients in the highest quartile for heart rate change had lower gait speeds than patients in the other 3 quartiles, suggesting physiologic impairment.A 100-foot walk test in clinic patients provides a practical functional assessment. Gait speed was slower in patients with multiple comorbidities and poor balance. Patients with increased heart rate responses during this test seem to have physiologic impairment. This test has the potential to predict adverse events and to quantitatively determine responses to therapeutic interventions but needs prospective evaluation in clinical studies.
View details for DOI 10.1097/MAJ.0b013e3181b2b4ff
View details for PubMedID 19794306
- Unusual pulmonary complication from Maloney dilation BLACKWELL PUBLISHING. 2007: S417
Lung retransplantation after posttransplantation lymphoproliferative disorder (PTLD): a single-center experience and review of literature of PTLD in lung transplant recipients.
The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation
2005; 24 (6): 671-9
Retransplantation in adult lung transplant recipients developing progressive bronchiolitis obliterans syndrome as a consequence of posttransplantation lymphoproliferative disorder (PTLD) therapy has not been reported in the literature. Literature on PTLD after lung transplantation is limited mostly to case reports or small case series, limiting the validity of conclusions.Retrospective chart review of patients at our center. Analysis of pooled data published on lung transplant patients developing PTLD.Two patients who underwent pulmonary retransplants for PTLD have functioning grafts 23 and 36 months postoperatively, with no evidence of PTLD recurrence. Review and analysis of published data and from our center revealed that incidence of PTLD, proportion of patients with thoracic involvement, and proportion of patients who were Epstein-Barr virus seronegative before transplantation decreased continuously as a function of time from transplant. Patients developing PTLD within the first 6 months after transplantation had a clinically distinct pattern of PTLD and a significantly better survival than patients developing PTLD more than 6 months after lung transplant.Lung retransplantation can be considered after careful selection for lung transplant recipients developing bronchiolitis obliterans syndrome as a consequence of reduced immunosuppression for PTLD. Acquisition of PTLD and pattern of organ involvement is a continuous process as a function of time. Defining "early PTLD" as occurring in the first 6 months more accurately predicts progress and prognosis of this disease than the traditional 1 year definition of early vs late onset PTLD.
View details for DOI 10.1016/j.healun.2004.04.011
View details for PubMedID 15949726
Effect of the new Medicare guideline on patient qualification for positive airway pressure therapy.
2003; 4 (1): 29-33
New Medicare criteria for prescribing continuous positive airway pressure (CPAP) recognize hypopnea as a sleep disordered breathing event. In so doing, hypopnea was redefined as requiring a 4% oxygen desaturation. The criteria omit electroencephalogram (EEG) arousals from the definition. This study was designed to assess how the new Medicare guideline changes CPAP eligibility.Polysomnograms from 113 consecutive patients with obstructive sleep apnea were scored using both a definition for hypopnea that considered EEG arousals and the new Medicare definition that does not consider EEG arousal. CPAP eligibility was evaluated and compared.Sixteen percent of all patients and 41% of patients apnea+hypopnea index =20 did not qualify for CPAP under the new Medicare guidelines.The new Medicare guidelines may underestimate OSA event occurrence and thereby deny CPAP therapy to many patients.
View details for DOI 10.1016/s1389-9457(02)00150-8
View details for PubMedID 14592357
Systemic lupus erythematosus in the intensive care unit.
Critical care clinics
2002; 18 (4): 781-803
SLE causes significant morbidity and mortality by multisystem organ involvement. Infections are the leading cause of morbidity and mortality in patients with SLE. Meticulous exclusion of infection is mandatory in patients with SLE, because infections may masquerade as exacerbation of underlying disease; and the immunosuppression used to treat severe forms of exacerbation of lupus can have catastrophic consequences in patients with infections. Corticosteroids are the first-line therapy for most noninfectious complications of SLE, with various adjuvant immunosuppressive agents such as cyclophosphamide being increasingly used in combination with plasmapheresis. Some recent series have shown an improved survival rate, but this improvement needs to be confirmed by further studies. Controlled trials comparing various therapeutic options are lacking, and optimal therapy has not been defined.
View details for DOI 10.1016/s0749-0704(02)00024-6
View details for PubMedID 12418441
Scedosporium apiospermum fungemia in a lung transplant recipient.
2002; 121 (5): 1714-6
Scedosporium apiospermum, the asexual anamorph of the cosmopolitan fungus Pseudallescheria boydii, is emerging as an important cause of disseminated infection in immunocompromised patients. We present our experience with the first reported case of S apiospermum fungemia in a lung transplant patient. Disseminated infection resulted in sepsis, multiorgan failure, and death. Review of the literature highlights the diagnostic difficulties related to the similarities between S. apiospermum and Aspergillus sp. This superficial resemblance has a significant impact on clinical outcomes considering the inherent resistance of Scedosporium to amphotericin B, the traditional antifungal of choice for disseminated hyalohyphomycoses.
View details for DOI 10.1378/chest.121.5.1714
View details for PubMedID 12006471
Human immunodeficiency virus infections in adolescents.
Adolescent medicine (Philadelphia, Pa.)
2000; 11 (2): 359-74
Human immunodeficiency virus (HIV) infection, once largely confined to adolescents with hemophilia, has come to involve the general adolescent population. Individuals younger than 22 years comprise up to 25% of the people newly infected with HIV. Unsafe sexual practices, intravenous drug abuse, homelessness, psychiatric disorders, and inadequate psychosocial support are only some of the factors that have contributed to the epidemic. Present data indicate that interventions have had a positive impact on adolescent behavior in preventing the continuing spread of the disease, but more needs to be accomplished before we consider the problem controlled. Although proper medical treatment and providing adequate psychological and social support to adolescents who are already infected constitute an important aspect of care, the true solution of the problem lies in altering the behavior and practices that lead to the acquisition of this infection.
View details for PubMedID 10916129
- A piece of my mind. Crossing over. JAMA 1997; 278 (21): 1721