Pulmonary Division Research Articles

Dramatic Reversal of Lymphocytic Interstitial Pneumonitis in Sjögren’s Syndrome With Rituximab

From the Divisions of *Pulmonary and Critical Care Medicine and †Rheumatology, Penn Presbyterian Medical Center, and ‡Penn Sjögren’s Syndrome Center, University of Pennsylvania School of Medicine, Philadelphia,PA. No funding was received for this study. The authors declare no conflict of interest. Correspondence: Morris A. Swartz, MD, Division of Pulmonary and Critical Care Medicine, Penn Presbyterian Medical Center, 51 N 39th St, Philadelphia, PA 19104. E-mail: [email protected].

History of the Vertebral Venous Plexus and the Significant Contributions of Breschet and Batson

Before the 18th century, the vertebral venous plexus (VVP) received scant mention, had no clinical relevance, and was largely ignored by anatomists, most likely because of its location and nondistensible nature. Gilbert Breschet in 1819 provided the first detailed anatomic description of the VVP, describing it as a large plexiform valveless network of vertebral veins consisting of 3 interconnecting divisions and spanning the entire spinal column with connections to the cranial dural sinuses distributed in a longitudinal pattern, running parallel to and communicating with the venae cavae, and having multiple interconnections. More than a century passed before any work of significance on the VVP was noted. In 1940, Oscar V. Batson reported the true functionality of the VVP by proving the continuity of the prostatic venous plexus with the VVP and proposed this route as the most plausible explanation for the distribution of prostate metastatic disease. With his seminal work, Batson reclassified the human venous system to consist of the caval, pulmonary, portal, and vertebral divisions. Further advances in imaging technology confirmed Batson's results. Today, the VVP is considered part of the cerebrospinal venous system, which is regarded as a unique, large-capacitance, valveless plexiform venous network in which flow is bidirectional that plays an important role in the regulation of intracranial pressure with changes in posture and in venous outflow from the brain, whereas in disease states, it provides a potential route for the spread of tumor, infection, or emboli.

The Wisdom of the PHAROS

In The Hermetica: The Lost Wisdom of the Pharaohs , Timothy Freke and Peter Gandy present a translation of the Greco-Egyptian sage Hermes Trismegistus’s writings1. Thought to have been written around 3000 BC, these teachings encompass the mystical philosophy of ancient Egypt and have been ascribed as inspiration for artists, philosophers, and scientists such as Leonardo da Vinci, Carl Jung, and Sir Isaac Newton. While the current study in this issue of The Journal may not have the same far-reaching impact, the potential for advancement of our understanding of pulmonary vascular disease related to systemic sclerosis (SSc) is significant. If the efficient study of rare diseases is quite challenging, the study of the intersection of 2 rare diseases is nearly impossible. SSc, with an estimated incidence of less than 20 persons per million per year in the United States, is significantly less common than other rheumatologic diseases such as systemic lupus erythematosus and rheumatoid arthritis, whose incidence in the US population is estimated at around 50 persons per million and over 300 persons per million, respectively2,3. While the incidence of pulmonary arterial hypertension (PAH) remains unknown in the US, results from the national registry in France suggest an incidence of 2.4 cases per million; this estimate includes persons with various forms of PAH including those related to connective tissue diseases4. In cohort studies of patients with SSc, the prevalence of PAH ranges from 8% to 14% when the diagnosis is based upon right heart catheterization (RHC)5. Despite its relatively low prevalence, PAH remains the second most common cause of death … Address correspondence to Dr. S. Mathai, Johns Hopkins University School of Medicine, Division of Pulmonary and Critical Care Medicine, 1830 E. Monument St., Room 516, Baltimore, MD 21205; E-mail: smathai4{at}jhmi.edu

Antibiotics in sepsis: Timing, appropriateness, and (of course) timely recognition of appropriateness*

Pulmonary, Allergy, and Critical Care Division, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA (Mikkelsen) Department of Emergency Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA (Gaieski) The authors have not disclosed any potential conflicts of interest.

Procalcitonin and pulmonary aspiration: Another possible interpretation

The Veterans Affairs Western New York Healthcare System, Buffalo, NY; and Western New York Respiratory Research Center, Division of Pulmonary, Critical Care, and Sleep Medicine, Departments of Medicine and Anesthesiology, Buffalo, NY

A Dozen Eggs

On Being a Doctor3 May 2011A Dozen EggsGulshan Sharma, MD, MPHGulshan Sharma, MD, MPHFrom The University of Texas Medical Branch at Galveston, Galveston, TX 77555-0561.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-154-9-201105030-00011 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Not every physician gets patted down daily in his own hospital. The security guard ran his fingers over my picture ID to ensure authenticity.“Sir, you are clear to enter.”As I walked the long tunnel connecting the outside world to the prison hospital, I couldn't prevent mixed feelings, but there was no time to explore them. At the end of the tunnel, I was buzzed in through a second hefty barred door. It opened into a circular enclosure housing the “command center,” manned by a uniformed guard. Seven doors defined the perimeter, with each door definitively shut. I stood ... Author, Article, and Disclosure InformationAffiliations: From The University of Texas Medical Branch at Galveston, Galveston, TX 77555-0561.Corresponding Author: Gulshan Sharma, MD, MPH, Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, The University of Texas Medical Branch at Galveston, 301 University Boulevard, JSA-5.112, UTMB, Galveston, TX 77555-0561. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 3 May 2011Volume 154, Issue 9Page: 640-641KeywordsChemotherapyEmotionsHispanic peopleIntensive care unitsNursesNutrientsOutpatient clinicsOxygenRespiratory rateWalking ePublished: 3 May 2011 Issue Published: 3 May 2011 Copyright & PermissionsCopyright © 2011 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...

Predictors of Response to a Nasal Expiratory Resistor Device and Its Potential Mechanisms of Action for Treatment of Obstructive Sleep Apnea

A one-way nasal resistor has recently been shown to reduce sleep disordered breathing (SDB) in a subset of patients with Obstructive Sleep Apnea Hypopnea Syndrome (OSAHS). The purpose of this study was to examine characteristics predictive of therapeutic response to the device and provide pilot data as to its potential mechanisms of action. PATIENTS, INTERVENTIONS, AND MEASUREMENTS: 20 subjects (15M/5F, age 54 ± 12 years, BMI 33.5 ± 5.6 kg/m²) with OSAHS underwent 3 nocturnal polysomnograms (NPSG) including diagnostic, therapeutic (with a Provent® nasal valve device), and CPAP. Additional measurements included intranasal pressures and PCO₂, closing pressures (Pcrit), and awake lung volumes in different body positions. In 19/20 patients who slept with the device, RDI was significantly reduced with the nasal valve device compared to the diagnostic NPSG (27 ± 29/h vs 49 ± 28/h), with 50% of patients having an acceptable therapeutic response. Among demographic, lung volume, or diagnostic NPSG measures or markers of collapsibility, no significant predictors of therapeutic response were found. There was a suggestion that patients with position-dependent SDB (supine RDI > lateral RDI) were more likely to have an acceptable therapeutic response to the device. Successful elimination of SDB was associated with generation and maintenance of an elevated end expiratory pressure. No single definitive mechanism of action was elucidated. The present study shows that the nasal valve device can alter SDB across the full spectrum of SDB severity. There was a suggestion that subjects with positional or milder SDB in the lateral position were those most likely to respond.

Evaluation of MolecuTech Real MTB-ID for MTB/NTM Detection Using Direct Specimens

Evaluation of MolecuTech Real MTB-ID for MTB/NTM Detection Using Direct Specimens Hye-young Wang*, Hyunwoo Jin*, Hyeeun Bang, Yeon-Im Choi, Eun-mi Park, Won-jung Koh, Hyeyoung Lee M&D, Inc. Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University, Wonju, YD Diagnostics, Yongin, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

Profile of aclidinium bromide in the treatment of chronic obstructive pulmonary disease.

Bronchodilators provide the mainstay of pharmacologic therapy for chronic obstructive pulmonary disease (COPD), and anticholinergic bronchodilators, in particular, appear to be the most effective. There are currently two anticholinergic agents available in the US for the treatment of COPD (ipratropium bromide and tiotropium bromide), but several others are in various stages of development. Aclidinium bromide, a novel, long-acting, anticholinergic bronchodilator, is currently in Phase III trials for the management of COPD. Available evidence suggests that aclidinium is a safe and well tolerated drug with a relatively rapid onset and a sufficient duration of action to provide once-daily dosing. This article will provide a pharmacologic profile of aclidinium bromide and review the preclinical and clinical studies evaluating its safety and efficacy in the treatment of COPD.

Initiating inspiration outside the medulla does produce eupneic breathing

ARTERIAL PCO2 IS DICTATED by the ratio between the level of pulmonary gas exchange and alveolar ventilation (VA), not minute ventilation. If so, how could isocapnia be maintained if only the magnitude (tidal volume, VT) and duration (TI and TTOT) of the neural output produced by the central pattern generator of breathing (CPG) can be altered? In other words, what is the strategy used by the respiratory control system to match its output to the level of pulmonary gas exchange to keep arterial blood gas homeostasis if this neural output con- tributes to dead space ventilation? In this Viewpoint, we will show that when the spontaneous breathing is replaced by a cortically triggered breathing pattern at various breathing frequencies (we will name this new rhythm an "ecto-rhythm"), the relationship between TTOT and VT has a positive intercept that averages the pulmonary dead space. As a result, the coupling between ventilation and the pulmonary gas exchange becomes possible (17). We will present the idea that whenever isocapnia is maintained during spontaneous or automatic breathing, the magnitude and dura- tion of breath cycles must display the same relationship as during an ecto-rhythm (15). Conversely, we will discuss the implications of the observation that breathing can display the same essential regulatory properties whether generated outside or within the pontomedullary CPG area (7). Ecto-rhythm, breathing pattern, and gas exchange: the re-

Research Highlights

Research Highlights

Multiple tracheal metastases of lung cancer: CT and integrated PET/CT findings

Multiple tracheal metastases of lung cancer: CT and integrated PET/CT findings E.Y. Kim , T.S. Kim *, J.Y. Choi , J. Han , H. Kim Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea

Should weight be a criterion for lung transplant selection?

“...a significant number of patients die while waiting for a lung transplant because of a lack of available organs.” Denis Hadjiliadis, MD, MHS, FRCP(C), FCCP Assistant Professor of Medicine, Division of Pulmonary, Allergy and Critical Care, University of Pennsylvania, PA, USA and Director, Adult Cystic Fibrosis Program, Associate Medical Director, Lung Transplantation Program, 835W Gates Building, Hospital of the University of Pennsylvania, 3600, Spruce Street, Philadelphia, PA 19104, USA Tel.: +1 215 615 3871 Fax: +1 215 662 3226 denis.hadjiliadis@ uphs.upenn.edu hadjiliadisdenis@ hotmail.com Lung transplantation is considered an acceptable treatment option for end-stage lung disease. The number of transplants performed has continued to increase over the years, reaching 2708 procedures worldwide [1] and 1465 in the USA during 2007 [2]. However, lung transplant outcomes remain inferior to other solid organ transplants with 1-year survival rates of 79% and 5-year survival rates of 52% [1]. In addition, a significant number of patients die while waiting for a lung transplant owing to a lack of available organs [2]. The number of waiting list deaths in the USA improved initially with the new lung allocation score and the donor increase initiative, but has now reached a plateau [2]. Therefore, it remains very important to select patients that have the best chance of survival after lung transplantation, to appropriately allocate this precious resource. According to the most recent guidelines by the International Society for Heart and Lung Transplantation, obesity is a relative contraindication to lung transplantation [3]. Obesity prevalence in the USA has dramatically increased over the last 15 years [101]. Using a definition of BMI above 30 kg/m, only one state in 2008 had a prevalence of obesity less than 20%, while six states had a prevalence of more than 30%. By contrast, in 1994 all 50 states had an obesity prevalence of less than 20% according to data from the CDC [101]. As a result of this rise in obesity, there is a significant increase in the number of obese patients requiring the provision of multiple healthcare services and clinicians frequently face questions on the appropriate management of these patients. These questions and dilemmas are likely to intensify over the next 5–10 years. Some patients with end-stage lung disease are at particular risk of obesity owing to steroid use (e.g., patients with idiopathic pulmonary fibrosis [IPF]). Most recent reports suggest that the effect of obesity is small on survival outcomes. In cardiac surgery, obesity leads to a small but significant increase in mortality [4] and wound infections [5]. In other solid organ transplants, there are conflicting data on the effect of obesity on posttransplant outcomes; most suggest that these patients have worse outcomes [6–8], and almost all of the studies have suggested increased post-transplant complications. In addition, all the aforementioned have mainly considered patients with extreme obesity (BMI >35, or even 40 kg/m).

Alpha-1-antitrypsin augmentation therapy in deficient individuals enrolled in the Alpha-1 Foundation DNA and Tissue Bank

Intravenous augmentation therapy with purified intravenous alpha-1 antitrypsin replaces the deficient protein and is the only currently approved treatment for alpha-1 antitrypsin deficiency (AATD) related lung disease. While augmentation therapy has been available for more than 20 years, there are a limited number of studies evaluating the effect of augmentation on lung function. We examined the decline in forced expiratory volume in one second (FEV(1)) in patients enrolled in the Alpha-1 Foundation DNA and Tissue Bank in relation to the use or not of alpha-1 antitrypsin augmentation therapy. For the purpose of our analysis we included 164 patients with AATD and PI ZZ genotype. Mean age of the patients was 60 years, 52% were females, 94% were white and 78% ex-smokers. The mean FEV(1) at baseline was 1.7 L and the mean FEV(1) % of predicted was 51.3%. The mean follow-up time was 41.7 months. A total of 124 (76%) patients received augmentation therapy (augmented group) while 40 patients (24%) did not received it (non-augmented group). When adjusted by age at baseline, sex, smoking status, baseline FEV(1) % of predicted, the mean overall change in FEV(1) was 47.6 mL/year, favoring the augmented group (DeltaFEV(1) 10.6 +/- 21.4 mL/year) in comparison with the non-augmented group (DeltaFEV(1) -36.96 +/- 12.1 mL/year) (P = 0.05). Beneficial DeltaFEV(1) were observed in ex-smokers and the group with initial FEV(1) % of predicted of <50%. No differences were observed in mortality. In conclusion, augmentation therapy improves lung function in subjects with AATD when adjusted by age, gender, smoking status and baseline FEV(1) % of predicted. The beneficial effects were noted in ex-smoker subjects with FEV(1) below 50% of predicted.

Chemotherapy-related delayed bilateral spontaneous pneumothorax and lung fibrosis: methotrexate or cyclophosphamide, or both?

A 27-year-old man was diagnosed with pre-T-cell acute lymphoblastic leukemia in November 2004 and underwent chemotherapy by German multicenter ALL (GMALL) protocol (including vincristine, daunorubicin, L-asparaginase, prednisolone, cyclophosphamide, Ara-C, intrathecal methotrexate (MTX), high dose MTX and mitoxantrone) between December 2004 and March 2005 with complete remission. Because the patient refused autologous stem cell transplantation, he received two cycles of high dose cyclophosphamide (2 g/m) and one cycle of high dose CEP (cyclophosphamide 3 g/m ¥ 2 days, etoposide 100 mg/m ¥ 4 days and cisplatin 50 mg/m ¥ 2 days) during July to September 2005 as intensive consolidation. Afterward, maintenance chemotherapy with weekly MTX (intravenous injection 40 mg) and daily mercaptopurine 50 mg was applied for 2 years. The last cycle of MTX was completed on 10 January 2008, and his disease status was determined in complete remission. The patient began to feel dyspnea since May 2008. His chest radiograph showed bilateral spontaneous pneumothorax and fibrotic change in the bilateral hilar area (Fig. 1). His chest computed tomography showed ground-glass appearance at the bilateral upper lung field (Fig. 2), and his pulmonary function test showed severe restrictive lung disease (forced vital capacity: 1.06 L; forced expiratory volume in 1 s: 0.78 L/s). Then the patient received video-assisted thoracoscopic surgery for bilateral wedge biopsy and pleurodesis. The pathology of lung tissue showed bilateral lung fibrosis without the evidence of microorganism involvement (Fig. 3). The etiology of bilateral pneumothorax with severe lung fibrosis was thought to be related to methotrexate or cyclophosphamide. The patient then received high dose prednisolone (60 mg daily), but his condition and pulmonary function responded poorly to steroid treatment. Now the patient is waiting for lung transplantation. Correspondence Chung-Jen Huang, MD, Division of Pulmonary and Intensive Care Medicine, Koo Foundation Sun Yat-Sen Cancer Center, 125 Lih-Der Road, Pei-Tou District, Taipei, Taiwan 11259. Tel: (886) 2-2897011 ext. 1720 Fax: (886) 2-8972233 email: huang600517@yahoo.com Figure 1. Chest radiograph showed bilateral pneumothorax, perihilar fibrosis and severe volume reduction. The Clinical Respiratory Journal FORUM

More life for a “terminal” cell

More life for a “terminal” cell

Design and Measurement of Quality Improvement Indicators in Ambulatory Pulmonary Care: Creating a “Culture of Quality” in an Academic Pulmonary Division

Quality improvement (QI) measures often are cited as goals for individual practices and medical centers and may someday form a component of reimbursement guidelines. Relatively few QI metrics relevant to ambulatory pulmonary medicine have been published. We describe the development and implementation of a QI program in an academic pulmonary division, including progress to date and lessons learned. Metrics for the pulmonary QI Dashboard were developed based on an extensive literature review. Patients were identified through International Classification of Diseases-based billing databases, and results data were obtained from a manual and automated review of the electronic medical record. The performance of the division was monitored and presented in regular faculty meetings. Quarterly, confidential, individual scorecards gave each clinician feedback about his or her performance and compared the feedback to that of the faculty of the entire division. Significant improvements were found in many QI measures during a 2-year period. The number of patients with asthma who received appropriately prescribed inhaled corticosteroids increased from a baseline of 76 to 92% to 98%. Flu shot and pneumococcal vaccine administration documentation for patients with COPD increased from baseline values of 11 to 32% and 11 to 34%, respectively, to 90% and 93%, respectively. The COPD Global Initiative for Obstructive Lung Disease pharmacotherapy guidelines adherence increased substantially for patients with all disease stages. Chest CT scan results notification documentation improved from a baseline of 67 to 76% to 98%. Comparison between baseline and QI periods yielded statistically significant increases for these indicators. QI measures for an ambulatory pulmonary practice can be designed, implemented, and monitored. Key components include a well-structured electronic medical record, measurable outcomes, strong QI leadership, and specific interventions, such as providing feedback through QI review meetings and individual "report cards."

PH in Patients with Lung Disease and Hypoxia

Global experts in pulmonary hypertension attended the 2009 American College of Chest Physicians meeting in San Diego. While there, Dr Nicholas Hill, Chief of the Pulmonary, Critical Care and Sleep Division, Tufts Medical Center, and Professor of Medicine, Tufts University, Boston; and Dr Steven Nathan, Medical Director, Lung Transplant and Advanced Lung Disease Program, Inova Fairfax Hospital, Falls Church, Virginia, talked with guest editor Dr Omar A. Minai to share their perspectives on current diagnosis, management, and future outlook for pulmonary hypertension patients with existing lung disease and hypoxia.

Use of multi-detector row angiography for the arrangement of video-assisted modified segmental resection

Video-assisted modified segmentectomy is segmental resection using an end-stapler without regards to anatomical broncho-segmental planes. This procedure is effective for deep pulmonary lesions, and preserves pulmonary function better as compared to lobectomy. However, the biggest disadvantage of this approach is the inability to manually palpate the lung. It is difficult to determine the staple line for pulmonary division during surgery as the tumour is located near the border of the burdened segments. This study evaluated whether multi-detector row computed tomographic angiography could contribute to the preoperative arrangement of video-assisted modified segmentectomy. Video-assisted modified segmentectomy was planned for nine patients with deep pulmonary tumours measuring 3 cm or smaller (Clinical T1N0M0 lung cancer, n=4; metastatic lung tumour, n=4 and undiagnosed lesions suspicious for lung cancer, n=1). All patients underwent contrast-enhanced multi-detector row computed tomography preoperatively to determine the vessels that were to be detached and the line for dividing the pulmonary parenchyma. All the lesions were resected with safe surgical margins under video view in keeping with the preoperative plan. Our experience suggests that multi-detector row computed tomographic angiography provides information for determining the division of the pulmonary vessels and lung parenchyma in video-assisted segmentectomy.

Evidence for Inflammatory Signaling in Idiopathic Pulmonary Artery Hypertension

Knowledge of molecular mechanisms underlying pulmonary arterial hypertension (PAH) continues to increase with the emerging theme that PAH is a heterogeneous disease involving multiple molecular abnormalities. Mutations in several genes have been identified in subsets of patients with PAH, and multiple signaling systems that influence vascular tone, function, and remodeling have been associated with PAH.1,2,3 In addition to mutations in BMPR2 , serotonin ( 5-HT ) and polymorphisms in its transporter ( SERT ) play a critical role in the pulmonary vascular smooth muscle hyperplasia and vascular remodeling found in PAH.4,5 Other genes and signals thought to contribute to the development of idiopathic pulmonary arterial hypertension (IPAH) include somatic mutations of BAX ,5 upregulation of Angiopoietin 1 ,6 transforming growth factor β1 polymorphisms,7 ALK1 mutation,8 SMAD8 mutation,9 and increased hyaluronic acid content associated with increased Hyaluronan Synthase 1 and decreased Hyaluronoglucosaminidase 1 gene expression.10 A recent observation also suggests that the noncanonical Wnt pathway is activated in IPAH.11 Article see p 2313 Several transient receptor potential canonical (TRPC) family …