DOCSLIB.ORG

Pulmonary Arteriole Gene Expression Signature in Idiopathic Pulmonary Fibrosis

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Pulmonary Arteriole Gene Expression Signature in Idiopathic Pulmonary Fibrosis Eur Respir J 2013; 41: 1324–1330 DOI: 10.1183/09031936.0084112 CopyrightßERS 2013 Pulmonary arteriole gene expression signature in idiopathic pulmonary fibrosis Nina M. Patel*,#, Steven M. Kawut", Sanja Jelic*, Selim M. Arcasoy*,#,+, David J. Lederer*,#,+ and Alain C. Borczuk1 ABSTRACT: A third of patients with idiopathic pulmonary fibrosis (IPF) develop pulmonary AFFILIATIONS hypertension (PH-IPF), which is associated with increased mortality. Whether an altered gene *Division of Pulmonary, Allergy and Critical Care Medicine, Columbia expression profile in the pulmonary vasculature precedes the clinical onset of PH-IPF is unknown. University, New York, NY, We compared gene expression in the pulmonary vasculature of IPF patients with and without PH #Interstitial Lung Disease Program, with controls. New York Presbyterian Hospital, New Pulmonary arterioles were isolated using laser capture microdissection from 16 IPF patients: York, NY, "Dept of Medicine and the Center for eight with PH (PH-IPF) and eight with no PH (NPH-IPF), and seven controls. Probe was prepared Clinical Epidemiology and from extracted RNA, and hybridised to Affymetrix Hu133 2.0 Plus genechips. Biometric Research Biostatistics, Perelman School of Branch array tools and Ingenuity Pathway Analysis software were used for analysis of the Medicine, University of Pennsylvania, microarray data. Philadelphia, PA, +Lung Transplantation Program, New Univariate analysis revealed 255 genes that distinguished IPF arterioles from controls York Presbyterian Hospital, New York, (p,0.001). Mediators of vascular smooth muscle and endothelial cell proliferation, Wnt signalling NY, and and apoptosis were differentially expressed in IPF arterioles. Unsupervised and supervised 1Dept of Pathology and Cell Biology, clustering analyses revealed similar gene expression in PH-IPF and NPH-IPF arterioles. Columbia University, New York, NY, USA. The pulmonary arteriolar gene expression profile is similar in IPF patients with and without coexistent PH. Pathways involved in vascular proliferation and aberrant apoptosis, which may CORRESPONDENCE contribute to pulmonary vascular remodelling, are activated in IPF patients. N.M. Patel Division of Pulmonary, Allergy and Critical Care Medicine KEYWORDS: DNA microarray, laser capture microdissection, pulmonary arterial hypertension, Columbia University usual interstitial pneumonia 622 W. 168th Street PH 8 East diopathic pulmonary fibrosis (IPF) is a studies have utilised DNA microarrays to eval- Room 101 New York uate gene expression in idiopathic pulmonary debilitating and fatal diffuse parenchymal NY 10032 arterial hypertension (PAH) and PH-IPF. Genes I lung disease with a median survival of USA ,3 years. More than a third of patients with IPF associated with transforming growth factor E-mail: [email protected] already have pulmonary hypertension (PH-IPF) (TGF)-b, extracellular signal-related kinase (ERK)/ at the time of initial evaluation for lung trans- mitogen-activated protein kinase (MAPK), platelet- Received: plantation, with an overwhelming majority derived growth factor (PDGF) and cAMP signalling May 29 2012 developing clinically overt PH by the time of are differentially expressed in whole-lung homo- Accepted after revision: transplantation [1, 2]. It is unclear if the subset of genates from patients with PAH compared with Aug 29 2012 First published online: IPF patients with PH have a distinct vascular patients with PH-IPF [4]. Decreased expression of Sept 20 2012 molecular phenotype, or whether all patients angiogenic genes and upregulation of genes asso- with IPF have molecular differences in pulmon- ciated with vascular remodelling have been ary vascular gene expression compared to con- observed in whole-lung homogenates in PH-IPF trols. It is valuable to discern the mechanism of [5]. Considering that the pulmonary vasculature pulmonary vascular dysfunction in IPF, as PH- accounts for a relatively small portion of gene IPF is associated with decreased functional status expression in whole-lung homogenates, differences and an increased risk of death [1, 3]. in gene expression observed in these studies may predominantly reflect changes in the lung parench- Pulmonary arterioles from patients with PH-IPF yma rather than the pulmonary vasculature. exhibit marked intimal hypertrophy, medial Ascertaining directly whether gene expression is smooth muscle cell proliferation and adventitial altered in the pulmonary vasculature of IPF patients thickening due to fibroblast accumulation and with and without PH is clinically relevant as extracellular matrix deposition [1]. Previous differences between the two groups would imply European Respiratory Journal Print ISSN 0903-1936 This article has supplementary material available from www.erj.ersjournals.com Online ISSN 1399-3003 1324 VOLUME 41 NUMBER 6 EUROPEAN RESPIRATORY JOURNAL N.M. PATEL ET AL. IDIOPATHIC PULMONARY FIBROSIS distinct vascular phenotypes. Differences in vascular gene and biotinylate RNA for a minimum goal of 15 mg RNA for expression in IPF compared with controls would suggest specific hybridisation. Target cRNA was hybridised to Affymetrix pathologic processes in IPF, which might lead to pulmonary Hu133 2.0 Plus oligonucleotide arrays (Affymetrix, Santa vascular remodelling. Clara, CA, USA). Biometric Research Branch array tools software v3.7.2. (Richard Simon and Amy Lam at the Thus, we assessed the gene expression of laser capture National Cancer Institute, Bethesda, MA, USA) was used for microdissected (LCM) pulmonary arterioles from IPF patients normalisation, filtering and initial quality control assessment free of PH (NPH-IPF) and those with coexistent PH and of the genechip data. Supervised analyses of differential gene compared it with controls. We sought to identify genes and expression between class assignments was performed using biological pathways that could potentially mediate the devel- univariate analyses with p,0.001. The false discovery rate for opment of vascular remodelling in IPF. Some of the results all comparisons was set at q,10%. A permutation analysis was have previously been reported as an abstract [6]. also performed utilising 10 000 random permutations, with a global p,0.01. Gene lists were further categorised into METHODS biological pathways using Ingenuity Pathways Analysis (IPA; Study population Ingenuity Systems, Redwood City, CA, USA). Please see the online supplementary material for full details. We identified potentially eligible study subjects by querying Paraffinised tissue blocks of 10 IPF cases (five PH-IPF and five the Columbia University Tissue Bank database for the terms NPH-IPF) and five normal donor lungs were sectioned and ‘‘lung’’ and ‘‘usual interstitial pneumonia’’ (UIP) and/or stained for antibodies against secreted frizzled-related protein ‘‘pulmonary hypertension’’. We included IPF patients who (SFRP)-2 (monoclonal rabbit antihuman) (Sigma-Aldrich Corp. met American Thoracic Society criteria (previous and current) St Louis, MO, USA), SPARC-related modular calcium binding for a diagnosis of IPF [7, 8]. Patients with IPF were considered (SMOC)-2 (polyclonal rabbit antihuman) (Lifespan Biosciences in the PH-IPF group if they had a mean pulmonary arterial Inc., Seattle, WA, USA) and signal transducer and activator of pressure (mPAP) .25 mmHg with a pulmonary capillary transcription (STAT1) (monoclonal rabbit antihuman) (Sigma) wedge pressure f15 mmHg measured by right heart cathe- using the DAKO Envision Dual Link kit (Dako, Glostrup, terisation, meeting World Health Organization (WHO) group 3 Denmark). Examination for statistical significance was per- criteria [9, 10]. IPF patients were included in the NPH-IPF formed using Fisher’s exact test (SPSS, v16.0; IBM North group if they had mPAP f25 mmHg. America, New York, NY, USA). We excluded patients with clinical evidence of collagen vascular RESULTS disease, another known aetiology for pulmonary hypertension We included eight patients with PH-IPF, eight with NPH-IPF (e.g. chronic obstructive pulmonary disease, obstructive sleep and seven controls (table 1). IPF patients were older than the apnoea and thromboembolic disease), left ventricular dysfunc- controls and predominantly male. Patients with PH-IPF and tion or left-sided valvular disease, missing haemodynamic or NPH-IPF were similar with regards to age, sex, race, smoking pulmonary function data and age ,18 years. history and lung function. Pulmonary function data revealed the presence of a restrictive impairment and the absence of 15 IPF samples were obtained from lung explant and one from obstructive physiology in both groups. One patient had mild surgical lung biopsy. Specimens from four unused donor lung upper lobe emphysema by computed tomography (CT); no shavings and three normal lung sections obtained during patients had significant emphysema histologically or by chest resection of pulmonary carcinoid tumours were used as CT. Notably, the degree of PH present in the PH-IPF group controls. Approval and a waiver of consent for clinical data was mild, with mPAP of 29 mmHg. collection were obtained from the Columbia University Institutional Review Board (IRB-AAAC0695). The raw gene expression values for four commonly expressed endothelial and epithelial genes were examined to confirm Processing and LCM of tissue samples the isolation of pulmonary arterioles while minimising the All lung tissues were obtained peri-operatively, snap-frozen in inclusion of lung parenchyma or airways. Endothelial gene liquid nitrogen and
Load more

Recommended publications
  • Right Heart Pressures in Bronchial Asthma
    Thorax: first published as 10.1136/thx.26.1.39 on 1 January 1971. Downloaded from Thorax (1971), 26, 39. Right heart pressures in bronchial asthma R. F. GUNSTONE St. George's Hospital, London S.W.1 Right heart pressures, electrocardiograms, blood gases, and peak expiratory flow rates were measured in nine patients admitted to hospital with severe bronchial asthma. Low or normal right heart pressures were found despite electrocardiographic changes in five patients consisting of right atrial P waves, abnormal right axis deviation, and in one patient T-wave changes in pre- cordial leads. These electrocardiographic changes reverted towards normal on recovery of the patient from the asthmatic attack. Electrocardiographic changes suggestive of right The procedure was carried out in the general ward heart embarrassment have been noted in acute with the patient in the sitting position supported at 60 bronchial asthma, particularly right atrial P waves to 90 degrees to the horizontal because orthopnoea (P and abnormal right axis deviation was always present. Immediately after catheterization pulmonale) the peak expiratory flow rate was measured with a (Harkavy and Romanoff, 1942; Miyamato, Wright peak flow meter (Wright and McKerrow, Bastaroli, and Hoffman, 1961; Ambiavagar, 1959) and blood (capillary or arterial) was taken for Jones and Roberts, 1967). These observations measurement of pH, Pco2, and standard bicarbonate raise the possibility that death in bronchial asthma by the Astrup method (Astrup, J0rgensen, Andersen, may be due to acute cor pulmonale although and Engel, 1960). The peak flow rate and electro- copyright. necropsy evidence is against this suggestion (Earle, cardiogram were repeated after recovery.
    [Show full text]
  • Severe Asthma Is Associated with a Remodeling of the Pulmonary Arteries in Horses
    bioRxiv preprint doi: https://doi.org/10.1101/2020.04.15.042903; this version posted April 17, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 1 Severe asthma is associated with a remodeling of the pulmonary arteries in horses Remodeling of pulmonary arteries in severe equine asthma Serena Ceriotti1,2, Michela Bullone1, Mathilde Leclere1, Francesco Ferrucci2, Jean-Pierre Lavoie1* 1 Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Montreal, Saint- Hyacinthe, Quebec, Canada 2 Department of Health, Animal Science and Food Safety, Università degli Studi di Milano, Milano, Italy Dr. Ceriotti current address is Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Auburn, Alabama, USA Dr. Bullone current address is Department of Veterinary Science, Università degli Studi di Torino, Grugliasco, Italy *Corresponding author: [email protected] Serena Ceriotti and Jean-Pierre Lavoie conceived and designed the work. Serena Ceriotti, Michela Bullone and Mathilde Leclere acquired clinical data, collected, processed and prepared histological and immunostained samples. Serena Ceriotti performed histomorphometric studies and statistical analysis. Serena Ceriotti, Jean-Pierre Lavoie and Francesco Ferrucci prepared and edited the manuscript prior to submission. Michela Bullone and Mathilde Leclere edited the manuscript prior to submission. 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.04.15.042903; this version posted April 17, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.
    [Show full text]
  • Allergic Bronchopulmonary Aspergillosis: Diagnostic and Treatment Challenges
    y & Re ar sp Leonardi et al., J Pulm Respir Med 2016, 6:4 on ir m a l to u r P y DOI: 10.4172/2161-105X.1000361 f M o e Journal of l d a i n c r i n u e o J ISSN: 2161-105X Pulmonary & Respiratory Medicine Review Article Open Access Allergic Bronchopulmonary Aspergillosis: Diagnostic and Treatment Challenges Lucia Leonardi*, Bianca Laura Cinicola, Rossella Laitano and Marzia Duse Department of Pediatrics and Child Neuropsychiatry, Division of Allergy and Clinical Immunology, Sapienza University of Rome, Policlinico Umberto I, Rome, Italy Abstract Allergic bronchopulmonary aspergillosis (ABPA) is a pulmonary disorder, occurring mostly in asthmatic and cystic fibrosis patients, caused by an abnormal T-helper 2 lymphocyte response of the host to Aspergillus fumigatus antigens. ABPA diagnosis is defined by clinical, laboratory and radiological criteria including active asthma, immediate skin reactivity to A. fumigatus antigens, total serum IgE levels>1000 IU/mL, fleeting pulmonary parenchymal opacities and central bronchiectases that represent an irreversible complication of ABPA. Despite advances in our understanding of the role of the allergic response in the pathophysiology of ABPA, pathogenesis of the disease is still not completely clear. In addition, the absence of consensus regarding its prevalence, diagnostic criteria and staging limits the possibility of diagnosing the disease at early stages. This may delay the administration of a therapy that can potentially prevent permanent lung damage. Long-term management is still poorly studied. Present primary therapies, based on clinical experience, are not yet standardized. These consist in oral corticosteroids, which control acute symptoms by mitigating the allergic inflammatory response, azoles and, more recently, anti-IgE antibodies.
    [Show full text]
  • Pulmonary Hypertension ______
    Pulmonary Hypertension _________________________________________ What is it? High blood pressure in the arteries that supply the lungs is called pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH). The blood pressure measured by a cuff on your arm isn’t directly related to the pressure in your lungs. The blood vessels that supply the lungs constrict and their walls thicken, so they can’t carry as much blood. As in a kinked garden hose, pressure builds up and backs up. The heart works harder, trying to force the blood through. If the pressure is high enough, eventually the heart can’t keep up, and less blood can circulate through the lungs to pick up oxygen. Patients then become tired, dizzy and short of breath. If a pre-existing disease triggered the PH, doctors call it secondary pulmonary hypertension. That’s because it’s secondary to another problem, such as a left heart or lung disorder. However, congenital heart disease can cause PH that’s similar to PH when the cause isn’t known, i.e., idiopathic or unexplained pulmonary arterial hypertension. In this case, the PAH is considered pulmonary arterial hypertension associated with congenital heart disease, such as associated with a VSD or ASD (either repaired or unrepaired). The problem is due to scarring in the small arteries in the lung. It’s important to repair congenital heart problems (when possible) before permanent pulmonary hypertensive changes develop. Intracardiac left-to-right shunts (such as a ventricular or atrial septal defect, a hole in the wall between the two ventricles or atria) can cause too much blood flow through the lungs.
    [Show full text]
  • Allergic Bronchopulmonary Aspergillosis
    Allergic Bronchopulmonary Aspergillosis Karen Patterson1 and Mary E. Strek1 1Department of Medicine, Section of Pulmonary and Critical Care Medicine, The University of Chicago, Chicago, Illinois Allergic bronchopulmonary aspergillosis (ABPA) is a complex clinical type of pulmonary disease that may develop in response to entity that results from an allergic immune response to Aspergillus aspergillus exposure (6) (Table 1). ABPA, one of the many fumigatus, most often occurring in a patient with asthma or cystic forms of aspergillus disease, results from a hyperreactive im- fibrosis. Sensitization to aspergillus in the allergic host leads to mune response to A. fumigatus without tissue invasion. activation of T helper 2 lymphocytes, which play a key role in ABPA occurs almost exclusively in patients with asthma or recruiting eosinophils and other inflammatory mediators. ABPA is CF who have concomitant atopy. The precise incidence of defined by a constellation of clinical, laboratory, and radiographic ABPA in patients with asthma and CF is not known but it is criteria that include active asthma, serum eosinophilia, an elevated not high. Approximately 2% of patients with asthma and 1 to total IgE level, fleeting pulmonary parenchymal opacities, bronchi- 15% of patients with CF develop ABPA (2, 4). Although the ectasis, and evidence for sensitization to Aspergillus fumigatus by incidence of ABPA has been shown to increase in some areas of skin testing. Specific diagnostic criteria exist and have evolved over the world during months when total mold counts are high, the past several decades. Staging can be helpful to distinguish active disease from remission or end-stage bronchiectasis with ABPA occurs year round, and the incidence has not been progressive destruction of lung parenchyma and loss of lung definitively shown to correlate with total ambient aspergillus function.
    [Show full text]
  • Cryptogenic Organizing Pneumonia
    462 Cryptogenic Organizing Pneumonia Vincent Cottin, M.D., Ph.D. 1 Jean-François Cordier, M.D. 1 1 Hospices Civils de Lyon, Louis Pradel Hospital, National Reference Address for correspondence and reprint requests Vincent Cottin, Centre for Rare Pulmonary Diseases, Competence Centre for M.D., Ph.D., Hôpital Louis Pradel, 28 avenue Doyen Lépine, F-69677 Pulmonary Hypertension, Department of Respiratory Medicine, Lyon Cedex, France (e-mail: [email protected]). University Claude Bernard Lyon I, University of Lyon, Lyon, France Semin Respir Crit Care Med 2012;33:462–475. Abstract Organizing pneumonia (OP) is a pathological pattern defined by the characteristic presence of buds of granulation tissue within the lumen of distal pulmonary airspaces consisting of fibroblasts and myofibroblasts intermixed with loose connective matrix. This pattern is the hallmark of a clinical pathological entity, namely cryptogenic organizing pneumonia (COP) when no cause or etiologic context is found. The process of intraalveolar organization results from a sequence of alveolar injury, alveolar deposition of fibrin, and colonization of fibrin with proliferating fibroblasts. A tremen- dous challenge for research is represented by the analysis of features that differentiate the reversible process of OP from that of fibroblastic foci driving irreversible fibrosis in usual interstitial pneumonia because they may determine the different outcomes of COP and idiopathic pulmonary fibrosis (IPF), respectively. Three main imaging patterns of COP have been described: (1) multiple patchy alveolar opacities (typical pattern), (2) solitary focal nodule or mass (focal pattern), and (3) diffuse infiltrative opacities, although several other uncommon patterns have been reported, especially the reversed halo sign (atoll sign).
    [Show full text]
  • PULMONARY HYPERTENSION in SCLERODERMA PULMONARY HYPERTENSION Pulmonary Hypertension (PH) Is High Blood Pressure in the Blood Vessels of the Lungs
    PULMONARY HYPERTENSION IN SCLERODERMA PULMONARY HYPERTENSION Pulmonary hypertension (PH) is high blood pressure in the blood vessels of the lungs. If the high blood pressure in the lungs is due to narrowing of the pulmonary arteries leading to increased pulmonary vascular resistance, it is known as pulmonary arterial hypertension (PAH). When the blood pressure inside the pulmonary vessels is high, the right side of the heart has to pump harder to move blood into the lungs to pick up oxygen. This can lead to failure of the right side of the heart. Patients with scleroderma are at increased risk for developing PH from several mechanisms. Frequently patients with scleroderma have multiple causes of their PH. Patients who have limited cutaneous scleroderma (formerly known as CREST syndrome) are more likely to have PAH than those patients who have diffuse cutaneous systemic sclerosis. PAH may be the result of the same processes that cause damage to small blood vessels in the systemic circulation of patients with scleroderma. The lining cells of the blood vessels (endothelial cells) are injured and excessive connective tissue is laid down inside the blood vessel walls. The muscle that constricts the blood vessel may overgrow and narrow the blood vessel. Other scleroderma patients may have PH because they have significant scarring (fibrosis) of their lungs. This reduces the blood oxygen level, which in turn, may cause a reflex increase in blood pressure in the pulmonary arteries. WHAT ARE THE SYMPTOMS OF PULMONARY HYPERTENSION? Patients with mild PH may have no symptoms. Patients with moderate or severe PH usually notice shortness of breath (dyspnea), especially with exercise.
    [Show full text]
  • Allergic Bronchopulmonary Aspergillosis
    Published online: 2021-07-30 CHEST RADIOLOGY Pictorial essay: Allergic bronchopulmonary aspergillosis Ritesh Agarwal, Ajmal Khan, Mandeep Garg1, Ashutosh N Aggarwal, Dheeraj Gupta Departments of Pulmonary Medicine and 1Radiodiagnosis, Postgraduate Institute of Medical Education and Research, Sector-12, Chandigarh - 160 012, India Correspondence: Dr. Ritesh Agarwal, Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research, Sector-12, Chandigarh - 160 012, India. E-mail: [email protected] Abstract Allergic bronchopulmonary aspergillosis (ABPA) is the best-known allergic manifestation of Aspergillus-related hypersensitivity pulmonary disorders. Most patients present with poorly controlled asthma, and the diagnosis can be made on the basis of a combination of clinical, immunological, and radiological findings. The chest radiographic findings are generally nonspecific, although the manifestations of mucoid impaction of the bronchi suggest a diagnosis of ABPA. High-resolution CT scan (HRCT) of the chest has replaced bronchography as the initial investigation of choice in ABPA. HRCT of the chest can be normal in almost one-third of the patients, and at this stage it is referred to as serologic ABPA (ABPA-S). The importance of central bronchiectasis (CB) as a specific finding in ABPA is debatable, as almost 40% of the lobes are involved by peripheral bronchiectasis. High-attenuation mucus (HAM), encountered in 20% of patients with ABPA, is pathognomonic of ABPA. ABPA should be classified based on the presence or absence of HAM as ABPA-S (mild), ABPA-CB (moderate), and ABPA-CB-HAM (severe), as this classification not only reflects immunological severity but also predicts the risk of recurrent relapses. Key words: Allergic bronchopulmonary aspergillosis; allergic bronchopulmonary aspergillosis; aspergillus; chest radiograph; computed tomography; High-resolution CT scan Introduction A.
    [Show full text]
  • Pulmonary Hypertension As a Rare Cause of Postopera- Tive Chylothorax
    TEHRAN HEART CENTER Case Report Pulmonary Hypertension as a Rare Cause of Postopera- tive Chylothorax Feridoun Sabzi, MD*, Samsam Dabiri, MD, Alireza Poormotaabed, MD Kermanshah University of Medical Sciences, Imam Ali Hospital, Kermanshah, Iran. Received 13 August 2012; Accepted 16 December 2013 Abstract Chylothorax in adult occurs most commonly in the wake of cardiac and thoracic procedures. Injuries to the common thoracic duct in the thorax or its branches in the mediastinum, injuries to the thymus tissues, dissection of the superior vena cava or ascending aorta, dissection of the aortic arch, disruption of the accessory lymphatics in the left or right thorax, and increased pressure in the systemic vein exceeding that of the thoracic duct (usually in the superior vena cava thrombosis, Glenn Shunt, and hemi-Fontan) have been proposed as the possible causes of chylothorax after surgery for congenital heart disease. However, pulmonary hypertension is an exceedingly rare cause of chylothorax in adults. We present a case of chylothorax after atrial septal defect surgery in a 30-year-old female patient with pulmonary hypertension. The postoperative period was complicated by chylothorax, which was confirmed by the high lipid content of chylous effusion. The patient was treated conservatively with diet therapy, and the effusion was abolished completely after two weeks. No recurrence of chylothorax was detected at 3 months' follow-up. J Teh Univ Heart Ctr 2014;9(2):93-96 This paper should be cited as: Sabzi F, Dabiri S, Poormotaabed A. Pulmonary Hypertension as a Rare Cause of Postoperative Chylothorax. J Teh Univ Heart Ctr 2014;9(2):93-96.
    [Show full text]
  • Shortness of Breath
    Christopher Taggart, MD St. Mary’s Medical Center, Department of Family Shortness of breath: Looking Medicine, Grand Junction, Colo beyond the usual suspects christopher.taggart@ sclhs.net COPD and pneumonia come to mind when a patient The authors reported no potential conflict of interest is short of breath. But the signs and symptoms detailed relevant to this article. here should lead you to suspect an uncommon cause. CASE u Joan C is a 68-year-old woman who presents to the of- PRACTICE RECOMMENDATIONS fice complaining of an enlarging left chest wall mass that ap- peared within the past month. She was treated for small-cell ❯ Consider diagnoses other lung cancer 11 years ago. She has a 45 pack-year smoking his- than asthma, COPD, heart failure, and pneumonia in tory (she quit when she received the diagnosis) and has heart patients with persistent or failure, which is controlled. Your examination reveals a large progressive dyspnea. C (5 cm) firm mass on her left chest wall. There is no erythema or tenderness. She has no other complaints. You recommend surgi- ❯ Avoid steroids in patients with acute pericarditis cal biopsy and refer her to surgery. because research shows Ms. C returns to your office several days later complaining that they increase the of new and worsening shortness of breath with exertion that be- risk of recurrence. B gan the previous day. The presentation is similar to prior asthma exacerbation episodes. She denies any cough, fever, chest pain, ❯ Consider anticoagulation with warfarin in patients with symptoms at rest, or hemoptysis. On exam she appears comfort- pulmonary arterial hyperten- able and not in any acute distress.
    [Show full text]
  • Pulmonary Hypertension in the Intensive Care Unit
    Pulmonary vascular disease ORIGINAL ARTICLE Heart: first published as 10.1136/heartjnl-2015-307774 on 6 April 2016. Downloaded from Pulmonary hypertension in the intensive care unit. Expert consensus statement on the diagnosis and treatment of paediatric pulmonary hypertension. The European Paediatric Pulmonary Vascular Disease Network, endorsed by ISHLT and DGPK Michael Kaestner,1 Dietmar Schranz,2 Gregor Warnecke,3,4 Christian Apitz,1 Georg Hansmann,5 Oliver Miera6 For numbered affiliations see ABSTRACT heterogeneous underlying conditions.1 Distinction end of article. Acute pulmonary hypertension (PH) complicates the between precapillary and postcapillary aetiologies Correspondence to course of several cardiovascular, pulmonary and other (or establishment of a combination of the two) is Dr. Oliver Miera, Department systemic diseases in children. An acute rise of RV important to initiate specific individual therapy. of Congenital Heart Disease afterload, either as exacerbating chronic PH of different and Paediatric Cardiology, aetiologies (eg, idiopathic pulmonary arterial Pathophysiology of acute PH and RV failure Deutsches Herzzentrum Berlin, hypertension (PAH), chronic lung or congenital heart Augustenburger Platz 1, Chronic PH causes adaptation and remodelling of Berlin 13353, Germany; disease), or pulmonary hypertensive crisis after corrective the RV to increased loading conditions. Pulmonary [email protected] surgery for congenital heart disease, may lead to severe hypertensive crisis (PHC) occurs when compensatory circulatory compromise. Only few clinical studies provide mechanisms fail, RV systolic function decompensates This manuscript is a product of evidence on how to best treat children with acute severe and LV preload acutely decreases resulting in abol- the writing group of the 23 European Paediatric Pulmonary PH and decompensated RV function, that is, acute RV ished cardiac output and coronary perfusion.
    [Show full text]
  • Pulmonary Hypertension in Children
    American Thoracic Society PATIENT EDUCATION | INFORMATION SERIES Pulmonary Hypertension in Children Pulmonary hypertension is a condition in which the pressure in the pulmonary artery and lungs is too high. This puts stress on the right side of the heart because the muscles on the right side are not used to pushing blood out to the lungs against such high pressures. Over time, the right side of the heart is strained and begins to fail. This is a rare but serious condition that can develop in children or adults at any age. This fact sheet talks about Pulmonary Hypertension in children. For more information about Pulmonary Hypertension in adults, see the ATS Patient Information Series at www.thoracic.org/patients. In a structurally normal heart, oxygen-poor blood flows to the childhood conditions, which may result in delay of diagnosis. right side of the heart from the body. The blood then flows into the These conditions often include asthma, behavioral concerns, or right atrium and finally into the right ventricle. The right ventricle seizures. Symptoms can progress over time and may differ based pumps this blood through the pulmonary artery into the lungs. In on the age of the child and other underlying conditions. The most the lungs, the blood becomes enriched with oxygen. This oxygen- common symptoms are related to difficulty with breathing. It is rich blood then flows to the left side of the heart so the body’s important to tell your healthcare provider of any new or worsening organs can get enough oxygen to function properly. symptoms.
    [Show full text]