Respirology. 2018 Jan 12. doi: 10.1111/resp.13250. [Epub ahead of print]

Pulmonary hypertension in interstitial lung disease: Limitations of echocardiography compared to cardiac catheterization.

Keir GJ^1,2, John Wort S^3,4, Kokosi M¹, George PM¹, Walsh SLF⁵, Jacob J⁵, Price L³, Bax S³, Renzoni EA¹, Maher TM^1,6, MacDonald P⁷, Hansell DM⁵, Wells AU¹.

Author information:

1. Interstitial Lung Disease Unit, Royal Brompton Hospital, London, UK.
2. Department of Respiratory Medicine, Princess Alexandra Hospital, Brisbane, QLD, Australia.
3. National Pulmonary Hypertension Service, Royal Brompton Hospital, London, UK.
4. Vascular Science, Imperial College, London, UK.
5. Department of Radiology, Royal Brompton Hospital, London, UK.
6. Fibrosis Research Group, National Heart and Lung Institute, Imperial College, London, UK.
7. Department of Cardiology, St Vincent’s Hospital, Sydney, NSW, Australia.

Abstract

BACKGROUND AND OBJECTIVE:

In interstitial lung disease (ILD), pulmonary hypertension (PH) is a major adverse prognostic determinant. Transthoracic echocardiography (TTE) is the most widely used tool when screening for PH, although discordance between TTE and right heart catheter (RHC) measured pulmonary haemodynamics is increasingly recognized. We evaluated the predictive utility of the updated European Society of Cardiology/European Respiratory Society (ESC/ERS) TTE screening recommendations against RHC testing in a large, well-characterized ILD cohort.

METHODS:

Two hundred and sixty-five consecutive patients with ILD and suspected PH underwent comprehensive assessment, including RHC, between 2006 and 2012. ESC/ERS recommended tricuspid regurgitation (TR) velocity thresholds for assigning high (>3.4 m/s), intermediate (2.9-3.4 m/s) and low (<2.8 m/s) probabilities of PH were evaluated against RHC testing. RESULTS: RHC testing confirmed PH in 86% of subjects with a peak TR velocity >3.4 m/s, and excluded PH in 60% of ILD subjects with a TR velocity <2.8 m/s. Thus, the ESC/ERS guidelines misclassified 40% of subjects as ‘low probability’ of PH, when PH was confirmed on subsequent RHC. Evaluating alternative TR velocity thresholds for assigning a low probability of PH did not significantly improve the ability of TR velocity to exclude a diagnosis of PH.

CONCLUSION:

In patients with ILD and suspected PH, currently recommended ESC/ERS TR velocity screening thresholds were associated with a high positive predictive value (86%) for confirming PH, but were of limited value in excluding PH, with 40% of patients misclassified as low probability when PH was confirmed at subsequent RHC.

© 2018 Asian Pacific Society of Respirology.

PMID: 29327393

SAGE Open Med. 2018 Jan 4;6:2050312117749159. doi: 10.1177/2050312117749159. eCollection 2018.

Coping, social support and information in patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension: A 2-year retrospective cohort study.

Ivarsson B^1,2, Rådegran G³, Hesselstrand R⁴, Kjellström B⁵.

Author information:

1. Division of Cardiothoracic Surgery, Department of Clinical Sciences Lund, Lund University and Skåne University Hospital, Lund, Sweden.
2. Medicine Services University Trust, Region Skåne, Lund, Sweden.
3. Section for Heart Failure and Valvular Disease, Division of Cardiology, Department of Clinical Sciences Lund, Lund University and Skåne University Hospital, Lund, Sweden.
4. Rheumatology, Department of Clinical Sciences Lund, Lund University and Skåne University Hospital, Lund, Sweden.
5. Department of Medicine, Karolinska Institute, Stockholm, Sweden.

Abstract

Objectives:

Pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension are severe diseases with complicated treatment that need care at specialist clinics. The aim was to investigate changes in the patients’ perceptions on coping, social support and received information when attending a newly started nurse-coordinated pulmonary arterial hypertension-outpatient clinic.

Methods:

The present study was a descriptive, questionnaire-based cohort study including 42 adult patients. To evaluate coping, the Pearlin Mastery Scale was used. Social support, information and health-related quality of life were measured using Social Network and Support Scale, QLQ-INFO25 and the EQ-5D.

Results:

Attending the pulmonary arterial hypertension-outpatient clinic increased coping ability (Mastery Scale) significantly (baseline 16.0 ± 3.3 points vs 2-year follow-up 19.6 ± 5.2 points, p < 0.001) while there was no difference in social network and support or in perception of received information after. Patients who improved their coping ability (67%) were younger, had better exercise capacity, experienced better health-related quality of life and were more satisfied with received information about treatment and medical tests than those who reduced the coping ability. There was no difference in gender, diagnosis, time since diagnose, pulmonary arterial hypertension-specific treatment, education level or civil status between the two groups.

Conclusion:

This study suggests that the pulmonary arterial hypertension-team, in partnership with the patient, can support patients to take control of their disease and increase their health-related quality of life.

PMCID: PMC5758958 Free PMC Article
PMID: 29326818

Ann Thorac Cardiovasc Surg. 2018 Jan 10. doi: 10.5761/atcs.cr.17-00084. [Epub ahead of print]

Severe Compression of the Left Main Coronary Artery in a Patient with Chronic Thromboembolic Pulmonary Hypertension.

Sugiyama K¹, Koizumi N¹, Ogino H¹.

Author information:

1. Department of Cardiovascular Surgery, Tokyo Medical University Hospital, Tokyo, Japan.

Abstract

Extrinsic compression of the left main coronary artery (LMCA) can occur in patients with an enlarged pulmonary artery trunk secondary to severe pulmonary hypertension (PH). This phenomenon rarely occurs in PH; moreover, few reports have shown that chronic thromboembolic PH can be a triggering factor for this syndrome. Herein, we describe a patient with extrinsic compression of the LMCA with chronic thromboembolic PH who underwent pulmonary endarterectomy and coronary artery bypass grafting successfully. Intravenous ultrasonography (IVUS) was effective for detecting and assessing the compression.

Free Article
PMID: 29321385

Circ Heart Fail. 2018 Jan;11(1):e004255. doi: 10.1161/CIRCHEARTFAILURE.117.004255.

Intersection of Pulmonary Hypertension and Right Ventricular Dysfunction in Patients on Left Ventricular Assist Device Support: Is There a Role for Pulmonary Vasodilators?

Sparrow CT¹, LaRue SJ¹, Schilling JD².

Author information:

1. From the Division of Cardiology, Department of Medicine (C.T.S., S.J.L., J.D.S.) and Department of Pathology and Immunology (J.D.S.), Washington University School of Medicine, St. Louis, MO.
2. From the Division of Cardiology, Department of Medicine (C.T.S., S.J.L., J.D.S.) and Department of Pathology and Immunology (J.D.S.), Washington University School of Medicine, St. Louis, MO. schillij@wustl.edu.

Abstract

Left ventricular assist devices (LVADs) improve survival and quality of life in patients with advanced heart failure. Despite these benefits, combined post- and precapillary pulmonary hypertension can be particularly problematic in patients on LVAD support, often exacerbating right ventricular (RV) dysfunction. Both persistently elevated pulmonary vascular resistance and RV dysfunction are associated with adverse outcomes, including death after LVAD. These observations have led to significant interest in the use of pulmonary vasodilators to treat pulmonary hypertension and preserve RV function among LVAD-supported patients. Although pulmonary vasodilators are commonly used for the treatment of pulmonary hypertension and RV dysfunction in LVADs, the benefits of this practice remain unclear. The purpose of this review is to highlight the current challenges in managing pulmonary vascular disease and RV dysfunction in patients with heart failure on LVAD support.

PMID: 29321132

Pediatr Crit Care Med. 2018 Jan 9. doi: 10.1097/PCC.0000000000001454. [Epub ahead of print]

Extracorporeal Membrane Oxygenation for Pertussis: Predictors of Outcome Including Pulmonary Hypertension and Leukodepletion.

Domico M¹, Ridout D², MacLaren G^3,4, Barbaro R⁵, Annich G⁶, Schlapbach LJ, Brown KL⁷.

Author information:

1. Division of Pediatric Critical Care, Children’s Hospital of Orange County, Orange, CA.
2. Population, Policy and Practice Programme, UCL Great Ormond St Institute of Child Health, London, United Kingdom.
3. Paediatric Intensive Care Unit, The Royal Children’s Hospital, University of Melbourne, Melbourne, VIC, Australia.
4. Cardiothoracic ICU, National University Hospital, Singapore.
5. Division of Pediatric Critical Care and Child Health Evaluation and Research Center, University of Michigan, Ann Arbor, MI.
6. Department of Critical Care Medicine, The Hospital for Sick Children, Toronto, ON, Canada.
7. Cardiac Intensive Care Unit, Great Ormond Street Hospital for Children, NHS Trust, London, United Kingdom.

Abstract

OBJECTIVE:

The recent increase of pertussis cases worldwide has generated questions regarding the utility of extracorporeal membrane oxygenation for children with pertussis. We aimed to evaluate factors associated with extracorporeal membrane oxygenation outcome.

DESIGN:

The study was designed in two parts: a retrospective analysis of the Extracorporeal Life Support Organization Registry to identify factors independently linked to outcome, and an expanded dataset from individual institutions to examine the association of WBC count, pulmonary hypertension, and leukodepletion with survival.

SETTING:

Extracorporeal Life Support Organization Registry database from 2002 though 2015, and contributions from 19 international centers.

PATIENTS:

Two hundred infants from the Extracorporeal Life Support Organization Registry and expanded data on 73 children.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Of the 200 infants who received extracorporeal membrane oxygenation for pertussis, only 56 survived (28%). In a multivariable logistic regression analysis, the following variables were independently associated with increased chance of survival: older age (odds ratio, 1.43 [1.03-1.98]; p=0.034), higher PaO2/FIO2 ratio (odds ratio, 1.10 [1.03-1.17]; p= 0.003), and longer intubation time prior to the initiation of extracorporeal membrane oxygenation (odds ratio, 2.10 [1.37-3.22]; p = 0.001). The use of vasoactive medications (odds ratio, 0.33 [0.11-0.99]; p = 0.047), and renal neurologic or infectious complications (odds ratio, 0.21 [0.08-0.56]; p = 0.002) were associated with increased mortality. In the expanded dataset (n =73), leukodepletion was independently associated with increased chance of survival (odds ratio, 3.36 [1.13-11.68]; p = 0.03) while the presence of pulmonary hypertension was adverse (odds ratio, 0.06 [0.01-0.55]; p = 0.01).

CONCLUSIONS:

The survival rate for infants with pertussis who received extracorporeal membrane oxygenation support remains poor. Younger age, lower PaO2/FIO2 ratio, vasoactive use, pulmonary hypertension, and a rapidly progressive course were associated with increased mortality. Our results suggest that pre-extracorporeal membrane oxygenation leukodepletion may provide a survival advantage.

PMID: 29319632

J Korean Med Sci. 2018 Jan 22;33(4):e24. doi: 10.3346/jkms.2018.33.e24.

Impact of Balloon Pulmonary Angioplasty on Hemodynamics and Clinical Outcomes in Patients with Chronic Thromboembolic Pulmonary Hypertension: the Initial Korean Experience.

Kwon W¹, Yang JH^1,2, Park TK¹, Chang SA¹, Jung DS³, Cho YS⁴, Kim SM⁵, Kim TJ⁵, Park HY⁶, Choi SH¹, Kim DK¹.

Author information:

1. Department of Cardiology, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
2. Department of Critical Care Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. jhysmc@gmail.com.
3. Department of Thoracic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
4. Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
5. Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
6. Department of Pulmonary and Critical Care Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Abstract

BACKGROUND:

The treatment of choice for chronic thromboembolic pulmonary hypertension (CTEPH) is pulmonary endarterectomy (PEA). However, not all patients are eligible for PEA, and some patients experience recurrence of pulmonary hypertension even after PEA.

METHODS:

Patients who underwent balloon pulmonary angioplasty (BPA) between December 2015 and April 2017 were enrolled from the Samsung Medical Center CTEPH registry. Enrolled patients underwent right heart catheterization, echocardiography, and 6-minute walk distance (6MWD) at baseline, 4 and 24 weeks after their first BPA session. We compared clinical and hemodynamic parameters at the baseline and last BPA session.

RESULTS:

Fifty-two BPA sessions were performed in 15 patients, six of whom had a history of PEA. BPA resulted in improvements in World Health Organization (WHO) functional class (2.9 ± 0.8 to 1.7 ± 0.6, P = 0.002), 6MWD (387.0 ± 86.4 to 453.4 ± 64.8 m, P = 0.01), tricuspid annular plane systolic excursion (14.1 ± 3.6 to 15.6 ± 4.3 mm, P = 0.03) and hemodynamics, including a decline in mean pulmonary artery pressure (41.1 ± 13.1 to 32.1 ± 9.5 mmHg, P < 0.001) and in pulmonary vascular resistance (607.4 ± 452.3 to 406.7 ± 265.4 dyne.sec.cm⁻⁵, P = 0.01) but not in cardiac index (2.94 ± 0.79 to 2.96 ± 0.93 L/min/m², P = 0.92). Six cases of complications were recorded, including two cases of reperfusion injury.

CONCLUSION:

BPA might be a safe and effective treatment strategy for both inoperable CTEPH patients and patients with residual pulmonary hypertension after PEA.

PMCID: PMC5760809 [Available on 2018-01-22] Free Article
PMID: 29318791

Conflict of interest statement
The authors have no potential conflicts of interest to disclose.

Respiration. 2018 Jan 9. doi: 10.1159/000484942. [Epub ahead of print]

Modern Invasive Hemodynamic Assessment of Pulmonary Hypertension.

Pagnamenta A^1,2,3, Lador F^3,4, Azzola A^1,5, Beghetti M^4,6.

Author information:

1 Department of Intensive Care Medicine, Ente Ospedaliero Cantonale (EOC), Intensive Care Units, Regional Hospital of Mendrisio and Lugano, Mendrisio, Switzerland.
2 Unit of Clinical Epidemiology, Ente Ospedaliero Cantonale (EOC), Bellinzona, Switzerland.
3 Division of Pneumology, University of Geneva, Geneva, Switzerland.
4 Pulmonary Hypertension Program, University of Geneva, Geneva, Switzerland.
5 Pneumology, Department of Internal Medicine, Regional Hospital of Lugano, Lugano, Switzerland.
6 Pediatric Cardiology Unit, Children’s University Hospital, University of Geneva, Geneva, Switzerland.

Abstract

Since 1998 pulmonary hypertension has been clinically classified into five well-defined, distinct categories. A definitive diagnosis of pulmonary hypertension requires the invasive confirmation of an elevated mean pulmonary artery pressure of 25 mm Hg or above during a right heart catheterization. From a hemodynamic point of view, pulmonary hypertension is classified into precapillary and postcapillary pulmonary hypertension on the basis of a pulmonary artery wedge pressure threshold value of 15 mm Hg. Pulmonary vascular resistance is better characterized by multi-point pressure/flow measurements than by single-point determination. Multi-point pulmonary vascular resistance calculation could be useful for early disease identification as well as for treatment response assessment. Occlusion analysis of the pulmonary artery pressure decay curve after balloon inflation at the tip of the pulmonary artery catheter permits locating the site of predominantly increased resistance and could be useful in differentiating proximal from distal vasculopathy, especially in chronic thromboembolic pulmonary hypertension. The pulsatile hydraulic load of the pulmonary circulation can be better appreciated by pulmonary vascular impedance or via the resistance-compliance relationship than by means of pulmonary vascular resistance. Determination of right ventriculo-arterial coupling permits assessing the impact of an elevated afterload on right ventricular function, which ultimately determines the symptoms and prognosis of patients with pulmonary hypertension. The clinical utility of combining different invasive hemodynamic approaches is still uncertain and remains to be determined.

PMID: 29316567

Pulm Circ. 2018 Jan 1:2045893218755325. doi: 10.1177/2045893218755325. [Epub ahead of print]

EXPRESS: Impaired systemic oxygen extraction in treated exercise pulmonary hypertension: a new engine in an old car?

Faria Urbina M¹, Oliveira R², Segrera SA³, Lawler L³, Waxman AB³, Systrom D.

Author information:

1. Brigham and Women’s Hospital.
2. Universidade Federal de Sao Paulo.
3. Brigham and Womens Hospital.

Abstract

Ambrisentan in 22 patients with pulmonary hypertension diagnosed during exercise (ePH) improved pulmonary hemodynamics; however, there was only a trend toward increased maximum oxygen uptake (VO2max) secondary to decreased maximum exercise systemic oxygen extraction (Ca-vO2). We speculate that improved pulmonary hemodynamics at maximum exercise “unmasked” a pre-existing skeletal muscle abnormality.

PMID: 29309261

Expert Opin Pharmacother. 2017 Oct;18(15):1661-1667. doi: 10.1080/14656566.2017.1378347. Epub 2017 Sep 19.

Oral treprostinil in the treatment of pulmonary arterial hypertension.

Feldman J¹, Habib N^2,3, Radosevich J², Dutt M^2,3.

Author information:

1 a Arizona Pulmonary Specialists , Phoenix , AZ , USA.
2 b St. Joseph’s Hospital & Medical Center , Phoenix , AZ , USA.
3 c Creighton University Internal Medicine Residency , Phoenix , AZ , USA.

Abstract

Pulmonary arterial hypertension (PAH) is a rare disease resulting in progressive remodeling of the pulmonary vasculature and eventual right ventricular failure. Despite the development of 13 therapies for PAH since 2000, the use of continuously infused prostanoids retains a special role. Infused medications present unique challenges, and the search for an efficacious oral prostanoid culminated in the FDA approval of oral treprostinil – a first in class oral prostanoid medication approved to treat pulmonary arterial hypertension (PAH). Areas covered: In this discussion, we review the pharmacologic properties of oral treprostinil, and discuss three original major registration studies that resulted in the approval and widespread use of the drug. We also review several post-approval analyses and transitional studies. We discuss administration issues including side effects, transitioning, cost, and comparative analysis with selexipag. Expert opinion: Though the prospects of harnessing the benefits of continuously infused prostanoid therapy in a pill form are tantalizing, the gap in efficacy between oral and infused treatment is substantial. Major side effects and exorbitant cost are further barriers to broad uptake. Competition from oral prostaglandin receptor agonist selexipag challenges the commercial success of oral treprostinil. The long-term viability of oral treprostinil rests largely on the outcome of the long-term event-driven study of the molecule added to background approved ERA or PDE5 inhibitor monotherapy.

PMID: 28922964 [Indexed for MEDLINE]

BMC Cardiovasc Disord. 2017 Sep 6;17(1):239. doi: 10.1186/s12872-017-0674-3.

Sildenafil dosed concomitantly with bosentan for adult pulmonary arterial hypertension in a randomized controlled trial.

Vizza CD¹, Jansa P², Teal S³, Dombi T⁴, Zhou D⁵.

Author information:

1. Unita’ di Ipertensione Polmonare, Dipartimento di Scienze Respiratorie e Cardiovascolari, Universita’ degli Studi di Roma La Sapienza, Viale del Policlinico, 155, Rome, Italy. dario.vizza@uniroma1.it.
2. Charles University, Ovocný trh 3-5, 116 36 Praha 1, Prague, Czech Republic.
3. Pfizer Limited, Tadworth, Berlin, UK.
4. Pfizer Inc, Eastern Point Rd, Groton, CT, 06340, USA.
5. Pfizer Inc, 4 E Carol Ave, Burlingame, New York, CA, 94010, USA.

Abstract

BACKGROUND:

Few controlled clinical trials exist to support oral combination therapy in pulmonary arterial hypertension (PAH).

METHODS:

Patients with PAH (idiopathic [IPAH] or associated with connective tissue disease [APAH-CTD]) taking bosentan (62.5 or 125 mg twice daily at a stable dose for ≥3 months) were randomized (1:1) to sildenafil (20 mg, 3 times daily; n = 50) or placebo (n = 53). The primary endpoint was change from baseline in 6-min walk distance (6MWD) at week 12, assessed using analysis of covariance. Patients could continue in a 52-week extension study. An analysis of covariance main-effects model was used, which included categorical terms for treatment, baseline 6MWD (<325 m; ≥325 m), and baseline aetiology; sensitivity analyses were subsequently performed.

RESULTS:

In sildenafil versus placebo arms, week-12 6MWD increases were similar (least squares mean difference [sildenafil-placebo], -2.4 m [90% CI: -21.8 to 17.1 m]; P = 0.6); mean ± SD changes from baseline were 26.4 ± 45.7 versus 11.8 ± 57.4 m, respectively, in IPAH (65% of population) and -18.3 ± 82.0 versus 17.5 ± 59.1 m in APAH-CTD (35% of population). One-year survival was 96%; patients maintained modest 6MWD improvements. Changes in WHO functional class and Borg dyspnoea score and incidence of clinical worsening did not differ. Headache, diarrhoea, and flushing were more common with sildenafil.

CONCLUSIONS:

Sildenafil, in addition to stable (≥3 months) bosentan therapy, had no benefit over placebo for 12-week change from baseline in 6MWD. The influence of PAH aetiology warrants future study.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00323297 (registration date: May 5, 2006).

PMCID: PMC5586020 Free PMC Article
PMID: 28874133 [Indexed for MEDLINE]

BMC Cardiovasc Disord. 2017 May 22;17(1):131. doi: 10.1186/s12872-017-0567-5.

The use of Macitentan in Fontan circulation: a case report.

Demetriades P¹, Aziz A², Condliffe R³, Bowater SE², Clift PF².

Author information:

1 Department of Adult Congenital Heart Disease, Queen Elizabeth Hospital, Birmingham, UK. polyvios.demetriades@nhs.net.
2 Department of Adult Congenital Heart Disease, Queen Elizabeth Hospital, Birmingham, UK.
3 Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, Sheffield, UK.

Abstract

BACKGROUND:

The Fontan circulation, a result of a palliative procedure in patients with single systemic ventricles, is defined by chronically elevated pulmonary vascular resistance. When traditional heart failure therapies fail, pharmacological agents that reduce pulmonary artery pressures may be used. These include endothelial-receptor antagonists, prostanoids and phosphodiesterase type 5 inhibitors. We report the first use of macitentan, an endothelin-receptor antagonist, in a patient with a Fontan circulation.

CASE PRESENTATION:

We describe the case of a 50 year old female with tricuspid atresia and transposition of the great arteries. Following complex surgery as a child, she subsequently underwent a fenestrated modified atrial pulmonary Fontan operation which was later converted to a total cavopulmonary anastomosis Fontan circulation. Due to failure of various medications to relieve her worsening symptoms, she was commenced on macitentan in April 2016. Few months later, she demonstrated a significant symptomatic improvement and associated increase in her incremental shuttle walking test distance.

CONCLUSIONS:

Macitentan has slower receptor dissociation kinetics compared to other endothelin-receptor antagonists, leading to enhanced pharmacological activity with promising effects in patients with pulmonary arterial hypertension. The patient we report has shown considerable improvement in exercise capacity following introduction of this medication and thus we suggest further randomised trials to establish the role of different endothelin-receptor antagonists in the management of the Fontan circulation.

PMCID: PMC5440995 Free PMC Article
PMID: 28532389 [Indexed for MEDLINE]

Histochem Cell Biol. 2017 Jun;147(6):707-719. doi: 10.1007/s00418-017-1551-y. Epub 2017 Mar 1.

Localization and pneumococcal alteration of junction proteins in the human alveolar-capillary compartment.

Peter A^1,2, Fatykhova D¹, Kershaw O³, Gruber AD³, Rueckert J⁴, Neudecker J⁴, Toennies M⁵, Bauer TT⁵, Schneider P⁶, Schimek M⁷, Eggeling S⁷, Suttorp N¹, Hocke AC¹, Hippenstiel S^8,9.

Author information:

1 Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.
2 Department for Bioanalytics, Institute of Biotechnology, Technische Universität Berlin, 13355, Berlin, Germany.
3 Department of Veterinary Pathology, Freie Universität Berlin, Robert-von-Ostertag-Strasse 15, 14163, Berlin, Germany.
4 Department of General, Visceral, Vascular and Thoracic Surgery, Charité-Universitätsmedizin Berlin, Chariteplatz 1, 10117, Berlin, Germany.
5 Lungenklinik Heckeshorn, HELIOS Klinikum Emil von Behring, Walterhöferstrasse 11, 14165, Berlin, Germany.
6 Department for General and Thoracic Surgery, DRK Clinics, Drontheimer Strasse 39-40, 13359, Berlin, Germany.
7 Vivantes Netzwerk für Gesundheit, Klinikum Neukölln, Klinik für Thoraxchirurgie, Berlin, Rudower Straße 48, 12351, Berlin, Germany.
8 Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany. stefan.hippenstiel@charite.de.
9 Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany. stefan.hippenstiel@charite.de.

Abstract

Loss of alveolar barrier function with subsequent respiratory failure is a hallmark of severe pneumonia. Although junctions between endo- and epithelial cells regulate paracellular fluid flux, little is known about their composition and regulation in the human alveolar compartment. High autofluorescence of human lung tissue in particular complicates the determination of subcellular protein localization. By comparing conventional channel mode confocal imaging with spectral imaging and linear unmixing, we demonstrate that background fluorescent spectra and fluorophore signals could be rigorously separated resulting in complete recovery of the specific signal at a high signal-to-noise ratio. Using this technique and Western blotting, we show the expression patterns of tight junction proteins occludin, ZO-1 as well as claudin-3, -4, -5 and -18 and adherence junction protein VE-cadherin in naive or Streptococcus pneumoniae-infected human lung tissue. In uninfected tissues, occludin and ZO-1 formed band-like structures in alveolar epithelial cells type I (AEC I), alveolar epithelial cells type II (AEC II) and lung capillaries, whereas claudin-3, -4 and -18 were visualised in AEC II. Claudin-5 was detected in the endothelium only. Claudin-3, -5, -18 displayed continuous band-like structures, while claudin-4 showed a dot-like expression. Pneumococcal infection reduced alveolar occludin, ZO-1, claudin-5 and VE-cadherin but did not change the presence of claudin-3, -4 and -18. Spectral confocal microscopy allows for the subcellular structural analysis of proteins in highly autofluorescent human lung tissue. The thereby observed deterioration of lung alveolar junctional organisation gives a structural explanation for alveolar barrier disruption in severe pneumococcal pneumonia.

PMID: 28247028 [Indexed for MEDLINE]

Anesth Analg. 2017 Aug;125(2):375-377. doi: 10.1213/ANE.0000000000002239.

Inhaled Pulmonary Vasodilators in Cardiac Surgery Patients: Correct Answer Is “NO”.

Ichinose F¹, Zapol WM.

Author information:

1. From the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
   Comment on

Aerosolized Vasodilators for the Treatment of Pulmonary Hypertension in Cardiac Surgical Patients: A Systematic Review and Meta-analysis. [Anesth Analg. 2017]

PMCID: PMC5644498 [Available on 2018-08-01]
PMID: 28731972 [Indexed for MEDLINE]

Eur Respir J. 2018 Jan 11;51(1). pii: 1701502. doi: 10.1183/13993003.01502-2017. Print 2018 Jan.

Balloon pulmonary angioplasty in sarcoid-related pulmonary hypertension.

Tramper J¹, Nossent EJ¹, Lely RJ², Krouwels FH³, Meijboom LJ², Vonk Noordegraaf A⁴.

Author information:

1 Dept of Pulmonary Diseases, VU University Medical Centre, Amsterdam, The Netherlands.
2 Dept of Radiology, VU University Medical Center (VUmc), Amsterdam, The Netherlands.
3 Dept of Respiratory Medicine, Spaarne Hospital, Hoofddorp, The Netherlands.
4 Dept of Pulmonary Diseases, VU University Medical Centre, Amsterdam, The Netherlands a.vonk@vumc.nl.

PMID: 29326329