Publications by authors named "Marli M Knorst"

10 Publications

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Altered Gut Microbiome Profile in Patients With Pulmonary Arterial Hypertension.

Hypertension 2020 04 24;75(4):1063-1071. Epub 2020 Feb 24.

From the Department of Physiology and Functional Genomics (S.K., E.M.R., M.K.R.), College of Medicine, University of Florida, Gainesville.

Pulmonary arterial hypertension (PAH) is considered a disease of the pulmonary vasculature. Limited progress has been made in preventing or arresting progression of PAH despite extensive efforts. Our previous studies indicated that PAH could be considered a systemic disease since its pathology involves interplay of multiple organs. This, coupled with increasing implication of the gut and its microbiome in chronic diseases, led us to hypothesize that patients with PAH exhibit a distinct gut microbiome that contributes to, and predicts, the disease. Fecal microbiome of 18 type 1 PAH patients (mean pulmonary arterial pressure, 57.4, SD 16.7 mm Hg) and 13 reference subjects were compared by shotgun metagenomics to evaluate this hypothesis. Significant taxonomic and functional changes in microbial communities in the PAH cohort were observed. Pathways for the synthesis of arginine, proline, and ornithine were increased in PAH cohort compared with reference cohort. Additionally, groups of bacterial communities associated with trimethylamine/ trimethylamine N-oxide and purine metabolism were increased in PAH cohort. In contrast, butyrate-and propionate-producing bacteria such as Coprococcus, Butyrivibrio, Lachnospiraceae, Eubacterium, Akkermansia, and Bacteroides were increased in reference cohort. A random forest model predicted PAH from the composition of the gut microbiome with 83% accuracy. Finally, virome analysis showed enrichment of Enterococcal and relative depletion of Lactococcal phages in the PAH cohort. In conclusion, patients with PAH exhibit a unique microbiome profile that has the high predictive potential for PAH. This highlights previously unknown roles of gut bacteria in this disease and could lead to new therapeutic, diagnostic, or management paradigms for PAH.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.14294DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7067661PMC
April 2020

Hepatopulmonary syndrome has low prevalence of pulmonary vascular abnormalities on chest computed tomography.

PLoS One 2019 18;14(10):e0223805. Epub 2019 Oct 18.

Programa de Pós-Graduação em Ciências Pneumológicas, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.

Purpose: Hepatopulmonary syndrome (HPS) is defined as an arterial oxygenation defect induced by intrapulmonary vascular dilatations associated with hepatic disease. This study aimed to assess the prevalence of type 1 and 2 pulmonary vascular abnormalities on chest computed tomography (CT) in patients with cirrhosis and HPS and to characterize intra- and interobserver reliability.

Materials And Methods: Two thoracic radiologists retrospectively evaluated chest CT scans from 38 cirrhosis patients with HPS. They classified the pulmonary vascular abnormalities as type 1 (multiple dilated distal pulmonary arteries), type 2(nodular dilatation or individual pulmonary arterial malformation), or absence of abnormality. Furthermore, they measured the diameters of the central pulmonary arteries and subsegmental pulmonary arteries and bronchi. We analyzed the prevalence, intraobserver reliability, and interobserver reliability of abnormal CT findings related to HPS, and the correlation of these findings with partial arterial oxygen pressure (PaO2).

Results: The overall prevalence of pulmonary vascular abnormalities was 28.9% (95% confidence intervals: 15.4%, 45.9%). Moreover, 26.3% of patients had type 1 abnormality (13.4%, 43.1%) and 2.6% of patients had type 2 abnormality (0.0%, 13.8%). The intraobserver reliability kappa value was 0.666 (0.40, 0.91) and the interobserver kappa value was 0.443 (0.12, 0.77). There was no correlation between pulmonary vascular abnormalities on CT and PaO2 values.

Conclusions: The prevalence of pulmonary vascular abnormalities on chest CT of patients with cirrhosis and HPS is low and not correlated with PaO2. These findings question the usefulness of chest CT for the evaluation of patients with cirrhosis and HPS.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0223805PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6799931PMC
March 2020

Tidal Flow-Volume Loop Enveloping at Rest in Advanced COPD.

Respir Care 2019 Dec 27;64(12):1488-1499. Epub 2019 Aug 27.

Programa de Pós-Graduação em Ciências Pneumológicas, Universidade Federal do Rio Grande do Sul, Rio Grande do Sul, Brazil.

Background: Expiratory flow limitation (EFL) is a key physiological abnormality in COPD. Comparing tidal-to-maximum flow-volume (F-V) loops is a simple and widely available method to assess EFL in patients with COPD. We aimed to investigate whether subjects with COPD showing significant resting tidal F-V enveloping (ie, > 50% tidal volume) would present with higher exertional operating lung volumes, which would lead to greater burden of dyspnea and poorer exercise tolerance compared to their counterparts.

Methods: 37 subjects with COPD (21 males; 63.1 ± 9.2 years old; FEV = 37 ± 12% predicted) and 9 paired controls (3 males; 55.9 ± 11.7 y old) performed an incremental cardiopulmonary exercise testing on a cycle ergometer. Dyspnea perception, inspiratory capacity maneuvers after 3-4 sequential tidal F-V loops, and esophageal and gastric pressures were measured during exercise.

Results: Most subjects (31 of 37, 84%) presented with significant tidal F-V enveloping. Critical inspiratory constraints and upward dyspnea inflection points (as a function of both work rate and ventilation) were reached earlier in these subjects, thereby leading to poorer exercise tolerance compared to their counterparts ( = .01). Abdominal muscle recruitment (ie, increase in gastric pressure ≥ 15%) during tidal expiration was significantly higher in the EFL+ group. However, this did not bear an influence on the operating lung volumes, inspiratory constraints, dyspnea, cardiocirculatory responses, or exercise tolerance ( > .05).

Conclusions: Tidal F-V loop enveloping at rest should be valued as it is related to relevant clinical outcomes, such as dyspnea burden and exercise tolerance in subjects with COPD.
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http://dx.doi.org/10.4187/respcare.06787DOI Listing
December 2019

Lung Ultrasound Prior to Spontaneous Breathing Trial Is Not Helpful in the Decision to Wean.

Respir Care 2018 07 17;63(7):873-878. Epub 2018 Apr 17.

Adult Intensive Care Unit of Hospital Moinhos de Vento, Porto Alegre, Brazil.

Background: Lung ultrasound is increasingly becoming a diagnostic tool in the critical care setting. B-pattern on a lung ultrasound is an artifact composed of multiple B-lines and correlates with interstitial edema. A randomized controlled trial concluded that bedside thoracic ultrasound could predict postextubation distress through changes in lung aeration during a weaning procedure; however, it could not screen patients before performance of a spontaneous breathing trial (SBT).

Methods: We conducted a 2-year, prospective, multicenter, observational study in 2 adult medical-surgical ICUs in southern Brazil. All enrolled subjects met eligibility criteria for ventilation liberation. Patients with tracheostomy were excluded. Lung ultrasound was performed immediately before SBT. B-predominance was defined as any profile with anterior bilateral B-pattern. The primary outcome was SBT failure, defined as the inability to tolerate a T-piece trial of 30-120 min, in which case subjects were not extubated.

Results: From 2011 to 2013, 250 subjects undergoing weaning procedures were evaluated. SBT failure occurred in 51 (20.4%) subjects. Subjects with a successful SBT were extubated on the first attempt in 75.6% of cases. B-predominance was a very weak predictor for SBT outcome, showing 47% sensitivity, 64% specificity, 25% positive predictive value, and 82% negative predictive value.

Conclusion: B-pattern detected by a simplified lung ultrasound protocol should not preclude hemodynamically stable, sufficiently oxygenated patients from performing an SBT.
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http://dx.doi.org/10.4187/respcare.05817DOI Listing
July 2018

Characteristics associated with mortality in patients with chronic obstructive pulmonary disease (COPD)-heart failure coexistence.

Prim Health Care Res Dev 2018 11 21;19(6):570-574. Epub 2018 Feb 21.

1Hospital de Clinicas de Porto Alegre (HCPA),Universidade Federal do Rio Grande do Sul (UFRGS),Porto Alegre,RS,Brazil.

AimTo investigate if cardiac/pulmonary functional tests and variables obtained from clinical practice (body mass index, dyspnea, functional class, clinical judgment of disability to perform an exercise test and previous hospitalization rate) are related to mortality in patients with overlap chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF). BACKGROUND: Although the coexistence of COPD and CHF has been growingly reported, description of survival predictors considering the presence of both conditions is still scarce. METHODS: Using a cohort design, outpatients with the previous diagnosis of COPD and/or CHF that performed both spirometry and echocardiography in the same year were followed-up during a mean of 20.9±8.5 months.FindingsOf the 550 patients initially evaluated, 301 had both spirometry and echocardiography: 160 (53%) with COPD on isolation; 100 (33%) with CHF on isolation; and 41 (14%) with overlap. All groups presented similar mortality: COPD 17/160 (11%); CHF 12/100 (12%); and overlap 7/41 (17%) (P=0.73). In the overlap group (n=41), inability to exercise and hospitalization rate were the unique parameters associated with higher mortality (seven events) in univariate analyses. In conclusion, inability to exercise and hospitalization rate emerged as the unique parameters associated with mortality in our sample.
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http://dx.doi.org/10.1017/S1463423618000117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6692830PMC
November 2018

Effects of Expiratory Positive Airway Pressure on Exercise Tolerance, Dynamic Hyperinflation, and Dyspnea in COPD.

Respir Care 2017 Oct 1;62(10):1298-1306. Epub 2017 Aug 1.

Programa de Pós-Graduação em Ciências Pneumológicas, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul (UFRGS), Serviço de Pneumologia Hospital de Clínicas de Porto Alegre, Brazil.

Introduction: The application of expiratory positive airway pressure (EPAP) in patients with COPD during exercise may reduce dynamic hyperinflation, while, on the other hand, it can increase the resistive work of breathing. Therefore, we evaluated the effects of 2 intensities of EPAP during exercise on tolerance, dynamic hyperinflation, and dyspnea in subjects with moderate to very severe COPD.

Methods: We performed a cross-sectional, experimental, 4-visit study. In visit 1, subjects performed symptom-limited cycling incremental cardiopulmonary exercise test (CPET). In visits 2-4, at least 48 h apart, in a randomized order, subjects performed constant CPET without EPAP, EPAP with 5 cm HO (EPAP5), or EPAP with 10 cm HO (EPAP10).

Results: The study included 15 non-hypoxemic subjects ranging from moderate to very severe COPD (mean FEV = 35 ± 11% predicted). Increasing intensities of EPAP during constant CPET tended to cause progressive reduction in exercise tolerance ( = .11). Of note, 10 of 15 subjects demonstrated significantly shorter average exercise duration with EPAP10 compared to the test without EPAP (-151 ± 105 s, = .03 or -41 ± 26%). Minute ventilation increment was constrained by EPAP, secondary to a limited increase in tidal volume ( = .01). Finally, dyspnea sensation and serial measurements of inspiratory capacity during exercise were similar when comparing the three interventions at isotime and at end-constant CPETs.

Conclusions: The application of EPAP5 or EPAP10 during exercise tended to cause a progressive reduction in exercise tolerance in subjects with COPD without improvement in dyspnea or dynamic hyperinflation at equivalent exercise duration.
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http://dx.doi.org/10.4187/respcare.05556DOI Listing
October 2017

Silicosis prevalence and risk factors in semi-precious stone mining in Brazil.

Am J Ind Med 2017 Jun;60(6):529-536

Federal University of Rio Grande do Sul, Graduate Program in Pulmonology, Porto Alegre, RS, Brazil.

Background: Underground mining generates large amounts of dust and exposes workers to silica. This study aims to determine the prevalence and predictor factors for the development of silicosis among semi-precious-stone mineworkers in southern Brazil working in a self-administered cooperative.

Methods: In a cross-sectional study of 348 current workers and retirees, demographic data, medical, and occupational history were collected through an interview performed by a nurse and medical record review. Risk factor associations were studied by Poisson multivariate regression.

Results: The overall prevalence of silicosis was 37%, while in current miners it was 28%. Several risk factors for silicosis were identified in the univariate analysis. Inadequate ventilation in the underground galleries combined with dry drilling, duration of silica exposure, and (inversely) education remained significant in the multivariate analysis (P < 0.05).

Conclusion: This study is unusual in studying semi-precious stone mineworkers in a self-administered worker cooperative with limited resources. The prevalence of silicosis was very high. A number of recommendations are made-including technical support for worker cooperatives, surveillance of silica exposure and silicosis, exposure reduction measures, and benefits allowing impaired miners to leave the industry.
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http://dx.doi.org/10.1002/ajim.22719DOI Listing
June 2017

Fire-Related Inhalation Injury.

N Engl J Med 2016 11;375(19):1903-1904

Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.

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http://dx.doi.org/10.1056/NEJMc1611256DOI Listing
November 2016

Inspiratory loading and limb blood flow in COPD: The modulating effects of resting lung hyperinflation.

Respir Physiol Neurobiol 2016 07 7;228:25-9. Epub 2016 Mar 7.

Laboratory of Clinical Exercise Physiology (LACEP), Division of Respirology, Dept. of Medicine, Queen's University and Kingston General Hospital, Kingston, Canada.

Inspiratory resistive loading (IRL) may have deleterious cardiocirculatory effects leading to poor peripheral perfusion in severely-hyperinflated patients with COPD. Nineteen patients (13 severely-hyperinflated with inspiratory capacity/total lung capacity ratio≤0.28) underwent calf blood flow (CBF) measurements by venous occlusion plethysmography at rest and during IRL at 60% maximal inspiratory pressure. Severely-hyperinflated patients had lower resting CBF and greater calf vascular resistance (CVR) than moderately-hyperinflated patients (p<0.05). All severely-hyperinflated patients had markedly reduced CBF (p=0.01). Opposite to our main hypothesis, however, IRL did not further reduce CBF in these patients (p>0.05). Conversely, it significantly decreased CBF and increased CVR in moderately-hyperinflated patients; in fact, end-trial CBF and CVR did not differ between the groups (p>0.05). In conclusion, marked impairments in resting appendicular blood flow in severely-hyperinflated patients with COPD were seen only after acute IRL in less hyperinflated patients. These findings set the stage for studies investigating the effects of lung deflation on peripheral hemodynamics in patients with severe hyperinflation.
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http://dx.doi.org/10.1016/j.resp.2016.03.004DOI Listing
July 2016

Attenuation of muscle metaboreflex in chronic obstructive pulmonary disease.

Med Sci Sports Exerc 2008 Jan;40(1):9-14

Exercise Pathophysiology Research Laboratory, Hospital of Clinics of Porto Alegre, Porto Alegre, Brazil.

Purpose: Abnormal skeletal muscle function is well documented in chronic obstructive pulmonary disease, but there is no information about the activity of muscle metabosensitive afferents. In this study, we tested the hypothesis that patients with chronic obstructive pulmonary disease would have abnormal reflex responses to stimulation of metabosensitive afferents in skeletal muscle when compared with healthy, matched subjects.

Methods: In 16 patients with moderate to severe chronic obstructive pulmonary disease and 13 healthy, age-matched control subjects, we evaluated heart rate, mean blood pressure, calf blood flow, and calf vascular resistance responses to static handgrip exercise at 30% of maximal voluntary contraction, followed by recovery with or without circulatory occlusion. Muscle metaboreflex control of calf vascular resistance was estimated by subtracting the area under the curve with circulatory occlusion from the area under the curve without circulatory occlusion.

Results: Mean blood pressure and heart rate responses were not significantly different in patients and controls during exercise and recovery. In the control group, calf vascular resistance increased significantly during exercise and remained elevated above baseline during circulatory occlusion, whereas in patients changes from rest were not significantly different in both trials. Estimated muscle metaboreflex control of calf vascular resistance was significantly reduced in the patients (controls: 31 +/- 22 units, patients: 8 +/- 31 units, P < 0.05).

Conclusion: Patients with chronic obstructive pulmonary disease have a reduced calf vascular resistance response to handgrip exercise and to selective activation of muscle metaboreflex when compared with healthy subjects.
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http://dx.doi.org/10.1249/mss.0b013e3181590bd9DOI Listing
January 2008
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