Publications by authors named "John A Sbarbaro"

13 Publications

  • Page 1 of 1

Association of obesity-related inflammatory pathways with lung function and exercise capacity.

Respir Med 2021 Jul 30;183:106434. Epub 2021 Apr 30.

From the Cardiovascular Research Center, Division of Massachusetts General Hospital, Boston, MA, USA; Cardiology Division of Massachusetts General Hospital, Boston, MA, USA. Electronic address:

Background: Obesity has multifactorial effects on lung function and exercise capacity. The contributions of obesity-related inflammatory pathways to alterations in lung function remain unclear.

Research Question: To examine the association of obesity-related inflammatory pathways with pulmonary function, exercise capacity, and pulmonary-specific contributors to exercise intolerance.

Method: We examined 695 patients who underwent cardiopulmonary exercise testing (CPET) with invasive hemodynamic monitoring at Massachusetts General Hospital between December 2006-June 2017. We investigated the association of adiponectin, leptin, resistin, IL-6, CRP, and insulin resistance (HOMA-IR) with pulmonary function and exercise parameters using multivariable linear regression.

Results: Obesity-related inflammatory pathways were associated with worse lung function. Specifically, higher CRP, IL-6, and HOMA-IR were associated with lower percent predicted FEV and FVC with a preserved FEV/FVC ratio suggesting a restrictive physiology pattern (P ≤ 0.001 for all). For example, a 1-SD higher natural-logged CRP level was associated with a nearly 5% lower percent predicted FEV and FVC (beta -4.8, s.e. 0.9 for FEV1; beta -4.9, s.e. 0.8 for FVC; P < 0.0001 for both). Obesity-related inflammatory pathways were associated with worse pulmonary vascular distensibility (adiponectin, IL-6, and CRP, P < 0.05 for all), as well as lower pulmonary artery compliance (IL-6 and CRP, P ≤ 0.01 for both).

Interpretation: Our findings highlight the importance of obesity-related inflammatory pathways including inflammation and insulin resistance on pulmonary spirometry and pulmonary vascular function. Specifically, systemic inflammation as ascertained by CRP, IL-6 and insulin resistance are associated with restrictive pulmonary physiology independent of BMI. In addition, inflammatory markers were associated with lower exercise capacity and pulmonary vascular dysfunction.
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http://dx.doi.org/10.1016/j.rmed.2021.106434DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144063PMC
July 2021

Metabolic Cost of Exercise Initiation in Patients With Heart Failure With Preserved Ejection Fraction vs Community-Dwelling Adults.

JAMA Cardiol 2021 Jun;6(6):653-660

Simches Cardiovascular Research Center, Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston.

Importance: Heart failure with preserved ejection fraction (HFpEF) is a joint metabolic and cardiovascular disorder with significant noncardiac contributions.

Objective: To define and quantify the metabolic cost of initiating exercise in individuals with and without HFpEF and its functional consequences.

Design, Setting, And Participants: This prospective cohort study included individuals with hemodynamically confirmed HFpEF from the Massachusetts General Hospital Exercise Study (MGH-ExS) and community-dwelling participants from the Framingham Heart Study (FHS). Analysis began April 2016 and ended November 2020.

Exposures: Internal work (IW), a measure of work equivalents required to initiate movement.

Main Outcomes And Measures: Using breath-by-breath oxygen uptake (V̇o2) measurements and V̇o2-work rate associations, cost of initiating exercise (IW) in patients with HFpEF (MGH-ExS) and in community-dwelling individuals (FHS) was quantified. Linear regression was used to estimate associations between IW and clinical/hemodynamic measures.

Results: Of 3231 patients, 184 (5.7%) had HFpEF and were from MGH-ExS, and 3047 (94.3%) were community-dwelling individuals from FHS. In the MGH-ExS cohort, 86 (47%) were women, the median (interquartile range) age was 63 (53-72) years, and the median (interquartile range) peak V̇o2 level was 13.33 (11.77-15.62) mL/kg/min. In the FHS cohort, 1620 (53%) were women, the median (interquartile range) age was 54 (48-60) years, and the median (interquartile range) peak V̇o2 level was 22.2 (17.85-27.35) mL/kg/min. IW was higher in patients with HFpEF and accounted for 27% (interquartile range, 21%-39%) of the total work (IW + measured external workload on the cycle), compared with 15% (interquartile range, 12%-20%) of that in FHS participants. Body mass index accounted for greatest explained variance in patients with HFpEF from MGH-ExS and FHS participants (22% and 18%, respectively), while resting cardiac output and biventricular filling pressures were not significantly associated with variance in IW in patients with HFpEF. A higher IW in patients with HFpEF was associated with a greater increase in left- and right-sided cardiac filing pressure during unloaded exercise, despite similar resting hemodynamic measures across IW.

Conclusions And Relevance: This study found that internal work, a new body mass index-related measure reflecting the metabolic cost of initiating movement, is higher in individuals with HFpEF compared with middle-aged adults in the community and is associated with steep, early increases in cardiac filling pressures. These findings highlight the importance of quantifying heterogeneous responses to exercise initiation when evaluating functional intolerance in individuals at risk for or with HFpEF.
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http://dx.doi.org/10.1001/jamacardio.2021.0292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970388PMC
June 2021

Exercise Intolerance in Heart Failure With Preserved Ejection Fraction: Arterial Stiffness and Aabnormal Left Ventricular Hemodynamic Responses During Exercise.

J Card Fail 2021 Jun 26;27(6):625-634. Epub 2021 Feb 26.

Corrigan Minehan Heart Center, Cardiology Division, Massachusetts General Hospital, Boston, Massachusetts. Electronic address:

Background: Arterial stiffness is thought to contribute to the pathophysiology of heart failure with preserved ejection fraction (HFpEF). We sought to examine arterial stiffness in HFpEF and hypertension and investigate associations of arterial and left ventricular hemodynamic responses to exercise.

Methods And Results: A total of 385 symptomatic individuals with an EF of ≥50% underwent upright cardiopulmonary exercise testing with invasive hemodynamic assessment of arterial stiffness and load (aortic augmentation pressure, augmentation index, systemic vascular resistance index, total arterial compliance index, effective arterial elastance index, and pulse pressure amplification) at rest and during incremental exercise. An abnormal hemodynamic response to exercise was defined as a steep increase in pulmonary capillary wedge pressure relative to cardiac output (∆PCWP/∆CO > 2 mm Hg/L/min). We compared rest and exercise measures between HFpEF and hypertension in multivariable analyses. Among 188 participants with HFpEF (mean age 61 ± 13 years, 56% women), resting arterial stiffness parameters were worse compared with 94 hypertensive participants (mean age 55 ± 15 years, 52% women); these differences were accentuated during exercise in HFpEF (all P ≤ .0001). Among all participants, exercise measures of arterial stiffness correlated with worse ∆PCWP/∆CO. Specifically, a 1 standard deviation higher exercise augmentation pressure was associated with 2.15-fold greater odds of abnormal LV hemodynamic response (95% confidence interval 1.52-3.05; P < .001). Further, exercise measures of systemic vascular resistance index, elastance index, and pulse pressure amplification correlated with a lower peak oxygen consumption.

Conclusions: Exercise accentuates the increased arterial stiffness found in HFpEF, which in turn correlates with left ventricular hemodynamic responses. Unfavorable ventricular-vascular interactions during exercise in HFpEF may contribute to exertional intolerance and inform future therapeutic interventions.
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http://dx.doi.org/10.1016/j.cardfail.2021.02.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180488PMC
June 2021

Exercise Pulmonary Hypertension Predicts Clinical Outcomes in Patients With Dyspnea on Effort.

J Am Coll Cardiol 2020 01;75(1):17-26

Cardiology Division, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts. Electronic address:

Background: Abnormal pulmonary arterial pressure (PAP) responses to exercise have been described in select individuals; however, clinical and prognostic implications of exercise pulmonary hypertension (exPH) among broader samples remains unclear.

Objectives: This study sought to investigate the association of exPH with clinical determinants and outcomes.

Methods: The authors studied individuals with chronic exertional dyspnea and preserved ejection fraction who underwent cardiopulmonary exercise testing with invasive hemodynamic monitoring. Exercise pulmonary hypertension was ascertained using minute-by-minute PAP and cardiac output (CO) measurements to calculate a PAP/CO slope, and exPH defined as a PAP/CO slope >3 mm Hg/l/min. The primary outcome was cardiovascular (CV) hospitalization or all-cause mortality.

Results: Among 714 individuals (age 57 years, 59% women), 296 (41%) had abnormal PAP/CO slopes. Over a mean follow-up of 3.7 ± 2.9 years, there were 208 CV or death events. Individuals with abnormal PAP/CO slope had a 2-fold increased hazard of future CV or death event (multivariable-adjusted hazard ratio: 2.03; 95% confidence interval: 1.48 to 2.78; p < 0.001). The association of abnormal PAP/CO slope with outcomes remained significant after excluding rest PH (n = 146, hazard ratio: 1.75; 95% confidence interval: 1.21 to 2.54; p = 0.003). Both pre- and post-capillary contributions to exPH independently predicted adverse events (p < 0.001 for both).

Conclusions: Exercise pulmonary hypertension is independently associated with CV event-free survival among individuals undergoing evaluation of chronic dyspnea. These findings suggest incremental value of exercise hemodynamic assessment to resting measurements alone in characterizing the burden of PH in individuals with dyspnea. Whether PH and PH subtypes unmasked by exercise can be used to guide targeted therapeutic interventions requires further investigation.
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http://dx.doi.org/10.1016/j.jacc.2019.10.048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7043927PMC
January 2020

It takes more than a village, it takes a whole country.

Int J Tuberc Lung Dis 2009 Oct;13(10):1191

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October 2009

Promoting adherence to treatment for tuberculosis: the importance of direct observation.

World Hosp Health Serv 2007 ;43(2):30-3

New York City Department of Health and Mental Hygiene, USA.

Since 1993, WHO has recommended a strategy through which national governments can meet their responsibility to treat patients and to prevent the spread of tuberculosis (TBI). Four of the major elements of the strategy, which came to be known as DOTS, were political commitment by governments, improved laboratory services, a continuous supply of good-quality drugs, and a reporting system to document the progress (and failure) of treatment for individual patients and of the programme. The fifth element, effective case management via direct observation of treatment by an independent and trained third party, was a response to decades of reports documenting the failure of patients to complete treatment. Put simply: direct observation of treatment is an integral and essential component of DOTS. The value of the direct observation component of DOTS has been questioned in a recent systematic review, in which it was suggested that direct observation of treatment is unnecessary and disrespectful of patients. Both self-administered treatment and treatment observation by a family member have been proposed as acceptable alternatives. This article challenges the validity of these assertions on the basis that, firstly, direct observation requires strong leadership and a lengthy commitment of human resources, which as yet is not universally employed. Secondly, it is believed that the ultimate ethical and legal responsibility for ensuring treatment completion and cure of a communicable disease belongs to the public health system and the community, and not to the individual patient. TB, this article will seek to argue, can be controlled when appropriate policies are implemented and continued, even in the absence of an outbreak or media attention. Just as patients may be tempted to change or stop an effective treatment regimen because of the long duration of treatment, public health policy-makers may be tempted to alter key elements of DOTS because of the persistence required to maintain effective programmes.
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October 2007

Promoting adherence to treatment for tuberculosis: the importance of direct observation.

Bull World Health Organ 2007 May;85(5):407-9

New York City Department of Health and Mental Hygiene, New York, NY, USA.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2636637PMC
http://dx.doi.org/10.2471/blt.06.038927DOI Listing
May 2007

Family observation of antituberculosis treatment.

Lancet 2006 Jun;367(9528):2055; author reply 2055-6

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http://dx.doi.org/10.1016/S0140-6736(06)68913-7DOI Listing
June 2006

The evolution of antimicrobial agents used for the management of CARTIs: a focus on a new class of antimicrobials--the ketolides.

Authors:
John A Sbarbaro

Am J Manag Care 2004 Oct;10(12 Suppl):S389-99

University Physicians, Inc, University of Colorado Health Sciences Center, Denver, USA.

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October 2004

Finding gold in the muddy waters of public health reports.

Authors:
John A Sbarbaro

Int J Tuberc Lung Dis 2004 Jun;8(6):689-90

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June 2004

The treatment of tuberculosis: reflections on Siberia.

Authors:
John A Sbarbaro

Int J Tuberc Lung Dis 2002 May;6(5):375-7

University of Colorado Health Sciences Center, Denver, USA.

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May 2002

The slippery slope to sloppy DOTS.

Int J Tuberc Lung Dis 2002 May;6(5):371-2

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May 2002

TB Control is Indeed an Exercise in Vigilance.

Authors:
John A Sbarbaro

Public Health Rep 1996 Jan;111(1):32-33

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1381738PMC
January 1996