About

Aili L. Lazaar, MD, is an Adjunct Associate Professor of Medicine in the Department of Medicine at the Perelman School of Medicine at the University of Pennsylvania. Her clinical expertise includes asthma, COPD, and COPD clinical trials. Her research focuses on respiratory conditions, with specific interest in COPD, critical care, pulmonary hypertension, respiratory viral infections, and Hepatitis B. Dr. Lazaar has contributed to understanding airway purines in COPD and has been involved in developing and testing novel pharmacological agents such as CXCR2 antagonists and phosphodiesterase 4 inhibitors. Her work includes investigating the immunomodulatory roles of airway smooth muscle cells and the molecular mechanisms underlying airway inflammation and remodeling.

Research topics

• Internal medicine
• Medicine
• Pathology
• Physical therapy
• Gastroenterology
• Immunology
• Pediatrics

Selected publications

• Study to Explore the Association of the Renin-Angiotensin System and Right Ventricular Function in Mechanically Ventilated Patients

  Journal of Clinical Medicine · 2022-07-27

  articleOpen access

  Background: Right ventricular (RV) dysfunction is associated with pulmonary vasoconstriction in mechanically ventilated patients. Enhancing the activity of angiotensin-converting enzyme 2 (ACE2), a key enzyme of the renin-angiotensin system (RAS), using recombinant human ACE2 (rhACE2) could alleviate RAS-mediated vasoconstriction and vascular remodeling. Methods: This prospective observational study investigated the association between concentrations of RAS peptides (Ang II or Ang(1–7)) and markers of RV function, as assessed by echocardiography (ratio of RV to left ventricular end-diastolic area, interventricular septal motion, and pulmonary arterial systolic pressure (PASP)). Results: Fifty-seven mechanically ventilated patients were enrolled. Incidence rates of acute cor pulmonale (ACP) and pulmonary circulatory dysfunction (PCD) were consistent with previous studies. In the 45 evaluable participants, no notable or consistent changes in RAS peptides concentration were observed over the observation period, and there was no correlation between Ang II concentration and either PASP or RV size. The model of the predicted posterior distributions for the pre- and post-dose values of Ang II demonstrated no change in the likelihood of PCD after hypothetical dosing with rhACE2, thus meeting the futility criteria. Similar results were observed with the other RAS peptides evaluated. Conclusions: Pre-defined success criteria for an association between PCD and the plasma RAS peptides were not met in the mechanically ventilated unselected patients.

  PublisherOA PDFDOI

• An open‐label, dose‐escalation study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single doses of GSK2586881 in participants with pulmonary arterial hypertension

  Pulmonary Circulation · 2021-12-17 · 15 citations

  articleOpen access

  Abstract Preclinical and early clinical studies suggest that angiotensin‐converting enzyme type 2 activity may be impaired in patients with pulmonary arterial hypertension (PAH); therefore, administration of exogenous angiotensin‐converting enzyme type 2 (ACE2) may be beneficial. This Phase IIa, multi‐center, open‐label, exploratory, single‐dose, dose‐escalation study (NCT03177603) assessed the potential vasodilatory effects of single doses of GSK2586881 (a recombinant human ACE2) on acute cardiopulmonary hemodynamics in hemodynamically stable adults with documented PAH who were receiving background PAH therapy. Successive cohorts of participants were administered a single intravenous dose of GSK2586881 of 0.1, 0.2, 0.4, or 0.8 mg/kg. Dose escalation occurred after four or more participants per cohort were dosed and a review of safety, tolerability, pharmacokinetics, and hemodynamic data up to 24 h postdose was undertaken. The primary endpoint was a change in cardiopulmonary hemodynamics (pulmonary vascular resistance, cardiac index, and mean pulmonary artery pressure) from baseline. Secondary/exploratory objectives included safety and tolerability, effect on renin‐angiotensin system peptides, and pharmacokinetics. GSK2586881 demonstrated no consistent or sustained effect on acute cardiopulmonary hemodynamics in participants with PAH receiving background PAH therapy ( N = 23). All doses of GSK2586881 were well tolerated. GSK2586881 was quantifiable in plasma for up to 4 h poststart of infusion in all participants and caused a consistent and sustained reduction in angiotensin II and a corresponding increase in angiotensin (1–7) and angiotensin (1–5). While there does not appear to be a consistent acute vasodilatory response to single doses of GSK2586881 in participants with PAH, the potential benefits in terms of chronic vascular remodeling remain to be determined.

  PublisherOA PDFDOI

• Effects of Recombinant Human Angiotensin-Converting Enzyme 2 on Response to Acute Hypoxia and Exercise: A Randomised, Placebo-Controlled Study

  Pulmonary Therapy · 2021-06-26 · 6 citations

  articleOpen access

  INTRODUCTION: Angiotensin-converting enzyme 2 (ACE2) is a key enzyme of the renin-angiotensin system (RAS) that has been implicated in the pathogenesis of acute respiratory distress syndrome (ARDS). Enhancing ACE2 activity using GSK2586881, a recombinant form of human ACE2, could be beneficial in diseases such as ARDS but may blunt the hypoxic pulmonary vasoconstriction (HPV) response and potentially impact systemic and tissue oxygenation. This study aimed to evaluate the effect of GSK2586881 0.8 mg/kg on HPV response in healthy adult volunteers during exercise under hypoxic conditions. METHODS: In this phase I, randomised, double-blind (sponsor open) study, GSK2586881 or placebo was administered as a single intravenous (IV) dose in a two-period crossover design. Treatment periods were separated by a washout period of 3-14 days. The primary endpoint was change from baseline in pulmonary artery systolic pressure (PASP) measured by echocardiography. Secondary endpoints included RAS peptides and oxygen saturation. RESULTS: Seventeen adults aged 18-40 years were randomised to treatment. There were no clinically relevant differences (defined as a reduction of ≥ 5 mmHg) in change from baseline in PASP between GSK2586881 and placebo. GSK2586881 was well tolerated, with no serious adverse events, no worsening of hypoxaemia and no evidence of immunogenicity. The study was terminated early after review of the data, which showed that the predefined success criteria had not been met. Following GSK2586881 administration, levels of the RAS peptide angiotensin II decreased while angiotensin (1-7) increased, as expected, indicating that GSK2586881 was pharmacologically active. CONCLUSIONS: A single IV dose of GSK2586881 0.8 mg/kg was well tolerated but did not impact the acute HPV response in healthy volunteers.

  PublisherOA PDFDOI

• Investigating the effect of TRPV4 inhibition on pulmonary-vascular barrier permeability following segmental endotoxin challenge

  Research Square · 2020-05-08

  preprintOpen access
  PublisherOA PDFDOI

• Investigating the effect of TRPV4 inhibition on pulmonary-vascular barrier permeability following segmental endotoxin challenge

  Pulmonary Pharmacology & Therapeutics · 2020-10-01 · 15 citations

  article
  PublisherDOI

• Neutrophil Extracellular Traps and CXCR2 Antagonism in Chronic Obstructive Pulmonary Disease: A Pilot Randomized Control Study

  2020-05-01

  articleOpen access
  PublisherOA PDFDOI

• Exploring the Patient Experience of Chronic Cough and Mucus in COPD Using Qualitative Methods

  2020-05-01

  articleOpen access
  PublisherOA PDFDOI

• Elevated Airway Purines in COPD

  UNC Libraries · 2020-11-01

  articleOpen access

  Adenosine and related purines have established roles in inflammation, and elevated airway concentrations are predicted in patients with COPD. However, accurate airway surface purine measurements can be confounded by stimulation of purine release during collection of typical respiratory samples.

  PublisherDOI

• SB-656933, a novel CXCR2 selective antagonist, inhibits ex vivo neutrophil activation and ozone-induced airway inflammation in humans

  UNC Libraries · 2020-10-31 · 11 citations

  articleOpen access

  To determine the safety and tolerability of a novel selective CXCR2 antagonist and assess its pharmacodynamic effects using measures of neutrophil activation and function, including CD11b expression in whole blood and ozone-induced airway inflammation in healthy subjects.

  PublisherDOI

• A nebulised antitumour necrosis factor receptor-1 domain antibody in patients at risk of postoperative lung injury: A randomised, placebo-controlled pilot study

  European Journal of Anaesthesiology · 2020-05-27 · 9 citations

  articleOpen accessCorresponding

  BACKGROUND: Tumour necrosis factor receptor 1 (TNFR1) signalling mediates the cell death and inflammatory effects of TNF-α. OBJECTIVE: The current clinical trial investigated the effects of a nebulised TNFR1 antagonist (GSK2862277) on signs of lung injury in patients undergoing oesophagectomy. DESIGN: Randomised double-blind (sponsor unblind), placebo-controlled, parallel group study. SETTING: Eight secondary care centres, the United Kingdom between April 2015 and June 2017. PATIENTS: Thirty-three patients undergoing elective transthoracic oesophagectomy. INTERVENTIONS: Patients randomly received a single nebulised dose (26 mg) of GSK2862277 (n = 17) or placebo (n = 16), given 1 to 5 h before surgery; 14 and 16, respectively competed the study. MAIN OUTCOME MEASUREMENTS: Physiological and biochemical markers of lung injury, pharmacokinetic and safety endpoints were measured. The primary endpoint was the change from baseline in pulmonary vascular permeability index (PVPI) at completion of surgery, measured using single-indicator transpulmonary thermodilution. Adjusted point estimates and 95% credible intervals (analogous to conventional confidence intervals) were constructed for each treatment using Bayesian statistical models. RESULTS: The mean change (with 95% credible intervals) from baseline in PVPI on completion of surgery was 0.00 (-0.23, 0.39) in the placebo and 0.00 (-0.24, 0.37) in the GSK2862277 treatment groups. There were no significant treatment-related differences in PaO2/FiO2 or Sequential Organ Failure Assessment score. Levels of free soluble TNFR1, Macrophage Inflammatory Protein-1 alpha and total protein were significantly reduced in the bronchoalveolar lavage fluid of patients treated with GSK2862277 (posterior probability of decrease with GSK2862277 vs. placebo:≥0.977; equivalent to P < 0.05). The frequency of adverse events and serious adverse events were distributed evenly across the two treatment arms. CONCLUSION: Pre-operative treatment with a single 26 mg inhaled dose of GSK2862277 did not result in significantly lower postoperative alveolar capillary leak or extra vascular lung water. Unexpectedly small increases in transpulmonary thermodilution-measured PVPI and extra vascular lung water index at completion of surgery suggest less postoperative lung injury than historically reported, which may have also compromised a clear assessment of efficacy in this trial. GSK2862277 was well tolerated, resulted in expected lung exposure and reduced biomarkers of lung permeability and inflammation. TRIAL REGISTRATION: clinicaltrials.gov: NCT02221037.

  PublisherOA PDFDOI

Recent grants

• NIH Grant R01HL064042

  NIH · $1.3M · 2005

Frequent coauthors

• Reynold A. Panettieri

  Rutgers, The State University of New Jersey

  99 shared

• Ruth Tal‐Singer

  GlaxoSmithKline (United States)

  79 shared

• Andrew I. Bayliffe

  GlaxoSmithKline (United Kingdom)

  76 shared

• William Powley

  GlaxoSmithKline (United Kingdom)

  74 shared

• Tracey J. Wright

  Pediatrics and Genetics

  69 shared

• Kelly Hardes

  66 shared

• Andrew Fowler

  66 shared

• Miguel Divo

  Brigham and Women's Hospital

  65 shared

Labs

• Aili L. Lazaar LabPI

Education

• B.A., Biochemistry

  Harvard University

  1982

• M.D., Medicine

  New York University

  1986