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Denis Hadjiliadis

Denis Hadjiliadis

· MD MHS PhDVerified

University of Pennsylvania · Rehabilitation Medicine

Active 1995–2025

h-index45
Citations6.9k
Papers19041 last 5y
Funding
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About

Denis Hadjiliadis, MD, MHS, PhD, is the Paul F. Harron, Jr. Professor in the Department of Medicine at the University of Pennsylvania's Perelman School of Medicine. He is the Director of the Adult Cystic Fibrosis Program and Co-Director of the Cystic Fibrosis Program at the university. His clinical expertise includes the diagnosis and management of cystic fibrosis, bronchiectasis, CFTR-related disorders, lung transplantation, and end-stage lung disease requiring transplant. He is a member of the Penn Lung Transplantation team and also takes care of patients within the Palliative Care team at the University of Pennsylvania. Hadjiliadis oversees one of the largest adult cystic fibrosis clinics in North America and is involved in multiple clinical trials related to cystic fibrosis and lung transplantation. His research focuses on cystic fibrosis, lung transplantation, bronchiectasis, bronchiolitis obliterans, database analysis, and infectious disease syndromes in thoracic organ transplants. His educational background includes a B.Eng in Chemical Engineering from McGill University, an MD from the University of Toronto, an MHS from Duke University Medical Center, and a PhD in Medicine from the University of Ioannina. His contributions to the field include extensive research and publications on cystic fibrosis, respiratory health, and transplantation.

Research topics

  • Medicine
  • Internal medicine
  • Intensive care medicine
  • Surgery
  • Gastroenterology

Selected publications

  • Contraceptive use and pregnancy in cystic fibrosis: Survey findings from 10 cystic fibrosis centers

    Journal of Cystic Fibrosis · 2025-01-22 · 3 citations

    articleOpen access
  • Development of a light-induced gas phase nitric oxide generator and its use in killing biofilm bacteria in vitro and ex vivo

    Journal of Controlled Release · 2025-12-02

    articleOpen access
  • 90-OR: Effects of Glucagon-Like Peptide 1 (GLP-1) Agonist Therapy on Islet Function in Adults with Pancreatic-Insufficient Cystic Fibrosis ( PI-CF) and Abnormal Glucose Tolerance (AGT)—Preliminary Results

    Diabetes · 2025-06-13

    article

    Introduction and Objective: Preserving β-cell function may delay or prevent progression to CF-related diabetes, a major comorbidity in people with PI-CF. This study aimed to evaluate whether weekly GLP-1 agonist therapy improves β- and α-cell function and post-prandial glucose tolerance in people with PI-CF and AGT. Methods: In this randomized, open-label, cross-over study, participants received dulaglutide 0.75 mg weekly for 6 doses, with a matched 6-week observation period. Mixed-meal tolerance tests (MMTT) were performed at each period start and end. Non-parametric methods estimated between-condition differences in change in biomarkers of islet function (C-peptide, glucagon, glucose) as assessed by area under the curve (AUC) at 30 and 180 min. Results: To date, 11 participants with PI-CF and AGT (mean±SE age 26.9 ± 2.2 y, BMI 27.3 ± 1.8 kg/m2, HbA1c 5.7 ± 0.1%) have completed the study. Early-phase C-peptide (incremental AUC at 30 min) in the dulaglutide period was lower when compared to observation (p<0.05), but when adjusted for glucose showed an increase (iAUCC-pep/iAUCglc ratio, Δ 0.25 ng-min/mg %, p<0.01). Total glucagon AUC at 180 min was lower in the dulaglutide period (16.4% decrease vs 1.8% increase, p<0.05). Glucose at 30 and 180 min trended lower in the dulaglutide period (-4202.3 mg-min/dL, p=0.06). A weak trend for weight reduction during treatment vs observation periods was observed (−1.88 kg ± 0.89 vs −0.14 kg ± 0.55, p=0.18). Some subjects reported worsening acid reflux (n=3) and constipation (n=4) in the dulaglutide period. Conclusion: GLP-1 agonist therapy in patients with PI-CF and AGT appears to enhance early-phase β-cell insulin secretion and suppress α-cell glucagon secretion. These effects may contribute to an improvement in post-prandial glucose tolerance. Patients with PI-CF should be cautioned regarding acid reflux and constipation when considering GLP-1 agonist therapy. Disclosure S. Reddy: None. R.R. Bhatia: None. A. Peleckis: None. P. Alvarado: None. R. Walega: None. D. Stefanovski: None. R.J. Gallop: None. D. Hadjiliadis: None. A. Flatt: Employee; Vertex Pharmaceuticals Incorporated. R.C. Rubenstein: None. C.L. Chan: None. A. Kelly: None. M.R. Rickels: Consultant; Vertex Pharmaceuticals Incorporated, Sernova, Corp. Research Support; Dompé, Tandem Diabetes Care, Inc. Consultant; Novo Nordisk. Funding National Institutes of Health (R01 DK97830, UL1 TR001878, and P30 DK019525)

  • Mental health and transplantation in cystic fibrosis

    Respiratory Medicine · 2025-10-10 · 1 citations

    article
  • Addressing pain in people living with cystic fibrosis: Cystic fibrosis foundation evidence-informed guidelines

    Journal of Cystic Fibrosis · 2024-12-06 · 6 citations

    reviewOpen access

    • Pain is common in CF and impacts health, function, and quality of life. • People living with CF desire effective, accessible pain management. • Effective pain management in CF requires an individualized, multimodal approach. • CF care teams and other specialists should collaborate to provide pain management. Even as many outcomes for people living with cystic fibrosis (PLwCF) improve, individuals still experience extensive symptom burdens. From birth, many PLwCF experience both pain as a symptom of their CF disease and procedural pain, posing detriments to health, functioning, and quality of life. Despite its prevalence and impact, there is no CF-specific guidance for the assessment and management of pain. Similarly, no guidance exists regarding communication with PLwCF about their pain experiences or its impact on their lives. Therefore, the Cystic Fibrosis Foundation (CFF) assembled an expert panel of clinicians, researchers, PLwCF, and caregivers to develop consensus recommendations for pain management in CF. We utilized literature review and expert opinion to develop 13 recommendations addressing pain assessment, management, and communication. Recommendations are centered on guiding principles of utilizing a multimodal approach to pain management, offering age and developmentally appropriate assessment and interventions, concurrently treating underlying conditions causing, contributing to, and/or exacerbated by pain, considering societal stigma of the pain experience, particularly for minoritized and marginalized people, and sensitivity to issues of access and cost. These recommendations are intended to guide clinicians in managing pain and improving quality of life for PLwCF with pain at all stages of illness and development.

  • Management of infectious disease syndromes in thoracic organ transplants and mechanical circulatory device recipients: a Delphi panel

    Transplant Infectious Disease · 2024-02-13 · 5 citations

    articleOpen access

    PURPOSE: Antimicrobial misuse contributes to antimicrobial resistance in thoracic transplant (TTx) and mechanical circulatory support (MCS) recipients. This study uses a modified Delphi method to define the expected appropriate antimicrobial prescribing for the common clinical scenarios encountered in TTx and MCS recipients. METHODS: An online questionnaire on managing 10 common infectious disease syndromes was submitted to a multidisciplinary Delphi panel of 25 experts from various disciplines. Consensus was predefined as 80% agreement for each question. Questions where consensus was not achieved were discussed during live virtual live sessions adapted by an independent process expert. RESULTS: An online survey of 62 questions related to 10 infectious disease syndromes was submitted to the Delphi panel. In the first round of the online questionnaire, consensus on antimicrobial management was reached by 6.5% (4/62). In Round 2 online live discussion, the remaining 58 questions were discussed among the Delphi Panel members using a virtual meeting platform. Consensus was reached among 62% (36/58) of questions. Agreement was not reached regarding the antimicrobial management of the following six clinical syndromes: (1) Burkholderia cepacia pneumonia (duration of therapy); (2) Mycobacterium abscessus (intra-operative antimicrobials); (3) invasive aspergillosis (treatment of culture-negative but positive BAL galactomannan) (duration of therapy); (4) respiratory syncytial virus (duration of antiviral therapy); (5) left ventricular assist device deep infection (initial empirical antimicrobial coverage) and (6) CMV (duration of secondary prophylaxis). CONCLUSION: This Delphi panel developed consensus-based recommendations for 10 infectious clinical syndromes seen in TTx and MCS recipients.

  • The Real-World Effectiveness of Antifungals in People with Cystic Fibrosis and <i>Aspergillus</i> -Positive Cultures

    Annals of the American Thoracic Society · 2024-10-10 · 1 citations

    articleOpen access

    Abstract Rationale The pathogenicity of Aspergillus in the cystic fibrosis (CF) airway is debated, leading to unclear clinical benefit of antifungal therapy for Aspergillus infection. Objective To determine the real-world effectiveness of antifungal use in people with CF (PwCF) with Aspergillus species in the United States. Methods We conducted a retrospective cohort study evaluating the association of antifungal use and respiratory outcomes in PwCF and Aspergillus-positive cultures using the Cystic Fibrosis Foundation Patient Registry. Marginal structural models using inverse-probability treatment weighted estimators were used to test whether antifungal exposure was associated with forced expiratory volume in 1 second percent predicted (FEV1pp) and pulmonary exacerbation rate while controlling for fixed and time-varying confounders. We conducted sensitivity analyses on individuals with persistent Aspergillus and without concomitant allergic bronchopulmonary aspergillosis (ABPA). Results A total of 14,754 individuals with Aspergillus-positive cultures between 2006 and 2019 were identified. Antifungals were prescribed to 3,575 (24.2%) unique PwCF during the study period. Antifungal use was not associated with FEV1pp (adjusted estimate = −0.96 percentage points; 95% confidence interval [CI] = −2.21, 0.29). Antifungal use was associated with 29% increased rate of pulmonary exacerbations requiring intravenous (i.v.) antibiotics (adjusted incidence rate ratio = 1.29, 95% CI = 1.22, 1.37). In sensitivity analyses limited to individuals without ABPA, antifungals were associated with 1.88 lower FEV1pp (95% CI = −3.35, −0.41) and an increased rate of pulmonary exacerbations (adjusted incidence rate ratio = 1.30; 95% CI = 1.21, 1.40), whereas in patients with persistent Aspergillus and persistent Aspergillus without concomitant ABPA, antifungals were not associated with FEV1pp. Conclusions Antifungal therapy in PwCF and Aspergillus-positive cultures was not associated with improvements in FEV1pp, suggesting no observed benefit. Although antifungal therapy was associated with increased risk for pulmonary exacerbations, this could reflect confounding by severity of disease. Randomized clinical trials examining the clinical efficacy of antifungals in Aspergillus infections in CF are warranted.

  • Impact of Cystic Fibrosis Transmembrane Conductance Regulator Modulators on Maternal Outcomes During and After Pregnancy

    CHEST Journal · 2024-09-27 · 21 citations

    article
  • Early-phase insulin secretion during mixed-meal tolerance testing predicts β-cell function and secretory capacity in cystic fibrosis

    Frontiers in Endocrinology · 2024-02-20 · 1 citations

    articleOpen access

    Insulin secretion within 30 minutes of nutrient ingestion is reduced in people with cystic fibrosis (PwCF) and pancreatic insufficiency and declines with worsening glucose tolerance. The glucose potentiated arginine (GPA) test is validated for quantifying β-cell secretory capacity as an estimate of functional β-cell mass but requires technical expertise and is burdensome. This study sought to compare insulin secretion during mixed-meal tolerance testing (MMTT) to GPA-derived parameters in PwCF. Methods Secondary data analysis of CF-focused prospective studies was performed in PwCF categorized as 1) pancreatic insufficient [PI-CF] or 2) pancreatic sufficient [PS-CF] and in 3) non-CF controls. MMTT: insulin secretory rates (ISR) were derived by parametric deconvolution using 2-compartment model of C-peptide kinetics, and incremental area under the curve (AUC) was calculated for 30, 60 and 180-minutes. GPA: acute insulin (AIR) and C-peptide responses (ACR) were calculated as average post-arginine insulin or C-peptide response minus pre-arginine insulin or C-peptide under fasting (AIR arg and ACR arg ), ~230 mg/dL (AIR pot and ACR pot ), and ~340 mg/dL (AIR max and ACR max ) hyperglycemic clamp conditions. Relationships of MMTT to GPA parameters were derived using Pearson’s correlation coefficient. Predicted values were generated for MMTT ISR and compared to GPA parameters using Bland Altman analysis to assess degree of concordance. Results 85 PwCF (45 female; 75 PI-CF and 10 PS-CF) median (range) age 23 (6-56) years with BMI 23 (13-34) kg/m 2 , HbA 1c 5.5 (3.8-10.2)%, and FEV1%-predicted 88 (26-125) and 4 non-CF controls of similar age and BMI were included. ISR AUC 30min positively correlated with AIR arg ( r =0.55), AIR pot ( r =0.62), and AIR max ( r =0.46) and with ACR arg ( r =0.59), ACR pot ( r =0.60), and ACR max ( r =0.51) (all P &amp;lt;0.001). ISR AUC 30min strongly predicted AIR arg (concordance=0.86), AIR pot (concordance=0.89), and AIR max (concordance=0.76) at lower mean GPA values, but underestimated AIR arg , AIR pot , and AIR max at higher GPA-defined β-cell secretory capacity. Between test agreement was unaltered by adjustment for study group, OGTT glucose category, and BMI. Conclusion Early-phase insulin secretion during MMTT can accurately predict GPA-derived measures of β-cell function and secretory capacity when functional β-cell mass is reduced. These data can inform future multicenter studies requiring reliable, standardized, and technically feasible testing mechanisms to quantify β-cell function and secretory capacity.

  • Have CFTR modulators changed the need for liver and lung transplantation among patients with cystic fibrosis? An analysis of the UNOS database

    Liver Transplantation · 2024-11-06 · 4 citations

    article

Frequent coauthors

Labs

  • Hadjiliadis LabPI

Awards & honors

  • Paul F. Harron, Jr. Professor
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