Publications and Presentations

Recent Articles

1. Aspergillus fumigatus is influenced by mucus accumulation, airway inflammation, and CFTR function
   6 Mar 2025ERJ Open Research01035-02024European Respiratory Society (ERS)
   Co-authors: Poore TS, Nguyen A, Schaefers L, Solomonik A, Rieglers A, Leal SM, Rowe SM, Birket S
   DOI: 10.1183/23120541.01035-2024 
   Background Aspergillus fumigatus (Af) is an inhaled mold found in people with CF (PwCF) that results in significant airway inflammation. Studies have shown allergic (Th2) inflammatory responses to Af, little change in allergic bronchopulmonary aspergillosis despite CFTR modulation, and associations with Pseudomonas sp (PsA) infections. We hypothesized that CF mucus inherently promotes Af growth in a concentration dependent fashion that is exacerbated by Th2 inflammation and preceding PsA infection.    
   Methods We collected mucus from primary nonCF and CF human bronchial epithelial cells (HBE) stimulated with IL-4, IL-1β, Pyocyanin (PYO), or coinfected with PsA. Paired sputum samples from PwCF pre and post elexacaftor/tezacaftor/ivacaftor (ETI) were also utilized. Af infection was then performed directly on each mucus sample and imaged with microscopy. Images were analyzed by ImageJ particle tracking.  
   Results Higher concentrations of CF and nonCF mucus promoted more Af growth. Af germinated more in IL-4 stimulated CF mucus than CF mucus alone as well as IL-4 stimulated nonCF mucus, even when controlling for percent solid content. PYO exposure showed increased Af growth in CF and nonCF mucus while co-infection of CF mucus with PsA and tobramycin treatment restored Af growth in both conditions. Paired sputum samples from PwCF showed more Af growth pre-ETI than post-ETI even when controlling for percent solid content.  
   Conclusion Af growth is reduced by mucus dilution, promoted by specific inflammatory cytokines and infection, and is influenced by CFTR function. CF mucus shows pathologic differences that promotes Af growth, suggesting an intrinsic defect in this population.
   
    
2. Chronic Coinfection with Pseudomonas aeruginosa and Normal Colony Staphylococcus aureus Causes Lung Structural Damage in the Cystic Fibrosis Rat
   1 Feb 2025American Journal of Pathology195(2):174-187
   Co-authors: Bollar GE, Keith JD, Stanford DD, Oden AM, Raju SV, Poore TS, Birket SE
   DOI: 10.1016/j.ajpath.2024.09.008
   Cystic fibrosis (CF) respiratory outcomes are heavily influenced by complications of infection. Pseudomonas aeruginosa and Staphylococcus aureus are the most common colonizers of the cystic fibrosis lung, and frequently overlap to cause chronic and persistent coinfections associated with severe disease. However, the dynamics of P. aeruginosa and S. aureus coinfection and its impacts on the development of CF lung structural damage are poorly understood. Additionally, small colony variants (SCVs) of S. aureus have been associated with P. aeruginosa infections in people with CF, but their role in disease progression is largely unknown. In this work, the CF rat was used to model chronic lung coinfection with P. aeruginosa and S. aureus, using clinically and laboratory-derived normal colony and SCV strains of S. aureus to evaluate the impact of phenotype on clinical outcomes. Rats coinfected with clinically derived S. aureus of both phenotypes experienced increased inflammation in the lung. However, only the combination of P. aeruginosa and clinically normal colony S. aureus led to lung structural decline, including mucus obstruction and bronchiectasis. Regression analyses showed that the damage was associated with a higher burden of P. aeruginosa. These data indicate that chronic coinfection with normal colony S. aureus and P. aeruginosa may support the progression CF lung decline driven by P. aeruginosa, which might be avoided when coinfecting S. aureus exhibits the SCV phenotype.
   
    
3. Cardiovascular complications in cystic fibrosis: A review of the literature
   Jan 2022Journal of Cystic Fibrosis21(1):18-25Elsevier
   Co-authors: Poore TS, Taylor-Cousar JL, Zemanick ET
   DOI: 10.1016/j.jcf.2021.04.016
   Cystic fibrosis is a genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, leading to dysfunction of the CFTR protein. CFTR dysfunction leads to disease in the respiratory and gastrointestinal systems. Disorders of the cardiovascular system in individuals with CF are usually attributed to secondary effects from progressive lung disease. However, CFTR has been localized to vascular endothelium and smooth muscle, suggesting that CFTR dysfunction may directly impact cardiovascular function. As treatments for CF improve and life-expectancy increases, the risk of vascular disease may increase in prevalence related to primary and secondary CFTR dysfunction, chronic systemic inflammation, nutritional health and hyperglycemia in individuals with CF related diabetes. Here we review the available literature on CF and the cardiovascular system, examining the secondary effects and evidence for direct CFTR dysfunction in the heart, aorta, pulmonary vessels, and vasculature, as well as future directions and treatment options.
   
    

Team’s involvement in the 2025 North American Cystic Fibrosis Conference
2025 Children’s of Alabama/UAB Speakers and Moderators

• Speakers:
  • Hector Gutierrez, MD – Until It’s Done for Everyone: Addressing Health Disparities and Transforming the International Landscape of Cystic Fibrosis Care
  • Heather Searcy, PharmD - Chameleon Color Change:  Adapting to the Changing CF Pharmacy Landscape
  • William T. Harris, MD
    • Functional Inhibition of Wild-Type CFTR: Role in COPD and other Chronic Diseases
    • Biomarkers of disease severity and outcome measures of therapeutic efficacy
    • Parameter D: A novel biomarker to detect small airway disease through spirometry in CF
    • Journal of Cystic Fibrosis: Tobacco smoke exposure is associated with diminished longitudinal benefit of ETI
  • Staci Self, LICSW – Delivering CF Care in Low- and Middle-Income Countries

Abstracts/Posters

1. Abstract 187:  Chronic Fungal Infection and allergic bronchopulmonary aspergillosis display unique TH1 and Th2 immune profiles in people with CF – T. Poore
2. Abstract 285: TGF-beta dependent miR-145 is inversely correlated with CFTR expression in ionocytes and other epithelial subtypes -W. Harris
3. Abstract 364:  Fibrosis and immune dysregulation in the kidneys of mice with F508del CFTR mutation – W. Harris
4. Abstract 367:  Absent CFTR function is associated with progressive kidney injury and abnormal mineral metabolism in an in vivo mouse model – W. Harris
5. Abstract 422:  Implementation and expansion of a REDCap-based CF registry in low and middle income countries – C. Mims, H. Gutierrez
6. Abstract 484:  Cigarette smoke exposure limits efficacy of CFTR modulator therapy in preclinical models – W. Harris
7. Abstract 521:  Adverse mental health outcomes of ETI in pediatric patients with CF:  a retrospective chart review – C. Fowler, K. Bell, H. Searcy
8. Abstract 543:  Impact of a smoking cessation intervention on hari nicotine levels in children with CF: Results from Clinical Effort Against Smoke Exposure in CF (CEAASE-CF) – C. Mims, S. Gamble, W. Harris
9. Abstract 623:  Alterations in exocrine pancreatic function with CFTR modulator use – J. Hughes, V. Vajner
10. Abstract 638:  Parameter D: a novel biomarker to detect small airway disease through spirometry in CF – W. Harris
11. Abstract 691:  Modulator and metabolites: pharmacokinetics of ETI in maternal blood, cord blood, the neonate and breast milk of a CF carrier mother/affected fetus dyad – C. Fowler
12. Abstract 815:  Early detection of liver disease in CF: a screening based approach – V. Vajner, E. Madision, J. Dunn, A. Cohen
13. Abstract 822:  Tools for tiny fighters – K.Villari, V. Vajner, S. Gamble
14. Abstract 846:  Implementation and sustainability of QI-focused management of CF care in low-resource settings – H. Guigno, C. Mims, V. Anderson (Vajner), S. Gamble, H. Gutierrez
15. Abstract 858:  Continuous improvement in interdisciplinary care:  experience of an adult CF center in Mendoza, Argentina – M. Kemnitz, C. Mims, S. Self, V. Vajner, S. Gamble, H. Gutierrez
16. Abstract 865:  Successful implementation of a CF REDCap-based data management/registry tool in low resources settings – M. Cestari, S. Self, C. Mims, H. Gutierrez
     

International Team Abstracts

1. Abstract 761:  Rapid dissemination of process improvement in a private CF center in Santiago Chile – L. Jakubson (Santiago, Chile)
2. Abstract 844:  Train-The-Trainer model to improve CF care in resource limited countries – M. Plubatsch (Buenos Aires, Argentina)