pulmonary exacerbation Archives

Beta-lactam and microbial diversity in cystic fibrosis

May 27, 2021

The study, published in the Journal of Investigative Medicine, examined the hypotheses that beta-lactam antibiotic PK and PD is associated with changes in richness and alpha diversity following treatment of a pulmonary exacerbations and determined associations between antibiotic PK, PD, antibiotic resistance and lung function.

Cystic fibrosis (CF) is a chronic lung disease that affects more than 30,000 people in the United States and 70,000 people worldwide. While this chronic disease is characterized by acute pulmonary exacerbations that are frequently treated with antibiotics, the impact of antibiotics on airway microbial diversity remains a critical knowledge gap.

A new study led by researchers at Children’s National Hospital found that beta-lactam antibiotic pharmacokinetic (PK) and pharmacodynamic (PD) target attainment during treatment is associated with suppressed recovery of microbial diversity, following a pulmonary exacerbation in children and adolescents with CF.

“By laying the groundwork for understanding how antibiotic PK may influence microbial diversity following pulmonary exacerbation, we hope to identify improved ways to guide antibiotic therapy in persons with CF,” says Andrea Hahn, M.D., M.S., an infectious diseases specialist at Children’s National and lead author of the study.

The study, published in the Journal of Investigative Medicine, examined the hypotheses that beta-lactam antibiotic PK and PD is associated with changes in richness and alpha diversity following treatment of a pulmonary exacerbations and determined associations between antibiotic PK, PD, antibiotic resistance and lung function.

“Beta-lactam antibiotics are frequently used to treat pulmonary exacerbations in persons with CF, yet are not routinely optimized,” says Dr. Hahn. “This study demonstrates the importance of beta-lactam PK’s on changes within the airway microbiome and provides context for care providers regarding the potential long-term impacts of antibiotic use in persons with CF, to ensure that we are optimizing therapy with each pulmonary exacerbation.”

Additional authors from Children’s National include: Aszia Burrell, Hollis Chaney, M.D., Iman Sami Zakhari, M.D., Anastassios Koumbourlis, M.D., M.P.H. and Robert Freishtat, M.D., M.P.H.

Pediatric Research names Andrea Hahn, M.D., M.S., early career investigator

April 19, 2021

“I am honored to be recognized by Pediatric Research and the Society of Pediatric Research (SPR) at large,” said Dr. Hahn. “SPR is an amazing organization filled with excellent scientists, and to be highlighted by them for my work is truly affirming.”

For her work on the impact of bacterial functional and metabolic activity on acute episodes of cystic fibrosis, the journal Pediatric Research recognized Andrea Hahn, M.D., M.S., as Pediatric Research’s Early Career Investigator.

Cystic fibrosis is an autosomal recessive genetic disease, affecting more than 70,000 people worldwide. The condition’s morbidity and mortality are recurrent and result in a progressive decline of lung function.

“I am honored to be recognized by Pediatric Research and the Society of Pediatric Research (SPR) at large,” said Dr. Hahn. “SPR is an amazing organization filled with excellent scientists, and to be highlighted by them for my work is truly affirming.”

The exact mechanisms of the bacteria that chronically infect the airway triggering acute cystic fibrosis episodes, also known as pulmonary exacerbations, remain unclear. Dr. Hahn’s research is one of the few to explore this gap and found an association with long-chain fatty acid production in cystic fibrosis inflammation.

“As a physician-scientist, there are many competing priorities between developing and executing good science — including writing manuscripts and grants — and providing excellent patient care both directly and through hospital-wide quality improvement initiatives,” said Dr. Hahn. “It is often easier to have successes and feel both effective and appreciated on the clinical side. This recognition of my scientific contributions to the medical community is motivating me to continue pushing forward despite the setbacks that often come up on the research side.”

The exposure to many programs and institutions gave Dr. Hahn the foundation to create a research program at Children’s National that helps decipher the complexities of antibiotic treatment and how it changes the airway microbiome of people with cystic fibrosis. The program also explores the impacts of antibiotic resistance and beta-lactam pharmacokinetics/pharmacodynamics (PK/PD) — the oldest class of antibiotics used to treat infections.

Dr. Hahn believes that the people and environment at Children’s National Hospital allowed her to grow and thrive as a physician-scientist.

“I was initially funded through an internal K12 mechanism, which was followed up by Foundation support, which was only possible because of the strong mentorship teams I have been able to build here at Children’s National,” said Dr. Hahn. “My division chief has also been very supportive, providing me with both protected time as well as additional resources to build my research lab.”

She is particularly appreciative of Robert Freishtat, M.D., M.P.H, senior investigator at the Center for Genetic Medicine Research, and Mary Callaghan Rose (1943-2016).

“Robert Freishtat has been a great advocate for me, and I am indebted to him for my success thus far in my career,” said Dr. Hahn. “Likewise, I want to specifically recognize Mary Rose. She was a great scientist at Children’s National until her death in 2016. She gave me the initial opportunity and support to begin a career studying cystic fibrosis, and she is missed dearly.”

You can learn more about Dr. Hahn’s research in this Pediatric Research article.

The role of long-chain fatty acids in cystic fibrosis inflammation

March 2, 2021

A recent study sheds light on the microbiologic triggers for lung inflammation and pulmonary exacerbations in cystic fibrosis.

Cystic fibrosis is an autosomal recessive disease that affects more than 70,000 people worldwide and results in a progressive decline of lung function. Patients with cystic fibrosis experience intermittent episodes of acute worsening of symptoms, commonly referred to as pulmonary exacerbations. While Staphylococcus aureus and Pseudomonas aeruginosa are thought to contribute to both lung inflammation and pulmonary exacerbations, the microbiologic trigger for these events remains unknown. Andrea Hahn, M.D., M.S., and her colleagues at Children’s National Hospital recently shed light on this matter by studying the changes in bacterial metabolic pathways associated with clinical status and intravenous (IV) antibiotic exposure in cystic fibrosis patients.

The researchers found increased levels of long-chain fatty acids (LCFAs) after IV antibiotic treatment in patients with cystic fibrosis. LCFAs have previously been associated with increased lung inflammation in asthma, but this is the first report of LCFAs in the airway of people with cystic fibrosis. This research indicates that bacterial production of LCFAs may be a contributor to inflammation in people with cystic fibrosis and suggests that future studies should evaluate LCFAs as predictors of pulmonary exacerbations.

Additional authors from Children’s National include: Hollis Chaney, M.D., Iman Sami Zakhari, M.D., Anastassios Koumbourlis, M.D., M.P.H. and Robert Freishtat, M.D., M.P.H.

Read the full study in Pediatric Research.

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