Study Reveals New Insights Into Sputum Microenvironment in Pediatric Cystic Fibrosis Patients

A study recently published in the journal mBio provided new insight into the conditions under which microorganisms that contribute to the development of cystic fibrosis (CF) survive and develop in children with the disease. The study was conducted by researchers at California Institute of Technology, the Howard Hughes Medical Institute and the University of Southern California, and is entitled “Pediatric Cystic Fibrosis Sputum Can Be Chemically Dynamic, Anoxic, and Extremely Reduced Due to Hydrogen Sulfide Formation.”

CF is a rare, life-threatening genetic disease in which a defective gene (CFTR) induces a salt imbalance, causing the body to form unusually thick, sticky mucus that can obstruct the airways and promote dangerous lung infections, resulting in serious respiratory and gastrointestinal manifestations. CF affects the cells that produce mucus, sweat and digestive juices. Microbial infections are the major cause of morbidity and mortality in CF patients, with the majority dying due to respiratory failure. Bacteria such as Staphylococcus aureus, Haemophilus influenzae and Pseudomonas aeruginosa can induce chronic pulmonary infections and a serious inflammatory response. There is no cure for the disease and it is estimated that almost 75,000 individuals worldwide suffer from CF, including 30,000 individuals in the United States.

The lung mucus of CF patients is characterized by a microbial diversity. In the study, researchers hypothesized that sputum is also characterized by a heterogeneous chemical environment within and among patients.

In order to test their hypothesis, researchers analyzed 48 sputum samples from 22 pediatric CF patients attended at the Children’s Hospital Los Angeles. The team used microsensors to measure the profiles of oxygen and sulfide levels in the sputum samples, and also determined the samples’ chemistry.

Researchers found that the microbiologic environment can differ among CF patients, and that even the same patient can exhibit a different microbe population at different points in time. The team found a very thin layer of oxygen at the surface of the samples on the sputum-air interface, and that the large majority of the samples were in fact depleted of oxygen below this interface.

“We found oxygen only at the very narrow interface between the air and samples,” explained the study’s co-senior author Dr. Wiebke Ziebis in a news release. “It’s not only a stratified environment, with different microbial communities at different depths of the sputum, but also temporarily dynamic — there were differences not only between patients but also at different time points for the same patients.”

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Hydrogen sulfide, a gas that reacts with and removes oxygen from the environment, was detected in some of the sputum samples. Interestingly, CF patients with detectable hydrogen sulfide in their sputum were found to be more likely to have less severe disease symptoms.

In total, 32 sputum samples were cultured for the identification of the microorganism promoting CF. Pseudomonas aeruginosa was found in 13 of the samples and Staphylococcus aureus in 12, while 5 sputum samples were positive for both microorganisms and 2 samples had neither of them.

The research team concluded that microbes associated with CF pathology are capable of surviving in secretions that are chemically heterogeneous, including in anaerobic conditions with little or no oxygen. Given this variability, the team suggests that it is important to consider both aerobic and anaerobic lifestyles when analyzing CF-related microorganisms.

“The diversity and adaptation of disease-causing microorganisms within the CF lung environment, in part, is what renders CF infections so difficult to eradicate,” noted the study’s co-senior author Dr. Dianne K. Newman. “Few studies have attempted to characterize the chemistry of mucus collecting in CF airways, yet such measurements are essential if we are to understand how microorganisms survive in the lung and impact the microenvironment.”

The team suggests that further studies are required to establish whether specific metabolic features can be correlated to disease progression, and which treatment options could be most effective. “A greater diversity of metabolic survival strategies need to be considered and understood, including ones that operate solely under no-oxygen conditions, because that represents an important reservoir within this habitat,” concluded Dr. Newman.