The lung is a living organ that can sometimes be a hospitable environment for the many pathogens living in it, given the right conditions. In this setting, unfriendly bacteria can grow, evolve, and cause harm. 

Bacterial infections of the lung in cystic fibrosis (CF) differ from typical acute respiratory infections in that organisms from acute infections tend to be cleared out once a course of antibiotics is finished. CF bacteria, however, persist for much longer, and continuously adapt to extend their stay. 

A number of distinct environments and atmospheres exist between the upper airway and the deepest alveolae; there are areas along the airway that have ample oxygenation and areas that are oxygen deprived. The spread of nutrients is likewise variable. 

An article in the Journal of Pediatric Infectious Diseases Society explains how bacteria persist so long in the CF lung. According to it author, Paul J. Planet, it is the remarkable adaptability and survivability of these bacteria that drive reinfection rate and trigger acute crises that require hospitalization. 

Read more about CF etiology

As mentioned, the human airway is a highly heterogeneous structure, with it various sections shaped and modeled differently. Nevertheless, bacteria that make their way into the airway can use all of the evolutionary tricks in the book to cause havoc. 

The role of antibiotics is to overwhelm any residual bacterial activity in the airway and to neutralize any threat. However, should antibiotics fail to get eradicate all targeted bacteria in the airway, antibiotic resistance may arise, presenting an added layer of complexity to the problem. 

We know that microorganisms associated with CF have developed a number of ways to evade antibiotic treatment. For example, Pseudomonas aeruginosa can undergo genetic mutation for multidrug reflux pumps and proteins, resulting in changes to the minimal inhibitory concentration of various antibiotics. Meanwhile, Burkholderia spp. can develop mutations in the porin genes, making it easier to develop antibiotic resistance. 

These bacteria are also adept at withstanding a future antibiotic challenge. For example, some can develop a protective biofilm that lowers their metabolic activity, thus evading antibiotics that target metabolically active microorganisms. 

“Antibiotic resistance is the most obvious clinical problem that arises from intra-host evolution,” Planet wrote. “High exposure to antibiotics can also lead to mutations in existing populations through antibiotic resistance or tolerance.” 

Removing the Evader

A traditional method of dislodging stubborn bacteria from the lungs is airway clearance therapy. The aim of this form of therapy is to enforce mucus clearance and reduce the risk of inflammation and infection. 

“Airway clearance is a necessity for maintenance of lung health by reducing mucus volume in the lungs,” Chaudary and Balasa wrote in the International Journal of General Medicine. “Long-term airway clearance is vital for reduction of bacterial infection-induced exacerbation frequency in CF patients.”

In the Cochrane Library, Wilson and colleagues conducted a review of airway clearance techniques and how they fare in improving the condition of patients with CF. 

In the lung, the mucus acts as a physical barrier for trapping oral microorganisms. Chest physiotherapists believe that certain mucus clearance techniques can remove bacteria from the body and help patients more fully recover from an acute episode of lung infection. 

Airway clearance entails various techniques that are powerfully synergistic when used together. These include chest physiotherapy, breathing techniques, and the use of devices to create positive expiratory pressure. Various vibrating and oscillating devices may be used to move the mucus around. Physical exercise is typically encouraged to maximize results. 

Read more about CF treatment

The goal is to allow patients to breathe and function better, while reducing the risk of infection. A study found that chest physiotherapy can result in improvements in the forced expiratory volume in 1 second after just half a year of treatment. 

How Effective Is Airway Clearance? 

Wilson and colleagues conducted a review of 6 studies to more fully understand the evidence surrounding airway clearance in CF. They reported that the evidence for airway clearance in CF is weak at best, and there is a high chance that any perceived benefit is anecdotal rather than representative. 

“The quality of the body of evidence comparing different airway clearance techniques for other outcomes was either low or very low,” they wrote. 

It appears that the main problem in many studies investigating the efficacy of airway clearance in managing CF is that the quality of evidence is wanting; there is not enough space devoted to individual preference of airway clearance technique, perceived improvements in health-related quality of life, and associated risks of various airway clearance methods. Crucially, many studies do not even attempt to quantify bacterial clearance. 

“Review authors need to clearly label the specific metrics that are being used [in their studies],” Wilson and colleagues wrote. “Authors should also consider how to best report on participant preference and satisfaction.” 

In summary, while antibiotics and airway clearance are the mainstay treatment options for the removal of pathogens from the lungs, they are far from adequate, given the high rate of rehospitalization among patients with CF. More research is needed to address this persistent problem. 


Planet PJ. Adaptation and evolution of pathogens in the cystic fibrosis lungJ Pediatric Infect Dis Soc. 2022;11(Suppl 2):S23-S31. doi:10.1093/jpids/piac073

Wilson LM, Morrison L, Robinson KA. Airway clearance techniques for cystic fibrosis: an overview of Cochrane systematic reviewsCochrane Database Syst Rev. 2019;1(1):CD011231. doi:10.1002/14651858.CD011231.pub2

Chaudary N, Balasa G. Airway clearance therapy in cystic fibrosis patients: insights from a clinician providing cystic fibrosis careInt J Gen Med. 2021;14:2513-2521. doi:10.2147/IJGM.S274196