Is aspiration of gastric juice harmful for patients with cystic fibrosis?
Why is this important?
Gastro-oesophageal reflux (GOR), the flow of stomach (gastric) contents back up into the oesophagus (food pipe), to the extent that these gastric contents go into the lungs (aspiration), is very common in patients with cystic fibrosis (CF). This is often treated with anti-acid medication (proton pump inhibitors (PPIs)) which reduces gastric acid. We have previously demonstrated in the laboratory that when healthy airway cells are exposed to gastric juice, as happens in aspiration, these cells produce high levels of the markers of inflammation. We know that patients with CF are more susceptible to lung inflammation, and so we wanted to study the effect of gastric juice on the airway cells of those patients.
What did you do?
We obtained airway cells from a lung transplant donor, who did not have CF, and a lung transplant recipient, who did have CF. We stimulated these cells with gastric juice from patients that were taking PPI therapy (gastric juice “on” PPI) and patients not on PPI therapy (gastric juice “off” PPI) and measured inflammatory markers.
What did you find?
We found that gastric juice from patients “on” PPI provoked higher levels of inflammation compared to gastric juice from patients “off” PPI, both in the non-CF as well as in the CF airway cells. Secondly, levels of inflammation were significantly higher in CF airway cells compared to non-CF airway cells. When we filtered the gastric juice from patients “on” PPI therapy, to eliminate large particles and bacterial sub-products, it resulted in a significant decrease of inflammatory markers.
What does this mean and reasons for caution?
Patients with CF, treated with PPI, have gastric juice with high levels of bacterial sub-products. These patients often have GOR and aspirate gastric contents into the lungs. The aspirated material (gastric juice “on” PPI) has a significantly enhanced inflammatory effect on CF airway cells. As chronic PPI treatment in CF may result in a paradoxically increased inflammatory effect in the airways, alternative anti-reflux therapies should be investigated for CF. These findings should be read with caution as what has been seen in the laboratory may not be the same as that seen in patients. More research is required.
In order to prevent aspiration, reflux should be reduced. Baclofen, an agent that reduces the number of reflux episodes, and some newer medications are currently undergoing clinical evaluation. Unfortunately, these drugs have significant side effects such as dizziness, nausea and headaches. To date, the only treatment that abolishes almost all reflux episodes is anti-reflux surgery. There have been some uncontrolled studies showing positive results in patients with CF after anti-reflux surgery, but controlled studies are needed to better define the safety and beneficial effects.