The findings were reported in the study, “Lung clearance index to detect the efficacy of Aztreonam lysine inhalation in patients with cystic fibrosis and near normal spirometry – A single-centre feasibility study,” published recently in the journal PLOS One.
The first clinical trials evaluating the effectiveness of inhaled antibiotics in patients with moderate or severe CF have used spirometry parameters, such as forced expiratory volume in one second (FEV1, the total amount of air a patient is able to exhale in one second after taking a deep breath), as a readout of lung function.
Previous studies showed that Gilead Sciences’ Cayston (aztreonam lysine), an inhaled antibiotic often used to treat infections caused by the bacteria Pseudomonas aeruginosa in CF patients, was found to be superior to tobramycin, another antibiotic normally prescribed to patients who develop P. aeruginosa lung infections.
However, “many patients have normal or near normal FEV1 despite chronic P. aeruginosa infection,” the researchers wrote. In addition, when working with small patient groups “it is difficult to detect changes after treatment using FEV1 as an endpoint [goal],” they added.
For that reason, scientists have been looking for alternative readouts that would be more sensitive than FEV1, and better suited to evaluate lung function in patients with milder forms of CF who have chronic lung infections caused by P. aeruginosa.
“At the CF Centre Innsbruck, we have been using the multiple breath washout (MBW) technique for many years to measure lung clearance index (LCI). Abnormal LCI is associated with early structural lung disease detectable by high resolution computerized tomography (HRCT) scans when FEV1 may still be normal,” the investigators wrote.
In the study, researchers reported the findings of an observational, open-label trial (2013-004295-35), in which the effects of several inhaled anti-pseudomonal antibiotics in patients with mild CF were assessed using the standard FEV1 and LCI parameters.
The study was divided into two treatment phases: in phase 1 (weeks 0-8), patients received standard treatment with inhaled tobramycin, using either TOBI (300 mg/5 ml, twice a day), or TOBI Podhaler (112 mg, twice a day). In phase 2 (weeks 8-16), patients received treatment with Cayston (75 mg, three times a day).
The study enrolled a total of eight CF patients between the ages of 15-49 (median age of 28 years), who had chronic lung infections caused by P. aeruginosa for more than six years, and had been taking inhaled anti-pseudomonal antibiotics for approximately four years.
At baseline, FEV1 ranged between 76.3% and 123.8%, with a median of 87%, which is considered normal or near normal. (FEV1 lower than 75% is indicative of lung function impairment.)
At baseline, LCI values ranged between 6.4 and 11.4, with a median of 8.59, which is above the upper limit of a normal range (7.0), indicating the presence of lung disease.
After four weeks of treatment with Cayston, LCI values decreased in seven of the eight patients participating in the study. Conversely, while receiving standard treatment with tobramycin, only half of the patients (four patients) experienced a significant improvement in LCI values.
No significant differences were found in FEV1 values while patients were receiving standard treatment with tobramycin, or afterward with Cayston.
“Respiratory symptoms showed clinically important improvements after AZLI [Cayston] treatment (median change +8.5), and better results than after tobramycin (median -3.0). Treatments were well tolerated, and no adverse events were reported,” researchers wrote.
Based on the results regarding the two lung function parameters tested, the team believes “lung clearance index can be used to detect treatment induced changes in subjects with mild lung disease,” and “should be considered as a clinical endpoint for trials.”
In line with their results, the team noted that expert committees have previously stated “LCI is a valuable potential outcome parameter in patients with normal FEV1, since LCI can detect treatment differences even in small patient groups,” they wrote.