ERS Roundup: Cell Transplant Boosts Lung Function in COPD Patients

MILAN — Research presented at this year’s annual European Respiratory Society congress included early successes in transplanting a patient’s own lung cells to ease chronic obstructive pulmonary disease (COPD), idrevloride treatment for primary ciliary dyskinesia, and using ultrasounds as a guide for more comprehensive pulmonary embolism screening.

Improved Gas Exchange Capacity in COPD Through Lung Cell Transplants

Autologous P63+ lung progenitor cell transplantation could help improve lung function for COPD patients, a phase I trial suggested.

After cell transplants, median diffusing capacity of the lungs for carbon monoxide increased from 30% to 39.7% after 12 weeks, then up to 40.3% after 24 weeks. Two patients who were previously experiencing mild emphysema also saw resolved symptoms after 24 weeks, which was confirmed though CT. Emphysema patients with more severe symptoms saw mild improvements.

“The intrapulmonary administration of cells is feasible and safe, and points to significant improvements in lung diffusion capacity after cell therapy,” said Wei Zuo, PhD, of Tongji University in Shanghai. “Mild emphysema, which was previously considered permanent, can be repaired by cell transplantation.”

Zuo explained that in this process, currently existing P63+ progenitor cells were extracted from COPD patients via bronchoscopic brush, cloned, then transplanted back into the donor patient through bronchoscopic injection. Patients received close medical monitoring for 24 weeks. Single doses of cloned progenitor cells consisted of approximately 0.6~5.2×10⁶ cells for every kg of the patient’s body weight.

The first-in-human study included 20 COPD patients, with three patients acting as a control group.

No grade ≥3 adverse events occurred in patients, while 47.1% of transplant patients and 33.3% of control patients experienced grade 1 events. Grade 2 adverse events were seen in 5.9% of treatment patients and 33.3% of control patients.

The average patient St. George’s Respiratory Questionnaire scores improved in 58.8% of the transplant group and 33.3% of the control group. Median 6-minute walk test results improved in two-thirds of treatment patients, while patients in the control group only saw maintenance or decreases in their scores. Forced expiratory volume in the first second (FEV₁) improved in 23.5% of treatment patients, while control patients saw no improvement.

A phase II trial of the transplantation treatment is currently approved for COPD, as is a phase I/II trial in idiopathic pulmonary fibrosis.

Idrevloride for Primary Ciliary Dyskinesia

Inhaling idrevloride for about 4 weeks led to significant improvements of lung function in primary ciliary dyskinesia (PCD) when compared to just hypertonic saline alone, the CLEAN-PCD study found.

After 28 days using idrevloride in hypotensive saline, percent predicted FEV₁ (ppFEV₁) improved 1.5% more than with hypotensive saline solution alone (P=0.044). This was also true when treatment was extended for 56 days. Findings from the phase II study were also recently published in Lancet Respiratory Medicine.

Presenter Thomas Ferkol, Jr., MD, of the University of North Carolina at Chapel Hill, said the idrevloride therapy will be studied as part of an upcoming year-long phase III study in PCD.

PCD is a rare genetic disorder, estimated to impact one person per 7,500 worldwide. Patients with PCD experience impairments of motile ciliary function, which can present itself in a wide array of symptoms ranging from chronic respiratory tract disease to subfertility.

Ferkol noted that studies on the disorder are far and few between, with only two previously published randomized controlled trials on the subject.

“Over 50 genes have been linked with primary ciliary dyskinesia, and at current, there is no specific therapy for this disease. In fact, most of the therapies we use have been borrowed from other diseases like cystic fibrosis and asthma,” he added.

Ultrasound as Gatekeeper to Imaging for Pulmonary Embolism

Utilizing ultrasounds could drastically cut down on the number of referrals to diagnostic imaging for pulmonary embolism (PE), but more work is needed to reduce false negatives.

In the ultrasound group of a randomized trial, PE was considered confirmed in patients who exhibited visible proximal deep venous or ventricular thrombus, two or more subpleural infarctions, and/or McConnell’s sign or D-sign. PE was dismissed if patients didn’t appear to have those signs, had an obvious differential diagnosis thanks to the ultrasound, and if PE was not considered a likely diagnosis.

Patients were only sent on for further imaging when they met neither set of criteria, resulting in referrals to such diagnostic imaging falling by 45.2% with the ultrasound strategy. PE was diagnosed in 20 out of 40 people who underwent diagnostic imaging in this group, with another three diagnosed through discovery of deep venous thrombosis.

However, ultrasound carried a 6.7% failure rate, as two out of 30 people turned out to have PE after having it dismissed initially, reported Casper Falster, MD, a PhD candidate at the Odense Respiratory Research Unit in Denmark, who stressed the possibility of failure with ultrasound as a detection method.

“It is very important to consider that if I wanted to reduce referral by half, I could just flip a coin,” he said.

Falster stated that while D-dimer is an existing test that can help diagnose PE, it gets less specific with patient age and comorbidity.

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