Endobronchial valve insertion to reduce lung volume in emphysema

Mortality was not statistically significantly different in patients treated by duckbill endobronchial valve (EBV) insertion compared with patients having standard medical care (SMC; odds ratio [OR] 1.07, 95% confidence interval [CI] 0.47 to 2.43, I²=0) in a meta-analysis of 5 randomised controlled trials (RCTs; n=703) included in a systematic review (SR). Mortality was not statistically significantly different in patients treated by umbrella EBV compared with those having SMC (OR 4.95, 95% CI 0.85 to 28.94, p=0.076, I²=0%) in a meta-analysis of 2 RCTs (n=350) in the SR. One patient died from tension pneumothorax 4 days after valve insertion in a case series of 91 patients. One patient died from a pneumothorax-induced cardiac arrest within 30 days of duckbill EBV insertion in 1 RCT of 97 patients.

The rate of adverse events was statistically significantly higher in patients treated by duckbill EBV compared with those having SMC (OR 5.85, 95% CI 2.16 to 15.84) in a meta-analysis of 3 RCTs (n=482) in the SR. Serious adverse events were reported on 22 occasions in patients treated by umbrella EBV and in 6 patients having SMC in 1 RCT (n=277) included in the SR. The rate of adverse events was statistically significantly higher in patients treated by umbrella EBV than in those having SMC (OR 3.41, 95% CI 1.48 to 7.84) in a meta-analysis of 2 RCTs (n=350) in the SR.

Chronic obstructive pulmonary disease (COPD) exacerbation episodes were not statistically significantly more frequent in patients treated by duckbill EBV (64% [16/25]) compared with those having SMC (80% [20/25]) in an RCT (n=50) reported in the SR (p=0.42). COPD exacerbation episodes were reported in patients treated with the umbrella valve in 2 RCTs included in the SR: 7 in the valve group and 2 in the SMC group in 1 RCT (n=277) and 2 in the valve group and 2 in the SMC group in another RCT (n=22).

Respiratory failure occurred on 4 occasions in patients treated by umbrella valve in 1 RCT included in the SR, and in 1 patient in a case series of 343 patients without collateral ventilation treated by duckbill EBV.

Pneumonia episodes were not statistically significantly more frequent in patients treated by duckbill EBV (n=2) compared with patients having SMC (n=0) in an RCT (n=50) reported in the SR (p=0.49). The pneumonia rate was not statistically significantly different in patients treated by duckbill EBV (6% [2/34]) compared with those having SMC (3% [1/34]) in 1 RCT reported in the SR (p=1.0). Pneumonia distal to the valve was reported in 4% (9/220) of patients treated by duckbill EBV in 1 RCT included in the SR. Pneumonia distal to the valve was reported in 7% (6/91) of patients and bacterial bronchitis was reported in 1 of 91 patients in the case series of 91 patients at 12‑month follow-up. Pneumonia was reported in 1 of the 14 patients who were treated bilaterally by EBV in a case series of 49 patients. Pneumonia distal to the valve was reported in 5% (2/40) of patients treated by EBV in a case series of 40 patients.

Pneumothorax episodes were not statistically significantly more frequent in patients treated by duckbill EBV (n=2) compared with patients having SMC (n=1) in an RCT (n=50) reported in the SR (p=1.0). The pneumothorax rate was reported as 26% (11/43) and 18% (6/34) in patients treated by duckbill EBV in 2 RCTs included in the SR. Pneumothorax occurred on 3 occasions in patients treated by umbrella EBV in 1 RCT included in the SR. The pneumothorax rate was 6% (25/421) in a case series of 421 patients treated by duckbill EBV; the mean duration of pneumothorax in this study was 11 days (range 2 to 73 days). Pneumothorax occurred in 10% (35/343) of patients in the case series of 343 patients. Pneumothorax within 12 months of valve insertion was reported in 12% (11/91) of patients in the case series of 91 patients; 5 of these were judged to be serious and definitely device related. Pneumothorax was reported in 21% (3/14) of patients in the bilateral group and in 8% (3/35) of patients in the unilateral group in the case series of 49 patients treated by EBV. One patient had contralateral pneumothorax 15 days after the procedure in the case series of 40 patients. Pneumothorax occurred in 1% (5/343) of patients reported in the case series of 343 patients. Pneumothorax happened in 18% (70/381) of patients treated by EBV with duckbill or umbrella valves in the case series of 381 patients. In these 70 patients, pneumothorax resolved under observation in 13% (9/70), and 87% (61/70) needed chest tube insertion. In 51% (31/61) of patients pneumothorax did not resolve and valve removal was necessary. Persistent fistula (despite chest drain and valve removal) was present in 45% (14/31) of patients and required further intervention. In the same study 73% (51/70) of cases of pneumothorax happened within 3 days of EBV treatment.

Four episodes of valve expectoration were reported in 1 RCT (n=50) of the duckbill EBV included in the SR. Valve replacement was reported in 7% (3/43) of patients treated by duckbill EBV in 1 RCT (n=93) included in the SR. Valve expectoration, migration or aspiration were reported on 14 occasions in 1 RCT (n=171) of duckbill EBV reported in the SR. Valve replacement was needed in less than 1% (3/343) of patients reported in the case series of 343 patients. Valve migration was reported in 14% (2/14) of patients treated bilaterally by duckbill EBV in the case series of 49 patients. Valve removal (duckbill EBV) was needed in 2 cases in 1 RCT (n=50), in 12% (5/43) of patients in another RCT and in 14% (21/220) of patients in another RCT included in the SR. Valve removal was reported in 18% (16/91) of patients in the case series of 91 patients treated by duckbill EBV, and in 1 patient treated by EBV in the case series of 40 patients.

Haemoptysis was reported in less than 1% (1/220) of patients treated by duckbill EBV in 1 RCT included in the SR. Mild haemoptysis occurred in 1 of 343 patients in the case series of 343 patients. Haemoptysis was reported in 14% (2/14) of patients treated bilaterally by EBV in the case series of 49 patients.

Bronchospasm was reported in 1 patient treated by umbrella EBV in 1 RCT included in the SR. Bronchospasm within 3 days of the procedure was reported in 9% (8/91) of patients in the case series of 91 patients. One of these was described as serious, and associated with respiratory failure and myocardial infarction that began the evening after the procedure; the patient had further episodes of bronchospasm and the valves were removed on day 21. A second patient had valve removal on day 3 because the bronchospasm did not resolve.

Placement of a valve in the incorrect lobe was reported in 1% (3/220) of patients in 1 RCT included in the SR.

Hypoxia was reported in 1% (4/343) of patients, fistula in less than 1% (2/343), pleural effusion in less than 1% (2/343) and increased sputum in less than 1% (1/343) of patients in the case series of 343 patients. Injury to bronchi was reported in 3% (3/91) of patients in the case series of 91 patients (not further described). In the same case series, 2% (2/91) of patients reported transient hypercarbia; 1 patient needed overnight ventilator support.

In addition to safety outcomes reported in the literature, specialist advisers are asked about anecdotal adverse events (events which they have heard about) and about theoretical adverse events (events which they think might possibly occur, even if they have never done so). For this procedure, specialist advisers listed no anecdotal adverse events in addition to those in the literature. They considered that the following were theoretical adverse events: worsening of hypercapnia and pulmonary hypertension.