Multiple breath washout lung function reveals ventilation inhomogeneity unresponsive to mechanical assisted cough in patients with neuromuscular disease.

Background: Respiratory involvement defines the clinical outcome of neuromuscular diseases (NMD). The lung clearance index (LCI) is a marker of lung ventilation inhomogeneity and indicates small airway disease. It is determined by mulitple breath washout lung function (MBW). The merit of LCI is undisputed for primary lung diseases like cystic fibrosis, but its role in NMD is unclear.

Methods: We investigated the role of MBW in patients with NMD and the effect of two different tracer gases and cough assist devices on the LCI. Patients and controls performed MBW with nitrogen (N) and sulfur hexafluoride (SF), whereas the latter analysis was repeated after the use of a cough assist device in the NMD group. LCI was compared to forced vital capacity (FVC) and peak cough flow (PCF).

Results: 24 NMD patients (12 Duchenne Muscular Dystrophy, 8 Spinal Muscular Atrophy, 4 other NMDs) and 15 healthy controls were enrolled. In the NMD group, overall LCI N was higher than LCI SF (9.67 ± 1.56 vs. 8.71 ± 1.47; mean ± SD; p < 0.033). In controls, LCI N did not differ significantly from LCI SF (7.03 ± 0.37 vs. 7.05 ± 0.67; p = 0.882). Both LCI N and LCI SF were significantly higher in NMD patients as in controls (9.67 ± 1.56 vs. 7.03 ± 0.37, p < 0.001, and 8.71 ± 1.478.65 vs. 7.05 ± 0.67, p < 0.001). In the NMD group, both LCI N and LCI SF showed a negative correlation to FVC (r = - 0.525; p = 0.008 and r = - 0.526; p = 0.008, respectively) and PCF (r = - 0.590; p = 0.002 and r = - 0.641; p = 0.001, respectively). LCI N and LCI SF correlated well in the NMD group. LCI SF did not change significantly after the use of the cough assist in NMD patients (n = 22; 8.65 ± 1.52 pre vs. 8.79 ± 2.03 post, p = 0.667).

Conclusion: Lung involvement of patients with neuromuscular diseases goes beyond weakness of respiratory muscles. MBW with both N and SF is suitable to detect ventilation inhomogeneity in NMD patients with respiratory impairment. Cough assist devices with low to moderate pressure levels do not immediately improve the LCI.