Electrical impedance tomography detects changes in ventilation after airway clearance in spinal muscular atrophy type I

https://doi.org/10.1016/j.resp.2021.103773Get rights and content

Highlights

  • Electrical impedance tomography visualizing regional ventilation in SMA I patients.

  • Pulmonary pulsatile perfusion images from EIT data collected during breathing pauses.

  • EIT can quantify changes in lung volume during insufflation and exsufflation with MIE.

Abstract

The effect of mechanical insufflation-exsufflation (MIE) for airway clearance in patients with spinal muscular atrophy type I (SMA‐I) on the distribution of ventilation in the lung is unknown, as is the duration of its beneficial effects. A pilot study to investigate the feasibility of using three dimensional (3-D) electrical impedance tomography (EIT) images to estimate lung volumes pre- and post-MIE for assessing the effectiveness of mechanical insufflation-exsufflation (MIE) was conducted in 6 pediatric patients with SMA‐I in the neuromuscular clinic at Children's Hospital Colorado. EIT data were collected before, during, and after the MIE procedure on two rows of 16 electrodes placed around the chest. Lung volumes were computed from the images and compared before, during, and after the MIE procedure to assess the ability of EIT to estimate changes in lung volume during insufflation and exsufflation. Images of pulsatile pulmonary perfusion were computed in subjects able to perform breath-holding. In four of the six subjects, lung volumes during tidal breathing increased after MIE (average change from pre to post MIE was 58.8±55.1 mL). The time-dependent plots of lung volume computed from the EIT data clearly show when the MIE device insufflates and exsufflates air and the rest periods between mechanical coughs. Images of pulmonary pulsatile perfusion were computed from data collected during breathing pauses. The results suggest that EIT holds promise for estimating lung volumes and ventilation/perfusion mismatch, both of which are useful for assessing the effectiveness of MIE in clearing mucus plugs.

Introduction

Spinal muscular atrophy is a progressive genetic disease affecting about 1 in 11,000 newborn babies each year (Pearn, 1973; Sugarman et al., 2012) characterized by anterior horn cell disease leading to weakness and atrophy of the skeletal muscles. It typically affects the proximal muscles more severely than distal muscles. Approximately one in 50 people in the United States is a carrier of the disease (Sugarman et al., 2012), which is caused by a missing or dysfunctional SMN1 gene (Lefebvre et al., 1995). The most common and most severe form is spinal muscular atrophy type I (SMA-I). Children with SMA-I cannot sit by themselves and have progressive bulbar and respiratory muscle weakness leading to inability to feed, aspiration, and respiratory failure. Respiratory muscle weakness prevents effective coughing and leads to the accumulation of mucus in the lungs that can result in air trapping, atelectasis, infection, and pneumonia. Respiratory complications are the leading cause of death in patients with SMA-I (Zerres and Rudnik-Schöneborn, 1995; Finkel et al., 2014; Kolb et al., 2017). In recent years, three SMA-specific therapies have been approved (Finkel et al., 2017; Al-Zaidy and Mendell, 2019; Food and Drug Administration, 2020), but not all patients are receiving them (Schorling et al., 2020). Assessing respiratory function in SMA-I is challenging since many patients are unable to perform standard pulmonary function tests due to age or bulbar function.

Mechanical insufflation-exsufflation (MIE) is used for airway clearance in patients with SMA-I, but there are many open questions about its optimal use and the duration of its beneficial effects. Knowing the effect of MIE on the distribution of ventilation in the lung could help answer these questions, yet at present, a clinical tool is lacking. Electrical impedance tomography (EIT) is a safe, non-invasive, non-ionizing imaging modality that can be performed as-needed, even during MIE. In EIT imaging, electrodes are placed on the skin around the torso, a low-frequency imperceptible current is applied, and the resulting voltages are measured on the electrodes (Holder, 2005; Brown, 2003; Frerichs et al., 2017; Martins et al., 2019). The measured data is used to solve an inverse problem numerically to compute the conductivity distribution in the chest. Since air, blood, muscle, and lung tissue all have different conductivity values, dynamic images of ventilation and perfusion can be formed from the reconstructions. Clinical validation against CT images has shown that EIT is effective for obtaining images of regional ventilation distribution (Frerichs et al., 2002a, b; Costa et al., 2009; Smit et al., 2004; Victorino et al., 2004). Regional information used to derive measures of spatial and temporal ventilatory heterogeneity have been used to detect changes in patients with chronic asthma pre- and post-bronchodilator inhalation (Frerichs et al., 2016) and cystic fibrosis (Lehmann et al., 2016). Cystic fibrosis patients were also the subjects of studies in which changes in EIT-derived spirometry measures demonstrated a positive correlation with standard spirometry (Krueger-Ziolek et al., 2016; Muller et al., 2018), and regions of air trapping were identified using EIT derived ventilation/perfusion maps (Mueller et al., 2018). Changes in lung volume using EIT images collected during spirometry have shown excellent correlation with pneumotachograph measurements (Coulombe et al., 2005; Marquis et al., 2006). EIT has also been shown to be effective for monitoring pulsatile pulmonary perfusion (Carlisle et al., 2010; Smit et al., 2004; Reinius et al., 2015), which is also relevant for SMA-1 patients because of the ventilation/perfusion mismatch that can result from their respiratory weakness (Iwan et al., 2019).

Lung volume measurement in children poses a challenge, particularly in patients with neuromuscular disorders. Traditional measurements of lung function include spirometry and lung volume measurement by plethysmography or gas dilution. Spirometry requires participation such that children younger than 5–6 years old cannot do them reliably. Plethysmography and gas dilution studies are limited by low lung volumes such that those with chest wall restriction may not be able to produce reliable results. These tests also cannot be done in patients on invasive or noninvasive ventilator support. Infant pulmonary function tests require sedation and can be misleading as artificial insufflation and exsufflation of the lungs during this technique overcomes respiratory muscle weakness. EIT may provide a non-invasive method of obtaining lung volume estimates without sedation. Here we present the results of a pilot study of six patients with SMA-I that demonstrates the feasibility of using regional ventilation and perfusion images from EIT data to obtain estimates of lung volumes before, during, and after MIE.

Section snippets

Data collection

This study was conducted in accordance with the amended Declaration of Helsinki. Data were collected at Children's Hospital Colorado (CHCO) in Aurora, Colorado, under the approval of the institutional review board (IRB) (approval number 18–1843). Informed parental consent and children's informed assent were obtained prior to participation. Six patients ages 4.0 ± 2.6 years diagnosed with SMA-I participated. Subject characteristics at the time of the study are provided in Table 1.

Two rows of 16

Images of regional ventilation and regional and global lung volumes

Fig. 4 (a) shows five frames from the ventilation sequence for Subject 1 post-MIE with red lines in the power waveform plot found below the images indicating the frame for each image. The power waveform of the impedance measurement was computed as the inner product of the measured voltages and applied currents and provides a plot of frame versus power in microwatts. A peak in the waveform corresponds to maximal inhalation and a trough to exhalation. Thus, respiratory rates can be calculated

Discussion

This is the first study investigating EIT as a tool for assessing lung function pre and post MIE in any patient population and for obtaining regional ventilation and perfusion images in patients with SMA. It is evident from the plots of estimated lung volume in Fig. 5 from EIT data collected during MIE that the volumes clearly indicate when the device insufflates and exsufflates air and the rest periods between cough simulations. Such plots could be useful in determining optimal MIE settings

Declaration of Competing Interest

Tzu-Jen Kao is employed by GE Research. Other authors have no declaration of interest to declare.

Acknowledgments

The authors thank Allison Keck for recruiting the volunteers that took part in this study and her assistance as Research Coordinator. They also wish to thank the children and families who participated in the study.

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