Functional Respiratory Imaging as a Tool to Personalize Respiratory Treatment in Patients With Unilateral Diaphragmatic Paralysis

Patient 1

A 57-y-old male patient (102 kg, 175 cm) with unilateral diaphragmatic paralysis since 1.5 y of age was referred to the hospital with recent complaints of increasing dyspnea and orthopnea. His medical history revealed asthma. On clinical examination, diminished vesicular breath sounds at the right lung base were heard. The previous practitioner prescribed the patient 4 daily doses of salmeterol at 25 μg and fluticasone at 250 μg (Seretide, GlaxoSmithKline, Philadelphia, Pennsylvania) and fluticasone at 250 μg (Flixotide, GlaxoSmithKline) to control the asthma exacerbation. PFT showed highly reduced lung function (Table 1) with both restrictive and obstructive elements. HRCT confirmed unilateral paralysis of the right diaphragm in combination with hypoventilation-induced atelectasis in the right middle and right lower lobes.

To investigate how well the right middle and right lower lobes were still ventilated, FRI analysis was performed. The HRCT scans were loaded into the Mimics 15.0 software suite (Materialise, Leuven, Belgium). This validated package (FDA K073468, Conformité Européenne Certificate BE 05/1191.CE.01) was used to generate 3-dimensional representations of the airways and lobes. The lobar expansion from FRC to TLC was considered a measure for lobar ventilation, as this represents the internal air-flow distribution as defined in the following equation: in which IAD_lobe is the internal air-flow distribution to a specific lobe, V_{TLC_lobe} is the volume of that lobe at TLC, V_{FRC_lobe} is the volume of that lobe at FRC, V_{TLC_lungs} is the total volume of all lobes at TLC, and V_{FRC_lungs} is the total volume of all lobes at FRC. Computational fluid dynamics calculations were performed using Fluent 14.0.0 (Ansys, Lebanon, New Hampshire) and provided measurements of local deposition of inhaled medication.² In this way, it was possible to assess to which zones the drug was delivered.

FRI analysis showed poor ventilation of the right lower lobe and no ventilation of the right middle lobe (Fig. 1). In addition, very low levels of drug deposition were found in these lobes (Fig. 2) when performing particle simulations using the compound data of Tarsin et al⁵ and Stein et al.⁶ The poor drug deposition results obtained by FRI explain why a combination of several inhaled compounds was needed to treat the asthma, as these zones were probably pharmacologically undertreated. Furthermore, a long-term non-ventilatory status of the right middle lobe could set the stage for repeated episodes of infection, accounting for a vicious cycle of recurring bouts of inflammation that may result in a non-functional lobe.⁷

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Fig. 1.

The internal air-flow distribution in the right upper lobe (red), right middle lobe (yellow), right lower lobe (orange), left upper lobe (blue), and left lower lobe (magenta) seen in patient 1 before and after surgery (A) and in patient 2 (B). FRC = functional residual capacity; TLC = total lung capacity.

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Fig. 2.

A visualization of drug deposition simulations of patient 1. The green dots are the locations where the particles deposited. The figure shows how much salmeterol and fluticasone deposited in the right upper lobe (red), right middle lobe (yellow), right lower lobe (orange), left upper lobe (blue), and left lower lobe (magenta). A: Preoperative. B: Postoperative.

In a recent review, Groth and Andrade⁸ concluded that diaphragmatic plication seems to be a promising surgical technique to improve ventilation in patients with diaphragmatic paralysis. Therefore, diaphragmatic plication was performed to place the paralyzed diaphragm in a position of maximal inspiration to relieve compression on the lung parenchyma and to allow its re-expansion.

The dyspnea was subjectively better 6 weeks postoperatively. This was confirmed by an improvement in PFT (see Table 1) and by FRI, which showed that the right middle and right lower lobes were much better ventilated than preoperatively (see Fig. 1). FRI also showed improved drug deposition in these regions (see Fig. 2). The amount of active compound reaching the right middle and right lower lobes increased from 38.2 μg (patient using additional fluticasone on top of the salmeterol/fluticasone combination) to 117.1 μg (patient only using the salmeterol/fluticasone combination). This was clinically confirmed, as the patient's asthma was kept stable using only 4 daily doses of salmeterol at 25 μg and fluticasone at 250 μg and as the obstructive components of the PFT improved despite the reduced medication.

Patient 2

A 57-y-old male patient (92 kg, 181 cm) with unilateral diaphragmatic paralysis since 11 months of age presented at follow-up with recent complaints of increasing dyspnea and orthopnea. Clinical examination determined diminished vesicular breath sounds at the left lung base. The patient did not use any inhaled medication. PFT showed significantly reduced lung function (see Table 1) of a restrictive nature. HRCT confirmed the unilateral paralysis of the left diaphragm, and associated atelectasis of the left lower lobe was observed.

Patient 2 underwent the same FRI analysis as patient 1. All lobar regions were ventilated (see Fig. 1). Taking into account these FRI results, the physician considered a further conservative approach with regular follow-up since spontaneous recovery of diaphragmatic function has been reported.⁹ After 6 months, the breathlessness was completely resolved, and TLC was significantly improved (see Table 1). No new FRI analysis was performed, as the physician found this unnecessary from a clinical point of view.