Unilateral diaphragmatic paralysis: inspiratory muscles, breathlessness and exercise capacity

Pulmonary function

After clinical and image evaluation, diaphragmatic dysfunction in the paralysis group was confirmed by a reduction of 35% in the FVC, with a further decrease of 12% when the FVC manoeuvre was performed with the patient in the supine position (Table 2). It is well established that unilateral diaphragmatic involvement is related to a mild decrease (10 to 30%) in VC and a further decrease of 10–20% with the patient in the supine position [1, 19, 20]. Koo et al. [21] described a change in VC performed in the supine position of 5.3% for normal diaphragm function, 13.8% for unilateral paralysis and 37% for bilateral paralysis.

Inspiratory muscle function

Our patients had significant inspiratory muscle weakness compared to control group, with 55% and 58% of predicted for P_Imax and SNIP, respectively (table 3). The sniff manoeuvre with pressure measurement also evidenced significant global inspiratory muscle weakness compared with the controls (table 3). Although there are no normal values described for the sniff manoeuvre, the range can vary between 52 to 150 cmH₂O for sniff P_oes and 82 to 204 cmH₂O for sniff P_di in healthy subjects [4, 22] and a variation has been described between subjects in the oesophageal and gastric pressures contribution to the sniff P_di [22]. Of note, the low sniff P_di in the paralysis group is probably related to the paradoxical response (negative values) in the P_ga during the manoeuvre, which reflects the impaired diaphragm contraction mechanism (figure 1; table 3). Recently, a paradoxical response of the P_ga during the sniff manoeuvre was described in a man with unilateral diaphragmatic dysfunction [23], but it is not described in the healthy control subjects. Mills et al. [24] suggest that the fall in P_ga during the sniff manoeuvre is due to the diaphragm being pushed up into the chest, reducing abdominal pressure.

The twitch P_di measurement evidenced substantial diaphragm weakness in the paralysis group compared with the control group (table 3). Although normal values for twitch P_di in adults are lacking, the literature shows that a twitch P_di of <15 cmH₂O [4] or <20 cmH₂O [2], and a unilateral twitch P_di of <10 cmH₂O [2] are indicative of diaphragmatic weakness. However, some variability must be considered even in healthy individuals, in which involves also technical aspects like pressure sensors and properties of tube [25]. Our results showed a unilateral twitch P_di of 2.5±1.1 cmH₂O (affected hemidiaphragm) in the paralysis group, in comparison to the control group, which agree with those described by Hart et al. [6], who consider a right and/or left twitch P_di <3.5 cmH₂O as indicative of UDP. In addition, a previous study [14] described this important reduction twitch P_di in patients with UDP, with impairment of the force generation even of the preserved contralateral hemidiaphragm.

Like the P_Imax and SNIP measurements, the sniff manoeuvre is a global measurement of the strength of the inspiratory muscle, that is, combined measures of diaphragmatic and nondiaphragmatic inspiratory muscle strength. On the other hand, the twitch P_di is useful to assess the diaphragm function specifically. However, it is an invasive technique and cause some patient discomfort. The ultrasound is a useful tool to evaluate the diaphragm function, since it is less invasive, simple and allows direct evaluation [2, 4]. In patients with UDP, the ultrasound is an important technique to assess the diaphragm mobility and thickness, as described previously [14].

Exercise testing

The paralysis group had similar V′_O2 and V_E compared with the controls at iso-work rate. However, they had reduced exercise capacity (lower peak work rate and V′_O2) with a significant decrease in V_E and V_T at peak exercise. Interestingly, patients had increased RR and dyspnoea in very early exercise progression (figure 2). According to Bonnevie et al. [5], these patients have exercise limited by a pathological ventilatory pattern (low Vt and excessive RR). Hart et al. [6] affirm that the exercise limitation is primarily associated with the reduced peak minute ventilation. However, in both studies the sample size is small and there was not any measurement of diaphragm or inspiratory accessory muscles, besides dyspnoea during exercise.

Inspiratory muscle function

Looking at diaphragm function and its mechanism of contraction during exercise, a higher P_oes generation along with a paradoxical response in the P_ga generation was observed, resulting in a very low P_di compared with that in the control group (figure 3a–c). Of note, the pathological contraction pattern characterised by the negative values of P_ga is present not only at rest but worsens with increasing work rate. It is probably the result of the diaphragm being suctioned into the chest (paradoxical movement during inspiration), as described during the sniff manoeuvre [24]. Hart et al. [6] had already described this pattern at rest and its correlation with a worse exercise performance and reduced ventilation. We observed this paradoxical movement of the P_ga at rest in 75% of the patients, with increase to 94% at 20 w and to 100% at other loads and peak of the exercise.

At iso-work rate, the paralysis group had a greater percentage of activation of scalene (EMGsca/EMGsca, max) and sternocleidomastoid (EMGscm/EMGscm, max) than the controls had. At peak exercise, they reached twice the percentage of the controls (figure 3d,e). This result indicates that, at submaximal exercise, paralysis group probably maintained similar ventilatory conditions to that in the control group at the expense of the scalene and sternocleidomastoid activation. This result is in line with the statement that in face of the impaired diaphragm contraction, the inspiratory function is supposed to be partially compensated by other inspiratory muscles than the diaphragm [26]. In addition, the high activation of these muscles explains the higher P_oes generation compared with controls (figure 3a) because the P_oes measured during hyperpnoea condition is the result not only of diaphragm contraction but also of the nondiaphragmatic inspiratory muscles. This recruitment certainly results in higher dyspnoea sensation during exercise, even at mild intensities.

Briefly, the paralysis group present an increased inspiratory muscle effort combined with reduced tidal volume and increased RR at a given work rate or ventilation compared to the controls. It may reflect a mismatch between the respiratory drive and the mechanical responses (neuromechanical dissociation), probably resulting in increased dyspnoea [27]. Despite it is a mechanism of better adaptation to achieve a higher ventilation, the ultimate consequence is an overload of inspiratory accessory muscles and higher breathlessness.

Although the static respiratory muscle function is well described in patients with diaphragmatic dysfunction [2, 3, 14, 19, 20, 24, 28], only two studies [5, 6] have described the influence of inspiratory muscle function on the exercise capacity in these patients. However, none of them applied the respiratory muscle function measurements during the exercise. This is the first study that shows a more comprehensive and dynamic evaluation of all inspiratory muscles and symptom-implication over the exercise. Our study measured the respiratory muscle function continuously throughout the exercise, with important results of over recruitment of the respiratory muscles and altered respiratory pressures responses in these patients compared to healthy subjects. Despite the statistical difference in the age between the groups, the average values (55.8±9.9 years for paralysis group and 49.8±6.4 years for control group) are clinically very similar.