Minute-Ventilation Variability During Cardiopulmonary Exercise Test Is Higher In Idiopathic Dyspnoea Subjects Compared To Subjects With Breathing Pattern Disorder.

Background: Patients with abnormal breathing responses often report presenting with debilitating symptoms that negatively impact both physical and mental quality of life. Objective: To compare time-domain variability of ventilatory components of Idiopathic dyspnoea and Breathing Pattern Disorder during a progressive maximal exercise test, evaluating their relationship to other variables usually obtained during a cardiopulmonary exercise test. Methods: Analysis of time-domain variability (RMSSD) of minute-ventilation (VE) during a maximal cardiopulmonary exercise test of 13 subjects with Idiopathic dyspnoea and 13 subjects with dysfunctional breathing pattern. Data was compared by a two-tailed Student T-test. Results: Idiopathic dyspnoea subjects exhibited a greater Minute-Ventilation Variability (31.5 ± 6.2 Vs 25.4 l/min ± 8.0, p >0.05). Inspiratory tidal volume time ratio (VTin/ti) (1.96 ± 0.7 Vs 2.58 ± 0.6, p >0.05) and Breathing Frequency (35 ± 9.3 Vs 43 breath/min ± 8.2 p >0.05) were also signicantly lower in Idiopathic Dyspnoea compared to Breathing Pattern Disorder subjects. Conclusions: Time-domain variability of minute ventilation during exercise is greater in Idiopathic Dyspnoea compared to the Breathing Pattern Disorder subject’s possible highlighting a lower ventilatory threshold.


Introduction
Many patients with Idiopathic dyspnoea (ID) or Breathing Pattern Disorder (BDP) such as Postural Orthostatic Tachycardia Syndrome, Hyperventilation or Dysautonomia present with debilitating symptoms that negatively impact both physical and mental quality of life 1

. Changes in normal breathing
can result in symptoms of; dizziness, blood pressure uctuations, paraesthesia and tachypnoea 2,3 .
Furthermore, abnormal breathing patterns are routinely seen in 20% of individuals with asthma 4 .
Therefore the quantitation of ventilatory variability may prove a signi cant prognostic indicator in this subject group.

Methods
Dyspnoea is defined as "a subjective experience of breathing discomfort that consists of qualitatively distinct sensations that vary in intensity" 5,6 . BPD was determined by either Physiotherapist assessment or by using The Brompton Breathing Pattern Assessment Tool (BPAT). A BPAT > 4 was seen as positive 7 .
26 subjects (13 ID, 13 BPD) underwent cardiopulmonary exercise test as part of routine clinical care. Table 1 shows the primary diagnoses for the ID cohort.
This study was approved by the Respiratory Medicine Research Committee at St Barts NHS Trust. Time-domain variability analysis of data was applied retrospectively. Root mean square successive difference (RMSSD) ( Figure 1) is widely used in cardiology to quantify heart-rate variability and is appropriate for this subject group 8, 9,10 .

Study Protocol
This was a retrospective, single centre study, all subjects performed a maximal cardiopulmonary exercise test using an electrically-braked cycle ergometer (VIAsprint 150 cycle ergometer, Vyaire Medical Products Ltd, Basingstoke, UK) following an individualised incremental ramp protocol up to exhaustion. All tests achieved at least two of the following criteria to be considered maximum: Post-exercise blood lactate levels ≥8

Results
There were no differences in demographic and anthropometric characteristics of both groups ( Table 2). Peak cardiopulmonary exercise data of both groups are shown in Table 3.
The ID group were significantly lower difference in Breathing Frequency, Minute Ventilation and Inspiratory Tidal Volume Time Ratio compared BPD group. Furthermore, ID subjects exhibited a significantly higher timedomain variability of minute-ventilation than BPD subjects during cardiopulmonary exercise test, as shown in Figure 1.

Discussion
The current study has shown that subjects with ID have greater minute ventilation variability during cardiopulmonary exercise than subjects with BPD. Interestingly however further analysis showed that ID subjects exhibit a reduction in Breathing Frequency and Inspiratory Tidal Volume Time Ratio during maximal graded exercise compared to BPD subjects.
From these ndings have emerged two con icting conclusions; (1) that a lower ventilatory threshold was seen in the Idiopathic Dyspnoea compared to the other group. It is known that in chronic populations such as Chronic Obstructive Pulmonary Disease a diminishing ventilatory threshold has if often the resultant of changes in pH and HCO 3 this may be cause of rapidly developing tachypnoea 8 .
(2) The con icting conclusion, do subjects with BPD in fact exhibit and abnormal ventilatory response whereas ID subjects have better chemoreceptor control and therefore breathe in a deeper and more e cient manner?

Conclusions
The present study adds information regarding the quanti cation of exercise minute-ventilation variability however the exact triggers that in uence ventilatory variability during exercise remain unclear.