The desat-max in 2-chair test appears to be a worthwhile parameter to identify sickness: An appraisal

Materials & Methods

This prospective study was undertaken by the department of General Pulmonology, Institute of Pulmocare and Research, Kolkata from March 2023 to March 2024 after ethical clearance.

The methodology included, (i) selecting participants from ill and symptomatic patients and ‘normal’ persons, (ii) collecting their subjective sickness score on a ‘0’ to ‘10’ scale based on severity, (iii) subjecting them uniformly to 2CT, and (iv) conducting statistical tests as appropriate to attain the stated objective.

Uniform application of 2-chair test

Experienced technicians ensured the quality of the test performed the 2CT in the both groups of participants (‘normal’ and diseased) according to the published protocol⁷.The test mandates a person to rest first on a chair till the pulse rate (PR) and SpO₂ are stabilized over 30 sec. Then, the person moves up to sit on another chair placed five feet away and facing the first one, and then immediately return to the first chair at his/her pace. The continuous performance of five such up and down movements completes the exercise protocol. The PR and SpO₂ are measured immediately following the cessation of exercise and then at every 10 sec for 2 min. We used a simple software capable of both graphical and numerical display of the collected data (Fig. 1). Any ‘normal’ person showing >1% desaturation at any point in the 2CT were excluded from the protocol.

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Fig. 1.

Numerical representation of the 2-chair test data by the software used for data collection.

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The PR-related variables were minimum PR (observed during the test at rest), maximum PR after exercise, maximum PR change (the difference between the minimum and the maximum PR), cumulative PR change (the summation of the deviation of PR at each point of measurements), and duration of tachycardia (PR>100). The maximum SpO₂ (recorded maximum saturation at rest), minimum SpO₂ (minimum saturation measured post-exercise), maximum desaturation or the desat-max (the maximum fall of saturation from baseline), and cumulative desaturation (adding up all the post-exercise desaturation values) formed the SpO₂ related variable.

Statistical calculations to serve the objective

The data collected were charted and compared between the ‘normal’ and the ‘symptomatic diseased group’ with an unpaired Student’s t-test. A significant difference was at the level of P<0.05. Selected 2CT variables showing a statistically significant intergroup difference were used independently to see co-relationship to the PPSS (Fig. 2) to identify the best correlating variable by preparing a correlation matrix using the correlation coefficients of all the variables of 2CT (Supplementary Fig. 2).

Supplementary Figure 2

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Fig. 2.

Displays the correlation between the desat max and the patients’ score of perceived sickness (PPSS).

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Further, we used a free web-tool ‘metaboanalyst-version 6.0’ ( https://dev.metaboanalyst.ca/ModuleView.xhtml ), to examine the relative importance of the different parameters to influence the sickness and displayed it in a VIP plot through multivariate analysis. We used the clustering of different groups based on 2CT parameters using orthogonal PLSDA 2D score plots. In addition, we made a principal component analysis of the two groups of participants (healthy and symptomatic) on the 2CT data separately. Simultaneously, the weight of the co-relation coefficients of different 2CT parameters was displayed using a pattern hunter chart.

Results

A total of 419 patients (Mean age in yr=55.046±17.231; M:F=280:139) and 30 ‘normal’ controls (Mean age in yr=43.166±10.357; M:F=19:11) were included for statistical comparison. The results (Table I) showed a very significant difference in PPSS score between the two groups (P=<0.0001). Out of the parameters of 2CT, the maximum PR change showed the best significance in differentiation between the normal and diseased persons (P=0.0086), followed by maximum or highest SpO₂ (P=0.0151), minimum SpO₂ (P=0.0270), and the desat-max (P=0.026) (Table I).

Further, we looked for correlations between the four parameters of the PPSS (differentiating the ‘sick’ patients from the ‘normal’ group significantly; Table I). It revealed that the desat-max performed the best of the four (change in PR max, minimum and maximum SpO₂, and desat-max) so far the correlation coefficients were concerned (Table II). The co-relationship of the desat-max with PPSS is displayed in figure 2.

Both the VIP plot and ‘pattern hunter’ displayed the desat-max as the best available 2CT parameters (Fig. 3A and B). The clustering (2-dimensional and 3-dimensional) of the two groups based on desat-max using orthogonal PLSDA 2D score plots are displayed in figure 4A and B (Supplementary Fig. 3; Supplementary Table I, II and III).

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Fig. 3.

Displays the relative strength of the desat-max being the best out of the all the other parameters to indicate the perceived sickness in the form of (A) VIP plot and (B) pattern hunter plot.

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Fig. 4.

Displays the scatter plot with the normal (red dots) and the symptomatic and diseased (green dots) in (A) 2 dimensional and (B) three dimensional.

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Discussion

The results of our investigation revealed that maximum PR change, minimum SpO₂, maximum SpO₂, and desat-max differed significantly between normal participants and diseased patients. Of them, the desat max correlated best to the PPSS and appeared most discriminating on the VIP and pattern-hunter plots.

It was intriguing how the desat-max turned out to be the parameter reflecting the PPSS while the change in maximum PR (PR max) and other parameters differentiated between ‘normal’ and symptomatic patients even better than desat-max (Table I). The reasons are likely embedded in the hosts’ multiple and complex physiological changes that need to be investigated with experiments on the physiology of post-exercise desaturation.

One possible mechanism could be that in the post-exercise state, the PR changes under autonomic control, reflecting a primary cardiac or cardiovascular functional recovery, while the change in SpO₂ (in both degree and pace of recovery) appears dependent on factors like mixed venous oxygen concentration, the ventilation/perfusion relationship, the FiO₂, and the performance of both the ventricles. In addition, the variation of PR is far bigger (60 to 100) than SpO₂ (95 to 100) in normal health. Hence, it is natural for a PR change to achieve a difference of significance far more easily than a SpO₂ change. Therefore, the SpO₂-based parameters achieving significance in the comparison between normal and abnormal may be considered more meaningful. It seems that the threshold for change has been set at a lower level for PR than SpO₂ both in normal and diseased states in post-exercise observations. Therefore, a relatively lower difference of significance (Table I) for the SpO₂ may reflect much bigger physiological disturbances.

The clusters showing an overlap between normal and abnormal appeared interesting. This reflects the following possibilities: (i) presence of a latent disease affecting the desaturation, (ii) a perceptual failure of subjects to appreciate sickness marked by de-saturation, or (iii) inclusion of some diseases that may not affect any SpO₂ change. All the three possibilities need investigations, and one needs to find a better and more objective parameter than the sickness score to appreciate the abnormal physiology. That a patient is sick but not de-saturating is also possible if the sensitivity of detection is low or the background physiological status remains good enough to compensate for the process of desaturation. Such situations mean that the desat-max is a poor parameter to reflect sickness in many. Thus, the exercise may be a way forward to determine or identify a poor perceptor and a good reservoir-holder reflecting two different physiological statuses of the population under research. We have seen such events of poor perception in patients having ‘happy hypoxia’ during the COVID-19 pandemic. This leads us to a very interesting interaction between the psycho-behavioural and cardiopulmonary domains. Since, theoretically, both respiratory and the cardiovascular pathology can cause and influence desaturation, it is important to understand the interaction between the two systems. Another possibility is that the co-relationship of desat-max with the PPSS might have been dragged to a lower level, possibly due to the poor association of perceived sickness in patients with relatively higher desaturation (Fig. 2). This could be possible because of psychological adjustment of patients with chronic debilitating illness or blunting of the perception quality of the seriousness of sickness. This merits future research. The overlap of parameters of the diseased patients in the normal range of desaturation is interesting. We chose patients with clinically isolated upper respiratory tract diseases (e.g., allergic rhinitis) that may have none or trivially significant cardiopulmonary effects altogether. The inclusion of such patients might have contributed to the overlap.

The measurement had a limitation that it could not capture values between two units (like 95 and 96% of SpO₂). A more sensitive measurement using a decimal scale recording (viz., 95.46%, 96.28%) could have helped identifying a more precise cut-off of desat-max. Our results were in favour of desat-max as the one to appreciate sickness by the 2CT. It implied that this simple parameter of post-exercise recovery response (PERR) could distinguish an abnormal state of cardio-pulmonary health from normal.

Exercise tests have been in vogue in clinical practice for a long time. The 6 MWT has been a useful validated test that counts the walk distance and has played important role in the assessment of the change in a disease state^11-13, functional status^4,14,15, and prognostications^16,17. Evolved to substitute the 6MWT, the 2CT appears to belong to a different class altogether. While the 6MWT measures the distance walked, or the functional capacity, the 2CT actually accounts for the post-exercise changes in PR and SpO₂ allowing it to be marked as a cardiopulmonary reserve-specific test.

Exercise means a complex integration where multiple systems act in tandem. The predominant output of the locomotor system is supported by the cardio-respiratory system and controlled by neurological inputs. However, when the subjects cease to exercise (i.e., at the immediate post-exercise state), the locomotor system is brought to rest, neural inputs change the pattern, and there is a readjustment of the cardio-pulmonary system to return to the pre-exercise status. This readjustment or the functional return of cardio-pulmonary systems is designated as PERR, the understanding of which, through the changes in PR and SpO₂ at the recovery response, appears novel. The desat-max of 2CT can identify poor cardiopulmonary readjustment in patients.

Post exercise physiology of recovery response has been an issue in research for a long time in sports medicine^18-21. The heart rate (HR) variation following exercise is regarded as a research domain on autonomic activity²². There have been several works on HR recovery despite methodological issues, and researchers have tried to appreciate the cardiac autonomic response using HR and systolic time interval²³. Delayed fall in HR after exercise was thought to be a prognostic marker, and a fall of less than 12 beats per minute from the peak rate was regarded as abnormal. Such delayed decrease in the heart rate response (HRR) was found to predictmortality²⁴. In applies to chronic heart failure patients where the parameter acted as an independent prognostic factor²⁵. Such HRR could predict mortality independently in suspected coronary artery disease, even after taking into account the left ventricular function, exercise capacity, and angiographic severity of CAD²⁶. Such post-exercise HRR has been seen to be accelerated in exercise and blunted in patients with chronic heart failure²⁷.

Exercise-induced desaturation has been noticed in COPD and interstitial lung disease (ILD) patients^28-30, but post-exercise desaturation has not received that much attention for any heart or lung disease, except some recent interests^2,3.

The present study had several limitations. A higher number of ‘normal’ participants or ‘controls’ would have been better. There is inclusion of patients from a pulmonary clinic only since we work in the subspecialty of pulmonology. However, including patients with primary cardiovascular diseases could have added strength to our investigation. Although we used PPSS due to ease of using and we chose ‘sickness’ as a yardstick of measurement of diseases, these were not specific to cardiopulmonary illness.

In conclusion, the role of 2CT in clinical practice for screening populations for diseases, identifying individuals for further evaluations, offering proper medications, monitoring the course of a disease, and assessing prognostication merits wider research.