Utility of 2-day Cardiopulmonary Exercise Testing Protocol in LONG-HAUL COVID (LHC) PATIENTS: PRELIMINARY DATA, 2023, Abbasi et al

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EndME

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UTILITY OF 2-DAY CARDIOPULMONARY EXERCISE TESTING PROTOCOL IN LONG-HAUL COVID (LHC) PATIENTS: PRELIMINARY DATA

Purpose: Long Haul COVID (LHC) patients have prominent symptoms of fatigue and exercise limitation. Comparisons have been made between Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) and LHC, especially with respect to post-exertional malaise (PEM). Cardiopulmonary exercise testing (CPET) is a reliable and reproducible non-invasive test to assess the various organ system functions and physiologic capacity. Day to day variation in CPET performance variables, such as peak oxygen uptake (V̇O2peak) and peak work rate (WRpeak) are typically small (< 5%). However, in the CFS/ME literature, using a two-day CPET protocol (non-invasive, maximal, ramp-incremental test repeated 24hr apart) has controversially suggested that day-two V̇O2peak and WRpeak are decreased relative to day-one, in contrast to control subjects that usually increase (or maintain) these variables on day two. Some authors have attributed this difference to post-exertional malaise (PEM). This two-day CPET protocol has therefore been suggested as a possible study protocol to investigate PEM in LHC patients.

Hypothesis: We hypothesize that LHC patients will have no decrement in day-two CPET performance despite the presence of PEM on standardized questionnaire .

Methods: 22 CPETs in 11 LHC patients [mean age 53 (11)yr, n=5 female, time since COVID infection 15.2 (7.2) m, 92% outpatient illness, BMI = 34.7(7.7)kg/m2, FEV1 = 87(13)% pred, FVC = 87 (10)% pred, DLCO = 90±9% pred, TLC = 85(15)% pred, V̇O2peak = 20.14(5.0) ml/min/kg] were studied with a two day CPET protocol. The ramp-incrementation rate was 10-20W/min and selected depending on fitness level. The day-two CPET occurred 24 hr after the day-one CPET, and performed with the same incrementation rate as day-one, with lactate threshold (LT), V̇O2peak and WRpeak measured using standard techniques. PEM was subjectively assessed using the DePaul Symptom Questionnaire, Question #5 ‘Physically drained or sick after mild activity’ (5-point Likert scale) prior to CPET testing. Ratings of perceived dyspnea and leg fatigue were recorded at peak exercise using the modified 0-10 Borg’s Scale. Paired T-Tests were used for variables comparison (day one vs day two).

RESULTS: PEM ratings for the group (DePaul Questionnaire) were 2.0 (1.1), frequency and 2.5 (1.1), severity.

Conclusions: The absence of any difference in 2-day CPET performance with the presence of PEM symptoms using the DePaul Symptom Questionnaire suggests a 2-day CPET protocol may not be useful to investigate PEM in LHC patients.

CLINICAL IMPLICATIONS: The 2 day CPET protocol may not be useful as a method to investigate PEM in LHC patients.

https://journal.chestnet.org/article/S0012-3692(23)04762-1/fulltext
 
Well, if you define PEM only as ‘Physically drained or sick after mild activity’ then you deliberately haven't correctly identified if your participants have PEM or not. Biased investigators will produce biased trials that will give biased results.
 
Whilst I'm not fully convinced by 2-day CPETs, I'm also very wary of some of the claims and understanding made with respect to PEM in Long-Covid. I've talked to several Long-Covid patients who've said they had PEM, but as it turned out some of them just got shortness of breath when they exercise, are a bit tired after eating, have to cough as they are more active or get a headache when doing sport.

Whilst it's great that the acknowledgment for PEM is growing, amongst Long-Covid patients and researchers there seems to be the belief that anything somehow related to tiredness or some discomfort that is activity related is now considered to be PEM.

I can't read the study yet and can't say whether they screened well for PEM using the full DePaul Symptom Questionnaire (DSQ), or at least the DePaul Symptom Questionnaire - Post-Exertional Malaise short form (DSQ-PEM), but I'm certain the person with shortness of breath during and shortly after exercise would have replied "yes" to only the question "Physically drained or sick after mild activity".
 
(cross post with Dolphin)
It's a good question to investigate.

However, in the CFS/ ME literature, using a two-day CPET protocol (non-invasive, maximal, ramp-incremental test repeated 24hr apart) has controversially suggested that day-two V_O2peak and WRpeak are decreased relative to day-one, in contrast to control subjects that usually increase (or maintain) these variables on day two. Some authors have attributed this difference to post-exertional malaise (PEM).
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Hypothesis: We hypothesize that LHC patients will have no decrement in day-two CPET performance despite the presence of PEM on standardized questionnaire .
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These researchers seemed inclined to find no second-day decline. This makes me suspect that they may not understand what PEM looks like.


22 CPETs in 11 LHC patients [mean age 53 (11)yr, n=5 female, time since COVID infection 15.2 (7.2) m, 92% outpatient illness, BMI = 34.7(7.7)kg/m2, FEV1= 87(13)% pred, FVC = 87 (10)% pred, DLCO = 909% pred, TLC = 85(15)% pred, V_O2peak = 20.14(5.0) ml/min/kg]
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With only 11 patients, this was not a big sample. The very high mean BMI makes me wonder how representative these people are of people with Long covid.

PEM was assessed with this:
PEM was subjectively assessed using the DePaul Symptom Questionnaire, Question #5 ‘Physically drained or sick after mild activity’ (5-point Likert scale) prior to CPET testing.
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I don't think this is a great test of PEM. I think people who are just unfit might tick that box.
PEM ratings for the group (DePaul Questionnaire) were 2.0 (1.1), frequency and 2.5 (1.1), severity.
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On a 5 point scale, these ratings don't indicate to me that everyone in the group had PEM.

How odd - there's a mention of one of the researchers having a relationship with Regeneron. I didn't see mention of the organisations these researchers are affiliated with.

This is just a presentation, so there isn't much detail. I think it could be worth poking into further, to find out why these researchers undertook the research. Unfortunately, I don't think this study is a helpful contribution, and that's not because of the negative result.
 
Hutan said:
These researchers seemed inclined to find no second-day decline. This makes me suspect that they may not understand what PEM looks like.
Click to expand...

Abstract said:
However, in the CFS/ME literature, using a two-day CPET protocol (non-invasive, maximal, ramp-incremental test repeated 24hr apart) has controversially suggested that day-two V_O2 peak and WRpeak are decreased relative to day-one, in contrast to control subjects that usually increase (or maintain) these variables on day two. Some authors have attributed this difference to post-exertional malaise (PEM).
Click to expand...

I think the bias is on full display.

As noted, small numbers, but <50% female (and high BMI), with reduced lung function parameters. As commented up-thread, doesn't sound like the ME/CFS phenotype of LC. "Question #5 ‘Physically drained or sick after mild activity’" would capture people with other post-Covid problems eg pulmonary fibrosis. I don't think they've investigated PEM here.
 
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