dyspnea – Page 2 – American ME and CFS Society

Serological Biomarkers at Hospital Admission Are Not Related to Long-Term Post-COVID Fatigue and Dyspnea in COVID-19 Survivors

Abstract:

Objective: The aim of this study was to investigate the association between serological biomarkers at the acute phase of infection at hospital admission with the development of long-term post-COVID fatigue and dyspnea.

Methods: A cohort study including patients hospitalized due to COVID-19 in one urban hospital of Madrid (Spain) during the first wave of the outbreak (from March 20 to June 30, 2020) was conducted. Hospitalization data, clinical data, and eleven serological biomarkers were systematically collected at hospital admission. Patients were scheduled for an individual telephone interview after hospital discharge for collecting data about the presence of post-COVID fatigue and dyspnea.

Results: A total of 412 patients (age: 62 years, standard deviation: 15 years; 47.5% women) were assessed with a mean of 6.8 and 13.2 months after discharge. The prevalence of post-COVID fatigue and dyspnea was 72.8% and 17.2% at 6 months and 45.4% and 13.6% at 12 months after hospital discharge, respectively. Patients exhibiting post-COVID fatigue at 6 or 12 months exhibited a lower hemoglobin level, higher lymphocyte count, and lower neutrophil and platelets counts (all, p < 0.05), whereas those exhibiting post-COVID dyspnea at 6 or 12 months had a lower platelet count and lower alanine transaminase, aspartate transaminase, and lactate dehydrogenase (LDH) levels (all, p < 0.05) than those not developing post-COVID fatigue or dyspnea, respectively. The multivariate regression analyses revealed that a lower platelet count and lower LDH levels were associated but just explaining 4.5% of the variance, of suffering from post-COVID fatigue and dyspnea, respectively.

Conclusion: Some serological biomarkers were slightly different in patients exhibiting post-COVID fatigue or dyspnea, but they could not explain the long-COVID problems in those patients.

Source: Fernández-de-Las-Peñas C, Ryan-Murua P, Rodríguez-Jiménez J, Palacios-Ceña M, Arendt-Nielsen L, Torres-Macho J. Serological Biomarkers at Hospital Admission Are Not Related to Long-Term Post-COVID Fatigue and Dyspnea in COVID-19 Survivors. Respiration. 2022 Apr 5:1-8. doi: 10.1159/000524042. Epub ahead of print. PMID: 35381597. https://www.karger.com/Article/FullText/524042 (Full text)

Dyspnea in Post-COVID Syndrome following Mild Acute COVID-19 Infections: Potential Causes and Consequences for a Therapeutic Approach

Abstract:

Dyspnea, shortness of breath, and chest pain are frequent symptoms of post-COVID syndrome (PCS). These symptoms are unrelated to organ damage in most patients after mild acute COVID infection. Hyperventilation has been identified as a cause of exercise-induced dyspnea in PCS. Since there is a broad overlap in symptomatology with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), causes for dyspnea and potential consequences can be deduced by a stringent application of assumptions made for ME/CFS in our recent review papers.

One of the first stimuli of respiration in exercise is caused by metabolic feedback via skeletal muscle afferents. Hyperventilation in PCS, which occurs early on during exercise, can arise from a combined disturbance of a poor skeletal muscle energetic situation and autonomic dysfunction (overshooting respiratory response), both found in ME/CFS. The exaggerated respiratory response aggravating dyspnea does not only limit the ability to exercise but further impairs the muscular energetic situation: one of the buffering mechanisms to respiratory alkalosis is a proton shift from intracellular to extracellular space via the sodium-proton-exchanger subtype 1 (NHE1), thereby loading cells with sodium. This adds to two other sodium loading mechanisms already operative, namely glycolytic metabolism (intracellular acidosis) and impaired Na⁺/K⁺ATPase activity.

High intracellular sodium has unfavorable effects on mitochondrial calcium and metabolism via sodium-calcium-exchangers (NCX). Mitochondrial calcium overload by high intracellular sodium reversing the transport mode of NCX to import calcium is a key driver for fatigue and chronification. Prevention of hyperventilation has a therapeutic potential by keeping intracellular sodium below the threshold where calcium overload occurs.

Source: Wirth KJ, Scheibenbogen C. Dyspnea in Post-COVID Syndrome following Mild Acute COVID-19 Infections: Potential Causes and Consequences for a Therapeutic Approach. Medicina (Kaunas). 2022 Mar 12;58(3):419. doi: 10.3390/medicina58030419. PMID: 35334595. https://www.mdpi.com/1648-9144/58/3/419/htm (Full text)

Evaluation of 3-month follow-up of patients with post-acute COVID-19 syndrome

Abstract:

Background: In addition to the highly variable clinical presentation of acute COVID-19 infection, it can also cause various post-acute signs and symptoms. This study aimed to evaluate patients with post-acute COVID-19 over 12 weeks of follow-up.

Methods: The study included 151 patients who were diagnosed with COVID-19 by real-time PCR of a nasopharyngeal swab 1 month earlier, had radiologic findings consistent with COVID-19 pneumonia, and presented to the post-COVID-19 outpatient clinic between May and August 2021. The patients were divided into three groups based on COVID-19 severity: non-severe pneumonia (group 1), severe pneumonia (group 2), and severe pneumonia requiring intensive care (group 3).

Results: Evaluation of laboratory parameters at 4 and 12 weeks showed that group 3 had higher lactose dehydrogenase (LDH) level and lower mean platelet volume than the other groups at both time points (p=0.001 for all). Group 3 also had lower FVC%, FEV1%, and DLCO/VA% compared to groups 1 and 2 at week 4 (p=0.001, 0.004, 0.001, respectively) and compared to group 1 at 12 weeks (p=0.002, 0.03, 0.001, respectively). Patients with persistent dyspnea at 12 weeks had significantly lower FEV1%, FVC%, DLCO/VA%, and saturation levels in room air and significantly higher LDH, pro-BNP, D-dimer, and heart rate compared to those without dyspnea (p=0.001 for all).

Conclusion: Although the lungs are most commonly affected after COVID-19 infection, vascular and endothelial damage also causes multisystem involvement. Our study indicates that laboratory values, radiological signs, and pulmonary functional capacity improved in most patients after 12 weeks of follow-up. This article is protected by copyright. All rights reserved.

Source: Kerget B, Çelik E, Kerget F, Aksakal A, Uçar EY, Araz Ö, Akgün M. Evaluation of 3-month follow-up of patients with post-acute COVID-19 syndrome. J Med Virol. 2022 Jan 9. doi: 10.1002/jmv.27579. Epub ahead of print. PMID: 35001367. https://pubmed.ncbi.nlm.nih.gov/35001367/

Use of Cardiopulmonary Stress Testing for Patients With Unexplained Dyspnea Post–Coronavirus Disease

Abstract:

Objectives: The authors used cardiopulmonary exercise testing (CPET) to define unexplained dyspnea in patients with post-acute sequelae of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection (PASC). We assessed participants for criteria to diagnose myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Background: Approximately 20% of patients who recover from coronavirus disease (COVID) remain symptomatic. This syndrome is named PASC. Its etiology is unclear. Dyspnea is a frequent symptom.

Methods: The authors performed CPET and symptom assessment for ME/CFS in 41 patients with PASC 8.9 ± 3.3 months after COVID. All patients had normal pulmonary function tests, chest X-ray, and chest computed tomography scans. Peak oxygen consumption (peak VO₂), slope of minute ventilation to CO₂ production (VE/VCO₂ slope), and end tidal pressure of CO₂ (PetCO₂) were measured. Ventilatory patterns were reviewed with dysfunctional breathing defined as rapid erratic breathing.

Results: Eighteen men and 23 women (average age: 45 ± 13 years) were studied. Left ventricular ejection fraction was 59% ± 9%. Peak VO₂ averaged 20.3 ± 7 mL/kg/min (77% ± 21% predicted VO₂). VE/VCO₂ slope was 30 ± 7. PetCO₂ at rest was 33.5 ± 4.5 mm Hg. Twenty-four patients (58.5%) had a peak VO₂ <80% predicted. All patients with peak VO₂ <80% had a circulatory limitation to exercise. Fifteen of 17 patients with normal peak VO₂ had ventilatory abnormalities including peak respiratory rate >55 (n = 3) or dysfunctional breathing (n = 12). For the whole cohort, 88% of patients (n = 36) had ventilatory abnormalities with dysfunctional breathing (n = 26), increased VE/VCO₂ (n = 17), and/or hypocapnia PetCO₂ <35 (n = 25). Nineteen patients (46%) met criteria for ME/CFS.

Conclusions: Circulatory impairment, abnormal ventilatory pattern, and ME/CFS are common in patients with PASC. The dysfunctional breathing, resting hypocapnia, and ME/CFS may contribute to symptoms. CPET is a valuable tool to assess these patients.

Source: Mancini DM, Brunjes DL, Lala A, Trivieri MG, Contreras JP, Natelson BH. Use of Cardiopulmonary Stress Testing for Patients With Unexplained Dyspnea Post-Coronavirus Disease. JACC Heart Fail. 2021 Dec;9(12):927-937. doi: 10.1016/j.jchf.2021.10.002. PMID: 34857177; PMCID: PMC8629098. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8629098/ (Full text)

Use of Cardiopulmonary Stress Testing for Patients With Unexplained Dyspnea Post-Coronavirus Disease

Abstract:

Background: Approximately 20% of patients who recover from coronavirus disease (COVID) remain symptomatic. This syndrome is named PASC. Its etiology is unclear. Dyspnea is a frequent symptom.

Methods: The authors performed CPET and symptom assessment for ME/CFS in 41 patients with PASC 8.9 ± 3.3 months after COVID. All patients had normal pulmonary function tests, chest X-ray, and chest computed tomography scans. Peak oxygen consumption (peak VO₂), slope of minute ventilation to CO₂ production (VE/VCO₂ slope), and end tidal pressure of CO₂ (PetCO₂) were measured. Ventilatory patterns were reviewed with dysfunctional breathing defined as rapid erratic breathing.

Results: Eighteen men and 23 women (average age: 45 ± 13 years) were studied. Left ventricular ejection fraction was 59% ± 9%. Peak VO₂ averaged 20.3 ± 7 mL/kg/min (77% ± 21% predicted VO₂). VE/VCO₂ slope was 30 ± 7. PetCO₂ at rest was 33.5 ± 4.5 mm Hg. Twenty-four patients (58.5%) had a peak VO₂ <80% predicted. All patients with peak VO₂ <80% had a circulatory limitation to exercise. Fifteen of 17 patients with normal peak VO₂ had ventilatory abnormalities including peak respiratory rate >55 (n = 3) or dysfunctional breathing (n = 12). For the whole cohort, 88% of patients (n = 36) had ventilatory abnormalities with dysfunctional breathing (n = 26), increased VE/VCO₂ (n = 17), and/or hypocapnia PetCO₂ <35 (n = 25). Nineteen patients (46%) met criteria for ME/CFS.

Perception of induced dyspnea in fibromyalgia and chronic fatigue syndrome

Abstract:

OBJECTIVE: Dyspnea perception is distorted in patients with medically unexplained dyspnea. The goals of this study were 1) to replicate these results in patients with fibromyalgia and/or chronic fatigue syndrome (CFS), and 2) to investigate predictors of distorted symptom perception within the patient group, with a focus on negative affectivity (NA), psychiatric comorbidity and somatic symptom severity.

METHODS: Seventy-three patients diagnosed with fibromyalgia and/or CFS and 38 healthy controls (HC) completed a rebreathing paradigm, consisting of a baseline (60s of room air), a rebreathing phase (150s, gradually increasing ventilation, partial pressure of CO2 in the blood, and self-reported dyspnea), and a recovery phase (150s of room air). Dyspnea, respiratory flow and FetCO2 levels were measured continuously.

RESULTS: Patients reported more dyspnea than HC in the recovery phase (p=0.039), but no differences between patients and HC were found in the baseline (p=0.07) or rebreathing phase (p=0.17). No significant differences between patients and HC were found in physiological reactivity. Within the patient group, the effect in the recovery phase was predicted by somatic symptom severity (p=0.046), but not by negative affectivity or by the number of psychiatric comorbidities.

CONCLUSION: This study extended earlier findings in patients with medically unexplained dyspnea to patients with fibromyalgia and CFS. This suggests that altered symptom perception is a non-symptom-specific mechanism underlying functional somatic syndromes in general, particularly in patients with high levels of somatic symptom severity. The results are discussed in a predictive coding framework of symptom perception.

Source: Van Den Houte M, Bogaerts K, Van Diest I, De Bie J, Persoons P, Van Oudenhove L, Van den Bergh O. Perception of induced dyspnea in fibromyalgia and chronic fatigue syndrome. J Psychosom Res. 2018 Mar;106:49-55. doi: 10.1016/j.jpsychores.2018.01.007. Epub 2018 Jan 11. https://www.ncbi.nlm.nih.gov/pubmed/29455899

Dyspnea in Chronic Fatigue Syndrome (CFS): comparison of two prospective cross-sectional studies

Abstract:

Chronic Fatigue Syndrome (CFS) subjects have many systemic complaints including shortness of breath. Dyspnea was compared in two CFS and control cohorts to characterize pathophysiology. Cohort 1 of 257 CFS and 456 control subjects were compared using the Medical Research Council chronic Dyspnea Scale (MRC Score; range 0-5). Cohort 2 of 106 CFS and 90 controls answered a Dyspnea Severity Score (range 0-20) adapted from the MRC Score. Subsets of both cohorts completed CFS Severity Scores, fatigue, and other questionnaires. A subset had pulmonary function and total lung capacity measurements.

Results show MRC Scores were equivalent between sexes in Cohort 1 CFS (1.92 [1.72-2.16]; mean [95% C.I.]) and controls (0.31 [0.23-0.39]; p<0.0001). Receiver-operator curves identified 2 as the threshold for positive MRC Scores in Cohort 1. This indicated 54% of CFS, but only 3% of controls, had significant dyspnea.

In Cohort 2, Dyspnea Score threshold of 4 indicated shortness of breath in 67% of CFS and 23% of controls. Cohort 2 Dyspnea Scores were higher for CFS (7.80 [6.60-9.00]) than controls (2.40 [1.60-3.20]; p<0.0001). CFS had significantly worse fatigue and other complaints compared to controls. Pulmonary function was normal in CFS, but Borg scores and sensations of chest pain and dizziness were significantly greater during testing than controls. General linear model of Cohort 2 CFS responses linked Dyspnea with rapid heart rate, chest pain and dizziness.

In conclusion, sensory hypersensitivity without airflow limitation contributed to dyspnea in CFS. Correlates of dyspnea in controls were distinct from CFS suggesting different mechanisms.

Source: Ravindran M, Adewuyi O, Zheng Y, Rayhan RU, Le U, Timbol C, Merck S, Esteitie R, Read C, Cooney M, Baraniuk J. Dyspnea in Chronic Fatigue Syndrome (CFS): comparison of two prospective cross-sectional studies. Glob J Health Sci. 2012 Dec 12;5(2):94-110. doi: 10.5539/gjhs.v5n2p94. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4209305/ (Full article)

Psychological profile and ventilatory response to inspiratory resistive loading

Abstract:

The purpose of this study was to explore the contribution of psychological state to both the ventilatory response and the intensity of dyspnea experienced after the addition of small inspiratory loads to breathing. We hypothesized that patients with either a specific psychiatric diagnosis or a specific psychological trait will associate a greater degree of dyspnea with a loaded breathing task than will control subjects.

To insure the inclusion of persons with relevant psychological profiles, we recruited both subjects enrolled in the Chronic Fatigue Center and normal control subjects. In all, 52 subjects inspired first through a small (1.34 cm H(2)O/L/s) and second through a moderate (3.54 cm H(2)O/L/s) inspiratory resistive load (IRL). Ventilation was monitored throughout the 5-min sessions. Dyspnea was quantified with the Borg scale at specified times during the protocol. Standard psychological tests were administered.

We found that subjects could be divided into two groups. One, the “responders,” reported Borg scores higher than those of the second, or “nonresponder” group, at all times during the protocol. By contrast, there was no difference between groups with respect to ventilation. Responders had higher scores on tests of depression (the Center for Epidemiological Study depression scale) than did nonresponders. We conclude that the variability observed in subjective responses to IRL is explained, in part, by differences in psychological state.

Source: Lavietes MH, Sanchez CW, Tiersky LA, Cherniack NS, Natelson BH. Psychological profile and ventilatory response to inspiratory resistive loading. Am J Respir Crit Care Med. 2000 Mar;161(3 Pt 1):737-44. http://www.ncbi.nlm.nih.gov/pubmed/10712316