[Occurrence of delayed symptoms after a challenge test with methacholine]. / Survenue de symptômes tardifs après un test de provocation par la méthacholine.

There are few prospective studies available on the development of delayed symptoms following challenge tests with methacholine (MCT) at the currently recommended doses. The objective of this study was to describe the nature and frequency of respiratory symptoms suggestive of bronchospasm developing within 24hours after a MCT. The study was offered to adult patients who underwent MCT seen consecutively between June and October 2015. Following the test, a questionnaire adapted from the GINA asthma control questionnaire bearing on diurnal and nocturnal symptoms (cough, dyspnoea, wheeze and tightness), was delivered to the patient and the replies collected by telephone 24hours later. Of the 101 patients included (initial FEV1 2.82±0.79L), 46 (46 %) were MCT+ and 55 (54 %) MCT-. Among the MCT-, 4 (7 %) presented with immediate symptoms (S+) and 4 (7 %) with delayed symptoms. Among the MCT+ patients, 36 (78 %) presented with immediate symptoms (P<0.001 compared with the MCT- patients), and 39 (85 %) with delayed symptoms (P<0.001 compared with the MCT- patients). Delayed symptoms developed with a mean of 5h30 after the provocation test. Immediate and delayed symptoms were more frequent in subjects having significant non-specific bronchial hyper-reactivity. Informing patients of the risk of developing delayed symptoms seems useful and allows optimization of their management after a MCT.

[Chronic fatigue syndrome: A new disorder?] / Le syndrome de fatigue chronique : une nouvelle maladie ?

More than 30 years after its individualization, chronic fatigue syndrome (CFS) remains a debilitating condition for the patient and a confusing one to the physicians, both because of diagnostic difficulties and poorly codified management. Despite the numerous work carried out, its pathophysiology remains unclear, but a multifactorial origin is suggested with triggering (infections) and maintenance (psychological) factors as well as the persistence of inflammatory (low grade inflammation, microglial activation…), immunologic (decrease of NK cells, abnormal cytokine production, reactivity to a variety of allergens, role of estrogens…) and muscular (mitochondrial dysfunction and failure of bioenergetic performance) abnormalities at the origin of multiple dysfunctions (endocrine, neuromuscular, cardiovascular, digestive…). The complexity of the problem and the sometimes contradictory results of available studies performed so far are at the origin of different pathophysiological and diagnostic concepts. Based on a rigorous analysis of scientific data, the new American concept of Systemic Disease Exertion Intolerance proposed in 2015 simplifies the diagnostic approach and breaks with the past and terminologies (CFS and myalgic encephalomyelitis). It is still too early to distinguish a new disease, but this initiative is a strong signal to intensify the recognition and management of patients with CFS and stimulate research.

Early ventilation-heart rate breakpoint during incremental cycling exercise.

Previous observations having reported a transient hypoxia at the onset of incremental exercise, we investigated the existence of concomitant ventilatory and heart rate (HR) breakpoints.33 subjects executed a maximal cycling exercise with averaging for successive 5-s periods of HR, ventilation, tidal volume (VT), mean inspiratory flow rate (VT/Ti), and end-tidal partial pressures of O2 (PETO2) and CO2. In 10 subjects, the transcutaneous partial pressure of O2 (PtcO2) was recorded and the venous blood lactic acid (LA) concentration measured.At the beginning of exercise, PETO2 decreased, reaching a nadir, then progressively increased until the exercise ended. PtcO2 varied in parallel. Whether or not a 0-W cycling period preceded the incremental exercise, the rate of changes in VE, VT, VT/Ti and HR significantly increased when the nadir PO2 was reached. The ventilatory/ HR breakpoint was measured at 33±4% of VO2max, whereas the ventilatory threshold (VTh) was detected at 67±4% of VO2max and LA began to increase at 45 to 50% of VO2max.During incremental cycling exercise, we identified the existence of HR and ventilatory breakpoints in advance of both lactate and ventilatory thresholds which coincided with modest hypoxia and hypercapnia.

Chronic fatigue syndrome: acute infection and history of physical activity affect resting levels and response to exercise of plasma oxidant/antioxidant status and heat shock proteins.

OBJECTIVES: A history of high-level physical activity and/or acute infection might constitute stress factors affecting the plasma oxidant-antioxidant status and levels of heat shock proteins (HSPs) in patients with chronic fatigue syndrome (CFS). DESIGN: This case-control study compared data from 43 CFS patients to results from a matched control group of 23 healthy sedentary subjects. SETTING AND SUBJECTS: Five patients had no relevant previous history (group I). Eighteen had practised high-level sport (group II), and severe acute infection had been diagnosed in nine patients (group III). A combination of sport practice and infection was noted in 11 patients (group IV). INTERVENTIONS: After examination at rest, all subjects performed a maximal cycling exercise test. Plasma levels of two markers of oxidative stress [thiobarbituric acid reactive substances (TBARS) and reduced ascorbic acid (RAA)] and both HSP27 and HSP70 were measured. RESULTS: At rest, compared with the control group, the TBARS level was higher in groups II, III and IV patients, and the RAA level was lower in groups III and IV. In addition, HSP70 levels were significantly lower in all CFS groups, compared with controls, but negative correlations were found between resting HSP27 and HSP70 levels and the history of physical activity. After exercise, the peak level of TBARS significantly increased in groups II, III and IV, and the variations in HSP27 and HSP70 were attenuated or suppressed, with the greatest effects in groups III and IV. CONCLUSION: The presence of stress factors in the history of CFS patients is associated with severe oxidative stress and the suppression of protective HSP27 and HSP70 responses to exercise.

EMG changes in thigh and calf muscles in fin swimming exercise.

Because previous researchers have reported a reduced lactic acid production that accompanies a delayed or an absent ventilatory threshold (VTh) in water-based exercise, we hypothesized that the metaboreflex, activated by muscle acidosis, might be absent in fin swimming. This motor response, delaying the occurrence of fatigue, is characterized by a decreased median frequency (MF) of electromyographic (EMG) power spectrum. Seven healthy subjects performed a maximal fin swimming exercise protocol with simultaneous recordings of surface EMGs in VASTUS MEDIALIS (VM), TIBIALIS ANTERIOR (TA) and GASTROCNEMIUS MEDIALIS (GM). We computed the root mean square (RMS) and MF and recorded the compound evoked muscle potential (M-wave) in VM. We also measured the propulsive force and oxygen uptake (VO (2)), and determined VTh. VTh was absent in 4/7 subjects and measured at 70-90% of VO (2max) in the other three. In the three studied muscles, the global EMG activity (RMS) increased while the MF decreased in proportion of VO (2), the MF changes being significantly higher in VM (-29%) and GM (-39%) than in TA (-19%). Because no M-wave changes were noted, the MF decline was attributed to the recruitment of low-frequency, fatigue-resistant motor units. Our most important finding is the persistence of the metaboreflex even in a situation of reduced muscle acidosis.

Chronic fatigue syndrome combines increased exercise-induced oxidative stress and reduced cytokine and Hsp responses.

OBJECTIVES: As heat shock proteins (Hsp) protect the cells against the deleterious effects of oxidative stress, we hypothesized that Hsp expression might be reduced in patients suffering from chronic fatigue syndrome (CFS) who present an accentuated exercise-induced oxidative stress. DESIGN: This case-control study compared nine CFS patients to a gender-, age- and weight-matched control group of nine healthy sedentary subjects. INTERVENTIONS: All subjects performed an incremental cycling exercise continued until exhaustion. We measured ventilation and respiratory gas exchange and evoked compound muscle potential (M-wave) recorded from vastus lateralis. Repetitive venous blood sampling allowed measurements of two markers of oxidative stress [thiobarbituric acid reactive substances (TBARS) and reduced ascorbic acid (RAA)], two cytokines (IL-6 and TNF-alpha) and two Hsp (Hsp27 and Hsp70) at rest, during maximal exercise and the 60-min recovery period. RESULTS: Compared with controls, resting CFS patients had low baseline levels of RAA and Hsp70. Their response to maximal exercise associated (i) M-wave alterations indicating reduced muscle membrane excitability, (ii) early and accentuated TBARS increase accompanying reduced changes in RAA level, (iii) absence of significant increase in IL-6 and TNF-alpha, and (iv) delayed and marked reduction of Hsp27 and Hsp70 variations. The post-exercise increase in TBARS was accentuated in individuals having the lowest variations of Hsp27 and Hsp70. CONCLUSIONS: The response of CFS patients to incremental exercise associates a lengthened and accentuated oxidative stress, which might result from delayed and insufficient Hsp production.

Fin swimming improves respiratory gas exchange.

Data in the literature suggest that compared to dry-land exercise fin swimming might delay the activation of the anaerobic metabolism. To verify this hypothesis, we explored indirect indices such as the oxygen pulse (VO(2)/HR), carbon dioxide production (VCO(2)), and ventilatory threshold, comparing fin swimming exercise to dry-land cycling. Thirteen participants, experienced or inexperienced in fin swimming, completed an incremental fin swimming exercise and a maximal exercise on a cycloergometer with breath-by-breath measurements of heart rate (HR), ventilation (VE), tidal volume (VT), VO(2), VCO(2), and VO(2)/HR and determination of the ventilatory threshold and maximal oxygen uptake (VO(2)max). Compared to dry-land cycling exercise, fin swimming resulted in elevated or absent ventilatory threshold. Although VO(2)max did not differ in either condition, in fin swimming the maximal HR value was lower (-18%, p=0.0072), maximal VO(2)/HR higher (+20%, p=0.0325), and maximal VCO(2) lower (-17%, p=0.0071). We also measured significant reduction of VE, VT, and HR variations for the same VO(2) increase. This study suggests that the anaerobic muscle metabolism might be delayed in fin swimming. An attenuated chemoreflex drive to the heart and respiratory centres exerted by muscle metabolites might explain the depressed cardiopulmonary response to fin swimming.

Statins alter oxidant-antioxidant status and lower exercise-induced oxidative stress.

Data on effects of statins on resting oxidant-antioxidant status are contradictory and no study has been published on the effects of statins on exercise-induced oxidative stress. We carried out a 6-month longitudinal study in 10 dyslipidemic patients receiving 10 mg/day atorvastatin and 13 healthy sedentary subjects. Thiobarbituric acid reactive substances (TBARS) and reduced ascorbic acid (RAA) were measured in plasma at rest and every 5 minutes after submaximal isometric thumb adduction and handgrip sustained until exhaustion. At inclusion, resting TBARS and RAA levels in controls and patients did not differ and exercise increased TBARS and decreased RAA. Atorvastatin reduced resting TBARS and RAA levels in a time-dependent but lipid-independent manner. The main effect was a post-exercise increase in TBARS, without affecting the post-exercise RAA levels. The reduction in oxidative stress occurred earlier in oxidative muscles involved in thumb adduction. In conclusion, atorvastatin lowers resting oxidant-antioxidant activity: exercise-induced oxidative stress occurs mainly in muscles having a high oxidative capacity.

Effect of long-term atorvastatin treatment on the electrophysiological and mechanical functions of muscle.

OBJECTIVE: To study alterations in muscle function combining physiological, electrophysiological and metabolic measurements in patients receiving a statin at various dosages during long-term therapy. MATERIAL: A 3-month (D0, D30 and D90) longitudinal physiological and electrophysiological muscle study was performed in 26 patients receiving 10, 40 or 80 mg/day atorvastatin. METHOD: All subjects performed maximal (MVC) and submaximal (60% MVC) isometric thumb adduction, handgrip and knee extension exercises during the recording of surface electromyograms (EMG) of the adductor pollicis (AP), flexor digitorum (FD) and vastus lateralis (VL). The compound muscle potential (M-wave) evoked by direct muscle stimulation was measured at rest and after 60% MVCs and the EMG power spectrum was analyzed during sustained effort. Blood was sampled from an antecubital vein for measurements of pH, lactate and potassium levels after thumb adduction and handgrip exercises. The measurements were repeated on Day 0 (D0), D30 and D90. RESULTS: Atorvastatin did not affect the MVC and endurance time to fatigue. Post-exercise M-wave alterations in the AP began at D30 with the 80 mg/day treatment and there was a reduced or suppressed leftward shift in the EMG power spectrum in the AP and VL with all 3 dosages. In the AP, the EMG changes appeared earlier (D30) with 80 mg/day whereas they only occurred at D90 on the lower dosages. Atorvastatin had no effect on the maximal postexercise variations in pHv and lactate but it significantly reduced the maximal increase in plasma potassium concentration after thumb adduction and handgrip exercise, the effects being only present at D90 on 10 mg/day but occurring as early as D30 with higher dosages. CONCLUSION: A 3-month atorvastatin treatment did not affect the maximal performance of skeletal muscle during voluntary efforts but EMG analysis revealed a reduced muscle excitability and an attenuated adaptation to fatigue. These effects prevailed in muscles containing the largest proportion of slow-oxidative fibers and were associated with a reduced outward flow of potassium.

Chronic fatigue syndrome: assessment of increased oxidative stress and altered muscle excitability in response to incremental exercise.

OBJECTIVES: Because the muscle response to incremental exercise is not well documented in patients suffering from chronic fatigue syndrome (CFS), we combined electrophysiological (compound-evoked muscle action potential, M wave), and biochemical (lactic acid production, oxidative stress) measurements to assess any muscle dysfunction in response to a routine cycling exercise. DESIGN: This case-control study compared 15 CFS patients to a gender-, age- and weight-matched control group (n=11) of healthy subjects. INTERVENTIONS: All subjects performed an incremental cycling exercise continued until exhaustion. MAIN OUTCOME MEASURES: We measured the oxygen uptake (VO2), heart rate (HR), systemic blood pressure, percutaneous O2 saturation (SpO2), M-wave recording from vastus lateralis, and venous blood sampling allowing measurements of pH (pHv), PO2 (PvO2), lactic acid (LA), and three markers of the oxidative stress (thiobarbituric acid-reactive substances, TBARS, reduced glutathione, GSH, and ascorbic acid, RAA). RESULTS: Compared with control, in CFS patients (i) the slope of VO2 versus work load relationship did not differ from control subjects and there was a tendency for an accentuated PvO2 fall at the same exercise intensity, indicating an increased oxygen uptake by the exercising muscles; (ii) the HR and blood pressure responses to exercise did not vary; (iii) the anaerobic pathways were not accentuated; (iv) the exercise-induced oxidative stress was enhanced with early changes in TBARS and RAA and enhanced maximal RAA consumption; and (v) the M-wave duration markedly increased during the recovery period. CONCLUSIONS: The response of CFS patients to incremental exercise associates a lengthened and accentuated oxidative stress together with marked alterations of the muscle membrane excitability. These two objective signs of muscle dysfunction are sufficient to explain muscle pain and postexertional malaise reported by our patients.