Atopy is characterized by an immune system that is biased to T helper cell, type 2 (Th2) activation. This condition predisposes to asthma, a disease in which a Th2 activation was found in blood and lungs. However, most blood studies have considered purified cells, which might give an incomplete view of immune reactions. In this study, we assessed in whole blood cultures the Th1/Th2 paradigm in atopy and asthma. Sixty-nine subjects (31 atopic asthmatics, six nonatopic asthmatics, 13 atopic nonasthmatics, and 19 control subjects) were included in this study. Interleukin-4 (IL-4), interferon gamma (IFN-gamma), and IL-12 were assayed in stimulated whole blood culture supernatants by using a flow cytometer microsphere-based assay. Intracellular IL-4 and IFN-gamma were detected in T cells and CD8(+) T cells by flow cytometry. Atopy was characterized by a higher production of IL-4, which was correlated to total IgE levels, and by an impairment of the T-cell capacity to produce IFN-gamma. This impairment was correlated to the number of positive skin tests. In asthma, the overproduction of IL-4 was still found if atopy was present. Unexpectedly, an overproduction of IFN-gamma was found, which was related to an increased capacity of CD8(+) T cells to produce IFN-gamma. The number of IFN-gamma-producing CD8(+) T cells was related to asthma severity, to bronchial hyperresponsiveness, and to blood eosinophilia. In addition, this number was correlated to IL-12 production. These results show that in addition to the well-known Th2 inflammation in asthma, there are IFN-gamma-producing CD8(+) T cells in the blood, possibly controlled by IL-12.

Impairment of muscle energy metabolism has been demonstrated in normal subjects with chronic hypoxaemia (altitude chronic respiratory failure). The purpose of this study was to verify the hypothesis that a comparable condition could develop in patients with sleep apnoea syndrome (SAS), considering that they are exposed to prolonged and repeated hypoxaemia periods. Muscle metabolism was assessed in 11 patients with SAS performing a maximal effort on cycloergometer. In comparison with normal subjects, SAS patients reached lower maximal loads [144 +/- 7 vs. 182 +/- 10 W (P < 0.005)] and lower peak oxygen uptakes [26.4 +/- 1.2 vs 33.2 +/- 1.4 ml kg-1 min-1 (P < 0.005)]. Abnormal metabolic features were found: maximal blood lactate concentration was significantly lower than in normal subjects [0.034 +/- 0.004 vs. 0.044 +/- 0.002 mmol l-1 W-1 (P < 0.05)]; and lactate elimination rate, calculated during a 30-min recovery period, was reduced [0.127 +/- 0.017 vs, 0.175 +/- 0.014 mmol l-1 min-1 (P < 0.025)]. The extent of these anomalies correlated with the severity of SAS. The patients also showed higher maximal diastolic blood pressures than normal subjects [104 +/- 5 vs. 92 +/- 4 mmHg (P < 0.05)]. These results can be interpreted as indications of an impairment of muscle energy metabolism in patients with SAS. Decrease in maximum blood lactate concentration suggests an impairment of glycolytic metabolism, while decrease in the rate of lactate elimination indicates a defect in oxidative metabolism. Since no respiratory pathology apart from SAS was found in this group of patients, it seems legitimate to link the genesis of these impairments to repeated bouts of nocturnal hypoxaemia.

1. Failure of muscle force during sustained fatiguing contraction is associated with myoelectrical and metabolic alterations. However, the inter-relationships between these two types of events remain unclear. The purpose of this study was to examine the effects of decreased oxygen availability during sustained contraction on myoelectrical and metabolic changes, thereby addressing the issue of fatigue. 2. 31P-Magnetic resonance spectra and surface electromyograms were simultaneously recorded in six subjects (three women and three men) performing isometric contraction of forearm flexor muscles sustained at 60% maximum value of force under aerobic or acute hypoxaemic conditions (inhalation of a gas mixture containing 12% O2). 3. The 5 min hypoxaemic rest preceding contraction did not affect the phosphocreatine level and pH value. Under both conditions of oxygen availability, the magnitude of metabolic changes remained similar and the duration of contraction was unaffected (similar workload). However, hypoxaemia significantly reduced the rate of changes in integrated surface electromyogram activity measured in the high-frequency band. Correlative analysis of magnetic resonance spectroscopy and surface electromyogram data shows that for a given surface electromyogram change, metabolic variations were always larger under hypoxaemic conditions. 4. These results suggest that hypoxaemia does not alter metabolic changes, i.e. decrease in pH and phosphocreatine during static contraction. The downward shift of the relationships between myoelectrical and metabolic changes under hypoxaemia points to the existence of a better excitation-contraction coupling in acute hypoxaemia compared with normoxia and this is indicative of an adaptative mechanism.

The consequences of chronic hypoxemia on maximal force and endurance time to sustained 80% of maximal isometric contraction of two skeletal muscles (adductor pollicis and vastus lateralis) and the diaphragm were studied in patients with chronic obstructive pulmonary disease (COPD). Compared to normal subjects, COPD patients have lower values of Fmax for the two skeletal muscle groups and Pmax (diaphragm). Endurance time was also shorter for the diaphragm and adductor pollicis. Chronic hypoxemia was associated with an accentuation in integrated EMG changes in both low and high frequency bands for adductor pollicis and diaphragm. Inhalation of oxygen enriched gas mixture for a 15-min period increased markedly Fmax and PImax values, prolonged the endurance time to sustained thumb adduction, and reduced the EMG changes in the low frequency band for adductor pollicis. The present observations provide evidence for altered maximal performances of skeletal muscles in chronic hypoxemic patients and also point out the virtues of oxygen breathing in these patients.

The consequences of general hypoxemia (PaO2 = 51 mmHg) on two muscle groups (adductor pollicis and diaphragm) sustaining 80% maximal isometric voluntary contraction were studied in healthy individuals. For adductor pollicis, contractions were also executed after 10-s or 3-min rest ischemia. Compared to control, i.e., normoxic, sustained isometric workloads, significant shortening of endurance time occurred only when adductor pollicis contracted under hypoxemic conditions. In both muscle groups, a 3-min ischemia test as well as hypoxemia reduced the rate of changes in integrated surface EMG in a low frequency band and lowered, or did not modify, the rate of change in the high above low frequency ratio. Recovery of normal patterns of EMG changes was prolonged only after the adductor pollicis contracted under hypoxemic conditions. The present data show that both hypoxemia and prolonged rest ischemia reduced the rate of changes in quantitative EMG activity, with the more significant effects being measured under hypoxemia.

During the 7.1-MPa hydrogen-helium-oxygen record human dive, we tested the hypothesis that the increased ambient pressure would alter the maximal muscle performance, specifically that breathing dense gas would lead to fatigue of the respiratory muscle. A group of hand muscles (adductor pollicis, AP) and the inspiratory muscles (IM) were studied in three professional divers. Maximal voluntary contractions (MVC) of AP and maximal inspiratory pressure (P(i(max))) generated by IM were measured prior to the dive, during compression and decompression, and then 1 and 2 months after the dive. The decrease in MVC (-22%) was significant at 3.1 MPa, i.e. at the beginning of the introduction of hydrogen into the breathing mixture, whereas P(i(max)) fell progressively during the dive and decompression (maximal DeltaP(i(max)) = -55%), a significant reduction still being measured 1 month after the dive. The altered IM function was attributed to the consequences of long-term ventilatory loading, a condition associated with breathing a dense gas. The transient decrease in MVC of the skeletal muscle would indicate a possible effect of the hyperbaric environment, possibly the high partial pressure of hydrogen, on neuromuscular drive.

Changes in EMG power spectrum during isometric voluntary contraction maintained until exhaustion in the range of 20-80% MVC were studied in three skeletal muscles (adductor pollicis or AP, vastus lateralis, and medialis) and two respiratory muscles (diaphragm and rectus abdominis). Quantitative EMG analysis consisted of computation of the median frequency (MF) of power spectra and also the continuous measurement of EMG power in two bands of high (EH) and low (EL) frequencies using bandpass filters. This allowed the calculation of the H/L ratio and its time constant of decay rate (TC delta H/L) throughout the sustained static contraction. The main results were: (1) highly significant, positive correlations between TC delta H/L and the maximal MF changes and also the endurance time to fatigue; (2) EMG changes were determined early, within the first 10-20 s of contraction; and (3) EL always increased throughout the fatiguing isometric contraction, but EH changes markedly varied within the five muscle groups studied. These observations are discussed in terms of the differences in muscle fiber composition and also the variations in motor unit recruitment.

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