Control of breathing in chronic obstructive pulmonary disease patients at rest and after beta-2 agonist inhalation.

Ventilatory function tests, ventilatory cycle analysis, mouth occlusion pressure (P0.1) and effective inspiratory impedance (P0.1/Vt/Ti) were measured in 11 healthy subjects and in 26 patients with chronic obstructive pulmonary disease (COPD). In COPD patients these measurements were repeated 20 min after inhalation of 400 micrograms of fenoterol. In patients we observed an increase of mean inspiratory flow (Vt/Ti), and a decrease of inspiratory time (Ti) and inspiratory duty cycle (Ti/Ttot). P0.1 and effective inspiratory impedance were significantly increased. Moreover, we found a direct correlation between forced expiratory volume in 1 s (FEV1) and ventilatory cycle components (Ti/Ttot, Ti) and an indirect correlation between FEV1 and Vt/Ti.P0.1 was directly correlated with Vt/Ti and indirectly correlated with ventilatory cycle components. These observations lead us to speculate on the possible role of two opposite mechanisms acting on the control of breathing of COPD patients. While the 'intensity' component of the ventilatory cycle would be set to maintain the tidal volume at a constant level, the 'timing' component would act in order to prevent inspiratory muscle fatigue. Furthermore, in patients responsive to beta 2-agonist drugs, fenoterol inhalation would act in synergy with the timing component of ventilatory cycle, lowering P0.1 and the effective inspiratory impedance.     

Inspiratory muscle function in patients with severe kyphoscoliosis

In 9 patients with severe kyphoscoliosis we studied inspiratory muscle function by measuring transdiaphragmatic pressure (Pdi) and its components: gastric (Pga) and esophageal (Pes) pressures during quiet breathing. Maximal Pdi and maximal inspiratory mouth pressure (Pimax) were also measured. The results showed that Pimax and Pdimax were significantly lower in patients than in normal subjects. During quiet breathing, all patients had positive swings in Pga, indicating an active contraction of the diaphragm, but Pes was significantly more negative, suggesting the recruitment of intercostal and accessory inspiratory muscles. We did not find significant correlations between Pimax, Pdimax, delta Pga/delta Pes, FVC, PaO2, or PaCO2 and the degree of spinal deformity. The FVC tended to correlate with Pimax (r = 0.63) and with Pdimax (r = 0.53). The Pdi correlated with PaO2 (r = 0.66) and with PaCO2 (r = -0.76; p less than 0.05). A significant correlation was also observed between Pimax and PaO2 (r = 0.785; p less than 0.05) and between Pimax and PaCO2 (r = -0.86; p less than 0.01). We conclude that impairment of inspiratory muscle function is related to the development of ventilatory failure in kyphoscoliosis.     

Control of breathing in patients with myasthenia gravis.

Control of breathing has seldom been investigated in patients with myasthenia gravis (MG). We evaluated lung volumes and respiratory muscle strength by measuring maximal inspiratory (MIP) and expiratory (MEP) pressures in 12 patients with moderate generalized (IIb) MG before and after an orally administered therapeutic dose (120 mg) of Mestinon, and in 11 age- and sex-matched normal subjects. Breathing pattern, mouth occlusion pressure (P0.1), and surface electromyographic activity of the diaphragm (EMGd) and intercostal (EMGint) muscles were evaluated during both room-air breathing and hypercapnic rebreathing. Before Mestinon, patients exhibited a slight decrease in VC, and normal TLC and FEV1/VC ratio. Compared with the normal control group, patients also exhibited respiratory muscle weakness (marked decrease in MIP and MEP; p less than 0.001 for both), and more rapid and shallower breathing (RSB): lower tidal volume (VT), inspiratory time (TI), expiratory time (TE), and greater respiratory frequency (f); mean inspiratory flow (VT/TI) and P0.1 were slightly supernormal, whereas both EMGd and EMGint were significantly higher in patients. During hypercapnic rebreathing, ventilation (VE) (p less than 0.001), VT (p less than 0.001), VT/TI, (p less than 0.003), P0.1 (p less than 0.003), and EMGd (p less than 0.001) response slopes to increasing PCO2 were found to be lower, whereas EMGint response slope was normal. At 60 mm Hg of PCO2 in the two groups the difference in terms of breathing pattern, P0.1, and EMGd were similar to that observed during room-air breathing. After Mestinon, VC (p less than 0.005), MIP (p less than 0.02), and MEP (p less than 0.01) significantly increased, whereas spontaneous breathing remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)     

Closing capacity and gas exchange in chronic heart failure

BACKGROUND: Although it is commonly assumed that pulmonary congestion and edema in patients with chronic heart failure (CHF) promotes peripheral airway closure, closing capacity (CC) has not been measured in CHF patients. PURPOSES: To measure CC and the presence or absence of airway closure and expiratory flow limitation (FL) during resting breathing in CHF patients. METHODS: In 20 CHF patients and 20 control subjects, we assessed CC, FL, spirometry, blood gas levels, control of breathing, breathing pattern, and dyspnea. RESULTS: The patients exhibited a mild restrictive pattern, but the CC was not significantly different from that in control subjects. Nevertheless, airway closure during tidal breathing (ie, CC greater than functional residual capacity [FRC]) was present in most patients but was absent in all control subjects. As a result of the maldistribution of ventilation and the concurrent impairment of gas exchange, the mean (+/- SD) alveolar-arterial oxygen pressure difference increased significantly in CHF patients (4.3 +/- 1.2 vs 2.7 +/- 0.5 kPa, respectively; p < 0.001) and correlated with systolic pulmonary artery pressure (r = 0.49; p < 0.03). Tidal FL is absent in CHF patients. Mouth occlusion pressure 100 ms after onset of inspiratory effort (P0.1) as a percentage of maximal inspiratory pressure (Pimax) together with ventilation were increased in CHF patients (p < 0.01 and p < 0.005, respectively). The increase in ventilation was due entirely to increased respiratory frequency (fR) with a concurrent decrease in Paco2. Chronic dyspnea (scored with the Medical Research Council [MRC] scale) correlated (r2= 0.61; p < 0.001) with fR and P0.1/Pimax. CONCLUSIONS: In CHF patients at rest, CC is not increased, but, as a result of decreased FRC, airway closure during tidal breathing is present, promoting the maldistribution of ventilation, ventilation-perfusion mismatch, and impaired gas exchange. The ventilation is increased as result of increased fR, and Pimax is decreased with a concurrent increase in P0.1, implying that there is a proportionately greater inspiratory effort per breath (P0.1/Pimax). These, together with the increased fR, are the only significant contributors to increases in the MRC dyspnea score.     

Plasma Adenosine during Investigation of Hypoxic Ventilatory Response

Adenosine, an endogenous nucleoside, is released by hypoxic tissue, causes vasodilation, and influences ventilation. Its effects are mediated by P1-purinoceptors. We examined to what extent the plasma adenosine concentration in the peripheral venous blood correlates with hypoxic ventilatory response (HVR) and ventilatory drive P0.1 to find out whether endogenously formed adenosine has an influence on the individual ventilatory drive under hypoxic conditions. While investigating the HVR of 14 healthy subjects, the ventilatory drive P0.1 was measured with the shutter of a spirometer. Determination of the ventilatory drive P0.1(RA) started under room air conditions (21% O₂) and then inspiratory gas was changed to a hypoxic mixture of 10% O₂in N₂to determine P0.1(Hyp). At the time of the P0.1 measurements, two blood samples were taken to determine the adenosine concentrations. After removal of cellular components and proteins, samples were analyzed by high-pressure liquid chromatography (HPLC). Both adenosine concentrations in plasma under room air (r = 0.59, p< 0.05) and adenosine concentrations under hypoxia (r = 0.75, p< 0.01) correlated significantly with the ventilatory drive P0.1. In addition, plasma adenosine concentrations during hypoxic conditions showed a significant correlation with HVR on the 0.01 level (r = 0.71, p< 0.01). The results indicate a possible role of endogenous adenosine in the regulation of breathing in humans. We assume that endogenous adenosine influences the HVR and the ventilatory drive, probably by modulating the carotid body chemoreceptor response to hypoxia.     

Breathing pattern and occlusion pressure during exercise in pre- and peripubertal swimmers

In two groups of young swimmers (prepubertal stage: group A; peripubertal stage: group B), the ventilatory response to graded exercise work with a cycle ergometer was studied. Ventilatory variables (ventilation, VE, tidal volume, VT, respiratory frequency,f, ratio between inspiratory period and total breath duration, TI/TTOT, and mean inspiratory flow, VT/TI) as well as mouth occlusion pressure measured at 100 msec (P0.1), effective impedance of the respiratory system (P0.1/VT/TI), inspiratory power for breathing (W) and O2 uptake (VO2) were measured during the third minute of each work load. At the same level of exercise both groups showed identical values of VT/TI, but VE was higher in group A individuals. This resulted from higher values of respiratory frequency with higher TI/TTOT ratios. P0.1, P0.1(VT/TI) and W were also much higher during work load in group A than in peripubertal subjects. When the above results were related to the same percentage of VO2 max, P0.1, W, respiratory frequency and duty cycle did not differ within both groups. However, VE, VT and VT/TI were lower in group A subjects with a higher P0.1/(VT/TI) ratio. Further corrections of VT, VT/TI and P0.1/(VT/TI) ratios by body weight cancelled all these differences. In conclusion, our results strongly suggest that biometric factors only determined interindividual differences in ventilatory response to exercise in prepubertal and peripubertal swimmers.     

Diaphragmatic performance during recovery from acute ventilatory failure in Guillain-Barré syndrome and myasthenia gravis

Diaphragmatic muscle performance during acute ventilatory failure due to Guillain-Barré syndrome and myasthenia gravis was assessed to evaluate (1) diaphragmatic function during weaning from ventilatory support and (2) diaphragmatic tension-time integral (TTdi) during ventilatory failure. We used a multilumen nasogastric tube and a pneumotachograph to measure transdiaphragmatic pressure per breath (Pdi), maximum transdiaphragmatic pressure (Pdimax), tidal volume (VT), and inspiratory time fraction during 74 spontaneous breathing trials in nine patients. Diaphragmatic performance was poor in all patients. The Pdi, Pdimax, and VT improved significantly, but values for Pdi and Pdimax remained low even after weaning. Improvement in Pdimax was the best predictor of recovery (r = 0.48; p less than 0.001). Maximal inspiratory force correlated with Pdimax (r = 0.48; p less than 0.005), but FVC did not. The TTdi rarely exceeded the expected fatigue threshold of 0.15 in spite of the patient's inability to sustain ventilation. Although our patients demonstrated diaphragmatic weakness, TTdi did not demonstrate diaphragmatic fatigue.     

Inspiratory muscle strength and respiratory drive in patients with rheumatoid arthritis

In 15 patients with rheumatoid arthritis (RA) and in 12 age- and sex-matched normal subjects, we evaluated inspiratory muscle strength and respiratory control system. Inspiratory muscle strength was assessed by measuring maximal inspiratory pressure (MIP). Respiratory drive was assessed by evaluating surface electromyographic activity of the diaphragm (EMGd) during both room-air breathing and hypercapnic rebreathing. Compared to the predicted value (mean +/- 1.65 SD), MIP was significantly reduced in nine patients (60%). All told, we noticed a significant inverse relationship in the patients between MIP and duration of steroid therapy (p less than 0.01). During room-air breathing, both EMGd and mouth occlusion pressure (P0.1), expressed both in actual values and as percentage of MIP, were significantly greater in patients than in the normal control group (p less than 0.001 for both). Both EMGd and P0.1 (%MIP) response slopes to CO2 were significantly greater in patients than in the normal control group (p less than 0.01 and p less than 0.001, respectively) and significantly related to the functional stage of disease. During quiet breathing and for a PETCO2 of 60 mm Hg, both EMGd (p less than 0.01 and p less than 0.05, respectively) and P0.1 (%MIP) (p less than 0.01 and p = 0.001, respectively) were inversely related to MIP. These results indicate that RA patients may exhibit inspiratory muscle weakness and increased respiratory drive. Steroid myopathy and rheumatoid myositis could explain the reduction in MIP, whereas neural afferents arising from respiratory muscle, lung, or joint receptors could be involved in the observed increase in neural drive.     

Inspiratory muscle activity during incremental exercise in obese men

OBJECTIVE: The aim of this study was to assess overall inspiratory muscle activity during incremental exercise in obese men and healthy controls using the non-invasive, inspiratory muscle tension-time index (T(T0.1)). We studied 17 obese subjects (mean age+/-s.d.; 49+/-13 years) and 14 control subjects (42+/-16) during an incremental, maximal exercise test. METHODS: Measurements included anthropometric parameters, spirometry, breathing patterns and inspiratory muscle activity. T(T0.1) was calculated using the equation T(T0.1)=P(0.1)/P(Imax) x T(I)/T(TOT) (where P(0.1) is mouth occlusion pressure, P(Imax) is maximal inspiratory pressure and T(I)/T(TOT) is the duty cycle). RESULTS: At same levels of maximal exercise (%W(max)) (20, 40, 60, 80, 100% W(max)), obese subjects showed higher P(0.1) (P<0.001) and P(0.1)/P(Imax) (P<0.001) values than controls. T(T0.1) was thus higher in obese subjects for each workload increment and at maximal exercise (P<0.001). CONCLUSIONS: During exercise, patients with obesity show alterations in inspiratory muscle activity as a result of both reduced inspiratory strength (as measured by maximal inspiratory pressure) and increased ventilatory drive (as reflected by mouth occlusion pressure), which prone obese subject to respiratory muscle weakness. Our results suggest that impaired respiratory muscle activity could contribute to a decrease in exercise capacity. T(T0.1) may be useful in our understanding concerning the benefits of endurance training.     

Effect of respiratory muscle fatigue on breathing pattern during incremental exercise

We examined the breathing pattern during incremental exercise before and after induction of inspiratory muscle fatigue. Our aim was to determine whether induction of fatigue alters the ventilatory response to exercise and in particular whether such changes are most apparent at high levels of exercise when minute ventilation and thus inspiratory load are greatest. A group of 10 healthy subjects was studied on a cycle ergometer. Fatigue was achieved by having the subject breathe against an inspiratory threshold load that required the subject to generate 80% of the predetermined maximal mouth pressure to initiate airflow. Breathing pattern, oxygen consumption (VO2), mouth occlusion pressure (P0.1), and a visual analog scale (VAS) for respiratory effort were obtained for 3 min at rest and at 25, 50, 75, and 100% of the subject's maximal work load (Wmax) as determined by preliminary testing. Exercise was performed on two separate occasions, once immediately after induction of fatigue and the other as a control. Induction of fatigue had no effect on resting breathing and only minimal effects at the lower work loads (25 and 50% Wmax). At the higher work loads (75 and 100% Wmax) induction of fatigue significantly altered the pattern of breathing during exercise. At 75% of Wmax the respiratory frequency (f) increased from 22.5 +/- 4.4 (SD) during control to 27.0 +/- 6.7 breaths/min (p less than 0.02) following induction of fatigue; tidal volume was not significantly altered, 2.15 +/- 0.65 versus 2.24 +/- 0.74 L during control. The increase in f was due to reductions in both inspiratory and expiratory time because fractional inspiratory time remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of 8-week, interval-based inspiratory muscle training and breathing retraining in patients with generalized myasthenia gravis

STUDY OBJECTIVE: To assess the effect of interval-based inspiratory muscle training (IMT) combined with breathing retraining (BR) in patients with generalized myasthenia gravis (MG) in a partial home program. DESIGN: A randomized controlled trial with blinding of outcome assessment. SETTING: A secondary-care respiratory clinic. PATIENTS: Twenty-seven patients with generalized MG were randomized to a control group or a training group. INTERVENTIONS: The training group underwent interval-based IMT associated with BR (diaphragmatic breathing [DB] and pursed-lips breathing [PLB]) three times a week for 8 weeks. The sessions included 10 min each of DB, interval-based IMT, and PLB. Interval-based IMT consisted of training series interspersed with recovery time. The threshold load was increased from 20 to 60% of maximal inspiratory pressure (P(Imax)) over the 8 weeks. MEASUREMENTS AND RESULTS: Lung function, respiratory pattern, respiratory muscle strength, respiratory endurance, and thoracic mobility were measured before and after the 8 weeks. The training group improved significantly compared to control group in P(Imax) (p = 0.001), maximal expiratory pressure (P(Emax)) [p = 0.01], respiratory rate (RR)/tidal volume (V(T)) ratio (p = 0.05), and upper chest wall expansion (p = 0.02) and reduction (p = 0.04). Significant differences were seen in the training group compared to baseline P(Imax) (p = 0.001), P(Emax) (p = 0.01), maximal voluntary ventilation (p = 0.02), RR/V(T) ratio (p = 0.003), Vt (p = 0.02), RR (p = 0.01), total time of RR (p = 0.01), and upper chest wall expansion (p = 0.005) and reduction (p = 0.005). No significant improvement was seen in lower chest wall or lung function. CONCLUSIONS: The partial home program of interval-based IMT associated with BR is feasible and effective in patients with generalized MG. Improvements in respiratory muscle strength, chest wall mobility, respiratory pattern, and respiratory endurance were observed.     

Effect of chronic altitude hypoxia on the behavior of the respiratory center. Study on normal subjects living at the altitude of Mexico City (2,240 meters)

Respiratory center (RC) output has been shown to be increased in hypoxemic Chronic Obstructive patients at sea level. In order to asses the separate role of chronic hypoxia on the RC output we studied 30 normal subjects all of them native and residents of Mexico City (altitude: 2,240 m, PaO2: 65-70 torr.). The parameters studied were: occlussion pressure (P0.1), mean inspiratory flow (Vi), and the ratio inspiratory time to total duration of the respiratory cycle (Ti/Ttot). The inspiratory impedance of the respiratory system as well as the minute ventilation (VE) and lastly to ensure isocapnic conditions, the end-tidal CO2 (PECO2), were also measured. These parameters were determined: 1) While breathing room air (RA), 2) after 30 min of breathing an inspired oxygen fraction (FiO2) of 30% and again 3) after 30 min of breathing and FiO2 of 100%. Fifteen of the subjects were studied on supine and the other 15 in the seated position. In most of the subjects the baseline (RA) values of P0.1 were found to be higher than those reported for normals at sea level. In every case, independent of body position, the P0.1 decreased (less than 0.01) to normal sea level values after 30 min of breathing O2 30%. Likewise, Vi and mechanical impedance also decreased (p less than 0.01) and no changes in Ti/Ttot were noted at this FiO2. No further changes occurred after breathing 100%. The above results show that: 1) The RC output in normal people at altitude (i.e. without mechanical abnormalities but with chronic hypoxia) is increased as compared to sea level.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ventilatory drive and respiratory muscle function in pregnancy

It has been demonstrated that during pregnancy expiratory reserve volume (ERV) decreases and minute ventilation (VE) increases initially and then stabilizes. In order to determine the role of thoracoabdominal mechanics, control of breathing, and inspiratory muscle function in these alterations, we studied inspiratory pressures, lung volumes, thoracic configuration, and respiratory drive in 18 normal pregnant women at Weeks 13, 21, 30, and 37 of pregnancy. Ten of them were studied 6 months after delivery. Transdiaphragmatic pressure (Pdi) was measured at Week 37 and 3 months after delivery in an additional group of seven women. VE as well as VT/TI increased early during gestation and remained unchanged thereafter. In contrast, mouth occlusion pressure (P0.1) increased progressively during pregnancy, from 1.53 +/- 0.16 (mean +/- SE) to 2.02 +/- 0.18 cm H2O, and fell significantly to 1.1 +/- 0.15 cm H2O after delivery, indicating that effective respiratory impedance increases during pregnancy. Mean P0.1 correlated with progesterone plasma levels (r = 0.918 p less than 0.05). No changes in Plmax, PEmax, and Pdimax, were observed. End-expiratory gastric pressure (Pga) increases significantly during pregnancy: 11.8 +/- 0.8 versus 8.4 +/- 1.12 cm H2O after delivery (p less than 0.012). This increment was correlated with the fall in ERV observed in late pregnancy (r = 0.74 p less than 0.05). Our results demonstrate that during pregnancy ventilatory drive and respiratory impedance increase with the consequent stabilization of VE, but our data do not permit us to differentiate whether the increment in P0.1 is secondary to the increase in impedance or to the rise in progesterone. Respiratory muscle function remains normal despite the alteration of thoracic configuration.     

Hypnosis effect on carbon dioxide chemosensitivity

Hypnosis is an induced state of heightened suggestibility during which certain physiologic variables can be altered. To investigate if carbon dioxide (CO2) chemosensitivity could be blunted during this suggestible state, we measured hypercapnic ventilatory response (HCVR, delta VE/delta PaCO2), oxygen consumption (VO2), breathing pattern (VT and f), inspiratory flow rate (VT/Ti), and inspiratory timing (Ti/Ttot) in 20 healthy subjects. Mouth occlusion pressures (P0.1) were measured in the last nine subjects. Resting oxygen consumption and minute ventilation were measured during awake and hypnotic control states. The HCVR was measured spontaneously and with the suggestion to maintain normal ventilation during both awake and hypnotic conditions. It was found that without a change in metabolism, ventilatory responses to CO2 could be blunted both voluntarily, and to a greater degree, with hypnotic suggestion. These findings may have important implications in clinical settings in which patients suffer from marked dyspnea secondary to increased ventilatory chemosensitivity.     

Ventilatory control in patients with hypoxemia due to obstructive lung disease.

In 20 patients with chronic hypoxemia due to chronic obstructive pulmonary disease, we measured responses to CO2 and hypoxia in terms of ventilation and P0.1, the pressure generated by the respiratory muscles during the first 0.1 s of inspiratory effort against a closed airway at functional residual capacity. These responses were compared to those of a control group of 17 patients with similar ventilatory abnormality but without hypoxemia. Hypoxemic patients demonstrated significantly less response to hypoxia than did control subjects in terms of both ventilation and P0.1 The decreased hypoxic response might be analogous to that reported in high altitude dwellers and patients with cyanotic congenital heart disease. Ventilatory responses to CO2 were depressed in hypoxemic patients, but P0.1 responses were not significantly decreased. While breathing at rest with arterial O2 saturation of 95 per cent, hypoxemic patients demonstrated the same minute ventilation as control subjects, but tidal volume was smaller, inspiratory duration was shorter, and breathing frequency was slightly higher. This breathing pattern appeared to be independent of whether or not these patients retained CO2.     

Naloxone does not alter response to hypercapnia or resistive loading in chronic obstructive pulmonary disease

To assess the role of endogenous opioid peptides in ventilatory control in patients with chronic obstructive lung disease, we measured the ventilatory and mouth occlusion pressure responses to hypercapnia and the compensatory response to an inspiratory resistive load in 11 male patients with COPD before and after intravenous administration of naloxone or placebo on 2 separate days. There were no statistically significant differences between naloxone and placebo administration in any index of ventilatory response to CO2 or resistive loading. When an inspiratory resistive load was added during CO2 rebreathing, minute ventilation at PETCO2 = 50 mm Hg in all 11 patients decreased significantly (p less than 0.05) with placebo and naloxone. In response to the inspiratory resistive load, in eight of the 11 patients mouth occlusion pressure (P0.1) did not increase; these eight subjects were classified as noncompensators. Naloxone did not affect the P0.1 response to inspiratory resistive loading, either in the group as a whole or in the subgroup of eight patients classified as noncompensators. Our study was unable to demonstrate that increased activity of endogenous opioid peptides suppresses the ventilatory response to CO2 or resistive loading in patients with chronic obstructive lung disease.     

Neural respiratory drive and neuromuscular coupling during CO2 rebreathing in patients with chronic interstitial lung disease

In 12 patients with CILD and 18 age-matched normal subjects we assessed the ventilatory control system at three levels: (a) neural, as assessed by EMGd (XP/Ti) and EMGint muscles via surface electrodes; (b) muscular, as assessed by mouth occlusion pressure (P0.1); and (c) ventilatory, as assessed by both ventilation (VE) and the related parameters, tidal volume (VT) and respiratory frequency (f). Compared with a normal control group, patients exhibited a significant decrease in lung volumes and in MIP; VT and inspiratory time (Ti) were significantly lower, while VT/Ti, P0.1, and both EMGd and EMGint were significantly greater in patients. During a CO2 rebreathing test, patients exhibited significantly greater EMGd, EMGint, and P0.1 responses to increasing PETCO2 than the control group. VE response slopes were similar in the two groups. For a given EMGd response slope (delta XP/Ti/delta PETCO2), the average P0.1 response slope (delta P0.1/delta PETCO2) was found to be significantly lower in patients than in the normal control group. Compared with normal subjects, CILD patients have a normal or increased neural component of respiratory activity and relatively low neuromuscular coupling (delta P0.1/delta XP/Ti). The decreased neuromuscular coupling could be explained in these patients by a reduced inspiratory muscle strength.     

Active inspiratory impedance and neuromuscular respiratory output during halothane anaesthesia in humans

The aim of this study was to measure, in 11 patients with healthy lungs, active inspiratory impedance during anaesthesia. In addition, we recorded changes in inspiratory occlusion pressure at 100 ms (P0.1) and ventilatory pattern while awake and during anaesthesia with a mean inspiratory fraction (FI) of 0.017 halothane in O2. The total active inspiratory resistance and elastance values were 5.4 +/- 3.3 hPa.l.1.s and 29.9 +/- 6.2 hPa.l.1, respectively. P0.1 and the ratio between P0.1 and mean inspiratory flow (P0.1/(VT/TI)) increased 124% (p less than 0.001) and 68% (p less than 0.001), respectively, during anaesthesia. Respiratory frequency rose significantly from 12.2 +/- 1.5 (mean +/- SD) to 24.6 +/- 4.6 cycles.min-1, while tidal volume and inspiratory duty cycle lowered significantly from 0.599 +/- 0.195 l and 0.44 +/- 0.04 to 0.372 +/- 0.088 l (p less than 0.001) and 0.40 +/- 0.04 (p less than 0.05), respectively. Minute ventilation (VE) and VT/TI did not change significantly. During halothane anaesthesia with an FI:0.017, the increase in neuromuscular respiratory output appears to compensate for the increased mechanical load, thus resulting in maintenance of VE at levels similar to those of an awake state.     

Timing and driving components of the breathing strategy in children with cystic fibrosis during exercise

The aim of this study was twofold: first, to determine the breathing strategies of children with cystic fibrosis (CF) during exercise, and secondly, to see if there was a correlation with lung function parameters. We determined the tension-time index of the inspiratory muscles (T(T0.1)) during exercise in nine children with CF, who were compared with nine healthy children with a similar age distribution. T(T0.1) was determined as followed T(T0.1) = P0.1/PImax . T(I)/T(TOT), where P0.1 is mouth occlusion pressure, PImax is maximal inspiratory pressure, and T(I)/T(TOT) is the duty cycle. CF children showed a significant decrease of their forced expiratory volume in 1 sec (FEV1), forced vital capacity (FCV), and FEV1/FVC, whereas the residual volume to total lung capacity ratio (RV/TLC) ratio and functional residual capacity (FRC) were significantly increased (P < 0.001). Children with CF showed mild malnutrition assessed by actual weight expressed by percentage of ideal weight for height, age, and gender (weight/height ratio; 82.3 +/- 3.6%). Children with CF showed a significant reduction in their PImax (69.3 +/- 4.2 vs. 93.8 +/- 7 cmH2O). We found a negative linear correlation between PImax and weight/height only in children with CF (r = 0.9, P < 0.001). During exercise, P(0.1), P0.1/PImax, and T(T0.1) were significantly higher, for a same percent maximal oxygen uptake in children with CF. On the contrary, T(I)/T(TOT) ratio was significantly lower in children with CF compared with healthy children. At maximal exercise, children with CF showed a T(T0.1) = 0.16 vs. 0.14 in healthy children (P < 0.001). We observed at maximal exercise that P0.1/PImax increased as FEV1/FVC decreased (r = -0.90, P < 0.001), and increased as RV/TLC increased (r = 0.92, P < 0.001) only in children with CF. Inversely, T(I)/T(TOT) decreased as FEV1/FVC decreased (r = 0.89, P < 0.001), and T(I)/T(TOT) decreased as RV/TLC increased (r = -0.94, P < 0.001). These results suggest that children with CF adopted a breathing strategy during exercise in limiting the increase of the duty cycle. Two determinants of this strategy were degrees of airway obstruction and hyperinflation.     

Ventilatory and neuromuscular responses to inspiratory positive pressure during CO2 breathing

We studied the effects of assisting respiration with inspiratory positive pressure (IPP) during air and CO2 breathing by measuring ventilatory and mouth occlusion (P0.1) responses in 15 normal human subjects. Switching from spontaneous breathing to IPP without added CO2 did not cause a significant change in mean PACO2, P0.1, or V1. During CO2 breathing, switching to IPP did not significantly alter tidal volume or frequency. The mean ventilatory response to CO2 during spontaneous breathing was 1.02 liters/min/mm Hg. With IPP at pressure limits of 5 and 7 cm H2O, the mean responses were 0.93 and 0.89 liters/min/mm Hg, respectively, not significantly different from spontaneous breathing. The mean spontaneous P0.1 response to CO2 was 0.32 cm H2O/mm Hg. With IPP at 5 and 7 cm H2), the responses were 0.29 and 0.36 cm H2O/mm Hg, also not significantly different from spontaneous breathing. Reduction of muscular work of breathing by IPP in normal human subjects does not induce a measurable change in either respiratory drive or ventilation, which appears to remain dependent on chemoreceptor input. Inspiratory effort continues during IPP, even though it may be less than during spontaneous breathing.