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.     

Noninvasive assessment of inspiratory muscle function during exercise

The use of esophageal and gastric balloons limits measurement of the tension-time index of inspiratory muscles (TTI) during exercise. The aim of this study was to assess whether a noninvasive tension-time index, TT(0.1), given by P(0.1)/PI(max) x TI/Ttot (where P(0.1) is mouth occlusion pressure, PI(max) is maximal inspiratory pressure, and TI/Ttot is duty cycle) could reliably assess TTI during exercise. In seven healthy young men and nine patients with COPD we measured TT(0.1) and TTI (i.e., Pes/Pes(max) x TI/Ttot where Pes is mean esophageal pressure and Pes(max) is maximal static Pes) at rest and during an incremental exercise test. A significant linear correlation (p < 0.02) was found between TT(0.1) and TTI in all normal subjects and patients with COPD. An equation for estimating TTI from TT(0.1) was established for each group. In the normal subjects there was good agreement between estimated and observed data. In five additional normal males studied prospectively, the agreement was also satisfactory and reproducible. In the COPD patients the agreement was poor. In conclusion, in young healthy subjects the changes in TT(0.1) during exercise reflect the changes in TTI, allowing satisfactory estimation of TTI from noninvasive measurements of TT(0.1).     

Noninvasive assessment of the tension-time index of inspiratory muscles at rest in obese male subjects

OBJECTIVE: The aim of this study was to investigate the effect of excessive mechanical load caused by obesity on the inspiratory muscle performance in obese men at rest. METHODS: We therefore measure at rest spirometric flows and the noninvasive tension time index of inspiratory muscle (TTmus = PI/PImax x TI/TTOT) in eight obese male subjects (body mass index (BMI) > 30) and 10 controls. RESULTS: Spirometric flow (FEV1% pred, FVC% pred) and maximal inspiratory pressure (PImax) were significantly lower in obese subjects compared to controls (P < 0.001). The mean TTmus was significantly higher in obese subjects than in controls (0.136 +/- 0.003 vs 0.045 +/- 0.01). The increase in TTmus was primarily due to an increase in the ratio of mean inspiratory pressure to maximal inspiratory pressure (PI/PImax) and the duty cycle (TI/TTOT). We found a significant negative relationship between PImax and BMI (r = -0.74, P < 0.001), a positive correlation between TTmus and BMI (r = 0.80, P < 0.001) and a negative correlation between TTmus and forced expiratory volume in 1 s (r = -0.85, P < 0.001). CONCLUSION: Excessive mechanical load caused by obesity imposes a great burden on the inspiratory muscle, which may predispose such subjects to respiratory muscle weakness at rest.     

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)     

Prognostic value of mouth occlusion pressure in patients with chronic ventilatory failure

BACKGROUND: Mouth occlusion pressure measurement is widely used for assessment of respiratory muscle function, particularly in patients with respiratory failure. However, its predictive value for long-term survival remains largely unexplored. METHODS: In 464 patients with chronic hypercapnic respiratory failure (CHRF) due to various underlying disorders and receiving non-invasive ventilation (NIV), maximal inspiratory mouth pressure (PI(max)), mouth occlusion pressure at 100 ms during quiet breathing (P(0.1)) and the ratio P(0.1)/PI(max) were assessed prior to and after treatment including NIV. Baseline data and changes at follow-up were used to evaluate their predictive value for long-term survival. RESULTS: Overall, median (quartiles) P(0.1) was 177.0 (109.2;287.0) %pred, PI(max) 35.0 (24.0;47.0) %pred, and P(0.1)/PI(max) 564.0 (275.7;1082.3) %pred. In multivariate analyses, P(0.1) was related to airflow obstruction, lung hyperinflation, haemoglobin (Hb) and leukocytes, and PI(max) to airflow obstruction and hyperinflation (p<0.05 each). All-cause mortality during follow-up (median 31.6 months) was 31.5%. Survival was associated with age, body-mass index (BMI), lung function, leukocytes, Hb, PI(max), P(0.1) and P(0.1)/PI(max) (p<0.01 each, univariate). Among these multivariate Cox regression identified age, BMI, FEV(1), leukocytes and P(0.1)/PI(max) as independent predictors (p<0.05 each). Furthermore, the decrease of P(0.1)/PI(max) at follow-up was associated with improved survival in patients with high baseline P(0.1)/PI(max) (>50th or 75th percentile; p<0.05). CONCLUSIONS: In patients with CHRF and current NIV therapy, P(0.1)/PI(max) was an independent predictor of long-term survival, in addition to previously established risk factors. Moreover, a decrease in P(0.1)/PI(max) after treatment including NIV was associated with an improved survival in patients with high baseline P(0.1)/PI(max) values.     

Orthopnea and tidal expiratory flow limitation in chronic heart failure

BACKGROUND: Tidal expiratory flow limitation (FL) is common in patients with acute left heart failure and contributes significantly to orthopnea. Whether tidal FL exists in patients with chronic heart failure (CHF) remains to be determined. PURPOSES: To measure tidal FL and respiratory function in CHF patients and their relationships to orthopnea. METHODS: In 20 CHF patients (mean [+/- SD] ejection fraction, 23 +/- 8%; mean systolic pulmonary artery pressure [sPAP], 46 +/- 18 mm Hg; mean age, 59 +/- 11 years) and 20 control subjects who were matched for age and gender, we assessed FL, Borg score, spirometry, maximal inspiratory pressure (Pimax), mouth occlusion pressure 100 ms after the onset of inspiratory effort (P(0.1)), and breathing pattern in both the sitting and supine positions. The Medical Research Council score and orthopnea score were also determined. RESULTS: In the sitting position, tidal FL was absent in all patients and healthy subjects. In CHF patients, Pimax was reduced, and ventilation and P(0.1)/Pimax ratio was increased relative to those of control subjects. In the supine position, 12 CHF patients had FL and 18 CHF patients claimed orthopnea with a mean Borg score increasing from 0.5 +/- 0.7 in the sitting position to 2.7 +/- 1.5 in the supine position in CHF patients. In contrast, orthopnea was absent in all control subjects. The FL patients were older than the non-FL patients (mean age, 63 +/- 8 vs 53 +/- 12 years, respectively; p < 0.03). In shifting from the seated to the supine position, the P(0.1)/Pimax ratio and the effective inspiratory impedance increased more in CHF patients than in control subjects. The best predictors of orthopnea in CHF patients were sPAP, supine Pimax, and the percentage change in inspiratory capacity (IC) from the seated to the supine position (r(2) = 0.64; p < 0.001). CONCLUSIONS: In sitting CHF patients, tidal FL is absent but is common supine. Supine FL, together with increased respiratory impedance and decreased inspiratory muscle force, can elicit orthopnea, whom independent indicators are sPAP, supine Pimax and change in IC percentage.     

Non-invasive assessment of inspiratory muscle performance during exercise in patients with chronic heart failure

Aims The aim of this study was to assess inspiratory performanceat rest and during exercise in patients with chronic heart failurein comparison with healthy controls using a non-invasive index:the tension-time index of inspiratory muscles (TTMUS). Methods We studied 13 patients with chronic heart failure (57±7years) and 10 control subjects (58±6 years) at rest andduring an incremental maximal exercise test. Measurements includedbreathing pattern (inspiratory time, total time of respiratorycycle, minute ventilation, tidal volume and respiratory frequency),mouth occlusion pressure and mean inspiratory pressure (calculatedas follows: 5xmouth occlusion pressurexinspiratory time). Themaximal inspiratory pressure was measured at rest. TTMUS wascalculated from the equation: TTMUS=PI/PIMAXxTI/TTOT, wherePI/PIMAX is the ratio of mean inspiratory pressure to maximalinspiratory pressure and TI/TTOT is the ratio of mean inspiratorytime to total time of the respiratory cycle. Results At rest, the results in patients showed non-significantly highermouth occlusion pressure, lower maximal inspiratory pressure(PP<0·001), and a higher ratio of mean inspiratorypressure to maximal inspiratory pressure (PP<0·01).There was no difference in the breathing pattern. TTMUS wasthus significantly higher in the patients with chronic heartfailure (PP<0·001). At maximal exercise (77±16Wfor patients with chronic heart failure vs 142±27W forcontrols,PP<0·001), the ratio of mean inspiratorytime to total time of respiratory cycle, the mouth occlusionpressure and the ratio of mean inspiratory pressure to maximalinspiratory pressure were not different. TTMUS was thus comparablein the two groups. During exercise, at comparable workloads(20, 40 and 60W), the patients showed higher mouth occlusionpressure (PP<0·01) and a higher ratio of mean inspiratorypressure to maximal inspiratory pressure (PP<0·001),whereas the ratio of mean inspiratory time to total time ofthe respiratory cycle was similar. TTMUS was thus higher inthe patients at each workload (PP<0·05). Conclusion This study shows that the determination of TTMUS at rest andduring exercise allows the observation of alterations in inspiratorymuscle performance as a result of both reduced inspiratory strength,as measured by the maximal inspiratory pressure, and increasedventilatory drive, as reflected by the mouth occlusion pressurein patients with chronic heart failure. The non-invasivenessof this new index is an additional argument for its use in aclinical setting.     

Impact of impaired inspiratory muscle strength on dyspnea and walking capacity in sarcoidosis

BACKGROUND: Dyspnea and fatigue are frequent but poorly understood symptoms in sarcoidosis patients. This study was aimed at assessing the clinical impact of inspiratory muscle impairment on dyspnea and exercise tolerance. This is the first study using nonvolitional tests that are independent of the patient's cooperation and motivation in addition to volitional tests of inspiratory muscle strength in patients with sarcoidosis. METHODS: Peak maximal inspiratory mouth pressure (Pimaxpeak), maximal inspiratory pressure sustained for 1.0 s (Pimax1.0), twitch mouth pressure (TwPmo), lung function test results, blood gas measurements, 6-min walking distance (6MWD), and Borg dyspnea scale (BDS) scores were assessed in 24 male sarcoidosis patients and 24 healthy male control subjects matched for age and body mass index. RESULTS: Mean (+/- SD) Pimaxpeak (95.2 +/- 25.3% vs 124.6 +/- 23.4% predicted, respectively; p < 0.001) and Pimax1.0 (85.6 +/- 31.4% vs 125.8 +/- 26.8% predicted, respectively; p < 0.001) were lower in sarcoidosis patients compared to control subjects. TwPmo tended to be lower in sarcoidosis patients, and there were three patients who had TwPmo values of < 1.0 kPa, which is a strong indicator of inspiratory muscle weakness. The mean 6MWD was 582 +/- 97 m in sarcoidosis patients and 638 +/- 65 in control subjects (p = 0.025). The mean BDS score was higher in sarcoidosis patients (3.3 +/- 1.7 vs 0.2 +/- 0.5, respectively; p < 0.001). Compared to maximal inspiratory pressure, lung function parameters, and blood gas levels, TwPmo was the strongest predictor for 6MWD (r = 0.663; p = 0.003) and BDS score (r = 0.575; p = 0.012) in sarcoidosis patients following multiple linear regression analysis. CONCLUSIONS: Impairment of inspiratory muscle strength occurs in sarcoidosis patients, and has been suggested to be an important factor causing dyspnea and reduced walking capacity, but this is only reliably detectable when using nonvolitional tests of inspiratory muscle strength.     

The progressive effects of ageing on chemosensitivity in healthy subjects

The aim of this study was to compare the central inspiratory drive (P(0.1)) response to hypoxia and hypercapnia between different age groups of elderly, nonsmoker, healthy subjects and young healthy controls. A random sample, proportionally stratified by age (65-69, 70-74, 75-79 and 80-84 yrs) from a sample of nonsmoker elderly subjects representative of a general population and 47 healthy subjects aged 20-40 were selected. Arterial blood gas, lung volumes, diffusing capacity, maximal respiratory pressure and oxygen uptake measurements were performed. Breathing pattern and mouth occlusion pressure, as well as P(0.1) responses to hyperoxic progressive hypercapnia and isocapnic progressive hypoxia were evaluated. The elderly subjects had lower P0.1 responses to hypoxia (0.017+/-0.006 vs. 0.031+/-0.008 kPa/%, P<0.001) and hypercapnia (0.042+/-0.018 vs. 0.051+/-0.030 kPa/mmHg, P=0.047) than the young healthy controls. Hypoxic sensitivity gradually decreased as age increased to 70-74 and remained unchanged from 75 years of age onward. CO(2) threshold was lower in the elderly groups than in young healthy controls. Lung volumes, inspiratory muscle strength and baseline metabolic rate were the principal determinants of hypoxic sensitivity. In summary, during old age, a progressive decline in hypoxic sensitivity and a decrease in the CO(2) threshold are experienced. These alterations remain stable from the age of 75 onward.     

Inspiratory muscle training using an incremental endurance test alleviates dyspnea and improves functional status in patients with chronic heart failure.

BACKGROUND: The benefits of inspiratory muscle training (IMT) in patients with chronic heart failure (CHF) have been inadequately studied. DESIGN AND METHODS: Using a prospective, age and sex-matched controlled study, we investigated 35 patients with moderate to severe CHF (NYHA class II-III and left ventricular ejection fraction 24.4+/-1.3% [mean+/-SEM]). An incremental respiratory endurance test using a fixed respiratory workload was provided by software with an electronic mouth pressure manometer interfaced with a computer. The training group (n=20) exercised at 60% of individual sustained maximal inspiratory pressure (SMIP) and the control group (n=15) at 15% of SMIP. All patients exercised three times weekly for 10 weeks. Pulmonary function, exercise capacity, dyspnea and quality of life were assessed, pre- and post-training. RESULTS: The training group significantly increased both maximum inspiratory pressure (Pimax), (111+/-6.8 versus 83+/-5.7 cmH2O, P<0.001), and SMIP (527822+/-51358 versus 367360+/-41111 cmH2O/sec x 10(-1), P<0.001). Peak VO2 increased after training (17.8+/-1.2 versus 15.4+/-0.9 ml/kg/min, P<0.005), as did the six-minute walking distance (433+/-16 versus 367+/-22 meters, P<0.001). Perceived dyspnea assessed using the Borg scale was reduced for both the treadmill (12.7+/-0.57 versus 14.2+/-0.48, P<0.005) and the walking (9+/-0.48 versus 10.5+/-0.67, P<0.005) exercise tests and the quality of life score was also improved (21.1+/-3.5 versus 25.2+/-4, P<0.01). Resting heart rate was significantly reduced with training (77+/-3.3 versus 80+/-3 beats/min, P<0.05). The control group significantly increased Pimax (86.6+/-6.3 versus 78.4+/-6.9 cmH2O, P<0.05), but decreased SMIP (274972+/-32399 versus 204661+/-37184 cmH2O/sec x 10(1), P<0.005). No other significant effect on exercise capacity, heart rate, dyspnea, or quality of life was observed in this group. CONCLUSION: Inspiratory muscle training using an incremental endurance test, successfully increases both inspiratory strength and endurance, alleviates dyspnea and improves functional status in CHF.     

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.     

A simple noninvasive pressure-time index at the mouth to measure respiratory load during acute exacerbation of COPD A comparison with normal volunteers

We assessed the validity of the pressure-time index (PTI) measured at the mouth as a noninvasive and simplified alternative to conventional tension-time index for assessing respiratory load and inspiratory muscle force reserve. PTI was measured within 48 h of hospital admission and at 24 h before discharge in 37 consecutive patients with acute exacerbation of chronic obstructive pulmonary disease (COPD) using the equation PTI = (P(awo)/MIP)(T(I)/T(T)) 100, where P(awo) is the mean airway pressure measured at the mouth, MIP the maximal inspiratory pressure, and T(I)/T(T) the inspiratory time (T(I)) to total cycle length (T(T)) ratio. Controls were 30 normal volunteers with similar anthropometric features. Mean (+/- SD) PTI values were significantly higher in COPD patients (0.29 +/- 0.10) than in controls (0.11 +/- 0.04) (P < 0.001) primarily because MIP and T(I)/T(T) were significantly lower and P(awo) was higher in the COPD population than in controls. As a result of improvement of the respiratory condition, PTI values were significantly lower at discharge (0.20 +/- 0.10 vs. 0.29 +/- 0.10, P < 0.001) due to a drop in P(awo) and an increase in MIP. The accuracy of different PTI cutpoints was assessed by comparison of the receiver operating characteristics curves. Best cutpoint values for differentiating COPD patients on admission and at hospital discharge from controls were 0.13 (positive predictive value 76%) and 0.17 (positive predictive value 92%) respectively. Noninvasive PTI measured at the mouth provides a valid and easy method for assessing respiratory muscle load and reserve. Changes in PTI values reflect functional improvement following treatment of acute exacerbation of COPD.     

Expiratory Muscle Endurance in Middle-Aged Healthy Subjects

To evaluate expiratory muscle endurance in middle-aged healthy subjects using incremental as well as constant expiratory loads, 14 healthy volunteers (51 +/- 16 years) were submitted to a specific endurance test, which was performed breathing against a threshold valve, and was divided into two parts. In part I, the load was progressively increased (50 g each 2 min) until task failure occurred. The mean mouth pressure generated against the highest load held for at least 60 sec was defined as the maximal expiratory sustainable pressure (Pth(max)). In part II, each subject breathed against a constant submaximal expiratory load (80% Pth(max)) until task failure occurred (expiratory endurance time or Tth(80)). Both parts of the test were repeated 24-48 h later. Progressive expiratory loading induced a linear increase in mouth expiratory pressure and the Pth(max) obtained was 141 +/- 43 cm H(2)O, representing 74 +/- 28% of the maximal expiratory pressure (PE(max)). Under constant loads, the Tth(80) was 17 +/- 9 min. At the end-point of both parts, the tension time index for expiratory muscles was dramatically increased (>0.25), and both EMG central frequency and PE(max) were decreased with no changes in maximal inspiratory pressure or inspiratory capacity. Extreme dyspnea was present in most of the subjects but no complications were observed. The endurance of expiratory muscles can be easily assessed in healthy subjects using this method, which has acceptable reproducibility and tolerance.     

Normal values for maximal static inspiratory and expiratory pressures in healthy children

Maximal static respiratory pressures are a simple measure of respiratory muscle strength. In order to construct a set of equations describing normal values, we measured maximal inspiratory (P(Imax)) and expiratory (P(Emax)) pressures in 296 children (144 boys and 152 girls), aged 7-14 years, in sitting and standing positions.The boys reached higher values in sitting and standing positions for P(Imax) (-8.29 +/- 2.69 and -8.19 +/- 2.73 kPa, respectively) and P(Emax) (8.02 +/- 2.32 and 7.94 +/- 2.32 kPa, respectively) than girls (-6.53 +/- 1.99 and -6.60 +/- 2.03 kPa for P(Imax) and 6.91 +/- 1.79 and 7.13 +/- 1.81 kPa for P(Emax) for sitting and standing positions, respectively); the differences between boys and girls were highly significant (P < 0.001 in all instances). There were no differences regarding body position during measurements in both genders. Multiple correlation analysis showed significant correlations of pressures to age in boys in all cases, but in girls only for P(Imax) in standing position. Therefore, equations describing reference values were constructed with respect to age as the independent variable. Maximal pressures also correlated with maximal inspiratory and expiratory flows.The measurements of P(Imax) and P(Emax) are useful in assessing respiratory muscle strength despite their relatively large variability. P(Imax) and P(Emax) also correlate with maximum peak expiratory and inspiratory flows. Children generate lower pressures and lower maximal flows than adolescents and adults.     

Abnormal ventilatory responses to hypoxia in Type 2 diabetes.

AIMS: The incidence of Type 2 diabetes is increasing, along with its associated micro- and macrovascular disease manifestations. Previous studies indicate that patients with Type 2 diabetes exhibit abnormal cardiopulmonary reflex responses to various stimuli, although the impact of hypoxia, a common physiological stimulus, on ventilatory responses has not previously been studied in humans with Type 2 diabetes. METHODS: Minute ventilation (V(E)) breathing pattern responses (total breath time, T(TOT); expiratory time, T(E); inspiratory time, T(I); inspiratory duty cycle, T(I)/T(TOT)) were measured during 5 min each of normoxia and isocapnic hypoxia (arterial O2 saturation approximately 85%) in eight subjects with Type 2 diabetes and seven age- and body mass index-matched healthy subjects. RESULTS: During normoxia, V(E) was similar in control and diabetic subjects (6.4+/-1.2, 6.4+/-1.1 l/min, respectively). In response to hypoxia, V(E) significantly increased in both groups (to 17.0+/-5.0 and 9.5+/-2.0 l/min, respectively, P<0.05), but the magnitude of increase in V(E) was significantly less in diabetic than in control subjects (P<0.05). In addition, the breathing pattern response to hypoxia differed between groups in terms of T(I)/T(TOT) and T(TOT) (P<0.05), with control subjects significantly decreasing T(TOT) and T(E) (P<0.05) while diabetic subjects tended to increase both. CONCLUSIONS: Relative to matched control subjects, Type 2 diabetic subjects exhibit blunted V(E) responses to acute isocapnic hypoxia, suggesting that this group of diabetic subjects possesses a chemoreflex ill-equipped to respond homeostatically to hypoxic challenge.     

Relationship between aerobic physical fitness and ventilatory control during exercise in young swimmers

The aim of this study was to specify in young trained swimmers, during progressive exercise, whether different aerobic physical fitness goes along with differences in breathing pattern and in mouth occlusion pressure used as a non-invasive index of neuromuscular output. Ten children (aged 10.5-16 years) with high VO2 max (57.6 +/- 3.6 ml.min-1.kg-1) and ten children (aged 11-17 years) with moderate VO2 max (44 +/- 3.8 ml.min-1.kg-1) realized a maximal exercise test on a cycle ergometer. During the last minute of each power level we measured the following parameters: VO2, VCO2, VEBW, f, VTBW/TI,TI/TTOT, as well as mouth occlusion pressure (P0.1) and 'effective impedance' of the respiratory system (P0.1/VTBW/TI). Our results showed that at a same VCO2, children with high VO2 max had significantly lower P0.1, P0.1/VTBW/TI and f than children with moderate VO2 max and same VEBW/TI. At different levels of VO2, in the twenty children of the two groups, we have found significant correlations between VO2 max of each subject and P0.1 (P less than 0.01), P0.1/VTBW/TI (P less than 0.001). At a same VO2, children with a higher VO2 max showed significantly lower P0.1, P0.1/VTBW/TI at all levels of VO2 and lower VEBW and VTBW/TI at high level of VO2. At a same VE, the two groups of children showed the same values of VT/TI and f. In conclusion this study shows first, that different aerobic physical fitness does not go along with different breathing pattern, and second, that swimmers with high physical fitness have a lower ventilatory response to exercise but a higher ventilatory and neuromuscular efficiency during exercise than children with moderate physical fitness.     

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.     

Inspiratory muscle dysfunction and unexplained dyspnea in systemic lupus erythematosus

The role of inspiratory muscle dysfunction in lung volume restriction and unexplained dyspnea was studied in 16 consecutive patients with systemic lupus erythematosus. Maximal mouth inspiratory pressure (PIM) and maximal transdiaphragmatic pressure (Pdi max) were measured. Pdi and its components were determined during quiet breathing. No significant association was found between the activity of the disease, several serologic markers, and the inspiratory muscle dysfunction. No specific anti-skeletal muscle antibody was found in these patients. Significant correlations were found between the degree of dyspnea and PIM (r = -0.69, P less than 0.01) and Pdi max (r = -0.75, P less than 0.001); however, dyspnea did not correlate with specific lung compliance. Vital capacity correlated significantly with the degree of dyspnea (r = -0.813, P less than 0.001) and with Pdi max (r = 0.544, P less than 0.05). No correlation was found between vital capacity and specific lung compliance. We conclude that inspiratory muscle dysfunction can be an important mechanism in the pathogenesis of the lung volume restriction and dyspnea in patients with systemic lupus erythematosus.     

Effects of different expiratory maneuvers on inspiratory muscle force output

We assessed the effects of two different expiratory maneuvers (fast [F] or slow [S]) on the ability of normal subjects (n = 12, age 35 +/- 6 yr) to generate maximal inspiratory pressures and maximal inspiratory flows near residual volume (RV). With the F maneuver, the subject exhaled rapidly to RV and immediately performed a maximal inspiratory effort, whereas with the S maneuver the subject exhaled slowly to RV, paused for 4 to 6 s at RV, and then inspired forcefully. Maximal static inspiratory pressure against an occluded airway (PImax), and maximal dynamic inspiratory pressure (PIdyn) and maximal inspiratory flow (V Imax) with no added resistance, as well as the electromyographic activity of the parasternal muscles, were measured during each maneuver. Both maneuvers were initiated from TLC and were performed randomly. In comparison with the S maneuver, the F maneuver yielded values of higher (mean +/- SE) PImax (148 +/- 5 cm H2O versus 135 +/- 7 cm H2O, p < 0.05), PIdyn (33 +/- 2 cm H2O versus 28 +/- 2 cm H2O, p < 0.05), and V Imax (12.3 +/- 0.4 L/s versus 11.4 +/- 0.6 L/s, p < 0.05). In addition, the rate of rise of PImax, the rate of rise of PIdyn, and the integrated peak electromyographic activity of the parasternal muscles were significantly greater with the F than with the S maneuver, suggesting greater inspiratory muscle (IM) activation. The enhanced IM activation may be related to a specific inspiratory-expiratory muscle interaction similar to the agonist-antagonist interactions described for a pair of skeletal muscles.     

Respiratory muscle dysfunction in idiopathic pulmonary arterial hypertension.

Idiopathic pulmonary arterial hypertension (IPAH) is a pulmonary vasculopathy of unknown aetiology. Dyspnoea, peripheral airway obstruction and inefficient ventilation are common in IPAH. Data on respiratory muscle function are lacking. This prospective single-centre study included 26 female and 11 male patients with IPAH in World Health Organization functional classes II-IV. Mean+/-SD pulmonary artery pressure was 48.6+/-16.9 in females and 53.1+/-22.9 mmHg in males; cardiac output was 3.7+/-1.3 and 4.2+/-1.7 L x min(-1). Maximal inspiratory pressure (PI,max) was lower in the female patients than in 20 controls (5.3+/-2.0 versus 8.2+/-2.0 kPa). In the male patients, PI,max was lower than in 25 controls (6.8+/-2.2 versus 10.5+/-3.7 kPa). Maximal expiratory pressure (PE,max) was lower in the female patients than in controls (6.2+/-2.6 versus 9.5+/-2.1 kPa), and in male patients as compared to controls (7.1+/-1.6 versus 10.3+/-3.9 kPa). There was no correlation between PI,max or PE,max and parameters of pulmonary haemodynamics or exercise testing. The ratio of mouth occlusion pressure within the first 0.1 s of inspiration and PI,max was higher in IPAH than in controls (females 0.067+/-0.066 versus 0.021+/-0.008; males 0.047+/-0.061 versus 0.023+/-0.016). In conclusion, this study provides the first evidence of inspiratory and expiratory muscle weakness in idiopathic pulmonary arterial hypertension. The pathomechanisms and the prognostic significance should be further investigated.