Hypoxemia and hypercapnia during exercise and sleep in patients with cystic fibrosis.

BACKGROUND: In patients with cystic fibrosis (CF), it has been proposed that hypoxemia and hypercapnia occur during episodes of stress, such as exercise and sleep, and that respiratory muscle weakness because of malnutrition may be responsible. METHODS: Pulmonary function, respiratory muscle strength, and nutrition were assessed and correlated with the degree of hypoxemia and hypercapnia during exercise and sleep in 14 patients with CF and 8 control subjects. RESULTS: Despite no differences in maximum static inspiratory pressure (PImax) between the two groups, the CF group developed more severe hypoxemia (minimum oxyhemoglobin saturation [SpO2], 89 +/- 5% vs 96 +/- 2%; p < 0.001) and hypercapnia (maximum transcutaneous CO2 tension [PtcCO2], 43 +/- 6 vs 33 +/- 7 mm Hg; p < 0.01) during exercise. Similarly, during sleep, the CF group developed greater hypoxemia (minimum SpO2, 82 +/- 8% vs 91 +/- 2%; p < 0.005), although CO2 levels were not significantly different (maximum PtcCO2, 48 +/- 7 vs 50 +/- 2 mm Hg). Within the CF group, exercise-related hypoxemia and hypercapnia did not correlate with FEV1, residual volume/total lung capacity ratio (RV/TLC), PImax, or body mass index (BMI). Hypoxemia and hypercapnia during sleep correlated with markers of gas trapping (RV vs minimum arterial oxygen saturation [r = -0.654; p < 0.05]), RV vs maximum PtcCO2 (r = 0.878; p < 0.001), and RV/TLC vs maximum PtcCO2 (r = 0.790; p < 0.01) but not with PImax or BMI. CONCLUSION: Patients with moderately severe CF develop hypoxemia and hypercapnia during exercise and sleep to a greater extent than healthy subjects with similar respiratory muscle strength and nutritional status. Neither respiratory muscle weakness nor malnutrition are necessary to develop hypoxemia or hypercapnia during exercise or sleep.     

Kurtosis and skewness of density histograms on inspiratory and expiratory CT scans in smokers

The aim of this study is to evaluate the relationship between lung function and kurtosis or skewness of lung density histograms on computed tomography (CT) in smokers. Forty-six smokers (age range 46?81 years), enrolled in the Lung Tissue Research Consortium, underwent pulmonary function tests (PFT) and chest CT at full inspiration and full expiration. On both inspiratory and expiratory scans, kurtosis and skewness of the density histograms were automatically measured by open-source software. Correlations between CT measurements and lung function were evaluated by the linear regression analysis. Although no significant correlations were found between inspiratory kurtosis or skewness and PFT results, expiratory kurtosis significantly correlated with the following: the percentage of predicted value of forced expiratory volume in the first second (FEV(1)), the ratio of FEV(1) to forced vital capacity (FVC), and the ratio of residual volume (RV) to total lung capacity (TLC) (FEV(1)%predicted, R = -0.581, p < 0.001; FEV(1)/FVC, R = -0.612, p < 0.001; RV/TLC, R = 0.613, p < 0.001, respectively). Similarly, expiratory skewness showed significant correlations with PFT results (FEV(1)%predicted, R = -0.584, p < 0.001; FEV(1)/FVC, R = -0.619, p < 0.001; RV/TLC, R = 0.585, p < 0.001, respectively). Also, the expiratory/inspiratory (E/I) ratios of kurtosis and skewness significantly correlated with FEV(1)%predicted (p < 0.001), FEV(1)/FVC (p < 0.001), RV/TLC (p < 0.001), and the percentage of predicted value of diffusing capacity for carbon monoxide (kurtosis E/I ratio, p = 0.001; skewness E/I ratio, p = 0.03, respectively). We conclude therefore that expiratory values and the E/I ratios of kurtosis and skewness of CT densitometry reflect airflow limitation and air-trapping. Higher kurtosis or skewness on expiratory CT scan indicates more severe conditions in smokers.     

Utility of the breathing reserve index at the anaerobic threshold in determining ventilatory-limited exercise in adult cystic fibrosis patients

OBJECTIVES: Cardiopulmonary exercise testing in cystic fibrosis (CF) patients is useful to assess functional status and prognosis. Using the current interpretation guidelines, the utility of this testing will be limited in those patients who cannot exercise to a near-maximal level. This study investigates the utility of the breathing reserve index at the anaerobic threshold (BRIAT), which is defined as minute ventilation at the anaerobic threshold (AT)/maximum voluntary ventilation (MVV), to distinguish ventilatory-limited (VL) CF patients from nonventilatory-limited (NVL) CF patients. DESIGN: Exercise studies on 53 adult CF patients at baseline clinical status performed from 1993 to 1999 were reviewed, of which 40 met the inclusion criteria. The studies were performed via ramp protocol to the symptom-limited maximum on a cycle ergometer with breath-by-breath expired gas analysis. AT was determined noninvasively via the V-Slope method. The patients were classified as VL if they had abnormal spirometry findings, reduced exercise capacity, and a breathing reserve index at maximum exercise (BRImax) of > or = 0.7. NVL patients had a normal BRImax and met the criteria for a maximal study. RESULTS: VL patients (21 patients) had significantly lower FVC, FEV(1), MVV, and body mass index than NVL patients (19 patients). The BRIAT for the VL group was significantly higher than that for the NVL group (p < 0.001). Logistic regression analysis revealed that BRIAT discriminated VL patients from NVL patients better than a variety of nonexercise variables tested. The BRIAT correlated extremely well with BRImax (r = 0.89; p < 0.01), FVC (r = -0.67; p < 0.001), FEV(1) (r = -0.76; p < 0.001), and FEV(1)/FVC ratio (r = -0.683; p < 0.001). A BRIAT value of 0.29 distinguished VL CF patients from NVL CF patients with 95.2% sensitivity and 84.2% specificity. CONCLUSIONS: The BRIAT assessed noninvasively correlates well with commonly used measurements of pulmonary function and accurately distinguishes CF patients with and without a ventilatory limitation to exercise. The BRIAT may have utility in the interpretation of exercise studies in CF patients who are unable to exercise to a maximal level.     

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.     

Contribution of lung function to exercise capacity in patients with chronic heart failure

BACKGROUND: The importance of exercise capacity as an indicator of prognosis in patients with heart disease is well recognized. However, factors contributing to exercise limitation in such patients have not been fully characterized and in particular, the role of lung function in determining exercise capacity has not been extensively investigated. OBJECTIVE: To examine the extent to which pulmonary function and respiratory muscle strength indices predict exercise performance in patients with moderate to severe heart failure. METHODS: Fifty stable heart failure patients underwent a maximal symptom-limited cardiopulmonary exercise test on a treadmill to determine maximum oxygen consumption (VO2max), pulmonary function tests and maximum inspiratory (PImax) and expiratory (PEmax) pressure measurement. RESULTS: In univariate analysis, VO2max correlated with forced vital capacity (r = 0.35, p = 0.01), forced expiratory volume in 1 s (r = 0.45, p = 0.001), FEV1/FVC ratio (r = 0.37, p = 0.009), maximal midexpiratory flow rate (FEF25-75, r = 0. 47, p < 0.001), and PImax (r = 0.46, p = 0.001), but not with total lung capacity, diffusion capacity or PEmax. In stepwise linear regression analysis, FEF25-75 and PImax were shown to be independently related to VO2max, with a combined r and r2 value of 0. 56 and 0.32, respectively. CONCLUSIONS: Lung function indices overall accounted for only approximately 30% of the variance in maximum exercise capacity observed in heart failure patients. The mechanism(s) by which these variables could set exercise limitation in heart failure awaits further investigation.     

Lymphocyte glutathione levels in children with cystic fibrosis.

OBJECTIVE: Lung disease in cystic fibrosis (CF) is characterized by a neutrophilic inflammatory response. This can lead to the production of oxidants, and to oxidative stress in the lungs. Glutathione (GSH) represents the primary intracellular antioxidant, and provides an important defense in the epithelial lining fluid. Evidence suggests that lymphocyte GSH reflects lung GSH concentrations, and so could potentially serve as a peripheral marker of lung inflammation. METHODS: We assessed peripheral blood lymphocyte GSH concentrations in 20 children (13 boys) with CF who were in stable condition at the time of evaluation. Values were compared with nutritional status and lung function parameters. RESULTS: Patients were 11.7+/-3.03 years old (mean +/- SD). Their percentage of ideal body weight was 101.8+/-17.92%; FEV1, 79.5+/-19.22% predicted; FEV1/FVC, 75.0+/-10.08%; and residual volume (RV)/total lung capacity (TLC), 31.3+/-10.47%. For the group, the GSH concentration was 1.31+/-0.52 micromol/10(6) lymphocytes, which was not different from laboratory control values. GSH values were correlated with nutritional status (percentage of ideal body weight: r = 0.49, p < 0.03) and the degree of gas trapping (RV/TLC: r = 0.50, p < 0.03), and were correlated inversely with airflow limitation (FEV1, percent predicted: r = -0.45, p < 0.05; FEV1/FVC: r = -0.48, p < 0.04), but not with age, height, or weight (p > 0.1). CONCLUSIONS: We interpret the inverse correlation between lymphocyte GSH concentration and lung function as a reflection of upregulation of GSH production by lung epithelial tissue in response to oxidative stress. We interpret the correlation between lymphocyte GSH concentration and nutritional status as a reflection of the role of cysteine in hepatic glutamine metabolism. Peripheral blood lymphocyte GSH concentration may potentially serve as a convenient marker of lung inflammation. Furthermore, the increased demand for GSH production in the face of ongoing inflammation suggests a potential role for supplementation with cysteine donors.     

Respiratory muscle strength in hyperthyroidism before and after treatment.

We undertook this study to investigate respiratory muscle strength in relation to thyroid function in 20 thyrotoxic patients and in a group of 20 normal subjects matched for age and sex. Global respiratory muscle strength was assessed by measuring mouth pressure during maximal static inspiratory (PImax) and expiratory (PEmax) efforts. We also measured VC, FVC, and FEV1 as well as thyroid-related hormones (T3, T4, TSH). Measurements were made once in normal subjects and twice in thyrotoxic patients, before and 3 months after medical treatment. Our results showed that both maximal pressures were significantly reduced (p less than 0.0001) before treatment in thyrotoxic patients in relation to the mean values of the normal subjects (p less than 0.0001), and they increased significantly (p less than 0.0003) after treatment. Lung volumes were significantly reduced (p less than 0.0001) before and increased significantly (p less than 0.008) after treatment. The ratio FEV1/FVC did not change. A statistically significant linear relationship was found when PImax of patients with thyrotoxicosis before treatment and of normal subjects were plotted against thyroid hormones (T3, T4) (r = -0.746 and r = -0.745, respectively, p less than 0.001). Similarly, a statistically significant linear relationship was found between PEmax and T3 and T4 (r = -0.837 and r = -0.838, respectively, p less than 0.001). No relationship was found between maximal pressures and TSH. Finally, a significant linear relationship was found between PImax and PEmax (r = 0.872, p less than 0.001). Our results confirm that in thyrotoxicosis respiratory muscle weakness occurs that affects both inspiratory and expiratory muscles.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relation between pulmonary ventilation parameters,exercise tolerance and quality of life in patients with chronic obstructive lung disease

Patients with chronic obstructive pulmonary disease (COPD) do usually have decreased tolerance of exercise capacity and impaired quality of life. Several studies have shown that exercise capacity is related relatively weakly to lung functions in this group of patients. The aim of the present study was to find parameter which could better reflect or predict maximal exercise capacity. 19 patients with the diagnosis COPD with mean value of forced expiratory volume in one second (FEV1) 46% predicted (range 21-79%) entering pulmonary rehabilitation program were included into the study. Enrolled patients were chosen to cover the whole range of airway obstruction severity. Post-bronchodilator static and dynamic ventilation parameters were used for evaluation and calculation. Quality of live was measured using St. George's respiratory questionnaire (SGRQ), evaluating symptoms, activity and impact of the disease with range from 0 (the best level) to 100 (the worst level). Values of FEV1 (p < 0.001) and ratio of FEV1 to vital capacity (FEV1/VC, p < 0.001) were significantly positively correlated with 6 minute walking distance (6MWD). FEV1/VC were closely related to 6MWD then FEV1. The degree of hyperinflation expressed by residual volume (RV, p < 0.005) and by ratio of residual volume to total lung capacity (RV/TLC, p < 0.001) significantly negatively correlated with 6MWD. Maximal occlusion mouth pressures (PImax, p < 0.05) were positively related to 6MWD. Total score of SGRQ correlated significantly to maximal exercise capacity. Pulmonary function tests and respiratory muscle function have important impact on exercise tolerance in patients with COPD. Tolerance of exercise capacity is significantly reflected by total score of quality of life in this group of patients.     

Improvement in spirometry following lung volume reduction surgery: application of a physiologic model.

According to a previously published theoretical model of emphysema, the ratio of RV to TLC (RV/TLC) reflects the size mismatch between the hyperinflated lungs in the disease and the surrounding chest. The model suggests that RV/TLC is an important predictor of improvement in FVC and that increased FVC is an important determinant of increased FEV(1) after lung volume reduction surgery (LVRS). We tested these predictions in 13 patients undergoing LVRS, in whom we made detailed measurements of lung mechanics. Using stepwise regression, we found that RV/TLC was the only preoperative independent predictor of the increase in FVC. Seventy percent of the increase in FEV(1) was attributable to increased FVC, with the remainder due to increased FEV(1)/FVC. In a separate group of 78 LVRS patients evaluated with standard preoperative pulmonary function tests, RV/TLC again was found to correlate with the increase in FVC, and changes in FEV(1) were also due largely to changes in FVC. However, RV/TLC was not predictive of the increase in FEV(1) among the group of 78 patients, because FEV(1)/FVC in patients with a low preoperative RV/TLC often increased despite little change in FVC. These findings support the proposed mechanism for increased FVC following LVRS. They also illustrate the limitations of the model, and suggest further hypotheses for selecting patients who may benefit from surgery.     

Factors associated with improvement in breathing capacity during exercise in patients with chronic obstructive pulmonary disease

OBJECTIVES: The aim of this study was to explore the relationship between resting pulmonary function indices and the ratio of minute ventilation at peak exercise to the maximal voluntary ventilation (VEmax/MVV) and to determine whether an improvement in breathing capacity during exercise (i.e. VEmax/MVV > 1) is associated with greater exercise capacity in patients with COPD. METHODOLOGY: The results of pulmonary function tests and incremental, symptom-limited cardiopulmonary exercise testing in 84 patients with predominantly moderate to severe COPD were reviewed. Multiple linear regression analysis was applied to determine the relationship of VEmax/MVV with selected independent variables at rest. Multiple logistic regression was used to determine significant predictors of VEmax/MVV 1. RESULTS: FEV1/FVC and inspiratory capacity (IC) were the only variables among resting pulmonary function indices that were significant independent determinants of VEmax/MVV and the stepwise analysis generated the following equation: VEmax/MVV = (-1.05E-02 x FEV1/FVC) + (0.15 x IC) + 1.28; r= 0.701, P < 0.001. Using multiple logistic regression with VEmax/MVV 1 as a dependent categorical variable, FEV1/FVC was the only significant predictor among resting pulmonary indices of a VEmax/MVV ratio of > 1 (Odds ratio 0.93, 95%CI 0.89, 0.97). There was a significant association between VEmax/MVV and peak oxygen uptake (VO2max) after adjusting for FEV1 (r = 0.66, P < 0.001). If the categorical variable of VEmax/MVV ( 1) was used instead of a continuous variable, a significant association with VO2max remained after adjusting for FEV1 (r = 0.60, P < 0.001). CONCLUSIONS: Among resting pulmonary function indices, the FEV1/FVC ratio is the best determinant of an improvement in breathing capacity during exercise in COPD patients. After adjusting for FEV1, an improvement in breathing capacity during exercise is associated with significantly higher exercise capacity.     

Tiotropium and simplified detection of dynamic hyperinflation

STUDY OBJECTIVE: To detect dynamic hyperinflation (DH) by evaluating reduction in inspiratory capacity (IC) during metronome-paced hyperventilation (MPH) in patients with moderate-to-severe COPD, studied before and after treatment with tiotropium. METHODS: IC and FEV(1) were measured before and immediately after MPH at two times resting the respiratory rate for 20 s in 60 COPD patients (28 men; mean age, 66 +/- 10 years [+/- SD]) before and after 30 days of treatment with tiotropium bromide, 18 mug. Patients were encouraged to maintain a constant tidal volume during MPH. RESULTS: At baseline, mean FEV(1) was 1.5 +/- 0.1 L (+/- SE) [57 +/- 1.6% of predicted], mean FVC was 2.6 +/- 0.1L (77 +/- 1.8% of predicted), and mean FEV(1)/FVC was 56 +/- 1%. After 180 mug of aerosolized albuterol sulfate, mean FEV(1) was 1.7 +/- 0.1 L (63 +/- 1.5% of predicted) [p < 0.001] and mean FEV(1)/FVC was 58 +/- 1%. Compared to baseline, after 30 days and 1.5 h after tiotropium there was an increase in IC of 0.18 +/- 0.04L (p < 0.0001); FEV(1) of 0.13 +/- 0.03 L (5.6 +/- 0.8% of predicted; p = 0.0002); FVC of 0.22 +/- 0.05 L (6.5 +/- 1.3% of predicted; p < 0.001); and decrease in end-expiratory lung volume (EELV)/total lung capacity (TLC) of - 3.1 +/- 0.6% (p = 0.0001); a decrease in end-inspiratory lung volume (EILV)/TLC of - 2.9 +/- 1.3% (p = 0.03); and no change in TLC (- 0.06 +/- 0.05 L). Results following MPH-induced DH at baseline and after 30 days of tiotropium were similar, with decreases in IC (- 0.35 +/- 0.03 L; p < 0.001); FEV(1) (- 0.05 +/- 0.04 L; p = 0.2); and FVC (- 0.22 +/- 0.03 L; p < 0.0001); no change in TLC; and increases in EELV/TLC (11.8 +/- 1.0% of predicted; p < 0.0001) and EILV/TLC (4.0 +/- 1.3% of predicted, p < 0.003). CONCLUSION: In patients with moderate-to-severe COPD, tiotropium did not reduce MPH-induced DH and reduction in IC, compared to baseline. However, because tiotropium induced bronchodilation and increased baseline IC, lower operational lung volumes may blunt the effect of MPH-induced DH. The noninvasive simplicity of MPH-induced DH provides a clinically useful screening surrogate to monitor changes in IC following treatment with tiotropium.     

慢阻肺患者支气管肺泡灌洗液中Cat S水平与肺功能和HRCT表型的相关性分析

目的检测慢阻肺患者支气管肺泡灌洗液中组织蛋白酶S的水平及与慢阻肺患者肺功能和高分辨CT表型的相关性研究。方法收集2014年1月至2018年1月在我院门诊治疗的稳定期慢阻肺患者72例,根据FEV 1占预计值%和FEV 1/FVC数值对患者进行GOLD分级,GOLDⅠ级17例、GOLDⅡ级25例、GOLDⅢ级21例、GOLDⅣ级9例,以及同期来我院就诊的并进行纤维支气管镜和BALF检测的健康志愿者23例;酶联免疫吸附试验检测BALF中组织蛋白酶S和γ-干扰素的水平;高分辨CT测量患者低衰减区域(LAA)占全肺体积的百分比(LAA%)、管壁面积占总横截面积比(WA)和2倍气道壁厚度与气道直径比(2T/D);组织蛋白酶S水平与患者肺功能指标和HRCT指标之间的相关性采用Pearson分析。结果对照组、GOLDⅠ级、GOLDⅡ级、GOLDⅢ级和GOLDⅣ级患者BALF中组织蛋白酶S的水平分别为(0.4±0.1)μg/L、(2.1±0.7)μg/L、(2.9±1.0)μg/L、(3.7±1.2)μg/L和(5.7±1.5)μg/L,组间比较差异具有统计学意义(F=12.47,P=0.000),且随着GOLD等级的增加而逐渐升高;对照组、GOLDⅠ级、GOLDⅡ级、GOLDⅢ级和GOLDⅣ级患者的肺功能检测指标FEV 1占预计值%、FEV 1/FVC、RV/TLC、DLCO和HRCT参数LAA%、2T/D和WA数值之间均有统计学差异;组织蛋白酶S水平与FEV 1占预计值%、FEV 1/FVC和DLCO占预计值的数值成负相关,(P<0.001)。组织蛋白酶S水平与RV/TLC、LAA、2T/D、WA和γ-干扰素的水平呈正相关,(P<0.001)。结论组织蛋白酶S的水平反应慢阻肺患者气流受限程度和肺气肿的表型,可能通过γ-干扰素参与慢阻肺的发生发展,有望成为慢阻肺的潜在标记物。     

Inspiratory force reserve of the respiratory muscles in children with chronic obstructive pulmonary disease

The purpose of this study was to evaluate inspiratory muscle force reserve in children with chronic obstructive pulmonary disease (COPD). In 15 hyperinflated (FRC/TLC, 65 +/- 0.7%) children, maximal mouth inspiratory static pressure (PImax) at FRC, mouth occlusion pressure (P0.1), tidal volume (VT), inspiratory time (TI), and total duration of the respiratory cycle (Ttot) were all measured. It was found that PImax at FRC was reduced compared with predicted values. However, after lung volume correction, PImax was in the normal range, and P0.1 was higher, TI was shorter, and Ti/Ttot was lower than predicted. The estimated mean inspiratory pressure for breathing at rest (PI) was significantly higher than predicted and was related to total pulmonary resistance (r = 0.74, p less than 0.001). The fraction of PImax developed by the respiratory muscles for breathing at rest (PI/PImax) significantly increased. The higher the PI/PImax ratio, the more the TI/Ttot ratio decreased (r = -0.64, p = 0.01). At rest, our subjects had to develop a mean inspiratory power (W) of as much as 48% (range, 30 to 76%) of the critical W above which fatigue occurs. Thus, even minimal increases in breathing load might expose children with COPD to respiratory muscle fatigue and to respiratory failure.     

The evaluation of dyspnea and quality of life in COPD

Dyspnea defined as an uncomfortable sensation of breathing is the main cause of disability in chronic obstructive pulmonary disease (COPD) patients. There is evidence that the underlying mechanisms of dyspnea are multifactorial. The aim of this study was to investigate these mechanisms causing dyspnea in COPD patients and the relationship between functional parameters, dyspnea scales and quality of life questionnaire. For this purpose 56 patients (11 female, 45 male) were recruited. Pulmonary function tests including airflow rates, lung volumes, maximal respiratory muscle forces, diffusing capacity, breathing pattern, arterial blood gas analyses as well as dyspnea scales MRC, baseline dyspnea index (BDI) and The Saint George Respiratory Questionnaire (SGRQ) were performed. The overall group showed moderate obstructive disease (FEV1%= 59.02 +/- 3.30) and mild hypoxemia with some air trapping (RV/TLC%= 52.00 +/- 2.00). MRC scale did not show any significant correlation with pulmonary function parameters. There was significant positive correlation between BDI and airflow rates, PImax, DLCO and air trapping. Breathing pattern parameters (Ti/Ttot, VT/Ti) also correlated with BDI. There was positive correlation between PaO2 and BDI (p< 0.001). SGRQ scores correlated significantly with FEV1, PImax, RV/TLC and P 0.1. There was also strong correlation between BDI and SGRQ scores. In conclusion, dyspnea is the result of multiple factors such as airflow limitation, decreased respiratory muscle strength, changes breathing pattern, hypoxemia, and air trapping which in turn affects quality of life in patients with COPD.     

Correlation between digital clubbing and pulmonary function in cystic fibrosis

The correlation between digital clubbing and certain pulmonary function derangements (hypoxemia and FEV(1)) was previously described. However, the relationship between digital clubbing and other measures of pulmonary function or the presence of liver disease in patients with cystic fibrosis (CF) is poorly defined. Hence we compared the digital clubbing index (CI: ratio of distal phalangeal depth to interphalangeal depth) of 100 patients with CF (43 males, 57 females; mean age, 15.7 +/- 7.3 years) with that of 100 age- and gender-matched healthy controls. Digital clubbing was defined as a CI > or = 1.00 (mean + 2.6 SD; 99% of normal subjects). The CI and its relationship to pulmonary function and to liver disease was then evaluated in the CF patients. Digital clubbing was present in 75/100 (75%) of CF patients but was absent in all controls (P < 0.0001). In CF patients, CI was inversely correlated with PaO(2) (r = -0.555; P < 0.001), FEV(1) (r = -0.499; P < 0.001), and FEF(25-75%) (r = -0.404; P < 0.001), and was positively correlated with RV (r = 0.285; P < 0.05) and the slope of phase 3 of single-breath nitrogen washout (SP3N(2)) (r = 0.532; P < 0.01). There was no significant correlation between CI and age (r = 0.020; P = 0.84), TLC (r = -0.097; P = 0.34), PaCO(2) (r = 0.167; P = 0.10), or history of liver disease (P = 0.08). We conclude that in CF, the degree of digital clubbing is related to degree of hypoxemia, airways obstruction, hyperinflation, and nonuniformity of ventilation.     

Prolonged oxygen kinetics during early recovery from maximal exercise in adult patients with cystic fibrosis

Study objectives: To explore the significance of oxygen kinetics during early recovery after maximal cardiopulmonary exercise testing (CPET) in the assessment of functional capacity and severity of the disease in cystic fibrosis (CF) patients. PARTICIPANTS: Eighteen patients with CF (9 male/9 female; mean +/- SD age, 23 +/- 13 years) and 11 healthy subjects (3 male/8 female; mean age, 29 +/- 4 years) underwent maximum CPET on a treadmill. Breath-by-breath analysis was used for measuring oxygen consumption (VO(2)), carbon dioxide production, and ventilation. Maximum VO(2) (VO(2)peak) and the first-degree slope of VO(2) decline during early recovery (VO(2)/t-slope) were calculated. To assess the severity of the disease, we used standard indexes like FEV(1) (% predicted), VO(2)peak, and a widely accepted system of clinical evaluation, the Schwachman score (SS). RESULTS: VO(2)/t-slope was significantly lower in CF patients compared to healthy subjects (0.61 +/- 0.31 L/min/min vs 1.1 +/- 0.13 L/min/min; p < 0.01) and was closely correlated to FEV(1)(r = 0.90, p < 0.001), VO(2)peak (r = 0.81, p < 0.001), and the SS (r = 0.81, p < 0.001). The multivariate analysis showed that the only independent predictor of the SS is the VO(2)/t-slope. CONCLUSION: We conclude that in CF patients, the prolonged oxygen kinetics during early recovery from maximal exercise is related to the disease severity.     

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.     

Assessing the usefulness of outcomes measured in a cystic fibrosis treatment trial

Forced expiratory volume in 1s (FEV(1)) is the usual primary outcome variable in clinical trials in cystic fibrosis (CF). Usually, several secondary outcomes are also measured. We assessed which secondary outcomes are likely to give additional clinically useful information about treatment effects, in order to inform the design of future studies. The study was performed as part of a trial comparing daily rhDNase with alternate day rhDNase and hypertonic saline in CF. The primary outcome was FEV(1). Secondary outcomes were forced vital capacity (FVC), forced expiratory flow at 25-75% of forced vital capacity (FEF(25-75)), number of pulmonary exacerbations, weight gain, quality of life (QOL), and exercise tolerance. The usefulness of each secondary outcome was investigated by assessing if the change in that outcome over the treatment period could be predicted from the primary outcome. Change in FEV(1) correlated with changes in FVC (r(2)=0.76, P=0.001), FEF(25-75) (r(2)=0.64, P=0.001), weight (r(2)=0.08, P=0.001), and change in oxygen saturation with exercise (r(2)=0.08, P=0.001). However, it did not correlate with changes in visual analogue score (VAS) with exercise, QOL, nor with the occurrence of pulmonary exacerbations. Only the outcomes QOL and VAS with exercise actually provided additional information to FEV(1) in this study.     

Acceleration of lung disease in children with cystic fibrosis after Pseudomonas aeruginosa acquisition

As part of the ongoing Wisconsin Cystic Fibrosis (CF) Neonatal Screening Project, we had the unique opportunity to study the longitudinal relationship between Pseudomonas aeruginosa (Pa) acquisition and infection and developing lung disease in children with CF. The primary objective was to determine whether acquisition of Pa was associated with a measurable change in the progression of lung disease. Two outcome measures were used to study 56 patients who were diagnosed through newborn screening: 1) Wisconsin additive chest radiograph score (WCXR), based on the average of scores from a pulmonologist and a radiologist, and 2) the highest forced expired volume in 1 sec (FEV(1))/forced vital capacity (FVC) ratio. We used two measures of Pa acquisition: 1) time of first positive protocol-determined oropharyngeal (with cough) culture, and 2) the magnitude of antibody titer detected by ELISA assays, using as antigen a crude cell lysate, purified exotoxin A, or an elastase toxoid prepared from three Pa strains. Other predictor variables included age, pancreatic status, height-for age, and weight-for-age-percentiles. The best regression model for predicting changes in the WCXR included time to first positive culture and antibody titer for Pa elastase. Prior to Pa acquisition, WCXR worsened by 0.45 points/year (P > 0.25); after Pa acquisition, the rate of worsening increased significantly (P < 0.001) to 1.40 points/year. Each antibody titer level (log base 2) increased the score by 0.48 points (P < 0.001). The best regression model for predicting change in the FEV(1)/FVC included only time to first positive culture. Prior to Pa acquisition, the FEV(1)/FVC ratio declined by 1.29%/year; after Pa infection, the rate of decrease significantly accelerated to 1.81%/year (P = 0.001). Our data show that Pa acquisition is associated with declining pulmonary status in children with CF, and that this effect is probably gradual rather than precipitous. Because these patients were diagnosed and treated aggressively, our estimates of the effects of Pa acquisition may be conservative. We also conclude that the WCXR appears to be more sensitive than FEV(1)/FVC in detecting early changes in lung disease associated with CF.     

Inspiratory muscle strength is a determinant of maximum oxygen consumption in chronic heart failure.

OBJECTIVE--To investigate the significance of respiratory muscle weakness in chronic heart failure and its relation both to maximum oxygen consumption during cardiopulmonary exercise testing and to skeletal muscle (quadriceps) strength. SUBJECTS--Seven healthy men aged 54.9 (SEM 4.3) years and 20 men with chronic heart failure aged 61.4 (1.6) years (P = 0.20) with radionuclide left ventricular ejection fraction of 25.4 (3.0)%. METHODS--Mouth pressures during maximum static inspiratory effort (PImax) at functional residual capacity (FRC) and residual volume (RV) were measured in all subjects and taken as indices of inspiratory muscle strength. Similarly, mouth pressures during maximum static expiratory effort (PEmax) at FRC and total lung capacity (TLC) were taken as indices of expiratory muscle strength. Cardiopulmonary exercise testing was performed in all subjects. All controls and 15 heart failure patients also had their right quadriceps muscle strength measured. RESULTS--There was respiratory muscle weakness in heart failure patients, with reduction of PImax at FRC (59.7) (6.3) v 85.6 (9.6) cm H2O, P = 0.045), PEmax at FRC (94.8 (6.2) v 134.6 (9.1) cm H2O, P = 0.004), and PEmax at TLC (121.7 (8.5) v 160.7 (13) cm H2O, P = 0.028). PImax at RV was also reduced but this did not reach statistical significance (77.3 (6.6) v 89.3 (13) cm H2O, P = 0.44). There was also significant weakness of the right quadriceps muscle (308.5 (22) v 446.2 (28) N, P = 0.001). PImax at both FRC and RV correlated with maximum oxygen consumption (r = 0.59, P = 0.006, and r = 0.45, P = 0.048 respectively) but not PEmax. There was, however, no significant correlation between PImax and right quadriceps strength. CONCLUSIONS--Respiratory muscle weakness is seen in chronic heart failure. The results suggest that inspiratory muscles are important in determining maximum oxygen consumption and exercise tolerance in these patients. The lack of correlation between respiratory and right quadriceps muscle strength further suggests that the magnitude and time course of respiratory and locomotor muscle weakness may differ in individual patients. Treatment aimed at improving the function of the involved muscle groups may alleviate symptoms.