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.     

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.     

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.     

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.     

The value of SF-36 questionnaire for the measurement of life quality in chronic obstructive pulmonary disease

This study was performed in chronic obstructive pulmonary disease (COPD) patients to compare the SF-36 questionnaire with pulmonary function tests and non-functional parameters. Fourty-five COPD patients diagnosed according to GOLD 2004 criteria were included in the study. The stable patients were evaluated by spirometry, static lung volumes, diffusion capacity, 6 MWD, BORG scale, MMRC dyspnea measurement and SF-36 life questionnaire performed on the same day. The mean age of the patients was 66 +/- 10 years and the female/male ratio was 4/41. The mean FEV1/FVC ratio was 0.49 (moderate COPD n = 18, severe COPD n = 27). The RV/TLC ratio was 0.52. Walking distance was less than normal, with a mean of 375 +/- 119 m. All the SF-36 scale except pain index are low compared to normal. General health perceptions, physical functioning, role physical, role emotional, social functioning, energy and mental health index are as follows: 47 +/- 24, 50 +/- 30, 35 +/- 38, 49 +/- 37, 63 +/- 33, 49 +/- 20, 59 +/- 20, respectively. When the general health scale compared with FVC and FEV1 revealed moderate correlation was found (r = 0.56, r = 0.55, respectively). Physical functioning compared with FVC, FEV1, RV/TLC and IC revealed moderate correlation (r = 0.62, r = 0.67, r = -0.54, r = 0.65, respectively). General health and physical functioning scales correlated with the non-functional parameters (MMRC, 6 MWD) (r = -0.51, r = 0.53, r = -0.61, r = 0.64 respectively). The SF-36 general quality of life questionnaire is a useful measurement instrument for the evaluation of therapeutic efficiency and follow up of COPD patients.     

Spirometry in 3- to 6-year-old children with cystic fibrosis

Spirometry is routinely used to assess pulmonary function of older children and adults with cystic fibrosis (CF); however, few data exist concerning the preschool age group. We have reported normative spirometric data for 3- to 6-year-old children. The current study was designed to assess a similarly aged group of clinically stable patients with CF. Thirty-three of 38 children with CF were able to perform 2 or 3 technically acceptable maneuvers. These patients had significantly decreased FVC, FEV(1), FEV(1)/FVC, and FEF(25-75) when expressed as z scores (number of SD from predicted): -0.75 +/- 1.63, -1.23 +/- 1.97, -0.87 +/- 1.33, and -0.74 +/- 1.63, respectively. There were significant positive correlations of the Brasfield radiological score with FVC and FEV(1) z scores (r(2) = 0.26, p < 0.01 and r(2) = 0.24, p < 0.01). In addition, homozygous patients for the DeltaF508 mutation had lower z scores for FVC (-1.21 versus 0.47, p < 0.01) and FEV(1) (-1.38 versus 0.21, p < 0.05) than heterozygous patients. Of the 14 patients who had full flow-volume spirometric measurements during infancy, 10 had FEF(25-75) z scores greater than -2 at both evaluations. Our findings suggest that spirometry can successfully be used to assess lung function in preschool children with CF and has the potential for longitudinal assessment from infancy through adulthood.     

Response of lung volumes to inhaled salbutamol in a large population of patients with severe hyperinflation

OBJECTIVES: Current criteria use FEV(1) to assess bronchodilator responsiveness, despite its insensitivity and inability to predict improvement in symptoms or exercise tolerance. Response in lung volumes remains largely unexplored even though volume parameters, such as inspiratory capacity (IC), closely correlate with functional improvements. Therefore, we assessed the response of lung volumes (i.e., by IC, total lung capacity [TLC], functional residual capacity [FRC], residual volume [RV], and FVC) to salbutamol and the relationship of these changes to improvements in the spirometry in these patients. DESIGN: A retrospective review of data extracted from a large database of patients who were undergoing spirometry and static lung volume measurements before and after the administration of 200 microg salbutamol. PATIENTS: Patients with an FEV(1)/FVC ratio of < 85% of predicted values were defined as being severely hyperinflated (SH) if TLC was > 133% of predicted and as being moderately hyperinflated (MH) if TLC was 115 to 133% of predicted. RESULTS: Two hundred eighty-one SH patients and 676 MH patients were identified. Salbutamol significantly reduced the mean (+/- SEM) TLC (SH patients, 222 +/- 23 mL; MH patients, 150 +/- 10 mL; p < 0.001), FRC (SH patients, 442 +/- 26 mL; MH patients, 260 +/- 39 mL; p < 0.001), and RV (SH patients, 510 +/- 28 mL; MH patients, 300 +/- 14 mL; p < 0.001) and increased both the IC (SH patients, 220 +/- 15 mL; MH patients, 110 +/- 11 mL; p < 0.001) and FVC (SH patients, 336 +/- 21 mL; MH patients, 204 +/- 13 mL; p < 0.001). FEV(1) improved in a minority of patients (SH patients, 33%; MH patients, 26%), but if lung volume measurements are also considered, the overall bronchodilator response may improve to up to 76% of the SH group and up to 62% of the MH group. Changes in volumes correlated poorly with changes in maximal airflows. CONCLUSIONS: Bronchodilators reduce hyperinflation. Measurements of lung volumes before and after bronchodilators add sensitivity when examining for bronchodilator responsiveness.     

Centrilobular nodules correlate with air trapping in diffuse panbronchiolitis during erythromycin therapy.

BACKGROUND: Low-dose erythromycin therapy improves airflow limitation and airway inflammation in patients with diffuse panbronchiolitis (DPB). However, to our knowledge there has been no study to determine whether physiologic improvement during erythromycin therapy correlates with radiologic findings. Study objective: To clarify whether improvement in pulmonary function correlates with specific changes on chest CT. DESIGN: The relationship between five CT findings and five pulmonary function parameters was evaluated before and 3 months after low-dose erythromycin therapy in 24 patients with DPB retrospectively. RESULTS: After erythromycin therapy, the predicted percentage of vital capacity (%VC; 87.0 +/- 3.07% vs 98.9 +/- 3.39%; p = 0.00006) and 50% of the maximum midexpiratory flow rate of FVC (1.41 +/- 0.26 L/s vs 1.61 +/- 0.27 L/s; p = 0.03) significantly increased, and the residual volume/total lung capacity ratio (RV/TLC%; 44.5 +/- 1.93% vs 40.7 +/- 1.83%; p = 0.0019) significantly decreased, but the FEV(1) to FVC ratio and 25% of the maximum expiratory flow rate of FVC did not. In five CT findings, centrilobular nodules (3.7 +/- 0.4 vs 1.5 +/- 0.3; p = 0.0001), peripheral bronchiolar wall thickness (3.8 +/- 0.3 vs 2.6 +/- 0.4; p = 0.0007), and peripheral bronchiolectasis (2.8 +/- 0.3 vs 2.2 +/- 0.4; p = 0.0058) had significantly improved, whereas low attenuation area and central bronchiectasis had not. There were positive correlations of improved scores of centrilobular nodules with improved %VC (r = 0.58, p = 0.0062) and RV/TLC% (r = 0.64, p = 0.0022). CONCLUSIONS: Decreased air trapping in DPB correlates with an improvement of centrilobular nodules, which reflects the obstructive lesions of bronchioles during the erythromycin therapy.     

Pulmonary function is negatively correlated with sputum inflammatory markers and cough clearability in subjects with cystic fibrosis but not those with chronic bronchitis

BACKGROUND: Polymorphonuclear neutrophil (PMN)-dominated inflammation is prominent in the airways of subjects with cystic fibrosis (CF) and chronic bronchitis (CB). Interleukin (IL)-8, myeloperoxidase (MPO), and DNA are markers of neutrophilic inflammation. We hypothesized that sputum MPO, DNA, and IL-8 concentrations would negatively correlate with pulmonary function and sputum transportability. METHODS: We measured pulmonary function and analyzed sputum IL-8, MPO, and DNA concentrations, as well as the transport properties of sputum samples obtained from 16 subjects with CF and 15 subjects with CB. We also evaluated changes in these measurements in paired sputum samples from these subjects obtained 2 to 12 months apart. RESULTS: IL-8 and MPO concentrations in the sputum of CF subjects was inversely correlated with FEV(1) percent predicted (IL-8: r = -0.40; p = 0.003; MPO: r = -0.38; p = 0.003) and FVC percent predicted (IL-8: r = -0.4; p = 0.02; MPO: r = -0.4; p = 0.02). IL-8 and DNA concentrations were inversely correlated with sputum cough transportability (CTR) [IL-8: r = -0.4; p = 0.02; DNA: r = -0.36; p = 0.048]. Changes in DNA concentration in sputum samples from CF subjects over time were inversely correlated with changes in FEV(1) percent predicted (r = -0.58; p = 0.02), FVC percent predicted (r = -0.74; p = 0.002), and CTR (r = -0.59; p = 0.02). There was no correlation among pulmonary function, sputum properties, and inflammatory markers in the sputum from subjects with CB. CONCLUSIONS: The sputum concentrations of IL-8, MPO, and DNA appear to be closely associated with pulmonary function in subjects with CF but not in subjects with CB.     

Quantitation of regional ventilation during the washout phase of lung scintigraphy: measurement in patients with severe COPD before and after bilateral lung volume reduction surgery

STUDY OBJECTIVES: We sought to investigate the effect of lung volume reduction surgery (LVRS) on regional lung ventilation. DESIGN: Retrospective analysis of routinely acquired data before and after LVRS. SETTING: Large, urban, university medical center. PATIENTS: Twenty-nine patients with severe emphysema. INTERVENTION: Bilateral LVRS. MEASUREMENTS AND RESULTS: (133)Xe washout curves during lung scintigraphy exhibit a biphasic pattern (the first component of the washout curve [m(r)] corresponds to an initial rapid phase in washout that reflects larger airways emptying, and the second component [m(s)] reflects a slower phase of washout that is attributed to gas elimination via smaller airways). We analyzed six standardized regions of the lung (upper, mid, and lower zones of the right and left lung), and calculated m(r) and m(s) for each lung region. The mean (+/- SE) baseline FEV(1) was 0.69+/-0.04 L, total lung capacity (TLC) was 139 +/-4% predicted, and the residual volume (RV)/TLC ratio was 65+/-2%. The mean improvement in FEV(1) 3 months post-LVRS was 38%. Post-LVRS, m(r) and m(s) increased in 79 and 74 lung regions, respectively, and there was no relationship with respect to lung regions that had or had not been operated on. The increase in m(s), however, significantly correlated with the increase in FEV(1) (r = 0.66; p<0.0001) and the decrease in RV/TLC (r = -0.67; p<0.0001). An increase in m(s) also correlated with a decrease in PaCO(2) (r = -0.39; p = 0.03), but m(r) showed no relationship with any parameter. CONCLUSIONS: Small airways ventilation in lung regions that had and had not been operated on is associated with a greater improvement in lung mechanics following LVRS.     

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.     

Effect and duration of lung volume reduction surgery: mid-term results of the Brompton trial

Although many studies have reported improvement in lung function following LVRS, the magnitude of improvement and subsequent decline has not been evaluated against medical therapy after the second year. METHODS: Existing pulmonary function records were collapsed for ech participant since randomisation from Brompton LVRS trial cohort. Longitudinal data analysis was used to profile th history of medically treated patients and the effect of LVRS. RESULTS: Pulmonary function results were collated from survivors over a median of 25 (17 to 39) months. The estimated immediate increase in mean FEV1, following surgery was +0.2591 (0.179, 0.339), with a rate of change of -0.0051 (-0.009, -0.001) per month compared to medical therapy (p < 0.001). The changes in the secondary outcome measures (LVRS compared to medical therapy) were an increase in FVC (p = 0.004), decrease in RV (p < 0.001) and TLC (p < 0.001), with differences that were maintained over time. The initial reduction in RV/TLC ration was sustained (p < 0.001), but the estimated initial increase in peak flow was accompanied by a gradual decline that was not statistically significant (p = 0.062). KCOc showed no immediate change, but there was a gradual sustained increase with time (p = 0.009). Mean oxygen saturations improved and continued to do so compared to patients on medical therapy (p = 0.001). CONCLUSIONS: The immediate increase in FEV1 is not sustained, although the mechanical improvements of LVRS on increasing FVC, reducing both the RV and RV/TLC ratio, appear to be maintained. The important benefits of LVRS may be the gradual and sustained increase in transfer factor accompanied by improved oxygen saturations.     

Physiological and symptom determinants of exercise performance in patients with chronic airway obstruction

To evaluate the physiological and symptom determinants of exercise performance (EP) as measured by a 6-min walking test (6MWD), Watt(max), and peak oxygen consumption (VO2 ml/min/kg), 105 patients with chronic airway obstruction (CAO) [50 chronic obstructive pulmonary disease (COPD): 44 men, aged 63+/-7 years, forced expiratory volume in 1 sec (FEV1) forced vital capacity (FVC)(-1)% 54+/-13; and 55 asthmatic: 23 men, aged 55+/-10 years, FEV1 FVC(-1) % 65+/-10] underwent evaluation of 6MWD, symptom limited cyclo-ergometer exercise test, spirometry, respiratory muscle function, arterial blood gases and sensation of dyspnoea [using the Borg scale, Visual Analogue Scale (VAS) and Baseline Dyspnoea Index (BDI)]. A hierarchical method of analysis identified the residual volume (RV), total lung capacity (TLC)(-1) ratio, BDI and the patient's age as the strongest and most consistent correlates of EP (r2 = 0.14-0.21). The correlation between EP and its various determinants was not influenced by diagnosis. The relationship between breathlessness and EP was different between men and women: at any given level of exercise, women were more breathless than men. In multivariate analyses that contained both RV TLC(-1) and BDI, the RV TLC(-1) ratio was the strongest correlate of EP, although the BDI remained a significant covariate. Overall, age was the major determinant of EP but inclusion of the RV TLC(-1) ratio and the BDI into the model explained a further 9-15% of the variance in EP. These three covariates together explained 26-34% of the variance between patients. We conclude that in stable CAO patients, the prediction of exercise capacity by anthropometric, demographic, clinical and physiological variables is likely to be low. Age, pulmonary hyperinflation and dyspnoea are the strongest and most consistent correlates of impaired exercise performance. Airways obstruction, measured during expiration using FEV1, does not appear to be a predictor of physiological impairment. These results underline the importance of performing exercise evaluation in CAO patients.     

Sources of error in flow-volume curves. Effect of expired volume measured at the mouth vs that measured in a body plethysmograph

The popularity of the maximum expiratory flow-volume curve (FVC) is in part due to the effort independence of expiratory flow. Of interest are expiratory flow rates at specific lung volumes, usually 50 and 25 percent of vital capacity (VC); Vmax50 and Vmax25, which make accurate assessment of lung volumes essential. Changes in lung volume during the test are due to both the volume of gas expired and the volume change due to gas compression (Vcomp). In normal subjects, Vcomp is small but may be considerable in those with airflow obstruction. When the FVC is measured in a plethysmograph (FVCp), both expired volume and Vcomp are measured. When the volume of the FVC is derived from gas expired at the mouth (FVCm), Vcomp is not considered and differences in Vmax25 or Vmax50 may occur. The magnitude of these errors was assessed in 30 children and young adults: nine normal subjects, ten with cystic fibrosis (CF) and 11 with asthma. For Vmax50, use of FVCm instead of FVCp resulted in an error of 8 +/- 7 percent (mean +/- 1 SD) in the normal subjects compared to 32 +/- 23 in those with CF (p less than 0.01) and 24 +/- 18 for those with asthma (p less than 0.05). For Vmax25, the errors were similar. These errors were not predictable from FEV1 or RV/TLC but were related to a combination of expiratory effort, the shape of the FVCp, and the absolute volume of gas that was being compressed (p less than 0.0001). These findings suggest that expiratory flows in the FVCm are not effort-independent in the face of significant airflow obstruction and that comparisons of values derived from an FVCp with those from an FVCm may not be valid.     

Effect of chronic airways obstruction on measurement of the single-breath carbon-monoxide-diffusing capacity

We have examined the effect of chronic airways obstruction on the measurement of the single-breath carbon-monoxide-diffusing capacity (DLCLSB). We reviewed the results of 136 consecutive pulmonary function tests (comprising standard spirometry, helium dilution lung volumes and DLCOSB) obtained in patients who had an FEV1/FVC less than 70%. We calculated DLCOSB using two different values for alveolar volume (VA). In the first method (HeDL), VA was measured by single-breath dilution of helium during the test. In the second method (RbDL), VA was measured as the sum of the inspiratory vital capacity, performed during the test, and the residual volume, determined separately by helium rebreathing. The mean HeDL/RbDL, reflecting disparity between computations of DLCOSB in individual subjects was 0.85 +/- 0.13 in patients with moderate obstruction (40 less than or equal to FEV1/FVC% less than 60) and was 0.80 +/- 0.14 in those with severe obstruction (FEV1/FVC% less than 40). The mean HeDL/RbDL was lowest (0.73 +/- 0.12) in those with severe elevation of RV/TLC (RV/TLC% greater than 60). HeDL/RbDL correlated best with RV/TLC (r = -0.71, p less than 0.001). Unexplained variance in HeDL/RbDL was not significantly reduced by including the relationship between HeDL/RbDL and pulmonary function indices commonly used to measure airways resistance. These data suggest (1) the difference between HeDL and RbDL in patients with moderate and severe chronic airways obstruction is greater than previously reported; (2) the disparity between HeDL and RbDL stems from slow space ventilation rather than from increased resistance to air flow, and (3) HeDL underestimates gas transfer in poorly ventilated lung compartments.     

Prognostic value of bronchoalveolar lavage lymphocyte count in recently diagnosed pulmonary sarcoidosis.

We prospectively looked at the prognostic value of bronchoalveolar lavage (BAL) lymphocyte count in 98 patients with recently diagnosed (less than 4 months) untreated sarcoidosis. These 50 men and 48 women (mean age, 37.4) were followed up for a period of 6 to 60 months (mean, 25.6), and were clinically evaluated every three to six months with repeated chest roentgenograms and pulmonary function tests. Twenty-four patients required steroid treatment during the study period. The proportion of treated patients was not significantly higher in the group presenting a BAL lymphocyte count less than or equal to 30 percent at diagnosis than in the group with fewer lymphocytes (31.9 and 17.7 percent of total group respectively, p = 0.10). No significant change in TLC, FRC, FVC, FEV1 or DLCO was found at follow-up between the groups with or without an initial high lymphocyte count. In the treated group, BAL lymphocyte percent weakly correlated with the improvement of FEV1 and FVC while on steroid treatment (mean duration: 3.5 months): r = 0.41, p = 0.031 and r = 0.36, p = 0.05 respectively; no correlation was found with lung volumes and DCO. We conclude that BAL lymphocyte count at the time of diagnosis is not a helpful predictor of lung function deterioration in recently diagnosed sarcoidosis and is not very useful in predicting response to treatment.     

肺移植对5例慢性阻塞性肺疾病患者肺功能的影响

目的研究单肺移植手术治疗慢性阻塞性肺疾病(COPD)对呼吸生理及肺功能的影响。方法5例患者均为Ⅳ级COPD男性患者,年龄51～63岁。术前2周测定患者用力肺活量(FVC)、第一秒用力呼气容积(FEV1)、FEV1/FVC、最大通气量(MVV)、残气容积(RV)、肺总量(TLC)、残总比(RV/TLC)、深吸气量(IC)、胸腔气体容积(TGV)、呼气峰流量(PEF)、总气道阻力(Rawtotal)、肺一氧化碳弥散量(DLCO)、每升肺泡容积肺一氧化碳弥散量(DLCO/V·A)、6分钟行走距离(6MWD)、动脉血氧分压(PaO2)、肺泡气动脉血氧分压差[P(Aa)O2]、动脉血氧饱和度(SaO2)、动脉血二氧化碳分压(PaCO2)及平均肺动脉压(mPAP)等参数。术后2个月再行上述测定。结果5例患者术前2周、术后2个月检测的参数为MVV(23.6±5.8)、(71.6±21.8)L,FEV1(0.68±0.21)、(1.85±0.46)L,FEV1/FVC(37.4±8.3)、(75.6±13.9)%,PaO2(60.0±9.1)、(86.2±2.9)mmHg(1mmHg=0.133kPa),SaO2(90.0±4.6)%、(96.8±0.5)%及mPAP(31.2±5.5)、(16.6±1.8)mmHg,均有显著改善(P均<0.05);3例患者IC[(1.16±0.26)、(1.83±0.35)L]、TGV[(6.52±0.27)、(4.52±0.29)L]、RV[(5.12±0.39)、(3.20±0.32)L]、RV/TLC[(71.0±5.6)、(51.3±2.5)%]及Rawtotal[(6.62±0.99)、(2.48±0.87)cmH2O·L-1·s-1]改善显著(P均<0.05);4例患者PEF[(1.65±0.40)、(3.92±1.63)L/s]、DLCO[(8.5±3.0)、(21.0±6.2)ml·min-1·mmHg-1]及6MWD[(46.8±14.7)、(246.8±51.9)m]也显著增加(P均<0.05);FVC[(1.85±0.40)、(2.45±0.49)L]、TLC[(7.19±0.15)、(6.26±0.73)L]、DLCO/V·A[(2.90±1.50)、(5.41±0.87)L·min-1·mmHg-1]、P(Aa)O2[(37.6±16.3)、(17.8±6.3)mmHg]及PaCO2[(44.6±7.7)、(37.4±3.4)mmHg]有所改善,但差异无统计学意义(P均>0.05)。结论COPD患者肺移植术后肺通气、气道阻力、残气、弥散、运动耐力及气体交换功能均明显改善。     

The levels of oxidant and antioxidant in patients with COPD

It is determinate that oxidant-antioxidant imbalance is responsible for pathogenesis of chronic obstructive pulmonary disease (COPD) and smoking is playing a part in the pathogenesis. It was aimed to investigate the oxidant-antioxidant imbalance in smokers and pathogenesis of COPD and their relations with lung functions. This study was done prospectively in Firat University Medical Faculty, Department of Chest Diseases. The levels of plasma malonyldialdehyde (MDA), erythrocyte reducted glutathione (GSH) and erythrocyte catalase were studied in 20 patients with COPD, in 20 smokers and in 20 nonsmokers. All of the cases were male. Pulmonary function tests were done to all cases and the predicted values of FEV1, FVC, and FEV1/FVC were measured. The levels of plasma MDA: 1.44 +/- 0.23 nmol/mL, 1.51 +/- 0.27 nmol/mL and 1.29 +/- 0.13 nmol/mL, the levels of erythrocyte GSH: 0.33 +/- 0.13 micromol/g.Hb, 0.34 +/- 0.17 micromol/g.Hb and 0.44 +/- 0.14 micromol/g.Hb and the levels of catalase were 22.82 +/- 17.47 k/g.Hb, 32.88 +/- 22.36 k/g.Hb and 55.73 +/- 26.56 k/g.Hb in patients with COPD, smokers and healthy nonsmokers respectively. There was no significance in each three parameters between smokers and patients with COPD. A significant difference was observed in each three parameters between nonsmokers and patients with COPD (MDA: p= 0.001, GSH: p= 0.028 and catalase: p< 0.001) and between smokers and nonsmokers (MDA: p= 0.035, GSH: p= 0.016 and catalase: p= 0.005). In all three groups, no significant correlation was found between FEV1 (predicted %), FEV1/FVC (predicted %) and the values of erythrocyte catalase, GSH and plasma MDA. In this study, there was an oxidant-antioxidant imbalance systemically in smokers and in patients with COPD. However, decreasing in the antioxidant capacity and/or increasing in the oxidant capacity either not correlate with spirometric measurements of airway obstruction in smokers or in patients with COPD were observed. We concluded that the use of cigarette increased oxidative stress by causing plasma lipid peroxidation and imbalance in erythrocyte antioxidant capacity.     

肺泡蛋白沉着症肺功能检查特点:附27例分析

目的 肺泡蛋白沉着症(PAP)在临床上极为罕见,其肺功能检查特点的报道也极少,本研究目的在于探讨肺功能检查在PAP诊断和治疗中的价值.方法 回顾性分析本院呼吸疾病研究所经肺组织病理(过碘酸雪夫反应阳性)确诊的27例PAP患者的临床资料.全部病例均给予肺通气和弥散功能测试,其中12例进行了肺容积测试.比较了10例行支气管肺泡灌洗(BAL)治疗的患者在灌洗前、后肺功能的改变情况.结果 27例患者入院后的基础通气肺功能情况:用力肺活量(FVC):(79.67±16.21)%;第1秒用力呼气容积(FEV1):(83.94±16.07)%,一秒率(FEV1/FVC):(89.20±5.50)%;最大呼气流量(PEF):(107.64±17.73)%;肺一氧化碳弥散量(DLCO):(49.27±21.83)%;DLCO与肺泡通气量比值(DLCO/VA):(69.92±20.11)%.肺总量(TLC):(80.60±19.56)%;残气容积(RV):(86.03±38.10)%;残总比(RV/TLC):(32.73±9.48)%;功能残气量(FRC):(84.91±28.08)%.27例患者基础肺功能下降的异常率:FVC:55.6%(15例);FEV1:44.4%(12例);FEV1/FVC:0%(0例);PEF:3.7 %(1例);DLCO:88.9%(24例);DLCO/VA:70.4%(19例).12例患者肺容积的异常率:TLC下降者占50%(6例);RV下降者占41.7%(5例),升高者占16.7%(2例);RV/TLC升高者占50%(6例);FRC下降者占33.3%(4例).10例进行BAL治疗的患者术后肺功能改善率:FVC:5.47%;FEV1:5.50%;DLCO:31.07%;DLCO/VA:20.35%.灌洗前后DLCO及DLCO/VA差异有统计学意义(t=-3.551,-3.159;P=0.006,0.012).结论 PAP的肺功能检查以肺限制性通气功能障碍及肺弥散功能障碍为常见,尤其为弥散功能障碍.PAP经BAL治疗后肺弥散功能有显著性改善.     

Alveolar and airway sites of nitric oxide inflammation in treated asthma

The goal of this study was to identify airway and alveolar site(s) of inflammation using exhaled nitric oxide (NO) as a marker in treated patients with asthma, including response to oral corticosteroids, and correlate these sites with expiratory airflow limitation. In 53 (24 male) patients with asthma, age 43 +/- 23 years (mean +/- SD) and all on inhaled corticosteroids, post 180 microg aerosolized albuterol, FEV(1) was 74 +/- 23% predicted and FEV(1)/FVC was 68 +/- 11%. Exhaled NO at 100 ml/second was 27 +/- 23 ppb (p < 0.001 compared with normal, 12 +/- 15 ppb). Bronchial NO maximal flux was 2.4 +/- 3.1 nl/second (p < 0.001 compared with normal, 0.85 +/- 0.55). Alveolar NO concentration was 7.0 +/- 7.4 ppb (p = 0.01 compared with the normal value, 3.2 +/- 2.0 ppb). There was no significant correlation between FEV(1) % predicted or lung elastic recoil and NO bronchial flux or alveolar concentration. However, there was a weak but significant correlation between NO bronchial flux and alveolar concentration (Spearman r = 0.50, p < 0.001). In 10 subjects with asthma on inhaled corticosteroids, 5 days of 30 mg prednisone resulted in isolated significant decreases in NO alveolar concentration, from 13 +/- 10 to 4 +/- 4 ppb (p = 0.002). Despite treatment, including inhaled corticosteroids, patients with asthma may have ongoing separate airway and alveolar sites of NO inflammation, the latter responsive to oral corticosteroids.