Alveolar volume determined by single-breath helium dilution correlates with the high-resolution computed tomography-derived nonemphysematous lung volume

BACKGROUND: The alveolar volume (V(A)), determined by single-breath helium dilution, is a measure for the total lung capacity (TLC) that is very sensitive to ventilatory disturbances. In chronic obstructive pulmonary disease (COPD), the emphysematous lung parts are less accessible to test gas; therefore, the V(A) is smaller than TLC measured by multiple-breath helium dilution (TLC(He)). OBJECTIVES: The aim of this study was to investigate whether the V(A) represents the nonemphysematous lung parts. METHODS: We measured V(A) as part of the diffusing capacity for carbon monoxide (DL(CO)), TLC(He) and spirometry in 50 patients with COPD. High-resolution computed tomography (HRCT) scans of all subjects were analyzed with the density mask method, where parts with an attenuation of less than -950 Hounsfield units were considered as emphysematous. RESULTS: A strong correlation was observed between the V(A) (mean 5.2 liters) and nonemphysematous HRCT lung volume (mean 5.2 liters, r(2) = 0.9) and between the TLC(He) (mean 6.6 liters) and total HRCT lung volume (mean 6.4 liters, r(2) = 0.9). Bland-Altman plots showed considerable disagreement between the V(A) and the nonemphysematous HRCT lung volume. A weak correlation between the forced expiratory volume in 1 s (mean 46% predicted) and DL(CO) (mean 46% predicted) versus the HRCT emphysema ratio (nonemphysematous/total HRCT lung volume) was observed (r(2) = 0.3 and 0.3, respectively). CONCLUSION: We concluded that the V(A) correlates with the nonemphysematous HRCT lung volume, although the two measurements are not equivalent, possibly due to technical factors.     

The 1-year impact of severe acute respiratory syndrome on pulmonary function, exercise capacity, and quality of life in a cohort of survivors

OBJECTIVE: To examine pulmonary function, exercise capacity, and health-related quality of life (HRQoL) among severe acute respiratory syndrome (SARS) survivors. METHODS: We evaluated survivors with confirmed SARS at the Prince of Wales Hospital, Hong Kong, at 3, 6, and 12 months after symptom onset. Our assessment included: lung volume (total lung capacity [TLC], vital capacity, residual volume, functional residual capacity), spirometry (FVC, FEV1), diffusing capacity of the lung for carbon monoxide (D(LCO)), inspiratory and expiratory respiratory muscle strength, 6-min walk distance (6MWD), chest radiographs (CXRs), and HRQoL by Medical Outcomes Study 36-Item Short-Form General Health Survey questionnaire. RESULTS: Ninety-seven patients completed the serial assessments. There were 39 male and 58 female patients, and 63 patients (70%) were health-care workers (mean age, 36.9 years [SD, 9.5 years]; body mass index, 23.7 kg/m2 [SD, 4.0 kg/m2]). At 1 year, 27 patients (27.8%) had abnormal CXR findings. Four patients (4.1%), 5 patients (5.2%), and 23 patients (23.7%) had FVC, TLC, and D(LCO) values < 80% of predicted values, respectively. The 6MWD at 12 months was 511.0 m (SD, 89.8 m), which was higher than at 3 months (mean difference, 47.0 m; 95% confidence interval [CI], 31.8 to 62.1 m; p < 0.01) but not different from 6 months (mean difference, 9.7 m; 95% CI, - 4.4 to 23.8 m; p = 0.18). The 6MWD was lower than that for normal control subjects of the same age groups, and there was impairment of HRQoL at 12 months. Patients who required ICU admission (n = 31) showed higher CXR scores (1.6 [SD, 3.1]; vs 0.4 [SD, 1.1]; p = 0.04) and lower percentage of predicted FVC, TLC, and Dlco than those who did not, but there were no differences in 6MWD and health status. CONCLUSION: Significant impairment in Dlco was noted in 23.7% of survivors 1 year after illness onset. Exercise capacity and health status of SARS survivors were remarkably lower than those of a normal population.     

Alveolar-capillary membrane conductance is the best pulmonary function correlate of exercise ventilation efficiency in heart failure patients

BACKGROUND: In heart failure (HF), changes in lung mechanics and gas diffusion are limiting factors to exercise. Their contribution to an increased exercise ventilation to CO2 production (VE/VCO2) slope is undefined. METHODS: A total of 67 stable HF patients underwent cardiopulmonary exercise and pulmonary function tests, including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), maximal voluntary ventilation (MVV), total lung capacity (TLC) and alveolar diffusing capacity with its subcomponents (alveolar-capillary membrane conductance (D(m)) and capillary blood volume (V(c))). RESULTS: Patients showed a mild restrictive pattern (FEV1=85+/-15% and FVC=75+/-13% of normal predicted) and a moderate D(m) reduction (32+/-12 ml min(-1) mm Hg(-1)). Average peak VO(2) was 15.6+/-4.0 ml min(-1) kg(-1) and the VE/VCO2 slope was 39.6+/-11.0. At simple Spearman correlation analysis, all variables, but V(c), correlated with peak VO2; only D(m) correlated with VE/VCO2 slope. At partial Spearman correlation, all variables lost the peak VO2 correlation, and D(m) still inversely correlated with VE/VCO2 slope (r=-0.35; p=0.005). In patients with a high VE/VCO2 slope (cutoff value 34), despite comparable lung volumes, D(m) was significantly more depressed (30+/-13 vs. 35+/-10 ml min(-1) mm Hg(-1); p<0.01). CONCLUSIONS: Pulmonary function tests and alveolar gas diffusing capacity poorly correlate with peak VO2. D(m) impairment rather than lung volumes correlates with exercise ventilation efficiency. This finding further adds to the pathophysiological relevance of an abnormal gas exchange in HF patients.     

Residual volume in a general population. Effects of body size, age, cigarette smoking, and respiratory symptoms.

Residual volume (RV) was obtained by subtracting vital capacity from total lung capacity determined by the single breath helium dilution (TLCsb) to measure CO diffusing capacity in 2,680 subjects (8 to 64 years old) of a general population sample. There were 712 normal subjects (243 male and 469 female subjects) selected to evaluate the pattern of RV by age and to derive reference values for internal comparisons. From 8 to 20 years old, RV showed an increase because of the cross-sectional body size effect; after 20 to 30 years, RV was still increasing, however, at a lower level. Age and height coefficients were significantly related to RV in younger and older ages, both in male and female subjects. The RV percent predicted and RV/TLC percent were higher in smokers when compared to nonsmokers and exsmokers (the difference was significant in male subjects). A dose-response effect was observed between RV percent predicted, RV/TLC percent, and pack-years. The RV percent predicted and RV/TLC percent were significantly higher in smokers and nonsmokers with FEV1 percent predicted below the normal limit (the difference was significant in male subjects). Moreover, higher values of RV percent predicted and RV/TLC percent were observed in subjects with wheezy symptoms in male smokers and nonsmokers. A negative significant correlation was observed between RV/TLC percent and the diffusing capacity adjusted for lung volume (DL/VA) in smokers, exsmokers and nonsmokers of both sexes, confirming the hypothesis that the decrease in DL/VA may be ascribed to the enlargement of terminal air spaces. In conclusion, determination of RV by the single breath helium dilution method is suitable in epidemiology, and it allows additional important information for understanding the physiopathologic mechanisms related to the pathogenesis of chronic obstructive lung disease.     

Long-term physiologic outcome after acute farmer's lung

We performed a follow-up study of 61 patients who had an acute episode of farmer's lung (54 men and seven women). Twenty-four subjects had ceased all contact with the barn, while 37 had continued farming. Pulmonary function tests for all subjects showed an initial improvement after the acute episode: 92.4 +/- 36.9 percent of predicted for carbon monoxide diffusing capacity (Dco) after one year, compared to 61.5 +/- 28.5 percent at diagnosis (p less than 0.01); and 6.01 +/- 1.50 L for total lung capacity (TLC) after three years, compared to 5.35 +/- 1.42 L (p less than 0.05). Subsequently, pulmonary function decreased over time. Five years or more after the acute episode, pulmonary function tests in subjects who had continued farm work were not worse than those of subjects who had ceased contact for Dco (68.1 +/- 21.4 percent of predicted vs 80.6 +/- 27.7 percent, respectively [p greater than 0.1]) and for TLC (5.55 +/- 1.31 L vs 5.90 +/- 0.84 L [p greater than 0.2]). This study shows that during a long-term follow-up, subjects with farmer's lung who stayed on the farm have subnormal values for pulmonary function but comparable values to those who left their farm.     

Pretransplant lung function, respiratory failure, and mortality after stem cell transplantation

RATIONALE: The role of pulmonary function before stem cell transplant as a potential risk factor for the development of early post-transplant respiratory failure and mortality is controversial. METHODS: We conducted a retrospective analysis of the pretransplant pulmonary function of 2,852 patients who received their transplant between 1990 and 2001. MEASUREMENTS: Pretransplant FEV(1), FVC, total lung capacity (TLC), diffusing capacity of carbon monoxide (DL(CO)), and the alveolar-arterial oxygen tension difference P(A-a)O(2) were measured and assessed for association with development of early respiratory failure and mortality in Cox proportional hazard logistic models. MAIN RESULTS: In multivariate analyses, progressive decrease of all lung function parameters was associated with a stepwise increase in risk of developing early respiratory failure and mortality when assessed in independent models. On the basis of a significant correlation between FEV(1) and FVC (r = 0.81), FEV(1) and TLC (r = 0.61), and FVC and TLC (r = 0.80), and a lack of correlation between FEV(1) and DL(CO), we developed a pretransplant lung function score based on pretransplant FEV(1) and DL(CO) to determine the extent of pulmonary compromise before transplant. Multivariate analysis indicated that higher pretransplant lung function scores are associated with a significant increased risk for developing early respiratory failure (category II hazard ratio [HR], 1.4; category III HR, 2.2; category IV HR, 3.1; p < 0.001) and death (category II HR, 1.2; category III HR, 2.2; category IV HR, 2.7; p < 0.005). CONCLUSIONS: These results suggest that not only does compromised pretransplant lung function contribute to the risk for development of early respiratory failure and mortality but this risk may be estimated before transplant by grading the extent of FEV(1) and DL(CO) compromise.     

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.     

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。     

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.     

A normal FEV1/VC ratio does not exclude airway obstruction

BACKGROUND: A decreased forced expiratory volume in 1 s/vital capacity (FEV(1)/VC) ratio is the hallmark of the definition of airway obstruction. We recently suggested that a lung function pattern, we called small airways syndrome (SAOS), has a normal FEV(1)/VC and total lung capacity (TLC) and reflects obstruction of small airways. OBJECTIVES: To substantiate our hypothesis we measured and compared lung function tests including maximal expiratory flow rates (MEFR), sensitive indicators of airway obstruction, in SAOS subjects and in matched controls. METHODS: We selected 12 subjects with the pattern of SAOS, but without chronic lung or heart disease (average age: 40.7 +/- 7.8 years) and 36 age-matched subjects with normal lung function (42.8 +/- 6.3 years). We measured static and dynamic lung volumes, MEFR and lung diffusing capacity (DL(CO)). RESULTS: SAOS subjects were heavier smokers (p < 0.05) and body mass index was less than in control subjects (p < 0.01). Both FEV(1)/VC ratio and TLC were comparable in the two groups. However, FEV(1), VC, DL(CO), and MEFR were lower and residual volume (RV) and RV/TLC ratio were higher (p < 0.05) in the SAOS group than in the control one. Furthermore, the MEFR curve of the SAOS group was displaced to the left without any change in slope, suggesting premature airway closure. CONCLUSION: Our results suggest that a normal FEV(1)/VC ratio does not exclude airway obstruction. A decrease of FEV(1), provided TLC is normal, reflects small airway obstruction.     

Rest and exercise cardiac output and diffusing capacity assessed by a single slow exhalation of methane, acetylene, and carbon monoxide

To study rest and exercise pulmonary capillary blood flow (Qc) and diffusing capacity (DLexh) assessed by the rapid analysis of methane, acetylene, and carbon monoxide during a single, slow exhalation, we evaluated 36 subjects during first-pass radionuclide angiography (RNA). At rest (N = 36) and at exercise (N = 21) there was no difference in the respective measurements of cardiac output (Qc = 6.0 +/- 1.7 and CORNA = 6.9 +/- 2.5 at rest; Qc = 13.7 +/- 3.2 and CORNA = 14.5 +/- 4.1 at exercise, L/min, mean +/- SD, r = .80). Mild maldistribution of ventilation, as manifested by an increased phase 3 alveolar slope for methane (CH4 slope), did not significantly influence the results. CH4 slope and DLexh did increase significantly with exercise, while total lung capacity remained unchanged (CH4 slope: 6.2 +/- 5.0 vs 12.5 +/- 6.8% delta CH4/L, mean +/- SD, p less than 0.001; Dsb: 27.7 +/- 9.2 vs 42.0 +/- 17.9 ml/min/mm Hg, mean +/- SD, p less than 0.001; TLC: 5.47 +/- .20 vs 5.96 +/- 1.20 L, mean +/- SD). DLexh was related to CORNA (r = .68) and RNA stroke volume (r = .50). Qc was significantly less than CORNA in the subset of studies with valvular regurgitation (VHD) (N = 7). On the other hand, Qc was significantly greater than CORNA in the setting of coronary artery disease (CAD) and severe wall motion abnormalities (N = 7). These differences may be attributed to regurgitant fractions in VHD, and the influence of wall motion abnormalities on the estimation of left ventricular volume by the area-length method in CAD. These two noninvasive methods compare well at rest and exercise in clinical subjects and may provide complementary information in certain cardiopulmonary diseases.     

Pulmonary complications of Type 1 (insulin-dependent) diabetic patients

Summary We have investigated the influence of diabetes mellitus including the presence of late complications on the pulmonary system. To check this relationship 31 Type 1 (insulin-dependent) diabetic patients (mean age 30.6±5.32 years, mean duration of diabetes 12.9±5.05 years) were admitted into the trial and compared with 18 control subjects. Pulmonary function tests were measured including spirometric parameters, diffusing capacity, specific diffusing capacity and dynamic compliance measured at 20 and 60 breaths per min. No disturbance of the spirometric parameters was observed in the diabetic patients. Diffusing capacity in the diabetic patients with complications was significantly lower than in both the diabetic patients without complications and the control group (81.2±16.2%, 104±13.7%, 99.3±2.8%; p<0.001, p<0.005 respectively). Specific diffusing capacity was significantly lower in the diabetic patients than in the control subjects (80.3±13.1% vs 89.4±12.9%; p<0.05). In the group with late complications specific diffusing capacity was lower than in the group without complications (69.7±9.17%; 87.2±10.7%, respectively; p<0.001). Dynamic compliance at 20 breaths per min in diabetic patients was 84.06±17.08% vs 95.2±11.59% in the control subjects (p<0.05). It was particularly low in the group with late complications 80.6±13.2% and patients with metabolic poor control, 80.3±12.02% (both p<0.005 vs the control group). Dynamic compliance at 60 breaths per min was 60.1±15.0% as compared to 83.2±13.3% in the control group (p<0.001). We conclude that the disturbances of dynamic compliance may be due to the local mosaic abnormalities of lung elasticity, caused by the non-enzymatic glycation of protein. Disturbances in diffusion in diabetic patients confirm the presence of microangiopathy in pulmonary vessels.     

Ventilation Distribution Heterogeneity at Rest as a Marker of Exercise Impairment in Mild-to-Advanced COPD

The difference between total lung capacity (TLC) by body plethysmography and alveolar volume (VA) from the single-breath lung diffusing capacity measurement provides an index of ventilation distribution inequalities in COPD. The relevance of these abnormalities to dyspnea and exercise intolerance across the continuum of disease severity remains unknown. Two-hundred and seventy-six COPD patients distributed across GOLD grades 1 to 4 and 67 healthy controls were evaluated. The “poorly communicating fraction” (PCF) of the TLC was estimated as the ratio (%) of TLC to VA. Healthy subjects showed significantly lower PCF values compared to GOLD grades 1 to 4 (10 ± 3% vs. 17 ± 8% vs. 27 ± 10% vs. 37 ± 10% vs. 56 ± 11%, respectively; p < 0.05). Pulmonary gas exchange impairment, mechanical ventilatory constraints and ventilation-corrected dyspnea scores worsened across PCF tertiles (p < 0.05). Of note, GOLD grades 1 and 2 patients with the highest PCF values had pronounced exercise ventilatory inefficiency and dyspnea as a limiting symptom. In fact, dyspnea was a significant contributor to exercise limitation only in those with “moderate” or “extensive” PCF (p < 0.05). A receiver operating characteristics curve analysis revealed that PCF was a better predictor of severely reduced maximal exercise capacity than traditional pulmonary function indexes including FEV₁ (area under the curve (95% confidence interval) = 0.85 (0.81–0.89), best cutoff = 33.4%; p < 0.01). In conclusion, PCF is a readily available functional marker of gas exchange and mechanical abnormalities relevant to dyspnea and exercise intolerance across the COPD grades.     

Resting Physiological Correlates of Reduced Exercise Capacity in Smokers with Mild Airway Obstruction

Smokers with minor spirometric abnormalities can experience persistent activity-related dyspnea and exercise intolerance. Additional resting tests can expose heterogeneous physiological abnormalities, but their relevance and association with clinical outcomes remain uncertain. Subjects included sixty-two smokers (≥20 pack-years), with cough and/or dyspnea and minor airway obstruction [forced expiratory volume in one-second (FEV₁) ≥80% predicted and >5th percentile lower limit of normal (LLN) (i.e., z-score >?1.64) using the 2012-Global Lung Function Initiative equations]. They underwent spirometry, plethysmography, oscillometry, single-breath nitrogen washout, and symptom-limited incremental cycle exercise tests. Thirty-two age-matched nonsmoking controls were also studied. Thirty-three (53%) of smokers had chronic obstructive pulmonary disease by LLN criteria. In smokers [n = 62; age 65 ± 11 years; smoking history 43 ± 19 pack-years; post-bronchodilator FEV₁ z-score ?0.60 ± 0.72 and FEV₁/FVC z-score ?1.56 ± 0.87 (mean ± SD)] versus controls, peak oxygen uptake (?VO₂) was 21 ± 7 vs. 32 ± 9 ml/kg/min, and dyspnea/?VO₂ slopes were elevated (both p < 0.0001). Smokers had evidence of peripheral airway dysfunction and maldistribution of ventilation when compared to controls. In smokers versus controls: lung diffusing capacity for carbon monoxide (D_LCO) was 85 ± 22 vs. 105 ± 17% predicted, and residual volume (RV)/total lung capacity (TLC) was 36 ± 8 vs. 31 ± 6% (both p < 0.01). The strongest correlates of peak ?VO₂ were D_LCO% predicted (r = 0.487, p < 0.0005) and RV/TLC% (r = ?0.389, p = 0.002). D_LCO% predicted was also the strongest correlate of dyspnea/?VO₂ slope (r = ?0.352, p = 0.005). In smokers with mild airway obstruction, associations between resting tests of mechanics and pulmonary gas exchange and exercise performance parameters were weak, albeit consistent. Among these, DLCO showed the strongest association with important outcomes such as dyspnea and exercise intolerance measured during standardized incremental exercise tests.     

The alveolar-capillary membrane diffusing capacity and the pulmonary capillary blood volume in heart transplant candidates

OBJECTIVES: To determine the mechanism of impairment of pulmonary transfer factor for carbon monoxide (TL(CO)) in heart transplant candidates, as this is the most common lung function abnormality. SETTING: Regional cardiopulmonary transplant centre. METHODS: TL(CO) and its components (the diffusing capacity of the alveolar-capillary membrane (D(M)) and the pulmonary capillary blood volume (V(C))) were measured using the Roughton and Forster method and the single breath technique in 38 patients with severe chronic heart failure awaiting heart transplantation (mean age 51 years, range 19 to 61; mean left ventricular ejection fraction 12.8%). Results were compared with data from 26 normal subjects (mean age 47 years, range 27 to 62). RESULTS: Mean per cent predicted TL(CO), D(M), and V(C) were significantly reduced in patients (69.9%, 81.4%, and 80.2% of predicted, respectively) compared with controls (97.7%, 100.1%, and 102.3% of predicted, respectively, p < 0.001). The relative contribution of the two components of TL(CO) in patients was similar to that of normal subjects, with each component accounting for approximately 50% of the total resistance to diffusion (1/TL(CO)). CONCLUSIONS: TL(CO) impairment in patients with severe chronic heart failure awaiting heart transplantation results from a proportionate reduction in both D(M) and V(C), suggesting a significant disturbance of the pulmonary vascular bed.     

Exercise Ventilatory Inefficiency Adds to Lung Function in Predicting Mortality in COPD

Severity of resting functional impairment only partially predicts the increased risk of death in chronic obstructive pulmonary disease (COPD). Increased ventilation during exercise is associated with markers of disease progression and poor prognosis, including emphysema extension and pulmonary vascular impairment. Whether excess exercise ventilation would add to resting lung function in predicting mortality in COPD, however, is currently unknown. After an incremental cardiopulmonary exercise test, 288 patients (forced expiratory volume in one second ranging from 18% to 148% predicted) were followed for a median (interquartile range) of 57 (47) months. Increases in the lowest (nadir) ventilation to CO₂ output (VCO₂) ratio determined excess exercise ventilation. Seventy-seven patients (26.7%) died during follow-up: 30/77 (38.9%) deaths were due to respiratory causes. Deceased patients were older, leaner, had a greater co-morbidity burden (Charlson Index) and reported more daily life dyspnea. Moreover, they had poorer lung function and exercise tolerance (p < 0.05). A logistic regression analysis revealed that ventilation/VCO₂ nadir was the only exercise variable that added to age, body mass index, Charlson Index and resting inspiratory capacity (IC)/total lung capacity (TLC) ratio to predict all-cause and respiratory mortality (p < 0.001). Kaplan–Meier analyses showed that survival time was particularly reduced when ventilation/VCO₂ nadir > 34 was associated with IC/TLC ≤ 0.34 or IC/TLC ≤ 0.31 for all-cause and respiratory mortality, respectively (p < 0.001). Excess exercise ventilation is an independent prognostic marker across the spectrum of COPD severity. Physiological abnormalities beyond traditional airway dysfunction and lung mechanics are relevant in determining the course of the disease.     

Reduction of lung distensibility in acromegaly after suppression of growth hormone hypersecretion.

Whether the growth of the lungs in acromegaly is due to alveolar hypertrophy or alveolar hyperplasia is a subject of debate. To discriminate these hypotheses, we compared pulmonary distensibility and diffusing capacity among 11 patients with active acromegaly and 11 matched control subjects, evaluating the response of pulmonary distensibility and diffusing capacity to suppression of growth hormone (GH) hypersecretion. We performed lineal and exponential analyses of quasistatic pressure-volume curves. Patients with active acromegaly had a greater TLC, lung compliance, and shape constant, K, than did normal subjects. We found no significant differences between the study groups in carbon monoxide diffusing capacity or diffusing capacity per unit of alveolar volume. After treatment, patients with inactive acromegaly showed a reduced TLC (6.95 +/- 1.40 [mean +/- SD] L versus 6.35 +/- 1.23 L), reduced lung compliance (3.61 +/- 0.90 L/kPa versus 2.36 +/- 0.79 L/ kPa), reduced K coefficient (2.62 +/- 0.65 kPa(-)(1) versus 1.35 +/- 0.40 kPa(-)(1)), and increased maximal recoil pressure (1.74 +/- 0.38 kPa versus 2.28 +/- 0.25 kPa). We conclude that the increased lung distensibility with normal diffusion capacity demonstrated in patients with active acromegaly, which was partly reversible after suppression of GH hypersecretion, suggests that lung growth in acromegaly may result from an increase in alveolar size.     

Maximal inspiratory flow rates in patients with COPD

OBJECTIVES: To assess the relevance of maximal inspiratory flow rates (MIFR) in the assessment of airway obstruction in COPD. SETTING: University teaching hospital. PARTICIPANTS: Ten consecutive COPD patients (O group; mean [+/- SD] age, 58.5+/-8.3 years) and 10 matched healthy subjects (H group; mean age, 58.7+/-7.4 years). MEASUREMENTS: Lung volumes, FEV(1), specific airway conductance, single-breath lung diffusing capacity, MIFR, and maximal expiratory flow rates (MEFR). RESULTS: Mean FEV(1)/vital capacity (VC) was 74.7% in the H group and 37.8% in the O group (p<0.001). Total lung capacity was higher (p<0.001) in the O group compared with the H group. Lung diffusing capacity was less than half in the O group compared with the H group (p<0.001). MEFR at all lung volumes were lower in the O group (p<0.001). MIFR were comparable in the two groups, except at 25% inspired VC, where MIFR were lower in the O group (p< 0.05). CONCLUSION: MIFR are less sensitive than MEFR to detect airway obstruction in COPD patients. Yet, the interest of MIFR lay in the possibility to separate intrinsic from extrinsic involvement of airways. A normal MIFR associated with low MEFR, as in the present study, suggests either a lack of parenchymal support, an increased collapsibility of the airways, or a reversible peripheral airway narrowing. A fixed, generalized airway narrowing would be associated with a decrease of both MIFR and MEFR.     

Respiratory muscle strength, lung function, and dyspnea in patients with sarcoidosis.

BACKGROUND: Sarcoidosis is a systemic granulomatous disorder that is estimated to involve the skeletal muscles in up to 50% of patients. There is little information on the relationship among respiratory muscle strength, lung volumes, and the degree of dyspnea in patients with sarcoidosis. Design and patients: Lung function and maximal respiratory muscle force generation were measured in 36 patients with sarcoidosis (24 patients with pulmonary parenchymal infiltration) and 25 control subjects free of cardiorespiratory disease. Dyspnea in the sarcoidosis patients was quantitated by a score based on an activity tolerance assessment scale (ranging from rest to climbing hills or stairs). SETTING: Outpatient clinics of two teaching hospitals. RESULTS: Mean FVC, maximal voluntary ventilation, total lung capacity (TLC), functional residual capacity, residual volume (RV), and diffusing capacity of the lung for carbon monoxide (DLCO) were all at least 16% less than corresponding control values (in all cases, p < 0.001), while maximal inspiratory mouth pressure (PImax) and maximal expiratory mouth pressure (PEmax) were 37% and 39% less, respectively, than control values (both at p < 0.0001). PImax and PEmax declined with increasing dyspnea in a more graded, steady manner than did spirometric and DLCO values. For all measurements, however, the lowest mean values were found in patients with the most severe level of dyspnea. Strong inverse relationships were observed between PEmax and PImax with dyspnea level (p < 0.0001 and p < 0.01, respectively). Both PImax and PEmax correlated best with absolute values of FVC, while only PEmax correlated with RV (absolute and percent predicted) and percent predicted values of TLC. CONCLUSIONS: Maximal respiratory pressures correlate more closely with dyspnea level than lung volumes and DLCO. Since dyspnea is the most common presentation in early to moderately advanced sarcoidosis, respiratory pressures may be a more reliable index of functional work capacity and reflection of activities of daily living than standard tests of lung function.