Effects of hyperoxia on ventilatory limitation during exercise in advanced chronic obstructive pulmonary disease

We studied interrelationships between exercise endurance, ventilatory demand, operational lung volumes, and dyspnea during acute hyperoxia in ventilatory-limited patients with advanced chronic obstructive pulmonary disease (COPD). Eleven patients with COPD (FEV(1.0) = 31 +/- 3% predicted, mean +/- SEM) and chronic respiratory failure (Pa(O(2)) 52 +/- 2 mm Hg, Pa(CO(2 ))48 +/- 2 mm Hg) breathed room air (RA) or 60% O(2) during two cycle exercise tests at 50% of their maximal exercise capacity, in randomized order. Endurance time (T(lim)), dyspnea intensity (Borg Scale), ventilation (V E), breathing pattern, dynamic inspiratory capacity (IC(dyn)), and gas exchange were compared. Pa(O(2)) at end-exercise was 46 +/- 3 and 245 +/- 10 mm Hg during RA and O(2), respectively. During O(2), T(lim) increased 4.7 +/- 1.4 min (p < 0.001); slopes of Borg, V E, V CO(2), and lactate over time fell (p < 0.05); slopes of Borg-V E, V E-V CO(2), V E-lactate were unchanged. At a standardized time near end-exercise, O(2) reduced dyspnea 2.0 +/- 0.5 Borg units, V CO(2) 0.06 +/- 0.03 L/min, V E 2.8 +/- 1.0 L/min, and breathing frequency 4.4 +/- 1.1 breaths/min (p < 0.05 each). IC(dyn) and inspiratory reserve volume (IRV) increased throughout exercise with O(2) (p < 0.05). Increased IC(dyn) was explained by the combination of increased resting IRV and decreased exercise breathing frequency (r(2) = 0.83, p < 0.0005). In conclusion, improved exercise endurance during hyperoxia was explained, in part, by a combination of reduced ventilatory demand, improved operational lung volumes, and dyspnea alleviation.     

Pulmonary gas exchange response to oxygen breathing in acute lung injury

The mechanisms and time course of the pulmonary gas exchange response to 100% O(2) breathing in acute respiratory failure needing mechanical ventilation were studied in eight patients with acute lung injury (ALI) (48 +/- 18 yr [mean +/- SD]) and in four patients (66 +/- 2 yr) with chronic obstructive pulmonary disease (COPD). We postulated that, in patients with ALI while breathing 100% O(2), the primary mechanism of hypoxemia, i.e., increased intrapulmonary shunt, would further worsen (increase) as a result of reabsorption atelectasis. Respiratory and inert gases, and systemic and pulmonary hemodynamics were measured at maintenance fraction of inspired oxygen (FI(O(2))-m), at 30 and 60 min while breathing 100% O(2), and then at 30 min of resuming FI(O(2))-m. During 100% O(2) breathing, in patients with ALI, Pa(O(2)) (by 207 and 204 mm Hg; p < 0.01 each), Pa(CO(2)) (by 4 mm Hg each) (p < 0.05 each), and intrapulmonary shunt (from 16 +/- 10% to 22 +/- 11% and 23 +/- 11%) (p < 0.05 each) increased respectively. By contrast, in patients with COPD, Pa(O(2)) (by 387 and 393 mm Hg; p < 0.001 each), Pa(CO(2)) (by 4 and 5 mm Hg) and the dispersion of pulmonary blood flow (log SDQ) (from 1.33 +/- 0.10 to 1.60 +/- 0.20 and 1.80 +/- 0.30 [p < 0.05]) increased, respectively. In patients with ALI, the breathing of 100% O(2) deteriorates intrapulmonary shunt owing to collapse of unstable alveolar units with very low ventilation-perfusion (V A/Q) ratios, as opposed to patients with COPD, in whom only the dispersion of the blood flow distribution is disturbed, suggesting release of hypoxic pulmonary vasoconstriction.     

Comparison of pulmonary hemodynamics in patients with COPD and patients with overlap syndrome with similar severity of airway obstruction and gas exchange

It may be assumed that pulmonary hypertension due to apnea related desaturations during sleep develops earlier in the natural course of the overlap syndrome (OS) than in patients with COPD only. We aimed to verify this hypothesis by comparing pulmonary haemodynamics in COPD patients and patients with OS with similar severity of airway limitation and of pulmonary gas exchange. We studied pulmonary haemodynamics in 17 males with OS--group I (mean AHI 63.9 +/- 18.9), and in 20 males with COPD--group II. Both groups were age (I = 51.4 +/- 8.3 years, II = 53.7 +/- 7.7 years), FVC (I = 2.7 +/- 0.7 L, II = 2.9 +/- 0.6 L), FEV1 (I = 1.5 +/- 0.7 L, II = 1.3 +/- 0.3 L), PaO2 (I = 56.9 +/- 9.5 mm Hg, II = = 61.7 +/- 14.6 mm Hg) and PaCO2 (I = 46.9 +/- 9.8 mm Hg, II = 48.3 +/- 6.6 mm Hg) matched. Haemodynamic measurements were performed at rest and in 7th minute of exercise if 40 Watts using Swan-Ganz thermodilution catheter. Both groups presented with similar severity of pulmonary hypertension at rest (mean PPA = 24.2 +/- 7.4 mm Hg in OS and 24.3 +/- 9.2 mm Hg in COPD) and on exercise (mean PPA 41.2 +/- 15.1 mm Hg in OS and 44.5 +/- 11.5 mm Hg in COPD). COPD patients had higher PVR than OS (335 +/- 138 d.s.cm-5 versus 229 +/- 97 d.s.cm-5, p < 0.005). We concluded that pulmonary hypertension in OS patients is not more advanced than in COPD patients with matched ventilatory and gas exchange impairment.     

Daytime predictors of sleep hypoventilation in Duchenne muscular dystrophy

Sleep hypoventilation is an inevitable consequence of Duchenne muscular dystrophy (DMD), usually preceding daytime respiratory failure. Appropriate scheduling of polysomnography and the introduction of noninvasive ventilation (NIV) during sleep are not defined. Our aim was to determine the parameters of daytime lung function associated with sleep hypoventilation in patients with DMD. As our method we chose a prospective comparison of wakeful respiratory function (spirometry, lung volumes, maximal mouth pressures, arterial blood gases) with outcomes of polysomnography. All measurements were made with subjects breathing air. Nineteen subjects were studied. The FEV(1) was correlated with Pa(CO(2)) (r = -0.70, p < 0.001) and base excess (r = -0.68, p < 0.01). All of these parameters were significantly related to sleep oxygenation (proportion of total sleep time spent at an Sa(O(2)) /= 2%); a Pa(CO(2)) of >/= 45 mm Hg was an equally sensitive (91%) but more specific (75%) indicator while a base excess of >/= 4 mmol/L was highly specific (100%) but less sensitive (55%). After introduction of NIV during sleep (n = 8), there was a significant reduction in wakeful Pa(CO(2)) (54 +/- 7.4 to 49.1 +/- 4 mm Hg, p < 0.02) over 0. 9 +/- 0.4 yr despite a further decline in FEV(1) (0.84 +/- 0.46 to 0. 64 +/- 0.39 L, p < 0.05). We conclude that in patients with DMD, (1) arterial blood gases should be performed once the FEV(1) falls below 40% of the predicted value; (2) polysomnography should be considered when the Pa(CO(2)) is >/= 45 mm Hg, particularly if the base excess is >/= 4 mmol/L; (3) the decrease in wakeful Pa(CO(2)) after NIV administered during sleep implicates sleep hypoventilation in the pathogenesis of respiratory failure; and (4) impaired ventilatory drive is a possible mechanism for respiratory failure, as the NIV-associated decrease in wakeful Pa(CO(2)) occurs despite a further decline in ventilatory capacity, suggesting continuing deterioration in respiratory muscle function.     

Gas exchange response to short-acting beta2-agonists in chronic obstructive pulmonary disease severe exacerbations

RATIONALE: Short-acting beta(2)-agonists are one of the mainstays of bronchodilator strategy for exacerbations of chronic obstructive pulmonary disease (COPD). The assessment of pulmonary gas exchange after salbutamol in COPD severe exacerbations remains unknown. OBJECTIVES: We investigated whether the effects of nebulized salbutamol during COPD severe exacerbations are associated with further deterioration of pulmonary gas exchange. METHODS: We examined patients with severe COPD when hospitalized for exacerbation (n = 9), and while in stable convalescence. MEASUREMENTS AND MAIN RESULTS: We assessed spirometry, arterial blood gases, systemic hemodynamics, and V/Q relationships 30 and 90 minutes after administration of 5.0 mg salbutamol. At exacerbation, compared with baseline, 30 minutes after salbutamol administration, cardiac output (Q) increased (from 6.5 +/- [SEM] 0.4 to 7.3 +/- 0.5 L . min(-1)) (p < 0.03) alone, without inducing changes in gas exchange indices. When in convalescence, compared with baseline, 30 minutes after salbutamol, there was an increase in Q (from 5.7 +/- 0.5 to 7.0 +/- 0.6 L . min(-1)) and Vo(2) (from 211 +/- 12 to 232 +/- 11 ml . min(-1)) (p < 0.002 each), whereas Pa(O(2)) decreased (from 71 +/- 4 to 63 +/- 3 mm Hg) and alveolar-arterial Po(2) difference increased due to increased perfusion of low-V/Q-ratio regions (from 4.5 +/- 2.6 to 9.6 +/- 4.1% of Q) (p < 0.05); Sa(O(2)) (93 +/- 2%) and Pa(CO(2)) (43 +/- 2 mm Hg) remained unchanged. This deleterious gas exchange response persisted at 90 minutes. CONCLUSIONS: At exacerbation, salbutamol does not aggravate pulmonary gas exchange abnormalities. When in convalescence, however, baseline lung function improvement was associated with a detrimental gas exchange response to salbutamol, resulting in further V/Q imbalance and small decreases in Pa(O(2)) compounded by small increases in Q and Vo(2).     

Dynamic hyperinflation and exercise intolerance in chronic obstructive pulmonary disease.

The role of dynamic hyperinflation (DH) in exercise limitation in chronic obstructive pulmonary disease (COPD) remains to be defined. We examined DH during exercise in 105 patients with COPD (FEV(1) = 37 +/- 13% predicted; mean +/- SD) and studied the relationships between resting lung volumes, DH during exercise, and peak oxygen consumption (VO(2)). Patients completed pulmonary function tests and incremental cycle exercise tests. We measured the change in inspiratory capacity (Delta IC) during exercise to reflect changes in DH. During exercise, 80% of patients showed significant DH above resting values. IC decreased 0.37 +/- 0.39 L or 14 +/- 15% predicted during exercise (p < 0.0005), but with large variation in range. Delta IC correlated best with resting IC, both expressed %predicted (r = -0.50, p < 0.0005). Peak VO(2) (%predicted maximum) correlated best with the peak tidal volume attained (VT standardized as % of predicted vital capacity) (r = 0.68, p < 0.0005), which, in turn, correlated strongly with IC at peak exercise (r = 0.79, p < 0.0005) or at rest (r = 0.75, p < 0.0005). The extent of DH during exercise in COPD correlated best with resting IC. DH curtailed the VT response to exercise. This inability to expand VT in response to increasing metabolic demand contributed importantly to exercise intolerance in COPD.     

Hypercapnic acidosis is protective in an in vivo model of ventilator-induced lung injury

To investigate whether hypercapnic acidosis protects against ventilator-induced lung injury (VILI) in vivo, we subjected 12 anesthetized, paralyzed rabbits to high tidal volume ventilation (25 cc/kg) at 32 breaths per minute and zero positive end-expiratory pressure for 4 hours. Each rabbit was randomized to receive either an FI(CO(2)) to achieve eucapnia (Pa(CO(2)) approximately 40 mm Hg; n = 6) or hypercapnic acidosis (Pa(CO(2)) 80-100 mm Hg; n = 6). Injury was assessed by measuring differences between the two groups' respiratory mechanics, gas exchange, wet:dry weight, bronchoalveolar lavage fluid protein concentration and cell count, and injury score. The eucapnic group showed significantly higher plateau pressures (27.0 +/- 2.5 versus 20.9 +/- 3.0; p = 0.016), change in Pa(O(2)) (165.2 +/- 19.4 versus 77.3 +/- 87.9 mm Hg; p = 0.02), wet:dry weight (9.7 +/- 2.3 versus 6.6 +/- 1.8; p = 0.04), bronchoalveolar lavage protein concentration (1,350 +/- 228 versus 656 +/- 511 micro g/ml; p = 0.03), cell count (6.86 x 10(5) +/- 0.18 x 10(5) versus 2.84 x 10(5) +/- 0.28 x 10(5) nucleated cells/ml; p = 0.021), and injury score (7.0 +/- 3.3 versus 0.7 +/- 0.9; p < 0.0001). We conclude that hypercapnic acidosis is protective against VILI in this model.     

Correlation of changes in quality of life after lung volume reduction surgery with changes in lung function, exercise, and gas exchange

STUDY OBJECTIVES: To evaluate correlations between improvement in quality of life (QOL) in patients with severe COPD before and after they undergo lung volume reduction surgery (LVRS) with changes in pulmonary function tests, gas exchange, exercise performance, and alterations in medical management. DESIGN: Case-series analysis. SETTING: University hospital. PATIENTS: Forty-two patients (mean [+/- SD] age, 56+/-8 years; 53% women) with severe airflow obstruction (FEV(1), 0.62+/-0.2 L), and moderate to severe hyperinflation (total lung capacity [TLC], 6.9+/-1.7 L). INTERVENTION AND MEASUREMENTS: All patients underwent bilateral LVRS via median sternotomy. Measurements of lung function, symptom-limited cardiopulmonary exercise testing, the total distance the patient was able to walk in 6 min in a corridor, and sickness impact profile (SIP) scores were made before and 3 months after LVRS. SIP scores are inversely proportional to the level of function and QOL. RESULTS: Compared to baseline, FEV(1) increased (0.87+/-0.3 vs. 0.62+/-0.2 L, respectively; p<0.01) while residual volume significantly decreased (3.2+/-1.8 vs. 6.3+/-1.2 L, respectively; p<0.004) at 3 months post-LVRS. On cardiopulmonary exercise testing, values increased from baseline to post-LVRS for total exercise time (9.0+/-2.2 vs. 6.0+/-1.5 min, respectively; p = 0.045), maximum oxygen uptake (VO(2)) (16+/-3 vs. 11+/-2 mL/kg/min, respectively; p = 0.01), and maximum minute ventilation (VE) (33+/-9 vs. 28+/-5 L/min, respectively; p = 0.03). The percentage change in the oxygen cost of breathing (VO2/VE ratio) from low to high workloads during exercise was significantly lower after LVRS (p = 0.002). There was no significant change in oxygenation after LVRS (PaO(2)/fraction of inspired oxygen, 331+/-27 vs. 337+/-39, respectively; p = 0.76), but PaCO(2) tended to be lower (41+/-9 vs. 48+/-6 mm Hg, respectively; p = 0.07). Overall SIP scores were significantly lower after LVRS than before (8+/-4 vs. 15+/-2, respectively; p = 0.002). Changes in SIP scores correlated with the change in VO2/VE ratio from low to high workloads, with patients having the smallest changes in VO2/VE ratio having the smallest changes in SIP scores after LVRS (r = 0.6; p = 0.01). Improved or lower SIP scores also tended to correlate with a reduction in residual volume/TLC ratio (r = 0.45; p = 0.09), and there was a linear correlation with a statistically significant Pearson r value with decreased steroid requirements (r = 0.7; p = 0.001). Moreover, changes in psychological SIP subscore tended to correlate with diminished oxygen requirements post-LVRS (r = 0.45; p = 0.09). However, there was no significant correlation between changes in SIP scores and routine measurements of lung function, exercise performance, or gas exchange. CONCLUSION: There is an association between an improvement in QOL and reduced hyperinflation after LVRS. Reduced hyperinflation may lead to more efficient work of breathing during exercise and, therefore, to an increased ability to perform daily activities. Changes in QOL scores correlate best with behaviorally based variables that directly affect the patient's well-being, such as systemic steroid administration.     

Gas exchange and pulmonary hemodynamics during lung resection in patients at increased risk: relationship with preoperative exercise testing

STUDY OBJECTIVES: To evaluate the intraoperative evolution of patients with COPD during lung resection and to test whether exercise testing could be helpful in the prediction of the intraoperative course. DESIGN: Prospective study. SETTING: University teaching hospital. PATIENTS: Forty patients (mean [+/- SD] age, 65 +/- 9 years) with COPD (ie, FEV(1), 55 +/- 11% of predicted) and resectable lung neoplasms. INTERVENTIONS: Preoperatively, pulmonary function testing, quantitative lung perfusion scanning, and exercise performance testing were administered. Intraoperatively, pulmonary, hemodynamic, and blood gas measurements were performed at five stages, including periods of two-lung ventilation (TLV) and periods of one-lung ventilation (OLV). RESULTS: During OLV, compared with TLV, the PaO(2)/fraction of inspired oxygen (FIO(2)) ratio decreased from 458 +/- 120 to 248 +/- 131 mm Hg (p < 0.05), whereas pulmonary artery pressure (PAP) increased from 18 +/- 5 to 23 +/- 5 mm Hg (p < 0.05). Cardiac output (t) also increased from 4.0 +/- 1.2 to 5.1 +/- 1.9 L/min (p < 0.05), yielding to a higher mixed venous PO(2). Both PaO(2) and t during OLV were significantly lower in patients who had undergone right thoracotomies compared with those who had undergone left thoracotomies. The PaO(2)/FIO(2) ratio during OLV correlated with the PaO(2) during exercise (r = 0.39; p = 0.01) and with the perfusion of the non-neoplastic lung (r = 0.44; p = 0.005). CONCLUSIONS: In COPD patients, OLV leads to a significant derangement of gas exchange, which is more pronounced in right thoracotomies. Preoperative measurement of PaO(2) during exercise and the distribution of perfusion by lung scan might be useful to identify those patients who are at the greatest risk of abnormal gas exchange during lung resections.     

Application of tracheal gas insufflation to acute unilateral lung injury in an experimental model

In unilateral lung injury, application of global positive end-expiratory pressure (PEEP) may cause overdistension of normal alveoli and redistribution of blood flow to diseased lung areas, thereby worsening oxygenation. We hypothesized that selective application of tracheal gas insufflation (TGI) will recruit the injured lung without causing overdistension of the normal lung. In eight anesthetized dogs, left lung saline lavage was performed until Pa(O(2))/FI(O(2)) fell below 100 mm Hg. Then, the dogs were reintubated with a Univent single lumen endotracheal tube that incorporates an internal catheter to provide TGI. After injury, increasing PEEP from 3 to 10 cm H(2)O did not change gas exchange, hemodynamics, or lung compliance. Selective TGI, while keeping end-expiratory lung volume (EELV) constant, improved Pa(O(2))/FI(O(2)) from 212 +/- 43 to 301 +/- 38 mm Hg (p < 0.01) while Pa(CO(2)) and airway pressures decreased (p < 0.01). During selective TGI, reducing tidal volume to 5.2 ml/kg while keeping EELV constant, normalized Pa(CO(2)), did not affect Pa(O(2))/FI(O(2)), and decreased end-inspiratory plateau pressure from 16.6 +/- 1.0 to 11.9 +/- 0.5 cm H(2)O (p < 0.01). In unilateral lung injury, we conclude that selective TGI (1) improves oxygenation at a lower pressure cost as compared with conventional mechanical ventilation, (2) allows reduction in tidal volume without a change in alveolar ventilation, and (3) may be a useful adjunct to limit ventilator-associated lung injury.     

Diffusing capacity for carbon monoxide is linked to ventilatory demand in patients with chronic obstructive pulmonary disease

Dyspnea is deemed to result from an imbalance between ventilatory demand and capacity. The single-breath diffusing capacity for carbon monoxide (DLCO) is often the best correlate to dyspnea in COPD. We hypothesized that DLCO contributes to the assessment of ventilatory demand, which is linked to physiological dead space /tidal volume (V(D)/V(T)) ratio. An additional objective was to assess the validity of non-invasive measurement of transcutaneous P(CO2) allowing the calculation of this ratio. Forty-two subjects (median [range] age: 66 [43-80] years; 12 females) suffering mainly from moderate-to-severe COPD (GOLD stage 2 or 3: n = 36) underwent pulmonary function and incremental exercise tests while taking their regular COPD treatment. DLCO% predicted correlated with both resting and peak physiological V(D)/V(T) ratios (r = -0.55, p = 0.0015 and r = -0.40, p = 0.032; respectively). The peak physiological V(D)/V(T) ratio contributed to increase ventilation (increased ventilatory demand), to increase dynamic hyperinflation and to impair oxygenation on exercise. Indirect (MRC score) and direct (peak Borg score/% predicted VO(2)) exertional dyspnea assessments were correlated and demonstrated significant relationships with DLCO% predicted and physiological V(D)/V(T) at peak exercise, respectively. The non-invasive measurement of transcutaneous P(CO2) both at rest and on exercise was validated by Bland-Altman analyses. In conclusion, DLCO constitutes and indirect assessment of ventilatory demand, which is linked to exertional dyspnea in COPD patients. The assessment of this demand can also be non invasively obtained on exercise using transcutaneous PCO(2) measurement.     

Effect of dynamic hyperinflation on exertional dyspnea, exercise performance and quality of life in COPD

There is increasing evidence that dynamic hyperinflation (DH) have negative effects on exercise performance and quality of life in chronic obstructive pulmonary disease (COPD) patients. The aim of this study was to investigate effect of dynamic hyperinflation on exertional dyspnea, exercise performance and quality of life in patients with COPD. 72 clinically stable patients with moderate to severe COPD and 30 healthy age-matched control subjects were included in this study. Pulmonary function tests including lung volumes and maximal respiratory muscle forces, arterial blood gas analyses, evaluation of exertional dyspnea with the Borg scale, and The Saint George Respiratory Questionnaire (SGRQ, Turkish version) were performed at rest and after a 6-min walk test. We measured the change in inspiratory capacity (AlphaIC) after exercise to reflect DH. 80% of patients with COPD significantly decreased IC after exercise (DH). AlphaIC were -0.27 +/- 0.26 L in COPD and 0.8 +/- 0.17 L in controls (p= 0.001). A stepwise multiple regression analysis showed that to be a patient with COPD, Basal Dyspnea Index (BDI) and AlphaIC were the best predictors of 6 MWD (r(2)= 0.53, p< 0.001). FEV1 added an additinal 9% to the variance in 6 MWD. Exertional dyspnea (AlphaBorg) correlated with AlphaIC (r= -0.44, p= 0.0001) and BDI (r= 0.34, p= 0.02). AlphaIC significantly correlated with symptom (r= -0.36, p= 0.008), activity (r= -0.31, p= 0.03) and total scores (r= -0.30, p= 0.04) of SGRQ. Dynamic hyperinflation can often occur during exersice in patients with COPD. Extent of dynamic hyperinflation could able to explain exercise capacity limitation, exercise dyspnea, and poor quality of life in patients with COPD.     

Peripheral and central ventilatory responses in central sleep apnea with and without congestive heart failure

Given that the apnea-ventilation cycle length during central sleep apnea (CSA) with congestive heart failure (CHF) is approximately 70 s, we hypothesized that rapidly responsive peripheral CO(2) ventilatory responses would be raised in CHF-CSA and would correlate with the severity of CSA. Sleep studies and single breath and rebreathe hypercapnic ventilatory responses (HCVR) were measured as markers of peripheral and central CO(2) ventilatory responses, respectively, in 51 subjects: 12 CHF with no apnea (CHF-N), 8 CHF with obstructive sleep apnea (CHF-OSA), 12 CHF-CSA, 11 CSA without CHF ("idiopathic" CSA; ICSA), and 8 normal subjects. Single breath HCVR was equally elevated in CHF-CSA and ICSA groups compared with CHF-N, CHF-OSA, and normal groups (0.58 +/- 0.09 [mean +/- SE] and 0. 58 +/- 0.07 versus 0.23 +/- 0.06, 0.25 +/- 0.04, and 0.27 +/- 0.02 L/min/PET(CO(2)) mm Hg, respectively, p < 0.001). Similarly, rebreathe HCVR was elevated in both CHF-CSA and ICSA groups compared with CHF-N, CHF-OSA, and normal groups (5.80 +/- 1.12 and 3.53 +/- 0. 29 versus 2.00 +/- 0.25, 1.44 +/- 0.16, and 2.14 +/- 0.22 L/min/PET(CO(2)) mm Hg, respectively, p < 0.001). Furthermore, in the entire CHF group, single breath HCVR correlated with central apnea-hypopnea index (AHI) (r = 0.63, p < 0.001) and percentage central/total apneas (r = 0.52, p = 0.022). Rebreathe HCVR correlated with awake Pa(CO(2)) (r = -0.61, p < 0.001), but not with central AHI or percentage central/total apneas independent of its relationship with single breath HCVR. In conclusion, in subjects with CHF, raised central CO(2) ventilatory response predisposes to CSA promoting background hypocapnia and exposing the apnea threshold to fluctuations in ventilation, whereas raised and faster-acting peripheral CO(2) ventilatory response determines the periodicity and severity of CSA.     

Outcome of patients with stable COPD receiving controlled noninvasive positive pressure ventilation aimed at a maximal reduction of Pa(CO2)

STUDY OBJECTIVES: The role of noninvasive positive pressure ventilation (NPPV) has been well established in the treatment of acute hypercapnic respiratory failure due to COPD. However, evidence for a sustained improvement in blood gas levels and survival in patients with stable hypercapnic COPD following NPPV is still lacking. There is concern that this might be due to low inspiratory pressures of < 18 cm H2O used in previous studies, which thereby did not achieve a reduction of Pa(CO2). Therefore, the 2-year survival and changes in lung function and blood gas levels were analyzed in patients with stable hypercapnic COPD in whom controlled pressure-limited NPPV was titrated to achieve a maximal improvement in Pa(CO2). DESIGN: Retrospective study between March 1997 and September 2003. SETTING: General ward of a university hospital. PATIENTS: Thirty-four consecutive patients with stable (mean pH 7.40 +/- 0.03) hypercapnic COPD (mean age, 63.4 +/- 9.7 years [+/- SD]; mean body mass index, 28.3 +/- 7.3 kg/m2). MEASUREMENTS AND RESULTS: Daytime Pa(CO2) during spontaneous breathing decreased by 6.9 +/- 8.0 (95% confidence interval, - 9.9 to - 3.9), from 53.3 +/- 4.8 to 46.4 +/- 7.0 mm Hg (p < 0.001); while daytime Pa(O2) increased by 5.8 +/- 9.4 (95% confidence interval, 2.3 to 9.3), from 51.7 +/- 8.8 to 57.5 +/- 9.3 mm Hg (p = 0.002); and FEV1 increased by 0.14 +/- 0.16 (95% confidence interval, 0.08 to 0.20), from 1.03 +/- 0.54 to 1.17 +/- 0.59 L (p < 0.001) after 2 months of NPPV. This was achieved with mean inspiratory pressures of 27.7 +/- 5.9 cm H2O (range, 17 to 40 cm H2O) at a mean respiratory rate of 20.8 +/- 2.5 breaths/min (range, 14 to 24 breaths/min). The 2-year survival rate was 86%. CONCLUSIONS: Controlled NPPV using a mean inspiratory pressure of 28 cm H2O is well tolerated over longer periods and can improve blood gas levels and lung function. Prospective, randomized controlled trials of high-intensity NPPV are required to evaluate its role in patients with stable hypercapnic COPD.     

慢性阻塞性肺疾病患者运动能力与其呼吸驱动及呼吸肌功能关系的研究

目的探究慢性阻塞性肺疾病（COPD）患者运动能力与呼吸驱动及呼吸肌功能之间的关系。方法对28例COPD患者和26名正常对照者分别检测静息常规肺功能、肺弥散功能（DLCO）、口腔阻断压（P0.1）、最大吸气压（PImax）及最大呼气压（PEmax）,并进行运动负荷试验观测氧耗量（VO2）、二氧化碳产生量（VCO2）、分钟通气量（E）、潮气量（T）等气体代谢指标,同时记录受试者运动中的呼吸困难指数（BorgScale）。运动负荷前、后检测动脉血气分析。结果（1）COPD组患者PImax（40±15）mmHg明显低于正常人组（53±19）mmHg（P<0.05）,PEmax在两组中差异无显著性（P>0.05）,COPD组患者P0.1（2.8±0.9）mmHg明显高于正常人组（2.0±0.7）mmHg（P<0.05）,P0.1/PImax（0.069±0.021）也明显高于正常人组（0.037±0.009）（P<0.01）。（2）COPD组患者VO2max与P0.1及PImax未发现明显的相关关系（P>0.05）,但与P0.1/PImax明显正相关（r=0.66,P<0.01）,BorgScale与P0.1/PImax明显正相关（r=0.49,P<0.05）。结论COPD患者运动能力下降除与气道阻塞程度及气体交换障碍等有关外,呼吸驱动相对增高及呼吸肌功能障碍也是其运动能力的限制因素。     

"Natural history" of pulmonary hypertension in a series of 131 patients with chronic obstructive lung disease.

The prognostic value and the evolution of pulmonary hypertension (PH) in patients with markedly hypoxemic chronic obstructive pulmonary disease (COPD), treated or not with long-term oxygen therapy (LTOT), has been extensively investigated. However, little is known in patients with mildly or moderately hypoxemic COPD not requiring LTOT. Therefore, we assessed the evolution of pulmonary hemodynamics in 131 patients with stable COPD by performing two right heart catheterizations at a mean (+/- SD) time interval of 6.8 +/- 2.9 yr. At inclusion (T0), no patient had PH (i.e., the mean pulmonary artery pressure [Ppa] at rest was < 20 mm Hg). Group 1 included 55 patients without exercising PH and group 2 included 76 patients with exercising PH, defined by a pulmonary arterial pressure (Ppa) > 30 mm Hg during a steady-state 40-W exercise. Group 2 patients compared with group 1 patients had a significantly higher resting Ppa (16 +/- 3 mm Hg versus 14 +/- 2 mm Hg, p = 0.001). At the second catheterization, 33 (25%) patients (9 of 55 in group 1, 24 of 76 in group 2, p = 0.048) showed a resting Ppa > 20 mm Hg, but PH was generally mild, ranging from 20 to 42.5 mm Hg. The mean Ppa at second evaluation was 16 +/- 5 mm Hg in group 1 and 19 +/- 7 mm Hg in group 2 (p = 0.01). The patients who developed resting PH at the second catheterization (T1) had higher resting and exercising Ppa (p = 0.001 and p = 0.002, respectively), and significantly lower resting and exercising Pa(O(2)) (p = 0.005 and p = 0.012, respectively) at T0. Logistic regression analysis showed that resting and exercising Ppa were independent predictors (at T0) for the subsequent development of PH (p = 0.029 and p = 0.027, respectively). The patients who developed resting PH (T1) had a significantly worsening of Pa(O(2)) (from 63.5 mm Hg at T0 to 60 mm Hg at T1, p = 0.047), whereas the Pa(O(2)) as a mean was stable in the remainder (69.5 mm Hg at T0 and T1). These results show the following. The progression of Ppa over time in patients with COPD with mild to moderate hypoxemia is rather slow, the average change for the group as a whole being of + 0.4 mm Hg/yr. Only about 25% of patients with COPD with mild to moderate hypoxemia and without resting PH at the onset will develop PH during a 6-yr follow-up. The patients with exercising PH at the onset have a significantly increased risk of developing PH over time. Only resting and exercising Ppa at the onset are independently related to the subsequent development of PH. However, in individual cases, the models of linear or logistic regression do not allow a pertinent prediction of the level of Ppa or the presence of PH at the second right heart catheterization.     

Superoxide dismutase improves gas exchange and pulmonary hemodynamics in premature lambs

RATIONALE: Oxidant stress may increase the severity of respiratory distress syndrome (RDS) after premature birth by altering vasoreactivity and increasing lung edema, but the acute effects of superoxide dismutase (SOD) treatment on gas exchange, lung compliance (CL), and pulmonary vascular resistance in premature animals with RDS are unknown. OBJECTIVE: We studied the effects of intratracheal recombinant human SOD treatment (rhSOD) on gas exchange, CL, and pulmonary hemodynamics in 46 premature lambs with RDS. Methods: After C-section delivery, lambs were randomly assigned to treatment with SOD (2.5-10 mg/kg) with or without inhaled nitric oxide (iNO, 5 ppm), and mechanically ventilated for 4 hours. At the end of the study, pressure-volume curves and wet-dry lung weights were measured to assess CL and edema, respectively. MAIN RESULTS: Despite an initial rise in Pa(O(2)), Pa(O(2)) in control animals progressively declined over the 4-hour treatment period (Pa(O(2)) = 25.0 +/- 7.5 mm Hg at 4 hours). In comparison with control animals, early treatment with SOD at 5 and 10 mg/kg improved Pa(O(2)) at 4 hours (167 +/- 44 and 269 +/- 33 mm Hg, respectively; p < 0.05 vs. control), but did not decrease lung edema or improve CL. In contrast, late treatment with SOD did not improve Pa(O(2)). Treatment with iNO increased Pa(O(2)) (196 +/- 22 vs. 25 +/- 8 mm Hg, control animals; p < 0.01), but the response to iNO was not augmented by combined therapy (SOD + iNO). After 4 hours of ventilation with FI(O(2)) = 1.00, rhSOD treatment lowered pulmonary vascular resistance compared with control animals. CONCLUSIONS: Early intratracheal rhSOD treatment improves oxygenation in premature lambs with RDS and prevents the development of pulmonary hypertension.     

Helium-hyperoxia, exercise, and respiratory mechanics in chronic obstructive pulmonary disease

RATIONALE: Hyperoxia and normoxic helium independently reduce dynamic hyperinflation and improve the exercise tolerance of patients with chronic obstructive pulmonary disease (COPD). Combining these gases could have an additive effect on dynamic hyperinflation and a greater impact on respiratory mechanics and exercise tolerance. OBJECTIVE: To investigate whether helium-hyperoxia improves the exercise tolerance and respiratory mechanics of patients with COPD. METHODS: Ten males with COPD (FEV(1) = 47 +/- 17%pred [mean +/- SD]) performed randomized constant-load cycling at 60% of maximal work rate breathing air, hyperoxia (40% O(2), 60% N(2)), normoxic helium (21% O(2), 79% He), or helium-hyperoxia (40% O(2), 60% He). MEASUREMENTS: Exercise time, inspiratory capacity (IC), work of breathing, and exertional symptoms were measured with each gas. RESULTS: Compared with air (9.4 +/- 5.2 min), exercise time was increased with hyperoxia (17.8 +/- 5.8 min) and normoxic helium (16.7 +/- 9.1 min) but the improvement with helium-hyperoxia (26.3 +/- 10.6 min) was greater than both these gases (p = 0.019 and p = 0.007, respectively). At an isotime during exercise, all three gases reduced dyspnea and both helium mixtures increased IC and tidal volume. Only helium-hyperoxia significantly reduced the resistive work of breathing (15.8 +/- 4.2 vs. 10.1 +/- 4.1 L . cm H(2)O(-1)) and the work to overcome intrinsic positive end-expiratory pressure (7.7 +/- 1.9 vs. 3.6 +/- 2.1 L . cm H(2)O(-1)). At symptom limitation, tidal volume remained augmented with both helium mixtures, but IC and the work of breathing were unchanged compared with air. CONCLUSION: Combining helium and hyperoxia delays dynamic hyperinflation and improves respiratory mechanics, which translates into added improvements in exercise tolerance for patients with COPD.     

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。     

Influence of diaphragmatic mobility on exercise tolerance and dyspnea in patients with COPD

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) present increased airway resistance, air trapping, pulmonary hyperinflation, and diaphragm muscle alterations, all of which affect pulmonary mechanics. PURPOSE: To evaluate the influence diaphragmatic mobility has on exercise tolerance and dyspnea in patients with COPD. MATERIALS AND METHODS: Fifty-four COPD patients with lung hyperinflation were evaluated to assess pulmonary function, diaphragm mobility, exercise tolerance, and dyspnea (score). Twenty healthy (age- and body mass index-matched) subjects were evaluated as controls. RESULTS: The COPD patients presented lower diaphragmatic mobility than did the controls (36.27+/-10.96 mm vs. 46.33+/-9.46 mm). Diaphragmatic mobility presented a linear correlation with distance covered on the 6-min walk test (6MWT) (r=0.38; p=0.005) and a negative correlation with dyspnea (r=-0.36; p=0.007). Patients were then divided into two subgroups based on the degree of diaphragmatic mobility: G1 (or=34 mm). Those in G1 presented poorer 6MWT performance and greater dyspnea upon exertion than did those in G2 (distance covered on the 6MWT: 454.76+/-100.67 m vs. 521.63+/-70.82 m; dyspnea score: 5.22+/-3.06 vs. 3.48+/-2.77). The G1 patients also presented greater residual volume (in liters) and lower maximal voluntary ventilation (in % of predicted values) than did the G2 patients (266.20+/-55.30 vs. 209.74+/-48.49 and 39.00+/-14.94 vs. 58.11+/-20.96). CONCLUSION: Diaphragmatic mobility influences dyspnea and exercise tolerance in patients with COPD.