Obstructive sleep apnea with severe chronic airflow limitation. Comparison of hypercapnic and eucapnic patients

The mechanism of sustained awake hypercapnia in the obstructive sleep apnea syndrome (OSA) is unknown. Recent work has implicated coexisting chronic airflow limitation (CAL) as an important contributing factor. We approached this question by studying consecutive patients with both OSA syndrome and severe CAL in detail and comparing those with and without retention of CO2 while awake. Of 28 patients with both severe OSA (mean NREM apnea index = 48 +/- 9, SEM) and severe CAL (mean FEV1 = 1.07 +/- 0.07 L), 14 had persistent awake hypercapnia (mean PaCO2 = 50 +/- 1 mm Hg), and 14 were normocapnic (mean PaCO2 = 40 +/- 1 mm Hg). When separated according to their PaCO2 level, there was no difference in the apnea indices in both non-rapid-eye-movement (NREM) sleep, or rapid-eye-movement (REM) sleep, although the hypercapnic group had lower average levels of oxyhemoglobin saturation in both NREM (SaO2 = 77 +/- 2% versus 85 +/- 3%, p less than 0.05) and REM (SaO2 = 60 +/- 4% versus 82 +/- 3%, p less than 0.001) sleep. The mean values for FEV1, VC, lung volumes, and diffusing capacity for CO measured while awake did not differ. The hypercapnic group had lower awake PaO2 levels (p less than 0.001), were heavier (p less than 0.05), had narrower upper airway size on CT scan measurements (p less than 0.01), and gave a history of much heavier alcohol intake (p less than 0.05). Our results demonstrate that some patients with severe OSA and severe CAL can maintain normal awake arterial CO2 levels.(ABSTRACT TRUNCATED AT 250 WORDS)     

Upper airway resistance during progressive hypercapnia and progressive hypoxia in normal awake subjects

Ventilatory motor output is known to influence the upper airway. Although inspiratory upper airway resistance decreases during progressive hypoxia or hypercapnia, the effects of hypoxia and hypercapnia on expiratory upper airway resistance remain unknown. In the present study, we attempted to examine whether the expiratory and the inspiratory upper airway resistances were modified in the same way by progressive hyperoxic hypercapnia or by progressive normocapnic hypoxia. Nine healthy subjects (five males, four females, 33+/-9 years) participated in the study. Inspiratory upper airway (iUAR) and expiratory upper airway resistances (eUAR) were calculated at flow 300 ml x s(-1). Both resistances were obtained during a baseline period and during progressive hyperoxic hypercapnia or progressive normocapnic hypoxia. In all subjects, iUAR and eUAR decreased significantly during hypercapnic or hypoxic challenge (P<0.05). eUAR was always lower than iUAR during hypercapnic challenge (P<0.0001) and during hypoxic challenge (P<0.0001). The authors conclude that expiratory upper airway resistance, as with inspiratory resistance, decreases during progressive hypercapnia or during progressive hypoxia. Pharyngeal dilator or constrictor muscle activities may be implicated.     

Ventilatory and cerebrovascular responses in normocapnic and hypercapnic COPD patients.

This study investigated the hypothesis that hypercapnia in some chronic obstructive pulmonary disease (COPD) patients may be related to a high cerebrovascular response to carbon dioxide (CO2). The relationship between responses of ventilation and of cerebral blood volume (CBV) to acute changes in carbon dioxide tension in arterial blood (Pa,CO2) was measured in 17 chronic hypercapnic (Pa,CO2 >6.0 kPa) and 16 normocapnic (Pa,CO2 < or = 6.0 kPa) COPD patients, who were matched for degree of airway obstruction (forced expiratory volume in one second 27% predicted). Results were compared with 15 age-matched healthy subjects. CBV was measured using near infrared spectroscopy during normo- and hypercapnia and related to inspired minute ventilation (V'I) and mouth occlusion pressure (P0.1). Hypercapnia (end-tidal pressure of carbon dioxide (deltaPET,CO2) > 1 kPa) was induced by giving adequate amounts of CO2 in the inspired air. During normocapnia, CBV (mL x 100 g(-1)) was 2.41+/- 0.66 and 2.90 +/- 0.60 (mean +/- SD) in the normocapnic and chronic hypercapnic patients, respectively, which was significantly lower compared to healthy subjects (3.53 +/- 0.77). All slopes of CO2 responsiveness (deltaCBV/deltaPa,CO2, deltaV'I/deltaPa,CO2, deltaP0.1/deltaPa,CO2) were significantly lower in both COPD groups relative to healthy subjects, but were not significantly different between the COPD groups. A poor but positive correlation between ventilatory and cerebrovascular CO2 responsiveness (deltaCBV/deltaPa,CO2 and deltaV'I/deltaPa,CO2) was found in COPD patients and healthy subjects. The findings do not support the hypothesis of abnormal cerebrovascular responses to carbon dioxide in hypercapnic chronic obstructive pulmonary disease patients.     

Effect of treatment with nasal continuous positive airway pressure on ventilatory response to hypoxia and hypercapnia in patients with sleep apnea syndrome

BACKGROUND: The increase in peripheral chemoreflex sensitivity in patients with obstructive sleep apnea (OSA) is associated with activation of autonomic nervous system and hemodynamic responses. Nasal CPAP (nCPAP) is an effective treatment for OSA, but little is known on its effect on chemoreflex sensitivity. OBJECTIVES: To assess the effect of nCPAP treatment or placebo (sham nCPAP) on ventilatory control in patients with OSA. SETTING: Sleep laboratory of Azienda Ospedaliera Garibaldi. PATIENTS: Twenty-five patients with moderate-to-severe OSA. DESIGN AND MEASUREMENTS: Patients were randomly assigned to either therapeutic nCPAP (use of optimal pressure, n = 15) or sham nCPAP (suboptimal pressure of 1 to 2 cm H2O, n = 10) in a double-blind fashion and treated for 1 month. A rebreathing test to assess ventilatory response to normocapnic hypoxia and normoxic hypercapnia was performed at basal condition and after 1 month of treatment. RESULTS: The use of therapeutic nCPAP or sham nCPAP did not affect daytime percentage of arterial oxygen saturation (SaO2%) or end-tidal P(CO2). The normocapnic hypoxic ventilatory response was reduced after 1 month of treatment with nCPAP (the slope was 1.08 +/- 0.02 L/min/SaO2% at basal condition and 0.53 +/- 0.07 L/min/SaO2% after 1 month of treatment, p = 0.008) [mean +/- SD], but not in patients treated with sham nCPAP (slope, 0.83 +/- 0.09 L/min/SaO2% and 0.85 +/- 0.19 L/min/SaO2% at basal condition and after 1 month, respectively). The normoxic hypercapnic ventilatory response remained unchanged after 1 month in both groups. No changes in ventilatory response to either hypoxia or hypercapnia were observed after a single night of nCPAP treatment. CONCLUSION: The ventilatory response to hypoxia is reduced during regular treatment, but not after short-term treatment, with nCPAP. Readjusted peripheral oxygen chemosensitivity during nCPAP treatment may be a side effect of both reduced sympathetic activity and increased baroreflex activity, or a possible continuous positive airway pressure-related mechanism leading to a reduced activation of autonomic nervous system per se.     

Determinants of hypercapnia in occlusive sleep apnea syndrome

To assess the relative contributions of age, gender, obesity, pulmonary function, and the severity of sleep-induced respiratory abnormalities to the development of alveolar hypoventilation in patients with occlusive sleep apnea syndrome, prospective data from III patients with occlusive sleep apnea were analyzed by stepwise logistic and multiple regression techniques. The significant variables in a logistic regression model predicting the presence of hypercapnia were daytime arterial oxygen pressure (PaO2; p less than 0.0001) and gender (p less than 0.04), the latter reflecting the higher number of hypercapnic women in our patient population. Multiple regression analysis performed in the hypercapnic group to study the determinants of the severity of elevation of arterial carbon dioxide tension (PaCO2) revealed significant contribution from the PaO2, the apnea-plus-hypopnea index (AHI), and the percent predicted forced vital capacity (r2 = 0.56; p less than 0.0001), whereas in the normocapnic patients, PaCO2 related to PaO2 only. These results suggest that daytime hypoxemia, mechanical impairment of the respiratory system due to obesity or obstructive airway disease (or both), and the severity of sleep-induced respiratory abnormalities as assessed by AHI contribute to the severity of carbon dioxide retention in patients with occlusive sleep apnea in a multifactorial fashion.     

Prevalence and mechanisms of diurnal hypercapnia in a sample of morbidly obese subjects with obstructive sleep apnoea

It is well known that obstructive sleep apnoea is especially frequent in the morbidly obese. In these subjects diurnal chronic hypercapnia, whose mechanism is still debated, may be present. Our study was performed to evaluate the prevalence and the mechanism of diurnal hypercapnia in the morbidly obese affected by obstructive sleep apnoea. From a population referred to our centre because of suspicion of sleep related breathing disorders, we selected 285 subjects without cardiopulmonary, neuromuscular or endocrinological diseases: 89 (36 M and 53 F, aged 46+/-13 years) had body mass index (BMI) > or = 40 kg m(-2) (MO group: morbidly obese subjects) and 196 (99 M and 97 F, aged 48+/-16 years) had BMI <40 kg m(-2) (NMO group: non-morbidly obese subjects). Then the MO group was divided into three subgroups: normocapnic subjects without obstructive sleep apnoea, normocapnic subjects with obstructive sleep apnoea, hypercapnic subjects with obstructive sleep apnoea; while we found no hypercapnic subject without obstructive sleep apnoea. All subjects underwent anthropometric evaluations and bioelectrical impedance analyses, respiratory function tests and arterial blood gas analysis, a modified version of the Sleep and Healthy questionnaire and a full night polysomnography. Our results showed that hypercapnia (PaCO2 > or = 45 mm Hg) associated with obstructive sleep apnoea [respiratory disturbance index (RDI) > or = 10 h(-1)] was found in 27% of the morbidly obese subjects, but only in 11% of the nonmorbidly obese ones (P<0.01). The comparison among the three subgroups, in which we divided the morbidly obese subjects, shows that those with hypercapnia and obstructive sleep apnoea had significantly more important ventilatory restrictive defects [forced vital capacity (FVC)% of pred 73.27+/-14 81 vs. 82.37+/-16.93 vs. 87.25+/-18.14 respectively; total lung capacity (TLC)% of pred 63.83+/-16.35 vs. 79.11+/-14.15 vs. 87.01+/-10.5], a significantly higher respiratory disturbance index (RDI 46.34+/-26.90 vs. 31.79+/-22.47 vs. 4.98+/-3.29) a longer total sleep time with oxyhaemoglobin saturation<90% [total sleeptime (TST)SaO2<90% 63.40+/-33.86 vs. 25.95+/-29.34 vs. 8.22+/-22.12] and a lower rapid eye movement (REM) stage (9.5+/-1.2 vs. 14.0+/-0.9 vs. 17.05+/-1.2) than normocapnic subjects with obstructive sleep apnoea or subjects without obstructive sleep apnoea. The best model to predict PaCO2 resulted from a combination of TSTSaO2<90% (r2 = 0.22, P<0.001), forced expiratory volume in 1 sec (FEV1)% of pred (r2 = 0.09, P<0.01), FVC % of pred (r2 = 0.075, P<0.01). In conclusion our study suggests that diurnal hypercapnia is frequently associated with obstructive sleep apnoea in the morbidly obese without chronic obstructive pulmonary disorder (COPD) and that ventilatory restriction and sleep related respiratory disturbances correlate to diurnal hypercapnia.     

Refractory hypertension and sleep apnoea: effect of CPAP on blood pressure and baroreflex.

This study was undertaken to determine whether abolition of obstructive sleep apnoea (OSA) by continuous positive airway pressure (CPAP) could reduce blood pressure (BP) in patients with refractory hypertension. In 11 refractory hypertensive patients with OSA, the acute effects of CPAP on nocturnal BP were studied during sleep and its longer term effects on 24-h ambulatory BP after 2 months. During a single night's application, CPAP abolished OSA and reduced systolic BP in stage 2 sleep from 138.3 +/- 6.8 to 126.0 +/- 6.3 mmHg. There was also a trend towards a reduction in average diastolic BP (from 77.7 +/- 4.5 to 72.9 +/- 4.5). CPAP usage for 2 months was accompanied by an 11.0 +/- 4.4 mmHg reduction in 24-h systolic BP. In addition, both the nocturnal and daytime components of systolic BP fell significantly by 14.4 +/- 4.4 and 9.3 +/- 3.9 mmHg, respectively. Diastolic BP was reduced significantly at night by 7.8 +/- 3.0 mmHg. In patients with refractory hypertension, acute abolition of obstructive sleep apnoea by continuous positive airway pressure reduces nocturnal blood pressure. These data also suggest that continuous positive airway pressure may reduce nocturnal and daytime systolic blood pressure chronically. Randomised trials are needed to confirm the latter results.     

Diurnal PaCO2 tension in obese women: relationship with sleep disordered breathing

OBJECTIVE: Several obese subjects show a wide array of respiratory disturbances during sleep due to an increased upper-airway resistance. The aim of the present study was to evaluate diurnal PaCO(2) tension in nonsmoking obese women and the possible relationship of this parameter with the presence of sleep disordered breathing (SDB). DESIGN: Cross-sectional study of PaCO(2) tension in obese women. PATIENTS AND METHODS: A total of 91 nonsmoking obese women (BMI > or =30 kg/m(2), aged 42.8+/-15.7 y) were recruited and evaluated for general and anthropometric parameters, respiratory function, sleep-related symptoms, and sleep disorders of breathing. RESULTS: A total of 10 subjects (10.9%) had diurnal hypercapnia (PaCO(2)> or =43 mmHg). Age, BMI, neck circumference, apnoea/hypopnoea index, and nocturnal desaturation (expressed as TST(SaO(2<90%)); TST(SaO(2<90%))=percentage of total sleep time with oxyhaemoglobin saturation <90%) were significantly higher in obese patients with diurnal hypercapnia, compared to normocapnic women. Moreover, hypercapnic patients had reduced forced expiratory volume in 1 s compared to normocapnic individuals. By using multiple regression analysis, the best fitting model (r=0.62, P<0.001) for predicting diurnal PaCO(2) tension in the study population showed that 24.23% of the variance may be explained by TST(SaO(2<90%)), according to the equation: PaCO(2)=0.09 age+0.07 TST(SaO(2<90%))+33.00. CONCLUSIONS: This study suggests that severity of SDB is the most important factor in determining diurnal PaCO(2) tension in apparently healthy nonsmoking obese women.     

Hypercapnia in obstructive sleep apnoea syndrome

BACKGROUND: The reports on the prevalence of hypercapnia in Obstructive Sleep Apnoea Syndrome (OSAS) are conflicting. We studied the prevalence of hypercapnia in a population of OSAS patients referred to a Department of Respiratory Medicine and the mechanism of the respiratory failure in OSAS associated with Obesity Hypoventilation Syndrome (OHS) or with Chronic Obstructive Pulmonary Disease (COPD) (Overlap syndrome). METHODS: We studied 219 consecutive OSAS patients during a period of 3 years. We recorded age and anthropomorphic data and performed polysomnography and pulmonary function tests. In relation to the value of PaCO(2), the patients were divided in hypercapnic (PaCO(2)>45 mmHg) patients and normocapnic patients. They were also divided into three groups in relation to the presence of "simple" or "pure" OSAS, to the presence of OSAS associated with COPD, to the presence of OSAS associated with OHS. RESULTS: Seventeen per cent of the patients were hypercapnic. They were significantly heavier, had more severe lung function test abnormalities and more severe nocturnal oxyhemoglobin desaturations than the normocapnic ones, while Forced Expiratory Volume in one second as a percentage of Forced Vital Capacity (FEV1/FVC %) and Apnoea/Hypopnoea Index (AHI) were similar. OHS patients (13%) were significantly younger and heavier, had lower PaO(2) and higher PaCO(2) than "simple" OSAS patients (77%) and Overlap patients (10%) and had more severe restrictive defect. There was no difference in terms of AHI among the three groups, but nocturnal oxyhemoglobin desaturations were more severe in OHS group. In OHS group hypercapnia was correlated to FVC% of predicted and FEV1% of predicted and to the mean nocturnal oxyhemoglobin saturation; in Overlap patients PaCO(2) was correlated to Forced Expiratory Flow rate at low Vital Capacity. CONCLUSION: Seventeen per cent of OSAS patients referred to a Department of Respiratory Medicine were hypercapnic. Hypercapnia in OHS patients correlates to the restrictive ventilatory defect whereas in Overlap patients it seems to correlate to peripheral airways obstruction. The distinction between patients with "simple" or "pure" OSAS and patients affected by OSAS associated with OHS or COPD could be important not only for clinical and prognostic implications, but also for the consequences in terms of ventilatory treatment.     

An analysis of nutritional status and pulmonary hypertension in patients with sequela of pulmonary tuberculosis and chronic obstructive pulmonary disease]

The prognostic value of hypercapnia and/or pulmonary hypertension differs in patients with sequela of pulmonary tuberculosis (TBseq) and those with chronic obstructive pulmonary disease (COPD) who are receiving home oxygen therapy (HOT). In an attempt to identify the factors, if any, that might explain this difference, we first compared nutritional status, respiratory function test results, dyspnea indexes, and other data for hypercapnic patients (PaCO2 > or = 45 Torr) and normocapnic patients (PaCO2 < 45 Torr) receiving HOT. Second, we examined the relationship between the degree of pulmonary hypertension and several respiratory function parameters for patients in each disease category. In 44 patients with TBseq, nutritional status estimated by body mass index and serum albumin was significantly better in the hypercapnic patients than in the normocapnic patients. However, this difference was not observed in 37 patients with COPD. In 30 patients with TBseq, the degree of pulmonary hypertension correlated significantly only with PaO2; in 32 patients with COPD, however, significant correlations were observed not only with PaO2 but also with PaCO2, %VC, and FEV1. These differences distinguishing groups of patients with the 2 diseases may provide an explanatory basis for the difference in prognostic value of hypercapnia and/or pulmonary hypertension in patients receiving HOT.     

Determinants of chronic hypercapnia in Japanese men with obstructive sleep apnea syndrome

STUDY OBJECTIVE: To identify the determinants of chronic hypercapnia (ie, PaCO(2), > or = 45 mm Hg) in men with obstructive sleep apnea syndrome (OSAS) without airflow obstruction. DESIGN: An analysis was conducted of 143 male patients with OSAS, which had been diagnosed by polysomnography (PSG), who had been referred to a university hospital. Patients were classified as hypercapnic (ie, PaCO(2), > or = 45 mm Hg) and normocapnic (ie, PaCO(2), < 45 mm Hg), and obese (ie, body mass index [BMI], > or = 30 kg/m(2)) or nonobese (ie, BMI, < 30 kg/m(2)). Patients with airflow obstruction (ie, FEV(1)/FVC ratio, < 70%) were excluded from the study. Baseline clinical characteristics, pulmonary function, PSG data, and blood gas data were compared between hypercapnic and normocapnic patients. Correlations between PaCO(2) and several anthropometric, respiratory, and polysomnographic variables were determined by stepwise multiple regression analysis. RESULTS: Fifty-five patients (38%) were hypercapnic. Hypercapnic patients were younger and heavier, and had more abnormalities on pulmonary and PSG testing. Stepwise multiple regression analysis revealed that the PaCO(2) level was influenced significantly by the mean level of arterial oxygen saturation (SaO(2)) during sleep and by the percent of vital capacity (%VC) (R(2) = 0.430; p < 0.0001), indicating that 43% of the total variance in the PaCO(2) could be explained by the mean SaO(2) and %VC in hypercapnic patients. In contrast, only 13% of the total variance in the PaCO(2) was accounted for by the mean SaO(2) and BMI in normocapnic patients (R(2) = 0.134; p = 0.0034). The mean SaO(2), %VC, and PaO(2) were selected as independent variables for predicting the PaCO(2) in obese patients. These variables explained 41% of the total variance in the PaCO(2) (R(2) = 0.407; p < 0.0001), whereas the mean SaO(2) only accounted for 13% of the total variance in PaCO(2) levels in nonobese patients (R(2) = 0.134; p = 0.0064). CONCLUSION: Nocturnal desaturation and restrictive pulmonary impairment play major roles in determining the PaCO(2) in hypercapnic and obese OSAS patients without airflow obstruction.     

阻塞性睡眠呼吸暂停低通气综合征与合并慢性阻塞性肺疾病患者的日间高碳酸血症的临床研究

目的 比较单纯阻塞性睡眠呼吸暂停低通气综合征(obstructive sleep apnea-hypopnea syndrome,OSAHS)与合并慢性阻塞性肺疾病即重叠综合征(overlap syndrome,OS)患者肺功能变化,日间高碳酸血症与睡眠呼吸紊乱之间的关系.方法 42例OSAHS患者,23例为单纯OSAHS患者组,19例为OS患者组,两组均做多导睡眠仪监测、肺功能检测、血气分析检测.比较两组睡眠紊乱指标、肺功能及PaCO2情况并做相关性分析.结果 两组患者在睡眠呼吸暂停低通气指数相似的情况下,OS组的PaCO2明显高于OSAHS组;OS组的肺功能指标明显差于OSAHS组;两组患者的日间PaCO2与睡眠呼吸暂停严蘑程度之间无明显线性相关关系.结论 OS组患者的肺功能较OSAHS组差;OS组的日问高PaCO2与是否台并OSAHS无关.     

Role of daytime hypoxemia in the pathogenesis of right heart failure in the obstructive sleep apnea syndrome

Although right heart failure is a recognized complication of obstructive sleep apnea, the incidence and pathogenesis of this complication have not been established. We therefore studied 50 consecutive patients with obstructive sleep apnea to determine the incidence of right heart failure and the factors involved in its development. Six patients (12%) were found to have right heart failure. There were no differences in the number of apneas between those with right heart failure (mean +/- SE, 30 +/- 10 per h sleep) and those without right heart failure (33 +/- 4 per h sleep). In contrast, mean nocturnal oxygen saturation was lower in patients with right heart failure (76 +/- 3%) than in those without right heart failure (90 +/- 1%; p less than 0.001). Furthermore, patients with right heart failure also had a substantially lower awake arterial PO2 (52 +/- 4 mmHg versus 75 +/- 2 mmHg; p less than 0.001) and a higher PCO2 (51 +/- 2 mmHg versus 36 +/- 1 mmHg; p less than 0.001) than those without right heart failure. Severe nocturnal hypoxemia in the absence of diurnal hypoxemia was not associated with right heart failure. Daytime hypoxemia in the patients with right heart failure was associated with a higher residual volume (p less than 0.001) and lower forced expiratory volume in one second (p less than 0.001) than in the patients without right heart failure. The findings suggest that sustained hypoxemia and/or hypercapnia over a 24-h period is a necessary prerequisite for the development of right heart failure in patients with obstructive sleep apnea, and that diffuse airway obstruction plays a major role in causing such hypoxemia.     

Pulmonary hypertension, hypoxemia, and hypercapnia in obstructive sleep apnea patients

To define the parameters of respiratory insufficiency in OSA, 114 consecutive patients (108 men, six women) were prospectively studied. In addition to standard polysomnography, they underwent pulmonary function tests, right heart catheterization, and ventilatory response tests to hypercapnia. Nineteen patients (19 percent) had a resting PAP greater than or equal to 20 mm Hg. Multiple regression analysis showed that FEV1 and PaO2 (both with a negative coefficient) and PaCO2 (with a positive coefficient) significantly contributed to PAP. Thirteen patients (12 percent) had a PaCO2 greater than or equal to 45 mm Hg. A multiple regression analysis showed that FEV1 and the minute ventilation at PETCO2 = 60 mm Hg (both with a negative coefficient) and the cumulative apnea duration (with a positive coefficient) significantly contributed to PaCO2. Thirty-seven patients (33 percent) had a PaO2 less than or equal to 65 mm Hg. A multiple regression analysis showed that FEV1 (with a positive coefficient) and the hypopnea + apnea index (with a negative coefficient) significantly contributed to PaO2. These data confirm that impaired daytime pulmonary function (diffuse airway obstruction) contributes to the development of daytime pulmonary hypertension, hypoxemia, and hypercapnia in OSA patients. They show that the amount of sleep-related breathing disorders also plays a significant role.     

Obesity hypoventilation syndrome as a spectrum of respiratory disturbances during sleep

OBJECTIVE: To identify the spectrum of respiratory disturbances during sleep in patients with obesity hypoventilation syndrome (OHS) and to examine the response of hypercapnia to treatment of the specific ventilatory sleep disturbances. DESIGNS AND METHODS: Twenty-three patients with chronic awake hypercapnia (mean [+/- SD] PaCO(2), 55 +/- 6 mm Hg) and a respiratory sleep disorder were retrospectively identified. Nocturnal polysomnography testing was performed, and flow limitation (FL) was identified from the inspiratory flow-time contour. Obstructive hypoventilation was inferred from sustained FL coupled with O(2) desaturation that was corrected with treatment of the upper airway obstruction. Central hypoventilation was inferred from sustained O(2) desaturation that persisted after the correction of the upper airway obstruction. Treatment was initiated, and follow-up awake PaCO(2) measurements were obtained (follow-up range, 4 days to 7 years). RESULTS: A variable number of obstructive sleep apneas/hypopneas (ie, obstructive sleep apnea-hypopnea syndrome [OSAHS]) were noted (range, 9 to 167 events per hour of sleep). Of 23 patients, 11 demonstrated upper airway obstruction alone (apnea-hypopnea/FL) and 12 demonstrated central sleep hypoventilation syndrome (SHVS) in addition to a variable number of OSAHS. Treatment aimed at correcting the specific ventilatory abnormalities resulted in correction of the chronic hypercapnia in all compliant patients (compliant patients: pretreatment, 57 +/- 6 mm Hg vs post-treatment, 41 +/- 4 mm Hg [p < 0.001]; noncompliant patients: pretreatment, 52 +/- 6 mm Hg vs post-treatment, 51 +/- 3 mm Hg; [difference not significant]). CONCLUSIONS: This study demonstrates that OHS encompasses a variety of distinct pathophysiologic disturbances that cannot be distinguished clinically at presentation. Sustained obstructive hypoventilation due to partial upper airway obstruction was demonstrated as an additional mechanism for OHS that is not easily classified as SHVS or OSAHS.     

The voluntary drive to breathe is not decreased in hypercapnic patients with severe COPD.

How do the respiratory centres of patients with chronic obstructive pulmonary disease (COPD) and hypercapnia respond to acute increases in inspiratory load? A depressed respiratory motor output has long been postulated, but studies on this issue have yielded inconsistent results, partly due to limitations of investigative techniques. Many of these limitations can be overcome by the twitch interpolation technique, which is capable of accurately quantifying the degree of diaphragmatic activation, termed the voluntary drive to breathe. The hypothesis that patients with COPD and hypercapnia compensate for an acute increase in mechanical load on the inspiratory muscles with a lower voluntary drive to breathe than is the case with normocapnic patients was tested. Measurements were obtained in 15 patients with COPD, six of whom displayed hypercapnia and nine normocapnia. The maximum degree of diaphragmatic activation, expressed as a voluntary activation index (mean +/- SEM), was higher in hypercapnic than in normocapnic patients (98.7 +/- 0.7 versus 94.5 +/- 0.9% (p = 0.006)), as was the mean value (94.5 +/- 0.7 versus 88.5 +/- 1.9% (p = 0.01)). Within-patient values of the index were also less variable in the hypercapnic patients (coefficients of variation, 3.4 +/- 0.3 versus 6.1 +/- 0.9%, p = 0.01). Multiple regression analysis revealed the ratio of dynamic elastance to maximum transdiaphragmatic pressure, an index of inspiratory muscle loading, and pH as the only variables that correlated with maximum voluntary activation index (r2 = 0.69, p = 0.02 for each variable). Contrary to the hypothesis, it was concluded that voluntary activation of the diaphragm was greater and less variable in hypercapnic patients than normocapnic patients with severe chronic obstructive pulmonary disease during an acute increase in inspiratory mechanical load. Whether greater diaphragmatic recruitment during episodes of a severe exacerbation of chronic obstructive pulmonary disease provides a survival advantage for hypercapnic patients with chronic obstructive pulmonary disease remains to be determined.     

Effects of acetazolamide and furosemide on ventilation and cerebral blood volume in normocapnic and hypercapnic patients with COPD

STUDY OBJECTIVES: Effects of chronic metabolic alkalosis and acidosis and their relation to central chemoregulation may differ between normocapnic and chronic hypercapnic patients with COPD. The relationship between responses of inspired ventilation (VI), mouth occlusion pressure (P(0.1)), and cerebral blood volume (CBV), to short-term changes in arterial PCO(2) was measured. PATIENTS AND METHODS: Seventeen patients with chronic hypercapnia and COPD (PaCO(2) > 6.0 kPa) and 16 normocapnic patients with COPD (PaCO(2) < or = 6.0 kPa) [FEV(1) 27% predicted] were studied under baseline metabolic conditions and after 1 week of treatment with oral furosemide, 40 mg/d, or acetazolamide, 500 mg/d. Hypercapnia (change in end-tidal carbon dioxide > 1 kPa) was induced by administering adequate amounts of carbon dioxide in the inspired air. CBV was measured using near-infrared spectroscopy. RESULTS: Compared with baseline metabolic condition, chronic metabolic acidosis and alkalosis did not change ventilatory (Delta VI/Delta PaCO(2)) and cerebrovascular (Delta CBV/Delta PaCO(2)) reactivity. Base excess (BE) decreased by 6.8 +/- 1.1 mEq/L and 6.9 +/- 1.6 mEq/L, respectively, in the normocapnic and chronic hypercapnic COPD groups during metabolic acidosis, resulting in a not-quite-significant leftward shift of both the ventilatory and cerebrovascular carbon dioxide response curve. BE increased by 2.3 +/- 1.2 mEq/L and 1.2 +/- 1.3 mEq/L, respectively, during chronic metabolic alkalosis in both COPD groups, without concomitant shift. Poor correlations between ventilatory and cerebrovascular carbon dioxide responsiveness (Delta CBV/Delta PaCO(2) and Delta VI/Delta PaCO(2), Delta CBV/Delta PaCO(2) and Delta P(0.1)/Delta PaCO(2), respectively) were found irrespective of baseline, respiratory condition, and induced metabolic state. CONCLUSIONS: Normocapnic and chronic hypercapnic COPD patients have the same ventilatory and cerebrovascular carbon dioxide responsiveness irrespective of induced metabolic state.     

Nocturnal asthma: role of snoring and obstructive sleep apnea

In this study, we documented the clinical features of patients who had obstructive sleep apnea (OSA) and coexisting asthma and assessed the safety of nocturnal nasal continuous positive airway pressure (nCPAP) therapy on the stability of asthma. Nine patients (8 men and 1 woman) with asthma and OSA confirmed on all-night sleep study were studied. All patients suffered from frequent nocturnal asthma attacks, resulting in hospitalizations and respiratory arrests in 3. All patients had symptoms of heavy snoring, nocturnal choking, frequent sleep arousals, and excessive daytime sleepiness. They recorded their daily peak expiratory flow rates (PEFR) in the mornings and evenings, before and after bronchodilator in three 2-wk periods consisting of control, nCPAP, and control. During the period of nCPAP therapy, all patients recorded improvement in their PEFR. The mean prebronchodilator and postbronchodilator PEFR for the 9 patients were significantly higher during nCPAP therapy than during both control periods. This study confirms that nCPAP therapy can be used safely in treating patients with OSA and coexisting asthma. Furthermore, nCPAP treatment improves the asthma control and, in particular, the nocturnal attacks in this group of patients. These results also suggest that recurrent upper airway obstruction and snoring may be important triggering mechanisms of nocturnal asthma attacks.     

Long-term reduction of hyperinflation in stable COPD by non-invasive nocturnal home ventilation

OBJECTIVE: The role of non-invasive positive pressure ventilation (NPPV) in stable COPD with chronic ventilatory failure remains controversial. The impact of long-term home nocturnal NPPV treatment on deflation has not yet been evaluated in detail. METHODS: Retrospective explorative study of 46 patients with stable COPD undergoing NPPV treatment. Effects of NPPV on body plethysmographic parameters, blood gas tensions and inspiratory muscle function after 6.2 (+/-1.7) and 12.7 (+/-2.1) months of treatment. Further, evaluation of 1-year survival, compliance and ventilation parameters. RESULTS: One-year survival was 89.1%. The effectiveness of ventilation was proven by a significant reduction in nocturnal and daytime PaCO2. We observed a decrease in the ratio of residual volume (RV) to total lung capacity (TLC) on the average of 5.2+/-9.8% (or 15.2+/-29.7% pred.; P<0.01) at six and 3.9+/-9.0% (or 12.9+/-18.6% pred.; P<0.001) at 12 months. As a consequence, we found significant improvements in inspiratory capacity (IC), vital capacity (VC) and forced expiratory volume in one second (FEV1). For patients with the most severe hyperinflation (RV/TLC>75%), we found a significant positive correlation between inspiratory positive airway pressure (IPAP) and reductions in PaCO2 (r=0.56; P<0.05) and RV/TLC (r=0.50; P<0.05). CONCLUSIONS: In severe hypercapnic stable COPD long-term nocturnal NPPV can reduce hyperinflation with sustained improved daytime blood gas parameters.     

Impact of CPAP on asthmatic patients with obstructive sleep apnoea.

The impact of continuous positive airway pressure (CPAP) treatment on the airway responsiveness of asthmatic subjects with obstructive sleep apnoea (OSA) has scarcely been studied. A prospective study was performed comparing the changes in airway responsiveness and quality of life in stable asthmatic OSA patients, before and 6 weeks after their nocturnal CPAP treatment. A total of 20 subjects (11 males and nine females) participated in the study. With the nocturnal CPAP treatment, the apnoea/hypopnoea index dropped from 48.1 +/- 23.6 x h(-1) to 2.6 +/- 2.5 x h(-1). There were no significant changes in airway responsiveness after CPAP treatment (provocative concentration causing a 20% fall in forced expiratory volume in one second (FEV(1); PC(20) 2.5 mg x mL(-1) (1.4-4.5)) compared with baseline (PC(20) 2.2 mg x mL(-1) (1.3-3.5)). There was no significant change in FEV(1) either. However, the asthma quality of life of the subjects improved from 5.0 +/- 1.2 at baseline to 5.8 +/- 0.9 at the end of the study. In conclusion, nocturnal continuous positive airway pressure treatment did not alter airway responsiveness or forced expiratory volume in one second in subjects with stable mild-to-moderate asthma and newly diagnosed obstructive sleep apnoea. However, nocturnal continuous positive airway pressure treatment did improve asthma quality of life.