Pulmonary hypertension (PH) is likely to complicate chronic obstructive pulmonary disease (COPD) in a large proportion of patients, especially those with severe disease. Majority of patients have a mild to moderate elevation in the pulmonary artery pressure that usually does not require specific treatment. A small subset of patients, however, develops severe PH that is "out-of-proportion" to the severity of COPD. Generally considered a consequence of chronic hypoxaemia, endothelial dysfunction has now been recognised to play an important role in the pathogenesis of PH in COPD. Pulmonary vessels remodelling characterised by intimal enlargement with proliferating smooth muscle cells, medial hypertrophy, arteriolar muscularisation and endothelial cell proliferation, especially affecting the small arterioles and arteries, leads to permanent changes in the vascular structure and function. Clinical recognition of PH is difficult. Echocardiography is used for screening while right heart catheterisation is the gold standard for diagnosis. In patients who have a moderate degree of chronic hypoxaemia, long term oxygen therapy is indicated and is the only therapeutic measure so far known to retard the progress of PH. Newer therapies targeting the specific abnormalities of vasoconstrictor-vasodilator balance, arising as a consequence of endothelial dysfunction, are under investigation and may offer a management option especially in severe PH associated with COPD.

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death in the US. Numerous studies have demonstrated that sleep disturbances are common in COPD patients, with more prominent complaints in patients with more severe disease and with increasing age. Sleep disturbances may occur due to the effects of breathing abnormalities on sleep and sleep disruption. However, other etiologies may include the medications used to treat COPD, concomitant anxiety and depression, and the presence of comorbid sleep disorders. The respiratory disturbances that occur in these patients during sleep have been evaluated by examining sleep-related oxygen desaturation, reduction in pulmonary function during sleep, and development of hypoventilation during rapid eye movement sleep. Treatment includes use of nocturnal oxygen therapy, noninvasive positive pressure ventilation, and long-acting medications. There has been little study on improving sleep quality beyond treating the respiratory disease, despite the fact that numerous studies show poor sleep quality, a high prevalence of insomnia, and tolerability of newer hypnotic agents in the setting of COPD. This article defines the scope of sleep problems in the setting of COPD, reviews the impact of sleep on ventilation, explores the role of obstructive sleep apnea in the setting of COPD, and reviews therapeutic options.

Pulmonary hypertension (PH) is a common complication of chronic respiratory diseases and particularly of chronic obstructive pulmonary disease (COPD) and interstitial lung diseases (ILD). Owing to its frequency COPD is by far the most common cause of PH. It is generally a mild to moderate PH, pulmonary artery mean pressure (PAP) usually ranging between 20 and 25 mm Hg, but PH may worsen during exercise, sleep, and particularly during exacerbations of the disease. These acute increases in PAP may lead to the development of right heart failure. A small proportion of COPD patients may present "disproportionate" PH defined by a resting PAP >35 to 40 mm Hg. The prognosis is particularly poor in these patients. PH is relatively frequent in advanced ILD and particularly in idiopathic pulmonary fibrosis. As in COPD the diagnosis is suggested by Doppler echocardiography, but the confirmation still requires right heart catheterization. As in COPD, functional (alveolar hypoxia) and morphological factors (vascular remodeling, destruction of the pulmonary parenchyma) explain the elevation of pulmonary vascular resistance that leads to PH. Also as in COPD PH is most often mild to moderate. In ILD the presence of PH predicts a poor prognosis. The treatment of PH relies on long-term oxygen therapy."New" vasodilator drugs have rarely been used in COPD and ILD patients exhibiting severe PH. In advanced ILD the presence of PH is a supplemental argument for considering lung transplantation.

Inspiratory muscles are uniquely adapted for endurance but their function is compromised in COPD due to increased loads, reduced mechanical advantage and increased ventilatory requirements. The hyperinflation of COPD reduces the flow and pressure generating capacity of the diaphragm. This is compensated by a three-fold increase in neural drive, adaptations of the chest wall and diaphragm shape to accommodate the increased volume, and adaptations of muscle fibres to preserve strength and increase endurance. Paradoxical indrawing of the lower costal margin during inspiration in severe COPD (Hoover's sign) correlates with high inspiratory drive and severe airflow obstruction rather than contraction of radially-oriented diaphragm fibers. The inspiratory muscles remain highly resistant to fatigue in patients with COPD and the ultimate development of ventilatory failure is associated with insufficient central drive. Sleep is associated with reduced respiratory drive and impairments of lung and chest wall function, which are exaggerated in COPD patients. Profound hypoxemia and hypercapnia can occur in REM sleep and contribute to the development of cor pulmonale. Inspiratory muscles adapt to chronic loading with an increased proportion of slow, fatigue-resistant fiber types, increased oxidative capacity and reduced fiber cross-sectional area but the capacity of the diaphragm to increase ventilation in exercise is compromised in COPD. In COPD neural drive to the diaphragm increases to near maximal levels in exercise but it does not develop peripheral muscle fatigue. The improvement in exercise capacity and dyspnea following lung volume reduction surgery is associated with a substantial reduction in neural drive to the inspiratory muscles. Key words: Diaphragm, Mechanics, Neural Drive, Fatigue.

Background: Oxy-Gen lite, a recently developed combined electrolysis and fuel cell technology, de-novo generates oxygen with high purity for medical use from distilled water and room air. However, its use in patients with chronic respiratory failure has never been evaluated.- Objectives: To test the clinical applicability and safety of Oxy-Gen lite technology, we enrolled 32 COPD patients with chronic hypoxemia and long-term oxygen therapy (LTOT) in a controlled, randomized, multicenter clinical trial.- Materials and Methods: Standard continuous oxygen therapy with a maximal flow rate of 2 L/min was tested against pulsatile oxygen delivery by Oxy-Gen lite. Oxygen saturation at seated-rest was recorded over 30 min and used as a primary read-out parameter. Oxygen saturation was also recorded during mild physical strain (speaking out loud) or overnight's sleep.- Results: Both methods of oxygen supply established oxygen saturations within the normal range (i.e., upper plateau of the sigmoid oxyhaemoglobin dissociation curve) compared to breathing room air (p<0.0001). Mean oxygen saturation under standard continuous oxygen flow or Oxy-Gen lite technology during rest, physical strain or sleep proved statistically equivalent (95%CI < 2.5% of reference saturation).- Conclusion: The use of Oxy-Gen lite in COPD patients with hypoxemia and LTOT =< 2 L/min is safe and results in oxygen saturation comparable to standard oxygen therapy. There is evidence that this form of oxygen supply is not only functional during rest but also during mild physical strain or overnight's sleep. Low noise, energy- and overhead-costs are particular advantages of this technology.

The overlap syndrome defines the relationship between obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD), and is a commonly noted but poorly studied disorder. Individuals who have the overlap syndrome have been recognized to have greater risk for pulmonary hypertension, right heart failure, and hypercapnia than patients who have either disorder alone. In patients who have advanced-stage COPD, concomitant OSA likely has significant adverse consequences. The interaction between these two diseases is unclear, however. Further clinical trials of the overlap syndrome are urgently needed.

The quality of sleep is significantly compromised in many patients with chronic obstructive pulmonary disease (COPD) and may be further diminished when certain comorbidities are present. A reduced sleep quality is associated with daytime consequences like fatigue, psychiatric problems and an impaired quality of life. Sleep induces physiologic alterations in respiratory function, which can become pathologic and may provoke or worsen hypoxemia and hypercapnia in COPD. Dyspnea, cough and excessive mucus production should be optimised to minimise causes for sleep disturbance. Pharmacological therapy may be helpful; sedatives like benzodiazepines and non-benzodiazepine benzodiazepine-receptor agonists (NBBRAs) are (equally) effective in improving sleep quality. Whether or not these hypnotics produce serious adverse respiratory effects during sleep, remains unclear due to opposing studies. Therefore, their use should be as short as possible.

Chronic obstructive pulmonary disease (COPD) is associated with significant morbidity and mortality. Its possible association with obstructive sleep apnea is a major cause of concern for clinicians. As the prevalence of both COPD and sleep apnea continues to rise, further investigation of this interaction is needed. In addition, COPD patients are at risk for hypoventilation during sleep due to the underlying respiratory dysfunction. In this study, 13 COPD subjects and 13 non-COPD control subjects were compared for the presence and severity of obstructive sleep apnea and nocturnal hypoventilation. All 26 subjects had presented to a sleep clinic and showed no signs of daytime hypoxemia. After matching for BMI and age, COPD subjects had a similar prevalence of sleep apnea with a lower degree of severity compared to the control subjects. However, less severe events, such as RERA, occurred at similar rates between the two groups. There was no significant difference between groups in the magnitude of oxyhemoglobin desaturation during sleep. Interestingly, severity and presence of nocturnal hypoxemia correlated with that of sleep apnea in the control group, but not in the COPD subjects. In conclusion, COPD without daytime hypoxemia was not a risk factor for sleep apnea or nocturnal hypoventilation in this study.

Patients with COPD may show slow, progressive deteriorations in arterial blood gases during the night, particularly during rapid eye movement (REM) sleep. This is mainly due to hypoventilation, while a deterioration of ventilation/perfusion mismatch plays a minor role. The severity of gas exchanges alterations is proportional to the degree of impairment of diurnal pulmonary function tests, particularly of partial pressure of oxygen (PaO2) and of carbon dioxide (PaCO2) in arterial blood, but correlations between diurnal and nocturnal blood gas levels are rather loose. Subjects with diurnal PaO2 of 60-70 mmHg are distinguished in "desaturators" and "nondesaturators" according to nocturnal oxyhemoglobin saturation behavior. The role of nocturnal hypoxemia as a determinant of alterations in sleep structure observed in COPD is dubious. Effects of the "desaturator" condition on pulmonary hemodynamics, evolution of diurnal blood gases, and life expectancy are also controversial. Conversely, it is generally accepted that occurrence of sleep apneas in COPD is associated with a worse evolution of the disease. Nocturnal polysomnographic monitoring in COPD is usually performed when coexistence of sleep apnea ("overlap syndrome") is suspected, while in most other cases nocturnal oximetry may be enough. Nocturnal oxygen attenuates sleep desaturations among stable patients, without increases in PaCO2 of clinical concern. Nocturnal treatment with positive pressure ventilators may give benefit to some stable hypercapnic subjects and patients with the overlap syndrome.

The objective of the present study was to compare anthropometry with bioelectrical impedance (BIA) in relation to densitometry (dual-energy X-ray absorptiometry; DEXA) as methods of nutritional assessment and body composition in out-patients with chronic pulmonary obstructive disease (COPD). We conducted a cross-sectional clinical study with sixty-one patients with COPD (forty-two men and nineteen women), mean age of 66.5 (sd 7.9) years and forced expiratory volume in 1 s of 1.3 (sd 0.6) litres (52.2 (sd 19.8)% predicted), referred to the Pulmonary Rehabilitation Center. The patients were evaluated regarding nutrition status and body composition as determined by anthropometry, BIA and DEXA. In the results, 34.4 % showed mild obstruction, 31.2 %, moderate and 34.4 %, severe obstruction. According to the BMI (mean 24.5 (sd 4.5) kg/m(2)), 45.9 % of the patients exhibited normal weight, while 27.9 % were underweight and 26.2 % were obese. Related to fat-free mass (FFM), anthropometry and BIA compared with DEXA presented high correlations (r 0.96 and 0.95 respectively; P<0.001) and high reliability between the methods (alpha 0.98; P<0.001). Agreement analysis between the methods shows that anthropometry overestimates (0.62 (sd of the difference 2.89) kg) while BIA underestimates FFM (0.61 (sd of the difference 2.82) kg) compared with DEXA. We concluded that according to the nutritional diagnosis, half of our population of patients with COPD showed normal weight, while the other half comprised equal parts obese and underweight patients. Body composition estimated by BIA and anthropometry presented good reliability and correlation with DEXA; the three methods presented satisfactory clinical accuracy despite the great disparity of the limits of agreement.

We measured ear oxygen saturation (SaO2), chest wall movement, and oronasal air flow, and took electroencephalographic tracings during nocturnal sleep in 20 healthy subjects and 20 similarly aged patients with chronic obstructive pulmonary disease (COPD), none of whom was obese. Thirteen of the patients with COPD were persistently hypoxemic and hypercapnic when awake ("blue and bloated", Type B); the remaining 7 maintained relatively normal arterial gas tensions when awake despite equally severe airways obstruction ("pink and puffing", Type A). Hypoxemic episodes (HE)(SaO2 falls of greater than 10%) occurred during sleep in all the blue bloaters but in only 3 of 7 pink puffers and 3 of 20 normal subjects. However, the maximal change in arterial oxygen tension (PaO2)(calculated from SaO2 values assuming normal pH) was similar in all 3 groups, averaging 24 mmHg. Furthermore, the cumulative duration of apnea and hypopnea was the same in each group. Only one patient COPD had more than 2 apneas per night, and obstructive apnea was seen only in the healthy subjects. Sleep apnea syndromes thus appear to be rare in nonobese patients with COPD. Of the 40 HE in patients with COPD, 29 occurred during periods of hypoventilation. In 10 blue bloaters whose arterial blood was sampled during sleep, the measured fall in PaO2 during the HE (mean, 11.2 mmHg) was greater than the rise in PaCO2 (mean, 4.2 mmHg). Although these changes in arterial gas tensions could be produced by an increase in ventilation-perfusion imbalance during the HE, it is suggested that unsteady-state gas exchange during transient hypoventilation could provide an alternative explanation.

Breathing patterns, ear oxygen saturation (SaO2), and EEG sleep-stage throughout an undisturbed night's sleep were compared in ten adult stable asthmatics and ten age-matched healthy subjects. The two groups slept equally long (5.0-7.2, mean 6.2 h), but the asthmatics slept less well; they had more periods of wakefulness and drowsiness and irregular breathing than did the healthy subjects. They also had greater and more frequent falls in SaO2. Most hypoxaemic episodes occurred in the rapid-eye movement phase of sleep and were associated with hypopnoea or apnoea, but no patient had a classical sleep-apnoea syndrome. The severity of nocturnal hypoxaemia was related to the level of SaO2 when the subjects were awake, but did not correlate with the fall in forced expiratory volume recorded in eight out of ten asthmatics after sleep.

We have shown that the Hewlett-Packard 47201A ear oximeter measures arterial O2 saturation within 95 per cent confidence limits of +/- 4 per cent when arterial blood saturation is more than 65 per cent, but at lower saturations the oximeter consistently provides a reading that is too low. The oximeter is sensitive to carboxyhemoglobin, progressively overestimating arterial saturation as carboxyhemoglobin concentration increases from 0 to 18 per cent. The time response is exponential, with a normal time constant of 3 sec, but this is halved in the fast mode or operation.

Characteristics of the episodes of wakefulness and drowsiness (stage 0 + 1) intervening in a night of electrophysiologically monitored sleep were compared in a homogeneous group of 13 patients (mean age 57 years) with severe hypoxic chronic bronchitis and emphysema (blue and bloated variety) and 8 age matched control subjects. The total amounts of stage 0 + 1 accumulated over one night (preceded by one night of adaptation) were high in both groups (28% in the patients, 22% in the control subjects). A significant difference was found in the number of brief arousals (episodes of stage 0 + 1 lasting for less than 1 min), which averaged 10/h of sleep in the patients, and 6/h of sleep in the control subjects (p less than 0.05, two tailed). The numbers of longer episodes of stage 0 + 1 were not significantly different and varied independently from the numbers of brief arousals in the individuals. Only a small proportion (8 %) of brief arousals was linked to episodes of hypopnea or apnea in the bronchitic patients. Large numbers of brief arousals/h of non rapid eye movement sleep inthe bronchitic patients correlated significantly with small percentages of stage 3 + 4 sleep (p less than 0.05), and were associated with smell numbers of hypoxemic episodes occurring predominantly in rapid eye movement sleep. The findings indicate a more fractionated sleep in the patients with chronic hypoxic bronchitis, and suggest that the brief arousals represent a limiting factor rather than a result of the nocturnal hypoxemic episodes occurring in these patients.

We have related the red cell mass (RCM) in 47 hypoxic patients with COPD (mean PO2, 52.5 +/- 5.2 SD mmHg; mean PCO2, 51.7 +/- 6.7 mmHg; mean/FEV1, 0.6 +/- 0.2 L; mean FVC, 1.7 +/- 0.6 L) to their smoking habits and outpatient carboxyhemoglobin concentrations. The mean RCM was 42.5 +/- 8.0 ml/kg in the 31 patients who still smoked, significantly (p less than 0.01) higher than in the 16 who were currently nonsmokers (RCM, 29.7 +/- 4.4 ml/kg). Measurements of arterial PO2, pH, P50, and COHb showed that the saturation of available hemoglobin (SO2A) was less well correlated (r =-0.36, p less than 0.05) with RCM in the smokers, than was SO2T (r =-0.58, p less than 0.001), SO2T including a corrective term for COHb. The RCM correlated well with the mean outpatient COHb measured repeatedly over 6 to 36 months in 40 of the patients but poorly with thier average arterial oxygen saturation (r = 0.15, p less than 0.1). In 15 patients given long-term oxygen therapy (15 hours/24-hour period) for 12 months RCM decreased significantly only in those who stopped smoking, as shown by a decrease in COHb. We conclude that cigarette smoking may determine the severity of secondary polycythemia in patients with hypoxic COPD, and prevent its correction by long-term oxygen therapy.

A computer program was developed to calculate the frequency dependence of dynamic compliance (Cdyn) using continuous data analysis. Cdyn was measured repeatedly in eight normal human subjects over a 2-yr period. Comparison with Cdyn results measured manually showed that the computer program improved 10-fold the ratio of variance within subjects to between subjects of the compliance at specific frequencies, but there was only slight improvement in indices of the slope of the frequency dependence of compliance. We suggest that the absolute compliance at specific frequencies merits further consideration as a pathophysiological measurement and that, if the frequency dependence of compliance continues to be used, standardization of its calculation should be applied and the wide normal range should be more widely appreciated. Measurements of Cdyn in subjects breathing 80% helium-20% oxygen confirm that inertia is insignificant when breathing with tidal volumes of less than 500 ml and frequency of less than 1.5 Hz.

We have studied arterial oxygen saturation (SaO2), breathing patterns, and electroencephalographic (EEG) sleep stage during nocturnal sleep in six patients with right-to-left cardiac or intrapulmonary shunts and six patients with chronic bronchitis and emphysema, chosen because they were equally hypoxaemic when awake (SaO2 during wakefulness: bronchitis 74-90%, mean 83%; shunt 77-89%, mean 83%). The patients with bronchitis had far greater falls in SaO2 when asleep than those with shunts (maximum fall in SaO2 during sleep: bronchitis 14-47%, mean 29%; shunt 5-10%, mean 8%; p less than 0.01). Significant episodes of hypoxaemia (defined as SaO2 falls greater than 10%) occurred in all six bronchitic patients, from once to seven times per night, but in none of the patients with shunts (p less than 0.05). Twenty-four of the 27 episodes of hypoxaemia occurred in rapid-eye-movement (REM) sleep and 24 were associated with hypopnoea. The two groups of patients had similar EEG sleep patterns and the same amount of hypopnoea during sleep. Thus the level of arterial oxygenation when the patient is awake is not the sole determinant of the degree of nocturnal hypoxaemia; the pathological process is also important.