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Chronic alveolar hypoventilation is a classic feature of the "pickwickian syndrome" (i.e. obesity-hypoventilation syndrome) but in fact hypercapnia is observed in a minority of obstructive sleep apnoea syndrome (OSAS) patients. Most recent studies having included large numbers of unselected, consecutive OSAS patients agree on a prevalence of 10-20% of alveolar hypoventilation. The mechanisms of hypercapnia in OSAS are not fully understood but the determining factors of daytime respiratory insufficiency are probably the presence of a marked obesity, leading to the obesity hypoventilation syndrome and, principally, the association of OSAS with chronic obstructive pulmonary disease. This association (the so-called "overlap syndrome") is observed in >10% of OSAS patients. Bronchial obstruction is generally mild to moderate and may be asymptomatic. The severity of the nocturnal events (apnoeas, hypopnoeas) and a (possible) diminished chemosensitivity to hypercapnic and hypoxic stimuli do not appear to be determining factors of hypercapnia. The most important consequence of chronic alveolar hypoventilation is pulmonary hypertension which is only observed in patients with daytime arterial blood gases disturbances, and which can lead to right heart failure. When nasal continuous positive airway pressure fails to correct sleep-related hypoxaemia, supplementary O, must be given or another way of assisted ventilation (BIPAP) must be considered. In the most severe patients (diurnal PaO(2) <55 mmHg) conventional O(2) therapy (>or=16h/24h) is required in addition to nocturnal ventilation.

Can daily short-duration hypoxemia (4-8 hours) induce pulmonary hypertension and right ventricular hypertrophy? A clinical model of this type of hypoxemia does exist: isolated nocturnal hypoxemia in patients with obstructive sleep apnea syndrome (OSAS) or chronic obstructive pulmonary disease (COPD). By investigating the pulmonary hemodynamics of these patients, it should be possible to determine whether nocturnal hypoxemia alone can induce pulmonary hypertension. Although nocturnal hypoxemia (in OSAS as well as in COPD) can induce acute episodes of pulmonary hypertension, it would not appear that nocturnal hypoxemia alone would be sufficient to provoke permanent diurnal pulmonary hypertension. This is the conclusion of recent studies concerning diurnal pulmonary hemodynamics in OSAS and COPD patients exhibiting minimal hypoxemia during the day but significant nocturnal desaturation. The therapeutic consequences of these data, particularly in COPD are important: current evidence is insufficient to treat with nocturnal oxygen therapy COPD patients who have minimal diurnal hypoxemia but significant nocturnal desaturation.

We have investigated pulmonary hemodynamics in 16 patients with COPD with respiratory insufficiency, exhibiting marked peripheral edema. All the patients had previously undergone, within the last 6 months (T1), a right heart catheterization, in a stable state of their disease, when they were free of edema. Patients were subdivided into two groups according to the level of right ventricular end-diastolic pressure (RVEDP) during the episode of edema (T2): patients with a markedly elevated RVEDP (> 12 mm Hg) indicating the presence of right ventricular failure (RVF) = group 1, n = 9; patients with a normal or slightly elevated RVEDP (< 12 mm Hg) = group 2 (no RVF), n = 7. In group 1 pulmonary artery mean pressure (PAP) increased very significantly from T1 (27 +/- 5) to T2 (40 +/- 6 mm Hg, p < 0.001) as did RVEDP, from 7.5 +/- 3.9 to 13.4 +/- 1.2 mm Hg (p < 0.001). These hemodynamic changes paralleled a marked worsening of arterial blood gases, PaO2 falling from 63 +/- 4 to 49 +/- 7 mm Hg (p < 0.01) and PaCO2 increasing from 46 +/- 7 to 59 +/- 14 mm Hg (p < 0.01). On the other hand, in group 2, PAP was stable during the episode of edema (from 20 +/- 6 to 21 +/- 5 mm Hg), as was RVEDP (from 5.5 +/- 2.4 to 5.1 +/- 1.5 mm Hg), and changes in arterial blood gases from T1 to T2 were small and nonsignificant. It is concluded that RVF is effectively present in at least some patients with COPD with peripheral edema and is associated with a significant increase of PAP from baseline, probably accounted for by hypoxic vasoconstriction. Thus, pressure overload may contribute to the development of RVF. In other patients there are no hemodynamic signs of RVF, PAP is stable, and the origin of edema is not well understood.

The Nocturnal Oxygen Therapy Trial (NOTT) and Medical Research Council (MRC) trial have clearly indicated that long-term oxygen therapy (LTO) improved survival in patients with hypoxemic chronic obstructive pulmonary disease (COPD), but the mechanisms accounting for this improved survival could not be established. In particular, there was no link between survival and changes in pulmonary hemodynamics. More recent studies have shown even better results of survival in patients under LTO after at least 5 years. LTO improves the quality of life in these patients by improving their neuropsychological condition, by increasing their walking distance, and by reducing the time spent in hospital. Whether LTO improves pulmonary hemodynamics and right ventricular function is still debated. No significant changes in mean pulmonary artery pressure (PAP) were observed in the MRC study in patients receiving O2 during greater than 15 h/day, whereas a modest but significant fall in PAP was noticed after 6 months in the NOTT patients receiving O2 during greater than 18 h/day. In our own study, confirmed by more recent data from our laboratory, a reversal in the progression of pulmonary hypertension was observed in patients receiving O2 during greater than 16 h/day, but it is not possible to say whether a rather small decrease in PAP and pulmonary vascular resistance will have favorable effects on life expectancy. Presently, we do not know whether LTO can reverse, at least partially, the structural changes in the pulmonary vessels possibly induced by chronic alveolar hypoxia, and we need to perform further studies in this field.

Almitrine bismesylate, a chemoreceptor agonist, improves hypoxaemia in a high percentage of chronic obstructive pulmonary disease (COPD) patients and its long-term use may thus be of interest in these patients. The course of pulmonary haemodynamics during a one year treatment was investigated in severe COPD patients (forced expiratory volume in one second FEV1 = 1,040 +/- 80 SEM ml) with persistent hypoxaemia (initial arterial oxygen tension (PaO2) in the range 6.6-8.6 kPa (50-65 mmHg]. Patients were given either almitrine (A, n = 27), 100 mg.day-1, during two consecutive months per quarter followed by a one month wash-out period (intermittent "schedule"), or placebo (P, n = 18) with the same schedule. Eleven patients in group A and 8 in group P could not complete the one year study because of lack of compliance, worsening of respiratory insufficiency, or for other reasons. In the remaining patients, PaO2 significantly increased in group A (n = 16) from 7.6 +/- 0.1 to 8.3 +/- 0.2 kPa (56.9 +/- 1.0 to 62.7 +/- 1.7 mmHg) (p less than 0.001) but not in group P (n = 10) from 7.5 +/- 0.3 to 7.9 +/- 0.3 kPa (56.1 +/- 2.3 to 59.1 +/- 2.1 mmHg). PaCO2 did not significantly change in either group. Pulmonary artery mean pressure (PAP) was stable in both groups: from 26.8 +/- 2.1 to 25.4 +/- 1.9 mmHg in group A, and from 20.6 +/- 1.1 to 20.9 +/- 1.5 mmHg in group P.(ABSTRACT TRUNCATED AT 250 WORDS)

Sleep apnea syndrome is responsible for repeated and sometimes deep arterial oxygen desaturations occurring during apneas, followed by episodes of transient pulmonary hypertension (PH). In chronic obstructive pulmonary disease (COPD) patients with respiratory insufficiency, a worsening of hypoxemia occurs during sleep, due to alveolar hypoventilation and/or ventilation-perfusion mismatching. This hypoxemia is also responsible for pulmonary hypertensive dips due to pulmonary hypoxic vasoconstrictiveness. But there is presently no evidence that sleep-related and transient PH may lead to daytime and permanent PH, in either sleep apnea syndrome or COPD. In fact permanent PH seems to be related, in most cases, to the presence of daytime (permanent) hypoxemia.

In order to study the frequency and the mechanisms of daytime pulmonary hypertension (PH) in obstructive sleep apnoea syndrome (OSAS) lung function tests, blood gas analysis and right-heart catheterization were performed in 46 consecutive patients. OSAS was assessed by polysomnography. 9 patients only (20%) had PH (mean pulmonary artery pressure (Ppa) greater than or equal to 20 mmHg). Patients with PH had lower daytime PaO2 (60.8 +/- 7.6 vs. 76.2 +/- 9.4 mmHg; p less than 0.001), higher daytime PaCO2 (44.8 +/- 4.2 vs. 38.0 +/- 4.0 mmHg; p less than 0.001), lower forced vital capacity (FVC) and forced expiratory volume (FEV1) (p less than 0.001), but the severity of OSAS was not different whether PH was present or not (apnoea index: 62 +/- 34 hour in the PH group vs. 65 +/- 40 hour, apnoea + hypopnoea index 102 +/- 33 hour in the PH group vs. 86 +/- 36 hour, lowest sleep SaO2: 59 +/- 21% in the PH group vs. 66 +/- 18%). There were significant correlations between Ppa and: daytime PaO2 (r = -0.61; p less than 0.001), PaCO2 (r = 0.55; p less than 0.001), FEV1 (r = -0.52; p less than 0.001) but not between Ppa and apnoea index, apnoea + hypopnoea index, lowest sleep SaO2. PH and daytime hypoxaemia were associated either with chronic airway obstruction or with severe obesity.

In 24 patients with severe chronic obstructive pulmonary disease (COPD), we investigated the evolution of pulmonary volumes, arterial blood gases (ABG) and mean pulmonary artery pressure (PAP), before (T0-T1) and during (T1-T2) long-term oxygen therapy (LTO). LTO was initiated at T1 on usual criteria (PaO2 persistently less than or equal to 55 mm Hg) and was given during greater than or equal to 16 h/day. The T0-T1 period ranged from 12 to 186 months (mean 53 +/- 41 months) and the T1-T2 period from 12 to 120 months (mean 44 +/- 30 months). There was a significant worsening of the obstructive pattern (FEV1 decreasing from 1,084 +/- 326 to 879 +/- 318 ml, p less than 0.005) and of ABG (PaO2 decreasing from 58.2 +/- 9.2 to 51.6 +/- 6.5 mm Hg, p less than 0.01) before the onset of LTO, whereas there was a rather good stability of ABG during LTO and the changes in pulmonary volumes were modest and statistically nonsignificant (FEV1 decreased from 879 +/- 318 to 809 +/- 247 ml). PAP tended to increase from T0 to T1 and to decrease from T1 to T2, but these changes only reached the level of statistical significance when they were expressed as changes per year (+1.0 +/- 2.7 vs. -1.3 +/- 4.5 mm Hg, p less than 0.05). The evolution of physiological variables was nearly identical in subgroups of patients who had died (n = 13) or were still alive (n = 11) at the time of data collection (T3) and this held particularly true for PAP.(ABSTRACT TRUNCATED AT 250 WORDS)

Permanent and marked hypoxemia (PaO2 less than or equal to 60 mmHg) is a major cause of pulmonary hypertension (PH) in patients with chronic obstructive lung disease (COLD). In these patients PH, although mild to moderate (with a mean pulmonary artery pressure generally comprised between 20 and 35 mmHg), is by itself an indicator of poor prognosis. During sleep, hypoventilation and exaggerated ventilation/perfusion ratio inequalities can induce severe desaturation dips responsible for sudden peaks of PH. However, in hypoxemic COLD patients, the prognostic value of sleep-related desaturation (and resulting PH) has not been demonstrated. In COLD patients without marked daytime hypoxemia (PaO2 greater than or equal to 60 mmHg) permanent PH in rather rare. Ventilatory changes during sleep may account for nocturnal desaturation and transient PH. Do these repeated transient pulmonary hypertensive peaks finally lead to permanent PH? This attractive hypothesis supposes that significant sleep desaturation can develop in patients without pronounced daytime hypoxemia, which has not been demonstrated yet. In fact very few studies have been devoted to the occurrence of nocturnal desaturation (and PH) in such patients and the above mentioned hypothesis could not be confirmed. Long-term oxygen therapy (greater than or equal to 16-18 h/day) is generally prescribed in COLD patients with marked and persistent daytime hypoxemia. Oxygen therapy including sleep time and several studies have shown that usual O2 flows (1, 5-3 l/mn) are efficient and increase O2 saturation during sleep over 90%, with a resulting improvement of nocturnal PH. It has been demonstrated that daytime PH is stabilized (or improved) in patients receiving long-term O2 therapy. In COLD patients with less severe daytime (and nighttime) hypoxemia, almitrine could be of interest. The benefit of isolated nocturnal oxygen therapy has not been yet clearly established.

Pulmonary hemodynamics have been extensively investigated in patients with chronic bronchitis or in 'mixed' patients (chronic bronchitis + emphysema) but rarely in patients with markedly predominant emphysema. We have investigated a large series (n = 151) of such patients, emphysema having been assessed on radiological, clinical and functional grounds. The mean age was 58 +/- 10 years; vital capacity (VC, % of predicted) = 81 +/- 19; forced expiratory volume in 1 s (FEV1) = 1,198 +/- 589 ml; FEV1/VC = 38 +/- 12%; PaO2 = 72 +/- 11 mm Hg; PaCO2 = 37.5 mm Hg. Pulmonary hypertension (PH), defined by a resting pulmonary artery pressure (PAP) of greater than or equal to 20 mm Hg, was present in only 31 of 151 patients. During steady-state exercise (40 W or less) an abnormally high PAP (greater than or equal to 30 mm Hg) was observed in 99 of 151 patients. Resting and exercising PAP were poorly correlated with resting PaO2 and PaCO2, but were better correlated with the amplitude of the respiratory pressure swings, FEV1, the transfer factor and exercising PaO2. Patients with PH (n = 31) showed significantly more obstruction and pulmonary distension than the remainder, but they did not differ from the non-PH patients with regard to resting PaO2. It is concluded that: (1) resting PH is not the rule in diffuse emphysema but exercising hypertension is frequent (2 of 3 patients), and (2) hypoxemia is not a determining factor of hemodynamic abnormalities in emphysema.

Fifty-four patients with obstructive sleep apnea (OSA) syndrome received long-term treatment with nasal continuous positive airway pressure (CPAP). The effects on daytime lung function and pulmonary hemodynamics were prospectively evaluated by repeating pulmonary function tests, including right heart catheterization after a follow-up period of at least 1 yr (554 +/- 28 days, mean +/- SEM). PaO2 increased in the patient group as a whole from 69.9 +/- 1.4 to 72.8 +/- 1.4 mm Hg (p less than 0.02). The increase in PaO2 was greater (from 60.4 +/- 1.0 to 66.4 +/- 2.1, p less than 0.01) in those patients who were hypoxemic prior to treatment. PaCO2 decreased significantly only in the subgroup of patients with significant hypercapnia prior to treatment (n = 7), from 48.5 +/- 1.3 to 44.5 +/- 1.5 mm Hg (p less than 0.01). The improvement in daytime blood gases seemed to be related to an increase in the alveolar ventilation, from 5.2 +/- 0.2 to 5.9 +/- 0.3 L/min without a change in the alveolar-arterial PO2 difference, as calculated in 25 patients. Both the red blood cell count and the hematocrit decreased significantly, from 5,347 +/- 90 to 5,024 +/- 61 10(3)/mm3 and from 49.4 +/- 0.9 to 47.1 +/- 0.6%, p less than 0.001 and p less than 0.02, respectively. No change was observed in the resting pulmonary arterial pressure. We conclude that nasal CPAP is effective in improving daytime blood gases in patients with OSA.

We studied alpha 1-antitrypsin deficiency in a large family of 10 siblings: 3 subjects had PiZZ phenotype, but only 1 had emphysema; 2 subjects had no respiratory complaint. The patient with emphysema was a heavy smoker. According to the literature, this case suggests that, in PiZZ phenotype, emphysema appears earlier and is more severe if the patients smoke.

We report a case of a 62 year old man who presented with effort dyspnoea accompanied by a cough and haemoptysis. The chest radiograph of the thorax showed atelectasis of the right upper lobe. Bronchoscopy showed evidence of a tumour like mass obstructing the right bronchus and this revealed itself to be a mass of organised fibrinous deposit in granulation tissue containing numerous colonies of Aspergillus. In fact it appeared to be an obstructive Aspergillus bronchitis, with a pseudo-tumour appearance attached to a carcinoid tumour which was obstructing the apical segment of the right upper lobe. Obstructive Aspergillus bronchitis makes up only a small percentage of overall respiratory disease caused by Aspergillus. They pose a problem of differential diagnosis with bronchopulmonary aspergillosis which is much more frequent.

The presence of pulmonary hypertension (PH) is not an obligatory prerequisite for prescribing long-term oxygen therapy (LTO) in patients with chronic obstructive pulmonary disease (COPD), at least when PaO2 is repeatedly less than 55 mmHg in a stable state of the disease. It is generally accepted that LTO is indicated in patients whose PaO2 is in the range 55-59 mmHg, but exhibiting polycythaemia, "cor pulmonale", and (or) PH. The clinical signs of "cor pulmonale" occur late and the noninvasive diagnosis of PH is not yet satisfactory; it ensues that right heart catheterization is useful in these patients, before prescribing LTO. Pulmonary hypertension is probably the most important consequence of long-standing hypoxaemia and, in our opinion, the presence and the degree of PH should be assessed in every patient before starting such a heavy therapy as LTO.

In patients with chronic obstructive pulmonary disease (COPD) exhibiting daytime hypoxaemia, a worsening of the latter occurs during sleep, particularly during REM sleep. The most efficient therapy of this sleep-related hypoxaemia is the nocturnal administration of O2 at a flow rate of 1.5-3 l/min. An alternative therapy, when daytime hypoxaemia is not too severe (PaO2 greater than 55 mmHg), is the use of almitrine (100 mg/day), a drug which improves daytime hypoxaemia in most COPD patients. The improvement of sleep hypoxaemia with almitrine is related to the increased daytime PaO2 and cannot be considered as a specific effect of almitrine on sleep-related respiratory events. It must be emphasized that almitrine is ineffective in about 25% of COPD patients ("nonresponders") and that almitrine can be used with conventional O2 therapy in patients with severe hypoxemia (daytime PaO2 less than 55 mmHg).

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.

In chronic obstructive bronchopneumopathies (COBP), pulmonary artery hypertension (PAH) is usually mild but may markedly intensify during episodes of acute respiratory failure, muscular exercise, and sleep, PAH may, even if of low level, lead to right heart failure. The prognostic value of PAH and its degree in COBP patients has been well established by a number of recent studies. Chronologic changes in pulmonary artery pressure (PAP) tend to be minimal in the majority of COBP patients (of the order of +0.5-0.6 mm Hg/year in most studies). However, in a minority of patients (about 30%) pulmonary hypertension worsens seriously due to progressive deterioration of arterial blood gases. Longterm oxygen therapy (LOT) for 16 h/day rarely serves to normalize PAP but may reverse the progress of pulmonary hypertension, particularly in patients with progressive aggravation thereof. Recent studies have made it clear that LOT has beneficial hemodynamic effects in a relatively large percentage of COBP patients with PAH.

In chronic airflow obstruction (CAO), there are grounds for distinguishing between the effects of acute alveolar hypoxia and those of chronic hypoxia. Acute hypoxia leads, in healthy subjects, to pulmonary vasoconstriction. In patients with CAO, there is however a great variability in the pulmonary vascular response to hypoxia. Chronic hypoxia leads in the long term to structural modifications in the pulmonary vessels (arteriolar muscularization, hypertrophy of the small arterial muscles, and intimal fibrosis), which are similar enough to those seen in residents at high altitude and which lead to an elevation of the pulmonary vascular resistance. These structural changes are potentially reversible but one does not know up to which point they are. This potential reversibility represents one of the justifications of long term oxygen therapy in these patients. The pulmonary arterial hypertension of CAO is generally moderated; it evolves slowly over years and years in the majority of cases; it certainly doesn't merit to be treated at any cost. Up to the present, pulmonary vasodilators have given rather disappointing results. Prolonged oxygen therapy (for greater than 16 hours in 24), which improves in other respects the expectation of life in patients is currently the most logical treatment for pulmonary hypertension in CAO.

The frequency of daytime pulmonary hypertension (PH) in patients with obstructive sleep apnea syndrome (OSAS) has not been well established and its mechanisms are still under debate. We have thus performed right heart catheterization, in addition to standard spirography and arterial blood gas measurements, in a series of 46 consecutive patients in whom OSAS was firmly diagnosed by whole-night polysomnography. Only 9 of the 46 patients (20%) had PH defined by a mean resting pulmonary arterial pressure (Ppa) greater than or equal to 20 mm Hg. Among the patients without resting PH, 14 had exercising PH (defined by a Ppa greater than 30 mm Hg during 40-watt, steady-state exercise). Patients with resting PH differed from the others by a lower daytime PaO2 (60.8 +/- 7.6 versus 76.2 +/- 9.4 mm Hg; p less than 0.001), a higher daytime PaCO2 (44.6 +/- 4.2 versus 38.0 +/- 4.0 mm Hg; p less than 0.001), and lower VC and FEV1 (p less than 0.001). There was no difference between the 2 groups with regard to apnea index (62 +/- 34 versus 65 +/- 40) or the lowest sleep SaO2 (59 +/- 21 versus 66 +/- 18%) or the time spent in apnea. For the group as a whole, there was a good correlation between Ppa and daytime PaO2 (r = -0.61; p less than 0.001), PaCO2 (r = 0.55; p less than 0.001), and FEV1 (r = -0.52; p less than 0.001), but there was no significant correlation between Ppa and the apnea index, the lowest sleep SaO2, or the time spent in apnea.(ABSTRACT TRUNCATED AT 250 WORDS)

The North-American Trial (NOTT) and the British MRC study clearly indicated that long-term oxygen therapy (LTO) increases the survival rate of patients with severe chronic obstructive long disease (COLD), but O2 must be given for more than 15 h/24 h. At present OT is largely prescribed in COLD patients whose (stable) PaO2 less than or equal to 55 mmHg. The pulmonary haemodynamic effects of OT are still a matter of debate. The first studies, in 1967, indicated that continuous O2 for 6-8 weeks could markedly improve pulmonary hypertension (PH). In the MRC study there was no change in pulmonary artery mean pressure (PAP) in patients receiving O2 for more than 15 h/day, whereas patients not receiving O2 exhibited a progressive increase of PH. In the NOTT study there was a modest but significant improvement of PAP after 6 months in those patients receiving "continuous OT" (in fact greater than 18 h/day), but not in patients receiving only nocturnal OT. In our own study, we found that OT could reverse the progression of PH in COLD patients. In 16 carefully studied patients, PAP increased from 23.3 +/- 6.8 to 28.0 +/- 7.4 mmHg (p less than 0.01) before the initiation of OT (mean duration of follow-up = 48 months) and then decreased to 23.9 +/- 6.6 mmHg (p less than 0.05) during OT (mean duration of follow-up = 31 months). The average yearly change in PAP was +1.5 mmHg before OT, and -2.1 mmHg under OT and the difference was highly significant (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)