Outcome of COPD patients with mild daytime hypoxaemia with or without sleep-related oxygen desaturation.

The aim of the present study was to compare the evolution of pulmonary haemodynamics and of arterial blood gases in chronic obstructive pulmonary disease (COPD) patients with mild-to-moderate hypoxaemia, with or without sleep-related oxygen desaturation. COPD patients with daytime arterial oxygen partial pressure in the range 56-69 mmHg were included prospectively. Sleep-related oxygen desaturation was defined as spending > or = 30% of the nocturnal recording time with arterial oxygen saturation <90%. From the 64 patients included, 35 were desaturators (group 1) and 29 were nondesaturators (group 2). At baseline (t0), patients with sleep-related desaturation had a significantly higher daytime (mean +/- SD) arterial carbon dioxide partial pressure (Pa,CO2) (44.9 +/- 4.9 mmHg versus 41.0 +/- 4.1 mmHg, p=0.001) whereas mean pulmonary artery pressure (mPAP) was similar in the two groups. After 2 yrs (t2) of follow-up, 22 desaturators and 14 nondesaturators could be re-evaluated, including pulmonary haemodynamic measurements. None of the nondesaturator patients became desaturators at t2. The difference between the two groups in terms of daytime Pa,CO2 was still present at t2. The mean changes in mPAP from t0 to t2 were similar between the two groups, as were the rates of death or requirement for long-term oxygen therapy (American Thoracic Society criteria) during follow-up of up to 6 yrs. The presence of sleep-related oxygen desaturation is not a transitional state before the worsening of daytime arterial blood gases, but is a characteristic of some chronic obstructive pulmonary disease patients who have a higher daytime arterial carbon dioxide partial pressure. Such isolated nocturnal hypoxaemia or sleep-related worsening of moderate daytime hypoxaemia does not appear to favour the development of pulmonary hypertension, nor to lead to worsening of daytime blood gases.

A randomized trial of nocturnal oxygen therapy in chronic obstructive pulmonary disease patients.

The beneficial effects of nocturnal oxygen therapy (NOT) in chronic obstructive pulmonary disease (COPD) patients with mild-to-moderate daytime hypoxaemia (arterial oxygen tension (Pa,O2) in the range 7.4-9.2 kPa (56-69 mmHg)) and exhibiting sleep-related oxygen desaturation remains controversial. The effectiveness of NOT in that category of COPD patients was studied. The end points included pulmonary haemodynamic effects after 2 yrs of follow-up, survival and requirement for long-term oxygen therapy (LTOT). Seventy-six patients could be randomized, 41 were allocated to NOT and 35 to no NOT (control). The goal of NOT was to achieve an arterial oxygen saturation of >90% throughout the night. All these patients underwent polysomnography to exclude an associated obstructive sleep apnoea syndrome. The two groups exhibited an identical meansD daytime Pa,O2 of 8.4+/-0.4 kPa (63+/-3 mmHg) at baseline. Twenty-two patients (12 in the NOT group and 10 in the control group, p=0.98) required LTOT during the whole follow-up (35+/-14 months). Sixteen patients died, nine in the NOT group and seven in the control group (p=0.84). Forty-six patients were able to undergo pulmonary haemodynamic re-evaluation after 2 yrs, 24 in the NOT and 22 in the control group. In the control group, mean resting pulmonary artery pressure increased from 19.8+/-5.6 to 20.5+6.5 mmHg, which was not different from the change in mean pulmonary artery pressure in the NOT group, from 18.3+/-4.7 to 19.5+/-5.3 mmHg (p= 0.79). Nocturnal oxygen therapy did not modify the evolution of pulmonary haemodynamics and did not allow delay in the prescription of long-term oxygen therapy. No effect of NOT on survival was observed, but the small number of deaths precluded any firm conclusion. These results suggest that the prescription of nocturnal oxygen therapy in isolation is probably not justified in chronic obstructive pulmonary disease patients.

Detection of benzo[a]pyrene-DNA adducts from leukocytes from heavy smokers.

Benzo[a]pyrene is a cigarette smoke component that is metabolized in the human body to the diol-epoxide derivative benzo[a]pyrene-trans- 7,8-dihydrodiol-9,10-epoxide (BPDE-I), which is the final carcinogen. BPDE-I binds covalently to DNA, producing BPDE-I-DNA adducts. A competitive immunoenzymetric assay was used to measure BPDE-I-DNA adducts in blood samples from 58 heavy smokers, 32 men and 26 women, attending a smoking cessation clinic. Cigarette consumption was evaluated based on urinary continine levels. None of the subjects worked in jobs involving exposure to polycyclic aromatic hydrocarbons (e.g., benzo[a]pyrene). Concentrations of BPDE-I-DNA adducts varied with cigarette consumption, ranging from 10.00 to 28.20 fmol/50 micrograms of DNA.

Sleep-related O2 desaturation and daytime pulmonary haemodynamics in COPD patients with mild hypoxaemia.

It has been hypothesized but not firmly established that sleep-related hypoxaemia could favour the development of pulmonary hypertension in chronic obstructive pulmonary disease (COPD) patients without marked daytime hypoxaemia. We have investigated the relationships between pulmonary function data, sleep-related desaturation and daytime pulmonary haemodynamics in a group of 94 COPD patients not qualifying for conventional O2 therapy (daytime arterial oxygen tension (Pa,O2) in the range 7.4-9.2 kPa (56-69 mmHg)). Nocturnal desaturation was defined by spending > or = 30% of the recording time with a transcutaneous O2 saturation < 90%. An obstructive sleep apnoea syndrome was excluded by polysomnography. Sixty six patients were desaturators (Group 1) and 28 were nondesaturators (Group 2). There was no significant difference between Groups 1 and 2 with regard to pulmonary volumes and Pa,O2 (8.4+/-0.6 vs 8.4+/-0.4 kPa (63+/-4 vs 63+/-3 mmHg)) but arterial carbon dioxide tension (Pa,CO2) was higher in Group 1 (6.0+/-0.7 vs 53+/-0.5 kPa (45+/-5 vs 40+/-4 mmHg); p<0.0001). Mean pulmonary artery pressure (Ppa) was very similar in the two groups (2.6+/-0.7 vs 2.5+/-0.6 kPa (19+/-5 vs 19+/-4 mmHg)). No individual variable or combination of variables could predict the presence of pulmonary hypertension. It is concluded that in these patients with chronic obstructive pulmonary disease with modest daytime hypoxaemia, functional and gasometric variables (with the noticeable exception of arterial carbon dioxide tension) cannot predict the presence of nocturnal desaturation; and that mean pulmonary artery pressure is not correlated with the degree and duration of nocturnal hypoxaemia. These results do not support the hypothesis that sleep-related hypoxaemia favours the development of pulmonary hypertension.

[Pulmonary lymphangiomyomatosis: a 3-year follow-up of medroxyprogesterone acetate therapy. Apropos of a case]. / La lymphangiomyomatose pulmonaire: suivi à trois ans sous acétate de médroxyprogestérone. A propos d'un cas.

A 41-year-old female patient presenting with chylothorax was found to have pulmonary lymphangiomyomatosis. Recurrence led to parietal pleurectomy. Lung biopsy performed at surgery confirmed the histology diagnosis. Hormone treatment with medroxyprogesterone acetate was initiated immediately and administered via intramuscular injections each month. The treatment was continued for three years and regular clinical, functional and radiologic follow-up provided evidence of response: radiologic and functional stability were achieved at the cost of major secondary effects of hormone therapy. This rare, apparently hormone-dependent, disease raises the problem of the long-term benefit of treatment.

Synchronized intermittent mandatory ventilation with and without pressure support ventilation in weaning patients with COPD from mechanical ventilation.

This prospective study compared two weaning modalities in COPD patients requiring mechanical ventilation (MV) for acute respiratory failure. Nineteen patients with COPD were studied when their precipitating illness was controlled. Although they satisfied the conventional bedside weaning criteria, they could not tolerate any reduction in the respirator rate below 10 cycles/min. At this time, patients were randomized into two groups receiving either synchronized intermittent mandatory ventilation (SIMV) with pressure support ventilation (PSV) (group 1) or SIMV alone (group 2). The volumetric support of ventilation (SIMV rate) was progressively decreased in both groups according to the patient's tolerance with a concurrent decrease in the barometric support of ventilation (PSV levels from 15 cm H2O to 6 cm H2O). At each step of SIMV rate, we found no difference between group 1 and group 2 in arterial blood gases, blood pressure, heart rate, airway occlusion pressure, maximal inspiratory pressure, and oxygen cost of breathing (OCB). At each step, however, group 1 patients showed significantly higher spontaneous tidal volume and lower spontaneous breathing frequency than did group 2 patients. We found a slight but not significant tendency to a shorter weaning period with than without PSV, but no difference in the weaning success. We concluded that (1) conventional weaning criteria might be inaccurate in COPD patients, (2) SIMV appeared very useful in weaning COPD patients from MV, (3) PSV marginally reduced the weaning period when added to SIMV, and (4) the OCB was not significantly improved with PSV.

[Goodpasture's syndrome presenting as acute respiratory distress. Favorable evolution with corticosteroids, cyclophosphamide and plasmapheresis]. / Détresse respiratoire aiguë inaugurant un syndrome de Goodpasture. Evolution favorable sous corticoïdes, cyclophosphamide et plasmaphérèses.

The authors report a case of a seventeen year old woman who was admitted to hospital for an extremely acute respiratory distress syndrome, which was revealed to be an exclusively pulmonary form of Goodpasture's syndrome. The positivity of the IgG immunofluorescence on open lung biopsy contrasted with the absence of circulating antibasement membrane antibody (ELISA). The combination of plasmapheresis, steroid therapy and cyclophosphamide enabled a rapidly favourable outcome and the patient could be weaned of the support therapy.

Sleep-related oxygen desaturation and daytime pulmonary haemodynamics in COPD patients.

It has been hypothesized that in chronic obstructive pulmonary disease (COPD), sleep-related hypoxaemia could lead to pulmonary hypertension (PH) and cor pulmonale, even in patients with only mild daytime hypoxaemia. We investigated the relationships between sleep variables and daytime pulmonary haemodynamics in 40 COPD patients with daytime arterial oxygen tension (PaO2) between 60-70 mmHg (8-9.3 kPa). Patients were considered as desaturators if they spent at least 30% of the sleep recording time with a transcutaneous O2 saturation (StcO2) less than 90%. Daytime arterial blood gases and pulmonary volumes could not discriminate desaturators "D" (n = 18) from non-desaturators "ND" (n = 22), but awake baseline StcO2, measured just prior to the onset of sleep, was lower in group D. Pulmonary artery mean pressure was significantly higher in group D (19.1 +/- 4.7 vs 16.8 +/- 1.9 mmHg, p less than 0.05) and all patients with PH (6 out of 40) belonged to group D. PH was observed in 6 of the 15 patients whose mean nocturnal StcO2 was less than 90% but in none of the 25 with a mean nocturnal StcO2 greater than 90%. The PH patients (n = 6), all desaturators, differed from the desaturators with no PH (n = 12), and from ND (n = 22) in having higher numbers of desaturation dips, longer durations of dips, and lower mean nocturnal arterial oxygen saturation (SaO2). We conclude that a causal relation between nocturnal desaturation and permanent PH is very likely. Further studies are needed to see whether oxygen therapy can prevent PH in these patients.

Survival in COPD patients with a daytime PaO2 greater than 60 mm Hg with and without nocturnal oxyhemoglobin desaturation.

There have been few studies examining the relationship between NOD and mortality in patients with COPD and none examining this relationship in those patients with a daytime PaO2 greater than 60 mm Hg. Is NOD related to early death, and if so, should nocturnal supplemental oxygen be considered as therapy for altering survival? We examined survival in 169 COPD subjects. Two definitions were used to classify subjects as NOD and non-NOD, one considering episodic desaturation associated mainly with REM sleep (definition 1) and one considering greater than 30 percent of time in bed spent below an SaO2 of 90 percent (definition 2) to be significant. Survival corrected for age was significantly better in non-NOD subjects. However, when stratified for supplemental oxygen use, survival remained better only in subjects separated by definition 1. There was a trend toward increased survival in 35 oxygen-treated vs 38 non-oxygen-treated NOD subjects (definition 1), but this difference was not statistically significant.

[Kidney function and chronic respiratory insufficiency: relation to the ventilatory method. A physiopathological hypothesis apropos of a case]. / Fonction rénale et insuffisance respiratoire chronique: relation avec le mode ventilatoire. Une hypothèse physiopathologique à propos d'une observation.

The authors report the case of a patient with chronic obstructive pulmonary disease (COPD) whose renal function depends on the ventilatory pattern. The data appeared in opposition with the standard physiopathological notions with an improvement of renal function during mechanical ventilatory assistance and a degradation while spontaneous breathing. The authors suggest an original hypothesis based upon the increase of oxygen cost of breathing (OCB) with a redistribution of the intravascular blood flow to the diaphragm.

Nocturnal hypoxemia and long-term oxygen therapy in COPD patients with daytime PaO2 60-70 mmHg.

Six European treatment centers contributed to a controlled trial to study nocturnal hypoxemia in COPD patients having daytime PaO2 of 60-70 mmHg. The trial is composed of two parts: first, patients inclusion, taking men aged under 70 years, excluding sleep apnea syndrome and all other concomitant pathologies leading to nocturnal desaturation. We described this population and determined the frequency and degree of nocturnal desaturation. Correlations between different daytime and sleep parameters have also been established. The second part concerns the study of the two sub-populations of nocturnal desaturators and nondesaturators. This is followed by random allocation of the desaturators to oxygen or no oxygen treatment. We defined significant nocturnal desaturation as cumulated unsaturation period, exceeding 30% of total time, in bed spent under SaO2 lower than 90%. Twenty out of 46 patients were desaturators (43%). Only the first part is dealt with in this article.

The SaO2/t diagram as a useful means to express nocturnal hypoxemia.

The computerization of SaO2 recording during polysomnographic monitoring allows the construction of a diagram expressing the percentage of TIB spent at different steps in saturation. We studied the value of this diagram in three groups of male patients: (1) nine healthy subjects (all volunteers); (2) 25 patients with COPD who had a mean daily SaO2 of 92.3 +/- 1.3 percent; and (3) 25 patients with SAS who had a mean daily SaO2 of 92.1 +/- 1.4 percent. The results show the existence of a discriminating quality in the diagram's morphology, the existence of strong correlations (p less than 0.01) between the percentage of TIB spent at SaO2 less than 85 percent, and the total duration of the desaturation dips.

Selection of patients for long-term oxygen therapy (LTO).

Serial blood gas measurement must be made for at least three months following an acute exacerbation of chronic obstructive pulmonary disease, to secure stable arterial oxygen tension (PaO2) values. The borderline indications of oxygen therapy concern the patients who have PaO2 over 8 kPa (60 mmHg), but have nocturnal hypoxaemia and/or pulmonary hypertension. The indications of specific drugs such as almitrine are still subject to discussion. The presence of obstructive sleep apnoeas together with ventilatory troubles related to chronic obstructive lung disease (overlap syndrome), is associated with many diagnostic and therapeutic problems.

[Chronic obstructive bronchopneumopathies. Changes in carbon dioxide pressure during sleep in environmental air and with oxygen]. / Bronchopneumopathies chroniques obstructives. Variations de la capnie au cours du sommeil en air ambiant et sous oxygène.

The effects of oxygen administration were studied in 10 patients with severe obstructive lung disease. Sleep variable and gas exchanges were measured during two nights: one when they were breathing environmental air, the other when they were receiving oxygen. Carbon dioxide saturation and partial pressure measured by the transcutaneous method were continuously recorded. Sleep was perturbed in all patients, but despite wide interindividual variations its amount and quality were improved by oxygen. None of the patients had sleep apnoea syndrome. Oxygen administration was accompanied by a nocturnal increase in carbon dioxide pressure that was about twice as high as that observed under environmental air. Thus, in patients with chronic obstructive lung disease without concomitant infection suppression of the hypoxic stimulus by oxygen therapy seems to result in an increase in carbon dioxide partial pressure identical with the increase produced by sleep alone. Correlations between diurnal and nocturnal oxygen saturation and carbon dioxide partial pressure indicate that patients with the highest degree of hypoxia and hypercapnia in daytime have the most severe nocturnal blood gas disorders.