Effects of long-term oxygen therapy on pulmonary hemodynamics in COPD patients: a 6-year prospective study.

OBJECTIVE: To investigate effects of 6 years of domiciliary oxygen therapy on pulmonary hemodynamics in a large group of COPD patients. DESIGN: Prospective longitudinal study with serial measurements. SETTING: Research institute of pulmonary diseases. PATIENTS: Ninety-five patients (72 men, 23 women), mean age 58+/-9 years, had COPD but were free of any other serious disease. Functional characteristics at entry, mean+/-SD, were as follows: FVC=2.24+/-0.51 L; FEV1=0.84+/-0.31 L; PaO2=55+/-6 mm Hg; PaCO2=48+/-9 mm Hg; mean pulmonary arterial pressure (PAP)=28+/-11 mm Hg; and pulmonary vascular resistance (PVR)=353+/-172 dynexsxcm(-5). METHODS: Pulmonary hemodynamics were investigated using Swan-Ganz thermodilution catheters. After initial assessment, all patients were started on a regimen of long-term oxygen therapy (LTOT). Follow-up consisted of medical examination, spirometry, and arterial blood gas analysis every 3 months. Pulmonary artery catheterization was repeated every 2 years. RESULTS: Seventy-three subjects survived 2 years of LTOT. In 39 subjects catheterized after 2 years, PAP fell from 25+/-8 to 23+/-6 mm Hg (not significant [NS]). From 31 patients who completed 4 years of LTOT, hemodynamic data were obtained in 20. In these 20 patients, PAP averaged 24+/-7 mm Hg at entry, and 23+/-5 and 26+/-6 mm Hg after 2 and 4 years, respectively (NS). In 12 patients who completed 6 years of LTOT, PAP was 25+/-7 at entry, and 21+/-4, 26+/-7, and 26+/-6 mm Hg at 2, 4, and 6 years, respectively (p < 0.01 for 2 vs 6 years). PVR was 313+/-159 dynexsxcm(-5) at entry, and 268+/-110, 344+/-82, and 332+/-205 dynexsxcm(-5) at 2, 4, and 6 years, respectively (NS). During 6 years of follow-up, PaO2 decreased from 61+/-3 to 46+/-9 mm Hg (p < 0.001) and PaCO2 increased from 44+/-13 to 49+/-9 mm Hg (p < 0.01). CONCLUSION: LTOT for 14 to 15 h/d resulted in a small reduction in pulmonary hypertension after the first 2 years followed by a return to initial values and subsequent stabilization of PAP over 6 years. The long-term stabilization of pulmonary hypertension occurred despite progression of the airflow limitation and of hypoxemia.

Respiratory effort sensation during exercise with induced expiratory-flow limitation in healthy humans.

Nine healthy subjects (age 31 +/- 4 yr) exercised with and without expiratory-flow limitation (maximal flow approximately 1 l/s). We monitored flow, end-tidal PCO2, esophageal (Pes) and gastric pressures, changes in end-expiratory lung volume, and perception (sensation) of difficulty in breathing. Subjects cycled at increasing intensity (+25 W/30 s) until symptom limitation. During the flow-limited run, exercise performance was limited in all subjects by maximum sensation. Sensation was equally determined by inspiratory and expiratory pressure changes. In both runs, 90% of the variance in sensation could be explained by the Pes swings (difference between peak inspiratory and peak expiratory Pes). End-tidal PCO2 did not explain any variance in sensation in the control run and added only 3% to the explained variance in the flow-limited run. We conclude that in healthy subjects, during normal as well as expiratory flow-limited exercise, the pleural pressure generation of the expiratory muscles is equally related to the perception of difficulty in breathing as that of the inspiratory muscles.

Effect of long-term oxygen therapy on survival in patients with chronic obstructive pulmonary disease with moderate hypoxaemia.

BACKGROUND: To date only two controlled studies have been published on the effects of domiciliary oxygen treatment on survival in patients with chronic obstructive pulmonary disease (COPD) with advanced respiratory failure. The survival in such patients despite oxygen treatment remains poor. The prescription of long term oxygen therapy (LTOT) in less severe disease remains controversial. The aim of this study was to evaluate the rationale for prescribing oxygen to patients with COPD with moderate hypoxaemia. METHODS: One hundred and thirty five patients with COPD, with PaO2 7.4-8.7 kPa (56-65 mmHg) and advanced airflow limitation (mean (SD) forced expiratory volume in one second (FEV1) 0.83 (0.28) 1), were randomly allocated to a control (n = 67) and LTOT (n = 68) group. The patients were followed every three months for at least three years or until death. RESULTS: The cumulative survival rate was 88% at one year, 77% at two years, and 66% at three years. No significant differences were found in survival rates between patients treated with LTOT and controls, nor did longer oxygen use (over 15 hours per day) improve survival. Younger age, better spirometric values, and higher body mass index predicted better survival. CONCLUSIONS: Domiciliary oxygen treatment does not prolong survival in patients with COPD with moderate hypoxaemia. Airway limitation seems to determine survival in this group of patients.

Causes of death in patients with COPD and chronic respiratory failure.

Although the factors associated with mortality, such as forced expiratory volume in one second (FEV1), arterial oxygen tension (Pa,O2) and pulmonary arterial pressure, have been well described, there is limited information on the circumstances of death in patients with chronic obstructive pulmonary disease (COPD). The aim of this study was to investigate the causes and circumstances of death in patients with COPD and chronic respiratory failure (Pa,O2 < 8.0 kPa (60 mmHg) breathing air), treated with long-term oxygen therapy (LTOT). Ten European centres participated in the study and data were collected from patients both during a period of clinical stability and at the time of death. Of the 215 patients evaluated (161 males and 54 females; aged 66 +/- 10 yrs), the major causes of death were: acute on chronic respiratory failure (38%); heart failure (13%); pulmonary infection (11%); pulmonary embolism (10%); cardiac arrhythmia (8%); and lung cancer (7%). Seventy five percent of patients died in hospital. There was no difference in the number of patients who died in the morning, afternoon and night hours. Twenty percent of the total died during sleep and in 26% death was unexpected. A lower arterial carbon dioxide tension (Pa,CO2), less oxygen usage per 24 h, and increased incidence of arrhythmias were seen in those patients who died suddenly. Drug therapy was not related to unexpected death. The majority of patients with chronic obstructive pulmonary disease on long-term oxygen therapy died from chronic or acute on chronic respiratory failure. Prevention and treatment of respiratory failure in patients with chronic obstructive pulmonary disease is likely to have the greatest impact in reducing mortality.

Comparison of static and dynamic intrinsic positive end-expiratory pressure using the Campbell diagram.

Intrinsic positive end-expiratory pressure (PEEPi) due to dynamic hyperinflation has been measured as a plateau airway opening pressure during airway occlusion (PEEPi,stat). PEEPi has also been dynamically determined as a fall in esophageal pressure (Pes) before the inspiratory flow starts (PEEPi,dyn). The aims of the current study were to systematically compare PEEPi,stat and PEEPi,dyn and to explain the underlying mechanisms of their difference. The study was performed in healthy subjects with dynamic hyperinflation induced by expiration through a Starling resistor. The Campbell diagram was constructed for each subject by determining the static pressure-volume curves of the lung (Pst,[l]) and chest wall (Pst,[w]). For a given end-expiratory volume, PEEPi,stat was measured on the Campbell diagram as the pressure difference between Pst(w) and -Pst(l). PEEPi,dyn was measured as mentioned above. The effects of respiratory muscle recruitment on PEEPi,dyn were estimated by the Pes values when Pes started to fall relative to Pst(w). We found that: (1) there was a great variability of the PEEPi,dyn/PEEPi,stat ratio among and within subjects; (2) expiratory muscle recruitment was evident on most occasions; (3) persistent inspiratory muscle activity during expiration was present in some subjects; (4) the Pes values at the start of inspiratory flow were frequently on the left of -Pst(l), which contributed to the difference between PEEPi,stat and PEEPi,dyn and implied a greater dynamic than static elastance presumably due to viscoelastic properties; (5) chest wall distortions characterized by inflation of the abdomen with deflation of the rib cage during the initial inspiratory efforts were observed in three subjects. In conclusion, interpretation of PEEPi,dyn needs to be cautious because both expiratory and tonic inspiratory muscle activities that lead to significant over- or underestimation of PEEPi by PEEPi,dyn, respectively, are associated with acute dynamic hyperinflation. In addition, the effects of viscoelastic properties and chest wall distortions on PEEPi,dyn need to be further investigated.

Psychological status of COPD patients before and after one year of long-term oxygen therapy.

Cognitive function, psychological status, and attitudes were investigated in 90 patients with chronic obstructive pulmonary disease before the initiation of long-term oxygen therapy and after one year of treatment. Assessment included clinical interview, Wechsler Intelligence Scale I.Q., Bourdon-Wiersma Test, Benton Verbal Retention Test, Rey's Test of Remembering 15 Words, Beck's Depression Scale, Taylor's Manifest Anxiety Scale, and Tylka's Psychological Evaluation Scale of the Effectiveness of Rehabilitation. The mean I.Q. of the patients studied was slightly above average at 107 points. Tests of cognitive function showed reduced performance. These included tests of repeating numbers, pictorial anecdotes and numerical symbols. Rey's Test of Word Memory was also below average but increased following treatment. In the Bourdon Test, there were 58 correct deletions and 7 omissions initially, improving to 67 and 8, respectively, after treatment. Poor visual and spatial memory did not improve after treatment. Before treatment, patients demonstrated depressed mood, low self-esteem with narrow interests, signs of anxiety, mental stress and depression. After a year of long-term oxygen therapy significant improvements in mood and attitudes were demonstrated. We conclude that long-term oxygen therapy may be capable of producing a significant improvement in emotional status. However, the effects of oxygen treatment are difficult to separate from effects of other aspects of care in producing a sense of increased security and well-being.

[Evaluation of prognostic factors and progress of disease in patients with COPD treated with long-term oxygen]. / Ocena czynników rokowniczych i postepu choroby u chorych na POChP leczonych przewlekle tlenem.

Long-term sequential evolution of pulmonary function, blood gas, body mass index (BMI) and oxygen breathing time was observed in 266 COPD patients with advanced airway obstruction (FEV1 = 0.80 L), and severe respiratory failure (PaO2 = 52 mmHg, PaCO2 = 49 mmHg) undergoing LTOT. There were significant differences between survivors and non-survivors at entry and during the treatment. Patients dying during LTOT had at entry lower BMI and more advanced airway limitation than survivors. They did not differ in blood gas values. During the follow-up (between 1-4 years) different trends in evolution of studied variables were observed in survivors (over 4 years on LTOT) and patients dying during LTOT (up to 4 years). Long term stabilization of spirometric and blood gas values as well as in mean oxygen breathing time (14 hours) were observed in survivors. In non-survivors a significant progression in airway limitation and respiratory failure coupled with better compliance with LTOT (oxygen use increased from 15 to 17 hours/ day) was observed especially in the last year before death. In survivors BMI increased significantly during the treatment, whereas in non-survivors no change was observed.

[Eight years of experience in Warsaw with domiciliary long term oxygen therapy]. / Osiem lat doswiadczen Warszawskiego osrodka domowego leczenia tTlenem.

Between August 1986-July 1994 45 1 patients with chronic hypoxaemia were referred to us for evaluation. 315 of them (70%) were qualified for LTOT according to national guidelines. There were 189 pts with COPD (60%), 40 with late sequelae of pulmonary tuberculosis (TB), 21 with interstitial pulmonary fibrosis (IPF), 15 with bronchiectasis (BE), 15 with severe kyphoscoliosis (KS) and 35 with other disease leading to chronic respiratory failure. All patients received oxygen from an oxygen concentrator and have been regularly followed-up. The best survival rate in patients followed up for at least 3 years was observed in KS (68%) and COPD pts (50%). The worst survival was seen in BE (9%) and IPF (21%). 183 pts died during the follow-up and in 3 pts (1%) LTOT was withdrawn. The most frequent cause of death were either acute (58%) or chronic (21%) cardiorespiratory failure.

[Prognostic value of pulmonary hypertension in patients with severe COPD]. / Prognostyczne znaczenie nadcisnienia plucnego w ciezkiej postaci POCHP.

UNLABELLED: There is a continuing debate on the role of pulmonary hypertension in the natural history of COPD. The aim of the study was to compare 2 groups of COPD pts, one investigated before domiciliary oxygen treatment era (Group I) with the other benefiting from LTOT (Group II). Both were followed-up for 5 years. INCLUSION CRITERIA: pure COPD, PaO2 < 60 mmHg, PAP > 20 mmHg. Group I consisted of 16 pts (13M, 3F), mean age 55 +/- 9y. On initial evaluation their FEV1 averaged 0.93 +/- 0.3L and PaO2 54 +/- 6 mmHg. Their mean pulmonary arterial pressure (PAP) was 37.9 +/- 9 mmHg. During five years 12 patients (75%) died. Mean survival time of pts who died was 18.9 +/- 14.7 months. Group II consisted of 34 pts (27M, 7F) mean age 56 +/- 8y (NS vs group I), FEVI 0.83 +/- 3L (NS). PaO2 53 +/- 6 mmHg (NS), PAP 30.9 +/- 8.5 mmHg (p < 0.02). During five years 26 pts (76.5%) died. Mean survival time was 25 +/- 16 months (NS). Mean oxygen breathing time was 14h/ day. The Cox's survival analysis did not show difference between patients group I and II. We conclude that high initial PAP in group I patients did not affect survival compared to patients with similar severity of respiratory failure and lower PAP. The finding that LTOT did not improve survival may depend on many other variables not included into analysis.

[Effect of altitude on blood oxygenation during sleep in patients with bronchial asthma]. / Wplyw wysokosci na utlenowanie krwi w czasie snu u chorych na astme oskrzelowa.

The aim of our study was to investigate the severity of overnight arterial blood desaturations in patients with asthma at the altitude of 3200 meters above sea level. 12 asthmatics and 12 healthy controls were investigated. Three overnight pulsoximetries were performed in all subjects, one at the lowland and on the 1st and 5th night at the altitude. Mean SaO2 at the lowland was significantly lower in asthmatics than in the controls (p < 0.01). After the ascent to high altitude severe fall in mean SaO2 was noted in both groups (from 94.3% to 85.8% in asthmatics and from 97.1% to 88.7% in controls) (p < 0.001 for both groups). After few days of acclimatization mean SaO2 rose to 88.8% in asthmatics and to 91.3% in controls, but was still significantly lower than at the lowland (p < 0.001 for both groups). At the altitude differences in mean SaO2 between two groups were not statistically significant. We conclude that severity of overnight desaturations at high altitude do not vary between asthmatics with impaired respiratory function and healthy subjects.

[Lung function and exercise tolerance in patients with chronic major vessel thromboembolic pulmonary hypertension]. / Czynnosc pluc i sprawnosc wysilkowa u chorych na nadcisnienie plucne spowodowane przewleklaa zatorowoscia duzych tetnic plucnych.

We studied 14 consecutive patients with severe pulmonary hypertension due to chronic major vessel thromboembolic pulmonary hypertension (CPTEH), clinical entity that may be successfully surgically treated by pulmonary thrombendarterectomy. Resting pulmonary mechanics and gas exchange were investigated. Exercise tolerance was studied by 3 different exercise tests. Pulmonary volumes and flows were normal. Some patients presented with decreased lung compliance and reduced diffusion capacity for carbon monoxide. Majority of patients had hypoxaemia and respiratory alkalosis. Exercise tolerance was very limited. In 6 minute walking test patients covered 346 +/- 95 meters. During Bruce test patients completed from 1 to 4 stages. During incremental maximal symptom limited test on cycloergometer patients achieved 56 +/- 18 watts. We concluded that patients with CPTEH present with resting hypoxaemia deteriorating further on exercise and severely limited exercise tolerance.

[Predictors of survival in patients with chronic obstructive pulmonary disease with moderate hypoxemia]. / Czynniki wplywajace na przezycie u chorych na przewlekla obturacyjna chorobe pluc z umiarkowana hipoksemia.

Long-term oxygen therapy (LTOT) is a well established method of treatment in patients with chronic obstructive pulmonary disease (COPD). There are two main qualification criteria for LTOT: severe hypoxaemia (PaO2 < 55 mmHg) and moderate hypoxemia (PaO2 > 55 mmHg) accompanied by signs of cor pulmonale. We were unable to find any controlled investigations on the effect of LTOT on survival in this group of patients. We studied 85 COPD patients with PaO2 between 56-65 mmHg. Fourty four patients were treated at theirs homes with LTOT, 41 formed a control group. Both groups presented with severe airway obstruction--FEV1 < 1L. All patients were followed up for at least 3 years. During this time 27 patients died from the LTOT group and 26 patients from the control group. Survivors were younger and had less severe airway obstruction than nonsurvivors. Cox's proportional hazard regression analysis showed that only age and spirometric parameters--VC, VC%N, FEV1 were good predictors of survival. LTOT did not improve prognosis in this group of patients. Results of our study suggest the need of verification of LTOT qualification criteria.

[Effects of home oxygen therapy on pulmonary hemodynamics in patients with chronic obstructive pulmonary disease]. / Wplyw domowego leczenia tlenem na hemodynamike krazenia plucnego u chorych na przewlekla obturacyjna chorobe pluc.

The aim of the study was to assess effects of long-term oxygen therapy (LTOT) on pulmonary haemodynamics in patients with chronic obstructive pulmonary disease (COPD). 93 pts (73M, 20F) mean age 58 years, entered the study. Their functional characteristics at entry for LTOT revealed: VC 2.33L, FEV1, 0.85L, FEV1/VC 37%, PaO2 55.5 mmHg, PaO2 46.7 mmHg, Hct 50%. Pulmonary haemodynamics showed: mild pulmonary hypertension (mean pulmonary arterial pressure PPA 25.9 mmHg), normal pulmonary wedge pressure (Pw) and increased driving pressure (PPA-Pw) 17.8 mmHg. Cardiac output (CO) was normal and pulmonary vascular resistance (PVR) averaged 313 dyne.s.cm-5. All enrolled patients were treated with oxygen at home and followed-up for at least 2 years. After 2 years of LTOT PPA and Pw fell by 2.4. and 2.6 mmHg, respectively, and (PPA-Pw) remained stable. An increase in CO by 0.31.min-1 was found while PVR was stable. After 4 years of treatment PPA, (PPA-Pw) and CO increased by 1.5, 1.7 mmHg and 0.9 l.min-1 respectively, while Pw and PVR remained stable. In 12 six years survivors PPA decreased after 2 years by 4.4 mmHg and cardiac output increased by 2 l.min-1 both returning to baseline after 6 years of LTOT. No significant changes in PVR were observed. Comparison of lung function tests before and after 6 years of LTOT showed deterioration of airways obstruction and of respiratory failure. LTOT for 14 h/d results in long-term stabilization of the hypoxic pulmonary hypertension despite of the progression of the natural course of COPD.

Effects of acetazolamide on overnight oxygenation and acute mountain sickness in patients with asthma.

The aim of the study was to assess effects of acetazolamide in prevention of acute mountain sickness (AMS) and on overnight oxygenation, in patients with asthma treated at the altitude of 3,200 m. Sixteen patients with asthma, 6 males and 10 females, mean age 32 yrs, were first investigated at low altitude (760 m). They presented with mild airways obstruction, normal arterial blood gases, and normal oxygenation at night studied by pulse oximetry. After initial investigations, patients were divided by random number into the treated (T) and control (C) groups of eight patients each. T group patients received acetazolamide, 750 mg daily for 2 days, before the ascent and on the first day at altitude (3,200 m). Symptoms of AMS developed in seven patients from group C and in three from group T. The overnight pulse oximetry, performed on the first night at altitude, revealed that group T patients had statistically higher (p < 0.05) initial, 91 vs 87%, mean, 90 vs 86%, and minimum, 84 vs 75%, arterial oxygen saturation than group C patients. Overnight pulse oximetry was repeated on the 5th, 10th and 17th day at altitude, and showed that in group C patients, from the 5th day onwards, oxygenation improved to the level observed in group T patients on the first night. We conclude that pretreatment with acetazolamide before the ascent prevented patients with asthma from developing symptoms of AMS, and alleviated acute changes in arterial oxygen saturation brought about by the high altitude hypoxia.

[Five years of home oxygen therapy in Poland]. / Piec lat systemu domowego leczenia tlenem w Polsce.

Long-term oxygen therapy (LTOT) is known since the second half of the present century. In Poland it was introduced in 1986. By the end of 1991, 37 regional LTOT centers, using almost 1000 oxygen concentrators as oxygen source, were organized all over the country. To LTOT are classified two groups of patients with the advanced chronic pulmonary disease complicated with fixed respiratory failure and frequently with cor pulmonale. One group consist of patients with severe hypoxemia (PaO2 < or = 7.3 kPa, i.e. < or = 55 mm Hg) accompanied by the signs of cor pulmonale or tissue hypoxia whereas another consists of patients with moderate hypoxemia (PaO2 7.4-7.8 kPa, i.e. 55-65 mm Hg). A 5-year history of the regional LTOT centres in Poland was assessed. According to questionnaires received from 27 centres, 971 patients (662 males and 309 females), aged 59.3 years on the average, were classified to the long-term oxygen therapy between August 1, 1986 and December 31, 1991. Six hundred fifty seven patients (67.6%) has COPD, 229 (23.6%) had non-COPD pulmonary disease, and 85 patients (8.8%)-other diseases. Six hundred forty four patients (66.3%) were given oxygen concentrators for severe hypoxemia and 327 patients (33.7%) for moderate hypoxemia wit co-existing signs of the cor pulmonale and tissue hypoxia. Mean time of oxygen use in 839 patients was 13.8 hours a day. Long-term oxygen therapy was ceased in 31 patients (3.2%).(ABSTRACT TRUNCATED AT 250 WORDS)

[Value of additional qualifying tests for home oxygen therapy in patients with chronic obstructive diseases and moderate hypoxemia]. / Wartosc dodatkowych badan kwalifikacyjnych do domowego leczenia tlenem u chorych na przewlekle obturacyjne choroby pluc z umiarkowana hipoksemia.

A value of pulmonary artery catheterization, exercise test and blood oxygenation at sleep was assessed. Such tests are considered as the additional possibility for classifying the patients with chronic obstructive disease, with moderate hypoxia, to the treatment with oxygen at home. Hemodynamic tests have shown pulmonary hypertension in 73% of patients. Clinical evaluation of the cor pulmonale seemed satisfactory. A decrease in arterial blood oxygenation during exercise below 88%, being a border value classifying to the treatment with oxygen at home, was found in 82% of patients. Marked decrease in blood oxygenation at sleep has been characteristic feature of all patients. Exercise test and oximetry at night may also valuable for classifying the patients to the treatment with oxygen under home conditions.