Severe Chronic Hypoxemia Research Articles

Экономическая эффективность длительной кислородотерапии у больных бронхолегочными заболеваниями с тяжелой хронической артериальной гипоксемией

Background: long-term oxygen therapy (LTOT) for chronic lung diseases associated with chronic hy-poxemia is effective in terms of increasing life expectancy. However, by now, the costs of LTOT are not reimbursed by the healthcare system of the Russian Federation. Aim: to evaluate the economic efficiency of respiratory therapy centers in providing pa-tients with chronic lung diseases and severe chronic hypoxemia with LTOT at home. Patients and Methods: direct medical and nonmedical costs associated with the introduc-tion of LTOT into clinical practice were identified and calculated. Costs of LTOT, outpatient management of patients without exacerbations, treatment for exacerbations, and disability-related payments were considered. Clinical and economic modeling was performed. A cost-effectiveness analysis was performed and the budget impact was assessed. Published data and the experience of St. Petersburg Regional Respiratory Support Center were used to evaluate LTOT efficacy. Results: additional costs for LTOT per patient for 5 years are 229,759 RUB. LTOT signif-icantly (by 74%) reduce the costs of treating patients with exacerbations of chronic obstructive pulmonary disease, mainly due to a reduction in exacerbation rate, including those requiring ad- mission to hospital. Analysis of budget impact over 5 years demonstrates a decrease in direct medical costs per 100 oxygen concentrators by 32% (from 181,666,728.90 RUB to 123,247,630.82 RUB). Given mortality, the estimated number of patients opting for LTOT using 100 oxygen concentrators over 5 years is 150. Conclusions: reimbursement for LTOT costs in Russian healthcare is economically reason-able. KEYWORDS: long-term oxygen therapy, economic efficiency, respiratory therapy center, cost-effectiveness analysis, chronic hypoxemia. FOR CITATION: Gomon Yu.M., Titova O.N., Kolbin A.S., Kuzubova N.A., Balykina Yu.E. Economic efficiency of long-term oxygen therapy in patients with chronic lung diseases and severe chronic hypoxemia. Russian Medical Inquiry. 2023;7(8):475–481 (in Russ.). DOI: 10.32364/2587-6821-2023-7-8-1.

Burden and Characteristics of Severe Chronic Hypoxemia in a Real-World Cohort of Subjects with COPD

BackgroundChronic respiratory failure may occur as a consequence of chronic obstructive pulmonary disease (COPD) and is associated with significant morbidity and mortality. Hypoxemia is determined by underlying disease characteristics and comorbidities. Severe hypoxemia is typically only found in subjects with severe airflow obstruction (FEV1<50% predicted). However, how hypoxemia relates to disease characteristics is not fully understood.MethodsIn the French Initiatives BPCO real-life cohort, arterial blood gases were routinely collected in most patients. Relationships between severe hypoxemia, defined by a Pa02<60 mmHg (8 kPa) and clinical/lung function features, comorbidities and mortality were assessed. In subjects with severe hypoxemia, clinical characteristics and comorbidities were compared between those with non-severe versus severe airflow limitation. Classification and regression trees (CART) were used to define clinically relevant subgroups (phenotypes).ResultsArterial blood gases were available from 887 subjects, of which 146 (16%) exhibited severe hypoxemia. Compared to subjects with a PaO2≥60 mmHg, the severe hypoxemia group exhibited higher mMRC dyspnea score, lower FEV1, higher RV and RV/TLC, more impaired quality of life, lower 6-minute walking distance, less frequent history of asthma, more frequent diabetes and higher 3-year mortality rate (14% versus 8%, p=0.026). Compared to subjects with Pa02<60 mmHg and FEV1<50% (n=115, 13%), those with severe hypoxemia but FEV1≥50% predicted (n=31) were older, had higher BMI, less hyperinflation, better quality of life and a higher rate of diabetes (29% versus 13%, p=0.02). Severe hypoxemia was better related to CART-defined phenotypes than to GOLD ABCD classification.ConclusionIn this cohort of stable COPD subjects, severe hypoxemia was associated with worse prognosis and more severe symptoms, airflow limitation and hyperinflation. Compared to subjects with severe hypoxemia and severe airflow limitation, subjects with severe hypoxemia despite non-severe airflow limitation were older, had higher BMI and more diagnosed diabetes.Trial Registration04–479.

Long-term oxygen therapy in COPD patients: population-based cohort study on mortality.

PurposeChronic obstructive pulmonary disease (COPD) is the fourth leading cause of death worldwide and is associated with a growing and substantial socioeconomic burden. Long-term oxygen therapy (LTOT), recommended by current treatment guidelines for COPD patients with severe chronic hypoxemia, has shown to reduce mortality in this population. The aim of our study was to assess the standardized mortality ratios of incident and prevalent LTOT users and to identify predictors of mortality.Patients and methodsWe conducted a 2-year follow-up population-based cohort study comprising all COPD patients receiving LTOT in the canton of Bern, Switzerland. Comparing age- and sex-adjusted standardized mortality ratios, we examined associations between all-cause mortality and patient characteristics at baseline. To avoid immortal time bias, data for incident (receiving LTOT <6 months) and prevalent users were analyzed separately.ResultsAt baseline, 475 patients (20% incident users, n=93) were receiving LTOT because of COPD (48/100,000 inhabitants). Mortality of incident and prevalent LTOT users was 41% versus 27%, respectively, p<0.007, and standardized mortality ratios were 8.02 (95% CI: 5.64–11.41) versus 5.90 (95% CI: 4.79–7.25), respectively. Type 2 respiratory failure was associated with higher standardized mortality ratios among incident LTOT users (60.57, 95% CI: 11.82–310.45, p=0.038).ConclusionTwo-year mortality rate of COPD patients on incident LTOT was somewhat lower in our study than in older cohorts but remained high compared to the general population, especially in younger patients receiving LTOT <6 months. Type 2 respiratory failure was associated with mortality.

Long-Term Oxygen Therapy in COPD: evidences and open questions of current indications

Long term oxygen therapy (LTOT) has been shown to improve the survival rate in Chronic Obstructive Pulmonary Disease (COPD) patients with severe resting hypoxemia by NOTT and MRC studies, published more than 25 years ago. The improved survival was found in patients who received oxygen for more than 15 hours/day. The effectiveness of LTOT has been documented only in stable COPD patients with severe chronic hypoxemia at rest (PaO2 < 55 mmHg (7.3 kPa) or PaO2 ranging from 56 to 59 mmHg (7.4-7.8 kPa) in presence of signs of Cor Pulmonale, hematocrit > 55%. In fact no evidence supports the use of LTOT in COPD patients with moderate hypoxemia (55 < PaO2 < 65 mmHg), and in those with decreased oxygen saturation (SO 2 <90%) during exercise or sleep. Furthermore, it is generally accepted without evidence that LTOT in clinical practice is warranted in other forms of chronic respiratory failure not due to COPD when a-terial blood gas criteria match those established for COPD patients. The prescription of oxygen in these circumstances, as for unstable patients, increases the number of patients receiving supplemental oxygen and the related costs. Comorbidities are likely to affect both prognosis and health outcomes in COPD patients, but at the moment we do not know if LTOT in these patients with complex chronic diseases and mild-moderate hypoxemia could be of any use. For these reasons a critical revision of the actual guide lines indications for LTOT in order to optimise effectiveness and costs, and future research in the areas that have not previously been addressed by NOTT and MRC studies, are mandatory.

Patient-Centric LTOT: No Room for Complacency

The benefits of the continuous administration of supplemental long-term oxygen therapy (LTOT) for the amelioration of the sequelae of severe chronic hypoxemia (baseline PaO2 ≤ 55 mg Hg or SpO2 ≤ 88%) secondary to COPD, are well established. When properly prescribed and delivered, LTOT improves

B-type natriuretic peptide, vascular endothelial growth factor, endothelin-1, and nitric oxide synthase in chronic mountain sickness

The pathogenesis of chronic mountain sickness (CMS) may involve vasoactive peptides. The aim of this study was to investigate associations between CMS and levels of B-type natriuretic peptide (BNP), vascular endothelial growth factor (VEGF), endothelin-1 (ET-1), and endothelial nitric oxide synthase (eNOS). A total of 24 patients with CMS and 50 control subjects residing at 4,300 m participated in this study. Mean pulmonary arterial pressure (mPAP) was measured by echocardiography. Serum BNP, VEGF, ET-1, and eNOS were measured. Receiver operator characteristic curves to assess the balance of sensitivity and specificity for CMS were constructed. As a result, patients with CMS had significantly greater mPAP compared with controls and had lower arterial O(2) saturation (Sa(O(2))). Both BNP and ET-1 correlated positively with mPAP and negatively with Sa(O(2)), whereas serum VEGF levels were inversely correlated with Sa(O(2)); eNOS correlated negatively with mPAP and positively with Sa(O(2)). Median concentrations of BNP were greater in patients with CMS compared with those without CMS: 369 pg/ml [interquartile range (IQR) = 336-431] vs. 243 pg/ml (IQR = 216-279); P < 0.001. Similarly, concentrations of VEGF [543 pg/ml (IQR = 446-546) vs. 243 pg/ml (IQR = 216-279); P < 0.001] and ET-1 [14.7 pg/ml (IQR = 12.5-17.9) vs. 11.1 pg/ml (IQR = 8.7-13.9); P = 0.05] were higher in those with CMS compared with those without, whereas eNOS levels were lower in those with CMS [8.90 pg/ml (IQR 7.59-10.8) vs. 11.2 pg/ml (9.13-13.1); P < 0.001]. The areas under the receiver operator characteristic curves for diagnosis of CMS were 0.91, 0.93, 0.77, and 0.74 for BNP, VEGF, ET-1, and eNOS, respectively. In age- and biomarker-adjusted logistic regression, BNP and VEGF were positively predictive of CMS, whereas eNOS was inversely predictive. In conclusion, severe chronic hypoxemia and consequent pulmonary hypertension in patients with CMS may stimulate release of natriuretic peptides and angiogenic cytokines. These vasoactive peptides may play an important role in the pathogenesis and clinical expression of CMS and may indicate potential prognostic factors in CMS that could serve as targets for therapeutic trials or clinical decision making.

Trasplante cardíaco en el ventrículo único

Univentricular heart is an uncommon congenital heart disease. A select group of these patients (those with severe pulmonary stenosis or atresia) can reach adult age with different degrees of heart failure and severe chronic hypoxemia. Patients with adequate pulmonary tree development are likely to undergo heart transplantation when usual palliative techniques are contraindicated. Three cases of univentricular heart with pulmonary stenosis in which heart transplantation was the optimal choice are reported. Different techniques used to assess pulmonary tree development are analysed.

Functional Consequences of Acute and Chronic Hypoxia on Respiratory and Skeletal Muscles in Mammals

Reduced oxygen supply to contracting muscles affects not only the metabolic paths but also modifies the gain of sensorimotor reflex loops initiated from the activation of specialized nervous endings that detect the changes in muscle metabolism and membrane outflow of potassium. Large differences are found between skeletal muscles and the diaphragm with respect to their sensitivity to acute or chronic hypoxia. The diaphragm tolerates much more hypoxemia than do skeletal muscles, namely those constituted by a large proportion of slow twitch oxidative fibers. Acute hypoxemia or ischemia accentuates the inhibitory influences exerted by the afferent paths from muscle metaboreceptors. This adaptative response may be responsible for enhanced muscle wisdom phenomenon during fatiguing contractions under hypoxic conditions. Prolonged and severe chronic hypoxemia markedly reduces muscle force generation by skeletal muscles and their endurance to fatigue. Restoration of normal PaO2 levels in these individuals immediately improves maximal muscle performance, perhaps through more efficient excitation-contraction coupling. Recent data on the consequences of hypoxia on muscle metabolism and the associated changes in sensorimotor control strongly suggest that local acidosis cannot entirely explain all electromyogram changes found during and after fatiguing exercise.

112 INCREASED OXYGENATION IN INFANTS WITH CANOTIC CONGENITAL HEART DISEASE DURING EXPOSURE TO 100% 02

Oxygen therapy is seldom recommended in infants with cyanotic congenital heart disease (CCHD) because of the small change in PaO2 that occurs with increased inspired oxygen concentrations. Arterial PO2 was measured in 25 infants with CCHD and C02 production (VC02) in 17 of them while breathing 21 and 100% 02. Pa02 increased from 31±7.9 to 41.4±17.3 mmHg within 3 minutes of breathing 100% 02. (P<0.001) This determined an increase in 02 content of 12 to 20%, depending on the initial Pa02 and the position of the Hb-O2 dissociation curve. Although the change in PaO2 was small, the increase in O2 content was considerable because it occurred in the steep part of the Hb-O2 dissociation curve. The increase in PaO2 cannot be explained solely by an increase in dissolved O2 in the blood perfusing the lungs but must be related to either an increase in pulmonary blood flow or to an increase in 02 saturation of the pulmonary venous blood. The latter would occur in case of an increased A/aO2 gradient due to co-existing pulmonary pathology. VCO2 increased from 7.6 before to 8.5 ml/minxkg 30 minutes after breathing 100% O2 (P< 0.005). This increase indicates that the basal metabolic rate may be depressed in infants with severe chronic hypoxemia and this can be at least partially reversed by a small increase in PaO2. These results suggest that 02 therapy may improve tissue oxygenation in some infants with CCHD.