The clinical significance of anaemia and disturbed iron homeostasis in chronic respiratory failure.

BACKGROUND: Anaemia is a frequent, clinically relevant condition in various chronic diseases. It seems also to be prevalent in patients with chronic respiratory failure (CRF). We studied the characteristics of anaemia in CRF and its associations with clinical outcome. METHODS: In a prospective design, 271 consecutive patients with CRF were evaluated; patients with other conditions often associated with anaemia were excluded. Haematological laboratory and physiological parameters, health-related quality of life (HRQL), dyspnoea and 48-month survival were determined. Anaemia was defined according to WHO [haemoglobin (Hb)< 13 g/l (male); Hb< 12 g/dl (female)] and using an established algorithm. RESULTS: Among 185 patients included, 18.4% showed anaemia, not depending on chronic obstructive pulmonary disease (COPD) vs. non-COPD (17.6% vs. 19.0%; p = 0.851) or on gender [16.5% (female) vs. 19.8% (male); p = 0.702]. Anaemic patients had higher age, creatinine (p < 0.05 each) and erythropoietin levels (p < 0.001), but lower transferrin saturation (TSAT), serum iron and vitamin B12 levels (p < 0.01 each). By definition, most anaemic patients (67.6%) had disturbances in iron homeostasis according to 'anaemia of chronic disease' and/or true iron deficiency anaemia. Hb was independently related to dyspnoea and HRQL, while TSAT ≥ 20% was linked to less dyspnoea and better subjective exercise capability. Non-survivors had lower Hb and serum iron levels (p < 0.05 each). In multivariate analysis, lower serum iron levels and TSAT were independently associated with mortality (p < 0.05 each). CONCLUSION: Anaemia was common in patients with CRF and often because of disturbed iron homeostasis. Hb and TSAT were linked to functional outcome and HRQL. Lower serum iron levels and TSAT were independent prognostic parameters.

Characteristics and outcomes of patients hospitalized for infection with influenza, SARS-CoV-2 or respiratory syncytial virus in the season 2022/2023 in a large German primary care centre.

BACKGROUND: In 2022/2023, Influenza A and Respiratory Syncytial Virus (RSV) reappeared in hospitalized patients, which was in parallel to ongoing SARS-CoV-2 infections. The aim of our study was to compare the characteristics and outcomes of these infections during the same time. METHODS: We included patients of all ages with a positive polymerase chain reaction (PCR) test for Influenza A/B, RSV, or SARS-CoV-2 virus hospitalized in the neurological, internal or paediatric units of the RoMed Hospital Rosenheim, Germany, between October 1st 2022 and February 28th 2023. RESULTS: A total of 906 patients were included (45.6% female; median age 68.0 years; 21.9% Influenza A, 48.2% SARS-CoV-2, 28.3% RSV). Influenza B (0.2%) and co-infections (1.5%) played a minor role. In patients aged ≥ 18 years (n = 637, 71%), Influenza A, SARS-CoV-2 and RSV groups differed in age (median 72, 79, 76 years, respectively; p < 0.001). Comorbidities, particularly asthma and COPD, were most prevalent for RSV. 103 patients were admitted to the intensive care unit (ICU) (16.3% Influenza A, 15.3% SARS-CoV-2, 19.2% RSV; p = 0.649), 56 died (6.8% Influenza A, 9% SARS-CoV-2, 11.1% RSV; p = 0.496). RSV showed the highest frequencies of low-flow oxygen supplementation for admission and stay. Differences in the length of stay were minor (median 7 days). Conversely, in patients aged < 18 years (n = 261, 28,8%), 19.5%, 17.6% and 60.2% were in the Influenza A, SARS-CoV-2 and RSV groups, respectively; 0.4% showed Influenza B and 2.3% co-infections. 17 patients were admitted to ICU (3.9% Influenza A, 9.6% RSV, 0% SARS-CoV-2); none died. RSV showed the highest frequencies of high- and low-flow oxygen supplementation, SARS-CoV-2 the lowest. CONCLUSION: When comparing infections with Influenza, SARS-CoV-2 and RSV in the winter 2022/2023 in hospitalized adult patients, rates of ICU admission and mortality were similar. RSV showed the highest frequencies of obstructive airway diseases, and of oxygen supplementation. The latter was also true in children/adolescents, in whom RSV dominated. Thus, in the situation of declining importance of SARS-CoV-2, RSV showed a disease burden that was relatively higher than that from Influenza and SARS-CoV-2 across ages, and this might be relevant for the seasons coming.

Anaemia in chronic respiratory failure.

BACKGROUND: In patients with severe chronic obstructive pulmonary disease (COPD), anaemia is common and associated with impaired long-term survival and quality of life. Whether anaemia is also prevalent in patients with other severe, non-inflammatory respiratory diseases has not yet been systematically tested. METHODS: In 595 patients with obstructive (OD, 54.8%) or restrictive disease (RD, 45.2%) and chronic respiratory failure (CRF), anthropometric data, laboratory parameters, lung function, blood gases and comorbidities were assessed prior to initiation of home mechanical ventilation. Patients were classified as anaemic based on haemoglobin (Hb) levels (Hb<12/13 g/dl, female patients/male patients). Patients with known causes for anaemia were excluded. RESULTS: In patients with CRF the prevalence of anaemia was 13.3% and not different between RD (11.5%) and OD (14.7%) (p=0.276). A sex-related difference occurred only in OD [7.9% (f) vs. 17.3% (m); p=0.035]. Patients with OD and anaemia presented with higher age (p=0.003), pH (p=0.014) and arterial oxygen pressure (PaO(2) ) (p=0.012), lower body mass index (BMI) (p=0.011) and total protein (p=0.012) and higher rates of coronary heart disease (p=0.01), cardiac arrhythmia (p=0.014) and diabetes mellitus (p=0.003) in comparison to non-anaemic patients. In patients with RD anaemia was associated with higher age, (p=0.008), pH (p=0.011) and lower leucocytes numbers (p=0.006). CONCLUSIONS: Anaemia is frequent not only in COPD but also in other severe respiratory diseases combined with CRF. It was associated with advanced age, several comorbidities, impaired nutritional state and elevations of pH and PaO(2) , probably because of hyperventilation. Its prognostic impact has to be elucidated in future studies.

[Non-invasive and invasive mechanical ventilation for treatment of chronic respiratory failure. S2-Guidelines published by the German Medical Association of Pneumology and Ventilatory Support]. / Nichtinvasive und invasive Beatmung als Therapie der chronischen respiratorischen Insuffizienz. S2-Leitlinie herausgegeben von der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin e. V.

The field of mechanical ventilation is highly important in pulmonary medicine. The German Medical Association of Pneumology and Ventilatory Support ["Deutsche Gesellschaft für Pneumologie und Beatmungsmedizin e. V. (DGP)"] therefore has formulated these guidelines for home mechanical non-invasive and invasive ventilation. Non-invasive home mechanical ventilation can be administered using various facial masks; invasive home mechanical ventilation is performed via a tracheostomy. Home mechanical ventilation is widely and increasingly accepted as a treatment option for chronic ventilatory failure which most often occurs in COPD, restrictive lung diseases, obesity-hypoventilation syndrome and neuromuscular disorders. Essential for the initiation of home mechanical ventilation are the presence of symptoms of ventilatory failure and the detection of hypoventilation, most importantly hypercapnia. These guidelines comprise general indication criteria along with disease-specific criteria summarised by treatment algorithms. In addition, the management of bronchial secretions and care of paediatric patients are addressed. Home mechanical ventilation must be organised around a specialised respiratory care centre with expertise in patient selection, the initiation and the control of home mechanical ventilation. In this regard, the guidelines provide detailed information about technical requirements (equipment), control and settings of mechanical ventilation as well as organisation of patient care. A key requirement for home mechanical ventilation is the qualification of specialised home-care services, which is addressed in detail. Independent living and the quality of respiratory care are of highest priority in patients receiving home mechanical ventilation, since home mechanical ventilation can interfere with the integrity of a patient and often marks a life-sustaining therapy. Home mechanical ventilation has been shown to improve health-related quality of life of patients with chronic ventilatory failure. Long-term survival is improved in most patient groups, even though the long-term prognosis is often severely limited. For this reason, ethical issues regarding patient education, communication with ventilated patients at the end of life, living will, testament and medical care during the dying process are discussed.

[Prognostic factors for COPD patients with chronic hypercapnic respiratory failure and home ventilation]. / Prognosefaktoren bei Patienten mit COPD mit chronisch-hyperkapnischer respiratorischer Insuffizienz und ausserklinischer Beatmungstherapie.

The prevalence of patients with severe COPD and chronic hypercapnic respiratory failure (CHRF) receiving non-invasive home ventilation has greatly increased. With regard to disease severity, a multidimensional assessment seems indicated. Base excess (BE), in particular, reflects the long-term metabolic response to chronic hypercapnia and thus constitutes a promising, easily accessible, integrative marker of CHRF. Infact, BE as well as nutritional status and lung hyperinflation have been identified as independent predictors of long-term survival. In addition and in a review with the literature, a broad panel of indices including frequent comorbidities are helpful for assessment and monitoring purposes of patients with CHRF. Accordingly, in view of the patients' individual risk profile, the decision about the initiation of NIV should probably not rely solely on symptoms and chronic persistent hypercapnia but include a spectrum of factors that specifically reflect disease severity. Owing to the physiologically positive effects of NIV and according to retrospective data, patients with COPD and recurrent hypercapnic respiratory decompensation and patients with prolonged mechanical ventilation and/or difficult weaning could also be considered for long-term non-invasive ventilation. This, however, has to be corroborated in future prospective trials.

Nutritional depletion and its relationship to respiratory impairment in patients with chronic respiratory failure due to COPD or restrictive thoracic diseases.

OBJECTIVE: While malnutrition, especially fat-free mass index (FFMI), is a predictor for mortality in chronic obstructive pulmonary disease (COPD), less information on prevalence and mechanisms is available in patients with chronic respiratory failure (CRF) due to restrictive thoracic diseases (RTD). DESIGN AND SETTING: Cross-sectional study of patients consecutively admitted to an in-patient primary pulmonary centre. SUBJECTS: One hundred and thirty-two patients (30% RTD; 70% COPD) with CRF and intermittent non-invasive positive pressure ventilation. INTERVENTIONS: Malnutrition was quantified by bioelectrical impedance analysis or body mass index (BMI), and its relationship to laboratory, lung function, inspiratory muscle and blood gas parameters and 6-min walking distance (6-MWD) was assessed. RESULTS: Malnutrition in terms of BMI<20 kg/m(2) occurred in 16.1% of patients with COPD but none of those with RTD. FFMI<17.4 (<15.0 in female patients) kg/m(2) was found in 35.4 and 30.7%, respectively. FFMI was correlated with airway obstruction (sR(aw), r = -0.50; FEV(1)/VC, r = -0.28; P< or = 0.01 each) and lung hyperinflation (intrathoracic gas volume, r = -0.41; total lung capacity (TLC), r = -0.50; P< or = 0.001 each) in COPD, and with lung restriction in RTD (TLC, r=0.40; P=0.011). Furthermore, malnourished patients showed a higher inspiratory load (P (0.1)) and reduced 6-MWD in both groups. In COPD, only hyperinflation and P (0.1) were independently related to FFMI. CONCLUSIONS: Malnutrition as indicated by low FFMI was similarly prevalent in patients with CRF and COPD or RTD, but inadequately represented by BMI. The correlations between lung function impairments specific for the disease and FFMI emphasized the link between malnutrition and respiratory mechanical load irrespective of its aetiology.

Effects of selective and unselective endothelin-receptor antagonists on prostacyclin synthase gene expression in experimental pulmonary hypertension.

OBJECTIVE: Compared to the unselective endothelin (ET) receptor antagonist (Bosentan), superior effects of selective ET-A-receptor blockage (Ambrisentan) for the treatment of pulmonary hypertension (PH) are expected due to ET-B-receptor mediated beneficial effects. Our hypothesis was that treatment with Ambrisentan leads to an increase in prostacyclin synthase I (PGIS) expression compared to Bosentan. MATERIAL AND METHODS: To test this hypothesis, rats were treated with either monocrotaline (MCT) only, MCT+Ambrisentan or MCT+Bosentan. After 4 weeks, right ventricular systolic pressure (RVSP), pulmonary vascular remodelling and right ventricular hypertrophy (RV/(LV+S)) were measured. RESULTS: In MCT only treated animals, significantly greater expression of PGIS mRNA was found in the lungs compared to control animals, and this was confirmed by immunohistochemical analysis indicating increased staining of PGIS in the very small pulmonary arteries (17 % greater expression of PGIS mRNA in MCT versus control, p = 0.002; Remmele score (RS): 51 versus 102, p = 0.009). Treatment with Bosentan resulted in a significantly lower expression of PGIS mRNA compared to Ambrisentan and MCT only (7 % versus 18 %, p = 0.003 and 7 % versus 17 %, p = 0.004). This observation was also confirmed by immunohistochemical analysis (RS very small arteries: 45 versus 81, p = 0.003; RS small arteries: 45 versus 108, p = 0.014). No difference was observed in RVSP, RV/(LV+S) or pulmonary vascular remodelling between the two treatment groups (RVSP: 28 versus 39 mmHg, p = 0.189; RV/(LV+S) 0.46 versus 0.48, p = 0.818; medial area: 78.3 % versus 75.2 %, p = 0.823). CONCLUSIONS: Treatment with Bosentan leads to lower PGIS expression in pulmonary arteries compared to Ambrisentan, although the greater PGIS expression by Ambrisentan treatment had no benefical effect on pulmonary haemodynamics.

Impact of noninvasive home ventilation on long-term survival in chronic hypercapnic COPD: a prospective observational study.

AIMS: The long-term benefit from noninvasive ventilation (NIV) in chronic hypercapnic chronic obstructive pulmonary disease (COPD) remains uncertain. METHODS: Within a prospective observational design, we compared the long-term survival of 140 patients with severe persistent hypercapnic COPD (FEV(1) 28.7 +/- 8.7% predicted; PaCO(2) 60.1 +/- 9.2 mmHg) with (n = 99) or without (n = 41) NIV. End-point was all-cause mortality, determined up to 4 years by Kaplan-Meier analysis. Additionally, Cox's proportional hazards regression and stratification by risk factors was performed. Patients were characterised by anthropometric and functional parameters, comorbidities and medical therapy. RESULTS: Adherence in patients with NIV was high (88.9%), daily ventilator use being 6.4 +/- 2.6 h/day and inspiratory pressures 21.0 +/- 4.0 cmH(2)O. One- and 2-year survival rates were 87.7% and 71.8%, respectively, in patients with NIV vs. 56.7% and 42.0% in patients without NIV. Survival rates were significantly higher in patients with NIV compared to those without this therapy (p = 0.001; hazard ratio 0.380; 95% confidence interval 0.138-0.606). The difference between groups was still significant after adjustment for differences in baseline characteristics. Moreover, stratification by risk factors revealed beneficial effects, particularly in patients with high base excess (BE; > 8.9 mmol/l), low pH (< 7.41), FEV(1) (< 27.5%) haemoglobin (< 13.8 g/dl) or large hyperinflation (residual volume-to-total lung capacity > 189% predicted) upon inclusion (p < 0.05 each). CONCLUSION: In patients with severe chronic hypercapnic COPD receiving NIV at high inspiratory pressure levels and showing high adherence to this therapy, long-term survival was significantly higher than in non-ventilated patients. Patients displaying more severe disease according to known risk factors seemed to benefit most from long-term NIV.

Mortality and prognostic factors in patients with obesity-hypoventilation syndrome undergoing noninvasive ventilation.

OBJECTIVES: The incidence of obesity-hypoventilation syndrome (OHS) has greatly increased over time, but data on long-term outcome are limited. We investigated survival and prognostic factors in these patients undergoing noninvasive positive pressure ventilation (NPPV). DESIGN: Retrospective descriptive analysis of patients with OHS and NPPV up to 10 years. METHODS: Long-term mortality and predictors of survival were assessed. Additionally, we evaluated changes in lung function, blood gas and laboratory parameters 5.7 +/- 2.5 months after initiation of NPPV. RESULTS: 126 patients (BMI 44.6 +/- 7.8 kg m(-2); PaCO(2) 55.5 +/- 7.7 mmHg) were followed for 41.3 +/- 27.6 months. Upon follow-up, blood gases (daytime and nighttime), as well as pulmonary function improved, whilst haemoglobin and BMI decreased (P < 0.001 each). Adherence to NPPV was high (94.5% continuing NPPV 6.5 +/- 2.3 h day(-1)). All-cause mortality was 12.7%, with 1-, 2- and 5-year survival of 97.1%, 92.0% and 70.2%, respectively. In univariate analysis, patients with PaO(2) <50 mmHg, C-reactive protein > or = 5.1 mg L(-1), leucocytes > or = 7.8 x 10(3) microl(-1), or pH > or = 7.44 at baseline had poor prognosis (P < 0.05 each). In Cox multivariate analysis, PaO(2), pH and leucocytes were independent predictors of mortality. Reduction in nocturnal PaCO(2) by > or =23.0% and haemoglobin at follow-up was associated with improved survival (P < 0.05 each) whilst a decrease in pH was a predictor of increased mortality. In contrast, neither baseline BMI nor its change was linked to survival. CONCLUSION: Gas exchange and lung function in OHS were improved after initiation of NPPV. Hypoxemia, high pH and elevated inflammation markers predicted poor survival. Overall, NPPV was well tolerated and survival was excellent when compared with data from historical matched controls.