Palliative Care for Patients with Severe Chronic Lung Diseases: A Swiss Position Paper

Nutritional status and long-term mortality in hospitalised patients with chronic obstructive pulmonary disease (COPD)

Nitric oxide mediates and modulates pulmonary transition from fetal to postnatal life. NO is synthesized by 3 nitric oxide synthase isoforms. One key pathway of nitric oxide metabolism results in nitrotyrosine, a stable, measurable marker of nitric oxide production. The purpose of this study was to assess, by semiquantitative immunohistochemistry, nitric oxide synthase isoforms and nitrotyrosine at different airway and vascular tree levels in the lungs of neonates at different gestational ages and to compare results in control groups to those in infants with chronic lung disease. Formalin-fixed, paraffin-embedded, postmortem lung blocks were prepared for immunohistochemistry using antibodies to each nitric oxide synthase isoform and to nitrotyrosine. Blinded observers evaluated the airway and vascular trees for staining intensity (0-3 scale) at 5 levels and 3 levels, respectively. The control population consisted of infants from 22 to 42 weeks' gestation who died in < 48 hours. Results were compared with gestation-matched infants with varying severity of chronic lung disease. In control and chronic lung disease groups, 22 to 42 weeks' gestation, staining for all 3 of the nitric oxide synthase isoforms was found in the airway epithelium from the bronchus to the alveolus or distal-most airspace. The abundance or distribution of nitric oxide synthase-3 staining in the airways did not show significant correlation with gestational age or severity of chronic lung disease. In the vascular tree, intense nitric oxide synthase-3 and moderate nitric oxide synthase-2 staining was found; nitric oxide synthase-1 was not consistently stained. Nitrotyrosine did stain in the pulmonary tree. Compared with controls where nitrotyrosine staining was minimal, regardless of gestation, in infants with chronic lung disease there was more than fourfold increase between severe chronic lung disease (n = 12) and either mild chronic lung disease or control infants (n = 16). All 3 of the nitric oxide synthase isoforms and nitrotyrosine are detectable by immunohistochemistry early in lung development. Nitric oxide synthase ontogeny shows no significant changes in abundance or distribution with advancing gestational age nor with chronic lung disease. Nitrotyrosine is significantly increased in severe chronic lung disease.

Outcomes in Patients With Severe Chronic Lung Disease Undergoing Index Cardiac Operations

Effect of medical and social risk factors on outcome of prematurity and very low birth weight

High levels of antibodies 6 months after COVID-19 vaccination in children with severe chronic diseases: A prospective longitudinal case series.

To determine whether the Score for Neonatal Acute Physiology, Version II (SNAP-II), improved prediction of severe (> or = grade III) intraventricular hemorrhage (IVH) and chronic lung disease (CLD) when compared to models using gestational age (GA) and traditional risk factors (e.g., Apgar score, small-for-gestational-age, sex, outborn status). We examined 4226 infants < or = 32 weeks' GA admitted to 17 Canadian neonatal intensive care units between 1996 and 1997. We compared prediction models for severe IVH and CLD, with and without SNAP-II. SNAP-II was a significant and independent predictor of severe IVH and CLD. Addition of SNAP-II to models using GA and traditional risk variables significantly (p<0.05) improved model prediction (AUC 0.8 for severe IVH; 0.83 for CLD). Models were well calibrated (p>0.05 for Hosmer-Lemeshow goodness of fit test). Addition of SNAP-II to models using GA and traditional risk factors significantly improves prediction of severe IVH and CLD.

Cardiac catheterization data from eight patients with severe chronic obstructive lung disease and pulmonary hypertension at rest (greater than 25 mm Hg) were compared with those obtained from 14 patients with mild to moderate disease whose pulmonary artery pressure was within the normal range at rest (mean 15 (SEM 1) mm Hg), but increased with exercise (30 (2) mm Hg). We obtained lung sections from necropsy material from the group with severe disease, and from surgical specimens in the group with mild to moderate disease, and compared the structure of the vasculature in these groups with that obtained from surgical specimens in a non-smoking control group of seven patients. Oxygen administration either at rest or during exercise did not greatly affect the pulmonary arterial pressures. When cardiac index was plotted against pulmonary artery pressure at rest and during exercise and extrapolated to the axis there was no evidence for a critical closing pressure in either group. The vessels in the groups with mild to moderate and severe chronic obstructive lung disease showed intimal thickening (each 19% (SD 0.5%)) by comparison with the non-smoking group (16% (0.5%]. The group with severe disease, in addition, had medial hypertrophy (27% (0.5%) versus 24% (SD 1%) in the non-smoking group). These data are consistent with the idea that the diseased vessels are distorted and rigid. The lack of effect of breathing oxygen on the vascular response at rest and during exercise suggests that hypoxic vasoconstriction has a minimal role in the pulmonary hypertension of chronic obstructive lung disease. The data suggest that the intimal changes could narrow the vessel calibre in those patients with mild to moderate disease, and that the thickened media present in the vessels from patients with severe disease may act in concert with the enlarged intima to produce more severe vascular obstruction.

Hospitalization as a measure of morbidity among very low birth weight infants with chronic lung disease

National Consensus Project for Quality Palliative Care: Clinical Practice Guidelines for Quality Palliative Care, Executive Summary

Severe pulmonary hypertension (PH) is not common even in patients with severe chronic lung disease (CLD) but data on hemodynamic characteristics among patients with severe CLD is scarce. All adult patients who had right heart catheterization for lung transplant assessment for severe CLD in the only lung transplant service and for PAH management in the only tertiary pulmonary hypertension service in Hong Kong from 2010 to 2020 were included and classified into CLD group and PAH group. Patient characteristics and hemodynamic parameters were analyzed. There were 153 patients included with 106 patients in the CLD group and 47 in the PAH group. There were only 19.8% of the patients in the CLD group had severe pulmonary hypertension. Patients in the CLD group had significantly lower systolic pulmonary arterial pressure (PAPs), lower mean pulmonary arterial pressure (PAPm), higher cardiac index, and lower PVR when compared with the PAH group (p < 0.001). The area under curve (AUC) of PAPs, PAPm, and PVR were excellent, 0.973, 0.970, and 0.938, respectively for discrimination between CLD and PAH on receiver operator characteristics curve analysis. Optimal cutoff values were 55.5 mmHg, 35.5 mmHg, and 6.1 Wood Units for PAPs, PAPm, and PVR with Youden Index 0.85, 0.80, and 0.82, respectively. There were distinct hemodynamic characteristics between the CLD group and the PAH group. Systolic pulmonary arterial pressure, mean pulmonary arterial pressure, and pulmonary vascular resistance are useful to discriminate between the phenotype of severe CLD and PAH.

The influence of the timing of surfactant replacement therapy for the treatment of neonatal respiratory distress syndrome was evaluated in a study of 182 neonates of less than 30 weeks' gestation who were randomly assigned prior to delivery to one of three study groups: control (dummy instillation of air given at birth), early surfactant (surfactant given at birth), or late surfactant (surfactant given at less than 6 hours of age). Subjects in the late surfactant group could avoid treatment if they had a clear chest roentgenogram and required no supplemental oxygen at a mean airway pressure of less than 7 cm of water. All treated neonates were eligible to receive up to three additional doses during the first 5 days of life. The three groups were comparable with respect to birth weight, gestational age, and other perinatal parameters with the exception of a lower cord arterial pH and 1-minute Apgar score in the early surfactant group. Of the 60 neonates randomly assigned to late treatment, 29 (48%) were deemed surfactant sufficient and thereby avoided treatment; the other 31 received their first dose at a mean age of 2.9 hours. There was a significant improvement in gas exchange during the first week of life in both surfactant groups compared with the control group, reflected by differences in fraction of inspired oxygen, arterial/alveolar PO2, and ventilation index (peak pressure x rate on the ventilator) (P less than .001). Surfactant therapy also resulted in a lower incidence of pulmonary air leak and severe chronic lung disease (defined as requirement for respiratory support beyond 36 weeks post-conceptional age). There were no differences between early and late surfactant groups in any of these parameters. The only statistically significant difference between the surfactant groups was that the early group had a higher incidence of mild chronic lung disease (respiratory support beyond 28 days of age) than the late treatment group (P less than .005). Neonates in the late treatment group were extubated earlier and had a shorter neonatal intensive care unit stay than control neonates (P less than .05), whereas those in the early group were not significantly different from control neonates in these parameters. It is concluded that replacement therapy with bovine lung surfactant extract in neonates of less than 30 weeks' gestation results in decreased oxygen and ventilatory requirements during the first week of life and a lower incidence of pulmonary air leak and severe chronic lung disease.(ABSTRACT TRUNCATED AT 400 WORDS)

Exercise protocols and training are used more and more in diagnostic procedures and as a tool in improving physical, social and psychological functioning in chronic obstructive lung disease patients. Before starting a training programme in chronic obstructive lung disease patients, one should exclude ventilatory-limited patients from the group. A maximal ergometer test with arterial blood samples or pulse oximetry must be performed. In mild forms of chronic obstructive lung disease with no ventilatory insufficiency demonstrable with exercise testing, the patient can be trained with no restrictions. Endurance training is permitted. It should be noted that it is possible to train the muscular and cardiovascular system up to a new, possible ventilatory maximum. In severe chronic obstructive lung disease endurance training is accompanied by hypoxia, with an associated risk of rhythm disturbances and right heart failure. Training with supplemental oxygen can reduce this risk, but should be done only under close medical supervision. In very severe chronic obstructive lung disease, when endurance training is only marginally possible even with supplemental oxygen, suppleness, coordination and relaxation exercises should be emphasised in rehabilitation programmes. Postural exercises and breathing control exercises can also give great subjective improvements in this often very disabled group of patients. Furthermore they can reduce fear and panic when dyspnoea occurs. Training of the respiratory muscles in patients with chronic obstructive lung disease must be regarded as an experimental therapy. The clinical importance remains uncertain. Exercise-induced bronchoconstriction should not limit exercises or training, provided it is treated correctly.

Serum pituitary and thyroid hormones, testosterone, and the response of pituitary hormones to thyrotrophin releasing hormone were measured in 20 inpatients (mean age 68, range 42-81 years) with severe chronic obstructive lung disease and in 15 control convalescent inpatients (mean age 73, range 57-83 years) who had normal respiratory function. No significant differences were found in total and free thyroid hormone concentrations and basal concentrations of thyrotrophin, growth hormone, and prolactin; and their increments after injection of thyrotrophin releasing hormone were similar in patients with chronic obstructive lung disease, and control patients. Three patients with chronic obstructive lung disease, however, had no thyrotrophin responses to thyrotrophin releasing hormone. In men, low testosterone concentrations were found both in patients with chronic obstructive lung disease and in controls. Luteinising hormone concentrations were higher in men with chronic obstructive lung disease (p less than 0.02), whereas concentrations of follicle stimulating hormone in the two groups were not significantly different. There was no significant correlation between arterial blood gas tensions and these hormone measurements. General effects of age and illness may be more important than direct effects of hypoxia in determining hypothalamic-pituitary function in elderly patients with chronic obstructive lung disease.

A case of a 19-year-old with severe chronic obstructive pulmonary disease is presented. This case illustrates genetic (severe alpha-1 antitrypsin deficiency) and host factors (such as developmental diaphragmatic hernia and the innate response to injury), and environmental (high oxidative stress and lung injury) interactions that lead to severe chronic obstructive lung disease. The development of chronic lung disease was caused by lung injury under high oxidative and inflammatory conditions in the setting of a diaphragmatic hernia. In the absence of normal alpha-1 antitrypsin levels, a pro-elastolytic environment in the early period of lung growth enhanced the development of severe hyperinflation and precocious airflow obstruction.

Palliative care services for patients with chronic obstructive pulmonary disease (COPD) have been limited in most health care schemes despite the significant impact its symptoms can have on quality of life (QOL). Palliative care must be integrated to address physical and emotional distress and QOL deterioration more effectively. Multi-factorial barriers in current health care systems impede the provision of palliative care, including the lack of familiarity among health care professionals. There are sparse evidence-based studies and guidelines for clinicians to better recognize the need for palliative care in COPD patients compared to the large experience and resources available to cancer patients and hospice care. The multidisciplinary approach of palliative care should help COPD patients navigate through the continuum of chronic disease management. Highest QOL, not necessarily the highest physiologic goals, with relief of physical and emotional suffering, are most important to patients. Hospice care, the last phase of palliative care, can be offered to COPD patients when their goal of care has changed from life-prolonging therapies to comfort treatment. We suggest a scheme for identifying COPD patients for palliative care and for delivering simultaneous disease-directed care to help patients live life to the fullest. Pulmonary rehabilitation offers the best venue for incorporating palliative care. We review the need for, barriers to, and key activities for integrating palliative care into the current health care management of patients living with COPD.