background Chronic obstructive pulmonary disease (COPD) is characterized by an incompletely reversible limitation in airflow. A physiological variable — the forced expiratory volume in one second (FEV 1 ) — is often used to grade the severity of COPD. However, patients with COPD have systemic manifestations that are not reflected by the FEV 1 . We hypothesized that a multidimensional grading system that assessed the respiratory and systemic expressions of COPD would better categorize and predict outcome in these patients. methods We first evaluated 207 patients and found that four factors predicted the risk of death in this cohort: the body-mass index (B), the degree of airflow obstruction (O) and dyspnea (D), and exercise capacity (E), measured by the six-minute–walk test. We used these variables to construct the BODE index, a multidimensional 10-point scale in which higher scores indicate a higher risk of death. We then prospectively validated the index in a cohort of 625 patients, with death from any cause and from respiratory causes as the outcome variables. results There were 25 deaths among the first 207 patients and 162 deaths (26 percent) in the validation cohort. Sixty-one percent of the deaths in the validation cohort were due to respiratory insufficiency, 14 percent to myocardial infarction, 12 percent to lung cancer, and 13 percent to other causes. Patients with higher BODE scores were at higher risk for death; the hazard ratio for death from any cause per one-point increase in the BODE score was 1.34 (95 percent confidence interval, 1.26 to 1.42; P<0.001), and the hazard ratio for death from respiratory causes was 1.62 (95 percent confidence interval, 1.48 to 1.77; P<0.001). The C statistic for the ability of the BODE index to predict the risk of death was larger than that for the FEV 1 (0.74 vs. 0.65).

https://www.taiss.com/gepoc/gecarp/gepubli/publdoc/026-026-cellibr-body-mass-index-airflow-obstruction-dyspnea.pdf

The Body-Mass Index, Airflow Obstruction, Dyspnea, and Exercise Capacity Index in Chronic Obstructive Pulmonary Disease

"Pulmonary rehabilitation is a process which systematically uses scientifically based diagnostic management and evaluation options to achieve the optimal daily functioning and health-related quality of life of individual patients, suffering from impairment and disability due to chronic respiratory disease as measured by clinically and/or physiologically relevant outcome parameters." This recent definition by the European Respiratory Society (ERS) task force "Rehabilitation and chronic care" [1] stresses the aims of a pulmonary rehabilitation treatment: "optimal daily functioning" and "quality of life". It also indicates that outcome parameters should be measured, and that they should be clinically and physiologically relevant. The ERS-position paper further requires that all existing treatment options available for the widest possible range of patients with chronic lung disease should be applied in rehabilitation. Components of such a programme are: exercise training; gymnastic exercise; respiratory muscle training; chest physiotherapy and breathing retraining; education; psychological counselling; nutritional therapy; ventilatory support, long-term oxygen therapy, and nursing care. Consequently, pulmonary rehabilitation is a very complex and expensive treatment, and should be performed by a team of several professionals working in close co-operation in one institute. The cost is such, that a careful selection of motivated patients, a scientifically based diagnosis and a meticulous quantification of the outcome is mandatory. The place for rehabilitation in asthma, cystic fibrosis, or in the context of lung volume reduction surgery has been outlined by several authors, but remains outside the scope of this editorial. The above suggests that the efficacy of all treatment modalities is unequivocal. This is not always true. Previously, there was an almost universal agreement that the impairment at the level of lung function can hardly be improved by rehabilitation. However, recent findings by C AS A BURI [2] showed that in patients with severe chronic obstructive pulmonary disease (COPD), the forced expiratory volume in one second (FEV1) can also improve by 9%. This seems to be a small change in FEV1, but considering the hyperbolic relationship between airway resistance and FEV1, this modest improvement in the low ranges of FEV1 means a considerable decrease in airway resistance. It is not clear how and why this change in FEV1 was brought about; it must have contributed to the improvement in exercise performance of 36%, probably by a less dynamic hyperinflation during exercise? The latter will contribute to a lower level of exercise dyspnoea [3]. Impairment of peripheral muscle function occurs in patients with COPD, due to a reduced amount of oxidative enzymes [4, 5]. Apart from the ventilatory limitation due to airway obstruction and limited respiratory muscle function, this peripheral muscle weakness substantially contributes to the exercise limitation in patients with COPD. G OS S E LI N K et al. [6] showed that the maximal oxygen consumption (V 'O2,max) and the 6 min walking distance correlated significantly with the maximal force of the quadriceps muscle. Nutritional depletion can be one of the factors in the malfunctioning of peripheral and respiratory muscles: the energy expenditure of patients with COPD often exceeds the caloric intake. Nutritional supplementation, anabolic steroids, and training can improve the function of these muscle groups, and also improve exercise performance [7, 8]. Dysfunction of peripheral muscles can be substantially reversed by training in patients with COPD. An increase in oxidative enzyme content in peripheral muscles was shown to occur after endurance training at 60% of pretreatment work loads, in patients with severe COPD (FEV1 36% pred), thus improving oxidative exercise capacity. The lactate threshold increased, and exercise hyperpnoea decreas

https://erj.ersjournals.com/content/erj/11/3/520.full.pdf

Pulmonary rehabilitation in chronic obstructive pulmonary disease.

A qualitative systematic overview of the measurement properties of functional walk tests used in the cardiorespiratory domain.

The American Thoracic Society/European Respiratory Society jointly created a Task Force on "Outcomes for COPD pharmacological trials: from lung function to biomarkers" to inform the chronic obstructive pulmonary disease research community about the possible use and limitations of current outcomes and markers when evaluating the impact of a pharmacological therapy. Based on their review of the published literature, the following document has been prepared with individual sections that address specific outcomes and markers, and a final section that summarises their recommendations.

/pdf/outcomes-for-copd-pharmacological-trials-from-lung-function-4a4k924y7q.pdf

Outcomes for COPD pharmacological trials: From lung function to biomarkers

Mortality after hospitalization for COPD.

Although patients with advanced pulmonary diseases have significant improvement in exercise ability and functional status following comprehensive out-patient pulmonary rehabilitation (OPR), their long-term prognosis once they have reached this stage of their diseases remains poor. To further evaluate predictors of increased mortality in these patients, we related patient characteristics and short-term outcome obtained during OPR assessment of 158 patients to subsequent survival. The time period from OPR to death or collection of survival data was 40.0 +/- 17.1 months. The following variables were tested individually and in stepwise fashion using a proportional hazards model: 1) age; 2) gender; 3) pulmonary diagnosis; 4) prebronchodilator forced expiratory volume in one second (FEV1); 5) arterial oxygen tension (Pa,O2) and arterial carbon dioxide tension (Pa,CO2); 6) body mass index (BMI); 7) pre- and post-OPR 12 min walking distance (12-MW); 8) pre- and post-OPR quality of life, using the Chronic Respiratory Disease Questionnaire (CRDQ); 9) number and type of nonpulmonary diagnoses; and 10) number of medications. Separate survival analyses were performed for all deaths (the total group), respiratory deaths only (nonrespiratory deaths excluded), and nonrespiratory deaths only (respiratory deaths excluded). Forty three patients (27%) died during the study period; and the 3 year survival was 80%. For all three survival analyses, the post-OPR 12-MW was the most significant variable related to prognosis: patients with low timed walking distance had increased mortality both from respiratory and nonrespiratory causes. Other variables related to increased mortality included: elevated Pa,CO2; low pre-OPR 12-MW; reduced Pa,O2; low FEV1; low BMI, increased number of medications, and increased CRDQ dyspnoea. These results indicate that the timed walking distance following out-patient pulmonary rehabilitation is an important predictor of survival in patients with advanced pulmonary disease.

https://erj.ersjournals.com/content/erj/9/3/431.full.pdf

Variables related to increased mortality following out-patient pulmonary rehabilitation

ABSTRACT Pulmonary alveolar proteinosis (PAP) is a rare lung disease with an incidence of 0.2 cases per million. PAP has multiple causes, including autoimmune, hereditary, congenital, or secondary. The latter includes hematologic conditions and exposure to different kinds of dust. Most patients present fever, dyspnea, and cough. The chest computed tomography (CT) may reveal the crazy-paving polygonal shapes with superimposed ground glass opacities delimited by thickened interlobular septa; however, this finding is more prevalent in patients with autoimmune PAP. Bronchoalveolar lavage (BAL) shows a milky-opaque appearance with PAS-positive debris on cytology. Treatment is focused on the underlying disease; however, some patients may require whole lung lavage for symptomatic management. We report a case of a 30-year-old female with a history of familial myelodysplastic syndrome (MDS) with GATA 2 mutation who presented to the outpatient clinic with several months of progressive dyspnea and nonproductive cough. The chest CT revealed bilateral ground-glass opacities prominently in the upper lobes. She underwent a bronchoscopy with lavage and biopsy, which revealed fragments of lung parenchyma with intra-alveolar coarse granular eosinophilic material strongly positive for PAS and d-PAS. The overall clinical presentation and histologic findings were diagnostic of PAP. Her GM-CSF was negative, and due to her history of MDS, secondary PAP (S-PAP) was strongly suspected. She underwent a successful allogeneic bone marrow pluripotent stem cell transplant to treat the myelodysplastic syndrome, with a follow-up chest CT showing clear lung parenchyma. The patient had resolution of symptoms about four months after the bone marrow transplant, confirming the diagnosis of S-PAP.

DA Gerardi

Papers

Variables related to increased mortality following out-patient pulmonary rehabilitation

Pulmonary Alveolar Proteinosis due to Familial Myelodysplastic Syndrome with resolution after stem cell transplant