Prognostic models are of little clinical value unless they are shown to work in other samples. Douglas Altman and colleagues describe how to validate models and discuss some of the problems

Prognosis and prognostic research: validating a prognostic model

Exacerbations of chronic obstructive pulmonary disease are of major importance in terms of their prolonged detrimental effects on patients, the acceleration in disease progression and high healthcare costs. There is still debate about how exacerbations should be defined and graded, and their mechanisms are poorly understood. The major causal agents are either bacteria or viral infections, or a combination of the two. Noninfective causes include air pollution and pulmonary embolus but, in some patients, no cause is identified. Exacerbations represent an increase in the inflammation that is present in the stable state, with increased numbers of inflammatory cells (particularly neutrophils), cytokines, chemokines and proteases in the airways, and increased concentrations of certain cytokines and C-reactive protein in the blood. There are presently no reliable biomarkers with which to predict exacerbations. Exacerbations have a long-lasting adverse influence on health status. High doses of bronchodilators are the mainstay of treatment and systemic corticosteroids have some benefit. The routine use of antibiotics remains controversial but they are of benefit with exacerbations of a bacterial origin. Noninvasive ventilation is beneficial in preventing the need for intubation and its important complications but it is not certain whether its use in stable patients prevents exacerbations. Although important advances have been made, more effective treatments are needed in the future for prevention and treatment of exacerbations.

https://erj.ersjournals.com/content/erj/29/6/1224.full.pdf

Exacerbations of chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is the fifth cause of morbidity and mortality in the developed world and represents a substantial economic and social burden. Patients experience a progressive deterioration up to end-stage COPD, characterised by very severe airflow limitation, severely limited and declining performance status with chronic respiratory failure, advanced age, multiple comorbidities and severe systemic manifestations/complications. COPD is frequently underdiagnosed and under-treated. Today, COPD develops earlier in life and is less gender specific. Tobacco smoking is the major risk factor for COPD, followed by occupation and air pollution. Severe deficiency for alpha(1)-antitrypsin is rare; several phenotypes are being associated with elevated risk for COPD in the presence of risk factor exposure. Any patient presenting with cough, sputum production or dyspnoea should be assessed by standardised spirometry. Continued exposure to noxious agents promotes a more rapid decline in lung function and increases the risk for repeated exacerbations, eventually leading to end-stage disease. Without major efforts in prevention, there will be an increasing proportion of end-stage patients who can live longer through long-term oxygen therapy and assisted ventilation, but with elevated suffering and huge costs. Smoking prevention and smoking cessation are the most important epidemiological measurements to counteract chronic obstructive pulmonary disease epidemics.

https://erj.ersjournals.com/content/erj/30/5/993.full.pdf

Definition, epidemiology and natural history of COPD

Background Despite exacerbations of chronic obstructive pulmonary disease (COPD) being both common and often fatal, accurate prognostication of patients hospitalised with an exacerbation is difficult. For exacerbations complicated by pneumonia, the CURB-65 prognostic tool is frequently used but its use in this population is suboptimal. Methods Consecutive patients hospitalised with an exacerbation of COPD were recruited. Admission clinical data and inhospital death rates were recorded. Independent predictors of outcome were identified by logistic regression analysis and incorporated into a clinical prediction tool. Results 920 patients were recruited: mean (SD) age was 73.1 (10.0) years; 53.9% were female subjects; mean (SD) forced expiratory volume in one second was 43.6 (17.2) % predicted; and 96 patients (10.4%) died in hospital. The five strongest predictors of mortality (extended MRC Dyspnoea Score, eosinopenia, consolidation, acidaemia, and atrial fibrillation) were combined to form the Dyspnoea, Eosinopenia, Consolidation, Acidaemia and atrial Fibrillation (DECAF) Score. The Score, which underwent internal bootstrap validation, showed excellent discrimination for mortality (area under the receiver operator characteristic curve =0.86, 95% CI 0.82 to 0.89) and performed more strongly than other clinical prediction tools. In the subgroup of patients with coexistent pneumonia (n=299), DECAF was a significantly stronger predictor of mortality than CURB-65. Conclusions The DECAF Score is a simple yet effective predictor of mortality in patients hospitalised with an exacerbation of COPD and has the potential to help clinicians more accurately predict prognosis, and triage place and level of care to improve outcome in this common condition.

https://thorax.bmj.com/content/thoraxjnl/67/11/970.full.pdf

The DECAF Score: predicting hospital mortality in exacerbations of chronic obstructive pulmonary disease

Physicochemical properties of mucus and their impact on transmucosal drug delivery

Knowing the likelihood of failure of noninvasive positive pressure ventilation (NPPV) in patients with exacerbation of chronic obstructive pulmonary disease (COPD) could indicate the best choice between NPPV and endotracheal intubation instituted earlier. For this purpose, two risk charts were designed (at admission and after 2 h of NPPV) that included all relevant measurable clinical prognostic indicators derived from a population representing the patients seen routinely in clinical practice. Risk stratification of NPPV failure was assessed in 1,033 consecutive patients admitted to experienced hospital units, including two intensive care units, six respiratory intermediate care units, and five general wards. NPPV was successful in 797 patients. Patients with a Glasgow Coma Score or =29, respiratory rate > or =30 breaths x min(-1) and pH at admission 70%. A pH 90%). The risk charts were validated on an independent group of 145 consecutive COPD patients treated with NPPV due to an acute ventilatory failure episode. To identify patients with a probability of failure >50%, the sensitivity and specificity were 33% and 96.7% on admission and 52.9% and 94.1% after 2 h of NPPV, respectively. The prediction chart, based on data from the current study, can function as a simple tool to predict the risk of failure of noninvasive positive pressure ventilation and thus improve clinical management of patients tailoring medical intervention.

https://erj.ersjournals.com/content/erj/25/2/348.full.pdf

A chart of failure risk for noninvasive ventilation in patients with COPD exacerbation

Inspiratory muscle training for diaphragm dysfunction after cardiac surgery

Rationale: Acidification of the airways seems to be involved in asthma pathophysiology, but its assessment might be difficult.Objectives: The aim of our study is to assess the feasibility and validity of airway acidification measurement by induced sputum and its clinical significance in asthma.Methods: Induced-sputum samples were obtained in 57 outpatients with asthma. The between-sample repeatability after 48 hours was measured in an independent population of 14 patients with asthma. pH was measured using a pH meter. The control of asthma was established by the Asthma Control Questionnaire.Measurements and Main Results: The pH measurement was feasible in all samples and repeatable both within (intraclass correlation coefficient [ICC], 0.96) and between samples (ICC, 0.621). The mean pH was significantly different between healthy subjects and patients with asthma, including in those with controlled (mean pH: 7.54 in healthy subjects vs. 7.28 in subjects with controlled asthma; p = 0.0105) and uncontrolled...

An investigation of airway acidification in asthma using induced sputum: a study of feasibility and correlation.

Background and objective: Exacerbations of COPD areoftencharacterizedbyincreasedmucusproduction that is difficult to treat and worsens patients’ outcome. This study evaluated the efficacy of a chest physiotherapy technique (expiration with the glottis open in the lateral posture, ELTGOL) during acute exacerbations of COPD using as outcome measures sputum volume, length of hospitalization, reduction in dyspnoea (Borg score), improvement in quality of life (assessed by the St George Respiratory Questionnaire) andincidenceofCOPDexacerbationsduringfollowup. Methods: The study recruited 59 patients hospitalized for the treatment of acute exacerbation of COPD, who were randomly assigned to a control group and an intervention group.The control group was treated with standardmedicaltherapywhiletheinterventiongroup was treated with ELTGOL plus medical therapy. A subgroup of patients was followed for 6 months to verify the effects on COPD exacerbations and need for hospitalizations. Results: At the time of hospital discharge there was no significant difference between the two groups in the outcome measures, with the exception of the Borg score,which was significantly improved in the ELTGOL group (4.3 1.5 in the control group vs 3.0 1.8 in the ELTGOL group,P = 0.004).After 6 months there was no significant difference in the other measured parameters between a subset of the groups available for follow up. During follow up, the ELTGOL group had numerically fewer exacerbations and less need for hospitalization though differences were not statistically significant. Conclusions: Chest physiotherapy using the ELTGOL technique has a limited role in patients with mild exacerbation of moderate to severe COPD with a tendency towards fewer exacerbations and hospitalizations.

Metka Kodric

Papers

A chart of failure risk for noninvasive ventilation in patients with COPD exacerbation

Inspiratory muscle training for diaphragm dysfunction after cardiac surgery

An investigation of airway acidification in asthma using induced sputum: a study of feasibility and correlation.

The effectiveness of a bronchial drainage technique (ELTGOL) in COPD exacerbations

Bosentan for patients with chronic thromboembolic pulmonary hypertension.