Roberto Rodriguez-Roisin

Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary.

Chronic obstructive pulmonary disease (COPD) is a global health problem, and since 2001, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) has published its strategy document for the diagnosis and management of COPD. This executive summary presents the main contents of the second 5-year revision of the GOLD document that has implemented some of the vast knowledge about COPD accumulated over the last years. Today, GOLD recommends that spirometry is required for the clinical diagnosis of COPD to avoid misdiagnosis and to ensure proper evaluation of severity of airflow limitation. The document highlights that the assessment of the patient with COPD should always include assessment of (1) symptoms, (2) severity of airflow limitation, (3) history of exacerbations, and (4) comorbidities. The first three points can be used to evaluate level of symptoms and risk of future exacerbations, and this is done in a way that splits patients with COPD into four categories-A, B, C, and D. Nonpharmacologic and pharmacologic management of COPD match this assessment in an evidence-based attempt to relieve symptoms and reduce risk of exacerbations. Identification and treatment of comorbidities must have high priority, and a separate section in the document addresses management of comorbidities as well as COPD in the presence of comorbidities. The revised document also contains a new section on exacerbations of COPD. The GOLD initiative will continue to bring COPD to the attention of all relevant shareholders and will hopefully inspire future national and local guidelines on the management of COPD.

Hepatopulmonary Syndrome — A Liver-Induced Lung Vascular Disorder

The hepatopulmonary syndrome is characterized by defects in oxygenation due to pulmonary abnormalities associated with chronic liver disease. Dyspnea and hypoxemia can be severe and often worsen in the upright position. Gross dilatation of the precapillary and capillary vessels occurs with ventilation–perfusion mismatch. The syndrome usually improves after liver transplantation.

Integrated care prevents hospitalisations for exacerbations in COPD patients

Hospital admissions due to chronic obstructive pulmonary disease (COPD) exacerbations have a major impact on the disease evolution and costs. The current authors postulated that a simple and well-standardised, low-intensity integrated care intervention can be effective to prevent such hospitalisations. Therefore, 155 exacerbated COPD patients (17% females) were recruited after hospital discharge from centres in Barcelona (Spain) and Leuven (Belgium). They were randomly assigned to either integrated care (IC; n = 65; age mean±sd 70±9 yrs; forced expiratory volume in one second (FEV1) 1.1±0.5 L, 43% predicted) or usual care (UC; n = 90; age 72±9 yrs; FEV1 1.1±0.05 L, 41% pred). The IC intervention consisted of an individually tailored care plan upon discharge shared with the primary care team, as well as accessibility to a specialised nurse case manager through a web-based call centre. After 12 months’ follow-up, IC showed a lower hospitalisation rate (1.5±2.6 versus 2.1±3.1) and a higher percentage of patients without re-admissions (49 versus 31%) than UC without differences in mortality (19 versus 16%, respectively). In conclusion, this trial demonstrates that a standardised integrated care intervention, based on shared care arrangements among different levels of the system with support of information technologies, effectively prevents hospitalisations for exacerbations in chronic obstructive pulmonary disease patients.

Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease 2017 Report. GOLD Executive Summary

This Executive Summary of the Global Strategy for the Diagnosis, Management, and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 report focuses primarily on the revised and novel parts of the document. The most significant changes include: (1) the assessment of chronic obstructive pulmonary disease has been refined to separate the spirometric assessment from symptom evaluation. ABCD groups are now proposed to be derived exclusively from patient symptoms and their history of exacerbations; (2) for each of the groups A to D, escalation strategies for pharmacologic treatments are proposed; (3) the concept of deescalation of therapy is introduced in the treatment assessment scheme; (4) nonpharmacologic therapies are comprehensively presented; and (5) the importance of comorbid conditions in managing chronic obstructive pulmonary disease is reviewed.

Characterization of pulmonary vascular remodelling in smokers and patients with mild COPD

Intimal enlargement of pulmonary arteries is an early change in chronic obstructive pulmonary disease (COPD). The cellular and extracellular components that are involved in this enlargement are unknown. The present study was designed to characterize the structural changes occurring in pulmonary muscular arteries in the initial disease stages. Lung specimens from patients with moderate COPD (n=8; forced expiratory volume in one second (FEV1), 66±10% predicted) and smokers without airflow obstruction (n=7; FEV1, 86±6% pred), were investigated by histochemistry to characterize extracellular matrix proteins and by immunohistochemistry to identify intrinsic cells of the vascular wall. In both COPD patients and smokers, the majority of cells present in the enlarged intimas were stained by specific smooth muscle cell (SMC) markers. No staining with endothelial or fibroblast markers was shown. A proportion of SMCs did not stain with desmin, suggesting cellular heterogeneity in this population. Elastin was the most abundant extracellular matrix protein and collagen was seen in a lower proportion. The amount of collagen was related to the intimal thickness (p<0.001). The findings demonstrated smooth muscle cell proliferation, as well as elastin and collagen deposition, in the thickened intimas of pulmonary arteries in moderate chronic obstructive pulmonary disease patients and smokers, suggesting that these abnormalities may originate at an early stage in cigarette smoke-induced respiratory disease.

Withdrawal of inhaled glucocorticoids and exacerbations of COPD.

BACKGROUND Treatment with inhaled glucocorticoids in combination with long-acting bronchodilators is recommended in patients with frequent exacerbations of severe chronic obstructive pulmonary disease (COPD). However, the benefit of inhaled glucocorticoids in addition to two long-acting bronchodilators has not been fully explored. METHODS In this 12-month, double-blind, parallel-group study, 2485 patients with a history of exacerbation of COPD received triple therapy consisting of tiotropium (at a dose of 18 μg once daily), salmeterol (50 μg twice daily), and the inhaled glucocorticoid fluticasone propionate (500 μg twice daily) during a 6-week run-in period. Patients were then randomly assigned to continued triple therapy or withdrawal of fluticasone in three steps over a 12-week period. The primary end point was the time to the first moderate or severe COPD exacerbation. Spirometric findings, health status, and dyspnea were also monitored. RESULTS As compared with continued glucocorticoid use, glucocorticoid withdrawal met the prespecified noninferiority criterion of 1.20 for the upper limit of the 95% confidence interval (CI) with respect to the first moderate or severe COPD exacerbation (hazard ratio, 1.06; 95% CI, 0.94 to 1.19). At week 18, when glucocorticoid withdrawal was complete, the adjusted mean reduction from baseline in the trough forced expiratory volume in 1 second was 38 ml greater in the glucocorticoid-withdrawal group than in the glucocorticoid-continuation group (P<0.001); a similar between-group difference (43 ml) was seen at week 52 (P=0.001). No change in dyspnea and minor changes in health status occurred in the glucocorticoid-withdrawal group. CONCLUSIONS In patients with severe COPD receiving tiotropium plus salmeterol, the risk of moderate or severe exacerbations was similar among those who discontinued inhaled glucocorticoids and those who continued glucocorticoid therapy. However, there was a greater decrease in lung function during the final step of glucocorticoid withdrawal. (Funded by Boehringer Ingelheim Pharma; WISDOM ClinicalTrials.gov number, NCT00975195.).

Worsening of pulmonary gas exchange with nitric oxide inhalation in chronic obstructive pulmonary disease

BACKGROUND Inhalation of nitric oxide (NO) causes selective pulmonary vasodilation and improves arterial oxygenation in acute respiratory distress syndrome. But some patients do not respond or gas exchange worsens when inhaling NO. We hypothesised that this detrimental effect might be related to the reversion of hypoxic vasoconstriction in those patients where this mechanism contributes to ventilation-perfusion (V(A)/Q) matching. METHODS We studied 13 patients with advanced chronic obstructive pulmonary disease (COPD). We compared their responses to breathing room air, NO at 40 parts per million in air, and 100% O2. Changes in pulmonary haemodynamics, blood gases, and V(A)/Q distributions were assessed. FINDINGS NO inhalation decreased the mean (SE) pulmonary artery pressure from 25.9 (2.0) to 21.5 (1.7) mm Hg (p = 0.001) and PaO2 from 56 (2) 53 (2) mm Hg (p = 0.014). The decrease in PaO2 resulted from worsening of V(A)/Q distributions, as shown by a greater dispersion of the blood-flow distribution (logSD Q) from 1.11 (0.1) to 1.22 (0.1) (p = 0.018). O2 breathing reduced the mean pulmonary arterial pressure to 23.4 (2.1) mm Hg and caused greater V(A)/Q mismatch (logSD Q, 1.49 [0.1]). The intrapulmonary shunt on room air was small (2.7 [0.9]%) and did not change when breathing NO or O2. INTERPRETATION We conclude that in patients with COPD, in whom hypoxaemia is caused essentially by V(A)/Q imbalance rather than by shunt, inhaled NO can worsen gas exchange because of impaired hypoxic regulation of the matching between ventilation and perfusion.

Physiological responses to the 6-min walk test in patients with chronic obstructive pulmonary disease

The 6-min walking test (6MWT) is frequently used to assess functional capacity in chronic cardiopulmonary disorders because of its simplicity. The study examines the physiological responses during encouraged 6MWT in patients with chronic obstructive pulmonary disease. Pulmonary oxygen (O2) uptake (V′O2) was measured in 20 male patients (age 66±6 yrs, forced expiratory volume in one second 45±14% predicted) during 6MWT and incremental cycling, in random order. O2 tension in arterial blood, carbon dioxide tension in arterial blood and arterial lactate concentration ([La]art) were obtained in the last 10 patients. During the 6MWT, V′O2 showed a plateau after the 3rd min (1.39±0.28, 1.42±0.31, and 1.40±0.30 L·min−1, 4th, 5th and 6th min, respectively), and minute ventilation (V′E) (42±8 L·min−1) was 91% maximal voluntary ventilation. No differences were shown between 6MWT (6th min) and peak cycling exercise in V′O2 (1.40±0.30 versus 1.41±0.28 L·min−1, respectively), cardiac frequency (126±13 versus 130±12 beats·min−1), or arterial respiratory blood gases. The two tests were significantly different in V′E (42±8 versus 47±8 L·min−1, 6MWT versus cycling, respectively), carbon dioxide production (1.30±0.31 versus 1.45±0.18 L·min−1) and [La]art (2.9±1.99 versus 5.9±1.51 M). The study demonstrates that an encouraged 6-min walking test generates a high but sustainable oxygen uptake. Since the oxygen uptake plateau reflects the integrated response of the system, it may explain the high prognostic value of the 6-min walking test.

Bacterial colonisation in patients with bronchiectasis: microbiological pattern and risk factors

Background: A study was undertaken to investigate the incidence, diagnostic yield of non-invasive and bronchoscopic techniques, and risk factors of airway colonisation in patients with bronchiectasis in a stable clinical situation. Methods: A 2 year prospective study of 77 patients with bronchiectasis in a stable clinical condition was performed in an 800 bed tertiary university hospital. The interventions used were pharyngeal swabs, sputum cultures and quantitative protected specimen brush (PSB) bacterial cultures (cut off point ≥102 cfu/ml) and bronchoalveolar lavage (BAL) (cut off point ≥103 cfu/ml). Results: The incidence of bronchial colonisation with potential pathogenic microorganisms (PPMs) was 64%. The most frequent PPMs isolated were Haemophilus influenzae (55%) and Pseudomonas spp (26%). Resistance to antibiotics was found in 30% of the isolated pathogens. When the sample was appropriate, the operative characteristics of the sputum cultures were similar to those obtained with the PSB taken as a gold standard. Risk factors associated with bronchial colonisation by PPMs in the multivariate analysis were: (1) diagnosis of bronchiectasis before the age of 14 years (odds ratio (OR)=3.92, 95% CI 1.29 to 11.95), (2) forced expiratory volume in 1 second (FEV1) <80% predicted (OR=3.91, 95% CI 1.30 to 11.78), and (3) presence of varicose or cystic bronchiectasis (OR=4.80, 95% CI 1.11 to 21.46). Conclusions: Clinically stable patients with bronchiectasis have a high prevalence of bronchial colonisation by PPMs. Sputum culture is a good alternative to bronchoscopic procedures for evaluation of this colonisation. Early diagnosis of bronchiectasis, presence of varicose-cystic bronchiectasis, and FEV1 <80% predicted appear to be risk factors for bronchial colonisation with PPMs.

The hepatopulmonary syndrome: new name, old complexities.

On the basis of previous work, our own experience and findings, and the considerations discussed above, we propose a set of four diagnostic criteria for the hepatopulmonary syndrome: 1. presence of chronic hepatic disease (alcoholic, postnecrotic, or primary biliary cirrhosis or active chronic hepatitis)--severe liver dysfunction may not be mandatory; 2. absence of intrinsic cardiopulmonary disease, with normal chest radiograph or with nodular basal shadowing; 3. pulmonary gas exchange abnormalities--an increased alveolar-arterial oxygen gradient (> or = 2.0 kPa) with or without hypoxaemia; 4. the extrapulmonary appearance of intravenous radiolabelled microspheres or a positive contrast enhanced echocardiogram, suggesting intrapulmonary vascular abnormalities. Although these four criteria appear straightforward, there may be other features that are not always present--namely: 1. low transfer factor (diffusing capacity); 2. shortness of breath, with or without platypnoea and orthodeoxia; 3. increased cardiac output and reduced pulmonary vascular pressures; 4. small (or no) increase in pulmonary vascular resistance when the patient is breathing low oxygen mixtures. From the physiological viewpoint, the hepatopulmonary syndrome provides an excellent model for clinical research in the pathophysiology of pulmonary gas exchange. So far it has been possible to show that arterial hypoxaemia in this condition is (1) partitioned into components resulting from VA/Q mismatching, intrapulmonary shunt, and limitations of oxygen diffusion; (2) modulated by the interplay between the intrapulmonary and the extrapulmonary determinants of PaO2, such as cardiac output and minute ventilation; (3) vulnerable to the influence of inadequate pulmonary vascular tone; and (4) resolved when the injured liver is replaced and hepatic function is restored to within normal limits.