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Since publication of the first edition of this book in 2005, there has been growing interest in the role of pulmonary rehabilitation (PR) for the management of chronic respiratory disease, which continues to increase as a major cause of global mortality and morbidity. Health providers and healthcare professionals, having become more aware of the improvements in function and quality of life associated with PR, are increasingly including it as an integral part of their approach to disease management. Since the joint European Respiratory Society and American Thoracic Society's 2013 major statements on PR, published guidelines from professional associations around the world have endorsed PR as the prevailing standard of care for those with chronic respiratory conditions.

To investigate possible changes in cells and molecular mediators of airway inflammation following inhaled steroid treatment of stable COPD patients. Six-week open preliminary prospective study. A university respiratory disease clinic. : Stable COPD patients with mild disease. Six-week treatment with inhaled beclomethasone (1.5 mg die). The levels of interleukin (IL)-8, myeloperoxidase, eosinophilic cationic protein and tryptase, and cell numbers in bronchial lavage specimens were determined, and the symptom score, the endoscopic bronchitis index, and functional parameters were recorded. After treatment there were significant reductions in the lavage levels of IL-8 ([mean +/- SEM] 1,603.4 +/- 331.2 vs 1,119.2 +/- 265.3 pg/mL, respectively; p = 0. 01) and myeloperoxidase (1,614.5 +/- 682.3 vs 511.2 +/- 144.2 microg/L, respectively; p = 0.05), in cell numbers (250.6 +/- 27.7 vs 186.3 +/- 11.5 cells x 10(3)/mL, respectively; p = 0.04), neutrophil proportion (59.7 +/- 14.3% vs 31.5 +/- 10.1%; p = 0.01), symptom score (4.5 +/- 0.6 vs 1.4 +/- 0.5; p = 0.01), and bronchitis index (8.5 +/- 0.8 vs 5.5 +/- 0.7; p = 0.007). In stable patients with COPD, inhaled steroid treatment may induce changes on some cellular and molecular parameters of airway inflammation.

BACKGROUND An earlier study documented that, in patients with chronic obstructive pulmonary disease (COPD), addition of ipratropium bromide at the clinically recommended dose (40 μg) does not produce any further bronchodilation than that achieved with salmeterol 50 μg alone. However, the dose of ipratropium bromide needed to produce near maximal bronchodilation is several times higher than the customary dosage. The full therapeutic potential of combined salmeterol plus an anticholinergic drug can therefore only be established using doses higher than those currently recommended in the marketing of these agents. A study was undertaken to examine the possible acute effects of higher than conventional doses of an anticholinergic agent on the single dose salmeterol induced bronchodilation in patients with stable and partially reversible COPD. METHODS Thirty two outpatients received 50 μg salmeterol or placebo. Two hours after inhalation a dose-response curve to inhaled oxitropium bromide (100 μg/puff) or placebo was constructed using one puff, one puff, two puffs, and two puffs—that is, a total cumulative dose of 600 μg oxitropium bromide. Dose increments were given at 20 minute intervals with measurements being made 15 minutes after each dose. On four separate days all patients received one of the following: (1) 50 μg salmeterol + 600 μg oxitropium bromide; (2) 50 μg salmeterol + placebo; (3) placebo + 600 μg oxitropium bromide; (4) placebo + placebo. RESULTS Salmeterol induced a good bronchodilation (mean increase 0.272 l; 95% CI 0.207 to 0.337) two hours after its inhalation. Oxitropium bromide elicited an evident dose-dependent increase in forced expiratory volume in one second (FEV1) and this occurred also after pretreatment with salmeterol with a further mean maximum increase of 0.152 l (95% CI of differences 0.124 to 0.180). CONCLUSIONS This study shows that acute pretreatment with 50 μg salmeterol does not block the possibility of inducing more bronchodilation with an anticholinergic agent when a higher than normal dosage of the muscarinic antagonist is used.

To evaluate whether office spirometry by general practitioners (GPs) is feasible and may improve the diagnosis of asthma and COPD. A prospective, randomized, comparative trial was planned involving 57 Italian pulmonology centers and 570 GPs who had to enroll consecutive subjects aged 18 to 65 years with symptoms of asthma or COPD without a previous diagnosis. Patients were randomized 1:1 into two groups with an interactive voice responding system: conventional evaluation alone vs conventional evaluation and spirometry. Office spirometry was performed by GPs who were trained by reference specialists using a portable electronic spirometer (Spirobank Office; MIR; Rome, Italy). Diagnosis was confirmed by the reference specialist center in blind fashion. Seventy-four GPs complied to the trial. Of 333 patients enrolled, 136 nonrandom violators completed the protocol. Per-protocol analysis showed a concordant diagnosis between GPs and specialists in 78.6% of cases in the conventional evaluation-plus-spirometry group vs 69.2% in the conventional evaluation group (p = 0.35). In the intention-to-treat analysis, the respective percentages of concordant diagnosis were 57.9 and 56.7 (p = 0.87). Office spirometry by GPs is feasible, but frequent protocol violation and inadequate sample size did not allow us to prove a significant advantage of office spirometry in improving the diagnosis of asthma and COPD in standard general practice as organized at present in Italy, thus reinforcing the need for close cooperation between GPs and specialists in respiratory medicine.

Background Involvement of the small airways may be related to increased severity and increased demand for health care services and incurring in high costs, private or for the healthcare system. The hyperinflation consequent to this involvement reduces lung volumes, such as FVC, FEV 1 and SVC. The aim of this study was to evaluate the correlation between the predicted values of FVC, FEV 1 and SVC with the demand for healthcare services by severe asthmatics. Methods We retrospectively evaluated in order of arrival, the medical records of 98 patients with severe asthma, in step 4 treatment in the intercritical period of the disease, correlating the number of times each patient sought health care services represented by admissions to the ER, ICU and hospital wards due to asthma, in the year before the last spirometry and the predicted values of FVC, FEV 1 and SVC. Results Our sample showed a clear and significant negative correlation between the predicted values of FVC, FEV 1 and SVC and demand for healthcare services. Conclusion For this sample we conclude, that reduced forced vital capacity correlated with asthma severity, defined by greater demand for care in the ER, ICU and hospital ward and was more evident in women.

There is now good evidence that inhaled salmeterol is an effective agent in chronic obstructive pulmonary disease (COPD),but, at the present time, data on the effects of bambuterol, which is an oral tarbutaline pro-drug, in patients with COPD are scarce. Moreover, no comparative study between bambuterol and salmeterol in patients with chronic obstructive airway disorders has been published. The objective of this research was, consequently, to compare the efficacy and safety of 20 mg oral bambuterol and 50 microg inhaled salmeterol in patients with partially reversible COPD. The speed and length of bronchodilation with 20 mg bambuterol and 50 microg inhaled salmeterol were compared in 16 patients with partially reversible COPD. The investigation and designed as a double-blind, double-dummy, cross-over, placebo controlled and randomised study. Lung function (FEV1, FVC) and systemic variables (subjective tremor, heart rate, blood pressure) were monitored prior to the administration of the drug and for 12 h after each agent on 3 non-consecutive days. Inhalation of salmeterol induced a significant (P < 0.05) increase of lung function when compared with placebo. In addition, oral bambuterol elicited good bronchodilation, with its maximum slightly later than for salmeterol. The mean (+/- SE) AUC(0-12h)S for all patients were 3.134 1 +/- 0.553 for salmeterol and 1963 1 +/- 0.573 for bambuterol. Both AUC(0-12h)S were significantly greater than for placebo (P < 0.05), but there was no significant difference (P = 0.077) between the salmeterol and bambuterol AUC(0-12h)S. Bambuterol, but not salmeterol, caused tremor in four patients. Moreover, it induced a higher heart rate when compared with salmeterol at each considered time after the administration of the drug; differences after 9 and 12 h were statistically significant (P < 0.05). Both oral bambuterol and inhaled salmeterol resulted in good bronchodilation in patients with stable COPD. However, bambuterol, but not salmeterol, caused tremor in several subjects and elicited a more pronounced tachycardia.

Background and aims. Hospitalisations for chronic obstructive pulmory disease (COPD) exacerbations are major events in the tural history of the disease in terms of survival, quality of life and risk of further episodes of exacerbation. The aims of study were to evaluate: 1. adherence to recommended standards of care; and 2. clinical factors influencing major outcomes during hospitalisation for an episode of COPD exacerbation and within a 6-month follow-up. Methods. An observatiol, prospective study was conducted in 68 centres. Assessment of standards of care included diagnostic procedures (such as pulmory function tests and microbiology) and magement options (such as drug therapies, vaccitions and rehabilitation). Outcome measures relevant to the hospitalisation were: survival, need for mechanical ventilation, and length of stay (LOS). Outcomes at 6-months were: survival, exacerbations and hospitalisations for an exacerbation. Multivariate logistic regression was applied to evaluate the relation between clinical factors and outcomes. Results. 931 patients were enrolled. Only 556 patients (59.7%) were diagnosed COPD and stratified for severity with the support of spirometry (FEV1/VC ‰¤0.7) and were considered for outcome alysis. Among treatments, pulmory rehabilitation and anti-smoking counselling were applied infrequently (14.5 and 8.1% of patients, respectively). Within six months 63 COPD patients (17.7%) had at least one episode of exacerbation prompting a further hospitalisation and 19 died (5.3%). Predictor of mortality was the co-morbidity Charlson index (odds ratio, OR 10.3, p=0.03 CI:1.25-84.96). A further hospitalisation was predicted by hospitalisation for an exacerbation in the previous 12 months (OR 3.59, p=0.003 CI:1.54-8.39). Conclusions. Standards of care were far lower than recommended, in particular 40% of patients were labelled as COPD without spirometry. COPD patients with a second hospitalisation in 12 months for an exacerbation had about 3 times the risk of suffering a new episode and hospitalisation in the following six months.

Introduction and objectivesThe airflow limitation of COPD results from small airway disease and emphysema. These phenotypes are likely to have independent genetic risk factors. It is not known if the heterogeneity of COPD accounts for the relatively weak association between pack-years smoked and forced expiratory volume in 1 s (FEV1) seen within smoking populations, or bronchodilator response (BDR). This study aimed to assess the effect of these phenotypes on the association between smoking and FEV1 and on BDR.MethodThe international COPD genetics network is a multi-centre study aimed at identifying genes that predispose to COPD, in which high resolution computed tomography (HRCT) was used to quantify components of the COPD phenotype: (i) emphysema detected by radiologists (RE), (ii) emphysema assessed as per cent low-attenuation area (%LAA) and (iii) airway wall thickness (AWT) for airways with an internal perimeter of 10 mm (Pi10), 20 mm (Pi20), and average per cent wall area (WA%). They were then assessed for their effect on the association between smoking and lung function (FEV1% predicted (FEV1%)), and on BDR.ResultsRE data were available for 1159 individuals, 745 had complete data for Pi10, Pi20, AWT% and %LAA. The association between pack-years smoked and FEV1% was greater in those without (r=−0.41), compared to those with, RE (r=−0.12, p<0.001 for difference in effect). AWT and RE correlated with FEV1% but had different relationships with smoking; AWT was positively associated with pack-years but there was no relationship between RE severity and pack-years smoked. RE, %LAA and AWT made independent contributions to FEV1%. Post-bronchodilator increase in FEV1 was inversely associated with severity of RE (Abstract S113 Table 1), even after adjustment for pre-bronchodilator FEV1 (p<0.01). BDR was also inversely associated with %LAA (p=0.02, and p≤0.05 adjusted for baseline FEV1).Abstract S113 Table 1Severity of REMild (5–25%)Moderate (25–50%)Severe (>50%)p (trend)Number228185266–BDR, FEV1 (mls)171.3±188.2134.4±174.7100.2±129.6≤0.0001ConclusionThe AWT component of COPD, but not the severity of RE, increases with pack-years smoked, and the association between pack-years and FEV1% is greatest in those with an airway predominant phenotype. This suggests different gene-smoking interactions between phenotypes. RE and %LAA independently contribute to FEV1% and therefore measure different components of emphysema, however both were inversely associated with BDR.

Background and Aim. The Italian Costs for Exacerbations in COPD (€œICE€) study, following a pharmacoeconomic assessment of costs due to COPD exacerbations (primary endpoint), aimed also at evaluating (secondary endpoint) which clinical factors, among those considered for cost-alysis, may, at follow up, present a risk of new exacerbations and re-admission to hospital. Materials and methods. A prospective, multicentre study was carried out on COPD patients admitted to 25 Hospital Centres as a result of an exacerbation from October- December 2002. Following discharge, a 6-month follow- up was performed in each patient via three bi-monthly telephone interviews with a questionire administered by an investigator clinician. Results. 570 patients were eligible for data processing, mean age 70.6 years (± 9.5 standard deviation, SD), males 69.2%. According to GOLD, severity stratification was as follows: moderate 36.4%; severe 31.3%; very severe 32.3%. 282 patients experienced at least one exacerbation at follow up, 42% of exacerbations requiring hospitalisation. No significant association was seen between exacerbations and GOLD stage or co-morbidities or treatments except LTOT. Conversely, COPD functiol severity influenced hospitalisations very significantly, with relative risks 2.6 (95% Confidence Interval, CI 1.8-3.8) and 2.0 (CI 1.3-2.8) (GOLD very severe versus moderate and severe, respectively), and 1.3 (CI 0.85-2.1) (GOLD severe versus moderate). Hospitalisations were also significantly associated with treatments denoting more severe conditions (oral corticosteroids, oral theophylline, and LTOT). Conclusions. Severity stratification of COPD patients according to respiratory function classes as outlined in GOLD guidelines and need for LTOT are confirmed as important predictors of hospitalisation for an exacerbation.