Chronic obstructive pulmonary disease: definition and classification of severity

Chronic obstructive pulmonary disease is characterized by airflow limitation that is not fully reversible and is usually both progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases, particularly tobacco smoke. Diagnosis of chronic obstructive pulmonary disease is primarily based on a reduction of forced expiratory volume in one second/forced vital capacity ratio < 70% post-bronchodilators. The characteristic symptoms of chronic obstructive pulmonary disease are cough, sputum, and dyspnea upon exertion. Based on airflow limitation as measured by spirometry, chronic obstructive pulmonary disease can be classified as mild, moderate, severe and very severe. Chronic obstructive pulmonary disease can coexist with asthma, although the inflammation characteristic of chronic obstructive pulmonary disease is distinct from that of asthma

Beclomethasone/formoterol fixed combination for the management of asthma: patient considerations

Drugs for asthma and other chronic obstructive diseases of the lungs should be preferably delivered by the inhalation route to match therapeutic effects with low systemic exposure. Inhaled drugs are delivered to the lungs via different devices, mainly metered dose inhalers and dry powder inhalers, each characterized by specific inhaler technique and instructions for use. The patient–device interaction is part of the prescribed therapy and can have a relevant impact on adherence and clinical outcomes. The most suitable device should be considered for each patient to assure the correct drug intake and adherence to the prescribed therapy. The development of new drugs/devices in the past decades improved the compliance with inhaler and possibly drug delivery to the bronchi. The present review focuses on the recently developed beclomethasone/formoterol extrafine fixed combination and technical aspects of drug delivery to the lungs in patient’s perspective

Does roflumilast decrease exacerbations in severe COPD patients not controlled by inhaled combination therapy? the REACT study protocol.

Many patients with chronic obstructive pulmonary disease (COPD) continue to suffer exacerbations, even when treated with maximum recommended therapy (eg, inhaled combinations of long-acting β(2)-agonist and high dose inhaled corticosteroids, with or without a long-acting anticholinergic [long-acting muscarinic antagonist]). Roflumilast is approved to treat severe COPD in patients with chronic bronchitis - and a history of frequent exacerbations - as an add-on to bronchodilators.PURPOSE:The REACT (Roflumilast in the Prevention of COPD Exacerbations While Taking Appropriate Combination Treatment) study (identification number RO-2455-404-RD, clinicaltrials. gov identifier NCT01329029) will investigate whether roflumilast further reduces exacerbations when added to inhaled combination therapy in patients still suffering from frequent exacerbations.PATIENTS AND METHODS:REACT is a 1-year randomized, double-blind, multicenter, phase III/IV study of roflumilast 500 μg once daily or placebo on top of a fixed long-acting β(2)-agonist/inhaled corticosteroid combination. A concomitant long-acting muscarinic antagonist will be allowed at stable doses. The primary outcome is the rate of moderate or severe COPD exacerbations. Using a Poisson regression model with a two-sided significance level of 5%, a sample size of 967 patients per treatment group is needed for 90% power. COPD patients with severe to very severe airflow limitation, symptoms of chronic bronchitis, and at least two exacerbations in the previous year will be recruited.CONCLUSION:It is hypothesized that because roflumilast (a phosphodiesterase-4 inhibitor) has a different mode of action to bronchodilators and inhaled corticosteroids, it may provide additional benefits when added to these treatments in frequent exacerbators. REACT will be important to determine the role of roflumilast in COPD management. Here, the design and rationale for this important study is described

Inhaled long-acting muscarinic antagonists in asthma - A narrative review

Long-acting muscarinic antagonists (LAMAs) have a recognised role in the management of chronic obstructive pulmonary disease. In asthma, muscarinic antagonists (both short- and long-acting) were historically considered less effective than β2-agonists; only relatively recently have studies been conducted to evaluate the efficacy of LAMAs, as add-on to either inhaled corticosteroid (ICS) monotherapy or ICS/long-acting β2-agonist (LABA) combinations. These studies led to the approval of the first LAMA, tiotropium, as an add-on therapy in patients with poorly controlled asthma. Subsequently, a number of single-inhaler ICS/LABA/LAMA triple therapies have been approved or are in clinical development for the management of asthma. There is now substantial evidence of the efficacy and safety of LAMAs in asthma that is uncontrolled despite treatment with an ICS/LABA combination. This regimen is recommended by GINA as an optimisation step for patients with severe asthma before any biologic or systemic corticosteroid treatment is initiated. This narrative review summarises the potential mechanisms of action of LAMAs in asthma, together with the initial clinical evidence supporting this use. We also discuss the studies that led to the approval of tiotropium for asthma and the data evaluating the efficacy and safety of the various triple therapies, before considering other potential uses for triple therapy

Energy Expenditure at Rest and during Walking in Patients with Chronic Respiratory Failure: A Prospective Two-Phase Case-Control Study

Measurement of Energy Expenditure (EE) at rest (REE) and during physical activities are increasing in interest in chronic patients. In this study we aimed at evaluating the validity/reliability of the SenseWear\uaeArmband (SWA) device in terms of REE and EE during assisted walking in Chronic Respiratory Failure (CRF) patients receiving long-term oxygen therapy (LTOT).In a two-phase prospective protocol we studied 40 severe patients and 35 age-matched healthy controls. In phase-1 we determined the validity and repeatability of REE measured by SWA (REEa) in comparison with standard calorimetry (REEc). In phase-2 we then assessed EE and Metabolic Equivalents-METs by SWA during the 6-minute walking test while breathing oxygen in both assisted (Aid) or unassisted (No-Aid) modalities. When compared with REEc, REEa was slightly lower in patients (1351\ub1169 vs 1413\ub1194 kcal/day respectively, p<0.05), and less repeatable ithan in healthy controls (0.14 and 0.43 coefficient respectively). COPD patients with CRF patients reported a significant gain with Aid as compared with No-Aid modality in terms of meters walked, perceived symptoms and EE.SWA provides a feasible and valid method to assess the energy expenditure in CRF patients on LTOT, and it shows that aided walking results in a substantial energy saving in this population

Clinical use of Levofloxacin in the long-term treatment of drug resistant tuberculosis.

Multidrug-resistant (MDR) tuberculosis (TB) is a form of TB that is resistant to some of the first-line drugs used for the treatment of the disease. It is associated both with a higher incidence of treatment failures and of disease recurrence, as well as with higher mortality than forms of TB sensitive to first-line drugs. Levofloxacin (LFX) represents one of the few second-line drugs recently introduced in the therapeutic regimens for MDR TB. We report our experience concerning in vitro activity and clinical safety of LFX in long term second-line regimens for MDR TB. IN VITRO ACTIVITY ON MYCOBACTERIA: The in vitro activity of ciprofloxacin, ofloxacin and LFX was studied on 28 strains belonging to different species of Mycobacteria. In Dubos medium, LFX inhibited the growth of both library and MDR clinical Mycobacteria strains in a range of 0.25-1 mcg/ml. In International Union Tuberculosis Medium (IUTM) the minimum inhibitory concentrations (MIC) were slightly higher, but LFX activity was not affected by the higher complexity of the medium. CLINICAL EXPERIENCE: Four patients with MDR TB were treated with a second-line regimen comprising oral LFX 500 mg twice daily, for at least 9 months. Two isolates obtained from the patients reported here showed multi resistance to isoniazid and rifampin, one to rifampin and streptomycin and one to isoniazid and ethambutol. During therapy, no significant alteration of either liver function tests, blood tests or any other described side effect of the fluoroquinolone class was observed. The 3 patients with pulmonary MDR TB showed radiologic and clinical improvement. CONCLUSION: We confirm the higher in vitro activity of LFX compared to older fluoroquinolones. Furthermore, in a limited number of MDR TB patients, second-line regimens comprising LFX 500 mg b.i.d. administered in a range of 9-24 months were well tolerated and safe

Diagnosis of Asthma and COPD

Publisher Summary The differential diagnosis between asthma and COPD is quite simple when the typical clinical and functional features of either disease are present. The difficulty comes when trying to make a diagnosis of asthma or COPD in a middle-aged or elderly patient, a smoker, who may be atopic or have a history of asthma, who complains of chronic dyspnea but not wheezing, chronic cough, or sputum, and who presents with poorly reversible airflow limitation. It is also difficult to make a diagnosis of asthma or COPD in a middle-aged or elderly patient who has a clear history of atopy and asthma, bronchodilator reversibility, and recurrent wheezing, but who also smokes and has chronic cough and sputum and dyspnea that are not suppressed by inhaled steroids. The diagnosis of asthma or COPD is based on clinical history and lung function tests, particularly peak expiratory flow (PEF) and spirometry, with assessment of spontaneous or postbronchodilator reversibility of airflow limitation. Allergy tests are also usually performed for the diagnosis of asthma, but not of COPD patients, to identify allergens responsible for asthma exacerbations and to consider the opportunity to treat the patient with immunotherapy. While the diagnosis and assessment of severity of asthma and COPD can be fully established on the basis of clinical history and lung function tests, additional tests might be helpful to better characterize individual patients

Characterisation of exacerbation risk and exacerbator phenotypes in the POET-COPD trial

Background: Data examining the characteristics of patients with frequent exacerbations of chronic obstructive pulmonary disease (COPD) and associated hospitalisations and mortality are scarce. Methods: Post-hoc analysis of the Prevention Of Exacerbations with Tiotropium in COPD (POET-COPD) trial, targeting exacerbations as the primary endpoint. Patients were classified as non-, infrequent, and frequent exacerbators (0, 1, or &gt;= 2 exacerbations during study treatment), irrespective of study treatment. A multivariate Cox regression model assessed the effect of covariates on time to first exacerbation. Results: In total, 7376 patients were included in the analysis: 63.5% non-exacerbators, 22.9% infrequent, 13.6% frequent exacerbators. Factors significantly associated with exacerbation risk were age, sex, body mass index, COPD duration and severity, smoking history, baseline inhaled corticosteroid use, and preceding antibiotic or systemic corticosteroid courses. Frequent exacerbators had greater severity and duration of COPD, received more pulmonary medication, and &gt;= 2 systemic corticosteroid or antibiotic courses in the preceding year, and were more likely to be female and ex-smokers. The small proportion of frequent exacerbators (13.6%) accounted for 56.6% of exacerbation-related hospitalisations, which, overall, were associated with a three-fold increase in mortality. Conclusion: The frequent exacerbator phenotype was closely associated with exacerbation-related hospitalisations, and exacerbation-related hospitalisations were associated with poorer surviva

Short-Term Efficacy of Upper-Extremity Exercise Training in Patients With Chronic Airway Obstruction: A Systematic Review.

Background, Objectives, and Measurements Patients with chronic airway obstruction (CAO) frequently experience dyspnea and fatigue during activities performed by accessory muscles of ventilation, which competitively participate in arm elevation. This systematic review of randomized controlled trials (RCTs) concerning patients with CAO addresses the effects of upper-extremity exercise training (UEET), added to lower-extremity training or comprehensive pulmonary rehabilitation, on the following patient-centered outcomes: exercise capacity, symptoms, ability to perform daily activities, and health-related quality of life. METHODS:/b&gt; Studies were retrieved using comprehensive database and hand-search strategies. Two independent reviewers determined study eligibility based on inclusion criteria. A detailed description of treatments was mandatory. Reviewers rated study quality and extracted information on study methods, design, intervention, and results. RESULTS: /b&gt; Forty publications were evaluated. Four RCTs met the inclusion criteria but had serious methodological limitations, which introduce possible biases that reduce their internal validity. The outcomes measured were heterogeneous, and the results were inconsistent regarding maximal exercise capacity, dyspnea, and health-related quality of life. No effect of UEET was demonstrated for measures of arm fatigue. Limitations and CONCLUSIONS:/b&gt; The limited methodological quality of the studies retrieved prevented us from performing a meta-analysis, the results of which could be misleading. This systematic review shows that there is limited evidence examining UEET and that the evidence available is of poor quality. Therefore, a recommendation for the inclusion or exclusion of UEET in pulmonary rehabilitation programs for individuals with CAO is not possible. Further research is needed to definitively ascertain the effects of this training modality on patient-centered outcomes

Short term efficacy of nebulized beclomethasone in mild-to-moderate wheezing episodes in pre-school children

<p>Abstract</p> <p>Background</p> <p>Few data are available on the usefulness of short term treatment with low-medium dose of inhaled corticosteroids (ICS) in pre-school children with wheezing exacerbations.</p> <p>Methods</p> <p>To compare the efficacy of one week treatment with 400 μg b.i.d. nebulized beclomethasone dipropionate (BDP), plus nebulized 2500 μg prn salbutamol (BDP group), versus nebulized b.i.d. placebo, plus nebulized prn 2500 μg salbutamol (placebo group), a post-hoc analysis was performed on data obtained in 166 pre-school children with multiple-trigger wheezing, recruited during an acute wheezing episode.</p> <p>Results</p> <p>The percentage of symptom-free days (SFDs) was significantly higher in the BDP group (54.7%) than in the placebo group (40.5%; p = 0.012), with a 35% relative difference. Day-by-day analysis showed that the percentage of SFDs was already higher in the BDP group after 2 days (7.4%), the difference reaching statistical significance at day 6 (12.3%; p = 0.035). Cough score was also reduced in the BDP group (0.11) as compared with the placebo group (0.39; p = 0.048), the difference reaching statistical significance after 5 days of treatment (0.18 and 0.47 respectively; p = 0.047). The mean number of nebulizations per day of prn salbutamol was lower in the BDP group as compared to the placebo group (0.26 and 0.34, respectively), but the difference was not significant (p = 0.366). There were no differences in positive effects of BDP treatment between children with and without risk factors for asthma.</p> <p>Conclusions</p> <p>A 1-week treatment with nebulized BDP and prn salbutamol is effective in increasing SFDs and improving cough in children with wheezing, providing a clinical rationale for the short term use of ICS in episodic wheeze exacerbations in pre-school children.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov (<a href="http://www.clinicaltrials.gov/ct2/show/NCT00497523">NCT00497523</a>)</p