Treatment Of Obstructive Pulmonary Disease Research Articles

The Impact of Treatment of Chronic Obstructive Pulmonary Disease (COPD) on Functional Status and Quality of Life of Patients

The Impact of Treatment of Chronic Obstructive Pulmonary Disease (COPD) on Functional Status and Quality of Life of Patients

Differentiating the Treatment of Asthma and Chronic Obstructive Pulmonary Disease in the Elderly Patient

The focus of this case is a 70-year-old female who was admitted to an assisted living community following a hospitalization for a severe asthma exacerbation. The diagnosis of asthma in the geriatric patient is often under-recognized, misdiagnosed, and improperly managed. Several factors may explain the misclassification and the undertreatment of asthma in the older patient. This case discusses the pharmacotherapeutic management of asthma in the geriatric patient and differentiates the clinical features of asthma from that of chronic obstructive lung disease. The comprehensive management of asthma should include an interprofessional approach because the consultant pharmacist is an essential member of the health care team.

Evaluation of in vivo behavior of controlled and pulsatile release pastilles using pharmacokinetic and γ-scintigraphic techniques

Objective: To evaluate the in vivo behavior of controlled and pulsatile release pastilles for chronic treatment of asthma and chronic obstructive pulmonary disease (COPD) and for the chronotherapeutic management of nocturnal asthma, respectively.Research design & methods: The prepared immediate release and controlled release pastilles were subjected to in vivo pharmacokinetic studies in rats. Whereas, pulsatile release formulation was subjected to γ-scintigraphic study in rats to study the gastrointestinal transit of the formulations and its results were correlated with the previous pharmacokinetic data.Results: The in vivo pharmacokinetic study of controlled release pastille formulation showed significant decrease in Cmax with increase in tmax, which indicates that the effect of dosage form would last for longer duration. Thus, the prepared formulation can be useful for the chronic treatment of asthma and COPD. The γ-scintigraphic study and pharmacokinetic data indicated that the pastilles coated with the enteric coat and the additional floating coat were effective in significantly delaying the in vivo drug release (by 4–5 h) required for the chronotherapeutic treatment of nocturnal asthma.Conclusion: This study opens a new alternative to the conventional tablet or capsule dosage form for the development of both immediate and modified release drug delivery systems.

The US and EU Regulatory Landscapes for Locally Acting Generic/Hybrid Inhalation Products Intended for Treatment of Asthma and COPD

This is a review of the current regulatory requirements associated with development and submission of abridged dossiers for locally acting inhalation drugs intended for the treatment of asthma and chronic obstructive pulmonary disease. The current EU law does not provide for submission of such products as generics due to the definition of bioequivalence and bioavailability; instead they must be submitted as hybrids. A guideline from 2009 is available that suggests a stepwise approach toward approval. An applicant should first consider the degree of in vitro match with the reference product; provided that the match is extensive, approval may be granted. If the in vitro match cannot be proven, the next step is comparison of lung deposition and systemic exposure. If this match is proven, approval may be granted; otherwise, the final step is pharmacodynamic evaluation. In the United States, submission as a generic is possible, but only a single specific guidance document from 1989 is in force. It describes in vitro requirements for comparison of albuterol and metaproterenol pressurized metered dose inhalers. Applicants are encouraged to seek dialogue with regulators prior to and during development. Although parallel scientific advice procedures have been established between the US Food and Drug Administration and the European Medicines Agency, the two authorities give independent and individual advice.

The cost-effectiveness of tiotropium for the treatment of chronic obstructive pulmonary disease (COPD): the importance of the comparator

The cost-effectiveness of tiotropium for the treatment of chronic obstructive pulmonary disease (COPD): the importance of the comparator

Risks associated with tiotropium in chronic obstructive pulmonary disease: overview of the evidence to date.

Tiotropium is a long-acting inhaled anticholinergic agent that is widely used in the treatment of chronic obstructive pulmonary disease (COPD). It was initially launched as the tiotropium HandiHaler formulation, but this was followed by a newer version based on a potentially more efficient drug delivery device, known as Respimat. This Respimat formulation is available worldwide but has not yet succeeded in gaining regulatory approval in the USA. In the past few years, the adverse effects profile of tiotropium has come under close scrutiny owing to concerns about the possibility of urinary and cardiovascular adverse effects. These concerns appeared to have been alleviated following the publication of data from the Understanding Potential Long-Term Impacts on Function with Tiotropium (UPLIFT) trial, which was a large trial of 4 years' duration. This trial did not show any excess myocardial infarction, renal or urinary adverse events with tiotropium compared with placebo. However, the risk of urinary retention has been in the spotlight again following publication of two observational studies reporting a significantly increased risk of urinary retention in men recently started on inhaled anticholinergics, especially when prostatic hyperplasia coexists. More recently, a meta-analysis of mortality data for the tiotropium Respimat formulation raised the possibility of an increased risk of death, including death from cardiovascular causes. It is unclear if the more efficient drug delivery offered by the Respimat device is hitting a different part of the dose-toxicity curve. In the absence of any evidence of superior clinical efficacy with tiotropium Respimat compared with tiotropium HandiHaler, some experts have argued that there is no compelling reason to choose the Respimat formulation given the new uncertainties about its safety profile.

The clinical observation of fluticasone salmeterol inhaler combined with salbutamol inhalation of oxygen-driven treatment of chronic obstructive pulmonary disease with acute exacerbation

Objective To observe the clinical efficacy of fluticasone salmeterol inhaler combined with salbutamol inhalation of oxygen-driven treatment of chronic obstructive pulmonary disease with acute exacerbation. Methods 60 patients of chronic obstructive pulmonary disease with acute exacerbation ,randomly divided into observation and control groups of 30 patients each. The control group on the basis of conventional treatment with salmeterol plus flutica sone inhalation powder compound and the oxygen-driven albuterol inhalation aerosol liquid, the other group by conventional therapy based on the use of oxygen-driven albuterol inhalation aerosol solution, then compare the clinical curative effects. Results There were 18 examples excellencely, i0 examples improve, 2 examples ineffective of observation group with total effective rate 93.3% ;9 examples excellencely, 11 examples improve, 10 examples ineffective of control group with total effective rate 66.7%. The contrast of total effective power with the two groups exists the staffstical significance （ X2 = 4.60,P 〈 0.05 ） o In the observation group, FEV1 and FVC of post-treatment, were better than pretherapy and post-treatment of control group （ t = 2. 629,2. 649,2.064,2.051, P 〈 0. 05 ）. Conclusion Salmeterol and fluticasone propionate inhalation powder hybrid atomizing inhalation of salbutamol effective than salbutamol alone. Key words: Pulmonary disease, chronic obstructive ; Administration, inhalation; Salmeterol, fluticasone ; Salbutamol

Effect of Myrtol standardized on mucus hypersecretion and clearance of Pseudomonas aeruginosa in a rat model of chronic obstructive pulmonary disease

This study aimed to investigate the effect of Myrtol standardized (GeloMyrtol forte) in the treatment of chronic obstructive pulmonary disease (COPD) in an animal model. A total of 93 experimental rats were randomly divided into 6 groups: control (n = 6), exposure to cigarette smoke (CS, n = 6), CS plus Myrtol standardized treatment (CS + M, n = 6), Pseudomonas aeruginosa (PA) infection (PA, n = 25), CS + PA (n = 25), and CS + PA + M (n = 25). For all 62 CS rats, they were exposed to cigarette smoke for a period of 12 weeks. During this time period the 31 CS + M rats (CS + M; CS + PA + M) received 300 mg/kg/day Myrtol standardized intragastrically always 30 min prior to smoke exposure. For CS + PA and CS + PA + M rats, intratracheal PA inoculation was performed after the 12 weeks of smoke exposure. All intratracheal PA inoculations were followed by a post-infection examination at 6, 12, 24, 48 and 72 h in each 5 rats. All study animals were euthanized and their lungs were excised; the left lung was homogenized for determination of bacterial load and measurements of TNF-alpha and IL-6, the right lungs were preserved for histo- and immunohistochemical examinations (e. g. MUC5AC). The lungs from CS rats were pathologically similar to those of COPD patients with the characteristics of goblet cell metaplasia and MUC5AC hypersecretion. CS animals had a significantly greater number of MUC5AC positive cells in the bronchial epithelial cells, and significantly increased expression levels of TNF-alpha and IL-6 after PA infection. However, the administration of Myrtol standardized significantly (p = 0.002) attenuated MUC5AC hypersecretion, measured as integrity optical density (IOD), in CS + M rats (45.98 +/- 6.25) as compared to CS alone (65.55 +/- 11.18) rats. The same applies at different time points between CS + PA rats (65.15 +/- 11.94, 75.88 +/- 7.42, 81.2 +/- 6.49, 75.14 +/- 6.85 and 67.32 +/- 10.61, respectively) and CS + PA + M rats (47.08 +/- 4.78, 54.22 +/- 6.59, 65.4 +/- 6.12, 59.98 +/- 4.96 and 48.43 +/- 7.29, respectively). Similar effects were found in the production of IL-6 and TNF-alpha in the CS + PA + M lungs. Similarly the bacterial load of 10,980 +/- 4,253 CFU in CS + PA + M was significantly lower compared to 42,400 +/- 3,296 CFU in CS + PA lungs after 72 h PA infection. In conclusion, this experimental study demonstrates a significant therapeutic effect of Myrtol standardized in treating common pathological conditions, such as airway mucus hypersecretion and defect of mucociliary functions in COPD.

Vitamin D Treatment of Chronic Obstructive Pulmonary Disease

Vitamin D Treatment of Chronic Obstructive Pulmonary Disease

Effect of β blockers in treatment of chronic obstructive pulmonary disease: a retrospective cohort study

Effect of β blockers in treatment of chronic obstructive pulmonary disease: a retrospective cohort study

Pulmonary Drug Delivery Systems, A Versatile Technique

Pulmonary drug delivery system has been widely used since decades for the treatment of lung diseases and is acclaimed for the treatment of asthma and chronic obstructive pulmonary diseases. Delivery of locally acting drugs directly to the site of action reduces the amount of dose needed to produce the pharmacological effect but now the lung has been studied as a possible route to administer the treatment of systemic diseases, like diabetes mellitus. The site of deposition that is on central or peripheral airways and whether the distribution of the inhaled drug is uniform or non-uniform may play a vital role in an inhaled drug’s effectiveness. Today, there are a number of different inhaled products of more than twenty active ingredients marketed to treat respiratory disease. In near future, more efficient and efficacious inhaled therapies for respiratory diseases, inhalable gene therapy and the treatment of systemic diseases may occur. Normal pulmonary circulation is a lowpressure high capacitance bed that receives 100% of the cardiac output. The intimal lining of all blood vessels is made of a continuous single layer of ECs (Endothelial cells). Due to this specific characteristic of lungs, pulmonary drug delivery system is a magnificent means of treatment of certain diseases. Pulmonary drug delivery offers local and systemically targeting for the treatment of respiratory diseases. Pulmonary delivery is apprehended by various ways like: a) Aerosols

Treatment of chronic obstructive pulmonary disease with salmeterol/fluticasone propionate and community intervention

Objective To investigate the effects of salmeterol/fluticasone (seretide) combined with community intervention on lung function and quality of life of chronic obstruetive pulmonary disease (COPD) patients in the stable period.Methods 96 cases with COPD in the stable period were divided into two groups randomly:Group A was treated only by seretide for six months,group B was treated by seretide combined with community intervention (health education,psychological intervention,exercise training,and nutritional guidance).6 months later,the lung function was determined and the quality of life was assessed by SGRQ.Results The lung function and the score of the quality of life in two groups after treatment [Group A:(1.78 ±0.16)L,(65 ±9)％ and 40 ± 18,36 ± 16,125 ±40;group B:(2.05 ±0.28)L,(73 ±9)％ and 21 ± 10,20 ± 11,58 ± 28,respectively] were improved than those before treatment [Group A:(1.59 ±0.15),(58 ±7) and 63 ±22,50 ±24,167 ±68;group B:(1.61 ±0.14)L,(58 ± 8)％ and 62 ±22,48 ± 22,163 ± 67,respectively] (P ＜ 0.05 );The lung function and the score of the quality of life in B group were improved than those in A group after treatment ( P ＜ 0.05 ).Conclusions Using community intervention combined with seretide in treatment of COPD patients has better effect than the single use of seretide therapy,it improves lung function and quality of life.It is a safe treatment method and worthy to spread widely. Key words: Pulmonary disease; chronic obstructive; Prognosis; Community intervention

Pharmacokinetic evaluation of roflumilast

Introduction: Roflumilast is a selective PDE4 inhibitor recently approved for oral, once-daily treatment of severe chronic obstructive pulmonary disease (COPD). Clinical trials have demonstrated the effect of roflumilast on reducing exacerbation frequency and improving lung function in COPD, while its mode of action may offer the potential to target the inflammatory processes underlying COPD. Roflumilast is, therefore, an important addition to current therapeutic options. It is catalyzed by cytochrome P450 (CYP) 1A2 and 3A4 to its active metabolite, roflumilast N-oxide, which accounts for > 90% of roflumilast total PDE4 inhibitory activity.Areas covered: This article reviews the pharmacokinetics of roflumilast and considers the effects of co-administration with CYP inhibitors or inducers, and other medications commonly used in patients with COPD, on the pharmacokinetics of roflumilast and roflumilast N-oxide.Expert opinion: Roflumilast has novel anti-inflammatory activity in COPD that provides the physician with a treatment option beyond bronchodilation. It can be co-administered with many medications commonly used by patients with COPD and its anti-inflammatory activity provides incremental benefits on top of existing therapies. Future research will further elucidate the impact of roflumilast on COPD and beyond, while alternative dosing regimens may offer a means to ameliorate transient tolerability issues.

Lipoxygenase-Derived Arachidonic Acid Metabolites in Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is characterized by a persistence of inflammation in large and small airways. We hypothesized that this could be caused by the inability of an inflammatory process to resolve. In the resolution of inflammation, a switching of arachidonic acid metabolism from the production of proinflammatory leukotriene B(4) (LtB(4)) to the synthesis of anti-inflammatory lipoxins plays an important role. The aim of our study was to determine the content of lipoxin A(4) (LXA(4)) and LtB(4) in induced sputum of patients with exacerbated COPD and to compare it to healthy controls, as well as to analyze the relationship between proinflammatory and anti-inflammatory mediators and an inflammatory cell spectrum in induced sputum. Induced sputum from 17 COPD patients and 7 healthy controls were analyzed for LXA(4) and LtB(4) content and inflammatory cell spectrum. COPD patients had a significantly lower sputum LXA(4) concentration and LtB(4)/LXA(4) ratio compared with healthy controls. A significant negative correlation was found between the LXA(4) concentration and the relative neutrophil count and between the LtB(4)/LXA(4) ratio and the relative macrophage count. COPD patients during the late phase of exacerbation had a suppressed production of LXA(4) and an elevated LtB(4)/LXA(4) ratio in induced sputum demonstrating a proinflammatory imbalance. The correction of a balance between proinflammatory and anti-inflammatory eicosanoids by the administration of stable analogues of lipoxins could improve the treatment of chronic obstructive pulmonary disease in the future.

Co-deposition of a triple therapy drug formulation for the treatment of chronic obstructive pulmonary disease using solution-based pressurised metered dose inhalers

The formulation of multi-drug pressurised metered dose inhalers (pMDIs) opens up exciting therapeutic opportunities for the treatment of asthma and chronic obstructive pulmonary disease (COPD). We have investigated the formulation of a solution-based triple therapy pMDI containing ipratropium, formoterol, budesonide and ethanol as co-solvent. This system was characterised for in-vitro performance and compared with marketed pMDIs (Atrovent and Symbicort). No significant difference was found in the stage deposition of each drug from the triple therapy formulation, suggesting that the droplets contained a fixed ratio of the three components used. Stage deposition of formoterol and budesonide from the suspension-based marketed Symbicort were significantly different, suggesting that the two drugs were deposited as separate entities. Calculation of the mass median aerodynamic diameter (MMAD) of each formulation suggested Atrovent (ipratropium, MMAD = 0.9 ± 0.0 µm) to have a small particle size, similar to the triple therapy formulation. Atrovent, like the triple therapy formulation was solution based and it contained ethanol as a co-solvent (triple therapy formulation, MMAD = 1.3 ± 0.0 µm). This study demonstrated the feasibility of formulating a solution-based pMDI containing a triple therapy with identical deposition pattern for the treatment of several respiratory diseases where multi-drug cell targeting is required.

Comparative study on the efficacy of tiotropium bromide inhalation and oral doxofylline treatment of moderate to severe stable chronic obstructive pulmonary disease

This study compared the efficacy and safety of tiotropium bromide inhalation powder (spiriva) and doxofylline oral tablet (doxofylline) in the treatment of chronic obstructive pulmonary disease (COPD). A multi-center, randomized, double-blind, double-dummy, parallel-controlled study involved 127 eligible stable moderate to severe COPD patients treated with inhaled tiotropium dry powder (18 μg/day) or oral doxofylline tablets (0.2 g/time, 2 times a day) for 12 and 24 weeks. Before and after treatment for 12 weeks and 24 weeks, respectively, pulmonary function, 6-min walking distance and dyspnea index were recorded. The results showed that in both tiotropium group and doxofylline groups, after 12-week treatment, FEV(1), FEV(1)/FVC% and 6-min walk distance were significantly higher than those before the medication, while dyspnea index decreased as compared with that before treatment. After 24-week treatment, a slight improvement in the measures was observed as compared with that of 12-weeks treatment, but the difference was not statistically significant. With both 12-week and 24-week treatment, the effect of tiotropium was slightly better than that of doxofylline tablets, with the difference being statistically insignificant. The major adverse events in the tiotropium group and doxofylline group were observed in 9 cases (9.9%) and 12 cases (12.9%), respectively, and no statistically significant difference was found between them. We are led to conclude that both tiotropium at 18 μg a day and doxofylline tablets at 0.2 g/day (two times a day) are effective and safe for the treatment of COPD.

Inhibitors of Phosphoinositol 3 Kinase and NFκB for the Treatment of Chronic Obstructive Pulmonary Disease

Chronic Obstructive Pulmonary Disease (COPD) is a preventable and treatable disease characterized mainly by pulmonary airflow limitation that is not fully reversible. New different pharmacological approaches to decrease inflammation of the airways and consequently disease progression and increase airway obstruction reversibility have been developed. In the present article, we review the new patents on phosphoinositide 3 kinase and NFκb inhibitors for future therapies.

Rationale and Emerging Approaches for Targeting Lung Repair and Regeneration in the Treatment of Chronic Obstructive Pulmonary Disease

Lung repair and regeneration are appropriate therapeutic targets for the treatment of chronic obstructive pulmonary disease (COPD). Abnormal repair results if fibrosis of the airways is a major contributor to fixed airflow limitation in airway disease. Inadequate repair in the face of tissue injury can contribute to the development of emphysema. With respect to the latter, acute exposure to cigarette smoke can impair repair responses of several cell types in the lung. Fibroblasts cultured from the lungs of patients with emphysema have persistent defects in repair that include modulation of extracellular matrix as well as production of growth factors that modulate other lung parenchymal cells. Some of the deficient repair functions appear to result from insensitivity to TGF-β and overproduction of prostaglandin E. Pharmacologic interventions targeting these pathways have the potential to at least partially reverse the abnormal repair. Alternate strategies that could modulate lung repair and regeneration could target resident or circulating stem/progenitor cells or potentially involve transplantation of new stem cells. Therapy directed at lung repair has the potential to restore lost lung function. In contrast to therapy designed to slow the progression of COPD, it may be much easier and less expensive to demonstrate efficacy for a therapy that restores lung function.

Advances in drug delivery: is triple therapy the future for the treatment of chronic obstructive pulmonary disease?

Introduction: Current therapies for chronic obstructive pulmonary disease (COPD) focus on the improvement of clinical symptoms via the use of bronchodilators: β2-adrenoreceptor agonists and muscarinic (M3) acetycholine receptor antagonists. The combination of inhaled corticosteroids (ICSs) and long-acting β2 agonists (LABAs), or LABAs and anticholinergics has become an efficient alternative to single therapies. These combinations consist of a LABA and an ICS together with an anticholinergic, such as ipratropium or tiotropium.Areas covered: This review summarizes the latest thinking and findings on the usefulness of triple therapy in the treatment and management of COPD. Drawing on commercial, clinical, scientific and intellectual property data and publications, it aims to provide an overview to understand the efficacy and need for COPD triple therapy. The reader will gain an in-depth view of the triple therapy approach in managing COPD, existing molecules in the market or in development as well as new chemical entities. Clinical evidence in support of triple therapy, formulations and products are also discussed.Expert opinion: There is limited documented clinical evidence for the use of triple therapy in COPD, reflected in the lack of commercial activity in the field. The future for the management of COPD may lie with triple therapy, but may equally rest on a better understanding of the disease and subsequent development of new chemical entities, such as dimer molecules, longer-acting β-agonists and antimuscarinics.

A Review of Salmeterol–Fluticasone Propionate in Combination: Its Use in the Treatment of Chronic Obstructive Pulmonary Disease

Tiotropium bromide (TIO), a long-acting anticholinergic bronchodilator, is now used world-wide for the treatment of Chronic Obstructive Pulmonary Disease (COPD). However, the GOLD guidelines recommend another, or additional medication for symptomatic patients with GOLD stage III or IV disease, forced expiratory volume in 1 second (FEV1) less than 50% of the predicted value, and repeated exacerbations. Several lines of evidence such as the TRISTAN study have shown the synergistic effects of a salmeterol–fluticasone propionate combination (SFC), with significant improvements of pulmonary function, health status, exacerbation rates, and quality of life in patients with COPD, compared with using individual components of SFC. But they didn’t obtain any improvement in the data for mortality, which is our major clinical concern. The TORCH study is a major study which investigated all-cause mortality rates, but it showed no significant difference of mortality among SFC, individual drugs and placebo groups. The INSPIRE study showed significant improvement of mortality in the SFC treatment group, compared with the TIO. However, the higher incidence of pneumonia in the SFC group remains a subject of debate. Some studies showed that SFC therapy has lower medical costs with good patient compliance, which may become a reason for choosing the therapy. The new 2010 NICE GOLD Guideline recommends the “triple” therapy with SFC and TIO, when the FEV1% predicted is less than 50% in the presence of persistent exacerbations or breathlessness. The advantages of “triple” therapy may outweigh the disadvantages of each medication. This review focuses upon the therapeutic potential of SFC for the treatment of COPD.