We describe an HIV-infected 44-year-old man who presented 1 month after discontinuation of HAART therapy with a large mass extending from the mediastinum, enclosing the heart and extending through ...the diaphragm to the epigastric region. Biopsies subsequently revealed a highly aggressive non-Hodgkin's lymphoma (NHL) producing sheets of cells with an organoid distribution. The cells had abundant basophilic cytoplasm and a plasmacytic appearance. Although immunohistochemistry failed to show either B- or T-cell markers, antigens consistent with plasma cells were found. An immunoglobulin heavy chain clonal rearrangement was identified by PCR analysis. These studies were supportive of a diagnosis of a plasmablastic lymphoma. While awaiting the results of these tests, the patient was reinitiated on his HAART regimen. He was found on follow-up a month later to have complete resolution of his bulky mediastinal mass. He remained free of disease for 3 months with subsequent rectal and abdominal recurrence. Treatment with CHOP chemotherapy with filgrastim support was begun which resulted in another remission. Plasmablastic lymphoma is now reported in some studies to account for 2.6% of all HIV-related NHL. Originally described in 1997 in a series of 16 patients, this entity is highly associated with HIV infection in its later stages. Often, patients present with oral or jaw lesions with a rapidly progressive course. The tumors have the morphologic appearance of a plasmacytoid tumor with high proliferative index. Markers are positive mainly for LCA, CD79a, VS38C, and CD138. Co-infection with HHV-8 and EBV has not been consistently reported. Therapy with standard regimens has variable response. One case has been reported with a 3.5 year disease free survival. The regression of disease after resumption of HAART therapy alone in this patient suggests that HAART has an important role in the treatment of lymphoma in the HIV infected patient.
In the last two decades several significant changes have been proposed in the receptor theory that describes how ligands can interact with G protein‐coupled receptors (GPCRs). Here we briefly ...summarize the evolution of receptor theory and detail recent prominent advances. These include: (i) the existence of spontaneously active GPCRs that are capable of signalling even though they are unoccupied by any ligand; (ii) the discovery of ligands that can inactivate these spontaneously active receptors; (iii) the notion that a ligand may simultaneously activate more than one GPCR signalling pathway; and (iv) the notion that certain ligands may be able to preferentially direct receptor signalling to a specific pathway. Because the data supporting these receptor theory ideas are derived primarily from studies using artificial expression systems, the physiological relevance of these new paradigms remains in question. As a potential example of how these new perspectives in receptor theory relate to drug actions and clinical outcomes, we discuss their relevance to the recent controversy regarding the chronic use of β2‐adrenoceptor agonists in the treatment of asthma.
LINKED ARTICLES This article is part of a themed issue on Respiratory Pharmacology. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.163.issue‐1
Summary
Asthma is a complex respiratory disorder characterized by marked heterogeneity in individual patient disease triggers and response to therapy. Several asthma phenotypes have now been ...identified, each defined by a unique interaction between genetic and environmental factors, including inflammatory, clinical and trigger‐related phenotypes. Endotypes further describe the functional or pathophysiologic mechanisms underlying the patient's disease. type 2‐driven asthma is an emerging nomenclature for a common subtype of asthma and is characterized by the release of signature cytokines
IL
‐4,
IL
‐5 and
IL
‐13 from cells of both the innate and adaptive immune systems. A number of well‐recognized biomarkers have been linked to mechanisms involved in type 2 airway inflammation, including fractional exhaled nitric oxide, serum IgE, periostin, and blood and sputum eosinophils. These type 2 cytokines are targets for pharmaceutical intervention, and a number of therapeutic options are under clinical investigation for the management of patients with uncontrolled severe asthma. Anticipating and understanding the heterogeneity of asthma and subsequent improved characterization of different phenotypes and endotypes must guide the selection of treatment to meet individual patients’ needs.
Major clinical gaps impede the evidence-based treatment of chronic obstructive pulmonary disease (COPD) in the primary care setting. Studies are needed to measure the effectiveness of continuing ...medical education (CME) on improving physician competency and performance toward evidence-based COPD care.
Between September 26, 2009 and December 12, 2009, 769 primary care physicians participated in a series of 12 regional, live, interactive, case-based, multiformat, half-day CME programs on COPD. A subgroup of randomly selected participants (n = 50) and demographically matched nonparticipants (n = 50) completed surveys that included case vignettes, a validated tool for measuring physician performance in clinical practice. Cohen's d was used to calculate the magnitude of difference between participants and nonparticipants in the delivery of evidence-based care.
Physicians who participated in CME programs were 50% more likely to provide evidence-based COPD care than physicians who did not participate. Compared with nonparticipants, participating physicians were more likely to recognize COPD correctly in a patient presenting with dyspnea (74% versus 94%, P = 0.007), recognize that women may have a greater susceptibility than men to the toxic effects of smoking (54% versus 90%, P < 0.001), and identify the mechanisms of action of emerging therapies (33% versus 65%, P = 0.003).
Physicians who participated in a half-day regional CME program on COPD diagnosis, staging, and treatment were significantly more likely than nonparticipants to deliver evidence-based COPD care. With multiformat, interactive, focused educational interventions, physicians can make diagnostic and therapeutic choices in the primary care setting that align more closely with current guidelines and clinical evidence in COPD management.
Abstract Background: Chronic obstructive pulmonary disease (COPD) is associated with substantial morbidity and mortality. Published practice guidelines and treatment algorithms for COPD are designed ...to increase awareness of the problem and improve patient care; however, <40% of subjects diagnosed with COPD are receiving appropriate maintenance therapy. Objective: This paper reviews the use of maintenance therapy in COPD and examines the optimal timing for initiating such therapy based on the available literature. Methods: Relevant publications were identified through a search of MEDLINE (1995-May 2007) using the terms COPD, guidelines, treatment, maintenance therapy, bronchodilator, ipratropium, tiotropium, β-agonist, salmeterol, and inhaled corticosteroid . English-language publications discussing pharmacologic maintenance therapy for COPD, including practice statements/guidelines, randomized controlled clinical trials, systematic reviews, and meta-analyses, with a focus on agents currently approved for use in the United States, were selected for inclusion. Results: Although guidelines and algorithms agree on the importance of regularly scheduled maintenance therapy to reduce symptoms of COPD, minimize activity limitations, and improve health status, the timing of the initiation of such therapy is debatable. In most instances, maintenance medications, which include long-acting β2 -agonists, long-acting anticholinergics, and combination products, are prescribed late in the disease process and mainly for patients with severe disease. However, there is increasing evidence that the use of maintenance therapy early in the disease process may be associated with improvements in such outcomes as lung function, symptoms, exercise tolerance, exacerbations of COPD, and quality of life. Conclusion: The high burden associated with COPD highlights the need to initiate maintenance therapy before a substantial decline in lung function has occurred.
Long-acting beta
2-agonists (LABAs) are recommended in the management of patients with chronic obstructive pulmonary disease (COPD). Previous studies have demonstrated that the LABA, salmeterol, ...improves lung function, symptoms and quality of life in patients with COPD. In this study, we have performed additional analyses of the combined data from two previous double-blind, placebo-controlled, parallel studies of salmeterol (50
μg, b.i.d) in patients with COPD. The new analyses reveal that the significant improvements seen in pre-dose and 2-h post-dose forced expiratory volume in 1
s (FEV
1) compared to placebo, occur early in the treatment period, and are sustained for at least 24 weeks. Moreover, improvements in peak expiratory flow rate occur as early as Day 1, and are sustained throughout the 24-week period. Additional analyses of 12-h FEV
1 data also show that salmeterol is associated with an increase in the area under the curve at Week 12 compared with Day 1, adding further support to evidence that it results in a sustained bronchodilator response, with no evidence of tolerance.
Annual influenza vaccination is currently recommended as a preventative measure for all patients with asthma. However, the effect of maintenance corticosteroid therapy on the immune response to ...influenza vaccine has received limited evaluation.
In this study, we evaluated the effect of corticosteroid therapy on the immune response to influenza vaccine in children and adults with asthma.
This was a substudy of a larger multicenter, randomized, double-masked, placebo-controlled, crossover study investigating the safety of trivalent influenza vaccine in patients with asthma. At baseline, 294 subjects were randomized to receive either placebo first (n=139) or inactivated trivalent split-virus influenza vaccine first (n=155). Study subjects were categorized into 2 groups: subjects in group 1 (n=148) were receiving medium-dose or high-dose inhaled corticosteroids (ICSs) or oral corticosteroids, whereas subjects in group 2 (n=146) were not receiving corticosteroids or were receiving low-dose ICSs. Serum hemagglutination inhibition antibody titers for the vaccine antigens were measured before and 4 weeks after the administration of placebo or vaccine.
Serologic responses to each influenza vaccine antigen were significantly higher in vaccine than in placebo recipients and were similar among influenza vaccine recipients in groups 1 and 2 for the following endpoints: rise in antibody titer, percent of participants who developed a serological response, and percent of subjects who developed a serum hemagglutination inhibition antibody titer ≥1:32. Post hoc subgroup analyses demonstrated an attenuated response to influenza B antigen in subjects receiving high-dose ICS compared with subjects who were steroid-naïve (P<.05).
The immune response to the A antigens of the inactivated influenza vaccine in subjects with asthma is not adversely affected by ICS therapy. High-dose ICS therapy may diminish the response to the B antigen of the vaccine, an observation that needs further investigation.
Chronic obstructive pulmonary disease (COPD) is a disease state characterized by airflow limitation that is usually progressive. In addition, an abnormal inflammatory response of the lungs to noxious ...particles or gases can be seen throughout the airways, parenchyma, and pulmonary vasculature. So far, anti-inflammatory medications (eg, inhaled corticosteroids) have failed to show a major effect on the decline of lung function in COPD patients. Novel anti-inflammatory therapies such as selective phosphodiesterase 4 (PDE4) inhibitors are in clinical development. Their potential role in the management of COPD is described in this review.
Some of the selective PDE4 inhibitors have demonstrated in vitro and in vivo anti-inflammatory activity on cells commonly linked to airway inflammation in COPD, such as neutrophils. While these agents seem to offer only a modest improvement in lung function compared with other bronchodilators, their anti-inflammatory effects appear to provide some substantial benefits in reducing exacerbations and improving health-related quality of life.
Based on the available data, the second generation of selective PDE4 inhibitors will likely provide additional therapeutic options for the management of COPD. These agents may become an important tool in the treatment of this disease, since they target three important components of COPD: airway obstruction, inflammation, and structural changes.
Introduction Simulation is denned as a process that substitutes or amplifies real patient encounters with artificial models, live actors, or virtual reality patients. ' Simulation-based learning ...(SBL) has increasingly been used as a learning tool in undergraduate and postgraduate medical curricula, to help the modern healthcare professional to achieve higher levels of competence and safer patient care. Trainee acceptance rate and confidence levels pre- and post-simulation of simulated cases vs non-simulated cases were compared by assessing the Chi-squared statistics.
Treatments for COPD Hanania, Nicola A.; Ambrosino, Nicolino; Calverley, Peter ...
Respiratory medicine,
12/2005, Letnik:
99
Journal Article, Conference Proceeding
Recenzirano
Odprti dostop
The multicomponent nature of chronic obstructive pulmonary disease (COPD) has provided a challenging environment in which to develop successful treatments. A combination of pharmacological and ...non-pharmacological approaches is used to combat this problem, and an overview of these approaches and their possible future direction is given.
Bronchodilators are the mainstay of COPD treatment and can be combined with inhaled corticosteroids for greater efficacy and fewer side effects. A new generation of pharmacotherapeutic agents, most notably phosphodiesterase-4 inhibitors, which are already in the advanced stages of clinical development, and leukotriene B
4 inhibitors (in early clinical development), may shape future treatment as further insight is gained into the pathological mechanisms underlying COPD.
Non-pharmacologic treatments for COPD include long-term oxygen therapy (LTOT), nasal positive pressure ventilation (nPPV), pulmonary rehabilitation and lung-volume-reduction surgery (LVRS). Apart from smoking cessation, LTOT is the only treatment to date which has been shown to modify survival rates in severe cases; thus its role in COPD is well defined. The roles of nPPV and LVRS are less clear, though recent progress is reported here.
In the future, it will be important to establish the precise value of the different treatments available for COPD—evaluating both clinical and physiological endpoints and using the data to more accurately define candidate patients accordingly. The challenge will be to develop this base of knowledge in order to shape future research and allow clinicians to deliver tailored COPD management programmes for the growing number of patients afflicted with this disease.
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