Evaluation of Imatinib Mesylate in the Treatment of Pulmonary Arterial Hypertension

Imatinib mesylate is a small molecule inhibitor that selectively inhibits the PDGF receptor kinase as well the cKIT and Abl kinases, among other targets. Various studies have implicated the PDGF pathway in the pathogenesis of pulmonary arterial hypertension (PAH). Inhibition with imatinib mesylate has shown efficacy in human case reports and experimental models of PAH. Results from a Phase II trial of imatinib mesylate in PAH did not meet the primary end point but showed improvement in several secondary end points and in a subgroup analysis. As suggested by this study as well as a few case reports, imatinib may be effective in a subset of patients with more severe disease. However, this remains to be further validated through a Phase III study, which is already underway. In conclusion, it appears that imatinib mesylate may hold promise as an adjunct drug in PAH therapy, especially since it is directed at a pathway not previously targeted. …

The Value of Computed Tomography Scanning for the Detection of Coronary Artery Disease in Patients with Idiopathic Pulmonary Fibrosis

BACKGROUND AND OBJECTIVE:
Patients with idiopathic pulmonary fibrosis (IPF) have a higher prevalence of coronary artery disease and this could have an impact on their outcomes. We investigated the predictive ability of coronary artery calcification, assessed by routine CT, which may predict the presence of coronary artery disease. METHODS:
The study cohort consisted of patients with IPF and with left heart catheterization data plus CT scans from July 2003 to July 2008. Grades of coronary calcification on CT were compared with left heart catheterization determination of coronary artery disease. RESULTS:
There were 57 patients in whom left heart catheterization review demonstrated significant coronary artery disease in 28.1% (16/57), mild disease in 40.3% (23/57) and none in 31.6% (18/57). The median time interval between the catheterization and the reviewed CT scan was 39 days. The sensitivity of moderate to severe calcification for significant coronary artery disease was 81%, while the specificity was 85%, with an associated odds ratio of 25.2 (4.64-166, P < 0.005). There was excellent agreement among three radiologists in the grading of coronary calcification. CONCLUSIONS: Coronary calcification, as assessed by routine CT of the chest, has very good performance characteristics in predicting underlying significant coronary artery disease in patients with IPF. The routine availability of this study enables the ready screening for coronary artery disease in IPF patients. ...

Achieving Symptom Control in Patients with Moderate Asthma

Disease severity in asthma can be classified as mild, moderate or severe based upon the frequency of symptoms or the severity of airflow obstruction. This review will focus on the treatment of youths greater than 12 years of age and adults with moderate persistent asthma. Moderate asthmatics may have daily symptoms that cause some limitation with normal daily activities and require use of a rescue inhaled short-acting beta(2)-agonist inhaler or experience nocturnal awakenings secondary to asthma that occur more than once per week. Furthermore, spirometry may reveal airflow obstruction with a reduction in FEV(1) to between 60% and 80% of predicted. Although inhaled corticosteroids (ICS) are the primary controller medication used to modify symptoms in moderate asthmatics, additional controller medications, such as inhaled long-acting beta(2)-agonists (LABA), leukotriene receptor antagonists (LTRA) or theophylline, are often needed to obtain optimal disease control. While the addition of an inhaled LABA to an ICS is very effective at improving disease control in moderate asthma, concerns have arisen over the safety of LABAs, in particular the risk of asthma-related death. Therefore, consideration may be given to initially adding a LTRA, rather than a LABA, to ICS when asthma symptoms are not adequately controlled by ICS alone. Furthermore, individualization of medication regimens, treatment of co-morbid conditions, and patient education are crucial to optimizing compliance with therapy, improving disease control, and reducing the risk of exacerbations. Lastly, the development of new asthma treatments, perhaps based upon personalized medicine, may revolutionize the future treatment of moderate asthma. …

Dynamic Patient Counseling: A Novel Concept in Idiopathic Pulmonary Fibrosis

BACKGROUND:
The characteristics of long-term survivors with idiopathic pulmonary fibrosis (IPF) have never been fully elucidated. We sought to illustrate the attenuated mortality and describe the characteristics of patients with IPF who survived at least 5 years beyond their initial presentation. METHODS:
Patients with IPF evaluated between 1997 and 2006 were identified through the clinic database. Patients who survived beyond 5 years from the time of their evaluation were compared with those who died or underwent lung transplantation within 5 years. Survival analyses were performed from the time of initial evaluation and contingent on annualized survival thereafter. RESULTS:
Eighty-seven patients who survived at least 5 years formed the comparator group to whom other patients were contrasted. These patients had a higher BMI, FVC % predicted, FEV1 % predicted, total lung capacity % predicted, and diffusing capacity of lung for carbon monoxide % predicted, but a lower FEV1/FVC ratio and lower mean pulmonary artery pressures. More than one-half of these patients had moderate or severe disease at the time of presentation. Our annualized contingent survival analyses revealed a progressively increasing median survival dependent on the duration of the disease. CONCLUSIONS:
Although we were able to demonstrate differences in our 5-year survivors, rather than being a distinct group, these patients appear to exist within a continuum of improving survival dependent on prior disease duration. This progressively improving time-dependent prognosis mandates the serial reevaluation of an individual patient’s projected outcomes. The implementation of dynamic counseling is an important concept in more accurately predicting life expectancy for patients…

Invasive Pneumococcal Disease and Pneumococcal Pneumonia: A Review of the Pertinent Clinical Issues

Invasive pneumococcal disease is defined as an infection confirmed by the isolation of Streptococcus pneumoniae from a normally sterile site. Its incidence in any population is affected by geographic location, time of year, serotype prevalence, age, and vaccination status, and in general invasive pneumococcal disease is more frequent in patients with certain underlying medical conditions or demographic risk factors. These include: age below 2 or 65 years and above; certain racial/ethnic groups; chronic cardiovascular, pulmonary, liver, or renal disease; diabetes mellitus; alcohol abuse; smoking; or immunosuppressive conditions. All over the world, routine vaccination in young children with pneumococcal conjugate vaccines causes significant decline in the incidence of invasive pneumococcal disease in children below 5 years (the age group targeted for vaccination), older children, and adults. As the mortality of pneumococcal pneumonia has not changed for many years despite the different available antimicrobial agents, prevention of pneumococcal infection by vaccination seems to be a rational approach to further decrease the public burden of the disease. …