Efficacy and adverse effects of drugs used to treat adult cystic fibrosis.

INTRODUCTION: Cystic fibrosis (CF) is an autosomal recessive disease and is the most commonly seen monogenetic disease in Caucasians. The disease has various manifestations resulting from the abnormal thick secretions, most common being chronic lung infection and airway obstruction. Many new promising drugs have appeared on the horizon over the years. This review here is an attempt to bring together the various treatments being used to prolong and enhance the quality of life of CF patients. AREAS COVERED: A literature review of published as well as ongoing clinical trials, meta-analysis and systematic reviews regarding the drugs used in CF management was carried out using PubMed and Ovid databases. EXPERT OPINION: New concepts have been formed and some positive results in this direction have already led to the approval of cystic fibrosis transmembrane conductance regulator potentiator drug. Gene therapy and stem cell therapy are under development. The current therapies such as dornase alfa and pancreatic enzymes targeting the symptoms continue to evolve as they play an important complementary role. Development of new simple and cost-effective markers, which help assess the efficacy and safety of these constantly emerging new drugs, is also being investigated.

Cardiac sarcoidosis: a comprehensive review.

Sarcoidosis is a multisystem granulomatous disease of unknown etiology characterized by noncaseating granulomas in involved organs. Organs involved with sarcoidosis include lymph nodes, skin, lung, central nervous system, and eye. Only 40-50% of patients with cardiac sarcoidosis diagnosed at autopsy have the diagnosis made during their lifetime. Cardiac sarcoidosis can manifest itself as complete heart block, ventricular arrhythmias, congestive heart failure, pericardial effusion, pulmonary hypertension, and ventricular aneurysms. Diagnostic tests such as the electrocardiogram, two-dimensional echocardiography, cardiac magnetic resonance imaging, positron emission tomography scan, radionuclide scan, and endomyocardial biopsy can be helpful in the early detection of cardiac sarcoidosis. Considering the increased risk of sudden death, cardiac sarcoidosis is an indication for early treatment with corticosteroids or other immunosuppressive agents. Other treatments include placement of a pacemaker or implantable defibrillator to prevent sudden death. In refractory cases, cardiac transplantation should be considered.

Prediction of moderate or severe pulmonary hypertension by main pulmonary artery diameter and main pulmonary artery diameter/ascending aorta diameter in pulmonary embolism.

We investigated the accuracy of computed tomographic measurements of main pulmonary artery diameter (MPAD) and of MPAD/ascending aorta diameter (AAD) in predicting moderate or severe pulmonary hypertension in 190 patients with acute pulmonary embolism. A pulmonary artery systolic pressure of > or = 50 mm Hg measured by Doppler echocardiography was considered moderate or severe pulmonary hypertension. A MPAD of > 28.6 mm and a MPAD/AAD ratio of > or = 1.00 measured by computed tomography were considered abnormal. A MPAD of > 28.6 mm had a 75% sensitivity and specificity, a 52% positive predictive value, a 89% negative predictive value, a 3.0 likelihood ratio for a positive test, and a 0.33 likelihood ratio for a negative test in predicting moderate or severe pulmonary hypertension. A MPAD/AAD ratio of > or = 1.00 had a 59% sensitivity, a 82% specificity, a 55% positive predictive value, a 84% negative predictive value, a 3.3 likelihood ratio for a positive test, and a 0.50 likelihood ratio for a negative test.

Prevalence of left ventricular hypertrophy in persons with and without obstructive sleep apnea.

We investigated the prevalence of left ventricular hypertrophy (LVH) in persons with and without obstructive sleep apnea (OSA). Fifty-three persons had a nocturnal polysomnogram to diagnose OSA and 2-dimensional echocardiograms to measure left ventricular mass. OSA was considered mild if the respiratory disturbance index (RDI) was 5 to 15, moderate if the RDI was 15 to 30, and severe if the RDI was >30. LVH was diagnosed if the left ventricular mass index was >110 g/m in women and >134 g/m in men. LVH was present in 21 of 27 persons (78%) with moderate or severe OSA, in 6 of 13 persons (46%) with mild OSA, and in 3 of 13 persons (23%) with no OSA (P < 0.001 comparing moderate or severe OSA with no OSA and P < 0.05 comparing moderate or severe OSA with mild OSA). OSA was a significant independent predictor of LVH after controlling the confounding effects of hypertension with an odds ratio of 3.579 (95% confidence interval, 1.589-8.058).

Association of reduced carbon monoxide diffusing capacity with moderate or severe left ventricular diastolic dysfunction in obese persons.

STUDY OBJECTIVES: To determine the association of reduced diffusing capacity of the lung for carbon monoxide (D(LCO)) with moderate or severe left ventricular diastolic dysfunction (LVDD) in obese persons. DESIGN: We investigated the association of D(LCO) with LVDD in 105 patients with a mean +/- SD body mass index of 49 +/- 5 kg/m2. An abnormal D(LCO) was < 80%. LVDD was investigated by Doppler and by tissue Doppler echocardiography. The Doppler echocardiographic data were analyzed blindly without knowledge of the clinical characteristics or whether the D(LCO) was normal or abnormal. SETTING: A university hospital. PATIENTS: The 105 patients included 19 men and 86 women (mean age, 45 +/- 9 years). RESULTS: An abnormal D(LCO) was present in 62 of 105 patients (59%). Moderate or severe LVDD was present in 35 of 105 patients (33%). Moderate or severe LVDD was present in 25 of 62 patients (40%) with an abnormal D(LCO) and in 10 of 43 patients (23%) with a normal D(LCO) (p < 0.05). CONCLUSION: Obese patients with a decreased D(LCO) have an increased prevalence of moderate or severe LVDD.

Efficacy of unfractionated heparin for thromboembolism prophylaxis in medical patients.

A common mode of deep vein thrombosis prophylaxis in medical inpatients is unfractionated heparin 5000 U subcutaneously (s.q.) twice daily. We examined the evidence in favor of using this dose of heparin in this group of patients. MEDLINE was searched for studies using the words deep vein thrombosis prophylaxis and heparin. All randomized controlled trials comparing heparin and placebo or heparin and a low molecular weight heparin were used. Relative risk was 0.4 (95% confidence interval 0.22-0.73) in studies comparing heparin 5000 U s.q. b.i.d. with placebo. Relative risk was 0.28 (95% confidence interval 0.21-0.38) in studies comparing heparin 5000 units s.q. t.i.d. versus placebo. In studies comparing unfractionated heparin with enoxaparin relative risk was 1.42 (95% confidence interval 0.99-2.05). Heparin 5000 U s.q. b.i.d. is less efficacious than low molecular weight heparins and unfractionated heparin 5000 U s.q. t.i.d.

Role of the 12-lead electrocardiogram in diagnosing pulmonary embolism.

We investigated the role of the standard 12-lead electrocardiogram (ECG) to improve the pretest probability of pulmonary embolism before performing computed tomographic (CT) pulmonary angiography. A retrospective chart analysis was performed on patients who underwent CT pulmonary angiography at a tertiary care hospital during a 30-month period. Comparison of 15 ECG parameters was made between those with CT pulmonary angiograms positive for pulmonary embolism and a matched control group with negative CT pulmonary angiograms. Data were analyzed by chi-squared tests and logistic regression. Sinus tachycardia (39% vs. 24%, P <0.01), an S1 Q3 T3 pattern (12% vs. 3%, P <0.01), atrial tachyarrhythmias (15% vs. 4%, P <0.005), a Q wave in lead III (40% vs. 26%, P <0.02), and a Q3 T3 pattern (8% vs. 1%, P <0.02) were the findings significantly associated with pulmonary embolism. We conclude that 1) standard 12-lead ECG findings can increase the pretest probability of pulmonary embolism before performing CT pulmonary angiography; and that 2) the ECG findings have relatively low likelihood ratios to have clinical use.

Cardiovascular consequences of sleep-related breathing disorders.

Sleep-related breathing disorders (SRBDs) represent a spectrum of abnormalities that range from simple snoring to upper airway resistance syndrome to sleep apnea. The clinical presentation may include obesity, snoring, neuropsychological dysfunction, and daytime hypersomnolence and tiredness. The acute hemodynamic alterations of obstructive sleep apnea include systemic and pulmonary hypertension, increased right and left ventricular afterload, and increased cardiac output. Earlier reports attributed the coexistence of SRBDs with cardiovascular diseases to the shared risk factors such as age, sex, and obesity. However, recent epidemiologic data confirm an independent association between SRBDs and the different manifestations of cardiovascular diseases. Possible mechanisms may include a combination of intermittent hypoxia and hypercapnia, repeated arousals, sustained increase in sympathetic tone, reduced baroreflex sensitivity, increased platelet aggregation, and elevated plasma fibrinogen and homocysteine levels. The strength of the association, its pathogenesis, and the impact of treatment of SRBDs on the health outcome of patients with cardiovascular diseases are issues to be addressed in future studies.