Pharmacogenetics offers the potential to optimize treatment for individual patients by using genetic information to improve efficacy or avoid side effects. While there are a number of examples in which the approach is already in routine clinical usage, exploitation of this approach in asthma is still under development. A number of examples of possible pharmacogenetic approaches that may prove of value in the management of asthma are discussed.

To evaluate whether the incidence of recurrent venous thromboembolism (VTE) events after therapy differs for patients treated with long-term low-molecular-weight heparin (LMWH) or oral anticoagulant therapy (OAT).

Restless legs syndrome (RLS) is a common and often disabling sensorimotor disorder. Epidemiologic studies suggest that RLS is an underrecognized and undertreated disorder affecting both children and adults. The diagnosis is based primarily on the following four essential criteria: (1) an urge to move, usually associated with paresthesias, (2) onset or exacerbation of symptoms at rest, (3) relief of symptoms with movement, and (4) symptoms manifesting in a circadian pattern. Supplemental workup including polysomnography, iron profile, and/or neuropathy screen can provide support for the diagnosis and aid in the treatment strategy. Behavioral techniques, dopaminergic agents, opiates, benzodiazepines, and antiepileptics all have potential value in treating this disorder. Dopaminergic agents continue to be the most effective RLS treatment. However, due to their potential long-term side effects, these agents should not be considered the sole treatment of choice. In the end, the therapeutic plan should be individualized to suit each patient's presentation and needs.

Studies of acute myocardial infarction, trauma, and stroke have been translated into improved outcomes by earlier diagnosis and application of therapy at the most proximal stage of hospital presentation. Most therapies for these diseases are instituted prior to admission to an ICU; this approach to the sepsis patient has been lacking. In response, a trial comparing early goal-directed therapy (EGDT) vs standard care was performed using specific criteria for the early identification of high-risk sepsis patients, verified definitions, and a consensus-derived protocol to reverse the hemodynamic perturbations of hypovolemia, vasoregulation, myocardial suppression, and increased metabolic demands. Five years after the EGDT publication, there has been much discussion generated with regard to the concepts of EGDT, as well as debate fueled regarding diagnostic and therapeutic interventions. However, during this time period further investigations by the primary investigators and others have brought additional contemporary findings. EGDT modulates some of the components of inflammation, as reflected by improved organ function. The end points used in the EGDT protocol, the outcome results, and the cost-effectiveness have subsequently been externally validated, revealing similar or even better findings than those from the original trial. Although EGDT is faced with challenges, a coordinated approach to sepsis management is necessary to duplicate the progress in outcomes seen in patients with conditions such as acute myocardial infarction, stroke, and trauma.

Pertussis, a highly contagious disease caused by Bordetella pertussis, is making a comeback globally despite good immunization coverage. The developed countries have also shown a shift in the epidemiology of the disease to the adolescent and the adult age group, leading to a revision of their vaccination policies. The disease epidemiology in the South East Asian region seems poised for a similar change. Outbreaks have been reported among children and adults in countries such as Afghanistan, Israel, and Taipei. The anticipation and early recognition of this change in the epidemiology is important because the affected adolescents and adults act as reservoirs of the disease to the vulnerable population of infants, for whom the disease can be life threatening. The clinical presentation can be atypical in the adolescent age group, and the disease is often misdiagnosed. With the availability of polymerase chain reaction and serology, the disease can be diagnosed even later in the course of the disease when culture results are often negative. The whole-cell pertussis vaccine dramatically reduced the incidence of the disease but fell into disrepute due to the rare serious neurologic side effects that led to the introduction of the acellular pertussis vaccine, which led to fewer adverse reactions and also proved to be safe and effective in the adolescent age group when used as a booster. However, the cost of the acellular vaccine is may be prohibitive for widespread use in the developing nations of the South East Asian region.

Assessing airway and lung inflammation is important for investigating the underlying mechanisms of asthma and COPD. Yet these cannot be measured directly in clinical research and practice because of the difficulties in monitoring inflammation. Noninvasive monitoring may assist in early recognition of asthma and COPD, assessment of its severity, and response to treatment, especially during disease exacerbations. There is increasing evidence that breath analysis may have an important place in clinical management of asthma and COPD. The article reviews the role of current noninvasive measurements of exhaled gases, such as nitric oxide (NO), inflammatory markers in exhaled breath condensate (EBC), and exhaled breath temperature, as well as novel methods in monitoring and management of asthma and COPD.

Current reviews on the use of inhaled corticosteroids (ICS) for acute asthma underestimated their early (minutes) clinical impact and produced conclusions of questionable validity.

Sleep problems are extremely common during childhood, from infancy to adolescence. Despite the prevalence of sleep problems, childhood sleep disorders are often underrecognized and undiagnosed, despite being either preventable or treatable. Sleep impacts almost all aspects of a child's functioning, and thus the increased recognition and treatment of sleep disorders will positively affect a child's well-being. Children experience the same broad range of sleep disturbances encountered in adults, including sleep apnea, insomnia, parasomnia, delayed sleep phase, narcolepsy, and restless legs, but their clinical presentation, evaluation, and management may differ. Although snoring and sleep apnea may be the most common indication for an overnight sleep study in a child, one quarter of children presenting to a sleep clinic for evaluation will have a second sleep diagnosis, which is often nonrespiratory in nature. Especially in children, ruling out sleep apnea is rarely the end point of the sleep evaluation. Clinicians involved in sleep medicine must be prepared to recognize, evaluate, and manage plans for sleep disorders across the lifespan of the patient. This article will provide an updated review of nonrespiratory pediatric sleep disorders within a developmental framework.

COPD affects up to one third of patients with chronic heart failure. The coexistence of COPD and chronic heart failure presents clinicians with diagnostic and therapeutic challenges. Measurement of B-type natriuretic peptide plasma levels facilitates the diagnosis of acute dyspnea in patients known to have both COPD and chronic heart failure. Patients with COPD or chronic heart failure have skeletal muscle abnormalities that limit functional capacity independently from primary organ failure. Exercise training reverses skeletal muscle abnormalities in patients with COPD or chronic heart failure and may be particularly indicated in patients with coexistent COPD and chronic heart failure.

In the United States, lung cancer kills more men and woman than the next three most common cancers combined. Unfortunately, the long-term outcome of lung cancer is still dismal with a 5-year survival rate of 15%. However, significant improvements in median survival times and 1-year and 2-year survival rates have been achieved in the last decade. This progress has been accomplished not only because of better surgical techniques but also because of the use of platinum-based regimens with newer chemotherapy agents and, more recently, targeted therapy. The role of chemotherapy as an integral part of the treatment of lung cancer has expanded significantly, particularly in the last few years with the proven benefit of adjuvant chemotherapy. For advanced stage non-small cell lung cancer (NSCLC), chemotherapy prolongs survival and improves quality of life in patients with good performance status, and appears to provide symptomatic improvement in patients with decreased performance status. Platinum-based doublet chemotherapy regimens are now the standard of care in patients with advanced stage NSCLC, and non-platinum-based combination therapies are reasonable alternatives in certain populations. The combination of the vascular endothelial growth factor inhibitor bevacizumab and chemotherapy has proven to prolong survival. As agents such as monoclonal antibodies, small molecules inhibitors of tyrosine kinase, and direct inhibitors of proteins involved in lung cancer proliferation are being developed and tested, we are optimistic that these agents will result in improvement in the survival and quality of life of lung cancer patients.

Exacerbations of asthma and COPD are major causes of morbidity, mortality, and health-care costs. Over the last decade, studies using new molecular diagnostic techniques have established that respiratory viruses are a major cause of exacerbations of both asthma and COPD. The most prevalent viruses detected during exacerbations are the rhinoviruses. Despite the burden of disease associated with exacerbations, little is known about the mechanisms of virus-induced exacerbations of airway diseases. Exacerbations are associated with increased airway inflammation in patients with both asthma and COPD, but many questions remain unanswered regarding the key inflammatory cells and mediators involved. Identifying the key inflammatory mediators involved in exacerbations holds the promise of developing diagnostic and prognostic markers of exacerbation. In addition, such studies can identify new therapeutic targets for the development of novel drugs for the prevention and treatment of exacerbations.

In the past decade, three classes of medications have been approved for the treatment of pulmonary arterial hypertension. A review of the clinical trial data for the prostanoids, endothelin antagonists, and phosphodiesterase-5 inhibitors has shown that all agents have similar efficacy on the 6-min walk distance over 12 to 16 weeks, which was the primary end point in the randomized clinical trials. However, little is known about their long-term efficacy or about how these drugs affect the underlying disease, if at all. Successful therapy is currently defined as an improvement in exercise tolerance over a 4-month period. Future trials need to better characterize how therapies affect the pulmonary vasculature pathologically, biologically, and hemodynamically, and whether survival is actually improved.

Hypersomnia related to CNS disorders can be due to a variety of conditions. In this review, we discuss the diagnosis and treatment of narcolepsy with and without cataplexy, idiopathic hypersomnia, recurrent hypersomnia, and related illnesses. Research has provided insight into the underlying etiologies of these disorders, such as the genetic influences on disease development and the fundamental role of hypocretins in narcolepsy. We define the current utility of diagnostic testing, including sleep studies, neuroimaging techniques, and laboratory investigations. New treatment options for hypersomnia are discussed.

The prevalence of a right-to-left shunt, both cardiac and pulmonary, is high in patients with migraines, especially migraine with aura. Percutaneous closure of a right-to-left shunt seems to be associated with a pronounced decrease in the number of migraine attacks or its prevalence. In this review, the relationship between migraine and right-to-left shunting is described by highlighting the different pathophysiologic hypotheses.

Gene therapy has not yet met the high expectations of "the early days." However, it is a promising new treatment for lung diseases. Not only single gene disorders such as CF are potential candidates for gene therapy, but also cancer and chronic lung diseases characterized by an imbalance of damaging and protective mechanisms. This review summarizes the recent advances in the development of more efficient gene transfer systems and highlights areas of clinical application of gene therapy.

Until relatively recently, critical care practitioners have focused on the survival of their patients and not on long-term outcomes. The incidence of chronic neurocognitive dysfunction has been underestimated and underreported, and only recently has it been studied in critically ill patients. However, neurocognitive outcomes have been the subject of extensive investigation in other medical populations for many years.

Patients receiving heparin for thromboprophylaxis or treatment may have new or recurrent venous thromboembolism (VTE) if immune-mediated heparin-induced thrombocytopenia (HIT) occurs or for other reasons, eg, if anticoagulation fails. We estimated from the literature how frequently a patient presenting with VTE during or following heparin therapy has HIT-associated VTE.

Parasomnias are undesirable behavioral or experiential phenomena arising from the sleep period. Once felt to be a unitary phenomenon, it is now clear that a wide variety of sleep disorders are capable of resulting in complex behaviors arising during sleep. The most common are disorders of arousal and rapid eye movement sleep disorder. Less common conditions include nocturnal seizures and psychogenic dissociative states. Malingering and Munchausen syndrome by proxy, while they are not actually parasomnias, may masquerade as parasomnias. Careful clinical and sleep laboratory evaluation can usually provide an accurate diagnosis with effective therapeutic implications. Due to the potential forensic implications, sleep medicine specialists may be asked to participate in legal proceedings resulting from sleep-related violence. An awareness of the spectrum of such behaviors, and their clinical and legal evaluation, is becoming more important in the practice of sleep medicine.