Role and pharmacogenomics of TNF-alpha in asthma.

Asthma is a chronic heterogeneous inflammatory disease of the respiratory system in which numerous cytokines play a significant role. Among them TNF-alpha (tumour necrosis factor alpha), a proinflammatory cytokine, has a predominant role in orchestrating airway inflammation and affecting treatment outcome. In this review we attempt to summarize the involvement of TNF-alpha in the pathogenesis of asthma, illustrate variations of TNF-alpha gene that potentially influence asthma phenotype and highlight promising therapies by blocking the production of TNF-alpha or inhibiting its action. A cytokine specific target therapy seems to be very promising since agents that block TNF-alpha slow disease progression, suppress inflammation and in some cases induce remission of chronic inflammation.

Pulmonary alveolar microlithiasis in a patient with rheumatic valvular heart disease.

Pulmonary alveolar microlithiasis is a rare disease characterized by widespread intra-alveolar calcification of both lungs that is asymptomatic in the early stages. The disease typically follows a protracted course, and death can occur in 5 to 41 years after the initial diagnosis. Rheumatic fever is a multisystemic inflammatory disease that afflicts the child and juvenile population, and it is still very common in developing countries. Valve failure is the condition most linked to increased morbidity and mortality rates in this population and is the most severe complication of rheumatic fever, with consequent onset of chronic heart valve disease. We present a case of a female patient with a potential diagnosis of pulmonary alveolar microlithiasis with concurrent rheumatic valvular disease.

Genetics of chronic obstructive pulmonary disease, beyond a1-antitrypsin deficiency.

It is known that only 10-20% of smokers develop COPD, implying that apart from environmental features, additional factors such as genetic variability contribute to smoke susceptibility. This proposal is in compatibility with the "Dutch Hypothesis", formulated in the early 60's. Alpha-1-antitrypsin gene was implicated in the pathogenesis of COPD, especially the homozygous state of z allele. Since then many other genes have stepped forward as possible contributors to COPD development. In the present review we attempt to summarize the majority of these, including the genes of matrix metalloproteinases and their inhibitors, elastin, serpine2, tumor necrosis factor - a, transforming growth factor beta, a variety of interleukins and their receptors and antagonists, high affinity IgE receptor , human calcium-activated chloride channel 1, heme oxygenase, vascular endothelial growth factor, microsomal epoxide hydrolase, glutathione S-transferase, cytochrome P45O, superoxide dismutase, vitamin D binding protein, beta2-adrenergic receptor, Toll like receptor, human B defensins, mucins, cystic fibrosis transmembrane regulator, surfactant protein and Nuclear Factor E2 Related Factor 2.