Respiration; international review of thoracic diseases
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Chronic Obstructive Pulmonary Disease (COPD) is one of the leading causes of morbidity and mortality in the industrialized and the developing countries. During 1997, COPD has been estimated to be the number four cause of death after cardiovascular diseases, tumors and cerebrovascular diseases in the United States. In 2020 COPD will probably become the third leading cause of death all over the world, following the trend of increasing prevalence of lung cancer. ⋯ Furthermore, in the etiology of COPD we must consider endogenous risk factors such as gender, genetic features, presence of respiratory troubles in childhood, and family history. To date, epidemiologic studies have been of great importance for the characterization of the disease at a population level, indicating possible causes and assessing its impact on the individual and on society as a whole. Unfortunately, international standards for the diagnosis of COPD are lacking, which complicates the organization of appropriate epidemiological surveys.
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There is a pressing need for more effective drug treatments for COPD. New bronchodilators include a long-acting anticholinergic tiotropium bromide and a dual beta2-dopamine2-receptor agonist. But no treatments prevent the progression of COPD. ⋯ These include phosphodiesterase-4 inhibitors, nuclear factor-kappaB inhibitors and p38 MAP kinase inhibitors. Small molecule protease inhibitors, including neutrophil elastase inhibitors and selective matrix metalloproteinase inhibitors are also in development. Future drug targets may be identified by gene array and proteomics.
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Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene which encodes a protein expressed in the apical membrane of exocrine epithelial cells. CFTR functions principally as a cAMP-induced chloride channel and appears capable of regulating other ion channels. Besides the most common mutation, DeltaF508, accounting for about 70% of CF chromosomes worldwide, more than 850 mutant alleles have been reported to the CF Genetic Analysis Consortium. ⋯ Besides patients with atypical CF, there are large numbers of so-called monosymptomatic diseases such as various forms of obstructive azoospermia, idiopathic pancreatitis or disseminated bronchiectasis associated with CFTR mutations uncharacteristic for CF. The composition, frequency and type of CFTR mutations/variants parallel the spectrum of CFTR-associated phenotypes, from classic CF to mild monosymptomatic presentations. Expansion of the spectrum of disease associated with the CFTR mutant genes creates a need for revision of the diagnostic criteria for CF and a dilemma for setting nosologic boundaries between CF and other diseases with CFTR etiology.
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Pulmonary infections decisively contribute to morbidity and mortality in immunocompromised patients. Bacterial, mycobacterial and infections with Pneumocystis carinii have been reviewed in an article in the last issue of Respiration. In this review, viral and fungal pulmonary infections are discussed in HIV-positive patients and in patients treated with high-dose chemotherapy, stem cell or solid-organ transplantation.
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Leadership will play a major role in the management of tuberculosis in the future. Many populations, such as immunocompromised patients and immigrants from countries with a higher prevalence of tuberculosis, create a challenge for care and diagnosis. Mycobacterial laboratory testing has undergone many changes in the past 10 years with the advent of nucleic acid probes for identification of Mycobacterium tuberculosis, and more recently nucleic acid amplification and beyond where computer technology meets molecular biology. ⋯ New technologies can be provided to all users of such a network within a short amount of time and health care providers can equally benefit from this novel approach. The tuberculosis laboratory cannot stand alone. It must work together with other players, in order to eliminate tuberculosis.