Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042384 (vasculitis)
 20,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a 59-year-old male patient, chronic dry cough and dyspnoea on exertion preexisting for several years became rapidly progressive within a few weeks prior to hospitalisation. He died one month after admission from respiratory failure. Three months before admission, history, pulmonary function tests, and computed tomography (CT) of the chest revealed no evidence of asthma, COPD, or any other lung disease. Clinical examination showed no clubbing, but end-inspiratory velcro-rales were audible over both lungs. Inhaled steroids and diuretics did not bring clinical amelioration. On admission there were basal consolidations, bronchiectases, and predominant fibrotic changes with honeycombing and subpleural thickening over both lungs, in the absence of any ground-glass pattern in the CT. At the same time lymphocytosis predominated in bronchoalveolar lavage (BAL). The search for pneumonia, viral infection, tumour, vasculitis, or a drug-related disorder remained negative. Pathological examination at autopsy showed nonuniform fibrosing alveolitis.
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PMID:[Rapidly progressing respiratory insufficiency of uncertain etiology]. 1168 68

Alpha-1 antitrypsin (AAT) is a protein that prevents enzymes such as elastin from degrading normal host tissue. Individuals who are deficient in AAT (those with levels < 11 micromol/L) are at risk for developing such clinical manifestations as emphysema, cirrhosis, panniculitis, and anticytoplasmic neutrophilic antibody (C-ANCA)-positive vasculitis (Wegener's granulomatosis). Estimates suggest that 75 to 85% of those with severe deficiency of AAT will develop emphysema. Smoking appears to be the most important risk factor for the development of emphysema among AAT deficient persons. Severe deficiency of AAT also seems to be associated with a shorter lifespan. Among smokers, mild to moderate reductions in AAT levels may be associated with a more rapid decline in lung function. Diagnosis of AAT deficiency is made by measuring serum levels of AAT and, if reduced, an effort should then be made to identify the genetic abnormality responsible for the reduction. A recent evidence-based review has offered testing recommendations for AAT deficiency and includes the recommendation that all patients with COPD be tested for AAT deficiency. Augmentation with an intravenous form of purified pooled human plasma has been shown to increase the serum levels of AAT among deficient patients and its use appears to impact the rate of forced expiratory volume in 1 second (FEV (1)) decline and overall survival; to date, no confirmatory, large, prospective, randomized trials are available.
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PMID:A review of alpha-1 antitrypsin deficiency. 1608 34

Alpha-1 antitrypsin (AAT) deficiency is a common but under-recognized disease. This hereditary disorder is characterized by low levels of AAT, and increased risks of panacinar emphysema at an early age, liver disease, vasculitis and panniculitis. Destruction of lung parenchyma and consequent emphysema result from an imbalance between different inflammatory proteases (in particular, leukocyte elastase), and the major natural antiprotease, AAT. To offer a review of key aspects of this important condition, we present the epidemiology, natural history, and pathogenesis of AAT deficiency and, in the context of recent data and the publication of an international standards document regarding the diagnosis and management of individuals with AAT deficiency, review current therapy of AAT deficiency.
COPD 2005 Jun
PMID:A review of alpha-1 antitrypsin deficiency. 1713 53

Pulmonary artery hypertension secondary to chronic lung diseases is a clinical entity with no specific symptoms that can develop as a result of parenchymal lung disorders (COPD-emphysema, sleep apnea syndrome, diffuse parenchymal lung diseases, etc.) and pulmonary vascular disorders (vasculitis, sarcoidosis, etc.). In the clinical history of these chronic and invalidating diseases, pulmonary vasculature goes through various degenerative and/or proliferative changes, responsible of the pulmonary arterial hypertension appearance. The rise in pulmonary artery pressure can be subtle and the progression from an asymptomatic disease to a more severe syndrome is often common in all forms of secondary pulmonary arterial hypertension. Etiopathology of pulmonary artery hypertension secondary to chronic lung diseases is based on one or more of the following mechanisms: hypoxic vasoconstriction, decreased area of pulmonary vascular bed, volume/pressure overload. In these forms, the above three mechanisms show common mediators, all responsible of disease progression but singularly potential reversible. Therapies for secondary pulmonary artery hypertension consist primarily on the treatment of the underlying disease. Therapy is most effective when initiated prior to the onset of irreversible pulmonary vascular damage. In the last two decades, new medical treatments (prostacyclins, endothelin receptor antagonists, phosphodiesterase inhibitors) for pulmonary arterial hypertension have been available for the sporadic and the secondary to systemic sclerosis forms. The role of these drugs in the other forms of pulmonary arterial hypertension has not been well studied yet. This review will go through the pathogenesis and the several therapeutic approaches for pulmonary artery hypertension secondary to chronic pulmonary diseases or pulmonary vasculature disorders.
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PMID:Pulmonary arterial hypertension secondary to chronic lung diseases: pathogenesis and medical treatment. 1803 16

The past 50 years have seen huge advances in our understanding of the pathogenesis of alpha-1 antitrypsin deficiency. It is widely accepted that the common severe Z deficiency allele causes mutant alpha-1 antitrypsin to be retained as inclusions of ordered polymers within hepatocytes. This causes circulating deficiency of an important proteinase inhibitor, an excess of neutrophil elastase and therefore tissue destruction and emphysema. However, the past two decades have led to a shift in the paradigm from a disease that results from simply an imbalance of enzymes and inhibitors to one in which there is growing recognition that the polymers themselves play a role, not only in the liver disease, but also in the associated emphysema, vasculitis and panniculitis. Much of this has been dealt with in previous, more detailed reviews. I have therefore taken this opportunity of the 50th anniversary of the discovery of alpha-1 antitrypsin deficiency to present a personal overview of the past 22 years. This review considers the description of alpha-1 antitrypsin polymers, an assessment of their role in the different components of alpha-1 antitrypsin deficiency, the role of polymers in other diseases and how our understanding of polymerisation can be exploited to develop novel therapeutic strategies. The ultimate aim of our work is to develop a cure for alpha-1 antitrypsin deficiency.
COPD 2013 Mar
PMID:Twenty years of polymers: a personal perspective on alpha-1 antitrypsin deficiency. 2352 23

Alpha-1 antitrypsin (AAT) is the most abundant serine protease inhibitor circulating in the blood. AAT deficiency (AATD) is an autosomal codominant condition affecting an estimated 3.4 million individuals worldwide. The clinical disease associated with AATD can present in a number of ways including COPD, liver disease, panniculitis and antineutrophil cytoplasmic antibody vasculitis. AATD is the only proven genetic risk factor for the development of COPD, and deficient individuals who smoke are disposed to more aggressive disease. Principally, AAT is a serine protease inhibitor; however, over the past number of years, the assessment of AAT as simply an antiprotease has evolved, and it is now recognized that AAT has significant anti-inflammatory properties affecting a wide range of cells, including the circulating neutrophil.
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PMID:The impact of alpha-1 antitrypsin augmentation therapy on neutrophil-driven respiratory disease in deficient individuals. 2961 37