Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034067 (emphysema)
 11,506 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Severe alpha1-antitrypsin (AAT) deficiency predisposes to emphysema development. Highly variable rates of decline in lung function are reported in PiZZ individuals. The annual decline in forced expiratory volume in one second (FEV1; delta FEV1) was analysed in relation to smoking status in a cohort of 608 adult PiZZ individuals included in the Swedish national AAT deficiency register. Delta FEV1 was analysed in 211 never-smokers, in 351 exsmokers, and in 46 current smokers after performing at least two spirometries during a follow-up time of 1 yr or longer (median 5.5 yrs, range 1-31). The adjusted mean delta FEV1 in never-smokers was 47 mL x yr(-1) (95% confidence interval (CI) 41-53 mL x yr(-1)), 41 mL x yr(-1) (95% CI 36-48 mL x yr(-1)) in exsmokers, and 70 mL x yr(-1) (95% CI 58-82 mL x yr(-1)) in current smokers. A dose-response relationship was found between cigarette consumption and delta FEV1 in current smokers and exsmokers. In never-smokers, a greater delta FEV1 was found after 50 yrs of age than before. No sex differences were found in delta FEV1. In conclusion, among PiZZ individuals, the change in forced expiratory volume in one second is essentially the same in never-smokers and exsmokers. Smoking is associated with a dose-dependent increase in the change in forced expiratory volume in one second.
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PMID:Decline in FEV1 related to smoking status in individuals with severe alpha1-antitrypsin deficiency (PiZZ). 1006 63

Although alpha(1)-antitrypsin (AAT) deficiency is one of the most common hereditary diseases and a recognized cause of emphysema in Caucasians, variants of this deficiency are extremely rare among Orientals. We present here a Japanese emphysema patient with the AAT deficiency variant originally identified as S(iiyama). After an 8-year follow-up period, the patient suffered from repeated pulmonary Pseudomonas aeruginosa infection for 4 years. He died suddenly of massive pulmonary hemorrhage. The pathologic examination revealed a necrotic hematoma in the right S10 lobe, which exhibited pneumonia due to cytomegalovirus (CMV) infection. Pulmonary hemorrhage due to CMV can occur and be fatal in patients with emphysema and AAT deficiency.
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PMID:Massive pulmonary hemorrhage due to cytomegalovirus infection in a Japanese patient with alpha-1-antitrypsin-deficient emphysema. 1046 Oct 90

Alpha-1-antitrypsin deficiency is a common genetic defect associated with the development of severe and rapidly progressive lung disease. This study was undertaken to determine whether respiratory physicians manage patients with alpha-1-antitrypsin (AAT) deficiency differently from patients with chronic obstructive pulmonary disease (COPD) without alpha-1-antitrypsin deficiency. In addition we obtained physicians' views on who should be tested for AAT deficiency. A questionnaire was administered to 88 respiratory physicians based throughout the U.K. (44 in teaching hospitals). The main outcome measures were pulmonary function tests, radiological assessment, frequency of repeat testing, follow-up and screening protocol for alpha-1-antitrypsin deficiency. Subjects with homozygous (PiZ) AAT deficiency were more likely to: 1. have baseline and full pulmonary function testing including dynamic flow rates, static lung volumes, and gas transfer; 2. have more comprehensive assessment with high resolution computed tomography (HRCT) thorax and repeated radiological assessment (with annual chest radiography); 3. be followed-up routinely; and 4. have family members tested for alpha-1-antitrypsin deficiency. Testing remains limited for AAT deficiency and is mainly restricted to young patients with COPD. COPD assessment and management is influenced by the presence of AAT deficiency, which may reflect the poorer prognosis of such patients due to more rapid decline. Assessment and monitoring could be simplified to forced expired manoeuvres, although limited HRCT thorax and tests of gas transfer may prove more sensitive to progression of emphysema. Testing for AAT deficiency in the U.K. remains restricted, which will influence the detection rate for AAT deficiency. A wider policy of testing was advocated by the WHO will detect more patients and also influence our understanding of the natural history of the condition.
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PMID:Chronic obstructive pulmonary disease, with and without alpha-1-antitrypsin deficiency: management practices in the U.K. 1046 35

alpha 1-antitrypsin (AAT) deficiency is an inherited condition characterized by low serum levels of AAT and an increased risk of developing pulmonary emphysema. The disease occurs mainly in Caucasians, but Southern Europe, including Italy, is considered a low prevalence area. We developed a national program in Italy in order to improve our knowledge of the epidemiology of AAT deficiency and to establish a registry of the AAT-deficient individuals. The program had two phases: the first lasted 36 months, during which blood from coupons mailed by respiratory physicians from throughout the country, was isoelectrofocused by the Central Laboratory in Rome. The second phase started in February 1996, and the Registry was established. Up to August 1998, 151 subjects with AAT deficiency have been identified and 64 have been enrolled in the Registry. We believe that such a program plays a crucial role in identifying AAT deficiency in a country such as Italy, with low prevalence and low awareness of this rare condition.
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PMID:A national program for detection of alpha 1-antitrypsin deficiency in Italy. Gruppo I.D.A. 1046 73

Patients with homozygous (PiZ) alpha(1)-antitrypsin (AAT) deficiency have not only low baseline serum AAT levels (approximately 10 to 15% normal) but also an attenuated acute phase response. They are susceptible to the development of premature emphysema but may also be particularly susceptible to lung damage during bacterial exacerbations when there will be a significant neutrophil influx. The purposes of the present study were to assess the inflammatory nature of acute bacterial exacerbations of chronic obstructive pulmonary disease (COPD) in subjects with AAT deficiency, to compare this with COPD patients without deficiency, and to monitor the inflammatory process and its resolution following appropriate antibacterial therapy. At the start of the exacerbation, patients with AAT deficiency had lower sputum AAT (p < 0.001) and secretory leukoprotease inhibitor (SLPI; p = 0.02) with higher elastase activity (p = 0.02) compared with COPD patients without deficiency. Both groups had a comparable acute phase response as assessed by C-reactive protein (CRP) but the AAT-deficient patients had a minimal rise in serum AAT (to < 6 microM). After treatment with antibiotics, in patients with AAT deficiency, there were significant changes in many sputum proteins including a rise in SLPI levels, and a reduction in myeloperoxidase (MPO) and elastase activity (p < 0. 005 for all measures); the sputum chemoattractants interleukin-8 (IL-8) and leukotriene B(4) (LTB(4)) fell (p < 0.01), and protein leak (sputum/serum albumin ratio) became lower (p < 0.01). The changes were rapid and within 3 d of the commencement of antibiotic therapy the biochemical markers had decreased significantly, but took a variable time thereafter to return to baseline values. In conclusion, patients with AAT deficiency had evidence of increased elastase activity at the start of the exacerbation when compared with nondeficient COPD patients which probably reflects a deficient antiproteinase screen (lower sputum AAT and SLPI). The increased bronchial inflammation at presentation resolved rapidly with 14 d of antibiotic therapy.
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PMID:Evidence for excessive bronchial inflammation during an acute exacerbation of chronic obstructive pulmonary disease in patients with alpha(1)-antitrypsin deficiency (PiZ). 1058 15

Alpha-1-antitrypsin deficiency results from point mutations that distort the structure of the protein to allow a unique protein-protein interaction that we have termed loopsheet polymerisation. Polymers of Z alpha 1-antitrypsin accumulate within hepatocytes to form inclusion bodies that are associated with juvenile cirrhosis and hepatocellular carcinoma. The lack of circulating protein predisposes the Z alpha 1-antitrypsin homozygote to emphysema. This process also occurs in other members of the serine proteinase inhibitor (serpin) superfamily, antithrombin, C1-inhibitor and alpha 1-antichymotrypsin, in association with thrombosis, angioedema and chronic obstructive pulmonary disease, respectively, and we have recently shown that it underlies a novel inclusion body dementia. The interaction provides a useful paradigm for other 'conformational diseases' such as Huntington's disease, Creutzfeldt-Jakob disease and the amyloidoses.
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PMID:Alpha-1-antitrypsin deficiency, the serpinopathies and conformational disease. 1090 27

We evaluated the ability of intravenous supplementation therapy with alpha(1)-antitrypsin (AAT) to reduce the rate of urinary excretion of desmosine (DES), a specific marker of elastin degradation, in eight men and four women with emphysema due to severe, congenital deficiency of AAT (range 17-69 mg/dl). Nine were former cigarette smokers, two were current smokers, and one reported never smoking; their mean age was 54 (SD 12) yr and their mean FEV(1) was 41 (18%) of predicted. Urinary DES was measured by isotope dilution and HPLC. Prior to the start of AAT supplementation, mean DES excretion was 13.0 (5.0) microg/g creatinine, 73% higher than in healthy nonsmokers. During 8 wk of supplementation therapy, mean urinary DES excretion was 13.0 (5.9) microg/g creatinine, unchanged from the baseline period (p = 0.85 by repeated measures ANOVA). We conclude that baseline levels of elastin degradation in emphysematous patients with severe AAT deficiency were abnormally high and that 8 wk of AAT supplementation therapy did not appreciably reduce the rate of elastin degradation. These findings raise the possibilities that protective levels of AAT in the lungs are insufficient or that elastin degradation in the lungs of these subjects is not dependent upon neutrophil elastase at this time.
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PMID:Short-term supplementation therapy does not affect elastin degradation in severe alpha(1)-antitrypsin deficiency. The American-Italian AATD Study Group. 1111 16

The patient had chronic incapacitating headaches for a period of eight years. Neurologic tests ruling out organic causes such as tumors and analysis of diet, allergies, stress levels, and chronic infections left the patient and physicians without an explanation. The headaches did not fit the patterns of common or classic migraines. The patient's energy level had significantly decreased during this same time period, and she had frequently become short of breath. Diagnosis of underlying pathology occurred when efforts were focused on explaining respiratory conditions. The patient had an oxygen saturation of 77% and a pulse of 98, following a brief walk around the building. Further testing by a pulmonary specialist confirmed diagnosis of emphysema secondary to a deficiency of Alpha-1 Antitrypsin (AAT). Background materials supporting this case history include: a model for AAT function, genetics of AAT deficiency, pathophysiology of both liver and pulmonary diseases, and a summary of treatment options and prognosis for AAT deficient patients.
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PMID:Eight years of unexplained headaches (why did the diagnosis take so long?). 1176 Aug 19

We report panniculitis revealing alpha-1 antitrypsin deficiency in 3 patients with different Pi phenotypes. The first patient, a 16-year-old woman, had inflammatory skin lesions on the abdomen for 6 months. The lesions regressed spontaneously. Serum alph-1 antitrypsin level was normal but the Pi phenotype was MS. The second case was observed in a 56-year-old man who developed erythematous subcutaneous nodules on the abdomen, legs and buttocks in a trauma context. Serum alpha-1 antitrypsin was very low and the Pi phenotype was ZZ. The third patient was a 40-year-old woman who presented red swelling nodules on the legs. Her serum alpha-1 antitrypsin level was at the lower limit of normal and the Pi phenotype was MZ. Alpha-1 antitrypsin deficiency is an autosomic codominant inherited disorder characterized by inefficient or non-functional serum alpha-1 antitrypsin. The principal clinical manifestations are panlobular emphysema and cirrhoses. About 30 cases of panniculitis have been reported in the literature. In patients presenting panniculitis, we suggest studying the Pi phenotype to determine functional deficiency even if the serum level of alpha-1 antitrypsin is normal.
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PMID:[Panniculitis revealing alpha-1 antitrypsin deficiency. Report of 3 cases]. 1193 84

Panacinar emphysema is the most characteristic pulmonary disease in patients with alpha1-antitrypsin deficiency (AAT). Bronchiectasis can also arise with AAT deficiency, although the association is much less common and no clear cause-effect relationship has yet been established. We report the case of a woman who presented with bronchiectasis and PiSZ-phenotype ATT deficiency, without emphysema. A review of the literature showed that the case is exceptional.
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PMID:[PiSZ-phenotype alpha 1-antitrypsin deficiency: a rare cause of bronchiectasis]. 1202 34


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