Alpha 1-antitrypsin Concentration Research Articles

THE RELATIONSHIP BETWEEN ALPHA-1 ANTITRYPSIN LEVELS AND LESS COMMON NON-MM PHENOTYPES IN SOUTHEASTERN KENTUCKY

PURPOSE: Non-MM phenotype's serum concentration of alpha-1 antitrypsin (AAT) were reported to be lower than the levels in MM phenotype subjects. This study is to determine the correlation between serum AAT levels and phenotype in less commonly reported phenotypes.

Dauersubstitution bei homozygotem α1-Antitrypsin-Mangel: Einfluß auf das Proteinasen-Antiproteinasen-Gleichgewicht in Plasma und Sputum

Long-term replacement with human alpha 1-antitrypsin (60 mg/kg once a week intravenously) was carried out in seven patients with homozygous alpha 1-antitrypsin deficiency (7 males, mean age 50.8 [40-59] years) and progressive pulmonary emphysema for an average of 16 (13-20) weeks. After at least 12 weeks' therapy the concentrations of alpha 1-antitrypsin, elastase-alpha 1-antitrypsin complex, alpha 2-macroglobulin, lactoferrin and elastase inhibition capacity in plasma and sputum were assayed, these assays being performed before starting the alpha 1-antitrypsin infusion and at various times during the following week. After the infusion the plasma concentration of alpha 1-antitrypsin rose from a depressed initial level (median 1.22 g/l) to a level approximately five times higher (median after 1 hour: 5.96 g/l, P less than 0.001), and then declined exponentially, though it never fell below the threshold of 35% of normal which is regarded as the protective level. Elastase inhibition capacity displayed similar changes (r = 0.85). The sputum concentration of alpha 1-antitrypsin rose more slowly than the plasma concentration; from the initial level (median 8 mg/l) it reached a maximum about four times higher after 24 hours (median 36 mg/l; P less than 0.02). Elastase inhibition capacity rose from 151 mIU/ml (median) before the alpha 1-antitrypsin infusion to 450 mIU/ml at 24 hours. These findings suggest that alpha 1-antitrypsin replacement will have beneficial effects on proteinase-antiproteinase equilibrium. Determination of elastase inhibition capacity in the sputum is suitable for monitoring dosage during replacement therapy.

Alpha-1 antitrypsin Null mutations and severity of emphysema

Alpha-1 antitrypsin (AAT) deficiency is an autosomal-codominant disorder, caused by mutations in the SERPINA1 gene on chromosome 14. Individuals affected by the most common mutations, SZ and ZZ, have serum AAT concentrations of 25% and 15% of normal levels, and present a higher risk of emphysema. Mutations causing total absence of serum AAT (Null mutations) were suggested to be associated with very early onset emphysema but their clinical phenotype is poorly known. Absence of AAT in Null mutations results in more severe emphysema as compared to ZZ and SZ. We genotyped all known Dutch subjects (n=12) with absent serum AAT, and compared their lung function values (FEV1 and KCO) with those of individuals with ZZ and SZ genotype, matched for age and smoking history. All subjects with absent serum AAT presented homozygous Null mutations. In three subjects, a new mutation in exon 2 of the SERPINA1 gene was found. Subjects with Null mutations showed significantly lower lung function values than SZ and ZZ individuals (p=0.000 and 0.001 for FEV1 and KCO, respectively). In all groups, there was a positive correlation between serum AAT and lung function values (p=0.025 and 0.014 for FEV1 and KCO, respectively). Serum levels of AAT are correlated with the severity of pulmonary phenotype. Subjects with Null mutations should be considered a subgroup at particularly high risk of emphysema within AAT deficiency (AATD). Early detection of carriers of this genotype would be important for preventive and therapeutic interventions.

Evaluation of a new Sebia isoelectrofocusing kit for α1-antitrypsin phenotyping with the Hydrasys® System

Laboratory evaluation of alpha 1-antitrypsin (A1AT) deficiency is generally performed by determination of A1AT concentrations and identification of specific allelic variants by phenotyping. For this purpose, we evaluated a new Hydragel 18 A1AT Isofocusing kit on the semi-automatic Hydrasys System (Sebia) for the determination of A1AT phenotypes by isoelectrofocusing on ready-to-use agarose gels with specific immunological detection. Serum samples from 66 patients were analysed with this new kit in comparison with the conventional and manually performed isoelectrofocusing method on polyacrylamide gels with Coomassie Blue staining. A1AT phenotypes showed comparable iso-electrofocusing patterns in both systems. The good within-gel reproducibility of this kit was demonstrated using two normal serum samples (M1 and M1M2 phenotypes) and six pathological serum samples with different phenotypes (MS, SS, SZ, MZ, ZZ). A sensitivity study was undertaken by performing serial dilutions on a serum with a ZZ phenotype containing 0.27 g/L A1AT. The detection limit was 0.050 g/L. This new method is highly specific, rapid and simple to perform. It improves identification of not only the most common but also various rare A1AT phenotypes. It appears to be suitable for routine analysis and screening applications in a clinical laboratory setting.

Relationship between serum sialic acid and sialylated glycoproteins in alcoholics

Total sialic acid (TSA) has been suggested as a marker for chronic alcohol abuse. It seems that the elevation of TSA during excessive alcohol consumption reflects the changes in sialylated glycoproteins in the sera. On the other hand, chronic ethanol consumption increases the desialylation rate of many serum glycoproteins. The aim of this study was to evaluate the relationship between the total and free form of sialic acid levels (FSA), and the concentration of sialylated glycoproteins in alcoholics. We determined the serum concentration of many glycoproteins (alpha1-antitrypsin, alpha1-acid glycoprotein, haptoglobin, ceruloplasmin, transferrin, complement C3 protein, fibrinogen and immunoglobulin G) in a sample of 100 alcoholics and 30 healthy controls. Total sialic acid was determined by the enzymatic method and its free form by using a modification of the thiobarbituric acid method. Among alcoholics, we found increased concentrations of alpha1-antitrypsin and alpha1-acid glycoprotein but decreased levels of transferrin. The concentrations of TSA and FSA were significantly higher in alcoholics than in healthy controls. The tested glycoproteins, except for transferrin and immunoglobulin G, positively correlated with TSA and FSA. The correlations with TSA were higher than that with FSA. Chronic alcohol abuse alters the concentrations of some sialylated glycoproteins in the sera. The alpha1-antitrypsin, alpha1-acid glycoprotein, and transferrin are the only affected glycoproteins. The serum level of total and free form of sialic acid in the sera of alcoholics depends on the concentration of the most sialylated glycoproteins.

ALPHA-1 ANTITRYPSIN PHENOTYPE AND GENOTYPE IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)

PURPOSE: Alpha-1 Antitrypsin (AAT) deficiency is one common lethal genetic cause of emphysema in adults. The World Health Organization (WHO) recommends detection of AAT level in patients with Chronic Obstructive Pulmonary Disease (COPD) and Asthma. The abnormally low plasma concentrations of AAT in individuals predisposes them to elevated risk of early pulmonary emphysema and in some occasions hepatic damage. The PiZZ phenotype is the most frequently associated with low plasma concentrations of AAT.However much of this data comes from fully developed regions such as North America and Europe.

Nasal inflammation and personal exposure to fine particles PM2.5 in asthmatic children

Outdoor and indoor air pollutants are suspected to induce harmful effects on respiratory health, raising the question of their involvement in allergic asthma and rhinitis. The potential effect of short-term personal exposure to particulate matter with a diameter of less than 2.5 microm (PM2.5) on nasal inflammation was examined in children living in the Paris area. Forty-one children with allergic asthma and 44 healthy children participated in this study. They were monitored during 48 hours for their personal exposure to PM2.5. At the end of the measurement period, children underwent one nasal lavage. Nasal lavage fluid was investigated for cellular (neutrophils and eosinophils) and soluble (albumin, urea, elastase, alpha1-antitrypsin, IL-6, and IL-8) mediators. Pollutant concentrations did not differ between the 2 groups. In asthmatic subjects, but not in healthy children, personal PM2.5 levels were correlated to nasal percentage of eosinophils and to albumin, urea, and alpha1-antitrypsin concentrations after adjustment for confounders (age, sex, house dust mites, pollens, cat, environmental tobacco smoke through urinary cotinine, barometric pressure, and respiratory infection). The association observed with the percentage of eosinophils supports recent speculations on fine particle involvement in allergic phenotype overexpression. This study highlights the link between personal fine particle exposures and nasal inflammation in asthmatic allergic children living in urban areas. Because the view of united airways is still not completely understood, the question of pulmonary inflammation in such a situation deserves further investigation.

Alpha‐1‐‐antitrypsin in aqueous humour from patients with corneal allograft rejection

To investigate the presence and concentration of alpha1-antitrypsin in aqueous humour at the time of corneal rejection and to compare results obtained from patients with reversible and irreversible rejection. Samples of aqueous humour were obtained from 17 patients with acute corneal endothelial allograft rejection. The presence of alpha1-antitrypsin in aqueous humour was confirmed by immunoblotting and measured employing a sandwich ELISA. Total protein concentrations in aqueous humour were measured using Bradford's method. The outcome of corneal rejection episodes was determined 1 month after diagnosing corneal rejection and described as reversible or irreversible rejection. alpha1-antitrypsin was detected in aqueous humour. Patients with reversible rejection had significantly higher alpha1-antitrypsin concentration than patients with irreversible rejection (p = 0.044). There was no significant difference in total protein concentrations (p = 0.745), and no correlation was found between alpha1-antitrypsin and total protein concentrations (p = 0.368). alpha1-antitrypsin in aqueous humour seems to signal a favourable outcome of corneal rejection. The possible mechanism is discussed.

Elastin metabolism in pelvic tissues: Is it modulated by reproductive hormones?

The purpose of this study was to investigate the effect of relaxin on extracellular matrix protein expression in pelvic fibroblasts that were cultured from women with stress urinary incontinence compared with asymptomatic control subjects. Periurethral vaginal wall fibroblasts from premenopausal women with stress urinary incontinence and continent women (in both the proliferative and secretory phase of the menstrual cycle) were stimulated with increasing concentrations of relaxin (0-500 ng/mL). The supernatant was sampled for matrix metalloproteinase-2 and -9 by zymography. Tissue inhibitors of metalloproteinase-1 and -2 and alpha-1 antitrypsin were evaluated with Western blot. Total elastase activity was measured by generation of free amino groups from succinylated elastin. Increasing concentrations of alpha-1 antitrypsin were added to cell lysate to evaluate total elastase activity inhibition. Proliferative-phase stress urinary incontinence fibroblasts demonstrated an increase in matrix metalloproteinase-2 and no change in matrix metalloproteinase-9 and tissue inhibitors of metalloproteinase-1 and -2 expressions with increasing relaxin concentrations. Cells from control subjects showed increased expression of matrix metalloproteinase-2 and -9, but no change in tissue inhibitors of metalloproteinases. Secretory-phase stress urinary incontinence fibroblasts showed no response in matrix metalloproteinase or tissue inhibitors of metalloproteinase expressions with relaxin stimulation. Secretory-phase control fibroblasts reacted by increasing matrix metalloproteinase-2 and -9 and tissue inhibitors of metalloproteinase-2. With respect to total elastase activity and alpha-1 antitrypsin expression, increasing doses of relaxin appear to increase elastolytic activity in stress urinary incontinence cells by decreasing the expression of alpha-1 antitrypsin in proliferative phase cells or increasing the total elastase activity in secretory phase cells. Fibroblast total elastase activity was inhibited by increasing concentrations of alpha-1 antitrypsin. Elastase activity appears to be increased in relaxin-stimulated stress urinary incontinence fibroblasts by either decreased inhibitor (alpha-1 antitrypsin) production or increased elastase activity.

α1‐Antitrypsin genotypes in Korean patients with chronic obstructive pulmonary disease

Alpha1-antitrypsin (AAT) deficiency is a recognized susceptible factor for chronic obstructive pulmonary disease (COPD) in Western countries, but its importance in Korea is unclear. To date, no definitive case of alpha1-antitrypsin deficiency has been reported in Korea. This study aimed to clarify whether alpha1-antitrypsin deficiency exists and to determine the distribution of alpha1-antitrypsin alleles in the Korean population. The serum concentrations of alpha1-antitrypsin were determined and polymorphisms of the alpha1-antitrypsin gene in 114 COPD patients and in 196 healthy controls were examined. Phenotyping by isoelectric focusing and the genotyping of alpha1-antitrypsin gene by polymerase chain reaction and restriction fragment length polymorphism were performed. No alpha1-antitrypsin level abnormality was found in the patients. M1(Val)/M1(Val) was found to be the most frequent genotype in both groups (69.2% and 66.8%, respectively), and M1(Val) the most frequent allele. The distributions of alpha1-antitrypsin alleles were similar in the patient and control groups, and no S or Z allele was found. Alpha1-antitrypsin deficiency is unlikely to be an important cause of chronic obstructive pulmonary disease in the Korean population.

Protein losing enteropathy in critically ill adult patients with burns: a preliminary report.

Few data have been published regarding protein losing enteropathy in adult patients with burns. This study characterised the presence of protein-losing enteropathy in adults with burns and examined the relationship between the magnitude of burn size and the severity of protein loss. Twenty adult patients with burns (BSA 31+/-25%, range 2-80%) were studied. Fluid resuscitation was based on the Parkland's formula. Protein loss into the gastrointestinal tract was measured using faecal alpha1-antitrypsin (FA-1-AT) concentrations. Serial measurements of serum protein and albumin concentrations were performed. Fourteen patients demonstrated elevations in FA-1-AT levels. The mean peak FA-1-AT level was 3.6+/-4.2 mg/g dry weight of stool. Two patients demonstrated elevated FA-1-AT excretion 1.5 months and 3 months after the burns. There was a good correlation between burn size and FA-1-AT excretion (R2=0.40). Protein losing enteropathy was demonstrable in patients with major burns. The magnitude of this phenomenon appears to be proportional to the burns size.

Fecal alpha1-antitrypsin concentrations as a measure of enteric protein loss after modified fontan operations.

Little is known about the enteric protein loss in patients after a modified Fontan operation before the appearance of overt symptoms or signs of protein-losing enteropathy (PLE). The authors examined the possibility of using fecal alpha1-antitrypsin concentration measurements for the early detection of postoperative PLE and in longer term postoperative monitoring of these patients. The authors compared fecal alpha1-antitrypsin concentrations in stool samples from 12 children 12.0 to 43.7 months after modified Fontan operations with those of 12 age-matched control subjects and examined the relationship between the alpha1-antitrypsin levels and time since operation. The authors also compared fecal alpha1-antitrypsin concentrations of stools from the same patients obtained at two different time points after surgery with intervals between samples ranging from 14.7 to 19.8 months. No significant differences in serum total protein and albumin levels were observed between patients after the modified Fontan operation and control subjects. The fecal concentrations of alpha1-antitrypsin in patients after the Fontan operation were significantly (P < 0.01) higher than those in control subjects. There was no significant correlation between fecal alpha1-antitrypsin concentrations and time elapsed after the Fontan operation. The fecal alpha1-antitrypsin concentration increased significantly (P < 0.01) over periods of 14.7 to 19.8 months after the first measurement. The results show that enteric protein loss begins before the appearance of hypoproteinemia in patients after a modified Fontan operation, and that the measurement of fecal alpha1-antitrypsin concentrations in random stool samples is useful as an early indicator. To watch for the development of PLE after Fontan operation, it may be important to perform longitudinal follow-up examinations of enteric protein loss by measuring fecal alpha1-antitrypsin concentrations early in the postoperative period.

Inhibition of proteinase 3 by [alpha]1-antitrypsin in vitro predicts very fast inhibition in vivo.

Neutrophil proteinase 3 (Pr3) cleaves elastin and other matrix proteins, and is thought to cause lung tissue destruction in emphysema and cystic fibrosis. Its deleterious action is theoretically prevented by alpha1-antitrypsin, a serpin present in lung secretions. We have evaluated the anti-Pr3 activity of this inhibitor to decide whether it may play a physiologic proteolysis-preventing function in vivo. We show that (i). the oxidized inhibitor does not inhibit Pr3; (ii). the inhibitor competes favorably with elastin for the binding of Pr3, but is less efficient for inhibiting elastin-bound proteinase than for complexing free enzyme; and (iii). the inhibition takes place in at least two steps: the enzyme and the inhibitor first form a high-affinity reversible inhibitory complex EI* with an equilibrium dissociation constant K*i of 38 nM; EI* subsequently transforms into an irreversible complex EI with a first-order rate constant k2 of 0.04 s-1. Because the alpha1-antitrypsin concentration in the epithelial lining fluid is much higher than K*i, any Pr3 molecule released from neutrophils will be taken up as an EI* complex within much less than 1 s, indicating very efficient inhibition in vivo.

Programa de cribado para el déficit de α-antitripsina en pacientes con EPOC mediante el uso de gota de sangre en papel secante

Alpha-1 antitrypsin (AAT) deficiency is an under-diagnosed disease and screening programs have therefore been recommended for patients with chronic obstructive pulmonary disease (COPD). We present the results of the pilot phase of a screening program for AAT deficiency in order to evaluate the technique used, the procedures for transporting samples and the results obtained. Over a period of one month, five centers collected samples from all COPD patients for whom plasma concentrations of AAT or Pi phenotype had not yet been determined. Capillary blood spots were dried on filter paper and then sent by surface mail to a central laboratory for study. An immunonephelometric assay was used to determine AAT and DNA phenotyping was done by use of a Light Cycler. Samples were analyzed from 86 COPD patients (76 men, 10 women) with a mean age of 68.2 years. AAT deficiency was ruled out for 74 patients (86%) who had concentrations above the cutoff established, although one of them was MZ heterozygote by genotype. Among the 12 remaining patients (13.9%), only two also had a Z allele. The rest were individuals with concentrations below the established threshold and no evidence of a Z allele (10 patients, 11.6%). The Z allele frequency observed (3/172; 1.74%) was very similar to that found in the general population. The results of this pilot study allowed us to confirm that the method used to collect samples worked well. The sampling method is applicable, easy and well-accepted by participating physicians. It allowed AAT concentrations and Z allele deficiency to be determined. The method correlates well with standard techniques used for samples in whole blood.

Effect of an 8-month treatment with omega-3 fatty acids (eicosapentaenoic and docosahexaenoic) in patients with cystic fibrosis.

Supplementation of the diet with eicosapentaenoic acid and docosahexaenoic acid, the main long-chain omega-3 fatty acids in cell membranes, may have beneficial effects in patients with cystic fibrosis. A prospective study involving 30 patients and 20 control subjects was carried out; eicosapentaenoic plus docosahexaenoic acid was equal to 1.3% of caloric intake in the cystic fibrosis patients. Our present study included the evaluation of eicosapentaenoic and docosahexaenoic acid incorporation into erythrocyte membranes and biological and clinical effects in response to long-term (8 months) supplementation with fish oil as a source of eicosapentaenoic and docosahexaenoic acids in patients with cystic fibrosis. Baseline erythrocyte membrane fatty acids showed low levels of linoleic acid and eicosapentaenoic acid and mild elevation of 18:3n6, but similar docosahexanoic acid and other fatty acids in cystic fibrosis patients compared with controls. Fish oil supplementation led to a 1.7-fold (p < .05) and 1.3-fold (not significant) increase of eicosapentaenoic acid in erythrocyte membrane phospholipids after 4 and 8 months of supplementation, respectively, and to a 1.67-fold (p < .05) and 1.38-fold (p < .05) increase of docosahexanoic acid, respectively. Along with these changes, there was a progressive decrease of arachidonic acid (from 8.51 to 6.67 g/100 fatty acids at 4 months and 4.83 g/100 fatty acids at 8 months; p < .05) and an increase of linoleic acid (p < .05) in membrane phospholipids. Analysis of inflammatory markers showed a significant decrease of serum immunoglobulin G (IgG) and of alpha-1 antitrypsin (p < .05) concentrations. Pulmonary function testing showed mild but significant improvement of forced expiratory volume (FEV)-1 from 61% +/- 19% to 57% +/- 19% of predicted values (p < .05). The number of days of antibiotic therapy during the study period was markedly lower compared with the preceding 8-month period (392 versus 721 days; p < .05). Long-term eicosapentaenoic plus docosahexanoic acid supplementation (8 months) has positive effects, such as decreasing inflammation, in cystic fibrosis.

Gene therapy progress and prospects: alpha-1 antitrypsin.

Over the 2 years covered here, there has been one clinical study in which a normal alpha-1 antitrypsin (AAT) gene was delivered to the nasal epithelium of AAT-deficient subjects using plasmid-liposome complexes; a second study using an adeno-associated vector should begin soon. Although progress in clinical studies has been slow, advances in both viral and nonviral vector designs show considerable promise. Strategies that combine liposome technology with imaginative vector design may permit long-term expression of a normal transgene that is sufficient to achieve therapeutic serum AAT concentrations. While reproducing the normal physiology by targeting normal AAT gene expression to the liver is logical, local expression in lung cells may be less demanding of the technology and offers therapeutic benefits that are produced neither by AAT protein therapy nor by AAT gene therapy targeted to the liver. Developing technologies may permit direct correction of the mutant AAT gene using innovative approaches to in vivo gene repair.

Immunoglobulin G and albumin levels in whole gut lavage fluid provide an objective measure of pouch ileitis.

Gut protein loss is a characteristic of inflammatory bowel disease (IBD), and immunoglobulin (Ig) G, albumin and alpha1-antitrypsin concentrations in whole gut lavage fluid (WGLF) correlate with clinical disease activity. If inflammation in ileoanal pouches is similar to IBD, then measurement of protein-losing enteropathy by analysis of WGLF may provide an objective assessment of disease activity in pouches. Forty-two patients who had restorative proctocolectomy for ulcerative colitis underwent whole gut lavage with a polyethylene glycol-electrolyte solution. The first clear effluent was filtered, processed by the addition of protease inhibitors and stored at - 70 degrees C. IgG, albumin and alpha1-antitrypsin were assayed in WGLF. The Pouchitis Disease Activity Index (PDAI) was calculated after pouchoscopy and biopsy; the Moskowitz criteria for pouchitis were also applied. There was a significant correlation of the pouchoscopy score and the PDAI with the concentration of WGLF IgG. All patients with 'pouchitis' according to the Moskowitz criteria had a WGLF IgG concentration greater than 10 microg/ml. The WGLF albumin level also showed a significant correlation with the PDAI, but alpha1-antitrypsin concentration did not. Analysis of WGLF for IgG and albumin may be useful in the assessment of disease activity in pouch inflammation.

Markers of inflammation in the feces of infants with cow's milk allergy.

Growing evidence exists that exposure to cow's milk elicits inflammation in the gut of infants with cow's milk allergy, irrespective of symptoms. To demonstrate inflammation and increased protein leakage from the gut during a cow's milk elimination-challenge test in fecal samples of infants presenting with different symptoms suggestive of cow's milk allergy, we measured the concentrations of alpha1-antitrypsin (AT), eosinophil cationic protein (ECP), immunoglobulin (Ig) A, and cow's milk-specific IgA antibodies, in fecal samples of 208 infants with a mean age of 7 months. Prechallenge samples were collected after a mean 3-week elimination period, and post-challenge samples were obtained 4 days after starting the challenge. Fecal levels of prechallenge total IgA (p = 0.02) and post-challenge AT (p = 0.001) were higher in infants with a positive challenge. Of these infants, pre- and post-challenge levels of ECP were higher in those reacting after 24 h than in those reacting within 1 h (p = 0.006 and p = 0.045). Prechallenge levels of ECP were higher in those showing intestinal symptoms (p = 0.008), and both pre- and post-challenge levels of total IgA were higher in those with an IgE-mediated reaction to cow's milk (p = 0.04 and p = 0.008). Regardless of the challenge result, total IgA increased during the challenge (p < 0.001 for both challenge-positive and -negative infants) and was higher in those breast-fed until the challenge than in those fed formula only (p < 0.01). Hence, in infants reacting to the cow's milk challenge, higher prechallenge levels of fecal IgA indicate increased antigenic stimuli in the gut, and higher post-challenge levels of AT reflect increased protein loss as a result of intestinal inflammation. In infants with slowly evolving gastrointestinal symptoms, increased fecal ECP may help in distinguishing patients from those who tolerate cow's milk. Individual serial follow-up of fecal IgA and ECP can be used to estimate the degree of inflammation in the gut and an appropriate time for a challenge test, but are not diagnostic tools for cow's milk allergy.

Decline in FEV1 in patients with PiZ alpha-1-antitrypsin deficiency: the Australian experience.

Alpha-1-antitrypsin (alpha1antitrypsin) deficiency is a rare hereditary disorder which characteristically presents with emphysema at an early age. The aim of the present study was to determine whether the rate of decline of lung function in alpha1antitrypsin-deficient subjects in Australia was similar to that found elsewhere. Patients registered with the Australian Alpha-1-Antitrypsin Replacement Program were studied. All patients (n = 50) had a serum alpha1antitrypsin concentration of < 0.3 g/L and had had spirometry measured over at least 2 years. They were compared with a group of normal volunteers (hospital staff, n = 107) with normal alpha1antitrypsin levels and phenotypes and with no clinical history of lung disease. All had spirometry measured for periods ranging from 2 to 6 years. The rate of decline of forced expiratory volume in 1 s (FEV1) for each subject was calculated by least squares linear regression using FEV1 against the time from entry into the study. The group mean (+/- SD) rate of decline in FEV1 was significantly greater (P < 0.01) in the alpha1antitrypsin-deficient patients (88 +/- 71 mL/year) than for the normal controls (-15 +/- 48 mL/year). There was no difference in decline in FEV1 when the data was analysed for gender and for index versus non-index cases. The results confirm previous reports of an accelerated rate of decline of FEV1 in patients with alpha1antitrypsin deficiency. Our results indicate that the rate of decline of lung function in alpha1antitrypsin deficient subjects in Australia is similar to that found in reported series from elsewhere.

Increased concentration of fecal alpha1-antitrypsin is associated with cow's milk allergy in infants with atopic eczema.

The use of fecal alpha1-antitrypsin in the monitoring of intestinal inflammation in infants with atopic eczema and food allergy was evaluated. The study material comprised 26 atopic infants with confirmed food allergy. Fecal samples were collected before an elimination diet and 3 months later for the determination of alpha1-antitrypsin. Nine (35%) of the 26 patients demonstrated an increased fecal concentration of alpha1-antitrypsin (median 3 mg/g; range 2.8-6.4 mg/g). In all nine patients (100%) the oral cow's milk challenge was positive as opposed to only six (35%) in those with normal alpha1-antitrypsin concentration (P = 0.0024). No further connections between alpha1-antitrypsin and other food allergies were detected. As a result of an adequate elimination diet, the fecal concentration of alpha1-antitrypsin was normalized in seven patients, with a favourable clinical response in atopic eczema in six and no improvement in one patient. Our results indicate that serial determinations of fecal alpha1-antitrypsin provide a useful non-invasive tool for the detection and follow-up of intestinal inflammation in a certain group of atopic infants with cow's milk allergy and severe inflammation of the gut.