Alcohol Use Predicts ER Visits in Individuals with Alpha-1 Antitrypsin Deficiency (AATD) Associated COPD

Abstract

Excessive alcohol use in COPD has been associated with increased mortality; however, little is known about alcohol use in AATD-associated COPD. A total of 538 individuals with AATD-associated COPD completed questionnaires at baseline and 330 also completed 2 years of follow-up questionnaires. Demographic and health information was collected, including information about alcohol use, ER visits for COPD, and hospitalizations for COPD. Problem alcohol use was characterized using the CAGE screening questionnaire and recent alcohol consumption. Demographic and clinical characteristics associated with problem drinking were identified using logistic regression. Problem drinking at baseline was examined as a predictor of ER visits and hospital admissions for COPD in the subsequent two years using logistic regression adjusting for demographic variables and baseline health status. 14% of the sample reported a history of problem drinking per the CAGE and 8% reported problem drinking in the past week. Problem drinking was associated with higher education and greater lifetime tobacco exposure. Recent alcohol consumption was a significant predictor of having an ER visit for COPD in the subsequent two years. Compared to individuals who reported problem drinking in the past week, individuals with no consumption (OR = 0.32, 95% CI = 0.10 to 0.97, p = .043) and individuals with low-to-moderate consumption (OR = 0.25, 95% CI = 0.08 to 0.77, p = .016) had significantly lower odds of an ER visit. Neither measure of problem drinking predicted hospital admission. Screening for recent excessive alcohol use in this population may identify individuals at risk for use of costly emergency health services.     

Measurements of desmosine and isodesmosine by mass spectrometry in COPD

OBJECTIVES: Application of mass spectrometry (MS) for direct measurements of desmosine (D) and isodesmosine (I) in urine, plasma, and sputum as markers of elastin degradation in patients with alpha(1)-antitrypsin deficiency (AATD) and non-AATD-related COPD. BACKGROUND: In COPD patients, the lungs undergo elastin injury, which can be monitored by measurements of D and I in body fluids as specific markers of elastin degradation using the specificity and sensitivity of MS. METHODS: Acid hydrolysis of blood plasma, 24-h urine and sputum measurements, followed by chromatographic separation for mass spectrometric analysis. RESULTS: Each patient group had levels of plasma D and I that were statistically significantly higher than those of control subjects. AATD patients had higher levels than COPD patients with normal alpha(1)-antitrypsin (AAT) levels. Twenty-four-hour urine measurements demonstrated no significant difference in total levels of D and I among control subjects and patients but showed a free (unbound) concentration of D and I in urine, which was statistically significantly higher in patients with COPD with and without AAT. The D and I levels in the sputum of patients with AATD exceeded the levels in COPD patients with normal AAT levels. CONCLUSIONS: MS allows a sensitive and specific analysis of D and I in body fluids. The quantification of D and I in sputum, along with increases of D and I in plasma and an elevated free component of D and I in urine provide indexes that characterize patients with COPD and can be followed in relation to the course of the disease and/or therapy.     

Influenza vaccination in subjects with alpha1-antitrypsin deficiency

BACKGROUND: Influenza vaccination is recommended for all subjects with COPD, including alpha(1)-antitrypsin deficiency (AATD), but immunization practices are below US national goals. Influenza vaccination practices and their relation to respiratory outcomes in AATD are unknown. METHODS: Nine hundred thirty-nine subjects with AATD were followed up prospectively by monthly telephone interviews during the 2003 to 2004 influenza season. Vaccination status, exacerbation rates, and health-care utilization were documented. Residence zip codes were used to group subjects as living in high or low influenza-like illness (ILI) prevalence areas according to published Centers for Disease Control and Prevention data for the same influenza season. RESULTS: Overall, 81.6% of subjects received influenza vaccination, with no differences noted by gender, age (median age 52 years), Global Initiative for Chronic Obstructive Lung Disease stage, or ILI prevalence area. No significant differences were noted in the overall acute exacerbation rates using two different criteria between vaccinated and unvaccinated subjects (mean, 1.5 +/- 1 exacerbations per subject). Similarly, no differences were noted in either the severity of exacerbations or the monthly exacerbation rates between the two groups. Unvaccinated subjects had more unscheduled physician visits than vaccinated subjects, but there were no significant differences in scheduled visits, emergency department visits, or hospitalizations between the two groups. Older age (> 60 years) or residence in a high ILI prevalence area had no effect on outcomes. CONCLUSION: Subjects with AATD in the United States receive adequate influenza vaccination regardless of age. However, we did not observe a significant impact of the vaccination on disease exacerbations and other respiratory outcomes during the 2003 to 2004 influenza season.     

Alpha-1 Antitrypsin Augmentation Therapy and Biomarkers of Elastin Degradation

Abstract

Background: Intravenous alpha-1 antitrypsin protein (AAT) augmentation is a prescribed therapy for severe, genetically determined, alpha-1 antitrypsin deficiency (AATD), a genetic basis for pulmonary emphysema. AAT, a predominant systemic inhibitor of neutrophil elastase thus far has not been shown to decrease elastin degradation in a significant number of patients on this therapy. The objective of this study was to compare levels of biomarkers of elastin degradation in plasma, bronchoalveolar lavage (BALF) fluid and urine before and after beginning AAT augmentation therapy in patients with AATD. Methods: Desmosine and isodesmosine (DI), which occur only in elastin, are amino acid cross-links in mature elastin. Levels of DI in body fluids measure degradation of elastin and can be measured more specifically by mass spectrometry. This method was used to measure DI levels in plasma, bronchoalveolar lavage fluid and urine in cohorts of severe AATD patients on augmentation, not on augmentation and before and after the initiation of augmentation therapy. Results: Statistically significant reductions in plasma DI and in BALF DI were demonstrated in AATD patients receiving intravenous (IV) augmentation therapy as compared with those not receiving it. Administration by aerosol also produced statistically significant reductions in levels of DI in BALF. Conclusions: Results indicate that the currently prescribed doses of AAT augmentation inhibit neutrophil elastase adequately to reduce elastin degradation, both systemically and in the lung per se. The currently prescribed doses did not reduce elastin degradation to control levels, which may be possible with higher doses.     

Alpha-1 Antitrypsin Deficiency Detection in a Portuguese Population

Alpha-1 antitrypsin deficiency (AATD) is an autosomal co-dominant disease characterised by low serum levels of this molecule. Its epidemiology remains unknown in many countries, mainly due to its underdiagnosed state and lack of patients’ registries. We aim to evaluate and characterise a sample of Portuguese individuals tested for AATD, between 2006 and 2015, based on a retrospective analysis from the database of a laboratory offering AATD genetic diagnosis service. 1684 individuals were considered, covering almost every region in Portugal. Genetic diagnosis resulted from requests of clinicians from different areas of expertise, mainly pulmonology (35.5%). Most subjects could be distributed into more common genotypes: MZ (25.4%, n = 427), MS (15.5%, n = 261), SZ (11.2%, n = 188), ZZ (9.4%, n = 158) and SS (5.6%, n = 95). 9.5% of the subjects were found to carry at least one rare deleterious allele, including the recently described P_Gaia, Q0_{Oliveira do Douro}, Q0_{Vila Real} and a novel S_Gaia variant. This study comprises 417 subjects (24.7%) with severe to very severe AATD and 761 carriers (45.2%), 22.7% of those identified by familial screening. The present study represents the most complete survey of AATD in Portugal so far and discloses a high rate of severe and very severe deficiency cases, attributed not only to ZZ and SZ genotypes but also to a large number of rare combinations with other null and deficiency alleles. It also uncovers a low awareness to AATD among the medical community, highlighting the need to create a Portuguese national registry and AATD guidelines and increase the awareness about this condition.