Chest

Chest

Volume 128, Issue 4, October 2005, Pages 2076-2081
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Clinical Investigations
α1-Antitrypsin Deficiency in 26-Year-Old Subjects: Lung, Liver, and Protease/Protease Inhibitor Studies

https://doi.org/10.1378/chest.128.4.2076Get rights and content

Background

Clinical and biochemical signs of lung and liver disease have been followed prospectively in a birth cohort of individuals with α1-antitrypsin (AAT) deficiency.

Objective

At age 26 years, the focus was on clinical health, lung and liver function tests, and plasma markers of the protease/antiprotease balance. The effect of early childhood environment and symptoms was also studied.

Methods

Eligible individuals were 26-year-old subjects with AAT deficiency (PiZ, n = 122; PiZ −, n = 2; PiSZ/S−, n = 53) and control subjects (PiMM, n = 44). Of the original AAT-deficient subjects, 119 completed the clinical examination and 134 answered the questionnaire.

Results

The prevalence of respiratory symptoms did not differ between the PiZ and SZ groups. Sixteen percent of PiZ and 14% of PiSZ subjects had asthma. Four current smokers (67%) and 22% of ex-smokers/never-smokers reported recurrent wheezing (p = 0.03). No difference in FEV1 or FEV1/FVC ratio was found between the PiZ, SZ (5% being smokers), and MM individuals (all nonsmokers). A decreased FEV1/FVC ratio was found in PiZ subjects with neonatal cholestasis, compared to remaining PiZ subjects (p = 0.02). Recurrent wheezers at age 2 years with AAT deficiency had decreased FEV1/FVC ratio (p = 0.025) at age 26 years. None had clinical symptoms of liver disease. Six percent of PiZ and 9% of PiSZ subjects had a marginal increase of serum alanine aminotransferase; 7% of PiZ and 4% of PiSZ had abnormal γ-glutamyl transferase test results. The PiZ and SZ individuals had decreased plasma albumin (p = 0.0002). Secretory leukocyte protease inhibitor (SLPI) was increased in PiZ and SZ subjects compared to PiMM subjects (p = 0.0001). Neutrophil lipocalin was decreased in PiZ subjects (p = 0.0004) and PiSZ subjects (p = 0.001) compared to PiMM individuals. The elastase/AAT complex concentration was lower in AAT-deficient subjects (p = 0.0001).

Conclusion

Twenty-six-year-old PiZ and SZ individuals (5% smokers) had normal lung function test results, and 4 to 9% had marginal deviations in liver test results. Analyses of SLPI and neutrophil lipocalin, a marker of neutrophil activity, indicate compensatory changes in the AAT-deficiency state.

Section snippets

Study Population

All surviving 178 AAT-deficient subjects (PiZ, n = 122; PiZ−, n = 2; and PiSZ,/PiS−, n = 53) identified by the 1972-to-1974 screening were invited to participate. Clinical examination, spirometry, and routine blood tests were performed by a chest physician at the local hospital. An age-matched control group was recruited from the University Hospital in Malmö.

Questionnaire

The physician answered a questionnaire concerning diagnosis, spirometry, and liver function tests. The patient completed a modified

Clinical Examination and Lung Function

Of the 178 AAT-deficient individuals, 119 subjects (67%) underwent clinical examination at age 26 years. The patient questionnaire was answered by 134 individuals (81%). The control group of healthy volunteers included 44 PiMM individuals (21 men) with a normal AAT concentration.

Lung function test results are shown in Table 1. No significant differences in lung function were found between the Pi subgroups. A reversibility test was performed in 71 AAT-deficient and 40 PiMM individuals. An

Discussion

This study was initiated in the 1970s to determine the natural histories of liver and lung disease in AAT deficiency and the possible effects of exogenous and endogenous factors. Other important aims were to prevent smoking and to study possible compensatory changes in the protease/protease inhibitor balance.

The 26-year-old individuals with AAT deficiency have normal lung function, as defined by a normal FEV1/FEV ratio and no difference from an age-matched control group. Seven percent of those

ACKNOWLEDGMENT

The authors thank the Swedish physicians who made this study possible by reporting data to the investigators.

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    This study was supported by grants from the Swedish Heart Lung Association.

    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).

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    Copyright © 2005 The American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.