Atopy, Asthma, and Emphysema in Patients with Severe α -1-Antitrypysin Deficiency

Abstract

Bronchial asthma is characterized by episodic airway obstruction and associated with wheezing, a bronchodilator response, an elevation in total serum IgE, and atopy. To determine whether asthma is more common in subjects with severe alpha 1-antitrypsin deficiency (alpha 1-ATD) and airway obstruction, we compared 38 patients who had this condition (Group 1) with 22 control patients with chronic obstructive pulmonary disease (COPD) (Group 2) and with five subjects with alpha 1-ATD and normal spirometry (Group 3). Subjects were evaluated with a symptom questionnaire, pulmonary function testing, intradermal allergen testing, and serum IgE measurement. Self-reported wheezing was a common symptom in all patient groups, but attacks of wheezing with dyspnea were significantly more common in Group 1. Of those patients with airway obstruction, more than 50% showed a bronchodilator response whether suffering from alpha 1-ATD or not. Atopy was more common in Group 1 than in Group 2 (48% versus 27%). Mean serum IgE for all groups was similar but significantly greater in patients with atopy. We estimated the prevalence of asthma in the study groups on the basis of the criteria of attacks of wheezing, reversible airway obstruction, atopy, and that increased IgE. The proportion of patients with asthma in Group 1 was significantly greater than that in Group 2 (22% versus 5%, p < 0.05). Our study shows that with control for the degree of airway obstruction, asthma, as defined, is more common in patients with alpha 1-ATD than in those without it. We suggest that a lack of alpha 1-AT in airways increases the propensity to develop asthma.

Αlpha-1 Antitrypsin Gene Polymorphism in the Egyptian Population: Association with Obstructive Lung Diseases

“…It is associated with cigarette smoking, 35 and may be a marker of airway inflammation. 27 However, it is unlikely that smoking was the causative factor in our study, since the proportion of current smokers in the COPD and the control groups did not show significant difference. In addition, there was no significant difference between smokers and non-smokers in mean total serum IgE concentrations.…”

“…In this regard, both an increased serum IgE titer and atopy have been associated with the development of chronic obstructive lung disease. 27 An increased serum IgE level is also not specific for asthma. It is associated with cigarette smoking, 35 and may be a marker of airway inflammation.…”

Alpha-1 antitrypsin deficiency: a commonly overlooked cause of lung disease: Figure 1:

“…Cigarette smoking is the best described risk factor, and smokers with alpha-1 antitrypsin deficiency tend to develop emphysema earlier than nonsmokers with the deficiency. 19 Other risk factors, including occupational exposure, 20 asthma 21 and male sex, 22 have been described.…”

“…24 Pulmonary function testing shows findings consistent with COPD; however, bronchodilator responsiveness may be seen and may be labelled as asthma. 21 Liver disease caused by the ZZ genotype manifests in various ways. Affected infants may present in the newborn period with cholestatic jaundice, sometimes with acholic stools (pale or clay-coloured) and hepatomegaly.…”

Polymerization and Oxidation of Alpha-1-Antitrypsin in Pathogenesis of Emphysema

“…The most frequent symptoms in A1ATD patients were dyspnea on exertion (in 84% of participants), selfreported wheezing during respiratory tract infections (76%), and wheezing independent of infections (65%), usual cough (45%), and "annual" cough in phlegm episodes (52%). Significant number of patients who initially diagnosed as asthma had symptoms that suggest airway hyper-responsiveness such as cough and wheezing, responded to aerosol bronchodilator moderately (Eden et al, 1997). It is interesting that a subgroup of individuals in the Registry with relatively normal lung function was younger, more likely to have never smoked and more likely to have come to medical attention owing to a family history of A1ATD.…”