Wheezing in preschool children is a common problem worldwide, affecting up to 50% of children under the age of 6 years [1]. Preschool wheezing is a heterogeneous group of diseases and various cohort studies (including ALSPAC) have proposed a number of phenotypes that differ in time-course, associated factors such as atopy and risk of asthma in later life [2].
The importance of identifying the phenotype in a wheezing child is apparent because of parental concern, treatment considerations, and long-term prognosis. A complex approach to a wheezy child is often needed and includes clinical course (including frequency and severity of individual episodes), family history of asthma and atopy, various biomarkers such as blood and nasal secretion eosinophils [3,4], total and specific IgE [5], exhaled fraction of nitric oxide [6], ICAM1 [7], and other exhaled breath condensate markers [8]. There are data that chronic obstructive diseases in adulthood, including asthma and COPD, start in childhood [9] and indeed the features of certain preschool wheezing phenotypes are similar to those of COPD [10].
Alpha-1 antitrypsin (AAT) is the major genetic factor of chronic obstructive pulmonary disease (COPD) [11]. More than three million people die each year due to COPD and about 90% of COPD-related deaths happen in low-income countries. It is the third most common condition to cause death in the United States [12]. More than 235 million people have asthma which is the most common chronic disease in childhood (WHO data, 2017; http://www.who.int/respiratory/en/). There is no curative treatment for COPD.
Since alpha-1 antitrypsin also exhibits numerous immunomodulatory functions and suppresses inflammatory response, all these features may play a role in the pathogenesis of preschool wheezing.
AAT’s primary function is inhibition of proteases but it has other functions apart from protease inhibition [13] and is involved in the inflammatory processes [14]. It has been noted that oxidative stress is of greater magnitude in children with variant AAT alleles [15] and the Pi*Z type has proinflammatory properties [16]. Protease inhibitors (including AAT) are thought to be involved in childhood asthma exacerbations [17]. It has also been suggested that COPD patients who are heterozygotes (MZ genotype) had experienced wheezing in early childhood but were symptom-free until late adulthood and developed COPD. All these findings suggest that AAT may play a role in the development of preschool wheezing disorders.

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