Asthma and AATD

Asthma and AATD

Relationship between Asthma and AATD

Prevalence of asthma in alpha-1 antitrypsin deficiency

The association between the two was first mentioned in 1978.

In this case, Larsson et al. reported a 4% asthma prevalence in 246 Swedish patients with severe AATD, the PiZ phenotype.

Since then, many studies have suggested an association between the two, albeit with a wide variability in asthma prevalence in patients with AATD (4–45%).

The AATD phenotype may play a role in the prevalence of asthma-AATD overlap.

Patients with the PiMZ phenotype have a three-fold higher prevalence of asthma as the sole diagnosis compared to those with the PiZZ phenotype.

Cases of asthma and AATD

Diagnosis of asthma and alpha-1 antitrypsin deficiency

Asthma is a syndrome that includes diverse clinical phenotypes that share similar clinical manifestations but likely different etiologies.

It is estimated that asthma affects approximately 235 million people worldwide.

What is asthma?

It is defined as a chronic inflammatory disease of the airways, involving various cells and inflammatory mediators.

Besides, it is partly caused by genetic factors and presents with bronchial hyperresponsiveness.

Also, it is caused by variable airflow obstruction, which is totally or partially reversible, either by medication or spontaneously.

The diagnosis is established by the presence of symptoms compatible with asthma along with reversible expiratory airflow limitation.

What is AATD?

AATD is a genetic disease inherited in an autosomal codominant manner.

In its severe forms, it predisposes to the development of chronic obstructive pulmonary disease (COPD) and emphysema, as well as liver disease.

Diagnosis is established by determining serum AAT levels, followed by phenotyping and genotyping.

However, currently, given its lower cost and ease of access, genotyping is performed directly rather than phenotyping.

What should be taken into account?

It should be noted that AAT is an acute phase reactant and may increase transiently in inflammatory processes.

For this reason, concomitant measurement of C-reactive protein is recommended.

• AAD is considered severe when the serum AAT concentration is below 57 mg/dL.
• The most common genotype is Pi*MM, which is present in approximately 95% of the population and confers normal AAT levels.
• The risk of developing disease in AAD is limited almost entirely to the ZZ phenotypes (96%).
• The remaining 4% is due to rare deficient variants and the very rare null phenotypes.

Without research there is no cure

Despite this known relationship, COPD due to AATD continues to be a highly underdiagnosed disease due to its low clinical suspicion.

AATD has also been linked to bronchiectasis and asthma, and therefore, it is recommended that it be investigated in patients with partially reversible bronchial asthma.

As described below.

Candidates for determining serum alpha-1 antitrypsin concentration.

1. COPD
2. Blood relatives of patients with known AATD
3. Symptoms of dyspnea and chronic cough in many family members
4. Liver disease of unknown cause
5. Absence of the alpha-1 peak in the proteinogram
6. Adults with bronchiectasis
7. Adult asthma with poorly reversible bronchial obstruction or signs of pulmonary emphysema
8. Neutrophilic panniculitis
9. Granulomatous polyangiitis

Recommendations for its detection

Symptoms in both include cough, excessive sputum production, dyspnea, and wheezing.

These symptoms frequently overlap, making it difficult to distinguish between these two conditions, which may be overlapping in some patients.

• AATD can be misdiagnosed as asthma, as asthma symptoms are frequently the first manifestation of AATD.
• In addition, they may present with bronchial hyperreactivity and obstruction that is poorly reversible after bronchial remodeling.
• Allergy and asthma often coexist with AATD, although the relationship between allergy, asthma, and AATD is unclear.
• Due to the overlap of symptoms, diagnosing a specific clinical entity remains difficult.
• There are no universal screening recommendations.

WHO recommends that all adult and adolescent patients with asthma and all patients with COPD be screened for AATD.

The American Thoracic Society (ATS) and the European Respiratory Society (ERS) issued a joint statement in 2003 outlining standards for diagnosing patients with AATD.

As part of this declaration, recommendations were made regarding the populations for diagnostic testing in adult patients with asthma and non-reversible airflow obstruction (strong recommendation with type A evidence).

The Spanish Society of Pulmonology and Thoracic Surgery (SEPAR) recommends AAT testing in adult patients with bronchial asthma.

This is especially true for those who develop progressive bronchial obstruction or who show signs of pulmonary emphysema.

Key factors

• It is important to understand that patients with AATD may present with characteristic asthma symptoms, such as atopy and bronchial hyperreactivity.
• Furthermore, it is important to understand why the guidelines recommend investigating AATD in patients with COPD or asthma with poorly reversible airway obstruction, given that there is likely a poorly understood overlap syndrome between the two.

For this reason, it is necessary to raise awareness among medical professionals about identifying asthma in patients with known AATD and in patients with known asthma.

Active screening for AATD is also considered in patients, specifically those with severe, uncontrolled asthma, poorly reversible airflow obstruction, or concomitant emphysema.

Conclusions

Alpha-1 antitrypsin deficiency (AATD) has been associated with asthma, with prevalence ranging from 4% to 45% in patients with AATD. Numerous studies have been conducted to determine this relationship, finding varying prevalences of asthma in different AATD phenotypes.

• The prevalence of asthma in patients with AATD varies significantly, from 4% to 45%, depending on the phenotype and the study performed.
• AATD phenotypes and asthma: Patients with the PiMZ phenotype have a three-fold higher prevalence of asthma than those with the PiZZ phenotype.
• One study reported a 35% rate of asthma diagnoses in 1,129 patients with AATD.
• While another study found a 21%–38% rate in patients with severe AATD.
• Overdiagnosis of asthma: There is concern about the overdiagnosis of asthma in patients with AATD, as symptoms may overlap with those of COPD.
• Asthma and atopy: Patients with AATD have a higher prevalence of atopy and allergic manifestations, which can complicate diagnosis.
• AATD in asthmatic patients: The prevalence of AATD in asthmatic patients has been documented to be as high as 30% in some studies.
• Diagnostic recommendations: It is suggested that all adult and adolescent patients with asthma be evaluated for AATD, especially those with poorly reversible bronchial obstruction.

Source: Centro Andaluz Alfa 1