Alpha-1 antitrypsin deficiency (AATD) predisposes affected patients to relevant medical conditions, in particular liver and pulmonary diseases. Respiratory manifestations typically involve basal panacinar emphysema.

Most (95%) cases of AATD-associated pulmonary emphysema are observed in patients with Pi*ZZ genotypes. Importantly, it is thought to be responsible for 1% to 2% of all chronic obstructive pulmonary disease (COPD) cases.

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In a review article published in Chronic Obstructive Pulmonary Diseases, Smith et al explained that “in contrast to non-AAT-deficient (usual) COPD, AATD COPD patients typically present at a younger age with a severity of lung dysfunction that is out of proportion to the relatively mild smoking burden, albeit with the same features of breathlessness, chronic cough, and regular sputum production.”

Additional AATD-related respiratory manifestations include chronic bronchitis and bronchiectasis.

Basis of Lung Volume Reduction Surgery

Lung volume reduction surgery (LVRS) emerged in the 1950s with Dr. Otto Brantigan and colleagues. “Brantigan reasoned that in patients with ‘idiopathic hypertrophic obstructive pulmonary emphysema,’ the removal of the periphery of the upper lobes would reduce lung hyperinflation, restore lung ‘elasticity’ and the circumferential pull that tethers open the bronchioles, improve diaphragmatic mechanics, and possibly improve cardiac function,” Cazzola et al explained.

The technique was adopted and modified by other practitioners in the following years. In particular, the work developed by Joel Cooper and colleagues in the 1990s contributed to the widespread use of LVRS. In 1998, the National Emphysema Treatment Trial (NETT) started enrolling patients to assess the use of LVRS in the treatment of advanced emphysema.

Different surgical approaches can be used in LVRS, but the most common approaches are median sternotomy, thoracotomy, and bilateral video-assisted thoracoscopic surgery (VATS). No significant differences in mortality, morbidity, or functional improvement were reported between patients undergoing thoracotomy and median sternotomy during the NETT study. On the other hand, VATS has been associated with decreased hospital cost and length of stay.

In spite of the initial incision, LVRS requires resection of 20% to 30% of each lung. During the postoperative period, patients are subjected to aggressive bronchial hygiene. Pneumonia and prolonged air leaks are the most common postoperative complications.

How Does LVRS Improve Pulmonary Function?

The mechanisms by which LVRS improves pulmonary function are not fully understood. According to Cazzola et al, “Restoring the size mismatch between the lungs and chest wall should improve the elastic recoil of the lung and thereby help to tether open the small and medium-sized airways, which would prevent premature airway closure and improve expiratory airflow.”

The decrease in lung and chest wall hyperinflation might help to restore the position and curvature of the diaphragm and the intercostal and scalene muscles. Hence, the synchrony reestablished between the diaphragm, intercostal muscles, scalene muscles, and other inspiratory muscles improves the chronic respiratory fatigue observed in patients with severe emphysema.

LVRS in the Management of AATD

The knowledge on LVRS in AATD is still limited, with few series published. Cazzola et al examined 8 series of patients with severe AATD (n=107) who underwent either LVRS (n=76) or endoscopic lung volume reduction (ELVR; n=41) via endobronchial valve. Patients had an average age range of 48 to 65 years, and most were men when considering the 5 studies that grouped participants by sex.

All 64 patients with reported alpha-1 antitrypsin (AAT) levels had severe AATD (<12 mmol/L or <65 mg/dL). Moreover, 96% (69/72) of patients had the Pi*ZZ allele. The classic AATD distribution of lower lobe-predominant emphysema was observed in 70 of 95 patients.

Regarding the surgical aspects of the LVRS studies, 3 included bilateral procedures, 1 included unilateral surgeries, and 1 included both unilateral and bilateral operations, with most being bilateral. In 4 studies, LVRS was performed exclusively via either VATS or thoracotomy.

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At 3 to 8 months postsurgery, the overall findings of the series suggested improvements in forced expiratory volume in 1 second (FEV1), total lung capacity (TLC), residual volume (RV), and partial pressure of oxygen (PaO2). However, most of the improvements were usually not sustained at 12 to 24 months postoperatively. For instance, only 2 LRVS and 1 ELVR series showed higher FEV1 than the baseline value at 12 to 24 months. In addition, the mean RV values were kept below baseline in 2 of 3 series.

Out of 6 series assessing dyspnea scores, 4 found a statistically significant reduction at 3 to 8 months postoperatively and 3 reported similar results at 12 to 24 months postsurgery. On the other hand, of the 3 series with follow-up data on diffusing capacity for carbon monoxide (DLCO), none reported a significant improvement.

The performance on the 6-minute walk test (6MWT) was improved in 3 of 6 series at 3 to 8 months. Additionally, 2 of 4 series reported similar results at 12 to 24 months.

Although patients with severe AATD showed an initial positive response to LVRS or ELVR in both the 6MWT and pulmonary function tests, the alterations were not sustained over 12 to 24 months postprocedure.

In conclusion, Cazzola et al would not recommend LVRS for patients with panacinar emphysema due to severe AATD. In their review article published in the European Respiratory Review, the authors stated, “The improvements in measured pulmonary function, exercise capacity, and quality of life metrics for individuals with advanced emphysema due to severe AATD following LVRS are inferior, both in magnitude and duration, to the improvements seen in individuals with severe emphysema who have normal AATD levels.”

References

Cazzola M, Stolz D, Rogliani P, Matera MG. α1-antitrypsin deficiency and chronic respiratory disorders. Eur Respir Rev. 2020;29(155):190073. doi:10.1183/16000617.0073-2019

Smith DJ, Ellis PR, Turner AM. Exacerbations of lung disease in alpha-1 antitrypsin deficiency. Chronic Obstr Pulm Dis. 2021;8(1):162-176. doi:10.15326/jcopdf.2020.0173