Alpha-1 Antitrypsin Deficiency (AATD)

Suspect it when emphysema shows up young - Emphysema in a patient in their 30s or 40s, a basilar rather than apical distribution, bronchiectasis, spontaneous pneumothorax, or unexplained liver disease. Diagnosis is a serum AAT level — below 11 micromol/L (about 57 mg/dL by nephelometry) is severe deficiency — with isoelectric focusing as the gold-standard phenotype test and PCR genotyping for the common F, I, S, and Z variants.

Grade the lung disease before the case - Post-bronchodilator FEV1 on spirometry is the number that matters; mortality rises as FEV1 falls below 35% of predicted, and an FEV1/FVC ratio under 0.7 defines the obstruction. Chest x-ray or CT shows the pattern and extent of the basilar emphysematous bullae, hyperinflation, and flattened diaphragms. Arterial blood gas if there is any question of CO2 retention.

Air trapping drives your ventilator settings - Airway collapse during exhalation traps gas, so hyperinflation and CO2 retention follow, and rising physiologic dead space widens the gap between PaCO2 and end-tidal CO2. Give a long expiratory time and a slow rate, watch the flow-volume loop and peak-to-plateau pressures for breath stacking, and trend blood gases rather than trusting the capnograph alone.

Bullae mean pneumothorax - Bullous bleb destruction releases air into the chest and produces spontaneous, traumatic, or tension pneumothorax; spontaneous pneumothorax can be the presenting manifestation of AATD. Keep airway pressures low, be sparing with PEEP, and avoid nitrous oxide, which expands closed gas spaces. New hypotension with rising airway pressures under positive-pressure ventilation is a tension pneumothorax until you rule it out.

Check the right heart - Hypoxemia causes diffuse pulmonary vasoconstriction, so advanced disease brings pulmonary hypertension. Echo for RV size and function and estimated pulmonary artery pressure when there are signs of right heart strain, and note that coexisting pulmonary hypertension worsens the prognosis.

Optimize the airway before an elective case - Short-acting beta-2 agonist with or without a short-acting antimuscarinic on the day of surgery. An active exacerbation gets oxygen, albuterol-ipratropium, and a short five-day course of prednisone first, plus a chest x-ray to look for pneumothorax or a new infiltrate. Respiratory infection is the usual trigger and a reason to postpone.

The liver is the other half of the disease - PI*ZZ and related genotypes accumulate polymer in hepatocytes. Check aminotransferases, alkaline phosphatase, bilirubin, platelet count (thrombocytopenia is the flag for cirrhosis), and coagulation studies, and dose hepatically cleared drugs to what you find. Cirrhosis in AATD carries a grave prognosis.

Augmentation therapy - Weekly IV infusion of pooled human alpha-1 proteinase inhibitor for patients with plasma AAT below 11 micromol/L and established airflow obstruction (FEV1 under 80% predicted). Reactions are uncommon and no perioperative hold is described — just document the schedule.

Favor regional where the case allows - Anything that avoids controlled positive-pressure ventilation reduces barotrauma and hyperinflation exposure in a lung full of basilar bullae.

Expect secretions and reactive airway - Cough, sputum production, wheezing, and chest tightness are the daily baseline and worsen with upper respiratory infection. Have suction and bronchodilator ready at induction and emergence.

Watch the skin and the vessels - Necrotizing panniculitis presents as hot, painful erythematous nodules or plaques on the thigh or buttock. Systemic vasculitis, urticaria, angioedema, glomerulonephritis, and intracranial or intra-abdominal aneurysms are also described. Look before you site a block or a line.

These are lung-transplant and LVRS candidates - Lung volume reduction surgery and transplantation are the end-stage options for bullous emphysema, so some of these patients arrive already worked up. Know which pathway they are on before you plan the anesthetic.

Alpha-1 antitrypsin (AAT) is a protease inhibitor made in the liver. It neutralizes neutrophil elastase and accounts for roughly 90% of the protection against elastolytic activity in the lower airways. Mutations in SERPINA1 on chromosome 14, inherited in autosomal co-dominant fashion, reduce circulating AAT — the Z allele produces very little, and PI*ZZ is the classic deficient genotype.

Unopposed elastase digests alveolar elastin and produces panacinar emphysema that, unlike smoking-related emphysema, is basilar predominant. That is a toxic loss of function. Separately, unsecreted mutant protein polymerizes inside hepatocytes — a toxic gain of function — causing chronic hepatitis, cirrhosis, and hepatocellular carcinoma.

Lung symptoms usually begin between ages 20 and 50, and the rate of decline in lung function depends heavily on cigarette smoking. So you get emphysematous lungs in a young patient, sometimes with liver disease alongside.