A 43-year-old male subject, Italian Caucasian, affected by asthma and atopy, with prick tests positive since the childhood for dog and cat dander and grass pollen, treated with inhaled corticosteroids, long-acting ß2-agonists (ICS/LABAs) and long-acting muscarinic antagonists (LAMAs). The patient referred to our outpatient clinic for recurrent bronchitis and exertional dyspnoea. He was a former smoker (about 10 cigarettes a day for 20 years, 10 pack/years) at the time of the visit and a manual worker with no previous exposure to any toxic or irritating agent.\nUpon auscultation, he presented a slightly reduced vesicular murmur, with wheezing during forced expiration; oxygen saturation (SatO2) was 96% breathing room air and the heart rate was 71 bpm. Arterial blood gas measurement in breathing room air produced the following results: pH 7.46, pCO2 37 mmHg, pO2 91 mmHg, HCO3 27 mmoL/L, and sO2 97%.\nAAT serum concentration was 64 mg/dL, with a PI*M2MMalton genotype.\nComplete abdomen ultrasound exam did not identify hepatic or aneurysmal disease. Total and fractioned bilirubin, creatine phosphokinase (CPK), gamma-glutamyl transferase (gamma GT), cholinesterase, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) blood tests were in the normal range, as well as urea and creatinine; anti-neutrophil cytoplasmic antibodies (C-ANCA) and anti-myeloperoxidase antibodies (anti-MPO) were negative, while a marked increase in total IgE was detected (1260 IU/mL). Autoantibodies and eosinophils were also in the normal range.\nLung function tests showed an extremely severe obstructive ventilatory defect. The bronchial reversibility test was positive (Fig. ; Table ). The chest high resolution computed tomography (HRCT) excluded pulmonary emphysema, bronchiectasis and fibrosis. The six-minute walking test (6MWT), performed without oxygen supplementation, did not register any clinically significant desaturation but a slight reduction in the distance walked (440 m measured/546 m predicted). Echocardiographic parameters were in the normal range.
A 57-year-old woman of Moroccan origin suffering from an end-stage kidney disease was admitted for pre-kidney transplant investigations. Her medical story revealed diabetes with various peripheral vascular complications but neither pulmonary nor hepatic dysfunction. Serum electrophoresis revealed a double α1-globulin peak, suggesting the presence of a Pi A1AT protein variant in the heterozygous state. The A1AT IEF phenotype was noted Pi M1/Pi M2 but because of an abnormally low serum concentration (69 mg/dL), DNA sequencing was performed and revealed a Pi M1/Pi Mmalton genotype.