Signs of Hyperinflation and Ventilation Heterogeneity in Individuals With Severe Alpha-1-Antitrypsin Deficiency at the Age of 42

Georg Rüdiger Schramm,1 Per Wollmer,2 Eeva Piitulainen,1 Suneela Zaigham,3,4 Hanan Tanash1 1Department of Internal Medicine, Skåne University Hospital, Malmö, Sweden, Lund University, Lund, Sweden; 2Department of Medical Imaging and Physiology, Skåne University Hospital, Malmö, Sweden, Lund University, Lund, Sweden; 3Department of Medical Sciences, Clinical Physiology, Uppsala University, Uppsala, Sweden; 4Department of Clinical Sciences, Lund University, Lund, SwedenCorrespondence: Georg Rüdiger Schramm, Department of Internal Medicine, Skåne University Hospital, Tora Kjellgrens Gata 17, Malmö, S – 205 02, Sweden, Tel +46 40 33 25 85, Fax +46 40 33 74 90, Email [email protected]: Severe alpha-1-antitrypsin deficiency (AATD) is a known risk factor for early development of emphysema and COPD. By the Swedish national screening program within the years 1972– 74 a cohort of individuals with severe AATD (PiZZ) was identified and regularly followed up. The aim of this study was to investigate alveolar volume (VA) and the ratio VA/Total lung capacity (VA/TLC) for the detection of signs of hyperinflation and ventilation heterogeneity in PiZZ individuals compared with an age-matched control group (phenotype PiMM), randomly selected from the population registry.Methods: All study participants underwent pulmonary function tests (PFT) including dynamic spirometry and total lung capacity (TLC), residual volume (RV), functional residual capacity (FRC) and alveolar volume (VA). They answered a questionnaire on smoking habits and symptoms. Quality of life was assessed by answering the Saint George´s Respiratory Questionnaire (SGRQ).Results: Fifty-six PiZZ and 66 PiMM individuals participated in the study. The PiZZ individuals had a significantly lower VA/TLC ratio (p=0.004) and significantly higher RV (p< 0.001) and RV/TLC ratio (p=0.001) than the PiMM individuals. The 13 PiZZ ever-smokers had a significantly higher TLC (p=0.025), RV (p=0.003) and FRC (p=0.003) and a significantly lower VA/TLC ratio (p=0.006) than the 24 PiMM ever-smokers. No significant differences in RV, TLC, VA, and VA/TLC ratio were found between the never-smoking PiZZ and PiMM individuals. The ratio RV/TLC was significantly higher in the PiZZ never-smokers than in the PiMM never-smokers (p=0.026).Conclusion: At the age of 42 the PiZZ ever-smokers have signs of hyperinflation and ventilation heterogeneity.Plain language summary: Uneven airflow in the lungs, also called uneven ventilation is known as an indicator for lung disease. It can be analysed by measurement of alveolar volume and total lung capacity. The presence of uneven ventilation has not been investigated in individuals with severe Alpha-1-antitrypsin deficiency (shortened to AATD).We invited 129 individuals from a known cohort with severe AATD to perform lung function tests. Furthermore, they answered questions about health, tobacco consumption and respiratory symptoms. To compare the results, we also invited a group of individuals without AATD and had them perform the same tests.We found that individuals with severe AATD show signs of uneven ventilation, especially when they are or have been smoking.Our results suggest that analysis of alveolar volume is a simple, safe and time-saving method for the early detection of lung disease in individuals with severe AATD.Keywords: alpha-1-antitrypsin-deficiency, alveolar volume, hyperinflation, smoking