Unsuspected mild emphysema in nonsmoking patients with chronic asthma with persistent airway obstruction  Arthur F. Gelb, MD, Alfred Yamamoto, MD, Thais Mauad, MD, PhD, Jozef Kollin, MD, Mark J. Schein, MD, Jay A. Nadel, MD  Journal of Allergy and Clinical Immunology  Volume 133, Issue 1, Pages 263-265.e3 (January 2014) DOI: 10.1016/j.jaci.2013.09.045 Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Microscopic section right-upper lobe (×4) in case 9, a 72-year-old woman with lifelong asthma who never smoked. There is mild centrilobular emphysema with irregularly enlarged air spaces and fractured alveolar septa (see arrows). Alcian blue/PAS stain as shown demonstrated mucin in lumen of terminal bronchioles (TB) with predominantly recruited neutrophils seen on higher magnification with the CD 15 stain. Sections from left-lower lobe were similar. BV, Blood vessel; PAS, periodic acid–Schiff. Journal of Allergy and Clinical Immunology 2014 133, 263-265.e3DOI: (10.1016/j.jaci.2013.09.045) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 A, Lung elastic recoil in 10 patients with chronic asthma whose studies were obtained when their clinical and physiologic status was better controlled after optimal treatment on 2 separate occasions. The lung elastic recoil pressure is plotted on the x-axis and the lung volume on the y-axis. The slope of each line describes the lung elastic recoil in each patient with asthma. The shaded area describes the normal limits to age 60 years, whereas the solid line immediately to the left of the shaded area describes the lower limit of normal for age more than 60 years.2 Shift of the lung elastic recoil curve to the left of age-matched control is interpreted as a loss of lung elastic recoil. This was present in all 10 patients with chronic moderate-to-severe asthma despite optimal therapy studied on 2 separate occasions. Their optimal FEV1 was 2.5 ± 0.4 L (69% ± 14% predicted), their FVC was 4.2 ± 1.0 L (95% ± 22% predicted), and their ACT8 score had improved to 16 to 19. Cases 4, 9, and 10 died of causes unrelated to acute asthma (dotted lines) and were autopsied. Static lung elastic recoil pressure (Pst(l)) at 100% predicted TLC was 11 (10-13) cmH2O, 40 (34-44)% predicted (median, 1-3 IQR); at 80% predicted TLC (equivalent to 70% observed TLC), it was 8 (7-10) cmH2O, 53 (48-66) % predicted; and at 70% predicted TLC (60% observed TLC), it was 3.5 (3.3-4.6) cmH2O, 47 (40-57) % predicted. Control case did not have measurement of lung elastic recoil. B, Determinants of maximal expiratory airflow limitation at 90% predicted TLC (equivalent to 78% observed TLC) in the 10 patients with asthma after optimal clinical and physiologic improvement as noted in Fig 1. (VmaxE) maximum expiratory airflow (lps) = (Pst(l)) lung elastic recoil (cmH2O) × (Gus) intrinsic upstream airway conductance (cmH2O/lps). The VmaxE at 90% predicted TLC is markedly reduced, as both lung elastic recoil and Gus remain markedly abnormal to a similar extent. Box plots include median, 1 to 3 IQR, and minimum and maximum value. C, Control case: 82-year-old woman with near-lifelong asthma, who never smoked, on ICS + LABA with normal spirometry, lung volumes, diffusing capacity, high-resolution thin-section lung CT including normal voxel quantification. Right upper-lobe (×2) transaxial section (H&E stain) demonstrated alveolar duct dilation (see arrows) with alveolar hyperinflation with mostly intact alveolar septa and homogenous enlargement of alveolar space. This is attributed to aging with no significant lung tissue breakdown. Areas from right and left upper and lower lobes were similar. ACT, Asthma Control Test; FVC, forced vital capacity; H&E, hematoxylin-eosin; ICS, inhaled corticosteroid; IQR, interquartile range; LABA, long-acting β2 agonist; TLC, total lung capacity. Journal of Allergy and Clinical Immunology 2014 133, 263-265.e3DOI: (10.1016/j.jaci.2013.09.045) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 A, Lung elastic recoil in 10 patients with chronic asthma whose studies were obtained when their clinical and physiologic status was better controlled after optimal treatment on 2 separate occasions. The lung elastic recoil pressure is plotted on the x-axis and the lung volume on the y-axis. The slope of each line describes the lung elastic recoil in each patient with asthma. The shaded area describes the normal limits to age 60 years, whereas the solid line immediately to the left of the shaded area describes the lower limit of normal for age more than 60 years.2 Shift of the lung elastic recoil curve to the left of age-matched control is interpreted as a loss of lung elastic recoil. This was present in all 10 patients with chronic moderate-to-severe asthma despite optimal therapy studied on 2 separate occasions. Their optimal FEV1 was 2.5 ± 0.4 L (69% ± 14% predicted), their FVC was 4.2 ± 1.0 L (95% ± 22% predicted), and their ACT8 score had improved to 16 to 19. Cases 4, 9, and 10 died of causes unrelated to acute asthma (dotted lines) and were autopsied. Static lung elastic recoil pressure (Pst(l)) at 100% predicted TLC was 11 (10-13) cmH2O, 40 (34-44)% predicted (median, 1-3 IQR); at 80% predicted TLC (equivalent to 70% observed TLC), it was 8 (7-10) cmH2O, 53 (48-66) % predicted; and at 70% predicted TLC (60% observed TLC), it was 3.5 (3.3-4.6) cmH2O, 47 (40-57) % predicted. Control case did not have measurement of lung elastic recoil. B, Determinants of maximal expiratory airflow limitation at 90% predicted TLC (equivalent to 78% observed TLC) in the 10 patients with asthma after optimal clinical and physiologic improvement as noted in Fig 1. (VmaxE) maximum expiratory airflow (lps) = (Pst(l)) lung elastic recoil (cmH2O) × (Gus) intrinsic upstream airway conductance (cmH2O/lps). The VmaxE at 90% predicted TLC is markedly reduced, as both lung elastic recoil and Gus remain markedly abnormal to a similar extent. Box plots include median, 1 to 3 IQR, and minimum and maximum value. C, Control case: 82-year-old woman with near-lifelong asthma, who never smoked, on ICS + LABA with normal spirometry, lung volumes, diffusing capacity, high-resolution thin-section lung CT including normal voxel quantification. Right upper-lobe (×2) transaxial section (H&E stain) demonstrated alveolar duct dilation (see arrows) with alveolar hyperinflation with mostly intact alveolar septa and homogenous enlargement of alveolar space. This is attributed to aging with no significant lung tissue breakdown. Areas from right and left upper and lower lobes were similar. ACT, Asthma Control Test; FVC, forced vital capacity; H&E, hematoxylin-eosin; ICS, inhaled corticosteroid; IQR, interquartile range; LABA, long-acting β2 agonist; TLC, total lung capacity. Journal of Allergy and Clinical Immunology 2014 133, 263-265.e3DOI: (10.1016/j.jaci.2013.09.045) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions