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Arterial remodelling in smokers and in patients with small airway disease and COPD: implications for lung physiology and early origins of pulmonary hypertension

Prem Bhattarai, Wenying Lu, Archana Vijay Gaikwad, Surajit Dey, Collin Chia, Josie Larby, Greg Haug, Ashutosh Hardikar, Andrew Williams, Gurpreet Kaur Singhera, Tillie-Louise Hackett, Mathew Suji Eapen, Sukhwinder Singh Sohal
ERJ Open Research 2022 8: 00254-2022; DOI: 10.1183/23120541.00254-2022
Prem Bhattarai
1Respiratory Translational Research Group, Dept of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, TAS, Australia
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Wenying Lu
1Respiratory Translational Research Group, Dept of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, TAS, Australia
2Launceston Respiratory and Sleep Centre, Launceston, TAS, Australia
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Archana Vijay Gaikwad
1Respiratory Translational Research Group, Dept of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, TAS, Australia
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Surajit Dey
1Respiratory Translational Research Group, Dept of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, TAS, Australia
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Collin Chia
1Respiratory Translational Research Group, Dept of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, TAS, Australia
2Launceston Respiratory and Sleep Centre, Launceston, TAS, Australia
3Dept of Respiratory Medicine, Launceston General Hospital, Launceston, TAS, Australia
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Josie Larby
1Respiratory Translational Research Group, Dept of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, TAS, Australia
3Dept of Respiratory Medicine, Launceston General Hospital, Launceston, TAS, Australia
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Greg Haug
1Respiratory Translational Research Group, Dept of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, TAS, Australia
3Dept of Respiratory Medicine, Launceston General Hospital, Launceston, TAS, Australia
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Ashutosh Hardikar
1Respiratory Translational Research Group, Dept of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, TAS, Australia
3Dept of Respiratory Medicine, Launceston General Hospital, Launceston, TAS, Australia
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Andrew Williams
1Respiratory Translational Research Group, Dept of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, TAS, Australia
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Gurpreet Kaur Singhera
4Dept of Cardiothoracic Surgery, Royal Hobart Hospital, Hobart, TAS, Australia
5Dept of Anaesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, BC, Canada
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Tillie-Louise Hackett
5Dept of Anaesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, BC, Canada
6Centre for Heart Lung Innovation, St Paul's Hospital, Vancouver, BC, Canada
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Mathew Suji Eapen
1Respiratory Translational Research Group, Dept of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, TAS, Australia
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Sukhwinder Singh Sohal
1Respiratory Translational Research Group, Dept of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, TAS, Australia
2Launceston Respiratory and Sleep Centre, Launceston, TAS, Australia
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  • For correspondence: sssohal@utas.edu.au
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  • FIGURE 1
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    FIGURE 1

    Methods for measurement of a) external and luminal diameter and b) categorisation based on external length. c) Strategy for the selection of an individual layer in the arterial wall.

  • FIGURE 2
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    FIGURE 2

    Representative images of Movat's pentachrome-stained pulmonary arteries (a–o) and parenchymal area (×4 magnification) (p–t) for never-smoker normal controls (NC), normal lung function smokers (NLFS), patients with small airway disease (SAD), current smokers with chronic obstructive pulmonary disease (COPD-CS) and ex-smokers with chronic obstructive pulmonary disease (COPD-ES). Arteries grouped by size as a–e) 100–300 µm (×20 magnification), f–j) 300–500 µm (×20 magnification) and k–o) 500–1000 µm (×10 magnification). In p–t, increased parenchymal tissue density and intimal thickening with luminal narrowing can be seen in the four pathological groups.

  • FIGURE 3
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    FIGURE 3

    Comparison of a) parenchymal tissue density, b) total number of arteries normalised to parenchymal tissue density and c) number of arteries normalised to parenchymal tissue density in arterial ranges of 100–300 µm, 300–500 µm and 500–1000 µm. NC: never-smoker normal controls; NLFS: normal lung function smokers; SAD: patients with small airway disease; COPD-CS: current smokers with chronic obstructive pulmonary disease; COPD-ES: ex-smokers with chronic obstructive pulmonary disease. *: p≤0.05; **: p≤0.01; ****: p≤0.0001.

  • FIGURE 4
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    FIGURE 4

    a) Total arterial wall thickness in the arterial range of 100–300 µm, 300–500 µm and 500–1000 µm. b) Correlation of total arterial thickness with smoking history in current smokers with chronic obstructive pulmonary disease (COPD-CS). c) Correlation of total arterial thickness with forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) % in COPD-CS group. NC: never-smoker normal controls; NLFS: normal lung function smokers; SAD: patients with small airway disease; COPD-ES: ex-smokers with chronic obstructive pulmonary disease. *: p≤0.05; **: p≤0.01; ***: p≤0.001.

  • FIGURE 5
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    FIGURE 5

    Comparison of individual layers of arterial wall between the groups for a) small arteries, b) medium arteries and c) large arteries. NC: never-smoker normal controls; NLFS: normal lung function smokers; SAD: patients with small airway disease; COPD-CS: current smokers with chronic obstructive pulmonary disease; COPD-ES: ex-smokers with chronic obstructive pulmonary disease. *: p≤0.05; **: p≤0.01; ***: p≤0.001.

  • FIGURE 6
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    FIGURE 6

    Correlation of intima thickness in current smokers with chronic obstructive pulmonary disease (COPD-CS) with a) smoking history in pack-years, b) forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) % and c) forced expiratory flow at 25–75% of FVC (FEF25–75%). d) Correlation of intima thickness in patients with small airway disease (SAD) with FEV1/FVC %.

  • FIGURE 7
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    FIGURE 7

    Comparison of sum elastin percentage for a) total arterial wall in different arterial ranges, b) individual layers in small arteries (100–300 µm), c) individual layers in medium arteries (300–500 µm) and d) individual layers in large arteries (500–1000 µm). NC: never-smoker normal control; NLFS: normal lung function smokers; SAD: patients with small airway disease; COPD-CS: current smokers with chronic obstructive pulmonary disease; COPD-ES: ex-smokers with chronic obstructive pulmonary disease. *: p≤0.05; **: p≤0.01.

  • FIGURE 8
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    FIGURE 8

    Correlation of thickness to elastin deposition in the a) intima, b) media and c) adventitia. Correlation calculated using Pearson's r’. The elastin deposition in the intima layer negatively correlated with thickness for all groups across sizes, except for large arteries in the never-smoker normal control (NC) group. The media layer also showed a similar trend except for large arteries in patients with small airway disease (SAD) and current smokers with chronic obstructive pulmonary disease (COPD-CS) and medium arteries in COPD-CS. No statistically significant correlations were observed for the adventitial layer. NLFS: normal lung function smokers; COPD-ES: ex-smokers with chronic obstructive pulmonary disease.

Tables

  • Figures
  • TABLE 1

    Participant demographics

    NCNLFSSADCOPD-CSCOPD-ES
    Subjects, n125+1#8+1#910
    Sex, n
     Female64753
     Male62247
    Age (years)42 (19–63)68.5 (52–79)59 (42–84)63 (59–78)68 (56–85)
    Smoking (pack-years)027 (1–60)40 (20–72)30 (2–50)30 (18–60)
     Passive smoking, n=11020
    FEV1 (% predicted)100 (87–143)83 (60–109)77 (57–109)81.5 (63–98)
    FEV1/FVC (%)81.5 (70–90)73.4 (69–78)66 (60–70)63.9 (55–69)
    FEF25–75% (% predicted)81.5 (71–116)46.5 (31–69)37 (28–47)38 (20–55)
    DLCO (% predicted)84.4 (50–95)78.1 (54–91)71 (34–84)78 (51–105)

    Data expressed as median (range), unless otherwise indicated. NC: never-smoker normal controls; NLFS: normal lung function smokers; SAD: patients with small airway disease; COPD-CS: current smokers with chronic obstructive pulmonary disease; COPD-ES: ex-smokers with chronic obstructive pulmonary disease; FEV1: forced expiratory volume in 1 s; FVC: forced vital capacity; FEF25–75%: forced expiratory flow at 25–75% of FVC (L·s−1); DLCO: diffusing capacity of the lungs for carbon monoxide. #: number of subjects with passive smoking history.

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    Arterial remodelling in smokers and in patients with small airway disease and COPD: implications for lung physiology and early origins of pulmonary hypertension
    Prem Bhattarai, Wenying Lu, Archana Vijay Gaikwad, Surajit Dey, Collin Chia, Josie Larby, Greg Haug, Ashutosh Hardikar, Andrew Williams, Gurpreet Kaur Singhera, Tillie-Louise Hackett, Mathew Suji Eapen, Sukhwinder Singh Sohal
    ERJ Open Research Oct 2022, 8 (4) 00254-2022; DOI: 10.1183/23120541.00254-2022

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    Arterial remodelling in smokers and in patients with small airway disease and COPD: implications for lung physiology and early origins of pulmonary hypertension
    Prem Bhattarai, Wenying Lu, Archana Vijay Gaikwad, Surajit Dey, Collin Chia, Josie Larby, Greg Haug, Ashutosh Hardikar, Andrew Williams, Gurpreet Kaur Singhera, Tillie-Louise Hackett, Mathew Suji Eapen, Sukhwinder Singh Sohal
    ERJ Open Research Oct 2022, 8 (4) 00254-2022; DOI: 10.1183/23120541.00254-2022
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