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Comparative Study
. 2018 Jun 15;197(12):1540-1551.
doi: 10.1164/rccm.201710-2028PP.

At the Root: Defining and Halting Progression of Early Chronic Obstructive Pulmonary Disease

Fernando J Martinez  1   2 , MeiLan K Han  2 , James P Allinson  3 , R Graham Barr  4 , Richard C Boucher  5 , Peter M A Calverley  6 , Bartolome R Celli  7 , Stephanie A Christenson  8 , Ronald G Crystal  1 , Malin Fagerås  9 , Christine M Freeman  2   10 , Lars Groenke  11 , Eric A Hoffman  12 , Mehmet Kesimer  5 , Kostantinos Kostikas  13 , Robert Paine 3rd  14   15 , Shahin Rafii  1 , Stephen I Rennard  11 , Leopoldo N Segal  16 , Renat Shaykhiev  1 , Christopher Stevenson  17 , Ruth Tal-Singer  18 , Jørgen Vestbo  19 , Prescott G Woodruff  8 , Jeffrey L Curtis  2   10 , Jadwiga A Wedzicha  3
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Comparative Study

At the Root: Defining and Halting Progression of Early Chronic Obstructive Pulmonary Disease

Fernando J Martinez et al. Am J Respir Crit Care Med. .

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Figures

Figure 1.
Figure 1.
Proposed trajectories for lung function. (A) Normal lung function natural history; (B) reduced lung growth during fetal development, childhood, or adolescence, which can reduce maximally attained lung function; (C) shortened plateau; (D) accelerated lung function loss during adulthood; (E) episodic loss of lung function without full recovery; (F) late accelerated loss of lung function. *Presence of early disease for each disease natural history. Reproduced by permission from Reference .
Figure 2.
Figure 2.
Epigenetic changes induced by smoking lead to progressive small airway damage and inflammation in early chronic obstructive pulmonary disease (COPD). (A and C) Normal small airways; (B and D) small airways in early COPD. (A) Normal distal epithelium contains self-renewing basal cells, which differentiate into ciliated, mucus-producing goblet, and secretory (club) cells, joined by tight junctions that form an impermeable barrier. Mucus is separated from the epithelial surface by a robust aqueous periciliary layer. (B) Smoking induces hyperplasia of basal and goblet cells, squamous metaplasia, loss of club and ciliated cells, decrease in the periciliary layer and ciliary damage and crowding, and junctional barrier loss. (C) In normal small airways, dimeric IgA (structure shown in inset) is transcytosed by the polymeric Ig receptor (pIgR) into the mucosal lumen. pIgR cleavage at the luminal surface liberates secretory IgA, which prevents bacterial invasion. (D) Smoking reduces pIgR expression, leading to localized secretory IgA deficiency in small airways, allowing bacteria to invade and induce sustained airway inflammation. NF-κB = nuclear factor-κB. Illustration by Patricia Ferrer Beals.
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References

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