Translational Animal Models in Drug Discovery and Development

Cigarette Smoke-Induced Translational Animal Models of Chronic Obstructive Lung Disease

Author(s): Andrew Churg and Joanne L. Wright

Pp: 196-216 (21)

DOI: 10.2174/978160805469511201010196

* (Excluding Mailing and Handling)

Abstract

Animal models of chronic obstructive lung disease (COPD) are complicated by the fact that COPD encompasses 4 different anatomic entities: emphysema, small airway remodeling, pulmonary hypertension, increased mucin secretory alterations (the pathology found in the clinical process, chronic bronchitis) and one clinical entity without distinct pathological association (acute exacerbations). Models using chronic cigarette smoke exposure can reproduce mild forms of some, but not all, of these lesions; however, cigarette smoke exposure never causes the disabling/lethal GOLD stage III or IV lesions associated with human COPD. Further complications of chronic smoke models relate to species differences, and, for mice, strain differences, as well as developmental abnormalities caused by genetic manipulation, abnormalities that can mimic changes of COPD. Numerous drug/genetic modification models using chronic smoke exposure appear to protect partially or completely against the changes of COPD, but trials of these same agents in humans have been disappointing, perhaps because animals are typically treated from day 1 of smoke exposure whereas treatment in humans is always a late intervention; this conclusion suggests that animal models should use late interventions and humans should be treated much earlier in the course of their disease.


Keywords: Animal model, cigarette smoke, COPD, drug discovery, drug development, emphysema, inflammation, pulmonary hypertension, small airway remodeling, translational model.

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      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 60060432 and j.to_ip >=60060432 )) and ((j.from_date <= 1740496020 and j.to_date >= 1740496020 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 4529) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 60060432 and j.to_ip >=60060432 )) and ((j.from_date <= 1740496020 and j.to_date >= 1740496020 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 4529) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 60060432 and j.to_ip >=60060432 )) and ((j.from_date <= 1740496020 and j.to_date >= 1740496020 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 4529)
      850μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ChapterController.php:1549
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` where `b`.`banner_ebook` = 1 and `bd`.`content_type` = 'B' and `bd`.`content_id` = 1119 and `b`.`banner_from_date` <= 1740496020 and `b`.`banner_to_date` >= 1740496020 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.48msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: B
      • 2: 1119
      • 3: 1740496020
      • 4: 1740496020
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select count(*) as aggregate from `uc_cart_products` where cart_id='f6141e5b637804bc22f0882feb1d9ab1'
      240μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._header:260
      • 18. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 20. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    App\Models\Keywords
    10Keywords.php#?
    App\Models\Chapter
    1Chapter.php#?
    App\Models\Ebook
    1Ebook.php#?
        _token
        PUFBNFTZZJ90NcJKBCDSF8gdOlALmGwV1EmQfKll
        _previous
        array:1 [ "url" => "https://alpha.eurekaselect.com/article/25675" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        uc_cart_id
        f6141e5b637804bc22f0882feb1d9ab1
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /chapter/4529
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
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        request_cookies
        0 of 0
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        response_headers
        0 of 0
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        session_attributes
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        ClearShow all
        Date ↕MethodURLData
        #12025-02-25 15:07:00GET/chapter/45291121912