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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">COPD treatment has been traditionally based on drugs aimed at either compensating airflow obstruction or reducing airway inflammation in a non-specific manner&#46; The first group&#44; which act on airflow obstruction&#44; mainly include adrenergic agents &#40;basically &#946;-adrenergic drugs&#41;&#44; which modulate the sympathetic response of the airway&#44; and molecules with an anticholinergic effect&#44; which neutralize the parasympathetic system&#46; Recent advances in these drug groups have consisted primarily of prolonging their effect and combining various molecules in a single device&#46; Surprisingly&#44; no drugs have yet appeared that regulate the &#8220;non-adrenergic&#44; non-cholinergic&#8221; &#40;NANC&#41; airway response system&#44; the mediators of which are different from those of the two conventional autonomous nervous systems mentioned above&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">1</span></a> The drugs generally associated with a reduction in airway inflammation are inhaled or systemic corticosteroids&#44; and more recently cyclic nucleotide phosphodiesterase &#40;PDE&#41; inhibitors&#44;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">2</span></a> such as roflumilast and theophylline&#44; initially used as a bronchodilator&#46; These drugs act by inhibiting the PDE4 isoenzyme&#44; although theophylline also inhibits PDE3 and increases histone deacetylase &#40;HDAC&#41; activity&#46; However&#44; in recent years&#44; other prophylactic and therapeutic approaches in COPD have been progressively gaining more importance&#46; Some of these&#44; such as alpha-1 antitrypsin deficiency replacement and respiratory rehabilitation&#44; already have been around for a long time&#46; The latter in particular involves a multidimensional approach&#44; in which both healthier living habits and exercise play a significant role&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">3</span></a> Healthy lifestyle interventions include stopping smoking and avoiding harmful exposures &#40;coal or wood smoke&#44; environmental pollution&#41;&#46; In the specific case of smoking&#44; numerous pharmacological and non-pharmacological options are now available&#44; such as motivational interventions&#44; nicotine replacement therapy&#44; bupropion&#44; varenicline&#44; etc&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">4</span></a> A healthy diet is also recommended&#44; and nowadays&#44; more emphasis is being given to an appropriate level of physical activity&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">5</span></a> Indeed&#44; physical activity is no longer thought to depend exclusively on the exercise capacity of the patient but rather on their lifestyle habits and motivation&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">5</span></a> It is clear nowadays that both dimensions &#40;capacity and lifestyle&#47;motivation&#41; must be taken into account when designing therapeutic interventions&#46; When improving the patient&#39;s level of physical activity is ineffective&#44; their program must be adjusted to include rehabilitation and physiotherapy&#44; the mainstays of which are muscle and cardiovascular training&#46;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">6&#44;7</span></a> Another area that is progressively gaining importance in the treatment of patients with COPD is home non-invasive mechanical ventilation &#40;NIMV&#41;&#46; The clear benefit of this therapy in patients with exacerbations has been complemented in recent years with robust evidence in stable&#44; carefully selected patients &#40;mainly with hypercapnia&#41;&#44; and even in patients who have recently suffered an exacerbation&#46;<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">8&#44;9</span></a> Nutritional supplements and even anabolic steroids can be useful in selected patients with weight loss or frank cachexia&#44; helping them to restore muscle function and exercise capacity&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">10</span></a> Nor should we forget the role of lung transplantation&#44; indicated in patients with advanced disease and both endoscopic and surgical lung volume reduction&#46; Finally&#44; the most novel approach witnessed to date is the emergence of biological response modulators &#40;BRM&#41;&#44; known more colloquially as &#8220;biologics&#8221;&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">11</span></a> Of particular interest are antibodies that target certain key molecules in different modalities of the inflamatory response &#40;interleukins and their receptors&#44; immunoglobulins&#44; etc&#46;&#41;&#44; kinase-transcription factor inhibitors&#44; and more speculatively&#44; potential microbiome modulators&#46; The most important of the first group are antibodies targeting TNF-&#945;&#44; IL-1 &#40;&#945; and &#946;&#41;&#44; IL-4&#44; IL-5&#44; IL-6&#44; IL-8&#44; IL-13&#44; IL-17&#44; IL-23&#44; IL-33&#44; TGF-&#946;&#44; CCL-11&#44; TSLP and IgE&#44; while the new kinase inhibitors &#40;in addition to the old faithfuls&#44; theophylline&#44; corticosteroids&#44; and the macrolides&#41; include IMD-1041 and IMD-0354&#44; losmapimod&#44; PH-797804&#44; RV-568&#44; SB-681323&#44; PF-03715455&#44; and trametinib&#44; solumetinib&#44; and thioredoxin&#46;<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">12&#44;13</span></a> We should also mention probiotics &#40;preparations which contain live microorganisms that are incorporated into the individual&#39;s flora&#41; and prebiotics &#40;inorganic compounds that can be used by beneficial microbiota&#41;&#44; although these products in particular still lack a firm conceptual basis&#44; since the respiratory microbiome in particular is relatively unknown&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">14</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">All of these treatments combine to address a relatively new concept of the disease&#44; in which a generic diagnosis of COPD is deemed insufficient&#46; Nowadays a number of individual traits must be taken into consideration&#44; with the aim of offering more precise&#44; and thus more personalized&#44; treatment&#46; Moreover&#44; these individual traits may be common to groups of individuals with the same disease&#44; and may&#44; as such&#44; constitute disease phenotypes&#46; With this approach&#44; COPD would be considered polyphenic &#40;a word that has not yet been generally adopted in the clinical setting&#44; despite being widely recognized in biology&#41;&#44; as it encompasses various phenotypes&#46; There is currently great interest in determining if the phenotypes &#40;or at least some of them&#41; correspond to specific endotypes&#44;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">15&#44;16</span></a> that is to say&#44; if they have common biological mechanisms&#46; This is important for 3 reasons&#58; to improve our knowledge of the different pathophysiological mechanisms of the disease&#59; to determine the most specific biomarkers possible for identifying the above-mentioned endotypes&#59; and to design more personalized treatments&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Funding</span><p id="par0015" class="elsevierStylePara elsevierViewall">This editorial is partially funded by SAF2014-54371 &#40;FEDER funds&#41;&#44; SEPAR 2015 and FUCAP&#46;</p></span></span>"
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Editorial
COPD Therapy: Beyond Conventional Pharmacology
La terapia de la EPOC, más allá de la farmacología clásica
Joaquim Gea
Servicio de Neumología, Hospital del Mar – IMIM. DCEXS, Universitat Pompeu Fabra. CIBERES, ISCIII, Barcelona, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">COPD treatment has been traditionally based on drugs aimed at either compensating airflow obstruction or reducing airway inflammation in a non-specific manner&#46; The first group&#44; which act on airflow obstruction&#44; mainly include adrenergic agents &#40;basically &#946;-adrenergic drugs&#41;&#44; which modulate the sympathetic response of the airway&#44; and molecules with an anticholinergic effect&#44; which neutralize the parasympathetic system&#46; Recent advances in these drug groups have consisted primarily of prolonging their effect and combining various molecules in a single device&#46; Surprisingly&#44; no drugs have yet appeared that regulate the &#8220;non-adrenergic&#44; non-cholinergic&#8221; &#40;NANC&#41; airway response system&#44; the mediators of which are different from those of the two conventional autonomous nervous systems mentioned above&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">1</span></a> The drugs generally associated with a reduction in airway inflammation are inhaled or systemic corticosteroids&#44; and more recently cyclic nucleotide phosphodiesterase &#40;PDE&#41; inhibitors&#44;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">2</span></a> such as roflumilast and theophylline&#44; initially used as a bronchodilator&#46; These drugs act by inhibiting the PDE4 isoenzyme&#44; although theophylline also inhibits PDE3 and increases histone deacetylase &#40;HDAC&#41; activity&#46; However&#44; in recent years&#44; other prophylactic and therapeutic approaches in COPD have been progressively gaining more importance&#46; Some of these&#44; such as alpha-1 antitrypsin deficiency replacement and respiratory rehabilitation&#44; already have been around for a long time&#46; The latter in particular involves a multidimensional approach&#44; in which both healthier living habits and exercise play a significant role&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">3</span></a> Healthy lifestyle interventions include stopping smoking and avoiding harmful exposures &#40;coal or wood smoke&#44; environmental pollution&#41;&#46; In the specific case of smoking&#44; numerous pharmacological and non-pharmacological options are now available&#44; such as motivational interventions&#44; nicotine replacement therapy&#44; bupropion&#44; varenicline&#44; etc&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">4</span></a> A healthy diet is also recommended&#44; and nowadays&#44; more emphasis is being given to an appropriate level of physical activity&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">5</span></a> Indeed&#44; physical activity is no longer thought to depend exclusively on the exercise capacity of the patient but rather on their lifestyle habits and motivation&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">5</span></a> It is clear nowadays that both dimensions &#40;capacity and lifestyle&#47;motivation&#41; must be taken into account when designing therapeutic interventions&#46; When improving the patient&#39;s level of physical activity is ineffective&#44; their program must be adjusted to include rehabilitation and physiotherapy&#44; the mainstays of which are muscle and cardiovascular training&#46;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">6&#44;7</span></a> Another area that is progressively gaining importance in the treatment of patients with COPD is home non-invasive mechanical ventilation &#40;NIMV&#41;&#46; The clear benefit of this therapy in patients with exacerbations has been complemented in recent years with robust evidence in stable&#44; carefully selected patients &#40;mainly with hypercapnia&#41;&#44; and even in patients who have recently suffered an exacerbation&#46;<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">8&#44;9</span></a> Nutritional supplements and even anabolic steroids can be useful in selected patients with weight loss or frank cachexia&#44; helping them to restore muscle function and exercise capacity&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">10</span></a> Nor should we forget the role of lung transplantation&#44; indicated in patients with advanced disease and both endoscopic and surgical lung volume reduction&#46; Finally&#44; the most novel approach witnessed to date is the emergence of biological response modulators &#40;BRM&#41;&#44; known more colloquially as &#8220;biologics&#8221;&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">11</span></a> Of particular interest are antibodies that target certain key molecules in different modalities of the inflamatory response &#40;interleukins and their receptors&#44; immunoglobulins&#44; etc&#46;&#41;&#44; kinase-transcription factor inhibitors&#44; and more speculatively&#44; potential microbiome modulators&#46; The most important of the first group are antibodies targeting TNF-&#945;&#44; IL-1 &#40;&#945; and &#946;&#41;&#44; IL-4&#44; IL-5&#44; IL-6&#44; IL-8&#44; IL-13&#44; IL-17&#44; IL-23&#44; IL-33&#44; TGF-&#946;&#44; CCL-11&#44; TSLP and IgE&#44; while the new kinase inhibitors &#40;in addition to the old faithfuls&#44; theophylline&#44; corticosteroids&#44; and the macrolides&#41; include IMD-1041 and IMD-0354&#44; losmapimod&#44; PH-797804&#44; RV-568&#44; SB-681323&#44; PF-03715455&#44; and trametinib&#44; solumetinib&#44; and thioredoxin&#46;<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">12&#44;13</span></a> We should also mention probiotics &#40;preparations which contain live microorganisms that are incorporated into the individual&#39;s flora&#41; and prebiotics &#40;inorganic compounds that can be used by beneficial microbiota&#41;&#44; although these products in particular still lack a firm conceptual basis&#44; since the respiratory microbiome in particular is relatively unknown&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">14</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">All of these treatments combine to address a relatively new concept of the disease&#44; in which a generic diagnosis of COPD is deemed insufficient&#46; Nowadays a number of individual traits must be taken into consideration&#44; with the aim of offering more precise&#44; and thus more personalized&#44; treatment&#46; Moreover&#44; these individual traits may be common to groups of individuals with the same disease&#44; and may&#44; as such&#44; constitute disease phenotypes&#46; With this approach&#44; COPD would be considered polyphenic &#40;a word that has not yet been generally adopted in the clinical setting&#44; despite being widely recognized in biology&#41;&#44; as it encompasses various phenotypes&#46; There is currently great interest in determining if the phenotypes &#40;or at least some of them&#41; correspond to specific endotypes&#44;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">15&#44;16</span></a> that is to say&#44; if they have common biological mechanisms&#46; This is important for 3 reasons&#58; to improve our knowledge of the different pathophysiological mechanisms of the disease&#59; to determine the most specific biomarkers possible for identifying the above-mentioned endotypes&#59; and to design more personalized treatments&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Funding</span><p id="par0015" class="elsevierStylePara elsevierViewall">This editorial is partially funded by SAF2014-54371 &#40;FEDER funds&#41;&#44; SEPAR 2015 and FUCAP&#46;</p></span></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Gea J&#46; La terapia de la EPOC&#44; m&#225;s all&#225; de la farmacolog&#237;a cl&#225;sica&#46; Arch Bronconeumol&#46; 2020&#59;56&#58;343&#8211;344&#46;</p>"
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ISSN: 15792129
Original language: English
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