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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The very frequent association between chronic obstructive pulmonary disease &#40;COPD&#41; and other chronic disorders sharing common risk factors&#44;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> has been widely recognized as a major burden on individuals and healthcare systems&#46; If we exclude lung cancer&#44; the most common co-existing conditions that can be objectively measured in COPD patients are cardiovascular diseases&#44; type II diabetes&#44; skeletal muscle dysfunction and osteoporosis&#44; which are represented in different clusters&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">In the last few years the term &#8220;comorbidities&#8221; has been replaced by &#8220;multimorbidities&#8221; to better reflect the nature of this link&#44; with clear reference to a shared pattern of metabolic abnormalities&#44; systemic inflammation and defined risk factors that identifies COPD as one component - not necessarily the most relevant - of the clinical phenotype of a chronic complex patient&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">In a recent study&#44; Miller et al&#46; demonstrated that cardiovascular diseases and diabetes have the highest impact on several patient-related outcomes in COPD patients&#44; even after adjusting for age&#44; sex and smoking history&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> As a matter of fact&#44; the mutual interaction between COPD and cardiac dysfunction is based not only on similar risk factors and pathobiological features such as systemic inflammation&#44; but also on pathophysiological mechanisms such as lung hyperdistension&#44;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> which may impair both ventilatory and cardiac function during effort&#44; thus limiting exercise performance both at maximal or submaximal level&#46; In particular&#44; the dynamic hyperinflation on exertion found in COPD patients with different degrees of airflow obstruction&#44; is associated with a reduction of cardiac output during exercise&#44; limiting both venous return and left ventricle filling volume&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> On the other hand&#44; it has been shown that airflow limitation could negatively impact exercise capacity and physical performance in patients with chronic heart failure&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Systemic hypertension has been related to the increased inflammatory subset observed in COPD&#59;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> the correlation between hypertension&#44; higher degree of dyspnea and reduced physical activity has also been reported&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> This seems even more important if we consider the effect of hypertension on coronary artery disease progression and left ventricular dysfunction&#44; with worsening in exercise tolerance&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> Furthermore&#44; Watz et al&#46; showed that the presence of the metabolic syndrome &#8211;where systemic hypertension and diabetes coexist- among COPD patients is definitely associated with impaired level of physical activity&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">In this issue of the journal&#44; Da Silva and co-workers conducted a cross-sectional study to investigate to what extent the presence of co-existing hypertension&#44; coronary heart disease and diabetes may affect functional capacity in a cohort of 79 patients with COPD&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> These comorbidities have been chosen from others according to their higher prevalence in the population of COPD<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> and relevant effect on major outcomes&#46; Patients were classified as having &#8220;<span class="elsevierStyleItalic">none</span>&#8221;&#44; &#8220;<span class="elsevierStyleItalic">one</span>&#8221;&#44; and &#8220;<span class="elsevierStyleItalic">two or three</span>&#8221; of these comorbidities&#44; and the individual&#39;s functional capacity has been measured objectively by means of spirometry and six-minute walked distance &#40;6MWT&#41;&#46; As well as the perceived health status&#44; 6MWT decreased progressively from &#8220;<span class="elsevierStyleItalic">none</span>&#8221; to &#8220;<span class="elsevierStyleItalic">two or three</span>&#8221; categories &#40;see <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Interestingly&#44; the number of comorbidities of interest was independently associated with the submaximal exercise performance after adjusting for main confounders &#40;age&#44; severity of COPD&#44; and score of health status&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">These findings need to be discussed in more depth&#44; ideally aspects such as weakness and strength should be addressed and clarified for the readers&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">In line with previous literature&#44;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> authors confirm the lack of association between the degree of airflow obstruction and the number of concomitant disorders&#46; However&#44; this study only provides the evidence about 3 comorbidities&#44; although they are the most important&#44; which relate to the individual&#39;s function&#46; Impaired 6MWT and 6MWT-derived variables &#40;speed&#44; work&#44; exercise-induced oxygen saturation&#41; have an additional predictive value of mortality in patients with COPD&#44;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> however this performance could be influenced by other coexisting diseases &#40;i&#46;e&#46; musculoskeletal disorders&#41; and factors that have not been taken into account by the authors&#46; In addition&#44; no information was given about the severity of each of these 3 comorbidities&#44; nor about ongoing therapies for managing them&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">We recognize that hypertension&#44; coronary heart disease and diabetes are frequent forms of multimorbidity influencing the individual&#39;s function as single diseases or clustering together&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;8&#44;14</span></a> Indeed&#44; authors have confirmed that these chronic diseases have a negative impact on the exercise capacity&#44; here recorded as both the reduction in meters walked and the increased scores of the items assessing function in the COPD Assessment Test &#40;CAT&#41;&#46; Therefore&#44; accurate assessment and count of comorbidities in the characterization of patients with COPD contribute to predicting their outcomes and risk of mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Another problem with the present data might be that the presence of hypertension&#44; coronary heart disease and diabetes was self-reported and&#47;or derived by the assumed medications&#44; there was no objective assessment&#46; Recently&#44; it has been shown that self-reporting may result in underestimation of chronic diseases and multimorbidity&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Walking performance&#44; however&#44; does not exclusively represent the functional capacity of patients with COPD&#46; We can only speculate on whether there is direct correlation between 6MWT and the individual&#39;s physical activity &#40;PA&#41;&#44; since a good degree of exercise tolerance is pivotal to performing complex kinds of activities in daily living&#46; In COPD subjects&#44; lower levels of PA are associated with higher degree of severity<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> and a worse prognosis&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> A decline to low PA over time is associated with an increased mortality risk in those with COPD but also those without&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> This suggests that it is important to assess and encourage PA in the earliest stages of COPD in order to maintain it at the highest possible level&#44; as this is associated with better prognosis&#46; However&#44; PA cannot be derived by the submaximal exercise test in the COPD population&#44; nor did authors measure PA in their study sample&#46; A deeper discussion on the existing links between exercise performance and PA should be taken in consideration in order to understand the extent to which other chronic co-existing diseases might limit function in patients with COPD&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">The cumulative effect of multimorbidity in limiting physical performance should be carefully considered when a COPD patient is assessed and managed&#44; paying particular attention to rehabilitation&#46; To date&#44; pulmonary rehabilitation&#44; including exercise training&#44; has proved to be one of the most effective therapies for COPD patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">19&#44;20</span></a> Furthermore&#44; recent studies have shown that even changes in the level of activity following rehabilitation have direct proportional effects on major outcomes in these patients&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> At present&#44; some retrospective studies have shown worse outcomes &#40;in terms of exercise tolerance&#44; and perceived well-being&#41; in COPD patients with associated heart and metabolic diseases undergoing pulmonary rehabilitation&#44; while others reported the opposite effect&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> The reason behind this difference might be the higher degree of impairment in these patients who are generally more dyspnoeic<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> and less physically active&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> However&#44; evidence from available literature is incomplete and there is a need for adjunctive data to understand the effective role of coexisting diseases on rehabilitation outcomes in the population of COPD&#46; For a given different pattern of response to exercise in the complex patients&#44; a tailored intervention could be thus supposed as most important&#46; Although the link between co-existing diseases and reduced performance during pulmonary rehabilitation has been clearly shown&#44; the present study by Da Silva<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> did not consider this aspect&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">In conclusion&#44; taking all the limitations of the present study into account&#44; results corroborate actual debate around the impact of COPD-associated multimorbidity on physical performance and the consequences when a physical therapy is applied to patients&#46; The topic seems to be of critical importance in order to ensure the most effective and personalized treatment for COPD patients referred for a rehabilitation course&#46;</p></span>"
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Editorial
Impaired function in the complex patient with COPD: a matter to be considered
R. Tonellia, E.M. Clinia,b,
Corresponding author
enrico.clini@unimore.it

Corresponding author. University of Modena-Reggio Emilia, Ospedale Villa Pineta, Pavullo n/F (Modena), Italy. Tel.: +39 0536 42039; fax: +39 0536 42039.
a DU of Medical and Surgical Sciences, University of Modena-Reggio Emilia, Italy
b Ospedale Villa Pineta, Pavullo n7F (Modena), Italy
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Relationship between number of the &#40;considered&#41; comorbidities and functional impairment as assessed by health status CAT score &#40;from ref&#35;11&#41;&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The very frequent association between chronic obstructive pulmonary disease &#40;COPD&#41; and other chronic disorders sharing common risk factors&#44;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> has been widely recognized as a major burden on individuals and healthcare systems&#46; If we exclude lung cancer&#44; the most common co-existing conditions that can be objectively measured in COPD patients are cardiovascular diseases&#44; type II diabetes&#44; skeletal muscle dysfunction and osteoporosis&#44; which are represented in different clusters&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">In the last few years the term &#8220;comorbidities&#8221; has been replaced by &#8220;multimorbidities&#8221; to better reflect the nature of this link&#44; with clear reference to a shared pattern of metabolic abnormalities&#44; systemic inflammation and defined risk factors that identifies COPD as one component - not necessarily the most relevant - of the clinical phenotype of a chronic complex patient&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">In a recent study&#44; Miller et al&#46; demonstrated that cardiovascular diseases and diabetes have the highest impact on several patient-related outcomes in COPD patients&#44; even after adjusting for age&#44; sex and smoking history&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> As a matter of fact&#44; the mutual interaction between COPD and cardiac dysfunction is based not only on similar risk factors and pathobiological features such as systemic inflammation&#44; but also on pathophysiological mechanisms such as lung hyperdistension&#44;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> which may impair both ventilatory and cardiac function during effort&#44; thus limiting exercise performance both at maximal or submaximal level&#46; In particular&#44; the dynamic hyperinflation on exertion found in COPD patients with different degrees of airflow obstruction&#44; is associated with a reduction of cardiac output during exercise&#44; limiting both venous return and left ventricle filling volume&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> On the other hand&#44; it has been shown that airflow limitation could negatively impact exercise capacity and physical performance in patients with chronic heart failure&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Systemic hypertension has been related to the increased inflammatory subset observed in COPD&#59;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> the correlation between hypertension&#44; higher degree of dyspnea and reduced physical activity has also been reported&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> This seems even more important if we consider the effect of hypertension on coronary artery disease progression and left ventricular dysfunction&#44; with worsening in exercise tolerance&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> Furthermore&#44; Watz et al&#46; showed that the presence of the metabolic syndrome &#8211;where systemic hypertension and diabetes coexist- among COPD patients is definitely associated with impaired level of physical activity&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">In this issue of the journal&#44; Da Silva and co-workers conducted a cross-sectional study to investigate to what extent the presence of co-existing hypertension&#44; coronary heart disease and diabetes may affect functional capacity in a cohort of 79 patients with COPD&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> These comorbidities have been chosen from others according to their higher prevalence in the population of COPD<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> and relevant effect on major outcomes&#46; Patients were classified as having &#8220;<span class="elsevierStyleItalic">none</span>&#8221;&#44; &#8220;<span class="elsevierStyleItalic">one</span>&#8221;&#44; and &#8220;<span class="elsevierStyleItalic">two or three</span>&#8221; of these comorbidities&#44; and the individual&#39;s functional capacity has been measured objectively by means of spirometry and six-minute walked distance &#40;6MWT&#41;&#46; As well as the perceived health status&#44; 6MWT decreased progressively from &#8220;<span class="elsevierStyleItalic">none</span>&#8221; to &#8220;<span class="elsevierStyleItalic">two or three</span>&#8221; categories &#40;see <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Interestingly&#44; the number of comorbidities of interest was independently associated with the submaximal exercise performance after adjusting for main confounders &#40;age&#44; severity of COPD&#44; and score of health status&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">These findings need to be discussed in more depth&#44; ideally aspects such as weakness and strength should be addressed and clarified for the readers&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">In line with previous literature&#44;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> authors confirm the lack of association between the degree of airflow obstruction and the number of concomitant disorders&#46; However&#44; this study only provides the evidence about 3 comorbidities&#44; although they are the most important&#44; which relate to the individual&#39;s function&#46; Impaired 6MWT and 6MWT-derived variables &#40;speed&#44; work&#44; exercise-induced oxygen saturation&#41; have an additional predictive value of mortality in patients with COPD&#44;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> however this performance could be influenced by other coexisting diseases &#40;i&#46;e&#46; musculoskeletal disorders&#41; and factors that have not been taken into account by the authors&#46; In addition&#44; no information was given about the severity of each of these 3 comorbidities&#44; nor about ongoing therapies for managing them&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">We recognize that hypertension&#44; coronary heart disease and diabetes are frequent forms of multimorbidity influencing the individual&#39;s function as single diseases or clustering together&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;8&#44;14</span></a> Indeed&#44; authors have confirmed that these chronic diseases have a negative impact on the exercise capacity&#44; here recorded as both the reduction in meters walked and the increased scores of the items assessing function in the COPD Assessment Test &#40;CAT&#41;&#46; Therefore&#44; accurate assessment and count of comorbidities in the characterization of patients with COPD contribute to predicting their outcomes and risk of mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Another problem with the present data might be that the presence of hypertension&#44; coronary heart disease and diabetes was self-reported and&#47;or derived by the assumed medications&#44; there was no objective assessment&#46; Recently&#44; it has been shown that self-reporting may result in underestimation of chronic diseases and multimorbidity&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Walking performance&#44; however&#44; does not exclusively represent the functional capacity of patients with COPD&#46; We can only speculate on whether there is direct correlation between 6MWT and the individual&#39;s physical activity &#40;PA&#41;&#44; since a good degree of exercise tolerance is pivotal to performing complex kinds of activities in daily living&#46; In COPD subjects&#44; lower levels of PA are associated with higher degree of severity<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> and a worse prognosis&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> A decline to low PA over time is associated with an increased mortality risk in those with COPD but also those without&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> This suggests that it is important to assess and encourage PA in the earliest stages of COPD in order to maintain it at the highest possible level&#44; as this is associated with better prognosis&#46; However&#44; PA cannot be derived by the submaximal exercise test in the COPD population&#44; nor did authors measure PA in their study sample&#46; A deeper discussion on the existing links between exercise performance and PA should be taken in consideration in order to understand the extent to which other chronic co-existing diseases might limit function in patients with COPD&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">The cumulative effect of multimorbidity in limiting physical performance should be carefully considered when a COPD patient is assessed and managed&#44; paying particular attention to rehabilitation&#46; To date&#44; pulmonary rehabilitation&#44; including exercise training&#44; has proved to be one of the most effective therapies for COPD patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">19&#44;20</span></a> Furthermore&#44; recent studies have shown that even changes in the level of activity following rehabilitation have direct proportional effects on major outcomes in these patients&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> At present&#44; some retrospective studies have shown worse outcomes &#40;in terms of exercise tolerance&#44; and perceived well-being&#41; in COPD patients with associated heart and metabolic diseases undergoing pulmonary rehabilitation&#44; while others reported the opposite effect&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> The reason behind this difference might be the higher degree of impairment in these patients who are generally more dyspnoeic<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> and less physically active&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> However&#44; evidence from available literature is incomplete and there is a need for adjunctive data to understand the effective role of coexisting diseases on rehabilitation outcomes in the population of COPD&#46; For a given different pattern of response to exercise in the complex patients&#44; a tailored intervention could be thus supposed as most important&#46; Although the link between co-existing diseases and reduced performance during pulmonary rehabilitation has been clearly shown&#44; the present study by Da Silva<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> did not consider this aspect&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">In conclusion&#44; taking all the limitations of the present study into account&#44; results corroborate actual debate around the impact of COPD-associated multimorbidity on physical performance and the consequences when a physical therapy is applied to patients&#46; The topic seems to be of critical importance in order to ensure the most effective and personalized treatment for COPD patients referred for a rehabilitation course&#46;</p></span>"
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