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it is a more complex systemic disease with significant extra pulmonary effects that impact on severity and which is associated with other chronic conditions&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#8211;6</span></a> It is estimated that two-thirds of the patients with COPD have one or two comorbidities&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> Arterial hypertension&#44; diabetes mellitus&#44; coronary artery disease&#44; heart failure&#44; respiratory infections and lung cancer are the most common comorbidities described in association with COPD&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> These chronic conditions play an important role in morbidity&#44; representing a significant impact on health status&#44; health care costs and prognoses&#46; In the final analysis&#44; many patients are more likely to die from comorbid disease than COPD itself&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#8211;10</span></a> As recently evidenced by Divo et al&#46;&#44; some comorbidities&#44; like coronary disease&#44; cancers &#40;lung&#44; esophageal&#44; pancreatic and breast&#41;&#44; anxiety&#44; arrhythmia and interstitial pulmonary fibrosis&#44; are independently associated with increased risk of death&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> For these reasons&#44; the treatment of COPD should focus not only on the symptom control and prevention of exacerbations&#44; but it should also be directed to the systemic manifestations and comorbidities&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Pulmonary rehabilitation &#40;PR&#41; is a non-pharmacological intervention that aims to restore the patient to his or her highest functional capacity and to promote social reintegration&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12&#44;13</span></a> PR is indicated in patients who remain symptomatic despite adequate pharmacologic therapy&#44; at all grades of severity and among all age groups&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> PR should be considered in patients with breathlessness &#40;while walking at their own pace on level ground&#41; and limitation in activities of daily life&#46; PR can improve symptoms&#44; the quality of life&#44; exercise tolerance&#44; physical and emotional participation in everyday activities and it can also reduce healthcare resources utilization&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;12</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Objectives</span><p id="par0020" class="elsevierStylePara elsevierViewall">The aim of this study was to determine the prevalence of chronic comorbidities in patients with COPD and to evaluate the influence of baseline characteristics as well as comorbidities on the outcomes of PR&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Methods</span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Patient selection</span><p id="par0025" class="elsevierStylePara elsevierViewall">This retrospective study included all COPD patients that attended a PRP in our unit in the last 5 years&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">The diagnosis and the spirometric classification were based on the Global Initiative for Chronic Obstructive Lung Disease &#40;GOLD&#41; guidelines&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Patients with chronic respiratory failure were considered GOLD IV&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">The clinical records were reviewed to collect demographic data &#40;age&#44; gender and body mass index&#41;&#44; clinical data &#40;smoking history&#44; long-term oxygen therapy &#8211; LTOT&#44; non-invasive ventilation &#8211; NIV&#41; and diagnostic work-up &#40;imaging&#44; pulmonary function tests&#44; blood gas analysis&#41;&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Comorbidities were recorded based on the patients&#8217; clinical records&#44; which included all medical data from different specialties and were duly confirmed by patients&#8217; medication list and diagnostic tests&#44; also available on their medical records&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Comorbidities</span><p id="par0045" class="elsevierStylePara elsevierViewall">Comorbidity is defined as the coexistence of another medical condition alongside COPD&#44; and does not imply causation&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">The frequency of each chronic disease and of the combined diseases was established&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">-</span><p id="par0055" class="elsevierStylePara elsevierViewall">cardiovascular &#40;arterial hypertension&#44; heart failure&#47;cor pulmonale&#44; coronary disease&#44; arrhythmia&#44; cerebrovascular disease and peripheral vascular disease&#41;&#44;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">-</span><p id="par0060" class="elsevierStylePara elsevierViewall">metabolic &#40;diabetes&#44; dyslipidemia&#44; overweight&#47;obesity&#41;&#44;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">-</span><p id="par0065" class="elsevierStylePara elsevierViewall">respiratory &#40;pulmonary tuberculosis sequels&#44; bronchiectasis&#44; obstructive sleep apnea&#44; pulmonary hypertension&#44; interstitial lung disease&#44; lung cancer&#41;&#44;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">-</span><p id="par0070" class="elsevierStylePara elsevierViewall">ostheoarticular pathology and</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">-</span><p id="par0075" class="elsevierStylePara elsevierViewall">anxiety&#47;depression&#46;</p></li></ul></p><p id="par0080" class="elsevierStylePara elsevierViewall">The patients were grouped according to the number of comorbidities &#40;0&#44; 1 and more than one&#41;&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Pulmonary rehabilitation</span><p id="par0085" class="elsevierStylePara elsevierViewall">All patients underwent a PRP with optimization of pharmacological therapy and&#47;or LTOT and&#47;or NIV&#46; The patients were also instructed in disease self-management education and in the modification of risk factors&#44; along with psychosocial and nutritional support&#44; breathing techniques and exercise training&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">The PRP included 8 weeks of physical training&#44; 3 times a week&#44; under the supervision of a physiotherapist&#46; The target training intensity was set at 80&#37; of the peak work rate attained during a previous cardiopulmonary exercise test&#46; The applied method of training was continuous&#44; the time was steadily increased and loaded according to the degree of dyspnea &#40;4&#8211;6 on the modified Borg scale 0&#8211;10&#41; and vital signs&#44; or interval training in patients with intense dyspnea&#46; Each training session lasted approximately 30&#8211;45<span class="elsevierStyleHsp" style=""></span>min&#46; Patients on LTOT exercised under oxygen administration in order to maintain a SpO<span class="elsevierStyleInf">2</span> of at least 90&#37;&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">There were no major changes in training protocol according to comorbidities&#46; However&#44; if patients complained of intense breathlessness during exercise sessions&#44; a slower intensity increment and&#47;or interval training was implemented&#44; instead of continuous training&#46; Some comorbidities needed to be more closely monitored&#44; for example blood glucose fast test in diabetes patients&#44; or ECG monitoring in arrhythmias&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">The response to PR &#91;minimum clinically important difference &#40;MCID&#41;&#93; was measured by the improvement in exercise tolerance &#91;&#43;30<span class="elsevierStyleHsp" style=""></span>m in the 6<span class="elsevierStyleHsp" style=""></span>min walking distance &#40;6MWD&#41;&#93;&#44;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> dyspnea &#91;&#43;1 point on the Mahler Dyspnea Index &#40;MDI&#41;&#93; and health status &#91;&#8722;4 points on the St&#46; George&#39;s Respiratory Questionnaire &#40;SGRQ&#41;&#93;&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15&#44;16</span></a> It was considered to have had an overall improvement when it occurred in those 3 parameters&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Statistics</span><p id="par0105" class="elsevierStylePara elsevierViewall">Data are presented as mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>standard deviation for continuous variables&#44; and frequencies and percentages for categorical variables&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">The comparison of variables was made using <span class="elsevierStyleItalic">&#967;</span><span class="elsevierStyleSup">2</span> test for nominal variables and <span class="elsevierStyleItalic">T</span> student test for quantitative variables&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">The significant variables were then entered in a logistic regression model&#44; taking MCID improvement of 6MWD&#44; SGRQ and MDI as dependent variables&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">All results were considered statistically significant at <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">All statistical analyses were performed using PASW software &#40;version 18&#59; SPSS inc&#46;&#44; Chicago&#44; IL&#44; USA&#41;&#46;</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Results</span><p id="par0130" class="elsevierStylePara elsevierViewall">This study included 114 patients with COPD&#44; corresponding to 77&#46;6&#37; of all respiratory patients who attended PR in our unit &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0135" class="elsevierStylePara elsevierViewall">Most patients were male &#40;83&#46;3&#37;&#41; and the average age was 65&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&#46;1&#46; Five &#40;4&#46;4&#37;&#41;&#44; 35 &#40;30&#46;7&#37;&#41;&#44; 19 &#40;16&#46;7&#37;&#41; and 55 &#40;48&#46;2&#37;&#41; were in grade I&#44; II&#44; III and IV of GOLD&#44; respectively&#46; Mean FEV<span class="elsevierStyleInf">1</span> was 45&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>16&#46;9&#37; of predicted&#46; The majority of patients &#40;65&#37;&#41; had respiratory failure&#44; with a predominance of hypoxemic respiratory failure&#46; Forty-four &#40;38&#46;6&#37;&#41; patients were on LTOT and ten &#40;8&#46;8&#37;&#41; on NIV &#40;Appendix Table 1&#41;&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Distribution according to number and group of comorbidities is shown in <a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#46; Overweight&#47;obesity &#40;63&#46;2&#37;&#41; was the most prevalent comorbidity&#44; followed by hypertension &#40;50&#46;9&#37;&#41;&#44; pulmonary tuberculosis sequels &#40;23&#46;7&#37;&#41;&#44; anxiety&#47;depression &#40;21&#46;1&#37;&#41;&#44; heart failure&#47;cor pulmonale &#40;20&#46;2&#37;&#41;&#44; bronchiectasis &#40;20&#46;2&#37;&#41;&#44; dyslipidemia &#40;19&#46;3&#37;&#41; and ischemic heart disease &#40;12&#46;3&#37;&#41; &#40;Appendix Table 2&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0145" class="elsevierStylePara elsevierViewall">Among these 114 patients with COPD&#44; 20 did not conclude the PRP&#46; The causes of PRP withdrawal were hospitalization with exacerbations&#44; psychiatric disorders and non-compliance with the program&#46; There were no significant differences in baseline characteristics and comorbidities between subjects who completed the PRP and the ones who dropped out &#40;Appendix Tables 1 and 2&#41;&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Of all the patients who concluded PRP&#44; 64&#46;9&#37;&#44; 64&#46;9&#37; and 51&#46;1&#37; improved beyond the MCID for 6MWD&#44; SGRQ and MDI&#44; respectively &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; Only ten &#40;10&#46;6&#37;&#41; patients did not improve in any parameter and 24 &#40;25&#46;5&#37;&#41; patients reported a positive change in all 3 outcomes&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0155" class="elsevierStylePara elsevierViewall">There were no statistically significant correlations between the number of comorbidities &#40;0&#44; 1 and more than one&#41; and PRP outcomes &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">However&#44; there was a significant correlation between some baseline characteristics and comorbidities and improvement in health status&#44; dyspnea and exercise tolerance&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">Respiratory failure was inversely correlated with improvement in health status &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#59; OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;17&#41; and in overall improvement &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;025&#59; OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;33&#41;&#46; Being on LTOT was inversely correlated with improvement in dyspnea &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;016&#59; OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;313&#41;&#44; in exercise tolerance &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;012&#59; OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;32&#41; and in overall improvement &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#59; OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;337&#41;&#46; Patients with lower arterial carbon dioxide tension &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;016&#41; and higher baseline SGRQ score &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;006&#41; had a more pronounced improvement of dyspnea&#46; Patients with lower FEV<span class="elsevierStyleInf">1</span>&#47;FVC &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41; had less improvement in exercise tolerance and those with lower DLCO had less improvement in exercise tolerance &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;032&#41; and in dyspnea improvement &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41; &#40;Appendix Table 3&#41;&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">In terms of comorbidities&#44; ischemic heart disease correlated inversely with improvement in health status &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;003&#59; OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;142&#41;&#44; anxiety&#47;depression with improvement in dyspnea &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;012&#59; OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;247&#41;&#44; bronchiectasis correlated positively with improvement in dyspnea &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;04&#59; OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#46;843&#41; and dyslipidemia with improvement in exercise tolerance &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;013&#59; OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>5&#46;86&#41; &#40;Appendix Table 4&#41;&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">Significant variables were then entered into logistic regression model &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; Respiratory failure and ischemic heart disease negatively influenced improvement in health status&#46; Anxiety&#47;depression predicted a lower improvement in dyspnea&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Discussion</span><p id="par0180" class="elsevierStylePara elsevierViewall">This study confirms that comorbidities are prevalent among COPD patients who are referred to PRP&#46; Other authors&#44; like Mapel and colleagues&#44; found an average of 3&#46;7 comorbidities in COPD patients compared with 1&#46;8 in healthy controls&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a></p><p id="par0185" class="elsevierStylePara elsevierViewall">The most common conditions associated with COPD were cardiovascular diseases&#44; other respiratory diseases and anxiety&#47;depression&#44; similar to what has been described in the literature&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;11</span></a> Following overweight&#47;obesity&#44; arterial hypertension was the second most prevalent comorbidity in our sample&#44; and the first one found by Divo et al&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> On the other hand&#44; a significant number of our patients presented comorbidities associated by these authors with a major risk of mortality&#44; such as congestive heart failure&#44; coronary artery disease and anxiety&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p><p id="par0190" class="elsevierStylePara elsevierViewall">The association with cardiovascular diseases is already known&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> FEV<span class="elsevierStyleInf">1</span> is an independent predictor of death from myocardial infarction&#46; Systemic arterial stiffness is a good predictor of vascular disease<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> and is increased in COPD&#46; The presence of systemic inflammation accelerates coronary atherosclerosis&#44; resulting in ischemia&#46; Thus&#44; COPD is an independent risk factor for coronary disease&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a></p><p id="par0195" class="elsevierStylePara elsevierViewall">Approximately 40&#8211;50&#37; of individuals of 60 years or more in industrialized countries meet the criteria for metabolic syndrome&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> This syndrome represents a cluster of risk factors &#40;abdominal obesity&#44; atherogenic dyslipidemia&#44; hypertension and insulin resistance&#41; that predispose patients to systemic inflammation&#44; cardiovascular disease and physical inactivity&#44; and frequently coexist with COPD&#46;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20&#8211;22</span></a></p><p id="par0200" class="elsevierStylePara elsevierViewall">Other respiratory diseases were frequently identified in our patients&#46; The high frequency of pulmonary tuberculosis sequels and bronchiectasis reflects the fact that tuberculosis is still common in Portugal&#44; although it has decreased in recent decades&#46;<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">23&#44;24</span></a> On the other hand&#44; prevalence of obstructive sleep apnea is probably due to the fact that a large part of the studied population is overweight&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">Anxiety&#47;depression is a highly prevalent comorbidity in COPD&#46; Hill et al&#46; also concluded that over 42&#37; of COPD patients had symptoms of anxiety&#47;depression&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> It is known that anxiety&#47;depression is related with the degree of dyspnea and feeling of incapacity in COPD patients&#46; Dyspnea is the most disturbing symptom that causes patients to reduce physical activity in order to avoid it&#46; This leads to a sedentary existence&#44; with less emotional and physical involvement in the activities of daily life&#44; and to the worsening of health status as well as to isolation&#46; Anxiety and depression are associated with higher morbidity of COPD&#44; with worse quality of life&#44; more dyspnea&#44; an increase in the utilization of healthcare resources and even higher mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> Previous studies show negative impact of anxiety&#47;depression on 6MWD and quality of life&#46;<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">27&#44;28</span></a> Similarly we found that anxious&#47;depressed patients present lower improvement in dyspnea&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">Patients with ischemic heart disease showed less gain in health status&#46; Crisafulli et al&#46; also concluded that cardiac pathology was inversely related with improvement of health status&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> Dyspnea&#44; fatigue and reduced muscle strength may explain a lower quality of life in these patients&#46; Vanfleteren et al&#46; concluded that ischemic ECG changes are common in patients with COPD and are associated with poor clinical outcomes in PRP&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> However&#44; rehabilitation has well known benefits in patients with coronary heart disease and chronic heart failure&#44; such as the improvement in functional capacity&#44; prognosis and well-being&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a></p><p id="par0215" class="elsevierStylePara elsevierViewall">The prevalence of at least one comorbidity in our cohort was higher &#40;96&#46;5&#37;&#41; than the prevalence reported in other studies &#40;65&#37;&#44; Crisafulli et al&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a>&#41;&#44; but similar to what Mapel documented &#40;only 6&#37; of patients with COPD did not have another chronic medical condition<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a>&#41;&#46;</p><p id="par0220" class="elsevierStylePara elsevierViewall">The high prevalence of comorbidities in our sample can be explained by the fact that the majority of patients had a history of smoking&#44; an average age of over 60 years and a predominance of grade IV COPD&#44; all factors that contribute to a more pronounced systemic inflammation&#46; Systemic inflammation is a common potential mechanism shared by several COPD systemic consequences and comorbidities&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;32&#8211;35</span></a></p><p id="par0225" class="elsevierStylePara elsevierViewall">The outcomes of PRP were similar across the comorbidity categories &#40;0&#44; 1 and more than one&#41;&#44; contrary to what was reported by Crisafulli et al&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a>&#59; he reported that benefits in dyspnea and quality of life were higher in those with fewer comorbidities&#46; However&#44; it should be said that the present study has a limitation concerning the number of patients without comorbidities&#46; This number is very small&#44; and there is an important sample size difference between the comorbid subgroups &#40;4 patients &#8211; 0 comorbidities&#59; 15 patients &#8211; 1 comorbidity&#59; 95 patients &#8211; &#62;1 comorbidity&#41; which mitigates against reaching a definite conclusion on the impact of comorbidities in PRP outcomes in this particular patient population&#46; This limitation might have been solved if there had been a larger patient sample&#46;</p><p id="par0230" class="elsevierStylePara elsevierViewall">Almost half &#40;48&#46;2&#37;&#41; of our patients were GOLD IV and only 16&#46;7&#37; were GOLD III&#46; Even though this is not the usual severity distribution observed in PRP in most centers&#44; this difference may be explained by the fact that our Respiratory Rehabilitation Unit also admits patients after acute exacerbations with respiratory failure &#40;65&#37;&#41;&#46; The authors included patients with chronic respiratory failure in GOLD IV&#44; as classified in GOLD guidelines previous to 2011&#46; Although in our sample we have a predominance of GOLD stage IV patients&#44; there were no statistically significant differences in the PRR outcomes concerning spirometric degrees of COPD&#44; reflecting the benefits at all grades of severity&#46;</p><p id="par0235" class="elsevierStylePara elsevierViewall">We noted that 83&#37; of our sample was composed of men&#44; and this is not the typical gender distribution observed in PRP in most centers&#46; However&#44; COPD in Portugal is more prevalent in men &#40;18&#46;7&#37; versus 10&#46;5&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a></p><p id="par0240" class="elsevierStylePara elsevierViewall">However&#44; the comorbidities &#40;both their number and their type&#41; did not differ between male and female patients &#40;data not shown&#41;&#46;</p><p id="par0245" class="elsevierStylePara elsevierViewall">Some baseline characteristics correlated with the outcomes&#46; Patients with respiratory failure presented a smaller gain in health status&#46; Hypoxemia might cause a low anaerobic threshold during exercise&#44; which determines an early increase of breathing frequency&#44; with a consequent increase in dynamic hyperinflation&#44; a greater degree of dyspnea and a major limitation in activities of daily life&#44; which&#44; in turn&#44; leads to further deconditioning and sedentarism&#46;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">37&#44;38</span></a></p><p id="par0250" class="elsevierStylePara elsevierViewall">Despite the correlations described&#44; patients with COPD and other chronic conditions are not poor candidates for PR and it does not necessarily mean they will improve less&#46; All patients can benefit from PR&#44; which is a holistic therapeutic approach of COPD&#44; and the benefits of exercise training in several comorbidities are already known&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a></p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Conclusions</span><p id="par0255" class="elsevierStylePara elsevierViewall">In patients with COPD&#44; comorbidities are important determinants of health status and prognosis&#46;</p><p id="par0260" class="elsevierStylePara elsevierViewall">Our study confirms that most patients referred to PRP present one or more comorbidities&#44; including metabolic&#44; cardiovascular&#44; respiratory&#44; anxiety&#47;depression and ostheoarticular pathology&#46;</p><p id="par0265" class="elsevierStylePara elsevierViewall">Management of patients with COPD should include the active identification of comorbidities&#44; in order to optimize the therapeutic strategy&#46; PR is a holistic approach that not only deals with respiratory symptoms&#44; but also with systemic effects&#46;</p><p id="par0270" class="elsevierStylePara elsevierViewall">Although some conditions such as respiratory failure and ischemic heart disease may reduce the impact of rehabilitation benefits&#44; this study emphasizes that comorbidities&#44; either alone or in combination&#44; if clinically controlled&#44; do not preclude access to rehabilitation&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Ethical disclosures</span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Protection of human and animal subjects</span><p id="par0275" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for this study&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Confidentiality of data</span><p id="par0280" class="elsevierStylePara elsevierViewall">The authors declare that they have followed the protocols of their work center on the publication of patient data and that all the patients included in the study received sufficient information and gave their written informed consent to participate in the study&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Right to privacy and informed consent</span><p id="par0285" class="elsevierStylePara elsevierViewall">The authors have obtained the written informed consent of the patients or subjects mentioned in the article&#46; The corresponding author is in possession of this document&#46;</p></span></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Authorship</span><p id="par0290" class="elsevierStylePara elsevierViewall">Alexandra Carreiro collected and analyzed data &#40;including a statistical analysis&#41;&#44; and wrote the draft text&#46;</p><p id="par0295" class="elsevierStylePara elsevierViewall">Joana Santos collected and analyzed data and collaborated in the writing up of the text&#46;</p><p id="par0300" class="elsevierStylePara elsevierViewall">F&#225;tima Rodrigues conceived the study&#44; collected data&#44; conducted its analysis and supervised all aspects of the work&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Conflicts of interest</span><p id="par0305" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare&#46;</p></span></span>"
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          "titulo" => "Keywords"
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              "identificador" => "sec0020"
              "titulo" => "Patient selection"
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            1 => array:2 [
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              "titulo" => "Comorbidities"
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            2 => array:2 [
              "identificador" => "sec0030"
              "titulo" => "Pulmonary rehabilitation"
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              "titulo" => "Statistics"
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              "titulo" => "Confidentiality of data"
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              "titulo" => "Right to privacy and informed consent"
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    "pdfFichero" => "main.pdf"
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    "fechaRecibido" => "2012-04-09"
    "fechaAceptado" => "2012-12-17"
    "PalabrasClave" => array:2 [
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        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec239416"
          "palabras" => array:4 [
            0 => "Pulmonary rehabilitation"
            1 => "Exercise"
            2 => "Comorbidities"
            3 => "Chronic obstructive pulmonary disease"
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        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palavras-chave"
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          "palabras" => array:4 [
            0 => "Reabilita&#231;&#227;o respirat&#243;ria"
            1 => "Exerc&#237;cio"
            2 => "Comorbilidades"
            3 => "Doen&#231;a pulmonar obstrutiva cr&#243;nica"
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    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Chronic obstructive pulmonary disease &#40;COPD&#41; represents an increasing burden worldwide&#46; COPD can no longer be considered a disease which only involves the lungs&#44; its systemic consequences make it an important risk factor for other chronic comorbidities&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0015">Aim</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">To determine the frequency of comorbidities in patients with COPD undergoing a pulmonary rehabilitation program &#40;PRP&#41; and to evaluate the influence of baseline characteristics as well as comorbidities on the outcomes of PRP&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0020">Methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The present study included all COPD patients who were admitted to a PRP in our unit&#46; The response to PR was measured by the improvement in exercise tolerance &#40;6<span class="elsevierStyleHsp" style=""></span>min walk test&#41;&#44; dyspnea &#40;Mahler&#39;s Dyspnea Index&#41; and health status &#40;St&#46; George&#39;s Respiratory Questionnaire&#41;&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">114 patients with COPD were included&#46; Most patients &#40;96&#46;5&#37;&#41; had at least one comorbidity&#46; Metabolic diseases &#40;71&#46;1&#37;&#41;&#44; cardiovascular diseases &#40;67&#46;5&#37;&#41;&#44; other respiratory conditions &#40;57&#46;9&#37;&#41; and anxiety&#47;depression &#40;21&#46;1&#37;&#41; were the most prevalent ones&#46; 64&#46;9&#37;&#44; 64&#46;9&#37; and 51&#46;1&#37; of the patients improved in terms of exercise tolerance&#44; quality of life and dyspnea&#44; respectively&#46;</p><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">The overall results were similar in all levels of the disease and in all comorbid subgroups&#46; Logistic regression analysis showed that respiratory failure and ischemic heart disease negatively influenced improvement in health status and anxiety&#47;depression predicted lower improvement in dyspnea&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0030">Conclusion</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">PR was associated with improvements in all comorbid subgroups of patients&#44; underlining the important role of exercise training in rehabilitation of those chronic diseases associated with COPD&#46; On the other hand&#44; the presence of comorbidities in COPD patients&#44; if clinically controlled&#44; should not preclude access to PR&#46;</p>"
      ]
      "pt" => array:2 [
        "titulo" => "Resumo"
        "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0040">Introdu&#231;&#227;o</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">A doen&#231;a pulmonar obstrutiva cr&#243;nica &#40;DPOC&#41; apresenta um impacto crescente a n&#237;vel mundial&#46; Devido ao seu impacto sist&#233;mico&#44; e porque constitui um importante fator de risco para outras comorbilidades cr&#243;nicas&#44; a DPOC n&#227;o pode j&#225; ser considerada uma doen&#231;a com envolvimento exclusivamente pulmonar&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0045">Objetivo</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Determinar a frequ&#234;ncia das comorbilidades em doentes com DPOC que s&#227;o submetidos a um programa de reabilita&#231;&#227;o respirat&#243;ria &#40;PRR&#41; e avaliar a influ&#234;ncia das suas caracter&#237;sticas basais&#44; bem como das suas comorbilidades nos resultados do PRR&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0050">M&#233;todos</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">O presente estudo incluiu todos os doentes com DPOC que foram admitidos na Unidade de Reabilita&#231;&#227;o Respirat&#243;ria para um PRR&#46; A resposta &#224; reabilita&#231;&#227;o respirat&#243;ria &#40;RR&#41; foi avaliada pela melhoria na toler&#226;ncia ao exerc&#237;cio &#40;prova de marcha de 6<span class="elsevierStyleHsp" style=""></span>min&#41;&#44; na dispneia &#40;&#237;ndice de dispneia de Mahler&#41; e na qualidade de vida relacionada com a sa&#250;de &#40;question&#225;rio respirat&#243;rio de St&#46; George&#41;&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0055">Resultados</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Foram inclu&#237;dos 114 doentes com DPOC&#46; A maioria dos doentes &#40;96&#44;5&#37;&#41; tinha pelo menos uma comorbilidade&#46; As doen&#231;as metab&#243;licas &#40;71&#44;1&#37;&#41;&#44; as doen&#231;as cardiovasculares &#40;67&#44;5&#37;&#41;&#44; outras patologias respirat&#243;rias &#40;57&#44;9&#37;&#41; e a ansiedade&#47;depress&#227;o &#40;21&#44;1&#37;&#41; foram as mais prevalentes&#46; Apresentaram melhoria na toler&#226;ncia ao exerc&#237;cio&#44; na qualidade de vida e na dispneia&#44; respetivamente&#44; 64&#44;9&#44; 64&#44;9 e 51&#44;1&#37; dos doentes&#46;</p><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">A globalidade dos resultados foi semelhante em todos os est&#225;dios da doen&#231;a e em todos os subgrupos de comorbilidades&#46; A an&#225;lise por regress&#227;o log&#237;stica demonstrou que a insufici&#234;ncia respirat&#243;ria e a doen&#231;a coron&#225;ria influenciaram negativamente a melhoria na qualidade de vida relacionada com a sa&#250;de&#44; e que a ansiedade&#47;depress&#227;o se relacionou com uma melhoria na dispneia menos acentuada&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0060">Conclus&#227;o</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">A RR proporcionou melhoria nos doentes de todos os subgrupos de comorbilidades&#44; salientando o papel fundamental do treino de exerc&#237;cio na reabilita&#231;&#227;o das doen&#231;as cr&#243;nicas associadas &#224; DPOC&#46; Por outro lado&#44; a presen&#231;a de comorbilidades em doentes com DPOC&#44; se clinicamente controladas&#44; n&#227;o deve impedir a sua inclus&#227;o na RR&#46;</p>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Carreiro A&#44; et al&#46; Impacto das comorbilidades num programa de reabilita&#231;&#227;o respirat&#243;ria em doentes com DPOC&#46; Rev Port Pneumol&#46; 2013&#46; <span class="elsevierStyleInterRef" id="intr0005" href="http://dx.doi.org/10.1016/j.rppneu.2012.12.004">http&#58;&#47;&#47;dx&#46;doi&#46;org&#47;10&#46;1016&#47;j&#46;rppneu&#46;2012&#46;12&#46;004</span>&#46;</p>"
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            "apendice" => "<p id="par0315" class="elsevierStylePara elsevierViewall">The following are the supplementary data to this article&#58;<elsevierMultimedia ident="upi0005"></elsevierMultimedia></p>"
            "etiqueta" => "Appendix A"
            "titulo" => "Supplementary data"
            "identificador" => "sec0090"
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      0 => array:7 [
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        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
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          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Patients admitted to the PRP with exercise training&#46; PRP&#44; pulmonary rehabilitation program&#59; COPD&#44; chronic obstructive pulmonary disease&#46;</p>"
        ]
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        "descripcion" => array:1 [
          "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">&#40;a&#41; Distribution according to the number of comorbidities&#46; &#40;b&#41; Most frequent comorbidities&#46;</p>"
        ]
      ]
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        "etiqueta" => "Table 1"
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                  \t\t\t\t" style="border-bottom: 2px solid black">Improvements&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">&#62;1 comorbidities&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t">Exercise Tolerance&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">61 &#40;64&#46;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">53&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;113&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Quality of life&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">61 &#40;64&#46;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">51&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">48 &#40;51&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">Overall&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">24 &#40;25&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;171&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab355068.png"
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                  \t\t\t\t" style="border-bottom: 2px solid black">Less&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">Upper&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Dyslipidemia&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
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                  \t\t\t\t">Quality of life improvement</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Respir&#46; failure&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">&#8722;1&#46;1588&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Ischemic heart disease&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#8722;1&#46;632&nbsp;\t\t\t\t\t\t\n
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