Chronic obstructive pulmonary disease (COPD) is the third most common cause of death around the world. The affected patients suffer not only from impaired lung function, but also from a wide variety of comorbidities. Their cardiac comorbidities, in particular, lead to increased mortality. This review is based on pertinent publications retrieved by a selective search in PubMed, including guidelines from Germany and abroad. The usual diagnostic criteria for COPD are a post-bronchodilator FEV1/FVC quotient below the fixed threshold of 0.7, or, preferably, below the lower limit of normal (LLN) according to the GLI reference values for the avoidance of over- and underdiagnosis. The overall prognosis is markedly affected by comorbidities of the lung itself and those that involve other organs; in particular, many persons with COPD die of heart disease. The potential presence of heart disease must be borne in mind in the evaluation of patients with COPD, as lung disease can impair the detection of heart disease. As patients with COPD are often multimorbid, the early diagnosis and adequate treatment not only of their lung disease, but also of their extrapulmonary comorbidities are very important. Well-established diagnostic instruments and well-tested treatments are available and are described in detail in the guidelines concerning the comorbidities. Preliminary observations suggest that more attention should be paid to the potential positive effects of treating comorbidities on the lung disease itself, and vice versa.

Although hyperlipidemia is common in COPD, its relationship to comorbidities, risk factors and lung function in COPD has not been studied in detail. Using the baseline data of the COSYCONET cohort we addressed this question. Data from 1746 COPD patients (GOLD stage 1–4; mean age 64.6 y, mean FEV1%pred 57%) were evaluated, focusing on the comorbidities hyperlipidemia, diabetes and cardiovascular complex (CVC; including arterial hypertension, cardiac failure, ischemic heart disease). Risk factors comprised age, gender, BMI, and packyears of smoking. The results of linear and logistic regression analyses were implemented into a path analysis model describing the multiple relationships between parameters. Hyperlipidemia (prevalence 42.9%) was associated with lower intrathoracic gas volume (ITGV) and higher forced expiratory volume in 1 second (FEV₁) when adjusting for its multiple relationships to risk factors and other comorbidities. These findings were robust in various statistical analyses. The associations between comorbidities and risk factors were in accordance with previous findings, thereby underlining the validity of our data. In conclusion, hyperlipidemia was associated with less hyperinflation and airway obstruction in patients with COPD. This surprising result might be due to different COPD phenotypes in these patients or related to effects of medication.

The COPD classification proposed by the Global Initiative for Obstructive Lung Disease was recently revised, and the A to D grouping is now based on symptoms and exacerbations only. Potential associations with comorbidities have not been assessed so far. Thus the aim of the present study was to determine the relationship between the revised (2017) GOLD groups A-D and major comorbidities. We used baseline data from the COPD cohort COSYCONET. Comorbidities were identified from patient self-reports and disease-specific medication: gastrointestinal disorders, asthma, sleep apnea, hyperuricemia, hyperlipidemia, diabetes, osteoporosis, mental disorders, heart failure, hypertension, coronary artery disease. The A-D groups were based on either the COPD Assessment Test or the modified Medical Research Council scale. Exacerbations were also categorized as per GOLD recommendations. Data from 2228 patients were analyzed. Using GOLD group A as a reference, group D was associated with nearly all comorbidities, followed by group B and C. When groups A-D were dichotomized as AC vs. BD (symptoms) and AB vs. CD (exacerbations), all comorbidities correlated with symptoms and/or exacerbations. This was true for both mMRC- and CAT-based categorizations. These findings suggest that the recently modified GOLD categorization is clinically relevant beyond being purely an assessment of symptoms and exacerbations. As the A-D groups correlated with the risk of important comorbidities, with some differences in terms of the correlation with symptoms and exacerbations, the findings underline the importance of identifying comorbidities in COPD, particularly in non-responders to therapy who have high symptoms and/or exacerbation rates.

Recent investigations showed single associations between uric acid levels, functional parameters, exacerbations and mortality in COPD patients. The aim of this study was to describe the role of uric acid within the network of multiple relationships between function, exacerbation and comorbidities. We used baseline data from the German COPD cohort COSYCONET which were evaluated by standard multiple regression analyses as well as path analysis to quantify the network of relations between parameters, particularly uric acid. Data from 1966 patients were analyzed. Uric acid was significantly associated with reduced FEV1, reduced 6-MWD, higher burden of exacerbations (GOLD criteria) and cardiovascular comorbidities, in addition to risk factors such as BMI and packyears. These associations remained significant after taking into account their multiple interdependences. Compared to uric acid levels the diagnosis of hyperuricemia and its medication played a minor role. Within the limits of a cross-sectional approach, our results strongly suggest that uric acid is a biomarker of high impact in COPD and plays a genuine role for relevant outcomes such as physical capacity and exacerbations. These findings suggest that more attention should be paid to uric acid in the evaluation of COPD disease status.

The diagnosis of depression, a frequent comorbidity of chronic obstructive pulmonary disease (COPD), is often supported by questionnaires, such as the Patient Health Questionnaire 9 (PHQ-9). It is unknown to which extent its single questions are affected by the clinical characteristics of COPD patients. We addressed this question in 2255 GOLD grade 1–4 patients from the COSYCONET (COPD and Systemic Consequences - Comorbidities Network) COPD cohort. The dependence on COPD severity was assessed using symptoms, exacerbation risk (GOLD A-D; modified Medical Research Council dyspnoea scale (mMRC)), and frequent comorbidities as predictors of PHQ-9 results, while including age, gender, body mass index (BMI) and smoking habits as covariates. Symptoms and exacerbation risk were associated with depression in an additive manner, with mean elevations in the PHQ-9 sum score by 2.75 and 1.44 points, respectively. Asthma, sleep apnoea, gastrointestinal disorders, osteoporosis and arthritis were linked to increases by 0.8 to 1.3 points. Overall, the COPD characteristics contributed to the mean PHQ-9 score by increases from 4.5 or 5.2 to 6.3 points, respectively, when either taking GOLD A as reference or the absence of comorbidities. This finding was independent of the diagnosis of mental disorder or the intake of antidepressants. The presence of COPD led to an increase in the proportion of scores indicating depression from 12 to 22%. Single item analysis revealed homogenous effects regarding GOLD groups, but heterogeneous effects regarding GOLD grades. These findings indicate specific effects of COPD severity on the PHQ-9 depression score, especially symptoms and exacerbation risk, explaining the high prevalence of depression in COPD. Alternative explanations like an overlap of COPD severity and PHQ-9 items are discussed. Of note, we also found COPD treatment effects on depression scores.