Cited by 660Chronic Obstructive Pulmonary Disease (COPD) ResearchAsthma and respiratory diseasesSmoking Behavior and Cessation

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Complex chronic comorbidities of COPD

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Fabbri, L. M., Luppi, F., Beghé, B., Rabe, K. F.·2008·European Respiratory Journal

DOI 10.1183/09031936.00114307

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Abstract

Chronic obstructive pulmonary disease (COPD) is defined by fixed airflow limitation associated with an abnormal pulmonary and systemic inflammatory response of the lungs to cigarette smoke. The systemic inflammation induced by smoking may also cause chronic heart failure, metabolic syndrome and other chronic diseases, which may contribute to the clinical manifestations and natural history of COPD. Thus COPD can no longer be considered a disease only of the lungs, as it is often associated with a wide variety of systemic consequences. A better understanding of the origin and consequences of systemic inflammation, and of potential therapies, will most likely lead to better care of patients with COPD. Medical textbooks and clinical guidelines still largely ignore the fact that COPD seldom occurs in isolation. As the diagnosis and assessment of severity of COPD may be greatly affected by the presence of comorbid conditions, the current authors believe that lung function measurement, noninvasive assessment of cardiovascular and metabolic functions, and circulating inflammatory markers (e.g. C-reactive protein) might help to better characterise these patients. Similarly, preventive and therapeutic interventions should address the patient in their complexity.

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Implementation of an Activity-Monitoring System in Hospital-Based COPD Patients: A Retrospective Cohort Study
Wilson, C. M., Burns, G., Bove, J., Ferranti, V., McCown, B., Seidell, J. W., & Colombo, R. (2019) · Journal of Acute Care Physical Therapy · doi:10.1097/jat.0000000000000102 · Cited by 2
“As COPD is a complex disease closely linked to chronic inflammation, it is often controlled by long-term steroids, which results in a number of systemic effects including myopathy, hyperglycemia, weight gain, and osteoporosis.(9) These factors may further complicate the implementation of exercise and mobility.”
Background
The Reasons for the Success of Non-pharmacological Interventions
Ninot, G. (2020) · Springer eBooks · doi:10.1007/978-3-030-60971-9_2 · Cited by 2
Post Hoc Analysis of Lung Function Improvement and Patient-Reported Outcomes With Revefenacin in Adults With Moderate-to-Very Severe COPD and Comorbid Anxiety or Depression
Yohannes, A. M., Iyer, A. S., Clay, C., Cochran, L. W., Chen, X., Lombardi, D. A., & Bhatt, S. P. (2024) · Chronic Obstructive Pulmonary Diseases Journal of the COPD Foundation · doi:10.15326/jcopdf.2023.0465 · Cited by 2
The efficacy and safety of Yiqi Huoxue Huatan granule in the treatment of stable COPD with chronic respiratory failure: A randomized, double-blind, placebo controlled trial
Yang, J.-Y., Wang, H., Zhao, K.-M., Yu, X., Huang, D., Wang, H., Wei, G.-S., Bai, L., Hou, Y., Huang, Q., et al. (2025) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2025.120228 · Cited by 2
Effects of the association of diabetes and pulmonary emphysema on cardiac structure and function in rats
Petta, A. D., Simas, R., Ferreira, C. L., Capelozzi, V. L., Salemi, V. M. C., Moreira, L. F. P., & Sannomiya, P. (2015) · International Journal of Experimental Pathology · doi:10.1111/iep.12146 · Cited by 2
STRUCTURAL AND FUNCTIONAL STATE OF BLOOD CELLS IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE, ASSOCIATED WITH ISCHEMIC HEART DISEASE
Shuper, S. V. (2018) · Ukrainian Pulmonology Journal · doi:10.31215/2306-4927-2018-100-2-25-30 · Cited by 2
Association between arterial hypertension and chronic obstructive pulmonary disease: role of AGT gene polymorphism
Марущак, М. І., Maksiv, K., Krynytska, І., & Kozak, K. (2019) · Pneumologia · doi:10.2478/pneum-2019-0036 · Cited by 2
“Frequent combinations of and interactions between these conditions may be attributable to several causes due to the presence of common links of pathogenesis (31).”
Background
Leg Atherosclerosis in Japanese COPD Patients: Prevalence of Undiagnosed Peripheral Artery Disease and Association between Leg Atherosclerosis and Clinical Indices
Matsuoka, H., Matsumoto, Y., Kimura, K., Koyama, M., Uzu, T., Koma, Y., Fukumitsu, K., Kasai, Y., Nakashima, N., Masuya, D., et al. (2013) · Open Journal of Respiratory Diseases · doi:10.4236/ojrd.2013.31005 · Cited by 2
“Recently, COPD has been recognized as a systemic disease [2,3], and in particular, is associated with a markedly increased risk of cardiovascular disease [4], which accounts for approximately 25% to 40% of mortality in COPD patients [5,6].”
Background
Clinical commentary – COPD is not a systemic disease
Donner, C. F., & Bjermer, L. H. (2009) · Respiratory Medicine · doi:10.1016/j.rmed.2009.03.021 · Cited by 2
Marcadores de inflamación sistémica en pacientes ex fumadores con enfermedad pulmonar obstructiva crónica en etapa estable
Arturo Morales, S., Jorge Dreyse, D., Orlando Díaz, P., Fernando Saldías, P., Carrasco, M., & Carmen Lisboa, B. (2010) · Revista médica de Chile · doi:10.4067/s0034-98872010000800003 · Cited by 2
Energy expenditure and respiratory diseases: is there a link?
Gregersen, N. T., Chaput, J., Astrup, A. V., & Tremblay, A. (2008) · Expert Review of Respiratory Medicine · doi:10.1586/17476348.2.4.495 · Cited by 2
A functional variant in the γ-glutamyltransferase (GGT)1 gene is associated with airflow obstruction in smokers
Morita, K., Masuda, N., Tanaka, T., Saruwatari, J., Oniki, K., Kajiwara, A., Otake, K., Ogata, Y., & Nakagawa, K. (2015) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm-2015-0331 · Cited by 2
“Cigarette smoke causes lung and systemic inflammation and systemic oxidative stress [10].”
BackgroundInfluential
Lungentransplantation bei Lungenemphysem - Wer? Wann? Wie? Lung Transplantation for Pulmonary Emphysema - Who, When, How?
Schreder, T., Gottlieb, J., Thieme, G., York, V. K. S. ·. N., Pneumologie, A., & Hochschule, M. (2010) · Cited by 2
The Natural History of COPD: Beyond Fletcher and Peto
Rennard, S. I., Agustí, Á., & Vestbo, J. (2015) · Barcelona Respiratory Network · doi:10.23866/brnrev:2015-m0011 · Cited by 2
Cardiovascular co-morbidity in patients with COPD in Bulgaria
Dimitrova, M. J., Kamusheva, M., Tachkov, K., Mitov, K., Doneva, M., Pencheva, V., Петрова, Д., Georgiev, O., Stoitchkov, J., & Petrova, G. I. (2020) · Biotechnology & Biotechnological Equipment · doi:10.1080/13102818.2020.1810591 · Cited by 2
Nutrition status and obesity paradox in chronic obstructive pulmonary disease
Drapkina, O. M., Avdeev, S. N., Budnevsky, A. V., Ovsyannikov, Е. S., Васильевна, К. А., & Дробышева, Е. С. (2021) · Voprosy Pitaniya · doi:10.33029/0042-8833-2021-90-6-42-49 · Cited by 2
Epidemiology of comorbidities in chronic obstructive pulmonary disease: clusters, phenotypes and outcomes
Aryala, S., Diaz‐Guzman, E., & Manninoa, D. M. (2012) · Italian Journal of Medicine · doi:10.4081/itjm.2012.276 · Cited by 2
The safety of beta-blocker use in chronic obstructive pulmonary disease patients with respiratory failure in the intensive care unit
Kargın, F., Takır, H. B., Saltürk, C., Gökşenoğlu, N. Ç., Karabay, C. Y., Moçin, Ö. Y., Adiguzel, N., Güngör, G., Balcı, M. K., Yalçınsoy, M., et al. (2014) · Multidisciplinary Respiratory Medicine · doi:10.4081/mrm.2014.365 · Cited by 2
Systemic Manifestations
Agustí, A. G. N. (2009) · Elsevier eBooks · doi:10.1016/b978-0-12-374001-4.00044-4 · Cited by 2
Review of chronic obstructive airway disease patients admitted at Maamoura Chest Hospital from 2009 to 2012
Helala, L. A., ELMaraghy, A. A., & ELBastawesy, A. A. (2015) · Egyptian Journal of Chest Diseases and Tuberculosis · doi:10.1016/j.ejcdt.2015.04.009 · Cited by 2
The comparative characteristic of level of matrix metalloproteinase-9 and high-sensitive C-reactive protein indicators at comorbid course of arterial hypertension and chronic obstructive pulmonary disease
Yatsenko, O. V. (2017) · ScienceRise Medical Science · doi:10.15587/2519-4798.2017.102579 · Cited by 2
Chronic obstructive pulmonary disease combined with arterial hypertension: efficacy and safety ofthesustained-release indapamide (Arifon® retard)
Si, O., Nersesyan, Z. N., & Морозова, Т. Е. (2014) · Systemic Hypertension · doi:10.26442/sg29026 · Cited by 2
Gene Promoter Methylation Is Associated With Lung Function In The Elderly: The Normative Aging Study
Lepeule, J., Baccarelli, A., Tarantini, L., Cantone, L., Litonjua, A. A., Sparrow, D., Vokonas, P., & Schwartz, J. D. (2012) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm-conference.2012.185.1_meetingabstracts.a5290 · Cited by 2
Chronic Obstructive Pulmonary Disease
Koczulla, A. R., Kenn, K., Bals, R., & Vogelmeier, C. F. (2012) · Springer eBooks · doi:10.1007/978-3-540-29807-6_46 · Cited by 2
Introducción
Álvarez-Sala, J. L., & de Miguel‐Díez, J. (2009) · Archivos de Bronconeumología · doi:10.1016/s0300-2896(09)72855-8 · Cited by 2
Prevalence of concealed and overt chronic renal failure in patients with COPD
Al-Aarag, A. H., mehy, G. F. A., Mohammad, O. I., Hendy, R. M., Tawfik, S. M., & Imam, M. H. (2016) · Egyptian Journal of Chest Diseases and Tuberculosis · doi:10.1016/j.ejcdt.2016.09.002 · Cited by 1
“But it is unknown to which extent it is associated with chronic renal failure [1].”
Background
Left ventricular dysfunction in chronic obstructive pulmonary disease
Varghese, S. (2018) · Journal of Indian College of Cardiology · doi:10.1016/j.jicc.2018.11.006 · Cited by 1
PSYCHIATRIC COMORBIDITIES IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE
SOOD, R., Ahuja, G., SHARMA, S., Sharma, D. D., MONICA, Sachin, S., & Sarkar, M. S. (2024) · International Journal of Current Pharmaceutical Research · doi:10.22159/ijcpr.2024v16i2.4026 · Cited by 2
Physiological analyses of swallowing changes due to chronic obstructive pulmonary disease in anesthetized male rats
Nagoya, K., Tsujimura, T., Yoshihara, M., Watanabe, M., Magara, J., Kawasaki, K., & Inoue, M. (2024) · Frontiers in Physiology · doi:10.3389/fphys.2024.1445336 · Cited by 1
Prevalence and Correlates of Osteoporosis and Metabolic Syndrome Among Patients With Chronic Obstructive Pulmonary Disease at a Rural Tertiary Healthcare Center in India
Roy, R., & Kumar, A. (2025) · Cureus · doi:10.7759/cureus.78759 · Cited by 1
Raising the bar in respiratory care by EUFOREA: report of the European Union Parliament Symposium, April 2024
Hellings, P. W., Conti, D. M., Bertels, X., Backer, V., Brusselle, G., Corso, E. D., Fokkens, W. J., Fox, A. T., Gevaert, P., Lau, S., et al. (2025) · Frontiers in Allergy · doi:10.3389/falgy.2025.1540499 · Cited by 1
“Also, COPD is rarely diagnosed in isolation; rather, it is frequently accompanied by other comorbidities (31).”
CAT score as a prognostic tool in low resource setting: Exploring the correlation between CAT score, exacerbation history with BODE Index in stable COPD
Joseph, J. A., & Pujari, V. (2025) · Lung India · doi:10.4103/lungindia.lungindia_633_24 · Cited by 1
“[2] The recognition of the systemic effects of COPD led to the development of a multidimensional grading system, the BODE index, for the categorization and prediction of mortality outcomes in COPD patients.”
Phase 2a, Randomized Trial of Mitiperstat Versus Placebo in Patients with COPD at High Risk of Exacerbation (CRESCENDO)
Hughes, R., Brailsford, W., Ferreira, J., Chalmers, J. D., Belvisi, M. G., Kocks, J. W. H., Masters, P., Thomson, P., Łyżwa, D., Rosengren, S., et al. (2025) · International Journal of COPD · doi:10.2147/copd.s524775 · Cited by 1
“4,6 Neutrophils also play a key role in systemic inflammation, and increased systemic neutrophilic inflammation is seen in patients who experience exacerbations.”
A Predicted FEV1/FVC Model Based on a Simple Respiratory Questionnaire for Early Diagnosis of COPD in Shimane Cohort, Japan
Nakao, M., Okimoto, T., Tanino, A., Amano, Y., Hotta, T., Hamaguchi, M., Hamaguchi, S., Tsubata, Y., Kawamura, T., & ISOBE, T. (2026) · International Journal of COPD · doi:10.2147/copd.s575341 · Cited by 1
“5,6 Regardless of the degree of airflow obstruction, patients with COPD may have impaired physical activity due to comorbidities, which also affects their prognosis.”
The Big Three Concept
de Verdier, M. G. (2012) · Proceedings of the American Thoracic Society · Cited by 1
An Integrated therapeutic approach: do COPD comorbidities justify it?
Drummond, M., & Soriano, J. B. (2014) · Revista Portuguesa de Pneumologia · doi:10.1016/j.rppnen.2013.12.002 · Cited by 2
Nocturnal Oxygen Desaturation Index is Inversely Correlated with Airflow Limitation in Patients with Chronic Obstructive Pulmonary Disease
Tamai, K., Matsuoka, H., Suzuki, Y., Yoshimatsu, H., Masuya, D., Nakashima, N., Okada, N., Oda, N., Inoue, S., Koma, Y., et al. (2015) · COPD Journal of Chronic Obstructive Pulmonary Disease · doi:10.3109/15412555.2015.1074995 · Cited by 1
The Patient Candidate for Long-Term Oxygen Therapy
Negro, R. D. D., & Hodder, R. (2012) · Springer eBooks · doi:10.1007/978-88-470-2580-6_1 · Cited by 1
“Indeed, it has been postulated that COPD is itself a systemic disease, or at least leads to systemic illness [228-229] and so has many potential phenotypes [230].”
Background
Systemic Features in Chronic Obstructive Pulmonary Disease
Batura‐Gabryel, H. (2009) · Advances in respiratory medicine · doi:10.5603/arm.27838 · Cited by 1

Authors: Fabbri, L. M., Luppi, F., Beghé, B., & Rabe, K. F.
Affiliations: University of Modena and Reggio Emilia (IT)
ORCID: Fabbri, L. M.
Luppi, F.
Beghé, B.
Rabe, K. F.
Venue: European Respiratory Journal
Publisher: European Respiratory Society (ERS)
Published: 2007-12-31
Volume: 31
Issue: 1
Pages: 204-212
ISSN: 0903-1936 (ISSN-L)
1399-3003
DOI: 10.1183/09031936.00114307
OpenAlex: W2165340553
Cited by: 660
References: 139
Citations by year: 2026: 8 · 2025: 16 · 2024: 20 · 2023: 17 · 2022: 26 · 2021: 19 · 2020: 35 · 2019: 25 · 2018: 36 · 2017: 48 · 2016: 31 · 2015: 50 · 2014: 68 · 2013: 55 · 2012: 59
FWCI: 28.24
Type: journal article
Language: en
Open access: green
hdl.handle.net
Licence: cc-by
Locations: European Respiratory Journal (publishedVersion)
PubMed (publishedVersion)
BOA (University of Milano-Bicocca) (submittedVersion)
IRIS UNIMORE (University of Modena and Reggio Emilia) (submittedVersion, cc-by)
INFM-OAR (INFN Catania) (submittedVersion, other-oa)
Topics: Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Chronic Obstructive Pulmonary Disease (COPD) Research
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Asthma and respiratory diseases
Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Smoking Behavior and Cessation
Keywords: chronic obstructive pulmonary disease, comorbidities, systemic inflammation, chronic heart failure, metabolic syndrome, cigarette smoking, C-reactive protein, inflammatory markers, COPD severity assessment, cardiovascular function, COPD management
MeSH terms: Chronic Disease, Health Status, Humans, Inflammation, Lung, Models, Biological, Prognosis, Risk Factors, Smoking, Pulmonary Medicine, Comorbidity, Guidelines as Topic, Pulmonary Disease, Chronic Obstructive, Overweight

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