Journal Logo


Inflammatory mechanisms associated with COPD

A principle-based concept analysis

Conley, Patricia B. MSN, RN, PCCN; Kelechi, Teresa J. PhD, RN, FAAN

Author Information
doi: 10.1097/01.CCN.0000511824.96474.5f
  • Free


A documented history identifies and describes inflammation as far back as 2,000 years ago (see Inflammation: A history). Understanding inflammation is necessary because of its impact on quality care, patient education, and research for evidence-based practice. Further, understanding the risk factors that cause airway and lung inflammation leading to airflow limitation and chronic obstructive pulmonary disease (COPD) is essential.1

Inflammation is a process triggered by tissue injury or infection that elicits the recruitment of plasma proteins and leukocytes to the affected site.2 The mediators that cause inflammation in COPD are mostly associated with pollutants, which is a key teaching point for nurses. Sources of pollutants include cigarette smoke and occupational, indoor, or outdoor sources. This includes being in close proximity to industrial or high-traffic areas, or being outside during high ozone alerts.1-3

COPD and lung inflammation have a historical and scientific background best understood using a principle-based concept analysis, which is a blueprint to uncover gaps in the clinical understanding of inflammation in COPD for professional nursing practice. Four principles—linguistic, logical, epistemological, and pragmatic—are involved.4 But first, some background.


Although inflammation can be beneficial, as in the process of wound healing, it can be detrimental if it causes structural changes and narrowing of the small airways, making breathing and air exchange difficult.5 Over time, chronic inflammation leads to the destruction of lung tissue, resulting in COPD (see Anatomy of the lung and Mechanisms of airflow obstruction in COPD).

COPD is the third leading cause of death in the United States and the fourth leading cause of death globally.5-9 COPD is a preventable and treatable disease characterized by persistent respiratory symptoms and chronic airflow limitation that is usually progressive and is associated with chronic inflammation of the airways and lungs.9 In healthcare, timely and accurate identification of an acute exacerbation of COPD (AECOPD) is critical. AECOPD often causes more frequent coughing with an increased production of sputum, worsening activity tolerance related to difficulty breathing, and increased dyspnea, potentially resulting in respiratory failure.9

The onset of COPD is most commonly progressive, compared with the critical manifestation that occurs in AECOPD. Inflammation contributes to the limitation of airflow in the lungs. In AECOPD, the impact on the pulmonary system is so severe that most patients do not fully recover. Although lung inflammation responsible for COPD is linked to physiologic mediators, it is still not completely understood.10

Inflammation analysis

A concept analysis of inflammation requires an understanding of its antecedents. These are a precursor or stimulus from which an individual is exposed to irritants, such as firsthand or secondhand cigarette smoke, or some type of air pollution. The stimulus in most cases is the trigger for detrimental inflammatory activity.11

The characteristic attributes of inflammation are redness, warmth, swelling, pain, and limited function.12 In AECOPD, an individual can exhibit some of the following clinical signs and symptoms: dyspnea or breathlessness, increased frequency of cough, and productive cough with colored sputum (yellow, green, or sometimes blood-tinged).5 (See Inflammation in COPD.)

Classification of airflow limitation in patients with COPD is measured by spirometry that calculates the volume of air an individual can exhale from the lungs following a maximum inspiration.9 The Global Initiative for Chronic Obstructive Lung Disease (GOLD) established that a forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) less than 70% of expected indicates persistent airflow limitation and confirms the diagnosis of COPD.9 GOLD classifies COPD severity as mild, moderate, severe, or very severe. Mild COPD is a FEV1 equal to or greater than 80%, while very severe COPD is determined by a FEV1 less than 30% of predicted.9

Literature review

A literature review conducted for this article produced several studies on the mediators of inflammation in patients with COPD. PubMed, CINAHL, Google Scholar, Cochrane via EBSCO interface, and Medline via EBSCO interface were searched using the following Medical Subject Headings: “pulmonary disease, chronic obstructive” and “inflammation-mediators.” Inclusion criteria were: adults, adults with COPD, mouse models examining causes of inflammation in COPD. Exclusion criteria were pediatric studies and those delivering treatments or interventions for lung inflammation. Ultimately, 15 articles were included in this principle-based concept analysis.

Linguistic principle

To fulfill the linguistic principle, a concept needs to have consistency in its use and meaning.4 The meaning of inflammation in COPD is used consistently throughout the literature, in that it is an abnormal response that results in airflow limitation.13 The literature reflects how empirical measurements have evolved to quantify the signs and symptoms of inflammation. However, there is no consensus in the evidence on mediators responsible for inflammation and how they exacerbate COPD. Therefore, although the concept of inflammation in COPD fulfills the linguistic principle for its chronic and acute process, (that is, it is recognized and used consistently in the literature), health science needs to direct its efforts to better define and understand the mediators of that inflammation.

Logical principle

A concept is logical if it maintains its framework within the limits of theory application.4 However, no agreed-upon theoretical framework specific to mediators signaling inflammation in COPD was found in the literature. Available theories focus on the care of symptoms and functional disability subsequent to COPD.

Anatomy of the lung

Some sources in the literature cited external inflammatory factors from cigarette smoking to ozone levels. Consistently, the literature cited cigarette smoking as the most common noxious stimuli eliciting cellular and molecular COPD inflammation mediators.14-16 Researchers found exposure to cigarette smoking caused an abnormal increase in Tc17 cells related to inflammation in COPD.17

Other mediators that may account for inflammation in COPD include the alteration in sirtuin-1 protein coding gene in the circadian molecular clock rhythm of cigarette smokers.18 In addition, precipitating sources such as ozone air pollution elicits a variety of identified mediators that can alter circadian rhythm. This disruption in the circadian rhythm resulted in a cascade reaction from proinflammatory mediators.3

Researchers also found that proteases in agricultural dust from enclosed animal feeding sites and household mite dust can be mediators.19 Barouchos and colleagues found tumor markers were related to inflammation of COPD and the degree of disease severity.20 Haw and colleagues reported an increase in tumor necrosis factor–related apoptosis-inducing ligand, a cytokine thought to be the key to the abnormal pathology of inflammation in COPD.21

Another study identified pathogenic microorganisms in sputum to be linked to inflammation in COPD.22,23 Increased levels of pigment epithelium-derived factor correlated with inflammation in COPD and decreased FEV1.24 Other studies revealed the amount of progranulin in sputum, the loss of glycerol dehydratase-positive Lactobacillus, and nuclear factor kappaB are related to lung inflammation in COPD.25-27

Based on these studies, it is clear that the scientific understanding of inflammatory mediators is underdeveloped at this time, and the data available are not well established or agreed upon. Ultimately, identification of which specific mediators of inflammation are responsible and how the process becomes chronic and/or results in AECOPD would help enable the development of more effective treatments and create a framework for diagnosis that would fulfill the logical principle.9,28

Mechanisms of airflow obstruction in COPD

Epistemological principle

A concept that is epistemologically sound is clearly defined and discernible from other concepts within the literature.4 Inflammation in COPD is defined as chronic inflammation of airways and lung tissue that alters gas exchange.29 Although clinical features such as airflow limitation that define COPD are also shared by other pulmonary diseases, including asthma, cystic fibrosis, and constrictive bronchiolitis, the mechanisms that are responsible for airflow limitation among these pulmonary diseases is what is different.30 In COPD, there is no definite set of mediators that are attributable to its abnormal inflammatory process. Therefore, based on the scientific literature available, the mediators of inflammation in COPD do not fulfill the epistemological principle.

Dyspnea is a common attribute of COPD. Some patients describe these acute episodes of shortness of breath as near-death experiences.31 Others have made an effort to quantify the degree of shortness of breath. One instrument that patients can use is the Borg visual analog scale that gives patients a range of 0 to 10, with 0 representing no effort in breathing and 10 requiring maximum difficulty breathing.10

Impaired functional endurance in patients with COPD is another predominant clinical attribute. Decreased activity tolerance impacts individuals with COPD in their ability to ambulate, do grocery shopping, and as the disease progresses, getting to the bathroom or kitchen becomes a major hurdle. Instruments that measure activity tolerance include body mass index and exercise capacity index.32

Pragmatic principle

The concept needs to be relevant in the realm of scientific inquiry in order to fulfill the pragmatic principle.4 Here, inflammation is a process that occurs as a result of infection, tissue injury from various airborne noxious stimuli, or parainflammation that is likely responsible for autoinflammatory diseases.2 Lately, cellular and molecular mediators are being identified as the culprit of inflammation in COPD. In the disease process of COPD, inflammation is defined for what it is: abnormal and chronic, with acute episodes involving the peripheral airways and lung parenchyma.13

Inflammation in COPD7,8,11,13,20,25,28,32

Further, to fulfill the pragmatic principle, a concept must be well operationalized, in that it can be measured. Indirect measurements of inflammation in COPD can be obtained with the following parameters: results of arterial blood gases, pulse oximeter readings, observational assessment for degree of respiratory distress, activity tolerance, and level of consciousness. Inflammation in COPD is not completely a mature (or pragmatic) concept because the responsible mediators that trigger the inflammatory process are not all completely understood. Also, there is a lack of universal standards to measure inflammatory mediators, based on the evidence found in the literature.

Analysis outcomes

This article uncovers the gap in current medical knowledge regarding specific mediators responsible for the chronic and acute inflammatory process related to COPD. Phenotyping patients with COPD could help target which specific mediators are linked to a definitive cause of a patient's inflammation.13 Despite a multitude of different mediators explored in the studies, no findings were conclusive. The implications of external and internal factors, along with genetic factors, clearly play a role in inflammation in COPD. Understanding the mediators for the inflammatory process would give deeper meaning to the concept of inflammation.

Nurse research scientists have a pivotal role in collaborating with other researchers to understand the mediators of COPD inflammation, as well as new treatment modalities.33 It is important to recognize that the analysis of inflammation is fluid, since medical inquiry is a dynamic process with new discoveries in pathogenesis that can improve assessment and interventions for patients with COPD. (See Key points for managing the critical care patient with COPD.)


This principle-based concept analysis provided a rigorous process to examine inflammation in COPD. Each principle was examined based on empirical data found in the literature, illustrating the heterogeneous nature of inflammatory mediators. Nurses, physicians, respiratory therapists, and bench scientists need to work together to phenotype individuals with COPD in order to identify the specific mediators eliciting the destructive inflammatory process. In the future, phenotyping could be linked to treatments for specific identified mediators, ideally ones more effective in slowing chronic inflammation in COPD and preventing AECOPD occurrences.

Inflammation: A history34-37

Inflammation has been poignantly referred to as “the old flame.” This alludes to the fact that inflammation can cause similar pain and discomfort to a burn. The term “edema” is a common descriptor involving inflammation that began with Hippocrates in the 5th century BCE, when he described edema as part of the healing process following tissue injury. During the 1st century CE, Celsus, a Roman encyclopedist, defined the four signs of inflammation: “rubor et tumor cum calore et dolore,” meaning redness and swelling with heat and pain. A fifth component was added by the Greek physician Galen, “function laesa,” describing the impaired function of an affected extremity. The definition of inflammation has dramatically changed since its origin almost 2,000 years ago. Currently, inflammation is determined by how it is assessed clinically or microscopically, at the cellular or molecular level.

Key points for managing the critical care patient with COPD10,38-40

  • Assess for alteration in respirations (pattern, frequency) and clearly document all changes
  • Assess for alteration in neurologic status related to impaired gas exchange
  • Identify anxiety related to dyspnea, provide interventions (offer reassurance and emotional support), and administer antianxiety medications (as ordered)
  • Management of hypoxia and/or hypercapnia (per orders: noninvasive positive pressure ventilation or mechanical ventilation)
  • Provide tissues for oral secretions or perform oral suctioning as needed
  • Assist with oral care every 2 to 4 hours and p.r.n.


1. Centers for Disease Control and Prevention. Chronic obstructive pulmonary disease. 2015.
2. Medzhitov R. Origin and physiological roles of inflammation. Nature. 2008;454(7203):428–435.
3. Pirozzi C, Sturrock A, Weng HY, et al. Effect of naturally occurring ozone air pollution episodes on pulmonary oxidative stress and inflammation. Int J Environ Res Public Health. 2015;12(5):5061–5075.
4. Penrod J, Hupcey JE. Enhancing methodological clarity: principle-based concept analysis. J Adv Nurs. 2005;50(4):403–409.
5. American Thoracic Society. Exacerbation of COPD. Am J Respir Crit Care Med. 2014;189:11–12.
6. National Institute of Health. Chronic obstructive pulmonary disease (COPD). 2013.
    7. Mackay AJ, Hurst JR. COPD exacerbations: causes, prevention, and treatment. Med Clin North Am. 2012;96(4):789–809.
      8. Schmidt SA, Johansen MB, Olsen M, et al. The impact of exacerbation frequency on mortality following acute exacerbations of COPD: a registry-based cohort study. BMJ Open. 2014;4(12):e006720.
        9. Global Strategy for the Diagnosis, Management and Prevention of COPD. Global initiative for chronic obstructive lung disease (GOLD). 2017.
        10. Boshuizen RC, Vincent AD, van den Heuvel MM. Comparison of modified Borg scale and visual analog scale dyspnea scores in predicting re-intervention after drainage of malignant pleural effusion. Support Care Cancer. 2013;21(11):3109–3116.
        11. Scott A, Khan KM, Roberts CR, Cook JL, Duronio V. What do we mean by the term “inflammation”? A contemporary basic science update for sports medicine. Br J Sports Med. 2004;38(3):372–380.
        12. Inflammation. Stedman's Medical Dictionary. 2013.
        13. Oh JY, Sin DD. Lung inflammation in COPD: why does it matter. F1000 Med Rep. 2012;4:23.
        14. Geraghty P, Hardigan A, Foronjy RF. Cigarette smoke activates the proto-oncogene c-src to promote airway inflammation and lung tissue destruction. Am J Respir Cell Mol Biol. 2014;50(3):559–570.
        15. Crotty Alexander LE, Shin S, Hwang JH. Inflammatory diseases of the lung induced by conventional cigarette smoke: a review. Chest. 2015;148(5):1307–1322.
          16. Heijink IH, Pouwels SD, Leijendekker C, et al. Cigarette smoke-induced damage-associated molecular pattern release from necrotic neutrophils triggers proinflammatory mediator release. Am J Respir Cell Mol Biol. 2015;52(5):554–562.
          17. Zhou H, Hua W, Jin Y, et al. Tc17 cells are associated with cigarette smoke-induced lung inflammation and emphysema. Respirology. 2015;20(3):426–433.
          18. Yao H, Sundar IK, Huang Y, et al. Disruption of sirtuin 1-mediated control of circadian molecular clock and inflammation in chronic obstructive pulmonary disease. Am J Respir Cell Mol Biol. 2015;53(6):782–792.
          19. Romberger DJ, Heires AJ, Nordgren TM, et al. Proteases in agricultural dust induce lung inflammation through PAR-1 and PAR-2 activation. Am J Physiol Lung Cell Mol Physiol. 2015;309(4):L388–L399.
          20. Barouchos N, Papazafiropoulou A, Iacovidou N, et al. Comparison of tumor markers and inflammatory biomarkers in chronic obstructive pulmonary disease (COPD) exacerbations. Scand J Clin Lab Invest. 2015;75(2):126–132.
          21. Haw TJ, Starkey MR, Nair PM, et al. A pathogenic role for tumor necrosis factor-related apoptosis-inducing ligand in chronic obstructive pulmonary disease. Mucosal Immunol. 2016;9(4):859–872.
          22. Tufvesson E, Bjermer L, Ekberg M. Patients with chronic obstructive pulmonary disease and chronically colonized with Haemophilus influenzae during stable disease phase have increased airway inflammation. Int J Chron Obstruct Pulmon Dis. 2015;10:881–889.
          23. Bafadhel M, Haldar K, Barker B, et al. Airway bacteria measured by quantitative polymerase chain reaction and culture in patients with stable COPD: relationship with neutrophilic airway inflammation, exacerbation frequency, and lung function. Int J Chron Obstruct Pulmon Dis. 2015;10:1075–1083.
          24. Li X, Wang T, Yang T, et al. Elevated plasma levels of pigment epithelium-derived factor correlated with inflammation and lung function in COPD patients. Int J Chron Obstruct Pulmon Dis. 2015;10:587–594.
          25. Ungurs MJ, Sinden NJ, Stockley RA. Progranulin is a substrate for neutrophil-elastase and proteinase-3 in the airway and its concentration correlates with mediators of airway inflammation in COPD. Am J Physiol Lung Cell Mol Physiol. 2014;306(1):L80–L87.
          26. Schuliga M. NF-kappaB Signaling in chronic inflammatory airway disease. Biomolecules. 2015;5(3):1266–1283.
            27. Sze MA, Utokaparch S, Elliott WM, Hogg JC, Hegele RG. Loss of GD1-positive Lactobacillus correlates with inflammation in human lungs with COPD. BMJ Open. 2015;5(2):e006677.
            28. Han MK, Agusti A, Calverley PM, et al. Chronic obstructive pulmonary disease phenotypes: the future of COPD. Am J Respir Crit Care Med. 2010;182(5):598–604.
            29. Mayo Foundation for Medical Education and Research. 2016.
            30. Tantucci C. Expiratory flow limitation definition, mechanisms, methods, and significance. Pulm Med. 2013;2013:749860.
            31. Bailey PH. Death stories: acute exacerbations of chronic obstructive pulmonary disease. Qual Health Res. 2001;11(3):322–338.
            32. Müllerova H, Maselli DJ, Locantore N, et al. Hospitalized exacerbations of COPD: risk factors and outcomes in the ECLIPSE cohort. Chest. 2015;147(4):999–1007.
            33. Deutschman CS, Ahrens T, Cairns CB, Sessler CN, Parsons PE. Multisociety task force for critical care research: key issues and recommendations. Crit Care Nurse. 2012;32(1):16–18.
            34. Granger DN, Senchenkova E. Inflammation and the Microcirculation. San Rafael, CA: Morgan & Claypool Life Sciences; 2010.
            35. Tedgui A. Focus on inflammation. Arterioscler Thromb Vasc Biol. 2011;31(5):958–959.
              36. Heidland A, Klassen A, Rutkowski P, Bahner U. The contribution of Rudolf Virchow to the concept of inflammation: what is still of importance. J Nephrol. 2006;19(Suppl 10):S102–S109.
                37. Scott A, Khan KM, Roberts CR, Cook JL, Duronio V. What do we mean by the term “inflammation”? A contemporary basic science update for sports medicine. Br J Sports Med. 2004;38(3):372–380.
                38. García Vicente E, Sandoval Almengor JC, Díaz Caballero LA, Salgado Campo JC. Invasive mechanical ventilation in COPD and asthma. Med Intensiva. 2011;35(5):288–298.
                39. Yohannes AM, Alexopoulos GS. Depression and anxiety in patients with COPD. Eur Respir Rev. 2014;23(133):345–349.
                  40. Conley P, McKinsey D, Graff J, Ramsey AR. Does an oral care protocol reduce VAP in patients with a tracheostomy. Nursing. 2013;43(7):18–23.

                  chronic obstructive pulmonary disease; COPD; inflammatory mediators; lung inflammation; principle-based concept analysis; pulmonary disease

                  Wolters Kluwer Health, Inc. All rights reserved.