Epidemiology
COPD is the fourth leading cause of death worldwide.[3] The death rate due to COPD increased over 100% between 1970 and 2002.[4] Globally, COPD has been shown to be responsible for 3.8% of deaths in high-income countries and 4.9% of deaths in low-income countries.[5]
Studies projecting future global COPD prevalence estimate up to 600 million cases worldwide by 2050, which represents a relative growth of 23% in the number of individuals with COPD compared with 2020. The steepest projected growth is among females and within low- and middle-income countries (LMICs).[6]
There is significant variability in the prevalence of COPD between countries.[7][8][9] In high-income countries, the increasing aging population likely contributes to the high disease burden of COPD. In LMICs, factors such as higher rates of smoking, environmental and occupational pollution, and insufficient healthcare resources likely are the main contributors to the disease burden of COPD.[1][10]
Men have higher rates of disease due to COPD. This difference has been thought to be due primarily to greater exposure to tobacco smoke and occupational pollutants. In an analysis of the Global Burden of Disease Study, from 1990-2021, the highest number of COPD cases were found in individuals ages 70-74 years, with approximately 14 million cases in males and 15 million cases in females.[10] However, disproportionate growth is projected among females.[6] This can be attributed to increased smoking among females and indoor air pollutant exposure to biomass smoke during cooking in poorly ventilated homes within LMICs.[6]
COPD contributes a significant burden of healthcare costs.[7] Exacerbations are responsible for much of the morbidity and mortality experienced by people with COPD, and the median number per year ranges between 1 and 3.[11][12] It has been clearly shown that patients with more severe manifestations of COPD have greater rates of mortality over time.[7] However, estimates of mortality may be underestimated, as deaths in this population are often attributed to other etiologies such as other respiratory disorders, lung cancer, and cardiovascular disease.[7]
Acute exacerbations of COPD are commonly triggered by viral or bacterial pathogens, pollutants, GERD, or changes in temperature and humidity, and present with an acute-onset, sustained worsening of the patient's respiratory symptoms, lung function, functional status, and quality of life.[1][13][14][15][16][17] Exacerbation rates and all-cause mortality tend to be higher during winter months.[18] Acute exacerbations of COPD, particularly those that are moderate to severe, have significant public health impact, with increased healthcare utilization and healthcare costs and increased mortality.[19][20][21][22][23] Early deaths among patients hospitalized with severe COPD exacerbation are often caused by concurrent problems such as pulmonary embolus, pneumonia, or congestive heart failure.[24] Patients may also be at risk of myocardial infarction and stroke in the post-exacerbation period.[25] Mortality relates to age, the presence of acidotic respiratory failure, ventilatory support, and comorbidities.[1]
Risk factors
It has been estimated that respiratory viruses are responsible for 22% to 64% of acute exacerbations.[33][34] Whereas previously, bacterial infections were thought to be the predominant cause of COPD exacerbations, the use of newer molecular techniques has demonstrated the importance of viral infection as triggers.[1][33]
One meta-analysis by the European Respiratory Society found viruses were detected in 36.6% (95% confidence intervals 33.6% to 39.6%) of all COPD exacerbations, with the most prevalent being rhinovirus (13.0%), influenza (8.0%), and respiratory syncytial virus [RSV] (5.6%).[68] The rhinovirus has consistently been isolated from patients with acute exacerbations of COPD more often than other viruses.[69] Other meta-analysis have shown similar results, with viral occurrence in up to 44% of COPD exacerbations, mainly from rhinovirus, influenza A and RSV, but also metapneumovirus, coronavirus, adenovirus, and parainfluenza viruses.[39][70] During the coronavirus disease 2019 (COVID-19) pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus infection was one of the most likely causes of acute COPD exacerbations, and SARS-CoV-2 has been shown to increase the risk of death and infection severity in COPD.[27][40][70][71]
Exacerbations associated with respiratory viruses have been shown to be more severe, and take longer to resolve, compared with those attributed to other triggers.[69][72] Co-infection with viruses and bacterial pathogens is not uncommon.
It has been hypothesized that the chronic presence of respiratory viruses in the lower respiratory tract may play a role in the pathogenesis of COPD, and that a different combination of bacterial species affects the lungs of COPD patients, with respect to healthy individuals.[70][73]
Though exacerbations are mainly triggered by respiratory viral infections, bacterial infections may amplify or initiate these events.[1][74] Evidence suggests that the presence of purulent sputum is frequently associated with a bacterial lower respiratory tract infection.[23] Application of quantitative polymerase chain reaction techniques has shown that the lungs of healthy individuals are colonized by a wide spectrum of bacteria.[70] There is mixed evidence as to whether greater bacterial colony counts over baseline levels are present in patients with an acute exacerbation of COPD.[75][76] However, bacterial infections are a known risk factor for acute exacerbations. In one meta-analysis of 118 studies, bacteria was isolated in nearly 50% of the total COPD exacerbations, and studies have confirmed a microbiota shift during acute exacerbations.[70][77][78] Alterations in the innate and/or adaptive immune response may result in cyclical perpetuation of inflammation and infection.[52]
The most frequently identified bacterial pathogens include Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis.[35][61][78] The role of other gram-positive pathogens such as Staphylococcus aureus and gram-negative pathogens such as Pseudomonas aeruginosa in the pathogenesis of acute exacerbations of COPD is less certain, but patients with more severe COPD and greater frequency and/or severity of exacerbations, or those who have been hospitalized recently or had recent (within 2 weeks) daily use of systemic corticosteroids (i.e., >10 mg/day of prednisone) are more likely colonized with these pathogens.[35][79] A recent study that evaluated COPD patients after the coronavirus disease 2019 (COVID-19) pandemic noted that the identification rates of S pneumoniae (15.3% vs. 6.2%, p <0.001) and H influenzae (6.4% vs. 2.4%, p =0.002) decreased, whereas the identification rates of P aeruginosa (9.4% vs. 13.7%, p =0.023), Klebsiella pneumoniae (5.3% vs. 9.8%, p =0.004), and methicillin-resistant S aureus (1.0% vs. 2.8%, p =0.023) increased.[80]
Concurrent infection with both bacterial and viral respiratory tract pathogens has been associated with more severe episodes.[60] Treatment of moderate to severe exacerbations with antibiotics has been associated with improved outcomes.[81][82] Influenza vaccination may have a protective effect in reducing risk of Pseudomonas aeruginosa infection.[35]
Gastroesophageal reflux and swallowing dysfunction with associated aspiration are common triggers for exacerbations of COPD.[16][17][45][46][47] A recent study looking at 104,439 patients with prevalent COPD who received proton pump inhibitors (PPI) treatment for GERD found that the risk of exacerbation was significantly reduced after PPI treatment compared with the nontreated period. They concluded that severe COPD exacerbation may increase due to uncontrolled GERD, but subsequently decrease following PPI treatment.[83]
Avoiding smoke and smoking cessation are the best measures not only to prevent the onset of COPD, but also to prevent progression of the severity of COPD.[1][84][85] Smoking cessation can also reduce the risk of exacerbations. Smoking cessation, counseling, and treatment are all recommended for people with COPD.[86][87] Avoidance of all forms of inhaled irritants (including e-cigarettes/vaping, inhaled marijuana, cocaine, hookah/shisha, and other environmental irritants) is also recommended.[1]
Increasing levels of air pollutants, specifically nitrogen dioxide (NO₂), sulfur dioxide (SO₂), ozone (O₃), and black smoke particulates including wood smoke, have been associated with a greater rate of acute exacerbations and hospital admissions for people with COPD.[91][92][93] Peaks of air pollution can also increase hospitalizations and mortality.[94] People exposed to inhalation of high doses of pesticides have a higher incidence of respiratory symptoms, airway obstruction, and COPD.[1]
Exposure to many of these pollutants has been found to induce an inflammatory response in the respiratory tract.[30] Exposure to other irritants, such as cleaning products, hair salon products, and other chemicals, also pose a risk for COPD exacerbation.[43]
Atypical organisms (Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella species) have been associated with acute exacerbations though with conflicting results.[88][89][90] There is insufficient evidence to suggest that antimicrobial coverage of atypical bacterial pathogens improves outcomes.
Changes in temperature and humidity are associated with increased risk for acute exacerbations of COPD.[30][95] However, it remains unclear whether changes in ambient temperature and/or humidity or changes in risk for infection due to respiratory viruses and/or other pathogens account for this association.
Exacerbation rates and all-cause mortality tend to be higher during winter months.[18] There is evidence that extremes of temperature, high pressure, more hours of sunshine and lower humidity is associated with an increased risk of an exacerbation of COPD.[1][96][97]
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