Acute exacerbation of chronic obstructive pulmonary disease
Epidemiology
COPD is the third leading cause of death worldwide, causing 3.23 million deaths in 2019.[1] 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.[3] The UK is among the top 20 countries for COPD mortality worldwide, with an age-standardised mortality rate of 210.7 per million of population between 2001 and 2010. In Europe, only Denmark and Hungary have higher death rates for COPD, while rates are higher in the US and New Zealand than in the UK.[4] In the US, the death rate due to COPD increased over 100% between 1970 and 2002.[5] No other major cause of death in the US has increased at this rate.
There is significant variability in the prevalence of COPD between countries.[6][7][8] This may be due to differing rates of exposure to tobacco smoke and indoor and occupational pollutants.[3] In the UK, the prevalence of COPD diagnosed by physicians between 1990 and 1997 was 2% in men and 1% in women.[9] In the past, men have experienced 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. Surveys have shown that the prevalence of COPD appears to be becoming more equally distributed between men and women.[7][10] COPD contributes a significant burden of healthcare costs.[6] 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.[6] However, estimates of mortality may be underestimated, as deaths in this population are often attributed to other aetiologies such as other respiratory disorders, lung cancer, and cardiovascular disease.[6]
Acute exacerbations of COPD are commonly triggered by bacterial or viral pathogens, pollutants, 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.[11][13][14][15][16][17][18] Exacerbation rates and all-cause mortality tend to be higher during winter months.[19] Acute exacerbations of COPD, particularly those that are moderate to severe, have significant public health impact, with increased healthcare utilisation and healthcare costs and increased mortality.[20][21][22][23][24] Early deaths among patients hospitalised with severe COPD exacerbation are often caused by concurrent problems such as pulmonary embolus, pneumonia, or congestive heart failure.[25] Patients may also be at risk of myocardial infarction and stroke in the post-exacerbation period.[26]
Risk factors
Bacterial pathogens are thought to be responsible for the majority of acute exacerbations of COPD. Evidence suggests that the presence of purulent sputum is frequently associated with a bacterial lower respiratory tract infection.[61] Because the lower respiratory tract in people with COPD is not sterile, the interpretation of culture results of both upper and lower respiratory tract specimens must be made with caution. There is mixed evidence as to whether greater bacterial colony counts over baseline levels are present in patients with an acute exacerbation of COPD.[62][63]
The most frequently identified bacterial pathogens include Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis.[34][54] 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 hospitalised recently or had recent (within 2 weeks) daily use of systemic corticosteroids (i.e., >10 mg/day of prednisolone) are more likely colonised with these pathogens.[34][64]
Of note, it has been shown that acquisition of a new strain of bacteria by people with COPD is a risk for an acute exacerbation.[65] Alterations in the innate and/or adaptive immune response may result in cyclical perpetuation of inflammation and infection.[45]
Concurrent infection with both bacterial and viral respiratory tract pathogens has been associated with more severe episodes.[53] Treatment of moderate to severe exacerbations with antibiotics has been associated with improved outcomes.[66][67] Influenza vaccination may have protective effect in reducing risk of Pseudomonas aeruginosa infection.[34]
Gastro-oesophageal reflux and swallowing dysfunction with associated aspiration are common triggers for exacerbations of COPD.[68][69] Few studies guide whether the treatment of reflux improves exacerbations of COPD. In one observational study of more than 600 patients with stable COPD, treatment with proton pump inhibitors did not decrease the risk for severe exacerbations.[70]
It has been estimated that respiratory viruses are responsible for 22% to 50% of acute exacerbations.[36]
The rhinovirus has been isolated from patients with acute exacerbations of COPD more often than other viruses.[71]
Influenza, respiratory syncytial virus, parainfluenza, coronavirus, adenovirus, and human metapneumovirus have also been associated with episodes.[34][37][38][72]
Exacerbations associated with respiratory viruses have been shown to be more severe and take longer to resolve compared with those attributed to other triggers.[71][73] Co-infection with viruses and bacterial pathogens is not uncommon.
It has been hypothesised that the chronic presence of respiratory viruses in the lower respiratory tract may play a role in the pathogenesis of COPD.[74]
Increasing levels of pollutants, specifically nitrogen dioxide (NO2), sulphur 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.[75][76][77] Peaks of air pollution can also increase hospitalisations and mortality.[78] 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.[31]
Short-term exposure to fine particulate matter is associated with increased hospitalisations for acute exacerbations and increased mortality.[1]
Atypical organisms (Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella species) have been associated with acute exacerbations though with conflicting results.[79][80][81] 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.[31][82] 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.[19]
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