History and exam

Key diagnostic factors

common

dyspnea

A sustained increase from the baseline level of dyspnea beyond day-to-day variation is usually observed in patients with an acute exacerbation.[10]

cough

A change in the character and frequency of cough is often identified.[10] This change should be beyond day-to-day variations of the patient's typical cough.[1]

wheeze

All patients with COPD have expiratory flow limitation, and this may lead to wheezing. Patients experiencing an acute exacerbation may be found to have greater severity of wheezing and prolongation of the expiratory phase of breathing on examination. However, wheezing is not identified in many patients.

changes in sputum volume/color/thickness

Changes in either volume or character (thickness, color) or both are frequently observed. The presence of purulent sputum appears to be sensitive and specific for high bacterial loads and may help identify subsets of patients who may most benefit from therapy with antibiotics.[125][126]

tachypnea

Tachypnea is frequently seen and may be severe. It is important to observe the patient for signs of respiratory failure.

uncommon

cyanosis

Possible sign of impending respiratory failure.

Other diagnostic factors

common

past medical history of COPD

A past medical history of COPD should be sought, as well as of other conditions that may impact the likelihood of another acute problem considered in the differential diagnosis. People with a history of two or more exacerbations in the preceding year or those with history of hospitalization due to exacerbation in the previous year are considered at high risk of subsequent exacerbations.[1]

tobacco use

It is important to determine if patients have a history of significant exposure to tobacco or other smoke, and whether they are currently smoking, using e-cigarette/vaping products, or other inhaled substances (e.g., marijuana, cocaine, hookah/shisha).

past medical history of gastroesophageal reflux/swallowing dysfunction

It is important to determine if patients have a history of heartburn, bitter/sour taste in the mouth, coughing or choking after eating, hiatal hernia, and/or gastroesophageal reflux or difficulty swallowing.[18][19][20][21][22] However, GERD should be considered as a potential cause of recurrent exacerbations even if the patient lacks the above-noted typical symptoms and signs of gastroesophageal reflux. Nighttime episodes of coughing may also signal the presence of GERD.

No available studies guide whether the treatment of reflux improves exacerbations of COPD.

malaise and fatigue

These symptoms and other nonspecific symptoms such as insomnia, decreased activity level and loss of appetite are commonly identified in people with an acute exacerbation of COPD.[111][124]

While these symptoms have great impact on the quality of life of the patient, they are generally not used to determine whether an exacerbation is present.

chest tightness

This may result from worsened airflow limitation and chest hyperinflation.[13] However, the possibility of a myocardial infarction or pneumothorax should be considered if marked chest tightness or other chest discomfort is present.

features of cor pulmonale

This may develop as a result of increased hypoxic vasoconstriction due to exacerbation-induced hypoxemia. The resulting increase in pulmonary vascular resistance and/or pulmonary artery pressure can lead to acute right heart failure. Elevated jugular venous pressure, hepatojugular reflux, peripheral edema, and relative hypotension may be present.

uncommon

environmental/occupational exposure to pollutants or dust

It should be determined whether the patient has a history of significant exposure to black smoke, such as wood smoke, dust, pesticides, and/or other pollutants, such as chemicals or small particulate matter.

change in mental status

Including drowsiness, confusion, and/or personality change.

fever

In general, <50% of people with acute exacerbations of COPD experience fever.[28][67][40]

The presence of a high and/or persistent fever should lead to consideration of the presence of bacterial pneumonia, influenza virus, or other infection.

accessory muscle use

Sign of impending respiratory failure.

paradoxical movements of abdomen

Sign of impending respiratory failure.

Risk factors

strong

viral infection

It has been estimated that respiratory viruses are responsible for 22% to 64% of acute exacerbations.[35][36] 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.[35]

The rhinovirus has been isolated from patients with acute exacerbations of COPD more often than other viruses.[66]

Influenza, respiratory syncytial virus, parainfluenza, coronavirus, adenovirus, and human metapneumovirus have also been associated with episodes.[67][39][40][41][68]

Exacerbations associated with respiratory viruses have been shown to be more severe, and take longer to resolve, compared with those attributed to other triggers.[66][69] Co-infection with viruses and bacterial pathogens is not uncommon. Coronaviruses are known triggers of COPD exacerbations.[35][70] While it is unclear whether SARS-CoV-2 (the virus that causes COVID-19) can precipitate exacerbations of COPD, it is presumed that this will be found to be the case, similar to other respiratory viruses.[1]

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.[71]

bacterial infection

Bacterial infections are thought to be a common trigger of exacerbations, although interactions between host factors, bacteria, viruses, and changes in air quality are also thought to cause, or contribute, toward exacerbations.[1][72] Evidence suggests that the presence of purulent sputum is frequently associated with a bacterial lower respiratory tract infection.[28] Because the lower respiratory tract in people with COPD may not be 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.[73][74]

The most frequently identified bacterial pathogens include Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis.[67][59] 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.[67][75]

It has been shown that acquisition of a new strain of bacteria by people with COPD is a risk for an acute exacerbation.[76] Alterations in the innate and/or adaptive immune response may result in cyclical perpetuation of inflammation and infection.[50]

Concurrent infection with both bacterial and viral respiratory tract pathogens has been associated with more severe episodes.[58] Treatment of moderate to severe exacerbations with antibiotics has been associated with improved outcomes.[77][78] Influenza vaccination may have a protective effect in reducing risk of Pseudomonas aeruginosa infection.[67]

gastroesophageal reflux/swallowing dysfunction

Gastroesophageal reflux and swallowing dysfunction with associated aspiration are common triggers for exacerbations of COPD.[18][19][20][21][22] No available studies guide whether the treatment of reflux improves exacerbations of COPD.

smoking

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.[79][80] Smoking cessation can also reduce the risk of exacerbations. Smoking cessation, counseling, and treatment are all recommended for people with COPD.[81][82] Avoidance of all forms of inhaled irritants (including e-cigarettes/vaping, inhaled marijuana, cocaine, hookah/shisha, and other environmental irritants) is also recommended.[1]

air pollutants

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.[86][87][88] Peaks of air pollution can also increase hospitalizations and mortality.[89] 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.[32] Exposure to other irritants, such as cleaning products, hair salon products, and other chemicals, also pose a risk for COPD exacerbation.[45]

weak

atypical bacterial infection

Atypical organisms (Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella species) have been associated with acute exacerbations though with conflicting results.[83][84][85] There is insufficient evidence to suggest that antimicrobial coverage of atypical bacterial pathogens improves outcomes.

change in weather

Changes in temperature and humidity are associated with increased risk for acute exacerbations of COPD.[32][90] 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.[23]

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