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An acute exacerbation of chronic obstructive pulmonary disease, or acute exacerbations of chronic bronchitis (AECB), is a sudden worsening of
chronic obstructive pulmonary disease Chronic obstructive pulmonary disease (COPD) is a type of progressive lung disease characterized by long-term respiratory symptoms and airflow limitation. The main symptoms include shortness of breath and a cough, which may or may not produce ...
(COPD) symptoms including
shortness of breath Shortness of breath (SOB), also medically known as dyspnea (in AmE) or dyspnoea (in BrE), is an uncomfortable feeling of not being able to breathe well enough. The American Thoracic Society defines it as "a subjective experience of breathing di ...
, quantity and color of
phlegm Phlegm (; , ''phlégma'', "inflammation", " humour caused by heat") is mucus produced by the respiratory system, excluding that produced by the nasal passages. It often refers to respiratory mucus expelled by coughing, otherwise known as sput ...
that typically lasts for several days. It may be triggered by an infection with bacteria or viruses or by environmental pollutants. Typically, infections cause 75% or more of the exacerbations; bacteria can roughly be found in 25% of cases, viruses in another 25%, and both viruses and bacteria in another 25%. Airway inflammation is increased during the exacerbation resulting in increased hyperinflation, reduced expiratory air flow and decreased gas exchange. Exacerbations can be classified as mild, moderate, and severe. As COPD progresses, exacerbations tend to become more frequent, the average being about three episodes per year.


Signs and symptoms

An acute exacerbation of COPD is associated with increased frequency and severity of coughing. It is often accompanied by worsened chest congestion and discomfort.
Shortness of breath Shortness of breath (SOB), also medically known as dyspnea (in AmE) or dyspnoea (in BrE), is an uncomfortable feeling of not being able to breathe well enough. The American Thoracic Society defines it as "a subjective experience of breathing di ...
and wheezing are present in many cases. Exacerbations may be accompanied by increased amount of
cough A cough is a sudden expulsion of air through the large breathing passages that can help clear them of fluids, irritants, foreign particles and microbes. As a protective reflex, coughing can be repetitive with the cough reflex following three ph ...
and
sputum Sputum is mucus that is coughed up from the lower airways (the trachea and bronchi). In medicine, sputum samples are usually used for a naked eye examination, microbiological investigation of respiratory infections and cytological investigatio ...
productions, and a change in appearance of sputum. An abrupt worsening in COPD symptoms may cause rupture of the airways in the
lung The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either side of ...
s, which in turn may cause a spontaneous pneumothorax. In infection, there is often weakness, fever and chills. If due to a bacterial infection, the sputum may be slightly streaked with blood and coloured yellow or green.


Causes

As the lungs tend to be vulnerable organs due to their exposure to harmful particles in the air, several things can cause an acute exacerbation of COPD: *
Respiratory infection Respiratory tract infections (RTIs) are infectious diseases involving the respiratory tract. An infection of this type usually is further classified as an upper respiratory tract infection (URI or URTI) or a lower respiratory tract infection (LRI ...
, being responsible for approximately half of COPD exacerbations. Approximately half of these are due to viral infections and another half appears to be caused by bacterial infections.Uppsala Academic Hospital > Guidelines for treatment of acute lung diseases. August 2004. Authors: Christer Hanson, Carl-Axel Karlsson, Mary Kämpe, Kristina Lamberg, Eva Lindberg, Lavinia Machado Boman, Gunnemar Stålenheim Common bacterial pathogens of acute exacerbations include ''
Haemophilus influenzae ''Haemophilus influenzae'' (formerly called Pfeiffer's bacillus or ''Bacillus influenzae'') is a Gram-negative, non-motile, coccobacillary, facultatively anaerobic, capnophilic pathogenic bacterium of the family Pasteurellaceae. The bact ...
'', ''
Streptococcus pneumoniae ''Streptococcus pneumoniae'', or pneumococcus, is a Gram-positive, spherical bacteria, alpha-hemolytic (under aerobic conditions) or beta-hemolytic (under anaerobic conditions), aerotolerant anaerobic member of the genus Streptococcus. They ar ...
'' and ''
Moraxella catarrhalis ''Moraxella catarrhalis'' is a fastidious, nonmotile, Gram-negative, aerobic, oxidase-positive diplococcus that can cause infections of the respiratory system, middle ear, eye, central nervous system, and joints of humans. It causes the inf ...
''. Less common bacterial pathogens include '' Chlamydia pneumoniae'' and '' MRSA''. Pathogens seen more frequently in patients with impaired lung function (FEV<35% of predicted) include '' Haemophilus parainfluenzae'' (after repeated use of antibiotics), '' Mycoplasma pneumoniae'' and
gram-negative Gram-negative bacteria are bacteria that do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. They are characterized by their cell envelopes, which are composed of a thin peptidoglycan cell wa ...
, opportunistic pathogens like ''
Pseudomonas aeruginosa ''Pseudomonas aeruginosa'' is a common encapsulated, gram-negative, aerobic– facultatively anaerobic, rod-shaped bacterium that can cause disease in plants and animals, including humans. A species of considerable medical importance, ''P. a ...
'' and '' Klebsiella pneumoniae''. *
Allergens An allergen is a type of antigen that produces an abnormally vigorous immune response in which the immune system fights off a perceived threat that would otherwise be harmless to the body. Such reactions are called allergies. In technical ter ...
, e.g., pollens, wood or cigarette smoke, pollution * Toxins, including a variety of different chemicals *
Air pollution Air pollution is the contamination of air due to the presence of substances in the atmosphere that are harmful to the health of humans and other living beings, or cause damage to the climate or to materials. There are many different type ...
* Failing to follow a drug therapy program, e.g. improper use of an inhaler In one-third of all COPD exacerbation cases, the cause cannot be identified.


Diagnosis

The diagnostic criteria for acute exacerbation of COPD generally include a production of sputum that is
purulent Pus is an exudate, typically white-yellow, yellow, or yellow-brown, formed at the site of inflammation during bacterial or fungal infection. An accumulation of pus in an enclosed tissue space is known as an abscess, whereas a visible collect ...
and may be thicker than usual, but without evidence of
pneumonia Pneumonia is an inflammatory condition of the lung primarily affecting the small air sacs known as alveoli. Symptoms typically include some combination of productive or dry cough, chest pain, fever, and difficulty breathing. The severit ...
(which involves mainly the
alveoli Alveolus (; pl. alveoli, adj. alveolar) is a general anatomical term for a concave cavity or pit. Uses in anatomy and zoology * Pulmonary alveolus, an air sac in the lungs ** Alveolar cell or pneumocyte ** Alveolar duct ** Alveolar macrophage * M ...
rather than the bronchi). Also, diagnostic criteria may include an increase in frequency and severity of coughing, as well as increased shortness of breath. A
chest X-ray A chest radiograph, called a chest X-ray (CXR), or chest film, is a projection radiograph of the chest used to diagnose conditions affecting the chest, its contents, and nearby structures. Chest radiographs are the most common film taken in me ...
is usually performed on people with fever and, especially,
hemoptysis Hemoptysis is the coughing up of blood or blood-stained mucus from the bronchi, larynx, trachea, or lungs. In other words, it is the airway bleeding. This can occur with lung cancer, infections such as tuberculosis, bronchitis, or pneumonia, a ...
(blood in the sputum), to rule out pneumonia and get information on the severity of the exacerbation. Hemoptysis may also indicate other, potentially fatal, medical conditions. A history of exposure to potential causes and evaluation of symptoms may help in revealing the cause the exacerbation, which helps in choosing the best treatment. A sputum culture can specify which strain is causing a bacterial AECB. An early morning sample is preferred. E-nose showed the ability to smell the cause of the exacerbation. The definition of a COPD exacerbation is commonly described as "lost in translation", meaning that there is no universally accepted standard with regard to defining an acute exacerbation of COPD. Many organizations consider it a priority to create such a standard, as it would be a major step forward in the diagnosis and quality of treatment of COPD.


Prevention

Acute exacerbations can be partially prevented. Some infections can be prevented by vaccination against pathogens such as influenza and ''Streptococcus pneumoniae''. Regular medication use can prevent some COPD exacerbations;
long acting beta-adrenoceptor agonist Long-acting β adrenoceptor agonists (LABAs, more specifically, long-acting β2 adrenergic receptor agonists) are usually prescribed for moderate-to-severe persistent asthma patients or patients with chronic obstructive pulmonary disease (COPD). ...
s (LABAs), long-acting anticholinergics, inhaled corticosteroids and low-dose theophylline have all been shown to reduce the frequency of COPD exacerbations. Other methods of prevention include: *
Smoking cessation Smoking cessation, usually called quitting smoking or stopping smoking, is the process of discontinuing tobacco smoking. Tobacco smoke contains nicotine, which is addictive and can cause dependence. As a result, nicotine withdrawal often m ...
and avoiding dust,
passive smoking Passive smoking is the inhalation of tobacco smoke, called secondhand smoke (SHS), or environmental tobacco smoke (ETS), by persons other than the intended "active" smoker. It occurs when tobacco smoke enters an environment, causing its inhala ...
, and other inhaled irritants * Yearly
influenza Influenza, commonly known as "the flu", is an infectious disease caused by influenza viruses. Symptoms range from mild to severe and often include fever, runny nose, sore throat, muscle pain, headache, coughing, and fatigue. These symptom ...
and 5-year pneumococcal vaccinations * Regular exercise, appropriate rest, and healthy nutrition * Avoiding people currently infected with e.g. cold and influenza * Maintaining good fluid intake and humidifying the home, in order to help reduce the formation of thick sputum and chest congestion.


Treatment

Based on the severity different treatments may be used. Mild exacerbations are treated with short acting bronchodilators (SABDs). Moderate exacerbations are treated with SABDs together with antibiotics or oral corticosteroids, or both. Severe exacerbations need hospital treatment, and the prognosis is poor.


Oxygen

Oxygen therapy Oxygen therapy, also known as supplemental oxygen, is the use of oxygen as medical treatment. Acute indications for therapy include hypoxemia (low blood oxygen levels), carbon monoxide toxicity and cluster headache. It may also be prophylactic ...
should be initiated if there is significantly low blood oxygen. High flow oxygen may be harmful in those with an acute exacerbation of COPD. In the prehospital environment those given high flow O2 rather than titrating their O2 saturations to 88% to 92% had worse outcomes. Antibiotics and steroids appear useful in mild to severe disease.


Medications

* Inhaled
bronchodilator A bronchodilator or broncholytic (although the latter occasionally includes secretory inhibition as well) is a substance that dilates the bronchi and bronchioles, decreasing resistance in the respiratory airway and increasing airflow to the lung ...
s open up the airways in the lungs. These include
salbutamol Salbutamol, also known as albuterol and sold under the brand name Ventolin among others, is a medication that opens up the medium and large airways in the lungs. It is a short-acting β2 adrenergic receptor agonist which works by causing rel ...
and terbutaline (both β2-adrenergic agonists), and ipratropium (an
anticholinergic Anticholinergics (anticholinergic agents) are substances that block the action of the neurotransmitter called acetylcholine (ACh) at synapses in the central and peripheral nervous system. These agents inhibit the parasympathetic nervous sys ...
). Medication can be administered via inhaler or nebuliser. There is no evidence to prefer a nebuliser over an inhaler. *
Antibiotics An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and preventio ...
are used if a bacterial infection is the suspected cause. However, antibiotics will not treat exacerbations caused by viruses. Viral infections will usually be cured with time with the aid of proper rest and care. Still, other medications may be needed to control symptoms. Lipid-soluble antibiotics such as
macrolide The Macrolides are a class of natural products that consist of a large macrocyclic lactone ring to which one or more deoxy sugars, usually cladinose and desosamine, may be attached. The lactone rings are usually 14-, 15-, or 16-membered. Ma ...
s,
tetracycline Tetracycline, sold under various brand names, is an oral antibiotic in the tetracyclines family of medications, used to treat a number of infections, including acne, cholera, brucellosis, plague, malaria, and syphilis. Common side effects in ...
s, and fluoroquinolones penetrate the lung tissue well. Macrolides are more active against ''
Streptococcus pneumoniae ''Streptococcus pneumoniae'', or pneumococcus, is a Gram-positive, spherical bacteria, alpha-hemolytic (under aerobic conditions) or beta-hemolytic (under anaerobic conditions), aerotolerant anaerobic member of the genus Streptococcus. They ar ...
'' than the tetracyclines and the older fluoroquinolones. Within the macrolides, newer ones are more active against ''
Haemophilus influenzae ''Haemophilus influenzae'' (formerly called Pfeiffer's bacillus or ''Bacillus influenzae'') is a Gram-negative, non-motile, coccobacillary, facultatively anaerobic, capnophilic pathogenic bacterium of the family Pasteurellaceae. The bact ...
'' than the older erythromycin. Regimens should generally be given for five days. Choice of antibiotics is also dependent on the severity of the symptoms: ** "Simple" COPD is generally where a person 65 years or less, has fewer than four exacerbations per year, has minimal or moderate impairment in respiratory function and no comorbid disease. In patients with "simple" COPD, therapy should be targeted towards ''Haemophilus influenzae'', ''Moraxella catarrhalis'', ''Streptococcus pneumoniae'', and possibly pathogens of atypical pneumonia. The first-line treatment is a
beta-lactam antibiotic β-lactam antibiotics (beta-lactam antibiotics) are antibiotics that contain a beta-lactam ring in their chemical structure. This includes penicillin derivatives (penams), cephalosporins and cephamycins (cephems), monobactams, carbapenems and ...
such as
amoxicillin Amoxicillin is an antibiotic medication used to treat a number of bacterial infections. These include middle ear infection, strep throat, pneumonia, skin infections, and urinary tract infections among others. It is taken by mouth, or less c ...
. The choice will depend on resistance patterns. In patients with penicillin allergy,
doxycycline Doxycycline is a broad-spectrum tetracycline class antibiotic used in the treatment of infections caused by bacteria and certain parasites. It is used to treat bacterial pneumonia, acne, chlamydia infections, Lyme disease, cholera, typhus ...
or trimethoprim are preferred. ** More complicated bronchitis may be when the patient is more than 65 years old, has four or more exacerbations per year, has an FEV1/FVC ratio of less than 50% on
spirometry Spirometry (meaning ''the measuring of breath'') is the most common of the pulmonary function tests (PFTs). It measures lung function, specifically the amount (volume) and/or speed (flow) of air that can be inhaled and exhaled. Spirometry is ...
, has failed to respond to previous antibiotic treatment, and/or has comorbidity. In these cases, treatment should be aimed at
Gram-negative bacteria Gram-negative bacteria are bacteria that do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. They are characterized by their cell envelopes, which are composed of a thin peptidoglycan cell wall ...
and the possibility of high
antibiotic resistance Antimicrobial resistance (AMR) occurs when microbes evolve mechanisms that protect them from the effects of antimicrobials. All classes of microbes can evolve resistance. Fungi evolve antifungal resistance. Viruses evolve antiviral resistance. ...
should be considered. Sputum culture results are of great value in determining antibiotic resistance. First-line treatment is cefuroxime or
co-amoxiclav Amoxicillin/clavulanic acid, also known as co-amoxiclav or amox-clav, sold under the brand name Augmentin, among others, is an antibiotic medication used for the treatment of a number of bacterial infections. It is a combination consisting of a ...
. Third-line treatment, as well as treatment in penicillin-allergic patients, is a fluoroquinolone such as
ciprofloxacin Ciprofloxacin is a fluoroquinolone antibiotic used to treat a number of bacterial infections. This includes bone and joint infections, intra abdominal infections, certain types of infectious diarrhea, respiratory tract infections, skin i ...
. An agent active against ''Streptococcus pneumoniae'' may have to be added. *
Corticosteroid Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are inv ...
s such as
prednisolone Prednisolone is a steroid medication used to treat certain types of allergies, inflammatory conditions, autoimmune disorders, and cancers. Some of these conditions include adrenocortical insufficiency, high blood calcium, rheumatoid arth ...
reduce inflammation in the airways. According to a 2018
systematic review A systematic review is a scholarly synthesis of the evidence on a clearly presented topic using critical methods to identify, define and assess research on the topic. A systematic review extracts and interprets data from published studies on t ...
, a shorter, five-day course of systemic corticosteroids is likely comparable to longer (10–14 day) therapy for treatment of COPD exacerbation (
Odds ratio An odds ratio (OR) is a statistic that quantifies the strength of the association between two events, A and B. The odds ratio is defined as the ratio of the odds of A in the presence of B and the odds of A in the absence of B, or equivalently (due ...
(OR) 0.72, 95% confidence interval (CI) 0.36 to 1.46). *
Theophylline Theophylline, also known as 1,3-dimethylxanthine, is a phosphodiesterase inhibiting drug used in therapy for respiratory diseases such as chronic obstructive pulmonary disease (COPD) and asthma under a variety of brand names. As a member of the ...
is generally not recommended. There should also be a "care plan" in case of future exacerbations. Patients may watch for symptoms, such as shortness of breath, change in character or amount of mucus, and start self-treatment as discussed with a health care provider. This allows for treatment right away until a doctor can be seen. The symptoms of acute exacerbations are treated using short-acting bronchodilators. A course of corticosteroids, usually in tablet or intravenous rather than inhaled form, can speed up recovery. The IV and oral forms of steroids have been found to be equivalent. Antibiotics are often used but will only help if the exacerbation is due to an infection. Antibiotics are indicated when a patient notes increased sputum production,
purulent Pus is an exudate, typically white-yellow, yellow, or yellow-brown, formed at the site of inflammation during bacterial or fungal infection. An accumulation of pus in an enclosed tissue space is known as an abscess, whereas a visible collect ...
sputum, increased
dyspnea Shortness of breath (SOB), also medically known as dyspnea (in AmE) or dyspnoea (in BrE), is an uncomfortable feeling of not being able to breathe well enough. The American Thoracic Society defines it as "a subjective experience of breathing di ...
, has an elevated white count, or is febrile. Examples of first-line antibiotics are amoxicillin, doxycycline, and
co-trimoxazole Trimethoprim/sulfamethoxazole, sold under the brand name Bactrim among others, is a fixed-dose combination antibiotic medication used to treat a variety of bacterial infections. It consists of one part trimethoprim to five parts sulfamethox ...
.


Mechanical ventilation

Severe exacerbations can require hospital care where treatments such as oxygen and
mechanical ventilation Mechanical ventilation, assisted ventilation or intermittent mandatory ventilation (IMV), is the medical term for using a machine called a ventilator to fully or partially provide artificial ventilation. Mechanical ventilation helps move a ...
may be required. Mechanical ventilation can be invasive (
endotracheal intubation Tracheal intubation, usually simply referred to as intubation, is the placement of a flexible plastic tube into the trachea (windpipe) to maintain an open airway or to serve as a conduit through which to administer certain drugs. It is frequentl ...
) or non-invasive forms of ventilation such as
continuous positive airway pressure Continuous positive airway pressure (CPAP) is a form of positive airway pressure (PAP) ventilation in which a constant level of pressure greater than atmospheric pressure is continuously applied to the upper respiratory tract of a person. The ...
(CPAP) or
bilevel positive airway pressure Positive airway pressure (PAP) is a mode of respiratory ventilation used in the treatment of sleep apnea. PAP ventilation is also commonly used for those who are critically ill in hospital with respiratory failure, in newborn infants ( neonate ...
(BiPAP).


Epidemiology

The incidence varies depending on which definition is used, but definitions by ''Anthonisen et al.'' the typical COPD patient averages two to three AECB episodes per year. With a COPD prevalence of more than 12 million (possibly 24 million including undiagnosed ones) in the United States, there are at least 30 million incidences of AECB annually in the US.


References


External links

{{DEFAULTSORT:Acute Exacerbation Of Chronic Obstructive Pulmonary Disease Lower respiratory tract diseases