chronic obstructive pulmonary disease 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 of copd include shortness of breath and a cough, which may or may not produce mucus. copd progressively worsens, with everyday activities such as walking or dressing becoming difficult. while copd is incurable, it is preventable and treatable. chronic obstructive pulmonary diseaseother nameschronic obstructive lung disease (cold), chronic obstructive airway disease (coad)section of a lung showing centrilobular emphysema, with enlarged airspaces in the centre of a lobule usually caused by smoking and a major feature of copdspecialtypulmonologysymptomsshortness of breath, chronic coughcomplicationsanxiety, depression, pulmonary heart disease, pneumothoraxusual onsetover 35 years olddurationlong termcausestobacco smoking, air pollution, geneticsdiagnostic methodspirometrydifferential diagnosisasthma, congestive heart failure, bronchiectasis, tuberculosis, obliterative bronchiolitis, diffuse panbronchiolitispreventionstopping smoking, improving indoor and outdoor air quality, tobacco control measurestreatmentpulmonary rehabilitation, long-term oxygen therapy, lung volume reduction,medicationinhaled bronchodilators and steroidsfrequency174.5 million (2015)deaths3.2 million (2019) the two most common conditions of copd are emphysema and chronic bronchitis and they have been the two classic copd phenotypes. emphysema is defined as enlarged airspaces (alveoli) whose walls have broken down resulting in permanent damage to the lung tissue. chronic bronchitis is defined as a productive cough that is present for at least three months each year for two years. both of these conditions can exist without airflow limitation when they are not classed as copd. emphysema is just one of the structural abnormalities that can limit airflow and can exist without airflow limitation in a significant number of people. chronic bronchitis does not always result in airflow limitation but in young adults who smoke the risk of developing copd is high. many definitions of copd in the past included emphysema and chronic bronchitis, but these have never been included in gold report definitions. emphysema and chronic bronchitis remain the predominant phenotypes of copd but there is often overlap between them and a number of other phenotypes have also been described. copd and asthma may coexist and converge in some individuals. copd is associated with low-grade systemic inflammation. the most common cause of copd is tobacco smoking. other risk factors include indoor and outdoor air pollution including dust, exposure to occupational irritants such as dust from grains, cadmium dust or fumes, and genetics, such as alpha-1 antitrypsin deficiency. in developing countries, common sources of indoor air pollution are the use of coal and biomass such as wood and dry dung as fuel for cooking and heating. most people living in european cities are exposed to damaging levels of air pollution. the diagnosis is based on poor airflow as measured by spirometry. most cases of copd can be prevented by reducing exposure to risk factors such as smoking and indoor and outdoor pollutants. while treatment can slow worsening, there is no conclusive evidence that any medications can change the long-term decline in lung function. copd treatments include smoking cessation, vaccinations, pulmonary rehabilitation, inhaled bronchodilators and corticosteroids. some people may benefit from long-term oxygen therapy, lung volume reduction and lung transplantation. in those who have periods of acute worsening, increased use of medications, antibiotics, corticosteroids and hospitalization may be needed. as of 2015, copd affected about 174.5 million people (2.4% of the global population). it typically occurs in males and females over the age of 35–40. in 2019 it caused 3.2 million deaths, 80% occurring in lower and middle income countries, up from 2.4 million deaths in 1990. the number of deaths is projected to increase further because of continued exposure to risk factors and an aging population. in the united states in 2010 the economic cost was put at us$32.1 billion and projected to rise to us$49 billion in 2020. in the united kingdom this cost is estimated at £3.8 billion annually. signs and symptoms signs and symptoms of stages of copd. shortness of breath a cardinal symptom of copd is the chronic and progressive shortness of breath which is most characteristic of the condition. shortness of breath (breathlessness) is often the most distressing symptom responsible for the associated anxiety and level of disability experienced. symptoms of wheezing and chest tightness associated with breathlessness can be variable over the course of a day or between days and are not always present. chest tightness often follows exertion. many people with more advanced copd breathe through pursed lips, which can improve shortness of breath. shortness of breath is often responsible for reduced physical activity and low levels of physical activity are associated with worse outcomes. in severe and very severe cases there may be constant tiredness, weight loss, muscle loss and anorexia. people with copd often have increased breathlessness and frequent colds before seeking treatment. cough the most often first symptom of copd is a chronic cough, which may or may not be productive of mucus as phlegm. phlegm coughed up as sputum can be intermittent and may be swallowed or spat out depending on social or cultural factors and is therefore not always easy to evaluate. however, an accompanying productive cough is only seen in up to 30% of cases. sometimes limited airflow may develop in the absence of a cough. symptoms are usually worse in the morning. a chronic productive cough is the result of mucus hypersecretion and when it persists for more than three months each year for at least two years, it is defined as chronic bronchitis. chronic bronchitis can occur before the restricted airflow diagnostic of copd. some people with copd attribute the symptoms to the consequences of smoking. in severe copd, vigorous coughing may lead to rib fractures or to a brief loss of consciousness. exacerbations an acute exacerbation is a sudden worsening of signs and symptoms that lasts for several days. the key symptom is increased breathlessness, other more pronounced symptoms are of excessive mucus, increased cough and wheeze. a commonly found sign is air trapping giving a difficulty in complete exhalation. the usual cause of an exacerbation is a viral infection, most often the common cold. the common cold is usually associated with the winter months but can occur at any time. other respiratory infections may be bacterial or in combination sometimes secondary to a viral infection. the most common bacterial infection is caused by haemophilus influenzae. other risks include exposure to tobacco smoke (active and passive) and environmental pollutants – both indoor and outdoor. during the covid-19 pandemic, hospital admissions for copd exacerbations sharply decreased which may be attributable to reduction of emissions and cleaner air. there has also been a marked decrease in the number of cold and flu infections during this time. smoke from wildfires is proving an increasing risk in many parts of the world and government agencies have published protective advice on their websites. in the us the epa advises that the use of dust masks do not give protection from the fine particles in wildfires and instead advise the use of well-fitting particulate masks. this same advice is offered in canada to the effects of their forest fires. bushfires in australia add to the high risk factors for copd and its worsening for farmers. the number of exacerbations is not seen to relate to any stage of the disease; those with two or more a year are classed as frequent exacerbators and these lead to a worsening in the disease progression. frailty in ageing increases exacerbations and hospitalization. acute exacerbations in copd are often unexplained and thought to have many causes other than infections. a study has emphasized the possibility of a pulmonary embolism as sometimes being responsible in these cases. signs can include pleuritic chest pain and heart failure without signs of infection. such emboli could respond to anticoagulants. other conditions copd often occurs along with a number of other conditions (comorbidities) due in part to shared risk factors. common comorbidities include cardiovascular disease, skeletal muscle dysfunction, metabolic syndrome, osteoporosis, depression, anxiety, asthma and lung cancer. alpha-1 antitrypsin deficiency (a1ad) is an important risk factor for copd. it is advised that everybody with copd be screened for a1ad. metabolic syndrome has been seen to affect up to fifty percent of those with copd and significantly affects the outcomes. when comorbid with copd there is more systemic inflammation. it is not known if it co-exists with copd or develops as a consequence of the pathology. metabolic syndrome on its own has a high rate of morbidity and mortality and this rate is amplified when comorbid with copd. tuberculosis is a risk factor for the development of copd, and is also a potential comorbidity. most people with copd die from comorbidities and not from respiratory problems. anxiety and depression are often complications of copd. other complications include a reduced quality of life and increased disability, cor pulmonale, frequent chest infections including pneumonia, secondary polycythemia, respiratory failure, pneumothorax, lung cancer, and cachexia (muscle wasting). cognitive impairment is common in those with copd as it is for other lung conditions that affect airflow. cognitive impairment is associated with the declining ability to cope with the basic activities of daily living. it is unclear if those with copd are at greater risk of contracting covid-19, though if infected they are at risk of hospitalization and developing severe covid-19. differentiating covid-19 symptoms from an exacerbation is difficult; mild prodromal symptoms may delay its recognition and where they include loss of taste or smell covid-19 is to be suspected. definition many definitions of copd in the past included chronic bronchitis and emphysema but these have never been included in gold report definitions. emphysema is defined as enlarged airspaces (alveoli) whose walls break down resulting in permanent damage to the lung tissue and is just one of the structural abnormalities that can limit airflow. the condition can exist without airflow limitation but commonly it does. chronic bronchitis is defined as a productive cough that is present for at least three months each year for two years but does not always result in airflow limitation although the risk of developing copd is great. these older definitions grouped the two types as type a and type b. type a were emphysema types known as pink puffers due to their pink complexion, fast breathing rate and pursed lips. type b were chronic bronchitic types referred to as blue bloaters due to low oxygen levels causing a bluish color to the skin and lips and swollen ankles. these differences were suggested to be due to the presence or not of collateral ventilation, evident in emphysema and lacking in chronic bronchitis. this terminology was no longer accepted as useful, as most people with copd have a combination of both emphysema and airway disease. these are now recognized as the two major phenotypes of copd – emphysematous phenotype and chronic bronchitic phenotype. subtypes it has since been recognized that copd is more complex, with a diverse group of disorders of differing risk factors and clinical courses that has resulted in a number of subtypes or phenotypes of copd being accepted and proposed. the two classic emphysematous and chronic bronchitic phenotypes are fundamentally different conditions with unique underlying mechanisms. another subtype of copd, categorized by some as a separate clinical entity, is asthma-copd overlap, which is a condition sharing clinical features of both asthma and copd. spirometry measures are inadequate for defining phenotypes and chest x-ray, ct and mri scans have been mostly employed. most cases of copd are diagnosed at a late stage and the use of imaging methods would allow earlier detection and treatment. the identification and recognition of different phenotypes can guide appropriate treatment approaches. for example, the pde4 inhibitor roflumilast is targeted at the chronic-bronchitic phenotype. two inflammatory phenotypes show a phenotype stability: the neutrophilic inflammatory phenotype and the eosinophilic inflammatory phenotype. mepolizumab, a monoclonal antibody, has been shown to have benefit in treating the eosinophilic inflammatory type rather than the use of oral corticosteroids, but further studies have been called for. another recognized phenotype is the frequent exacerbator. the frequent exacerbator has two or more exacerbations a year, has a poor prognosis and is described as a moderately stable phenotype. a pulmonary vascular copd phenotype has been described due to cardiovascular dysfunction. a molecular phenotype of cftr dysfunction is shared with cystic fibrosis. a combined phenotype of chronic bronchitis and bronchiectasis has been