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 COPD
The main symptoms of COPD include shortness of breath and a cough, which may or may not produce mucus.[4] Respiratory symptoms can be more severe during acute episodes or flare-ups known as exacerbations.[17] COPD progressively worsens, with everyday activities such as walking or dressing becoming difficult.[3] While COPD is incurable, it is preventable and treatable.[18]
GOLD initially classified COPD in terms of a 4-level staging system based on severity of functional impairment.[11] The 2023 GOLD report introduced a new definition of COPD, a revision of its assessment tool, and a new taxonomic classification of COPD based on contributory causes or etiotypes.[18][17][12]
COPD has often been described in terms of phenotypes, based on symptoms such as emphysema and chronic bronchitis, which may relate to different underlying mechanisms. Most people with COPD display a combination of symptoms reflective of these and other vascular diseases.[19][20][21] 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 limitations 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.[22][23] Chronic bronchitis does not always result in airflow limitation. However, in young adults with chronic bronchitis who smoke, the risk of developing COPD is high.[24]
As of 2021, COPD affected about 213million people (2.7% of the global population).[9] It typically occurs in males and females over the age of 35–40.[1][3] In 2021, it was the fourth biggest cause of death, responsible for approximately 5% of total deaths.[3] In 2021, COPD caused 3.65million deaths.[10] Almost 90% of COPD deaths in those under 70 years of age occur in low and middle income countries.[3] The number of deaths is projected to increase further because of continued exposure to risk factors and an aging population.[11] In the United States, costs of the disease were estimated in 2010 at $50billion, most of which is due to exacerbation.[11]
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.[4] 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.[4] Many people with more advanced COPD breathe through pursed lips, which can improve shortness of breath.[33] Shortness of breath is often responsible for reduced physical activity, and low levels of physical activity are associated with worse outcomes.[34][35] 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.[4]
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.[4] Symptoms are usually worse in the morning.[36]
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.[24] Chronic bronchitis can occur before the restricted airflow diagnostic of COPD.[11] Some people with COPD attribute the symptoms to the consequences of smoking. In severe COPD, vigorous coughing may lead to rib fractures or to abrief loss of consciousness.[4]
Exacerbations
An acute exacerbation is a sudden flare-up or worsening of signs and symptoms that occurs over several days [37] (GOLD 2024, <14 days).[38] Worsening of symptoms can involve increased breathlessness, increase in mucus volume, change in mucus character, or change in cough or wheeze.[37][38] A commonly found sign is air trapping, giving difficulty in complete exhalation.[39]
Flare-ups are often associated with inflammation resulting from viral or bacterial airway infection or environmental insults to the airways such as indoor or outdoor air pollution, smoking, and use of biomass fuels.[38]Viral infections such as the common cold account for 70% of flare-ups.[24] The common cold is usually associated with the winter months but can occur at any time.[40] Bacterial respiratory infections are the second most frequent triggers, including Haemophilus influenzae,[41][38], Pseudomonas aeruginosa[42][38] and Streptococcus pneumoniae.[38] Bacterial infections may occur in combination or be secondary to a viral infection.[43]
Other risks include exposure to tobacco smoke (active and passive) and environmental pollutants (indoor and outdoor).[44]Smoke from wildfires is proving an increasing risk in many parts of the world due to climate change,[45] and government agencies have published protective advice on their websites. In the US the EPA advises that the use of dust masks does not give protection from the fine particles in wildfires and instead advises the use of well-fitting particulate masks.[46] This same advice is offered in Canada and Australia to the effects of their forest fires.[47][48]
The risk of developing a COPD exacerbation is higher in women; in people with one or more exacerbations within the last year; those with more severe COPD as measured by forced expiratory volume in one second (FEV1); and those with chronic bronchitis or related conditions such as gastroesophageal reflux, pulmonary hypertension[38] or pulmonary embolism.[49] People with two or more flare-ups a year are classed as frequent exacerbators, who are associated with worse disease progression.[39] Exacerbations are associated with more rapid decline in lung function, lower quality of life, and higher morbidity and mortality.[38]Frailty in ageing increases exacerbations and hospitalization.[50]
People with COPD have up to 83% higher risk of pneumonia, atrial fibrillation, and heart failure, and 78% higher risk of depression.[52] Both anxiety and depression are often complications of COPD.[2][1]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.[56]
Metabolic syndrome has been seen to affect up to fifty percent of those with COPD and significantly affects the outcomes.[57] When comorbid with COPD there is more systemic inflammation.[57] 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.[24]
There is also an associated risk of developing pulmonary hypertension. The estimated prevalence of pulmonary hypertension complicating COPD was reported at 39% in a meta-analysis.[58] Of the people with COPD listed for lung transplantation, 82% were documented as having pulmonary hypertension via right heart catheterization, noting a mean pulmonary arterial pressure greater than 20mm Hg.[58] Despite pulmonary hypertension being relatively rare in people with COPD, mild elevations of pulmonary arterial pressure can lead to worse outcomes, including risk of death.[58]
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. However, laboratory and clinical studies are showing a possibility of certain inhaled corticosteroids for COPD providing a protective role against COVID-19.[60] 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.[61]
People with COPD have more additional health issues than those without COPD.[52] Multimorbidity is associated with a worse COPD prognosis.[51] People with COPD are more likely to die of respiratory or heart-related causes than those without COPD, and to die at younger ages.[52] People with COPD often die as a result of comorbidities rather than from respiratory problems.[62]
Categorization
Therapeutic approaches often attempt to identify distinct COPD subtypes to support more targeted treatment strategies for patients.[63][18] A phenotype refers to a collection of observable characteristics including symptoms, frequency of episodes, and other details of patient history that are used in clinical practice. An endotype links such observable traits to underlying mechanisms. One phenotype may be related to multiple endotypes.[18] A genotype is based on the presence or absence of a genetic factor and its effects on underlying mechanisms.[64] An etiotype is a grouping based on contributory causes. Individuals can be affected by multiple causes. Specific causes may be related to particular phenotypes.[18]
Emphysema and chronic bronchitis phenotypes
Historically, phenotypic definitions of COPD have often focused on symptoms related to emphysema and chronic bronchitis.[18] 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 involves it.[22] Chronic bronchitis is defined as a productive cough that is present for at least three months each year for two years. It does not always result in airflow limitation, although the risk of developing COPD is great.[24]
Early definitions used physical examination to group these as type A and type B. Type A (emphysema types) were known as pink puffers due to their pink complexion, fast breathing rate and pursed lips. Type B (chronic bronchitic types) were referred to as blue bloaters due to low oxygen levels causing a bluish color to the skin and lips and swollen ankles.[19][20]
Prior to 2023, these phenotypic definitions were not included in the GOLD report definitions for COPD.[18][11] More recently, it has been suggested that these proposed phenotypes may reflect unique underlying mechanisms: an "emphysematous phenotype" that involves extensive alveolar destruction and a "chronic bronchitis phenotype" that is associated with neutrophilic airway inflammation.[18][65] Most people with COPD have a combination of symptoms reflecting both emphysema and airway disease.[19]
Other phenotypes
COPD is complex, and is increasingly recognized as a diverse group of disorders with differing risk factors and clinical courses. This has resulted in other subtypes or phenotypes of COPD being proposed.[66][67] Another subtype of COPD, categorized by some as a separate clinical entity, is asthma-COPD overlap (ACO phenotype), which is a condition sharing clinical features of both asthma and COPD.[68][18]
Another recognized phenotype is the frequent exacerbator.[65] The frequent exacerbator has two or more exacerbations a year, has a poor prognosis, and is described as a moderately stable phenotype.[39]
A pulmonary vascular COPD phenotype has been described due to cardiovascular dysfunction.[69] A molecular phenotype of CFTR dysfunction is shared with cystic fibrosis.[21] A combined phenotype of chronic bronchitis and bronchiectasis has been described, with a difficulty noted in determining the best treatment.[70]
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 inhibitorroflumilast is targeted at the chronic-bronchitic phenotype.[71]
Genotypes
The alpha-1 antitrypsin deficiency (AATD) genetic subtype involves a rare mutation in the SERPINA1 gene that is linked to proteinase-antiprotease imbalance. In this genotype, unchecked neutrophil elastase activity leads to early-onset panacinar emphysema. This has a specific treatment, involving augmentation with purified AAT protein.[18][64][13]
Endotypes
An endotype is based on identification of a biological or molecular mechanism that explains why a given patient has certain observable disease features.[18][53] Two well-defined COPD endotypes related to inflammation mechanisms are the neutrophil-centric inflammasome pathway ("T2-low" COPD) and eosinophil-dependent type 2 immunity ("T2-high" COPD).[18]
Neutrophil-centric inflammasome pathway ("T2-low" COPD). The T2-low endotype (neutrophil-predominant) is marked by inflammation of neutrophils, a type of white blood cell that deals with injury and infection. Environmental stressors (e.g. cigarette smoke, air pollution) cause inflammation of neutrophils in the dominant airway, resulting in a well-defined molecular cascade involving interleukin (IL)−1, IL-8, Th17 and other mediators. Patients display elevated levels of IL-17 and other neutrophil-specific factors. Their symptoms align with the classical smoking-associated chronic bronchitis phenotype. This endotype correlates with accelerated decline in lung function and recurrent infectious exacerbations.[18][53]
Eosinophil-dependent type 2 immunity ("T2-high" COPD). The T2-high endotype (eosinophil-predominant) is characterized by type 2 inflammation of eosinophils, white blood cells involved in allergies and asthma. The T2-high COPD pathway may involve non-IgE-related mast cell activation, release of alarmins, Th2 cell differentiation, and the production of cytokines IL-4, IL-5, and IL-13. Mechanisms are similar to those in allergen response, and similar, but not identical, to those in asthma. 20–40% of COPD patients display elevated eosinophil counts in blood or sputum, as well as activation of type 2 immune pathways. These individuals have "asthma-like" symptoms, and heightened risks of acute exacerbation and hospital readmission. This endotype may overlap with the ACO phenotype.[18][72][53]
Etiotypes
The 2023 GOLD report recognized the variety of causes contributing to COPD and introduced a new classification system based on etiotypes, categorizing COPD in terms of underlying causes and risk factors. The 2023 GOLD report identifies seven distinct etiologic subtypes:[18][12]
cigarette smoking COPD (COPD-C)
biomass and pollution exposure COPD (COPD-P)
genetically determined COPD (COPD-G)
COPD due to abnormal lung development (COPD-D)
COPD with asthma (COPD-A)
COPD due to infections (COPD-I)
COPD of unknown cause (COPD-U)
This framework better reflects variation in COPD causes and progression across global populations. For example, COPD that is related to biomass exposure (COPD-P) and repeated childhood infection (COPD-I) is prevalent in low-and middle-income countries.[18]
Identification of causes has implications for disease management. Etiologic subtypes can be related to specific clinical phenotypes. For example, biomass-associated COPD tends to involve greater airway fibrosis, while tobacco-related disease involves more emphysematous damage.[18]
Identification of such differences emphasizes the need to address underlying issues. Providing clean energy cooking fuels can reduce biomass exposure. Health programs such as early-life lung development can be part of COPD prevention and management. Vaccination can help to prevent respiratory infections such as influenza, pneumococcus, and RSV, reducing dangerous COPD exacerbations.[18]
Causes
The most common cause of the development of COPD is the exposure to harmful particles or gases, including tobacco smoke, that irritate the lung, causing significant or long-term inflammation that interacts with several host factors.[11] The greatest risk factor for the development of COPD is tobacco smoke,[25] accounting for up to 70% of cases in first-world countries.[53] Exposure can be either active (smoking yourself) or passive (living in a house where someone else smokes).[73] However, up to 30% of COPD cases occur in people who have never smoked, and many heavy smokers do not develop COPD, so other factors also need to be considered.[73][74]
These include exposure to indoor and outdoor pollutants, particulate matter, allergens, occupational exposure, and host factors.[36][24] In developing countries, poorly ventilated cooking and heating fires are a common cause of COPD, particularly for women.[24] Another known causes of COPD is exposure to occupational irritants[7] such as dust from farming (e.g. grains), manufacturing (e.g. cadmium dust or fumes), mining[27], and construction. The three main types of construction dust are silica dust, non-silica dust (e.g., dust from gypsum, cement, limestone, marble and dolomite) and wood dust.[75]
Host factors include genetic susceptibility.[24]Alpha-1 antitrypsin deficiency (A1AD) is an important genetic risk factor for COPD.[76] It is advised that everybody with COPD be screened for A1AD.[55]
Other host factors are associated with poverty,[77] physical inactivity and aging.[24] The role of lung function trajectories throughout life, and mechanisms such as abnormal lung development and accelerated lung function, is increasingly being recognized. Some early-life factors contributing to poor lung development have the potential to be prevented, such as poor nutrition, low physical activity, early alcohol consumption, and exposure to smoking and biomass fumes.[73] A host factor of an airway branching variation, arising during development, has been identified.[78] In Europe, airway hyperresponsiveness is rated as the second most important risk factor after smoking.[24] It can contribute to asthma, which is recognized as an additional risk factor.[24]
Alcohol abuse can lead to alcoholic lung disease and is seen to be an independent risk factor for COPD.[79]Mucociliary clearance is disrupted by chronic exposure to alcohol; macrophage activity is diminished and an inflammatory response promoted.[80][81] The damage leads to a susceptibility for infection, including COVID-19,[82] more so when combined with smoking; smoking induces the upregulation of the expression of ACE2, a receptor for the SARS-CoV-2 virus.[79]
Smoking
The greatest risk factor for the development of COPD globally is tobacco smoking.[25][53] Exposure can be either active (smoking yourself) or passive (living in a house where someone else smokes).[73] The second most frequent substance to be smoked is marijuana. Although marijuana smoking carries a lower risk for COPD than tobacco smoking, chronic marijuana smoking is still associated with increased respiratory symptoms similar to those of chronic bronchitis.[83] The highest level of risk is associated with smoking both marijuana and tobacco. This carries a higher symptom burden and increased risk of developing COPD compared to smoking tobacco only or to marijuana only.[83]
Tobacco
Smokers and ex-smokers have a higher rate of developing COPD.[11][25] In high-income countries smoking is associated with over 70% of COPD cases, while in low and middle income countries, it accounts for 30% to 40% of cases.[53] In the United States and United Kingdom, of those with COPD, 80–95% are either current or previous smokers.[84][85][86] About 20% of those who smoke will develop COPD,[84] and about 50% of heavy smokers will get COPD.[11]
Several studies indicate that women are more susceptible than men to the harmful effects of tobacco smoke.[87] For the same amount of cigarette smoking, women have a higher risk of COPD than men.[88] Women who smoke during pregnancy, and during the early life of their child, increase the risk factor for that child's later development of COPD.[89] Epigenetic studies support this link, showing that ACSF3 is differentially methylated in smoke-exposed fetal lungs, and an integrative study identified it as a key regulator of COPD.[90]
Inhaled smoke triggers the release of excessive proteases in lungs, which then degrades elastin, the major component of alveoli.[25] Smoke also impairs the action of cilia, inhibiting mucociliary clearance that clears the bronchi of mucus, cellular debris and unwanted fluid.[25]
Other methods of inhaling tobacco smoke, such as cigar, pipe, water-pipe and hookah use, also confer a risk.[24] Water-pipe or hookah smoke appears to be as harmful or even more harmful than smoking cigarettes.[91]
Marijuana
Marijuana is the second most commonly smoked substance.[92] Less evidence is available about marijuana use and COPD than about tobacco use and COPD. Both cannabis and tobacco smoke contain toxic and carcinogenic compounds such as polycyclic aromatic hydrocarbons (PAHs), volatile organic compounds (VOCs) and reactive oxygen species. These damage DNA and are linked to mechanisms of oxidative stress and chronic inflammation involved in COPD. However, there are differences in the effects of marijuana and tobacco use.[83]
Tobacco smoke has a bronchoconstrictive effect that can increase airway constriction. In contrast, marijuana use has a bronchodilatory effect that temporarily counteracts airflow obstruction. Evidence suggests that lower levels of cannabis smoking (a few joints per month) do not cause the structural damage in small airways. This type of damage leads to airflow limitation and severe shortness of breath, characteristic of emphysema and caused by tobacco smoking. Heavy prolonged cannabis use (>20 uses per month) does impair large airway function, likely due to the effects of PAHs and VOCs and chronic inflammation.[83]
Chronic cannabis use is associated with increased respiratory symptoms similar to those in chronic bronchitis, such as cough, mucous production and wheezing. While emphysema was uncommon among cannabis-only users, one study reported that damaging effects on large airway function of a single cannabis joint were comparable to 2.5 to 5 tobacco cigarettes.[83] Also, marijuana smokers typically reported onset of respiratory symptoms ten years earlier than tobacco smokers.[92] A noted difference between marijuana use and tobacco is that cannabis-related respiratory symptoms appear to resolve if users stop smoking, whereas tobacco smokers continue to decline despite stopping.[92]
Combined tobacco and marijuana use
However, when someone smokes both marijuana and tobacco, either in combination or separately, their risk increases in a synergistic effect. Those who smoke both tobacco and cannabis show a higher symptom burden and COPD risk than those who smoke only tobacco (known to affect both large and small airway dysfunction), or only marijuana (known to affect large airway function). Compounded risk was particularly noticeable at high levels of cumulative cannabis exposure (>50 joints lifetime).[83] Using both marijuana and tobacco may have a cumulative toxic effect, suggesting combined use as a risk factor for conditions such as bullous emphysema,[93] spontaneous pneumothorax, and lung cancer.[83][94][92][95]
Air pollution is a major cause of COPD, contributing an estimated 50% of the total attributable risk of COPD worldwide. It is the leading known risk factor for COPD in life-long nonsmokers, and has no safe threshold. Air can contain a mix of potentially harmful suspended particles and chemicals such as carbon monoxide, heavy metals, lead, ozone, nitrogen oxides (NOx), sulfur oxides, polycyclic aromatic hydrocarbons, benzene and acrolein. Both particulate matter and gases in air pollution are factors in COPD pathophysiology.[97][98]
The harmfulness of particulate matter depends on the size, structure and composition of the particles involved. Particulate matter can carry toxic metals and organic matter and transport them through the lower and upper respiratory tracts deep into the lungs.[97][98] Exposure to particulates can contribute to the development of COPD and trigger flare-ups (exacerbations) either directly through irritation or indirectly due to infections. Those with COPD are more susceptible to the harmful effects of exacerbations triggered by such infections.[57]
Air pollution is often described in terms of ambient (outdoor) and household (indoor) air pollutants.[97] Major sources of ambient air pollution include suspended dusts, combustion of fossil fuels and biofuels, industrial emissions,[97][98] waste disposal,[99] and wildfire smoke. Combustion releases fine and ultrafine particulates, greenhouse gases and other pollutants. Photochemical reactions between sunlight, nitrogen oxides (NOx) and volatile organic compounds (VOCs) produce ozone,[97] which increases the risk of death from COPD.[98]Black carbon or soot is an air pollutant associated with an increased risk of hospitalization from exacerbations. Long-term exposure brings with it an increased rate of mortality in COPD.[57][98]
The main indoor air pollutants include particulate matter, VOCs, nitrogen oxides, sulfur dioxide, carbon monoxide, ozone, radon, toxic metals, and microorganisms.[100] Smoking is a major contributor to indoor air pollution, as is the burning of wood and other biomass fuels for heating and cooking. Building materials and furnishings can be sources of formaldehyde, asbestos, and lead dust. Chemicals in cleaning products, paints, varnishes, pesticides, fragrances, air fresheners, and office equipment can release VOCs and aerosols. Microorganisms include mold, fungi, bacteria, and dust mites.[100] Workplace-related exposures in occupations such as farming, cleaning and industrial work[101] include dust from grinding, blasting, and sanding,[7] grain dust[101] and pesticides.[102] Radon gas occurs naturally and can enter buildings through cracks in foundations and walls. Pollutants from outdoor air can also enter buildings.[100]
Comparisons of COPD rates between cities and rural areas can vary widely and tend to reflect underlying factors such as gender, smoking (rural people may smoke more), work-related pollutant exposure (grain dust and pesticides in rural areas, manufacturing in cities), and accessibility to health care.[103][104][105] Areas with poor outdoor air quality, including that from exhaust gas, generally have higher rates of COPD.[106] 97% of the major cities in the world fail to meet the World Health Organization (WHO)'s safety standards for particulate matter in ambient air.[97] Urban air pollution significantly affects the developing lung and its maturation, and contributes a potential risk factor for the later development of COPD.[24]
Patients with COPD in rural areas experience greater morbidity and obstacles to care than those in urban areas. Racial/ethnic minorities and those with low incomes-particularly in rural areas-are also at greater risk of forgoing doctor visits due to cost.[104]
Measures to prevent and control air pollution and reduce emissions have been taken by some governments, and have significantly reduced both pollution and COPD incidence. When pollution levels outdoors are high, people can reduce risk by wearing personal protective equipment such as an N95 mask, and by reducing the time and intensity of outdoor activities. Stopping smoking, using clean fuels for heating and cooking, and improving ventilation are important steps for improving indoor air quality and reducing COPD risk. [98]
Biomass fuels
Between 2 and 3 billion people (most of whom are in low-income countries) cook, heat or light their homes using solid biomass fuels such as wood, crop wastes, charcoal, or dry dung.[107][108] Poorly ventilated open fires and simple stoves used for cooking and heating are often fueled by biomass fuels, kerosene, or coal, generating very high levels of indoor air pollution.[24][107] Globally, 50% of all households and 90% of rural households are estimated to use such fuels.[107] They are the main source of energy in 80% of homes in India, China and sub-Saharan Africa.[106] Wood is also used for household heating in developed countries (e.g. Canada, Australia, USA), but use tends to be seasonal and involve lower exposure levels.[107]
Use of biomass fuels increases indoor air pollution and is one of the most common causes of COPD in developing countries. Women tend to do the work of cooking and other tasks at home. This increases women's exposure to indoor pollutants and the level to which they are affected.[24] Small children who tend to be at home, and whose lungs are still developing, are also likely to be more affected.[109] Exposure to indoor biomass smoke has been associated with acute lower respiratory infections in children younger than five, and with COPD in men and women age 30 or more. The overall risk of COPD for indoor biomass exposure was estimated at 3.2 for women and 1.8 for men.[107]
Changing from biomass fuel to biogas when cooking and improving kitchen ventilation has been shown to reduce COPD and poor FEV1. Improving conditions for longer periods of time more effectively countered decline in lung function. Improving cookstoves and kitchen ventilation, and using clean fuels for heating and cooking, are important steps for reducing indoor COPD risk.[98][98]
Exposure to workplace dusts, chemicals and fumes in a wide variety of industries increases the risk of COPD in smokers, nonsmokers[101][7][110] and never-smokers.[111][8][110] In the United States, workplace exposure is estimated to be the cause of COPD in 31.1% of cases in never smokers and 19.2% of all cases. Workplace exposure probably represents a greater risk in countries with insufficient regulations.[24] In China, the highest occupational risks were associated with agriculture (farming, forestry, animal husbandry, and fishery), followed by manufacturing and mining. Exposure level (low, medium or high) correlated with severity of COPD.[27]
The negative effects of occupational exposure and smoking are interrelated and the two factors may be additive or synergisticly reinforce each other.[7] Symptoms differ. Compared to smokers with COPD, never-smoking patients with COPD are more likely to have symptoms of asthma and bronchiectasis, and a history of pulmonary tuberculosis, and less likely to have symptoms of emphysema.[8]
Occupational exposures may be under-diagnosed, particularly in never-smokers. Taking a detailed occupational history and identifying possible occupational causes is important for intervention and management of COPD. Exposure to dusts and gases in the workplace is potentially reduceable through regulation, education and training, and increased use of safety measures and protective equipment.[7][8]
Genetics
Genetics plays a role in the development of COPD. It is more common among relatives of those with COPD who smoke than among unrelated smokers.[24] The most well known genetic risk factor is alpha-1 antitrypsin deficiency (AATD) and this is the only genotype (genetic subtype) with a specific treatment.[64] This risk is particularly high if someone deficient in alpha-1 antitrypsin (AAT) also smokes.[112] It is responsible for about 1–5% of cases[112][113] and the condition is present in about three to four in 10,000 people.[114]
The COPDGene study is an ongoing longitudinal study into the epidemiology of COPD, identifying phenotypes and looking for their likely association with susceptible genes. Genome-wide analyses in concert with the International COPD Genetics Consortium has identified more than 80 genome regions associated with COPD. Whole genome sequencing is an ongoing collaboration (2019) with the National Heart, Lung and Blood Institute (NHLBI) to identify rare genetic determinants.[116]
Abnormal lung development
The role of lung function trajectories throughout life is increasingly being recognized.[73] It has been suggested that having smaller airways relative to lung size is a possible indicator of whether someone is likely to develop COPD.[117] Mechanisms such as abnormal lung development and accelerated lung function decline, beginning early in life, can lead to COPD in late adulthood. Some early-life factors that contribute to poor lung development may be preventable, such as poor nutrition, low physical activity, early alcohol consumption, and exposure to smoking.[73]
A host factor of an airway branching variation, arising during development, has been described.[78] The respiratory tree is a filter for harmful substances, and any variant has the potential to disrupt this.[jargon] A variation is associated with the development of chronic bronchitis, and another with the development of emphysema. A branch variant in the central airway is specifically associated with an increased susceptibility for the later development of COPD. A genetic association for the variants has been sometimes found with FGF10.[78][118]
In Europe, airway hyperresponsiveness (AHR) is rated as the second most important risk factor after smoking.[24] In AHR, dysfunctional airway smooth muscle[jargon] can be more sensitive. As a result, bronchoconstriction increases in response to stimuli inhaled from the environment (direct AHR), or mediators[jargon] released by mast cells (indirect AHR). This drives inflammation and may lead to airway structural changes known as remodeling and airflow obstruction. In those with asthma, AHR can contribute to breathlessness, wheeze, and chest tightness.[119] AHR is associated with type 2 (T2) inflammation and eosinophilic[jargon] COPD, and may be a treatable trait.[120][121]
Asthma
A history of asthma in childhood is associated with decreases in adult lung function and higher susceptibility to COPD.[122][123] Asthma is a recognized risk factor, as the comorbidity of COPD is reported to be 12 times higher in patients with asthma after adjusting for smoking history.[24] Asthma commonly starts in childhood, with variable symptoms of breathlessness, chest tightness, cough and wheeze. Appearance of symptoms may relate to times of day and to identifiable triggers such as dust, pollen, and grass.[124] In contrast, COPD has a later onset and is progressive; airflow limitation in COPD is poorly reversible; and respiratory symptoms in COPD are persistent.[125]
Asthma predominantly involves eosinophilic and type 2 helper T lymphocyte-driven airway inflammation.[124] It has been suggested that a diagnosis of asthma in childhood may be associated with poor lung function in adulthood.[73] The occurrence of both asthma and COPD, referred to as Asthma-COPD overlap (ACO), is associated with increased severity of respiratory symptoms, increased hospital admission, and worse quality of life, compared to either asthma or COPD alone[125] Asthma patients who have been exposed to higher levels of air pollution are observed to be almost three times more likely to develop ACO.[98] Higher incidence of ACO is related to specific industries and occupations, indicating the importance of workplace exposures on respiratory health.[125]
Infections
A history of respiratory infections in childhood is associated with decreases in adult lung function and higher susceptibility to COPD.[122][126] Both tuberculosis and pneumonia in childhood are risk factors for COPD, with adult COPD patients experiencing worse symptoms and poorer lung function as measured by spirometry.[127][8]
COPD and non-COPD patients tend to experience different types of infections. COPD patients are more likely to report infections from gram-negative bacteria (Pseudomonas aeruginosa, Haemophilus influenzae) and fungal pathogens.[42]
Pathophysiology
Normal lungs shown in upper diagram. Lungs damaged by COPD in the lower diagram with an inset showing a cross-section of bronchioles blocked by mucus and damaged alveoli.
COPD is a progressive lung disease in which chronic, incompletely reversible poor airflow (airflow limitation) and an inability to breathe out fully (air trapping) exist.[128] The poor airflow is the result of small airways disease and emphysema (the breakdown of lung tissue).[129] The relative contributions of these two factors vary between people.[11] Air trapping precedes lung hyperinflation.[130]
COPD develops as a significant and chronic inflammatory response to inhaled irritants which ultimately leads to bronchial and alveolar remodelling in the lung[53] known as small airways disease.[131][132][133] Thus, airway remodelling with narrowing of peripheral airway and emphysema are responsible for the alteration of lung function.[134]Mucociliary clearance is particularly altered with a dysregulation of cilia and mucus production.[135] Small airway disease sometimes called chronic bronchiolitis, appears to be the precursor for the development of emphysema.[136]
The inflammatory cells involved include neutrophils and macrophages, two types of white blood cells. Those who smoke additionally have cytotoxic T cell involvement, and some people with COPD have eosinophil involvement similar to that in asthma. Part of this cell response is brought on by inflammatory mediators such as chemotactic factors. Other processes involved with lung damage include oxidative stress produced by high concentrations of free radicals in tobacco smoke and released by inflammatory cells and breakdown of the connective tissue of the lungs by proteases (particularly elastase) that are insufficiently inhibited by protease inhibitors. The destruction of the connective tissue of the lungs leads to emphysema, which then contributes to the poor airflow and finally, poor absorption and release of respiratory gases. General muscle wasting that often occurs in COPD may be partly due to inflammatory mediators released by the lungs into the blood.[24]
Narrowing of the airways occurs due to inflammation and subsequent scarring within them. This contributes to the inability to breathe out fully. The greatest reduction in air flow occurs when breathing out, as the pressure in the chest is compressing the airways at this time.[137] This can result in more air from the previous breath remaining within the lungs when the next breath is started, resulting in an increase in the total volume of air in the lungs at any given time, a process called air trapping which is closely followed by hyperinflation.[137][138][130] Hyperinflation from exercise is linked to shortness of breath in COPD, as breathing in is less comfortable when the lungs are already partly filled.[139] Hyperinflation may also worsen during an exacerbation.[140] There may also be a degree of airway hyperresponsiveness to irritants similar to those found in asthma.[114]
Low oxygen levels and eventually, high carbon dioxide levels in the blood, can occur from poor gas exchange due to decreased ventilation from airway obstruction, hyperinflation and a reduced desire to breathe.[24] During exacerbations, airway inflammation is also increased, resulting in increased hyperinflation, reduced expiratory airflow and worsening of gas transfer. This can lead to low blood oxygen levels, which, if present for a prolonged period, can result in narrowing of the arteries in the lungs, while emphysema leads to the breakdown of capillaries in the lungs. Both of these conditions may result in pulmonary heart disease also classically known as cor pulmonale.[59]
Diagnosis
A person blowing into a spirometer. Smaller handheld devices are available for office use.
The diagnosis of COPD should be considered in anyone over the age of 35 to 40 who has shortness of breath, a chronic cough, sputum production, or frequent winter colds and a history of exposure to risk factors for the disease. Spirometry is then used to confirm the diagnosis.[4][141]
Spirometry
Spirometry measures the amount of airflow obstruction present and is generally carried out after the use of a bronchodilator, a medication to open up the airways.[142] Two main components are measured to make the diagnosis, the forced expiratory volume in one second (FEV1), which is the greatest volume of air that can be breathed out in the first second of a breath and the forced vital capacity (FVC), which is the greatest volume of air that can be breathed out in a single large breath.[143] Normally, 75–80% of the FVC comes out in the first second[143] and a FEV1/FVC ratio less than 70% in someone with symptoms of COPD defines a person as having the disease.[142] Because pulmonary function declines with ageing, use of this fixed threshold will lead to over-diagnosis of COPD in the elderly.[15] The National Institute for Health and Care Excellence criteria additionally require a FEV1 less than 80% of predicted.[144] People with COPD also exhibit a decrease in diffusing capacity of the lung for carbon monoxide due to decreased surface area in the alveoli, as well as damage to the capillary bed.[145] Testing the peak expiratory flow (the maximum speed of expiration), commonly used in asthma diagnosis, is not sufficient for the diagnosis of COPD.[144]
Screening using spirometry in those without symptoms has uncertain effects and is generally not recommended; however, it is recommended for those without symptoms but with a known risk factor.[55]
A number of methods can be used to assess the effects and severity of COPD.[141][55] The MRC breathlessness scale or the COPD assessment test (CAT) are simple questionnaires that may be used.[146][141] The St George Respiratory Questionnaire (SGRQ), can be used with patients who have chronic bronchitis to identify patients at risk of COPD exacerbation.[37]
GOLD refers to a modified MRC scale that if used, needs to include other tests since it is simply a test of breathlessness experienced.[55][147] Scores on CAT range from 0–40 with the higher the score, the more severe the disease.[148] Spirometry may help to determine the severity of airflow limitation.[4] This is typically based on the FEV1 expressed as a percentage of the predicted "normal" for the person's age, gender, height and weight.[4] Guidelines published in 2011 by American and European medical societies recommend partly basing treatment recommendations on the FEV1.[149] The GOLD guidelines group people into four categories based on symptoms assessment, degree of airflow limitation and history of exacerbations.[147] Weight loss, muscle loss and fatigue are seen in severe and very severe cases.[55]
Use of screening questionnaires, such as the COPD diagnostic questionnaire (CDQ), alone or in combination with hand-held flow meters, is appropriate for screening of COPD in primary care.[150]
Other tests
A chest X-ray is not useful to establish a diagnosis of COPD, but it is of use in either excluding other conditions or including comorbidities such as pulmonary fibrosis and bronchiectasis. Characteristic signs of COPD on X-ray include hyperinflation (shown by a flattened diaphragm and an increased retrosternal air space) and lung hyperlucency.[5] A saber-sheath trachea may also be shown that is indicative of COPD.[151]
A CT scan is not routinely used except for the exclusion of bronchiectasis.[5]Pulse oximetry measurement of peripheral oxygen saturation is recommended in people with clinical signs of respiratory failure or right heart failure.[5] An analysis of arterial blood is recommended in those with a peripheral oxygen saturation of 92% or less to determine actual blood oxygen level and assess for high levels of carbon dioxide in the blood, which may have therapeutic implications such as need for non-invasive ventilation or oxygen supplementation.[13]WHO recommends that all those diagnosed with COPD be screened for alpha-1 antitrypsin deficiency.[55]
Chest X-ray demonstrating severe COPD, displaying small heart size in comparison to the lungs
A lateral chest X-ray of a person with emphysema, displaying barrel chest and flat diaphragm
Lung bulla as seen on chest X-ray in a person with severe COPD
A severe case of bullous emphysema
Axial CT image of the lung of a person with end-stage bullous emphysema
Very severe emphysema with lung cancer on the left (CT scan)
Many cases of COPD are potentially preventable through decreasing exposure to tobacco smoke and other indoor and outdoor pollutants.[30] It may be possible to prevent development of COPD in later life by improving additional conditions that affect lung development in early life, such as frequent respiratory illness, poor nutrition, low physical activity, and early alcohol consumption.[73]
The policies of governments, public health agencies and antismoking organizations can reduce smoking rates by discouraging people from starting and encouraging people to stop smoking.[153]Smoking bans in public areas and places of work are important measures to decrease exposure to secondhand smoke, and while many places have instituted bans, more are recommended.[106]
In those who smoke, stopping smoking is a crucial strategy shown to slow down the worsening of COPD.[154][155][156] In the short term, quitting smoking can reduce respiratory symptoms. In the longer term, quitting can improve lung function, exercise capacity, perceived quality of life, and survival of those with COPD.[154] It can reduce flare-ups and hospitalizations.[157] Even at a late stage of the disease, it can reduce the rate of worsening lung function and delay the onset of disability and death.[158] Quitting earlier in life and not smoking for longer periods (>10 years) show greater benefits.[157]
Often, several attempts are required before long-term abstinence is achieved.[153] Attempts over 5 years lead to success in nearly 40% of people.[159][154] Some smokers can achieve long-term smoking cessation through willpower alone. Smoking, however, is highly addictive, and many smokers need further support.[160] The chance of quitting is improved with social support, engagement in a smoking cessation program and the use of medications such as nicotine replacement therapy, bupropion, or varenicline.[153][156][159] Combining smoking-cessation medication with behavioral therapy is more than twice as likely to be effective in helping people with COPD stop smoking, compared with behavioral therapy alone.[161]
Occupational health
Measures to reduce occupation exposure in at-risk industries include public policy and regulation to support healthy workplaces; identifying risky work settings and exposures; actionable steps to reduce exposure to risk factors and exacerbations; education of workers, management and medical professionals about risks, diagnosis, and management; promoting smoking cessation; checking workers for early signs of COPD; and using equipment such as respirators for better control of dust and gases.[162][52][163][164] Effective dust control can be achieved by improving ventilation, using water sprays and by using mining techniques that minimize dust generation.[165] If a worker develops COPD, further lung damage can be reduced by avoiding ongoing dust exposure, for example by changing their work role.[166]
Both indoor and outdoor air quality can be improved, which may prevent COPD and slow the worsening of existing disease. This may be achieved by public policy efforts, cultural changes and personal involvement.[30][167][168] Some countries have successfully improved outdoor air quality through regulations, resulting in improvements in the lung function of their populations.[98]
Cities or other organizations may monitor air quality, sometimes sharing data with the public through air quality indices and alerts.[169][170] Individuals are often advised to avoid or reduce exposure to irritants in indoor and outdoor pollution through smoking cessation, engaging in activities at times and places when exposure to pollutants is lower, and using protective gear (e.g. N95 masks, air filtration).[30] It is becoming increasingly possible to monitor individual exposures to air pollution and adapt behavior accordingly.[171][172]
In developing countries, a key effort is to reduce exposure to smoke from cooking and heating fuels through improved ventilation of homes and user of cleaner fuels, stoves and chimneys.[30][173] Proper stoves may improve indoor air quality by 85%. Using alternative energy sources such as solar cooking and electrical heating is also effective.[106] However, poverty is often a barrier to the adoption of better fuels. Higher-income families may use modern fuels such as natural gas or electricity, which cause less pollution and can lead to better health outcomes. Electricity supply, however, is often insufficient to meet a family's heating needs. If electricity is supplemented with low-quality biofuels, indoor air-pollution levels will increase and negatively affect health outcomes.[173]
Management
COPD currently has no cure,[174] but the symptoms are treatable and its progression can be delayed, particularly by stopping smoking.[1][6] If COPD is detected early, while symptoms are still mild, interventions to prevent decline in lung function have a greater effect. For both individual treatment and public health, early diagnosis and intervention are recommended. In cases of early and mild COPD, pulmonary rehabilitation may help to improve exercise capacity and quality of life.[7][52][175]
The major goals of management are to reduce exposure to risk factors including offering non-pharmacological treatments such as help with stopping smoking. Stopping smoking can reduce the rate of lung function decline and also reduce mortality from smoking-related diseases such as lung cancer and cardiovascular disease.[1] Other recommendations include pneumococcal vaccination and yearly influenza vaccination to help reduce the risk of exacerbations; as of 2024 CDC and GOLD also recommend RSV vaccine for individuals above 60 years.[176][13] Guidance is also advised as to managing breathlessness and stress.[6]
Other illnesses are also being managed. An action plan is drawn up and is to be reviewed.[30] Providing people with a personalized action plan, an educational session and support for use of their action plan in the event of an exacerbation, reduces the number of hospital visits and encourages early treatment of exacerbations.[177] When self-management interventions, such as taking corticosteroids and using supplemental oxygen, are combined with action plans, health-related quality of life is improved compared to usual care.[178] In those with COPD who are malnourished, supplementation with vitamin C, vitamin E, zinc and selenium can improve weight, strength of respiratory muscles and health-related quality of life.[31] Significant vitamin D deficiency is common in those with COPD and can cause increased exacerbations. Supplementation when deficient can give a 50% reduction in the number of exacerbations.[39][179]
In those with a severe exacerbation, antibiotics improve outcomes.[180] Several different antibiotics may be used, including amoxicillin, doxycycline and azithromycin; whether one is better than the others is unclear.[181] There is no clear evidence of improved outcomes for those with less severe cases.[180] The FDA recommends against the use of fluoroquinolones when other options are available due to higher risks of serious side effects.[182] In treating acute hypercapnic respiratory failure (acutely raised levels of carbon dioxide), bilevel positive airway pressure (BPAP) can decrease mortality and the need of intensive care.[183]
Beta2–adrenergic agonists target receptors in the smooth muscle cells in bronchioles causing them to relax and allow improved airflow. They reduce shortness of breath, tend to reduce dynamic hyperinflation and improve exercise tolerance.[6][186] Short-acting bronchodilators have an effect for four hours and for maintenance therapy long acting bronchodilators with an effect of over twelve hours are used. In times of more severe symptoms, a short-acting agent may be used in combination.[6] An inhaled corticosteroid used with a long-acting beta-2 agonist is more effective than either one on its own.[187]
Which type of long-acting agent, long-acting muscarinic antagonist (LAMA) such as tiotropium or long-acting beta agonist (LABA), is better is unclear, and trying each and continuing with the one that works best may be advisable.[188] Both types of agent appear to reduce the risk of acute exacerbations by 15–25%.[183] The combination of LABA/LAMA may reduce COPD exacerbations and improve quality-of-life compared to long-acting bronchodilators alone.[189] The 2018 NICE guideline recommends use of dual long-acting bronchodilators with economic modelling suggesting that this approach is preferable to starting one long-acting bronchodilator and adding another later.[190]
Several short-acting β2 agonists are available, including salbutamol (albuterol) and terbutaline.[6] They provide relief of symptoms for four to six hours.[6] A long-acting beta agonist (LABA) such as salmeterol, formoterol and indacaterol are often used as maintenance therapy, with a duration of action of 12 to 24 hours.[6] Some feel the evidence of benefits is limited,[191] while others view the evidence of benefit as established.[192][193][194] Long-term use of LABAs appears safe in COPD,[195] with adverse effects include shakiness and heart palpitations.[183] When used with inhaled steroids they increase the risk of pneumonia.[183] While steroids and LABAs may work better together,[191] it is unclear if this slight benefit outweighs the increased risks.[196] There is some evidence that combined treatment of LABAs with long-acting muscarinic antagonists (LAMA), an anticholinergic, and LABA +ICS (inhaled corticosteroid) may be similar in benefits in terms of fewer exacerbation's and quality of life measures for moderate to severe COPD, but LAMA+LABA offers better improvements in forced expiratory volume (FEV1%) and a lower risk of pneumonia.[197] All three together, LABA, LAMA and ICS, have some evidence of benefits.[198] Indacaterol requires an inhaled dose once a day and is as effective as the other long-acting β2 agonist drugs that require twice-daily dosing for people with stable COPD.[194]
The two main anticholinergics used in COPD are ipratropium and tiotropium. Ipratropium is a short-acting muscarinic antagonist (SAMA), while tiotropium is long-acting muscarinic antagonist (LAMA). Tiotropium is associated with a decrease in exacerbations and improved quality of life,[199] and tiotropium provides those benefits better than ipratropium.[200] Tiotropium does not appear to affect mortality or the overall hospitalization rate.[199] Anticholinergics can cause dry mouth and urinary tract symptoms.[183] They are also associated with increased risk of heart disease and stroke.[201]Aclidinium, another long-acting agent, reduces hospitalizations associated with COPD and improves quality of life.[202][203][204] The LAMA umeclidinium bromide is another anticholinergic alternative.[205] When compared to tiotropium, the LAMAs aclidinium, glycopyrronium, and umeclidinium appear to have a similar level of efficacy, with all four being more effective than placebo.[206] Further research is needed comparing aclidinium to tiotropium.[204]
Corticosteroids
Inhaled corticosteroids are anti-inflammatories that are recommended by GOLD as a first-line maintenance treatment in COPD cases with repeated exacerbations.[207][208] Their regular use increases the risk of pneumonia in severe cases.[39] Studies have shown that the risk of pneumonia is associated with all types of corticosteroids; is related to the disease severity and a dose-response relationship has been noted.[207] Oral glucocorticoids can be effective in treating an acute exacerbation.[187] They appear to have fewer side effects than those given intravenously.[209] Five days of steroids work as well as ten or fourteen days.[210]
The use of corticosteroids is associated with a decrease in the number of lymphoid follicles (in the bronchial lymphoid tissue).[136] A triple inhaled therapy of LABA/LAMA/ICS improves lung function, reduces symptoms and exacerbations and is seen to be more effective than mono or dual therapies.[211][187] NICE guidelines recommend the use of ICSs in people with asthmatic features or features suggesting steroid responsiveness.[190]
PDE4 inhibitors
Phosphodiesterase-4 inhibitors (PDE4 inhibitors) are anti-inflammatories that improve lung function and reduce exacerbations in moderate to severe illness. Roflumilast is a PDE4 inhibitor used orally once daily to reduce inflammation; it has no direct bronchodilatory effects. It is essentially used in treating those with chronic bronchitis along with systemic corticosteroids.[212] Reported adverse effects of roflumilast appear early in treatment, become less with continued treatment and are reversible. One effect is dramatic weight loss, and its use is to be avoided in underweight people. It is also advised to be used with caution in those who have depression.[212]
Methylxanthines such as theophylline are widely used. Theophylline is seen to have a mild bronchodilatory effect in stable COPD. Inspiratory muscle function is seen to be improved, but the causal effect is unclear. Theophylline is seen to improve breathlessness when used as an add-on to salmeterol. All instances of improvement have been reported using sustained-release preparations.[6] Methylxanthines are not recommended for use in exacerbations due to adverse effects.[39]
Mucolytics may help to reduce exacerbations in some people with chronic bronchitis, as noticed by fewer hospitalizations and fewer days of disability in one month.[216]Erdosteine is recommended by NICE.[217] GOLD also supports the use of some mucolytics that are advised against when inhaled corticosteroids are being used and singles out erdosteine as having good effects regardless of corticosteroid use. Erdosteine also has antioxidant properties, but there is not enough evidence to support the general use of antioxidants.[212] Erdosteine has been shown to significantly reduce the risk of exacerbations, shorten their duration and hospital stays.[218]
Cough medicines are not recommended.[219]Beta blockers are not contraindicated for those with COPD and should only be used where there is concomitant cardiovascular disease.[212]
Recent studies show that metformin plays a role in reducing systemic inflammation by reducing biomarker levels that are increased during COPD exacerbations.[220]
Supplemental oxygen is recommended for those with low oxygen levels in respiratory failure at rest (a partial pressure of oxygen less than 50–55mmHg or oxygen saturations of less than 88%).[31] When taking into account complications including cor pulmonale and pulmonary hypertension, the levels involved are 56–59 mmHg.[221] Oxygen therapy is to be used for between 15 and 18 hours per day and is said to decrease the risk of heart failure and death.[221] In those with normal or mildly low oxygen levels, oxygen supplementation (ambulatory) may improve shortness of breath when given during exercise, but may not improve breathlessness during normal daily activities or affect the quality of life.[222] During acute exacerbations, many require oxygen therapy; the use of high concentrations of oxygen without taking into account a person's oxygen saturations may lead to increased levels of carbon dioxide and worsened outcomes.[223][224] In those at high risk of high carbon dioxide levels, oxygen saturations of 88–92% are recommended, while for those without this risk, recommended levels are 94–98%.[224] Once prescribed long-term oxygen therapy, patients should be re-assessed after 60 to 90 days, to determine whether supplemental oxygen is still indicated and if prescribed supplemental oxygen is effective.[13][225]
Rehabilitation
Pulmonary rehabilitation is a program of exercise, disease management and counseling, coordinated to benefit the individual.[226] A severe exacerbation leads to hospital admission, high mortality and a decline in the ability to carry out daily activities. Following a hospital admission, pulmonary rehabilitation has been shown to significantly reduce future hospital admissions, mortality and improve quality of life.[71]
The optimal exercise routine, use of noninvasive ventilation during exercise and intensity of exercise suggested for people with COPD, is unknown.[227][228] Performing endurance arm exercises improves arm movement for people with COPD and may result in a small improvement in breathlessness.[229] Performing arm exercises alone does not appear to improve quality of life.[229]Pursed-lip breathing exercises may be useful.[33]Tai chi exercises appear to be safe to practice for people with COPD and may be beneficial for pulmonary function and pulmonary capacity when compared to a regular treatment program.[230] Tai Chi was not found to be more effective than other exercise intervention programs.[230] Inspiratory and expiratory muscle training (IMT, EMT) have been suggested and may provide some improvements when compared to no treatment.[231] A combination of IMT and walking exercises at home may help limit breathlessness in cases of severe COPD.[232] Additionally, the use of low amplitude high velocity joint mobilization together with exercise improves lung function and exercise capacity.[233] The goal of spinal manipulation therapy is to improve thoracic mobility in an effort to reduce the work on the lungs during respiration, however, the evidence supporting manual therapy for people with COPD is very weak.[233][234]
Airway clearance techniques (ACTs), such as postural drainage, percussion/vibration, autogenic drainage, hand-held positive expiratory pressure (PEP) devices and other mechanical devices, may reduce the need for increased ventilatory assistance, the duration of ventilatory assistance and the length of hospital stay in people with acute COPD.[235] In people with stable COPD, ACTs may lead to short-term improvements in health-related quality of life and a reduced long-term need for hospitalizations related to respiratory issues.[235]
Being either underweight or overweight can affect the symptoms, degree of disability and prognosis of COPD. People with COPD who are underweight can improve their breathing muscle strength by increasing their calorie intake. When combined with regular exercise or a pulmonary rehabilitation program, this can lead to improvements in COPD symptoms. Supplemental nutrition may be useful in those who are malnourished.[31][236]
Management of exacerbations
People with COPD can experience exacerbations (flare-ups) that are commonly caused by respiratory tract infections. The symptoms that worsen are not specific to COPD and differential diagnoses need to be considered.[39] Acute exacerbations are typically treated by increasing the use of short-acting bronchodilators, including a combination of a short-acting inhaled beta agonist and short-acting anticholinergic.[39] These medications can be given either via a metered-dose inhaler with a spacer or via a nebulizer, with both appearing to be equally effective.[212][237] Nebulization may be easier for those who are more unwell.[212]Oxygen supplementation can be useful. Excessive oxygen; however, can result in increased CO2 levels and a decreased level of consciousness.[238] Corticosteroids given orally can improve lung function and shorten hospital stays but their use is recommended for only five to seven days; longer courses increase the risk of pneumonia and death.[39]
Room temperature
Maintaining room temperature of at least 21°C (70°F) for a minimum of nine hours a day was associated with better health in those with COPD, especially for smokers.[239] The World Health Organization (WHO) recommends indoor temperatures of a slightly higher range between 18 and 24°C (64 and 75°F).[240]
Room humidity
For people with COPD, the ideal indoor humidity levels are 30–50% RH. Maintaining indoor humidity can be difficult in the winter, especially in cold climates where the heating system is constantly running.[241]
Keeping the indoor relative humidity above 40% RH significantly reduces the infectivity of aerosolized viruses.[242]
For severe emphysema that has proved unresponsive to other therapies lung volume reduction surgery (LVRS) may be an option.[243][244] LVRS involves the removal of damaged tissue, which improves lung function by allowing the rest of the lungs to expand.[183] It is considered when the emphysema is in the upper lobes and when there are no comorbidities.[245]
Minimally invasive bronchoscopic procedures may be carried out to reduce lung volume. These include the use of valves, coils, or thermal ablation.[31][246]Endobronchial valves are one-way valves that may be used in those with severe hyperinflation resulting from advanced emphysema; a suitable target lobe and no collateral ventilation are required for this procedure. The placement of one or more valves in the lobe induces a partial collapse of the lobe that ensures a reduction in residual volume that improves lung function, the capacity for exercise and quality of life.[247]
The placement of nitinol coils instead of valves is recommended where there is collateral ventilation that would prevent the use of valves.[248] Nitinol is a biocompatible alloy.
Both of these techniques are associated with adverse effects, including persistent air leaks and cardiovascular complications. Thermal vapor ablation has an improved profile. Heated water vapor is used to target lobe regions, which leads to permanent fibrosis and volume reduction. The procedure can target individual lobe segments, can be carried out regardless of collateral ventilation, and can be repeated with the natural advance of emphysema.[249]
Other surgeries
In very severe cases, lung transplantation might be considered.[243] A CT scan may be useful in surgery considerations.[114]Ventilation/perfusion scintigraphy is another imaging method that may be used to evaluate cases for surgical interventions and also to evaluate post-surgery responses.[250] A bullectomy may be carried out when a giant bulla occupies more than a third of a hemithorax.[245]
Prognosis
Chronic obstructive pulmonary disease deaths per million persons in 2012:
COPD is progressive and can lead to premature death. It is estimated that 3% of all disability is related to COPD.[252] The proportion of disability from COPD globally has decreased from 1990 to 2010 due to improved indoor air quality primarily in Asia.[252] The overall number of years lived with disability from COPD, however, has increased.[253]
There are many variables affecting the long-term outcome in COPD and GOLD recommends the use of a composite test (BODE) that includes the main variables of body-mass index, obstruction of airways, dyspnea (breathlessness) and exercise and not just spirometry results.[55] NICE recommends against the use of BODE for the prognosis assessment in stable COPD; factors such as exacerbations and frailty need to be considered.[246] Other factors that contribute to a poor outcome include older age, comorbidities such as lung cancer and cardiovascular disease and the number and severity of exacerbations needing hospital admission.[39]
Epidemiology
Estimates of prevalence have considerable variation due to differences in analytical and surveying approach and the choice of diagnostic criteria.[254] An estimated 213million people had COPD in 2021, corresponding to a global prevalence of 2.7%,[9] whereas epidemiological studies indicated an estimation of 384million having COPD in 2010, corresponding to a global prevalence of 12%.[11]
The disease affects both men and women[3] but risk is heavily influenced by age, gender, lifestyle, and socioeconomic factors,[8][126][255] and prevalence varies with countries and regions.[255] A higher rate of COPD is found in those over 40 years and this increases greatly with advancing age with the highest rate found in those over 60 years.[11] Sex differences in the anatomy of the respiratory system in women include smaller airway lumens and thicker airway walls, contributing to greater severity of COPD symptoms and frequency of COPD exacerbation.[256] In never-smokers, COPD is more common in women than men.[8] However, men are more likely to smoke, the top risk factor.[8]
A review of data from 201 countries between 1990 to 2021 shows a variety of changes in age-standardized prevalence and death rates of COPD. Rates in some countries increased, some were stable, and some decreased. Changes in prevalence appear to reflect changes in rates of smoking and air polliution. In addition, the use of biomass fuels for cooking is related to increased COPD prevalence, particularly in women, while gas cooking is related to reduced prevalence. The universal thermal climate index and various climatic conditions also correlate with COPD prevalence.[255] Globally, incidence and mortality rates declined slightly between 1990 and 2021, but this was not true for all demographics.[255][257]
In 2023, COPD was the third-leading cause of death globally.[258] In low-income countries, COPD does not appear in the Top 10 causes of death; in other income groups, it is in the Top 5.[259] Around three million people die of COPD each year.[11] Tobacco use, ambient air pollution, and socioeconomic factors are all associated with higher death rates.[255] In some countries, mortality has decreased in men but increased in women.[260][258] This may reflect rates of smoking in women and men becoming more similar.[260]
In the UK, three million people are reported to be affected by COPD–two million of these being undiagnosed. On average, the number of COPD-related deaths between 2007 and 2016 was 28,600. The estimated number of deaths due to occupational exposure was estimated to be about 15% at around 4,000.[254]
In the United States in 2018, almost 15.7 million people had been diagnosed with COPD and it is estimated that millions more have not been diagnosed.[261] In the United States in 2021, about 11.7 million insured individuals were identified with COPD. There were 1.8 million COPD-related acute inpatient hospitalizations. Both COPD prevalence and COPD-related hospitalization rates varied widely among states.[262]
The name chronic obstructive pulmonary disease is believed to have first been used in 1965.[263] Previously it has been known by a number of different names, including chronic obstructive bronchopulmonary disease, chronic airflow obstruction, chronic obstructive lung disease, nonspecific chronic pulmonary disease, and diffuse obstructive pulmonary syndrome.[263]
The terms emphysema and chronic bronchitis were formally defined as components of COPD in 1959 at the CIBA guest symposium and in 1962 at the American Thoracic Society Committee meeting on Diagnostic Standards.[263]
Early descriptions of probable emphysema began in 1679 by T. Bonet of a condition of "voluminous lungs" and in 1769 by Giovanni Morgagni of lungs which were "turgid particularly from air".[263][264] In 1721, the first drawings of emphysema were made by Ruysh.[264]René Laennec, used the term emphysema in his book A Treatise on the Diseases of the Chest and of Mediate Auscultation (1837) to describe lungs that did not collapse when he opened the chest during an autopsy. He noted that they did not collapse as usual because they were full of air and the airways were filled with mucus.[263] In 1842, John Hutchinson invented the spirometer, which allowed the measurement of vital capacity of the lungs. However, his spirometer could only measure volume, not airflow. Tiffeneau and Pinelli in 1947 described the principles of measuring airflow.[263]
Air pollution and the increase in cigarette smoking in Great Britain at the start of the 20th century led to high rates of chronic lung disease, though it received little attention until the Great Smog of London in December 1952. This spurred epidemiological research in the United Kingdom, Holland and elsewhere.[265] In 1953, George L. Waldbott, an American allergist, first described a new disease he named smoker's respiratory syndrome in the 1953 Journal of the American Medical Association. This was the first association between tobacco smoking and chronic respiratory disease.[266]
Modern treatments were developed during the second half of the 20th century. Evidence supporting the use of steroids in COPD was published in the late 1950s. Bronchodilators came into use in the 1960s following a promising trial of isoprenaline. Further bronchodilators, such as short-acting salbutamol, were developed in the 1970s and the use of long-acting bronchodilators began in the mid-1990s.[267]
Society and culture
It is generally accepted that COPD is widely underdiagnosed and many people remain untreated. In the US the NIH has promoted November as COPD Awareness Month to be an annual focus on increasing awareness of the condition.[268]
Economics
Globally, as of 2010, COPD is estimated to result in economic costs of $2.1trillion, half of which occurring in the developing world.[269] Of this total an estimated $1.9trillion are direct costs such as medical care, while $0.2trillion are indirect costs such as missed work.[270] This is expected to more than double by 2030.[269] In Europe, COPD represents 3% of healthcare spending.[11] In the United States, costs of the disease were estimated at $50billion in 2010, most of which is due to exacerbation.[11] In the United Kingdom this cost was in 2021 estimated at £3.8 billion annually.[271]
The effectiveness of alpha-1 antitrypsin augmentation treatment for people who have alpha-1 antitrypsin deficiency is unclear.[273]
Metabolomic approaches to diagnosing and differentiating subtypes of COPD are being studied.[274][275][276]
Research continues into the use of telehealthcare to treat people with COPD when they experience episodes of shortness of breath; treating people remotely may reduce the number of emergency-room visits and improve the person's quality of life.[277]
American people with COPD and their caregivers consider the following COPD-related research areas as the most important: family/social/community research, well-being of people with COPD, curative research, biomedical therapies, policy, and holistic therapies.[278]
Other animals
Chronic obstructive pulmonary disease may occur in a number of other animals and may be caused by exposure to tobacco smoke.[279] Most cases of the disease, however, are relatively mild.[280] In horses it is known as recurrent airway obstruction (RAO) or heaves. RAO can be quite severe and most often is linked to exposure to common allergens.[281] COPD is also commonly found in old dogs.[282]
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