Cigarette smoking is a key environmental risk factor for COPD. Cigarette smokers have a higher prevalence of respiratory symptoms and lung function abnormalities, a greater annual rate FEV1 decline and a greater COPD mortality rate than non-smokers5; yet fewer than 50% of heavy smokers develop COPD.6 Passive exposure to cigarette smoke, other types of tobacco smoke (e.g., pipe, cigar, water pipe),7–9 and marijuana10 are also risk factors for COPD.11 Smoking during pregnancy poses a risk for the fetus, by altering lung growth and development in utero, and possibly priming the immune system for abnormal/enhanced responses in the future.4,12

In low- and middle-income countries (LMICs), COPD in nonsmokers may be responsible for up to 60–70% of cases.13 Because the LMICs contribute to over 85% of all COPD cases, non-smoking risk factors account for over 50% of the global burden of COPD.13 Wood, animal dung, crop residues, and coal (i.e., biomass), typically burned in poorly functioning stoves, may lead to very high levels of household air pollution,14 which is associated with increased COPD risk, although the extent to which household air pollution versus other poverty-related exposures explain the association is unclear.15,16 Compared to COPD in smokers, COPD nonsmokers is more common in females, of younger age, and exhibit similar (or milder) respiratory symptoms and quality of life impairment. They have similar spirometric indices but greater small airways obstruction, less emphysema and lesser rate of lung function decline. Finally they show lower neutrophil count, higher eosinophil numbers in the sputum13 and a similar defect in macrophage phagocytosis of pathogenic bacteria.17 Research is needed to understand how interventions aimed at decreasing household air pollution can reduce the risk of COPD as well as what is the most appropriate pharmacotherapy for this type of COPD.13

Occupational exposures, including organic and inorganic dusts, chemical agents, and fumes, are an under-appreciated environmental risk factor for COPD.18,19 The U.S. National Health and Nutrition Examination Survey III estimated the fraction of COPD attributable to workplace exposures was 19.2% overall, and 31.1% among never-smokers.20

Air pollution, which typically consists of particulate matter (PM), ozone, oxides of nitrogen or sulfur, heavy metals, and other greenhouse gases, is a major worldwide cause of COPD, responsible for ∼50% of the attributable risk for COPD in LMICs.1 The risk of air pollution to individuals is dose-dependent with no apparent “safe” threshold. Even in countries with relatively low ambient air pollution levels, chronic exposure to PM<2.5μm and nitrogen dioxides significantly impairs lung growth in children,21 accelerates lung function decline in adults and increases the risk for COPD, especially among those with additional risk factors.22 Air pollution also increases the risk of COPD exacerbations, hospitalizations, and mortality.23

The most relevant genetic risk factor for COPD identified are mutations in SERPINA1, leading to α-1 antitrypsin deficiency, a major circulating inhibitor of serine proteases.24 The PiZZ genotype affects 0.12% of COPD patients, and its prevalence ranges from 1/408 in Northern Europe to 1/1274 in Eastern Europe.25 There is no increased COPD risk in heterozygotes (MZ and SZ) in the absence of smoking.26

Other genetic variants have also been associated with reduced lung function and risk of COPD, their individual effect size is small although their co-occurrence may increase disease susceptibility.27

At birth, the lungs are not fully developed. They grow and mature until about 20–25 years of age (earlier in females), when lung function reaches its peak.5 This is followed by a relatively short plateau and a final phase of mild lung function decline due to physiological lung aging. This normal lung function trajectory can be altered by processes occurring during gestation, birth, childhood, and adolescence that affect lung growth (hence, peak lung function) and/or processes shortening the plateau phase and/or accelerating the aging phase.28 Indeed, in the general population there is a range of lung function trajectories through the lifetime.28 Trajectories below the normal range are associated with a higher prevalence and earlier incidence of multi-morbidity and premature death,29 whereas those above the normal range are associated with healthier aging, fewer cardiovascular and respiratory events, as well as with a survival benefit.30,31

Factors in early life termed “childhood disadvantage factors”, including prematurity, low birth weight, maternal smoking during pregnancy, repeated respiratory infections and poor nutrition, among others, are key determinants of peak lung function attained in early adulthood.32–39 Reduced peak lung function in early adulthood increases the risk of COPD later in life.32,40,41 In fact, approximately 50% of patients develop COPD due to accelerated decline in FEV1 over time while the other 50% develop it due to abnormal lung growth and development (with normal lung function decline over time).42

The prevalence of COPD in developed countries is now almost equal in males and females.43 Women report more dyspnea, worse health status scores and have a higher incidence of exacerbations compared with men at similar severity of airflow limitation.44

Poverty and lower socioeconomic status are consistently associated with airflow obstruction45 and increased risk of COPD.46 It is likely that this reflects exposures to household and outdoor air pollutants, crowding, poor nutrition, infections, or other factors related to low socioeconomic status.

Many different studies have reported that asthma and atopy in infancy may be a significant risk factor for COPD in adulthood.47,48 However, it is important to remember that abnormal lung development in childhood and adolescence can cause asthma-like symptoms. Given that poor lung development is associated with COPD in adulthood (see above), some of these infants and adolescents may have been mislabeled as “asthma”.

Severe respiratory infections in childhood have been associated with reduced lung function and increased respiratory symptoms in adulthood.47,49 In adults, chronic bronchial infection, particularly with Pseudomonas aeruginosa, is associated with accelerated FEV1 decline.50 In many parts of the world, tuberculosis51 and HIV infection52 are also important risk factors for COPD.

The word “early” means “near the beginning of a process”. Because COPD can start early in life and take a long time to manifest clinically, identifying “early” COPD is difficult. Further, a biological “early” related to the initial mechanisms that eventually lead to COPD should be differentiated from a clinical “early”, which reflects the initial perception of symptoms, functional limitation and/or structural abnormalities noted. Thus, GOLD proposes to use the term “early COPD” only to discuss the “biological” first steps of the disease in an experimental setting.

Some studies have used “mild” airflow obstruction as a surrogate for “early” disease.61 This assumption is incorrect because not all patients started their journey from a normal peak lung function in early adulthood, so some of them may never suffer “mild” disease in terms of “severity” of airflow obstruction.28 Further, “mild” disease can occur at any age and may progress, or not, over time.60 Accordingly, GOLD proposes that “mild” should be used only to describe the severity of airflow obstruction measured spirometrically.

The term “young COPD” is seemingly straightforward because it directly relates to the “chronological” age of the patient.62 Given that lung function peaks at around 20 years5 and starts to decline around 40–50 years, GOLD proposes to operationally consider “young COPD” in patients aged 20–50 years,63 whether from having never achieved normal peak lung function in early adulthood and/or from shorter plateau and/or early lung function decline.64,65 COPD in “young” people may be associated with significant structural and functional lung abnormalities with substantial impact on health.65,66 A family history of respiratory diseases and/or early-life events (including hospitalizations before the age of 5 years) is reported by a significant proportion of young patients with COPD.65

This term has been proposed to identify individuals of any age, with respiratory symptoms and/or other detectable structural (e.g., emphysema) and/or functional abnormalities (e.g., hyperinflation, reduced lung diffusing capacity, or rapid FEV1 decline), in the absence of airflow obstruction on post-bronchodilator spirometry (i.e., FEV1/FVC>0.7).67 These patients may (or not) develop persistent airflow obstruction (i.e., COPD) over time.67 Yet, people with pre-COPD so defined should already be considered “patients” because they suffer symptoms and/or have functional and/or structural abnormalities. Currently, there is no evidence on what the best treatment is for these patients.68 There urgently is a need for RCTs, both in patients with ‘Pre-COPD’, and in young people with COPD.69 Research in this area would benefit from pediatric-to-adulthood cohorts and more active case-finding strategies.

This term has been proposed to describe individuals with FEV1/FVC ≥0.7 and FEV1 <80% of reference after bronchodilation.70,71 Its prevalence ranges from 7.1% to 20.3%,71 is particularly high in current and former smokers, and is associated with increased all-cause mortality.71 PRISm can transition to normal, obstructive or restrictive spirometry over time.71 Despite an increasing body of literature on PRISm, significant knowledge gaps remain in relation to its pathogenesis and treatment.71

GOLD 2023 modifies the ABCD assessment tool of previous editions74 to recognize the clinical impact of exacerbations independently of the level of symptoms of the patient75 (Fig. 2). The thresholds proposed for symptoms (X axis) and history of exacerbations in the previous year (Y axis) are unchanged from previous GOLD documents, so the A and B groups remain unchanged, while the former C and D groups are now merged into a single group termed “E” (for “Exacerbations”). This has implications for the initial pharmacological treatment recommendations, as discussed below. The practical value of this proposal needs to be validated by appropriate clinical research.

Fig. 2.

GOLD ABE assessment tool. Exacerbation history refers to exacerbations suffered the previous year. mMRC: modified Medical Research Dyspnea Questionnaire. CAT: COPD Assessment Test.

Reproduced with permission from www.goldcopd.org.

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A chest X-ray cannot confirm a diagnosis of COPD. However, radiological changes associated with COPD may include signs of lung hyperinflation (flattened diaphragm and increased retrosternal air space), lung hyperlucency, and rapid tapering of the vascular markings. On the other hand, a chest X-ray can help exclude alternative diagnoses and establishing the presence of significant comorbidities such as concomitant pulmonary fibrosis, bronchiectasis, pleural diseases, kyphoscoliosis, and cardiomegaly.

CT of the chest can provide information of potential clinical relevance, including: (1) presence, severity, and distribution of emphysema. This has implications for potential surgical or endoscopic lung volume reduction, is associated with faster FEV1 decline, higher mortality and increased risk of lung cancer76; (2) about 30% of COPD patients have bronchiectasis visible on CT, which are associated with increased exacerbation frequency and mortality77; (3) most COPD patients fulfill the inclusion/exclusion criteria for lung cancer screening in the general population,78,79 so they should be offered a similar strategy1; (4) quantification of airway abnormalities, although these methods are less well standardized than those used for emphysema quantification80–82; and, (5) a CT offers information about COPD comorbidities including coronary artery calcifications, pulmonary artery enlargement, bone density and muscle mass, some of which are associated with all-cause mortality independently of the severity of airflow obstruction.83 Thus, GOLD 2023 recommends chest CT in COPD patients with persistent exacerbations, symptoms out of proportion to airflow limitation severity, severe airflow obstruction with significant hyperinflation and gas trapping, or for those who meet criteria for lung cancer screening.

Because inhaled therapy is the cornerstone of COPD treatment, the appropriate use of these devices is crucial to optimize the benefit–risk ratio of any inhaled therapy. Achieving this goal requires educating and training the providers and the patients in the correct use of the device. Regular assessment at follow-up is necessary to maintain their effective use. Details on the choice of device can be found in the complete GOLD 2023 document and include availability, patient preferences and ability to perform the correct inhalation maneuver.84

Fig. 3 shows the 2023 GOLD recommendation for initiation of pharmacological therapy. The treatment of patients in Group A has not changed. In contrast, for patients in Group B, a dual long-acting bronchodilator combination (β2 adrenergic (LABA)+anti-muscarinic (LAMA) bronchodilators) is now recommended since dual therapy is more effective than monotherapy with similar side-effects.85–87 For patients in Group E, LAMA+LABA is also the recommended initial therapy, except for those patients with blood eosinophils ≥300cells/μL, in whom starting triple therapy (LABA+LAMA+ICS) can be considered. This is a practical recommendation; direct evidence is not available to guide therapy in naïve individuals. The role of the blood eosinophil count for the reduction of the exacerbation risk with ICS is explicitly discussed below. The use of LABA+ICS in COPD is no longer encouraged. If there is an indication for an ICS, then LABA+LAMA+ICS has been shown to be superior to LABA+ICS and is therefore the preferred choice.88,89 If patients with COPD have concomitant asthma, they should be treated as if they have asthma.90

Fig. 3.

Initial pharmacological treatment. Exacerbation history refers to exacerbations suffered the previous year. *: single inhaler therapy may be more convenient and effective than multiple inhalers. mMRC: modified Medical Research Dyspnea Questionnaire. CAT: COPD Assessment Test. LAMA: long-acting anti-muscarinic antagonist; LABA: long-acting β2 receptor agonist; ICS: inhaled corticosteroid; eos: eosinophils.

Reproduced with permission from www.goldcopd.org.

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Following initial therapy, patients should be reassessed guided by the principles of first review and assess, then adjust if needed.

GOLD 2023 continues to recommend that follow-up treatment be based on two key treatable traits (TTs)91: dyspnea and occurrence of exacerbations (Fig. 4). TTs can be identified based on clinical recognition (phenotypes) and/or on deep understanding of critical causal pathways (endotypes) through validated biomarkers (e.g., circulating eosinophils to guide treatment with inhaled corticosteroids (ICS) in COPD patients with evidence of T2 inflammation).91 Importantly, TTs can co-exist in the same patient92 and change with time (spontaneously or because of treatment). GOLD 2023 recommendations for follow-up treatment for both TTs (dyspnea and exacerbations) broadly follow previous recommendations but no longer include LABA+ICS for the reasons stated above (see initial treatment).

Fig. 4.

Follow-up pharmacological treatment. *: single inhaler therapy may be more convenient and effective than multiple inhalers; **: consider de-escalation of ICS if pneumonia or other considerable side-effects. In case of blood eos ≥300cells/μl de-escalation is more likely to be associated with the development of exacerbations. Exacerbation history refers to exacerbations suffered the previous year. mMRC: modified Medical Research Dyspnea Questionnaire. CAT: COPD Assessment Test. LAMA: long-acting anti-muscarinic antagonist; LABA: long-acting β2 receptor agonist; ICS: inhaled corticosteroid; eos: eosinophils.

Reproduced with permission from www.goldcopd.org.

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For patients with persistent dyspnea or exercise limitation on bronchodilator monotherapy, a step up to LABA+LAMA is recommended. If this does not improve symptoms clinicians should consider switching inhaler device or molecules, as well as investigating and treating other causes of dyspnea.

For patients continuing to have exacerbations (with or without dyspnea) on bronchodilator monotherapy, escalation to LABA+LAMA is recommended, except for patients with blood eosinophils ≥300cells/μL who may be escalated to LABA+LAMA+ICS. For patients with persistent exacerbations on LABA+LAMA, escalation to LABA+LAMA+ICS is recommended if they have blood eosinophils ≥100cells/μL. For patients continuing to exacerbate despite therapy with LABA+LAMA+ICS or those who have an eosinophil count of <100cells/μL, the addition of roflumilast (particularly in patients with chronic bronchitis and an FEV1 <50% predicted)93–95 or a macrolide (particularly in patients who are not current smokers) may be considered.96,97

Patients whose pharmacological treatment is modified should be closely monitored. Treatment escalation has not been systematically tested and trials of de-escalation are limited to withdrawing ICS.98 As indicated in Fig. 4, ICS de-escalation can be considered if pneumonia or other considerable side-effects. In case of blood eos ≥300cells/μl, ICS de-escalation is more likely to be associated with development of exacerbations. Finally, if a patient with COPD and no features of asthma has already been treated – for whatever reason – with LABA+ICS and is well controlled in terms of symptoms and exacerbations, then LABA+ICS could be continued. However, if they remain dyspneic switching to LABA+LAMA should be considered, and if they have further exacerbations, treatment should be escalated to LABA+LAMA+ICS.

All patients should receive basic information about COPD and its treatment (respiratory medications and inhalation devices), strategies to minimize dyspnea, and advice about when to seek help.

Approximately 40% of people with COPD continue to smoke despite knowing they have the disease, and this behavior has a negative impact on prognosis and progression of the disease.108 All patients who continue to smoke should be offered help and treatment to quit.

Depending on local guidelines, patients should be offered vaccination against influenza, pneumococcus, COVlD-19, pertussis, herpes zoster, if they have not already received these.1

Physical activity is decreased in COPD patients109 so all COPD patients should be encouraged to keep active. The challenge is promoting and maintaining physical activity.110,111 Technology-based interventions have the potential to provide convenient and accessible means to enhance exercise self-efficacy, and to educate and motivate patients to make healthy lifestyle changes.112

Pulmonary Rehabilitation (PR), including community and home-based, is beneficial.1 Accordingly, patients with high symptom burden and risk of exacerbations (GOLD groups B and E) should be recommended to take part in a formal PR program designed and delivered in a structured manner, considering the individual's COPD characteristics and comorbidities.113–116

Tele-rehabilitation has been proposed as an alternative to the traditional approaches. This has become even more relevant in the COVID-19 pandemic era where in-person PR has not been feasible. However, it is important to distinguish between evidence-based tele-rehabilitation models and pandemic-adapted models. Multiple trials performed in groups and individuals with a large variety of tele-rehabilitation delivery platforms (videoconferencing, telephone only, website with telephone support, mobile application with feedback, centralized “hub” for people to come together) suggest that telerehabilitation is safe and has similar benefits to those of center-based PR across a range of outcomes.117 However, the optimal form of delivery, content and duration are not yet established.118,119

The criteria for prescribing long term oxygen therapy and ventilator support remain unchanged and are described in detail in the GOLD 2023 report.1

In selected patients with symptomatic heterogeneous or homogenous emphysema and significant hyperinflation refractory to optimized medical care, surgical or bronchoscopic modes of lung volume reduction may be considered (Fig. 7). In patients with a large bulla, surgical bullectomy is an option, and in selected patients with very severe COPD and without relevant contraindications, lung transplantation may be considered.

Fig. 7.

Surgical and interventional therapies in advanced emphysema. Note: not all therapies are available in all countries. Long term ELVR outcomes or direct comparisons to LVRS are unknown. Homogeneous emphysema was defined as <10% difference in emphysematous destruction between the targeted and ipsilateral non-targeted lobe undergoing lung reduction as measured by quantitative chest CT imaging. By contrast, greater than 10% difference between the targeted and non-targeted lobe is considered a heterogeneous pattern of emphysematous destruction. Definition of abbreviations: CV: collateral ventilation measure by Chartis; FI+: fissure integrity >90% by HRCT; FI−: fissure integrity <90% by HRCT; ELVR: endoscopic lung volume reduction; EBV: endobronchial vale; VA: vapor ablation; LVRC: lung volume reduction coil; LVRS: lung volume reduction surgery.

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All patients with advanced COPD should be considered for end of life and palliative care support to optimize symptom control and allow patients and their families to make informed choices about future management.

Exacerbations of COPD (ECOPD) negatively impact health status, disease progression and prognosis.120 The previous GOLD definition of ECOPD was highly non-specific (“acute worsening of respiratory symptoms that results in additional therapy”).3

Besides, the severity of ECOPD was determined post facto (mild, moderate or severe) based on the use of healthcare resources,3 which is useless to guide treatment at the point of care.

To address these limitations, GOLD 2023 has adopted the recent consensus Rome proposal120 which defines ECOPD as: “an event characterized by dyspnea and/or cough and sputum that worsen over ≤14 days, which may be accompanied by tachypnea and/or tachycardia and is often associated with increased local and systemic inflammation caused by airway infection, pollution, or other insult to the airways”.

Patients with COPD are at increased risk of other acute events, particularly decompensated heart failure, pneumonia and/or pulmonary embolism that may mimic or aggravate an ECOPD (Fig. 8).121 Thus, while worsening of dyspnea, particularly if associated with cough and, purulent sputum, and no other symptoms or signs in a patient with COPD may be diagnosed as an ECOPD, other patients may have worsening of respiratory symptoms, particularly dyspnea without the classic characteristics of ECOPD, that should prompt careful consideration and/or search of those potential confounders, or contributors.121

Fig. 8.

Classification of the severity of COPD exacerbations. Definition of abbreviations: VAS: visual analog scale; RR: respiratory rate; HR: heart rate; CRP: C-reactive protein. SaO2: arterial oxygen saturation; PaO2: arterial partial pressure of oxygen; ABG: arterial blood gases; ABG should show new onset/worsening hypercapnia or acidosis since a few patients may have chronic hypercapnia. Adapted from Ref. 120.

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Based on a thorough review of the available literature and using a Delphi approach to agree on the variable thresholds, the Rome proposal suggests using easy to obtain clinical variables to define the severity of ECOPD (mild, moderate or severe) at the point of care (Fig. 8).120 In the primary care setting, severity can be determined with the easily obtainable dyspnea intensity (using a VAS 0–10 dyspnea scale with zero being not short of breath at all and 10 the worst shortness of breath you have ever experienced), respiratory rate, heart rate and oxygen saturation level. Where available, measuring blood C-reactive protein (CRP) levels is recommended (Fig. 8). To determine the need for ventilatory support (usually in the emergency room or hospital setting) arterial blood gases should be measured. To move from a mild to a moderate level, three of the variables need to exceed the established thresholds.

It is hoped that prospective validation will help better define exacerbations and their severity at point of contact, and that documented validation may confirm or help modify the proposed thresholds of the variables now included.122 Likewise, it is proposed that prospective research can help determine a more specific marker of lung injury than the more generic CRP, as has been true for acute events of other organs (e.g., troponin level in patients with acute myocardial infarction).

There are no standards to the timing and nature of hospital discharge but early readmissions during the first 90 days after discharge are frequent and constitute a significant health care problem. A systematic review has shown that comorbidities, previous exacerbations and hospitalization, and increased length of stay were significant risk factors for 30- and 90-day all-cause readmission after a hospitalized COPD exacerbation.151 Hence, after an exacerbation it is good practice to cover education on correct use of the medications, provide support at home and a follow-up plan before discharge.152 Early follow-up (within one month) should also be scheduled as it has been related to less exacerbation-related readmissions.153 Additional follow-up at three months is recommended to ensure return to a stable clinical state and permit a review of the patient's symptoms, lung function, and where possible the assessment of prognosis using multiple scoring systems such as the BODE.154 In addition, arterial oxygen saturation and arterial blood gas assessment will determine the need for long-term oxygen therapy more accurately.155 The effects of initiation of pulmonary rehabilitation in the first 4 weeks post hospital discharge are unclear.156,157

Long-term prognosis following hospitalization for COPD exacerbation is poor, with a five-year mortality rate of about 50%.158 Factors independently associated with poor outcome include older age, lower BMI, comorbidities (e.g., cardiovascular disease or lung cancer), previous hospitalizations for COPD exacerbations, clinical severity of the index exacerbation and need for long-term oxygen therapy at discharge.159–161

Cardiovascular diseases are common in COPD, their prevalence ranging from 20 to 70%.164 The types of cardiovascular comorbid conditions are diverse and span the spectrum from congestive heart failure to ischemic heart disease, arrythmias, peripheral vascular disease and hypertension.164 All these conditions should be treated in patients per established guidelines independent of the COPD diagnosis, including the use of selective β1-blockers when a clear cardiovascular indication is present.

Lung cancer occurs frequently in patients with COPD.165 Like the general population, annual low-dose CT scan is recommended for lung cancer screening in COPD due to smoking.78,79 In patients with COPD not due to smoking, there is insufficient data to establish benefit over harm from lung cancer screening.

Bronchiectasis affects approximately 30% of patients with COPD.166 Increased sputum production, recurrent infections, and more frequent exacerbations hallmark bronchiectasis when it accompanies COPD. A chest CT scan is recommended if bronchiectasis is suspected.

Sleep apnea occurs in approximately 14% of COPD patients.167 This worsens their prognosis since they have more frequent episodes of oxygen desaturation and a longer sleep time with hypoxemia and hypercapnia than OSA patients without COPD.

Osteoporosis in COPD is often under-diagnosed and associated with poor health status and prognosis.168 Recurrent use of systemic corticosteroids increases the risk of osteoporosis and should be avoided if possible.

Studies show that diabetes is more frequent in COPD and the latter is likely to affect prognosis.164 The prevalence of metabolic syndrome has been estimated to be more than 30%.169 Diabetes and metabolic syndrome should be treated according to usual guidelines. COPD should be treated as usual.

GERD is an independent risk factor for exacerbations and is associated with worse health status.170,171 The mechanisms responsible for increased risk of exacerbations are not yet fully established. Proton pump inhibitors are often used for treatment of GERD. One small, single-blind study suggested that these agents decrease the risk of exacerbation,172 but their value in preventing these events remains controversial, and the most effective treatment for this condition in COPD has yet to be established.173

Anemia is frequent in patients with COPD.174 These patients are generally older, have more frequent cardiometabolic comorbidities, greater dyspnea, worse quality of life and airflow obstruction, reduced exercise capacity, and an increased risk of severe exacerbations with a higher mortality.

Secondary polycythemia may be associated with pulmonary hypertension175,176 venous thromboembolism176 and mortality. Although the prevalence of polycythemia in COPD has decreased following the introduction of long-term oxygen therapy (LTOT),177 one study reported its presence in 8.4% of patients with severe COPD receiving LTOT.178

Anxiety and depression are important and underdiagnosed comorbidities in COPD.179–182 Both are associated with poor prognosis,181,183 younger age, female sex, smoking, lower FEV1, cough, higher SGRQ score, and a previous history of cardiovascular disease.179,182,184 Cognitive impairment occurs in 32% of people with COPD, but neuropsychological testing suggests that up to 56% of them may suffer from it.185,186

An increasing number of aging patients suffer multi-morbidity, defined as the presence of two or more chronic conditions. These patients have symptoms from multiple diseases making their presentation complex in the acute or chronic state. Multimorbidity results in frailty hallmarked by the presence of weakness, fatigue, exhaustion, low physical activity, and unintentional weight loss,187 a condition that has been reported to be more prevalent in patients with COPD.