Emphysema is an enlargement of the air spaces (alveoli) distal to the terminal bronchioles, with destruction of their walls [40]. The destruction of air space walls reduces elastic recoil and the surface area available for the exchange of oxygen and carbon dioxide during breathing. These airways can collapse, leading to further limitation in airflow. Emphysema can be classified by location as panacinar/panlobular and centriacinar/centrilobular [41].

Cigarette smoking is the predominant and primary risk factor for COPD, and approximately 15% of all persons who smoke will develop clinically apparent COPD. Smokers of more than 40 pack-years exposure have a much higher likelihood of developing COPD than nonsmokers. The combined exposure to tobacco smoke and certain occupational dusts and chemicals magnifies the risk for COPD [6,7,8,9,10,11]. In developing countries, COPD has been attributed to chronic exposure to smoke from burning biomass fuels for indoor cooking and heating purposes. The COPD caused by smoking is associated with more rapid disease progression and more severe emphysema than COPD from biomass exposure, which is characterized primarily by airway-wall thickening and improved lung function in response to the use of bronchodilators [11]. Smokers with pre-existing airway reactivity also have a greater susceptibility to developing COPD.

It is believed that a variety of genes play an important role in COPD pathogenesis. A genetic disorder that causes alpha-1 antitrypsin deficiency is an important cause of emphysema in nonsmokers and increases susceptibility to disease in smokers. People with severe hereditary deficiency of alpha-1 antitrypsin are genetically predisposed to developing COPD. Alpha-1 antitrypsin deficiency stimulates neutrophil elastase activity, which leads to parenchymal destruction in the lungs and causes emphysema.

It is suggested that neutrophils play a primary role in the generation of mucous metaplasia in chronic bronchitis and the destruction of lung tissue in emphysema. The neutrophilic inflammatory response appears to account for the excessive mucus secretion observed in response to an acute secretagogue and for augmentation of the bronchial mucus-producing apparatus observed in these patients [34,35]. There is a strong correlation between peripheral airway dysfunction in COPD and sputum neutrophil counts [36].

Macrophages are the predominant inflammatory cells present in lavage fluid in patients with COPD [37]. Numerous studies have demonstrated a direct correlation between the number of alveolar macrophage in the lung tissue and the severity of lung destruction [38].

There is a direct correlation between degree of inflammation, fibrosis, and luminal exudates in small airways and the reduction in FEV1 and FEV1/forced vital capacity (FVC) ratio. The effect on airflow is pronounced in the smaller (<2 mm in diameter) conducting airways. The resultant peripheral airway obstruction produces alveolar hyperinflation and air trapping during expiration. Hyperinflation diminishes inspiratory capacity and increases functional residual capacity, which causes dyspnea and limitation of exercise capacity.

The cardinal signs and symptoms of COPD are chronic cough, sputum production, breathlessness (shortness of breath and dyspnea), and limited exercise tolerance. Other common signs that may be present in COPD include:

Clubbing of the fingers may be present in patients with COPD, in part caused by chronic oxygen deprivation. However, it is relatively uncommon. Clubbing is more likely indicative of other chronic diseases such as congenital heart defect, bronchiectasis, infectious endocarditis, or cirrhosis of the liver.

A clinical diagnosis of COPD should be considered in the patient who presents with shortness of breath or dyspnea, chronic productive cough, and easy fatigue, especially if combined with a history of risk factor exposure (e.g., long-term exposure to tobacco or dust and chemicals, age, genetics). The diagnosis should then be confirmed by spirometry. The presence of a Tiffeneau index or postbronchodilator FEV1/FVC less than 0.70 and FEV1 less than 80% predicted confirms the presence of airflow limitation that is not fully reversible [199].

As with any illness, a careful history is critical in determining the correct diagnosis. The goals of history taking are to identify possible causes of dyspnea and other symptoms and to screen for COPD risk factors. An inadequate history may result in misdiagnosis or delayed diagnosis, with ramifications on disease course. A comprehensive medical history of an individual presenting with COPD symptoms should include:

The BODE index is a multidimensional grading method used to assess clinical risk in patients with COPD based on four factors: body mass index (BMI), obstruction, dyspnea, and exercise (Table 10) [5,57]. It is a better prognostic marker of subsequent survival than any other component alone [5,57]. Each component of the BODE index is graded and a score out of 10 is obtained; higher scores are indicative of greater mortality risk. This method reflects the effect of both pulmonary and extrapulmonary factors on prognosis and survival in COPD.

Computed tomography (CT) of the chest has advanced understanding of COPD and has an important role in the clinical assessment of selected patients. Chest CT can identify the presence and extent of disease patterns that impact prognosis and influence the management of patients with COPD [10]. CT imaging features that are associated with adverse clinical outcomes include early interstitial lung abnormalities, bronchiectasis, presence and pattern of emphysema, airway wall thickness, and expiratory gas trapping [224]. The addition of expiratory CT scans has enabled measurement of small airway disease. Chest CT also may reveal extrapulmonary findings of importance, such as coronary artery calcification, cardiac chamber enlargement, and early-stage lung cancer. The presence of predominantly upper-lobe emphysema on CT imaging identifies the patient who is a good candidate for surgical lung-volume reduction [60].

White patients who experience COPD at a young age (i.e., younger than 45 years) or who have a positive family history of COPD may be screened for alpha-1 antitrypsin deficiency. A serum concentration of alpha-1 antitrypsin less than 15% to 20% of the normal expected value indicates a high probability of homozygous alpha-1 antitrypsin deficiency.

Behavioral interventions are nonpharmacologic treatments delivered directly to individual smokers [209]. The main disadvantage of this approach is that relatively few smokers (about 5%) are interested in attending specific classes at any given time [210]. Therefore, group sessions appear to be the most cost-effective approach to delivering smoking cessation interventions [211]. Although relatively few patients want to go to classes, healthcare professionals should still have a list of referral smoking cessation clinics in their area for those smokers who express an interest in attending them and for those who have failed to respond to other approaches. Simple computer-tailored cessation messages may also be an effective alternative for behavioral support, doubling the cessation rates. This concept has been incorporated into patient support programs provided by several manufacturers of smoking cessation products [210].

The first-line pharmacologic interventions for smoking cessation are NRT, bupropion, and varenicline [217,218]. However, no pharmacotherapy has been approved for use among pregnant or nursing women. The five forms of NRT available are the patch, gum, lozenge, nasal spray, and inhaler.

Methylxanthines have weak bronchodilator and respiratory stimulant properties. Both of the available methylxanthines (aminophylline and theophylline) are administered orally and have variable durations of action (up to 24 hours). The inhaled bronchodilators are preferred over these oral agents, as the latter tends to be less predictable and more toxic. Although useful for some patients, the methylxanthines are a third-line option in the treatment of stable COPD [199].

Pulmonary rehabilitation can address nonpulmonary conditions that are not addressed by the medical management of COPD, including:

Long-term oxygen therapy is usually indicated in stage 4 COPD for patients who have [199]:

Lung volume reduction surgery (LVRS) is a surgical procedure in which damaged parts of the lung are resected to reduce hyperinflation, thus improving efficacy of respiratory muscles. LVRS also improves expiratory flow rates by increasing the elastic recoil pressure of the lung. LVRS is considered for patients with bilateral emphysema on HRCT and severe obstruction with hyperinflation and air trapping [194]. As with bullectomy, certain characteristics may indicate the likelihood of a favorable or unfavorable outcome with LVRS (Table 16) [73].

The selection criteria for NIV are based on clinical observations and gas exchange measurements. Patients with moderate-to-severe dyspnea with signs of increased breathing load (i.e., use of accessory muscles and paradoxical abdominal motion) and tachypnea (>25 breaths per minute) as well as moderate-to-severe acidosis (pH ≤7.35) and/or hypercapnia (PaCO₂ >6.0 kPa OR 45 mm Hg) are considered candidates for NIV [199]. Relative contraindications include [199]:

Only patients with respiratory failure require assessment of pulmonary artery pressure; otherwise, its measurement is not recommended. The development of respiratory failure is indicated by a PaO₂ less than 8.0 kPa (60 mm Hg) with or without PaCO₂ greater than 6.7 kPa (50 mm Hg) in arterial blood gas measurements while breathing air at sea level. Patients may be screened with pulse oximetry and arterial blood gases if SaO₂ is less than 92%.

Pneumonia is the most common comorbid condition in patients with COPD. Pneumonia can present as a part or a trigger of COPD exacerbations; however, there are important clinical differences between pneumonia and acute COPD exacerbations without pneumonia. COPD exacerbation with pneumonia has a more rapid onset of symptoms, more severe illness, longer length of hospital stay, and higher rate of ICU admission and mortality compared to an exacerbation without pneumonia [144].