Centriacinar emphysema occurs preferentially in the upper lobes and produces holes in the center of secondary pulmonary lobules. The walls of emphysematous spaces are usually imperceptible, but central vessels may be visible (image 4). In contrast, the walls of cysts in pulmonary Langerhans histiocytosis, another cystic lung disease of cigarette smokers, are thicker Panacinar emphysema more commonly involves the lung bases and involves the entire secondary pulmonary lobule (image 6). Panacinar emphysema can cause a generalized paucity of vascular structures. Among patients with alpha-1 antitrypsin deficiency, panacinar emphysema is the more common pattern. Paraseptal (distal acinar) emphysema produces small, subpleural collections of gas located in the periphery of the secondary pulmonary lobule

Spirometry demonstrating airflow limitation (ie, a forced expiratory volume in one second/forced vital capacity [FEV /FVC] ratio less than 0.7 or less than the lower limit of normal [LLN] PLUS an FEV less than 80 percent of predicted) that is incompletely reversible after the administration of an inhaled bronchodilator Absence of an alternative explanation for the symptoms and airflow limitation (table 3) [8]. The differential diagnosis of COPD is discussed below

Among patients who present in mid or later life with dyspnea, cough, and sputum production, the differential diagnosis is broad (eg, heart failure, COPD, interstitial lung disease, thromboembolic disease Typically, the finding of persistent airflow limitation on pulmonary function testing and the absence of radiographic features of heart failure or interstitial lung disease direct the clinician to a narrower differential of COPD, chronic obstructive asthma, bronchiectasis, tuberculosis, constrictive bronchiolitis, and diffuse panbronchiolitis [8]. Importantly, these conditions can commonly occur together, for example, patients with asthma may develop COPD and patients with COPD may have concurrent bronchiectasis.

In some patients with chronic asthma, a clear distinction from COPD is not possible. As an example, a patient, who has had atopic asthma since childhood and smoked cigarettes for 15 years in their twenties and thirties could present in their fifties with a combination of asthma and COPD.

Heart failure is a common cause of dyspnea among middle-aged and older patients and some patients experience chest tightness and wheezing with fluid overload due to heart failure. Occasionally, airflow limitation is noted, although a restrictive pattern is more common. Heart failure is usually differentiated by the presence of fine basilar crackles, radiographic evidence of an increased heart size and pulmonary edema. The brain natriuretic peptide is typically increased in heart failure, but can also be increased during right heart strain from cor pulmonale

Lymphangioleiomyomatosis (LAM) is seen primarily in young women of childbearing age. Pulmonary function testing frequently reveals mild airflow obstruction, although a mixed obstructive-restrictive pattern may be seen. CT scans typically demonstrate small, thin-walled cysts that can at times be confused with emphysema. However, the airspaces in emphysema are not actually cysts but are caused by the destruction of alveolar walls and permanent enlargement of distal airspaces, so the "walls" are typically inapparent.

Routine screening spirometry is generally not indicated for adults who have none of the features suggestive of COPD (eg, no dyspnea, cough, sputum production or progressive decline in activity), as asymptomatic mild airflow obstruction does not require treatment [51,101]. Asymptomatic and nonsmoking subjects with mild airflow obstruction, but no history of asthma, do not have the same progressive decline in lung function that is observed among individuals who have a similar degree of airflow obstruction and are symptomatic or continue to smoke

GOLD also recommends annual spirometry to track decline in FEV . Spirometry is also essential to decision-making for lung volume reduction and lung transplantation.

GOLD system — The therapeutic strategy of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines suggests using a combined assessment based on an individual's symptoms and exacerbation history to guide therapy [ Group A: Low risk, less symptoms: 0 to 1 exacerbation per year and no prior hospitalization for exacerbation; and CAT score <10 or mMRC grade 0 to 1. ● Group B: Low risk, more symptoms: 0 to 1 exacerbation per year and no prior hospitalization for exacerbation; and CAT score ≥10 or mMRC grade ≥2. ● Group C: High risk, less symptoms: ≥2 exacerbations per year or ≥1 hospitalization for exacerbation; and CAT score <10 or mMRC grade 0 to 1. Group D: High risk, more symptoms: ≥2 exacerbations per year or ≥1 hospitalization for exacerbation; and CAT score ≥10 or mMRC grade ≥2.

SG ● 0: Normal spirometry ● SG 1: Mild, postbronchodilator FEV1/FVC ratio <0.7, FEV1 ≥60 percent predicted ● SG 2: Moderate, postbronchodilator FEV1/FVC ratio <0.7, 30 percent ≤FEV1 <60 percent predicted ● SG 3: Severe, postbronchodilator FEV1/FVC ratio <0.7, FEV1 <30 percent predicted ● SG U: Undefined, postbronchodilator FEV1/FVC ratio >0.7, FEV1 <80 percent predicted

"COPD is a common, preventable, and treatable disease that is characterized by persistent respiratory symptoms and airflow limitation that is due to airway and/or alveolar abnormalities usually caused by significant exposure to noxious particles or gases. The chronic airflow limitation that characterizes COPD is caused by a mixture of small airways disease (eg, obstructive bronchiolitis) and parenchymal destruction (emphysema), the relative contributions of which vary from person to person. Chronic inflammation causes structural changes, small airways narrowing, and destruction of lung parenchyma. A loss of small airways may contribute to airflow limitation and mucociliary dysfunction, a characteristic feature of the disease."

Chronic bronchitis is defined as a chronic productive cough for three months in each of two successive years in a patient in whom other causes of chronic cough (eg, bronchiectasis) have been excluded

These changes include abnormal and permanent enlargement of the airspaces distal to the terminal bronchioles that is accompanied by destruction of the airspace walls, without obvious fibrosis. While emphysema can exist in individuals who do not have airflow obstruction, it is more common among patients who have moderate or severe airflow obstruction

Asthma is a chronic inflammatory disorder of the airways in which many cells and cellular elements play a role. The chronic inflammation is associated with airway responsiveness that leads to recurrent episodes of wheezing, breathlessness, chest tightness, and coughing, particularly at night or in the early morning. These episodes are usually associated with widespread, but variable, airflow obstruction within the lung that is often reversible either spontaneously or with treatment

Patients with asthma whose airflow obstruction is completely reversible are not considered to have COPD (subset nine in the figure). Patients with asthma whose airflow obstruction does not remit completely are considered to have COPD (subsets six, seven, and eight in the figure). The etiology and pathogenesis of the COPD in such patients may be different from that of patients with chronic bronchitis or emphysema. ● Chronic bronchitis and emphysema with airflow obstruction commonly occur together (subset five in the figure) [24]. Some of these patients may also have asthma (subset eight in the figure). ● Individuals with asthma may develop a chronic productive cough, either spontaneously or due to exposure (eg, cigarette smoke, allergen). Such patients are often referred to as having asthmatic bronchitis, although this terminology has not been officially endorsed in clinical practice guidelines (subset six in the figure). ● Persons with chronic bronchitis, emphysema, or both are not considered to have COPD unless they have airflow obstruction (subsets one, two, and eleven in the figure) [25,26]. ● Patients with airflow obstruction due to diseases that have a known etiology or a specific pathology (eg, cystic fibrosis, bronchiectasis, obliterative bronchiolitis) are not considered to have COPD (subset 10 in the figure). However, these exclusions are loosely defined [27].