Approach Considerations
COPD is diagnosed based on clinical symptom and history of exposure to risk factors. [1] Spirometry is required to confirm diagnosis. Further assessments are made to determine the level of airflow limitation, the impact of disease on health status, and the risk of exacerbations, in order to guide therapy.
AATD
The workup of an individual with AATD-related emphysema should include testing for early detection and follow-up of a variety of associated conditions including liver disease, granulomatosis with polyangiitis, and panniculitis. . For example, the Alpha-1 Foundgation recommends patients be regularly monitored for liver disease with liver ultrasound and laboratory testing of AST, ALT, GGT, albumin, bilirubin, INR, and platelets, [16]
Asthma-COPD overlap
Asthma, COPD and asthma-COPD overlap are differentiated based on a comparison of the number of features characteristic of each possible diagnosis. Spirometry and peak expiratory flow measurement is performed to confirm of exclude diagnoses. Referral to a pulmonologist for diagnosis may be necessary under the following circumstances:
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Diagnosis is uncertain or alternative diagnoses such as bronchiectasis, post-tuberculous scarring, bronchiolitis, pulmonary fibrosis, pulmonary hypertension need to be excluded
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Atypical or additional signs and symptoms (e.g., hemoptysis, weight loss, night sweats, signs of bronchielctasis or other structural lung disease) are present
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Chronic airway disease is suspected but few features of asthma and COPD are present
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Comorbidities are present that may interfere with assessment of airway disease
Laboratory Studies
The following laboratory studies are useful:
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Arterial blood gas analysis: Patients with mild chronic obstructive pulmonary disease (COPD) have mild-to-moderate hypoxemia without hypercapnia. As the disease progresses, hypoxemia worsens and hypercapnia develops.
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Hematocrit: Chronic hypoxemia may lead to polycythemia. A hematocrit value higher than 52% in men and higher than 47% in women is indicative of the condition. Patients should be evaluated for hypoxemia at four times: at rest, with ambulation, with exertion, and during sleep. Correction of hypoxemia should reduce secondary polycythemia in patients who have quit smoking.
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Serum bicarbonate: Chronic respiratory acidosis leads to compensatory metabolic alkalosis. In the absence of blood gas measurements, serum bicarbonate levels are useful for following disease progression.
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Sputum evaluation: In patients with stable chronic bronchitis and in emphysema, the sputum is mucoid and the predominant cells are macrophages. With an exacerbation, the sputum becomes purulent, with excessive neutrophils and a mixture of organisms visualized through Gram staining. Streptococcus pneumoniae and Haemophilus influenzae are pathogens frequently cultured during exacerbations.
AATD Testing
All individuals with COPD regardless of age or ethnicity should be tested for AATD. [2, 16, 27] Of the approximately 75 different alleles for alpha1-antitrypsin (AAT) deficiency variants, 10-15 are associated with serum levels below the protective threshold of 11 mmol/L. The diagnosis of severe AAT deficiency is confirmed when the serum level falls below the protective threshold value (ie, 3-7 mmol/L). More than 95% of all severely AAT deficient individuals have either the ZZ or SZ genotype. In addition MZ individuals who smoke are also at increased risk for airflow obstruction. [16]
AAT levels cannot be used alone to identify at risk individuals because the AAT level vary with inflammation, pregnancy, and in children. Confirmatory testing using a second method such as proteinase inhibitor (Pi) typing and/or AAT genotyping is required. More advanced testing, such as expanded genotyping for rare AAT alleles and gene sequencing, may also be considered confirmatory testing. [16]
Imaging Studies
Chest radiograph
Frontal and lateral chest radiographs reveal signs of hyperinflation: flattening ("coving") of diaphragms, increased retrosternal air space (see on lateral chest films), and a long narrow heart shadow. Rapid tapering vascular shadows accompanied by hyperlucency of the lungs are signs of emphysema. With complicating pulmonary hypertension, the hilar vascular shadows become prominent; right ventricular enlargement and an opacity in the lower retrosternal air space may also occur.
Note the images below.





CT scan
High-resolution CT (HRCT) scanning is more sensitive than standard chest radiography. HRCT scanning is highly specific for diagnosing emphysema and outlines bullae that are not always observed on radiographs. A CT scan is indicated when the patient is being considered for a surgical intervention such as bullectomy or lung-volume reduction surgery. A CT scan is not indicated in the routine care of patients with COPD.
Note the images below.
Other Tests
Pulmonary function tests
These measurements are necessary for the diagnosis of obstructive airway disease and for assessments of its severity. In addition, spirometry is helpful for assessing responses to treatment and disease progression.
Forced expiratory volume in 1 second (FEV1) is a reproducible test and is the most common index of airflow obstruction. Lung volume measurements show an increase in total lung capacity, functional residual capacity, and residual volume. The vital capacity is decreased.
DLCO is decreased in proportion to the severity of emphysema.
Lung mechanics and gas exchange worsen during acute exacerbations.
As many as 30% of patients have an increase in FEV1 of 15% or more after inhalation of a bronchodilator. The absence of bronchodilator response does not justify withholding bronchodilator therapy. Studies have shown that most patients with emphysema and COPD will have a small but significant degree of reversibility of airflow obstruction (defined as 12% and at least 200 mL improvement in the FEV1).
Note the images below.


Staging
The FEV1 is used to stage the severity of COPD. It is normalized as a percentage of predicted for healthy controls. The following Global Initiative for Chronic Obstructive Lung Disease staging system is widely used (note that the postbronchodilator FEV1 is used) [2] :
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Stage I (mild) - FEV1 of 80% or more of predicted
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Stage II (moderate) - FEV1 of less than 80% and 50% or more of predicted
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Stage III (severe) - FEV1 less than 50% and 30% or more of predicted
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Stage IV (very severe) - FEV1 less than 30% of predicted or FEV1 less than 50% and chronic respiratory failure
Respiratory failure is defined as a PaO2 less than 60 mm Hg (kPa 8.0) or a PaCO2 higher than 50 mm Hg (kPa 6.7).
The COPD Foundation Pocket Consultant Guide (PCG) uses 5 grades as follows [28] :
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Stage 0 (normal) - Normal spirometry does not rule out emphysema, chronic bronchitis, asthma or risk of developing either exacerbations or COPD
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Stage I (mild) - FEV1 of more than 60% of predicted
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Stage II (moderate) - FEV1 of less than 60% and 30% or more of predicted
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Stage III (severe) - FEV1 less than 30% of predicted
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Stage U (undefined) - FEV1/ FVC ratio more than 0,7, FEV1 less than 80% of predicted. This is consistent with restriction muscle weakness and other pathologies
The PCG 5 grades allow for a normal category as well as an undefined category of reduced lung function without criteria for chronic obstruction. The other 3 categories fit with the 2011 American College of Physicians, American College of Chest Physicians, American Thoracic Society, European Respiratory Society Consensus Statement that identified high levels of evidence to support using an FEV1 < 60% of predicted (moderate COPD) as the cut off for increased risk of exacerbation and an FEV1 < 30% of predicted (severe COPD) as the cut off where hypoxemia is more likely to require continuous oxygen therapy. [29]
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Emphysema. Gross pathology of bullous emphysema shows bullae on the surface of the lungs.
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Emphysema. Gross pathology of emphysema shows bullae on the lung surface.
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Emphysema. At high magnification, loss of airway walls and dilated airspaces are observed in emphysema.
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Emphysema. This chest radiograph shows hyperinflation, flattened diaphragms, increased retrosternal space, and hyperlucency of the lung parenchyma in emphysema.
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Emphysema. A computed tomography scan shows emphysematous bullae in the upper lobes.
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Emphysema. Diffuse emphysema secondary to cigarette smoking.
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Emphysema. A pressure-volume curve is drawn for a patient with restrictive lung disease and obstructive disease and is compared to healthy lungs.
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Emphysema. A flow-volume curve of lungs with emphysema shows a marked decrease in expiratory flows, hyperinflation, and air trapping (patient B) compared to a patient with restrictive lung disease, who has reduced lung volumes and preserved flows (patient A).
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Emphysema. Forced expiratory volume in 1 second (FEV1) can be used to evaluate the prognosis in patients with emphysema. The benefit of smoking cessation is shown here because the deterioration in lung function parallels that of a nonsmoker, even in late stages of the disease.
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Emphysema. A computed tomograph scan showing severe emphysema and bullous disease.
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Emphysema. An emphysematous lung shows an increased anteroposterior (AP) diameter, increased retrosternal airspace, and flattened diaphragms on posteroanterior (PA) film.
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Emphysema. An emphysematous lung shows an increased anteroposterior (AP) diameter, increased retrosternal airspace, and flattened diaphragms on a lateral chest radiograph.
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Emphysema. The differential diagnosis of a unilateral hyperlucent lung includes pulmonary arterial hypoplasia and Swyer-James syndrome. The expiratory chest radiograph exhibits evidence of air trapping and is helpful in making the diagnosis. Swyer-James syndrome is unilateral bronchiolitis obliterans, which develops during early childhood.
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Emphysema. A lateral chest radiograph of Swyer-James syndrome may demonstrate some of the features of emphysema.
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Emphysema. Paraseptal emphysema. Courtesy of Dr Frank Gaillard, Radiopaedia.org (http://radiopaedia.org/cases/emphysema-diagrams).
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Emphysema. Panlobular emphysema. Courtesy of Dr Frank Gaillard, Radiopaedia.org (http://radiopaedia.org/cases/emphysema-diagrams).
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Emphysema. Centrilobular emphysema. Courtesy of Dr Frank Gaillard, Radiopaedia.org (http://radiopaedia.org/cases/emphysema-diagrams).
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Emphysema. Early stethoscope drawing circa 1819. From Wikipedia.
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Emphysema. Laennec's early stethoscope made of brass and wood circa 1820. From Wikipedia.