Obstructive lung disease implies a reduced capacity to get air through the conducting airways and out of the lungs. This reduction in airflow may be caused by a decrease in the diameter of the airways (bronchospasm), a loss of their integrity (bronchomalacia/bronchiectasis), or a reduction in elastic recoil (emphysema) with a resulting decrease in driving pressure. The most common diseases associated with obstructive pulmonary functions are asthma, emphysema, and chronic bronchitis; however, bronchiectasis, infiltration of the bronchial wall by tumor or granuloma, aspiration of a foreign body, and bronchiolitis also cause obstructive PFTs. The standard test used to evaluate airway obstruction is the spirometry.
Standard spirometry and flow–volume loop measurements include many variables; however, according to ATS guidelines, the diagnosis of obstructive and restrictive ventilatory defects should be made using the basic measurements of spirometry.4,6 A reduction in FEV1 (with normal FVC) establishes the diagnosis of obstruction. In restrictive lung disease, the patient has an inability to get air into the lung, which results in a reduction of all expiratory volumes (FEV1, FVC, and SVC). In obstructed patients, a better measurement is the ratio FEV1/FVC. Patients with restrictive lung disease have reduced FEV1 and reduced FVC, but FEV1/FVC remains normal. Although a normal FEV1/FVC ratio is greater than 75% to 80% (0.75-0.80), the ratio is age-dependent, and slightly lower values may be normal in older patients. Younger children have increased lung elastic recoil and may have higher ratios. Children should have a FEV1/FVC greater than or equal to 90% (0.90). According to the 2018 National Asthma Education and Prevention Program and the most recent Global Imitative for Asthma (GINA) guidelines any value below this value should be considered a sign of obstruction, even if the FEV1 and FVC are within the normal range.2 Caution should be used in interpreting obstruction when FEV1/FVC is below normal, but both FEV1 and FVC are within the normal range, because this pattern can be seen with healthy, athletic subjects as well as subjects with mild asthma. Clinical judgment and response to bronchodilator challenge are often required to separate out these two groups. In children, the improvement in FEV1 often is the only way to document mild-to-moderate obstructive lung disease.
In screening spirometry performed in office practice, forced expiratory volume in 6 seconds (FEV6) can be used in place of FVC. FEV6 is a more reproducible number when obtained by less skilled personnel. The measurement of FEF25%-75% also is abnormal in patients with obstructive airways disease. This test has so much variability that it adds little to the measurement of FEV1 and FEV1/FVC.
Although there is no standardization for interpretation of severity of obstruction, most pulmonary laboratories state that FEV1/FVC less than 70% (0.70) of the predicted value is diagnostic for obstruction, and the degree of obstruction then is based on the percent predicted of FEV1. FEV1 between 80% and 100% of the predicted value is a mild obstruction, 79% and 50% of the predicted value is a moderate obstruction, between 49% and 30% is consistent with severe obstruction and less than 30% of the predicted value is classified as very severe obstruction.18 In patients with obstruction, a dose of a bronchodilator (eg, albuterol or isoproterenol) by metered-dose inhaler is given during the initial examination. An increase in FEV1 of greater than 12% and greater than 0.2 L suggests an acute bronchodilator response.4,6 It is important to remember that bronchodilator responsiveness is variable over time and therefore the lack of an acute bronchodilator response should not preclude a short trial of albuterol and/or corticosteroids.
Although all patients with obstructive lung disease of any etiology will have reduced flow rates on forced exhalation, the pattern on PFTs may be helpful in differentiating among the various etiologies (Table e42-3). Asthma is characterized by variable obstruction that often improves or resolves with appropriate therapy. Because asthma is an inflammatory disorder of the airways (predominantly () large airways), DLCO is usually normal or even slightly above the normal range. Most patients with acute asthma have a bronchodilator response greater than 15% to 20%; chronic bronchitis may be limited to the airways, but the vast majority of patients with chronic bronchitis and airway obstruction have a mixture of bronchitis and emphysema and have a reduction in DLCO. Therefore, DLCO is the best PFT for separating asthma from COPD.
TABLE e42-3Specific Patterns of Pulmonary Function in Patients with Chronic Obstructive Pulmonary Disease |Favorite Table|Download (.pdf) TABLE e42-3 Specific Patterns of Pulmonary Function in Patients with Chronic Obstructive Pulmonary Disease
| ||COPD |
| ||Asthma ||Chronic Bronchitis ||Emphysema |
|Decreased FEV1 ||++++ ||++++ ||++++ |
|Decreased FEV1/FVC ||++++ ||++++ ||++++ |
|Increased airway resistance ||++++ ||++++ ||+ |
|Decreased DLCO ||– ||–/++a ||++++ |
|Response to bronchodilators ||++++ ||+b ||–b |
A recently described entity Asthma-COPD overlap syndrome (ACOS) encompasses patients with persistent airflow limitation as seen in COPD and several features typically associated with asthma including airway hyperresponsiveness and marked bronchodilator response. After the diagnosis of obstructive airways disease is established, the course and response to therapy are best followed by serial spirometry.
Airway hyperreactivity or hyperresponsiveness is defined as an exaggerated bronchoconstrictor response to physical, chemical, or pharmacologic stimuli. Individuals with asthma, by definition, have hyperresponsive airways. The Lung Health Study Research Group observed nonspecific hyperresponsiveness in a significant number of patients with COPD. This group of patients with airway hyperreactivity appears to have a worse prognosis and an accelerated rate of decline in FEV1.19
Some patients with asthma (especially cough-variant asthma) present with no history of wheezing and normal PFTs. The diagnosis of asthma still can be established by demonstrating hyperresponsiveness to provocative agents. The agents used most widely in clinical practice are methacholine and mannitol. Other agents used for bronchial provocation include distilled water, hypertonic saline, cold air, histamine, and exercise. Medications that can potentially affect the test giving false negative results include β2 agonist (short and long acting), antimuscarinic agents (short and long acting), theophylline and leukotriene receptors antagonists2 (Table e42-4). During a typical methacholine bronchoprovocation test, baseline FEV1 is measured after inhalation of isotonic saline, and then increasing doses of methacholine are given at set intervals. Hyperresponsiveness is defined as a decline in FEV1 greater than or equal to 20% and reversibility of obstruction to bronchodilators. The result can best be expressed as the provocative concentration needed to cause a 20% fall in FEV1 (PC20). A test is considered positive if methacholine demonstrates a PC20 less than or equal to 4 mg/mL or less than 60 to 80 cumulative breath units. The test is considered negative if the PC20 is greater than 16 mg/mL. Values between 4 and 16 are considered borderline.19 The bronchoprovocation tests (methacholine, mannitol test) is contraindicated in severe airway obstruction (FEV1 less than 60% or 1.5 L), uncontrolled hypertension (SBP greater than 200 mm Hg DBP greater than 100 mm Hg), recent myocardial infarction or cerebrovascular accident (in the 3 previous months), known aortic aneurysm and recent eye surgery or intracranial pressure elevation risk.20
TABLE e42-4Recommended Time to Withhold Medication Prior to Bronchoprovocation Study |Favorite Table|Download (.pdf) TABLE e42-4 Recommended Time to Withhold Medication Prior to Bronchoprovocation Study
8 hours- short-acting β2 agonist
12 hours- inhaled corticosteroids
12 hours- short-acting anticholinergics
24 hours- inhaled corticosteroids plus long-acting β2 agonists
24 hours- long-acting β2 agonists
24 hours- theophylline
72 hours- antihistamines
96 hours- leukotriene-receptor antagonists
Mannitol comes in inhaled dry-powder capsules of graduated doses, which makes its administration convenient.21 When using mannitol, a drop in FEV1 greater than or equal to 15% from baseline (0 mg) up to a dose of 635 mg or a 10% reduction in FEV1 between consecutive doses is considered significant and is referred to as provocative dose 15 (PD15). This test is used most frequently to establish a diagnosis of asthma in patients with normal PFTs, but it also may be useful in following patients with occupational asthma, establishing the severity of asthma, and assessing the response to treatment.
Obstruction of airflow by abnormalities in the upper airway often goes undiagnosed or misdiagnosed because of improper interpretation of PFTs. Patients have obstructive physiology and often are misclassified as having asthma or COPD. The shape of the flow–volume loop, which includes inspiratory and expiratory flow–volume curves, and the ratio of forced expiratory and inspiratory flow at 50% of VC (FEF50%/FIF50% greater than 1) may be useful in the diagnosis of upper airway obstruction.4,22
The shape of the flow–volume curve differs depending on whether the obstruction is fixed or variable (Fig. e42-5). Fixed lesions, as in strictures from previous intubations or tracheostomy, cause a uniform caliber of the airway during inspiration and expiration. With variable lesions, the airway caliber changes with changes in intrathoracic pressure. Variable lesions are sub-classified into variable intrathoracic and variable extrathoracic. If the lesion is intrathoracic, as with tumors of the trachea, the negative pressure generated during inspiration opens the obstruction, whereas the positive pressure during expiration worsens the obstruction. If the lesion is a variable extrathoracic obstruction, as with vocal cord dysfunction, the negative pressure within the airways will pull the vocal cord toward the midline and potentiate the obstruction. In this case, there will be a plateau on the inspiratory limb of the flow–volume loop, and FEF50%/FIF50% will be greater than 1. Typical flow–volume curves from upper airway obstruction are shown in Fig. e42-5. While 80% of subjects with vocal cord dysfunction demonstrate the classical variable extrathoracic pattern, 18% present with a pattern of variable intrathoracic obstruction, and 2% present with a pattern of fixed obstruction.
Maximum expiratory flow–volume curves from patients with fixed obstruction, variable extrathoracic obstruction, and variable intrathoracic obstruction. (RV, residual volume; TLC, total lung capacity.)
Restrictive lung disease is defined as an inability to get air into the lungs and to maintain normal lung volumes. Restrictive lung disease reduces all the subdivisions of lung volumes (IRV, TV, ERV, and RV) without reducing airflow. Patients have normal airway resistance and FEV1/FVC greater than 70% (0.70). A combined consensus statement from the ATS and the ERS defines restrictive and obstructive disorders.23
Although restriction could be defined as a reduction in vital capacity (VC or FVC) with normal FEV1/FVC, poor effort also will reduce FVC with normal FEV1/FVC. A reduction in TLC is the most accurate measurement of restrictive lung function. As discussed before, TLC can be measured by various techniques. The gas dilution methods (eg, helium dilution and nitrogen washout) are unable to measure gas trapped in cysts or bullae and may underestimate the true lung volume. Therefore, TLC is best measured by plethysmography. Most restrictive lung diseases are associated with impairment or destruction of the alveolar–capillary membrane; therefore, DLCO is reduced in most patients with restrictive lung disease. The reduction in DLCO may occur prior to a reduction in lung volumes and is used as a marker of early interstitial (restrictive) lung disease. DLCO may be abnormal even with a normal chest x-ray film, and thin-sliced high-resolution computed tomographic scans of the chest (HRCT = 0.625-1.5 mm thickness) or a CT with thin cuts (2-3 mm thickness) may be required to diagnose early interstitial lung disease. Because peribronchiolar inflammation and fibrosis occur in some patients with restrictive parenchymal lung disease, FEF25%-75% may be reduced and fail to respond to bronchodilators.
The severity of restrictive disease has not been standardized; however, many laboratories classify patients with reduced TLC as mild (TLC less 80%-70%), moderate (TLC 69%-60%), or severe (TLC less than or equal to 60%). These definitions are completely arbitrary because a patient with obstructive lung disease may start with TLC above the upper limit of normal (ie, 120%) and subsequently develop restrictive lung disease while maintaining TLC within the normal range. On flow-volume loop, patients with restrictive disease have normal-shaped curves with a reduction in the height and width of the curve because both PEF rate and VC depend on the amount of air within the lung prior to performance of expiratory maneuvers (see Figs. e42-03 and e42-04 D).
Restrictive lung function is caused by increased elastic recoil of the lung parenchyma (interstitial lung disease), respiratory muscle weakness, mechanical restrictions (chest wall deformities), and/or poor effort. Table e42-5 lists common causes of restrictive lung disease.
TABLE e42-5Causes of Restrictive Lung Disease |Favorite Table|Download (.pdf) TABLE e42-5 Causes of Restrictive Lung Disease
|Interstitial lung diseases |
Idiopathic pulmonary fibrosis
Collagen vascular disease
Drug-induced lung disease
Infiltrative lung diseases
Chest wall diseases
Restrictive lung function from parenchymal lung disease usually can be differentiated from processes causing mechanical restriction as a result of chest bellows malfunction (Table e42-6). Restrictive parenchymal diseases are associated with a reduction in VA and an increase in lung elastic recoil. All lung volumes, as well as DLCO, are reduced. Compared to patients with restriction secondary to neuromuscular disease, in patients with interstitial lung disease, the RV/TLC (normally less than or equal to 30%) and measurements of maximal inspiratory pressure (normal = –75 cm H2O [-7.4 kPa] in males, –50 cm H2O [-4.9 kPa] in females) remain normal. In addition, patients exhibit mild resting hypoxemia that worsens with exercise. Monitoring gas exchange during exercise may be the most sensitive test for detecting progression of interstitial lung disease; however, this involves obtaining arterial blood during exercise and DLCO and exercise pulse oximetry is often used in its place.
TABLE e42-6Patterns of Pulmonary Function |Favorite Table|Download (.pdf) TABLE e42-6 Patterns of Pulmonary Function
| ||Obstructive Lung Disease ||Restrictive Lung Disease |
| ||Asthma ||COPD ||Parenchymal Disease ||Chest Bellows Disease |
|FVC ||Nl or I ||Nl or I ||D ||D |
|FEV1 ||D ||D ||D ||D |
|FEV1/FVC ||<70% (0.70) ||<70% (0.70) ||≥75%-80% (0.75-0.80) ||≥75%-80% (0.75-0.80) |
|TLC ||Nl or I ||Nl or I ||D ||D |
|RV/TLC ||Nl or I ||Nl or I ||Nl ||I |
|Airway resistance ||I ||I ||N ||Nl |
|DLCO ||Nl ||D ||D ||Nl |
Mechanical restriction caused by chest bellows malfunction may result from chest wall or skeletal deformity, loss of neuromuscular function, fibrosis of the pleural space, and abdominal overdistension causing upward displacement of the diaphragm, as well as decreased diaphragm movement. The most common pulmonary function pattern seen in these patients is a decrease in TLC and VC with only a slight decrease in RV. RV is maintained in these diseases because lung compliance remains normal. DLCO is normal or only minimally reduced, and DLCO/VA (corrected for VA) is normal. RV/TLC often is increased in patients with restrictive chest bellows disease.