Spirometry

Spirometry is the most common technique used to assess pulmonary function. It is helpful to understand several key elements of spirometric assessment before discussing the role of this test in patient care. First, values obtained by spirometry are reported as absolute volume and, more importantly, in reference to that predicted for normal lung function based on the age, sex, height and race or ethnicity of the patient. Therefore, it is critical that these demographic factors are correctly noted and used. If spirometry test results are unexpectedly higher or lower than suggested by the history and examination, one is wise to double-check the accuracy of these demographic data. Second, the quality of both patient technique and effort will greatly affect spirometry data. Studies suggest that many tests performed in routine outpatient clinics are of suboptimal quality but that limited staff training can significantly improve this. Most children can learn to perform spirometry tests with reasonable quality by the age of 5 to 7 years. Third, those interpreting spirometry tests should be properly trained. Physicians should be familiar with useful quality criteria that have been published by the American Thoracic Society/European Respiratory Society (ATS/ERS), including forced expiratory time, repeatability and back extrapolated volume. However, data suggest that the clinical utility of spirometry data in children may depend more on the experience of the interpreter than on rigid numerical test parameters. In other words, pediatric spirometry test results that do not meet published numerical quality standards are often still useful – especially when considered in the context of an individual patient.

Providers should also be aware of important efforts to improve spirometry interpretation. A notable international collaboration has recently produced the largest reference data set for spirometry to date. The Global Lung Function Initiative (GLI) reference equations include over 74,000 spirometric measurements from healthy, nonsmoking males and females aged 3 to 95 years, provided by over 70 organizations worldwide. This includes spirometric indices from five ethnic groups and over 30,000 healthy young people between 2.5 and 18 years old. Using modern statistical techniques, these data have been used to generate the Quanjer GLI-2012 prediction equations, endorsed by all major respiratory societies and incorporated by manufacturers into many lung function devices. Ongoing efforts will contribute even greater representation of ethnic backgrounds into this reference data set, providing more reliable normal values across age and demographic characteristics. Also, many providers have moved to reporting data as Z-scores rather than percent predicted of normal. A Z-score of −1.64 represents the 5 ^th percentile and has been proposed as a lower limit of normal for spirometry. Ninety-five percent of healthy subjects will fall within ± 2 Z-scores. Interpretation by lower limit of normal using Z-score is independent of age, height, sex and ethnic group, and may more clearly show how abnormal (i.e. far from the median) an individual’s lung function is at the time of testing. Similar prevalence rates for impaired FEV ₁ /FVC ratio and FEV ₁ have been reported when transitioning from the familiar Hankinson and Wang equations to the GLI-2012.

A

Airflow Limitation

The usual method of measuring the degree of airflow limitation is to assess lung function during a maximal forced exhalation. The subject exhales forcibly from total lung capacity (TLC) to residual volume (RV) into either a spirometer or through a flow meter by which flow is integrated to give volume. The results are usually expressed as either a time-based recording of expired volume (spirogram) or a plot of instantaneous airflow against lung volume (maximal expiratory flow-volume [MEFV] curve). The tests of lung function derived from a spirogram are the forced vital capacity (FVC; TLC minus RV), the forced expiratory volume during the first second of exhalation (FEV ₁ ), and the forced expiratory flow from 25% to 75% of the FVC (FEF _25–75 ). From the flow-volume curve, the maximal expiratory flow rate (MEFR) achieved approximates the peak expiratory flow rate (PEFR) obtained from a flow meter. Flow rates at and below 50% of the vital capacity (VC) are also obtained as part of this maneuver. Because airflow is related to lung volume, plethysmography combined with the MEFV maneuver plotted as a flow-volume curve or loop allows assessment of the relationship between airflow and absolute lung volumes ( Figure 30-1 ). Measurement of flow rates in this manner may be informative when an isovolumetric shift occurs (discussed later). The effect of lung volume on airflow also highlights the importance of subject effort and technique.

Maximal inspiratory and expiratory curves that together constitute a flow-volume loop are shown in a patient with asthma when the disease is under control (left loop) and when control is lost (right loop). Flow is shown on the y-axis, whereas absolute lung volume is displayed on the x-axis. The point of maximal inspiration (TLC) is the point of zero flow on the left side of the loops while the point of maximal expiration (RV) is the point of zero flow at the right side of the loops. When asthma control is lost, hyperinflation is noted, with an increase in RV. In addition, expiratory flow rates decrease, as demonstrated in the maximal expiratory portion of the curve, which becomes concave. With milder instability, as shown in this example, the inspiratory portion of the loop is fairly well preserved. With more severe obstruction, inspiratory flows will be more compromised.

(From Wenzel SE, Larsen GL. Assessment of lung function: pulmonary function testing. In: Bierman CW, Pearlman DS, Shapiro GS, Busse WW, editors. Allergy, asthma, and immunology from infancy to adulthood. 3rd ed. Philadelphia: WB Saunders; 1996.)

In subjects with airflow obstruction due to asthma, the expected pattern of altered flow rates during an exacerbation can be predicted based on airway pathology and obstructive physiology. On spirometry, both the FEV ₁ and FEF _25–75 are diminished, although the former is more preserved as a percent of predicted than the latter. Since the FVC is usually relatively preserved, the FEV ₁ /FVC ratio is reduced. On the MEFV curve, the expiratory portion of the loop typically becomes concave, or ‘scooped out’ (see Figure 30-1 ) due to a greater impairment in flows at low lung volumes. These flows are the first to decrease and the last to return to normal. The MEFR, like its counterpart, the FEV ₁ , is more preserved during acute attacks and is quicker to normalize.

In a minority of cases, the spirogram or MEFV curve alone will not reflect significant airway obstruction. However, if subjects are studied with both an MEFV maneuver and plethysmography to assess lung volumes, they will have a displacement of the flow-volume curve to a higher lung volume without a change in the configuration of the curve itself. Thus, if flow is measured as a percent of the VC, no change in flow is appreciated. However, when the same curve is plotted as a function of the absolute lung volumes present before and after onset of symptoms, substantial changes in flow become apparent at the same lung volume, that is, at an isovolume. This represents an isovolumetric shift to a higher lung volume. The factors responsible for isovolumetric shifts are poorly defined but may include closure of some airways with loss of the contribution of these more obstructed units to the flow-volume pattern.

In acute asthma, loss of symptoms and signs of asthma does not mean that lung function has returned to normal. Classic studies by McFadden and colleagues demonstrated that when patients with severe, acute asthma became asymptomatic, the overall mechanical function of their lungs in terms of the FEV ₁ was still only 40% to 50% of predicted normal values. Thus loss of clinical signs of airway obstruction does not necessarily mean there has been physiologic recovery. This highlights the important role of measuring lung function when managing patients with asthma, especially those prone to severe airflow obstruction or those who have difficulty appreciating decline in lung function.

The use of peak flow meters within the home is an inexpensive method of monitoring a flow rate to assess asthma stability. Although there are limitations, in that the PEFR may be normal while other spirometric indices are abnormal, home monitoring of lung function can contribute to the care of selected patients. In this respect, significant changes in PEFR may be manifest before symptoms are evident, particularly in patients with limited recognition of early disease exacerbation. These devices may also be especially helpful in defining the presence and severity of nocturnal asthma. The diurnal variation of PEFR (i.e. the difference between morning and evening measurements) is normally less than 10%. A PEFR variability of greater than 15% to 20% has been used as one defining feature of nocturnal asthma. Patients with such variability should be regarded as having more severe asthma and inadequate disease control. Additionally, given that excessive diurnal variations in lung function during recovery from status asthmaticus have been associated with an increased risk of sudden death, this vulnerable period of time may warrant close monitoring both in the hospital and home environment. Therefore, in more severe patients or those with limited recognition of signs and symptoms of exacerbation, monitoring the PEFR as part of their daily routine may allow for earlier recognition of loss of control with more timely intervention. Finally, it should be noted that the PEFR maneuver is technique- and effort-dependent with most home meters. This should be considered in younger patients and those who may have secondary gain with asthma-related illness.

B

Heightened Airway Responsiveness

Airway responsiveness is commonly defined as the ease with which airways narrow in response to various nonallergic and nonsensitizing stimuli, including inhaled pharmacologic agents (e.g. histamine, methacholine, mannitol) as well as natural physical stimuli (e.g. exercise, exposure to cold air). Heightened airway responsiveness to several stimuli causing bronchoconstriction and reduced airflow is a hallmark of asthma. Even when conventional assessments of lung function are normal in children with chronic stable asthma, the airways often exhibit this heightened responsiveness. The most common method of quantifying airway responsiveness is to assess lung function (usually FEV ₁ ) before and after inhaling increasing concentrations of methacholine. The test is concluded when a defined decrease in lung function has been achieved; for the FEV ₁ , this is usually a 20% decrease from baseline values. The more responsive the airways, the less methacholine is needed to decrease lung function. Exercise often increases FEV ₁ in healthy patients, therefore a decrease of as little as 10% from baseline may reflect exercise-induced bronchoconstriction.

The level of airway responsiveness to pharmacologic agents has been noted to correlate roughly with the severity of disease in both adults and children. Thus asthmatic subjects who are the most responsive are generally the most symptomatic (wheeze, cough, chest tightness) and require more medications to control their disease. Although there can be great variability in responsiveness within groups of patients classified by disease severity, the concept that the level of responsiveness correlates with disease severity is important when considering factors that lead to loss of asthma control. In this respect, the level of airway responsiveness is not static in either normal individuals or asthmatic subjects but may increase or decrease in response to various stimuli. When responsiveness increases, control of the disease is often lost in that this is when asthmatic subjects develop signs and symptoms of their disease. In general, stimuli that increase responsiveness are found in our environment and induce or exacerbate airway inflammation. For children, these stimuli commonly include various viral respiratory infections, air pollutants (including cigarette smoke) and allergens.

A viral respiratory infection is a common antecedent to acute episodes of asthma in children. This has been documented for several respiratory viruses, including respiratory syncytial virus and rhinovirus. In terms of air pollutants, both nitrogen dioxide and ozone have been shown to enhance airway responsiveness. Cigarette smoke is arguably the most serious environmental air pollutant in terms of the respiratory health of children and has been implicated in the onset as well as the perpetuation of the disease. In addition, exposure of atopic individuals to relevant allergens can lead to significant increases in airway responsiveness that persist for days to months. These classes of disease precipitants are often considered separately, but they assuredly have combined effects in an asthmatic subject’s airways which contribute to disease instability.

Just as airway responsiveness will increase in response to certain stimuli that lead to airway inflammation, the level of responsiveness will also decrease if measures are taken to decrease inflammation within airways. These measures include use of medications with anti-inflammatory properties (e.g. inhaled corticosteroids), long-acting bronchodilators and the avoidance of relevant allergens (atopic asthmatic subjects) and cigarette smoke.

C

Improved Airflow in Response to Bronchodilators

Increased pulmonary function, often measured by FEV ₁ or FEV _25–75 and in response to short-acting bronchodilators such as inhaled β-agonists, is another defining feature of asthma. An increase in FEV ₁ by 12% predicted or more is often used to define a significant response to bronchodilator medication. Greater improvement in FEF _25–75 is typically required (e.g. 25% predicted) and this more variable parameter is not used by all centers to determine response to bronchodilators. When testing response to other forms of inhaled bronchodilators it is important to understand the pharmacokinetics and predicted time needed for a medication to take effect.

Lung Volumes

During an exacerbation of asthma, all of the various capacities and volumes of gas contained in the lung may be altered to some extent. The RV, functional residual capacity (FRC) and TLC are usually increased (RV > FRC > TLC), whereas the VC and its subdivisions are decreased (see Figure 30-1 ). These alterations have been described during natural exacerbation of asthma in adults and children. Although laboratory induced changes in lung volumes (exercise, histamine challenge) may be immediately normalized with inhalation of a bronchodilator, it may take weeks after an episode of severe, acute asthma for the RV to return to a normal range. The mechanisms responsible for the increases in RV, FRC (hyperinflation) and TLC (overdistension) are not completely understood. However, several factors have been identified that may contribute, including a generalized decrease in the elastic properties of the lung, a ball-valve phenomenon caused by swollen and mucus-plugged airways, and tonic activity in the intercostal muscles and diaphragm during episodes of obstruction.

Arterial Blood Gases

The primary function of the lung is to provide for gas exchange such that oxygen is taken up and delivered to the body while carbon dioxide is eliminated. This function may be altered when control of asthma is lost. Several studies of acute asthma have correlated arterial blood gases with the level of airway obstruction. One of the classic descriptions is the work of McFadden and Lyons. These authors studied a large population (101 subjects) who, because of age (14 to 45 years) and medical history, were unlikely to have their asthma complicated by bronchitis and emphysema. This study and others (cited later) provide an important description of the expected abnormalities in gas exchange as a function of the degree of airway obstruction.

Oxygen Tension

McFadden and Lyons found that the characteristic blood gas pattern in patients who were experiencing acute asthma was hypoxemia associated with respiratory alkalosis. The hypoxemia was the most consistent abnormality found in their study. A near linear correlation was found between values of FEV ₁ and arterial oxygen tension ( Figure 30-2, top ). Patients with an FEV ₁ of 50% to 85% of their predicted normal values were arbitrarily classified as having mild airway obstruction; those with values of 26% to 50%, moderate obstruction; and those with values of less than 25%, severe obstruction. The mean values of arterial oxygen tension (in mm Hg as measured at sea level) ranked by disease severity were 82.8, 71.3 and 63.1, respectively. Thus there was almost a 20-mm Hg difference in arterial oxygen tensions between the mild and severe groups. Just as important, it was also noted that some degree of hypoxemia was encountered at all levels of airway obstruction. In terms of studies in children, Weng and colleagues noted similar findings in asthmatic subjects who were 14 months to 14 years old. The study found that all symptomatic asthma patients were hypoxemic, with the level of hypoxemia correlating with the degree of airflow obstruction.

The relationship between arterial oxygen (mm Hg) and degree of airway obstruction (FEV ₁ as a percent of predicted) (top) and the relationship between arterial carbon dioxide (mm Hg) and FEV ₁ (bottom). Although the level of hypoxemia correlates with the level of airway obstruction, an elevation in carbon dioxide levels is seen only when the FEV ₁ is markedly compromised.

(Data from McFadden ER Jr, Lyons HA. N Engl J Med 1968;278:1027–32.)

Several mechanisms are likely to contribute to the hypoxemia just described. The primary mechanism is thought to be an alteration in ventilation-perfusion ratios. For severely obstructed subjects, in whom atelectatic alveoli are still being perfused, transitory anatomic shunts may also contribute to the hypoxemia. In the most severely obstructed subjects, alveolar hypoventilation is also likely to be important.

The normal response of the body to a decrease in arterial oxygen is to increase ventilation. A reduced chemosensitivity to hypoxia coupled with a blunted perception of dyspnea may predispose patients to fatal asthma attacks. Kikuchi and colleagues found that adult patients with a history of near-fatal asthma had respiratory responses to hypoxia that were significantly lower than responses in normal subjects and in asthmatic subjects without near-fatal attacks. The lower hypoxic response was seen in conjunction with a blunted perception of dyspnea. These abnormalities could occur because of preexisting genetic factors as well as adaptation of the body to recurrent hypoxia. The relative importance of these and other factors is unknown. Children with poor perception of airway obstruction may be at risk for fatal or near-fatal asthma.