Which of the following pulmonary function tests would best determine the patients ability to cough?

Major Patterns on Pulmonary Function Tests

Pulmonary function test results can be classified into the following major patterns: normal, obstructive ventilatory defect, restrictive ventilatory defect, mixed pattern (when lung volumes are available) or a pattern that is not clearly obstructive or restrictive (when lung volumes are not available), and a nonspecific pattern (Fig. 32.1). Patient effort and cooperation are essential for acquiring valid spirometry; hence spirometry efforts should be assessed for quality before interpretation. TheAmerican Thoracic Society (ATS) andEuropean Respiratory Society (ERS) guidelines recommend that at least three acceptable spirograms should be obtained.1,2 Testing should be repeated until the two largestforced vital capacity (FVC) measurements and the two largestforced expiratory volume in 1 second (FEV1) measurements from acceptable spirograms are within 150 mL of each other, or, if this is not achieved, until a practical upper limit of eight efforts have been made.1,2 Failure to meet acceptability criteria should be noted in the report and considered when interpreting results.

Reference Equations and Limits of Normality

Unlike many laboratory tests, lung function parameters vary greatly with body size and age, so the expected values must be determined on an individual basis. Numerous prediction equations have been derived from spirometric surveys of normal reference populations. Currently accepted studies exclude all smokers as well as persons who have any thoracic or cardiopulmonary disease. Most studies have found that lung function parameters can be predicted on the basis of gender, age, and height, and that the addition of other body size measurements does not improve the accuracy of the equations. The prediction equations give the midpoint of the normal range, which is unfortunately wide for most spirometry measurements.

The lower limit of normal (LLN) must be established from the variability among individual subjects who have the same prediction parameters. The limits of the normal range are chosen to exclude 5% of a normal population; that is, 5% will be misclassified as having disease. In screening a generally healthy population for a rare disease, a borderline-low result is more likely to reflect this misclassification than to represent true identification of disease. However, when spirometry is done for persons at risk for lung disease, or with suggestive symptoms, the probability that a borderline result reflects a true abnormality is much higher. For the spirometry measurements, only low values are considered of concern, so the LLN is set at the 5th percentile of the reference sample. Because the distribution of values in the reference population is adequately symmetric above and below the mean, the 5th percentile LLN often is taken as the predicted value minus 1.645 times the standard error of the estimate (SEE) of the regression equation. The predicted value and the LLN both are readily calculated from the reference data programmed into the spirometry equipment, and both should be reported for comparison against the actual measured value.

Spirometry reference data from a large, systematic survey of the U.S. population (the Third National Health and Nutrition Examination Survey [NHANES III]) are recommended for use in North America. Equations are provided for Caucasians, African Americans, and Mexican Americans ranging in age from 8 to 80 years. No single reference source currently is recommended for use in Europe, but an international effort is under way to merge the NHANES data with those for many reference populations from throughout Europe and elsewhere, to generate a new, widely applicable reference dataset.

The use of a percentage of the predicted value as a lower limit is convenient but less accurate than the 5th percentile, because it causes the normal range to vary with the magnitude of the predicted value, whereas the true variance is similar around small and large values. A lower limit value equal to 80% of the predicted value has been widely used in spirometric interpretation. Although this is a reasonable approximation of the LLN for FEV1 and FVC at the midrange of age and height, it creates an overly broad normal range for younger, taller persons (in whom the true LLN is approximately 82% to 83%), and it is overly sensitive for older or smaller subjects (in whom the LLN may be as low as 73% to 75%). An 80% lower limit is quite inappropriate for FEF25–75, because the normal range extends to 65% of the predicted value in the young and below 50% of predicted in older persons. The normal value for FEV1/FVC varies little with height but does decline progressively with age (e.g., from 0.87 at age 20 to 0.77 at age 70 in females, and from 0.84 to 0.74 in males). The LNN is approximately 0.10 below the predicted ratio. Because the ratio often is expressed as a percentage, reporting this value as a percent of the predicted value is potentially confusing.

Definition

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Lung function tests (Table E1) measure a person’s ventilatory capacity in comparison with that of normal subjects. By adjusting for sex, height, ethnicity, and age, the values for a given individual can be compared with those from otherwise normal individuals.

Basic tests for preliminary assessment and for monitoring disease progression include spirometry, which is a record of exhaled volume versus time during a forced exhalation (with or without determination of the response to an inhaled bronchodilator for possible reversible airflow); diffusion capacity, which measures the transfer of carbon monoxide to indicate how well inspired gases cross the alveolar-interstitial-capillary endothelial interface into blood; and noninvasive pulse oximetry, for oxygen saturation measured at rest or during ambulation.

Pulmonary function tests (PFTs) performed after graduated exercise on a treadmill or a timed walking test on a level surface provide a more dynamic assessment of pulmonary function and correlate well with prognosis in patients with chronic pulmonary conditions such as lung fibrosis and chronic obstructive disease.

More specialized tests include body plethysmography to determine total lung volumes and airway resistance as well as maximal cardiopulmonary exercise testing to assess cardiac function and oxygen uptake and consumption. The clinical utility of these tests can be appreciated by understanding how they can be applied to representative types of patients1 (Table E2).

Lung volume: The volume of air in the lung at any given time can be partitioned (Fig. E1). The air that remains in the lung after a maximal expiratory effort is the residual volume. The amount of air in the lungs at the relaxation point, when muscle effort is minimized and the inward recoil of the lung is balanced by the outward recoil of the chest wall, is the functional residual capacity (FRC). The difference between FRC and residual volume is the expiratory reserve volume. The volume exhaled in a normal breath is the tidal volume. The volume that can be inhaled above tidal volume is the inspiratory reserve volume.1

Maximal voluntary ventilation (MVV) is an indication of the maximal ventilation a patient can perform, expressed in liters per minute. MVV estimates a person’s upper limit of ventilatory capacity. Reductions in MVV may be due to inspiratory obstruction, muscle weakness, or poor performance. Because MVV is effort dependent, it may be a better predictor of postoperative respiratory complications than is FEV1.

TABLE E1. Alveolar Filling Disorders

CT, Computed tomography;GM-CSF, granulocyte-macrophage colony-stimulating factor.

From Goldman L, Schafer AI:Goldman-Cecil medicine, ed 26, Philadelphia, 2019, Elsevier.

TABLE E2. Common Changes Associated with Patterns of Lung Function Abnormality

From Goldman L, Schafer AI:Goldman-Cecil medicine, ed 26, Philadelphia, 2019, Elsevier.

Enzyme Replacement Therapy

Enzyme replacement therapy is based on the principle that the patient, by regular intravenous infusion, receives the enzyme that is missing. The enzyme for Hunter syndrome (idursulfase) is produced in a continuous human cell line by recombinant gene technology. Based on the encouraging results of animal experiments, clinical trials were initiated in patients with Hunter syndrome. After several months of treatment, a significant reduction in urinary glycosaminoglycan excretion, and a decrease in liver and spleen volumes were observed. In addition, enzyme replacement therapy leads to an improvement in the 6-min walk test, lung function, left ventricular mass, and joint range of motion. In 2006, idursulfase was approved for enzyme replacement therapy for patients affected by Hunter syndrome. It is administered intravenously at a dose of 0.5 mg kg−1 body weight every week. Data from an international Hunter registry, the Hunter Outcome Survey (HOS), have shown that the clinically meaningful benefits seen during the clinical trials such as increased 6-min walk test, improvement of lung function, and shoulder range of motion were sustained. Enzyme replacement therapy, however, has some limitations and is not able to treat all aspects of the disorders to the same degree. Several organs such as cartilage, bone, and heart valve do not respond to this treatment. Additionally, many symptoms of Hunter syndrome are no more reversible even after long-term treatment. And as intravenously applied enzyme cannot pass the blood–brain barrier, it does not have any influence on the manifestation of the central nervous system.

Treatment with idursulfase is generally well tolerated, and, in general, adverse events such as fever, headache, cough, respiratory tract infections, and diarrhea are consistent with complications that are expected to be seen in untreated patients with Hunter syndrome. Most of the infusion-related adverse events are mild or moderate in severity and are seen between weeks 4 and 12 of treatment. In summary, idursulfase shows a risk–benefit profile that is similar to that reported for other replacement therapies.

Special Tests and Considerations in Pediatric Pulmonary Function Testing

It is important to realize that pulmonary physiology in children does not simply reflect a smaller version of pulmonary physiology in adults. In particular, the airways, lung parenchyma and chest wall continue to grow and develop until the early to mid-20s. In accordance, lung function varies over this time period in a way not predicted by lung function in adults. The best example of this is consideration of the FEV1/FVC ratio. The normal lower limit in young children is substantially higher than that in adults, and particularly higher than the fixed cut-off ratio of 0.7 advocated by the Global Initiative for Chronic Obstructive Lung Disease guidelines. The main reason for this is the enhanced elastic recoil of the lung at younger age.

Common clinical pulmonary function testing with spirometry may be performed in children as young as 3 to 5 years. Because of their increased lung recoil and smaller lung volume, children may reach an end-of-test criterion sooner than adults, and FEV less than 1 second may be more clinically significant, such as FEV0.75. However, both the FEV0.75 and the popular FEF25%–75% have been shown to be no more useful in general than the FEV1/FVC ratio for diagnosing obstruction in both children and adults.234 Similarly, bronchodilator responsiveness may be significant at 10% change in FEV1. The Global Lung Function Initiative reference equations have been published for children as young as 3 years of age.

Other tests of respiratory mechanics performed in children include the forced oscillatory technique and measurement of respiratory resistance by the interrupter technique. Both of these methods have been discussed previously and may be useful in children with asthma, CF, or bronchopulmonary dysplasia.235 Another test commonly performed in children is the MBNW, primarily to measure FRC and lung volumes, and also LCI as a measure of ventilation heterogeneity. The LCI has become popular as a measurement in children with CF as it appears more sensitive than spirometry to detection of early bronchiectasis.

There are a few highly specialized lung function tests that are performed in infants.236 One is the use of forced deflation to assess for obstruction by means of the rapid thoracic compression technique. This is performed by rapidly inflating a rubber bladder that surrounds the chest of the sedated infant when lung volume is close to FRC. A modification of this technique is also used, called the raised volume rapid thoracic compression technique, where the infant’s lung is first inflated to close to TLC before rapid compression. Lung volumes in infants may be measured by gas dilution or body plethysmography. Lung mechanics can be assessed during muscle relaxation after the induction of the Hering-Breuer reflex to elicit a brief apnea. During this apneic period, the passive deflation pressure and flow at the mouth is recorded to calculate respiratory system compliance. Ventilation heterogeneity can be measured in infants using tidal breathing of an inert gas rather than 100% oxygen as is used in the MBNW technique. Predicted values for all of these methods in infants are limited, but the methods are used in specialized centers to evaluate infants with chronic lung disease or unexplained symptoms and signs of respiratory illness.237

4.2 Metabolic profiling of asthma patients based on different clinical parameters

Another study investigated the possible link between oxidative stress and clinical characteristics of asthma, such as lung function, eosinophilia as a marker of inflammation and disease severity [26]. Targeted urinary metabolomic analysis was performed using aliphatic aldehydes and alkanes as targets, by solid-phase microextraction (SPME) followed by a high-resolution GC-TOF-MS on 57 asthmatic patients (mean age 45 years), including 17 obese. Concerning the clinical characteristics, disease severity was assessed with severity scores (severity of asthma score (SOA)) and control scores (asthma control test (ACT), lung function was measured with (FEV1 (%), FEV25–75 (%)), and eosinophilia measured by FeNO, percentage of eosinophils in the blood (%), and serum levels of IgE (log UI)). The analysis was performed, including 34 aliphatic alkanes and aldehydes, to correlate urinary metabolomic profile of lipid peroxidation with the clinical characteristics, excluding obese patients as obesity is a possible confounder for asthma severity and oxidative stress. Based on the results, significant models were obtained for SOA, FEV1, FeNO, blood eosinophils, and serum IgE, suggesting that there is a correlation between metabolic profiles and clinical characteristics of asthma that could be used in the diagnosis and personalized treatment.

Another very recent study aimed to correlate the levels of urinary organic acids with measurements from pulmonary diagnostic tests in a population of Greek children with asthma [51]. Seventy-two asthmatic children (5–12 years old) were included in the study. Spirometry and exhaled nitric oxide analysis (eNO) were used to assess pulmonary function, and results from the Asthma Control Questionnaire were evaluated to evaluate asthma control. Targeted metabolomic analysis using GC–MS methodology in 34 single metabolites showed that lactic acid (P = 0.03) and asthma control (P = 0.02) were statistically significantly different between the two sexes. Some of the statistically significant correlations found, included the ones between lactic acid and FEV1-FVC, 4- hydroxyphenylacetic acid and FEV1-FVC, 5-hydroxyindoleacetic acid and FEV1/FVC-FeNO, as well as glycolic acid with Peak Expiratory Flow (PEF) and malic acid with asthma control. Thus, the associated metabolites with the conventional clinical measurements can be potential biomarkers, and further validation studies will indicate their potential application in early diagnosis and targeted treatment of asthma.

Preoperative Evaluation

A detailed preoperative airway evaluation is crucial for tubeless anesthetic thoracic surgery. The anesthesiologist should review the patient medical history and symptoms and carefully evaluate any underlying respiratory diseases, which may put the patient at risk or jeopardize the procedure.4 In addition to the preoperative evaluation, pulmonary and cardiac function tests are indispensable in patients with hypersensitivity syndrome, asthma, chronic obstructive pulmonary disease (COPD) or a long-term smoking history. A bronchodilator challenge is recommended, depending on the patient medical history and his current medication. Furthermore, these underlying diseases should be evaluated preoperatively as a team approach in collaboration with the surgeon and the pulmonologists. The patients with poorly controlled respiratory diseases or pulmonary infection, including AECOPD (acute exacerbated COPD), should have a preoperative adequate antibiotics regime and surgery should be postponed until the therapy is completed. When tracheal or laryngeal surgeries are planned, characteristic signs and symptoms including stridor, hoarseness, and shortness of breath should raise a red flag as they usually indicate the presence of upper respiratory tract obstruction.5–8 A preoperative communication between anesthesiologists and surgeons is necessary for a smooth and safe procedure.

Patients with a high body mass index (BMI) are not candidates for tubeless anesthesia because these patients have high oxygen consumption and carbon dioxide production owing to the high metabolic activity of body, tissue, and an increase in respiration work.9–11 An increased intraabdominal pressure decreases the compliance of the thoracic cavity and restricts lung expansion. Moreover, excessive adipose tissue in the pharyngolaryngeal area would cause upper airway obstruction and hypoventilation usually associated with sleep apnea. Most importantly, if indicated, they may be difficult to intubate in an emergency during the procedure. Therefore patients with a higher BMI should have an extensive evaluation and if the procedure is not urgent, they should be encouraged to lose weight.12–14 The criteria for patient selection for tubeless procedures are depicted in Box 37.1. Most importantly the patient should not have a difficult airway if the tubeless procedure needs to be converted to general anesthesia with an endotracheal tube.

In case of emergency during the surgical procedure, a difficult airway cart should be immediately available. The cart should contain topical anesthetic medications, video laryngoscopy (Fig. 37.1A) and angulated video-bronchoscopy with all sizes of endotracheal tubes, including nasal Ring-Adair-Elwyn (RAE), oral RAE, microlaryngeal tube, flexometallic tubes and DLTs.7,14