Overview of pulmonary function testing in children

INTRODUCTION — Pulmonary function testing (PFT) in children plays an important role in the evaluation of the child with known or suspected respiratory disease. A basic approach to PFT for the primary care provider is presented here. The goal is to encourage pediatric primary care clinicians to obtain PFT to diagnose and monitor the pathophysiologic aspects of their patients' respiratory conditions, thereby improving management.

Conventional tests that are frequently performed in the evaluation of pediatric respiratory conditions include measurements that identify:

●Airway obstruction

●Restrictive lung, chest wall, and respiratory muscle defects

●Diffusion defects (those that impair diffusion of gas through the alveolar-capillary membrane)

●Respiratory muscle weakness

Measurements of flow and volume are most useful in the office setting. Spirometry, which provides both these measures, requires neither sophisticated technology nor expensive equipment, is easily interpreted, and is reliable when performed correctly. A brief discussion of the technique, clinical applications for and limitations of more sophisticated measurements of lung volume, diffusion capacity, and respiratory muscle function also is provided so that referrals for such testing can be made appropriately.

Readers interested in a more comprehensive review of PFT in children are referred elsewhere [1,2].

Interpretation of arterial blood gas analyses and exhaled nitric oxide, exercise testing, assessment of bronchial hyperresponsiveness, sleep studies, measurements of control of breathing, and PFT in adults are discussed separately. (See "Measures of oxygenation and mechanisms of hypoxemia" and "Exhaled nitric oxide analysis and applications" and "Exercise testing in children and adolescents: Principles and clinical application" and "Bronchoprovocation testing" and "Evaluation of suspected obstructive sleep apnea in children", section on 'Polysomnography' and "Control of ventilation" and "Overview of pulmonary function testing in adults" and "Pulmonary function testing in asthma".)

ROLE OF PULMONARY FUNCTION TESTING — PFT allows for assessment of the:

●Normal lung and airway growth and development

●Progression/regression of chronic disease (eg, bronchopulmonary dysplasia, cystic fibrosis [CF], kyphoscoliosis)

●Site and type of obstruction (central versus peripheral, intrathoracic versus extrathoracic, fixed versus variable)

●Degree of airway reactivity

●Degree of impairment

●Impact of environmental factors (eg, tobacco smoke, toxic gases) on disease state

●Impact of therapies (eg, bronchodilators, glucocorticoids, diuretics, mucolytics)

●Need for additional assessment, such as polysomnography, in children and adolescents with progressive restrictive lung disease who are at risk for developing sleep-disordered breathing

In addition, PFT may aid with the perioperative assessment and management of the child with chronic lung disease or neuromuscular weakness. PFT is also used for monitoring disease progression and prognosis. Forced vital capacity (FVC), for example, is a key parameter to monitor for progression of effects of scoliosis on the lungs, while forced expiratory volume in the first second (FEV₁) has prognostic value with regards to mortality in some diseases such as CF.

The asthma guidelines of the National Asthma Education and Prevention Program (NAEPP) [3] and the Global Initiative for Asthma (GINA) [4] both use spirometric values to classify asthma severity and subsequent ongoing determination of asthma control to guide asthma management. The development of compact and affordable instruments enables pediatric lung function testing in the primary care setting.

SPIROMETRY

Overview — Spirometry is the measurement of air flow over time. It includes measures of volume and flow generated by a forced and complete exhalation from full lung volume to residual volume (RV) after a full inspiration. The volume-time curve graphic presentation (figure 1) has been largely replaced in clinical practice by the flow-volume curve (figure 2 and figure 3), which provides a more immediate visual and intuitive perception of obstructive and restrictive disorders. However, the two graphic depictions are complementary and optimally should be analyzed together. Spirometry also includes the measurement of flow and volume with inspiration; however, inspiratory parameters that are predominantly indicators of extrathoracic obstruction are less commonly measured and are not discussed here. (See "Flow-volume loops".)

Production of a reliable, sustained expiration requires coaching from the clinician and both coordination and focus on the part of the subject. Thus, quality spirometry is usually not reliable in children younger than six years. However, exceptions exist, and even lesser-quality measurements may have clinical value as well as serving as a training opportunity for future measurements in the younger child. Modern spirometers are often equipped with software with age-adjusted animated incentives that help coach the young child through the respiratory maneuver using a dynamic graphic display.

Spirometry is most useful for evaluation of common pediatric obstructive lung diseases such as asthma, cystic fibrosis (CF), non-CF bronchiectasis, and the sequelae of bronchopulmonary dysplasia.

The following discussion of spirometry focuses on the measured parameters, interpretation, and clinical applications most relevant to the primary care provider. Methodology and interpretation of spirometry in children are discussed in greater detail in guidelines published by the American Thoracic Society (ATS) [5], accessed through the ATS website.

Measured parameters — The key parameters derived from spirometry include:

●Indices of volume:

•Forced vital capacity (FVC)

•Slow vital capacity (SVC) performed with a submaximal expiratory effort (nonstandard)

●Indices of flow:

•Forced expiratory volume in the first second (FEV₁)

•Flow between 25 and 75 percent of the vital capacity (FEF25-75%), also known as the maximal midexpiratory flow rate (MMEFR)

•Peak expiratory flow rate (PEFR)

The air remaining in the lungs at the end of expiration (RV) cannot be measured by spirometry. Thus, any lung capacity measurement that includes RV as a component cannot be derived by spirometry.

The measured values for these parameters are compared with normative data and are reported as the percent of predicted value for subjects of similar height, sex, and race using normative scales that are multiethnic and hence global [6]. Spirometry is most commonly used to monitor chronic conditions by comparing the measured values over repeated encounters [3,4].

Interpretation

Verifying technique and reproducibility — The first step in interpreting spirometry is to verify that the technique and reproducibility were adequate. The criteria for acceptability and usability were updated by the ATS and European Respiratory Society in 2019 [5] and include:

●Back-extrapolated volume <5 percent of FVC, or less than 0.1 liter.

●No cough during the first second of expiration.

●No glottic closure during the maneuver.

●Adequate evidence of end-of-forced-expiration:

•Expiratory plateau lasting for at least one second.

•Expiratory time >15 seconds (however, the likelihood of a child maintaining an expiratory effort for this length of time is low).

•FVC within repeatability criteria or greater than previously measured FVC.

●No evidence of mouthpiece obstruction or leak.

●Repeatability criteria:

•In subjects >6 years of age – For both FVC and FEV₁, the two largest values must be within 0.15 liters of each other.

•In subjects <6 years of age – For both FVC and FEV₁, the two largest values must be within 0.1 liters of each other or 10 percent of the highest value, whichever is higher.

Indices of flow and volume — The interpretation of spirometry depends upon the measurements affected (table 1). As a general rule, obstructive disorders affect indices of flow, and restrictive disorders affect indices of volume. Combined restrictive and obstructive defects may be more challenging to interpret. Any reduction in FVC exceeding 80 percent of predicted value may indicate a restrictive disorder. These patients can be referred to a pulmonary function laboratory for additional testing.

●Flow – FEV₁, FEF25-75%, and PEFR are decreased in obstructive disorders. FEF25-75% is generally viewed as representative of flow in smaller conducting airways. It is less effort dependent than the other measurements, and is especially useful in picking up milder intrathoracic airway obstruction. It may be reduced by 25 percent or more even while the patient is symptom free and/or has a normal lung examination and in the presence of normal FEV₁ and PEFR [7], As such, it is often a sensitive diagnostic tool for subtle morbidity, such as mild asthma. Reduction in FEF25-75% is visually reflected by scooping of the descending limb of the flow-volume curve (figure 3).

●Volume – FVC is often decreased in restrictive disorders (figure 4). However, such decreases may be misleading in that the FVC may also be reduced due to air trapping in obstructive defects. Restrictive disorders may also reduce flow. FEV1, a measure of volume over time, is reduced because it is affected by the total volume available for exhalation, the FVC. Thus, a restrictive disorder should be considered when flow indices are proportionally reduced with the FVC. This is done by assessing the FEV₁/ FVC ratio, normally >85 percent. When the FVC and FEV₁ are symmetrically reduced with a normal ratio, this suggests that the decrease in airflow may be due to volume reduction rather than to obstructed flow. In this setting, measurements of lung volume using methods that are typically unavailable in the primary care setting should be undertaken to confirm the restrictive respiratory disorder. (See 'Lung volume measurement' below.)

Flow-volume curve — The flow-volume curve is a graphic representation of individual forced inspiratory and expiratory maneuvers. It is included in most spirometry reports, although only the expiratory limb is typically displayed and analyzed in standard clinical conditions (figure 2). Obstructive defects usually manifest as scooping of the descending limb of the curve (figure 3), a change that can be easily detected by visual inspection. The graphic display of the flow-volume curve also provides the most effective measure of quality control. Good technical performance of the expiratory maneuver should lead to reproducible repeated maneuvers for a patient. As such, reliable measurements should have at least three flow-volume curves that can be closely superimposed graphically.

Examination of the inspiratory flow-volume curve is helpful when flow obstruction derives from the extrathoracic airways, most commonly in the larynx or upper trachea. These often useful parameters are not always included in the flow-volume curves reported by standard spirometers. Flow-volume patterns in upper-airway obstruction are discussed in detail separately. (See "Flow-volume loops".)

Use of spirometry in asthma — Office spirometry is a valuable tool for primary care clinicians to use in the evaluation and management of their patients with asthma. It can be used to support a diagnosis of asthma by demonstrating reversible airflow obstruction. This may be particularly helpful in children with isolated symptoms (eg, persistent cough, exercise intolerance) or atypical or equivocal presentations. In such patients, spirometry may also guide the clinician to an alternative diagnosis (eg, restrictive lung disease). (See "Asthma in children younger than 12 years: Initial evaluation and diagnosis".)

Once an obstructive pattern has been identified on spirometry, the reversibility of the obstruction can be assessed by measuring FEV₁ before and after inhalation of a bronchodilating agent (eg, albuterol). As a general rule, persons without bronchial hyperreactivity have a <5 percent increase in FEV₁ after inhalation of a bronchodilator [8]. A postbronchodilator increase in FEV₁ of >12 percent and 200 mL constitutes a reversible obstructive lung defect and supports the diagnosis of asthma. However, this definition for bronchodilator response (BDR) positivity was established in adults. An increase in FEV₁ of ≥8 percent may be a better definition for BDR in children, although it remains an insensitive test [9-11].

The interpretation of airway reactivity should be viewed with caution, particularly with borderline results. The degree of reversible obstruction can vary from one visit to the next, and the ongoing use of bronchodilators, particularly long-acting muscarinic antagonists (eg tiotropium), may persist for up to 48 hours, impacting the degree of reversibility measured [5]. Positive bronchodilator responses may be seen in children who have FEV₁ >110 percent predicted as their baseline values. These children may still demonstrate sufficient improvement to confirm reversible airway obstruction that suggests asthma. Other features of asthma, such as clinical response to bronchodilators, should be taken into account when making the diagnosis in children with mild asthma to buttress the finding of changes in lung function after a bronchodilator.

Monitoring of asthma with spirometry, used in conjunction with daily symptoms and exacerbation frequency, is also useful in evaluating response to therapy and changes in asthma severity over time in children with asthma [12]. Performance of spirometry at the start of treatment and during the first six months of follow-up were both associated with a decreased risk of hospitalization in the subsequent year in 27,193 Danish children aged 6 to 14 years with asthma [13]. Regular measurements in children with uncomplicated asthma are recommended by multiple asthma guidelines, such as the National Asthma Education and Prevention Program (NAEPP) [3] and Global Initiative for Asthma (GINA) guidelines [4].

The midexpiratory flows measure (FEF25-75%), while highly variable in repeat measurements, may also be a sensitive parameter to indicate an obstructive defect since it may be reduced in patients who are otherwise asymptomatic and have a normal FEV₁ [7].

Barriers to performance of spirometry in the primary care setting include poor technique due to lack of time and training, particularly in interpretation of results [14].

Peak expiratory flow rate — The PEFR measurement (often referred to as the peak flow measurement), unlike full spirometry, requires only a short expiratory blast, without the subject having to sustain a prolonged expiratory effort, and is therefore feasible for younger children four to six years of age. Typically, the highest of three PEFRs is reported. The portability and ease of use of inexpensive versions of the Wright Peak Flow Meter have made this device commonplace in the primary care setting and the home.

PEFR meters should not be viewed as "the poor man's spirometer," though they do have several important limitations [7,15,16]. The measurements obtained by PEFR meters are highly effort dependent and can be manipulated by children [17]. In addition, intrapersonal variability can be substantial and is particularly affected by circadian rhythms (although diurnal variability is a notable characteristic of asthma, with symptoms increasing at night concurrent to the ebb in endogenous glucocorticoid production). Because mini peak flow meters are not precise tools, wide variation of recorded PEFR can be observed between devices, even of the same brand. Thus, measurements performed by devices other than those customarily used by the patient should be interpreted with caution.

Peak flow meters have a limited role in establishing the diagnosis of asthma in the office. However, they can be useful in gauging the severity of asthma exacerbations, both by comparing PEFR measurements with population-specific normative data (table 2) [18] and, more importantly, to preestablished baseline ("personal best") values. Such PEFR measurements are commonly used to assist in determining levels of interventions according to predetermined asthma management plans (Action Plans). The optional use of PEFR has also been incorporated into the NAEPP guidelines for asthma management [3]. The use of PEFR monitoring in asthma is discussed in detail separately. (See "Peak expiratory flow monitoring in asthma".)

Multiple options of electronic handheld spirometers, some at low cost, that measure FVC and FEV₁ often with PEFR are available for use in the home setting [19-22]. The availability of FEV₁, a more robust and reliable spirometric parameter, should replace PEFR for individual monitoring with relatively modest increase in cost.

Bronchial challenge tests — Bronchial challenge, or bronchoprovocation, tests are designed to provoke an asthmatic response in children suspected of having bronchial hyperreactivity. The determination of a positive response is based upon detecting a decline (the degree of which varies between tests) from a baseline FEV₁ in response to the provocation. Methacholine, exercise, and/or cold air may be used as the challenge agent. Bronchial challenge tests are performed when there is uncertainty about the diagnosis of asthma, degree of exercise limitation, or to determine response to therapeutic interventions. Bronchial challenges using exercise are particularly useful to uncover exercise-induced airway reactivity, a common and often underdiagnosed condition in childhood asthma. Bronchial challenge testing should be performed only in specialized centers [3,23] not only for expertise, but also because it has the potential to induce severe bronchospasm that requires staff experienced in managing acute airway obstruction. Bronchial challenge tests are covered in greater detail separately. (See "Bronchoprovocation testing".)

Spirometry in the care of cystic fibrosis — FEV₁ is a key outcome measure in CF. It is routinely used to monitor the rate of progression of the lung disease, the need for interventions such as the administration of antibiotics or new drugs, and the effectiveness of such interventions. (See "Cystic fibrosis: Clinical manifestations of pulmonary disease", section on 'Pulmonary function testing'.)

LUNG VOLUME MEASUREMENT — Lung volume measurement is typically undertaken in specialized pulmonary function laboratories with adult-based services, which limits use of this measurement in children. The measurement of lung volumes is important in clinical conditions in which a restrictive lung defect and/or air trapping may be present. It is also important when addressing possible diffusion capacity defects. The partitioning of lung volumes is depicted in the figure (figure 1). (See 'Diffusion capacity measurement' below.)

Methods — There are two conventional methods of measuring lung volumes in children: whole-body plethysmography and gas dilution (using helium or nitrogen washout). Both methods measure the functional residual capacity (FRC), which is the residual air in the lung at the end of exhalation during tidal breathing (figure 1). The thoracic gas volume (TGV) measured equals FRC because the measurement is begun at end expiration, after a stable baseline end-expiratory volume is achieved. The FRC is unobtainable by spirometry since it includes the residual volume (RV). The use of spirometry together with measures of FRC allows division of lung volumes, as depicted in the figure (figure 1). Demonstration of reduced total lung capacity (TLC) is the gold standard for the diagnosis of restrictive respiratory disease in both adults and children.

Plethysmography — Plethysmography involves placing the child inside a whole-body plethysmograph or “body box,” a sealed structure similar to a telephone booth. This is typically done with the child alone, although the measurements can be performed with the child seated on the lap of a parent or caregiver. The plethysmograph is tightly sealed, and the child is asked to breathe normally at tidal volume (TV) through a mouthpiece.

The TV is measured, and the mouthpiece is briefly occluded by a shutter at end expiration (FRC). With the child panting against the closed shutter, pressure oscillations are simultaneously measured at the mouthpiece and within the plethysmograph. This maneuver results in alternating compression and decompression of the intrathoracic gas, which is measured at the mouth and within the box. By employing Boyle's law, which states that the product of pressure and volume remains constant in a closed system (P1V1 = P2V2), the FRC is calculated.

Plethysmography requires cooperation on the part of the subject and is therefore difficult to obtain in children younger than six years. Reliance on complex maneuvers, such as panting against a closed shutter, is the major limitation. In addition, some children find enclosure within the plethysmograph frightening.

To conform to repeatability standards, at least three FRC_pleth measurements should be obtained that are within 5 percent of each other.

Plethysmography measures the total gas volume, including areas not communicating with the central airways (eg, cysts, areas distal to airway obstruction), while gas dilution measures only those areas of the lungs in direct communication with the measurement apparatus. Dilution techniques, therefore, will underestimate FRC in conditions in which there is significant air trapping. Thus, plethysmography is preferred in obstructive conditions, in which air trapping may occur [23].

Novel technologies of integrated apparatus that use methods that are less demanding for patients and hence offer novel opportunities for total PFTs in children are discussed below. (See 'Novel technologies for pulmonary function determination' below.)

Gas dilution — The gas dilution methods of lung volume determination are based upon the assessment of helium or nitrogen concentrations and can be done either as a single breath measurement or, more commonly, with multiple breaths. Gas dilution methods require less cooperation from the child compared with plethysmography. These methods are a good alternative for patients who cannot physically fit in a plethysmograph (eg, children who require full-time wheelchair use) or those who experience claustrophobia when sitting in the sealed body box. A sealed face mask for gas dilution testing can be used in children whose buccal musculature is too weak to maintain a seal around a mouthpiece.

●In the multiple breath helium dilution method, the subject inhales a gas mixture containing a known concentration of helium in a known volume; the subject continues to inhale and exhale into a closed circuit until equilibrium is obtained. FRC is derived from the proportionate change of the helium concentration before and after equilibrium is reached (diluted by the gas inside the chest).

●Multiple breath nitrogen washout is performed via an open circuit measurement by having the child breathe 100 percent oxygen for several minutes until the nitrogen content of the exhalate is less than 1 percent, at which point virtually all the nitrogen in the lung has been exhaled into the spirometer. A rapid nitrogen analyzer measures the exhaled nitrogen in each exhalate as it is "washed out" with the 100 percent oxygen being inhaled. The volume of exhaled nitrogen is measured throughout the procedure. FRC can be calculated by dividing the total volume of nitrogen obtained by the difference in concentrations obtained.

Clinical application and interpretation

Restrictive disease — Restrictive lung defects are defined by reduction in functional lung volumes and can only be confirmed by measurements thereof. In these conditions, the TLC is reduced to below 80 percent of that predicted by age, height, and sex. The RV may remain unchanged with hypotonia and some instances of chest wall disease. Thus, the RV/TLC ratio is increased in children with these disorders, which mainly affect inspiratory, or vital capacity (VC).

The most common pathologic conditions in which lung volume determination is useful include:

●Interstitial lung disease

●Chest wall pathologies (eg, scoliosis)

●Neuromuscular diseases (eg, Duchenne muscular dystrophy)

In restrictive defects caused by interstitial lung disease, the RV is often also reduced, resulting in a normal RV/TLC ratio. In restrictive lung defects caused by neuromuscular weakness and chest and spine deformities, the RV may remain normal or almost normal, resulting in an increased RV/TLC ratio (table 1).

Obstructive disease — Lung volume measurements are not necessary to define obstructive defects, although such defects can lead to air trapping, defined as an increased RV/TLC ratio in the setting of airway obstruction (a reduced FEV₁/FVC ratio). When air trapping is present, the TLC may be normal or increased, the VC normal or decreased, and the RV increased. These changes may be the earliest abnormalities detected in early airway pathologies, such as cystic fibrosis (CF). The finding(s) of a reduced VC and/or symmetrically reduced VC and FEV₁ should prompt lung volume measurement.

DIFFUSION CAPACITY MEASUREMENT — Diffusion capacity is typically measured in specialized centers because of the cost and complexity of the required equipment. The diffusing capacity of the lungs for carbon monoxide (DLCO) and alveolar volume (VA) are measured in conditions in which impairment of gas diffusion across the alveolar-capillary membrane or a reduction in the alveolar-capillary surface area is suspected (eg, in children with exercise intolerance unrelated to bronchospasm, especially when associated with oxyhemoglobin desaturation, unexplained dyspnea or hypoxemia, interstitial lung disease, or pulmonary fibrosis). The DLCO is used diagnostically to detect the presence of diffusion abnormalities when diseases of the pulmonary interstitium or vasculitis are suspected. It is often used clinically to track effects of interventions for those diseases or side effects of therapies or interventions known to cause pulmonary fibrosis (eg, bleomycin and bone marrow transplantation, respectively).

As with other PFT measurements, proper technique of performance is critical to accurately interpret the data collected [24]. These include:

●The inspiratory volume (Vi) should be equal or greater to 90 percent of the largest vital capacity (VC) measurement in the same session, or equal or greater to 85 percent of the largest vital capacity (VC) measurement in the same session and within 200 mL or 5 percent of the largest alveolar volume (VA) from previous acceptable maneuvers.

●Eighty-five percent of the Vi should be inhaled within under four seconds.

●The breath-hold should last 10 to 12 seconds without Valsalva or Mueller maneuvers.

●Sample collection should be completed within four seconds of start of exhalation.

DLCO and DLCO/VA are reduced in intrinsic lung disease, such as the interstitial lung diseases and idiopathic pulmonary fibrosis as well as in pulmonary fibrosis secondary to cytotoxic or radiation therapy. Less frequently, pulmonary edema and pulmonary vascular diseases, including vasculitides associated with rheumatologic disease, can also reduce DLCO. The DLCO is increased above the normal range in pulmonary hemorrhage due to the presence of hemoglobin within the alveoli. It may also be increased if the Vi is less than 90 percent of VC. The DLCO test is discussed in greater detail separately. (See "Diffusing capacity for carbon monoxide".)

NOVEL TECHNOLOGIES FOR PULMONARY FUNCTION DETERMINATION — Two novel technologies offer compact, portable, desktop-sized devices that integrate spirometry, lung volume, and DLCO measurements.

●One device is a cabin-free compact unit that includes a spirometer and a flow-interruption device that rapidly measures absolute lung volumes [25]. The measurement of lung volume in this system includes spirometry and a tidal breathing maneuver in which periodic interruptions are introduced automatically by the device. The technique is based in part upon comparing gas pressures and airflows between the subject and a known reservoir. It also offers single-breath DLCO testing.

●Another device also requires no sealed box and is not based on Boyle's law. Lung volume calculation is determined by helium dilution. The air of the thorax equilibrates with a known volume of air containing a small concentration of helium or methane. The final dilution of these gases is used to calculate the total volume of air in the thorax. This technique does not measure air that does not communicate with the airway, (eg, air within cysts or bullae). It does measure the lung clearance index (LCI) by applying the multiple breath nitrogen washout technique [26-28]. The device measures the starting amount of nitrogen concentration when the patient initiates the maneuver. The patient is then switched to tidal breathing on 100 percent oxygen. The rate of clearing nitrogen from the lungs determines LCI, and total lung capacity can be calculated by integrating the total amount of exhaled nitrogen and dividing this volume by the initial nitrogen concentration.

Both these devices consolidate advanced and often complex measurements of pulmonary functions into a single compact device. They also eliminate cabin-based plethysmography and reduce maneuvers such as panting and, with that, facilitate difficult measurements and render the determination of the related parameters more achievable. This is particularly attractive for pediatrics, where studies beyond spirometry are often not feasible in the younger child. Publications from the adult literature confirm good agreement between the various parameters measured by these two devices when compared with the conventional measuring devices; however, such comparisons have not been published for pediatrics. Hence, caution should be exercised by the pediatric practitioner in prematurely relying on these devices until such time that pediatric-based comparative studies are published.

RESPIRATORY MUSCLE PRESSURE MEASUREMENTS — Determinations of respiratory muscle pressures are typically measured in specialized centers. These measurements evaluate the global strength of the inspiratory muscles (maximal inspiratory pressure [PImax]) and expiratory muscles (maximal expiratory pressure [PEmax]). The tests consist of a forceful inhalation and exhalation into tubing connected to a pressure manometer. The values obtained are compared with normative data for subjects of similar height, age, and sex.

These tests are useful in determining whether decreases in expiratory flows or lung volumes are caused by weakness of various respiratory muscles. They are particularly valuable to assess progression of muscle weakness in children with progressive neuromuscular disorders, such as Duchenne muscular dystrophy, since they can help determine when therapies such as assistance with coughing should be instituted [29] or indicate deterioration towards respiratory failure. These tests are discussed in greater detail separately. (See "Tests of respiratory muscle strength" and "Respiratory muscle weakness due to neuromuscular disease: Clinical manifestations and evaluation" and "Duchenne and Becker muscular dystrophy: Clinical features and diagnosis".)

EXHALED NITRIC OXIDE — Attention has focused on biomarkers that reflect pathologic processes, such as airway inflammation. The most widely studied of these measures is fractional exhaled nitric oxide (FeNO or eNO) [30,31]. Increased levels of this gas reflect the degree of (presumably predominantly) eosinophilic airway inflammation in asthma and atopy. Altered levels of exhaled FeNO are also seen in other diseases. FeNO measurement is easily performed, even in preschool-age children, and relatively inexpensive equipment is available. FeNO is not a reliable tool for assessing inflammation in cystic fibrosis (CF). Measurement of nasal FeNO is a key diagnostic tool for the diagnosis of primary ciliary dyskinesia (PCD) but requires specialized and costly equipment [32]. The measurement of FeNO and its role in the diagnosis and management of asthma are discussed in greater detail separately. (See "Exhaled nitric oxide analysis and applications".)

EVALUATION OF PULMONARY FUNCTION IN EARLY CHILDHOOD AND INFANCY — Spirometry is usually difficult to obtain in children younger than six years of age. However, technically acceptable and reproducible spirometry was reportedly performed by experienced pediatric pulmonary function technicians in children as young as three years of age [33]. Technical standards and reference data differ from those used for older children and adults; age-specific standards must be used [34]. In this young age group, forced expiratory volume in the first second (FEV₁) is often more than 95 percent of predicted. An alternative index to follow that is more sensitive is the forced expiratory volume at 0.5 seconds (FEV_0.5). The advent of interactive software for incentive spirometry facilitates performance of spirometry in preschool children [35]. Important advances have been made in development of predictive values for children that are more globally applicable but are beyond the scope of this topic.

Alternative measurements that require less patient cooperation have been developed for use in young children because of the difficulties in obtaining reliable forced expiratory maneuvers in this age group [36,37]. Of these, respiratory system resistance (Rrs) is the most commonly evaluated and can be assessed by whole-body plethysmography, the interrupter technique (R[int]) [34], and the forced oscillation technique [34,38-40]. None of these measurements are widely available. The uses and limitations of techniques are reviewed in a statement by the American Thoracic Society (ATS) [34].

Respiratory morbidity is frequent in children younger than two years, making evaluation of pulmonary function all the more important in these children. Significant advances in the assessment of spirometry and plethysmography in this age group have been made since the 1990s [41]. These techniques, however, are beyond the scope of this review since the need for sedation, expensive equipment, and a high level of training limits them to a few and decreasing numbers of specialty centers.

PREOPERATIVE EVALUATION — Lung function testing, including spirometry, lung volumes, and maximal respiratory pressures in patients who have known restrictive lung disease and spirometry in patients with chronic obstructive lung diseases, such as cystic fibrosis (CF), can help anticipate which patients may have a more difficult time with extubation and/or require prolonged ventilatory assistance. (See "Evaluation of perioperative pulmonary risk".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Asthma in children" and "Society guideline links: Pulmonary function testing".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topic (see "Patient education: Breathing tests (The Basics)")

SUMMARY

●Overview – Pulmonary function tests (PFTs) can measure obstructive, restrictive, and diffusion defects and respiratory muscle function. Measurements of flow and volume are most useful in the office setting. Spirometry, which provides both these measures, requires neither sophisticated technology nor expensive equipment, is easily interpreted, and is reliable when performed correctly. (See 'Introduction' above.)

●Parameters measured with spirometry – The important parameters derived from spirometry include indices of flow, including forced expiratory volume in the first second (FEV₁); flow between 25 and 75 percent of the vital capacity (FEF25-75%), also known as the maximal midexpiratory flow rate (MMEFR); and, less importantly, peak expiratory flow rate (PEFR) (table 1). Indices of volume are also measured, including forced vital capacity (FVC). (See 'Measured parameters' above.)

●Interpretation of spirometry parameters – FEV₁, FEF25-75%, and PEFR are decreased in obstructive disorders. FVC typically is decreased in restrictive disorders and in obstructive diseases where air trapping is substantial. An FEV₁/FVC ratio >85 percent suggests that an observed decrease in flow is due to volume reduction rather than airway obstruction and requires direct lung volume assessment for confirmation. (See 'Interpretation' above.)

●Use of spirometry in diagnosis and monitoring of asthma – Spirometry can be used to support a diagnosis of asthma by demonstrating reversible airflow obstruction. Spirometry is also helpful in monitoring the response to long-term therapy and changes in the degree of obstruction over time. While spirometry is the gold standard, PEFR, as measured by a peak flow meter, may also be used to gauge the severity of asthma exacerbations, provided that caretakers and providers understand their limitations (table 2). (See 'Use of spirometry in asthma' above.)

●Lung volume measurement – The measurement of lung volumes is important in clinical conditions in which a restrictive lung defect and/or air trapping may be present. It is also important when addressing possible diffusion capacity defects. (See 'Lung volume measurement' above.)

Lung volume measurement is typically undertaken in specialized centers. There are two conventional methods of measuring lung volumes in children: whole-body plethysmography and gas dilution. Both methods measure the functional residual capacity (FRC), which is the residual air in the lung at the end of exhalation during tidal breathing (figure 1). This value is unobtainable by spirometry.

Restrictive lung defects are defined by reduction in functional lung volumes and can only be confirmed by such measurements. In these conditions, the total lung capacity (TLC) is reduced to below 80 percent of that predicted by age, height, and sex.

Novel integrated desktop instruments to measure lung volume in addition to spirometry and diffusing capacity of the lungs for carbon monoxide (DLCO) have been introduced. These are compact and simplify the measurements. However, the reliability of their use for pediatric patients has yet to be determined.

●Other types of PFTs – Additional types of PFTs that are typically performed at specialized centers include measurement of DLCO, respiratory muscle pressure, and fractional exhaled nitric oxide (FeNO). (See 'Diffusion capacity measurement' above and 'Respiratory muscle pressure measurements' above and 'Exhaled nitric oxide' above.)

●Alternative measurements in young children – Alternative measurements that require less patient cooperation have been developed for use in young children because of the difficulties in obtaining reliable forced expiratory maneuvers in this age group. Of these, respiratory system resistance (Rrs) is the most commonly evaluated and can be assessed by the forced oscillation technique, whole-body plethysmography, or the interrupter technique (R[int]). (See 'Evaluation of pulmonary function in early childhood and infancy' above.)