PEDIATRIC ALLERGY, IMMUNOLOGY, AND PULMONOLOGY Volume 24, Number 2, 2011 ª Mary Ann Liebert, Inc. DOI: 10.1089/ped.2010.0060 Clinical Applications of Pediatric Pulmonary Function Testing: Lung Function in Recurrent Wheezing and Asthma Jason Debley, M.D., M.P.H.,1 Amy G. Filbrun, M.D., M.S.,2 and Padmaja Subbarao, M.D., M.Sc. (Epid), FRCP(C)3 Pulmonary function testing remains the gold standard for the diagnosis and management of wheezing disorders in older children and adults. Although wheezing disorders are among the most common clinical problems in pediatrics, most young children and toddlers cannot perform most of the currently clinically available pulmo- nary function tests. In this article, we review the different types of pulmonary function tests available and discuss the applicability and utility in the different age groups with specific reference to suitability in the diagnosis and management of wheezing disorders. Introduction In this review, we will attempt to concisely review the literature of currently available pulmonary function tech- sthma is a chronic reversible obstructive airway dis- niques in children to assist in the diagnosis and management ease. In school-age children objective measurement of of asthma and recurrent wheezing. A lung function is essential to the diagnosis and evaluation of asthma, as medical history and physical examination are not reliable means of assessment.1 Although clinicians are gen- Spirometry 2 erally able to identify airflow obstruction clinically, they are Childhood unable to assess the degree or reversibility of the airflow obstruction.3 In a recent study, up to a third of children with Spirometry is the gold standard for the diagnosis and moderate-to-severe asthma were reclassified to a more se- management of asthma. It is the most commonly used method vere asthma category when spirometry was assessed in ad- to assess lung function. Recent NIH guidelines7 recommend 4 dition to symptom frequency. In contrast, another study the use of spirometry, specifically FEV1 and FEV1/FVC found that most children with mild-to-moderate asthma by [forced vital capacity (spirometry)] ratio for the diagnosis and symptom classification were found to have normal lung management of children older than 5 years. This is in part due function by FEV1 [forced expiratory volume in one second to the fact that pulmonary function has been found to be more (spirometry)].5 These seemingly contradictory findings em- sensitive than clinical examination2,3 or symptoms for the phasize the importance of including pulmonary function detection of obstructive pathology.4 The greatest value in di- testing (PFT) in a comprehensive assessment of asthma. agnosing asthma with the use of spirometry is the docu- Recurrent wheezing affects 20%–30% of infants and tod- mentation of reversibility with short acting bronchial agonist. dlers, yet resolves in at least half of these children by school The degree of reversibility has been correlated with the degree age. Eighty percent of school-age children with persistent of airway inflammation8 and postbronchodilator measures asthma were symptomatic by age 6 years, with more than can be used to follow lung growth and remodeling.9 Further, half symptomatic by age 3 years.6 However, differentiating those children with the greatest reversibility with a short transient wheezing from persistent asthma in the early years acting bronchial agonist are most at risk for remodeling and is problematic since the 2 syndromes have only been de- loss of lung function over time.10 scribed epidemiologically. Therefore, practical methodolo- Other factors making spirometry a useful test in the as- gies to objectively assess lung function in infants and sessment of asthma and bronchodilator response (BDR) in- toddlers for the purposes of accurately diagnosing asthma clude portability of the measurement device, ease of use for are highly desirable. the operator, and repeatability of the maneuver. Spirometry 1Seattle Children’s Hospital, University of Washington, Seattle, Washington. 2C.S. Mott Children’s Hospital, University of Michigan, Ann Arbor, Michigan. 3Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada. 69 70 DEBLEY, FILBRUN, AND SUBBARAO is the least variable of the pulmonary function maneuvers dividual asthmatic children had evidence of airflow ob- currently commercially offered in most clinical laboratories. struction by FEV1 or FEF25–75 [forced expiratory flow at 25% The coefficient of variation for FEV1 ranges from 2.7% to 5%, to 75% of expiration (spirometry)], suggesting that preschool whereas the variability of other measures such as specific spirometry may provide clinically useful information for a airway resistance (sRaw), respiratory resistance during in- substantial subset of individual patients in this age group. terruption (interrupter resistance) (Rint), and respiratory impedance (forced oscillation technique) (Xrs) are at least Infants double to triple.11,12 This low coefficient of variation would Although infants and toddlers are not capable of inde- suggest that FEV1 would be the most sensitive test to detect BDR; however, most studies have not assessed the between- pendently performing spirometric maneuvers, the raised- occasion repeatability in disease states.13 Only 1 study in volume rapid thoracoabdominal compression (RVRTC) adults studied this phenomenon and suggested that the technique can be used to measure forced expiratory flows and volumes in children £ 3 years of age under sedation with variability of FEV1 was significantly higher in disease states, thus suggesting that other measures may be more sensitive chloral hydrate. During the RVRTC maneuver an infant’s to BDR assessment.13 This conclusion requires further study. lungs are inflated to near total lung capacity (TLC) followed by a forced expiration.21–23 The RVRTC technique allows gener- Other limitations of FEV1 relate to the physiology under- lying its measurement. Asthma is primarily a disease of the ation of flow–volume curves that are similar to adult-type small airways14 and studies in well-controlled asthmatics flow–volume curves. RVRTC-forced expiratory flows and volumes have been used to assess infants with bronchiolitis have shown continued obstruction and airway inflammation 24,25 in the small airways despite normal measures of the large and recurrent wheezing, and bronchodilator responsive- ness in healthy infants.26 Reference values from healthy infants airways. The FEV1 may remain preserved despite significant 27 small airway obstruction, and hence the need for more sen- are published, and 2 devices to perform infant PFT (iPFT) sitive measures of small airway obstruction. This is an active using the RVRTC method are commercially available. area of research and may in the near future lead to the de- However, there are several important barriers to using the velopment of novel strategies to monitor disease progression. RVRTC technique to obtain lung function measurements for clinical use. Little data exist regarding the within- and At the current time, FEV1 remains the most studied lung function measure in asthma and remains the most re- between-occasion repeatability of RVRTC measurements. commended physiological assessment for the diagnosis and Performing RVRTC measurements is complex and time con- management of wheezing disorders in childhood. suming, requires sedation of the patient, and must be per- formed using expensive equipment operated by highly trained personnel. For these reasons, the ability to obtain high- Preschool children quality RVRTC measurements is limited to a small number of Children as young as 3 years of age are capable of per- laboratories around the world. Published normative data forming spirometry under ideal laboratory conditions when were derived from a relatively small sample size (n = 155), trained by technicians skilled in performing spirometry in limiting its generalizability to populations around the world with different ethnicities as well as social and environmental this age group. In 2007 the American Thoracic Society (ATS) 27 and European Respiratory Society (ERS) published a state- backgrounds. Further, longitudinal studies assessing the ment that included technical recommendations for the per- predictive value of RVRTC lung function values for per- formance of spirometry in preschool children to facilitate sistent asthma among infants with recurrent wheezing is comparison of data between centers.11 Several studies de- lacking. Although published data describing forced ex- piratory volumes and flows following administration of al- scribing spirometric data in healthy preschool-age children 26 have been published over the past decade,15–18 and recently buterol in healthy children exist, a consensus does not yet Stanojevic et al. published robust reference equations for reached on the definition of a clinical BDR during RVRTC children ages 3 through 7 years based on an analysis of maneuvers. Although infant lung function testing using the preschool lung function data from 3,777 children collated RVRTC technique is a powerful research tool, the technical from 15 centers in 11 countries.19 issues summarized above may limit its use as a routine clin- An important limitation to clinical use of preschool spi- ical tool in assessing infants and toddlers with wheezing rometry is the lack of repeatability data, thus limiting inter- disorders. pretations of change in lung function following a clinical intervention, such as response to bronchodilators or corti-