Pediatr allergy Immunol Pulmonol.2013 Sep;26(3):115-121.

Asthma, FEF25-75, and Hospitalizations in Children.

Elizabeth R. Gibb, Shannon M. Thyne, Daniel N. Kaplan, and Ngoc P. Ly.

Division of Pulmonary Medicine, Department of Pediatrics, Benioff Children’s Hospital, University of California, San Francisco, California.


Asthma is a common chronic pediatric respiratory disease associated with significant morbidity. Current guidelines recommend monitoring forced expiratory volume in 1 s (FEV1) as part of the assessment of asthma severity and control; however, many children with asthma have a normal FEV1 despite significant symptoms. Reduced forced expiratory flow between 25%–75% of forced vital capacity (FEF25–75) may be an important measure of asthma severity and control in children with normal FEV1. This study examines the association between FEF25–75 and asthma-related hospitalizations. Pulmonary function tests and records of 925 children ≤19 years of age seen for an initial evaluation of physician-diagnosed asthma at a community-based asthma clinic between 1999 and 2011 were reviewed. FEV1 ≥80% predicted and FEF25–75 ≥60% were considered normal. The associations between FEV1 and FEF25–75 and asthma-related hospitalizations were examined using logistic regression models. Thirteen percent (n=118) of the children were hospitalized for asthma at least once in the previous year. Fifty four percent (n=501) of the children met criteria for uncontrolled asthma symptoms. Asthma-related hospitalization was associated with reducing categories of FEF25–75, but not FEV1. Among the 693 children with normal FEV1 (≥80%), those with FEF25–75 <60% were more likely to have been hospitalized in the previous year (odds ratio 2.50, confidence interval 1.17–5.35) as compared to those with FEF25–75 ≥60% of predicted. In a diverse urban cohort of children with asthma, asthma-related hospitalization in the previous year was associated with reduced FEF25–75 even among those with normal FEV1. Our results suggest that FEF25–75 may provide important information in the assessment and management of asthma in children.

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Asthma is a common chronic pediatric respiratory disease associated with significant morbidity. The National Asthma Education and Prevention Program (NAEPP) 2007 Guidelines define asthma severity (in patients not on a daily controller) and control (for those on a daily controller) based on the frequency of asthma related symptoms, hospitalizations, ER visits and courses of systemic corticosteroids. Additionally, monitoring of spirometric measurements, in particular, forced expiratory volume in 1 second (FEV1), is recommended as an objective measure of asthma severity and control.(1) However, studies have found that FEV1 was normal in many children even when they reported having asthma symptoms.(2-4)  Similarly, in the clinic, we have found that many children have significant asthma symptoms despite having a normal FEV1.

In contrast, the forced expiratory flow between 25 and 75% of forced vital capacity, (FEF25-75) has been shown to be reduced in children with acute wheezing(5, 6)and active asthma.(7-11).  FEF25-75 measures the airways which empty later, and is thought by many to be a more sensitive indicator of small airways disease.  Despite concerns of test-to-test variability and lack of a clearly defined normal range,(12) recent data suggests that FEF25-75 is clinically relevant and reproducible in children with asthma.  Similarly, in the clinic, we noted that even among children with normal FEV1, those with lower FEF25-75, were more likely to have wheezing on exam and more likely to have exacerbations. We hypothesized that FEF25-75 may be a sensitive indicator of small airway disease and may provide additional information regarding asthma severity and control in children, particularly those with normal FEV1. In Figure 1, we show the Forced Vital Capacity (FVC), FEV1 and FEF25-75 in a single patient followed at our asthma clinic. In this patient, and many others we follow in the clinic, the FEF25-75  is reproducible and a reliable predictor of asthma symptoms. Furthermore, the FEF25-75  was found to be abnormal when the patient was reporting asthma symptoms, despite having a normal FEV1.

In this study, we performed retrospective data analyses of the relationships between spirometric values (FEF25-75 and FEV1) and asthma severity measures, specifically asthma related hospitalization in a large and diverse cohort of asthmatic children followed in an urban asthma clinic.   We found reduced FEF25-75 is strongly associated with poor asthma symptom control in the previous 2 weeks and asthma-related hospitalizations in the previous year. In particular, having an FEF25-75 <60% was associated with increased odds of asthma-related hospitalizations whether FEV1 was normal (³80%) or not. Our results suggest that having an FEF25-75 < 60% may be an important indicator of the clinically significant small airway obstruction in children and should be considered in the evaluation of asthma in children. Prospective studies are needed to determine if aggressive treatment of children with reduced FEF25-75, particularly less than 60%, would lead to reduced asthma morbidity.

Ngoc Ly-1


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