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ICD Code: 493. Asthma

ICD Code: 493. Article Review
Title: Spahn JD et al; "Clinical Assessment of Asthma Progression in Children and Adults." Journal of Allergy and Clinical Immunology; V.121; No.3; 3/08; p548
      CHILDHOOD AND ADULT PREVALENCE: Asthma is among the most common chronic diseases in both children and adults. According to the latest report from the Centers for Disease Control and Prevention, for the 3-year period between 2001 and 2003, about 20 million persons in the U.S. had asthma. Of these, 6.2 million were children and 13.8 million were adults. Current asthma prevalence was higher for children (8.5%) than adults (6.7%). In addition, boys (9.6%) had higher prevalence than girls (7.4%), whereas prevalence among women was higher (8.4%) than among men (4.9%). These statistics suggest that a considerable number of patients with asthma in childhood outgrow the disease, and those most likely to undergo asthma remission are male patients.
      RECURRENT WHEEZE IN EARLY CHILDHOOD: Cohort studies that enroll children at birth are among the most helpful in understanding the inception of asthma early in life, yet they have inherent limitations such as the difficulty in making the diagnosis of asthma and the multitude of other conditions that can mimic asthma in this age group. Recurrent wheezing in infants and young children is common and is made up of a heterogeneous group of conditions with different risk factors and prognoses. A 1995 study was among the first to characterize the various wheezing phenotypes in preschool children and to identify risk factors for persistence of asthma in school age. In this unselected birth cohort study, more than 1200 newborns were enrolled. At 6 years of age, 49% had reported at least 1 episode of wheezing. Transient wheeze was noted in 20%. Transient wheezers had at least 1 episode of wheeze during the first 3 years of life but were no longer wheezing by 6 years. Children with late-onset wheeze made up 15% of the cohort. These children did not wheeze during the first 3 years of life but had wheezing by 6 years. Those with persistent wheezing accounted for 14% of the cohort and were characterized by having had wheezing before 3 years that persisted at 6 years. Thus, only a minority of children who wheezed with viral respiratory tract infections during the first 3 years of life went on to develop asthma in childhood. Transient wheezers had diminished airway function in infancy, were less likely to be atopic, and had a history of maternal smoking, whereas persistent wheezers were more likely to have a positive maternal history of asthma, elevated serum IgE levels, and diminished lung function at 6 years.
      In summary, less than 50% of children with early-onset wheezing will go on to develop asthma. This is a clinically important point with respect to disease progression in that only those children at risk for subsequent asthma are likely to benefit from inhaled glucocorticoid therapy.
      ASTHMA REMISSION: Remission rates ranging from 10% to 70% have been reported in unselected population-based or preselected cohorts. The variability in reported remission rates stems largely from the various definitions used to define remission, because there is no universally accepted definition for what constitutes remission. Most studies include the absence of respiratory symptoms and asthma medication use, whereas others also include normal lung function and/or absence of bronchial hyperresponsiveness (BHR). Studies of children with asthma from more than 25 years ago, and before the use of currently available medications, reported remission rates ranging from 22% to 55%, whereas rates from recent hospital-based cohorts of children with asthma range from 28% to 57% at follow-up 20 years later.
      The authors of a 2004 study followed a cohort of 119 children with asthma over a period of 30 years with the main purpose to identify factors contributing to asthma remission in adulthood. In that study, two definitions were used. "Complete remission" was defined as having no wheeze or asthma exacerbations in the past 3 years, no use of inhaled glucocorticoids, normal lung function, and the absence of BHR, whereas "clinical remission" was defined as the absence of wheeze and exacerbations and no use of inhaled glucocorticoids. The cohort was studied at 5 to 14 years (visit 1), at 21 to 33 years (visit 2), and at 32 to 42 years (visit 3). Complete remission was noted in 22% of the cohort, whereas 30% of the cohort was in clinical remission at visit 3. Two factors were found to be associated with both complete and clinical remission: higher FEV1 (forced expiratory volume at 1 second) at visit 1 and an improvement in FEV1 (% predicted) from visit 1 to visit 2. Of note, all of the subjects in clinical remission, despite having no asthma symptoms, had diminished lung function, the presence of BHR, or both.
      A large cross-sectional study of more than 18,000 subjects from 1998 to 2000 evaluated the incidence and remission rates of asthma from birth to age 44 years. Remission in this study was defined as the absence of asthma attacks and no asthma medications for 2 years. The overall remission rate was 45.8%, and when adjusted for potential confounders, age at asthma onset was the main determinant of remission. Patients who underwent asthma remission had an earlier age at onset and a shorter duration of asthma. In addition, the probability of remission was strongly and inversely related to the age at onset.
      In 1964, the longest longitudinal study of the natural history of asthma began in Melbourne, Australia, using a 1957 birth cohort of 30,000 children. The most recent update from this cohort at age 42 years was published in 2002. Important findings from this study with respect to asthma remission included the following: 55% of subjects with wheezing before 7 years had no wheezing in adolescence and remained wheeze-free at 21 years. Children with infrequent wheezing in childhood were more likely to undergo remission than children with frequent wheeze (60% versus 40%) between 14 and 21 years of age. The majority of children with intermittent viral-induced wheezing episodes at age 7 years had a benign course, with 60% having no asthma by adult life, whereas only 30% of children who carried the diagnosis of asthma at age 7 years were wheeze-free at age 42 years, and 50% had troublesome asthma well into adult life.
      Determining whether patients in asthma remission had evidence for ongoing subclinical airway inflammation was the goal of one study group. In their first study (2000), subjects in asthma remission (defined as having no symptoms for at least 1 year) had elevated exhaled nitric oxide levels compared with the controls, with levels similar to those with active asthma. In their second study (2001), subjects whose asthma was in remission were noted to have elevated numbers of T cells, eosinophils, and mast cells and elevated IL-5 expression within their airways compared with subjects without asthma. Thickening of the reticular basement membrane was also noted among those in remission and was of similar magnitude to those with active asthma.
      DISCUSSION: Loss of lung function over time is the best-studied measure of asthma progression. Studies in adult patients with asthma have consistently demonstrated accelerated lung function decline. Whether children are at risk for accelerated decline remains to be further elucidated. The available data suggest that about 25% of children with mild to moderate asthma will have progressive loss of lung function. Risk factors include male sex, younger age, shorter asthma duration, and high baseline FEV1. Children with greater disease severity asthma are likely to be at greater risk for progressive lung function decline, which results in compromised lung function in early adult life. Airway inflammation and airway remodeling are thought to contribute to disease progression over time, although few longitudinal studies support this paradigm. Last, whether any currently available asthma controller medication can prevent asthma progression remains an important but unresolved question.

Search Criteria: Text - Journal of Allergy and Clinical Immunology; V.121; No.3; 3/08; p548