Patterns of Growth and Decline in Lung Function in Persistent Childhood Asthma

Abstract

BACKGROUND Tracking longitudinal measurements of growth and decline in lung function in patients with persistent childhood asthma may reveal links between asthma and subsequent chronic airflow obstruction. METHODS We classified children with asthma according to four characteristic patterns of lung-function growth and decline on the basis of graphs showing forced expiratory volume in 1 second (FEV1), representing spirometric measurements performed from childhood into adulthood. Risk factors associated with abnormal patterns were also examined. To define normal values, we used FEV1 values from participants in the National Health and Nutrition Examination Survey who did not have asthma. RESULTS Of the 684 study participants, 170 (25%) had a normal pattern of lung-function growth without early decline, and 514 (75%) had abnormal patterns: 176 (26%) had reduced growth and an early decline, 160 (23%) had reduced growth only, and 178 (26%) had normal growth and an early decline. Lower baseline values for FEV1, smaller bronchodilator response, airway hyperresponsiveness at baseline, and male sex were associated with reduced growth (P<0.001 for all comparisons). At the last spirometric measurement (mean [±SD] age, 26.0±1.8 years), 73 participants (11%) met Global Initiative for Chronic Obstructive Lung Disease spirometric criteria for lung-function impairment that was consistent with chronic obstructive pulmonary disease (COPD); these participants were more likely to have a reduced pattern of growth than a normal pattern (18% vs. 3%, P<0.001). CONCLUSIONS Childhood impairment of lung function and male sex were the most significant predictors of abnormal longitudinal patterns of lung-function growth and decline. Children with persistent asthma and reduced growth of lung function are at increased risk for fixed airflow obstruction and possibly COPD in early adulthood. (Funded by the Parker B. Francis Foundation and others; ClinicalTrials.gov number, NCT00000575.)

Genetics and Genomics of Longitudinal Lung Function Patterns in Individuals with Asthma

“…CAMP was a randomized, placebocontrolled trial of inhaled antiinflammatory treatments for mild to moderate childhood asthma followed by three phases of observational follow-up; the trial and all followup phases included at least annual spirometry (21,22 (2).…”

“…In individuals with lung disease, including asthma, divergences from the canonical pattern can manifest as reduced growth, early decline, rapid decline, or a combination of these (2). A pattern of FEV 1 growth and decline characterized by early decline has been associated with smoking and respiratory symptoms (3,4), and reduced level of lung function has been associated with increased incidence of laterlife chronic obstructive pulmonary disease (COPD) (5).…”

“…We have previously investigated the determinants of FEV 1 pattern and natural history of participants of the CAMP (Childhood Asthma Management Program) cohort, who were recruited at ages 5-12 years and followed for up to 18 years (2). We report here a GWAS of the impact of SNPs on longitudinal lung function growth patterns.…”

Matrix Metalloproteinase-1 Activation Contributes to Airway Smooth Muscle Growth and Asthma Severity

“…and abnormal lung function in adulthood (5,6). Changes observed in airway remodeling include epithelial desquamation, goblet cell hyperplasia, reticular basement membrane thickening, increased airway smooth muscle (ASM) mass, and abnormal extracellular matrix (ECM) deposition (1,7).…”

Which CD8+T-cells in asthma? Attacking or defending?

“…In adults with asthma and fixed airflow limitation, which is now often labelled as asthma-COPD overlap syndrome, lung function decline is affected by the age of recognition of asthma, being steeper in those with late asthma onset and much slower in those with an early onset of the disease [4,5]. This information complements the emerging picture in childhood asthma, which shows that most children with persistent asthma have a reduced growth of lung function and are at increased risk for fixed airflow obstruction in early adulthood [7,8]. Thus, the presence of chronic airflow obstruction in asthma may be the result of either a reduced lung function growth in early childhood or a steeper decline in adulthood.…”