Allergy Asthma Immunol Res.  2018 Nov;10(6):614-627. 10.4168/aair.2018.10.6.614.

Lung Function Trajectory Types in Never-Smoking Adults With Asthma: Clinical Features and Inflammatory Patterns

• Kim JH
• Chang HS
• Shin SW
• Baek DG
• Son JH
• Park CS
• Park JS

• KMID: 2441812
• DOI: http://doi.org/10.4168/aair.2018.10.6.614

Abstract

PURPOSE
Asthma is a heterogeneous disease that responds to medications to varying degrees. Cluster analyses have identified several phenotypes and variables related to fixed airway obstruction; however, few longitudinal studies of lung function have been performed on adult asthmatics. We investigated clinical, demographic, and inflammatory factors related to persistent airflow limitation based on lung function trajectories over 1 year.
METHODS
Serial post-bronchodilator forced expiratory volume (FEV) 1% values were obtained from 1,679 asthmatics who were followed up every 3 months for 1 year. First, a hierarchical cluster analysis was performed using Ward's method to generate a dendrogram for the optimum number of clusters using the complete post-FEV1 sets from 448 subjects. Then, a trajectory cluster analysis of serial post-FEV1 sets was performed using the k-means clustering for the longitudinal data trajectory method. Next, trajectory clustering for the serial post-FEV1 sets of a total of 1,679 asthmatics was performed after imputation of missing post-FEV1 values using regression methods.
RESULTS
Trajectories 1 and 2 were associated with normal lung function during the study period, and trajectory 3 was associated with a reversal to normal of the moderately decreased baseline FEV1 within 3 months. Trajectories 4 and 5 were associated with severe asthma with a marked reduction in baseline FEV1. However, the FEV1 associated with trajectory 4 was increased at 3 months, whereas the FEV1 associated with trajectory 5 was persistently disturbed over 1 year. Compared with trajectory 4, trajectory 5 was associated with older asthmatics with less atopy, a lower immunoglobulin E (IgE) level, sputum neutrophilia and higher dosages of oral steroids. In contrast, trajectory 4 was associated with higher sputum and blood eosinophil counts and more frequent exacerbations.
CONCLUSIONS
Trajectory clustering analysis of FEV1 identified 5 distinct types, representing well-preserved to severely decreased FEV1. Persistent airflow obstruction may be related to non-atopy, a low IgE level, and older age accompanied by neutrophilic inflammation and low baseline FEV1 levels.

Keyword

Adult; asthma; disease progression; forced expiratory volume; inflammation; phenotype

MeSH Terms

Adult*
Airway Obstruction
Asthma*
Disease Progression
Eosinophils
Forced Expiratory Volume
Humans
Immunoglobulin E
Immunoglobulins
Inflammation
Longitudinal Studies
Lung*
Methods
Neutrophils
Phenotype
Sputum
Steroids
Immunoglobulin E
Immunoglobulins
Steroids

Figure

• 

  Fig. 1 Flowchart of the study protocol. FEV1, forced expiratory volume in 1 second.

• 

  Fig. 2 Trajectory analysis of post-bronchodilator FEV1% values in 1,679 asthmatics and serial changes in the mean FEV1 values. Data are presented as mean ± standard deviation. FEV1, forced expiratory volume in 1 second.

• 

  Fig. 3 Comparison of eosinophilic, neutrophilic, mixed and pauci-granulocytic inflammation in sputum between trajectories 4 (n = 82) and 5 (n = 117). There is a significant difference in the granulocytic patterns between the 2 trajectories (P = 0.001 by χ2 test).

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