Sputum analysis, bronchial hyperresponsiveness, and airway function in asthma: Results of a factor analysis

Abstract

Background: Recent studies have shown weak associations among FEV 1 , bronchial hyperresponsiveness (BHR), sputum eosinophils, and sputum eosinophil cationic protein (ECP), suggesting that they are nonoverlapping quantities. The statistical method of factor analysis enables reduction of many parameters that characterize the disease to a few independent factors, with each factor grouping associated parameters. Objective: The purpose of this study was to demonstrate, by using factor analysis, that reversible airway obstruction, BHR, and eosinophilic inflammation of the bronchial tree, as assessed by cytologic and biochemical analysis of sputum, may be considered separate dimensions that characterize chronic bronchial asthma. Methods: Ninety-nine clinically stable patients with a previous diagnosis of asthma underwent spirometry, sputum induction, and histamine inhalation tests. Results: Most patients were nonobstructed (FEV 1 , 91% ± 20%); a low level of bronchial reversibility (FEV 1 increase after β 2 -agonist, 7.8% ± 9.2%) and BHR (histamine PC 20 FEV 1 geometric mean, 0.98 mg/mL) were found. Sputum eosinophil differential count (12.4% ± 17.7%) and sputum ECP (1305 ± 3072 µg/mL) were in the normal range of our laboratory in 38 and 22 patients, respectively. Factor analysis selected 3 different factors, explaining 74.8% of variability. Measurements of airway function and age loaded on factor I, PC 20 FEV 1 and β 2 -response loaded on factor II, and sputum ECP and eosinophils loaded on factor III. Additional post hoc factor analyses provided similar results when the sample was divided into 2 subgroups by randomization, presence of airway obstruction, degree of BHR, percentage of sputum eosinophils, or concentration of sputum ECP. Conclusions: We conclude that airway function, baseline BHR, and airway inflammation may be considered separate dimensions in the description of chronic asthma. Such evidence supports the utility of routine measurement of all these dimensions. (J Allergy Clin Immunol 1999;103:232-7.)

Reduction in bronchodilation following a deep inhalation is poorly related to airway inflammation in asthma

“…Recently, CRIMI et al [34] and ROSI et al [35] were able to demonstrate that BHR is independent of the number of inflammatory cells in the airway lumen or mucosa. The present results, showing the independence among sputum cellular and biochemical profile, volume history and BHR are in line with the results of these studies [34,35].…”

Intérêt de la mesure de l’inflammation en clinique dans l’asthme

“…Une analyse factorielle a toutefois révélé que l'inflammation des voies aériennes et l'hyperréactivité bronchique à la méthacholine donnent des informations différentes [88] . Une étude récente a objectivé un seuil de FE NO Intérêt pour la prédiction des exacerbations, du déclin de la fonction respiratoire, du contrôle et de la sévérité de l'asthme, de la réponse au traitement et de l'adaptation du traitement anti-inflammatoire…”

Biomarkers in asthma and allergic rhinitis

“…In view of the disease heterogeneity, traditional disease markers, such as clinical symptoms and lung function parameters, appeared inadequate to differentiate across the various subsets or to monitor disease activity and the response to (targeted) therapy, since they appeared poorly correlated with the underlying airway inflammation [15]. In addition, several factor and cluster analyses revealed that symptoms and lung function, markers of airway inflammation and airway hyperresponsiveness provide complementary information on the severity and activity of asthma in both adults and children and can help to differentiate into different asthma phenotypes [16][17][18][19]. In this respect, the development of non-invasive airways sampling methods and detection techniques, allowing identification of several components of the airway inflammation including the determination of useful biomarkers, has greatly contributed to our current insight into the inflammatory cascades within several asthma subsets and the link to customized, targeted therapies [13,20,21].…”