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.)

Results -Neutrophils predominated in the sputum of subjects with COPD while eosinophils predominated in the sputum of those with chronic asthma. However, in 28% of asthmatic subjects an increased percentage of neutrophils was found. In asthmatic patients the differential count of eosinophils was inversely related to the FEV1, FEV1NVC, and bronchial hyperresponsiveness, and directly related to clinical scores.Conclusions -The cellular profile of sputum in normal subjects and in patients with asthma and COPD is different. The concentration of eosinophils in the sputum correlates with the severity of asthma.

There is much evidence that eosinophils play an important role in bronchial epithelial damage in asthma by releasing cationic proteins. However, the extent to which eosinophil inflammation relates to indices of asthma severity in chronic stable asthma is still a matter of debate.We studied 46 clinically stable patients with mild to severe chronic asthma (forced expiratory volume in one second (FEV1) 50-126% of predicted value). The clinical severity of asthma was graded from 1 to 4 according to the Aas scoring system. Twelve normal subjects were also studied as controls. Induction of sputum was performed by hypertonic saline to determine differential cell count, and eosinophil cationic protein (ECP) by the so-called "plug technique". The concentration of ECP was measured by a fluoroimmunoassay. Bronchial hyperresponsiveness was recorded by inhaling progressive concentrations of histamine, and the concentration that caused a 20% decrease in FEV1 (PC20) was calculated.Sputum eosinophils (range 0-61%), sputum ECP (range 24-10,800 µg·L -1 ) and serum ECP (range 4-61 µg·L -1 ) were significantly greater in asthmatics than in normal subjects, and distinguished the most severe group with the highest Aas score from the others. Sputum eosinophils and sputum ECP were strongly related to each other. The relationships between sputum or serum ECP and PC20 (range 0.016-7.5 mg·mL -1 ), and between sputum ECP and FEV1 were found to be weak.In conclusion, sputum outcomes of eosinophil activation and serum eosinophilic cationic protein appear to be useful indicators of disease. They do not accurately reflect current clinical or functional indices of asthma severity in chronic stable patients, and might therefore provide complementary data disease monitoring.

The inter-relationship between the perception of bronchoconstriction, bronchial hyper-responsiveness and temporal adaptation in asthma is still a matter of debate. In a total of 52 stable asthmatic patients, 32 without airway obstruction ¿forced expiratory volume in 1 s (FEV(1))/vital capacity (VC) 84.1% (S.D. 7.9%), and 20 with airway obstruction [FEV(1)/VC 60% (4%)], we assessed the perception of bronchoconstriction during methacholine inhalation by using: (i) the slope and intercept of the Borg and VAS (Visual Analog Scale) scores against the decrease in FEV(1), expressed as a percentage of the predicted value; and (ii) the Borg and VAS scores at a 20% decrease in FEV(1) from the lowest post-saline level (PB(20)). Bronchial hyper-responsiveness was assessed as the provocative concentration of methacholine causing a 20% fall in FEV(1) (PC(20)FEV(1)). The reduction in FEV(1) was significantly related to the Borg and VAS scores, with values for the group mean slope and intercept of this relationship of 0.13 (S.D. 0.08) and -1.1 (3.02) for Borg, and 1.5 (1.19) and -12.01 (35) for VAS. PB(20) was 3 (1.75) with Borg scores and 34.6 (20.5) with VAS scores. Compared with the subgroup without airway obstruction, the obstructed subgroup exhibited similar slopes, but lower Borg and VAS intercepts. For similar decreases in FEV(1) (5-20% decreases from the lowest post-saline values), the Borg and VAS scores were lower in the non-obstructed than in the obstructed subgroup. PC(20)FEV(1) was significantly related to both Borg PB(20) and VAS PB(20) when considering all patients. When assessing the subgroups, PC(20)FEV(1) was related to Borg PB(20) and VAS PB(20) in the non-obstructed subjects, but not in the obstructed subjects. In neither subgroup was the log of the cumulative dose related to the Borg and VAS scores at the end of the test. We conclude that, unlike in previous studies, the ability to perceive acute bronchoconstriction may be reduced as background airflow obstruction increases in asthma. Bronchial hyper-responsiveness did not play a major role in perceived breathlessness in patients without airway obstruction, and even less of a role in patients with obstruction. The cumulative dose of agonist did not appear to influence the perception of bronchoconstriction.

Dyspnea is often used as a marker of asthma severity although a wide variation in dyspnea perception associated with bronchoconstriction (PB) has been described in asthmatic patients. Our hypothesis is that changes of airway inflammation, airway narrowing and hyperinflation may account for a part of the variability of breathlessness in spontaneous asthma attack. In asthmatic patients with exacerbation of the disease, we evaluated respiratory function, dyspnea (using visual Analogue Scale--VAS) and peak expiratory flow (PEF) values and variability (amplitude % mean), and sputum cellular and biochemical profile before (day I) and after (day II) therapy with i.v. corticosteroids and inhaled beta2-agonists, as appropriate. By day II, forced expiratory volume in 1 s (FEV1), inspiratory capacity (IC), PEF or VAS values and variability, sputum eosinophils and eosinophilic cationic protein (ECP) had improved. Improvement of dyspnea expressed as a decrease in VAS and reduction in variability of dyspnea sensation significantly correlated with increase in FEV1 %predicted value (%pv) (P=0.03; p=0.72 and P=0.02; p=0.74, respectively). No significant correlation was found between IC and VAS either in absolute values or as changes from days I and II, nor between sputum outcomes and PEF or VAS, regardless of how they were measured. We conclude that in acute asthmatic patients, dyspnea measurement, functional measurements and sputum analysis may be useful in monitoring disease activity, response to therapy and can provide different information on the state of the disease.