Spirometric Changes in Bronchodilation Tests as Predictors of Asthma Diagnosis and Treatment Response in Patients with FEV1 ≥ 80% Predicted.

BACKGROUND: Many patients with mild asthma are undiagnosed and untreated due to the low diagnostic sensitivity of bronchodilation test (BDT). OBJECTIVE: To investigate whether airway reversibility in BDT and fractional exhaled nitric oxide (Feno) can predict the response to antiasthma therapy (RAT) in patients with suspected asthma. METHODS: This open-label, prospective cohort study included patients with chronic recurrent asthma symptoms, normal FEV1, and negative BDT results. Inhaled corticosteroids and long-acting ß agonists were given for 4 weeks. A positive RAT was defined as improved symptoms and an increase of more than 200 mL in FEV1 after inhaled corticosteroid/long-acting ß agonist treatment. Lung tissues from another 19 patients who underwent pneumectomy for lung nodules were also analyzed. RESULTS: Of 110 patients recruited, 102 completed the study. Patients in the positive RAT group had a higher Feno and greater absolute (Δ) and percent (Δ%) improvements in forced vital capacity, FEV1, and forced expiratory flows (FEFs) in BDT than in the negative RAT group. The area under the curves of Feno, ΔFEV1%, ΔFEF25-75% (percent improvement in FEF at 25%-75% of forced vital capacity), and ΔFEF75% (percent improvement in FEF at 75% of forced vital capacity) for positive RAT were 0.703, 0.824, 0.736, and 0.710, with cutoff values of 33 parts per billion and 3.50%, 15.26%, and 26.04%, respectively. A joint model of Feno and ΔFEV1% increased the area under the curve to 0.880. Inflammatory cytokines were higher in the lung tissues of patients with predicted positive RAT than in those with predicted negative RAT. CONCLUSIONS: ΔFEV1% in BDT together with Feno predicted a positive RAT and an asthma diagnosis in patients with a normal FEV1 and negative BDT. Evidence of pathological changes increases the credibility of the predictive model.

Application of Inflammatory Markers in Induced Sputum in Stable Chronic Obstructive Pulmonary Disease Patients with Positive Bronchodilation Tests.

Positive bronchodilation (BD) tests can be noticed in some stable chronic obstructive pulmonary disease (COPD) patients. The characteristics of airway inflammation in this entity remain unclear. Our study aimed to identify the characteristics of airway inflammation in stable COPD patients with positive BD tests. The airway inflammation was assessed in 88 patients with stable COPD using the examination of induced sputum in the aftermath of lung function and BD tests. Cellular counts and the levels of molecular markers including eosinophil cationic protein (ECP), myeloperoxidase (MPO), interleukin-5 (IL-5), and IL-8 were assayed by Wright's stain, Immuno-CAP system, and ELISA, RT-PCR. Among the 88 patients with stable COPD, 20 (22.7%) showed positive BD tests. The values of eosinophils (4.7%±3.4%) and ECP (90.1±41.6 ng/mL) in induced sputum in stable COPD patients with positive BD tests were markedly elevated as compared with those in stable COPD patients with negative BD tests or in healthy controls (all P>0.05), but significantly lower than those in asthmatic patients (all P<0.01). The IL-5 in sputum supernatant was significantly decreased in stable COPD patients with positive BD tests as compared with the patients with asthma (12.5±7.8 vs. 48.2±26.0 ng/mL;.P<0.01). However, healthy controls exhibited similar concentrations of IL-5 in induced sputum with patients with stable COPD, whether with positive or negative BD tests (all P>0.05). Moreover, the values of neutrophils (61.8%±15.1%), MPO (574.0±111.8 ng/mL), and IL-8 (32.6±13.4 ng/mL) in induced sputum in stable COPD patients with positive BD tests were significantly higher than those in asthmatics or normal controls (all P<0.01). However, the values of the above inflammatory markers in induced sputum were similar among stable COPD patients with positive or negative BD tests (all P>0.05). The stable COPD patients with positive BD tests may present not only eosinophilic airway inflammation but also neutrophilic airway inflammation.