Comorbidities are associated with different features of severe asthma.

BACKGROUND: According to ATS/ERS document on severe asthma (SA), the management of these patients requires the identification and proper treatment of comorbidities, which can influence the control of asthma. METHODS: The aim of this study was to assess the independent effect of different comorbidities on clinical, functional and biologic features of SA. Seventy-two patients with SA according to GINA guidelines were examined. We collected demographic data, smoking habit, asthma history, and assessment of comorbidities. Pulmonary function, inflammatory biomarkers, upper airway disease evaluation, asthma control and quality of life were carefully assessed. RESULTS: The mean age of patients was 59.1 years (65.3% female, 5.6% current smokers). Comorbidities with higher prevalence were: chronic rhinosinusitis with or without nasal polyps (CRSwNP or CRSsNP), obesity and gastro-esophageal reflux (GERD), with some overlapping among them. In an univariate analysis comparing patients with single comorbidities with the other ones, asthmatics with CRSwNP had lower lung function and higher sputum eosinophilia; obese asthmatics had worse asthma control and quality of life, and tended to have lower sputum eosinophils; asthmatics with GERD showed worse quality of life. In multivariate analysis, obesity was the only independent factor associated with poor asthma control (OR 4.9), while CRSwNP was the only independent factor associated with airway eosinophilia (OR 16.2). Lower lung function was associated with the male gender and longer duration of asthma (OR 3.9 and 5.1, respectively) and showed a trend for the association with nasal polyps (OR 2.9, p = 0.06). CONCLUSION: Our study suggests that coexisting comorbidities are associated with different features of SA.

Asthma control test (ACT): comparison with clinical, functional, and biological markers of asthma control.

BACKGROUND: Asthma Control Test (ACT) is a simple tool for assessing the level of asthma control in clinical practice, and it has been validated in comparison with a general clinical assessment of asthma control, including forced expiratory volume in the first second (FEV(1)). OBJECTIVE: To evaluate the relationship between ACT score and clinical and functional findings of asthma control and biomarkers of airway inflammation. METHODS: A total of 68 asthmatic patients observed in our asthma clinic (33 regularly treated with inhaled corticosteroids (ICS) and 35 ICS-naïve) filled ACT questionnaire and underwent the following measurements: (a) FEV(1) before and after salbutamol; (b) exhaled nitric oxide; (c) bronchial hyperresponsiveness to methacholine; (d) sputum eosinophil count; and (e) daytime and nighttime symptoms, rescue salbutamol, and twice-daily peak expiratory flow (PEF) recording on a 4-week diary card. RESULTS: ACT score significantly correlated with symptom score, rescue medication use, and PEF variability, but not with FEV(1), FEV(1) reversibility, and markers of airway inflammation, which could not distinguish controlled from uncontrolled patients according to ACT, regardless of ICS treatment. CONCLUSION: ACT score is a valid tool to simply assess the current level of asthma control in terms of symptoms, rescue medication use, and PEF variability. Pulmonary function and biomarkers of airway inflammation are not related to the clinical asthma control as assessed by ACT and may represent additional measurements potentially useful in asthma management.

Beclomethasone dipropionate blunts allergen-induced early increase in urinary LTE4.

BACKGROUND: The inhibitory effect of corticosteroids (CS) on the secretions of cysteinyl-leukotrienes (Cys-LTs) in asthma is controversial. The aim of this study was to evaluate the effect of CS on allergen-induced increase in urinary leukotriene E4 (uLTE4) during early (EAR) and late (LAR) asthmatic responses in mild untreated asthmatics. MATERIAL AND METHODS: Nine subjects with mild untreated allergic asthma performed two allergen challenges, after 1-week treatment with beclomethasone dipropionate (BDP, 500 microg b.i.d) or placebo. Forced Expiratory Volume in one second 1 (FEV1) was monitored to assess EAR and LAR, and uLTE4 was measured before and during EAR and LAR. RESULTS: After placebo, uLTE4 increased significantly during EAR, but not during and after LAR, in comparison with baseline values. Beclomethasone dipropionate induced a significant attenuation of the uLTE4 increase during EAR, in comparison with placebo, in association with a good protection of LAR (P = 0.002) and a mild protection of EAR (P = 0.07). CONCLUSIONS: Beclomethasone dipropionate blunts the early increase in uLTE4 excretion due to allergen challenge, in association with a significant effect on the severity of LAR. These data support the hypothesis that inhaled CS may inhibit the allergen-induced release of cys-LTs in asthma.

Biological markers in induced sputum of patients with different phenotypes of chronic airway obstruction.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease characterized by a combination of 3 different disorders, namely chronic asthma, chronic bronchitis and pulmonary emphysema, sometimes simultaneously present in the same subject. OBJECTIVES: The aim of our study was to compare sputum inflammatory markers in patients with different phenotypes of chronic airway obstruction. METHODS: Forty-five subjects (forced expiratory volume in 1 s/vital capacity, FEV(1)/VC: 58.8 +/- 12.2%; FEV(1): 49.8 +/- 11.5% of predicted) were classified as chronic asthma (n = 10) or COPD patients (n = 35); the latter were further divided into patients with prevalent chronic bronchitis (n = 24) or prevalent pulmonary emphysema (n = 11) according to clinical history and functional evaluation, and underwent sputum induction and analysis of inflammatory cell and soluble mediators. RESULTS: Patients with chronic asthma showed higher sputum eosinophil percentages and eosinophilic cationic protein levels, and lower neutrophil percentages and neutrophil elastase levels than COPD patients. Neutrophil chemotactic activity in sputum supernatant was higher than the pool of normal subjects both in chronic asthma and COPD patients. No difference in sputum cell composition and levels of soluble mediators was observed between patients with chronic bronchitis and patients with pulmonary emphysema. CONCLUSIONS: The pattern of airway inflammation in induced sputum of patients with chronic asthma is different from that of COPD patients with a similar FEV(1). Among COPD patients, however, the pattern of airway inflammation shows no difference between chronic bronchitis and patients with pulmonary emphysema, suggesting that these two clinically and functionally distinct phenotypes share a common inflammatory pattern as detected by induced sputum.

Tolerance to the protective effect of salmeterol in mild untreated asthmatics.

The aim of this study was to assess the distribution of the occurrence of tolerance to the protective effect of salmeterol on allergen challenge in a large sample of asthmatic subjects. We investigated 53 subjects (45 male and eight female), mean age 24+/-8.2 years, with mild intermittent asthma, in stable phase of the disease, never previously treated with regular beta2-agonists. All subjects with a previous positive early airway response (EAR) to a screening allergen challenge underwent, in double blind randomized, cross-over manner, three further allergen challenges: after placebo (T0), after a single dose (50 microg) of inhaled salmeterol (T1), and after regular treatment with inhaled salmeterol (50 microg bid) for 1 week (T2). All subjects showed an EAR after placebo treatment (T0), and were completely protected against EAR by the single dose of salmeterol (T1). After 1-week regular treatment with salmeterol (T2). 24 out of 53 subjects (45%) were still protected, whereas 29 subjects (55%) showed a significant EAR. The distribution of the response to allergen challenge, which was quite homogeneous at T0 and T1, showed considerable heterogeneity at T2. Tolerance to the protective effect of salmeterol on allergen challenge can be observed in a large group of previously untreated mild asthmatic subjects. This phenomenon is heterogeneously distributed, with some subjects still showing a complete protection similar to that obtained after a single dose of salmeterol and others showing a response similar to that obtained after placebo. The reason of this heterogeneity needs to be elucidated.