Margherita Neri

Inhaler mishandling remains common in real life and is associated with reduced disease control.

Proper inhaler technique is crucial for effective management of asthma and COPD. This multicentre, cross-sectional, observational study investigates the prevalence of inhaler mishandling in a large population of experienced patients referring to chest clinics; to analyze the variables associated with misuse and the relationship between inhaler handling and health-care resources use and disease control. We enrolled 1664 adult subjects (mean age 62 years) affected mostly by COPD (52%) and asthma (42%). Respectively, 843 and 1113 patients were using MDIs and DPIs at home; of the latter, the users of Aerolizer®, Diskus®, HandiHaler® and Turbuhaler® were 82, 467, 505 and 361. We have a total of 2288 records of inhaler technique. Critical mistakes were widely distributed among users of all the inhalers, ranging from 12% for MDIs, 35% for Diskus® and HandiHaler® and 44% for Turbuhaler®. Independently of the inhaler, we found the strongest association between inhaler misuse and older age (p = 0.008), lower schooling (p = 0.001) and lack of instruction received for inhaler technique by health caregivers (p < 0.001). Inhaler misuse was associated with increased risk of hospitalization (p = 0.001), emergency room visits (p < 0.001), courses of oral steroids (p < 0.001) and antimicrobials (p < 0.001) and poor disease control evaluated as an ACT score for the asthmatics (p < 0.0001) and the whole population (p < 0.0001). We conclude that inhaler mishandling continues to be common in experienced outpatients referring to chest clinics and associated with increased unscheduled health-care resource use and poor clinical control. Instruction by health caregivers is the only modifiable factor useful for reducing inhaler mishandling.

Metabolic syndrome in obstructive sleep apnea and related cardiovascular risk

Background There is little evidence available about the relationship between metabolic syndrome as a comprehensive clinical entity and obstructive sleep apnea (OSA) with respect to the cardiovascular risk of patients with coexisting metabolic syndrome and OSA. Methods Eighty-nine consecutive patients (males 85%, aged 62 ± 11 years) with newly-diagnosed OSA were evaluated for the presence of metabolic syndrome and the incidence of cardiovascular events after implementation of continuous positive airway pressure (CPAP) therapy was registered during medium-term follow-up. The diagnosis of OSA and metabolic syndrome was obtained by overnight polygraphy [with a presence of an apnea-hypopnea index (AHI) ≥ 15] and following NCEP ATP III recommendations, respectively. Results Forty-seven (53%) OSA patients had coexisting metabolic syndrome, with increased waist circumference (98%), high blood pressure (89%) and decreased high-density lipoprotein-cholesterol (83%) as the most frequent features. OSA patients with metabolic syndrome were also younger (58 ± 11 years versus 65 ± 4 years, P < 0.001) and presented an higher AHI (43.5 ± 20.2 versus 34.8 ± 17.3, P < 0.05) as compared to those without metabolic syndrome. Follow-up lasted 22 ± 10 months. OSA patients who also presented metabolic syndrome suffered events less frequently compared to those who did not (6% versus 24%, P < 0.05), whereas the single end-points for follow-up (i.e. death, acute coronary syndrome, cerebrovascular event, peripheral vascular event, venous thromboembolism) did not significantly differ between the two groups. Conclusions Metabolic syndrome was a frequent comorbidity in OSA patients, reflecting higher degrees of sleep-disordered breathing, and did not increase the risk of cardiovascular events after adoption of CPAP therapy.

Bronchial vascular remodelling in patients with COPD and its relationship with inhaled steroid treatment

Background: Only a few studies have evaluated microvascular changes and proangiogenetic mediators in the bronchial mucosa of patients with chronic obstructive pulmonary disease (COPD), and the results have been discordant. Furthermore, the role of inhaled corticosteroids (ICS) in COPD has not been extensively studied. A study was undertaken to evaluate vascular remodelling, its relationship with inflammatory cells and treatment effects in the bronchial mucosa of patients with COPD. Methods: The study comprised three groups: (1) 10 non-treated patients with COPD (COPD); (2) 10 patients with COPD treated with nebulised beclomethasone dipropionate 1600–2400 μg daily (equivalent to 800–1200 μg via metered dose inhaler) (COPD/ICS); and (3) 8 control subjects (CS). Bronchial biopsies were evaluated for number and size of vessels and vascular area. Specimens were also examined for vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and transforming growth factor β (TGF-β) expression and inflammatory cell counts were performed. Results: Vascular area, vessel size, VEGF+ cells, bFGF+ cells and TGF-β+ cells were significantly increased in the COPD group compared with the COPD/ICS and CS groups (all p<0.05). In addition, bFGF+ cells were significantly increased in the COPD/ICS group compared with the CS group, and CD8+ and CD68+ cells were significantly increased in the COPD group compared with the COPD/ICS and CS groups (p<0.05). In the COPD group the VEGF+ cells correlated with the number of vessels (p<0.05), vascular area (p<0.01) and vessel size (p<0.05), and TGF-β+ cells correlated significantly with vascular area (p<0.05). Conclusion: Bronchial vascular remodelling in patients with COPD is mainly related to morphological changes of the mucosal microvessels rather than to new vessel formation, and may be reduced in patients treated with steroids.

Validation of the surveillance system for new cases of tuberculosis in a province of Northern Italy

In Italy tuberculosis (TB) surveillance is hampered by several problems (inconsistency of data and underreporting). A tuberculosis surveillance system was established in Varese Province (VSS) in 1992. The aim of the present study was, using VSS, to estimate: 1) coverage and validity of data collected by the national Compulsory Surveillance System (CSS); 2) validity of diagnosis and risk factors for tuberculosis; 3) tuberculosis incidence. A specifically designed form, including the same items as the CSS form and 10 more questions on risk factors and diagnostic issue, was completed in all the existing health facilities in the province for each new tuberculosis case diagnosed, collected by the study co-ordinator during monthly supervision after a review of clinical records, and stored in a database at the co-ordinating centre. Routine notifications collected at national level by CSS for the province were nominally linked with VSS data. To evaluate coverage and data validity, a comparison was made between VSS and CSS data after removal of duplicates. Quality of data, risk factors and incidence were evaluated on VSS data (gold standard). CSS coverage was 63% with a significant underreporting of extrapulmonary cases. Within CSS, 20% of data were missing (particularly diagnostic information: 42-72%). According to VSS, smear was performed on 88% of cases and culture on 66%. Half of the cases had no risk factors. The overall incidence of tuberculosis in Varese Province was 15 per 100,000. We estimated the coverage and validity of the data collected by CSS, validity of diagnosis, risk factors for and incidence of tuberculosis and proposed several suggestions to improve CSS nationwide.

Bronchoalveolar lavage causes decrease in PaO2, increase in (A-α) gradient value and bronchoconstriction in asthmatics

The aims of this study were to (1) record the changes of (arterial oxygen partial pressure) PaO2, (arterial carbon dioxide partial pressure) PaCO2, (percentage saturation of haemoglobin with oxygen in arterial blood) SaO2 and alveolar-arterial (A-a) oxygen gradiant resulting from bronchoalveolar lavage (BAL) in asthmatic and normal subjects; (2) measure changes in forced expiratory volume in 1 s (FEV1), vital capacity forced (FVC) associated with BAL; and (3) assess possible predictive factors for the degree of hypoxaemia and impairment of spirometry resulting from BAL. Bronchoscopy and BAL (150 ml) were performed in 24 asthmatics and 15 healthy subjects. Serial arterial blood samples (radial artery) were obtained in all subjects: T1 and before T2 after local anaesthesia; T3 at end of bronchoscopy; T4 after BAL and 5 min, 15 min, 1 h, 2 h, 8 h and 24 h (T5-T10) after the procedure, FEV1 and FVC were measured immediately before and 5 min afer bronchoscopy. Baseline PaO2 was lower in asthmatics (10.2 +/- 0.8 kPa) than in healthy subjects (10.8 +/- 0.8). Both groups showed a significant decrease in PaO2, and a significant widening in (A-a) oxygen tension gradiant at T3-9, with respect to T1 (P < 0.05). PaO2 reached a significantly lower value in asthmatics (7.1 +/- 0.6 kPa) than in HS (7.7 +/- 0.5; P < 0.05). In asthmatics, FEV1, FVC and the ratio FEV1/FVC decreased significantly after BAL (P < 0.001). In healthy subjects, FEV1 and FVC decreased significantly (P < 0.001), whereas FEV1/FVC did not. The fall in FEV1 after BAL was significantly greater in asthmatics (32.4 +/- 10.0%) than in healthy subjects (17.7 +/- 4.6; P < 0.001). Severity of asthma, basline FEV1 or initial PaO2 did not predict the degree of hypoxaemia or the fall of FEV1. It is concluded that BAL causes more severe hypoxaemia and a greater decrease in FEV1 in asthmatics compared to healthy subjects, strongly supporting the recommendation of special caution and careful monitoring when BAL is undertaken in asthmatics.

Chronic bronchial asthma from challenge to treatment: epidemiology and social impact

Asthma is an important cause of chronic morbidity and a crucial health problem among children and adults worldwide, with high prevalence rates particularly in many developed countries.1 2 Increasing morbidity, hospital admission rates, use of medical services, drug use and, in some countries, increasing mortality rates have been reported.3 However, controversy still exists regarding the epidemiology of asthma. There are two serious problems which need to be considered when trying to obtain reliable data on the prevalence, morbidity, and mortality of asthma. The first relates to definition; despite substantial advances in understanding the pathogenesis, genetics, and clinical characteristics of asthma, we do not have a useful definition of asthma for epidemiological purposes.2 The second problem concerns the different methods used to collect epidemiological data and information. More recently two international studies—the European Community Respiratory Health Survey (ECRHS)4 and the International Study of Asthma and Allergies in Childhood (ISAAC)5—have used the same internationally standardised questionnaire to provide important data on the prevalence of asthma. In the ISAAC study the prevalence of symptoms in 13–14 years old subjects was highly …

Validity and reproducibility of morphologic analysis of nasal secretions obtained using ultrasonic nebulization of hypertonic solution

BACKGROUND Collection of nasal secretions is important for the evaluation of upper airways inflammation in many nasal disorders. OBJECTIVE To study the validity and reproducibility of nasal secretion cellularity induced by nebulization of hypertonic solution in patients with allergic rhinitis (AR), patients with nonallergic rhinitis with eosinophilia syndrome (NARES), and control subjects. METHODS Sixty-eight individuals (29 with AR [mean +/- SD age, 33.3 +/- 16.9 years], 23 with NARES [mean +/- SD age, 46.4 +/- 16.6 years], and 16 controls [mean +/- SD age, 42.1 +/- 15.1 years]) underwent ultrasonic nebulization of hypertonic (4.5%) saline solution on 2 different occasions to study the validity and reproducibility of total and differential cell counts of nasal secretions. RESULTS The mean +/- SD percentage of eosinophils was significantly higher in samples from patients with AR (20.8% +/- 23.1%) and NARES (18.7% +/- 22.8%) than in samples from controls (0.6% +/- 0.6%; P < .001 for both). There was a significant correlation between 2 samples of nasal secretions obtained on 2 different occasions for percentages of macrophages, neutrophils, eosinophils, and epithelial cells. CONCLUSIONS The analysis of nasal secretions obtained using ultrasonic nebulization of hypertonic solution can distinguish patients with AR and NARES from controls. The reproducibility of this technique is good for macrophages, neutrophils, eosinophils, and epithelial cells. This method could be used to detect nasal airway inflammation in clinical settings.

Time Required to Rectify Inhaler Errors Among Experienced Subjects With Faulty Technique

BACKGROUND: Regardless of the device used, many patients have difficulty maintaining proper inhaler technique over time. Repeated education from caregivers is required to ensure persistence of correct inhaler technique, but no information is available to evaluate the time required to rectify inhaler errors in experienced users with a baseline faulty technique and whether this time of re-education to restore inhaler mastery can differ between devices. METHODS: This was a multi-center, single-visit, open-label, cross-sectional study in a large group of 981 adult subjects (mean ± SD age 64 ± 15 y) experienced with inhaler use, mainly suffering from COPD and asthma, who showed faulty inhaler technique at a follow-up visit in chest clinics. These subjects received face-to-face practical education from trained caregivers until proper inhaler use could be demonstrated, and the time of instruction was recorded. RESULTS: The mean times (95% CIs) in minutes of instruction required for rectifying misuse and demonstrating inhaler mastery were 5.0 (3.6–6.4) min for the Diskus (n = 199), 5.3 (3.7–6.8) min for the HandiHaler (n = 219), 8.1 (5.6–10.5) min for the metered-dose inhaler (MDI) (n = 532), and 6.0 (5.0–7.0) min for the Turbuhaler (n = 169). The time to demonstrate good inhaler use for MDIs was higher (P < .05) than for all dry powder inhalers (DPIs). Between the DPIs, only the HandiHaler required more time for achieving mastery than the Diskus (P = .005). The variables associated with increasing time for correcting inhaler errors were an older age (0.05 min/y, 95% CI 0.03–0.07), a lower level of education (0.4 min/schooling level, 95% CI 0.7–0.1), and no reported previous instruction in inhaler use (1.96 min, 95% CI 1.35–2.58). CONCLUSIONS: In experienced subjects with baseline faulty inhaler use, the mean time of education required to achieve and demonstrate mastery with DPIs was lower than with MDIs.