Marcello Ferrari

The Coexistence of Asthma and Chronic Obstructive Pulmonary Disease (COPD): Prevalence and Risk Factors in Young, Middle-aged and Elderly People from the General Population

Background The joint distribution of asthma and chronic obstructive pulmonary disease (COPD) has not been well described. This study aims at determining the prevalence of self-reported physician diagnoses of asthma, COPD and of the asthma-COPD overlap syndrome and to assess whether these conditions share a common set of risk factors. Methods A screening questionnaire on respiratory symptoms, diagnoses and risk factors was administered by mail or phone to random samples of the general Italian population aged 20–44 (n = 5163) 45–64 (n = 2167) and 65–84 (n = 1030) in the frame of the multicentre Gene Environment Interactions in Respiratory Diseases (GEIRD) study. Results A physician diagnosis of asthma or COPD (emphysema/chronic bronchitis/COPD) was reported by 13% and 21% of subjects aged <65 and 65–84 years respectively. Aging was associated with a marked decrease in the prevalence of diagnosed asthma (from 8.2% to 1.6%) and with a marked increase in the prevalence of diagnosed COPD (from 3.3% to 13.3%). The prevalence of the overlap of asthma and COPD was 1.6% (1.3%–2.0%), 2.1% (1.5%–2.8%) and 4.5% (3.2%–5.9%) in the 20–44, 45–64 and 65–84 age groups. Subjects with both asthma and COPD diagnoses were more likely to have respiratory symptoms, physical impairment, and to report hospital admissions compared to asthma or COPD alone (p<0.01). Age, sex, education and smoking showed different and sometimes opposite associations with the three conditions. Conclusion Asthma and COPD are common in the general population, and they coexist in a substantial proportion of subjects. The asthma-COPD overlap syndrome represents an important clinical phenotype that deserves more medical attention and further research.

Allergic rhinitis and asthma comorbidity in a survey of young adults in Italy

Background:  Several studies have provided evidence of a strong association between asthma and allergic or nonallergic rhinitis, leading to the hypothesis that allergic rhinitis (AR) and asthma represent a continuum of the same disease.

The impact of climate and traffic-related NO2 on the prevalence of asthma and allergic rhinitis in Italy

Background Environmental factors are likely to be involved in explaining the wide geographical variation in asthma and atopic diseases that has been documented in many recent epidemiological studies.

Sleep apnoea syndrome is highly prevalent in acromegaly and only partially reversible after biochemical control of the disease

BACKGROUND Whether sleep apnoea syndrome (SAS) subsides after biochemical and clinical remission of acromegaly is controversial. OBJECTIVE To assess the presence of SAS in a cohort of acromegalic patients, which included a subgroup with active disease and a subgroup in remission, and to evaluate clinical and biochemical independent predictors of SAS. DESIGN Cross-sectional and longitudinal study. SETTING Italian university department of internal medicine. PATIENTS About 36 acromegalic patients: 18 active and 18 controlled. MEASUREMENTS Polysomnography was performed in all patients and repeated in six with active acromegaly and SAS after achieving disease control. Echocardiographic parameters were also measured. RESULTS The prevalence of SAS was 47% in the overall acromegalic population: 56% in the active group and 39% in the controlled one. In a multivariate analysis IGF1, male gender, age, body mass index, and disease duration were associated with SAS. Impaired glucose tolerance or diabetes was more prevalent in patients with SAS, particularly in the severe cases. Among the six patients of the longitudinal study, five showed improvement of SAS, but none recovered. No correlation was found between echocardiographic parameters and severity of SAS. CONCLUSION SAS can persist after recovery of acromegaly in several patients. Given the negative prognostic significance of this respiratory disorder, polysomnography should be included as routine procedure in the work-up of the acromegaly, even if in remission, being mandatory in those patients considered at high risk (elderly males, overweight, diabetic). Appropriate intensive treatment should be implemented to minimize the clinical impact of SAS in acromegaly.

The role of climate on the geographic variability of asthma, allergic rhinitis and respiratory symptoms: results from the Italian study of asthma in young adults

Background:  Variations in the prevalence of respiratory symptoms according to geo‐climatic factors could provide important clues to the knowledge of the aetiology of asthma.

Cough threshold in reflux oesophagitis: influence of acid and of laryngeal and oesophageal damage

BACKGROUND Gastro-oesophageal reflux is often associated with cough. Patients with reflux show an enhanced tussive response to bronchial irritants, even in the absence of respiratory symptoms. AIM To investigate the effect of mucosal damage (either oesophageal or laryngeal) and of oesophageal acid flooding on cough threshold in reflux patients. PATIENTS We studied 21 patients with reflux oesophagitis and digestive symptoms. Respiratory diseases, smoking, and use of drugs influencing cough were considered exclusion criteria. METHODS Patients underwent pH monitoring, manometry, digestive endoscopy, laryngoscopy, and methacholine challenge. We evaluated the cough response to inhaled capsaicin (expressed as PD5, the dose producing five coughs) before therapy, after five days of omeprazole therapy, and when oesophageal and laryngeal damage had healed. RESULTS In all patients spirometry and methacholine challenge were normal. Thirteen patients had posterior laryngitis and eight complained of coughing. Twenty patients showed an enhanced cough response (basal PD5 0.92 (0.47) nM; mean (SEM)) which improved after five and 60 days (2.87 (0.82) and 5.88 (0.85) nM; p<0.0001). The severity of oesophagitis did not influence PD5 variation. On the contrary, the response to treatment was significantly different in patients with and without laryngitis (p=0.038). In patients with no laryngitis, the cough threshold improved after five days with no further change thereafter. In patients with laryngitis, the cough threshold improved after five days and improved further after 60 days. Proximal and distal oesophageal acid exposure did not influence PD5. Heartburn disappeared during the first five days but the decrease in cough and throat clearing were slower. CONCLUSIONS Patients with reflux oesophagitis have a decreased cough threshold. This is related to both laryngeal inflammation and acid flooding of the oesophagus but not to the severity of oesophagitis. Omeprazole improves not only respiratory and gastro-oesophageal symptoms but also the cough threshold.

Tobacco Smoke Exposure and Serum Cotinine in a Random Sample of Adults Living in Verona, Italy

Abstract In this study, the authors attempted to validate answers to smoking-habit questions contained in the European Community Respiratory Health Survey questionnaire. The respondents were invited to visit the chest clinic at Verona, Italy, and their serum cotinine levels were measured. The authors invited each of 504 subjects to complete a respiratory interview and to give a blood sample for a radioimmunoassay serum cotinine measurement. A total of 375 subjects responded, of whom 129 were smokers (34.4%), 79 were exsmokers (21.1%), and 167 (44.5%) had never smoked. Exposure to environmental tobacco smoke was reported by 216 subjects (57.6% [mean exposure = 3.8 hr/day {± 3.4 hr/day standard deviation}]). In smokers, serum cotinine levels were directly related to the number of cigarettes smoked/day. The authors excluded from analysis nonsmokers who had serum cotinine levels that were ≥ 14 ng/ml, and the resulting mean values were 1.7 ng/ml (± 2.1 ng/ml standard deviation) in nonsmokers unexposed to environmental tobacco smoke and 2.6 ng/ml (± 2.6 ng/ml standard deviation) (p < .002) in nonsmokers exposed to environmental tobacco smoke. There was a relationship between serum cotinine levels and hours of exposure to environmental tobacco smoke (R 2 = .136, p < .05). Serum cotinine, which is an objective and accepted measure of tobacco exposure, confirmed the validity of the European Community Respiratory Health Survey questionnaire with respect to smoking habits and environmental tobacco smoke exposure.

Substrate-product relation of 1-hydroxylase activity in primary hyperparathyroidism.

The synthesis of the active form of vitamin D, 1,25-dihydroxyvitamin D (1,25-(OH)2D), is thought to be relatively insensitive to the serum concentration of its precursor, 25-hydroxyvitamin D (25-OH-D). We compared the effect of oral administration of 25-OH-D3 (50 micrograms per day for one month) on serum concentrations of calcium, phosphate, parathyroid hormone, 25-OH-D, and 1,25-(OH)2D in five healthy adults and in six patients with primary hyperparathyroidism. In normal adults the mean (+/- S.D.) serum level of 25-OH-D rose from 18 +/- 9 to 136 +/- 47 ng per milliliter; no significant changes were observed in the other serum levels. In contrast, comparable increases in the levels of circulating 25-OH-D in patients with primary hyperparathyroidism caused a consistent slight rise in serum calcium and phosphate levels, a partial suppression of parathyroid hormone, and a sharp increase in the level of 1,25-(OH)2D. During this period a significant positive correlation was found between serum concentrations of 25-OH-D and 1,25-(OH)2D (P less than 0.001). These results provide evidence that in patients with primary hyperparathyroidism, levels of circulating 1,25-(OH)2D may be more dependent on the prevailing serum concentrations of 25-OH-D than they are in normal adults.

Evidence of the rapid protective effect of formoterol dry-powder inhalation against exercise-induced bronchospasm in athletes with asthma.

Background: Although formoterol, a new long-acting β2-adrenergic agonist, has a rapid bronchodilating action, no studies have previously examined whether it can provide equally rapid protection against exercise-induced bronchospasm (EIB). Aim: The aim of the study was to assess the effect of inhaled formoterol against EIB 15 min and 4 h after administration in asthmatic athletes. Methods: The protective effect of a formoterol (12 µg) dry-powder inhalation was evaluated in 14 EIB-positive asthmatic athletes (13 males, mean age 16.8 years), in a double-blind, placebo-controlled, two-period cross-over study. On each treatment day, the subjects underwent two cycloergometric exercise tests 15 min and 4 h after receiving formoterol or placebo. Results: Formoterol induced significant bronchodilation in comparison with placebo both 15 min and 4 h after administration (p = 0.007 and p = 0.004); placebo treatment had no effect on EIB, the maximum percent fall in FEV1 after exercise being 29.3 ± 14.3% and 22.9 ± 13.7% at 15 min and 4 h, respectively. Formoterol offered good protection against EIB in 12 athletes (86%) who experienced a decrease in FEV1 after exercise <10% both 15 min and 4 h after administration. The mean maximum percent fall in FEV1 after formoterol was 5.9±7.2% at 15 min (p < 0.0001), and 5.8 ± 6.9% at 4 h (p < 0.0001). There was no statistically significant difference in resting heart rate before and after medication with placebo or formoterol, nor was the heart rate at the end of exercise significantly different on the 2 treatment days. No side effect was observed in either group. Conclusions: This study demonstrates that formoterol dry powder inhalation is effective in protecting asthmatic athletes as early as 15 min after dosing. Furthermore, the data confirm the long duration of its protective effect and the absence of any significant adverse effects after acute administration.

The Gene-Environment Interactions in Respiratory Diseases (GEIRD) project.

The role of genetic and environmental factors, as well as their interaction, in the natural history of asthma, allergic rhinitis and chronic obstructive pulmonary disease (COPD) is largely unknown. This is mainly due to the lack of large-scale analytical epidemiological/genetic studies aimed at investigating these 3 respiratory conditions simultaneously. The GEIRD project is a collaborative initiative designed to collect information on biomarkers of inflammation and oxidative stress, individual and ecological exposures, diet, early-life factors, smoking habits, genetic traits and medication use in large and accurately defined series of asthma, allergic rhinitis and COPD phenotypes. It is a population-based multicase-control design, where cases and controls are identified through a 2-stage screening process (postal questionnaire and clinical examination) in pre-existing cohorts or new samples of subjects. It is aimed at elucidating the role that modifiable and genetic factors play in the occurrence, persistence, severity and control of inflammatory airway diseases, by way of the establishment of a historical multicentre standardized databank of phenotypes, contributed by and openly available to international epidemiologists. Researchers conducting population-based surveys with standardized methods may contribute to the public-domain case-control database, and use the resulting increased power to answer their own scientific questions.