Effects of rituximab therapy on B cell differentiation and depletion.

Rituximab is a human/murine chimeric anti-CD20 monoclonal antibody. It is largely used to treat B cell malignancies and has become standard in the management of B cell­mediated diseases such as rheumatoid arthritis and granulomatosis with polyangitis. The effects of rituximab need to be monitored by B cell phenotyping. Evaluate possible surface markers for monitoring B cell development in response to rituximab treatment. This review discusses the literature on the B cell surface markers analysed by flow cytometry in patients treated with rituximab. A panel of biomarkers of response to treatment to monitor by flow cytometry is also suggested. B cell phenotyping is useful to predict clinical relapses after rituximab treatment. The proposed panel of biomarkers includes CD38++CD24++IgD+/- immature B cells and IgD-CD38+/- memory B cells. In responders, Th1/Th2 balance and tolerance cells (CD4+CD25+CD127-/low Treg cells and CD19+CD24hiCD38hi Breg cells) tend to be restored after rituximab therapy. Furthermore, in responder patients, indirect depletion of CD19+/-CD27++CD38++ preplasma cells can be proposed as a predictor of response. Flow cytometric analysis of samples from patients treated with rituximab is a useful strategy to stratify patients according to response to treatment. Identification of B cell differentiation stages by means of a specific flow cytometry panel could improve monitoring of rituximab effects and enable non-responders to be distinguished from good responders.

Omalizumab treatment in Samter's triad: case series and review of the literature.

OBJECTIVE: Samter's triad is the combination of asthma, aspirin sensitization, and nasal polyposis. Few data are available on the use of omalizumab in this disease. The study aimed to describe the impact of omalizumab on clinical and functional parameters and the quality of life of a series of patients with Samter's triad. Moreover, we aimed to provide a review of the literature on this topic. PATIENTS AND METHODS: We retrospectively described four patients with Samter's triad undergoing omalizumab therapy. Clinical, functional, and immunological data of these patients were collected at baseline and follow-up. RESULTS: Reduction of asthma exacerbations and salbutamol rescue therapy were observed in all patients after anti-IgE treatment together with an improvement in the quality of life. A significant improvement in FEV1, FVC, and FEF25-75 was observed. No major side-effects were observed. A total of 14 studies regarding omalizumab in aspirin-exacerbated respiratory diseases were included in the review, comprising 78 patients. All studies reported a good efficacy in improving asthma control; restoration of aspirin tolerance was repeatedly reported. CONCLUSIONS: The results of our case series and review of the literature suggest that omalizumab effectively improves asthma control, lung function tests, and quality of life in patients with Samter's triad.

NK and NKT-like cells in granulomatous and fibrotic lung diseases.

ABTRACT: Background The pathogenetic and regulatory roles of natural killer (NK) and natural killer T-like cells in interstitial lung diseases (ILDs), fibrotic and granulomatous of unknown etiology are unclear. Objectives Here we investigated NK and NKT-like cells in peripheral blood (PB) and Bronchoalveolar lavage (BAL) from patients with ILDs. Method 190 patients (94 male mean age 61 ± 14.3 years) and 8 controls undergoing bronchoscopy for ILD diagnostic work-up were enrolled consecutively; 115 patients sarcoidosis, 24 chronic fibrotic hypersensitivity pneumonitis and 43 patients other ILDs [32 idiopathic pulmonary fibrosis (IPF) and 11 non-specific interstitial pneumonia (NSIP)]. PB and BAL were processed by flow cytometry using monoclonal antibodies to differentiate NK and NKT-like cells. Results NK% in BAL was significantly different among ILDs (p = 0.02). Lower NK% was observed in BAL from sarcoidosis than other ILDs (p < 0.05). Similar findings were observed for NKT-like, whereas no differences were found for PB NK%. Difference of NK% was observed between BAL and PB in all groups (p < 0.001). Sarcoidosis patients reported the best area under the curve for NKT-like (AUC = 0.678, p = 0.0015) and NK cells (AUC = 0.61, p = 0.001). In the IPF-NSIP subgroup, NK% cell was inversely correlated with FVC% (r = - 0.34, p = 0.03) and DLCO% (r = - 0.47, p = 0.0044). Conclusions NK and NKT-like were expressed differently in BAL from patients with different ILD and were significantly depleted in sarcoidosis respect to other ILDs. This suggests that these cells may play a protective role in the pathogenesis of sarcoidosis.

Pleuroparenchymal fibroelastosis (PPFE) associated with giant cell arteritis: A coincidence or a novel phenotype?

Pleuroparenchymal fibroelastosis (PPFE) is a rare interstitial lung disease characterized by the fibrotic thickening of subpleural and parenchymal areas of the upper lobes. It may be both idiopathic or secondary to infections, interstitial lung diseases and/or drug exposure. Often PPFE patients report recurrent lower respiratory tract infections, suggesting that repeated inflammatory alterations induced by pulmonary infections may contribute to the development/progression of PPFE. Here, we report for the first time the case of a patient affected by Giant cell Arteritis with histologically proven PPFE. The lung involvement in GCA is rare and interstitial lung diseases are usually reported as an uncommon clinical manifestation of GCA. Our patient is probably the first case presenting PPFE associated with GCA and we wonder if this is a real associative disease or a coincidence perhaps, secondary to drug effects.

Pulmonary lymphatic vessel morphology: a review.

Our understanding of lymphatic vessels has been advanced by the recent identification of relatively specific lymphatic endothelium markers, including Prox-1, VEGFR3, podoplanin and LYVE-1. The use of lymphatic markers has led to the observation that, contrary to previous assumptions, human lymphatic vessels extend deep inside the pulmonary lobule, either in association with bronchioles, intralobular arterioles or small pulmonary veins. Pulmonary lymphatic vessels may thus be classified into pleural, interlobular (in interlobular septa) and intralobular. Intralobular lymphatic vessels may be further subdivided in: bronchovascular (associated with a bronchovascular bundle), perivascular (associated with a blood vessel), peribronchiolar (associated with a bronchiole), and interalveolar (in interalveolar septa). Most of the intralobular lymphatic vessels are in close contact with a blood vessel, either alone or within a bronchovascular bundle. A minority is associated with a bronchiole, and small lymphatics are occasionally present even in interalveolar septa, seemingly independent of blood vessels or bronchioles. The lymphatics of the interlobular septa often contain valves, are usually associated with the pulmonary veins, and connect with the pleural lymphatics. The large lymphatics associated with bronchovascular bundles have similar characteristics to pleural and interlobular lymphatics and may be considered conducting vessels. The numerous small perivascular lymphatics and the few peribronchiolar ones that are found inside the lobule are probably the absorbing compartment of the lung responsible for maintaining the alveolar interstitium relatively dry in order to provide a minimal thickness of the air-blood barrier and thus optimize gas diffusion. These lymphatic populations could be differentially involved in the pathogenesis of diseases preferentially involving distinct lung compartments.

School air quality related to dry cough, rhinitis and nasal patency in children.

Controls for indoor air quality (IAQ) in schools are not usually performed throughout Europe. The aim of this study was to assess the effects of IAQ on respiratory health of schoolchildren living in Norway, Sweden, Denmark, France and Italy. In the cross-sectional European Union-funded HESE (Health Effects of School Environment) Study, particulate matter with a 50% cut-off aerodynamic diameter of 10 microm (PM(10)) and CO(2) levels in a day of normal activity (full classroom) were related to wheezing, dry cough at night and rhinitis in 654 children (10 yrs) and to acoustic rhinometry in 193 children. Schoolchildren exposed to PM(10) >50 microg x m( -3) and CO(2) >1,000 ppm (standards for good IAQ) were 78% and 66%, respectively. All disorders were more prevalent in children from poorly ventilated classrooms. Schoolchildren exposed to CO(2) levels >1,000 ppm showed a significantly higher risk for dry cough (OR 2.99, 95% CI 1.65-5.44) and rhinitis (OR 2.07, 95% CI 1.14-3.73). By two-level (child, classroom) hierarchical analyses, CO(2) was significantly associated with dry cough (OR 1.06, 95% CI 1.00-1.13 per 100 ppm increment) and rhinitis (OR 1.06, 95% CI 1.00-1.11). Nasal patency was significantly lower in schoolchildren exposed to PM( 10) >50 microg x m(-3) than in those exposed to lower levels. A poor IAQ is frequent in European classrooms; it is related to respiratory disturbances and affects nasal patency.

Exhaled carbon monoxide in sarcoidosis.

BACKGROUND: Exhaled Carbon monoxide has been proposed as a non-invasive marker in several inflammatory diseases of the lung, but no data are available in patients with sarcoidosis. METHODS: We evaluated the levels of exhaled CO in 78 nonsmoker patients with sarcoidosis and we compared the results with 25 healthy non smoker controls, of 25 patients with a variety of interstitial lung diseases, and 77 smokers. RESULTS: Mean value of exhaled CO in sarcoidosis was 3.3 (2.9-3.8) ppm (GM with 95% CI in parenthesis), resulting significantly higher than both normal controls, 1.4 (1.2-1.7) ppm (p<0.001), and clinical controls, 2.1 (1.7-2.7) ppm (p<0.02). All these levels, however, were markedly lower than those observed in smokers, 14.6 (12.7-16.9) ppm. No correlation was found with radiological stage, steroid therapy, respiratory function, or serum ACE activity. Using an upper normal value of 4 ppm, an increased level of exhaled CO was found in 50% of patients with sarcoidosis, in 24% of clinical controls, and in 97% of smokers. CONCLUSIONS: Our data indicate that significant release of endogenous CO occurs in sarcoidosis. It is unlikely that the measurement of exhaled CO could be of diagnostic usefulness, due to its low specificity and to the possible influence by occasional or passive smoke.

Prevalence of respiratory symptoms in migrant children to Italy: the results of SIDRIA-2 study.

BACKGROUND: Epidemiological studies have documented large international variations in the prevalence of asthma, and 'westernization' seems to play an important role in the development of the disease. The aims of this study were to compare the prevalence of respiratory symptoms in migrant and nonmigrant children resident in Italy, and to examine the effect of length of time living in Italy. METHODS: Data were collected in a large cross-sectional study (SIDRIA-2) performed in 12 Italian centres, using standardized parental questionnaires. For the 29 305 subjects included in the analysis (6-7 and 13-14 years old), information about place of birth and parental nationality was available. RESULTS: There were 1012 children (3%) born outside of Italy, mainly in East Europe. Lifetime asthma and current wheeze were generally significantly less common among children born abroad than among children born in Italy (lifetime asthma: 5.4% and 9.7% respectively, P < 0.001; current wheeze: 5.2% and 6.9%, respectively, P = 0.04). Lower risks for lifetime asthma (prevalence odds ratio, POR = 0.39; 95% CI: 0.23-0.66) and current wheeze (POR = 0.72; 95% CI: 0.47-1.10) were found for children who had lived in Italy <5 years, while migrant children who had lived in Italy for 5 years or more had risks very similar to Italian children. CONCLUSIONS: Migrant children have a lower prevalence of asthma symptoms than children born in Italy. Prevalence increased with the number of years of living in Italy, suggesting that exposure to environmental factors may play an important role in the development of asthma in childhood.

A survey on hospitalised community-acquired pneumonia in Italy.

BACKGROUND AND AIM: Community Acquired Pneumonia (CAP) remains a major cause of disease and death. We evaluated the levels of care, the outcome and the characteristics of hospitalised patients with CAP in a primary hospital in Italy. We also investigated the value of both the Pneumonia Severity Index (PSI) and the modified Appropriateness Evaluation Protocol (AEP) for recognising both the outcome and the unnecessary admissions and stay of hospitalised patients with CAP. METHODS: A retrospective review of all the charts of adult patients with CAP at Manerbio, Brescia, Italy between January 2001 and December 2002 was performed. RESULTS: We evaluated 148 patients; their mean age (+/-SD) was 70 (+/-17) years; 34% were female. Most patients (87%) had at least a concomitant co-morbid disease. The overall survival rate at 30 days was 88%. All but one death occurred in the high-risk group of patients according to the PSI. On the contrary, the death rate of patients with inappropriate hospital admission according to the AEP was high. Patients with high PSI score had a significantly longer hospital length of stay than the low-risk group. However, a substantial part of the hospital stay did not show any justification into the charts. CONCLUSIONS: The PSI, but not the AEP, upon hospital admission, was useful for evaluating the outcome of patients with CAP. The PSI score and the modified AEP can be useful for assessing the appropriateness of hospitalisation for patients with CAP. There is the need for a practical and validated tool to support physicians in their decision making regarding the early and safe discharge of hospitalised patients with CAP.

Retrospective analysis of evidence base for tests used in diagnosis and monitoring of disease in respiratory medicine.

OBJECTIVES: To determine how many common clinical tests used in a respiratory medicine outpatient clinic are based on high quality evidence. DESIGN: Retrospective review of case notes. Record of first three tests for each patient. Diagnostic tests, tests used to assess existing condition, explicit trials of therapy were included. Literature search for supporting evidence and grading of best evidence for each test. SETTING: Inner city university teaching hospital in the United Kingdom. PARTICIPANTS: All new outpatients referred to a single respiratory medicine team over a period of three months. MAIN OUTCOME MEASURES: Proportion of tests supported by level 1a-1c evidence (scale developed by Centre for Evidence Based Medicine). RESULTS: Only half the tests that were used to make or exclude a diagnosis and a fifth of the tests used to assess a known condition were supported by level 1a-1c evidence. There was no evidence to support trials of therapy. CONCLUSIONS: A large proportion of clinical tests in respiratory medicine are not supported by level 1a-1c evidence. None of the therapeutic trials that were used were supported by evidence.

Regular inhaled short acting beta2 agonists for the management of stable chronic obstructive pulmonary disease: Cochrane systematic review and meta-analysis.

BACKGROUND: Despite the lack of reversibility, patients with chronic obstructive pulmonary disease (COPD) often report symptomatic improvement with inhaled short acting beta(2) agonist bronchodilators (ISABAs) in the management of both stable and acute exacerbations of COPD. A review of the literature was undertaken to determine the effectiveness of regular treatment with ISABAs compared with placebo in stable COPD. METHODS: A search for randomised controlled trials was carried out using the Cochrane Collaboration database of trials up to and including May 2002. RESULTS: Thirteen studies of 7 days to 8 weeks in duration on 237 patients aged 56-70 years with forced expiratory volume in 1 second (FEV(1)) 60-70% predicted were included in the review. All studies used a crossover design with adequate washout periods and were of high methodological quality. ISABA was delivered either through a nebuliser or a pressurised metered dose inhaler. Spirometric tests performed at the end of the study and after the treatment (post-bronchodilator) showed a slight but significant increase in FEV(1) and forced vital capacity (FVC) compared with placebo. In addition, both morning and evening peak expiratory flow rate (PEFR) were significantly better during active treatment than during placebo. An improvement in the daily breathlessness score was observed with ISABA treatment. The risk of treatment failure was reduced by more than 50% with ISABA. Preference for ISABA was nine times higher than for placebo. CONCLUSIONS: Use of ISABA on a regular basis for at least 7 days in patients with stable COPD is associated with improvements in post-bronchodilator lung function and decreases in both breathlessness and treatment failure. This review has shown that regular administration of ISABAs is an effective and inexpensive treatment for the management of patients with stable COPD.

Perception of dyspnea during exercise-induced bronchoconstriction.

UNLABELLED: After strenuous physical exercise, many subjects show a significant bronchoconstriction and report dyspnea. Despite this clinical condition being a commonly encountered situation during daily life, which may be responsible for substantial disability there is little information on the relationship between the perception of dyspnea and exercise-induced bronchoconstriction (EIB) after a standardized exercise challenge. For these reasons, we evaluated 200 consecutive outpatients (median age 13 years, ranging from 5 to 56 years) referred to our laboratory to perform an exercise test out of suspicion of EIB. On exercise challenge, perception of dyspnea was rated on a modified bipolar Borg scale immediately before each FEV1 measurement. Sixty-nine (35%) subjects had a positive exercise challenge, defined as a decrease of at least 20% in FEV1 from baseline. Both the onset and the decay of dyspnea preceded those of bronchoconstriction. Overall, the rating of dyspnea in the laboratory was well related with the reports of exercise-related symptoms. Similarly, 36 of 77 (47%) asthmatics with a history of exertional symptoms and 24 of 65 patients (40%) without a history had a positive challenge. Asthmatics reporting exertional symptoms perceived a greater magnitude of dyspnea after exercise independently from the degree of bronchoconstriction. Overall, dyspnea was significantly but loosely correlated to the magnitude of decrease in FEV1, being also influenced by age, gender and BMI. CONCLUSIONS: We conclude that dyspnea recorded in the laboratory after exercise test is related to exertional symptoms reported during real life, but not completely related to EIB. The rating of dyspnea is a well-suited model to study naturally occurring exercise-induced dyspnea and a useful tool to enlarge the results of an exercise challenge.

GENEBU Project. Equipment and drugs used for home nebulizer therapy in Italy.

The GENEBU Project is an open, observational survey evaluating home nebulizer practices in Italy. It consecutively included patients who were referred to one of the 27 participating chest clinics from May to December 1999 and who had been using a home nebulizer in the previous six months. The information source was a self-administered questionnaire compiled by the enrolled subjects. We collected 1257 questionnaires. The nebulizer equipment was heterogeneous, with at least 92 different models. Jet nebulizers were 90% of the total; 53% of these had a glass reservoir. Almost 80% of the patients selected the nebulizer themselves without any medical advice. In addition, most patients (> 80%) did not receive information on both the interface system and the optimal fill volume of the nebulizer. Corticosteroid nebulisation was widespread (74%), for both occasional and regular daily use, for both acute and chronic diseases from upper to lower airways. Beta 2-agonist (55%), anticholinergic (37%), mucolytic (32%) drugs were also often nebulised. More than 90% of patients mixed some active drugs. We conclude that the nebulizer equipment for home aerosol therapy was very heterogeneous and, probably, not always utilised at its best in Italy. The mixing of drugs and the widespread use of corticosteroids were peculiarities of home nebulizer therapy in Italy.

Short-acting beta 2 agonists for stable chronic obstructive pulmonary disease.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is a chronic condition characterised by progressive airflow limitation that is at most partially reversible. Despite the lack of reversibility patients often report symptomatic improvement with short-acting beta-2 bronchodilator medication. Short-acting beta-2 bronchodilators are used in the management of both stable and acute exacerbations of COPD. OBJECTIVES: To determine the clinical effectiveness and assess the adverse effects of regular treatment with short-acting beta-2 agonists bronchodilators in patients with stable COPD. SEARCH STRATEGY: A search was carried out using the Cochrane Airways Group database. In addition, the reference lists of review articles and the randomised controlled trials (RCTs) retrieved in full text were searched for other potentially relevant citations. SELECTION CRITERIA: RCTs of at least one week in duration comparing treatment with inhaled short-acting beta-2 agonists with placebo in patients with stable COPD. DATA COLLECTION AND ANALYSIS: Data extraction and study quality assessment was performed independently by two reviewers. Where further or missing data was required, authors of studies were contacted. The data was analysed using the Cochrane Review Manager 4.1. MAIN RESULTS: Thirteen studies were included in this review. All studies used a crossover design and were of high quality. Spirometry performed at the end of the study period and after the administration of treatment (post-bronchodilator) showed a slight but significant increase in FEV1 and FVC when compared to placebo (WMD=0.14 L; 95%CI=0.04,0.25 & WMD=0.30 L; 95%CI=0.02,0.58, respectively). In addition, both morning and evening PEFR were significantly better during active treatment than during placebo (WMD=29.17 L/min; 95%CI=0.25,58.09 & WMD=36.75 L/min; 95%CI=2.56,70.94, respectively). A significant improvement in daily breathlessness score was observed during treatment with beta-2 agonist when compared to placebo (SMD=1.33; 95%CI=1.0,1.65). The risk of dropping out of the study (treatment failure) when on treatment with placebo was almost twice that of patients on treatment with beta-2 agonists (RR=0.49; 95%CI=0.33,0.73). Patients preferred beta-2 agonists almost 10 times more frequently to placebo (OR=9.04; 95%CI=4.64,17.61). One study that used a validated questionnaire for 'quality of life' assessment, found highly significant improvements in the scores for dyspnoea (p=0.003) and fatigue (p=0.0003) during treatment with salbutamol. No studies reported serious side effects during treatment with inhaled beta-agonists. However, none of the studies were of sufficient length or size in order to allow any meaningful information on long-term occurrence of side effects. REVIEWER'S CONCLUSIONS: Use of short-acting beta-2 agonists on a regular basis for at least seven days in stable COPD is associated with improvements in post bronchodilator lung function and a decrease in breathlessness. Patients are far more likely to prefer treatment with beta-2 agonists than placebo, and less likely to drop out from such treatment. None of the studies included in this review reported sufficient data or were of sufficient length or size in order to provide reliable information on adverse effects. Therefore large scale, parallel, longer term studies would be needed to investigate the effect of treatment with regular inhaled beta-2 agonists on mortality, disease progression and side effects. Newer, long acting bronchodilators (including long-acting beta-2 agonists) are currently available and they may be more practical and/or effective in these patients. However, this review indicates that treatment with these older, inexpensive drugs is beneficial in patients with COPD.

[Organizational appropriateness of recoveries: results of the evaluation of recoveries by AEP/PRUO at the Careggi Hospital in Florence in 1995-1998]. / Appropriatezza organizzativa dei ricoveri: risultati della valutazione con AEP/PRUO dei ricoveri dell'AO Careggi di Firenze. Anni 1995 e 1998.

The organizational appropriateness of hospital stays is an expression of a hospital's efficiency and aim of the management control. The AEP (American Version)/PRUO (Italian Version) protocol is specific for measuring the organizational appropriateness of hospital stays. The aim of this study is the comparative analysis of the organizational appropriateness of hospital stays in Careggi Hospital of Florence and in all hospital Departments in 1995 and 1998. In 1998 the AEP/PRUO protocol was applied to 2148 samples of hospital stays out of 38,968 eligible hospitalizations, and in 1995 a sample of 1989 hospital stays out of 35,108. In 1998 2,148 admissions and 15,338 days of hospitalization were tested. In 1995, 1989 admission days and 12,264 days of hospitalization were tested, 63 departments were studied. In 1995 the first edition of the protocol was applied, in 1998 the second. A sample of 218 of the 1998 hospital stays was tested with both editions to evaluate the impact of differences. In 1998, with the second edition of the protocol, the inappropriateness rate of admission days and hospitalization days and the rate of in-patients inappropriate hospital stays was respectively 38.0%, 43.8% and 18.5%. Compared with 1995 results, the rates increased +6.2%, 6% and +7.5% respectively. Instead, with the first edition of the protocol, the rates were 29.7%, 37.6% and 10.7% and, compared with 1995, they were reduced -2.1%, -0.6% and -0.3%. The longitudinal multilevel analysis has allowed the evaluation of the performance of each department.

GENebu Project: home nebulizer use and maintenance in Italy.

Due to the lack of information on this topic, the Educational Group of the Italian Association of Hospital Pneumologists performed an open, multicentre, observational survey to evaluate home nebulizer practices in Italy. From May-December 1999, all patients attending one of the 27 participating chest clinics throughout Italy and who were or had been using a home nebulizer in the previous 6 months were consecutively enrolled. All patients completed a self-administered questionnaire on their current practices of home nebulization. Of the 1,721 questionnaires delivered, 1,257 were returned with an overall response rate of 73%. Most patients (82.8%) reported using their nebulizer for bronchopulmonary symptoms and the remaining patients only used theirs for upper respiratory tract diseases. Subjects using their nebulizer for lower respiratory symptoms were older (p<0.001), predominantly female (p<0.001) and used their nebulizer more frequently (p<0.001). Forty per cent of patients >60 yrs old used their nebulizer regularly, at least once a day. More than 60% of respondents never received any information from healthcare workers on the correct usage of their nebulizer, and >75% received no information on nebulizer hygiene and care. Patients who received information on the use and maintenance of their nebulizer from caregivers more commonly attended to these practices (p<0.01). The present survey suggests that home nebulizer use and maintenance in Italy are heterogeneous, and there is the need to implement better nebulizer practice.

Tobacco smoking habits, attitudes and beliefs among nurse and medical students in Tuscany.

In this study we evaluated the smoking habits, beliefs and attitudes of nurse and medical students at the University of Siena and Florence, Italy. Students who entered the 1st year of school in 1998 were asked to complete a self-administered anonymous questionnaire. Two hundred medical students completed the questionnaire; they had a mean age (+/-SD) of 19.8+/-1.7 years and 68% were females. A total of 205 nurse respondents answered to the questionnaire; they had a mean age of 21.8+/-4.1 years and females were 83% of the total. The overall response rate among students always remained higher than 85%. Thirty per cent of medical students were current smokers, and 5% former-smokers. A total of 43% of nurse students were current smokers and 11.5% former-smokers. Nurse students were more likely to smoke than medical students (p = 0.001). Among current smokers, the number of daily cigarettes smoked and the degree of nicotine addiction did not differ between groups. The prevalence of maternal smoking were higher among nurse students. In spite of students' beliefs the knowledge about smoking remained generic in both groups. Nurse students were less aware than medical students of their special responsibility towards people about tobacco smoking. Such a difference remained significant also after adjustment for smoking status (p < 0.01). Students overestimated the prevalence of current smokers among health caregivers of the local hospitals, and Italian people and adolescents. Targeted and continuous training about smoking prevention should be mandatory in Italian medical and nurse schools.

Acoustic parameters of voluntary cough in healthy non-smoking subjects.

OBJECTIVE: The aim of this study was to explore cough in healthy subjects. METHODOLOGY: We studied 234 coughs generated by 24 (12 males) healthy non-smokers (forced expiratory volume in 1 s (FEV1) 103+/-8% of predicted), who had no significant differences in FEV1 and age between males and females. For each subject, several bouts of voluntary coughing were recorded using a personal computer with an A/D converter (sampling rate 10 kHz, 8 bit resolution) and the first and second coughs of each bout were analysed using short-time Fast Fourier Transformation. For each cough we studied the three phases that are produced. In particular, we studied the duration of the three parts, loudest frequency in the first part, lowest and highest frequencies, number of continuous frequencies and lowest and highest continuous frequencies in the second part, and the loudest frequency of the third part if present. RESULTS: We found significant differences between males and females in length of the first part (41.4+/-14 vs 44.7+/-10.4 msec, P = 0.04), loudest frequency of the first part (362+/-145 vs 449+/-145 Hz), lowest frequencies (282+/-100 vs 348+/-135 Hz) and highest continuous frequencies (3877+/-571 vs 4147+/-362 Hz; P < 0.001) of the second part. An interesting finding was that healthy males and females had the same number of continuous frequencies. Different frequencies are probably a consequence of anatomical differences in airway geometry involved in the cough. CONCLUSION: In cough frequency spectrum studies the differences between the two sexes should be taken into account to reduce the variability of the results.