Giuseppe Maria Corbo

Road traffic and adverse respiratory effects in children. SIDRIA Collaborative Group.

OBJECTIVES: To investigate the relation between traffic indicators in the area of residence and the occurrence of chronic respiratory disorders in children. METHODS: A population based survey was conducted in 10 areas of northern and central Italy (autumn 1994 to winter 1995) in two age groups (6-7 and 13-14 years). Information on several respiratory disorders and on traffic near residences was collected with a questionnaire given to children and to their parents. The sample analysed included 39,275 subjects (response rate 94.4%). Outcomes were: (a) early (first 2 years of life) respiratory diseases, and (b) current respiratory disorders (asthma, wheeze, cough, or phlegm in the past year). Odds ratios (ORs) and 95% confidence intervals (95% CIs), adjusted for several potential confounders, were estimated from logistic regression models. Main results were stratified by level of urbanisation (metropolitan areas, other centres). RESULTS: In the metropolitan areas, high frequency of lorry traffic in the street of residence was associated with significantly increased risks for many adverse respiratory outcomes. Among early respiratory diseases, the strongest associations were found for recurrent bronchitis (OR 1.69, 95% CI 1.24 to 2.30), bronchiolitis (1.74, 1.09 to 2.77) and pneumonia (1.84, 1.27 to 2.65), although no association was detected for episodes of wheezing bronchitis. All the current respiratory disorders were positively and consistently associated with frequency of lorry traffic, particularly the most severe bronchitic and wheezing symptoms: persistent phelgm for > 2 months (1.68; 1.14 to 2.48), and severe wheeze limiting speech (1.86; 1.26 to 2.73). No or weaker associations with heavy vehicular traffic were detected in urban and rural areas and no increased risks were found in the whole sample with the reported traffic density in the zone of residence. After extensive evaluations, the potential of reporting bias seems unlikely. CONCLUSION: Exposure to exhausts from heavy vehicular traffic may have several adverse effects on respiratory health of children living in metropolitan areas, increasing the occurrence of lower respiratory tract infections early in life and of wheezing and bronchitic symptoms at school age.

Dietary factors associated with wheezing and allergic rhinitis in children

The effect of dietary factors on asthma is controversial. This study examined food consumption and the use of fats in relation to wheezing and allergic rhinitis in children. Baseline questionnaire data on individual and family characteristics were recorded by parents of 5,257 children aged 6–7 yrs living in central Italy participating in the International Study on Asthma and Allergies in Childhood study. A total of 4,104 children (78.1%) were reinvestigated after 1 yr using a second parental questionnaire to record occurrence of respiratory symptoms over the intervening 12 months. Consumption of foods rich in antioxidants, such as vitamins C and E, animal fats, and food containing omega‐3 fatty acids were investigated using a food-frequency questionnaire. Frequency of use of fats was also evaluated. Wheezing, shortness of breath with wheeze, and symptoms of allergic rhinitis in the past 12 months were considered. Intake of cooked vegetables, tomatoes, and fruit were protective factors for any wheeze in the last 12 months and shortness of breath with wheeze. Consumption of citrus fruit had a protective role for shortness of breath with wheeze. Consumption of bread and margarine was associated with an increased risk of wheeze, while bread and butter was associated with shortness of breath with wheeze. Dietary antioxidants in vegetables may reduce wheezing symptoms in childhood, whereas both butter and margarine may increase the occurrence of such symptoms.

Adjuvant radiotherapy in non-small cell lung cancer with pathological stage I: definitive results of a phase III randomized trial

BACKGROUND AND PURPOSE To evaluate the benefits and the drawbacks of post-operative radiotherapy in completely resected Stage I (a and b) non-small cell lung cancer (NSCLC). MATERIALS AND METHODS Patients with pathological Stages Ia and Ib NSCLC have been randomized into two groups: Group 1 (G1) received adjuvant radiotherapy, Group 0 (G0) the control group did not receive any adjuvant therapy. Local control, toxicity and survival have been evaluated. RESULTS Between July 1989 and June 1997, 104 patients with pathological stage I NSCLC have been enrolled in this study. Fifty-one patients were randomized to G1 and 53 to G0. Six patients have been excluded from the study due to incomplete follow-up data. Regarding local control, one patient in the G1 group had a local recurrence (2.2%) while in the G0 12 local recurrences have been observed (23%). Seventy-one percent of patients are disease-free at 5 years in G1 and 60% in G0 (P=0.039). Overall 5-year survival (Kaplan-Meier) showed a positive trend in the treated group: 67 versus 58% (P=0.048). Regarding toxicity in G1, six patients experienced a grade 1 acute toxicity. Radiological evidence of long-term lung toxicity, with no significant impairment of the respiratory function, has been detected in 18 of the 19 patients who have been diagnosed as having a post-radiation lung fibrosis. CONCLUSIONS Adjuvant radiotherapy gave good results in terms of local control in patients with completely resected NSCLC with pathological Stage I. Overall 5-year survival and disease-free survival showed a promising trend. Treatment-related toxicity is acceptable.

Socioeconomic status, number of siblings, and respiratory infections in early life as determinants of atopy in children.

Asthma and allergic disorders have been on the increase in recent decades, especially among children living in affluent countries; some aspects of the “Western” way of life may explain this trend. We evaluated the relation of aeroallergen skin test reactivity with socioeconomic status, number of siblings, and respiratory infections in early life. We examined a total of 2,226 schoolchildren, ages 7–11 years, in three areas of Lazio, Italy. Skin prick tests were performed to assess atopic status, and self‐administered questionnaires were completed by the parents. The prevalence of prick test positivity was greater among children whose fathers were in the highest educational level than among those in the lowest [prevalence ratio (PR) = 1.58; 95% confidence interval (CI) = 1.21–2.06]. There was also a lower prevalence of atopy among larger sibships (PR = 0.38 for subjects with four or more siblings vs those without siblings; 95% CI = 0.14–0.99). A history of bronchitis or bronchiolitis before age 2 years was weakly associated with an increased risk of atopy, whereas a history of pertussis or pneumonia was not. Both the effect of fathers education and the influence of larger sibship size remained when we adjusted for several potential confounding factors, including respiratory infections in early life. We infer that higher socioeconomic status and lower sibling number are determinants of atopy in this Italian population. Protection arising from early severe respiratory infections does not explain this association, although we cannot exclude a role for other viral infections.

Effects of environment on atopic status and respiratory disorders in children

BACKGROUND We investigated whether living in areas with higher air pollution levels increases the prevalence of positive skin reactivity in children and the possible synergic effect of air pollution exposure and atopy on respiratory disorders. METHODS This cross-sectional study was conducted in an urban area, in an industrialized area, and in a rural control area in the Latium region of Italy. A total of 2226 subjects, aged 7 to 11 years, were studied. RESULTS The prevalence of children with positive skin test results did not vary significantly over the areas (urban area = 21.0%, industrialized area = 22.0%, rural area = 20.2%). Children living in polluted areas experienced significantly more cough and phlegm (odds ratio [OR] = 1.5), rhinitis (OR = 1.7), pneumonia (OR = 1.7), and early respiratory infections (OR = 1.4) than control subjects. The pattern of the odds ratios for atopy and air pollution suggested that the two factors were probably additive in affecting asthma and early respiratory infections (synergy index [SI] = 1.04 and 1.27, respectively), whereas they seemed to act synergically in regard to cough and phlegm (SI = 1.59), rhinitis (SI = 3.01), and pneumonia (SI = 2.75). CONCLUSION Environmental air pollution seems not to increase the prevalence of atopic status; it seems, however, to enhance the development of clinical symptoms among already sensitized subjects.

The impact of parental smoking on asthma and wheezing. SIDRIA Collaborative Group. Studi Italiani sui Disturbi Respiratori nell'Infanzia e l'Ambiente.

To evaluate the impact of parental smoking on childhood asthma and wheezing, we studied two random samples of subjects ages 6–7 and 13–14 years in ten areas of northern and central Italy. Standardized questionnaires were completed by parents of 18,737 children and 21,068 adolescents (response rates, 92.8% and 96.3%, respectively) about their smoking habits and the respiratory health of their children. Adolescents were asked about their respiratory health and personal smoking. We compared two groups of cases with healthy subjects: “current asthma” (children, 5.2%; adolescents, 6.2%) and “current wheezing” not labeled as asthma (children = 4.5%, adolescents = 8.5%). Exposure to smoke of at least one parent increased the relative risk of current asthma among children [odds ratio (OR) =.34; 95% confidence interval (CI) = 1.11–1.62] and of current wheezing among adolescents OR = 1.24; 95% CI = 1.07–1.44). Maternal smoking had a stronger effect than paternal smoking. Maternal smoking during pregnancy was associated with current asthma (OR = 1.62; 95% CI = 1.34–1.96) and current wheezing in children (OR = 1.31; 95% CI = 1.06–1.62); the effects were lower among adolescents. Among subjects with a negative history of parental asthma, maternal smoking was associated with current wheezing in both age groups, whereas among those with a positive history of parental asthma it was associated with current asthma in children, but not in adolescents. We estimated that 15% (95% CI = 12–19) of the current asthma cases among children and 11% (95% CI = 8.3–14) of the current wheezing cases among adolescents are attributable to parental smoking in Italy. (Epidemiology 1999;10:692–698)

Phase I Trial of Weekly Gemcitabine and Concurrent Radiotherapy in Patients With Inoperable Non–Small-Cell Lung Cancer

PURPOSE To report the evidence of a phase I trial planned to determine the maximum-tolerated dose (MTD) and related toxicity of weekly gemcitabine (GEM) and concurrent radiotherapy in patients with non--small-cell lung cancer (NSCLC). In addition, the response to treatment was evaluated and reported. PATIENTS AND METHODS Thirty-six patients with histologically confirmed NSCLC deemed unresectable because of advanced stage were observed and treated according to a combined chemoradiation protocol with GEM as chemotherapeutic agent. GEM was given weekly for 5 consecutive weeks as a 30-minute intravenous infusion concurrent with radiotherapy (1.8 Gy/d; total dose, 50.4 Gy). The initial dose was 100 mg/m(2). Pulmonary, esophageal, cardiac, hematologic, and skin toxicities were assessed. The dose of GEM was increased by 50 mg/m(2) up to a dose of 250 mg/m(2); an additional increase by 25 mg/m(2) up to the MTD was planned and realized. Three patients were enrolled for each dose level. RESULTS Dose-limiting toxicity was identified for the 375-mg/m(2) level with two episodes of grade 2 esophagitis and two of grade 3 pulmonary actinic interstitial disease. The weekly dose of GEM 350 mg/m(2) was well tolerated. CONCLUSION A weekly GEM dose of 350 mg/m(2) concurrent with radiotherapy was well tolerated. Promising results regarding response to treatment were observed and reported.

Wheeze and asthma in children: associations with body mass index, sports, television viewing, and diet.

Background: Obesity, physical activity, and dietary habits are distinct but strongly interrelated lifestyle factors that may be relevant to the prevalence of wheeze and asthma in children. Our goal was to analyze the relationship of body mass index (BMI), regular sports participation, TV viewing, and diet with current wheezing and asthma. Methods: We investigated 20,016 children, aged 6–7 years, who were enrolled in a population-based study. Parents completed standardized questionnaires. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs), while adjusting for several confounders and simultaneously considering BMI, regular sports activity, TV viewing and selected dietary items. Results: A total of 1575 children (7.9%) reported current wheezing and 1343 (6.7%) reported current asthma. In a multivariate model, an elevated BMI was associated with wheeze and current asthma: children from the highest quintile (compared with the lowest quintile) had an increased risk of wheeze (OR = 1.47; CI = 1.20–1.82) or current asthma (1.61; 1.28–2.01). Wheeze or asthma was not associated with regular sports activity. Subjects who spent 5 or more hours per day watching television were more likely to experience wheeze (1.53; 1.08–2.17) or current asthma (1.51; 1.04–2.2) compared with those who viewed TV less than 1 hour a day. Adding salt to food was strongly and independently associated with current wheeze (2.58; 1.41–4.71) and current asthma (2.68; 1.41–5.09). Conclusions: Our data support the hypothesis that high body weight, spending a lot of time watching television, and a salty diet each independently increase the risk of asthma symptoms in children.

Validation of leukotriene B4 measurements in exhaled breath condensate.

Abstract:Objective: To qualitatively validate an enzyme immunoassay to measure leukotriene B4 in exhaled breath condensate. Exhaled breath condensate is a new non-invasive method to monitor airway inflammation.¶Subjects: Twenty-two subjects with different lung diseases attended the outpatient clinic on one occasion for exhaled breath condensate collection.¶Methods: Samples were pooled together and purified by reverse-phase high-performance liquid chromatography. The fractions eluted were assayed for leukotriene B4 by enzyme immunoassay.¶Results: A single peak of leukotriene B4-like immunoreactivity co-eluting with leukotriene B4 standard (retention time: 24 min) was identified by enzyme immunoassay. Reverse phase-high performance liquid chromatography peak of leukotriene B4 was clearly separated from those of 6-trans- leukotriene B4 (retention time: 14 min) and leukotriene B5 (retention time: 18 min) for which the antiserum used in the enzyme immunoassay had the highest cross-reactivity. Leukotriene B4 recovery was 64%.¶Conclusions: This study provides evidence for the presence of leukotriene B4 in the exhaled breath condensate and the specificity of the enzyme immunoassay used.

Respiratory symptoms in children living near busy roads and their relationship to vehicular traffic: results of an Italian multicenter study (SIDRIA 2).

BackgroundEpidemiological studies have provided evidence that exposure to vehicular traffic increases the prevalence of respiratory symptoms and may exacerbate pre-existing asthma in children. Self-reported exposure to road traffic has been questioned as a reliable measurement of exposure to air pollutants. The aim of this study was to investigate whether there were specific effects of cars and trucks traffic on current asthma symptoms (i.e. wheezing) and cough or phlegm, and to examine the validity of self-reported traffic exposure.MethodsThe survey was conducted in 2002 in 12 centers in Northern, Center and Southern Italy, different in size, climate, latitude and level of urbanization. Standardized questionnaires filled in by parents were used to collect information on health outcomes and exposure to traffic among 33,632 6–7 and 13–14 years old children and adolescents. Three questions on traffic exposure were asked: the traffic in the zone of residence, the frequency of truck and of car traffic in the street of residence. The presence of a possible response bias for the self-reported traffic was evaluated using external validation (comparison with measurements of traffic flow in the city of Turin) and internal validations (matching by census block, in the cities of Turin, Milan and Rome).ResultsOverall traffic density was weakly associated with asthma symptoms but there was a stronger association with cough or phlegm (high traffic density OR = 1.24; 95% CI: 1.04, 1.49). Car and truck traffic were independently associated with cough or phlegm. The results of the external validation did not support the existence of a reporting bias for the observed associations, for all the self-reported traffic indicators examined. The internal validations showed that the observed association between traffic density in the zone of residence and respiratory symptoms did not appear to be explained by an over reporting of traffic by parents of symptomatic subjects.ConclusionChildren living in zones with intense traffic are at higher risk for respiratory effects. Since population characteristics are specific, the results of validation of studies on self-reported traffic exposure can not be generalized.