CIRCULATING TUMOR CELLS IN MINIMALLY INVASIVE FOLLICULAR THYROID CARCINOMA AND BENIGN THYROID TUMORS WITH A FOLLICULAR PATTERN: PILOT EXPERIENCE.

PURPOSE: Minimally invasive follicular thyroid carcinomas (MIFCs) are uncommon; literature offers limited guidance on their natural history and management. Starting January 2015 we measured circulating tumor cells (CTCs) in patients with MIFC (n=22) or benign thyroid tumors with follicular features (n=4). METHODS: In a retrospective analysis, we assessed detectability of and serial changes in CTC, compared demographic/clinical differences between CTC-positive versus CTC-negative subgroups using Student's t-test, and examined correlations between CTC status and serum thyroglobulin using Spearman's test. CTCs were quantitated via immunomagnetic separation/microscopic inspection. RESULTS: Thirteen patients (50%: 12/22 MIFC, 1/4 benign tumor) were initially CTC-positive; 3 remained CTC-positive in ≥1 subsequent measurement. CTC-positive patients had larger tumors and more frequent multifocality and vascular invasion versus CTC-negative patients (n=13). However, no tested variable differed significantly between the subgroups. After 17.2±10.5 months, neither subgroup showed evidence of disease. Significant correlation was absent (p ≥ 0.263) between CTC and Tg negativity (r = 0.243; n=13 evaluable) or initial CTC positivity and Tg positivity (r = -0.418; n=9 evaluable). CONCLUSIONS: In the studied settings, CTC measurement is feasible, has unclear clinical/outcome implications, but may provide different information versus thyroglobulin testing. Lengthier assessment is warranted in larger series.

A double-blind, placebo-controlled randomized trial to evaluate the efficacy of docosahexaenoic acid supplementation on hepatic fat and associated cardiovascular risk factors in overweight children with nonalcoholic fatty liver disease.

BACKGROUND AND AIMS: Very little information is available on whether docosahexaenoic acid (DHA) supplementation has a beneficial effect on liver fat and cardiovascular disease (CVD) risk factors in children with nonalcoholic fatty liver disease (NAFLD). In a double-blind, placebo-controlled randomized trial we investigated whether 6-month treatment with DHA improves hepatic fat and other fat depots, and their associated CVD risk factors in children with biopsy-proven NAFLD. METHODS AND RESULTS: Of 58 randomized children, 51 (25 DHA, 26 placebo) completed the study. The main outcome was the change in hepatic fat fraction as estimated by magnetic resonance imaging. Secondary outcomes were changes in visceral adipose tissue (VAT), epicardial adipose tissue (EAT), and left ventricular (LV) function, as well as alanine aminotransferase (ALT), triglycerides, body mass index-standard deviation score (BMI-SDS), and insulin sensitivity. At 6 months, the liver fat was reduced by 53.4% (95% CI, 33.4-73.4) in the DHA group, as compared with 22.6% (6.2-39.0) in the placebo group (P = 0.040 for the comparison between the two groups). Likewise, in the DHA group VAT and EAT were reduced by 7.8% (0-18.3) and 14.2% (0-28.2%), as compared with 2.2% (0-8.1) and 1.7% (0-6.8%) in the placebo group, respectively (P = 0.01 for both comparisons). There were no significant between-group changes for LV function as well as BMI-SDS and ALT, while fasting insulin and triglycerides significantly decreased in the DHA-treated children (P = 0.028 and P = 0.041, respectively). CONCLUSIONS: DHA supplementation decreases liver and visceral fat, and ameliorates metabolic abnormalities in children with NAFLD.

Detection and quantification of EBV, HHV-6 and CMV DNA in the gastrointestinal tract of HIV-positive patients.

Human herpes viruses (HHVs) have been frequently detected in the gastrointestinal (GI) tract and may contribute to the development of gastric cancer. In the present study, the detection rate and viral load of Epstein Barr virus (EBV), HHV-6 and Cytomegalovirus (CMV) were assessed in the GI tract of human immunodeficiency virus (HIV) positive patients and of uninfected patients. The analysis revealed a significantly higher detection rate of EBV and HHV-6 in HIV-infected individuals than in uninfected subjects (88.5 vs 63%; p = 0.03). Moreover, EBV DNA load was significantly higher in the stomach of HIV patients than in controls. These data suggest that the HIV infection status may increase the persistence of these viruses in the GI compartment. Intriguingly, CMV DNA was undetectable in all biopsy specimens analyzed.

Association of serum triglyceride-to-HDL cholesterol ratio with carotid artery intima-media thickness, insulin resistance and nonalcoholic fatty liver disease in children and adolescents.

BACKGROUND AND AIMS: The triglyceride (TG)/high-density lipoprotein-cholesterol (HDL-C) ratio has been reported as a useful marker of atherogenic lipid abnormalities, insulin resistance, and cardiovascular disease. We evaluated in a large sample of children and adolescents the association of TG/HDL-C ratio with early signs of morphological vascular changes and cardiometabolic risk factors including nonalcoholic fatty liver disease (NAFLD). METHODS AND RESULTS: The study population, including 548 children (aged 6-16 years), of whom 157 were normal-weight, 118 overweight, and 273 obese, had anthropometric, laboratory, liver and carotid ultrasonography (carotid artery intima-media thickness-cIMT) data collected. Subjects were stratified into tertiles of TG/HDL-C. There was a progressive increase in body mass index (BMI), BMI-SD score (SDS), waist circumference, blood pressure (BP), liver enzymes, glucose, insulin, homeostasis model assessment of insulin resistance, high-sensitivity C-reactive protein (hsCRP), and cIMT values across TG/HDL-C tertiles. The odds ratios for central obesity, insulin resistance, high hsCRP, NAFLD, metabolic syndrome, and elevated cIMT increased significantly with the increasing tertile of TG/HDL-C ratio, after adjustment for age, gender, pubertal status, and BMI-SDS. In a stepwise multivariate logistic regression analysis, increased cIMT was associated with high TG/HDL-C ratio [OR, 1.81 (95% CI, 1.08-3.04); P < 0.05], elevated BP [5.13 (95% CI, 1.03-15.08); P < 0.05], insulin resistance [2.16 (95% CI, 1.30-3.39); P < 0.01], and NAFLD [2.70 (95% CI, 1.62-4.56); P < 0.01]. CONCLUSION: TG/HDL-C ratio may help identify children and adolescents at high risk for structural vascular changes and metabolic derangement.

Sometimes it is better to just make it simple. De-escalation of oncoplastic and reconstructive procedures.

Simple breast conservation surgery (sBCS) has technically advanced onto oncoplastic breast procedures (OBP) to avoid mastectomy and improve breast cancer patients' psychosocial well-being and cosmetic outcome. Although OBP are time-consuming and expensive, we are witnessing an increase in their use, even for cases that could be managed with sBCS. The choice between keeping it simple or opting for more complex oncoplastic procedures is difficult. This review proposes a pragmatic approach in assisting this decision. Medical literature suggests that OBP and sBCS might be similar regarding local recurrence and overall survival, and patients seem to have higher satisfaction levels with the aesthetic outcome of OBP when compared to sBCS. However, the lack of comprehensive high-quality research assessing their safety, efficacy, and patient-reported outcomes hinders these supposed conclusions. Postoperative complications after OBP may delay the initiation of adjuvant RT. In addition, precise displacement of the breast volume is not effectively recorded despite surgical clips placement, making accurate dose delivery tricky for radiation oncologists, and WBRT preferable to APBI in complex OBP cases. With a critical eye on financial toxicity, patient satisfaction, and oncological outcomes, OBP must be carefully integrated into clinical practice. The thoughtful provision of informed consent is essential for decision-making between sBCS and OBP. As we look into the future, machine learning and artificial intelligence can potentially help patients and doctors avoid postoperative regrets by setting realistic aesthetic expectations.

Rhinovirus bronchiolitis and recurrent wheezing: 1-year follow-up.

The association between bronchiolitis and recurrent wheezing remains controversial. In this prospective study, we assessed risk factors for recurrent wheezing during a 12-month follow-up in 313 infants aged <12 months hospitalised for their first episode of bronchiolitis. Demographic, clinical and laboratory data were obtained with a questionnaire and from medical files. A total of 14 respiratory viruses were concurrently assayed in nasal washings. Parents were interviewed 12 months after hospitalisation to check whether their infants experienced recurrent wheezing. The rate of recurrent wheezing was higher in infants with bronchiolitis than in controls (52.7 versus 10.3%; p<0.001). Multivariate analysis identified rhinovirus (RV) infection (OR 3.3, 95% CI 1.0-11.1) followed by a positive family history for asthma (OR 2.5, 95% CI 1.2-4.9) as major independent risk factors for recurrent wheezing. In conclusion, the virus most likely to be associated with recurrent wheezing at 12 months after initial bronchiolitis is RV, a viral agent that could predict infants prone to the development of recurrent wheezing.

Food allergy and the development of asthma symptoms.

Allergies are multifactorial diseases the onset of which depends also on genetic and environmental factors in early life. Thus, environmental factors can affect the immune response and modify lung development, thereby leading to asthma. The role of the factors used to date to predict asthma development is modest, and clinical criteria should always be considered in association with familiarity for atopy. The aim of this study is to evaluate the risk of asthma in a population with positive skin prick test (SPT) (which is a reliable marker of atopy) to food allergens, regardless of clinical manifestations in the early years of life. The cohort of children enrolled in our study who had a positive SPT to food in the first three years of life had a prevalence of asthma after 7-14 years, double that of the general pediatric population. This prevalence increased significantly in patients with SPT positivity for food and inhalant allergens. We identified a correlation between the sensitization profile in children under the age of 36 months and the development of asthma during a period of 7-14 years. This study confirms that early sensitization is an important risk factor for the development of asthma, particularly in association with sensitization to inhalants, and that the persistence of food sensitization in school-age children and adolescents is associated to more severe asthma.

Survival After Lung Transplant for Cystic Fibrosis in Italy: A Single Center Experience With 20 Years of Follow-up.

OBJECTIVES: Lung transplantation is currently the only treatment for end-stage respiratory failure in patients with cystic fibrosis (CF). In this study we retrospectively analyzed our experience since the start of the transplantation program in 1996 with focus on survival analysis. METHODS: All patients with CF who underwent lung transplant at our center were included (1996-2016). Survival analysis after lung transplant was performed using the Kaplan-Meier estimate, comparing by sex and by 4 eras (1996-2000, 2001-2005, 2006-2010, and 2011-2016). RESULTS: In a 20-year period, 243 patients with CF were listed for lung transplant; 123 patients (61 male, 62 female) underwent transplant, and 85 died while waiting for donor organs. The mean (SD) and median age at transplant was 27.7 (8.7) years and 26.9 years (range, 9.1 - 52.1 years), respectively. Mean (SD) forced expiratory volume in the first second was 27.6 (9.7)% predicted; 115 patients (92.0%) were pancreatic insufficient, and 43 patients (34.0%) had CF-related diabetes. Removing patients with CF who died within the first 3 postoperative months, the mean (SD) and median survival after transplant were 8.2 (5.7) years and 7.5 years (range, 3 months-20 years), respectively. Overall post-lung transplant 1-year survival was 93.6%, 5-year survival was 71.4%, 10-year survival was 53.6%, 15-year survival was 36.7%, and 20-year survival was 31.6%. We found no difference in survival between sex (P = .22) and among the 4 eras (P = .56). CONCLUSIONS: Survival after lung transplant in our single center is similar to international data.

Gastrointestinal symptoms in infancy: a population-based prospective study.

BACKGROUND: During the first months of life, infants can suffer from many 'minor' gastroenterological disturbances. However, little is known about the frequency of these problems and the factors which predispose or facilitate their onset. AIMS: (a) To ascertain the frequency of the most common gastrointestinal symptoms in infants during the first 6 months after birth; (b) to evaluate the influence of some variables on the onset of the symptoms. STUDY DESIGN AND PATIENTS: Each of the 150 paediatricians distributed throughout Italy followed 20 consecutive infants from birth to 6 months. 2879 infants (1422 f, 1457 m) concluded the study. The presence of the following symptoms was evaluated: constipation, diarrhoea, vomiting, regurgitation, failure to thrive and prolonged crying fits (colic). Symptoms were recorded whenever the parents requested a clinical check-up or during a set monthly examination. RESULTS: 1582/2879 (54.9%) infants suffered from one of the gastrointestinal symptoms. Regurgitation was the most common disturbance (present in 23.1% of infants), followed by colic (20.5%), constipation (17.6%), failure to thrive (15.2%), vomiting (6%) and diarrhoea (4.1%). Low birth weight was the factor most frequently associated with the onset of gastrointestinal symptoms, followed by low gestational age. Feeding habits did not influence the onset of symptoms, with the exception of constipation, which was linked to a low frequency of breast-feeding. Ninety-three infants (3.2%) were hospitalised for one or more of the gastrointestinal symptoms which were considered. During the whole study period the type of formula-milk was changed in 60% of the infants with one or more gastrointestinal symptoms, and in 15.5% of the infants who did not suffer from any gastrointestinal troubles. CONCLUSIONS: Gastrointestinal symptoms are very common in infants during the first 6 months after birth. These symptoms required hospitalisation only in a small percentage of cases, but led to the prescription of a 'dietary' milk formula in approximately 60% of the cases. Low birth weight and low gestational age were the main factors influencing the onset of the symptoms.

Genetic association of ARHGAP21 gene variant with mandibular prognathism.

Mandibular prognathism (MP) is a recognizable phenotype associated with dentoskeletal class III malocclusion. MP is a complex genetic trait, although familial recurrence also suggests the contribution of single inherited variations. To date, the genetic causes of MP have been investigated using linkage analysis or association studies in pooled families. Here for the first time, next-generation sequencing was used to study a single family with a large number of MP-affected members and to identify MP-related candidate genes. A 6-generation kindred with MP segregating as an autosomal dominant character was recruited. To identify family members affected by MP, a standard cephalometric procedure was used. In 5 MP subjects separated by the largest number of meioses, whole-exome sequencing was performed. Five promising missense gene variants (BMP3, ANXA2, FLNB, HOXA2, and ARHGAP21) associated with MP were selected and genotyped in most other family members. In this family, MP seemed to consist of 2 distinct genetic branches. Interestingly, the Gly1121Ser variant in the ARHGAP21 gene was found to be shared by all MP individuals in the larger branch of the family with nearly complete penetrance. This variant is rare in the Caucasian population (frequency 0.00034) and is predicted as damaging by all bioinformatic algorithms. ARHGAP21 protein strengthens cell-cell adhesions and may be regulated by bone morphogenetic factors, thus influencing mandibular growth. Further studies in both animal models and human patients are required to clarify the significance of this association.

Physical performance in patients with thalassemia before and after transfusion.

Patients with thalassemia who are on chronic transfusion programs have chronic ventilatory and cardiocirculatory abnormalities. We studied flow-volume curves, blood gas exchange, and cardiorespiratory responses to exercise in 12 patients with thalassemia major (TM) before and 24 hours after transfusions. Cardiorespiratory fitness was assessed with an exercise tolerance test on a cycle-ergometer. Ten healthy controls underwent the same protocol twice, first at baseline and then 24 hours later, without having had transfusions. We identified two subgroups of patients with a questionnaire: 1) those with no history of airway disease; and 2) those with a history of airway obstruction. Patients with no history of airway disease had normal baseline expiratory flows and no posttransfusion changes; those with a history of airway obstruction had lower pretransfusion expiratory flows rates and significantly decreased posttransfusion forced expiratory volume in 1 second (FEV1) and forced expiratory flow at 25-75% of forced vital capacity (FEV25-75%). As a group, TM patients had significantly lower pretransfusion cardiorespiratory function than controls; TM patients' maximum workload was 33% lower, maximum ventilation was 38% lower, maximum oxygen uptake was 25.7% lower, oxygen pulse was 28.6% lower, dyspnea index was 10.6% lower, and ventilatory equivalent for oxygen was 27.1% lower than in control subjects. Although cardiorespiratory responses to exercise improved in both subgroups after transfusion, patients with a history of airways obstruction had a significant posttransfusion increase in their dyspnea index (P = 0.05) and further increased their already abnormally high values of PETCO2 (43 mmHg). These results suggest that the transfusion worsened relative hypoventilation at the maximum workload only in the subgroup with a history of airway obstruction.

Serum haptoglobin appearance during neonatal period is associated with acid phosphatase (ACP1) phenotype.

Erythrocyte acid phosphatase (ACP1) is a polymorphic enzyme found in many tissues and acts in vivo as a flavin-mononucleotide phosphatase. We have recently observed a relation between this enzyme and length of gestation. The present study shows that the pattern of appearance of serum haptoglobin during the neonatal period is associated with ACP1 phenotype suggesting some important function of this polymorphic enzyme in human development.

Hepatic steatosis and thyroid function tests in overweight and obese children.

Objectives. Associations between thyroid function and nonalcoholic fatty liver disease (NAFLD) are unknown in childhood. Thus, the aim of the present study was to investigate in 402 consecutive overweight/obese children the association between thyroid function tests and hepatic steatosis as well as metabolic variables. Methods. Hepatic steatosis was diagnosed by ultrasound after exclusion of infectious and metabolic disorders. Fasting serum samples were taken for determination of thyroid function (TSH, FT4, and FT3), along with alanine aminotransferase (ALT), lipid profile, glucose, insulin, and insulin resistance (IR). Results. Eighty-eight children (21.9%) had TSH above the normal range (>4.0 mIU/L). FT3 and FT4 were within the reference intervals in all subjects. Elevated TSH was associated with increased odds of having hepatic steatosis (OR 2.10 (95% CI, 1.22-3.60)), hepatic steatosis with elevated ALT (2.42 (95% CI, 1.29-4.51)), hypertriglyceridemia, elevated total cholesterol, and IR as well as metabolic syndrome (considered as a single clinical entity), after adjustment for age, gender, pubertal status, and body mass index-SD score (or waist circumference). Conclusions. In overweight/obese children, elevated TSH concentration is a significant predictor of hepatic steatosis and lipid and glucose dysmetabolism, independently of the degree of total and visceral obesity.

Upper limit of normal for alanine aminotransferase: quo vadis?

Several studies suggest that a substantial number of patients with normal serum alanine aminotransferase (ALT) levels, defined by current thresholds, have ongoing hepatic necro-inflammation and fibrosis, and are at risk of liver disease progression. A major problem lies in the definition of normality. The current upper limit of normal (ULN) for ALT was established in the 1980s when reference populations were likely to include many persons with hepatitis C virus infection and nonalcoholic fatty liver disease. Because ALT may be influenced, not only by liver disease, but also by other medical conditions, changing lifestyle factors and demographic determinants, the current ALT ULN threshold has recently been challenged. This review not only highlights current evidence on why and how ALT ULN should be redefined, but also discusses the current concerns about updating the ULN threshold for ALT.

Low 25(OH)D3 levels are associated with total adiposity, metabolic syndrome, and hypertension in Caucasian children and adolescents.

OBJECTIVES: Evidence of the association between vitamin D and cardiovascular risk factors in the young is limited. We therefore assessed the relationships between circulating 25-hydroxyvitamin D(3) (25(OH)D(3)) and metabolic syndrome (MetS), its components, and early atherosclerotic changes in 452 (304 overweight/obese and 148 healthy, normal weight) Caucasian children. METHODS: We determined serum 25(OH)D(3) concentrations in relation to MetS, its components (central obesity, hypertension, low high-density lipoprotein (HDL)-cholesterol, hypertriglyceridemia, glucose impairment, and/or insulin resistance (IR)), and impairment of flow-mediated vasodilatation (FMD) and increased carotid intima-media thickness (cIMT) - two markers of subclinical atherosclerosis. RESULTS: Higher 25(OH)D(3) was significantly associated with a reduced presence of MetS. Obesity, central obesity, hypertension, hypertriglyceridemia, low HDL-cholesterol, IR, and MetS were all associated with increased odds of having low 25(OH)D(3) levels, after adjustment for age, sex, and Tanner stage. After additional adjustment for SDS-body mass index, elevated blood pressure (BP) and MetS remained significantly associated with low vitamin D status. The adjusted odds ratio (95% confidence interval) for those in the lowest (<17 ng/ml) compared with the highest tertile (>27 ng/ml) of 25(OH)D(3) for hypertension was 1.72 (1.02-2.92), and for MetS, it was 2.30 (1.20-4.40). A similar pattern of association between 25(OH)D(3), high BP, and MetS was observed when models were adjusted for waist circumference. No correlation was found between 25(OH)D(3) concentrations and either FMD or cIMT. CONCLUSIONS: Low 25(OH)D(3) levels in Caucasian children are inversely related to total adiposity, MetS, and hypertension.

Respiratory syncytial virus, human bocavirus and rhinovirus bronchiolitis in infants.

OBJECTIVE: To investigate the prevalence of 14 viruses in infants with bronchiolitis and to study demographic and clinical differences in those with respiratory syncytial virus (RSV), human bocavirus (hBoV) and rhinovirus (RV) infection. METHODS: 182 infants aged <12 months hospitalised for bronchiolitis were enrolled. Infants underwent nasal washing for the detection of RSV, influenza virus A and B, human coronavirus OC43, 229E, NL-63, HUK1, adenovirus, RV, parainfluenza 1-3, human metapneumovirus and hBoV. Demographic, clinical and laboratory data were obtained from parents and from patient medical files. Main outcome measurements were age, breastfeeding history, family smoking habits, family history for asthma and atopy, blood eosinophil count, chest radiological findings, clinical severity score and number of days of hospitalisation. RESULTS: A virus was detected in 57.2% of the 182 infants. The most frequently detected viruses were RSV (41.2%), hBoV (12.2%) and RV (8.8%). Infants with dual infections (RSV and hBoV) had a higher clinical severity score and more days of hospitalisation than infants with RSV, RV and hBoV bronchiolitis (mean+/-SD: 4.7+2.4 vs 4.3+/-2.4 vs 3.0+/-2.0 vs 2.9+/-1.7, p<0.05; and 6.0+/-3.2 vs 5.3+/-2.4 vs 4.0+/-1.6 vs 3.9+/-1.1 days; p<0.05). Infants with RV infection had higher blood eosinophil counts than infants with bronchiolitis from RSV and hBoV (307+/-436 vs 138+/-168 vs 89+/-19 n/mm(3); p<0.05). CONCLUSIONS: Although the major pathogen responsible for bronchiolitis remains RSV, the infection can also be caused by RV and hBoV. Demographic characteristics and clinical severity of the disease may depend on the number of viruses or on the specific virus detected.

Fever episodes in early life and the development of atopy in children with asthma.

The hygiene hypothesis proposes that declining exposure to infections may contribute to the allergy and asthma "epidemic", but studies to identify the infections involved have so far provided conflicting data. An alternative approach could be based on an attempt to identify the mechanisms common to several different infections, which may exert an atopy "protective" effect. One of these mechanisms may be fever, which is frequently associated with infections and may stimulate the synthesis of interferon-gamma. The aim of this study was to test whether the frequency of fever episodes in the first years of life are related to the development of atopy. Asthmatic (cases, n=317) and nonasthmatic children (controls, n=304) attending the outpatients' allergy clinic were enrolled. The number of fever episodes in the first 2 yrs of life was retrospectively assessed by parental report via a questionnaire completed by interview. Atopy was determined by skin-prick tests to 10 prevalent inhalant allergens at the time of examination. Fever episodes in the first or in the second year of life were significantly more frequent among children with asthma. However, this difference was totally accounted for by a subgroup of children who started wheezing in the first 12 months of life. A significant inverse association between fever episodes in the first 12 months of life and atopy was found among cases, but not in controls. The association persisted after adjusting for age, sex, daycare attendance and family history of atopic disease and this was totally accounted for by asthmatic children who started wheezing after the first 12 months of life. No significant association was found between fever episodes in the second year of life and atopy for cases and controls. The data presented here suggests that fever episodes early in life may affect the natural history of asthma by preventing the development of atopy and highlights the need to monitor fever episodes of any kind in longitudinal studies aimed at investigating the hygiene hypothesis prospectively.

Passive smoking in childhood--tobacco smoke.

Prevalence of cigarette smoking varies widely in different countries, ranging, at the age of 13, from 2% to 5% (Sweden, United States) to more than 30% (Australia, Uruguay). Even if the prevalence of smokers among male adolescents is decreasing in western countries, it is increasing among girls and, in developing countries, male adolescent smokers still reach 40% (and up to 70%-80%). The determination of saliva cotinine levels, a product of nicotine metabolism, is an useful indicator of exposure to passive or active smoking. In a study of 210 children aged 9-13 years, we found detectable levels of saliva cotinine in 13% of children who lived in nonsmoking families and denied being regular smokers and in only 60% of children living in families with heavy cigarette consumption. This wide variations of a marker of smoking exposure may explain the differences in reported consequences of tobacco smoke in investigations conducted in different places and on different target populations. We later studied the effects of environmental tobacco smoke (ETS) in a sample of 166 nine-year-old children. The relationship between parental smoking and degree of bronchial responsiveness in males was significant. Also, prick skin test reactivity to allergens was significantly increased in children of smoking parents. Many studies concerning the effects of ETS exposure seem to demonstrate that not only the lungs and not only children are affected even if the difficulty of the epidemiology in such a field must suggest caution in interpreting the results.(ABSTRACT TRUNCATED AT 250 WORDS)