Serum level of testosterone, dihydrotestosterone and IGF-1 during an acute exacerbation of COPD and their relationships with inflammatory and prognostic indices: a pilot study.

AIM: Acute exacerbations (AECOPD) of negatively influence the natural history of chronic obstructive pulmonary (COPD) and they are related to muscle dysfunction. In this pathway hypogonadism could play a pivotal role. Our study wants to evaluate possible relationships among prognostic indexes of AECOPD, represented by Acute Physiology and Chronic Health Evaluation (APACHE) II, inflammation (serum amyloid A, SSA) and anabolic hormones, especially less studied steroids, like dihydrotestosterone (DHT) e free-testosterone (f-T). METHODS: Twenty-four patients (17 males; age 75 ± 13 yrs) were studied. On admission and at discharge a blood sample for total testosterone (T), DHT, insulin like grow factor 1 (IGF-1) and Serum Amyloid A (SSA) was obtained. f-T was calculated using Vermeulen's formula. RESULTS: Descriptive statistical analysis shows reduced of T values (1.85 ± 2.28 ng/mL), f-T (0.028 ± 0.030 ng/mL), DHT (0.18 ± 0.19 ng/mL) and IGF-1 (91.840 ± 74.19 pg/mL). Calculating tertile for Apache II and SSA and using them as cut off point, three categories were made and used in the analysis (SSA< 10 mg/mL; 10-160 mg/mL; > 160 mg/mL); (APACHE II ≤ 10; 11-12; > 12). Using this classification, an inverse correlation between SAA and T (P = 0.01), f-T (0.01), DHT (0.001) and IGF-1 (P = 0.05) was found. Data show the same inverse relationship between APACHE II tertiles on one hand and T (P = 0.01) and f-T (P = 0.02) on the other hand. CONCLUSION: Our data confirm systemic effects of AECOPD and the role of endocrinological derangements, suggesting a possible mechanism explaining them.

Relationship between plasma antioxidants and thyroid hormones in chronic obstructive pulmonary disease.

BACKGROUND: A low-T3 syndrome is observed in chronic diseases, but its treatment is still debated. Chronic obstructive pulmonary disease (COPD) has not been conclusively studied under this aspect. COPD is a complex condition, which cannot be considered a lung-related disorder, but rather a systemic disease also associated to increased oxidative stress. We evaluated thyroid hormones and antioxidant systems, the lipophilic Coenzyme Q10 (CoQ10) and total antioxidant capacity (TAC) in COPD patients to reveal the presence of a low-T3 syndrome in COPD and investigate the correlation between thyroid hormones, lung function parameters and antioxidants. METHODS: We studied: 32 COPD patients and 45 controls, evaluating thyrotropin (TSH), free-triiodotyronine (fT3), free-tetraiodotyronine (fT4), CoQ10 (also corrected for cholesterol) and TAC. CoQ10 was assayed by HPLC; TAC by the metmyoglobin-ABTS method and expressed as latency time (LAG) in radical species appearance. RESULTS: We found significantly lower LAG values, fT3 and fT4 levels and significantly higher TSH in COPD patients vs. controls. LAG values significantly correlated with fT3 concentration. 12 out of 32 patients exhibited fT3 levels lower than normal range. So we divided COPD patients in 2 groups on the basis of the fT3 concentration (normal fT3 COPD and low fT3 COPD). We observed lower LAG values in normal fT3-COPD, compared to healthy subjects, with a further significant reduction in low fT3-COPD patients. Moreover higher TSH concentration was present in normal fT3-COPD, compared to healthy subjects, with a further significant increase in low fT3-COPD patients. CoQ10/cholesterol ratio was higher in low fT3-COPD vs. normal fT3-COPD, with a nearly significant difference. CONCLUSIONS: These data seem to indicate an increased oxidative stress in low fT3-COPD and a role of fT3 in modulating antioxidant systems. However low fT3 levels are joined to metabolic indexes of true hypothyroidism, suggesting that elevated CoQ10 expresses a reduced tissue utilization. These data might suggest the need of thyroid replacement therapy in such a condition.

Do we need different treatments for very elderly COPD patients?

Population ageing is a new challenge for physicians because of the clinical complexity of the elderly. Although geriatric pharmacology is an emerging issue, very little is known and the choice of different treatments for the very elderly is still an important question. Chronic obstructive pulmonary disease is one of the most common chronic diseases throughout the world affecting prevalently older people. Despite the increasing burden of chronic obstructive pulmonary disease in older people, underdiagnosis and undertreatment in this age group are still common problems. Some patients are frail as they have impaired homeostatic mechanisms, deteriorated physiological systems, and limited functional reserve. Pharmacotherapeutic decisions should be combined with a careful assessment of comorbidity, polypharmacy, and age-related changes in pharmacokinetics and pharmacodynamics in order to minimize adverse drug events, drug-drug or drug-disease interactions, and nonadherence to treatment. There are few studies that specifically examine age as a factor influencing the pharmacokinetics and pharmacodynamics of inhaled therapies, the cornerstone of treatment for chronic obstructive pulmonary disease. This review provides a summary of age-related physiological changes and their impact on pharmacokinetics and pharmacodynamics, with particular regard to the drugs implicated in chronic obstructive pulmonary disease treatment, in order to optimize drug therapy.

Is pulmonary function damaged by neoadjuvant lung cancer therapy? A comprehensive serial time-trend analysis of pulmonary function after induction radiochemotherapy plus surgery.

OBJECTIVE: We have analyzed short- and long-term variations of pulmonary function in locally advanced non-small cell lung cancer after induction chemoradiotherapy. METHODS: Twenty-seven patients with stage IIIA (N2) non-small cell lung cancer underwent resection with radical intent after induction chemoradiotherapy in the period 2003 to 2006. Pulmonary function has been evaluated by spirometry, diffusing capacity of the lung for carbon monoxide, and blood gas analysis before induction chemoradiotherapy (T0), 4 weeks after induction chemoradiotherapy and before surgery (T1), and 1 (T2), 3 (T3), 6 (T4), and 12 months (T5) after surgery. RESULTS: A 22.80% decrease of diffusing capacity of the lung for carbon monoxide (P < .001) was observed at T1. At T2 significant decreases in the following were present: vital capacity, -20.50% (P < .001); forced vital capacity, -22.50% (P < .001); forced expiratory volume in 1 second, -23.00% (P < .001); peak expiratory flow, -29.0 (P < .001); forced expiratory flow 25% to 75%, -13.7% (P = .005); and diffusing capacity of the lung for carbon monoxide, 43.6% (P < .001). However, in the interval between T2 and T5, a progressive improvement of lung function in most parameters was observed, but only diffusing capacity of the lung for carbon monoxide presented a significant increase (P < .001). Within the same time gap (T2 to T5), subjects 65 years of age or younger showed an increasing trend for vital capacity, forced expiratory volume in 1 second, total lung capacity, and residual volume significantly different from that of elderly patients, in whom a decrease in these parameters is reported. CONCLUSIONS: An impairment of respiratory function is evident in the immediate postoperative setting in patients with non-small cell lung cancer receiving induction chemoradiotherapy. In the long-term period, a general recovery in diffusing capacity of the lung for carbon monoxide was found, whereas an improvement of forced expiratory volume in 1 second, vital capacity, total lung capacity, and residual volume was detected in the younger population only.

Induction cisplatin-gemcitabine-paclitaxel plus concurrent radiotherapy and gemcitabine in the multimodality treatment of unresectable stage IIIB non-small cell lung cancer.

BACKGROUND: To evaluate feasibility and safety of induction three-drugs combination chemotherapy and concurrent radio-chemotherapy in stage IIIB NSCLC. PATIENTS AND METHODS: Patients with stage IIIB NSCLC were treated with three courses of induction chemotherapy, cisplatin 50 mg/m(2), paclitaxel 125 mg/m(2) and gemcitabine 1000 mg/m(2) on days 1,8 of every 21 day cycle. Patients without distant progressive disease were then treated with radiotherapy and concurrent weekly gemcitabine (250 mg/m(2)). Toxicity and response of radio-chemotherapy treatment have been assessed. RESULTS: Between Jan 01 and Nov 02, 46 patients were enrolled. Grade 3+ hematological and non-hematological toxicity during the induction phase were 41.3% and 13.1%, respectively. In 38 patients a Clinical Response or Stable Disease was recorded and these patients underwent to concurrent radio-chemotherapy. Grade 3+ hematological and non-hematological toxicities were 8.2% in this group. Further response was observed in 66% of patients. Overall median survival time was 17.8 months, with a 3-year survival rates of 23%. CONCLUSION: Three-drugs induction chemotherapy and concurrent radio-chemotherapy with weekly gemcitabine in locally advanced stage IIIB NSCLC is feasible and safe.

Relationships between plasma CoQ10 levels and thyroid hormones in chronic obstructive pulmonary disease.

In previous works we demonstrated an inverse correlation between plasma Coenzyme Q 10 (CoQ10) and thyroid hormones; in fact, CoQ10 levels in hyperthyroid patients were found among the lowest detected in human diseases. On the contrary, CoQ10 is elevated in hypothyroid subjects, also in subclinical conditions, suggesting the usefulness of this index in assessing metabolic status in thyroid disorders. On the other hand, a low-T3 syndrome, due to reduced peripheral conversion from the prohormone T4, is observed in different chronic diseases: this condition is considered an adaptation mechanism, usually not to be corrected by replacement therapy. In order to perform a metabolic evaluation, we have studied a group of 15 patients, aged 69-82 ys, affected by chronic obstructive pulmonary disease (COPD), comparing respiratory indexes, thyroid hormones and CoQ10 levels (also normalized with cholesterol levels) in patients with low (group A) or normal (group B) free-T3 (FT3) concentrations. We found that CoQ10 levels were significantly higher in patients of group A than in B (0.91+/- 0.03 vs 0.7 +/- 0.04 microg/ml respectively); the same difference was observed when comparing the ratios between CoQ10/cholesterol in the two groups (200.16 +/- 8.96 vs 161.08 +/- 7.03 nmol/mmol respectively). These preliminary data seem to indicate that low T3 levels are accompanied by metabolic indexes of a true hypothyroidism in COPD patients. Whether this datum supports the need to perform a replacement therapy in such a condition requires further studies.

Neoadjuvant concurrent radiochemotherapy in locally advanced (IIIA-IIIB) non-small-cell lung cancer: long-term results according to downstaging.

BACKGROUND: To report the efficacy of induction treatment (IT) protocol with concurrent radiochemotherapy in locally advanced non-small-cell lung cancer (NSCLC), and to analyze downstaging as a surrogate end point. PATIENTS AND METHODS: Patients with histo- or cytologically confirmed stage IIIA or IIIB NSCLC were treated according to an IT protocol followed by surgery. Downstaging was assessed for all resected patients. RESULTS: In the period between February 1992 and July 2000, 92 patients were enrolled in the study (57 IIIA, 35 IIIB). Response was observed in 63 patients; 56 patients underwent radical resection. Patients downstaged to stage 0-I (DS 0-I) showed a statistically significant improved disease-free survival (26.2 months pStage 0-I versus 11.2 months pStage II-III; P=0.0116) and overall survival (median 32.5 months pStage 0-I versus 18.3 months pStage II-III; P=0.025). Patients with DS 0-I had a significantly lower probability (P=0.0353) of developing distant metastases estimated in 0.2963 odds ratio. CONCLUSION: Neoadjuvant radiochemotherapy is feasible with good pathological DS results. Pathological downstaging was confirmed to have high predictive value. Its use is suggested in the short-term evaluation of induction protocols efficacy in locally advanced NSCLC.

Passive smoking and lung function in alpha(1)-antitrypsin heterozygote schoolchildren.

BACKGROUND: A study was performed to determine whether Pi heterozygotes exposed to smoking have a higher risk of reduced lung function than Pi M homozygotes. METHODS: The effect of passive smoking on lung function was investigated in a cross sectional study of 997 primary and secondary schoolchildren aged 11-13 years categorised by Pi phenotype as either PiM homozygotes or Pi heterozygotes. Data on respiratory health and risk factors were collected by questionnaire, lung function was measured by spirometric tests, bronchial hyperresponsiveness was evaluated by methacholine test, atopic status was evaluated by skin prick testing, and a blood sample was collected to determine Pi phenotype. Urinary cotinine and creatinine concentrations were determined and assessment of exposure was made from questionnaire data and urinary cotinine concentrations. The results were analysed by multiple regression analysis. RESULTS: Sixty one subjects (6.1%) were found to be Pi heterozygotes. Lung function did not differ between homozygotes and heterozygotes. There was a reduction in lung function in subjects exposed to parental smoking in the overall sample: FEV(1)/FVC ratio (-0.78%), FEF(25-75) (-0.11 litres), and FEF(75) (-0.13 litres). Interaction terms between parental smoking and Pi status were significant with regard to FEV(1)/FVC ratio (p=0.035) and FEF(50) (p=0.023). In subjects exposed to parental smoking the decrement in lung function in Pi heterozygotes tended to be greater (FEV(1)/FVC ratio = -2.57, FEF(25-75) = -0.30, FEF(50) = -0.43, and FEF(75) = -0.29) than in PiM homozygotes. These results did not change significantly when the urinary cotinine concentration was used as an exposure variable. CONCLUSIONS: The detrimental effect of environmental tobacco smoke on lung function in schoolchildren is confirmed. This harmful effect is greater in Pi heterozygotes than in PiM homozygotes.

Snoring in 9- to 15-year-old children: risk factors and clinical relevance.

OBJECTIVE: Our objective was to investigate the occurrence of snoring in a general population sample of children and to evaluate the association with anthropometric data and clinical findings of oropharynx and nasal airways. METHODS: A cross-sectional study was conducted with children from primary and secondary schools in Civitavecchia and Viterbo in the Latium region in central Italy. The total sample of the survey included 2439 schoolchildren. A total of 2209 children who were ages 10 to 15 years were selected (response rate: 90.5%) according to their snoring frequency during sleep: never, only with colds, occasionally apart from with colds, often. Children in the last category were defined as habitual snorers. Data were collected by means of questionnaires and clinical examination. A blood sample was collected to determine the concentration of hemoglobin in the blood. Logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals. RESULTS: The prevalence of habitual snorers was 5.6%. Boys who were older than 15 years and had a body mass index greater than the 90th percentile were significantly more likely to be snorers. Habitual snoring was strongly associated with decreased nasal patency (rhinitis OR: 2.13; septal deviation OR: 2.75; nasal obstruction OR: 2.20). Children who had undergone adenoidectomy or had markedly enlarged tonsils were at greater risk of being habitual snorers (OR: 4.28 and 5.07, respectively). Last, habitual snorers had a significantly higher concentration of hemoglobin in the blood compared with other children. CONCLUSION: Body weight and nasal and pharynx patency seem to be the main determinants of snoring. The finding of higher values of blood hemoglobin concentration in snorers than in nonsnorers suggests that these children could be experiencing oxyhemoglobin desaturation during sleep. Taking into consideration the relationship between these different risk factors could lead to a better clinical approach to the snoring child.

Effect of gas cooking on lung function in adolescents: modifying role of sex and immunoglobulin E.

BACKGROUND: A study was undertaken to investigate the effect of gas cooking on the lung function of adolescents while considering serum IgE level as a possible effect modifier. METHOD: The cross sectional study was performed in 702 subjects aged 11-13 years from primary and secondary schools in Civitavecchia and Viterbo ( Latium region in Central Italy), categorised according to how often they were in the kitchen while the mother cooked (never, sometimes, often). Data were collected by questionnaire and lung function was measured by spirometric tests. Bronchial hyperresponsiveness was evaluated by the methacholine test, atopic status by a skin prick test, and a blood sample was collected to determine serum IgE levels. The results were analysed separately for boys and girls. Multiple regression analysis was performed, taking functional parameters (FEV(1), FEV(1)/FVC, FEF(25-75), FEF(50), FEF(75)) as the dependent variables and age, height, parental smoking, and father's education as independent variables. RESULTS: There was no association between time spent in the kitchen and lung function level in boys, but a reduction in lung function was detected in girls which was statistically significant for FEF(75) (sometimes -10.3%, often -11.1%). After stratifying boys and girls into four groups on the basis of the IgE serum level (below and above the median value of IgE), the reduction in lung function was significant in girls with a high IgE value whereas no significant deleterious effects were evident in girls with a low IgE value or in boys with either a low or high IgE. The results remained substantially unchanged after excluding girls with a response to methacholine below the concentration of 4 mg/ml, asthmatic patients, and those with positive skin prick tests. CONCLUSION: Gas cooking has a harmful effect on the lung function of girls with a high serum level of IgE. We do not know whether serum IgE, a marker of allergic susceptibility, is a simple indicator that an inflammatory process is in progress or whether it is involved in the pathogenesis of injury leading to bronchial obstruction.

Short term respiratory effects of acute exposure to chlorine due to a swimming pool accident.

OBJECTIVE: Acute exposure to chlorine causes lung damage, and recovery may proceed slowly for several weeks. The short term respiratory effects of acute chlorine inhalation during a swimming pool accident were examined. METHODS: A total of 282 subjects (134 children, aged <14 years) inhaled hydrogen chloride and sodium hypochlorite during an accident caused by a malfunction of the water chlorinating system in a community pool in Rome in 1998. Most people received bronchodilators and cortisone at the emergency room; five children were admitted to hospital. A total of 260 subjects (92.2%) were interviewed about duration of exposure (<3, 3--5, >5 minutes), intensity of exposure (not at all or a little, a moderate amount, a lot), and respiratory symptoms. Lung function was measured in 184 people (82 children) after 15--30 days. The effects of exposure to chlorine were analysed through multiple linear regression, separately in adults and in children. RESULTS: Acute respiratory symptoms occurred among 66.7% of adults and 71.6% of children. The incidences were highest among those who had chronic respiratory disease and had a longer duration of exposure. In about 30% of the subjects, respiratory symptoms persisted for 15--30 days after the accident. Lung function levels were lower in those who reported a high intensity of exposure than in those who reported low exposure, both in children and in adults (mean (95% confidence interval (95% CI)) differences in forced expiratory volume in 1 second (FEV(1,)) were -109 (-310 to 93) ml, and -275 (-510 to -40) ml, respectively). CONCLUSION: Persistent symptoms and lung function impairment were found up to 1 month after the incident. Although community pool accidents happen rarely, the medical community needs to be alerted to the possible clinical and physiological sequelae, especially among susceptible people.

Radiotherapy versus follow-up in the treatment of pathological stage Ia and Ib non-small cell lung cancer. Early stopped analysis of a randomized controlled study.

OBJECTIVE: This is an analysis of a randomized controlled clinical trial planned to evaluate the effects of adjuvant radiotherapy (AR) on the local recurrence rate in patients with non-small cell lung cancer (NSCLC) with pathological stage (pStage) Ia (pT1N0) and Ib (pT2N0). The effects of AR on the long-term survival have also been marginally evaluated. MATERIALS AND METHODS: This clinical trial was planned with the hypothesis that AR on pStage Ia and Ib, R0 NSCLCs was effective on local recurrence rate. From July 1989 through March 1997, 104 patients with NSCLC who presented with pStage Ia and Ib have been observed and treated and entered the study. Male/female ratio was 91:13; the mean age was 62 years (range 41-75 years). All patients underwent major pulmonary resection and homolateral standard hilar and mediastinal lymph node dissection. pStage was T1N0 in 29 and T2N0 in 75 cases. Patients have been randomized 'by chance' into two groups (G1 and G2). G1 received radiotherapy, G2 did not receive any adjuvant treatment. Fifty-two patients entered G1 and 52 entered G2. RESULTS: Post-operative mortality was nil. Seven patients have been excluded from the study (four in G1 and three in G2), due to incomplete follow-up data. We do not report any radiotherapy-related complication or deterioration of lung function. The treatment effect on the local recurrence rate demonstrated a clearly significant protective effect of the AR. No statistically significant difference was found from the comparison of the 5-year survival rate of the treated (83%) versus untreated (70%) patients. No detrimental effect of the radiotherapy has been assessed. CONCLUSIONS: AR in the treatment of pStage Ia and Ib NSCLC has been well tolerated and had a significant relative effect on the local recurrence rate but did not significantly modify overall survival even if a positive trend in the group of treated patients is reported.

Repeatability of the ISAAC video questionnaire and its accuracy against a clinical diagnosis of asthma.

The objective of the study was to evaluate the performance of the International Study of Asthma and Allergies in Childhood (ISAAC) video questionnaire in terms of repeatability and accuracy against a clinical diagnosis of asthma achieved according to the National Heart, Lung and Blood Institute (NHLBI) algorithm. Two hundred and forty-one subjects, aged 13-14 years from two secondary schools in Rome, Italy, were enrolled. Video and written ISAAC questionnaires were completed twice, 3 months apart, by 194 and 190 adolescents, respectively. Two months later, 106 subjects were visited by two physicians blinded to the results of questionnaires. Sixteen subjects were classified as having clinical asthma (CA) at the clinical visit, and eight of them as having clinical active asthma (CAA) on the basis of at least one positive outcome of the NHLBI algorithm. The repeatability of video questionnaire was similar to that of the written questionnaire for items on exercise wheeze and nocturnal cough and, to a lesser degree, for items concerning any wheeze in the past. The video questionnaire showed a worse performance than the written questionnaire for items on asthma attack: K-value (95% CL) = 0.59 (0.37-0.80) for video scene no. 5 and K-value (95% CL) = 0.86 (0.74-0.98) for written question no. 6. The overall accuracy of the video questionnaire, estimated as a positive answer to any video scene, was lower in terms of sensitivity than that of any written question when CA was used as a gold standard (0.50 vs. 0.81, P=0.025) and increased with respect to CAA (0.75 vs. 0.87, P = 0.317). The specificity of any video scene was better than that of any written question, independently from the gold standard used. In conclusion, the video questionnaire showed a fairly good accuracy, although slightly lower than that of the written questionnaire and provided sufficiently reliable results. However, samples of subjects from different geographic areas and cultures should be studied in order to conclusively define the performance of the ISAAC video questionnaire.

Risk factors for early, persistent, and late-onset wheezing in young children. SIDRIA Collaborative Group.

Wheezing in childhood is not a single disorder and different wheezing-associated respiratory illnesses have been recently described. We investigated the association between wheezing conditions and familial, pre-, peri-, and postnatal risk factors. We studied 16,333 children, 6 to 7 yr old, enrolled in a population-based study. Standardized questionnaires were filled in by parents. A total of 1,221 children had transient early wheezing, 671 had persistent wheezing, 918 had late-onset wheezing, and 13,523 never had wheezing or asthma (control group). Maternal asthma or chronic obstructive airway disease were significantly (p < 0.0001) more associated with persistent wheezing than with transient early and late-onset wheezing. The same pattern was observed for exposure to maternal smoke during pregnancy. Having a mother > 35 yr old was protective against transient early wheezing (odds ratio [OR]: 0.68, 95% confidence intervals [95% CI]: 0.53 to 0.86). Breast feeding >/= 6 mo was slightly protective against transient early wheezing (OR: 0.82, 95% CI: 0.68 to 0.97), whereas it was a moderate risk factor for late-onset wheezing (OR: 1.22, 95% CI: 0.99 to 1.50). On the contrary, having siblings and attending a day care center were both risk factors for transient early wheezing (OR: 1.41 [95% CI: 1.21 to 1.64] and 1.70 [95% CI: 1.48 to 1.96], respectively) and protective factors against wheezing of late onset (OR: 0.83 [95% CI: 0.70 to 0.97] and 0.72 [95% CI: 0.59 to 0.88]). There was a stronger (p < 0.0001) positive association between personal history of eczema or allergic rhinitis and persistent and late-onset wheezing than transient early wheezing. Our findings suggest a different contribution of risk factors to wheezing conditions in childhood.

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: (1) "current asthma" (children, 5.2%; adolescents, 6.2%) and (2) "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) = 1.34; 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.

Prevalence of sinusitis in young asthmatics and its relation to bronchial asthma.

In this paper, we present data on the prevalence of sinusitis and its relationship to bronchial asthma in 120 young male asthmatics evaluated without exacerbations of their disease. All patients reported respiratory symptoms during the preceding year, and in the most of them (74%), the severity of asthma was mild. Sinusitis was observed in 52 patients (43.3%), and the maxillary sinus was involved in 36 asthmatics. Sixteen of 52 patients with sinusitis had never had nasal symptoms of rhinitis. In all patients, physical examination of the lung was negative for wheezing. All patients had FEV1 (forced expiratory volume/forced vital capacity x 100 in 1 second of expiration) values in the normal range, and bronchial hyperresponsiveness was detected in 101 asthmatics (84.2%). One hundred sixteen patients (96.6%) were found to be skin reactors. We did not find statistical differences between asthmatics with or without sinusitis with regard to severity of asthma, basal lung function, and bronchial hyperresponsiveness. We suggest that antibiotic therapy for sinusitis should be given only to asthmatics with worsening respiratory symptoms and obvious signs of chronic sinusitis.

Slow compartment features and gas exchange impairment in mild asthma: effects of beta agonist inhalation.

Static and dynamic lung volumes, arterial blood gases, alveolar ventilation and ventilation-perfusion (VA/Q) relationships were studied in 14 mild asthmatic patients and in 7 normal subjects (as controls) before and after fenoterol inhalation. Multiple nitrogen washout curves were analyzed by a bicompartmental distribution model, in order to assess the distribution of ventilation and VA/Q mismatch. At baseline, asthmatics showed mild airway obstruction and gas exchange impairment [forced expiratory volume in 1 s (FEV1) = 79% pred; PaO2 = 87.4; alveolar-arterial oxygen tension gradient (AaPO2) = 22.9 mm Hg]. By analysing nitrogen washout curves, an alveolar slow space representing 45.1% of total lung volume (vs. 36.8% in normals; p = 0.044) was identified; its alveolar ventilation per minute per unit lung volume (VA2/L2) was lower than in normals (p = 0.01). beta-Agonist inhalation by the asthmatics, which reversed airway obstruction (FEV1 = 98% pred.; p < 0.001) and improved gas exchange (PaO2 = 92.6 mm Hg, p < 0.001; AaPO2 = 16.8 mm Hg, p = 0.003), led to a highly significant increase in VA2/L2 (p = 0.001). The improvement in PaO2 was associated with the increase in VA2/L2 (r2 = 0.39; p = 0.017), but not with the increase in FEV1. Lastly, the changes in FEV1 and VA2/L2 were not correlated with each other. We conclude that even in mild stable asthma there is substantial unevenness of ventilation, detectable by bicompartmental analysis of nitrogen washout curves, which is responsible for gas exchange impairment and is not related to common spirometric parameters. In addition, the improvement in gas exchange is probably due to the effect of fenoterol on the tributary airways of the alveolar slow compartment. This effect can be assessed by this simple method, which can be used in clinical pharmacology studies and in the follow-up of asthmatic patients.

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 father's 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.