Determinants of response to hypercapnia and to progressive and transient hypoxia in obstructive sleep apnea patients.

BACKGROUND: The knowledge regarding the control of breathing during wakefulness in patients affected by obstructive sleep apnea (OSAS) is still challenging. The aim of this study is firstly to analyze hypoxic and hypercapnic ventilatory response in OSA patients in comparison to controls and secondly, to investigate correlations between chemosensivity and both lung function tests, such as arterial blood gas analysis and spirometric parameters, and clinical characteristics, such as age and BMI. METHODS: Seventeen never treated OSA patients (16M; 53±13.2 years; BMI=34.5±8.1; AHI=45±14.7) underwent nocturnal cardiopulmonary monitoring test, complete lung function tests (spirometry, lung volumes and arterial blood gas analysis on room air). Read's rebreathing test was used to evaluate hypercapnic ventilatory response (HVRCO2); hypoxic ventilatory response (HVRO2) was studied through progressive and transient methods. The response was expressed in terms of slope of linear regression for HVRCO2 and of hyperbolic curve for HVRO2 between minute ventilation (VE) or mean inspiratory flow (VT/Ti) and PetCO2 or PetO2. RESULTS: The OSA group showed increased transient, but not progressive, HVRO2 and a lower HVRCO2. A lower HVRCO2 was predicted by greater values of BMI (P<0.01). Progressive HVRO2 increased with age and lower FEV1/VC, while transient HVRO2 (P<0.05) was inversely correlated with the nocturnal lowest SaO2 (P<0.01). CONCLUSIONS: Nocturnal intermittent hypoxic stimuli increases daytime glomic reactivity to transient hypoxia, while BMI is the main independent determinants of the bulbar response to hypercapnia in normocapnic OSAS patients.

Irritable Bowel Syndrome and Nickel Allergy: What Is the Role of the Low Nickel Diet?

BACKGROUND/AIMS: Irritable bowel syndrome (IBS) is characterized by chronic abdominal pain or discomfort accompanied by abnormal bowel movements. In sensitized subjects, ingested nickel (Ni) may induce gastrointestinal symptoms similar to IBS, in addition to typical systemic cutaneous lesions (systemic nickel allergy syndrome [SNAS]). A low nickel diet could improve the systemic manifestations. We evaluated prevalence of nickel allergy in IBS and effects of low Ni diet on (1) gastrointestinal symptoms control, (2) intestinal barrier function, (3) quality of life, and (4) psychological status of patients with IBS and Ni-sensitized patients. METHODS: Twenty consecutive patients affected by IBS and suspected SNAS underwent intestinal permeability tests. Gastrointestinal symptoms were evaluated using the visual analogue scale before and after 3 months low Ni diet. Subjects with increased intestinal permeability at baseline repeated nuclear examination after the diet. RESULTS: The most frequent profile was diarrhea-predominant IBS (8/20). The low Ni diet induced a significant and constant improvement of gastrointestinal symptoms and an equally significant improvement of visual analogue scale. Mean urinary output of 5¹Chromium ethylene-diamine-tetra-acetate (5¹Cr-EDTA) was 5.91%/24 hr (± 2.08), significantly different from the control group (2.20%/24 hr ± 0.60, P < 0.0001). CONCLUSION: This pilot study shows that low Ni diet improves gastrointestinal symptoms in patients with IBS and SNAS.

Look at the lung: can chest ultrasonography be useful in pregnancy?

BACKGROUND: This study aimed to evaluate the clinical value of chest ultrasound (US) in the detection, diagnosis and follow-up of pathologic processes of both peripheral lung parenchyma and pleural space in pregnant women. FINDINGS: Pregnant women admitted to Obstetric Pathology Hospital Department for respiratory diseases were enrolled. Chest US examination was performed when there was a respiratory disease highly suggestive of pneumonia and/or pleural effusion and chest X-ray (CXR) should have been obtained. Three chest US patterns were identified: lung consolidation (LC), pleural effusion (PE) and focal sonographic interstitial syndromes (SIS). When chest US pathologic signs were reported, one or more subsequent chest US examinations were performed to follow-up the patient until their complete resolution. Sixteen inpatients underwent 54 chest US evaluations. We identified: 9 LCs, 6 PEs and 11 SISs. Total number of CXRs was 7 (10 females avoided X-rays exposure and one underwent 2 CXR evaluations on the advice of Gynecologist). Chest US follow-up, during and after therapy, showed complete resolution of echographic patterns previously described. CONCLUSIONS: Chest US evaluation during pregnancy is a useful diagnostic tool to detect and monitor respiratory diseases, avoiding excessive X-rays exposure.

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.

Parental smoking and lung function: misclassification due to background exposure to passive smoking.

We evaluated the role played by background exposure (i.e. exposure to Environmental Tobacco Smoke, ETS, from sources other than parental smoking) when evaluating the effect of parental smoking on lung function of adolescents. We performed a cross-sectional survey (937 adolescents) in the Lazio Region. Data were collected by a questionnaire, lung function tests and urinary cotinine to creatinine ratios (CCR) were measured. We found that 62.1% of subjects were exposed to current parental smoke. Among the 355 adolescents not exposed to parental smoke, a total of 92 (25.9%) had CCR levels greater than the median value of the distribution (17.3 ng/mg). Subjects with smoking parents had higher FVC and significant lower FEV(1)/FVC ratios than subjects without smoking parents. When "Background" ETS exposure was removed from the unexposed group by separately studying those without parental exposure but with CCR>17.3, results showed a reduction in lung function due to parental smoking which is greater compared to the previous model. Our study adds further evidence regarding the detrimental effect of ETS on lung function of adolescents. Negative results on the effect of parental smoking on lung function should be revisited if background exposure has not been considered in the analysis.

Multimodality treatment of unresectable stage III non-small cell lung cancer: interim analysis of a phase II trial with preoperative gemcitabine and concurrent radiotherapy.

OBJECTIVE: We report the preliminary results of a phase II trial undertaken to determine the feasibility and efficacy of gemcitabine and concurrent radiotherapy in patients with inoperable stage III non-small cell lung cancer. METHODS: Between February 2001 and June 2003, a total of 46 patients (37 male and 9 female, median age 64 years) with clinical stage III non-small cell lung cancer (41 cIIIA and 5 cIIIB) were enrolled in a combined chemoradiation protocol with gemcitabine as the chemotherapeutic agent. Gemcitabine (350 mg/m2) was administered weekly for 5 consecutive weeks as a 30-minute intravenous infusion before radiotherapy (total dose 50.4 Gy, 1.8 Gy/d). Toxicity was routinely assessed. Those patients with disease judged to be resectable at restaging underwent surgery. RESULTS: Toxicity was moderate, with the exception of 1 grade 3 thrombocytopenia. All but 5 patients were available for restaging. No complete responses were observed. Thirty-four patients (82.9%) had partial responses, 5 (12.2%) had stable disease, and 2 (4.9%) had progressive disease. Twenty-nine of 46 patients (63%, 27 cIIIA and 2 cIIIB) underwent surgery. Radical resection was possible in all cases. Surgery included 17 lobectomies, 4 bilobectomies, and 8 pneumonectomies. There were no deaths. Morbidity was 13.8% (4/29). Pathologic downstaging to stage 0 or I was observed in 18 patients (39%, 18/46). After a median follow-up of 13 months (range 2-28 months), 24 of the patients who had undergone operation (86.2%) were alive, with a median disease-free survival of 16 months. Overall 2-year survival was 66.1%, with a significant difference between resected and unresected disease (82% vs 36%, P = .0002). CONCLUSION: The results of this induction trial confirm the feasibility and the efficacy of gemcitabine with concurrent radiotherapy.

Rhinitis and snoring as risk factors for hypertension in post-menopausal women.

OBJECTIVE: Several studies have suggested an association between snoring and hypertension. An association between rhinitis and hypertension has been recently indicated in men but not in women. Since menopausal status is an important determinant of blood pressure, we evaluated the relationship between rhinitis, snoring and blood pressure taking into account the modifying effect of menopausal status. DESIGN: Cross-sectional survey. SETTINGS: Four areas of Italy: the Po river Delta, Pisa (Tuscany), Viterbo (Lazio) and Rome. MAIN OUTCOME MEASURES: Data were collected by a questionnaire and a medical visit. PARTICIPANTS: One thousand five hundred and fifty-four female non-smokers. RESULTS: Systolic blood pressure (SBP) was significantly related to both occasional and habitual snoring in the overall sample. No associations were found between SBP, snoring, and rhinitis in pre-menopausal women. Both occasional and habitual snoring, but not rhinitis, were significant risk factors for increased SBP in women who stopped menstruating fewer than 11 years previously (beta=10.27 mmHg, 95% confidence interval (CI)=3.5, 17.01 and beta=9.91 mmHg, 95% CI=2.3, 17.5, respectively). However, women who had been menopausal for more than 11 years were found to have an increased SBP if they were occasional snorers (beta=8.94 mmHg 95% CI=1.2, 16.6) or habitual snorers (beta=8.01 mmHg, 95% CI=0.10, 15.9). The increase in SBP was even greater in these women when habitual snoring was associated with rhinitis (beta=11.96 mmHg, 95% CI=1.01, 22.9). CONCLUSION: We suggest that the association of snoring with rhinitis may facilitate the development of apnea during sleep, which in post-menopausal women may increase the risk of developing hypertension.

[Dietary habits, life styles and respiratory symptoms in childhood]. / Alimentazione, stili di vita e disturbi respiratori infantili.

Asthma and obesity in children are common chronic conditions and both disorders have been increasing in the last 2 to 3 decades. The changes of dietary habits and a sedentary life style could have played a role in increasing the prevalence of both conditions. The aim of this report is to analyse the relation between some respiratory conditions (current wheezing, asthma and chronic cough) with dietary habits, body mass index (BMI), the physical activity and the habit to watch television. A total of 19,995 children (10,294 males and 9701 females) were investigated. Current wheezing is associated with increased BMI (V quintile OR=1.65), TV watching (more than 5 h/day OR=1.53), adding salt to the foods (OR=2.45), and fizzy drink (5 times or more per week OR=1.31). Children who often eat tomatoes, fruits, cooked vegetables and citrus fruits have a lower risk of current wheeze. The pattern of association is similar for asthma. High BMI, TV watching, adding salt to foods, and fizzy drink are risk factors for chronic cough. An increased BMI and TV watching are strongly related to respiratory symptoms. Our data confirm that dietary factors such as salt, vegetables and fruits are associated with the prevalence of respiratory symptoms in children.

Preoperative evaluation and risk factors of lung cancer.

Based on a review of the literature on resectable lung cancer, pulmonary risk factors before, during and after surgery are discussed. The role of preoperative evaluation in order to determine the patient ability to withstand radical resection is considered. Spirometric indexes as forced expired volume (FEV1) and diffusing lung carbon monoxide capacity (DLCO) should be measured first. If FEV1 and DLCO are > 60% of predicted, patients are at low risk for complications and can undergo pulmonary resection. However, if FEV1 and DLCO are <60% of predicted, further evaluation with a quantitative lung scan is required. If predicted postoperative values for FEV1 and DLCO are >40%, patients can undergo lung resection, otherwise exercise testing is necessary. If the latter shows maximal oxygen uptake (VO2max) of > 15ml/Kg, surgery can be performed; if VO2max is <15 ml/Kg, patients are inoperable.

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.

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.

[Respiratory effects of exposure to chlorine vapors during a swimming pool accident in a recreational center in Rome]. / Effetti respiratori dell'esposizione a vapori di cloro in seguito a un incidente in una piscina di un centro sportivo di Roma.

When inhaled, chlorine is a highly irritating gas that can damage larger airways as well as distal lung structure. We examined the short-term respiratory effects of acute chlorine inhalation during a swimming pool accident. On October 22, 1998, an emission of chlorine vapours occurred in the chlorinating maintenance procedures room of a recreational center in Rome. A total of 282 subjects (134 children) inhaled hydrogen chloride and sodium hypochlorite. Most people received bronchodilators and cortisone at the emergency room; five children were hospitalised. A telephone follow-up was taken on 260 (92.2%) subjects to obtain information about duration of exposure (less than 3 minutes, 3-5 minutes, more than 5 minutes), intensity of exposure (not at all/a little, a fair amount, a lot), and acute respiratory symptoms. A total of 236 (90.7% of the target) individuals underwent clinical examinations, which took place 15-30 days after the accident. Lung function was measured in 184 people (82 children) after 15-30 days. A multiple linear regression was run to test the association between chlorine exposure and lung function, separately in adults and in children. Acute respiratory symptoms occurred among 66.7% adults and 71.6% children. The incidence rates 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 15-30 days after the accident. Lung function levels were reduced among those who reported high intensity of exposure in comparison to those who reported low exposure, both in children and in adults (forced expiratory volume in one second, FEV1, ml differences: -109 (CI 95%: -310, 93) and -275 (CI 95%: -510, -40). Given high prevalence of potential exposed people, findings from this study should alert public health authority about the possible clinical consequences.