The prevalence of sleep impairments and predictors of sleep quality among patients with asthma.

BACKGROUND: Sleep is a significant dimension of daily life. However, only a few studies have examined the sleep quality of asthmatics in a real-world clinical settings. OBJECTIVE: This study is aimed to estimate the prevalence of sleep impairments among asthmatic patients and examine the relationship between sleep quality, asthma control, rhinitis symptoms, and sociodemographic characteristics. METHODS: The present study adopted the observational cross-sectional research design that has been designed by the Italian Respiratory Society and used valid assessments to measure the study variables. RESULTS: Data from 1150 asthmatic patients (mean age 51.01 years ± 16.03) were subjected to analysis. 58.3% of the patients had impaired sleep quality (Pittsburgh Sleep Quality Index [PSQI] total scores > 5), and their mean PSQI score was 5.68 (SD = 3.4). A significant correlation emerged between sleep quality and asthma control (p = 0.0001) and a significant albeit weak correlation emerged between PSQI total scores and Total 5 Symptoms Score (r = 0.24, p = 0.0001). Sleep quality was significantly associated health-related quality of life [HRQoL]. (r = 0.50, p < 0.001). After exclusion of patients at risk for Obstructive Sleep Apnea Syndrome (OSAS) and Gastro Esophageal Reflux Disease (GERD), the most important determinants of PSQI score were HRQoL, In the entire sample asthma control is the strongest predictor of both sleep quality and HRQoL. CONCLUSIONS: The results of this real-world study highlight the prevalence, impact and predictors of sleep disturbances in asthmatic patients and suggest the need for physicians to detect poor sleep quality.

Italian real-life experience of omalizumab.

Omalizumab is a humanized murine monoclonal antibody directed toward a portion of the IgE indicated in Europe for the treatment of severe persistent allergic asthma, inadequately controlled despite high-dose of ICS (mean BDP equivalent dose of inhaled corticosteroid 2224.68microg/die) in association with long-acting beta(2) agonists. Our aim was to describe the experience, efficacy and safety in a cohort of Italian patients treated with omalizumab in a real-life clinical setting. One hundred and forty two patients from 13 Italian Centers were observed and analysed. The dosage of omalizumab was established according to the labelling indication, with a median dose of IgE of 297.38IU/ml or kU/l. During the previous year, all patients experienced frequent exacerbations (mean=4.87), emergency visits (mean=4.45) and hospitalisation (mean=1.53). Following treatment with omalizumab, the annual rate of exacerbations, emergency visits and hospitalisation decreased by 79%, 88% and 95%, respectively. The proportion of patients without exacerbation, not needing emergency visits and hospitalization increased by 610%, 154% and 28%, respectively. The response to omalizumab measured with the GETE (global evaluation of treatment effectiveness) scale rated as good to excellent in 77% of patients. Overall, 9.6% (n=9) of the patients experienced one single adverse effect. Only one patient reported a serious adverse event (local reaction at the site of injection) leading to interruption of treatment. The observed reduction of asthma-related events in particularly poorly controlled patients in this Italian real-life setting is consistent with the results of other observational studies.

Feasibility and validation of telespirometry in general practice: The Italian "Alliance" study.

INTRODUCTION: At variance from office spirometry, telespirometry has not been tested as a tool for improving the ability of general practitioners (GPs) to manage chronic airway diseases. METHODS: After adequate training, 937 Italian GPs agreed to perform telespirometry in subjects attending their clinics who had risk factors, persistent respiratory symptoms, or a previous diagnosis of asthma or COPD. Each subject performed at least three forced expiratory manoeuvres using a turbine spirometer. Traces were sent by telephone to a Telespirometry Central Office, where they were interpreted by a pulmonary specialist, according to defined criteria. The result was sent in real time to the GP to assist the management of the patient. RESULTS: During 2 years, 20,757 telespirometries were performed, with a mean of 22.2+/-25.2 examinations for each GP. 70% of the tests met the criteria for good or partial co-operation, allowing spirometric abnormalities to be detected in more than 40% of the tracings. The rate of telespirometries that could not be evaluated at all was reasonably low (9.2%). For a subset of the telespirometries, a comparison between acceptability criteria for telespirometry and those recommended for laboratory (ATS) or office spirometry showed that the majority of telespirometries with good co-operation satisfied completely, or with minor deviations, the ATS and Office criteria. CONCLUSIONS: Telespirometry was well accepted by Italian GPs, who obtained acceptable screening traces in a large percentage of subjects. Therefore it might be considered a useful alternative to office spirometry in improving the management of chronic airway diseases by GPs.

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

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

Comparison of early and late asthmatic responses between patients with allergic rhinitis and mild asthma.

Allergic rhinitic subjects without symptoms of asthma show airway hyperresponsiveness, but to a lesser degree than asthmatics. As airway responsiveness is a determinant of the bronchial response to allergen, rhinitic subjects should also respond to allergen challenge, but to a lesser extent than asthmatics. However, studies have so far failed to show quantitative differences in allergen responses between patients with rhinitis and patients with asthma. We studied 123 allergic subjects classified, on the basis of a scored symptom questionnaire, as follows: pure rhinitics without any symptom of asthma (Group 1, n = 39), true asthmatics with or without rhinitis (Group 2, n = 41), and subjects with borderline symptoms of asthma (Group 3, n = 43). All subjects underwent both methacholine and allergen inhalation challenges, with pollen challenges performed out of season. When the three groups were pooled, the asthma symptom score was directly correlated with the sensitivities both to methacholine and allergen, whilst both the sensitivity to allergen and the severity of late-phase response were correlated with the sensitivity to methacholine. The percentage of subjects with a positive early-phase asthmatic response to allergen was similar in Groups 1 and 2. Group 2 had higher sensitivities both to methacholine and to allergen than Group 1. A late-phase asthmatic response occurred more frequently in Group 2 than in Group 1, and this difference was due to a higher occurrence of late-phase response in subjects allergic to house dust mite in Group 2. This study confirms that the bronchial response to allergen can be predicted, in rhinitic as well as in asthmatic allergic subjects, on the basis of airway responsiveness to methacholine. We conclude that the presence or the absence of asthma symptoms in allergic subjects may be related to a quantitatively different airway responsiveness to allergen.

Biologic and clinical effects of continuous infusion interleukin-2 in patients with non-small cell lung cancer.

BACKGROUND: Interleukin-2 (IL-2) has shown antitumor activity in some neoplasms, such as melanoma and renal carcinoma, but toxicity derived from bolus administration is significant, particularly at the cardiorespiratory level. METHODS: To test feasibility, antitumor activity, pulmonary and systemic immunologic effects, and pulmonary function changes of continuous-infusion recombinant IL-2 given to patients with non-small cell lung cancer, eleven subjects with Stage III-IV disease were treated in a standard pulmonary medicine unit with a dose of 18 million IU/m2/day from day 1 to day 13 with 1-day rest on day 7. A second induction course was given after a 3-week rest. In patients with nonprogressive disease, four maintenance courses of 6 days' duration at the same dose were planned. Immunologic tests, including lymphocyte phenotype analysis and assays for the detection of tumor necrosis factor (TNF) and of anti-IL-2 antibodies, were performed before and after treatment in serum and bronchoalveolar lavage fluid (BAL). Cardiopulmonary function tests, including spirometry, arterial blood gas analysis, diffusion capacity, and echocardiography, were obtained before, during, and after treatment. RESULTS: Twenty-one cycles (15 induction courses plus 6 maintenance courses) were administered. No patient was able to complete the six planned courses, and only 3 patients entered the maintenance phase. Reasons for discontinuation included progressive disease in five cases, toxicity in three cases, and patient request in three cases. The most common side effects were fever, hypotension, oliguria, and elevated serum creatinine and liver enzyme levels. No patient required intubation or intensive care. No objective response was seen, and the median survival time was 10 months. Lymphocytosis and eosinophilia were observed in all patients. Surface marker analysis revealed a statistically significant increase in the percentage of CD3+, CD4+, CD25+ and DR+ cells in peripheral blood. Lymphoid cells derived from BAL disclosed an increased natural killer activity after IL-2 treatment, and TNF was increased in BAL fluid. Pulmonary function tests evidenced an increased alveolar-arterial difference for oxygen allied with a decrease of forced expiratory volume in 1 second, forced vital capacity, and carbon monoxide transfer coefficient consistent with a significant, albeit not clinically relevant, interstitial lung defect. CONCLUSION: Continuous-infusion IL-2 is feasible in patients with advanced lung cancer even outside an intensive care unit, but overall compliance is poor. Although clinical pulmonary toxicity is negligible, small but statistically significant alterations of the pulmonary function are evident. In addition, this regimen produces a significant activation of the immune system at the pulmonary level.

Bronchial and bronchoalveolar lavage after allergen challenge in atopic patients.

Twenty patients with allergic rhinitis and/or asthma sensitised to Dermatophagoides pteronyssinus were studied. On two consecutive days they underwent methacholine challenge and allergen bronchial challenge. 72 h after allergen challenge, fibreoptic bronchoscopy with bronchial (BL) and bronchoalveolar (BAL) lavage was performed. Specific IgE antibodies were measured both in serum and in BL from 14 patients. Both BAL and BL cell differentials were similar in patients with isolated early response to allergen and in patients with dual response. Patients with dual response to allergen showed higher levels of antigen specific IgE antibodies in BL than patients with isolated early response, while IgE levels in serum were similar in the two groups.

Antiinflammatory-antioxidant treatment with a methane sulfonanilide in allergen-induced asthma.

Two groups of six asthmatic patients with biphasic bronchospastic response to inhaled Dermatophagoides pteronyssinus allergen extract were studied in a double-blind fashion. Early and late asthmatic reactions to allergen inhalation challenge were determined before and at the end of a 2-week treatment period with nimesulide (100 mg bid orally), a sulfonanilide with antioxidant properties, or placebo. Bronchial responsiveness to methacholine was evaluated 24 hours before and after allergen inhalation challenges. The dose of allergen causing EAR (15% decrease in FEV1) and the severity of LAR (maximum FEV1 fall) were similar before and at the end of the treatment period in both groups. In patients treated with nimesulide, bronchial responsiveness to methacholine was significantly increased after allergen inhalation challenge both before and at the end of the treatment period. These results do not support the hypothesis that the production of oxygen-free radicals plays a significant role in the development of bronchial hyperresponsiveness and late phase reaction to allergen in asthma.

Alternating chemotherapy with cyclophosphamide, doxorubicin, vincristine and cisplatin, etoposide followed by prophylactic cranial and thoracic irradiation for small cell lung cancer (SCLC): long-term results.

Both CAV (Cyclophosphamide, Doxorubicin, Vincristine) and PE (Cisplatin, Etoposide) are effective and non cross-resistant regimens in the treatment of SCLC. We designed a chemotherapeutic scheme including CAV and PE given in an alternating fashion with the following schedule: Cyclophosphamide 1000 mg/sm, Doxorubicin 50 mg/sm, Vincristine 2 mg/sm I.V. on day 1, alternated every 21 days with Cisplatin 20 mg/sm and Etoposide 80 mg/sm I.V. days 1-5 for 6 cycles. Following chemotherapy (CT) chest radiotherapy in patients (pts) with limited disease (LD) in complete response (CR) or partial response (PR) and prophylactic cranial irradiation (PCI) in CRs were given, 32 pts entered the study and 27 were evaluable: 9/27 (33.3%) had CR (8/15 with LD had CR) and 15/27 (55.5%) PR. The overall median survival was 53.71 weeks: 79.85 weeks for LD pts and 32.86 for ED.4 pts with LD were alive after 2 years and 2 of them are still alive without disease at 44 and 46 months. Toxicity was acceptable in all patients. Alternating chemotherapy with CAV and PE followed by chest and brain RT in responding LD pts is an effective induction treatment for SCLC although long-term survival still remains disappointing.

Bronchial responsiveness is not increased by bronchoalveolar and bronchial lavage performed after allergen challenge.

Nonspecific bronchial responsiveness was studied in 23 allergic patients with a history of rhinitis and/or bronchial asthma who underwent fiberoptic bronchoscopy with bronchoalveolar and bronchial lavage (BAL-BL) 4h (Group A) or 24 h (Group B) after an allergen inhalation challenge. In all patients, the dose of methacholine causing an FEV1 fall of 15% (PD15) was determined at baseline, 24 h before allergen challenge. Methacholine bronchial challenge was repeated 1 h before BAL-BL in patients of both groups and again 12 to 14 h after BAL-BL in Group A and 24 h after BAL-BL in Group B. In patients of Group A, the values of methacholine PD15 after BAL-BL were not significantly different from those determined before BAL-BL. This was also the case in patients in whom bronchial responsiveness was increased after allergen challenge. In patients of Group B, methacholine PD15 was significantly decreased after allergen challenge, and this decrease was correlated with the occurrence and the severity of the late asthmatic reaction. Even in patients who showed dual asthmatic reactions and an increased responsiveness after allergen challenge, methacholine PD15 was not further decreased after BAL-BL. These data support the safety of a procedure combining bronchial allergen challenge with BAL-BL, which can be used for studies on the pathophysiology of bronchial asthma.

Oral chemotherapy for poor risk small-cell lung cancer patients with combined idarubicin and etoposide.

Sixteen patients with previously untreated small-cell lung cancer, unsuitable for standard aggressive intravenous chemotherapy due to advanced age or poor performance status or very advanced disease including brain metastases or either extensive liver or marrow involvement with impaired organ function, were treated with combined oral chemotherapy including 4-demethoxydaunorubicin (IMI30, idarubicin) 30 mg/sm on day 1 and etoposide (VP16) 150 mg/sm on days 2,3,4 every 4 weeks. Out of 13 evaluable patients 1 had a complete response and 2 had a partial response with an overall objective response rate of 23% (95% confidence-limits 5-53.8%). Toxicity was generally very mild. Although the compliance of this regimen is excellent, its antitumor activity seems unsatisfactory even in this category of poor-risk small-cell lung cancer patients.

Reduced conversion of dehydroepiandrosterone into estrogens in women having hypogonadotropic hypogonadism associated with weight loss.

The purpose of this study was to evaluate, without using radioisotopes, the peripheral contribution of dehydroepiandrosterone (D) to estrogens and to androstenedione (A) in patients with hypogonadotropic hypogonadism associated with weight loss (HH) and in normal menstruating women (N). Unlabelled D was infused for 48 h in 12 normal women and in 12 women affected by HH. Plasma levels of D, dehydroepiandrosterone sulfate (DS), A, estrone (E1), estrone sulfate (E1s) and estradiol (E2) were measured before and after 48 h of infusion. Metabolic clearance rates of D (MCRD), production rates of D (PRD), and increases in plasma concentration of DS, A, E1, E1s and E2, relative to the corresponding increase in plasma concentration of D, were determined. The baseline plasma levels of all steroids studied were found to be significantly lower in the patient group than in the control. The MCRD in the normal and the HH groups were similar (1420 +/- 340 l/day versus 1670 +/- 569 l/day, P greater than 0.05). No significant difference was found in PRD between the 2 groups (mean +/- SD 10.3 +/- 5 versus 13.3 +/- 5.5 mg/day, P greater than 0.05). Administration of D increased the levels of estrogen in the normal group but not in the HH group. The relative increase in plasma levels of DS resulting from infusion of D (delta cDS/delta cD) was found to be larger in the HH group than in the normal group (40.4 +/- 17 versus 26.3 +/- 11.8, P less than 0.05). Furthermore, relative increases in plasma levels of A derived from infusion of D were larger in the HH group than in the normal group (0.0495 +/- 0.0021 versus 0.192 +/- 0.0071, P less than 0.001). We conclude from these results that in the HH patients there is a blockage of the peripheral conversion of D to E1 and E1s and an enhancement of the peripheral conversions of D to DS and to A. These metabolic changes may account for the androgenization of the patients under study.

Estrone sulphate plasma levels in postmenopausal women with and without endometrial cancer.

Plasma estrone sulphate ( E1S ) and estrone (E1) concentrations were determined in healthy postmenopausal women and in postmenopausal women with endometrial cancer, matched for body weight, age, and years since menopause. E1S levels (mean +/- SD) were significantly higher (P less than 0.05) in cancer patients with normal weight (511 +/- 200 pg/ml) than in control subjects (303 +/- 99 pg/ml). E1S levels were also higher in obese cancer patients (691 +/- 328 pg/ml) than in obese control subjects (610 +/- 139 pg/ml). Both cancer groups showed similar plasma E1 levels as compared with their respective controls. The E1S /E1 ratio was higher in both groups of cancer patients than in control subjects. These data suggest that estrogen conjugates should be taken into account during studies on estrogen balance and endometrial cancer.

Metabolic clearance rate of oestrone sulphate in post-menopausal women.

The feasibility of using constant infusions of unlabelled oestrone sulphate (E1S) for the purposes of calculating its metabolic clearance rate (MCRE1S) and its conversion ratios to oestrone (E1) and oestradiol (E2) in post-menopausal women was exploited in this study. The results obtained by the infusion of unlabelled E1S were similar to those obtained by the infusion of labelled steroid. The MCRE1S values seen in our group of post-menopausal women fell within the range previously reported for fertile women. The contribution of E1S to circulating E1 averaged 18% (range 14-24%), indicating that the E1S-E1 equilibrium should be taken into account during studies on oestrogen balance in post-menopausal women.

Estrone sulfate, estrone and estradiol concentrations in normal and cirrhotic postmenopausal women.

Circulating levels (mean +/- SD) of estrone sulfate (E1S), estrone (E1) and estradiol-17 beta (E2) were measured in normal and cirrhotic postmenopausal women matched for body weight and age. In cirrhotic postmenopausal women, the E1S concentrations (201 +/- 46 pg/ml), while both E1 and E2 levels showed an increase (46 +/- 7 and 30 +/- 8 pg/ml) compared to control subjects (32 +/- 6 and 18 +/- 7 pg/ml). These data suggest that the liver plays an important role on the control of estrogen sulfation.

Preliminary report on progesterone effect on peripheral estrone sulfate metabolism.

The effect of progesterone (P) on peripheral estrone sulfate (E1S) was investigated in postmenopausal women using E1S constant infusions. The metabolic clearance rate of E1S (MCRE1S) was significantly lowered by P administration (p less than 0.01), while no significant changes were observed for E1S----E1 conversion ratio. The present findings suggest that P can affect the E1S peripheral fate inducing deep changes in estrogen equilibrium.

Androstenedione metabolism in human uterine tissues: endometrium, myometrium and leiomyoma.

Androstenedione was metabolized in vitro by human endometrium, myometrium and leiomyoma, to its 5 alpha-reduced metabolites: 5 alpha-androstan-3,17-dione (5 alpha-androstanedione) and androsterone as well as to testosterone, 17 beta-hydroxy-5 alpha-androstan-2-one (5 alpha-DHT) and 5 alpha-androstan-3 alpha,17 beta-diol (3 alpha-diol). Uterine tissue showed a similar enzymatic profile to the androgen responsive tissues; these data suggest that androgens may have a functional role in the uterine pathophysiology.

Estrone sulphate and estrone splanchnic extraction in postmenopausal women.

The splanchnic extraction of estrone sulphate (E1 S) and estrone (E1) was calculated in post-menopausal women undergoing cardiac catheterization for diagnostic purposes. The results showed a net uptake for E1 by the splanchnic area, liver included, whereas the splanchnic extraction of E1 S was not similar for each subject. Anyway the results clearly showed that the splanchnic area does not release significant amount of E1 S into the blood in the post-menopausal women.

Estrogen provocation test: lack of correlation between LH and 17-beta-estradiol basal levels and LH peak response in hypothalamic chronic anovulation.

Estrogen provocation test was performed in 27 women with hypothalamic chronic anovulation: all patients received I mg of estradiol benzoate (EB) as a single im injection. Plasma 17-beta-estradiol (E2) levels were monitored during the test performed and then compared; no significant correlation was found between mean basal values of LH and E2 and the LH peak response (r = 0.246, P = 0.108 for LH; r = 0.124, P = 0.278 for E2). These data seem to indicate that basal LH values reflect the tonic secretion but not the hypothalamic responsiveness to the estrogen positive feedback; moreover, this latter seems not be influenced by the endogenous E2 levels.