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Background: Urinary leukotriene E4 (LTE4) excretion is a good marker of the rate of total body production of sulfidopeptide leukotrienes released during allergen challenge. Methods: Twenty‐three subjects with allergic asthma were challenged with inhaled allergen, and the urinary excretion of LTE4 was determined by immunoenzymatic assay (associated with HPLC separation) at various intervals after challenge. Results: Allergen challenge caused an early airway response (EAR) with a drop in FEV1 of 40.3±9.9%. This was associated with an increase in urine LTE4 excretion for 0–3 h after allergen inhalation (296±225.25 pg/mg creatinine) in comparison with baseline values obtained during the night before challenge (101.02±61.97 pg/mg creatinine). Urinary LTE4 excretion was significantly higher in subjects who inhaled a higher dose of allergen during challenge (LTE4 during EAR: 211±192 pg/mg creatinine in subjects with inhaled total dose of allergen <0.1 biologic units; 408±223 pg/mg creatinine in subjects with inhaled total dose >0.1 biologic units). All subjects showed a late airway response (LAR) to allergen of different severity, from mild (FEV1 fall: 15–20%) to severe (>30%); no correlation was found between the increase in urine LTE4 excreted during LAR (3–7 h after challenge) and the severity of LAR, but only subjects with severe LAR showed a significant increase in LTE4 during LAR in comparison with baseline value. Conclusions: A release of sulfidopeptide leukotrienes, as evaluated by urinary LTE4 excretion, can be documented during EAR and LAR to allergen in relation to the dose of inhaled allergen, and it can represent a useful index of the events underlying the airway inflammatory responses during allergen challenge. [ABSTRACT FROM AUTHOR]

Background: The inhibitory effect of corticosteroids (CS) on the secretions of cysteinyl-leukotrienes (Cys-LTs) in asthma is controversial. The aim of this study was to evaluate the effect of CS on allergen-induced increase in urinary leukotriene E4 (uLTE4) during early (EAR) and late (LAR) asthmatic responses in mild untreated asthmatics., Material and Methods: Nine subjects with mild untreated allergic asthma performed two allergen challenges, after 1-week treatment with beclomethasone dipropionate (BDP, 500 microg b.i.d) or placebo. Forced Expiratory Volume in one second 1 (FEV1) was monitored to assess EAR and LAR, and uLTE4 was measured before and during EAR and LAR., Results: After placebo, uLTE4 increased significantly during EAR, but not during and after LAR, in comparison with baseline values. Beclomethasone dipropionate induced a significant attenuation of the uLTE4 increase during EAR, in comparison with placebo, in association with a good protection of LAR (P = 0.002) and a mild protection of EAR (P = 0.07)., Conclusions: Beclomethasone dipropionate blunts the early increase in uLTE4 excretion due to allergen challenge, in association with a significant effect on the severity of LAR. These data support the hypothesis that inhaled CS may inhibit the allergen-induced release of cys-LTs in asthma.

We describe the case of a 36 old woman with a right massive hydrothorax resulting from Controlled Ovarian Hyperstimulation (COH) for infertility. This complication is defined as Ovarian Hyperstimulation Syndrome (OHSS) which usually includes abdominal pain, nausea and ascites, rarely involving the respiratory apparatus. The usual determining factors of OHSS are the presence of high serum estradiol levels and pregnancy. In the case that we describe the serum estradiol levels during COH were monitored and were slightly higher than the COH alarm threshold and the patient was not pregnant.

The main objective of this study was to examine the perception of the first symptom during methacholine bronchoconstriction as soon as it occurred, and in the second instance to quantify the intensity of the breathlessness by means of the Borg Scale performed at the end of challenge so to not determine any difficulties for identification of the first symptom. A methacholine challenge test was carried out in 139 symptom-free asthmatics with a normal pulmonary function. When the first symptom was reported by the subject, the forced expiratory volume in one second (FEV1) was measured immediately. FEV1 was expressed as a percentage of the best personal value (FEV1%BPV). The intensity of the breathlessness was rated using a modified Borg Scale at the end of the challenge test so as not to confuse the patient. Seven subjects felt nothing during challenge. The first symptoms varied: constriction behind the breastbone (49%), inspiratory shortness (16.5%), coughing (10%), wheezing, throat constriction, general chest tightness, pain behind the sternum, and a sensation of rheum behind the sternum. FEV1%BPV at the first symptom was 80.5 +/- 10 (range 41-99). No symptom was perceived by 42% of the subjects within the 80-100 range of FEV1%BPV. FEV1%BPV at the first symptom was related to the log of the provocative dose causing a 20% fall in FEV1 (r = 0.2, p < 0.05). An inverse correlation between Borg Score and final FEV1%BPV (r = -0.25, p < 0.01) was found at the end of challenge. A subgroup of 39 subjects with similar final FEV1%BPV values (68-72) showed a correlation between the Borg Score at end of challenge and FEV1%BPV at the first symptom (r = 0.59, p < 0.001). The first symptom of the methacholine-induced bronchoconstriction varies in asthmatics and may be atypical, the bronchoconstriction level at which it is felt also varies among individuals, highly methacholine-responsive subjects perceive the bronchoconstriction later, while late perceivers of the first symptom show less intense breathlessness at the end of challenge. The measurement of the patient's ability to perceive asthmatic symptoms during the methacholine challenge test could be used to single out poor perceivers.

16 patients with advanced small cell lung cancer were treated with a combination of cyclophosphamide (1000 mg/m2 day 1), epidoxorubicin (60 mg/m2 day 1) and vincristine (1.4 mg/m2 day 1) every 14 days for six cycles followed by a combination of cisplatin (40 mg/m2 days 1 & 2) and etoposide (100 mg/m2 days 1-3) every 14 days for four cycles. Shortening of intervals was obtained with the prophylactic employment of granulocyte colony-stimulating factor (filgrastim, 300 mcg subcutaneously from day 5 to dsy 10). In 11 patients ratio between actually delivered dose intensity and planned dose intensity of > 80% was obtained. Toxicity was acceptable and no life-threatening toxicities were observed. An objective response (partial or complete) was observed in 11 patients. The new regimen, incorporating the concepts of dose-intensification and sequential administration of regimens, is feasible and may be considered for further studies.

A 1-yr multicentre two-tailed randomized open study was conducted in 15 centres in Italy, with the aim of comparing the clinical efficacy (over 3 months) and tolerability (over 1 yr) of salmeterol with those of oral theophylline in patients with reversible chronic obstructive pulmonary disease (COPD). Patients with reversible COPD (forced expiratory volume in one second (FEV1) 50-80%, FEV1 after bronchodilator > 12%, n = 138) were randomized to receive salmeterol powder (50 micrograms b.i.d. with Diskhaler, n = 66) or individually dose-titrated slow-release oral theophylline capsules so as to obtain a serum concentration of theophylline ranging 10-20 micrograms.mL-1 (n = 72). During the 2-week run-in period, nonadmitted medications were discontinued and patients had to present with respiratory symptoms on at least four of the last seven days. Following randomization, patients were required to monitor daytime and night-time symptoms, additional use of as-required salbutamol, and morning and evening peak expiratory flow (PEF) for 3 months. Spirometric measurements and assessment of the quality of life were performed every 3 months for 1 yr. Salmeterol was proven to be statistically more effective than theophylline in: 1) increasing the maximum value of morning PEF; 2) increasing the percentages of days and nights without symptoms; 3) reducing the need for additional salbutamol during daytime and night-time; and 4) increasing quality of life in terms of physical and social activities, mental health and psychophysical energy, assessed 3 months after the beginning of treatment. Salmeterol was no more effective than theophylline in increasing: 1) forced vital capacity and FEV1 at the various measurements; 2) maximum evening PEF value; and 3) quality of life after the first 3 months of treatment. Neither treatment induced significant side-effects over the 1-yr treatment. This study confirms that inhaled salmeterol is more effective than oral theophylline in long term treatment of reversible obstructive pulmonary disease.

In order to evaluate the relationship between allergen-induced heat-stable neutrophil chemotactic activity (HS-NCA) release during early asthmatic reaction (EAR) and the presence of a late asthmatic reaction (LAR), serum HS-NCA was measured at three serum dilutions (1:5, 1:40, 1:200) during EAR induced by allergen in 26 atopic asthmatics, 13 with isolated EAR and 13 with EAR followed by LAR. HS-NCA was measured using a 48-well microchamber with 5-micron-pore-size nitrocellulose filters, using isolated neutrophils from healthy donors and the leading front technique. Subjects with LAR developed EAR after inhalation of a lower dose of allergen than subjects with isolated EAR. Increase in serum HS-NCA during EAR was significantly higher in subjects with isolated EAR than in subjects with EAR plus LAR at the 1:5 dilution, while it was significantly higher in subjects with EAR plus LAR than in the subjects with isolated EAR at the 1:200 dilution; the 1:40 dilution gave similar results in both groups. Changes in serum HS-NCA during EAR significantly correlated with the maximum decrease in forced expiratory volume in 1 s (FEV1) during LAR: a higher decrease in FEV1 during LAR was associated with a lower increase in HS-NCA at the 1:5 dilution (Spearman's rho = 0.43, rho = 0.03), and with a higher increase in NCA at the 1:200 dilution (Spearman's p = -0.46, p = 0.02). These results can be explained by the 'high-dose-inhibition' phenomenon. Assuming that HS-NCA is associated with mast cell degranulation in the airways after allergen challenge, these findings demonstrate that higher mast cell activation during EAR is present in subjects with a subsequent LAR than in subjects with isolated EAR.

Leukotrienes have been demonstrated to play an important role as mediators of many pathophysiologic alterations of asthma. Pharmaceutical companies have thus promode many efforts to synthesize new drugs with inhibitory activity on 5-lypoxygenase or with functional antagonism on cystenyl leukotriene receptors. Several compounds have been studied in humans, and some of them should soon be on the market. One of these compounds, ICI 204,219 ("accolate"), a receptor antagonist active by the oral route, has been proven capable of preventing bronchoconstriction induced by several stimuli (allergen, exercise, cold air, etc.) and of improving symptoms and lung function in spontaneous asthma. This effect augments the bronchodilation induced by inhaled beta 2-agonists. On the other hand, no relevant side effects have been reported. However, antiinflammatory properties of this compound must be demonstrated. This new category of antiasthmatic drugs should be recommended for mild-to-moderate asthma, although future studies might demonstrate their efficacy in potentiating or substituting inhaled steroids.

In order to assess whether treatment with oral slow-release theophylline prevents early (EAR) and/or late (LAR) airway responses to allergen, we treated six asthmatic subjects with either placebo or oral theophylline (350 mg b.i.d.) for one week before specific bronchial provocation test (sBPT) with allergen, in a double-blind, cross-over, placebo-controlled study. All subjects had previously shown both EAR and LAR to allergen sBPT. On the day of sBPT, serum theophylline concentration was > 9 micrograms.ml-1 in all subjects treated with theophylline except one (mean 9.8 +/- 2.6 micrograms.ml-1). The total dose (TD) of inhaled allergen, and the provocative dose of allergen causing a 15% fall in forced expiratory volume in one second (PD15FEV1) during sBPT was mildly but significantly lower during theophylline-sBPT than during placebo-sBPT. Theophylline treatment reduced EAR (maximum FEV1 fall from baseline: 26.3 +/- 6.7 vs 32.2 +/- 9.5% after placebo treatment) but not LAR (19.5 +/- 6.5 vs 26.3 +/- 6.1%). A significant protection of LAR (a reduction in FEV1 fall after theophylline treatment 50% more than after placebo treatment) was observed in only 2 out of 6 subjects. Area under the curve was not significantly different after the two treatments. There was no relationship between serum theophylline levels and the degree of protection on EAR or LAR. The decrease in PD15FEV1 methacholine observed at the end of LAR was similar in the two treatments.(ABSTRACT TRUNCATED AT 250 WORDS)

The role of peak expiratory flow (PEF) monitoring in the diagnosis of occupational asthma has recently been assessed by several studies, which agree that this procedure should always be used to confirm the relationship between symptoms and occupational exposure. Some specific issues should be satisfied: a minimum number of four PEF measurements in a day; several weeks of monitoring in and out of work; and the presence of specific patterns of PEF changes. The sensitivity and specificity of PEF monitoring to detect occupational asthma, in comparison with the specific challenge test in the laboratory (the "gold standard") have been shown to be fairly high, although many authors believe that PEF monitoring cannot substitute for the specific challenge test. Limitations include: the low sensitivity of PEF to detect mild changes in airway calibre with respect to forced expiratory volume in one second (FEV1); the blunting effect of pharmacological treatment; the episodic and irregular exposure to the sensitizer in the workplace; and the compliance and honesty of the subject. Further studies are required to select the best indices of daily and day-to-day variability to be used in the evaluation of PEF changes between work and out-of-work periods.

In order to investigate if bronchial asthma is associated with enhanced markers of activation in peripheral neutrophils, the migratory capacity of neutrophils in venous blood was measured by means of the Boyden chamber technique in 29 subjects with bronchial asthma of differing severity. Random migration (random motility), but not locomotion toward 10% Escherichia coli supernatant as chemoattractant (chemotaxis), was increased in asthmatic subjects with respect to 11 normal subjects (98 +/- 20 microns vs. 85 +/- 6 microns; p < 0.05). When asthmatic subjects were subdivided into groups of different disease severity, subjects with mild and mild to moderate asthma showed significantly higher values for random motility and chemotaxis than normal subjects; on the other hand, subjects with more severe disease showed the lowest values for migratory activity. No correlation was found between migratory activity and clinical findings of asthma, except for baseline FEV1 (% of the predicted value), which showed a slight but significant positive correlation with chemotaxis (r = 0.44, p < 0.05). Subjects with atopic or occupational asthma had higher values for migratory activity than subjects with nonallergic asthma. Thirteen asthmatic subjects repeated all evaluations after 1 month of treatment with high doses of inhaled glucocorticoids (beclomethasone dipropionate 1500 micrograms/day). Random motility (95 +/- 24 microns vs. 75 +/- 15 microns; p < 0.05) and chemotaxis (130 +/- 22 microns vs. 105 +/- 25 microns; p < 0.05) were significantly reduced after treatment, as well as the symptom score; on the other hand, symptom score but not bronchial hyperresponsiveness to methacholine challenge significantly changed.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term change in nonspecific and specific bronchial hyperresponsiveness was studied in 16 subjects with asthma induced by toluene diisocyanate (TDI). A significant positive correlation between months of follow-up and provocative dose inducing a 20 percent fall in FEV1 (PD20FEV1) methacholine was observed in 5 of 16 subjects. In 4 of these 5 subjects, a PD20FEV1 > 1 mg of methacholine was observed 30 to 48 months after the end of TDI exposure. In most subjects, nonspecific bronchial hyperresponsiveness did not change. Nine of 16 subjects became nonresponsive to TDI at follow-up examination, but only 3 of these showed a significant increase in PD20FEV1 methacholine. Seven subjects were still responsive to TDI. Recovery from TDI-induced asthma can occur and only after long-term work cessation. Nonspecific bronchial hyperresponsiveness to methacholine can persist even in the absence of bronchial hyperresponsiveness to TDI, suggesting permanent chronic damage to mechanisms controlling airway tone.

Although alpha-fetoprotein may play a role in fetal immune function or in maintenance of osmotic pressure, its exact function is unknown. We report two infants documented to have congenital deficiency of alpha-fetoprotein. One infant had cord blood levels less than 0.5 ng/ml. The second infant had a neonatal level of 120 ng/ml, which is about 2% of the usual concentration for a term newborn. These infants document the existence of congenital deficiency of serum alpha-fetoprotein. Because it is homologous to albumin, congenital deficiency of alpha-fetoprotein may be analogous to analbuminemia, a benign genetic trait.