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Biomedical subjects

P Sestini

Publications and source records attributed to P Sestini.

At least 19 recordsLinked to original sources

A survey on hospitalised community-acquired pneumonia in Italy.

BACKGROUND AND AIM: Community Acquired Pneumonia (CAP) remains a major cause of disease and death. We evaluated the levels of care, the outcome and the characteristics of hospitalised patients with CAP in a primary hospital in Italy. We also investigated the value of both the Pneumonia Severity Index (PSI) and the modified Appropriateness Evaluation Protocol (AEP) for recognising both the outcome and the unnecessary admissions and stay of hospitalised patients with CAP. METHODS: A retrospective review of all the charts of adult patients with CAP at Manerbio, Brescia, Italy between January 2001 and December 2002 was performed. RESULTS: We evaluated 148 patients; their mean age (+/-SD) was 70 (+/-17) years; 34% were female. Most patients (87%) had at least a concomitant co-morbid disease. The overall survival rate at 30 days was 88%. All but one death occurred in the high-risk group of patients according to the PSI. On the contrary, the death rate of patients with inappropriate hospital admission according to the AEP was high. Patients with high PSI score had a significantly longer hospital length of stay than the low-risk group. However, a substantial part of the hospital stay did not show any justification into the charts. CONCLUSIONS: The PSI, but not the AEP, upon hospital admission, was useful for evaluating the outcome of patients with CAP. The PSI score and the modified AEP can be useful for assessing the appropriateness of hospitalisation for patients with CAP. There is the need for a practical and validated tool to support physicians in their decision making regarding the early and safe discharge of hospitalised patients with CAP.

Adolescent↗

Retrospective analysis of evidence base for tests used in diagnosis and monitoring of disease in respiratory medicine.

OBJECTIVES: To determine how many common clinical tests used in a respiratory medicine outpatient clinic are based on high quality evidence. DESIGN: Retrospective review of case notes. Record of first three tests for each patient. Diagnostic tests, tests used to assess existing condition, explicit trials of therapy were included. Literature search for supporting evidence and grading of best evidence for each test. SETTING: Inner city university teaching hospital in the United Kingdom. PARTICIPANTS: All new outpatients referred to a single respiratory medicine team over a period of three months. MAIN OUTCOME MEASURES: Proportion of tests supported by level 1a-1c evidence (scale developed by Centre for Evidence Based Medicine). RESULTS: Only half the tests that were used to make or exclude a diagnosis and a fifth of the tests used to assess a known condition were supported by level 1a-1c evidence. There was no evidence to support trials of therapy. CONCLUSIONS: A large proportion of clinical tests in respiratory medicine are not supported by level 1a-1c evidence. None of the therapeutic trials that were used were supported by evidence.

Diagnostic Techniques, Respiratory System↗

Perception of dyspnea during exercise-induced bronchoconstriction.

UNLABELLED: After strenuous physical exercise, many subjects show a significant bronchoconstriction and report dyspnea. Despite this clinical condition being a commonly encountered situation during daily life, which may be responsible for substantial disability there is little information on the relationship between the perception of dyspnea and exercise-induced bronchoconstriction (EIB) after a standardized exercise challenge. For these reasons, we evaluated 200 consecutive outpatients (median age 13 years, ranging from 5 to 56 years) referred to our laboratory to perform an exercise test out of suspicion of EIB. On exercise challenge, perception of dyspnea was rated on a modified bipolar Borg scale immediately before each FEV1 measurement. Sixty-nine (35%) subjects had a positive exercise challenge, defined as a decrease of at least 20% in FEV1 from baseline. Both the onset and the decay of dyspnea preceded those of bronchoconstriction. Overall, the rating of dyspnea in the laboratory was well related with the reports of exercise-related symptoms. Similarly, 36 of 77 (47%) asthmatics with a history of exertional symptoms and 24 of 65 patients (40%) without a history had a positive challenge. Asthmatics reporting exertional symptoms perceived a greater magnitude of dyspnea after exercise independently from the degree of bronchoconstriction. Overall, dyspnea was significantly but loosely correlated to the magnitude of decrease in FEV1, being also influenced by age, gender and BMI. CONCLUSIONS: We conclude that dyspnea recorded in the laboratory after exercise test is related to exertional symptoms reported during real life, but not completely related to EIB. The rating of dyspnea is a well-suited model to study naturally occurring exercise-induced dyspnea and a useful tool to enlarge the results of an exercise challenge.

Adolescent↗

Regular inhaled short acting beta2 agonists for the management of stable chronic obstructive pulmonary disease: Cochrane systematic review and meta-analysis.

BACKGROUND: Despite the lack of reversibility, patients with chronic obstructive pulmonary disease (COPD) often report symptomatic improvement with inhaled short acting beta(2) agonist bronchodilators (ISABAs) in the management of both stable and acute exacerbations of COPD. A review of the literature was undertaken to determine the effectiveness of regular treatment with ISABAs compared with placebo in stable COPD. METHODS: A search for randomised controlled trials was carried out using the Cochrane Collaboration database of trials up to and including May 2002. RESULTS: Thirteen studies of 7 days to 8 weeks in duration on 237 patients aged 56-70 years with forced expiratory volume in 1 second (FEV(1)) 60-70% predicted were included in the review. All studies used a crossover design with adequate washout periods and were of high methodological quality. ISABA was delivered either through a nebuliser or a pressurised metered dose inhaler. Spirometric tests performed at the end of the study and after the treatment (post-bronchodilator) showed a slight but significant increase in FEV(1) and forced vital capacity (FVC) compared with placebo. In addition, both morning and evening peak expiratory flow rate (PEFR) were significantly better during active treatment than during placebo. An improvement in the daily breathlessness score was observed with ISABA treatment. The risk of treatment failure was reduced by more than 50% with ISABA. Preference for ISABA was nine times higher than for placebo. CONCLUSIONS: Use of ISABA on a regular basis for at least 7 days in patients with stable COPD is associated with improvements in post-bronchodilator lung function and decreases in both breathlessness and treatment failure. This review has shown that regular administration of ISABAs is an effective and inexpensive treatment for the management of patients with stable COPD.

Administration, Inhalation↗

GENebu Project: home nebulizer use and maintenance in Italy.

Due to the lack of information on this topic, the Educational Group of the Italian Association of Hospital Pneumologists performed an open, multicentre, observational survey to evaluate home nebulizer practices in Italy. From May-December 1999, all patients attending one of the 27 participating chest clinics throughout Italy and who were or had been using a home nebulizer in the previous 6 months were consecutively enrolled. All patients completed a self-administered questionnaire on their current practices of home nebulization. Of the 1,721 questionnaires delivered, 1,257 were returned with an overall response rate of 73%. Most patients (82.8%) reported using their nebulizer for bronchopulmonary symptoms and the remaining patients only used theirs for upper respiratory tract diseases. Subjects using their nebulizer for lower respiratory symptoms were older (p<0.001), predominantly female (p<0.001) and used their nebulizer more frequently (p<0.001). Forty per cent of patients >60 yrs old used their nebulizer regularly, at least once a day. More than 60% of respondents never received any information from healthcare workers on the correct usage of their nebulizer, and >75% received no information on nebulizer hygiene and care. Patients who received information on the use and maintenance of their nebulizer from caregivers more commonly attended to these practices (p<0.01). The present survey suggests that home nebulizer use and maintenance in Italy are heterogeneous, and there is the need to implement better nebulizer practice.

Adolescent↗

Short-acting beta 2 agonists for stable chronic obstructive pulmonary disease.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is a chronic condition characterised by progressive airflow limitation that is at most partially reversible. Despite the lack of reversibility patients often report symptomatic improvement with short-acting beta 2 bronchodilator medications. They are used on either an "as required" or a "regular plus as required basis" and they may be used in conjunction with other bronchodilator medicines such as ipratropium and methylxanthines. These medicines are used in the management of both stable and acute exacerbations of COPD. This review examined the effect of short-acting beta 2 bronchodilators given by inhalation in stable COPD. OBJECTIVES: To determine the clinical effect and assess the adverse effects of inhaled short-acting beta 2 agonist bronchodilators compared with placebo in stable COPD. SEARCH STRATEGY: Only randomised controlled trials (RCTs) were considered. RCTs were identified using the Cochrane Airways Group database (CENTRAL). In addition, the reference lists of review articles and RCTs retrieved in full were searched for other potentially relevant citations. SELECTION CRITERIA: Only trials with adult patients with stable COPD, as defined by internationally accepted guidelines (ATS, ERS or BTS) were included in this review. All trials had a minimum duration of 7 days of regular treatment with short-acting beta 2 bronchodilators given by inhalation and compared with placebo. Data from trials where beta 2 agonists were used alone or in combination with other medicines (e.g. ipratropium bromide) were used only if there was a direct comparison between beta 2 bronchodilator alone and placebo. DATA COLLECTION AND ANALYSIS: Outcomes were analysed as continuous or dichotomous outcomes, using standard statistical techniques. For continuous outcomes, the weighted mean difference (WMD) and 95% confidence intervals were calculated and for dichotomous outcomes, the odds ratio was calculated with 95% confidence intervals by Peto's methods. Funnel plots were used to test for publication bias. MAIN RESULTS: Thirteen studies were included in this review. Most had small sample sizes and some of the sutides used very short-acting outdated compounds. All the studies used a cross-over design and were of high quality. Spirometry done at the end of study period was measured after administration of treatment (post-bronchodilator) which showed both FEV1 (0.150 L/min, 95%CI: 0. 02-0.28) and FVC (0.310 L, 95%CI: 0.00-0.62) to improve significanly but slightly when compared to placebo. A few studies measured FRC, airway resistance or conductance at the end of the study period. In all cases these measurements were done several hours after treatment, and no significant differences (p>0.05 in all cases) were found between the bronchodilator and placebo groups. Walking test Large increases in 6MW distance was observed in two studies, however one study did not show any positive improvements. There was a large increase in the 12MW distance as shown by one study. Due to the small number of studies reporting this outcome no significant differences were found in the walking distance between the bronchodilator and placebo groups. Peak Flow Rate Both morning (36. 04 L/min; 95%CI: 0.80-71.27) and evening (36.68 L/min; 95%CI: 2. 47-70.89) PEFR were significantly higher during active treatment than during placebo. Symptoms Breatlessness was measured on various scales therefore data that were presented in a suitable form were combined using standardized means for inclusion in the analysis. A significant improvement (-0.33; 95%CI: -0.58 to -0.07 with p=0.01) in the breathlessness score was observed during treatment with beta-2 agonist when compared to placebo. Cough was reported to improve significantly (data not usable) during treatment with beta2 agonist in one study but not in two others. A non-significant decrease in sputum production was reported by Wilson 1980, however four other studies reported no

Administration, Inhalation↗

Distribution of novel polymorphisms of the interleukin-8 and CXC receptor 1 and 2 genes in systemic sclerosis and cryptogenic fibrosing alveolitis.

OBJECTIVE: To search for single-nucleotide polymorphisms in the interleukin-8 (IL-8) and IL-8 receptor CXCR-1 and CXCR-2 genes, and to compare their distribution among patients with systemic sclerosis (SSc) with fibrosing alveolitis (FASSc) or without fibrosing alveolitis (NFASSc), or patients with cryptogenic fibrosing alveolitis (CFA), and normal healthy subjects. METHODS: Fifty control subjects were screened for potential polymorphisms by using polymerase chain reaction in association with sequence-specific primers incorporating mismatches at the 3' end. The novel polymorphisms were subsequently examined in British Caucasian subjects, including 194 healthy controls, 71 patients with CFA, and 128 patients with SSc who were further subdivided into 78 FASSc patients and 50 NFASSc patients. RESULTS: Three novel biallelic polymorphisms were identified in the IL-8 gene (all in noncoding areas of the gene), 1 was found in the CXCR-1 gene (resulting in a conservative amino acid change), and 3 were observed in the CXCR-2 gene, of which the first resulted in a silent codon change and the others were in the 3' untranslated area of exon 3. Compared with controls, a significant increase in the frequency of the CXCR-2 +785 CC homozygote and of the CXCR-2 +1208 TT homozygote was found in the SSc patients (37% versus 22% [P = 0.01] and 33% versus 17% [P = 0.003], respectively). A subgroup analysis revealed this association to be significant both in the FASSc patients and in the NFASSc patients. CONCLUSION: This report describes an association between SSc and 2 polymorphisms occurring close to each other in the CXCR-2 gene. This finding and its functional significance need to be confirmed and analyzed in future studies.

Antigens, CD↗

Tobacco smoking habits, attitudes and beliefs among nurse and medical students in Tuscany.

In this study we evaluated the smoking habits, beliefs and attitudes of nurse and medical students at the University of Siena and Florence, Italy. Students who entered the 1st year of school in 1998 were asked to complete a self-administered anonymous questionnaire. Two hundred medical students completed the questionnaire; they had a mean age (+/-SD) of 19.8+/-1.7 years and 68% were females. A total of 205 nurse respondents answered to the questionnaire; they had a mean age of 21.8+/-4.1 years and females were 83% of the total. The overall response rate among students always remained higher than 85%. Thirty per cent of medical students were current smokers, and 5% former-smokers. A total of 43% of nurse students were current smokers and 11.5% former-smokers. Nurse students were more likely to smoke than medical students (p = 0.001). Among current smokers, the number of daily cigarettes smoked and the degree of nicotine addiction did not differ between groups. The prevalence of maternal smoking were higher among nurse students. In spite of students' beliefs the knowledge about smoking remained generic in both groups. Nurse students were less aware than medical students of their special responsibility towards people about tobacco smoking. Such a difference remained significant also after adjustment for smoking status (p < 0.01). Students overestimated the prevalence of current smokers among health caregivers of the local hospitals, and Italian people and adolescents. Targeted and continuous training about smoking prevention should be mandatory in Italian medical and nurse schools.

Adolescent↗

Acoustic parameters of voluntary cough in healthy non-smoking subjects.

OBJECTIVE: The aim of this study was to explore cough in healthy subjects. METHODOLOGY: We studied 234 coughs generated by 24 (12 males) healthy non-smokers (forced expiratory volume in 1 s (FEV1) 103+/-8% of predicted), who had no significant differences in FEV1 and age between males and females. For each subject, several bouts of voluntary coughing were recorded using a personal computer with an A/D converter (sampling rate 10 kHz, 8 bit resolution) and the first and second coughs of each bout were analysed using short-time Fast Fourier Transformation. For each cough we studied the three phases that are produced. In particular, we studied the duration of the three parts, loudest frequency in the first part, lowest and highest frequencies, number of continuous frequencies and lowest and highest continuous frequencies in the second part, and the loudest frequency of the third part if present. RESULTS: We found significant differences between males and females in length of the first part (41.4+/-14 vs 44.7+/-10.4 msec, P = 0.04), loudest frequency of the first part (362+/-145 vs 449+/-145 Hz), lowest frequencies (282+/-100 vs 348+/-135 Hz) and highest continuous frequencies (3877+/-571 vs 4147+/-362 Hz; P < 0.001) of the second part. An interesting finding was that healthy males and females had the same number of continuous frequencies. Different frequencies are probably a consequence of anatomical differences in airway geometry involved in the cough. CONCLUSION: In cough frequency spectrum studies the differences between the two sexes should be taken into account to reduce the variability of the results.

Acoustics↗

Consumption of fresh fruit rich in vitamin C and wheezing symptoms in children. SIDRIA Collaborative Group, Italy (Italian Studies on Respiratory Disorders in Children and the Environment).

BACKGROUND: A beneficial effect of fresh fruit consumption on lung function has been observed in several studies. The epidemiological evidence of the effect on respiratory symptoms and asthma is limited. The consumption of fruit rich in vitamin C was examined in relation to wheezing and other respiratory symptoms in cross sectional and follow up studies of Italian children. METHODS: Standardised respiratory questionnaires were filled in by parents of 18 737 children aged 6-7 years living in eight areas of Northern and Central Italy. The winter intake of citrus fruit and kiwi fruit by the children was categorised as less than once per week, 1-2 per week, 3-4 per week, and 5-7 per week. A subset of 4104 children from two areas was reinvestigated after one year using a second parental questionnaire to record the occurrence of wheezing symptoms over the intervening period. RESULTS: In the cross sectional analysis, after controlling for several confounders (sex, study area, paternal education, household density, maternal smoking, paternal smoking, dampness or mould in the child's bedroom, parental asthma), intake of citrus fruit or kiwi fruit was a highly significant protective factor for wheeze in the last 12 months (odds ratio (OR) = 0.66, 95% confidence intervals (CI) 0.55 to 0.78, for those eating fruit 5-7 times per week compared with less than once per week), shortness of breath with wheeze (OR = 0.68, 95% CI 0.56 to 0.84), severe wheeze (OR = 0.59, 95% CI 0.40 to 0.85), nocturnal cough (OR = 0.73, 95% CI 0.65 to 0.83), chronic cough (OR = 0.75, 95% CI 0.65 to 0.88), and non-coryzal rhinitis (OR = 0.72, 95% CI 0.63 to 0.83). In the follow up study fruit intake recorded at baseline was a strong and independent predictor of all symptoms investigated except non-coryzal rhinitis. In most cases the protective effect was evident even among children whose intake of fruit was only 1-2 times per week and no clear dose-response relationship was found. The effect was stronger (although not significantly so (p = 0.13)) in subjects with a history of asthma; those eating fresh fruit at least once a week experienced a lower one year occurrence of wheeze (29. 3%) than those eating fruit less than once per week (47.1%) (OR = 0. 46, 95% CI 0.27 to 0.81). CONCLUSIONS: Although the effect of other dietary components cannot be excluded, it is concluded that the consumption of fruit rich in vitamin C, even at a low level of intake, may reduce wheezing symptoms in childhood, especially among already susceptible individuals.

Ascorbic Acid↗

Differences in parental- and self-report of asthma, rhinitis and eczema among Italian adolescents. SIDRIA collaborative group. Studi Italiani sui Disordini Respiratori dell' Infanzia e l'Ambiente.

Epidemiological and clinical information on respiratory and allergic disorders in adolescents has been collected from the adolescents themselves or from their parents, but little is known about the differences between these two sources of information. This study compared the responses to 10 identically worded questions from the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire on asthma, rhinitis and eczema between written self- and parent-completed questionnaires in a large sample of 21,068 adolescent Italians aged 13-14 yrs. The effects of sex, latitude of residence, urbanization, socioeconomic status, previous diagnosis of asthma, family history of allergic diseases and adolescent's smoking habits on the prevalence estimates obtained with the two questionnaires were analysed using multiple logistic regression. Prevalence of self-reported symptoms was significantly higher in self-reported for all questions except for lifetime eczema, which was higher in parental report. Agreement between the two sources of information was poor, although it was slightly better for questions relative to clinical diagnosis of asthma, hay fever or eczema than for related symptoms, and for respiratory with respect to cutaneous disorders. When compared with self-reported, parent-reported was consistently higher in males and was more affected by socioeconomic level and by a diagnosis of asthma or family history of allergic diseases, whereas self-reported was more sensitive to the effect of the adolescent's smoking habits. It is concluded that, in adolescents, parent- and self-reported respiratory and allergic symptoms differ significantly and are differently affected by several constitutional and environmental factors. Obtaining direct information from adolescents may be essential for a correct evaluation of respiratory symptoms.

Adolescent↗

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.

Adolescent↗

Different effects of inhaled aspirinlike drugs on allergen-induced early and late asthmatic responses.

Little is known about the anti-asthmatic effects of powerful anti-inflammatory agents such as aspirin-like drugs. We compared the effects of two aspirin-like drugs with different pharmacologic activities, sodium salicylate (SSA) and indomethacin, with the effect of lysine acetylsalicylate (LASA), inhaled 30 min before challenge, on the early and the late asthmatic response induced by a single dose of allergen causing a 25% decrease in FEV1 in a preliminary challenge. Inhaled SSA partially prevented both the early and late response, providing a protection with respect to placebo of 22 +/- 6% in the early phase and 23 +/- 9% in the late phase of the response. These values were lower (but not significantly) than those of LASA (41 +/- 9% and 39 +/- 11%, respectively). In a second group of patients, indomethacin failed to affect the early response, while LASA provided a protection of 31 +/- 7%. However, these two drugs were equally effective in reducing the late response (44 +/- 18% and 39 +/- 17% protection for LASA and indomethacin, respectively). In subjects with an early response, despite being ineffective in preventing allergen-induced bronchoconstriction, indomethacin blocked the allergen-induced increase in bronchial hyperresponsiveness measured 2 h after challenge. We conclude that inhaled salicylates, but not indomethacin, exert a protective activity against the early allergic response. This difference is not explained by the different pattern of cyclooxygenase inhibitory activity of these drugs.

Administration, Inhalation↗

Road traffic and adverse respiratory effects in children. SIDRIA Collaborative Group.

OBJECTIVES: To investigate the relation between traffic indicators in the area of residence and the occurrence of chronic respiratory disorders in children. METHODS: A population based survey was conducted in 10 areas of northern and central Italy (autumn 1994 to winter 1995) in two age groups (6-7 and 13-14 years). Information on several respiratory disorders and on traffic near residences was collected with a questionnaire given to children and to their parents. The sample analysed included 39,275 subjects (response rate 94.4%). Outcomes were: (a) early (first 2 years of life) respiratory diseases, and (b) current respiratory disorders (asthma, wheeze, cough, or phlegm in the past year). Odds ratios (ORs) and 95% confidence intervals (95% CIs), adjusted for several potential confounders, were estimated from logistic regression models. Main results were stratified by level of urbanisation (metropolitan areas, other centres). RESULTS: In the metropolitan areas, high frequency of lorry traffic in the street of residence was associated with significantly increased risks for many adverse respiratory outcomes. Among early respiratory diseases, the strongest associations were found for recurrent bronchitis (OR 1.69, 95% CI 1.24 to 2.30), bronchiolitis (1.74, 1.09 to 2.77) and pneumonia (1.84, 1.27 to 2.65), although no association was detected for episodes of wheezing bronchitis. All the current respiratory disorders were positively and consistently associated with frequency of lorry traffic, particularly the most severe bronchitic and wheezing symptoms: persistent phelgm for > 2 months (1.68; 1.14 to 2.48), and severe wheeze limiting speech (1.86; 1.26 to 2.73). No or weaker associations with heavy vehicular traffic were detected in urban and rural areas and no increased risks were found in the whole sample with the reported traffic density in the zone of residence. After extensive evaluations, the potential of reporting bias seems unlikely. CONCLUSION: Exposure to exhausts from heavy vehicular traffic may have several adverse effects on respiratory health of children living in metropolitan areas, increasing the occurrence of lower respiratory tract infections early in life and of wheezing and bronchitic symptoms at school age.

Adolescent↗

Protective effect of inhaled lysine acetylsalicylate on allergen-induced early and late asthmatic reactions.

Conflicting results have been reported on the effect of non-steroidal antiinflammatory drugs on allergen-induced asthmatic responses. The aim of this study was to investigate the effect of inhaled lysine acetylsalicylate (LASA) on the early and late allergen-induced responses. We studied 16 patients with mild, stable asthma who had an early asthmatic response and 10 patients with a dual (early and late) response. Each patient underwent two challenges with a single dose of allergen assessed in a preliminary test, after inhalation of either 720 mg of LASA in 4 ml of saline solution or placebo, according to a randomized, double-blind protocol. Allergen-induced hyperreactivity to methacholine was measured in six patients from each of the early and the dual response groups 2 hours and 24 hours after the challenge, respectively. In the patients with early response, the maximum fall in FEV1 after challenge was 24% +/- 1% after inhalation of placebo and 14% +/- 2% after inhalation of LASA (p < 0.005). No protection was observed in four patients who received the drug orally instead of by inhalation. In the patients with a dual response, the maximum FEV1 decrease during the early response was 27% +/- 2% after placebo and 21% +/- 2% after LASA (p < 0.025). During the late response (between 3 and 8 hours), the maximum decrease in FEV1 was 28% +/- 4% after placebo and 16% +/- 4% after LASA (p < 0.005). In both groups allergen challenge caused a significant reduction in methacholine PD20 after treatment with placebo but not with LASA. Without allergen challenge, LASA had no effect on methacoline reactivity. We conclude that inhaled LASA significantly reduces both the early and the late asthmatic response to allergen challenge and that it prevents the allergen-induced airway hyperresponsiveness that follows these responses.

Administration, Inhalation↗

Attenuation of aspirin-induced bronchoconstriction by sodium cromoglycate and nedocromil sodium.

The protective activity of nedocromil sodium and of sodium cromoglycate against aspirin-induced asthma has never been investigated in controlled studies. Because it has been reported that aspirin-induced platelet-mediated cytotoxic activity in vitro is inhibited after treatment in vivo with nedocromil but not with cromoglycate, we investigated whether these compounds also exhibit a different protective activity against aspirin-induced bronchoconstriction. Ten patients with aspirin-induced asthma underwent three bronchial challenges with a single dose of lysine acetylsalicylate (LASA) that caused a decrease in FEV1 of 25% or more in a preliminary dose-response test 30 min after inhalation of 4 mg nedocromil sodium, 10 mg sodium cromoglycate, or placebo. FEV1 and SRaw were recorded at intervals for 195 min. After placebo, LASA caused a maximal decrease in FEV1 of 42 +/- 4% of baseline. After cromoglycate and nedocromil the maximal decrease in FEV1 was reduced to 20 +/- 3% and 18 +/- 4%, respectively (p < 0.01 versus placebo for both treatments), without significant differences between the two treatments. Similar results were observed with SRaw. We conclude that, at the recommended therapeutic doses, sodium cromoglycate and nedocromil sodium are equally effective in attenuating aspirin-induced bronchoconstriction and that it is unlikely that platelet activation participates in the pathogenesis of aspirin-induced asthma.

Anti-Asthmatic Agents↗