Decomposing neural responses to melodic surprise in musicians and non-musicians: Evidence for a hierarchy of predictions in the auditory system.

Neural responses to auditory surprise are typically studied with highly unexpected, disruptive sounds. Consequently, little is known about auditory prediction in everyday contexts that are characterized by fine-grained, non-disruptive fluctuations of auditory surprise. To address this issue, we used IDyOM, a computational model of auditory expectation, to obtain continuous surprise estimates for a set of newly composed melodies. Our main goal was to assess whether the neural correlates of non-disruptive surprising sounds in a musical context are affected by musical expertise. Using magnetoencephalography (MEG), auditory responses were recorded from musicians and non-musicians while they listened to the melodies. Consistent with a previous study, the amplitude of the N1m component increased with higher levels of computationally estimated surprise. This effect, however, was not different between the two groups. Further analyses offered an explanation for this finding: Pitch interval size itself, rather than probabilistic prediction, was responsible for the modulation of the N1m, thus pointing to low-level sensory adaptation as the underlying mechanism. In turn, the formation of auditory regularities and proper probabilistic prediction were reflected in later components: The mismatch negativity (MMNm) and the P3am, respectively. Overall, our findings reveal a hierarchy of expectations in the auditory system and highlight the need to properly account for sensory adaptation in research addressing statistical learning.

Survival of localized NSCLC patients without active treatment or treated with SBRT.

BACKGROUND: Little information on the natural history of patients with localized NSCLC is available since many of the studies covering the subject lack information on pathological confirmation, staging procedures and comorbidity. No randomized studies have compared SBRT with no treatment for patients with localized NSCLC. The purpose of this study was to evaluate whether SBRT has influence on overall survival for patients with localized NSCLC and investigate the effect of baseline ventilatory lung function on overall survival. MATERIAL AND METHODS: From 2007 to 2013, 136 patients treated with SBRT at Odense University Hospital were prospectively recorded. The thoracic SBRT consisted of three fractions of 15-22 Gy delivered in 9 days. For comparison, a national group of 73 untreated patients in the same time period was extracted from the Danish Lung Cancer Registry. All patients had histologically/cytologically proven NSCLC T1-2N0M0 with a tumour diameter ≤5 cm. RESULTS: The 5-year relative survival was 44% versus 7% for the SBRT and untreated groups, respectively. In a propensity score matched comparison the median overall survival was 47 months versus 11 months for the SBRT and untreated groups, respectively (p < .05). On multivariate analysis, SBRT was significantly associated with improved prognosis while ECOG performance status 2+ and tumour diameter ≥3 cm significantly predicted poorer prognosis. Severe to very severe reduction of forced expiratory volume in one second (FEV1) did not predict poorer survival for the SBRT treated patients with localized NSCLC. CONCLUSIONS: SBRT offers more favourable survival than no treatment for patients with localized NSCLC. Performance status of 0-1, tumour diameter less than 3 cm and SBRT predicted improved survival. SBRT should not be withheld for patients with localized NSCLC based on poor ventilatory lung function.

Oxytocin improves synchronisation in leader-follower interaction.

The neuropeptide oxytocin has been shown to affect social interaction. Meanwhile, the underlying mechanism remains highly debated. Using an interpersonal finger-tapping paradigm, we investigated whether oxytocin affects the ability to synchronise with and adapt to the behaviour of others. Dyads received either oxytocin or a non-active placebo, intranasally. We show that in conditions where one dyad-member was tapping to another unresponsive dyad-member - i.e. one was following another who was leading/self-pacing - dyads given oxytocin were more synchronised than dyads given placebo. However, there was no effect when following a regular metronome or when both tappers were mutually adapting to each other. Furthermore, relative to their self-paced tapping partners, oxytocin followers were less variable than placebo followers. Our data suggests that oxytocin improves synchronisation to an unresponsive partner's behaviour through a reduction in tapping-variability. Hence, oxytocin may facilitate social interaction by enhancing sensorimotor predictions supporting interpersonal synchronisation. The study thus provides novel perspectives on how neurobiological processes relate to socio-psychological behaviour and contributes to the growing evidence that synchronisation and prediction are central to social cognition.

Rate of fall-applied liquid swine manure: effects on runoff transport of sediment and phosphorus.

Reducing the delivery of phosphorus (P) from land-applied manure to surface water is a priority in many watersheds. Manure application rate can be controlled to manage the risk of water quality degradation. The objective of this study was to evaluate how application rate of liquid swine manure affects the transport of sediment and P in runoff. Liquid swine manure was land-applied and incorporated annually in the fall to runoff plots near Morris, Minnesota. Manure application rates were 0, 0.5, 1, and 2 times the rate recommended to supply P for a corn (Zea mays L.)-soybean [Glycine max (L.) Merr.] rotation. Runoff volume, sediment, and P transport from snowmelt and rainfall were monitored for 3 yr. When manure was applied at the highest rate, runoff volume and sediment loss were less than the control plots without manure. Reductions in runoff volume and soil loss were not observed for spring runoff when frozen soil conditions controlled infiltration rates. The reduced runoff and sediment loss from manure amended soils compensated for addition of P, resulting in similar runoff losses of total P among manure application rates. However, losses of dissolved P increased with increasing manure application rate for runoff during the spring thaw period. Evaluation of water quality risks from fall-applied manure should contrast the potential P losses in snowmelt runoff with the potential that incorporated manure may reduce runoff and soil loss during the summer.

Herbicide banding and tillage system interactions on runoff losses of alachlor and cyanazine.

Herbicides transported to surface waters by agricultural runoff are partitioned between solution and solid phases. Conservation tillage that reduces upland erosion will also reduce transport of herbicides associated with the solid phase. However, transport of many herbicides occurs predominantly in solution. Conservation tillage practices may or may not reduce transport of solution-phase herbicides, as this depends on the runoff volume. Reducing herbicide application rate is another approach to minimize off-site transport. Herbicide banding can reduce herbicide application rates and costs by one-half or more. Our objective was to compare herbicide losses in runoff from different tillage practices and with band- or broadcast-applied herbicides. The herbicides alachlor [2-chloro-2',6'-diethyl-N-(methoxymethyl)acetanilide] and cyanazine [2-[[4-chloro-6-(ethylamino)-1,3,5-triazin-2-yl]amino]-2-methylpropionitrile] were broadcast- or band-applied to plots managed in a moldboard plow, chisel plow, or ridge till system. Herbicide concentration in runoff was largest for the first runoff event occurring after application and then decreased in subsequent events proportional to the cumulative rain since the herbicide application. When herbicides were broadcast-applied, losses of alachlor and cyanazine in runoff followed the order: moldboard plow > chisel plow > ridge till. Conservation tillage systems reduced runoff loss of herbicides by reducing runoff volume and not the herbicide concentration in runoff. Herbicide banding reduced the concentration and loss of herbicides in runoff compared with the broadcast application. Herbicide losses in the water phase averaged 88 and 97% of the total loss for alachlor and cyanazine, respectively. Cyanazine was more persistent than alachlor in the soil.

Impact of airway lability, atopy, and tobacco smoking on the development of asthma-like symptoms in asymptomatic teenagers.

AIM: To investigate the impact of airway lability, atopy, and tobacco smoking on the development of asthma-like symptoms in asymptomatic subjects. METHODS: In this prospective, community-based study, 271 asymptomatic adolescents with an average age at inclusion of 13.9 years were followed for 6.4 years. Airway lability was assessed at baseline by three tests, including exercise challenge, airway provocation with methacholine, and monitoring of peak expiratory flow. Atopy was defined by one or more positive reactions (> or = 3-mm weal) to 10 common aeroallergens by skin prick testing. The influence of airway lability, atopy, and smoking on the development of asthma-like symptoms was assessed by logistic regression. RESULTS: During the 6-year study period, 68 of the previously asymptomatic teenagers (25%) developed asthma-like symptoms. Among those, 50% reported cough only, 29% reported wheezing only, and 21% reported both wheezing and coughing. Hyperresponsiveness to methacholine (odds ratio [OR], 3.5; 95% confidence interval [CI], 1.1 to 11.6), smoking (OR, 2.1; 95% CI, 1. 2 to 3.8), and atopy (OR, 3.5; 95% CI, 1.8 to 6.8) each contributed independently to explain symptom development (wheezing and cough together). Girls, but not boys, with airway lability were less likely to take up smoking, compared with subjects of that set with no airway lability (32% vs 51%; p < 0.05). No effect of airway lability on the likelihood of giving up smoking could be demonstrated, nor did the presence of atopy have any significant impact on smoking behavior. CONCLUSION: Hyperresponsiveness to methacholine, atopy, and smoking were independent risk factors for the development of asthma-like symptoms during adolescence. The presence of airway lability may prevent girls from taking up smoking.

Increased eosinophil cation protein level in sensitized nonasthmatics is linked to subsequent hyperresponsiveness to methacholine. The Odense Schoolchild Study.

BACKGROUND: Increased levels of eosinophil cation protein (ECP) in sensitized subjects may reflect early stages of an ongoing inflammatory process and therefore precede asthma and bronchial hyperreactivity. AIM: To study whether nonasthmatic subjects with sensitization to allergens and increased ECP levels are at a higher risk for subsequent increased bronchial reactivity compared with sensitized nonasthmatics with normal ECP levels. METHODS: A prospective study of 240 schoolchildren with a mean age of 13.9 years (range: 12.6-15.9) who were followed up after 6.3 years. Bronchial reactivity was assessed by methacholine provocation testing. Sensitization was defined by one or more positive reactions (>3 mm wheal) to 10 common aeroallergens by skin prick testing. Increased ECP was defined as values above 20 microg/l. This separated the subjects into four categories: group 1: healthy controls without sensitization (n = 147); group 2: sensitized subjects with a serum ECP below 20 microg/l (n = 55); group 3: sensitized subjects with an ECP level at or above 20 microg/l (n = 16), and group 4: all asthmatics (n = 22). RESULTS: Bronchial reactivity was similar in subjects of groups 2 and 3 at baseline (p = 0.8). Six years later, subjects from group 3 were more responsive to methacholine compared with subjects from group 2 (median: 12.7 versus 20.5 micromol; p < 0.05). In a logistic regression with hyperresponsiveness to methacholine at follow-up as dependent variable, the odds ratios (OR) for the groups were, with group 1 as reference: group 2: OR = 2.2 (0.8-6.6: p = 0.2), group 3: 5.9 (1. 6-21.7: p < 0.01). CONCLUSION: Subjects with sensitization and increased ECP levels are subsequently more airway-responsive to methacholine compared with sensitized subjects with normal ECP levels. This supports the hypothesis that sensitization is linked to increased bronchial reactivity through a process in which markers of inflammation are involved.

Enterobacter cloacae bloodstream infections traced to contaminated human albumin.

In August 1996, a patient in Kansas developed an Enterobacter cloacae bloodstream infection (BSI) shortly after receiving Albuminar, a brand of human albumin. Albuminar contamination was suspected. A case-control study of patients with primary gram-negative bacterial BSIs showed that patients with E. cloacae BSIs were significantly more likely than patients with non-E. cloacae gram-negative BSIs to have received Albuminar within 3 days of developing their BSIs (3 of 5 vs. 0 of 9; OR, undefined; P=.03). The E. cloacae isolate from the Kansas patient was found by pulsed-field gel electrophoresis to be identical to the isolate from the patient's Albuminar vial, to isolates from 2 previously unopened Albuminar vials, and to an isolate from a Wisconsin patient who had received Albuminar. A worldwide recall of approximately 116,000 Albuminar vials took place. This multistate outbreak was detected because of clinical astuteness and prompt reporting. Combined epidemiological and laboratory approaches are valuable when investigating potentially contaminated blood components and plasma derivatives.

Low physical fitness in childhood is associated with the development of asthma in young adulthood: the Odense schoolchild study.

Intense physical activity in children may either improve fitness and protect against asthma, or may trigger symptoms. The aim of this study was to determine whether physical fitness in childhood has an impact on the development of asthma. In this prospective, community-based study, 757 (84%) asymptomatic children with an average age at inclusion of 9.7 yrs were followed for 10.5 yrs. In both surveys a maximal progressive exercise test on a bicycle ergometer was used to measure physical fitness (maximal workload) and to induce airway narrowing. A methacholine provocation test was performed in the subjects at follow-up. During the 10-yr study period, 51 (6.7%) of the previously asymptomatic children developed asthma. These subjects had a lower mean physical fitness in 1985 than their peers: (3.63 versus 3.89 W x kg(-1); p=0.02) in boys and (3.17 versus 3.33 W x kg(-1); p=0.02) in girls. A weak correlation was found between physical fitness in childhood and airway responsiveness to methacholine at follow-up when adjusted for body mass index, age and sex (r=0.11; p<0.01). In a multiple regression analysis, physical fitness was inversely related to the development of physician diagnosed asthma, odds ratio=0.93 (0.87-0.99). Thus, the risk for the development of asthma during adolescence is reduced 7% by increasing the maximal workload 1 W x kg(-1). In conclusion, this study showed that physical fitness in childhood is weakly correlated with the development of asthma during adolescence and that high physical fitness seems to be associated with a reduced risk for the development of asthma.

A randomized clinical trial of alpha(1)-antitrypsin augmentation therapy.

We have investigated whether restoration of the balance between neutrophil elastase and its inhibitor, alpha(1)-antitrypsin, can prevent the progression of pulmonary emphysema in patients with alpha(1)-antitrypsin deficiency. Twenty-six Danish and 30 Dutch ex-smokers with alpha(1)-antitrypsin deficiency of PI*ZZ phenotype and moderate emphysema (FEV(1) between 30% and 80% of predicted) participated in a double-blind trial of alpha(1)-antitrypsin augmentation therapy. The patients were randomized to either alpha(1)-antitrypsin (250 mg/kg) or albumin (625 mg/kg) infusions at 4-wk intervals for at least 3 yr. Self-administered spirometry performed every morning and evening at home showed no significant difference in decline of FEV(1) between treatment and placebo. Each year, the degree of emphysema was quantified by the 15th percentile point of the lung density histogram derived from computed tomography (CT). The loss of lung tissue measured by CT (mean +/- SEM) was 2.6 +/- 0.41 g/L/yr for placebo as compared with 1.5 +/- 0.41 g/L/yr for alpha(1)-antitrypsin infusion (p = 0.07). Power analysis showed that this protective effect would be significant in a similar trial with 130 patients. This is in contrast to calculations based on annual decline of FEV(1) showing that 550 patients would be needed to show a 50% reduction of annual decline. We conclude that lung density measurements by CT may facilitate future randomized clinical trials of investigational drugs for a disease in which little progress in therapy has been made in the past 30 yr.

Asymptomatic bronchial hyperresponsiveness to exercise in childhood and the development of asthma related symptoms in young adulthood: the Odense Schoolchild Study.

BACKGROUND: Exercise testing may be of value in identifying a group of children at high risk of subsequently developing respiratory symptoms. As few longitudinal studies have investigated this issue, the bronchial hyperresponsiveness to exercise in asymptomatic children was evaluated as a risk factor for developing asthma related symptoms in young adulthood. METHODS: A community based sample of 1369 schoolchildren, first investigated in 1985 at a mean age of 9.7 years, was followed up after a mean of 10.5 years. Nine hundred and twenty children (67%) were asymptomatic in childhood and 777 (84.9%) of these were re-investigated at follow up. At the first examination a maximum progressive exercise test on a bicycle ergometer was used to induce airway narrowing. The forced expiratory volume in one second (FEV1) after exercise was considered abnormal if the percentage fall in FEV1 was more than 5% of the highest fall in the reference subjects characterised by having no previous history of asthma or asthma related symptoms. The threshold for a positive test was 8.6% of pre-exercise FEV1. RESULTS: One hundred and three subjects (13%) had wheeze within the last year at follow up and, of these, nine (9%) had been hyperresponsive to exercise in 1985. One hundred and seventy subjects (22%) had non-infectious cough within the previous year, 11 of whom (6%) had been hyperresponsive to exercise in 1985. Multiple regression analysis showed that subjects with hyperresponsiveness to exercise had an increased risk of developing wheeze compared with subjects with a normal response to exercise when the fall in FEV1 after exercise was included as a variable (threshold odds ratio (OR) 2.3 (95% CI 1.1 to 5.5)). The trend was not significant when exercise induced bronchospasm was included as a continuous variable (OR 1.02 (95% CI 0.97 to 1.06)). CONCLUSIONS: Asymptomatic children who are hyperresponsive to exercise are at increased risk of developing new symptoms related to wheezing but the predictive value of exercise testing for individuals is low.

Are young adults with asthma treated sufficiently with inhaled steroids? A population-based study of prescription data from 1991 and 1994.

1. We conducted a descriptive cross-sectional study of asthma therapy among young adults to assess to what extent the current guidelines for asthma therapy have been implemented. In particular, we examined the use of inhaled corticosteroids in heavy users of inhaled beta-adrenoceptor agonists. 2. Data were retrieved from a population-based prescription database. For each of the years 1991 and 1994, all 20 to 44-year-olds who redeemed anti-asthma medication in the Odense area (210,000 inhabitants) were studied. 3. We identified the number of users and total sales volume for specific anti-asthma medications in defined daily doses (DDD) as well as the number of users and median annual doses of common regimens. Combined use of inhaled corticosteroids and inhaled beta-adrenoceptor agonists was also described. 4. The annual sales volume of anti-asthma drugs increased by 23% to 927,636 DDD from 1991 to 1994. Inhaled corticosteroids were mainly responsible for this with a 52% increase in number of users and an 88% increase in DDD. Inhaled beta-adrenoceptor agonists used in monotherapy remained the most popular regimen in 1994 (1685 users = 39%). Inhaled corticosteroids in combination with inhaled beta-adrenoceptor agonist were the second most popular regimen in 1994 (1308 users = 30%), increasing by 64% as compared with 1991. However, among patients with an annual use of inhaled beta-adrenoceptor agonist of 200 DDD (1600 "puffs') or more the percent of patients not receiving inhaled corticosteroids at all only fell from 37 to 33%. Though the number of patients being treated with inhaled corticosteroids has increased, there is still evidence of a substantial underuse.

Salbutamol powder inhaled from the Diskhaler compared to salbutamol as nebulizer solution in severe chronic airways obstruction.

The bronchodilatory effect of four doses of salbutamol powder (1.6 mg) from a multi-dose dry powder inhaler, the Diskhaler, was compared to the effect of 2.5 ml salbutamol nebulizer solution (1 mg ml-1) from a jet nebulizer, Pari Inhalierboy, in a randomized, double-blind, double-dummy, cross-over study performed on 2 consecutive days. Thirty-two patients with severe chronic obstructive pulmonary disease (COPD), a mean FEV1 = 29% of predicted value, and at least a 15% increase in FEV1 after inhaling 5 mg nebulized terbutaline were included. Twenty-eight patients were evaluated: 17 women and 11 men with a mean age of 67 years (range 53-82 years). The mean increases in FEV1 were greater after inhalation via the Diskhaler, although there was no difference in the patients' subjective assessment of the treatments. The powder inhaler was also effective in patients with the lowest baseline FEV1 and the lowest inspiratory peak flow through the inhaler. The study demonstrates that dry powder inhalation of salbutamol via a Diskhaler is at least as effective as inhalation of salbutamol via a jet nebulizer in providing bronchodilation in patients with severe COPD.

Orally administered N-acetylcysteine may improve general well-being in patients with mild chronic bronchitis.

Oral N-acetylcysteine (NAC) exerts a beneficial action in chronic bronchitis by reducing the number of exacerbations. There have been few studies of the effect of NAC (or of any other drug) on general well-being in chronic bronchitis. We used an established psychiatric instrument (General Health Questionnaire; GHQ) and a visual analogue scale (VAS) to measure well-being in a 22-week, placebo-controlled, double-blind, parallel-group study of NAC administered as sustained release tablets 600 mg b.i.d., including during the winter months, to patients with mild chronic bronchitis. One hundred and fifty-three patients were accepted for randomized treatment, 129 finished the study (59 NAC, 70 placebo), and well-being was measured in 105 (46 NAC, 59 placebo). The number of observed exacerbations was unexpectedly low in both groups. The number was lowest in the NAC group, however, the difference did not reach statistical significance in the present study (P = 0.08). There were no statistically significant differences between NAC and placebo in subjective symptom scores, FEV1 or FVC. The distribution of GHQ score at baseline was uneven, but NAC was significantly superior to placebo in terms of a favourable effect on GHQ score. GHQ score correlated with the number of exacerbations, and VAS correlated with GHQ score. This study therefore demonstrates the validity of measuring general well-being in patients with mild chronic bronchitis. Future studies of the treatment of chronic bronchitis should use a battery of more specifically adapted instruments which are now becoming available to measure well-being.

Terbutaline inhalations by the Turbuhaler as replacement for domiciliary nebulizer therapy in severe chronic obstructive pulmonary disease.

Patients with chronic obstructive pulmonary disease (COPD) are often treated with high dose inhalations of beta 2-agonists. We compared domiciliary therapy with terbutaline administered by the Turbuhaler and by a jet nebulizer. Forty nebulizer users with severe COPD were included in the randomized, double-blind, cross-over study. Terbutaline was inhaled t.i.d. for 2 weeks as dry powder (5 doses = 2.5 mg) by Turbuhaler or as solution (2 ml = 5 mg) by jet nebulizer (Pari Inhalierboy). The mean age of the 25 completing patients was 66 years (range: 54-81), the mean FEV1 was 0.73 l or 29% of predicted (range: 11-55%). The period where the Turbuhaler delivered the active drug was preferred by 16 patients, the nebulizer period by seven (P = 0.09). The median score concerning feeling of control over the disease--according to the Chronic Respiratory Disease Questionnaire--was better after the Turbuhaler period (P = 0.01). Other scores concerning disease related quality of life, the daily peak expiratory flow rates, the additional use of a metered dose inhaler were not significantly different for the two types of treatment. It is concluded that high dose domiciliary terbutaline treatment by Turbuhaler can replace nebulizer treatment in most patients with severe COPD.

Evaluation of peak expiratory flow variability in an adolescent population sample. The Odense Schoolchild Study.

The validity of peak expiratory flow (PEF) recordings and the sensitivity of PEF variability indices in asthma and asthma-like conditions were examined in an adolescent population. Recordings from 245 randomly selected subjects and from an additional 181 subjects reporting or considered at risk for developing asthma were analyzed. Subjects recorded PEF twice daily for 2 wk using Mini-Wright meters, completed a symptoms questionnaire, and were tested for airway responsiveness to methacholine. The first three recording days showed significant accumulation of lowest PEF values recorded (41%) and were excluded from further analysis. Among nine PEF variability indices, the Two-lowest%mean (the mean of the two lowest PEF values as a percentage of the period mean) had the best sensitivity for physician-diagnosed asthma (28%). The sensitivity of the methacholine dose-response slope (DRS) was 69%. Combining these indices, a sensitivity of 77% for diagnosed asthma was obtained. Among subjects with asthma-like symptoms but no diagnosis of asthma, 14% had increased Two-lowest%mean and the DRS was increased in 17%, but only 3% were identified by both tests. In conclusion, inhomogeneity of PEF data could be corrected by disregarding the first three recording days. PEF variability indices identified some diagnosed asthmatics, and particularly some symptomatic "nonasthmatics," not identified by the DRS, suggesting that the combined use of these indices might be helpful.

Individual utilization of anti-asthma medication by young adults: a prescription database analysis.

OBJECTIVES: To analyse and evaluate current practice of asthma therapy by use of computerized prescription data. DESIGN: Descriptive, non-interventive. SETTING: A pharmacoepidemiological database on computerized refund claims from pharmacies in the Odense region in Denmark. SUBJECTS: Persons aged 20-44, presenting prescriptions for asthma drugs during the period 1 October 1990 to 30 September 1991. MAIN OUTCOME MEASURES: Prevalence of asthma drug use, the regimes chosen, relationship between beta-agonist and steroid use by the individual patient. RESULTS: In all, 3020 persons used anti-asthma drugs, corresponding to a crude 1-year prevalence of 3.6%. Sixty per cent were women. The subjects had an average anti-asthma drug consumption corresponding to 86% of the population's average. The four most common regimes were inhaled beta-agonist monotherapy, inhaled beta-agonist and corticosteroid, oral beta-agonist monotherapy and inhaled corticosteroid monotherapy, altogether accounting for 79% of users. The proportion of corticosteroid users increased with increasing individual use of beta-agonists. With an annual beta-agonist purchase of 100-200 defined daily doses, still less than half also used steroids. CONCLUSION: The majority of patients use a regime agreeing with current guidelines, except that more patients should be prescribed corticosteroids. The observed large increase in asthma drug use is likely to be explained by an intensified treatment of individual patients, rather than an increased prevalence.

N-acetylcysteine by metered dose inhaler in the treatment of chronic bronchitis: a multi-centre study.

Sixty-five patients with chronic bronchitis were studied at five different centres in a double-blind, randomized trial. Two parallel groups were treated with either N-acetylcysteine or placebo by metered dose inhalers for 16 weeks. Following a 1-week run-in period, each patient recorded subjective impressions of the drug action on their bronchitic symptoms in a diary once a week. In addition, exacerbations were registered. Lung function testing and adverse effects were evaluated by four visits to the chest clinics during the 16 weeks. We could not demonstrate that N-acetylcysteine by metered dose inhalers had any significant effect on patients' feeling of well-being, sensation of dyspnoea, intensity of coughing, mucus production, or expectoration or lung function. Its effect in reducing exacerbations could not be estimated because of a very low number of exacerbations reported. N-acetylcysteine inhalation was safe when used over a 16-week period.

Precipitating antibodies against pigeon bloom antigens as a specific and sensitive measure of pigeon exposure.

Precipitating antibodies against pigeon bloom antigen and pigeon serum were evaluated as a measure of pigeon exposure in 62 male pigeon breeders compared with 40 unexposed control subjects. We found a combination of highly antigenic bloom extract and a sensitive counter current immunoelectrophoresis suitable for clinical estimation of pigeon exposure. The sensitivity of the test was 86% in never-smokers and 73% in smokers at the 98% specificity level. Smoking significantly reduced the humoral immune response to both antigens.