Lack of clinical exacerbations in adults with chronic asthma after immunization with killed influenza virus.

The effects of immunization with killed influenza virus vaccine were assessed by comparison with placebo in a double-blind study of 318 adult patients with chronic asthma. The patients were randomly allocated to active vaccine and placebo. No difference was observed in peak expiratory flow rate or in clinical symptoms of bronchial obstruction between the groups receiving active vaccine and placebo during the first week after immunization. The data were analyzed separately for age, sex, duration of the disease, hypersensitivity to aspirin (acetylsalicylic acid), atopic status, patients with a history of attacks of asthma induced by viral infections, patients with a diurnal variation of baseline peak expiratory flow of 20 percent or more, and patients receiving continuous oral steroid medication, but none of these factors seemed to predict any short-term adverse effects of vaccination. Follow-up for eight months after the vaccination revealed no differences in asthmatic symptoms between the patients treated with active vaccine and those receiving placebo. The antiviral antibody response to vaccination was normal. The possible protection provided by the vaccination against exacerbation of asthma induced by influenza could not be evaluated, since the influenza epidemic expected during the season failed to occur in Finland. It is concluded that immunization with killed influenza vaccine is safe and is not associated with any significant side effects in adult patients with chronic asthma.

Adjustable maintenance dosing with budesonide/formoterol compared with fixed-dose salmeterol/fluticasone in moderate to severe asthma.

BACKGROUND: Current asthma guidelines recommend that patients are educated to adjust their medication according to their asthma severity using physician-guided self-management plans. However, many patients take a fixed dose of their controller medication and adjust their reliever medication according to asthma symptoms. OBJECTIVES: This study examined whether asthma control improved if patients adjusted the maintenance dose of budesonide/formoterol (Symbicort Turbuhaler* 160/4.5 microg) according to asthma severity compared with traditional fixed dosing (FD) regimens. METHODS: Symptomatic patients with asthma (n = 658, mean symptom score 1.5, mean inhaled corticosteroids 735 microg/day, mean forced expiratory volume in 1 second [FEV(1)] 84% predicted) were randomised after 2 weeks' run-in to either: budesonide/formoterol adjustable maintenance dosing (AMD), budesonide/formoterol FD or salmeterol/fluticasone (Seretide Diskus dagger 50/250 microg) FD. In a 4-week double-blind period, both budesonide/formoterol AMD and FD groups received two inhalations twice daily (bid) and salmeterol/fluticasone FD patients received one inhalation bid. In the following 6-month open extension, both FD groups continued with the same treatment. Patients in the AMD group with well-controlled asthma stepped down to one inhalation bid; others continued with two inhalations bid. All AMD patients could increase to four inhalations bid for 7-14 days if symptoms worsened. All patients used terbutaline or salbutamol for symptom relief throughout. The primary variable was the odds of achieving a well-controlled asthma week (WCAW). RESULTS: The odds ratio for achieving a WCAW did not differ between the FD regimens; however, during the open period, budesonide/formoterol AMD increased the odds of achieving a WCAW vs. budesonide/formoterol FD (odds ratio 1.335; 95% CI: 1.001, 1.783; p = 0.049) despite a 15% reduction in average study drug use. Budesonide/formoterol AMD patients had a lower exacerbation rate over the study: 40% lower vs. salmeterol/fluticasone FD (p = 0.018); 32% lower vs. budesonide/formoterol FD (NS). During the double-blind period, there were no clinically relevant differences between the budesonide/formoterol FD and salmeterol/fluticasone FD groups. Budesonide/formoterol AMD patients used less reliever medication in the open extension: 0.58 vs. 0.92 occasions/day for budesonide/formoterol FD (p = 0.001) and 0.80 occasions/day for salmeterol/fluticasone FD (p = 0.011). CONCLUSIONS: Adjustable maintenance dosing with budesonide/formoterol provides more effective asthma control by reducing exacerbations and reliever medication usage compared with fixed-dose salmeterol/fluticasone.

The availability of smoking cessation advice from health professionals--a census from one East London District.

A survey of 382 hospital inpatients and a survey of 500 adults attending a GP open access chest X-ray service showed that 18% and 25% respectively were current smokers. Sixty per cent of the inpatient smokers and three quarters of the community smokers expressed a wish to stop smoking, and 44% of the inpatient smokers and 62% of the community smokers reported having received advice from their primary care physician to stop smoking. However, when the community smokers were asked about more specific advice they had received to help them stop smoking, only 13% had received advice regarding nicotine replacement therapies and under 5% had been given the telephone number of a smoking cessation support service (Smokers Quitline). Use of nicotine replacement therapies nearly doubles the success rate for smoking cessation, and it is essential for all health professionals to be able to give specific advice as to how smokers may be able to quit.

Airway inflammation and basement membrane tenascin in newly diagnosed atopic and nonatopic asthma.

Previous studies have shown both similar and distinct inflammatory changes in atopic and nonatopic asthma. This study was set to investigate the bronchial inflammatory cell infiltrate and subepithelial basement membrane (BM) tenascin deposition in subjects with newly diagnosed asthma and bronchial hyperresponsiveness (BHR). Seventy-nine asthmatic subjects (age 18-60 years) were recruited and 58 were atopic according to skin prick testing. The patients recorded asthma symptoms and peak flow measurements for 14 days. Lung function and BHR were measured by spirometry and histamine challenge. Serum eosinophil cationic protein (ECP) and blood eosinophils were assessed. Fiberoptic bronchoscopy was performed to obtain bronchial biopsies. Serum ECP was higher in the atopic group but eosinophil counts did not differ. There were no differences in inflammatory cells studied (activated eosinophils, T-lymphocytes, mast cells or macrophages) between nonatopic and atopic subjects. BM tenascin layer was significantly thicker in atopic compared with nonatopic subjects (7.6 vs 6.3 microm, P = 0.007). The thickness of tenascin correlated with eosinophil, T-lymphocyte, and macrophage counts, as well as with IL-4-positive cell counts and the correlation was seen only in atopic asthmatics. These findings suggest that inflammatory cells may have a regulatory role in tenascin expression in atopic asthma.

Randomised comparison of guided self management and traditional treatment of asthma over one year.

OBJECTIVE: To compare the efficacy of self management of asthma with traditional treatment. DESIGN: 12 month prospective randomised trial. SETTING: Outpatient clinics in Finland. SUBJECTS: 115 patients with mild to moderately severe asthma. INTERVENTIONS: Patient education and adjustment of anti-inflammatory therapy guided by peak flow measurements. MAIN OUTCOME MEASURES: Unscheduled admissions to hospital and outpatient visits, days off work, courses of antibiotics and prednisolone, lung function, and quality of life. RESULTS: The mean number of unscheduled visits to ambulatory care facilities (0.5 v 1.0), days off work (2.8 v 4.8), and courses of antibiotics (0.4 v 0.9) and prednisolone (0.4 v 1.0) per patient were lower and the quality of life score (16.6 v 8.4 at 12 months) higher in the self management group than in the traditionally treated group. In both groups admissions for asthma were rare. CONCLUSIONS: Self management reduces incidents caused by asthma and improves quality of life.

Acute respiratory infection, influenza vaccination and airway reactivity in asthma.

One of the characteristic features of asthma is its tendency to become exacerbated during acute infections of the respiratory tract. There are only a few studies on the relation between infection and the exacerbation of asthma in adult asthmatics. Epithelial damage and airway inflammation, leading to transient increase in bronchial reactivity, are believed to be some of the mechanisms whereby respiratory infections cause asthmatic exacerbations. A total of 150 patients with asthma were studied. Study I, which dealt with the effect of respiratory infections on the exacerbation of asthma, comprised 92 asthmatics. The patients evaluated the severity of their disease daily by recording a symptom score in a follow-up chart. Peak expiratory flow (PEF) was measured by the patients with a mini-Wright peak flow meter twice a day. In order to detect respiratory infections, the occurrence of fever, sore throat and symptoms of rhinitis were also recorded. The daily self-observation by the patients was augmented by monthly examinations by a physician and an interview by a nurse. In the course of study I, 253 episodes of exacerbation of asthma were observed in 67 of the 92 patients. 63 (25%) of these 253 exacerbations were found in association with symptomatic respiratory infection (SRI). The mean duration of exacerbations associated with SRI was 11.4 days, significantly longer than the mean duration of 8.1 days of the other exacerbations. A series of 39 patients were entered in study II concerning the effect of vaccination on airway conductance and respiratory symptoms, and 27 asthmatics were assigned to study III which dealt with bronchial reactivity after vaccination with killed influenza virus vaccine. Study IV (bronchial reactivity after influenza A infection) comprised 13 patients. 21 members of hospital staff, without a history of chest disease, participated in studies II and IV as healthy controls. The virus vaccines in studies II, III and IV were provided by the manufacturers. The subjects were seen by the investigators immediately before and 2, 3 and either 14 or 21 days after vaccination. The presence of respiratory symptoms was assessed at each visit. In order to detect changes in respiratory function after vaccination, Raw and ITGV were measured at each visit. The results were expressed as specific airway conductance (SGaw). In studies III and IV, airway reactivity to inhaled histamine before and after vaccination was also measured.(ABSTRACT TRUNCATED AT 400 WORDS)

Effect of respiratory infections on exacerbation of asthma in adult patients. A six-month follow-up.

The peak expiratory flow values and asthma symptom scores of 92 adults with extrinsic and intrinsic asthma were recorded daily from September 1981 to April 1982 in order to study the effects of symptomatic respiratory infections (SRI) on the course of asthma. During the follow-up, 253 exacerbations of asthma were observed in 67 patients. 68 subjects had 141 episodes of SRI. 63 of 253 exacerbations (25%) were found in association with SRI. The mean duration of the exacerbations associated with SRI was 11.4 days, significantly different (P less than 0.01) from the mean duration of 8.1 days recorded for the other exacerbations. The results confirm the high incidence of asthmatic exacerbations during respiratory infections and suggest that the recovery from an exacerbation is slower in association with infection.

Effects of killed and live attenuated influenza vaccine on symptoms and specific airway conductance in asthmatics and healthy subjects.

Killed and live influenza virus vaccines were given to asthmatics and healthy subjects to investigate symptoms and alterations in their respiratory performance after vaccination. Polyvalent killed influenza virus vaccine was given to 16 asthmatics and live attenuated influenza virus vaccine to 23 asthmatics and 21 healthy subjects. Fourteen of the 16 asthmatics vaccinated with the killed vaccine displayed a significant rise in serum antibody level as measured by a single radial haemolysis in gel (SRH test). 11 of the 23 asthmatics and 14 of the 21 healthy subjects vaccinated with the live attenuated vaccine displayed a significant rise in the SRH test. Among the subjects with no measurable initial antibodies and with a significant rise in the SRH test, one asthmatic vaccinated with the killed vaccine experienced symptoms of common cold with fever and dyspnoea 1 week after vaccination. Three asthmatics and four healthy subjects vaccinated with live attenuated vaccine experienced mild symptoms, mainly rhinorrhoea, cough and sore throat 2 to 3 days after vaccination. No alterations in specific airway conductance in asthmatics or in healthy subjects were observed. We conclude that both killed and live attenuated influenza virus vaccines are tolerated well by asthmatics and appear to be safe for asthma patients.

Bronchial reactivity following uncomplicated influenza A infection in healthy subjects and in asthmatic patients.

Live attenuated influenza A virus (R.I.T. 4050) was administered to 12 healthy subjects and to 13 asthmatics by the use of nasal drops alone. Serum antibody level to influenza A virus (Victoria 3/75) was measured before, 14 and 28 days after the virus inoculation by a single radial haemolysis in gel test (HIG-test). In order to study the effect of influenza infection upon bronchial reactivity, 1.6 per cent solution of histamine diphosphate was administered by the use of a DeVilbiss nebulizer No 40 for ten tidal breaths before, and 2, 3 and 14 days after the virus inoculation. Ten of the 12 healthy subjects displayed a significant rise in the HIG-test. No change was apparent in the bronchial reactivity to 10 breaths of 1.6% histamine in these healthy subjects. Out of seven of the asthmatics with low antibody levels, six displayed a significant increase between 14 and 28 days subsequent to inoculation. Six of the asthmatics had the initial HIG-levels so high before inoculation that infection could not occur, and they acted as controls. In six asthmatics with serological infection, the histamine-induced change in specific airway conductance increased significantly three days subsequent to the virus inoculation. The increased response to histamine was prevented by the prior administration of both salbutamol (Ventoline, Glaxo), and ipratropium bromide (Atrovent, Boehringer-Ingelheim). In six asthmatics with high HIG-titre before virus inoculation no change was apparent in the bronchial histamine reactivity subsequent to inoculation.

Unchanged bronchial reactivity after killed influenza virus vaccine in adult asthmatics.

Polyvalent killed influenza virus vaccine or saline was administered subcutaneously to 27 asthmatics to investigate the effect of influenza vaccine on respiratory function and on airway responsiveness to inhaled histamine. The patients were adults with mild to moderate asthma. Airway resistance (Raw) and intrathoracic gas volume (ITGV) were measured immediately before and 2, 3 and 21 days after vaccine or saline injection. Raw and ITGV values were used to calculate specific airway conductance (SGaw). Bronchial reactivity was expressed as the provocative dose of histamine diphosphate producing a decrease of 40% in SGaw (PD40). Fourteen (87%) of 16 asthmatics who received killed virus vaccine displayed a significant rise in serum antibody level as measured by single radial haemolysis in gel test. No significant alterations in mean Raw, ITGV and SGaw values were observed after viral vaccination. The median PD40 values for histamine also remained unchanged. However, an increased bronchial reactivity was observed in some patients after administration of virus vaccine or saline. Subclinical natural infection or allergen exposure cannot be excluded as possible causes of the increased airway reactivity in these patients. The side-effects of vaccination were minimal and no more harmful than those produced by saline injection. We conclude that the killed influenza virus vaccine used is effective in boosting serum antibody levels and is suitable for adult asthmatics when prophylactic immunisation is indicated.

Non-specific bronchial reactivity and ultrastructure of the airway epithelium in patients with sarcoidosis and allergic alveolitis.

There are subgroups of subjects showing increased bronchial responsiveness to histamine among patients with sarcoidosis and with allergic alveolitis (farmer's lung). In these subjects the airway reactivity is comparable with that usually encountered in patients with asthma and in many cases of bronchitis. In many of our patients with hyperreactive sarcoidosis and alveolitis, the increased reactivity was transient, lasting for one to two months during the acute stage of the disease. By electron microscopy we have shown that some of these patients have extensive epithelial damage which could increase epithelial permeability and uncover superficial afferent nerve endings. Indeed, superficial epithelial afferent nerves were found, and it is possible that irritation of these nerve endings causes enhanced bronchoconstriction via the vagal reflex. The transient nature of the hyperreactivity observed in patients with sarcoidosis and alveolitis may indicate that the epithelial changes are readily reversible. The recovery of the epithelium could perhaps be demonstrated by taking serial bronchial biopsies during the course of the disease. Because the electron microscopic specimens represented only a small area of bronchial epithelium, it is difficult to draw any conclusions as to a quantitative relationship between the amount of total epithelial damage and the degree of bronchial reactivity.

Damage of the airway epithelium and bronchial reactivity in patients with asthma.

We measured bronchial reactivity to inhaled histamine and prepared electron micrographs from bronchial biopsies from 8 asthmatic patients who never smoked (2 females, 6 males, 18 to 62 yr of age). Judging from their clinical histories and the need for medication and long-term follow-up of PEF values, 2 of them had mild asthma, 3 moderately severe, and 3 severe asthma. They had not experienced respiratory infections for at least 2 months prior to the study. The result, obtained from the cumulative dose-response curve, was expressed as the provocative dose (PD20) of histamine producing a 20% fall in forced expiratory volume in one second (FEV1). In 5 patients, the PD20 varied from 0.049 mg to 2.234 mg. In the sixth patient, only PD15 could be measured (5.187 mg). In 2 patients, the low initial FEV1 values, because of severe, partly irreversible obstruction, prevented the measurement of bronchial reactivity. Bronchial biopsies were taken with rigid tube bronchoscopy from 3 levels: (1) at the carina of the right upper lobe, (2) at the opening of the right middle or lower lobe, and (3) inside the right lower lobe. The specimens were prepared for both light and electron microscopy. Fresh biopsies showed that asthma patients can have epithelial destruction at all levels of the airways. The ciliated cells appeared to be the most destroyed cell type in the epithelium. Intraepithelial nerves and mast cells were seen. Epithelial destruction in the respiratory tract of the asthma patients with mild to severe bronchial hyperresponsiveness was prominent enough to expose the epithelial nerves for specific or nonspecific stimuli.

Effects of reducing or discontinuing inhaled budesonide in patients with mild asthma.

BACKGROUND: In a previous study, we found that two years of treatment with an inhaled corticosteroid, budesonide, was more effective than treatment with an inhaled beta 2-agonist, terbutaline, in patients with newly diagnosed, generally mild asthma. We continued this study for a third year to investigate whether the steroid dose could be reduced or discontinued and what effect crossover of patients from beta 2-agonist therapy to corticosteroid therapy would have. METHODS: A total of 37 patients treated for two years with inhaled budesonide at a dose of 1200 micrograms per day were randomly assigned to treatment with 400 micrograms of budesonide per day (19 patients) or placebo (18 patients) in a double-blind manner. Another 37 patients, who had received terbutaline during the first two years, were crossed over in an open-label manner to treatment with 1200 micrograms of budesonide per day during the third year. RESULTS: Treatment with the reduced dose of budesonide was sufficiently effective in 74 percent of the patients to maintain bronchial responsiveness at a level similar to that achieved with the higher dose. In contrast, improvement was maintained in only 33 percent of the patients receiving placebo, and the differences in pulmonary function between the steroid and placebo groups were significant (for forced expiratory volume in one second, P = 0.007; for bronchial responsiveness to histamine, P = 0.025; and for peak expiratory flow in the morning, P = 0.040). The condition of patients who were crossed over from terbutaline therapy to treatment with 1200 micrograms of budesonide per day improved. However, the degree of improvement in these patients appeared to be less than in those who were treated with budesonide at the beginning of the three-year study. CONCLUSIONS: Early treatment with inhaled budesonide results in long-lasting control of mild asthma. Maintenance therapy can usually be given at a reduced dose, but discontinuation of treatment is often accompanied by exacerbation of the disease.