Effect of long-term treatment with salmeterol on asthma control: a double blind,randomised crossover study.

OBJECTIVES: To determine the effect of adding salmeterol 50 micrograms twice daily for six months to current treatment in subjects with asthma who control their inhaled corticosteroid dose according to a management plan. DESIGN: A double blind, randomised crossover study. SETTING: Nottingham. SUBJECTS: 101 subjects with mild or moderate asthma taking at least 200 micrograms twice daily of beclomethasone dipropionate or budesonide. INTERVENTIONS: Salmeterol 50 micrograms twice daily and placebo for six months each, with a one month washout. Subjects adjusted inhaled steroid dose according to guidelines. MAIN OUTCOME MEASURE: Reduction in inhaled steroid use, exacerbations of asthma, and use of oral steroids. RESULTS: Data were available for 87 subjects. When compared with placebo salmeterol treatment was associated with a 17% reduction in inhaled steroid use (95% confidence interval 12% to 22%) with no significant difference in the number of subjects who had an exacerbation (placebo 25%, salmeterol 16%) or use of oral steroids. For secondary end points salmeterol treatment was associated with higher morning and evening peak expiratory flow and forced expiratory volume in one second; a reduction in symptoms, bronchodilator use and airway responsiveness to methacholine; and no effect on serum potassium concentration, 24 hour heart rate, or the final forced expiratory volume in one second achieved during a salbutamol dose-response study. CONCLUSIONS: In subjects who adjusted their inhaled steroid treatment according to guidelines the addition of salmeterol 50 micrograms twice daily was associated with a reduction in inhaled steroid use and improved lung function and symptom control.     

Substitution of inhaled beclomethasone dipropionate for ingested prednisone in steroid-dependent asthmatics

The effect of inhaled beclomethasone dipropionate (dose, 400 μg daily) was investigated in 31 prednisone-dependent asthmatics. In a double-blind noncrossover study of 25 patients dependent on a daily prednisone dose of 17.5 mg or less, the dose of ingested prednisone was significantly diminished through the use of beclomethasone as compared with placebo (P < 0.001). In a subsequent single-blind study of the 12 patients who had received placebo, a similar decrease in prednisone dose was possible when these patients received beclomethasone. In all 25 patients the effect of beclomethasone was maintained for 2 years; 9 came to require less beclomethasone and 1 required more. In an additional single-blind study of six patients with severe asthma, dependent on prednisone in a dose of 20 to 25 mg/d, the response to beclomethasone was more variable and less significant (P < 0.01). However, at 2 years there was no significant benefit (P > 0.05) and there were two treatment failures.In patients in whom reduction of dose or discontinuation of prednisone was possible plasma cortisol values before and after corticotropin administration increased significantly (P < 0.001). Prednisone reduction was associated with the appearance of mild musculoskeletal steroid-withdrawal symptoms of short duration in 15 patients, and recurrence of symptoms of rhinitis in 15 patients. Side effects of beclomethasone included episodes of hoarseness in 6 and easily treated oropharyngeal Candida albicans infection in 14.     

Community study of role of viral infections in exacerbations of asthma in 9-11 year old children.

OBJECTIVE--To study the association between upper and lower respiratory viral infections and acute exacerbations of asthma in schoolchildren in the community. DESIGN--Community based 13 month longitudinal study using diary card respiratory symptom and peak expiratory flow monitoring to allow early sampling for viruses. SUBJECTS--108 Children aged 9-11 years who had reported wheeze or cough, or both, in a questionnaire. SETTING--Southampton and surrounding community. MAIN OUTCOME MEASURES--Upper and lower respiratory viral infections detected by polymerase chain reaction or conventional methods, reported exacerbations of asthma, computer identified episodes of respiratory tract symptoms or peak flow reductions. RESULTS--Viruses were detected in 80% of reported episodes of reduced peak expiratory flow, 80% of reported episodes of wheeze, and in 85% of reported episodes of upper respiratory symptoms, cough, wheeze, and a fall in peak expiratory flow. The median duration of reported falls in peak expiratory flow was 14 days, and the median maximum fall in peak expiratory flow was 81 l/min. The most commonly identified virus type was rhinovirus. CONCLUSIONS--This study supports the hypothesis that upper respiratory viral infections are associated with 80-85% of asthma exacerbations in school age children.     

Study of 8-year-old children with a history of respiratory syncytial virus bronchiolitis in infancy.

Thirty-five children known to have had respiratory syncytial virus bronchiolitis in infancy were examined at the age of 8 and their respiratory function tested. The results were compared with those in 35 controls matched for age, sex, and social class. Although 18 of the children who had had bronchiolitis in infancy had experienced subsequent episodes of wheezing, these were neither severe nor frequent in most cases and had apparently ceased by the age of 8. Nevertheless, the mean exercise bronchial lability of the children who had had bronchiolitis was significantly higher than that of the control children and the mean peak expiratory flow rate at rest significantly lower. Atopy, assessed by family and personal history alone, did not seem to be related to either bronchiolitis or wheezing episodes after bronchiolitis. The parents of the children who had had bronchiolitis smoked significantly more cigarettes during the infant''s first year of life than those of the control children. The results suggest that bronchiolitis and childhood asthma are not closely related. Bronchial hyperreactivity might be inherited independently of atopy, but environmental factors seem the most likely link between severe respiratory infection in infancy and chronic or recurrent respiratory illness in adult life.     

肺炎支原体肺炎伴喘息儿童血清25(OH)D_3、Th17/Treg表达水平与肺功能的关系

目的:探讨肺炎支原体肺炎伴喘息儿童血清25羟基维生素D3[25(OH)D_3]、辅助性17细胞/调节性T细胞(Th17/Treg)表达水平与肺功能的关系。方法:将新疆医科大学第五附属医院收治的肺炎支原体肺炎伴喘息患儿26例作为肺炎伴喘息组,肺炎支原体肺炎不伴有喘息患儿54例作为肺炎不伴喘息组,另选取健康儿童30例作为对照组,比较各组血清25(OH)D_3、白细胞介素(IL)-10、IL-17、Th17细胞及Treg细胞占CD4+T细胞比例及肺功能,并分析其相关性。结果:肺炎伴喘息组血清25(OH)D_3、IL-10、Treg细胞占CD4+T细胞比例低于肺炎不伴喘息组、对照组,Th17细胞占CD4+T细胞比例、Th17/Treg、IL-17高于肺炎不伴喘息组、对照组(P0.05)。各组第一秒最大呼气量占用力肺活量百分比(FEV1/FVC)比较差异无统计学意义(P0.05),肺炎伴喘息组FEV1占预计值百分比(FEV1%pred)、峰值呼气流量(PEF)低于肺炎不伴喘息组、对照组(P0.05),肺炎不伴喘息组与对照组FEV1%pred、PEF比较无统计学意义(P0.05)。肺炎伴喘息组患儿血清25 (OH)D_3与Th17/Treg、IL-17呈负相关(P0.05),与IL-10、FEV1%pred、PEF呈正相关(P0.05),血清Th17/Treg与IL-10、FEV1%pred、PEF呈负相关(P0.05),与IL-17呈正相关(P0.05)。结论:肺炎支原体肺炎伴喘息儿童血清25(OH)D_3、Th17/Treg表达水平异常,肺功能下降,且25(OH)D_3、Th17/Treg表达水平与肺功能相关。     

Effects of prematurity and intrauterine growth on respiratory health and lung function in childhood.

OBJECTIVE--To determine whether birth weight and gestational age are associated with respiratory illness and lung function in children aged 5-11 years. DESIGN--Cross sectional analysis of parent reported birth weight, gestational age, and respiratory symptoms; parental smoking and social conditions; forced vital capacity (FVC), forced expiratory volume in one second (FEV1), forced expiratory rates between 25% and 75% and 75% and 85% (FEF25-75 and FEF75-85), and height. SETTING--Primary schools in England and Scotland in 1990. SUBJECTS--5573 children aged 5-11 (63.3% of eligible children) had respiratory symptoms analysed and 2036 children (67.1% of eligible children) had lung function measured. MAIN OUTCOME MEASURES--Symptoms of asthma, bronchitis, occasional and frequent wheeze, cough first thing in the morning, and cough at any other time and lung function. RESULTS--Birth weight adjusted for gestational age was significantly associated with all lung function measurements, except FEF25-75. The association remained for FVC (b = 0.475, 95% confidence interval 0.181 to 0.769) and FEV1 (b = 0.502, 0.204 to 0.800) after adjustment for gestational age, parental smoking, and social factors. FEF75-85 was the only lung function related to gestational age. Respiratory symptoms, especially wheeze most days (adjusted odds ratio 0.9, 0.84 to 0.97) were significantly associated with prematurity. Every extra week of gestation reduced the risk of severe wheeze by about 10%. CONCLUSIONS--Lung function is affected mainly by intrauterine environment while respiratory illness, especially wheezing, in childhood is related to prematurity.     

Bronchoconstrictor and antibronchoconstrictor properties of inhaled prostacyclin in asthma

Prostacyclin (PGI2) is generated in appreciable amounts during allergic reactions in human lung tissue. To define its activity on human airways we have studied the effects of doubling concentrations of inhaled PGI2 and its hydrolysis product 6-oxoprostaglandin F1 alpha (6-oxo-PGF1 alpha) on specific airway conductance (sGaw), maximum expiratory flow at 30% vital capacity (Vmax30), forced expiratory volume in 1 s (FEV1), and static lung volumes in subjects with mild allergic asthma. In a second study the effect of inhaled PGI2 on bronchoconstriction provoked by increasing concentrations of inhaled prostaglandin (PG) D2 and methacholine was observed. Inhalation of PGI2 up to a concentration of 500 micrograms/ml had no significant effect on sGaw but produced a concentration-related decrease in FEV1 and Vmax30 in all subjects. In two of four subjects inhalation of PGI2 also increased residual volume and decreased vital capacity but had no effect on total lung capacity. PGI2, but not 6-oxo-PGF1 alpha, protected against bronchoconstriction provoked by either PGD2 or methacholine whether airway caliber was measured as sGaw, FEV1, or Vmax30. The apparent disparity between the bronchoconstrictor and antibronchoconstrictor effects of PGI2 might be explained by its potent vasodilator effect in causing airway narrowing through mucosal engorgement and reducing the spasmogenic effects of other inhaled mediators by increasing their clearance from the airways.     

Effect of normobaric hyperoxia on airways of normal subjects

Airway responsiveness to inhaled cholinergic agonist during the early stage of pulmonary O2 toxicity was examined to determine whether normobaric hyperoxia alters airway function. Eight healthy nonsmoking males with moderate base-line methacholine responsiveness breathed normobaric O2 (greater than or equal to 95%) over 12 h and on another occasion breathed air in an identical protocol. Vital capacity, expiratory flow, airway responsiveness to methacholine, and respiratory symptoms were measured at 0, 4, 8, and 12 h while subjects breathed O2 and 12 h afterwards. After 12 h, forced vital capacity was significantly decreased with O2 breathing but not with air breathing. At 4, 8, or 12 h of exposure and 12 h after exposure, there was no difference in methacholine sensitivity or reactivity between O2 and air-exposure trials. The earliest manifestations of pulmonary normobaric O2 toxicity in normal adults include diminished vital capacity and the onset of respiratory symptoms, but early O2 toxicity does not produce altered responsiveness to inhaled methacholine.     

Beclomethasone dipropionate dry-powder inhalation compared with conventional aerosol in chronic asthma.

In a double-blind study beclomethasone dipropionate inhaled as a dry powder in doses of 100 microgram four times daily and 150 microgram four times daily was compared with the conventional aerosol dose of 100 microgram four times daily in 20 outpatients with chronic asthma. Each of the three treatments was given for four weeks. The dry powder in a dose of 150 microgram four times daily had advantages over the other two treatments in terms of FEV1 and the number of exacerbations of asthma during the study. There were no adverse reactions to inhaling dry-powder beclomethasone. It was concluded that this new way of administering the drug was effective in chronic asthma, and should allow most patients with chronic asthma who cannot use conventional pressurised aerosols efficiently to benefit from inhaled corticosteroid treatment.     

Comparison of Beclomethasone Dipropionate Aerosol and Prednisolone in Reversible Airways Obstruction

This paper describes a double-bond crossover trial of prednisolone and beclomethasone dipropionate aerosol in 38 steroid-dependent patients with reversible diffuse airways obstruction. Altogether there was no difference in the patient''s preference of the two treatment groups or in the number of times they used their bronchodilator aerosol, or in the forced expiratory volume in one second, vital capacity, or peak expiratory flow rate in the two treatment groups. The plasma cortisol levels when the patients were on the aerosol were much higher than when they were on prednisolone. The use of inhaled aerosol steroids seems to be preferable as it eliminates the usual complications of oral steroid therapy.     

Lower Respiratory Tract Infections Associated with Rhinovirus during Infancy and Increased Risk of Wheezing during Childhood. A Cohort Study

Background and Objectives

Although association between respiratory syncytial virus infection and later asthma development has been established, little is known about the role of other respiratory viruses. Rhinovirus was considered a mild pathogen of the upper respiratory tract but current evidence suggests that rhinovirus is highly prevalent among children with lower respiratory tract infections (LRTI). The aim of the study was to evaluate whether LRTI hospitalization associated with rhinovirus during infancy was associated with an increased risk of wheezing – a proxy measure of asthma – during childhood.

Methods

During a 12 months period, all infants <1 year admitted to Manhiça District Hospital with symptoms of LRTI who survived the LRTI episode, were enrolled in the study cohort. Nasopharyngeal aspirates were collected on admission for viral determination and study infants were classified according to presence or not of rhinovirus. The study cohort was passively followed-up at the Manhiça District Hospital for up to 4 years and 9 months to evaluate the association between LRTI associated with rhinovirus in infancy and wheezing during childhood.

Findings and Conclusions

A total of 220 infants entered the cohort; 25% of them had rhinovirus detected during the LRTI episode as opposed to 75% who tested negative for rhinovirus. After adjusting for sex and age and HIV infection at recruitment, infants hospitalized with LRTI associated with rhinovirus had higher incidence of subsequent visits with wheezing within the year following hospitalization [Rate ratio=1.68, (95% confidence interval=1.02-2.75); Wald test p-value = 0.039]. No evidence of increased incidence rate of visits with wheezing was observed for the remaining follow-up period. Our data suggest a short term increased risk of wheezing after an initial episode of LRTI with RV.     

Controlled trial of budesonide given by the nebuhaler in preschool children with asthma.

OBJECTIVE--To determine whether the inhaled corticosteroid budesonide, given by a Nebuhaler spacing device, was effective in prophylaxis of asthma in preschool children. DESIGN--Double blind, placebo controlled, random order crossover trial with two week practice run in period. SETTING--Outpatient clinic referrals in secondary referral centre. PATIENTS--39 children aged 2-6 years selected for the following: able to use Nebuhaler; parents able to complete record card; poorly controlled asthma (defined); not already on systemic or inhaled steroids. Eleven withdrew for various reasons not connected with intolerance to budesonide. Age, sex, other atopies, and symptoms during run in period were similar in the 28 children who completed the trial and in the 11 who withdrew. INTERVENTIONS--Budesonide 200 micrograms or placebo (both one puff) given twice daily during 6-week treatment or control periods, using Nebuhaler after prior training. Three week "washout" at crossover. Compliance monitored by weighing canisters. Patients withdrawn if their acute attacks required treatment with systemic steroids. END POINT--Control of asthma. MEASUREMENTS AND MAIN RESULTS--Peak expiratory flow rate measured twice daily where cooperation allowed. Diary of symptoms and concomitant drug use kept daily. Results showed mean peak flow significantly higher (12% in mornings, 14% in evenings) in second three weeks of intervention compared with control period (95% confidence intervals 6.3-17.3% and 7.2-21.0%). Supplementary bronchodilator drugs reduced by 50% during intervention periods. CONCLUSIONS--Budesonide given by Nebuhaler is effective prophylaxis for preschool children with frequent asthma.     

Effect of homoeopathic medicines on daily burden of symptoms in children with recurrent upper respiratory tract infections.

OBJECTIVE--To investigate the intrinsic effects of individually prescribed homoeopathic medicines. DESIGN--Randomised double blind placebo controlled study. SETTING--Paediatric outpatient department of university hospital. PATIENTS--175 children with frequently recurring upper respiratory tract infections. Of the 170 children evaluable, 86 were randomised to homoeopathic medicines (47 boys, 39 girls; median age at start 4.2 years; median number of episodes in past year 4) and 84 to placebo (43 boys, 41 girls; median age at start 3.6 years; median number of episodes in past year 4). MAIN OUTCOME MEASURES--Mean score for daily symptoms, number of antibiotic courses, and number of adenoidectomies and tonsillectomies over one year of follow up. RESULTS--The mean daily symptom score was 2.61 in the placebo group and 2.21 in the treatment group (difference 0.41; 95% confidence interval -0.02 to 0.83). In both groups the use of antibiotics was greatly reduced compared with that in the year before entering the trial (from 73 to 33 in the treatment group and from 69 to 43 in the placebo group). The proportion of children in the treatment group having adenoidectomies was lower in the treatment group (16%, 8/50) than in the placebo group (21%, 9/42). The proportion having tonsillectomies was the same in both groups (5%). CONCLUSION--Individually prescribed homoeopathic medicines seem to add little to careful counselling of children with recurrent upper respiratory tract infection in reducing the daily burden of symptoms, use of antibiotics, and need for adenoidectomy and tonsillectomy.     

Relation of birth weight and childhood respiratory infection to adult lung function and death from chronic obstructive airways disease.

OBJECTIVE--To examine whether birth weight, infant weight, and childhood respiratory infection are associated with adult lung function and death from chronic obstructive airways disease. DESIGN--Follow up study of men born during 1911-30 whose birth weights, weights at 1 year, and childhood illnesses were recorded at the time by health visitors. SETTING--Hertfordshire, England. SUBJECTS--5718 men born in the county during 1911-30 and a subgroup of 825 men born in the county during 1920-30 and still living there. MAIN OUTCOME MEASURES--Death from chronic obstructive airways disease, mean forced expiratory volume in one second (FEV1) and forced vital capacity (FVC), and respiratory symptoms. RESULTS--55 men died of chronic obstructive airways disease. Death rates fell with increasing birth weight and weight at 1 year. Mean FEV1 at age 59 to 70 years, adjusted for height and age, rose by 0.06 litre (95% confidence interval 0.02 to 0.09) with each pound (450 g) increase in birth weight, independently of smoking habit and social class. Bronchitis or pneumonia in infancy was associated with a 0.17 litre (0.02 to 0.32) reduction in adult FEV1 and with an increased odds ratio of wheezing and persistent sputum production in adult life independently of birth weight, smoking habit, and social class. Whooping cough in infancy was associated with a 0.22 litre (0.02 to 0.42) reduction in adult FEV1. CONCLUSIONS--Lower birth weight was associated with worse adult lung function. Intrauterine influences which retard fetal weight gain may irrecoverably constrain the growth of the airways. Bronchitis, pneumonia, or whooping cough in infancy further reduced adult lung function. They also retarded infant weight gain. Consistent with this, death from chronic obstructive airways disease in adult life was associated with lower birth weight and weight at 1 year. Promoting lung growth in fetuses and infants and reducing the incidence of lower respiratory tract infection in infancy may reduce the incidence of chronic obstructive airways disease in the next generation.     

Prevention and treatment of respiratory syncytial virus bronchiolitis and postbronchiolitic wheezing

Respiratory syncytial virus (RSV) is the primary cause of hospitalization for acute respiratory tract illness in general and specifically for bronchiolitis in young children. The link between RSV bronchiolitis and reactive airway disease is not completely understood, even though RSV bronchiolitis is frequently followed by recurrent episodes of wheezing. Therapy with ribavirin does not appear to significantly reduce long-term respiratory outcome of RSV lower respiratory tract infection, and corticosteroid or bronchodilator therapy may possibly improve outcomes only on a short-term basis. No vaccine against RSV is yet available. It is not known whether prophylaxis with RSV intravenous immune globulin or palivizumab can reduce postbronchiolitic wheezing.     

An epidemiological study of respiratory syncytial virus associated hospitalizations in Denmark

Respiratory syncytial virus (RSV) is the primary cause of hospitalization for acute respiratory tract illness in general and specifically for bronchiolitis in young children. The link between RSV bronchiolitis and reactive airway disease is not completely understood, even though RSV bronchiolitis is frequently followed by recurrent episodes of wheezing. Therapy with ribavirin does not appear to significantly reduce long-term respiratory outcome of RSV lower respiratory tract infection, and corticosteroid or bronchodilator therapy may possibly improve outcomes only on a short-term basis. No vaccine against RSV is yet available. It is not known whether prophylaxis with RSV intravenous immune globulin or palivizumab can reduce postbronchiolitic wheezing.     

Effect of inhalation therapy with beclomethasone dipropionate on unspecific bronchial hyperreactivity in patients with asthma]

An effect of beclomethasone dipropionate (Beclocort-Polfa) was investigated in the group of 24 patients with atopic and non-atopic bronchial asthma who have shown unspecific bronchial hyperreactivity to histamine during the periods of remission. The drug was administered in the form of aerosol in a daily dose of 1.0 mg for 4 weeks. Provocative histamine dose was established with Bronchoscreen device (Jaeger) thrice:prior to the treatment, after 1 week of placebo therapy, and after 1 month of beclomethasone administration. Statistically significant increase in histamine dose for provocation of bronchospasm (p < 0.01) being nearly twice higher than the baseline value has been noted in patients treated with beclomethasone dipropionate aerosol. It advocates such a treatment in unspecific bronchial hyperreactivity independently of the type of the bronchial asthma.     

肺炎支原体肺炎患儿外周血白介素的表达与肺功能变化的相关性

目的:探讨肺炎支原体(MPP)肺炎患儿外周血中IL-10、IL-17的表达水平与肺功能变化的相关性。方法:选取70例肺炎支原体肺炎患儿为研究对象,以是否有哮鸣音分为喘息组和非喘息组,以30例健康儿童为对照组,空腹采血5ml,分离血清,ELISA检测血清中IL-10、IL-17的表达水平,肺功能检测仪检测受检者的第一秒用力呼气容积(PEV1),最大呼气流量(PEF),用力肺活量(FEV1/FVC)。结果:喘息组中IL-10的表达水平与对照组相比差异显著(P0.05),喘息组中IL-10的表达水平与非喘息组相比差异显著(P0.05),喘息组中IL-17的表达水平与对照组相比差异显著(P0.05),喘息组中IL-17的表达水平与非喘息组相比差异显著(P0.05)。喘息组和非喘息组中IL-10水平均低于对照组,喘息组和非喘息组中IL-17水平均高于于对照组。非喘息组较喘息组PEV1、PEF、PVE1/FVC值高,差异显著(P0.05)。肺炎支原体肺炎患儿血清中的IL-10的水平与PEV1、PEF、PVE1/FVC呈正相关,肺炎支原体肺炎患儿血清中的IL-17的水平与PEV1、PEF、PVE1/FVC呈负相关。结论:肺炎支原体肺炎患儿血清中IL-10、IL-17的表达水平与肺功能密切相关。     

体描箱在评估婴幼儿急性下呼吸道感染肺功能改变中的价值

摘要 目的：探讨体描箱评估婴幼儿急性下呼吸道感染（ALRTI）肺功能改变的价值。方法：收集2020年10月至2021年6月于我院收治的76例ALRTI婴幼儿,根据感染部位分为肺炎组与支气管炎组,根据有无喘息症状分为喘息性组和非喘息性组,采用体描箱测量潮气呼吸参数、体描箱特有指标,分别进行两组间肺功能比较,分析各参数之间相关性,采用受试者工作特征（ROC）曲线评估体描特有指标在婴幼儿ALRTI中的诊断价值。结果：肺炎组与支气管炎组比较,各潮气呼吸参数及功能残气量（FRCp）无明显差异（P>0.05）,而有效气道阻力（Reff）和特殊有效气道阻力（sReff）有明显差异（P<0.05）;对于喘息性组与非喘息性组,sReff有显著差异（P<0.05）;76例ALRTI患儿潮气量（VT）与每公斤体质量潮气量（VT/kg）呈正相关（P<0.05）,VT、VT/kg均与呼吸频率（RR）、达峰时间比（TPTEF/TE）呈负相关（P<0.05）, TPTEF/TE与达峰容积比（VPTEF/VE）呈正相关（P<0.05）,sReff与FRCp、Reff均呈正相关（P<0.05）;ROC曲线显示,sReff在诊断肺炎与支气管炎、喘息性和非喘息性的价值最高,ROC曲线下面积分别为0.704、0.688。结论：对于ALRTI患儿,体描箱参数Reff和sReff可帮助判断感染部位,且sReff可直接反映小气道阻塞情况,诊断价值较高,值得临床推广应用。     

Airway reactivity to methacholine in nonatopic asymptomatic adults

We studied 50 nonsmoking volunteers, ages 18-35 yr, with no past or present history or physical examination findings of asthma, rhinitis, allergic disease, or recent respiratory infections, to evaluate the usefulness of the methacholine bronchoprovocation challenge (MBPC) as a screening test for asthma. All were skin-test-negative to 29 aeroallergens and had base-line pulmonary function values greater than 80% predicted. Fourteen (28%) subjects had a drop in forced expiratory volume in 1 s (FEV1) of 20% or greater at a provocative dose (PD20FEV1) less than or equal to 225 breath units. Moreover, when these subjects were compared with 21 asymptomatic allergic asthmatics, there was significant overlap between the two groups in concentration of methacholine causing this decline in FEV1. A positive MBPC at methacholine concentrations less than or equal to 5 mg/ml was not diagnostic of asthma, and a negative MBPC at methacholine concentrations greater than or equal to 10 mg/ml did not rule out asthma. These data strongly suggest that MBPC should not be used as the sole factor for the diagnosis of clinically significant asthma. A positive MBPC is one indication of the presence of airway hyperresponsiveness and thus is only one of many factors that must be considered in the diagnosis of asthma.