Asymptomatic Bronchial Hyperresponsiveness Research Articles

FeNO for detecting lower airway involvement in patients with allergic rhinitis.

Allergic rhinitis (AR) is a risk factor for asthma development. The value of fractional exhaled nitric oxide (FeNO) in detecting lower airway involvement in the progress of AR-asthma march has not been evaluated. The aim of the present study was to investigate the value of FeNO in assessing lower airway inflammation and predicting bronchial hyperresponsiveness (BHR) in AR with or without asthma. FeNO and eosinophil count in induced sputum, and a methacholine bronchial provocation test were performed in 93 subjects, including: 45 AR patients (AR group); 20 patients with AR and asthma (AR with asthma group); and 28 normal controls (control group). The AR group was divided into two sub-groups: AR with asymptomatic BHR group and AR without BHR group. Correlation between FeNO and eosinophil count was assessed. Receiver operating characteristic (ROC) curve was applied to evaluate the predictive and diagnostic value of FeNO in detecting BHR. The values of FeNO in the AR and AR with asthma groups were higher [29.5 (22.0) ppb and 61.5 (33.0) ppb] compared with the normal control group (16.0 (10.0) ppb), where the values in brackets indicate the interquartile range of the values. The percentages of eosinophils in induced sputum were 2.43±3.56, 7.36±4.98 and 18.58±11.26% in the control, AR and AR with asthma groups, respectively. For the diagnosis of BHR, the area under the curve (AUC) was 0.910 (95%CI 0.836, 0.984), with the sensitivity and specificity 0.846 and 0.817 when the cut-off value takes 31.5 ppb. For diagnosis of asthma, the AUC was 0.873 (95%CI 0.753, 0.992) with sensitivity 0.857 and specificity 0.847 when taking the cut-off value to be 38.0 ppb. The value of FeNO was well correlated with eosinophil count in the sputum. The measurement of FeNO is an effective method in detecting lower airway involvement in AR developing to asthma.

Less small airway dysfunction in asymptomatic bronchial hyperresponsiveness than in asthma

Bronchial hyperresponsiveness (BHR) can be present in subjects without any respiratory symptoms. Little is known about the role of the small airways in asymptomatic subjects with BHR. We investigated small airway function assessed by spirometry and impulse oscillometry, as well as Borg dyspnea scores at baseline and during a methacholine provocation test in 15 subjects with asymptomatic BHR, 15 asthma patients, and 15 healthy controls. At baseline, small airway function (R5 -R20 and X5 ) was comparable between subjects with asymptomatic BHR and healthy controls, whereas asthma patients showed small airway dysfunction as reflected by higher R5 -R20 and lower X5 values. During methacholine provocation, small airway dysfunction was more severe in asthma patients than in subjects with asymptomatic BHR. Interestingly, a higher increase in small airway dysfunction during methacholine provocation was associated with a higher increase in Borg dyspnea scores in subjects with asymptomatic BHR, but not in asthma patients. Subjects with asymptomatic BHR may experience fewer symptoms in daily life because they have less small airway dysfunction.

PARTICLE CLEARANCE FROM THE AIRWAYS OF SUBJECTS WITH BRONCHIAL HYPERRESPONSIVENESS AND WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE

The aim of this study was to determine particle clearance and retention from non-alveolated airways of 14 healthy subjects (HS), 10 subjects with asymptomatic bronchial hyperresponsiveness (BHR), and 23 patients with chronic obstructive pulmonary disease (COPD). Monodisperse iron oxide particles of 1.6 μ m geometric and 3.5 μ m aerodynamic diameter labeled with 99mTc were delivered to the airways by inspiration of small aerosol boli into shallow volumetric lung depths. In each subject the penetration front depth of the aerosol boli was adjusted to 55% of the Fowler dead space of the airways. Particle deposition was enhanced by about 7 seconds of breath-holding after bolus inhalation. Retention of the particles in the airways during the 48 hours after their administration was assessed by measuring the decline in lung activity with a sensitive gamma counter. Particle deposition was not significantly different among study groups. Twenty-four hour particle retention in the airways was not different among study groups. Sixty-one percent of the particles were retained at 24 hours in HS, 58% in BHR, and 64% in COPD. However, subjects with BHR showed accelerated mucociliary clearance compared to healthy subjects, whereas clearance was retarded in COPD patients. This long-term particle retention in the airways has to be taken into account in aerosol toxicology risk assessment and aerosol therapy dose evaluation.

Comparison of Percentage Fall in FVC at the Provocative Concentration of Methacholine Causing a 20% Fall in FEV1 Between Patients With Asymptomatic Bronchial Hyperresponsiveness and Mild Asthma

A significant proportion of individuals who have no symptoms of asthma or other respiratory diseases show bronchial hyperresponsiveness (BHR). BHR is usually assessed by measuring the provocative concentration of methacholine causing a 20% fall in FEV(1) (PC(20)). The percentage fall in FVC at the PC(20) (DeltaFVC) has been suggested to reflect maximal airway response and to be a more useful index of disease severity in asthma than PC(20). The aim of this study was to investigate whether asymptomatic BHR would differ from symptomatic BHR with regard to DeltaFVC. Methacholine bronchial challenge tests were conducted in children with no past or current symptoms of asthma, allergic rhinitis, or other respiratory diseases, who were identified among siblings of children with asthma. Forty-three children with asymptomatic BHR (PC(20) < 16 mg/mL) were recruited, and 43 children with mild asthma who were matched for age, sex, and PC(20) were selected (mild asthma group). The DeltaFVC on methacholine concentration-response curves was retrospectively analyzed in the two groups. There were no differences in the frequency of atopy, blood eosinophil counts, serum IgE levels, and spirometric values between the asymptomatic BHR and mild asthma groups. Mean (+/- SD) DeltaFVC was significantly (p = 0.005) lower in the asymptomatic BHR group (14.5 +/- 3.6%) than in the mild asthma group (16.9 +/- 4.3%). Our results suggest that children with asymptomatic BHR have a lower level of maximal airway response than mild asthmatics with a similar degree of BHR. This may be a possible explanation for the lack of symptoms in subjects with asymptomatic BHR.

Prevalence of lower airway diseases in patients with chronic rhinosinusitis

Conclusion. There is high prevalence of lower airway diseases in patients with chronic rhinosinusitis and frequently co-existing lower airway diseases have not been diagnosed before. Objectives. To examine the prevalence of lower airway diseases in patients with chronic rhinosinusitis. Methods. Seventy-three consecutive patients with chronic rhinosinusitis were enrolled in this prospective study. With routine physical examination, spirometry and methacholine bronchial provocation test were performed and chest simple radiograph or chest computed tomography was taken. Results. Thirty patients (41.1%) had lower airway diseases. There were 8 patients with asthma, 5 with asymptomatic bronchial hyperresponsiveness, 11 with small airway disease, 2 with chronic obstructive pulmonary disease and 4 with bronchiectasis. Of these 30 patients, 21 patients (70.0%) were first diagnosed as having lower airway diseases in this study.

Oxidative stress in nonallergic nasal polyps associated with bronchial hyperresponsiveness1

Nasal polyposis (NP) is a chronic inflammatory disease of upper airway with unknown etiology. NP is frequently associated with asthma; the interaction between these comorbidities remains interesting. Oxidative stress has been implicated in the pathophysiology of NP and asthma. The aim of this study is to investigate the significance of oxidative stress in sinonasal microenvironments by evaluating its association with clinopathological parameters and its impacts on the pathogenesis of bronchial hyperresponsiveness (BHR) in NP. Polyp biopsy specimens were obtained from 20 nonallergic patients; control mucosas were obtained from 20 volunteers. The levels of free radicals in the tissues and in blood were determined by a sensitive chemiluminescence (CL) method. NP patients were substratified into three subgroups, NP without BHR, NP with asymptomatic BHR, and NP with BHR and asthma by the results of provocative testing. Four histological characteristics of NP, inflammatory cells, eosinophil infiltration, edema and fibrosis were estimated and applied to correlate with the tissue-CL. The mean CL level in polyp-tissues, but not in blood, was higher than in the control specimens. In NP patients, tissue-CL was associated with endoscopy score; high tissue-CL levels were positively correlated with the abundance of inflammatory cells and eosinophils. Tissue-CL and endoscopy score were associated with BHR/asthma phenotype. These results suggest an important role for oxidative stress in the pathophysiology of NP and a causal relation between oxidative stress and inflammatory cells, especially the eosinophils. Free radical levels in polyp-tissues associated with NP severity and with BHR/asthma phenotype in nonallergic NP patients.

Vocational and working career of asthmatic adolescents is only slightly affected

The aim of this study was to investigate whether teenagers and adolescents (10-22 years) with asthma or asymptomatic bronchial hyperresponsiveness, were more likely to experience vocational or professional career limitations in the future, as compared to non-asthmatic contemporaries. Data were used from a 14-year follow-up study in general practice, investigating the relationship between respiratory health in childhood and adolescence. At follow-up, the respiratory health status and information about career limitations were obtained. There were no statistical significant differences between asthmatics (n=52) and non-asthmatics (n=154) in the proportion currently employed subjects, or contract type. Most examined career limitations were infrequently reported in both groups, but seemed to occur slightly more frequent among asthmatics. Asthmatics seemed to have an increased risk for limitations in daily activities both attributable to their respiratory health (OR=2.6, 95% CI [1.0; 7.0]) and all-cause (OR=1.8, 95% CI [0.9; 3.3]), and for absence from work all-cause (OR=1.7, 95% CI [0.9; 3.3]). However, the differences were in most cases in the magnitude of only a few days per year. Neither lung function nor bronchial hyperresponsiveness did predict absence from work, or limitations in daily activities. Asthmatic young adults seem to experience somewhat more limitations in their vocational and professional careers. Nonetheless, the majority of the young asthmatics seem to be only slightly limited in their careers. In non-asthmatic young adults the presence of asymptomatic bronchial hyperresponsiveness does not seem to lead to career limitations.

Involvement of IL-9 in the bronchial phenotype of patients with nasal polyposis

Background Nasal polyposis (NP) is frequently associated with asthma. In this disease, asymptomatic bronchial hyperresponsiveness (BHR) is thought to precede the development of asthma. IL-9 and its receptor have been reported as candidate genes for asthma and to be associated with BHR. Objective The objective of this study was to assess the contribution of IL-9 to the pathogenesis of BHR in NP by comparing the expression of IL-9 and its receptor in bronchial biopsy specimens from three groups of patients with NP: NP without BHR, NP with asymptomatic BHR, and NP with BHR and asthma. Methods Bronchial biopsy specimens were examined in terms of cellular infiltration and in terms of expression of IL-9 protein and mRNA as well as of its receptor by using immunohistochemistry and in situ hybridization. Results Patients with NP with asthma as compared with the two other groups exhibited an increased bronchial infiltration of basophils, eosinophils, and T cells that correlated with the asthma score. The two groups of patients with NP with BHR showed an increased expression in IL-9 protein and mRNA as well as an increase in the expression of IL-9R mRNA at the epithelial level. These modifications were inversely correlated with the airway responsiveness to methacholine, producing a 20% fall in FEV 1. There was a close association between IL-9 + cells, IL-5 mRNA expression, and eosinophil infiltration that correlated with each other. Conclusions These results suggest an important role for IL-9 in the pathogenesis of BHR and a causal relation between IL-9 and the development of bronchial eosinophilia in asthma.

Bronchial interleukin-5 and eotaxin expression in nasal polyposis. Relationship with (a)symptomatic bronchial hyperresponsiveness.

An eosinophilic bronchial inflammation was previously demonstrated in patients with nasal polyposis (NP) and asymptomatic bronchial hyperresponsiveness (BHR) similar to that observed in asthmatic patients with NP, whereas patients with NP without BHR did not. The aim of the study was to investigate the contribution of interleukin 5 (IL-5) and eotaxin to the pathogenesis of BHR associated with NP. Eleven patients with NP without BHR (Group A), 8 patients with NP and asymptomatic BHR (Group B), and 9 patients with NP and asthma (Group C) were included. Bronchial biopsies were studied for IL-5 and eotaxin immunoreactivity and IL-5 mRNA expression. IL-5 levels were determined in bronchial lavage (BL). Compared with Groups A and B, Group C patients exhibited higher numbers of IL-5 protein(+) cells, IL-5 mRNA(+) cells, and eotaxin(+) cells in bronchial submucosa. Compared with Group A, Group B patients showed an increased number of IL-5 protein(+) cells, whereas the number of IL-5 mRNA(+) cells and eotaxin(+) cells was similar. IL-5 levels in BL were increased only in Group C. Our study provides evidence of IL-5 involvement in bronchial eosinophilia and in the pathogenesis of asymptomatic BHR associated with NP, whereas both IL-5 and eotaxin are involved in asthma associated with NP.

Increased frequency of asymptomatic bronchial hyperresponsiveness in nonasthmatic patients with food allergy.

Subclinical inflammation in gut mucosa has been demonstrated in bronchial asthma suggesting the whole mucosal system is involved in allergic diseases. The presence of subclinical bronchial involvement was assessed by nonspecific bronchial hyperresponsiveness (BHR) in nonasthmatic patients with food allergy (FA). BHR was studied in 35 patients with various manifestations of FA without food-induced asthma. Sixteen had a previous history of asthma and/or rhinitis to aeroallergens (group A), whereas 19 patients (group B) did not. BHR was defined by a provocative dose causing a 20% fall in forced expiratory volume in one second of (PC20) <8 mg.mL(-1) of methacholine. Asymptomatic BHR occurred frequently in nonasthmatic patients with FA (10 of 19, 53%); this did not significantly differ from patients with FA and a previous history of asthma and/or rhinitis to aeroallergens (13 of 16, 81%). PC20 was significantly lower in group A (1.84+/-0.53 mg.mL(-1)) than in group B (3.35+/-0.74 mg.mL(-1); p<0.05). The number of patients with positive skin tests to aeroallergens was similar between groups. Sequential evaluation, performed 1 year after initial evaluation, in 7 nonasthmatic patients (group B) demonstrated a similar level of BHR. The present study demonstrated that BHR is a frequent finding in nonasthmatic patients with food allergy which may be due, at least in part, to a subclinical inflammatory process in the bronchi.

Eosinophilic airway inflammation in nasal polyposis

Background: Asthma and asymptomatic bronchial hyperresponsiveness (BHR) are frequent findings in patients with nasal polyposis (NP). Objective: To elucidate mechanisms responsible for the development of BHR, we initiated a prospective study of bronchial inflammation as assessed by bronchial lavage (BL) and bronchial biopsy specimens in 35 patients with noninfectious NP. Methods: BHR was determined with methacholine provocation testing. Differential cell count, ECP, and histamine and tryptase levels were determined in BLs. Pathologic examination of bronchial biopsy specimens was performed with May-Grünwald-Giemsa stain to assess the number of lymphocytes. Indirect immunoenzymatic methods were used to identify eosinophils and mast cells. Results: Fourteen patients did not exhibit BHR (group A); 7 patients had asymptomatic BHR (group B); and 14 patients had BHR associated with asthma (group C). Patients of group C tended to have a longer duration of nasal symptoms than those of groups A and B. FEV 1 (L) was significantly lower in group C than in groups A and B. The number and percentage of eosinophils were significantly higher in BLs in groups B and C than in group A ( P < .05). Patients of groups B and C had a significantly higher number of eosinophils in bronchial submucosa (14.0 ± 1.5/mm 2 and 19.0 ± 1.9/mm 2 , respectively) than patients of group A (0.1 ± 0.1/mm 2 ). The number of lymphocytes was also higher in groups B and C than in group A. FEV 1 (percent of predicted value) and eosinophil number within bronchial mucosa correlated negatively. Conclusion: Our results demonstrate that patients with NP and asymptomatic BHR had an eosinophilic bronchial inflammation similar to that observed in asthmatic patients with NP, whereas patients with NP without BHR do not feature eosinophilic lower airways inflammation. The clinical relevance of these results requires careful follow-up to determine whether eosinophilic inflammation in these patients precedes and is responsible for the development of obvious asthma. (J Allergy Clin Immunol 1999;104:85-92.)

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

BACKGROUNDExercise 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...

The relationship of skin test positivity, high serum total IgE levels, and peripheral blood eosinophilia to symptomatic and asymptomatic airway hyperresponsiveness.

The relationships of skin test positivity, high serum total IgE levels (> 100 kU/L), and peripheral blood eosinophilia (>/= 275 cells/microliter) to symptomatic (either chronic cough, chronic phlegm, bronchitis episodes, dyspnea, wheeze, or asthma) and asymptomatic bronchial hyperresponsiveness (BHR) were studied cross-sectionally in 620 adult subjects who participated in the Vlagtwedde-Vlaardingen Study of 1989 and 1990. Eosinophilia (OR = 2.06, 95% CI = 1.28 to 3.31) and skin test positivity (OR = 1.66, 95% CI = 1.02 to 2.71) were both significantly associated with BHR independent of age, sex, smoking, and urban area of residence. High serum total IgE levels were not associated with BHR (OR = 1.29, 95% CI = 0.81 to 2.03). Separate analyses for symptomatic and asymptomatic subjects showed that the higher risk of BHR with skin test positivity applied only to symptomatic subjects (OR = 5.78, 95% CI = 1.63 to 20.51), independent of eosinophilia and high serum total IgE levels. The higher risk of BHR with eosinophilia was not different between symptomatic and asymptomatic subjects, and independent of skin test positivity and high serum total IgE levels. The results of this study show that, in the general adult population, eosinophilia is associated with BHR both in symptomatic and asymptomatic persons, whereas skin test positivity is associated with BHR only in symptomatic subjects.

Factors associated with increased bronchial responsiveness in adolescents and young adults: The importance of adjustment for prechallenge FEV 1

Asymptomatic increased bronchial responsiveness (BR) appears to be a major risk factor for later development of asthma, but risk factors for increased BR are not well established. The relationship of age, gender, house dust mite allergy, number of blood eosinophils, and FEV1 to the degree of nonspecific BR was studied in a population sample of 665 adolescents and young adults, aged 13 to 23 years. Case history, especially concerning smoking habits and respiratory symptoms, was obtained by interview and a self-administered questionnaire. Pulmonary function, number of blood eosinophils, BR to inhaled histamine, and skin test reactivity to house dust mites were measured with standard techniques. BR was analyzed as both a continuous variable (dose-response slope) and a categorical variable (cutoff: PC20 16 mg/ml). Increasing number of blood eosinophils, sensitivity to house dust mite, and former or current symptoms of asthma were associated with increasing levels of BR, independently of the level of FEV1. Adjustment for prechallenge FEV1 revealed a strong association between lower prechallenge FEV1 and increasing level of BR (p less than 0.0001), whereas the previously observed association between female gender and higher level of BR vanished. Repeating the analyses after exclusion of subjects with former or current asthma (n = 85) showed an unchanged relationship between house dust mite allergy and level of BR whether or not prechallenge FEV1 was included in the regression model, whereas gender only influenced the level of BR when no adjustment was made for prechallenge FEV1. On the contrary, the number of blood eosinophils was only significantly associated with BR after adjustment for baseline FEV1. Comparable findings were observed when patients with former or current symptoms of asthma and subjects with a prechallenge FEV1 less than 80% of predicted value (n = 46) were excluded from the analyses. This analysis suggests that adjustment for prechallenge level of FEV1 should be considered in studies concerned with risk factors for symptomatic and asymptomatic bronchial hyperresponsiveness.

Asymptomatic bronchial hyperreactivity and the development of asthma and other respiratory tract illnesses in children.

It is not clear whether asymptomatic bronchial hyperresponsiveness (BHR) in children is a risk factor for the subsequent development of asthma. A longitudinal study was conducted to determine the predictive value of BHR for the development of asthma in a primary care patient population. A standard free running asthma screening test (FRAST) was applied to 956 schoolchildren aged between 4 and 11 years in 1985. Peak expiratory flow (PEF) rates were measured before hard running for six minutes and following a three minute rest period. Children with a fall in PEF of more than 15% were labelled as having a positive FRAST. Clinical data from the patients' notes and from symptom questionnaires were compared with age and sex matched controls for children known to have asthma, and for those with a positive FRAST but no asthma (BHR group). Over the ensuing six years to 1991 further clinical data were gathered to compare the development of asthma and other diseases of the airways in both the BHR groups and their controls. Of the 956 children exercised in 1985, 60 who were not known to have asthma had an abnormal test. Of the 55 of these studied in 1991, 32 (58%) had developed asthma. The sensitivity of a positive FRAST for the development of asthma was 58%, its specificity 97%, and positive predictive value 72%. Hay fever, eczema, otitis media, "bronchitis," and family history of atopy also occurred more commonly in this group. Asymptomatic BHR, as shown by exercise challenge, can predict the development of clinical asthma. This study has also shown a relation between BHR, asthma, and other diseases of the airways, notably upper respiratory tract infection, "bronchitis," and otitis media.

Is Asymptomatic Bronchial Hyperresponsiveness an Indication of Potential Asthma?: A Two-Year Follow-up of Young Students with Bronchial Hyperresponsiveness

To determine the possibility that asymptomatic bronchial hyperresponsiveness (BHR) develops into symptomatic asthma, a two-year follow-up study was conducted in 81 students (48 male, 33 female; 11 to 17 years) who were found to have BHR in a 3,067 population survey (BHR group). Eighty-eight age-matched students (48 male, 40 female) with normal bronchial responsiveness served as control subjects. Daily symptom cards were recorded. Peak expiratory flow rate was measured for 24 h when symptoms occurred. Histamine inhalation tests were performed at the beginning of the study and at the end of the first and the second year. In the BHR group, 58 students remained bronchial hyperresponsive at the end of follow-up. Nine of 31 students with initially diagnosed bronchial asthma had their symptoms relieved entirely, but ten asymptomatic students developed asthma. The incidence of newly diagnosed asthma (12.5 percent in the BHR group or 20 percent in the asymptomatic BHR group) and the total percentage of diagnosed asthma (39.5 percent) in the BHR group were significantly higher than those (2.27 percent, 2.27 percent) in the control group. FVC and FEV1 showed no significant difference between two groups. PD20 FEV1 values in newly diagnosed asthmatics were significantly lower than those in asymptomatic students both at the beginning (3.05 +/- 1.56 mumol vs 6.14 +/- 1.60 mumol, p < 0.05) or the end (3.47 +/- 1.73 mumol vs 6.55 +/- 1.51 mumol, p < 0.05). The percentage of early respiratory illness was significantly higher in those with newly diagnosed asthma (80 percent) than in asymptomatic students (22.3 percent), but atopic index and the percentage of parental asthma showed no difference between two groups. In nine asthmatics whose symptoms were relieved entirely in the two-year follow-up, PD20 FEV1 was undetectable within the cumulative dose of 7.8 mumol of histamine in three students and rose from 4.58 +/- 1.85 mumol to 7.62 +/- 1.02 mumol in the remaining six. The higher the BHR, the more likely the students developed asthma. About 45 percent of asymptomatic students with PD20 < or = 3.2 mumol developed asthma in the following two years and 80 percent of them had a history of early respiratory illness, suggesting that they may have subclinical or potential asthma.

Prevalence and predictors of bronchial hyperresponsiveness in children aged 7-16 years.

To study the prevalence and possible predictors of bronchial responsiveness we examined a cross-section of 527 children aged 7-16 years from Copenhagen. The method used included an interview with the child and the parents, skin prick test with common allergens and se-IgE. Bronchial responsiveness was measured by a histamine inhalation test. We found that 79 (16%) of the children had bronchial hyperresponsiveness (BH), defined as a 20% fall in FEV1 with a provoking concentration of histamine (PC20) at 8 mg/ml or less. Atopic symptoms defined as asthma, rhinitis or eczema were significantly (P less than 0.001) correlated to BH both in prevalence and degree of BH. None of the children with urticaria had BH. The degree of bronchial responsiveness was also significantly influenced (P less than 0.001) by family disposition to atopy, whereas we found no correlation between BH and "passive" smoking, specific skin test in unselected children, or elevation of IgE in children without atopic symptoms. We conclude that BH is severest in children with asthma, independent of elevated IgE or positive skin prick test. Children with rhinitis, dermatitis, or asymptomatic BH have the same degree of BH; this differed from that in children with asthma.

Asymptomatic bronchial hyperresponsiveness in rhinitis

Methacholine inhalation tests are used to help in the diagnosis of asthma when spirometry is normal. However, the significance of increased methacholine responsiveness in patients with rhinitis and no symptoms of asthma is not known. One possibility is that it is a false positive result; another possibility is that it indicates subclinical asthma. We investigated these possibilities in 25 patients with rhinitis, whose attending physician had not made a diagnosis of asthma, by comparing responsiveness to methacholine expressed as the provocation concentration to cause a fall in FEV 1 of 20% (PC 20) with responsiveness to the natural stimulus of isocapnic hyperventilation of cold air and the diurnal variation of peak flow rate. Asthma was recognized objectively by variable airflow obstruction documented by one of the latter two tests. The PC 20 ranged between 4 and >64 mg/ml. In 10 patients the PC 20 was <16 mg1ml. Five of these patients had bronchoconstriction in response to hyperventilation, and a further two patients demonstrated increased variability of peak flow rates. Thus, in seven of 10 patients, increased bronchial responsiveness was confirmed by the use of two different methods, although they were asymptomatic, and the increased response to methacholine was not a false positive result. In the remaining three patients the PC 20 was borderline increased (8 to 16 mg/ml). The results indicate that methacholine responsiveness in the asthmatic range in patients with rhinitis is associated with variable airflow obstruction and subclinical asthma.