Methacholine Bronchoprovocation Test Research Articles

Airway Hyperresponsiveness, but Not Bronchoalveolar Inflammatory Cytokines Profiles, Is Modified at the Subclinical Onset of Severe Equine Asthma.

Airway hyperresponsiveness (AHR) and inflammation are both observed in human and equine asthma. The aim of this study was to assess the timeline and relationship of both features at the subclinical onset of severe equine asthma (SEA). First, the repeatability of the pulmonary function test (PFT) using impulse oscillometry system, and the methacholine bronchoprovocation test (BPT) were assessed at a 1-day interval on six SEA horses in clinical remission and six control horses. Then, clinical and ancillary tests were performed before and after a 1-week low-dust environmental challenge, including weighted clinical score, respiratory endoscopy, bronchoalveolar fluid cytology, PFT, and BPT. Both PFT and BPT showed acceptable repeatability. No test allowed SEA horses in clinical remission to be distinguished from control, unlike in human patients. Because of the low-dust environment, no significant difference was observed in the results of clinical and conventional ancillary examinations after the challenge. However, SEA horses showed increased AHR after the environmental challenge. At that stage, no signs of inflammation or changes in pro-inflammatory cytokines profiles (quantification and gene expression) were observed, suggesting AHR is present at an earlier stage of equine asthma than airway inflammation. This feature indicates SEA could present in a different disease pathway than neutrophilic human asthma.

Diagnostic approach to lower airway dysfunction in athletes: a systematic review and meta-analysis by a subgroup of the IOC consensus on ‘acute respiratory illness in the athlete’

ObjectivesTo compare the performance of various diagnostic bronchoprovocation tests (BPT) in the assessment of lower airway dysfunction (LAD) in athletes and inform best clinical practice.DesignSystematic review with sensitivity and specificity...

Aerosol Generation and Mitigation During Methacholine Bronchoprovocation Testing: Infection Control Implications in the Era of COVID-19.

Methacholine bronchoprovocation or challenge testing (MCT) is commonly performed to assess airway hyper-responsiveness in the setting of suspected asthma. Nebulization is an aerosol-generating procedure, but little is known about the risks of MCT in the context of the ongoing coronavirus disease 2019 (COVID-19) pandemic. We aimed to quantify and characterize aerosol generation during MCT by using different delivery methods and to assess the impact of adding a viral filter. Seven healthy subjects performed simulated MCT in a near particle-free laboratory space with 4 different nebulizers and with a dosimeter. Two devices continuously sampled the ambient air during the procedure, which detected ultrafine particles, from 0.02-1 μm, and particles of sizes 0.3, 0.5, 1.0, 2.0, 5.0, and 10 µm, respectively. Particle generation was compared among all the devices, with and without viral filter placement. Ultrafine-particle generation during simulated MCT was significant across all the devices. Ultrafine-particle (0.02-1 μm) concentrations decreased 77%-91% with the addition of a viral filter and varied significantly between unfiltered (P < .001) and filtered devices (P < .001). Ultrafine-particle generation was lowest when using the dosimeter with filtered Hudson nebulizer (1,258 ± 1,644 particle/mL). Ultrafine-particle concentrations with the filtered nebulizer devices using a compressor were higher than particle concentrations detected when using the dosimeter: Monaghan (3,472 ± 1,794 particles/mL), PARI (4,403 ± 2,948), Hudson (6,320 ± 1,787) and AirLife (9,523 ± 5,098). The high particle concentrations generated during MCT pose significant infection control concerns during the COVID-19 pandemic. Particle generation during MCT was significantly reduced by using breath-actuated delivery and a viral filter, which offers an effective mitigation strategy.

The Arg16Gly Polymorphism in the B2-Adrenergic Receptor Gene is Associated with Bronchial Hyperresponsiveness and Allergic Rhinitis in the Bulgarian Population

ABSTRACTBronchial Hyperresponsiveness (BHR) is a risk factor for asthma but it can be observed in allergic rhinitis (AR) and healthy subjects, too. The mechanisms of genetic susceptibility to BHR are unknown. In general, it is thought to result from both genetic and environmental factors. Some studies have demonstrated that nonspecific airway hyperresponsiveness is associated with a specific β2-adrenergic receptor (β2-AR) genotype in asymptomatic healthy subjects. The present study was performed to determine the impact of single nucleotide polymorphism (SNP) on allergic rhinitis patients with evidence for bronchial hyperresponsiveness. One hundred allergic rhinitis patients analyzed for BHR and forty healthy controls were genotyped for polymorphism of the β2-AR gene. Nonspecific airway hyperesponsiveness was measured using the methacholine bronchoprovocation (BPT) test. Polymerase chain reaction (PCR) was used to identify (Arg16/Gly) polymorphism at codon 16 in the β2-AR gene. It was observed that allergic rhinitis patients who are homozygous for the Gly16 allele are more responsive to methacholine than patients who carry the Arg16 allele.

Relationships between Fraction of Nitric Oxide, Airway Hyperresponsiveness, Blood Eoshinophil Counts and Serum Eosinophil Cationic Protein in Asthmatic Children

Purpose:The measurement of fraction of nitric oxide (FeNO) is a noticeable tool that reflects airway inflammation in asthmatic patients. We wanted to find out the relationship between pulmonary function, bronchial hyperresponsiveness (AHR), blood eosinophilic inflammatory markers and FeNO level before and after methacholine bronchoprovocation test in asthmatic patients. Methods:Fifty-five children, who visited the Allergy Clinic of Korea University Anam Hospital from March 2011 to February 2012, due to asthmatic symptoms, such as history of episodic wheezing or dyspnea during the previous year and resolved after using bronchodilators, were enrolled. We performed the baseline pulmonary function and methacholine bronchoprovocation test in the enrolled patients. Blood eosinophil counts and blood eosinophil cationic protein (ECP) were measured. FeNO levels were measured before and after the methacholine bronchoprovocation test. Results:The mean FeNO levels (36.3 ppb) fell after methacholine bronchoprovocation test (25.7 ppb). Forced expiratory volume in one second (FEV1) %pred inversely correlated both with FeNO level before (R 2 =0.07, P=0.029) and after (R 2 =0.059, P=0.01) methacholine bronchoprovocation test. The provocative concentration, causing a 20% decrease in FEV1 to methacholine (methacholine PC20) inversely correlated both with FeNO levels before (R 2 =0.086, P=0.001) and after (R 2 =0.141, P=0.001) the challenge. FeNO level measured at bronchoconstriction state significantly correlated with blood eosinophil counts (R 2 =0.112, P=0.028). Serum ECP levels correlated FeNO level, neither before nor after bronchoprovocation. Conclusion:The baseline FeNO levels were higher in asthmatic children. However, FeNO levels rather decreased after methacholine induced bronchoconstriction. Repeated spirometry maneuver was considered to have an effect on reducing FeNO levels. FeNO correlated with pulmonary function, airway AHR and blood eosinophil counts. (Pediatr Allergy Respir Dis(Korea) 2012;22:282-291)

Asthma diagnosis and treatment: Filling in the information gaps

Current approaches to the diagnosis and management of asthma are based on guideline recommendations, which have provided a framework for the efforts. Asthma, however, is emerging as a heterogeneous disease, and these features need to be considered in both the diagnosis and management of this disease in individual patients. These diverse or phenotypic features add complexity to the diagnosis of asthma, as well as attempts to achieve control with treatment. Although the diagnosis of asthma is often based on clinical information, it is important to pursue objective criteria as well, including an evaluation for reversibility of airflow obstruction and bronchial hyperresponsiveness, an area with new diagnostic approaches. Furthermore, there exist a number of treatment gaps (ie, exacerbations, step-down care, use of antibiotics, and severe disease) in which new direction is needed to improve care. Amajor morbidity in asthmatic patients occurs with exacerbations and in patients with severe disease. Novel approaches to treatment for these conditions will be an important advance to reduce the morbidity associated with asthma.

Rising prevalence of asthma is sex-specific in a US farming population

Asthma prevalence is increasing worldwide in most populations, likely due to a combination of heritable factors and environmental changes. Curiously, however, some European farming populations are protected from asthma, which has been attributed to their traditional lifestyles and farming practices. We conducted population-based studies of asthma and atopy in the Hutterites of South Dakota, a communal farming population, to assess temporal trends in asthma and atopy prevalence and describe the risk factors for asthma. We studied 1325 Hutterites (ages 6-91 years) at 2 time points from 1996 to 1997 and from 2006 to 2009 by using asthma questionnaires, pulmonary function and methacholine bronchoprovocation tests, and measures of atopy. The overall prevalence of asthma increased over the 10- to 13-year study period (7.5%-11.1%, P= .049), whereas the overall prevalence of atopy did not change (45.0%-44.8%, P= .95). Surprisingly, the rise in asthma was only among females (5.8%-11.2%, P= .02); the prevalence among males remained largely unchanged (9.4%-10.9%, P= .57). Atopy, which was not associated with asthma risk in 1996 to 1997, was the strongest risk factor for asthma among Hutterites studied in 2006 to 2009 (P=.003). Asthma has increased over a 10- to 13-year period among Hutterite females and atopy has become a significant risk factor for asthma, suggesting a change in environmental exposures that are either sex limited or that elicit a sex-specific response.

Negative methacholine challenge tests in subjects who report physician-diagnosed asthma

The frequency of adults reporting a history of asthma is rising. However, it is unclear whether this increased prevalence accurately demonstrates a rising trend or if it reflects an overall increase in asthma awareness. To determine the frequency of negative methacholine bronchoprovocation tests in adults who report physician-diagnosed asthma and to explore the clinical characteristics of subjects with negative tests. Data from methacholine challenge, spirometry, and physician assessment were analysed from 304 adults who reported physician-diagnosed asthma and responded to community-based advertising for asthma research studies. The clinical characteristics of methacholine-positive and -negative subjects were compared and a predictive model was tested to identify those characteristics associated with a negative test. Of the 304 subjects tested, 83 (27%) had a negative methacholine test. A negative test was positively associated with an adult-onset of symptoms (P<0.001), normal forced expiratory volume in 1 s (P<0.001), and having no history of exacerbation requiring oral steroids (P=0.03). Over half (60%) of those with a negative test reported weekly asthma-like symptoms (cough, dyspnoea, chest tightness, or wheeze), while 39% reported emergency department visits for asthma-like symptoms. A sizeable percentage of subjects who report physician-diagnosed asthma have a negative methacholine challenge test. These subjects are characterized by diagnosis of asthma as an adult and by normal or near normal spirometry. Caution should be exercised in the assessment and diagnosis of adults presenting with asthma-like symptoms, because they may not have asthma. Further diagnostic studies, including bronchoprovocation testing, are warranted in this patient group, especially if their spirometry is normal.

Bronchial Hyper‐Reactivity in Migraine Without Aura: Is It a New Clue for Inflammation?

We attempted to investigate the relationship between migraine without aura (MwoA) and bronchial hyper-reactivity to postulate inflammation as an underlying mechanism in migraine. Comorbidity of migraine and atopic diseases such as asthma has been an argument for suspected immune system dysfunction in migraineurs. Twenty patients with MwoA and 5 control subjects without history of atophy and asthma were included in study. Subjects with abnormal physical examination and chest radiographs were excluded. After a normal spirometry, methacholine bronchoprovocation test was performed in all subjects and controls according to 5 breath dosimeter methods. Sixteen of 20 patients and 2 of 5 control subjects were women. Mean ages were 37.5 (19-56) and 33.8 (26-43) years, respectively. Methacholine bronchoprovocation test was positive in 3 patients (15%) but was normal in all controls (0%). The relationship between MwoA and bronchial hyper-reactivity may help to postulate the inflammation in migraine as an underlying mechanism.

Nasal Polyps: An Independent Risk Factor for Bronchial Hyperresponsiveness in Patients with Allergic Rhinitis

Many studies were conducted to figure out the relationship between allergic rhinitis (AR) and lower airway diseases. This study was designed to elucidate the clinical parameters that could predict the coexistence of bronchial hyperresponsiveness (BHR) in AR and suggest a guideline for lower airway evaluation in these patients. One hundred seventy-three patients newly diagnosed with AR were evaluated for the lower airway with the methacholine bronchoprovocation test. BHR was more prevalent in patients with nasal polyps (p = 0.01), in patients complaining of moderate to severe symptoms (p = 0.023), with higher serum total IgE levels (p = 0.001), and with blood eosinophil count (p = 0.008). No statistically significant difference was observed between intermittent and persistent AR patients (p = 0.364). Blood eosinophil count that could predict BHR was calculated as 320 cells/μL (p = 0.004). Instead of a routine lower airway evaluation for all AR patients, we recommend lower airway evaluation for the selected patients with nasal polyps, moderate to severe symptoms, and high blood eosinophil count.

Preventive effects of mycobacteria and their culture supernatants against asthma development in BALB/c mice

PurposeLive Mycobacterium bovis Bacille Calmette-Guérin (BCG) has a suppressive effect on asthma, but its use in clinical practice may be limited due to adverse reactions. To develop a product that is effective for suppressing asthma with minimal adverse reactions, we investigated whether the heat-killed body or culture supernatants of mycobacteria could also prevent asthma development.MethodsFemale BALB/c mice were treated with live BCG, the heat-killed body, or culture supernatants of BCG or Mycobacterium tuberculosis intraperitoneally, while sensitizing and provoking with ovalbumin. Then they underwent a methacholine bronchoprovocation test, and the peribronchial inflammatory cell numbers and cytokine levels in splenocyte culture supernatants were assessed.ResultsThe airway sensitivity to methacholine decreased significantly after treatment with not only live BCG (30.8 versus 10.0 mg/mL, P<0.001) but also with the culture supernatant (BCG, 23.0 mg/mL, P<0.05; M. tuberculosis, 20.5 mg/mL, P<0.05). In contrast, heat-killed mycobacteria did not effectively decrease airway sensitivity. The peribronchial eosinophil counts and the goblet cell proportions in total epithelial cells decreased significantly in most of the groups. The interferon-γ/interleukin-5 ratios increased significantly in most of the treatment groups except for the heat-killed groups, and were significantly related to airway sensitivity (r=0.312, P<0.01) and peribronchial eosinophil counts (r=-0.416, P<0.001). Interleukin-17A level was inversely related to airway sensitivity (r=-0.212, P<0.05) and was significantly lower in the live BCG group than in the control (137±20 versus 308±57 pg/mL, P<0.05).ConclusionsBCG and mycobacteria culture supernatants may effectively prevent the development of asthma associated with altered Th1/Th2 cytokines and interleukin-17A levels.

Predictors of bronchial hyperresponsiveness in chronic rhinosinusitis with nasal polyp

Chronic rhinosinusitis with nasal polyposis (CRSNP) and asthma are inflammatory lesions of the respiratory epithelium. This study was conducted to evaluate predictive factors of bronchial hyperresponsiveness (BHR) in patients with CRSNP. BHR was evaluated using a methacholine bronchoprovocation test (MBPT) in 122 consecutive patients newly diagnosed with CRSNP at Seoul National University Hospital from January 2004 to June 2006. The following parameters were analyzed and compared between the BHR and non-BHR groups: symptoms, atopic status, current smoking, disease severity of CRSNP based on the Lund-Mackay scoring system of sinus CT, and counts of eosinophils in the serum and nasal tissues. Thirty-five percent of the patients were found to have BHR, and BHR was found to occur more frequently in patients that were currently suffering from sneezing (P = 0.007). In addition, the mean eosinophil counts of the serum and nasal tissues were higher in the BHR group than in the non-BHR group (P = 0.001 for the serum, P = 0.045 for the nasal tissues), and the eosinophil counts of the serum correlated to those of the nasal tissues (r = 0.334, P = 0.013). The disease severity, as determined by the Lund-Mackay scoring system, was not different between the two groups (P > 0.05). The best cutoff serum eosinophil count for predicting BHR in CRSNP patients was determined to be 300 cells/microl (sensitivity 70%, specificity 70%). Taken together, these results indicate that moderate to severe sneezing and a serum eosinophil count > or = 300 cells/microl may be predictive factors for BHR in patients with CRSNP.

Diagnosing asthma in children: What is the role for methacholine bronchoprovocation testing?

To determine whether measurement of airways responsiveness to methacholine can help physicians diagnose asthma in children. Children from the 1995 Manitoba birth cohort were assessed by asthma specialists, had skin testing and measurement of airways responsiveness to methacholine (PC20). We selected children with doctor-diagnosed asthma and healthy children as controls (no asthma, no allergic rhinitis, negative skin tests). Sensitivities and specificities for asthma were calculated. Receiver operating curves were calculated to determine the best fit of the methacholine challenge as a diagnostic test. 640 children were assessed. Two hundred fifteen children with doctor diagnosed asthma and 197 healthy controls successfully completed a methacholine challenge. Airways hyperresponsiveness was a moderately sensitive and specific measure for the diagnosis of asthma in girls, whether atopic (sensitivity of 71% and specificity of 69% at PC20 < or = 4.0 mg/ml) or not (sensitivity of 77% and specificity of 53% at PC20 < or =8.0 mg/ml). Airways hyperresponsiveness was also helpful for the diagnosis of asthma in atopic boys (sensitivity of 67% and specificity of 75% at PC20 < or =2.0 mg/ml), but of absolutely no help in the diagnosis of asthma in nonatopic boys. Measurement of airways hyperresponsiveness to methacholine can be useful in children who are atopic and of some value in nonatopic girls. The presence or absence of airways hyperresponsiveness to methacholine is of no help for the diagnosis of asthma in nonatopic boys. Laboratory tests must be placed in context of the clinical assessment of children for asthma.

Health in early adulthood: the contribution of the 1978/79 Ribeirão Preto birth cohort

The increase in non-communicable chronic diseases of adults is due to demographic changes and changes in the risk factors related to physical activity, smoking habits and nutrition. We describe the methodology for the evaluation of persons at 23/25 years of age of a cohort of individuals born in Ribeirão Preto in 1978/79. We present their socioeconomic characteristics and the profile of some risk factors for chronic diseases. A total of 2063 participants were evaluated by means of blood collection, standardized questionnaires, anthropometric and blood pressure measurements, and methacholine bronchoprovocation tests. The sexes were compared by the chi-square test, with alpha = 0.05. Obesity was similar among men and women (12.8 and 11.1%); overweight was almost double in men (30.3 vs 17.7%). Weight deficit was higher among women than among men (8.6 and 2.6%). Women were more sedentary and consumed less alcohol and tobacco. Dietary fat consumption was similar between sexes, with 63% consuming large amounts (30 to 39.9 g/day). Metabolic syndrome was twice more frequent among men than women (10.7 vs 4.8%), hypertension was six times more frequent (40.9 vs 6.4%); altered triglyceride (16.1 vs 9.8%) and LDL proportions (5.4 vs 2.7%) were also higher in men, while women had a higher percentage of low HDL (44.7 vs 39.5%). Asthma and bronchial hyper-responsiveness were 1.7 and 1.5 times more frequent, respectively, among women. The high prevalence of some risk factors for chronic diseases among young adults supports the need for investments in their prevention.

Diagnostic Value of Negative Expiratory Pressure for Airway Hyperreactivity

To examine the value of negative expiratory pressure (NEP) in the assessment of methacholine bronchoprovocation testing (BPT). Prospective, observational study. Pulmonary function laboratory in a university hospital. Fifty-nine patients with chronic cough referred from outpatient clinics for methacholine BPT. Each subject inhaled successive doubling concentrations of methacholine (from 0.049 to 25 mg/mL) until the FEV(1) decreased for > 20% or the maximum concentration of methacholine was inhaled. NEP was measured in the sitting position during tidal breathing before and after methacholine BPT. The FEV(1) and forced oscillation airway resistance (Rrs) and interrupter airway resistance (Rint) were also obtained simultaneously. A positive BPT result was defined as a fall in FEV(1) > or = 20%. At baseline, only five patients had expiratory flow limitation as demonstrated by NEP (EFL-N). There were 39 patients with positive BPT results, and the other 20 patients had negative results. Among the BPT-positive patients, only 13 patients (33.3%) had EFL-N after methacholine challenge. The sensitivity indexes (absolute change/SD) of FEV(1), NEP, Rrs, and Rint were 16.0 +/- 9.6%, 1.1 +/- 1.6%, 3.8 +/- 4.5%, and 5.89 +/- 4.4% (mean +/- SD), respectively. The percentage changes in FEV(1) in BPT-positive patients correlated with the percentage changes in Rrs (r = 0.419, p = 0.008) and only marginally with the percentage changes in Rint (r = 0.307, p = 0.058), but not with the changes in EFL-N (r = 0.048, p = 0.77). These data suggest that NEP at sitting position is not sensitive in the assessment of methacholine bronchoprovocation as compared to FEV(1) and airway resistance measurements.

Gender differences in asthma prevalence may depend on how asthma is defined

Background: Asthma may be defined either as wheeze within the previous 12 months (current wheeze), doctor-diagnosed asthma (DDA), or current wheeze plus confirmed airway hyperresponsiveness (AHR). Aims: We wanted to estimate asthma prevalence in randomly selected adolescents based on different criteria for asthma diagnosis, study gender differences in reported asthma-like symptoms vs DDA, and relate our findings to measurements of AHR, levels of exhaled nitric oxide (ENO) and total IgE. Methods: As part of the health survey of North-Trøndelag (HUNT), 8571 adolescents aged 13–19 years were investigated with an interview on allergic and respiratory symptoms (phase I study). Of these, 401 subjects who reported wheeze within the previous 12 months (current wheeze) and 213 non-symptomatic controls were randomly selected and investigated with allergy screening, methacholine bronchoprovocation test and measurements of ENO (phase II study). Results : In the phase I study, prevalence of current wheeze was 26% (30% in girls and 23% in boys, P < 0.01). Prevalence of DDA was 10.8% (10.5% in girls and 11% in boys). Among subjects with current wheeze, the likelihood of having DDA was reduced in girls compared to boys, odds ratio (95% CI) 0.82 (0.68-0.98) which was partly explained by a longer history of wheeze among boys. In the phase II study, although more girls than boys with current wheeze had AHR (62% versus 50%, P < 0.02), more boys than girls reported DDA (44% vs . 32%, P < 0.02). Of the objective parameters, increased levels of ENO most strongly increased the risk of having DDA. Conclusions: When asthma is defined as DDA, there is a risk of underestimating the prevalence of asthma, especially among girls.

Dysfonctionnement nasal chronique et obstruction des voies aériennes périphériques

Allergic rhinitis often occur at the same time with many upper and lower airway diseases in which there is asthma. Many patients without clinical asthma may have an asymptomatic bronchial hyperreactivity and an allergic rhinitis at the same time. An overview of these actual knowledges is done including clinical, respiratory functional explorations, therapeutic studies, as well as those observed in chronic nasal dysfunctions (allergic or non allergic eosinophilic rhinitis, nasal polyposis, chronic rhinitis). Objectives. – The aim of this study is to determine bronchial hyperresponsiveness of a chronic nasal dysfunction population having allergic or non allergic rhinitis. Material and methods. – Retrospective study of respiratory functional explorations (using a methacholine provocation test) among non asthmatic patients consulting for rhinology-allergy diseases but with broncho-pulmonary symptomatology. Results. – It has been observed an allergic rhinitis population without upper bronchial hyperreactivity but with a small airway obstruction revealed or worsened during the methacholine bronchoprovocation test. Conclusion. – Chronic nasal dysfunction and small airway obstruction are correlated. This association shows an airway inflammation from the nose through the small bronchi. As upper bronchial hyperreactivity can precede asthma, a small airway obstruction could precede a bronchial hyperreactivity. Nasal chronic dysfunction treatment could act upon small airway obstruction, or central bronchial hyperreactivity or asthma appearance.

A study of the association between exercise-induced wheeze and exercise versus methacholine-induced bronchoconstriction in adolescents.

Among asthmatics, exercise-induced wheeze (EIW) is a frequent symptom, and 40-77% of asthmatics demonstrate exercise-induced bronchoconstriction (EIB). In the North-Trøndelag population-based survey of 8,571 adolescents (YOUNG-HUNT), 26% reported wheeze during the previous 12 months (current wheeze). Of those subjects, 50% reported EIW. The aim of the present study was to investigate the association between EIW and EIB in randomly selected adolescents with EIW as the only or predominant asthma-like symptom, and to relate our findings to results from methacholine bronchoprovocation tests (MT) and measurements of exhaled nitric oxide (ENO). Sixty-three subjects with current wheeze induced by exercise, but not by allergen exposure, were investigated using a treadmill exercise test (ET) and measurements of ENO. Fifty-eight subjects completed a MT on a separate study day. EIB was defined as a fall of >or= 10% in the forced expiratory volume in 1 second (FEV1) after exercise (DeltaFEV1%ex). Twenty-one subjects (33%) had EIB and 33 (57%) had a positive MT. The degree of reported dyspnea during the ET was not correlated to the DeltaFEV1%ex. The correlation between EIB and methacholine-induced bronchoconstriction (MIB) was poor, and the DeltaFEV1%ex was more pronounced in smokers than in non-smokers. Moreover, ENO was not increased in subjects with positive vs. negative ET. Hence, EIW, when reported as the only or predominant asthma-like symptom, was linked to EIB in only one-third of the patients. We conclude that EIW is a poor predictor of EIB in epidemiological studies. The poor correlation between EIB and MIB indicates that these two tests measure different mechanisms of bronchial hyper-responsiveness.

Pulmonary Function Characteristics in Patients With Different Patterns of Methacholine Airway Hyperresponsiveness

The American Thoracic Society guidelines for methacholine-induced airway hyperresponsiveness include a > or = 20% reduction in FEV(1) or a > or = 40% reduction in specific airway conductance (sGaw). The objectives of the current study are to assess the concordance between these two criteria and to characterize the pulmonary function and respiratory symptoms of patients with different patterns of methacholine hyperresponsiveness. A prospective study of 248 consecutive patients referred for methacholine bronchoprovocation testing. Positive methacholine hyperresponsiveness was noted in 179 patients; 139 patients (78%) had a > or = 20% reduction in FEV(1), whereas 40 patients (22%) had a > or = 40% reduction in sGaw alone without a significant change in FEV(1). The former group had the following: (1) higher baseline lung volumes, (2) lower baseline values of FEV(1) and sGaw, (3) forced expiratory flow between 25% and 75% of vital capacity (FEF(25-75))/FVC ratios compared to patients with a reduction in sGaw alone (0.72 +/- 0.26 vs 0.97 +/- 0.28, mean +/- SD; p < 0.0001), and (4) more frequent presence of wheezing and chest tightness (p < 0.05). First, a substantial number of patients have a reduction in SGaw alone in response to methacholine, and secondly, this response is seen in patients with a higher FEF(25-75)/FVC ratio. Since the FEF(25-75)/FVC ratio is thought to be an index of airway size relative to lung size, we speculate that the larger intrinsic airway size relative to lung size may explain the differences in baseline parameters and patterns of methacholine hyperresponsiveness.

The Diagnostic Value of Isocapnic Hyperventilation of Cold Air in Adults with Suspected Asthma

Background Asthmatic patients frequently suffer cold-weather-associated respiratory symptoms. The sensitivity, specificity, accuracy and diagnostic value of isocapnic hyperventilation of cold air(IHCA) using a multistep method was investigated in patients suspected to have asthma. Method One hundred and 29 adult patients who had an IHCA performed between july 1999 and December 2000, had an methacholine bronchoprovocation test because of a clinical suspicion of asthma. Results According to strict criteria, 50 were defined as asthmatics and 79 as symptomatic nonashmatics. There were no differences in age, sex and smoking state between the asthmatic and symptomatic nonasthmatic groups. There was a significant decrease in the percentage reduction in the forced expiratory volume in 1 second(FEV1) after the IHCA between the asthmatics(-10.0±6.8%) and the symptomatic nonasthmatics(-2.3±2.5%). The factors associated with a reactivity to IHCA were FEV1/FVC, FEF25-75/FVC and FEV1(% of predicted). The accuracy was highest using a 7% fall in FEV1; the sensitivity was 76% and the specificity 96%. Conclusion IHCA is a specific, although not a sensitive, test for diagnosing asthma in adult patients. Furthermore, the diagnostic cut-off value of the different methods of IHCA need to be determined.