Methacholine Bronchial Challenge Research Articles

Standard technical specifications for methacholine chloride (Methacholine) bronchial challenge test (2023)

Standard technical specifications for methacholine chloride (Methacholine) bronchial challenge test (2023)

Is asthma over-diagnosed in Cyprus? A clinical study at the outpatient’s primary care level

Background: Although asthma is a common disease accurate diagnosis is missing and it has been reported that often it is over or under-diagnosed. Aim: To investigate if a physician’s diagnosis of asthma in Cyprus is correct by using a structured algorithm at the outpatient primary care level. Subjects and Methods: Sixty adults with a self-reported physician diagnosis of asthma, mean age of 47,8 years (29 males and 31 females) were included in the study. Medical history and physical examination, pre-post bronchodilation spirometry and methacholine bronchial challenge test was used to confirm or rule out the diagnosis as well as a three months follow-up. In addition, the cost of treatment was estimated. Results: Sixteen subjects (27%) had a positive pre-post bronchodilation spirometric test and were considered asthmatics. In 9 out of the 44 remaining subjects a positive Methacholine provocation test confirmed the diagnosis of asthma. The rest of the subjects (n = 35) went into a 3 months observational period during which only 2 showed asthmatic symptoms and were considered asthmatics by a second methacholine test that confirmed the diagnosis. Therefore, a correct asthma diagnosis was established in only 27(45%) of subjects. The annual average cost of medication for asthma confirmed the group was 313 euro/patient (171-454, 95% CI) and the average 2-year unnecessary (asthma ruled-out group) cost of treatment was approximately 297 euro/patient. (179-415, 95% CI). Conclusions: Physician-diagnosed asthma overestimates the actual prevalence of disease in adults in Cyprus since it was shown that more than half of the participants did not have Asthma. These individuals consume unneeded medications at a significant cost. Thus, the correct diagnosis of Asthma should be made by using more specific tests starting at the primary care level.

Prevalence of Asthma among Norwegian Elite Athletes.

Asthma is a common problem among elite athletes and represents a health risk interfering with the athlete's performance status. This study aimed to evaluate the asthma prevalence among Norwegian summer and winter elite athletes and asthma prevalence across sport categories. We also aimed to examine whether bronchial hyperresponsiveness (BHR), lung function, fraction of exhaled nitric oxide (FENO), and allergy status differed between asthmatic and non-asthmatic elite athletes. Norwegian athletes qualifying for the Beijing Olympic Summer Games 2008 (n = 80) and the Vancouver Olympic Winter Games 2010 (n = 55) were included. The athletes underwent clinical respiratory examination including lung function measurement, methacholine bronchial challenge for assessment of BHR, FENO, and skin prick testing. Asthma was diagnosed based on respiratory symptoms and clinical examination including objective measurements. Asthma was more prevalent among winter athletes (50%) than summer athletes (20%). Thirty-three (52%) endurance athletes, 3 (6%) team sport athletes, and 7 (33%) technical sport athletes had medically diagnosed asthma. Significantly lower lung function (p < 0.001) and higher prevalence of severe BHR (p < 0.001) were found in asthmatic athletes compared with non-asthmatic athletes. Asthma is common among Norwegian elite athletes, with winter and endurance athletes showing the highest prevalence. Asthmatic athletes were characterized by lower lung function and more severe BHR compared with non-asthmatic counterparts. The high prevalence among winter and endurance athletes demonstrates a need for increased attention to prevent and reduce the prevalence of asthma among those athletes.

New insights into the regulation of TGF-β/Smad and MPK signaling pathway gene expressions by nasal allergen and methacholine challenge test in asthma.

BackgroundAsthma is a heterogeneous chronic inflammatory disease of the bronchi, the course of which is significantly influenced by extrinsic factors (specific and non‐specific).MethodsThe aim of this study was to evaluate the effect of these factors represented by nasal allergen challenge (specific factors) and methacholine challenge test (non‐specific) on changes in mRNA expression of genes encoding the TGF‐β (TGF‐β1 and TGF‐β3)‒Smad (mitogen‐activated protein kinase 1/3 [MPK1/3], Smad1/3/6/7) signaling pathway in asthmatic patients.ResultsSeventy‐five subjects were included in the study, of whom 27 were applied an intranasal allergen provocation and 48 a methacholine provocation. There were 9 men and 18 women in the intranasal provocation group, and 17 men and 31 women in the methacholine test group. We found that both examined the types of challenges contributed to changes in the relative expression of genes of the TGF‐β (TGF‐β1 and TGF‐β3)‒Smad (MPK1/3, Smad1/3/6/7) signaling pathway in asthmatic patients. A decrease was noted for MAPK1, MAPK3, Smad3, Smad6, and Smad7 genes and an increase of up to 2.5 times for TGF‐β1 gene.ConclusionsOur experiment allows us to conclude that the change in the mRNA expression of the TGF‐β1–MPK1/3 and Smad3/6/7 genes occurs after an intranasal allergen and bronchial methacholine challenge.

Response of upper and lower airway inflammation to bronchial challenge with house dust mite in Chinese asthmatics: a pilot study.

BackgroundAllergen nasal challenge can induce increase of eosinophils in sputum, but report about eosinophilic inflammation in upper airway after allergen bronchial challenge in Chinese asthmatics was rare. The article aims to evaluate response of upper and lower airways to house dust mite (HDM) allergen bronchial challenge.MethodsHDM allergen bronchial challenge was carried out in asthmatic patients with allergic rhinitis (AR). Bronchial methacholine challenge and blood test were performed before and at 24 hours after allergen challenge. Nasal lavage and induced sputum for differential cells count and fractional exhaled nitric oxide (FeNO) measurement were performed before, 7 and 24 hours after allergen challenge.ResultsEighteen asthmatic patients with AR underwent HDM allergen bronchial challenge with no serious adverse events reported. Fifteen patients showed dual asthmatic response (DAR), while 2 patients showed early (EAR) and 1 late asthmatic response (LAR) only. At 24 hours after allergen bronchial challenge testing, average PC20FEV1 to methacholine significantly decreased (1.58 to 0.81 mg/mL, P=0.03), while both FeNO and the percentage of eosinophils in blood and sputum were significantly increased [52.0 (54.0) to 69.0 (56.0) ppb, P=0.01; 4.82% to 6.91%, P<0.001; 20.70% to 27.86%, P=0.03, respectively], but with no significant differences found in the percentage of eosinophils in nasal lavage (39.36% to 38.58%, P=0.89). However, at 7 hours after allergen challenge, the eosinophils in sputum were significant increased to 40.45% (P<0.001), but there was an increase (39.36% to 48.07%) with no statistical difference (P=0.167) found in nasal lavage.ConclusionsHDM allergen bronchial challenge induced different response of airway inflammation in upper and lower airways.

The Efficacy of the Dyson Air Purifier in Improving Asthma Control: Protocol for a Single-Center, Investigator-Led, Randomized, Double-Blind, Placebo-Controlled Trial.

BackgroundIndoor air quality has been shown to influence asthma control and outcomes. Air purifiers and high-efficiency particulate air filtration devices can improve indoor air quality by reducing the indoor levels of air pollution and allergens. However, the influence of this improved indoor air quality on asthma control remains unclear; hence, randomized controlled trials are needed to further elucidate this phenomenon.ObjectiveThis study aims to investigate the effect of reducing the levels of allergens and pollutants in the bedroom and living room through the use of Dyson air purifiers (Dyson Pure Cool) on asthma control.MethodsThis is an 18-month long, investigator-led, randomized, double-blinded, placebo-controlled, single-center trial. Subjects will be randomized in a 1:1 ratio to active or placebo Dyson filters. The primary outcome is the change in the scores of Asthma Control Questionnaire 6 and Asthma-specific Quality of Life Questionnaire from baseline. Secondary outcomes include changes in lung function (forced expiratory volume in one second, forced expiratory volume in one second/forced vital capacity ratio, and midexpiratory flows), peak expiratory flow measurements, airway hyperresponsiveness (assessed by methacholine bronchial challenge), fractional exhaled nitric oxide, and indoor air pollutant levels. The sample size will be 50 subjects, and all subjects will have a confirmed diagnosis of mild persistent to moderate persistent asthma along with an Asthma Control Questionnaire 6 score of >1.5.ResultsThis study was approved by the West Midlands Research Ethics Committee (18/WM/0277). The study results will be published in peer-reviewed scientific journals; presented at relevant scientific conferences; and shared in plain English with participants in our newsletters, in our clinics, and via the David Hide Asthma and Allergy Research Centre website. Our trial began in September 2019 and is expected to end in August 2021.ConclusionsThis is a double-blinded, placebo-controlled, randomized, investigator-led study to investigate the efficacy of a novel air purifier in improving asthma control in adults. The trial period of 18 months will facilitate the collection of robust data and will therefore generate clear signals. However, this extended trial duration may lead to patient withdrawal. Furthermore, this trial is conducted at a single center and in a location with a homogenous cohort of people, which may affect translatability. Nonetheless, it is hoped that the findings of this trial may help further inform clinicians regarding the utility of this novel device as an adjunct in asthma care.Trial RegistrationClinicalTrials.gov NCT04729530; https://clinicaltrials.gov/ct2/show/NCT04729530International Registered Report Identifier (IRRID)DERR1-10.2196/28624

Association between sensitization and allergic diseases in 7-years-old Korean children.

Sensitization is associated with the exacerbation, severity, and prognosis of allergic diseases in children. We characterized the association between sensitization patterns and allergic diseases. A cohort of 548 children was enrolled from Panel Study of Korean Children (PSKC) study. Skin prick tests (SPTs) for 18 common allergens, blood tests, and methacholine bronchial challenge tests were performed at age 7. The Korean version of International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire was used. The sensitization rate on SPTs was 46.4%. Sensitization to indoor allergens showed an association with symptoms of asthma (adjusted odds ratio [aOR], 2.39; 95% confidence intervals [95% CIs], 1.10-5.23), allergic rhinitis (AR, aOR 2.08, 95% CIs 1.42-3.06), and atopic dermatitis (AD, aOR 2.36, 95% CIs 1.24-4.50) in the preceding 12 months. In contrast, sensitization to outdoor allergens was associated with AR diagnosis only (aOR 2.40, 95% CIs 1.30-4.41). The number of sensitized allergens was associated with a lifetime diagnosis and symptoms in the preceding 12 months of AR and asthma, but not with AD or BHR. A higher degree of sensitization to indoor allergens was associated with symptoms in the preceding 12 months of asthma, AR, AD, and that for outdoor allergens was associated with symptoms in the prior 12 months of asthma and AR. The sensitization patterns including allergen type, number, and degree of sensitization are helpful for interpreting the association between sensitization and allergic diseases and identifying the pathophysiologies and diverse phenotypes of allergic diseases.

Predictive value of non-specific bronchial challenge testing for respiratory symptoms and lung function in aluminium smelter workers

ObjectiveTo assess the predictive value of bronchial hyper-responsiveness (BHR) for the subsequent development of respiratory symptoms, airflow limitation and decline in lung function among aluminium smelter workers.MethodsAn inception cohort study...

Diagnostic comparison of methacholine and mannitol bronchial challenge tests for identifying bronchial hyperresponsiveness in asthma: a systematic review and meta-analysis

Objective Bronchial hyperresponsiveness (BHR) is a representative feature of asthma. Although methacholine and mannitol are commonly used for bronchial challenge tests, the optimal roles of the two agents for assessing BHR remain unclear. We compared the diagnostic performance of methacholine and mannitol in bronchial challenge tests. Methods A systematic literature search was performed using MEDLINE, EMBASE, and the Cochrane Central Register. The sensitivity, specificity, diagnostic odds ratio (DOR), and a hierarchical summary of the receiver-operating characteristic curve (HSROC) of the two agents for detecting BHR in asthma were pooled using meta-analysis. A meta-regression analysis was used to identify potential sources of heterogeneity within the selected studies. Results We identified six studies comprising 565 patients. The pooled sensitivity, specificity, and DOR of methacholine were 0.61 (95%CI, 0.44-0.76), 0.93 (95%CI, 0.70–0.99), and 23.47 (95% CI, 2.51–219.89), respectively. The pooled sensitivity, specificity, and diagnostic odds ratio of mannitol were 0.50 (95%CI, 0.28–0.73), 0.97 (95% CI, 0.94–0.99), and 35.22 (95% CI, 8.82–140.62), respectively. The area under the HSROC for mannitol was higher than that for methacholine (0.97 vs. 0.81, p < 0.01). Considerable between-study heterogeneity was present for sensitivity and specificity in studies of both index tests. Univariate meta-regression analysis revealed that age and sex of the study participants were probable sources of heterogeneity for specificity in studies of methacholine. Conclusion Although mannitol showed better diagnostic performance than methacholine for identifying BHR in asthma, substantial between-study heterogeneity necessitates caution when interpreting the data.

Correlations of induced sputum eosinophils with blood allergic markers in pediatric asthma and eosinophilic bronchitis

Purpose: Induced sputum eosinophil count is useful for the evaluation and diagnosis of asthma and eosinophilic bronchitis (EB). The aim of this study was to evaluate the correlation of induced sputum eosinophil count with various allergic indicators, including the peripheral blood eosinophil count, in pediatric asthma and EB. Methods: From May 2014 to July 2018, 126 children visited Kyungpook National University Children’s Hospital, and underwent methacholine bronchial challenge test and sputum induction. Peripheral blood eosinophil counts, serum eosinophil cationic pro tein (ECP), serum total IgE, immunoCAP for inhalant allergens, and skin prick test were performed in the study subjects. Results: In the asthma group, the eosinophil count of induced sputum correlated with peripheral blood eosinophils (r=0.279, P=0.043). The concordance rates of sputum and peripheral blood eosinophil count in the asthma and EB groups were 64.1% and 25.7%, re spectively. The number of eosinophils in the sputum also correlated with serum total IgE, ECP, and specific IgE to Dermatophagoides farinae, Dermatophagoides pteronyssinus, and Aspergillus in the asthma group. Conclusion: The number of eosinophils in the induced sputum correlated with peripheral blood in the asthma group. However, a third of subjects were discordant. Therefore, we need to keep in mind the possibility of discordance when predicting the degree of airway eosinophilic inflammation using the peripheral blood eosinophils. In EB, the number of induced sputum eosinophils did not correlate with the number of peripheral blood eosinophils, which may be attributed to the difference in mechanism. Further studies are warranted. (Allergy Asthma Respir Dis 2020;8:220-226)

Bronchodilation Test with Inhaled Salbutamol Versus Bronchial Methacholine Challenge to Make an Asthma Diagnosis: Do They Provide the Same Information?

Methacholine bronchial challenge and bronchodilation to salbutamol are key tests in clinical practice to make asthma diagnosis. To assess the concordance between the 2 tests and to see whether they actually identify the same population of asthmatics. We conducted a retrospective study using our asthma clinic database to see how methacholine bronchial challenge compared to bronchodilation to salbutamol in untreated patients with recurrent or chronic symptoms suspicious of asthma. We identified 194 untreated patients with baseline forced expiratory volume in 1 second (FEV1) ≥70% predicted who had both a bronchodilation test with salbutamol and a methacholine bronchial challenge 7 to 14 days apart. A positive bronchial challenge was a provocative concentration of methacholine causing a 20% fall in FEV1 ≤16 mg/mL, whereas a positive bronchodilation test was a reversibility to 400 μg inhaled salbutamol ≥12% from baseline and 200 mL. Overall, asthma diagnosis was confirmed in 91% of cases leaving 9% of subjects with double negative tests. Isolated positive methacholine challenge was found in 71% of subjects, double positive tests in 17%, whereas isolated significant bronchodilation to salbutamol was rare (3%). There was no correlation between provocative concentration of methacholine causing a fall in FEV1 of 20% (PC20M) and the magnitude of salbutamol reversibility (P= .10). Baseline FEV1/forced vital capacity ratio inversely correlated with reversibility to salbutamol (P < .001) but not with PC20M (P= .1). No difference was found between the groups regarding demographic and immunoinflammatory features, including the proportion of eosinophilic asthma. We conclude that methacholine challenge outperforms reversibility to salbutamol to diagnose asthma without selecting patients with distinct inflammatory profile. Baseline airway obstruction predicts magnitude of reversibility but not hyperresponsiveness.

Nocturnal symptoms perceived as asthma are associated with obstructive sleep apnoea risk, but not bronchial hyper-reactivity.

Obstructive sleep apnoea (OSA) and asthma are associated, and nocturnal breathing difficulty that is usually identified as asthma-like symptoms can be present in both conditions. We investigated how nocturnal asthma-like symptoms (NAS) and bronchial hyper-reactivity (BHR) contribute to the association between OSA risk and current asthma, which is currently unknown but a clinically important question. We used data from 794 middle-aged participants in a population-based cohort who provided information on OSA risk (defined by a STOP-Bang questionnaire score of at least 3), current asthma and NAS, and underwent methacholine bronchial challenge testing. Using regression models, we examined the association between OSA risk and current asthma-NAS subgroups and investigated any effect modification by BHR. The participants were aged 50 years (49.8% male). OSA risk was associated with NAS with or without current asthma (odds ratio (OR): 2.6; 95% CI = 1.3-5.0; OR: 4.2; 95% CI = 1.1-16.1, respectively), but not with current asthma in the absence of NAS. BHR was associated with current asthma with or without NAS (OR: 2.9; 95% CI = 1.4-5.9; OR: 3.4; 95% CI = 2.0-7.0, respectively) but not with NAS in the absence of current asthma. The associations between OSA risk and current asthma were neither modified nor mediated by BHR. Our findings suggest that some of the nocturnal symptoms perceived as asthma may be OSA symptoms. Patients with nocturnal asthma symptoms should be considered for possible OSA.

Effects of plant features on symptoms and airway inflammation in compost workers followed over 18 months

This study investigated the plant features associated with increased irritation symptoms and levels of inflammation markers among compost workers (CWs). Ninety CWs were followed over 18 months, using questionnaires on respiratory symptoms, fractional exhaled nitric oxide measurements, spirometry, a methacholine bronchial challenge test, and quantification of specific immunoglobulins E (IgE) and G. CWs in plants processing the highest quantities of waste exhibited more airway irritation symptoms. So did the CWs in partially and fully indoor plants as compared to those in plants entirely outdoors. Working in sewage sludge versus green waste plants and having a high level of exposure were associated with higher levels of different IgE. The duration of employment decreased the FEV1 by 16 ml per year. Working in an indoor plant is linked to symptoms and inflammation markers in CWs.

Study of airway hyperresponsiveness in patients with pulmonary tuberculosis

Background Airway hyperresponsiveness (AHR) is an overstated constrictor response of the airways to a diverse types of specific plus nonspecific stimuli, and it is a major, but not necessarily unique, feature of asthma. Aim This study aims to detect the presence or absence of AHR in patients with pulmonary tuberculosis (TB). Patients and methods This study included 40 patients with TB and 20 healthy age-matched and sex-matched volunteers. They were divided into three groups: group A included 20 patients with pulmonary TB under anti-TB medication after the initial phase (2 months) of treatment with successful sputum conversion, group B included 20 cured cases with past history of pulmonary TB that completed the full supervised course, and group C included 20 volunteers with matched age and sex. They were subjected to spirometry as well as methacholine bronchial challenge test and computed tomographic chest examination. Results There was a significant negative correlation between postmethacholine AHR and time passed since completion of phase of anti-TB medications in group A after initiation phase (rs=−0.642, P=0.002). The more time passed since completion of treatment, the less number of patients who had AHR. However, there is no significant correlation between them in group B after continuation phase (P=0.81). Conclusion AHR could be a prevalent feature in patients with TB under TB therapy and with past TB history. Accomplishment of anti-TB medication course might lessen the influence of AHR on patient conditions.

Effect of CPAP on airway reactivity and airway inflammation in children with moderate-severe asthma.

Asthma is characterized by airway hyperreactivity and airway inflammation. We previously demonstrated that adults with mild well-controlled asthma exhibited a marked decrease in airway reactivity (PC20 increased >2-fold) after using nocturnal continuous positive airway pressure (CPAP) for 1 week. If CPAP produces a similar suppression of airway reactivity in children with moderate-severe asthma, who require chronic use of corticosteroids, then this non-pharmacological therapy might provide a beneficial alternative or supplemental therapy in these subjects. Children aged 8-17 years with moderate-severe asthma were treated with 4 weeks of nocturnal CPAP (8-10 cm H2 O) or sham CPAP (<2 cm H2 O). Adherence was monitored with a modem installed in the equipment or by memory cards. Airway reactivity, assessed by methacholine bronchial challenge, was measured prior to and following treatment. The percentage of subjects adherent to treatment was similar in both groups (19/27 CPAP vs 19/28 sham, ~70%). There was a tendency for PC20 to increase with treatment in both groups (3.0-5.3 mg/mL CPAP vs 3.2 to 4.3 mg/mL sham, P = 0.083); however, the change did not differ significantly between groups (P = 0.569). We found that the 4-week treatment with nocturnal CPAP did not produce a twofold suppression of airway reactivity in children with moderate-severe asthma.

The Role of Airway Inflammation and Bronchial Hyperresponsiveness in Athlete's Asthma.

Asthma is frequently reported in endurance athletes. The aim of the present study was to assess the long-term airway inflammatory response to endurance exercise in high-level athletes with and without asthma. In a cross-sectional design, 20 asthmatic athletes (10 swimmers and 10 cross-country skiers), 19 athletes without asthma (10 swimmers and 9 cross-country skiers), and 24 healthy nonathletes completed methacholine bronchial challenge, lung function tests, and sputum induction on two separate days. All athletes competed on a national or international level and exercised ≥10 h·wk. The nonathletes exercised ≤5 h·wk and reported no previous lung disease. Bronchial hyperresponsiveness (BHR) was defined as a methacholine provocation dose causing 20% decrease in the forced expiratory volume in 1 s of ≤8 μmol. BHR was present in 13 asthmatic athletes (62%), 11 healthy athletes (58%), and 8 healthy nonathletes (32%), and the prevalence differed among groups (P = 0.005). Sputum inflammatory and epithelial cell counts did not differ between groups and were within the normal range. Median (25th to 75th percentiles) sputum interleukin-8 was elevated in both asthmatic (378.4 [167.0-1123.4]) and healthy (340.2 [175.5-892.4]) athletes as compared with healthy nonathletes (216.6 [129.5-314.0], P = 0.02). No correlations were found between provocation dose causing 20% decrease and sputum cell counts. Independent of asthma diagnosis, a high occurrence of BHR and an increased sputum interleukin-8 were found in athletes as compared with nonathletes. Airway inflammation or epithelial damage was not related to BHR.

Vitamin D, high-sensitivity C-reactive protein, and airway hyperresponsiveness in infants with recurrent respiratory symptoms

BackgroundVitamin D insufficiency might be associated with biased T-cell responses resulting in inflammatory conditions such as atopy and asthma. Little is known about the role of vitamin D in low-grade systemic inflammation and airway hyperresponsiveness (AHR) in young children. ObjectiveTo evaluate whether vitamin D insufficiency and increased serum high-sensitivity C-reactive protein (hs-CRP) are linked to AHR in symptomatic infants. MethodsSeventy-nine infants with recurrent or persistent lower respiratory tract symptoms underwent comprehensive lung function testing and a bronchial methacholine challenge test. In addition, skin prick tests were performed and serum 25-hydroxyvitamin D (S-25-OHD), hs-CRP, total immunoglobulin E, and blood eosinophil levels were determined. ResultsS-25-OHD was lowest in infants with blood eosinophilia and AHR (n = 10) compared with those with eosinophilia only (n = 6) or AHR only (n = 50) or those with neither (n = 13; P = .035). Moreover, vitamin D insufficiency (S-25-OHD <50 nmol/L) was most common in infants with blood eosinophilia and AHR (P = .041). Serum hs-CRP was lower in infants with recurrent physician-diagnosed wheezing (P = .048) and in those with blood eosinophilia (P = .015) than in infants without these characteristics and was not associated with S-25-OHD or AHR. S-25-OHD levels were significantly lower (median 54 nmol/L) during the autumn-winter season than in the spring-summer season (median 63 nmol/L; P = .026). ConclusionVitamin D insufficiency could underlie eosinophilia and AHR in infants with troublesome lung symptoms, whereas hs-CRP–mediated low-grade systemic inflammation is rare in early childhood wheezing.

Perceived exercise limitation in asthma: The role of disease severity, overweight, and physical activity in children.

Children with asthma may be less physically active than their healthy peers. We aimed to investigate whether perceived exercise limitation (EL) was associated with lung function or bronchial hyper-responsiveness (BHR), socioeconomic factors, prenatal smoking, overweight, allergic disease, asthma severity, or physical activity (PA). The 302 children with asthma from the 10-year examination of the Environment and Childhood Asthma birth cohort study underwent a clinical examination including perceived EL (structured interview of child and parent(s)), measure of overweight (body mass index by sex and age passing through 25 kg/m2 or above at 18 years), exercise-induced bronchoconstriction (forced expiratory volume in one-second (FEV1 ) pre- and post-exercise), methacholine bronchial challenge (severe BHR; provocative dose causing ≥20% decrease in FEV1 ≤ 1 μmol), and asthma severity score (dose of controller medication and exacerbations last 12 months). Multivariate logistic regression analyses were conducted to assess associations with perceived EL. In the final model explaining 30.1%, asthma severity score (OR: 1.49, (1.32, 1.67)) and overweight (OR: 2.35 (1.14, 4.82)) only were significantly associated with perceived EL. Excluding asthma severity and allergic disease, severe BHR (OR: 2.82 (1.38, 5.76)) or maximal reduction in FEV1 post-exercise (OR: 1.48 (1.10, 1.98)) and overweight (OR: 2.15 (1.13, 4.08) and 2.53 (1.27, 5.03)) explained 9.7% and 8.4% of perceived EL, respectively. Perceived EL in children with asthma was independently associated with asthma severity and overweight, the latter doubling the probability of perceived EL irrespectively of asthma severity, allergy status, socioeconomic factors, prenatal smoking, or PA.

Parasympathetic Activity and Bronchial Hyperresponsiveness in Athletes.

A high prevalence of asthma and bronchial hyperresponsiveness (BHR) is reported in swimmers and cross-country skiers. It has been suggested that increased parasympathetic nervous activity is involved in asthma development in endurance athletes. We aimed to assess the associations of BHR to parasympathetic activity in healthy and asthmatic swimmers and cross-country skiers and healthy nonathletes. Parasympathetic activity was measured by pupillometry and heart rate variability at the onset of exercise with the cardiac vagal index calculated in 28 cross-country skiers (♂18/♀10), 29 swimmers (♂17/♀12), and 30 healthy nonathlete controls (♂14/♀16) on two different days. All subjects performed a methacholine bronchial challenge with the provocation dose causing 20% decrease in the forced expiratory volume in 1 s calculated (PD20met). Data were analyzed by robust regression analysis and presented as β coefficients with 95% confidence intervals (CI). PD20met was negatively associated with cardiac vagal index (-13.9, 95% CI = -26.8 to -1.0) in all subjects. When adjusted to the type of sport, this association was stronger in swimmers (-8.3, 95% CI = -13.0 to -3.6) as compared with controls and nonsignificant in cross-country skiers. Percent pupil constriction was significantly associated with PD20met in swimmers (-9.4, 95% CI = -15.4 to -3.4) only after adjusting for the type of sport. Fourteen swimmers (48%) and 16 cross-country skiers (57%) had doctor-diagnosed asthma in combination with current BHR and/or current use of asthma drugs. Seventy-two percent swimmers, 44% cross-country skiers, and 39% controls had a PD20met ≤8 μmol (P = 0.015). Fourteen swimmers had a PD20met ≤2 μmol as compared with one cross-country skier (P < 0.001). Parasympathetic activity measured in the heart is more closely related to BHR as compared with parasympathetic activity measured in the pupils. The type of sport influences BHR severity and its relationship to parasympathetic activity.

Eosinophilic airway inflammation is common in subacute cough following acute upper respiratory tract infection.

Patients presenting with refractory postinfectious cough may respond to glucocorticosteroids but it is unclear whether airway eosinophilic inflammation exists in those patients. We aimed to determine the airway inflammation and causes of subacute cough following acute upper respiratory tract infection (AURTI). One hundred and sixteen patients with persistent cough lasting 3-8 weeks after upper respiratory tract infection were evaluated with differential cell count in induced sputum, spirometry and methacholine bronchial challenge testing. In patients with subacute cough, sputum eosinophilia (median 8.5%,3.0-73.0%) was identified in 35 (33.6%) patients, 22 (18.5%) without bronchial hyperresponsiveness (BHR) were diagnosed as non-asthmatic eosinophilic bronchitis (NAEB), 13 (14.3%) of whom with BHR were diagnosed as cough variant asthma (CVA). Cough in patients with sputum eosinophilia improved after treatment with corticosteroids. Compared with postinfectious cough (PIC) and NAEB, CVA had significantly higher median eosinophil count in induced sputum (0.5% vs 7.5% vs 20.0%, P < 0.01). MMEF in CVA was significantly lower than PIC and NAEB (P < 0.05). The common causes of subacute cough following acute upper respiratory tract infection (AURTI) were PIC (37.8%), NAEB (18.5%), CVA (14.3%) and upper airway cough syndrome (UACS) (10.1%). Atopic cough (AC) (5.2%) and gastroesophageal reflux-related cough (GERC) (3.4%) were less common in subacute cough following AURTI, while 9 (7.8%) patients had unexplained cough. Subacute cough following AURTI can be attributed to different entities, eosinophilic airway inflammation is common. Induced sputum should be considered when evaluating patients with subacute cough following acute upper respiratory tract infection.