Bronchial Challenge Research Articles

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.

Prueba de reto bronquial con ejercicio. Recomendaciones y procedimiento

La prueba de reto bronquial con ejercicio (PRBE) permite evaluar el efecto del ejercicio sobre la funcion respiratoria medida mediante espirometria; con ello, es posible explorar si el ejercicio induce obstruccion bronquial. Esta prueba es particularmente util en aquellos pacientes que presentan sintomas de obstruccion bronquial, pero cuya espirometria en reposo es normal, o bien, para pacientes q ue presentan sintomas respiratorios unicamente al realizar ejercicio. Aun cuando se han publicado las recomendaciones generales para llevar a cabo la PRBE, consideramos que existen aspectos tecnicos y de interpretacion que no estan su fi cientemente de fi nidos. Con el objetivo de mejorar el control de calidad y facilitar la realizacion de esta prueba, revisamos las recomendaciones internacionales en materia de este procedimiento y emitimos lineamientos locales que podran contribuir a un mejor proceso de estandarizacion

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.

FoxO1 is a critical regulator of M2-like macrophage activation in allergic asthma.

The pathogenesis of asthma and airway obstruction is the result of an abnormal response to different environmental exposures. The scientific premise of our study was based on the finding that FoxO1 expression is increased in lung macrophages of mice after allergen exposure and human asthmatic patients. Macrophages are capable of switching from one functional phenotype to another, and it is important to understand the mechanisms involved in the transformation of macrophages and how their cellular function affects the peribronchial stromal microenvironment. We employed a murine asthma model, in which mice were treated by intranasal insufflation with allergens for 2-8weeks. We used both a pharmacologic approach using a highly specific FoxO1 inhibitor and genetic approaches using FoxO1 knockout mice (FoxO1fl/fl LysMcre). Cytokine level in biological fluids was measured by ELISA and the expression of encoding molecules by NanoString assay and qRT-PCR. We show that the levels of FoxO1 gene are significantly elevated in the airway macrophages of patients with mild asthma in response to subsegmental bronchial allergen challenge. Transcription factor FoxO1 regulates a pro-asthmatic phenotype of lung macrophages that is involved in the development and progression of chronic allergic airway disease. We have shown that inhibition of FoxO1 induced phenotypic conversion of lung macrophages and downregulates pro-asthmatic and pro-fibrotic gene expression by macrophages, which contribute to airway inflammation and airway remodeling in allergic asthma. Targeting FoxO1 with its downstream regulator IRF4 is a novel therapeutic target for controlling allergic inflammation and potentially reversing fibrotic airway remodeling.

DYSPNEA, DYSPHAGIA, AND URTICARIA WITH ANGIOEDEMA AFTER CHILDBIRTH

Introduction Our case highlights the challenge in differentiating between hypereosinophilic syndrome (HES) and eosinophilia exacerbating atopic disease. Case Description A 29-year-old woman presents with dyspnea, dysphagia, urticaria and angioedema after childbirth. Evaluation revealed an eosinophil count of 3800/mcL. Infectious, cardiac, and chest imaging studies were normal. Lung function demonstrated FEV1/FVC at 0.85. Bronchial challenge with methacholine was positive. Bone marrow was normocellular with eosinophilia without evidence of PDGFRA, CHIC2, and FIP1L1 rearrangement. Upper endoscopy demonstrated esophageal eosinophilia. She improved on prednisone 40 mg daily, mometasone-formoterol, and montelukast. Dysphagia improved after esophageal dilation. Eosinophil counts remained elevated at 1500/mcL, with difficulty tapering prednisone due to dyspnea. She started interferon-alpha and continued prednisone 20 mg daily for 6 years with significant weight gain. She presented to our center and started mycophenolate-mofetil, discontinued interferon-alpha, and tapered prednisone to 5 mg daily. She then started mepolizumab and stopped prednisone. Six months later she developed dyspnea and urticaria. She switched to omalizumab with improvement and is stable on omalizumab, mycophenolate-mofetil, mometasone-formoterol, and montelukast. Discussion Asthma endotyping prompts checking eosinophil counts to assess for potential benefit with anti-IL5 therapy. Recent data demonstrates mepolizumab improves glucocorticoid sensitive HES, yet our patient responded better to omalizumab. The different biologics can help delineate the differential pathophysiology behind a patient's clinical presentation. Given the emerging overlap in therapeutic management, our case emphasizes the importance to shift the paradigm of understanding eosinophilic inflammation as a spectrum of disease rather than isolated entities, in consideration of both biologic and immune modulating medications.

Pearls and pitfalls in the diagnosis of cough variant asthma.

Cough alone may sometimes be the sole presenting symptom of asthma. Patients experience cough without wheeze or shortness of breath and with normal baseline pulmonary function test results. These patients do, however, demonstrate bronchial hyperreactivity. They also respond to specific traditional asthma therapy. These patients are considered to have a specific asthma phenotype: cough variant asthma (CVA).In prospective studies of patients with chronic cough, an average of 25% have CVA. Patients have chronic cough, normal baseline pulmonary function tests, positive bronchial inhalation challenge results, and response to specific asthma therapy. What makes these patients cough is still unknown. The cough reflex is complex. The specific cause of cough in CVA may be similar to cough mechanisms seen in typical bronchial asthma.All therapies for typical bronchial asthma have been successful in controlling cough in patients with CVA. The overall prognosis of CVA is excellent, with most patients requiring chronic inhaled corticosteroid therapy.

ERS technical standard on bronchial challenge testing: pathophysiology and methodology of indirect airway challengetesting.

Recently, this international task force reported the general considerations for bronchial challenge testing and the performance of the methacholine challenge test, a "direct" airway challenge test. Here, the task force provides an updated description of the pathophysiology and the methods to conduct indirect challenge tests. Because indirect challenge tests trigger airway narrowing through the activation of endogenous pathways that are involved in asthma, indirect challenge tests tend to be specific for asthma and reveal much about the biology of asthma, but may be less sensitive than direct tests for the detection of airway hyperresponsiveness. We provide recommendations for the conduct and interpretation of hyperpnoea challenge tests such as dry air exercise challenge and eucapnic voluntary hyperpnoea that provide a single strong stimulus for airway narrowing. This technical standard expands the recommendations to additional indirect tests such as hypertonic saline, mannitol and adenosine challenge that are incremental tests, but still retain characteristics of other indirect challenges. Assessment of airway hyperresponsiveness, with direct and indirect tests, are valuable tools to understand and to monitor airway function and to characterise the underlying asthma phenotype to guide therapy. The tests should be interpreted within the context of the clinical features of asthma.

Bronchial Allergen Challenge of Patients with Atopic Asthma Triggers an Alarmin (IL-33, TSLP, and IL-25) Response in the Airways Epithelium and Submucosa

The alarmin cytokines IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) play a critical role in asthma pathogenesis by inducing mucosal Th2-type cytokine production. Although environmental exposure to aeroallergens has been proposed as an alarmin trigger in asthma, there has been no systematic parallel study of the effects of allergen exposure on the expression of these cytokines in the airways of human asthmatics. Using single and sequential double immunohistochemistry, we evaluated the numbers and phenotypes of IL-25-, IL-33-, and TSLP-immunoreactive cells in sections of bronchial biopsies from mild atopic asthmatics (n = 16) before and 24 h after allergen inhalational challenge. Allergen challenge highly increased expression of baseline immunoreactivity for IL-25, IL-33, and TSLP, both in the bronchial epithelium and submucosa (p < 0.001), to a degree that correlated with the extent of the late phase of airway obstruction. Aside from epithelial cells, the principal source of immunoreactivity for all three alarmins, TSLP, and IL-33 immunoreactivity colocalized principally with endothelial cells and mast cells, neutrophils, and fibroblasts, whereas IL-25 immunoreactivity colocalized principally with eosinophils as well as endothelial cells, mast cells, and fibroblasts. The data implicate that allergen challenge directly increases airway alarmin expression in atopic asthmatics to a degree correlating with increase late-phase airway obstruction, affirming these molecules as potential molecular targets for the inhibition of allergen-induced airway inflammation and obstruction.

Identification and molecular characterization of allergenic non-specific lipid-transfer protein from durum wheat (Triticum turgidum).

Common wheat (Triticum aestivum) and durum wheat (T.turgidum) are both involved in Baker's asthma (BA) and food allergy (FA) including wheat-dependent exercise-induced asthma (WDEIA). However, allergens in durum wheat have not been described, and the over-expression of T.turgidum non-specific lipid-transfer protein (nsLTPs) is considered to increase resistance to phytopathogens. To identify and assess the allergenicity of nsLTP from T.turgidum. Recombinant T.turgidum nsLTP Tri tu 14 was generated and tested for structural integrity (circular dichroism-spectroscopy) and purity (SDS-PAGE). Thirty-two wheat allergic patients were enrolled: 20 Spanish patients (BA) with positive bronchial challenge to wheat flour, and 12 Italian patients (wheat FA/WDEIA) with positive double-blind placebo-controlled food challenge/open food challenge (OFC) to pasta. IgE values to wheat, Tri tu 14, Tri a 14 (T.aestivum) and Pru p 3 (P.persica) were determined by ImmunoCAP testing. Allergenic potency (invitro mediator release) and IgE cross-reactivity were investigated. Tri tu 14 was found to share 49% and 52% amino acid identity with Tri a 14 and Pru p 3, respectively. Among 25 Tri a 14 CAP positive sera, 23 (92%) were reactive to wheat extract, 22 (88%) to Tri tu 14 and 20 (80%) to Pru p 3. The correlation between Tri a 14 and Tri tu 14 specific IgE levels was r=0.97 (BA) and r=0.93 (FA/WDEIA), respectively. FA/WDEIA patients showed higher specific IgE values to Tri tu 14 and Pru p 3 than BA patients. Tri tu 14 displayed allergenic activity by mediator release from effector cells and IgE cross-reactivity with Pru p 3. The degree of IgE cross-reactivity between the two wheat nsLTPs varied between individual patients. Sensitization to Tri tu 14 likely appears to be more important in wheat FA/WDEIA than in BA. Over-expression of Tri tu 14 in wheat would represent a risk for patients with nsLTP-mediated FA.

Between-Visit Variability in FEV1 as a Diagnostic Test for Asthma in Adults.

The reliability of using between-visit variation in forced expiratory volume in 1 second (FEV1) to diagnose asthma is understudied, and hence uncertain. To determine whether FEV1 variability measured over recurrent visits is significantly associated with a diagnosis of current asthma. Randomly selected adults (N = 964) with a history of physician-diagnosed asthma were studied from 2005 to 2007 and from 2012 to 2016. A diagnosis of current asthma was confirmed in those participants who exhibited bronchial hyperresponsiveness to methacholine and/or acute worsening of asthma symptoms while being weaned off asthma medications. Regression analyses and receiver operating curves were used to evaluate the ability of between-visit FEV1 variability to diagnose asthma. A current diagnosis of asthma was confirmed in 584 of 964 participants (60%). Between-visit absolute variability in FEV1 was significantly greater in those in whom current asthma was confirmed, compared with those in whom current asthma was ruled out (7.3% vs. 4.8%; mean difference between the two groups, 2.5%; 95% confidence interval, 1.7-3.3%). However, a 12% and 200-ml between-visit variation in FEV1, which is the diagnostic threshold recommended by Global Initiative for Asthma, exhibited a sensitivity of only 0.17 and a specificity of 0.94 for confirming current asthma. A between-visit absolute variability in FEV1 ≥ 12% and 200 ml increased the pretest probability of asthma from 60% to a posttest probability of 81%. A 12% and 200-ml between-visit variation in FEV1, if present, has reasonably good specificity for diagnosing asthma, but has poor sensitivity compared with bronchial challenge testing. Between-visit variability in FEV1 is a relatively unhelpful test to establish a diagnosis of asthma.

Identifying phenotypes and factors impacting outcomes in older adults with asthma: A research protocol and recruitment results

Success in testing research outcomes requires identification of effective recruitment strategies in the targeted population. In this paper, we present the protocol for our NIH-funded study as well as success rates for the various recruitment strategies employed. This longitudinal observational study is: developing a phenotyping algorithm for asthma in older adults, exploring the effects of the asthma phenotype and of volatile organic compounds on asthma control, and developing a predictive model of asthma quality of life. A sub-aim is to characterize barriers to successful medication management in older adults with asthma. Individuals are eligible if they are ≥60 years, have a positive response to at least 1 of 6 asthma screening questions, are non-smokers, and demonstrate bronchodilator reversibility or a positive bronchial challenge test with methacholine. Exclusion criteria are smokers who quit <5 years ago or with a >20 pack year smoking history, and those having other chronic pulmonary diseases. Participants (N = 190) complete baseline pulmonary function testing, questionnaires, sputum induction, skin prick testing, and have blood drawn for Vitamin D and Immunoglobulin E. Home environmental assessments are completed including 24-hr particulate and volatile organic compound measurements. At 9-months post-baseline, home spirometry, medication assessment, and assessment of asthma quality of life and asthma control are assessed. At 18-months post-baseline, home spirometry, completion of baseline questionnaires, and a home environmental assessment are completed. We have employed multiple recruitment efforts including referrals from clinical offices, no-cost media events, flyers, and ads. The most successful efforts have been referrals from clinical offices and media events.

Predicting asthma in older adults on the basis of clinical history

The diagnosis of asthma is not always straightforward and can be even more challenging in older adults. Asthma is ideally confirmed by demonstration of variable expiratory airflow limitation. However, many patients with asthma do not demonstrate airflow obstruction nor show bronchodilator reversibility. We aimed to investigate predictors for a positive bronchial challenge test with methacholine in older adults being evaluated for asthma. This is a diagnostic accuracy study with a cross-sectional design. Participants ≥60 years with suspected asthma and a negative postbronchodilator response on spirometry were included. All participants underwent a methacholine challenge test (MCT). We assessed the value of standard asthma screening questions and additional clinical questions to predict the MCT results. A multivariable logistic regression model was developed to assess the variables independently impacting the odds of a positive MCT result. Our study included 71 participants. The majority were female (n = 52, 73.2%) and the average age was 67.0 years. Those with a positive MCT (n = 55, 77.5%) were more likely to have wheezing or coughing due to allergens (n = 51, 92.7% vs. n = 12, 75.0%; P = 0.004) and difficulty walking several blocks (n = 14, 25.5% vs. n = 1, 6.3%, P = 0.009). After adjustment, having wheezing or coughing due to allergens (OR = 4.2, 95% CI 1.7-7.8, P = 0.012) remained the only significant independent predictor of a positive MCT. In older adults with suspected asthma, questioning about wheezing or coughing due to allergens provides a modest independent value to predict a MCT result in those who previously had a negative postbronchodilator response on spirometry.

The usefulness of bronchial challenge tests in the diagnosis of occupational asthma

Bronchial hyperresponsiveness (BHR) is the individual ability to respond with bronchoconstriction to a variety of specific and nonspecific stimuli which do not cause these symptoms among healthy subjects. Bronchial hyperresponsiveness is one of the hallmark features of asthma. The degree of bronchial hyperresponsiveness is variable among individuals with asthma and may correlate to its severity (the more severe asthma the higher bronchial hyperreactivity). Bronchial hyperresponsiveness is evaluated by performing bronchial provocation test (BPT). Provocation tests are classified - according to their mechanisms - into direct and indirect tests. Direct challenge tests are highly sensitive and they are used primarily to rule out asthma. In contrast, provocation tests with indirect stimuli are less sensitive but more specific to the direct tests; they are used generally to confirm the diagnosis of asthma and they allow for more accurate conclusions about inflammatory lesions in the case of a patient. Bronchial provocation tests play a significant role in occupational medicine. They are particularly relevant to be performed prior to employment, during periodic examinations, and to diagnose and monitor both occupational asthma and work-related asthma. This article presents selected bronchial provocation tests and their usefulness in the diagnosis of occupational asthma. Med Pr 2018;69(4):457-471.

Bacterial Outer Membrane Vesicles Induce Vitronectin Release Into the Bronchoalveolar Space Conferring Protection From Complement-Mediated Killing.

Pathogens causing pneumonia utilize the complement regulator vitronectin to evade complement-mediated killing. Although vitronectin is associated with several chronic lung diseases, the role of bronchoalveolar vitronectin in pneumonia has not been studied. This study sought to reveal the involvement of vitronectin in the bronchoalveolar space during pneumonia, to assess the effect of outer membrane vesicles and endotoxin on vitronectin release, and to determine whether bacterial pathogens utilize pulmonary vitronectin for evasion. Vitronectin was analyzed in cell-free bronchoalveolar lavage fluid harvested from patients with pneumonia (n = 8) and from healthy volunteers after subsegmental endotoxin instillation (n = 13). Vitronectin binding by Pseudomonas aeruginosa and Haemophilus influenzae was analyzed, and subsequent complement evasion was assessed by serum challenge. The effects of outer membrane vesicles on vitronectin production in mouse lungs and human type II alveolar epithelial cells (A549) were determined. We detected increased vitronectin concentrations in lavage fluid during pneumonia (p = 0.0063) and after bronchial endotoxin challenge (p = 0.016). The capture of vitronectin by bacteria significantly reduced complement-mediated lysis. Following challenge with vesicles, vitronectin was detected in mouse bronchoalveolar space, and mouse alveolar epithelial cells in vivo as well as A549 cells in vitro contained increased levels of vitronectin. Taken together, outer membrane vesicles and endotoxin from Gram-negative bacteria induce vitronectin, which is released into the bronchoalveolar space, and used for evasion of complement-mediated clearance.

Pattern of Response to Bronchial Challenge with Histamine in Patients with Non-Atopic Cough-Variant and Classic Asthma.

Background: The aim of this study was to establish whether non-atopic patients with cough variant asthma (CVA) have different pattern of response to direct bronchoconstrictors than non-atopic patients with classic asthma (CA). Method: A total of 170 patients of both sexes with stable CVA and CA were screened for the study and 153 were included. Patients with proven atopy were not included and 17 patients with worsening of their condition or with verified bronchial obstruction during screening were excluded. All included patients performed spirometry and underwent a bronchial challenge with histamine according to long-standing protocol in our laboratory. Results: Significantly higher frequency of bronchial hyper-responsiveness (BHR) was found in patients with CA than in patients with CVA (63.9% vs. 44.9%, respectively; p < 0.05). Sensitivity was significantly lower in patients with CVA (p < 0.05), while no significant difference was found in maximal response and responsiveness. Only patients with positive challenge tests were included in the analysis. Conclusion: Adult non-atopic patients with CVA and CA have a pattern of response to non-specific bronchial stimuli similar to atopic patients with same conditions, with the exception of similar maximal response, which may reflect the efficacy of previous treatment. We believe that further studies are needed to clarify the mechanisms involved in airway response to non-specific stimuli in CVA and CA, especially in non-atopic patients. Further studies should also clarify whether this response pattern has any implications on clinical presentation or on treatment options.

Patterns of bronchial challenge testing in Canada.

BackgroundBronchial challenge testing (BCT) measures airway hyperresponsiveness; asthma guidelines recommend using BCT when symptoms manifest despite normal spirometry. Improper application of these guidelines commonly results in the misdiagnosis of asthma. Yet, statistics concerning BCT remain largely obscure. The current paper addresses this gap and explores how various health variables may elucidate adherence to asthma guidelines and patterns of BCT across Canadian provinces.MethodsUsing the Access to Information Act, medical financial claims for BCT (or equivalent procedures) were requested from each of the Canadian provinces and territories. Based on the available information (from provinces only), correlations between frequency of BCT claims and medical demographics (e.g., prevalence of respirologists, health expenditures) are reported.ResultsControlling for population or for people with asthma, physicians from Québec claim four times more BCT per year than those in other provinces; physicians from Alberta close to eight-fold fewer. The number of respirologists per capita and BCT per capita correlated moderately, r(132) = 0.582, p < 0.001, [95% CI 0.421, 0.716]. Excluding “outliers” (i.e., British Columbia, Alberta, and Saskatchewan) greatly strengthened this correlation, r(87) = 0.930, p < 0.001, [95% CI 0.883, 0.958].DiscussionThese findings demonstrate that provinces vary in their use of BCT. This result seems to stem, at least in part, from differences in the prevalence of respirologists. Interestingly, geographic region appears to wield a strong influence; in the correlation between number of tests and number of respirologists, physicians from Western provinces (i.e., Alberta, Saskatchewan, and British Columbia) administered fewer tests than their Eastern colleagues. Given the association between inadequate application of BCT and misdiagnosis of asthma, physicians should pay special attention to the Canadian guidelines when considering an asthma diagnosis.

ИЗМЕНЕНИЯ БОКАЛОВИДНОГО ЭПИТЕЛИЯ В ОТВЕТ НА ХОЛОДОВУЮ БРОНХОПРОВОКАЦИЮ У БОЛЬНЫХ БРОНХИАЛЬНОЙ АСТМОЙ С ХОЛОДОВОЙ ГИПЕРРЕАКТИВНОСТЬЮ ДЫХАТЕЛЬНЫХ ПУТЕЙ

Destruction of bronchial epithelium in patients with bronchial asthma (BA) is at the bottom of the mechanism of epithelial dysfunction, mucociliary insufficiency and bronchial remodeling. The aim of the work is to assess the character of changes that happen in the structural organization of cell elements and secretory activity of bronchial goblet epithelium in response to cold bronchial challenge in BA patients with cold airway hyperresponsiveness (CAHR). 28 patients with mild BA took part in the research. In the first day of the research the collection of the induced sputum was done, then the next day there was conducted a standard 3-minute test of isocapnic hyperventilation with cold (-20ºC) air (IHCA), after that the collection of sputum was done again. In cytograms of the sputum the percentage, the degree of destruction and cytolysis intensity of cell elements was determined; the contents of glycoproteins in goblet epithelial cells (GS) was studied. The first group included 14 patients with CAHR, the group of comparison (the 2nd group) included 14 patients with BA who did not have airway response to IHCA (ΔFEV1=-19.9±1.6 and -2.8±1.3%, respectively, p=0.00001). After IHCA in cytograms of the sputum of the patients with CAHR there was an increase of the number of neutrophils in relation to the basic one (from 39.9±2.8 till 54.0±2.3%, respectively, p=0.0004), the decrease of the number of macrophages (from 45.3±3.4 till 31.4±2.6%, p=0.005) without the changes of the number of eosinophils (10.0±2.2 and 10.4±1.6%, p=0.14) against intensified cytolysis (2.4±0.16 and 3.1±0.16%, p=0.0007). There was a decrease of the number of GC in relation to the initial one (from 0.22±0.02 till 0.16±0.02%; p=0.037) without significant changes of the number of epithelial cells (1.6±0.54 and 1.5±1.20%; p=0.97). The total index of destruction of GC was 0.45±0.02 and 0.51±0.02 (p=0.045); the index of cytolysis intensiveness of GC was 0.20±0.04 and 0.20±0.02 (p=0.27). A high number of GC that had a normal structure (0 and 1 class of destruction) as well as an increase of the number of cells in relation to initial values of the number of cells of II class against the absence of changes of III and IV classes of destruction were quite noticeable. Under cytochemical reaction the number of alcian blue stained GC actively synthesizing and secreting glycoproteins in response to IHCA increased in relation to the basic value (from 59.8±3.3 till 70.8±4.0%, p=0.0002, respectively). There was found a close correlation between the intensified production of GC glycoproteins in response to bronchial challenge and intensification of bronchial response (∆FEV1) to IHCA (r=-0.37; p=0.029). Thus, in the patients with BA and CAHR a short-term cold air exposure leads to the increase of the number of neutrophils and the decrease of the number of GC under intensive production of glycoproteins in them.

What does lung function tell us about respiratory multimorbidity in childhood and early adulthood? Results from the MAS birth cohort study

Interaction between respiratory multimorbidity and lung function has not been examined in longitudinal population studies. We aimed to assess the association of multimorbidity of asthma and rhinitis with lung function and bronchial hyperresponsiveness in comparison with single and no allergies from early school age to young adulthood. In 1990, the Multicenter Allergy Study birth cohort recruited 1314 newborns from 5 German cities. At 7, 13, and 20years, we performed lung function and bronchial challenge tests. We assessed symptoms, medications, and doctor's diagnoses for asthma and rhinitis for 3 outcomes: current multimorbidity (both coexisting), asthma only, and rhinitis only. From 7 to 20years, multimorbidity prevalence more than doubled from 3.5% to 7.7%, current asthma only (without rhinitis co-occurring) decreased by half from 2.8% to 1.3%, and current rhinitis only (without asthma co-occurring) increased from 14.3% to 41.6%. Resting lung function parameters differed between allergic and asymptomatic participants but showed no considerable differences between the allergic phenotypes. Frequency and severity of bronchial hyperresponsiveness were particularly associated with multimorbidity. At the age of 20years, participants with multimorbidity showed a clearly higher severity in hyperresponsiveness compared to participants who suffered only asthma (P=.049) or rhinitis (P=.008) or were asymptomatic (P<.001). Single lung function measurements from childhood ongoing do not seem to discriminate between subjects with multimorbidity, single allergies, and no allergy. Our results show that multimorbidity is associated with more severe symptoms compared to those suffering only a single allergic disease.

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.

Cough reflex sensitivity after exercise challenge testing in children with asthma

Bronchial challenge tests are commonly used in clinical medicine and research. The aim of this study was to clarify changes of cough reflex sensitivity before and after exercise challenge testing in asthma children.42 asthmatic children were submitted to cough reflex sensitivity measurement – capsaicin aerosol in doubling concentrations (from 0.61 to 1250 micromol/l) was inhaled by a single breath method – before and after exercise challenge testing. Concentrations of capsaicin causing two (C2) and five coughs (C5) were reported. Children' (31 boys and 11 girls, mean age 14.05 ± 2.08 yrs) cough reflex sensitivity (median, with the 95% CI) for C2 was before exercise challenge testing 9.77 (6.10–10.99) micromol/l vs. children' C2 after it 7.32 (6.10–14.65) (P = 0.58 for the Wilcoxon two sample paired test). Children' C5 was before exercise challenge testing 19.53 (14.65–80.57) micromol/l vs. C5 after it 39.06 (24.42–58.59) micromol/l (P = 0.09 for the Wilcoxon two sample paired test).We conclude that cough reflex sensitivity was not significantly changed after exercise challenge testing in children with asthma.