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1.
J Korean Med Sci ; 36(19): e130, 2021 May 17.
Article in English | MEDLINE | ID: mdl-34002550

ABSTRACT

BACKGROUND: Most epidemiological studies depend on the subjects' response to asthma symptom questionnaires. Questionnaire-based study for childhood asthma prevalence may overestimate the true prevalence. The aim of this study was to investigate the prevalence of "Current asthma" using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire and methacholine challenge test in Korean children. METHODS: Our survey on allergic disease included 4,791 children (age 7-12 years) from 2010 to 2014 in Korean elementary schools. Bronchial hyperresponsiveness (BHR) was defined as provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (FEV1) (PC20) ≤ 16 mg/mL. "Current asthma symptoms" was defined as positive response to "Wheezing, current," "Treatment, current," or "Exercise, current." "Current asthma" was defined when the subjects with "Current asthma symptoms" showed BHR on the methacholine challenge test or had less than 70% of predicted FEV1 value. RESULTS: The prevalence of "Wheezing, ever," "Wheezing, current," "Diagnosis, ever," "Treatment, current," "Exercise, current," and "Current asthma symptoms" was 19.6%, 6.9%, 10.0%, 3.3%, 3.5%, and 9.6%, respectively, in our cross-sectional study of Korean elementary school students. The prevalence of BHR in elementary school students was 14.5%. The prevalence of BHR in children with "Wheezing, ever," "Wheezing, current," "Diagnosis, ever," "Treatment, current," and "Exercise, current" was 22.3%, 30.5%, 22.4%, 28.8%, and 29.9%, respectively. BHR was 26.1% in those with "Current asthma symptoms." The prevalence of "Current asthma" was 2.7%. CONCLUSIONS: Our large-scale study provides 2.7% prevalence of current asthma in Korean elementary school children. Since approximately one third of the children who have "Current asthma symptoms" present BHR, both subjective and objective methods are required to accurately predict asthma in subjects with asthma symptoms.


Subject(s)
Asthma/epidemiology , Bronchial Hyperreactivity/epidemiology , Bronchial Provocation Tests/methods , Bronchoconstrictor Agents/administration & dosage , Methacholine Chloride/administration & dosage , Asthma/diagnosis , Bronchial Hyperreactivity/diagnosis , Bronchial Provocation Tests/adverse effects , Bronchoconstrictor Agents/adverse effects , Child , Cross-Sectional Studies , Female , Forced Expiratory Volume/physiology , Humans , Male , Methacholine Chloride/adverse effects , Prevalence , Republic of Korea/epidemiology , Respiratory Sounds/etiology , Surveys and Questionnaires
2.
BMC Pulm Med ; 21(1): 49, 2021 Feb 03.
Article in English | MEDLINE | ID: mdl-33536015

ABSTRACT

BACKGROUND: Cough variant asthma (CVA) is one of the special populations of asthma. The aim of the study was to compare small airways, the degree of bronchial hyperresponsiveness (BHR) and airway inflammatory subtypes between CVA and classic asthma (CA), and investigate the relationship between these markers to determine the accuracy as indicators of CVA. METHODS: A total of 825 asthmatic patients participated in the study and 614 were included. 614 patients underwent spirometry and a bronchial challenge with methacholine and 459 patients performed induction sputum cell test. RESULTS: The number of CVA patients showed less small airway dysfunction than those of CA patients (p < 0.005). The degree of small airways dysfunction was higher in the CA group compared with the CVA group (p < 0.001). Small airways dysfunction was severer in the eosinophilic airway inflammatory subtype compared with other subtypes (p < 0.05).The area under curve of MMEF, FEF50 and FEF75 (% predicted) was 0.615, 0.621, 0.606, respectively. 0.17mcg of PD20 and 4.7% of sputum eosinophils was the best diagnostic value for CVA with an AUC of 0.582 and 0.575 (p = 0.001 and p = 0.005, respectively). CONCLUSIONS: The eosinophilic airway inflammatory subtype may be increased small airway dysfunction. The value of small airways, BHR and induction sputum cells in CVA prediction, which reflected significant, but not enough to be clinically useful.


Subject(s)
Asthma/immunology , Bronchial Hyperreactivity/immunology , Eosinophil Cationic Protein/immunology , Eosinophils/immunology , Sputum/immunology , Adult , Asthma/complications , Bronchial Hyperreactivity/chemically induced , Bronchial Provocation Tests , Bronchoconstrictor Agents/administration & dosage , Bronchoconstrictor Agents/adverse effects , Cough/immunology , Dose-Response Relationship, Drug , Eosinophil Cationic Protein/analysis , Female , Forced Expiratory Volume/drug effects , Humans , Leukocyte Count , Male , Methacholine Chloride/administration & dosage , Methacholine Chloride/adverse effects , Middle Aged , Multivariate Analysis , Retrospective Studies
4.
Sci Rep ; 10(1): 1962, 2020 02 06.
Article in English | MEDLINE | ID: mdl-32029879

ABSTRACT

Mechanisms mediating the protective effects of molecular hydrogen (H2) are not well understood. This study explored the possibility that H2 exerts its anti-inflammatory effect by modulating energy metabolic pathway switch. Activities of glycolytic and mitochondrial oxidative phosphorylation systems were assessed in asthmatic patients and in mouse model of allergic airway inflammation. The effects of hydrogen treatment on airway inflammation and on changes in activities of these two pathways were evaluated. Monocytes from asthmatic patients and lungs from ovalbumin-sensitized and challenged mice had increased lactate production and glycolytic enzyme activities (enhanced glycolysis), accompanied by decreased ATP production and mitochondrial respiratory chain complex I and III activities (suppressed mitochondrial oxidative phosphorylation), indicating an energy metabolic pathway switch. Treatment of ovalbumin-sensitized and challenged mice with hydrogen reversed the energy metabolic pathway switch, and mitigated airway inflammation. Hydrogen abrogated ovalbumin sensitization and challenge-induced upregulation of glycolytic enzymes and hypoxia-inducible factor-1α, and downregulation of mitochondrial respiratory chain complexes and peroxisome proliferator activated receptor-γ coactivator-1α. Hydrogen abrogated ovalbumin sensitization and challenge-induced sirtuins 1, 3, 5 and 6 downregulation. Our data demonstrates that allergic airway inflammation is associated with an energy metabolic pathway switch from oxidative phosphorylation to aerobic glycolysis. Hydrogen inhibits airway inflammation by reversing this switch. Hydrogen regulates energy metabolic reprogramming by acting at multiple levels in the energy metabolism regulation pathways.


Subject(s)
Asthma/drug therapy , Glycolysis/drug effects , Hydrogen/administration & dosage , Leukocytes, Mononuclear/drug effects , Oxidative Phosphorylation/drug effects , Animals , Asthma/blood , Asthma/chemically induced , Asthma/immunology , Bronchoconstrictor Agents/adverse effects , Cells, Cultured , Disease Models, Animal , Female , Glycolysis/immunology , Humans , Lactic Acid/metabolism , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/metabolism , Lung/drug effects , Lung/immunology , Lung/pathology , Male , Methacholine Chloride/adverse effects , Mice , Middle Aged , Ovalbumin/immunology , Primary Cell Culture
5.
Stomatologiia (Mosk) ; 96(3): 52-54, 2017.
Article in Russian | MEDLINE | ID: mdl-28617409

ABSTRACT

The paper presents the analysis of studies of local anesthesia in patients with bronchial asthma. It was found that the diagnosis of hypersensitivity to sodium metabisulfite in patients with bronchial asthma must be optimized for development of local anesthesia selection algorithm in outpatient dentistry.


Subject(s)
Anesthesia, Dental/methods , Anesthesia, Local/methods , Asthma/complications , Bronchoconstrictor Agents/adverse effects , Dental Care , Drug Hypersensitivity/diagnosis , Sulfites/adverse effects , Algorithms , Anesthesia, Dental/adverse effects , Anesthesia, Local/adverse effects , Drug Hypersensitivity/complications , Drug Hypersensitivity/prevention & control , Female , Humans
6.
Dermatitis ; 26(4): 162-5, 2015.
Article in English | MEDLINE | ID: mdl-26172484

ABSTRACT

BACKGROUND: The prevalence of contact allergy to sodium metabisulfite (SMB) has increased from the range of 1.4% to 1.7% to the range of 3.4% to 6.8% in published series over the past 20 years. AIMS: The aims of this study were to review contact allergy to SMB in our cohort and to investigate different concentrations to define the most appropriate concentration for patch testing. METHODS: Patient records were reviewed between February 2009 and December 2011 to obtain information on patient demographics, clinical presentation, and prevalence of contact allergy to SMB. Patients attending for patch testing, between January 2012 and June 2013, were tested with 3 strengths of SMB as part of the British standard series (1%, 0.1%, and 0.01%). RESULTS: Nine hundred ninety-six patients were patch tested to the British standard series including SMB 1% in petrolatum between February 2009 and June 2013, and 70 (7%) were positive. In the prospective group, 380 were tested to 3 concentrations of SMB (1.0%, 0.1%, and 0.01%). Fourteen patients (3.68%) had a positive patch test with 1% SMB, 7 to 0.1% SMB, and 3 to 0.01% SMB. There was exposure to SMB in 10 patients who cleared with avoidance at review 3 months later. The most frequent location of rash included face, hands, vulval, and perianal region. CONCLUSIONS: Our study confirms reports of increasing prevalence of SMB allergy. A detailed review of exposure in the prospective study showed that SMB is relevant in most patients, and 1% in petrolatum is the best concentration for patch testing.


Subject(s)
Bronchoconstrictor Agents/adverse effects , Dermatitis, Allergic Contact/etiology , Facial Dermatoses/etiology , Hand Dermatoses/etiology , Patch Tests/methods , Sulfites/adverse effects , Adult , Aged , Cohort Studies , Dermatitis, Allergic Contact/diagnosis , Dermatitis, Allergic Contact/epidemiology , Facial Dermatoses/diagnosis , Facial Dermatoses/epidemiology , Female , Hand Dermatoses/diagnosis , Hand Dermatoses/epidemiology , Humans , Male , Middle Aged , Prevalence , Prospective Studies
7.
Iran J Allergy Asthma Immunol ; 13(5): 317-23, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25150072

ABSTRACT

Increased arginase activity in the airways decreases L-arginine and causes deficiency of bronchodilating and anti-inflammatory nitric oxide (NO) in asthma. As, it is suggested that L-arginine may have therapeutic potential in asthma treatment, we aimed to investigate the effects of inhaled L-arginine on oxygen saturation (SaO2) and airway histology in a murine model of acute asthma. Twenty eight BALB/c mice were divided into four groups; I, II, III and IV (control). All groups except the control were sensitized and challenged with ovalbumin. After establishement of acute asthma attack by metacholine administration, the mice were treated with inhaled L-arginine (Group I), saline (Group II) and budesonide (Group III), respectively. SaO2was measured by pulse oximeter just before and 5 min after methacholine. A third measurement of SaO2was also obtained 15 min after drug administration in these study groups. Inflammation in the lung tissues of the sacrificed animals were scored to determine the effects of the study drugs. The number of eosinophils in bronchoalveolar lavage (BAL) was determined. The results indicated that inflammatory scores significantly improved in groups receiving study drugs when compared with placebo and L-arginine was similar in decreasing scores when compared with budesonide. SaO2had a tendency to increase after L-arginine administration after acute asthma attack and this increase was statistically significant (p=0.043). Eosinophilia in BAL significantly reduced in group receiving L-arginine when compared with placebo (p<0.05). Thus in this study we demonstrated that L-arginine improved SaO2and inflammatory scores in an acute model of asthma.


Subject(s)
Arginine/pharmacology , Asthma/drug therapy , Nitric Oxide/immunology , Acute Disease , Animals , Asthma/immunology , Asthma/pathology , Bronchoconstrictor Agents/adverse effects , Bronchoconstrictor Agents/pharmacology , Bronchodilator Agents/pharmacology , Budesonide , Disease Models, Animal , Male , Methacholine Chloride/adverse effects , Methacholine Chloride/pharmacology , Mice , Mice, Inbred BALB C , Time Factors
8.
Am J Physiol Lung Cell Mol Physiol ; 305(2): L118-29, 2013 Jul 15.
Article in English | MEDLINE | ID: mdl-23666750

ABSTRACT

Inhalation of ozone (O3), a common environmental pollutant, causes pulmonary injury, pulmonary inflammation, and airway hyperresponsiveness (AHR) in healthy individuals and exacerbates many of these same sequelae in individuals with preexisting lung disease. However, the mechanisms underlying these phenomena are poorly understood. Consequently, we sought to determine the contribution of osteopontin (OPN), a hormone and a pleiotropic cytokine, to the development of O3-induced pulmonary injury, pulmonary inflammation, and AHR. To that end, we examined indices of these aforementioned sequelae in mice genetically deficient in OPN and in wild-type, C57BL/6 mice 24 h following the cessation of an acute (3 h) exposure to filtered room air (air) or O3 (2 parts/million). In wild-type mice, O3 exposure increased bronchoalveolar lavage fluid (BALF) OPN, whereas immunohistochemical analysis demonstrated that there were no differences in the number of OPN-positive alveolar macrophages between air- and O3-exposed wild-type mice. O3 exposure also increased BALF epithelial cells, protein, and neutrophils in wild-type and OPN-deficient mice compared with genotype-matched, air-exposed controls. However, following O3 exposure, BALF neutrophils were significantly reduced in OPN-deficient compared with wild-type mice. When airway responsiveness to inhaled acetyl-ß-methylcholine chloride (methacholine) was assessed using the forced oscillation technique, O3 exposure caused hyperresponsiveness to methacholine in the airways and lung parenchyma of wild-type mice, but not OPN-deficient mice. These results demonstrate that OPN is increased in the air spaces following acute exposure to O3 and functionally contributes to the development of O3-induced pulmonary inflammation and airway and lung parenchymal hyperresponsiveness to methacholine.


Subject(s)
Asthma/metabolism , Bronchoconstrictor Agents/adverse effects , Lung/metabolism , Methacholine Chloride/adverse effects , Neutrophil Infiltration/drug effects , Neutrophils/metabolism , Osteopontin/metabolism , Oxidants, Photochemical/adverse effects , Ozone/adverse effects , Animals , Asthma/chemically induced , Asthma/genetics , Asthma/pathology , Bronchoalveolar Lavage , Bronchoconstrictor Agents/pharmacology , Female , Lung/pathology , Lung Injury/chemically induced , Lung Injury/genetics , Lung Injury/metabolism , Lung Injury/pathology , Macrophages, Alveolar/metabolism , Macrophages, Alveolar/pathology , Methacholine Chloride/pharmacology , Mice , Mice, Mutant Strains , Neutrophils/pathology , Osteopontin/genetics , Oxidants, Photochemical/pharmacology , Ozone/pharmacology , Pneumonia/chemically induced , Pneumonia/genetics , Pneumonia/metabolism , Pneumonia/pathology
9.
Chest ; 143(5): 1269-1276, 2013 May.
Article in English | MEDLINE | ID: mdl-23370456

ABSTRACT

BACKGROUND: Fractional exhaled nitric oxide measured at expiratory flow of 50 mL/s (Feno50), a biomarker of airway inflammation, is affected by changes in airway caliber. Whether a lower Feno50 level during bronchoconstriction is only an artifact due to the strong flow dependence of this parameter is controversial. METHODS: We aimed to evaluate the dynamics of airway and alveolar nitric oxide (NO) during acute bronchoconstriction induced by methacholine. Exhaled NO was measured at expiratory flows of 10, 50, 100, 150, and 250 mL/s before and after metacholine in 26 responders to methacholine and 37 nonresponders. Flow-independent parameters (airway wall NO flux, airway NO diffusing capacity, airway wall NO concentration, alveolar NO concentration) were calculated using a two-compartment model, and correction for NO axial back diffusion was applied. RESULTS: Bronchoconstriction in responders was associated with a decrease in Feno50 (-28%, P < .0001), in airway wall NO flux (-34%, P < .0001), and in airway NO diffusing capacity (-15%, P < .05). In contrast, alveolar NO concentration was not affected by bronchoconstriction. Postmethacholine changes in Feno50 were more strictly related to the ventilation distribution, assessed by single-breath carbon monoxide uptake, than to larger airways caliber, assessed by FEV1. When bronchoconstriction was reversed by salbutamol, airway wall NO flux and airway NO diffusing capacity returned to values comparable to those measured premethacholine. CONCLUSIONS: The changes in airway caliber induced by noninflammatory stimuli alter NO transport in the lung. The changes in NO dynamics are limited to conductive airways and are characterized by a reduction of NO flow to luminal space.


Subject(s)
Bronchoconstriction/physiology , Exhalation/physiology , Nitric Oxide/metabolism , Pulmonary Alveoli/metabolism , Respiratory Mechanics/physiology , Adult , Albuterol/pharmacology , Bronchial Provocation Tests , Bronchoconstriction/drug effects , Bronchoconstrictor Agents/adverse effects , Bronchoconstrictor Agents/pharmacology , Bronchodilator Agents/pharmacology , Female , Forced Expiratory Volume/physiology , Humans , Male , Methacholine Chloride/adverse effects , Methacholine Chloride/pharmacology , Pulmonary Alveoli/physiopathology , Time Factors
11.
J Med Assoc Thai ; 94 Suppl 1: S66-71, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21728272

ABSTRACT

BACKGROUND: The addition of ipratropium, a synthetic cholinergic antagonist, to beta2-agonist therapy provides an additive improvement in adult with acute severe asthma and COPD because of increased vagal tone in the airways. We asked whether ipratropium in combination with fenoterol (Ipraterol) improved pulmonary function in comparison with original Berodual. MATERIAL AND METHOD: In order to determine the effects of nebulized a single dose of Ipraterol, the study was conducted in a double-blind, randomized and crossover manner by comparing the effect of nebulized a single dose of Berodual on methacholine-induced bronchoconstriction. The study consisted of an 1-week run-in phase and two study visits separated by a washout period of 7 days. PATIENTS: We studied 20 patients who ranged from 18 to 80 years of age and had mild to moderate persistent asthma. RESULTS: Nebulized Ipraterol provided a rapid onset of bronchodilation effect similar to nebulized Berodual within 5 minutes by significantly increasing FEV, from 1.19 L to 1.73 L (p < 0.001) and from 1.19 to 1.69 L (p = 0.0001), respectively. This effect of Ipraterol lasted as long (up to 6 hours) and was similar to that of Berodual. The absolute FEV1 values at 360 min after Ipraterol treatment was still higher than the baseline values. We also found that there were no significant differences in the degree of improvement in FEV1 and hypokalemia following treatment with Ipraterol and Berodual. CONCLUSION: Our data suggest that nebulized Ipraterol offers a statistically significant improvement in pulmonary function without significant systemic absorption causing hypokalemia, with the improvement being comparable to that achieved with nebulized Berodual.


Subject(s)
Asthma/drug therapy , Bronchoconstriction/drug effects , Bronchodilator Agents/therapeutic use , Fenoterol/therapeutic use , Ipratropium/therapeutic use , Administration, Inhalation , Adolescent , Adult , Asthma/physiopathology , Bronchoconstrictor Agents/adverse effects , Bronchodilator Agents/pharmacology , Child , Cross-Over Studies , Double-Blind Method , Drug Combinations , Female , Fenoterol/pharmacology , Forced Expiratory Volume/drug effects , Humans , Ipratropium/pharmacology , Male , Methacholine Chloride/adverse effects , Middle Aged , Nebulizers and Vaporizers , Respiratory Function Tests , Spirometry , Treatment Outcome , Young Adult
12.
Respir Med ; 104(12): 1825-33, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20584595

ABSTRACT

RATIONALE: Patient-reported outcomes provide new insights into the dynamics of asthma management. Further to asthma control and quality of life, self-reported side effects of treatment can be assessed with the validated Inhaled Corticosteroid Questionnaire (ICQ). OBJECTIVES: To compare patient-reported side effects between the inhaled corticosteroids ciclesonide and fluticasone propionate. METHODS: Patients with moderate or moderate-to-severe asthma, pre-treated with a constant dose and type of medication, were randomized in three separate studies: 1) once daily ciclesonide 320 µg (n = 234) or twice daily fluticasone propionate 200 µg (n = 240); 2) twice daily ciclesonide 320 µg (n = 255) or twice daily fluticasone propionate 375 µg (n = 273); and 3) twice daily ciclesonide 320 µg (n = 259) or twice daily fluticasone propionate 500 µg (n = 244). Patients rated the side effect questions of the 15 domain ICQ on a 7-point Likert scale (0 = not at all, 6 = a very great deal) during scheduled visits. RESULTS: The majority of side effect scores remained similar with ciclesonide but worsened statistically significantly with fluticasone propionate from baseline to the end of the study in within-treatment analyses. In between-treatment analyses of studies 1 and 3 ciclesonide significantly improved total side effect scores (p < 0.025) and 14 out of 30 individual local and systemic domain scores (p < 0.025) compared with fluticasone propionate. In Study 2, although ciclesonide improved the majority of scores compared with fluticasone propionate only 'oropharyngeal itching' reached statistical significance (p < 0.025, one-sided). CONCLUSION: Patient-perceived side effects differ depending on the type of inhaled corticosteroids used. Patients with moderate-to-severe asthma report less intense side effects assessed with ICQ with ciclesonide than with fluticasone propionate. CLINICAL TRIAL REGISTRATION: The reported trials were completed before July 1 2005 and, therefore, are not registered.


Subject(s)
Androstadienes/adverse effects , Anti-Asthmatic Agents/adverse effects , Asthma/drug therapy , Bronchoconstrictor Agents/adverse effects , Pregnenediones/adverse effects , Administration, Inhalation , Adolescent , Adult , Aged , Anti-Asthmatic Agents/administration & dosage , Asthma/physiopathology , Asthma/psychology , Bronchoconstrictor Agents/administration & dosage , Child , Female , Fluticasone , Forced Expiratory Volume , Humans , Male , Middle Aged , Quality of Life/psychology , Surveys and Questionnaires , Treatment Outcome , Young Adult
13.
Am J Sports Med ; 38(6): 1154-9, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20348285

ABSTRACT

BACKGROUND: Recent clinical and basic science investigations have revealed the chondrotoxicity of local anesthetics, especially those containing epinephrine, administered via an intra-articular pain pump. However, the exact mechanism of toxicity is unknown. This study evaluates the chondrotoxicity of low pH, epinephrine, and preservatives found in commonly used local anesthetics. HYPOTHESIS: The chondrotoxicity of local anesthetics containing epinephrine is due to low pH, epinephrine, or the preservative sodium metabisulfite. STUDY DESIGN: Controlled laboratory study. METHODS: Human chondrocytes were harvested and cultured in a custom bioreactor designed to simulate metabolism of medication. Pain pumps were used to infuse one of the following medications into the culture system: control media; media titrated to pH 4.5, 5.0, 5.5, 6.0, 6.5; media with 1:100000 or 1:200000 epinephrine only; media with 0.5 mg/mL of sodium metabisulfite preservative; media with 0.5 mg/mL of methylparaben preservative, 0.25% bupivacaine, 0.25% bupivacaine with epinephrine, 1% lidocaine, and 1% lidocaine with epinephrine. Cultures were perfused for 24 hours and then were stained with live/dead cell viability assay. The chondrocytes were then examined by fluorescence microscopy and counted, and the percentage of cell death was calculated. RESULTS: Cultures containing media titrated to pH 4.5 and 5.0 and local anesthetics containing epinephrine (pH 4.0-5.5) had high cell death rates compared with controls at all time points (P < .001), while cultures containing 1:100000 and 1:200000 epinephrine alone had no increased death rate. Also, 0.5 mg/mL sodium metabisulfite preservative had a significant effect on cell death (P < .034); however, the preservative methylparaben had no effect (P > .05). The percentage of cell death was not significant for 1% lidocaine (12.5%; P > .943) and 0.25% bupivacaine (16.5%; P > .609). CONCLUSION: The marked chondrotoxicity of local anesthetics containing epinephrine appears to be a combined effect of low pH, as these medications are titrated to pH 4.0 to 5.5 for product stability, and the preservative sodium metabisulfite. Extreme caution should be exercised when using intra-articular pain pumps with local anesthetics containing epinephrine. CLINICAL RELEVANCE: Understanding the causes of chondrotoxicity using local anesthetics containing epinephrine is critical to decrease complications associated with this class of medications.


Subject(s)
Adrenergic Agonists/pharmacology , Anesthetics, Local/adverse effects , Bronchoconstrictor Agents/adverse effects , Cartilage Diseases/chemically induced , Chondrocytes/drug effects , Epinephrine/pharmacology , Sulfites/adverse effects , Anesthetics, Local/chemistry , Epinephrine/administration & dosage , Humans , Hydrogen-Ion Concentration
14.
Immunol Cell Biol ; 88(3): 269-74, 2010.
Article in English | MEDLINE | ID: mdl-20101253

ABSTRACT

Substantial evidence has been accumulated to indicate that gammadelta T cells take part in type 2 immune responses. It is not yet clear, however, in what capacity. Apparently, gammadelta T cells themselves can not only take the function of follicular T helper (T(H)) cells in certain responses, but also can support responses that are dependent on classical help provided by alphabeta T cells. Furthermore, the gammadelta T cells engage as regulators of T(H2) immunity. Here, we consider two mouse models that depend on type 2 immunity, non-specific airway hyperresponsiveness to methacholine after allergen inhalation challenge and the primary IgE response induced by alum-aided immunization, and examine the function of gammadelta T cells. In either case, gammadelta T cells regulate type 2 immunity through balanced enhancing and inhibitory influences. However, after airway allergen exposure, suppressive gammadelta T cells become dominant. The underlying mechanisms are discussed.


Subject(s)
Receptors, Antigen, T-Cell, gamma-delta/immunology , Th2 Cells/immunology , Allergens/immunology , Animals , Bronchoconstrictor Agents/adverse effects , Bronchoconstrictor Agents/pharmacology , Disease Models, Animal , Humans , Hypersensitivity/immunology , Immunity, Cellular/drug effects , Immunity, Cellular/immunology , Immunoglobulin E/immunology , Methacholine Chloride/adverse effects , Methacholine Chloride/pharmacology , Mice , Receptors, Antigen, T-Cell, alpha-beta/immunology
15.
Pharmacol Res ; 61(2): 121-8, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19683054

ABSTRACT

Regular use of beta(2)-adrenoceptor agonists may enhance non-specific airway responsiveness and inflammation. In earlier experimental studies, we showed that prolonged in vitro fenoterol exposure induced airway sensitization via perturbed epithelial regulation of bronchoconstriction. The aim of the present work was to examine the involvement of inflammatory mediator genes and proinflammatory cells and to investigate the role of the bronchial epithelium in these untoward effects. Bronchial tissues were surgically removed from 17 ex-smokers. Bronchial rings and primary cultures of bronchial epithelial cells were incubated with 0.1microM fenoterol for 15h. Levels of mRNA-expression were analyzed using a real-time quantitative reverse transcription-polymerase chain reaction array. Bronchial rings were contracted with endothelin-1 and immune cell infiltration was assessed by immunohistochemistry. Compared to paired controls, fenoterol up-regulated the mRNAs of cytokines/proteins implicated in the recruitment of T and B cells or the activation and proliferation of bronchial epithelial cells (CCL20/MIP-3alpha, FOXA2, PPAR-gamma) in isolated bronchi and in cultured epithelial cells. Fenoterol exposure significantly enhanced CD8(+)-T and differentiated CD138(+)-B-cells infiltration into the bronchi, especially the subepithelial area. Increase in CD8 or CD138 labeling-intensity strongly correlated with rise in maximal contraction to endothelin-1 induced by fenoterol exposure. In summary, our results show that fenoterol modulates the T and B cells chemotaxis possibly via the epithelial chemokine secretion in isolated bronchi from ex-smokers. They also suggest that the infiltration of resident T and B cells into the subepithelial area is associated with an increase in airway responsiveness due to fenoterol exposure.


Subject(s)
Adrenergic beta-Agonists/pharmacology , B-Lymphocytes/drug effects , Bronchi/drug effects , Bronchial Hyperreactivity/immunology , Bronchoconstrictor Agents/pharmacology , CD8-Positive T-Lymphocytes/drug effects , Chemotaxis, Leukocyte/drug effects , Epithelial Cells/drug effects , Fenoterol/pharmacology , Receptors, Adrenergic, beta/drug effects , Adrenergic beta-Agonists/adverse effects , Aged , B-Lymphocytes/immunology , Bronchi/immunology , Bronchi/metabolism , Bronchial Hyperreactivity/chemically induced , Bronchial Hyperreactivity/metabolism , Bronchoconstriction/drug effects , Bronchoconstrictor Agents/adverse effects , CD8-Positive T-Lymphocytes/immunology , Cells, Cultured , Chemotaxis, Leukocyte/genetics , Cytokines/genetics , Cytokines/metabolism , Dose-Response Relationship, Drug , Endothelin-1/pharmacology , Epithelial Cells/immunology , Epithelial Cells/metabolism , Female , Fenoterol/adverse effects , Gene Expression Regulation , Humans , Immunohistochemistry , Inflammation Mediators/metabolism , Lung Neoplasms/immunology , Lung Neoplasms/metabolism , Male , Middle Aged , Pulmonary Disease, Chronic Obstructive/immunology , Pulmonary Disease, Chronic Obstructive/metabolism , RNA, Messenger/metabolism , Receptors, Adrenergic, beta/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Smoking Cessation , Time Factors
16.
Respirology ; 14(7): 1035-41, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19740263

ABSTRACT

BACKGROUND AND OBJECTIVE: Currently there are few data available regarding the use of impulse oscillometry parameters to assess airflow obstruction during standardized methacholine challenge testing. METHODS: Methacholine challenge tests were performed using impulse oscillometry and conventional spirometry in 64 healthy and 39 asthmatic children, in order to determine airway resistance (R) and reactance (X) at frequencies of 5-35 Hz, as well as FEV(1). RESULTS: Baseline R and X were significantly different between the healthy and asthmatic children, with the most discriminating parameter being resistance at 5 Hz (R5). In asthmatic children BHR was well demonstrated by FEV(1), X5 and X10, but not by R5. However, when the actual R5 values obtained in this study were compared with the predicted values, there appeared to be differences in the lung function measures that corresponded to varying methacholine concentrations. In addition, the PC20_FEV(1) and PC70_X5 were significantly more sensitive than other parameters for methacholine challenge testing. CONCLUSIONS: Measuring resistance at 5 Hz using impulse oscillometry facilitates significant differentiation of baseline lung function between asthmatic and healthy children. Additionally, X may be a suitable replacement for PC20 in methacholine challenge testing.


Subject(s)
Airway Resistance/physiology , Asthma/physiopathology , Bronchial Hyperreactivity/physiopathology , Lung/physiopathology , Asthma/chemically induced , Bronchial Hyperreactivity/chemically induced , Bronchoconstrictor Agents/adverse effects , Case-Control Studies , Child , Dose-Response Relationship, Drug , Female , Forced Expiratory Volume/physiology , Humans , Male , Methacholine Chloride/adverse effects , Oscillometry , Spirometry
17.
Pediatr Pulmonol ; 44(7): 728-30, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19504562

ABSTRACT

Asthma is associated with increases in sickle cell disease (SCD)-related morbidity and mortality. A thorough evaluation for asthma in children with SCD is important and may involve methacholine challenge (MCh). In this report, we present a 14-year-old male with SCD who was admitted for an acute painful episode following MCh. Pain events after MCh have not been previously reported in children with SCD. The risk-benefit ratio should be strongly considered prior to performance of MCh in this patient population, and all possible complications, including an acute painful episode, should be openly discussed with the parents and pediatric patient.


Subject(s)
Anemia, Sickle Cell/complications , Asthma/complications , Bronchial Provocation Tests/adverse effects , Bronchoconstrictor Agents/adverse effects , Chest Pain/chemically induced , Methacholine Chloride/adverse effects , Adolescent , Asthma/diagnosis , Humans , Male
19.
Arch. bronconeumol. (Ed. impr.) ; 44(8): 402-407, ago.2008. ilus, tab
Article in Es | IBECS | ID: ibc-67336

ABSTRACT

OBJETIVO: La prueba de provocación bronquial es un procedimiento habitual en el diagnóstico del asma, pero su realización resulta larga y tediosa. Por ello se han propuesto métodos que acortan su duración. Sin embargo, en los últimos años se ha señalado que dichos métodos pueden dar lugar a broncoconstricciones excesivas (BE). Los objetivos del presente estudio han sido: a) determinar la frecuencia de BE en pacientes con asma tras la aplicación del método abreviado de la prueba de provocación bronquial, y b) cuantificar si la determinación de óxido nítrico en aire exhalado (ONE) puede predecir la aparición de BE. PACIENTES Y MÉTODOS: Se ha realizado un estudio prospectivo sobre 210 asmáticos a quienes se determinó el ONE y se realizó una prueba de provocación bronquial siguiendo el protocolo abreviado de la European Respiratory Society (ERS). Se definió BE como una caída superior al 20% del volumen espiratorio forzado en el primer segundo tras la primera dosis, después de suprimir una dosis o tras el diluyente. Se construyó una curva de eficacia diagnóstica para determinar el mejor punto de corte del ONE para predecir BE y se calculó la probabilidad preprueba de presentar BE, siguiendo el teorema de Bayes. RESULTADOS: La frecuencia de BE en nuestra serie fue del 30%. Hubo diferencias significativas en el ONE, siendo la concentración más elevada en el grupo que presentó BE (32,6 frente a 16,2 ppb). El punto de corte de ONE elegido fue 19,5 ppb, con una sensibilidad del 80%, especificidad del 77% y valor predictivo negativo del 88%. El área bajo la curva de eficacia diagnóstica fue de 0,83 (intervalo de confianza del 95%, 0,77-0,89). CONCLUSIONES: La prueba de provocación bronquial abreviada que recomienda la ERS da lugar a un 30% de BE. La determinación de ONE podría identificar a los pacientes con mayor probabilidad de presentar BE. Una concentración de ONE inferior a 19,5 ppb permite realizar la prueba de provocación bronquial abreviada con seguridad


OBJECTIVE: The bronchial challenge test is commonly used to diagnose asthma but it is a tedious, time-consuming procedure. Although in recent years, several shortened methods have been proposed, it has been shown that they can give rise to exaggerated bronchoconstriction. The aims of the present study were a) to determine the frequency of exaggerated bronchoconstriction in patients with asthma following the application of a shortened bronchial challenge test, and b) to determine if the fraction of exhaled nitric oxide (FENO) can be used to predict the onset of exaggerated bronchoconstriction. PATIENTS AND METHODS: We performed a prospective study of 210 patients with asthma in whom FENO levels were measured in accordance with the abbreviated protocol recommended by the European Respiratory Society (ERS). Exaggerated bronchoconstriction was defined as a decrease of more than 20% in forced expiratory volume in 1 second after the first challenge, after a skipped dose, or after administration of saline. A receiver operating characteristic (ROC) curve was generated to determine the best FENO cutoff value for predicting exaggerated bronchoconstriction. The pretest probability of developing exaggerated bronchoconstriction was also calculated using Bayes' theorem. RESULTS: The frequency of exaggerated bronchoconstriction in our series was 30%. Patients who developed exaggerated bronchoconstriction had significantly higher FENO levels than those who did not (32.6 vs 16.2 parts per billion [ppb]). The chosen FENO cutoff of 19.5 ppb had a sensitivity of 80%, a specificity of 77%, and a negative predictive value of 88%. The area under the ROC curve was 0.83 (95% confidence interval, 0.77-0.89). CONCLUSIONS: The abbreviated bronchial challenge test recommended by the ERS led to exaggerated bronchoconstriction in 30% of the patients studied. FENO measurements could possibly be used to identify patients at increased risk of exaggerated bronchoconstriction. The shortened challenge test can be performed safely in individuals with a FENO of <19.5 ppb


Subject(s)
Humans , Male , Female , Adult , Nitric Oxide , Bronchoconstriction , Asthma/diagnosis , Bronchial Provocation Tests , Sensitivity and Specificity , Predictive Value of Tests , Prospective Studies , Bronchoconstrictor Agents/adverse effects , Spirometry/methods
20.
Respir Res ; 9: 45, 2008 May 27.
Article in English | MEDLINE | ID: mdl-18505586

ABSTRACT

BACKGROUND: Nitric oxide (NO) and carbon monoxide (CO) in exhaled breath are considered obtainable biomarkers of physiologic mechanisms. Therefore, obtaining their measures simply, non-invasively, and repeatedly, is of interest, and was the purpose of the current study. METHODS: Expired NO (ENO) and CO (ECO) were measured non-invasively using a gas micro-analyzer on several strains of mice (C57Bl6, IL-10-/-, A/J, MKK3-/-, JNK1-/-, NOS-2-/- and NOS-3-/-) with and without allergic airway inflammation (AI) induced by ovalbumin systemic sensitization and aerosol challenge, compared using independent-sample t-tests between groups, and repeated measures analysis of variance (ANOVA) within groups over time of inflammation induction. ENO and ECO were also measured in C57Bl6 and IL-10-/- mice, ages 8-58 weeks old, the relationship of which was determined by regression analysis. S-methionyl-L-thiocitrulline (SMTC), and tin protoporphyrin (SnPP) were used to inhibit neuronal/constitutive NOS-1 and heme-oxygenase, respectively, and alter NO and CO production, respectively, as assessed by paired t-tests. Methacholine-associated airway responses (AR) were measured by the enhanced pause method, with comparisons by repeated measures ANOVA and post-hoc testing. RESULTS: ENO was significantly elevated in naïve IL-10-/- (9-14 ppb) and NOS-2-/- (16 ppb) mice as compared to others (average: 5-8 ppb), whereas ECO was significantly higher in naïve A/J, NOS-3-/- (3-4 ppm), and MKK3-/- (4-5 ppm) mice, as compared to others (average: 2.5 ppm). As compared to C57Bl6 mice, AR of IL-10-/-, JNK1-/-, NOS-2-/-, and NOS-3-/- mice were decreased, whereas they were greater for A/J and MKK3-/- mice. SMTC significantly decreased ENO by ~30%, but did not change AR in NOS-2-/- mice. SnPP reduced ECO in C57Bl6 and IL-10-/- mice, and increased AR in NOS-2-/- mice. ENO decreased as a function of age in IL-10-/- mice, remaining unchanged in C57Bl6 mice. CONCLUSION: These results are consistent with the ideas that: 1) ENO is associated with mouse strain and knockout differences in NO production and AR, 2) alterations of ENO and ECO can be measured non-invasively with induction of allergic AI or inhibition of key gas-producing enzymes, and 3) alterations in AR may be dependent on the relative balance of NO and CO in the airway.


Subject(s)
Bronchoconstrictor Agents/adverse effects , Carbon Dioxide/metabolism , Methacholine Chloride/adverse effects , Nitric Oxide/metabolism , Pneumonia/chemically induced , Pneumonia/metabolism , Animals , Breath Tests , Exhalation , Heme Oxygenase (Decyclizing)/antagonists & inhibitors , Heme Oxygenase (Decyclizing)/metabolism , Interleukin-10/genetics , Interleukin-10/metabolism , MAP Kinase Kinase 3/genetics , MAP Kinase Kinase 3/metabolism , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Mitogen-Activated Protein Kinase 8/genetics , Mitogen-Activated Protein Kinase 8/metabolism , Nitric Oxide Synthase/antagonists & inhibitors , Nitric Oxide Synthase/metabolism , Nitric Oxide Synthase Type II/genetics , Nitric Oxide Synthase Type II/metabolism , Nitric Oxide Synthase Type III , Regression Analysis
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