PURPOSE: Cold weather exercise is common in many regions of the world; however, it is unclear whether respiratory function and symptom worsen progressively with colder air temperatures. Furthermore, it is unclear whether high-ventilation sport background exacerbates dysfunction and symptoms. METHODS: Seventeen active females (measure of the maximum volume of oxygen [VO(2max)]: 49.6±6.6 mL·kg⁻¹·min⁻¹) completed on different days in random order 5 blinded running trials at 0℃, -5℃, -10℃, -15℃, and -20℃ (humidity 40%) in an environmental chamber. Distance, heart rate, and rating of perceived exertion (RPE) were measured within each trial; forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), forced expiratory flow at 25%-75% (FEF₂₅₋₇₅), and forced expiratory flow at 50% (FEF₅₀) were measured pre- and post-test (3, 6, 10, 15, and 20 minutes). Respiratory symptoms and global effort were measured post-test spirometry. RESULTS: Mean decreases were found in FEV1 (4%-5% at 0℃, -5℃, -10℃, and -15℃; 7% at -20℃). FEF₂₅₋₇₅ and FEF₅₀ decreased 7% and 11% at -15℃ and -20℃, respectively. Post-exertion spirometry results were decreased most at 3 to 6 minutes, recovering back to baseline at 20 minutes. Respiratory symptoms and global effort significantly increased at -15℃ and -20℃ with decreased heart rate. High-ventilation sports decreased function more than low-ventilation participants but had fewer symptoms. CONCLUSIONS: These results indicate that intense exercise at cold air temperatures up to -20℃ is achievable; however, greater effort along with transient acute bronchoconstriction and symptoms of cough after exercising in temperatures colder than -15℃ are likely. It is recommended that individuals cover their mouth and reduce exercise intensity to ameliorate the effects of cold weather exercise.
Asthma, Exercise-Induced ; Athletes ; Bronchoconstriction ; Cold Climate ; Cough ; Female ; Forced Expiratory Volume ; Heart Rate ; Humans ; Mouth ; Oxygen ; Running ; Spirometry ; Sports ; Ventilation ; Vital Capacity ; Weather

PURPOSE: Exercise-induced bronchoconstriction (EIB) is common in “high ventilation” athletes, and the Eucapnic Voluntary Hyperpnea (EVH) airway provocation test is the standard EIB screen. Although the EVH test is widely used, the in-test performance in high ventilation athletes as well as the reproducibility of that performance has not been determined. Reproducibility of pre- and post-test spirometry and self-reported atopy/cough was also examined. METHODS: High ventilation athletes (competitive swimmers; n=11, 5 males) completed an atopy/cough questionnaire and EVH testing (operator controlled FiCO₂) on 2 consecutive days. RESULTS: Swimmers achieved 85%±9% and 87%±9% of target FEV1 volume on days 1 and 2, respectively, (P=0.45; ICC 0.57 [0.00-0.86]) resulting in a total ventilation of 687 vs 684 L [P=0.89, ICC 0.89 (0.65-0.97]) equating to 83%±8% and 84%±9% of predicted total volume (ICC 0.54 [0.00-0.85]) between days 1 and 2. FiCO₂ required to maintain eucapnic conditions was 2.5%. Pre-test FEV1 was less on day 2 (P=0.04; ICC >0.90). Day 1 to 2 post-test FEV1 was not different, and 4 swimmers were EIB positive (>10% fall in pre-post FEV1) on day 1 (3 on day 2). CONCLUSIONS: EVH in-test performance is reproducible however required less FiCO₂ than standard protocol and the swimmers under-ventilated by 125 and 139 L/min for days 1 and 2, respectively. How this affects EIB diagnosis remains to be determined; however, our results indicate a post-test FEV1 fall of ≥20% may be recommended as the most consistent diagnostic criterion.
Asthma, Exercise-Induced ; Athletes* ; Bronchoconstriction ; Cough ; Diagnosis ; Humans ; Respiratory Hypersensitivity ; Spirometry ; Swimming ; Ventilation*

PURPOSE: Several lines of evidence indicate that the Hippo/Yes-associated protein 1 (YAP1) pathways might play a role in the pathogenesis of asthma. To investigate the possible role of the Hippo/YAP1 pathway in the pathogenesis of asthma or its phenotypes. METHODS: The levels of gene expressions of the members of the Hippo/YAP1 were compared. The presence of the proteins of the YAP1 and FRMD6 were analyzed with Western blot in induced sputum of 18 asthmatic subjects and 10 control subjects. Fourteen single nucleotide polymorphisms (SNPs) in the YAP1 gene were genotyped in 522 asthmatic subjects and 711 healthy controls. The results were evaluated with traditional frequentist methods and with Bayesian network-based Bayesian multilevel analysis of relevance (BN-BMLA). RESULTS: The mRNA of all the members of the Hippo/YAP1 pathway could be detected in the induced sputum of both controls and cases. A correlation was found between YAP1 mRNA levels and sputum bronchial epithelial cells (r=0.575, P=0.003). The signal for the FRMD6 protein could be detected in all sputum samples while the YAP1 protein could not be detected in the sputum samples, of the healthy controls and severe asthmatics, but it was detectable in mild asthmatics. The rs2846836 SNP of the YAP1 gene was significantly associated with exercise-induced asthma (odds ratio [OR]=2.1 [1.3-3.4]; P=0.004). The distribution of genotypes of rs11225138 and certain haplotypes of the YAP1 gene showed significant differences between different asthma severity statuses. With BN-BMLA, 2 SNPs, genetic variations in the FRMD6 gene proved to be the most relevant to exercise-induced asthma and allergic rhinitis. These 2 SNPs through allergic rhinitis and exercise-induced asthma were in epistatic interaction with each other. CONCLUSIONS: Our results provided additional evidence that the FRMD6/Hippo/YAP1 pathway plays a role in the pathogenesis of asthma. If additional studies can confirm these findings, this pathway can be a potential novel therapeutic target in asthma and other inflammatory airway diseases.
Asthma* ; Asthma, Exercise-Induced ; Blotting, Western ; Epithelial Cells ; Gene Expression ; Genetic Variation ; Genetics ; Genotype ; Haplotypes ; Hypersensitivity* ; Multilevel Analysis ; Phenotype ; Polymorphism, Single Nucleotide ; Rhinitis ; Rhinitis, Allergic ; RNA, Messenger ; Sputum

Asthma is a prevalent and serious health problem in Korea. Recently, the Korean Asthma Guideline has been updated by The Korean Academy of Tuberculosis and Respiratory Diseases (KATRD) in an effort to improve the clinical management of asthma. This guideline focuses on adult patients with asthma and aims to deliver up to date scientific evidence and recommendations to general physicians for the management of asthma. For this purpose, this guideline was updated following systematic review and meta-analysis of recent studies and adapting some points of international guidelines (Global Initiative for Asthma [GINA] report 2014, National Asthma Education and Prevention Program [NAEPP] 2007, British Thoracic Society [BTS/SIGN] asthma guideline 2012, and Canadian asthma guideline 2012). Updated issues include recommendations derived using the population, intervention, comparison, and outcomes (PICO) model, which produced 20 clinical questions on the management of asthma. It also covers a new definition of asthma, the importance of confirming various airflow limitations with spirometry, the epidemiology and the diagnostic flow of asthma in Korea, the importance and evidence for inhaled corticosteroids (ICS) and ICS/formoterol as a single maintenance and acute therapy in the stepwise management of asthma, assessment of severity of asthma and management of exacerbation, and an action plan to cope with exacerbation. This guideline includes clinical assessments, and treatment of asthma-chronic obstructive pulmonary disease overlap syndrome, management of asthma in specific conditions including severe asthma, elderly asthma, cough variant asthma, exercise-induced bronchial contraction, etc. The revised Korean Asthma Guideline is expected to be a useful resource in the management of asthma.
Adrenal Cortex Hormones ; Adult ; Aged ; Asian Continental Ancestry Group ; Asthma* ; Asthma, Exercise-Induced ; Cough ; Education ; Epidemiology ; Humans ; Korea ; Lung Diseases, Obstructive ; Spirometry ; Tuberculosis

Leukotriene (LT) modifiers are composed of leukotriene receptor antagonists and 5-lipoxygenase inhibitors. LTs, C4, D4, and E4 are collectively termed cysteinyl LTs and best are the characterized receptors for cysLTs are cysLT1 and cysLT2. cysLT1 ligation mediates sustained bronchial contraction, mucosal secretion, and edema, which are central to the pathogenesis of asthma. cysLT2 ligation is thought to contribute to edema, inflammation, and tissue fibrosis in asthma. LT modifiers attenuate bronchoconstriction responses and exert anti-inflammatory effects, reflected by reduced eosinophil counts in the peripheral blood, sputum, and bronchoalveolar lavage fluid of asthmatic patients. Inhaled corticosteroids are generally superior to LT modifiers as a first-line controller. However, LT modifiers are easy to administer, have good compliance, and have excellent safety. LT modifiers are recommended for asthmatic children aged < or =5 years as a first-line controller. The Japanese Guideline for Childhood Asthma recommends LT modifiers, as a first-line controller prior to inhaled corticosteroid for children aged <2 years. LT modifiers can improve asthma control as add-on therapy with ICS. They can also be effective for exercise-induced asthma. LT modifiers are recommended for the treatment of allergic rhinitis in combination with H1-antihistamines or as a first-line drug for patients who cannot or do not wish to use intranasal corticosteroids. LT modifiers can also be considered for add-on therapy in the treatment of chronic urticaria, atopic dermatitis, and other allergic diseases.
Adrenal Cortex Hormones ; Asian Continental Ancestry Group ; Asthma ; Asthma, Exercise-Induced ; Bronchoalveolar Lavage Fluid ; Bronchoconstriction ; Child ; Compliance ; Dermatitis, Atopic ; Edema ; Eosinophils ; Fibrosis ; Humans ; Inflammation ; Leukotriene Antagonists ; Ligation ; Lipoxygenase Inhibitors ; Rhinitis ; Sputum ; Urticaria

BACKGROUND: Exercise-induced bronchoconstriction (EIB), which describes acute airway narrowing that occurs as a result of exercise, is associated with eosinophilic airway inflammation, bronchial hyperresponsiveness. The forced expiratory volume in one second (FEV₁) is the most commonly used spirometric test in the diagnosis of EIB in exercise challenge in asthma. Other parameters such as forced expiratory flow at 50% of the vital capacity (FEF(50%)) and peak expiratory flow (PEF) are used less often in the diagnosis of EIB. OBJECTIVE: The purpose of this study is to evaluate the association of FEV₁ and FEF(50%), PEF parameters, blood eosinophil counts in EIB in children with mild asthma. METHODS: Sixty-seven children (male: 39, female: 28) with mild asthma were included in this study. Pulmonary functions were assessed before and at 1, 5, 10, 15, and 20 minutes after exercise. The values of spirometric FEV₁, FEF50(%), PEF, and blood eosinophil counts were evaluated in EIB in children with mild asthma. RESULTS: There was a positive correlation between FEV₁ with FEF(50%) and PEF values (p < 0.05; FEF(50%), r=0.68; PEF, r=0.65). Also, a positive correlation was found between blood eosinophil counts and the values of spirometric FEV₁, FEF(50%), and PEF (p < 0.05; FEV₁, r=0.54; FEF(50%), r=0.42; PEF, r=0.26). In addition to these correlations, in the exercise negative group for FEV₁, the FEF(50%) and PEF values decreased more than the cutoff values in 3, and 2 patients, respectively. CONCLUSION: According to the presented study, eosinophil may play a major role in the severity of EIB in mild asthma. FEF(50%) and PEF values can decrease in response to exercise without changes in FEV₁ in mild asthmatic patients.
Asthma ; Asthma, Exercise-Induced ; Bronchoconstriction ; Child ; Diagnosis ; Eosinophils ; Female ; Forced Expiratory Volume ; Humans ; Inflammation ; Respiratory Function Tests ; Spirometry ; Vital Capacity

PURPOSE: We previously demonstrated seasonal variation in sensitization to aeroallergens in a small group of patients with exercise-induced asthma. This study was performed to confirm the relationship in a much larger population. METHODS: The charts of 1,891 patients who received allergy skin prick tests were reviewed retrospectively. The test results from subjects aged < or =60 years were compared between the groups classified according to the season when the patients received the tests (spring: March-May, summer: June-August, fall: September-November, winter: December-February). The data from 25 respiratory allergy patients who received the tests two or more times and showed a positive response at least once were analyzed longitudinally. RESULTS: The most prevalent among 29 tested aeroallergens were house dust mites (HDMs) Dermatophagoides pteronyssinus and D. farinae. The skin sensitization rates to D. pteronyssinus (23.2% vs. 32.1%, P=0.004) and D. farinae (22.2% vs. 30.2%, P=0.009) were significantly lower in the summer and higher in the fall (38.3% vs. 26.6% and 35.6% vs. 25.3%; P=0.001 respectively) than those in other seasons in patients with a respiratory allergy (n=1,102). The sensitization rates to weed pollens in the fall (13.9% vs. 8.3%, P=0.006) and to Aspergillus fumigatus in the winter (2.9% vs. 0.7%, P=0.005) were significantly higher. In patients with non-respiratory allergy such as urticaria/anaphylaxis (n=340), the D. farinae sensitization rate was significantly lower in the summer also but higher in the spring. The trend of the HDM sensitization rate being lower in the summer and higher in the fall was observed in the longitudinal study. CONCLUSIONS: Skin sensitivity to aeroallergens such as HDMs, pollens, and molds demonstrates seasonal variation in respiratory allergy patients. Non-respiratory allergy patients also showed seasonal variation in sensitivity to aeroallergens, which might be related to the "priming" effect of allergens.
Aged ; Allergens ; Aspergillus fumigatus ; Asthma, Exercise-Induced ; Dermatophagoides pteronyssinus ; Fungi ; Humans ; Hypersensitivity ; Pollen ; Pyroglyphidae ; Retrospective Studies ; Seasons ; Skin

PURPOSE: Exercise-induced bronchoconstriction (EIB) in patients with asthma occurs more frequently in winter than in summer. The concentration of house dust mite (HDM) allergens in beds also shows seasonal variation. This study examined the relationship between seasonal differences in the prevalence of EIB and sensitization to HDMs in patients with asthma. METHODS: The medical records of 74 young adult male patients with asthma-like symptoms who underwent bronchial challenge with methacholine, 4.5% saline and exercise, and allergen skin prick tests, were reviewed. The subjects were divided into summer (n=27), spring/fall (n=26) and winter (n=21) groups according to the season during which they underwent testing. RESULTS: The positive responses to exercise differed according to season (48.1% in summer, 73.1% in spring/fall, and 90.5% in winter; P<0.01). In addition, the prevalence of positive responses to HDM (70.4%, 88.5%, and 95.2%, respectively; P<0.05) and pollen skin tests (37.0%, 19.2%, and 0%, respectively; P<0.01) also showed significant seasonal differences. Severe responses to 4.5% saline showed a similar trend, although it was not statistically significant (44.4%, 50.0%, and 71.4%, respectively; P=0.07). Skin test reactivity to HDMs was significantly related to maximal fall in forced expiratory volume in one second (FEV1) following exercise (r=0.302, P<0.01) and the index of airway hyperresponsiveness (AHR) to 4.5% saline (r=-0.232, P<0.05), but not methacholine (r=-0.125, P>0.05). CONCLUSIONS: Positive skin test reactions to HDMs and EIB occurred in winter, spring/fall, and summer in decreasing order of frequency. Seasonal variation in the prevalence of EIB may be related to seasonal variation in sensitization to HDMs, accompanied by differences in indirect, but not direct, AHR.
Allergens ; Asthma ; Asthma, Exercise-Induced ; Bronchoconstriction ; Forced Expiratory Volume ; Humans ; Male ; Medical Records ; Methacholine Chloride ; Pollen ; Prevalence ; Pyroglyphidae ; Seasons ; Skin ; Skin Tests ; Young Adult

BACKGROUND/AIMS: Atopy is closely related to asthma and is a risk factor for the development and exacerbation of asthma. The aim of this study was to evaluate the association between exercise-induced asthma (EIA) and atopy in adult patients with asthma-like symptoms. METHODS: Forty young male patients with asthma-like symptoms were enrolled. Skin prick, methacholine bronchial provocation, and exercise provocation tests were performed. Current and ex-smokers were excluded. RESULTS: Exercise provocation tests were positive in 21 patients (52.5%). Airway hyperresponsiveness (AHR) to methacholine (85.7% vs. 42.1%, p = 0.007) and atopy (85.7% vs. 47.4, p = 0.017) was found more frequently in patients with EIA than in those without EIA. EIA was significantly associated with atopy score (16.5 +/- 3.0 vs. 6.5 +/- 2.0, p = 0.011), atopy index (2.1 +/- 0.3 vs. 1.0 +/- 0.3, p = 0.004), and positive responses to Dermatophagoides pteronyssinus (76.2% vs. 42.1%, p = 0.028) and Dermatophagoides farinae (76.2% vs. 36.8%, p = 0.012), but not with positive responses to pollen allergens. AHR to methacholine (odds ratio [OR]: 14.3, 95% confidence interval [CI]: 1.86-109.4) and atopy (OR: 16.9, 95% CI: 2.04-140.74) were significant risk factors for EIA. CONCLUSIONS: Atopy was a risk factor for EIA in young adult men, and sensitization to house dust mites was associated with EIA.
Adult ; Allergens ; Asthma ; Asthma, Exercise-Induced ; Bronchial Hyperreactivity ; Dermatophagoides farinae ; Dermatophagoides pteronyssinus ; Humans ; Male ; Methacholine Chloride ; Pollen ; Pyroglyphidae ; Risk Factors ; Skin ; Young Adult

BACKGROUND/AIMS: Atopy is closely related to asthma and is a risk factor for the development and exacerbation of asthma. The aim of this study was to evaluate the association between exercise-induced asthma (EIA) and atopy in adult patients with asthma-like symptoms. METHODS: Forty young male patients with asthma-like symptoms were enrolled. Skin prick, methacholine bronchial provocation, and exercise provocation tests were performed. Current and ex-smokers were excluded. RESULTS: Exercise provocation tests were positive in 21 patients (52.5%). Airway hyperresponsiveness (AHR) to methacholine (85.7% vs. 42.1%, p = 0.007) and atopy (85.7% vs. 47.4, p = 0.017) was found more frequently in patients with EIA than in those without EIA. EIA was significantly associated with atopy score (16.5 +/- 3.0 vs. 6.5 +/- 2.0, p = 0.011), atopy index (2.1 +/- 0.3 vs. 1.0 +/- 0.3, p = 0.004), and positive responses to Dermatophagoides pteronyssinus (76.2% vs. 42.1%, p = 0.028) and Dermatophagoides farinae (76.2% vs. 36.8%, p = 0.012), but not with positive responses to pollen allergens. AHR to methacholine (odds ratio [OR]: 14.3, 95% confidence interval [CI]: 1.86-109.4) and atopy (OR: 16.9, 95% CI: 2.04-140.74) were significant risk factors for EIA. CONCLUSIONS: Atopy was a risk factor for EIA in young adult men, and sensitization to house dust mites was associated with EIA.
Adult ; Allergens ; Asthma ; Asthma, Exercise-Induced ; Bronchial Hyperreactivity ; Dermatophagoides farinae ; Dermatophagoides pteronyssinus ; Humans ; Male ; Methacholine Chloride ; Pollen ; Pyroglyphidae ; Risk Factors ; Skin ; Young Adult